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J. Pers. Med., Volume 13, Issue 7 (July 2023) – 163 articles

Cover Story (view full-size image): Precision medicine programs aim to utilize novel technologies to identify personalized treatments for children with cancer. Delivering these programs requires interdisciplinary efforts, yet the many groups involved are understudied. This study explored the experiences of a broad range of professionals delivering Australia’s first precision medicine trial for children with poor-prognosis cancer: the PRecISion Medicine for Children with Cancer (PRISM) national clinical trial of the Zero Childhood Cancer Program. We conducted semi-structured interviews with 85 PRISM professionals from eight professional groups, including oncologists, surgeons, clinical research associates, scientists, genetic professionals, pathologists, animal care technicians, and nurses. View this paper
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14 pages, 251 KiB  
Review
Pharmacogenomics and the Management of Mood Disorders—A Review
by Kristian Kleine Schaars and Roos van Westrhenen
J. Pers. Med. 2023, 13(7), 1183; https://doi.org/10.3390/jpm13071183 - 24 Jul 2023
Cited by 2 | Viewed by 2454
Abstract
Due to the chronic relapsing nature of mental disorders and increased life expectancy, the societal burden of these non-communicable diseases will increase even further. Treatments for mental disorders, such as depression, are available, but their effect is limited due to patients’ (genetic) heterogeneity, [...] Read more.
Due to the chronic relapsing nature of mental disorders and increased life expectancy, the societal burden of these non-communicable diseases will increase even further. Treatments for mental disorders, such as depression, are available, but their effect is limited due to patients’ (genetic) heterogeneity, low treatment compliance and frequent side effects. In general, only one-third of the patients respond to treatment. Today, medication selection in psychiatry relies on a trial-and-error approach based mainly on physicians’ experience. Pharmacogenetic (PGx) testing can help in this process by determining the person-specific genetic factors that may predict clinical response and side effects associated with genetic variants that impact drug-metabolizing enzymes, drug transporters or drug targets. PGxis a discipline that investigates genetic factors that affect the absorption, metabolism, and transport of drugs, thereby affecting therapy outcome. These genetic factors can, among other things, lead to differences in the activity of enzymes that metabolize drugs. Studies in depressed patients show that genotyping of drug-metabolizing enzymes can increase the effectiveness of treatment, which could benefit millions of patients worldwide. This review highlights these studies, gives recommendations and provides future perspectives on how to proceed with PGx testing. Finally, it is recommended to consider genotyping for CYP2D6 and CYP2C19, when there is an indication (side effects or inefficacy). Full article
17 pages, 3529 KiB  
Article
Early MRI Predictors of Relapse in Primary Central Nervous System Lymphoma Treated with MATRix Immunochemotherapy
by Isabel Cornell, Ayisha Al Busaidi, Stephen Wastling, Mustafa Anjari, Kate Cwynarski, Christopher P. Fox, Nicolas Martinez-Calle, Edward Poynton, John Maynard and Steffi C. Thust
J. Pers. Med. 2023, 13(7), 1182; https://doi.org/10.3390/jpm13071182 - 24 Jul 2023
Viewed by 1628
Abstract
Primary Central Nervous System Lymphoma (PCNSL) is a highly malignant brain tumour. We investigated dynamic changes in tumour volume and apparent diffusion coefficient (ADC) measurements for predicting outcome following treatment with MATRix chemotherapy in PCNSL. Patients treated with MATRix (n = 38) [...] Read more.
Primary Central Nervous System Lymphoma (PCNSL) is a highly malignant brain tumour. We investigated dynamic changes in tumour volume and apparent diffusion coefficient (ADC) measurements for predicting outcome following treatment with MATRix chemotherapy in PCNSL. Patients treated with MATRix (n = 38) underwent T1 contrast-enhanced (T1CE) and diffusion-weighted imaging (DWI) before treatment, after two cycles and after four cycles of chemotherapy. Response was assessed using the International PCNSL Collaborative Group (IPCG) imaging criteria. ADC histogram parameters and T1CE tumour volumes were compared among response groups, using one-way ANOVA testing. Logistic regression was performed to examine those imaging parameters predictive of response. Response after two cycles of chemotherapy differed from response after four cycles; of the six patients with progressive disease (PD) after four cycles of treatment, two (33%) had demonstrated a partial response (PR) or complete response (CR) after two cycles. ADCmean at baseline, T1CE at baseline and T1CE percentage volume change differed between response groups (0.005 < p < 0.038) and were predictive of MATRix treatment response (area under the curve: 0.672–0.854). Baseline ADC and T1CE metrics are potential biomarkers for risk stratification of PCNSL patients early during remission induction therapy with MATRix. Standard interim response assessment (after two cycles) according to IPCG imaging criteria does not reliably predict early disease progression in the context of a conventional treatment approach. Full article
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<p>Patient inclusion and exclusion criteria.</p>
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<p>An example of the response groups defined for statistical analysis. T1CE-weighted images with manually segmented tumours before treatment (first column) and after completion of 2 and 4 cycles of MATRix immunotherapy (second and third columns, respectively) in a patient with complete response (Group 0, (<b>a</b>–<b>c</b>)), a patient with partial response (Group 1, (<b>e</b>–<b>g</b>)) and a patient with lack of response and with appearance of a new lymphoma deposit from 2 to 4 cycles of treatment (Group 2, (<b>i</b>–<b>k</b>)). Corresponding ADC images at baseline are shown for each example (Group 0, (<b>d</b>); Group 1, (<b>h</b>); Group 2, (<b>l</b>)).</p>
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<p>Boxplot demonstrating difference in Baseline Volumes between treatment response groups.</p>
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<p>Boxplot demonstrating difference in Baseline ADC<sub>min</sub> between groups.</p>
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<p>Boxplot demonstrating difference in Baseline ADC<sub>mean</sub> between groups.</p>
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<p>Receiver Operator Characteristic curve for ADC<sub>mean</sub> at baseline.</p>
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24 pages, 9118 KiB  
Article
Validation of Gait Measurements on Short-Distance Walkways Using Azure Kinect DK in Patients Receiving Chronic Hemodialysis
by Zhi-Ren Tsai, Chin-Chi Kuo, Cheng-Jui Wang, Jeffrey J. P. Tsai and Hsin-Hsu Chou
J. Pers. Med. 2023, 13(7), 1181; https://doi.org/10.3390/jpm13071181 - 24 Jul 2023
Cited by 4 | Viewed by 1537
Abstract
Muscle dysfunction, skeletal muscle fibrosis, and disability are associated with weakness in patients with end-stage renal disease. The main purpose of this study was to validate the effectiveness of a proposed system for gait monitoring on short-distance 1.5 m walkways in a dialysis [...] Read more.
Muscle dysfunction, skeletal muscle fibrosis, and disability are associated with weakness in patients with end-stage renal disease. The main purpose of this study was to validate the effectiveness of a proposed system for gait monitoring on short-distance 1.5 m walkways in a dialysis center. Gaits with reduced speed and stride length, long sit-to-stand time (SST), two forward angles, and two unbalanced gait regions are defined in the proposed Kinect v3 gait measurement and analysis system (K3S) and have been considered clinical features in end-stage renal disease (ESRD) associated with poor dialysis outcomes. The stride and pace calibrations of the Kinect v3 system are based on the Zeno Walkway. Its single rating intraclass correlation (ICC) for the stride is 0.990, and its single rating ICC for the pace is 0.920. The SST calibration of Kinect v3 is based on a pressure insole; its single rating ICC for the SST is 0.871. A total of 75 patients on chronic dialysis underwent gait measurement and analysis during walking and weighing actions. After dialysis, patients demonstrated a smaller stride (p < 0.001) and longer SST (p < 0.001). The results demonstrate that patients’ physical fitness was greatly reduced after dialysis. This study ensures patients’ adequate physical gait strength to cope with the dialysis-associated physical exhaustion risk by tracing gait outliers. As decreased stride and pace are associated with an increased risk of falls, further studies are warranted to evaluate the clinical benefits of monitoring gait with the proposed reliable and valid system in order to reduce fall risk in hemodialysis patients. Full article
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<p>Flowchart of patient selection.</p>
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<p>Four suggested workflow steps of K3S; Kinect v3′s 32 virtual skeleton joints are labeled No. 1–No. 32.</p>
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<p>Before coordinate transformation, the interpolation plane of the virtual foot coordinates was generated using No. 22 (x, y, z) and No. 26 (x, y, z) of <a href="#jpm-13-01181-f002" class="html-fig">Figure 2</a> in the region of the ground plane from SW to EW. The calibrated ground plane was obtained after coordinate transformation.</p>
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<p>K3S experiments encountered some unreasonable movements and their solvers: (<b>a</b>) Suddenly stopping and bending over to pick up some objects. (<b>b</b>) Walking back and forth. (<b>c</b>) Sitting in a wheelchair to move on the walkway. (<b>d</b>) The result of one-way trajectory detection for the walking case <b>b</b>. (<b>e</b>) Standard stride length of the right foot. (<b>f</b>) A generalized stride length of feet is a modified version extended from <b>e</b> for patients.</p>
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<p>K3S experiments encountered some unreasonable movements and their solvers: (<b>a</b>) Suddenly stopping and bending over to pick up some objects. (<b>b</b>) Walking back and forth. (<b>c</b>) Sitting in a wheelchair to move on the walkway. (<b>d</b>) The result of one-way trajectory detection for the walking case <b>b</b>. (<b>e</b>) Standard stride length of the right foot. (<b>f</b>) A generalized stride length of feet is a modified version extended from <b>e</b> for patients.</p>
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<p>Detection of the personal DWF and DSSF outliers for patient 1 is based on (<b>a</b>) DWF boundaries for patient 1. (<b>b</b>) DSSF boundaries for patient 1.</p>
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<p>Detection of the personal unbalanced gait of patient 1. (<b>a</b>) Outliers in green and yellow boxes for the phase portrait of CM(x)−No.22(x). (<b>b</b>) Outliers in green and yellow boxes for the phase portrait of CM(x)−No.26(x).</p>
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<p>Two sensors (A and B) of a pressure insole.</p>
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<p>Calibration design of the sit-and-stand time (SST) algorithm: (<b>a</b>) Seated photo of male subject 2 (the current front and side view), (<b>b</b>) standing photo of the same participant (the current front and side view), and t(B) time value obtained after standing up, standing, and just leaving pressure sensor B. (<b>c</b>) The peak and valley positions of the pelvis z(t) curve measured by K3S calculated by the rise time algorithm for the Kinect v3 origin of the coordinate system. (<b>d</b>) The pelvis z position of the sitting posture and its time point “o” calculated by the standing up time algorithm, and the starting point “Δ” of the pelvis z position of the just completed standing and walking posture. (<b>e</b>) The pressure sensor A is installed under the foot of the chair; the pressure sensor B is the point stepped on when standing up; assume time t; B pressure curve is t(B) at the end of the pressure after being compressed; A pressure curve is at the beginning of the pressure. When it is falling, it is t(A), then the time for a single rise is SST≡ t(B)−t(A). (<b>f</b>) The average sampling time Δt is approximately 0.02 s.</p>
Full article ">Figure 8 Cont.
<p>Calibration design of the sit-and-stand time (SST) algorithm: (<b>a</b>) Seated photo of male subject 2 (the current front and side view), (<b>b</b>) standing photo of the same participant (the current front and side view), and t(B) time value obtained after standing up, standing, and just leaving pressure sensor B. (<b>c</b>) The peak and valley positions of the pelvis z(t) curve measured by K3S calculated by the rise time algorithm for the Kinect v3 origin of the coordinate system. (<b>d</b>) The pelvis z position of the sitting posture and its time point “o” calculated by the standing up time algorithm, and the starting point “Δ” of the pelvis z position of the just completed standing and walking posture. (<b>e</b>) The pressure sensor A is installed under the foot of the chair; the pressure sensor B is the point stepped on when standing up; assume time t; B pressure curve is t(B) at the end of the pressure after being compressed; A pressure curve is at the beginning of the pressure. When it is falling, it is t(A), then the time for a single rise is SST≡ t(B)−t(A). (<b>f</b>) The average sampling time Δt is approximately 0.02 s.</p>
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<p>A clinical trial using three locations of the Dialysis Center of China Medical University Hospital (CMUH) was implemented as a unified coordinate system of the three walkways (<b>a</b>–<b>c</b>) was obtained after coordinate transformation.</p>
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<p>Zeno 426.72 cm × 121.92 cm walkway measures the stride and pace data analyzed by PKMAS software, and its spatial resolution is 1.27 cm. Calibration setting for the four strides and their paces measured by the Zeno Walkway and K3S.</p>
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<p>Comparison results for stride and pace measured using the Zeno Walkway and Kinect v3.</p>
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<p>Stability analysis experiment design of the main virtual joints. (<b>a</b>) The adhesive tape lines on tiles of a short-distance 1.6 m walkway in the laboratory indicate that the size of a tile is a 40 cm square. (<b>b</b>) This participant was standing on an 80 cm position (which has an adhesive tape line). (<b>c</b>) This participant stands at three positions (40 cm, 80 cm, and 120 cm) which correspond to Kinect v3 virtual skeleton frames to check the stability of joints for the new origin of the coordinate system.</p>
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<p>Reliability and validity analysis experiment of the actual forward angles (<b>a</b>) 5 degrees, (<b>b</b>) 35 degrees, and (<b>c</b>) 60 degrees of male subject 2.</p>
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<p>The SST calibration result is illustrated using the correlation of Kinect v3’s and two pressure sensors’ SST data.</p>
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<p>Analysis results of gait statistics of 75 patients (12 November 2021–18 May 2022) in this study: (<b>a</b>) Maximum stride length outliers are defined below the median–SD boundary. (<b>b</b>) The height histogram of all participants. (<b>c</b>) Normalized maximum stride length outliers are defined below the median–SD boundary. (<b>d</b>) Pace outliers are defined below the median–SD boundary. (<b>e</b>) SST outliers are defined beyond the median + SD boundary. (<b>f</b>) Shows the distributed numbers of the DWF outliers of all participants whose warning DWF outliers are defined beyond the median + SD boundary of these distributed numbers. (<b>g</b>) Shows the distributed numbers of the UPN of all participants whose warning UPN outliers are defined beyond the median + SD boundary of these distributed numbers.</p>
Full article ">Figure 15 Cont.
<p>Analysis results of gait statistics of 75 patients (12 November 2021–18 May 2022) in this study: (<b>a</b>) Maximum stride length outliers are defined below the median–SD boundary. (<b>b</b>) The height histogram of all participants. (<b>c</b>) Normalized maximum stride length outliers are defined below the median–SD boundary. (<b>d</b>) Pace outliers are defined below the median–SD boundary. (<b>e</b>) SST outliers are defined beyond the median + SD boundary. (<b>f</b>) Shows the distributed numbers of the DWF outliers of all participants whose warning DWF outliers are defined beyond the median + SD boundary of these distributed numbers. (<b>g</b>) Shows the distributed numbers of the UPN of all participants whose warning UPN outliers are defined beyond the median + SD boundary of these distributed numbers.</p>
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14 pages, 3610 KiB  
Article
Influence of the Bile Acid Transporter Genes ABCB4, ABCB8, and ABCB11 and the Farnesoid X Receptor on the Response to Ursodeoxycholic Acid in Patients with Nonalcoholic Steatohepatitis
by Henriette Kreimeyer, Katharina Vogt, Tobias Götze, Jan Best, Oliver Götze, Jochen Weigt, Alisan Kahraman, Mustafa Özçürümez, Julia Kälsch, Wing-Kin Syn, Svenja Sydor, Ali Canbay and Paul Manka
J. Pers. Med. 2023, 13(7), 1180; https://doi.org/10.3390/jpm13071180 - 24 Jul 2023
Cited by 1 | Viewed by 1754
Abstract
The prevalence of NAFLD and NASH is increasing worldwide, and there is no approved medical treatment until now. Evidence has emerged that interfering with bile acid metabolism may lead to improvement in NASH. In this study, 28 patients with elevated cholestatic liver function [...] Read more.
The prevalence of NAFLD and NASH is increasing worldwide, and there is no approved medical treatment until now. Evidence has emerged that interfering with bile acid metabolism may lead to improvement in NASH. In this study, 28 patients with elevated cholestatic liver function tests (especially GGT) were screened for bile acid gene polymorphisms and treated with UDCA. All patients had a bile acid gene polymorphism in ABCB4 or ABCB11. Treatment with UDCA for 12 months significantly reduced GGT in all patients and ALT in homozygous patients. No difference in fibrosis was observed using FIb-4, NFS, and transient elastography (TE). PNPLA3 and TM6SF2 were the most common NASH-associated polymorphisms, and patients with TM6SF2 showed a significant reduction in GGT and ALT with the administration of UDCA. In conclusion, NASH patients with elevated GGT should be screened for bile acid gene polymorphisms, as UDCA therapy may improve liver function tests. However, no difference in clinical outcomes, such as progression to cirrhosis, has been observed using non-invasive tests (NITs). Full article
(This article belongs to the Special Issue Novel Challenges and Therapeutic Options for Liver Diseases)
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<p>Number of polymorphisms per patient. Most patients showed 4 or 5 polymorphisms regarding all analyzed bile acid transporter genes and NAFLD-associated genes.</p>
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<p>AST level at baseline and after 6 and 12 months in all patients. Median AST level was 46 (23–104) U/l at baseline vs. 35.4 (19–94.2) U/l at 6 months, <span class="html-italic">p</span> = 0.031. No further significant reduction was observed after 12 months (32.3 (19–102) U/l, <span class="html-italic">p</span> = 0.546 (0 vs. 12 months) and <span class="html-italic">p</span> = 1 (6 vs. 12 months).</p>
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<p>GGT and ALT level in patients with polymorphism in <span class="html-italic">ABCB4</span>, respectively, <span class="html-italic">A</span> total cohort, <span class="html-italic">B</span> wildtype, <span class="html-italic">C</span> heterozygote, <span class="html-italic">D</span> homozygote. (<b>I</b>) GGT is significantly reduced in heterozygote and homozygote polymorphism in <span class="html-italic">ABCB4</span> c.504 C&gt;T after 6 months. (<b>II</b>) ALT is significantly reduced in heterozygote and homozygote polymorphism in <span class="html-italic">ABCB4</span> c.504 C&gt;T after 6 and 12 months, respectively. (<b>III</b>,<b>IV</b>) GGT and ALT are significantly reduced in homozygote polymorphism in <span class="html-italic">ABCB4</span> c. 711 A&gt;T after 6 and 12 months.</p>
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<p>GGT and ALT level in patients with polymorphism in <span class="html-italic">ABCB11</span>, respectively, <span class="html-italic">A</span> total cohort, <span class="html-italic">B</span> wildtype, <span class="html-italic">C</span> heterozygote, <span class="html-italic">D</span> homozygote. (<b>I</b>) GGT is significantly reduced in heterozygote and homozygote polymorphism in <span class="html-italic">ABCB11</span> c. 3084 A&gt;G after 6 months in heterozygote and after 12 months in homozygote patients. (<b>II</b>) ALT is significantly reduced in homozygote polymorphism in <span class="html-italic">ABCB11</span> c.3048 A&gt;G after 12 months. (<b>III</b>) GGT is significantly reduced in heterozygote and homozygote polymorphism in <span class="html-italic">ABCB11</span> c. 1331 T&gt;C after 12 months in heterozygote and after 6 and 12 months in homozygote patients. (<b>IV</b>) ALT is significantly reduced in homozygote polymorphism in <span class="html-italic">ABCB11</span> c. 1331 T&gt;C after 12 months.</p>
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<p>GGT and ALT level in patients with polymorphism in <span class="html-italic">PNPLA3</span>, respectively, <span class="html-italic">A</span> heterozygote and <span class="html-italic">B</span> homozygote. (<b>I</b>) GGT is significantly reduced in homozygote polymorphism in <span class="html-italic">PNPLA3</span> after 6 and 12 months. (<b>II</b>) ALT is significantly reduced in homozygote polymorphism in <span class="html-italic">PNPLA3</span> after 6 months.</p>
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13 pages, 2101 KiB  
Article
Analysis of the Comorbid Course of Chronic Obstructive Pulmonary Disease
by Stanislav Kotlyarov
J. Pers. Med. 2023, 13(7), 1179; https://doi.org/10.3390/jpm13071179 - 24 Jul 2023
Cited by 2 | Viewed by 1639
Abstract
(1) Background. Chronic obstructive pulmonary disease (COPD) has a heterogeneous natural history, manifested both in the variability of clinical features and in association with various comorbid pathologies. Atherosclerotic cardiovascular disease (ASCVD) is of great clinical importance and contributes significantly to the natural history [...] Read more.
(1) Background. Chronic obstructive pulmonary disease (COPD) has a heterogeneous natural history, manifested both in the variability of clinical features and in association with various comorbid pathologies. Atherosclerotic cardiovascular disease (ASCVD) is of great clinical importance and contributes significantly to the natural history and prognosis of COPD. The present study aimed to evaluate the nature of the comorbid course of COPD during a 15-year follow-up. (2) Methods: A total of 170 male COPD patients were included in this study. Spirometry values, symptom severity, presence of risk factors, and comorbidities were considered. Prognostic factors were evaluated using the Kaplan–Meier method. (3) Results: ASCVD was the most common comorbidity and the main cause of death in patients with COPD. Patients with comorbid COPD and ASCVD had more severe dyspnea, higher frequency of COPD exacerbations, and worse survival than patients without ASCVD (p < 0.01). Among patients with COPD, the risk of death from ASCVD was higher in those older than 60 years (OR 3.23, 95% CI [1.72, 6.07]), those with rapidly declining FEV1 (OR 4.35, 95% CI [2.28, 8.30]), those with more than two exacerbations per year (OR 3.21, 95% CI [1.71, 6.11]), and those with a pack year index greater than 30 (OR 2.75, 95% CI [1.38, 5.51]. High Charlson comorbidity index scores in patients with COPD were associated with a more severe disease course, including severity of dyspnea, frequency of exacerbations, and multivariate index scores. A high Charlson comorbidity index score was an adverse prognostic factor. (4) Conclusions: ASCVD influences the course of the disease and is a major cause of mortality in COPD patients. Full article
(This article belongs to the Special Issue Current Challenges and Advances in Chronic Respiratory Diseases)
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<p>Study design.</p>
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<p>Results of univariate logistic regression analysis of factors influencing COPD and ASCVD deaths.</p>
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<p>CCI in patients with different severity of dyspnea and frequency of COPD exacerbations. Note: The figures show CCI values for different severity of mMRC dyspnea and different frequency of exacerbations (&lt;2 and ≥2 per year).</p>
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<p>Kaplan–Meier survival curve plot and ROC curve for the CCI. Note: CCI subgroup 1 is a score of 1 to 4, subgroup 2 is a score of 5 to 6, and subgroup 3 is a score of 7 or higher.</p>
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<p>Kaplan–Meier curve plots of survival according to the presence of comorbid PAD and CAD.</p>
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9 pages, 623 KiB  
Article
Feasibility and Surgical Outcomes of Hybrid Robotic Single-Site Hysterectomy Compared with Single-Port Access Total Laparoscopic Hysterectomy
by Joseph J. Noh, Jung-Eun Jeon, Ji-Hee Jung and Tae-Joong Kim
J. Pers. Med. 2023, 13(7), 1178; https://doi.org/10.3390/jpm13071178 - 24 Jul 2023
Cited by 1 | Viewed by 1491
Abstract
We compared surgical outcomes between single-port access total laparoscopic hysterectomy (SPA-TLH) and hybrid robotic single-site hysterectomy (RSSH), a new technique of combining the benefits of SPA-TLH with RSSH in this study. A total of 64 patients were retrospectively analyzed. They underwent either hybrid [...] Read more.
We compared surgical outcomes between single-port access total laparoscopic hysterectomy (SPA-TLH) and hybrid robotic single-site hysterectomy (RSSH), a new technique of combining the benefits of SPA-TLH with RSSH in this study. A total of 64 patients were retrospectively analyzed. They underwent either hybrid RSSH or SPA-TLH for benign gynecologic disease between December 2018 and August 2021. To assess the feasibility of hybrid RSSH, the clinical characteristics and surgical outcomes were compared between the hybrid RSSH group (n = 29) and the SPA-TLH group (n = 35). All of the surgeries were completed without requiring additional ports or conversion to laparotomy. The surgical outcomes including total operative time, uterine weight, estimated blood loss, hemoglobin changes, length of hospital stay, and postoperative pain scores were not significantly different between the two groups. The colpotomy time, including the detachment of the uterosacral and cardinal ligaments, was shorter in the hybrid RSSH group than in the SPA-TLH group (8.0 min vs. 14.0 min; p = 0.029). However, the vaginal cuff closure time was longer in the hybrid RSSH group than in the SPA-TLH group (15.0 min vs.10.0 min; p = 0.001). No difference was observed with regards to intraoperative and postoperative complications. Hybrid RSSH appears to be a feasible procedure for hysterectomy in patients with benign gynecologic diseases. Full article
(This article belongs to the Section Methodology, Drug and Device Discovery)
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<p>Surgical procedure steps for hybrid RSSH and SPA-TLH.</p>
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10 pages, 2775 KiB  
Case Report
Transesophageal Echocardiography Guidance to Prevent and Manage Pitfalls from Abdominal Normothermic Regional Perfusion and Optimize Timing during Organ Retrieval from a Donor after Circulatory Death
by Amedeo Bianchini, Cristiana Laici, Noemi Miglionico, Maria Giacinta Bianchi, Elena Tarozzi, Enrico Bernardi, Jessica Toni, Erika Cordella, Giovanni Vitale and Antonio Siniscalchi
J. Pers. Med. 2023, 13(7), 1177; https://doi.org/10.3390/jpm13071177 - 24 Jul 2023
Viewed by 1544
Abstract
An essential means of collecting more abdominal donor organs is controlled donation after circulatory death (cDCD). The organs are typically preserved during cDCD using the abdominal normothermic regional perfusion (A-NRP) technique to recirculate oxygenated blood flow following cardiac arrest and the withdrawal of [...] Read more.
An essential means of collecting more abdominal donor organs is controlled donation after circulatory death (cDCD). The organs are typically preserved during cDCD using the abdominal normothermic regional perfusion (A-NRP) technique to recirculate oxygenated blood flow following cardiac arrest and the withdrawal of life support. One of the challenges of A-NRP is ensuring the correct vascular devices’ positionings, specifically extracorporeal membrane oxygenation cannulae and aortic balloons, typically achieved through fluoroscopy with or without contrast agents. Here, we present a case report in which transesophageal echocardiography (TEE) helped the transplant team to effectively procure viable abdominal organs from a cDCD donor in the shortest time frame, as minimizing time is one of the most crucial factors in maintaining organ viability. TEE use leads to a more effective and efficient A-NRP procedure with limited complications. In addition, it allows us to observe the circulation of both the thoracic and part of the abdominal organs using one fast exam. This case is the first report describing TEE as a primary guide and useful tool for DCD donors. However, prospective studies are needed to confirm that TEE could be used as standard practice during all DCD organ retrieval procedures. Full article
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<p>(<b>A</b>). Mid-esophageal bicaval view. The guidewire (*) was inserted through the inferior vena cava into the right atrium. (<b>B</b>). Mid-esophageal descending aorta long-axis view. The aortic occlusion catheter is visualized in the thoracic aorta; the deflated balloon is located just above the diaphragm. (<b>C</b>). Mid-esophageal descending aorta long-axis view during A-NRP. The position of the AB (inflated) remained unchanged above the diaphragm. IVC—inferior vena cava; RA—right atrium; SVC—superior vena cava; * guidewire; Ao—aorta; AOC—aortic occlusion catheter; LA—lung atelectasis; Dia – diaphragm; DB—desufflated balloon; IB—inflated balloon.</p>
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<p>(<b>A</b>). Mid-esophageal descending aortic long-axis view scan: the endovascular occluder (RELIANT<sup>®</sup> catheter balloon, Tamworth, UK) is visible in the descending thoracic aorta. (<b>B</b>). Incomplete occlusion of the thoracic aorta during the initial phase of regional extracorporeal support for organ retrieval. Transesophageal color Doppler echocardiography documents the passage of blood around the aortic occluder. (<b>C</b>). Complete occlusion of the thoracic aorta after additional filling of the RELIANT<sup>®</sup> AB. Absence of blood flow in the thoracic aorta above the occluder. LA—lung atelectasis.</p>
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<p>(<b>A</b>). Transesophageal color Doppler echocardiography with transgastric approach during the initial phase of regional extracorporeal support. Slow hepatic artery flow is sampled due to incomplete aortic occlusion (continuous right hepatic artery flow velocity = 7 cm/s). Portal vein flow was absent. (<b>B</b>). Color Doppler ultrasound with convex probe after complete aortic occlusion. Right hepatic artery flow was increased (velocity 25 cm/s) and the portal flow was sampled (velocity 12 cm/s). (<b>C</b>). Absence of flow in the left ventricle and atrium after complete aortic occlusion (mid-esophageal two-chamber view).</p>
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<p>Visual timeline of the events in subjects undergoing the DCD process at IRCCS Azienda Ospedaliero-Universitaria di Bologna. A-NRP—abdominal normothermic regional perfusion; AOC—aortic occlusion catheter; ICU—intensive care unit; IU—international units; Kg—kilograms; NRP—normothermic regional perfusion; TEE—transesophageal echocardiography. * TEE echocardiographic guide is used to verify correct placement. ** According to the direct Seldinger technique.</p>
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<p>Role of TEE to guide abdominal DCD organ donation. E—extracorporeal membrane oxygenator; Cd—drainage cannula; Cr—re-infusion cannula; AOC—aortic occlusion catheter; M—pressure monitors; P—TEE probe.</p>
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16 pages, 1400 KiB  
Review
Immune Biomarkers in Triple-Negative Breast Cancer: Improving the Predictivity of Current Testing Methods
by Francesca Maria Porta, Elham Sajjadi, Konstantinos Venetis, Chiara Frascarelli, Giulia Cursano, Elena Guerini-Rocco, Nicola Fusco and Mariia Ivanova
J. Pers. Med. 2023, 13(7), 1176; https://doi.org/10.3390/jpm13071176 - 23 Jul 2023
Cited by 11 | Viewed by 4002
Abstract
Triple-negative breast cancer (TNBC) poses a significant challenge in terms of prognosis and disease recurrence. The limited treatment options and the development of resistance to chemotherapy make it particularly difficult to manage these patients. However, recent research has been shifting its focus towards [...] Read more.
Triple-negative breast cancer (TNBC) poses a significant challenge in terms of prognosis and disease recurrence. The limited treatment options and the development of resistance to chemotherapy make it particularly difficult to manage these patients. However, recent research has been shifting its focus towards biomarker-based approaches for TNBC, with a particular emphasis on the tumor immune landscape. Immune biomarkers in TNBC are now a subject of great interest due to the presence of tumor-infiltrating lymphocytes (TILs) in these tumors. This characteristic often coincides with the presence of PD-L1 expression on both neoplastic cells and immune cells within the tumor microenvironment. Furthermore, a subset of TNBC harbor mismatch repair deficient (dMMR) TNBC, which is frequently accompanied by microsatellite instability (MSI). All of these immune biomarkers hold actionable potential for guiding patient selection in immunotherapy. To fully capitalize on these opportunities, the identification of additional or complementary biomarkers and the implementation of highly customized testing strategies are of paramount importance in TNBC. In this regard, this article aims to provide an overview of the current state of the art in immune-related biomarkers for TNBC. Specifically, it focuses on the various testing methodologies available and sheds light on the immediate future perspectives for patient selection. By delving into the advancements made in understanding the immune landscape of TNBC, this study aims to contribute to the growing body of knowledge in the field. The ultimate goal is to pave the way for the development of more personalized testing strategies, ultimately improving outcomes for TNBC patients. Full article
(This article belongs to the Special Issue Cancer Biomarkers and Therapy)
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<p>Overview and applications of digital and computational pathology to enhance testing of immune-related biomarkers in TNBC. PD-L1 (CPS): programmed death-1 ligand (combined positive score); PD-L1 (IC): programmed death-1 ligand (immune cell score); TILs: tumor-infiltrating lymphocytes; MMR: mismatch repair; MSI: microsatellite instability.</p>
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15 pages, 904 KiB  
Review
The Role of Matrix Metalloproteinases in Hemorrhagic Transformation in the Treatment of Stroke with Tissue Plasminogen Activator
by Valentina A. Babenko, Ksenia S. Fedulova, Denis N. Silachev, Parvaneh Rahimi-Moghaddam, Yulia N. Kalyuzhnaya, Svetlana V. Demyanenko and Egor Y. Plotnikov
J. Pers. Med. 2023, 13(7), 1175; https://doi.org/10.3390/jpm13071175 - 23 Jul 2023
Cited by 2 | Viewed by 1881
Abstract
Ischemic stroke is a leading cause of disability and mortality worldwide. The only approved treatment for ischemic stroke is thrombolytic therapy with tissue plasminogen activator (tPA), though this approach often leads to a severe complication: hemorrhagic transformation (HT). The pathophysiology of HT in [...] Read more.
Ischemic stroke is a leading cause of disability and mortality worldwide. The only approved treatment for ischemic stroke is thrombolytic therapy with tissue plasminogen activator (tPA), though this approach often leads to a severe complication: hemorrhagic transformation (HT). The pathophysiology of HT in response to tPA is complex and not fully understood. However, numerous scientific findings suggest that the enzymatic activity and expression of matrix metalloproteinases (MMPs) in brain tissue play a crucial role. In this review article, we summarize the current knowledge of the functioning of various MMPs at different stages of ischemic stroke development and their association with HT. We also discuss the mechanisms that underlie the effect of tPA on MMPs as the main cause of the adverse effects of thrombolytic therapy. Finally, we describe recent research that aimed to develop new strategies to modulate MMP activity to improve the efficacy of thrombolytic therapy. The ultimate goal is to provide more targeted and personalized treatment options for patients with ischemic stroke to minimize complications and improve clinical outcomes. Full article
(This article belongs to the Special Issue Neurological Diseases: From Molecular Mechanisms to Clinical Practice)
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<p>Dynamics of the level and activity of MMP-2 and MMP-9 in the brain during ischemic stroke.</p>
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<p>Mechanisms related to the influence of tPA on MMPs. tPA interacts with low-density lipoprotein receptor-related proteins (LRP) to activate intracellular signaling pathways, ultimately leading to increased MMP activity. Moreover, tPA activates the plasminogen-mediated proteolytic cascade, culminating in MMP activation. In addition, tPA has been shown to interact directly with MMPs, leading to their activation. It has been demonstrated that tPA can induce degranulation of neutrophils, whose granules are known to contain MMPs. Under conditions of hyperglycemia, tPA triggers TXNIP–NLRP3 inflammatory signaling. TXNIP binds to the NLRP3 protein and activates a post-ischemic inflammatory process that affects VEGF signaling, which, in turn, increases MMP levels (question mark indicates putative mechanism). Formation of plasmin based on the activity of tPA triggers activation of the PAR1 receptor, which relays a signal via the G protein Gαq that leads to the release of pro-MMP-9.</p>
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10 pages, 4587 KiB  
Article
Immune Status of Cervical Lymph Nodes in Head and Neck Cancer—A Surgical Oncology Perspective
by Hiromu Nakamura, Tetsuya Ogawa, Shunpei Yamanaka, Daisuke Inukai, Takashi Maruo, Taishi Takahara, Akira Satou, Toyonori Tsuzuki, Susumu Suzuki, Ryuzo Ueda and Yasushi Fujimoto
J. Pers. Med. 2023, 13(7), 1174; https://doi.org/10.3390/jpm13071174 - 22 Jul 2023
Cited by 2 | Viewed by 1795
Abstract
Neck dissection for cervical lymph node metastasis is an established procedure for head and neck cancer (HNC). However, with the advent of immunotherapy, head and neck surgical oncologists need to rethink removing all lymph nodes, including those with immune function. We investigated the [...] Read more.
Neck dissection for cervical lymph node metastasis is an established procedure for head and neck cancer (HNC). However, with the advent of immunotherapy, head and neck surgical oncologists need to rethink removing all lymph nodes, including those with immune function. We investigated the anti-cancer immune response of the cervical lymph nodes in four patients with human papillomavirus type 16 (HPV16)-positive head and neck squamous cell carcinoma. Using lymphocytes extracted from local, metastatic, and non-metastatic lymph nodes and peripheral blood from these patients, we performed an intracellular flow cytometric cytokine assay using anti-IFNγ and anti-TNF-α monoclonal antibodies to detect HPV16 E6- and E7-specific T cells. HPV status and p16 immunostaining were determined by in situ detection using the HPV RNAscope method and immunohistochemistry. In one case, E6-specific and E7-specific CD8+ T cells were detected in proximal metastatic nodes and distal non-metastatic nodes. This finding suggests that non-metastatic nodes should be preserved for their immune function during neck dissection and that the immune function of non-metastatic lymph nodes is important when administering immunotherapy. In this context, head and neck surgical oncologists treating HNC should consider the place of immunotherapy and neck dissection in the treatment of HNC. Full article
(This article belongs to the Special Issue Head and Neck Cancer—Diagnostics, Prevention and Management)
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<p>p16-Immunostained micrographs in case 1.</p>
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<p>RNAscope targeting human papillomavirus type 16 E6 and E7 mRNA.</p>
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<p>Detection of HPV16 E6-specific and E7-specific T cells in lymphocytes from peripheral blood and lymph nodes in case 1. PBL, MLN, PLN, and DLN were co-cultured with HPV16 E6 or E7 overlapping peptide pools (OPP) for 2 weeks and then restimulated with the cognate peptides. Next, intracellular IFN-γ and TNF-α were detected with flow cytometry. The cells gated on the CD8+ fraction or CD4+ fraction were separated into 2 dimensions with IFN-γ (vertical axis) and TNF-α (horizontal axis) and divided into quadrants. E6+ and E7+ indicate the cells that were restimulated with each OPP, while E6- and E7- indicate the cells that were not restimulated with any peptides. The numbers in each cytogram indicate the frequency in each quadrant as a percentage. In the event that the IFN-γ and/or TNF-α positive frequencies in restimulated cells were more than twice those in non-restimulated cells, the reaction to restimulation was judged to be specific. Red frames indicate specific reactions. (<b>A</b>) HPV16 E6-specific CD8+ T cells are detected in MLN and DLN. (<b>B</b>) HPV16 E7-specific CD8+ T cells detected in MLN and PLN. (<b>C</b>,<b>D</b>) Neither HPV16 E6-specific nor HPV16 E7-specific CD4+ T cells were detected in cells at any site. DLN, distal lymph nodes; HPV16, human papillomavirus type 16; IFN, interferon; MLN, metastatic lymph nodes; PBL, peripheral blood lymphocytes; PLN, proximal lymph nodes; TNF, tumor necrosis factor.</p>
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16 pages, 1131 KiB  
Article
Characterization and Factors Associated with Poor Asthma Control in Adults with Severe Eosinophilic Asthma
by Clara Padró-Casas, María Basagaña, María Luisa Rivera-Ortún, Ignasi García-Olivé, Carlos Pollan-Guisasola, Aina Teniente-Serra, Eva Martínez-Cáceres, José-Tomás Navarro, Jorge Abad-Capa, Antoni Rosell, Albert Roger and Carlos Martínez-Rivera
J. Pers. Med. 2023, 13(7), 1173; https://doi.org/10.3390/jpm13071173 - 22 Jul 2023
Cited by 4 | Viewed by 1412
Abstract
A study was conducted in 98 adult patients diagnosed with severe eosinophilic asthma (73.5% women, mean age 47.2 years) and followed prospectively for 1 year. The aim of the study was to characterize this population and to identify factors associated with poor prognosis [...] Read more.
A study was conducted in 98 adult patients diagnosed with severe eosinophilic asthma (73.5% women, mean age 47.2 years) and followed prospectively for 1 year. The aim of the study was to characterize this population and to identify factors associated with poor prognosis at 1 year of follow-up. At the initial visit, uncontrolled severe asthma was diagnosed in 87.7% of patients. Allergic sensitization was observed in 81.7% (polysensitization in 17.3%), with clinically significant allergic asthma in 45%. The mean percentage of sputum eosinophils was 4.7% (standard deviation(SD) 6.3%) and the mean (SD) blood eosinophil count 467 (225) cells/µL. Almost half of the patients (48.3%) had sputum eosinophilia (>3% eosinophils). Sputum eosinophils correlated significantly with peripheral eosinophilia (p = 0.004) and, to a lesser extent, with fractional exhaled nitric oxide (FeNO) (p = 0.04). After 1 year, 48 patients (49%) had uncontrolled asthma in all visits, and 50 (51%) had controlled asthma in some visits. Airway obstruction (FEV1 < 80% predicted) was the main reason for uncontrolled asthma. In the multivariate analysis, an obstructive pattern (odds ratio (OR) 7.45, 95% confidence interval (CI) 2.41–23.03, p < 0.0001) and the patient’s age (OR 1.045, 95% CI 1.005–1.086, p = 0.026) were independent predictors of poor asthma control. In adult-onset and long-standing asthma, serum interleukin (IL) IL-17 was higher in the uncontrolled asthma group. This study contributes to characterizing patients with severe eosinophilic asthma in real-world clinical practice. Full article
(This article belongs to the Section Mechanisms of Diseases)
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<p>Correlation between sputum eosinophils and blood eosinophil count (<b>left</b>) and FeNO (<b>right</b>).</p>
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<p>Percentage of patients with uncontrolled asthma at the initial visit and during the 12-month follow-up period considering the criteria of an ACT score &lt; 20, number of exacerbations in the previous year, and airflow obstructive pattern (FEV<sub>1</sub> &lt; 80% predicted) separately.</p>
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<p>Percentage of patients with uncontrolled asthma at the initial visit and during the 12-month follow-up period considering the combined criteria of an ACT score &lt; 20, number of exacerbations in the previous year, and airflow obstructive pattern (FEV1 &lt; 80% predicted).</p>
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<p>Boxplot of the relationship between NCR<sup>+</sup>ILC3 cells and asthma control at 12 months pf follow-up in patients diagnosed with asthma when they were older than 18 years of age (<b>left</b>). Relationship between serum IL-17 level and asthma control at 12 months of follow-up in the subgroup of patients with asthma duration between 20 and 35 years (<b>right</b>).</p>
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22 pages, 4892 KiB  
Article
Stability of Multi-Parametric Prostate MRI Radiomic Features to Variations in Segmentation
by Sithin Thulasi Seetha, Enrico Garanzini, Chiara Tenconi, Cristina Marenghi, Barbara Avuzzi, Mario Catanzaro, Silvia Stagni, Sergio Villa, Barbara Noris Chiorda, Fabio Badenchini, Elena Bertocchi, Sebastian Sanduleanu, Emanuele Pignoli, Giuseppe Procopio, Riccardo Valdagni, Tiziana Rancati, Nicola Nicolai and Antonella Messina
J. Pers. Med. 2023, 13(7), 1172; https://doi.org/10.3390/jpm13071172 - 22 Jul 2023
Cited by 3 | Viewed by 1873
Abstract
Stability analysis remains a fundamental step in developing a successful imaging biomarker to personalize oncological strategies. This study proposes an in silico contour generation method for simulating segmentation variations to identify stable radiomic features. Ground-truth annotation provided for the whole prostate gland on [...] Read more.
Stability analysis remains a fundamental step in developing a successful imaging biomarker to personalize oncological strategies. This study proposes an in silico contour generation method for simulating segmentation variations to identify stable radiomic features. Ground-truth annotation provided for the whole prostate gland on the multi-parametric MRI sequences (T2w, ADC, and SUB-DCE) were perturbed to mimic segmentation differences observed among human annotators. In total, we generated 15 synthetic contours for a given image-segmentation pair. One thousand two hundred twenty-four unfiltered/filtered radiomic features were extracted applying Pyradiomics, followed by stability assessment using ICC(1,1). Stable features identified in the internal population were then compared with an external population to discover and report robust features. Finally, we also investigated the impact of a wide range of filtering strategies on the stability of features. The percentage of unfiltered (filtered) features that remained robust subjected to segmentation variations were T2w—36% (81%), ADC—36% (94%), and SUB—43% (93%). Our findings suggest that segmentation variations can significantly impact radiomic feature stability but can be mitigated by including pre-filtering strategies as part of the feature extraction pipeline. Full article
(This article belongs to the Special Issue Precision Medicine in Radiomics and Radiogenomics)
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<p>Mid-level axial slice of the prostate gland with ROI annotation. (<b>a</b>) T2w, ADC, SUBwin, and SUBwout images associated with a random patient sampled from the internal population; (<b>b</b>) T2w, ADC, and SUB images associated with a random patient sampled from the external population.</p>
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<p>Illustration of in-plane augmentation. The width, w, and height, h, associated with the contour drawn by the radiologist (left in green) in the axial plane are allowed to undergo random perturbation by a delta value—dw, dh ~ U (−2.7 mm, 2.7 mm). This results in a transformed contour (right in red) with width, w’ = w + dw, and height, h’ = h + dh. In addition to this, the contour is also allowed to randomly rotate in the z-axis at an angle, α ~ U(−5°, +5°).</p>
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<p>Illustration of various out-plane augmentation scenarios with respect to the true ROI. This augmentation type simulates the variability in the choice of the ROI boundary slice in the craniocaudal direction. The yellow box highlights the slices encompassing the ROI; The vertical dotted green lines indicate the original prostate boundary slices.</p>
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<p>Schematic representation of the workflow involved in the stability study on prostate radiomic features extracted from T2w, DWI, and DCE sequences to variations in segmentation. Manual prostate annotation provided for the T2w sequence was co-registered with the other sequences. The segmentations were then augmented to generate 15 synthetic contours (in the figure as an example, 3 synthetic contours are generated + the original segmentation). A total of 1224 radiomic features were extracted from each of the image-mask pairs. The stability of the features was analyzed using ICC (1,1).</p>
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<p>Stability and robustness of filtered/unfiltered T2w radiomics features subjected to in and out-plane-systematic segmentation variations. A feature is considered stable if the lower bound of the 95% CI of the ICC estimate &gt; 0.90. (<b>a</b>) Stable v/s unstable feature heatmap—grey cells indicate unstable features, with darker shades of grey indicating lower ICC bounds. All the green cells represent stable features. (<b>b</b>) ICC plot portrays the overlap computed as the minimum stability value of a feature in the internal and external dataset grouped by both unfiltered and best-filtered configurations. For simplicity, we are only displaying the best filter(s) that yielded the highest ICC lower bound after overlap. The dotted green line indicates the stability threshold.</p>
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<p>Stability and robustness of filtered/unfiltered ADC radiomics features subjected to in and out-plane-systematic segmentation variations. A feature is considered stable if the lower bound of the 95% CI of the ICC estimate &gt; 0.90. (<b>a</b>) Stable v/s unstable feature heatmap—grey cells indicate unstable features, with darker shades of grey indicating lower ICC bounds. All the green cells represent stable features. (<b>b</b>) ICC plot portrays the overlap computed as the minimum stability value of a feature in the internal and external dataset grouped by both unfiltered and best-filtered configurations. For simplicity, we are only displaying the best filter(s) that yielded the highest ICC lower bound after overlap. The dotted green line indicates the stability threshold.</p>
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<p>Stability and robustness of filtered/unfiltered SUBwin radiomics features subjected to in and out-plane-systematic segmentation variations. A feature is considered stable if the lower bound of the 95% CI of the ICC estimate &gt; 0.90. (<b>a</b>) Stable v/s unstable feature heatmap—grey cells indicate unstable features, with darker shades of grey indicating lower ICC bounds. All the green cells represent stable features. (<b>b</b>) ICC plot portrays the overlap computed as the minimum stability value of a feature in the internal and external dataset grouped by both unfiltered and best-filtered configurations. For simplicity, we are only displaying the best filter(s) that yielded the highest ICC lower bound after overlap. The dotted green line indicates the stability threshold.</p>
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<p>Stability and robustness of filtered/unfiltered SUBwout radiomics features subjected to in and out-plane-systematic segmentation variations. A feature is considered stable if the lower bound of the 95% CI of the ICC estimate &gt; 0.90. (<b>a</b>) Stable v/s unstable feature heatmap—grey cells indicate unstable features, with darker shades of grey indicating lower ICC bounds. All the green cells represent stable features. (<b>b</b>) ICC plot portrays the overlap computed as the minimum stability value of a feature in the internal and external dataset grouped by both unfiltered and best-filtered configurations. For simplicity, we are only displaying the best filter(s) that yielded the highest ICC lower bound after overlap. The dotted green line indicates the stability threshold.</p>
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<p>The histogram plot presents a summary of the frequency at which a robust feature is associated with a particular filter/filter-family subjected to systematic-in and out-plane augmentation across all image sequences.</p>
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12 pages, 957 KiB  
Review
The Use of Radio and Telemedicine by TMAS Centers in Provision of Medical Care to Seafarers: A Systematic Review
by Gopi Battineni, Nalini Chintalapudi, Giulio Gagliardi and Francesco Amenta
J. Pers. Med. 2023, 13(7), 1171; https://doi.org/10.3390/jpm13071171 - 22 Jul 2023
Cited by 6 | Viewed by 2240
Abstract
Objective: From medicine via radio to telemedicine, personalized medical care at sea has improved significantly over the years. Currently, very little research has been conducted on telemedicine services and tools at sea. This study aims to review real-time case studies of seafarers’ [...] Read more.
Objective: From medicine via radio to telemedicine, personalized medical care at sea has improved significantly over the years. Currently, very little research has been conducted on telemedicine services and tools at sea. This study aims to review real-time case studies of seafarers’ personalized treatment via telemedical devices published in medical journals. Methods: A literature search was conducted using three libraries such as PubMed (Medline), Cumulative Index to Nursing and Allied Health Literature (CINAHL), BioMed Central, and Google Scholar. The Medical Subject Headings (MeSH) were used for information retrieval and document selection was conducted based on the guidelines of preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 flowchart. Selected articles were subjected to quality checks using the Newcastle–Ottawa scale (NOS). Results: The literature search produced 785 papers and documents. The selection was conducted in three stages such as selection, screening, and inclusion. After applying predefined inclusion and exclusion criteria, only three articles on real-time medical assistance with telemedical tools were identified. It is reported that medical attention is delivered to seafarers in real time thanks to advancements in telemedicine, satellite technology, and video conferencing. Conclusions: By improving the quality of medical care and reducing response times for medical emergencies at sea, lives have been saved. There are still several gaps despite these advancements. Medical assistance at sea should therefore be improved to address many of the still unsolved issues. Full article
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<p>PRISMA 2020 flow diagram for new systematic reviews which included searches of databases only (* searched database).</p>
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<p>Different communication technologies are used for requests of medical assistance at sea.</p>
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<p>On-board telemedicine case containing medical devices courtesy of TelePharmaTec, the spin-off of Camerino University, Italy.</p>
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17 pages, 1383 KiB  
Review
Chlamydial and Gonococcal Genital Infections: A Narrative Review
by Rafaela Rodrigues, Pedro Vieira-Baptista, Carlos Catalão, Maria José Borrego, Carlos Sousa and Nuno Vale
J. Pers. Med. 2023, 13(7), 1170; https://doi.org/10.3390/jpm13071170 - 21 Jul 2023
Cited by 5 | Viewed by 2881
Abstract
Sexually transmitted infections (STIs) constitute one of the leading causes of disease burden worldwide, leading to considerable morbidity, mortality, health expenditures, and stigma. Of note are the most common bacterial STIs, chlamydial and gonococcal infections, whose etiological agents are Chlamydia trachomatis (CT) and [...] Read more.
Sexually transmitted infections (STIs) constitute one of the leading causes of disease burden worldwide, leading to considerable morbidity, mortality, health expenditures, and stigma. Of note are the most common bacterial STIs, chlamydial and gonococcal infections, whose etiological agents are Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), respectively. Despite being usually asymptomatic, in some cases these infections can be associated with long-term severe complications, such as pelvic inflammatory disease, chronic pelvic pain, infertility, ectopic pregnancy, and increased risk of other STIs acquisition. As the symptoms, when present, are usually similar in both infections, and in most of the cases these infections co-occur, the dual-test strategy, searching for both pathogens, should be preferred. In line with this, herein we focus on the main aspects of CT and NG infections, the clinical symptoms as well as the appropriate state-of-the-art diagnostic tests and treatment. Cost-effective strategies for controlling CT and NG infections worldwide are addressed. The treatment for both infections is based on antibiotics. However, the continuing global rise in the incidence of these infections, concomitantly with the increased risk of antibiotics resistance, leads to difficulties in their control, particularly in the case of NG infections. We also discuss the potential mechanism of tumorigenesis related to CT infections. The molecular bases of CT and NG infections are addressed, as they should provide clues for control or eradication, through the development of new drugs and/or effective vaccines against these pathogens. Full article
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<p>Common clinical conditions associated with chlamydial and gonococcal genital infections according to gender. PID—pelvic inflammatory disease; STI—sexually transmitted infection.</p>
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<p><span class="html-italic">Chlamydia trachomatis</span> cell cycle of infection. This pathogen alternates between two distinct forms. The infectious form, named the elementary body (EB), when in contact with a host cell, can reach the cell cytoplasm by adhesion and internalization into a vacuole. Herein, EBs are converted into the alternative non-infectious form, the reticulate body (RB). These can go through the replication process, using the host’s resources, and using the cell’s energy and nutrients; when they reach a critical volume, the RBs transform into the previous form, the EBs. Finally, there are two possible mechanisms for the extracellular EB release, (1) lysis of the host cell or (2) extrusion. This cycle occurs repeatedly in the adjacent cells [<a href="#B12-jpm-13-01170" class="html-bibr">12</a>]. Figure created using BioRender.</p>
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<p><span class="html-italic">Neisseria gonorrhoeae</span> (NG) infection. Briefly, NG infection starts with the host cell interaction, establishing contact through some host cell receptors (CD46 and CR3) and type IV pili communication. After cell adhesion, this bacterium starts its replication and invasion processes, via transcytosis. Concomitantly, NG releases some cellular fragments, such as peptidoglycans and lipo-oligosaccharides (LOS), which, in contact with some cell surface molecules, namely, asialoglycoprotein receptor (ASGP-R) and carcinoembryonic antigen-related cell adhesion molecule family (CEACAM), can activate some signaling pathways (such as NF-kB pathway), triggering processes such as pro-inflammatory cytokine and chemokine production (including IL-1, IL-6, IL-8). In addition, this pro-inflammatory gradient of molecules drives the immune cell recruitment to the local, mainly dendritic, cells, macrophages, and neutrophils. Although these immune cells’ role is to trigger pathogen destruction, mostly through phagocytosis by neutrophils, up to the infection clearance, NG can frequently survive, and the infection can persist. Figure created using BioRender.</p>
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12 pages, 1902 KiB  
Article
Accuracy of Computed Tomography Angiography for Diagnosing Extracranial Mural Lesions in Patients with Acute Internal Carotid Artery Occlusion: Correlation with Digital Subtraction Angiography
by Miriam Fernández-Gómez, Félix Gallo-Pineda, Carlos Hidalgo-Barranco, Gracia Castro-Luna and Patricia Martínez-Sánchez
J. Pers. Med. 2023, 13(7), 1169; https://doi.org/10.3390/jpm13071169 - 21 Jul 2023
Viewed by 1707
Abstract
Extracranial carotid mural lesions (CML), caused by atherosclerosis or dissection, are frequently observed in acute internal carotid artery (ICA) occlusion, often requiring angioplasty or stenting. This study aimed to assess the diagnostic accuracy of computed tomography angiography (CTA) in differentiating extracranial CML from [...] Read more.
Extracranial carotid mural lesions (CML), caused by atherosclerosis or dissection, are frequently observed in acute internal carotid artery (ICA) occlusion, often requiring angioplasty or stenting. This study aimed to assess the diagnostic accuracy of computed tomography angiography (CTA) in differentiating extracranial CML from thromboembolic etiology in acute ICA occlusion in patients eligible for endovascular treatment. Two neuroradiologists retrospectively studied patients with apparent extracranial ICA occlusion on CTA. Patients were divided into two groups: thromboembolism and CML, based on findings from CTA and digital subtraction angiography (DSA). CTA sensitivity and specificity were calculated using DSA as the gold standard. Occlusive patterns and cervical segment widening were evaluated for atherosclerosis, dissection, and thromboembolism etiologies. CTA had a sensitivity of 84.91% (74.32–95.49%) and a specificity of 95.12% (87.31–100%) in detecting extracranial CML. Atherosclerosis was the most common cause, distinguishable with high accuracy using CTA (p < 0.001). No significant differences were found in occlusive patterns between dissection and thromboembolism (p = 0.568). Cervical segment widening was only observed in dissection cases due to mural hematoma. Conclusions: CTA accurately differentiates extracranial CML from thromboembolic etiology in acute ICA occlusion. The pattern of the occlusion and the artery widening help to establish the location and the etiology of the occlusion. Full article
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<p>Right extracranial ICA occlusion caused by thromboembolism in a patient with a history of atrial fibrillation. CTA (<b>A</b>,<b>B</b>) shows an extracranial short progressive contrast decline (blue arrow), with calcifications in the origin of the ICA, proximal to the occlusion site. DSA (<b>C</b>) confirms a cervical ICA occlusion (green arrow) due to thromboembolism, without carotid mural lesions. ICA = internal carotid artery; CTA = computed tomography angiography; DSA = digital subtraction angiography.</p>
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<p>Acute intracranial ICA occlusion caused by thromboembolism. CTA (<b>A</b>) demonstrates a progressive contrast decay in the extracranial region, extending towards the distal right ICA (blue arrow), while maintaining patency of the terminal bifurcation. DSA images (<b>B</b>,<b>C</b>) confirm an isolated intracranial occlusion while indicating the patency of the extracranial segment (green arrow). ICA = internal carotid artery; CTA = computed tomography angiography; DSA = digital subtraction angiography.</p>
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<p>Patient with left origin ICA occlusion attributed to an atherosclerotic plaque. Axial and sagittal CTA images (<b>A</b>,<b>B</b>) exhibit a well-delimited occlusion at the origin of the ICA, resulting from an atherosclerotic plaque with calcifications (blue arrow). DSA confirms the occlusion of the ICA from its origin (green arrow). (<b>C</b>). ICA = internal carotid artery; CTA = computed tomography angiography; DSA = digital subtraction angiography.</p>
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<p>Patient presenting with left extracranial ICA occlusion caused by dissection. Axial and Sagittal-MIP CTA images (<b>A</b>,<b>C</b>) demonstrate a progressive contrast decay and stenosis of the cervical ICA, associated with an arterial widening (blue arrow). NCCT (<b>B</b>) reveals a wall hematoma in the left ICA near the skull base (green arrowhead). DSA (<b>D</b>) and fluoroscopy (<b>E</b>) confirm the diagnosis of cervical ICA dissection. ICA = internal carotid artery; NCCT = non-contrast computed tomography; MIP = maximum intensity projection; CTA = computed tomography angiography; DSA = digital subtraction angiography.</p>
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11 pages, 1198 KiB  
Review
Surgical Approaches to Pancoast Tumors
by Francesco Petrella, Monica Casiraghi, Luca Bertolaccini and Lorenzo Spaggiari
J. Pers. Med. 2023, 13(7), 1168; https://doi.org/10.3390/jpm13071168 - 21 Jul 2023
Cited by 1 | Viewed by 2991
Abstract
Pancoast tumors, also defined as superior sulcus tumors, still represent a complex clinical condition requiring high technical surgical skills within more articulated multimodality treatment. The morbidity and mortality rates after Pancoast tumor treatments range from 10 to 55% and 0 to 7%, respectively, [...] Read more.
Pancoast tumors, also defined as superior sulcus tumors, still represent a complex clinical condition requiring high technical surgical skills within more articulated multimodality treatment. The morbidity and mortality rates after Pancoast tumor treatments range from 10 to 55% and 0 to 7%, respectively, and the 5-year survival rate has significantly improved in recent years thanks to the advancement of treatments. Although a multimodality approach combining chemotherapy, radiotherapy, and surgery allows for radical resection and effective local control in the vast majority of patients, many patients cannot receive surgical resection or complete the whole programmed therapeutic regimen. Systemic relapse, particularly cerebral recurrence, still poses a significant issue in this cohort of patients. Surgical resection still plays a pivotal role within the multimodality approach. Here, we focus on surgical approaches to both anterior and posterior Pancoast tumors: the anterior transclavicular approach (Dartevelle); the anterior transmanubrial approach (Grunenwald–Spaggiari); the anterior trap-door approach (Masaoka, Nomori); the posterior approach (Shaw–Paulson); the hemiclamshell approach; and hybrid approaches. Global clinical condition, tumor histology, and long-term perspectives should always be taken into consideration when embarking on such a demanding oncologic scenario. Full article
(This article belongs to the Special Issue Innovative Approaches in Lung Cancer Treatment)
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<p>(<b>A</b>) Patient decubitus; (<b>B</b>) Cervicothoracic incision; (<b>C</b>) Vascular dissection; (<b>D</b>) Costoclavicular joint reconstruction.</p>
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<p>The Masaoka Nomori approach (trap door).</p>
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<p>(<b>A</b>) Costovertebral joint infiltration at preoperative CT scan; (<b>B</b>) surgical view after costovertebral disarticulation; (<b>C</b>) chest wall closure; (<b>D</b>) postoperative view.</p>
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15 pages, 1483 KiB  
Article
Age-Related Changes in Epilepsy Characteristics and Response to Antiepileptic Treatment in Autism Spectrum Disorders
by Beliz Su Gundogdu, John Gaitanis, James B. Adams, Daniel A. Rossignol and Richard E. Frye
J. Pers. Med. 2023, 13(7), 1167; https://doi.org/10.3390/jpm13071167 - 21 Jul 2023
Cited by 2 | Viewed by 3865
Abstract
Despite the high prevalence of epilepsy in individuals with autism spectrum disorder (ASD), there is little information regarding whether seizure characteristics and treatment effectiveness change across age. Using an online survey, seizure characteristics, effectiveness of antiepileptic treatments, comorbidities, potential etiologies, and ASD diagnosis [...] Read more.
Despite the high prevalence of epilepsy in individuals with autism spectrum disorder (ASD), there is little information regarding whether seizure characteristics and treatment effectiveness change across age. Using an online survey, seizure characteristics, effectiveness of antiepileptic treatments, comorbidities, potential etiologies, and ASD diagnosis were collected from individuals with ASD and seizures. We previously reported overall general patterns of treatment effectiveness but did not examine the effect of seizure characteristics or age on antiepileptic treatment effectiveness. Such information would improve the personalized medicine approach to the treatment of seizures in ASD. Survey data from 570 individuals with ASD and clinical seizures were analyzed. Seizure severity (seizure/week) decreased with age of onset of seizures, plateauing in adolescence, with a greater reduction in generalized tonic–clonic (GTC) seizures with age. Seizure severity was worse in those with genetic disorders, neurodevelopmental regression (NDR) and poor sleep maintenance. Carbamazepine and oxcarbazepine were reported to be more effective when seizures started in later childhood, while surgery and the Atkins/modified Atkins Diet (A/MAD) were reported to be more effective when seizures started early in life. A/MAD and the ketogenic diet were reported to be more effective in those with NDR. Interestingly, atypical Landau–Kleffner syndrome was associated with mitochondrial dysfunction and NDR, suggesting a novel syndrome. These interesting findings need to be verified in independent, prospectively collected cohorts, but nonetheless, these data provide insights into novel relationships that may assist in a better understanding of epilepsy in ASD and provide insight into personalizing epilepsy care in ASD. Full article
(This article belongs to the Special Issue Autism Spectrum Disorder and Epilepsy)
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<p>Seizure severity (as indexed by seizure frequency/week when seizures are under the worst control) by age of onset of seizures for those with generalized seizures and those with non-generalized seizures. The size of the circles are proportional to the number of responders with the specific frequency.</p>
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<p>Changes in effectiveness ratings as a function of age of seizure onset for (<b>A</b>) antiepileptic drugs, (<b>B</b>) other seizure treatments, (<b>C</b>) dietary treatments and (<b>D</b>) supplements. Size of the circle is proportional to the number of responders with the specific frequency. Please see caption for explanation of the individual colors in each graph.</p>
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<p>Changes in effectiveness ratings as a function of age of seizure onset for (<b>A</b>) antiepileptic drugs, (<b>B</b>) other seizure treatments, (<b>C</b>) dietary treatments and (<b>D</b>) supplements. Size of the circle is proportional to the number of responders with the specific frequency. Please see caption for explanation of the individual colors in each graph.</p>
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7 pages, 814 KiB  
Case Report
Full Endoscopic Treatment for a Fibrosis Complication after Psoas Abscess
by Álvaro Dowling Montalva, Rui Nei de Araujo Santana Junior and Marcelo Molina
J. Pers. Med. 2023, 13(7), 1166; https://doi.org/10.3390/jpm13071166 - 20 Jul 2023
Viewed by 1250
Abstract
Background: Psoas abscess is a challenging disease that may sometimes lead to a devastating prognosis. Early diagnosis and treatment are mandatory for better results in their treatments and to avoid complications. Purpose: There is no article regarding a fibrosis treatment of the psoas [...] Read more.
Background: Psoas abscess is a challenging disease that may sometimes lead to a devastating prognosis. Early diagnosis and treatment are mandatory for better results in their treatments and to avoid complications. Purpose: There is no article regarding a fibrosis treatment of the psoas muscle with a psoas abscess that is treated with full endoscopic debridement (FED). Study design: a case report and literature review. Result: we successfully treated this case, who suffered from psoas fibrosis with a clinical and MRI diagnosis, with full endoscopic debridement. Conclusions: FED is a viable alternative to open debridement for this rare complication of a psoas muscle abscess. Full article
(This article belongs to the Special Issue The Path to Personalized Pain Management)
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<p>Shows a preoperative MRI scan of a 69-year-old female who initially presented back pain due to spondylodiscitis. The patient developed a psoas abscess shown as a round enhancing lesion on the T2-weighted axial MRI scan with intravenous contrast (<b>a</b>). The lesion was surgically treated with full endoscopic debridement (FED) with the working cannula placed in the center of the lesion below the left L4 transverse process (<b>b</b>,<b>c</b>). A fibrotic lesion was found intraoperatively (<b>d</b>,<b>e</b>), which was resected with the use of rongeurs (<b>f</b>) until the healthy red psoas muscle was visualized (<b>g</b>). A radiofrequency probe was used to achieve hemostasis. (<b>h</b>) A similar MRI scan was taken six weeks after the index FED confirmed the lesion’s successful removal. The patient recovered rapidly after surgery. The postoperative hip flexor weakness spontaneously resolved.</p>
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11 pages, 298 KiB  
Article
The Occurrence of Gluten-Related Antibodies, Sensitization to Selected Food Allergens, and Antibodies against Intrinsic Factor in Adult Patients with Diarrhea-Predominant Irritable Bowel Syndrome
by Joanna B. Bierła, Bożena Cukrowska, Barbara Skrzydło-Radomańska, Beata Prozorow-Król, Anetta Kurzeja-Mirosław, Halina Cichoż-Lach, Katarzyna Laskowska, Agnieszka Sowińska and Emilia Majsiak
J. Pers. Med. 2023, 13(7), 1165; https://doi.org/10.3390/jpm13071165 - 20 Jul 2023
Cited by 3 | Viewed by 1680
Abstract
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Due to the possible overlap of IBS clinical symptoms with gluten-related diseases, food allergies, and autoimmune gastritis (AIG), the aim of this study was to present the frequency of anti-tissue transglutaminase 2 (TTG2) [...] Read more.
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Due to the possible overlap of IBS clinical symptoms with gluten-related diseases, food allergies, and autoimmune gastritis (AIG), the aim of this study was to present the frequency of anti-tissue transglutaminase 2 (TTG2) autoantibodies, anti-deamidated gluten peptide (DGP) antibodies, specific immunoglobulin E antibodies (sIgE) to selected food allergens, and anti-intrinsic factor (IF) autoantibodies in adult patients with diarrhea-predominant IBS (IBS-D). The study involved 244 patients (170 women) aged 18–75 years. The antibodies were measured with the use of multiparametric immunoassays. Elevated antibody concentrations, irrespective of the class of tested antibody, occurred in 44 patients (17.6%), including 11 patients (4.5%) with positive DGP antibodies, four patients (1.6%) with TTG2 autoantibodies, six patients (2.5%) with IF autoantibodies, and 31 patients (12.7%) with sIgE to food allergens. Sensitization to gluten, proteins from cow’s milk, and bovine serum albumin was found in 2.1%, 5.3%, and 9.0% of patients, respectively. Our study showed a high percentage of positive results for the tested antibodies in the IBD-D patients, which indicates the need to perform serological tests for CD, food allergies, and AIG in this group of patients. Full article
(This article belongs to the Special Issue Biomarkers for Inflammatory and Metabolic Disorders)
17 pages, 2450 KiB  
Perspective
The First Exploratory Personalized Medicine Approach to Improve Bariatric Surgery Outcomes Utilizing Psychosocial and Genetic Risk Assessments: Encouraging Clinical Research
by Panayotis K. Thanos, Colin Hanna, Abrianna Mihalkovic, Aaron B. Hoffman, Alan R. Posner, John Busch, Caroline Smith, Rajendra D. Badgaiyan, Kenneth Blum, David Baron, Lucy D. Mastrandrea and Teresa Quattrin
J. Pers. Med. 2023, 13(7), 1164; https://doi.org/10.3390/jpm13071164 - 20 Jul 2023
Cited by 5 | Viewed by 1959
Abstract
It is predicted that by 2030, globally, an estimated 2.16 billion adults will be overweight, and 1.12 billion will be obese. This study examined genetic data regarding Reward Deficiency Syndrome (RDS) to evaluate their usefulness in counselling patients undergoing bariatric surgery and gathered [...] Read more.
It is predicted that by 2030, globally, an estimated 2.16 billion adults will be overweight, and 1.12 billion will be obese. This study examined genetic data regarding Reward Deficiency Syndrome (RDS) to evaluate their usefulness in counselling patients undergoing bariatric surgery and gathered preliminary data on the potential use in predicting short term (6-month) weight loss outcomes. Methods: Patients undergoing bariatric surgery (n = 34) were examined for Genetic Addiction Risk Severity (GARS) [measures the presence of risk alleles associated with RDS]; as well as their psychosocial traits (questionnaires). BMI changes and sociodemographic data were abstracted from Electronic Health Records. Results: Subjects showed ∆BMI (M = 10.0 ± 1.05 kg/m2) and a mean % excess weight loss (56 ± 13.8%). In addition, 76% of subjects had GARS scores above seven. The homozygote risk alleles for MAO (rs768062321) and DRD1 (rs4532) showed a 38% and 47% prevalence among the subjects. Of the 11 risk alleles identified by GARS, the DRD4 risk allele (rs1800955), was significantly correlated with change in weight and BMI six months post-surgery. We identified correlations with individual risk alleles and psychosocial trait scores. The COMT risk allele (rs4680) showed a negative correlation with EEI scores (r = −0.4983, p < 0.05) and PSQI scores (r = −0.5482, p < 0.05). The GABRB3 risk allele (rs764926719) correlated positively with EEI (r = 0.6161, p < 0.01) and FCQ scores (r = 0.6373, p < 0.01). The OPRM1 risk allele showed a positive correlation with the DERS score (r = 0.5228, p < 0.05). We also identified correlations between DERS and BMI change (r = 0.61; p < 0.01). Conclusions: These data support the potential benefit of a personalized medicinal approach inclusive of genetic testing and psychosocial trait questionnaires when counselling patients with obesity considering bariatric surgery. Future research will explore epigenetic factors that contribute to outcomes of bariatric surgery. Full article
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<p>GARS results represented as the percent frequency of gene type for each risk allele analyzed within the patient population (<span class="html-italic">n</span> = 34). The homozygote category represents having two copies of the risk allele, heterozygous represents one copy of the risk allele, and the low-risk category represents no copies of the risk allele per gene.</p>
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<p>Frequency of patients with a GARS score qualifying them for high risk or low risk of alcohol addiction. Risk category is based on total number of GARS risk alleles.</p>
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<p>(<b>a</b>–<b>j</b>). BMI and specific psychosocial inventory outcomes are correlated with GARS: (<b>a</b>) <span class="html-italic">DRD4</span> risk allele positively correlated with preop weight (<span class="html-italic">r</span> = 0.4331, R<sup>2</sup> = 0.1876, <span class="html-italic">p</span> = 0.0345)<span class="html-italic">;</span> (<b>b</b>) <span class="html-italic">DRD4</span> risk allele positively correlated with change in weight (<span class="html-italic">r</span> = 0.4726, R<sup>2</sup> = 0.2234, <span class="html-italic">p</span> = 0.0197); (<b>c</b>) <span class="html-italic">DRD4</span> risk allele positively correlated with change in BMI (<span class="html-italic">r</span> = 0.4577, R<sup>2</sup> = 0.2095, <span class="html-italic">p</span> = 0.0245) (<b>d</b>) <span class="html-italic">COMT</span> risk allele negatively correlated with EEI scores (<span class="html-italic">r</span> = −0.4983, R<sup>2</sup> = 0.2483, <span class="html-italic">p</span> = 0.0418); (<b>e</b>) <span class="html-italic">COMT</span> risk allele negatively correlated with PSQI scores (<span class="html-italic">r</span> = −0.5482, R<sup>2</sup> = 0.3005, <span class="html-italic">p</span> = 0.0279); (<b>f</b>) <span class="html-italic">GABRB3</span> risk allele positively correlated with EEI scores (<span class="html-italic">r</span> = 0.6161, R<sup>2</sup> = 0.3796, <span class="html-italic">p</span> = 0.0084); (<b>g</b>) <span class="html-italic">GABRB3</span> risk allele positively correlated with FCQ scores (<span class="html-italic">r</span> = 0.6373, R<sup>2</sup> = 0.4062, <span class="html-italic">p</span> = 0.0044); (<b>h</b>) <span class="html-italic">OPRM1</span> risk allele positively correlated with DERS scores (<span class="html-italic">r</span> = 0.5228, R<sup>2</sup> = 0.2733, <span class="html-italic">p</span> = 0.0260). (<b>i</b>) DERS scores negatively correlated with preop BMI (<span class="html-italic">r</span> = −0.5142, R<sup>2</sup> = 0.2644, <span class="html-italic">p</span> = 0.0290); (<b>j</b>) DERS scores negatively correlated with BMI 6 months post-surgery (<span class="html-italic">r</span> = −0.6137, R<sup>2</sup> = 0.3766, <span class="html-italic">p</span> = 0.0068).</p>
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<p>(<b>a</b>–<b>c</b>). Heterosis in <span class="html-italic">DRD4</span> gene: (<b>a</b>) significant difference (<span class="html-italic">t</span> = 2.400, <span class="html-italic">p</span> = 0.03) of mean change in weight at 6 months between patients with 0 and 1 copies of the <span class="html-italic">DRD4</span> risk allele; (<b>b</b>) significant difference (<span class="html-italic">t</span> = 2.234, <span class="html-italic">p</span> = 0.04) of mean change in BMI at 6 months between patients with 0 and 1 copies of the <span class="html-italic">DRD4</span> risk allele; (<b>c</b>) significant difference (<span class="html-italic">t</span> = 2.418, <span class="html-italic">p</span> = 0.03) of %EWL at 6 months between patients with 0 and 1 copies of the <span class="html-italic">DRD4</span> risk allele. Data are M ± SEM Student’s <span class="html-italic">t</span> test.</p>
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11 pages, 783 KiB  
Article
A Validation Study of cT-Categories in the Swedish National Urinary Bladder Cancer Register—Norrland University Hospital
by Erik Wiberg, Andrés Vega, Victoria Eriksson, Viqar Banday, Johan Svensson, Elisabeth Eriksson, Staffan Jahnson and Amir Sherif
J. Pers. Med. 2023, 13(7), 1163; https://doi.org/10.3390/jpm13071163 - 20 Jul 2023
Viewed by 1302
Abstract
Background: In Sweden, all patients with urinary bladder cancer (UBC) are recorded in the Swedish National Register for Urinary Bladder Cancer (SNRUBC). The purpose of this study was to validate the registered clinical tumour categories (cT-categories) in the SNRUBC for Norrland University Hospital, [...] Read more.
Background: In Sweden, all patients with urinary bladder cancer (UBC) are recorded in the Swedish National Register for Urinary Bladder Cancer (SNRUBC). The purpose of this study was to validate the registered clinical tumour categories (cT-categories) in the SNRUBC for Norrland University Hospital, Sweden, from 2009 to 2020, inclusive. Methods: The medical records of all 295 patients who underwent radical cystectomy for the treatment of UBC were reviewed retrospectively. Possible factors impacting the cT-categories were identified. To optimise cT-classification, computed tomography urography of all patients with suspected tumour-associated hydronephrosis (TAH) or suspected tumour in bladder diverticulum (TIBD) were retrospectively reviewed by a radiologist. Discrepancy was tested with a logistic regression model. Results: cT-categories differed in 87 cases (29.5%). Adjusted logistic regression analysis found TIBD and TAH as significant predictors for incorrect registration; OR = 7.71 (p < 0.001), and OR = 17.7, (p < 0.001), respectively. In total, 48 patients (68.6%) with TAH and 12 patients (52.2%) with TIBD showed discrepancy regarding the cT-category. Incorrect registration was mostly observed during the years 2009–2012. Conclusion: The study revealed substantial incorrect registration of cT-categories in SNRUBC. A major part of the misclassifications was related to TAH and TIBD. Registration of these variables in the SNRUBC might be considered to improve correct cT-classification. Full article
(This article belongs to the Special Issue Advances in Treatment of Urinary Bladder Cancer)
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<p>Flow chart of inclusion and results of all evaluated patients. UBC: urinary bladder cancer. SNRUBC: Swedish National Register of Urinary Bladder Cancer. Tx: there is insufficient information for stage classification. cT: clinical classification of the primary tumour. TIBD: tumour in bladder diverticulum. TAH: tumour-associated hydronephrosis.</p>
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<p>Percent discrepancy in cT-categories between data in the SNRUBC and the re-registration per year. cT: clinical classification of the primary tumour.</p>
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10 pages, 2005 KiB  
Case Report
A Single Intradermal Injection of Autologous Adipose-Tissue-Derived Stem Cells Rejuvenates Aged Skin and Sharpens Double Eyelids
by Masamitsu Ichihashi, Masaki Tanaka, Takashi Iizuka, Hiroko Totsuka, Ekuko Tominaga, Yuka Hitomi, Hideya Ando, Takahiro Nishikata and Ken-Ichi Mizutani
J. Pers. Med. 2023, 13(7), 1162; https://doi.org/10.3390/jpm13071162 - 20 Jul 2023
Cited by 1 | Viewed by 3118
Abstract
Facial skin aging is the most visible manifestation of aging in the body. In this study, we aimed to rejuvenate aging skin via a one-time intradermal injection of autologous adipose-derived stem cells (ADSCs). Eight patients were enrolled for study. Photographs of patients taken [...] Read more.
Facial skin aging is the most visible manifestation of aging in the body. In this study, we aimed to rejuvenate aging skin via a one-time intradermal injection of autologous adipose-derived stem cells (ADSCs). Eight patients were enrolled for study. Photographs of patients taken immediately before and 1, 3, 6, and 12 months after ADSC injections were comparatively evaluated for visible skin manifestations. ADSCs were cultured from the abdominal-skin-derived subcutaneous fat tissue, and 1 × 108 cultured ADSCs were injected intradermally into the facial skin. Cultured myoblasts were incubated with the supernatant derived from ADSCs, and the effect was evaluated via glucose consumption and lactic acid production in the medium. Eight cases showed the shallowing and disappearance of wrinkles, including those of the glabella, lower eyelids, crow`s feet, and forehead and nasolabial grooves, a month to several months after treatment. Double eyelids became prominent, and facial pores significantly reduced in size. These effects lasted for over one year. Myoblasts cultured in the presence of an ADSC-derived exosome were activated compared to that of ADSCs cultured without supernatant. The result supports the role of muscle in ADSC skin rejuvenation. The present study first reports that a single intradermal administration of cultured ADSCs rejuvenates aged facial skin over the course of one year. Further, patients exhibited definite double eyelids and pore shrinkage, strongly indicating the active involvement of muscle, which was supported by an in vitro study. Our study also suggested the important role of biological factors delivered from injected stem cells, although the detailed mechanism of rejuvenation effects of ADSC skin injection remains to be clarified. Full article
(This article belongs to the Special Issue Stem Cells-Based Approaches in Regenerative Medicine)
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<p>Facial skin manifestation of 5 female cases before and after treatment with intradermal injection of ADSC.</p>
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<p>Photographs of 58 year-old lady, case 6, before (<b>a</b>,<b>c</b>,<b>e</b>) and 8 months after ADSC treatment (<b>b</b>,<b>d</b>,<b>f</b>). Reduced wrinkle of forehead 8 months after ADSC injection (<b>b</b>,<b>d</b>) and neck (<b>b</b>,<b>f</b>) and shallowing of nasolabial grooves was confirmed by comparison of (<b>a</b>) to (<b>b</b>).</p>
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<p>Photographs of case 7, 53-year-old male before and after ADSC treatment. Improvement of tear trough deformity and reduced hair follicle size was observed by comparing (<b>a</b>) with (<b>b</b>).</p>
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<p>Effect of ADSCs skin injection on wrinkles and nasolabial grooves of 61-year-old male. Nasolabial grooves of (<b>b</b>) (one month after treatment) and (<b>c</b>) (3 months after treatment) were shallower than those of (<b>a</b>) before treatment, showing rejuvenation effect of ADSC skin injection of 50′s male. Tear trough deformity was improved with reduced wrinkles of lower eyelids. Wrinkles of forehead was time dependently reduced, in (<b>b</b>) (1 month after treatment) and (<b>c</b>) (3 months after treatment) V, by comparison of (<b>a</b>).</p>
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<p>ADSC injection induced clear double eyelids. Clear eyelids of (<b>b</b>,<b>d</b>,<b>f</b>,<b>h</b>,<b>j</b>) (after treatment) compared to (<b>a</b>,<b>c</b>,<b>e</b>,<b>g</b>,<b>i</b>) (before treatment), indicate apparent effect of ADSC injection on double eyelids appearance.</p>
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<p>Effect of ADSC on eyelids. Eye exposure ratio (b/a) of maximal exposure length between upper and lower eyelids (b) divided by longitudinal eyeball diameter (a) was used to evaluate ADSC effect on eyelids. b/a ration increased in cases 6, 7 and 8 in whom b/a ration was evaluated, indicates that ADSC injection make double eyelids clear and makes longitudinal eyeball diameter larger.</p>
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<p>Effect on hair follicles. Hair follicles of 48y lady (<b>b</b>) and 53y male (<b>d</b>) 6 months and 5 months after ADSC treatment, respectively, are significantly smaller than those of (<b>a</b>,<b>c</b>), before treatment, showing rejuvenation effect of ADSC injection on skin texture.</p>
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<p>Effect of cultured ADSC-derived supernatant on C2C12 myoblasts activation. Glucose consumption rate (mmol/L) of cultured C2C12 cells slightly enhanced by the incubation with ADSC-derived supernatant for 24 h and 48 h incubation (<b>a</b>), and accumulation of glycolysis derived lactic acid level (mmol/L) was significantly increased by the incubation of ADSC-supernatant compared to untreated control (<b>b</b>). Statistical analysis was conducted using T-test. A <span class="html-italic">p</span>-value of less than 0.05 is considered statistically significant (**: <span class="html-italic">p</span> &lt; 0.01, *: <span class="html-italic">p</span> &lt; 0.05). N = 3.</p>
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16 pages, 3698 KiB  
Article
Evaluation of microRNA Expression Features in Patients with Various Types of Arterial Damage: Thoracic Aortic Aneurysm and Coronary Atherosclerosis
by Ange Veroniqe Ngo Bilong Ekedi, Andrey N. Rozhkov, Dmitry Yu. Shchekochikhin, Nina A. Novikova, Philippe Yu. Kopylov, Afina A. Bestavashvili, Tatiana V. Ivanova, Andrey V. Zhelankin, Eduard V. Generozov, Dmitry N. Konanov and Anna S. Akselrod
J. Pers. Med. 2023, 13(7), 1161; https://doi.org/10.3390/jpm13071161 - 20 Jul 2023
Cited by 4 | Viewed by 1690
Abstract
Circulating serum miRNA are increasingly used as biomarkers and potential treatment targets in several clinical scenarios, including cardiovascular diseases. However, the current data on circulating miRNA in thoracic aorta aneurism (TAA) patients are inconclusive. The aim of the present study is to compare [...] Read more.
Circulating serum miRNA are increasingly used as biomarkers and potential treatment targets in several clinical scenarios, including cardiovascular diseases. However, the current data on circulating miRNA in thoracic aorta aneurism (TAA) patients are inconclusive. The aim of the present study is to compare the levels of several circulating miRNA in patients with degenerative TAA, coronary artery disease (CAD), and controls for special profile identification. We have identified several candidates for the role of new biomarkers: miR-143-3p, miR-181-5p, miR-126-3p, miR-126-5p, miR-145-5p, miR-150-5p, and miR-195-5p. Materials and methods: Serum samples of 100 patients were analyzed, including 388 TAA patients scheduled for elective surgery, 67 patients with stable CAD and 17 controls, were used for miRNA isolation and identification. Results: More specific for TAA with very high predictive ability in ROC analysis was an increase in the levels of miR-21-5p, miR-29b-5p, miR-126-5p/-3p, miR-181b-5p, and miR-92a-3p, with the latter microRNA being investigated as a novel potential marker of TAA for the first time. Conclusion: TAA and CAD patients demonstrated a significant increase in the levels of circulating miR-126-5p/-3p, miR-181b-5p, and miR-29b-3p. More specific for TAA with very high predictive ability in ROC analysis was an increase in the levels of miR-21-5p, -29b-5p, -126-5p/-3p, 181b-5p, and -92a-3p, with the latter microRNA being investigated as a potential marker of TAA for the first time. Full article
(This article belongs to the Special Issue Precision Medicine in Coronary Artery Disease)
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<p>Block diagram of the study.</p>
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<p>Results of comparison of miRNA relative plasma levels in patients with damaged arteries.</p>
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<p>Results of sensitivity and specificity analysis of miR-126-5p, miR-126-3p, miR-181b-5p, and -29b-3p relative plasma levels increase as a marker of arteries damage. ROC curves.</p>
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<p>Results of sensitivity and specificity analysis with AUC &gt; 0.8 of the selected miRNA relative plasma levels increase as a marker of TAA. ROC curves.</p>
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<p>Results of comparison of miRNA relative plasma levels in patients with and without CAD.</p>
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<p>Results of sensitivity and specificity analysis of the selected miRNA relative plasma levels increase as a marker of CAD. ROC curves.</p>
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<p>Spearman rank correlation matrix of selected clinical parameters with relative plasma levels of miRNA adjusted for multiple comparisons.</p>
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<p>Pearson rank correlation matrix of selected clinical parameters with relative plasma levels of miRNA adjusted for multiple comparisons.</p>
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<p>Association of HDL levels with the presence of TAA.</p>
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14 pages, 2151 KiB  
Article
Randomized Clinical Trial to Evaluate the Efficacy and Tolerability of Nebulized Hyaluronic Acid and Xylitol Based Solution after Septoturbinoplasty
by Peter Baptista, Antonio Moffa, Lucrezia Giorgi and Manuele Casale
J. Pers. Med. 2023, 13(7), 1160; https://doi.org/10.3390/jpm13071160 - 20 Jul 2023
Viewed by 2043
Abstract
Septoplasty and turbinate surgery are among the most frequent surgical procedures to improve nasal obstruction and quality of life. These procedures usually imply the presence of congestion, secretions, and crusting related to the movement of the instruments during surgery. However, the use of [...] Read more.
Septoplasty and turbinate surgery are among the most frequent surgical procedures to improve nasal obstruction and quality of life. These procedures usually imply the presence of congestion, secretions, and crusting related to the movement of the instruments during surgery. However, the use of nasal lavage may reduce this situation. The addition of Hyaluronic acid or Xylitol offers advantages in these washes. This study was a randomized, double-blind, controlled trial. All patients underwent endoscopic septoplasty with inferior turbinate submucosal resection without posterior nasal packing. SNOT-22, main VAS, NOSE, Modified Lund-Kennedy endoscopic scale, number of crusts and adhesions were quantified before and on the day of the surgery, visit three (seven days), visit four (fourteen days), and visit five (twenty-eight days). Forty-seven patients completed the study, divided into a standard saline arm (group 1, 22 patients) and normal saline plus HA and Xylitol arm (group 2, 27 patients). Both treatment groups improved their quality of life and objective parameters during the four weeks of the study. All patients tolerated the nasal irrigations well, and none discontinued the treatments. The study concludes that nasal washes of Aluneb Isotónico® offer several benefits to patients as a protective and preventative agent. Full article
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<p>Mean (95% confidence interval) Modified Lund-Kennedy endoscopic scale (MLK) Oedema Scale along time according to the intervention group. D0: Day 0; D7: Day 7; D14: Day 14; D28: Day 28.</p>
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<p>Mean (95% confidence interval) Modified Lund-Kennedy endoscopic scale (MLK) Discharge Scale along time according to the intervention group. D0: Day 0; D7: Day 7; D14: Day 14; D28: Day 28.</p>
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<p>Mean (95% confidence interval) Sino-Nasal-Outcome-Test 22 (SNOT-22) Score along time according to the intervention group. D0: Day 0; D7: Day 7; D14: Day 14; D28: Day 28.</p>
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<p>Mean (95% confidence interval) Nose Obstruction Symptom Evaluation (NOSE) Scale along time according to the intervention group. D0: Day 0; D7: Day 7; D14: Day 14; D28: Day 28.</p>
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<p>Mean (95% confidence interval) Visual Analogue Scale (VAS) Score along time according to the intervention group. D0: Day 0; D7: Day 7; D14: Day 14; D28: Day 28.</p>
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12 pages, 555 KiB  
Article
Bari Shoulder Telemedicine Examination Protocol (B-STEP): A Standard Protocol for Personalized Remote Shoulder Examination
by Lorenzo Moretti, Davide Bizzoca, Giacomo Farì, Alessandro Caricato, Francesco Angiulli, Giuseppe Danilo Cassano, Giuseppe Solarino and Biagio Moretti
J. Pers. Med. 2023, 13(7), 1159; https://doi.org/10.3390/jpm13071159 - 20 Jul 2023
Viewed by 1442
Abstract
The COVID-19 pandemic drastically changed many aspects of the traditional functioning of health systems all around the world. In Italy, as reported by the CIO, compared to the previous year, there was a significant reduction in 2020 in overall outpatient activities by up [...] Read more.
The COVID-19 pandemic drastically changed many aspects of the traditional functioning of health systems all around the world. In Italy, as reported by the CIO, compared to the previous year, there was a significant reduction in 2020 in overall outpatient activities by up to 75%. These data support the need for telemedicine, which represents a current challenge and can no longer be postponed in the future. This study aims to elaborate on a possible model for remote shoulder examination based on traditional tests to improve the quality of telemedicine in orthopedic and rehabilitation. Between May 2020 and November 2020, ten orthopedic surgeons individually examined six patients with a known shoulder disorder, both in hospital and via webcam according to the previously shared protocol (B-STEP). According to the 10 observers, completing 100% of the ASES score and at least 87.5% of the Constant score is possible. Shoulder ROM and many specific tests are also reproducible via webcam, but with less sensitivity, according to the subjective opinion of observers. The B-STEP is a useful protocol for the standardization of the objective examination of the shoulder via webcam. Further studies are necessary to determine if the B-STEP protocol is useful for diagnosing pathology in unknown patients and evaluating its sensitivity and specificity for each pathology. Full article
(This article belongs to the Special Issue Personalized Management in Orthopedics and Traumatology)
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<p>The Bari Shoulder Telemedicine Exam Protocol (B-STEP).</p>
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8 pages, 998 KiB  
Case Report
Identification of a Novel Variant in Myelin Regulatory Growth Factor by Next-Generation Sequencing Led to the Detection of a Clinically Inapparent Congenital Heart Defect in a Patient with a 46,XY Disorder of Sex Development
by Lourdes Correa Brito, Romina P. Grinspon, Jimena Lopez Dacal, Paula Scaglia, María Esnaola Azcoiti, Agustín Izquierdo, María Gabriela Ropelato and Rodolfo A. Rey
J. Pers. Med. 2023, 13(7), 1158; https://doi.org/10.3390/jpm13071158 - 19 Jul 2023
Cited by 1 | Viewed by 1834
Abstract
In patients with 46,XY disorders of sex development (DSDs), next-generation sequencing (NGS) has high diagnostic efficiency. One contribution to this diagnostic approach is the possibility of applying reverse phenotyping when a variant in a gene associated with multiple organ hits is found. Our [...] Read more.
In patients with 46,XY disorders of sex development (DSDs), next-generation sequencing (NGS) has high diagnostic efficiency. One contribution to this diagnostic approach is the possibility of applying reverse phenotyping when a variant in a gene associated with multiple organ hits is found. Our aim is to report a case of a patient with 46,XY DSDs in whom the identification of a novel variant in MYRF led to the detection of a clinically inapparent congenital heart defect. A full-term newborn presented with ambiguous genitalia, as follows: a 2 cm phallus, penoscrotal hypospadias, partially fused labioscrotal folds, an anogenital distance of 1.2 cm, and non-palpable gonads. The karyotype was 46,XY, serum testosterone and AMH were low, whereas LH and FSH were high, leading to the diagnosis of dysgenetic DSD. Whole exome sequencing identified a novel, heterozygous, nonsense variant in MYRF, classified as pathogenic according to the ACMG criteria. MYRF encodes a membrane-bound transcriptional factor expressed in several tissues associated with OCUGS syndrome (ophthalmic, cardiac, and urogenital anomalies). In the patient, oriented clinical assessment ruled out ophthalmic defects, but ultrasonography confirmed meso/dextrocardia. We report a novel MYRF variant in a patient with 46,XY DSDs, allowing us to identify a clinically inapparent congenital heart defect by reverse phenotyping. Full article
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<p>MYRF candidate variant by NGS. Integrative Genome Viewer (IGV) visualisation of variant MYRF: NC_000011.9(NM_001127392.3):c.965G&gt;A. Green indicates reads of an adenine (A), brown of guanine (G), blue of cytosine (C) and red of thymine (T).</p>
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<p>Family segregation results by Sanger sequencing: chromatograms of proband and parents. Pedigree: the arrow indicates index case; circle indicates phenotypic female; square indicates phenotypic male; and full black circle indicates complete phenotype (46,XY DSDs).</p>
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16 pages, 2377 KiB  
Article
Prognostic Survival Significance of Signet Ring Cell (SRC) Gastric Cancer: Retrospective Analysis from a Single Western Center
by Luigina Graziosi, Elisabetta Marino, Nicola Natalizi and Annibale Donini
J. Pers. Med. 2023, 13(7), 1157; https://doi.org/10.3390/jpm13071157 - 19 Jul 2023
Cited by 1 | Viewed by 7879
Abstract
Introduction: Signet ring cell carcinoma accounts for 35% to 45% of all gastric cancer. Despite the acknowledgment of its more aggressive pathological features, various controversies surrounding this topic still exist. Thus, we investigate the clinical pathological characteristics and survival prognostic significance of signet [...] Read more.
Introduction: Signet ring cell carcinoma accounts for 35% to 45% of all gastric cancer. Despite the acknowledgment of its more aggressive pathological features, various controversies surrounding this topic still exist. Thus, we investigate the clinical pathological characteristics and survival prognostic significance of signet ring cell components in patients affected by gastric cancer. Methods: From January 2004 to December 2020, in a retrospective study, we enrolled 404 patients with gastric cancer who were curatively treated in our department. The male-to-female ratio was 249/142, and the median age was 75 (range 37–94). We dichotomized patients into two groups (75 patients vs. 316 patients) based on the signet ring cell presence; according to preoperative, operative, and postoperative characteristics, we performed a univariate and multivariate analysis for overall survival. Results: Signet ring cell carcinoma indicated an increasing incidence trend over the time analyzed. Overall median survival of signet ring cell and non-signet ring cell carcinoma were, respectively, 16 vs. 35 months, p < 0.05. In early gastric cancer, the prognosis of the signet ring cell is better than that of the non-signet ring cell, as opposed to advanced cancer. Among the entire population in the multivariate analysis, the only independent factors were preoperative serum albumin level, complete surgical resection, level of lymphadenectomy, and pathological stage. Recurrence occurred more frequently in patients affected by signet ring cell, but in our data, we could not identify a peculiar site of recurrence. Conclusions: Signet ring cell carcinoma has a specific oncogenetic phenotype and treatment resistance heterogeneity; however, it is not always associated with poor prognosis. According to our results, a radical surgical procedure associated with an adequate lymphadenectomy should be advocated to improve patients survival. Gastric cancer patients with signet ring cell components should draw clinicians’ attention. Full article
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<p>Epidemiological changes in incidence over time; GSRCC incidence is indicating a constant increase significantly different from the N-GSRCC population.</p>
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<p>Overall survival according to histological subtypes; SRC and N-SRC do not reach a statistically significant difference; number at risk table.</p>
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<p>Overall survival according to median age in both N-SRC and SRC cancer patients; number at risk table.</p>
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<p>(<b>a</b>) Gender distribution among GSRCC and N-GSRCC patients; (<b>b</b>) overall survival according to gender in the N-GSRCC group, <span class="html-italic">p</span> &lt; 0.05; number at risk table.</p>
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<p>Overall survival according to AJCC/TNM pathological stage; N-SRC and SRC show a completely different stratification of stages; number at risk table.</p>
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<p>OS according to disease stage; early gastric cancer (EGC) is showing a significantly better survival in patients showing SRC features (<span class="html-italic">p</span> &lt; 0.05); this difference is not reached in the advanced gastric cancer (AGC) group and number at risk table.</p>
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<p>Overall survival in SRC patients according to (<b>a</b>) lymphadenectomy extension and (<b>b</b>) lymph node ratio; <span class="html-italic">p</span> &lt; 0.05 and number at risk tables.</p>
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10 pages, 730 KiB  
Article
Ultrasound as a Method for Early Diagnosis of Breast Pathology
by Rute Santos, Ana Raquel Ribeiro and Daniela Marques
J. Pers. Med. 2023, 13(7), 1156; https://doi.org/10.3390/jpm13071156 - 18 Jul 2023
Viewed by 2235
Abstract
Introduction: Ultrasound is a non-invasive, low-cost technique that does not use ionising radiation and provides a “real-time” image, and for these reasons, this method is ideal in several situations. Purpose: To demonstrate breast ultrasound evaluation as a first-line diagnostic method and to evaluate [...] Read more.
Introduction: Ultrasound is a non-invasive, low-cost technique that does not use ionising radiation and provides a “real-time” image, and for these reasons, this method is ideal in several situations. Purpose: To demonstrate breast ultrasound evaluation as a first-line diagnostic method and to evaluate the variation of breast characteristics with age. Material and Methods: A total of 105 women with a mean age of 30 years participated and were divided into three age groups: 18–39, 40–59, and 60–79 years, excluding participants subject to mastectomy. After completing the informed consent, all participants answered personal and sociodemographic questions, such as personal and family history, menstrual cycle, pregnancy, ultrasound, and mammography, among others. They were then submitted to a bilateral breast ultrasound examination. Subsequently, all the images and their data were analysed, and a technical report of the examination was given to all the participants. Results: A total of 105 women with a mean age of 30 years participated, 58 of whom underwent the examination for the first time. In 31, changes (of which only 7 were known) were diagnosed. It was verified that, according to age group, the density of the breast stroma varied; older women have less breast density. Conclusions: Ultrasound is a good method for breast evaluation and can be considered important for the early evaluation of breast pathology and follow-up of the pathology. Full article
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<p>Percentage of participants in each group, according to age.</p>
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<p>Graph representing the answers given by the participants to the sociodemographic questionnaire.</p>
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17 pages, 3434 KiB  
Article
Mid-Regional Pro-Adrenomedullin and N-Terminal Pro-B-Type Natriuretic Peptide Measurement: A Multimarker Approach to Diagnosis and Prognosis in Acute Heart Failure
by Silvia Spoto, Josepmaria Argemi, Roberta Di Costanzo, Juan Josè Gavira Gomez, Nahikari Salterain Gonzales, Stefania Basili, Roberto Cangemi, Antonio Abbate, Luciana Locorriere, Francesco Masini, Giulia Testorio, Rodolfo Calarco, Giulia Battifoglia, Fabio Mangiacapra, Marta Fogolari, Sebastiano Costantino and Silvia Angeletti
J. Pers. Med. 2023, 13(7), 1155; https://doi.org/10.3390/jpm13071155 - 18 Jul 2023
Cited by 8 | Viewed by 2147
Abstract
Background: Acute heart failure (AHF) is a major cause of hospitalization and mortality worldwide. Early and accurate diagnosis, as well as effective risk stratification, are essential for optimizing clinical management and improving patient outcomes. In this context, biomarkers have gained increasing interest in [...] Read more.
Background: Acute heart failure (AHF) is a major cause of hospitalization and mortality worldwide. Early and accurate diagnosis, as well as effective risk stratification, are essential for optimizing clinical management and improving patient outcomes. In this context, biomarkers have gained increasing interest in recent years as they can provide important diagnostic and prognostic information in patients with AHF. Aim and Methods: The primary objective of the present study was to compare the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), and C-reactive protein (CRP) between patients diagnosed with acute heart failure (AHF) and those without AHF and sepsis. Furthermore, the study aimed to assess the diagnostic and prognostic value of the use of a multimarker approach in AHF patients. To achieve these objectives, a total of 145 patients with AHF and 127 patients without AHF and sepsis, serving as the control group, were consecutively enrolled in the study. Results: Levels of MR-proADM (median: 2.07; (25th–75th percentiles: 1.40–3.02) vs. 1.11 (0.83–1.71) nmol/L, p < 0.0001), and NT-proBNP (5319 (1691–11,874) vs. 271 (89–931.5) pg/mL, p < 0.0001) were significantly higher in patients with AHF compared to controls, whereas CRP levels did not show significant differences. The mortality rate in the AHF group during in-hospital stay was 12%, and the rate of new re-admission for AHF within 30 days after discharge was 10%. During in-hospital follow-up, Cox regression analyses showed that levels of NT-proBNP > 10,132 pg/mL (hazard ratio (HR) 2.97; 95% confidence interval (CI): 1.13–7.82; p = 0.0284) and levels of MR-proADM > 2.8 nmol/L (HR: 8.57; CI: 2.42–30.28; p = 0.0009) predicted mortality. The combined use of MR-proADM and NT-proBNP provided significant additive predictive value for mortality and new re-admission for AHF at 30 days after discharge. A logistic regression analysis showed that the presence of NT-proBNP pg/mL > 12,973 pg mL and/or MR-proADM > 4.2 nmol/L predicted hospital re-admission within 30 days (OR: 3.23; CI: 1.05–9.91; p = 0.041). Conclusion: The combined assay of MR-proADM and NT-proBNP could be helpful in accurately identifying AHF and in defining prognosis and re-admission for AHF. The complementary use of these biomarkers can provide a useful clinical evaluation of AHF while also orienting clinicians to the pathophysiology underlying heart damage and assisting them in tailoring therapy. Full article
(This article belongs to the Section Disease Biomarker)
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<p>ROC curves for NT-proBNP (<b>A</b>), MR-proADM (<b>B</b>), CRP (<b>C</b>), and creatinine (<b>D</b>) in AHF patients compared to the control group.</p>
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<p>ROC curves for NT-proBNP (<b>A</b>), MR-proADM (<b>B</b>), creatinine (<b>C</b>), and NT-proBNP at discharge (<b>D</b>) in relation to mortality in AHF patients.</p>
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<p>KM curves for 30-day mortality of NT-proBNP (<b>A</b>), MR-proADM (<b>B</b>), and NT-proBNP patients at discharge (<b>C</b>), creatinine (<b>D</b>), combination of NT-proBNP and MR-proADM (<b>E</b>), and combination of NT-proBNP, MR-proADM, and NT-proBNP at discharge (<b>F</b>) * Log-rank test.</p>
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<p>Stratification of AHF patients in agreement with LVEF. AHF—acute heart failure; ARNI—angiotensin receptor–neprilysin inhibitor; HFmrEF—heart failure with mildly reduced ejection fraction; HFpEF—heart failure with preserved ejection fraction; HFrEF—heart failure with reduced ejection fraction; LOS—length of stay; LVEF—left ventricular ejection fraction.</p>
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<p>ROC curve of NT-proBNP at time 0 and mortality in ARNI patients (<b>A</b>); ROC curve of MR-proADM at time 0 and mortality in ARNI patients (<b>B</b>); ROC curve of NT-proBNP at discharge and mortality in non-ARNI HFrEF patients (<b>C</b>).</p>
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14 pages, 2568 KiB  
Article
Glissonean Pedicle Isolation Focusing on the Laennec’s Capsule for Minimally Invasive Anatomical Liver Resection
by Mamoru Morimoto, Yoichi Matsuo, Keisuke Nonoyama, Yuki Denda, Hiromichi Murase, Tomokatsu Kato, Hiroyuki Imafuji, Kenta Saito and Shuji Takiguchi
J. Pers. Med. 2023, 13(7), 1154; https://doi.org/10.3390/jpm13071154 - 18 Jul 2023
Cited by 5 | Viewed by 2913
Abstract
Background: Inflow control is one of the most important procedures during anatomical liver resection (ALR), and Glissonean pedicle isolation (GPI) is one of the most efficacious methods used in laparoscopic anatomical liver resection (LALR). Recognition of the Laennec’s capsule covering the liver parenchyma [...] Read more.
Background: Inflow control is one of the most important procedures during anatomical liver resection (ALR), and Glissonean pedicle isolation (GPI) is one of the most efficacious methods used in laparoscopic anatomical liver resection (LALR). Recognition of the Laennec’s capsule covering the liver parenchyma is essential for safe and precise GPI. The purpose of this study was to verify identification of the Laennec’s capsule, to confirm the validity of GPI in minimally invasive surgery, and to demonstrate the value of GPI focusing on the Laennec’s capsule using a robotic system that has been developed in recent years. Methods: We used a cadaveric model to simulate the Glissonean pedicle and the surrounding liver parenchyma for pathologic verification of the layers. We performed 60 LALRs and 39 robotic anatomical liver resections (RALRs) using an extrahepatic Glissonean approach, from April 2020 to April 2023, and verified the layers of the specimens removed during LALR and RALR based on pathologic examination. In addition, the surgical outcomes of LALR and RALR were compared. Results: Histologic examination facilitated by Elastica van Gieson staining revealed the presence of Laennec’s capsule covering the liver parenchyma in a cadaveric model. Similar findings were obtained following LALR and RALR, thus confirming that the gap between the Glissonean pedicle and the Laennec’s capsule can be dissected without injury to the parenchyma. The mean GPI time was 32.9 and 27.2 min in LALR and RALR, respectively. The mean blood loss was 289.7 and 131.6 mL in LALR and RALR, respectively. There was no significant difference in the incidence of Clavien–Dindo grade ≥III complications between the two groups. Conclusions: Laennec’s capsule is the most important anatomical landmark in performing a safe and successful extrahepatic GPI. Based on this concept, it is possible for LALR and RALR to develop GPI focusing on the Laennec’s capsule. Furthermore, a robotic system has the potential to increase the safety and decrease the difficulty of this challenging procedure. Full article
(This article belongs to the Special Issue Minimally Invasive Liver Resection)
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<p><b>Extrahepatic left Glissonean pedicle isolation in a cadaveric model.</b> After dissection between the arantius plate and the liver parenchyma, the dorsal aspect of the left Glissonean pedicle is non-blindly dissected while preserving the Laennec’s capsule (<b>A</b>). The right side of the left Glissonean pedicle and the Laennec’s capsule were separated (<b>B</b>). Pathologic examination using Elastica van Gieson staining proved the presence of the Laennec’s capsule in low- (<b>C</b>) and in high-power fields (black arrows)) (<b>D</b>).</p>
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<p><b>Laparoscopic second and third branches of the Glissonean pedicle isolation in a live body.</b> Right anterior Glissonean pedicle isolation was performed in laparoscopic right hepatectomy to validate the appropriate layer to be dissected. The space between the cystic plate and the Laennec’s capsule was dissected to expose the Laennec’s capsule (<b>A</b>). The dissection in the same layer as the cystic plate cholecystectomy was continued to the ventral side of the right anterior Glissonean pedicle (<b>B</b>). The Laennec’s capsule on the liver parenchyma and exfoliated right anterior Glissonean pedicle of a live body is shown in low- (<b>C</b>) and high-power fields (black arrows) (<b>D</b>). Glissonean pedicle 8 isolation was performed during a laparoscopic segmentectomy 8. Blunt dissection between the right anterior Glissonean pedicle and the Laennec’s capsule in the direction of the peripheral Glissonean pedicle allowed identification of the Glissonean pedicle 8 (G8) and Glissonean pedicle 5 (G5) (<b>E</b>). The dissection was performed while looking directly at the dorsal aspect of G8 using the laparoscopic magnification effect (<b>F</b>). The Laennec’s capsule on the liver parenchyma and exfoliated G8 is shown in low- (<b>G</b>) and high-power fields (black arrows) (<b>H</b>).</p>
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<p><b>Robotic second and third branches of Glissonean pedicle isolation in a live body.</b> Right posterior Glissonean pedicle isolation was performed during robotic right posterior sectionectomy. The junction of the right anterior and posterior Glissonean pedicles was identified and exposed the Laennec’s capsule (<b>A</b>). Blunt dissection between the Laennec’s capsule and the right posterior Glissonean pedicle from the caudal view while directly observing the dorsal view with a robotic endoscope (<b>B</b>). The Laennec’s capsule on the liver parenchyma and the exfoliated right posterior Glissonean pedicle of a live body is shown in low- (<b>C</b>) and high-power fields (black arrows) (<b>D</b>). Glissonean pedicle 4a (G4a), 4b (G4b), and 4c (G4c) isolation was performed in robotic segmentectomy 4b. The gap between the umbilical plate and the Laennec’s capsule was separated (<b>E</b>). All responsible branches of the Glissonean pedicle can be isolated without misidentification while directly observing the branches (<b>F</b>). The Laennec’s capsule on the liver parenchyma and the exfoliated Glissonean pedicle is in low- (<b>G</b>) and high-power fields (black arrows0 (<b>H</b>).</p>
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