Journal of Clinical Medicine

20 pages, 3418 KiB

Open AccessReview

Unraveling the Underlying Molecular Mechanism of ‘Silent Hypoxia’ in COVID-19 Patients Suggests a Central Role for Angiotensin II Modulation of the AT1R-Hypoxia-Inducible Factor Signaling Pathway

by Christian Albert Devaux and Jean-Christophe Lagier

J. Clin. Med. 2023, 12(6), 2445; https://doi.org/10.3390/jcm12062445 - 22 Mar 2023

Cited by 5 | Viewed by 3385

Abstract

A few days after being infected with SARS-CoV-2, a fraction of people remain asymptomatic but suffer from a decrease in arterial oxygen saturation in the absence of apparent dyspnea. In light of our clinical investigation on the modulation of molecules belonging to the [...] Read more.

A few days after being infected with SARS-CoV-2, a fraction of people remain asymptomatic but suffer from a decrease in arterial oxygen saturation in the absence of apparent dyspnea. In light of our clinical investigation on the modulation of molecules belonging to the renin angiotensin system (RAS) in COVID-19 patients, we propose a model that explains ‘silent hypoxia’. The RAS imbalance caused by SARS-CoV-2 results in an accumulation of angiotensin 2 (Ang II), which activates the angiotensin 2 type 1 receptor (AT1R) and triggers a harmful cascade of intracellular signals leading to the nuclear translocation of the hypoxia-inducible factor (HIF)-1α. HIF-1α transactivates many genes including the angiotensin-converting enzyme 1 (ACE1), while at the same time, ACE2 is downregulated. A growing number of cells is maintained in a hypoxic condition that is self-sustained by the presence of the virus and the ACE1/ACE2 ratio imbalance. This is associated with a progressive worsening of the patient’s biological parameters including decreased oxygen saturation, without further clinical manifestations. When too many cells activate the Ang II-AT1R-HIF-1α axis, there is a ‘hypoxic spillover’, which marks the tipping point between ‘silent’ and symptomatic hypoxia in the patient. Immediate ventilation is required to prevent the ‘hypoxic spillover’. Full article

(This article belongs to the Collection Coronavirus Disease 2019: Clinical Presentation, Pathogenesis and Treatment)

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Structure of the renin–angiotensin–(aldosterone) system and the role of ACE2 in this physiological system. ACE1 catalyzes the conversion of angiotensin I (Ang I) to angiotensin II (Ang II). ACE2 catalyzes the conversion of Ang I to angiotensin-(1-9) and the conversion of Ang II to angiotensin-(1-7). There are also known interactions between the RAS and the Kininogen–(kallikrein)–Bradykinin system (not shown). Under normal physiological conditions, ACE2 converts Ang II into Ang-(1-7), which exhibits vasodilatory, anti-proliferative, and anti-inflammatory effects via the G protein-coupled receptor called Mas-1. Ang-(1-7) counterbalances the vasoconstrictor and inflammatory effect of Ang II. Upon SARS-CoV-2 entry, the downregulation of ACE2 decreases its ability to generate angiotensin (1-9) from Ang I and angiotensin-(1-7) from Ang II, leading to renin–angiotensin system (RAS) imbalance and overactivation of the Ang II -AT1R axis. For more details, see reference [<a href="#B70-jcm-12-02445" class="html-bibr">70</a>]. Full article ">Figure 2
Schematic diagram illustrating the dual regulation of HIF-1α. (a) At normal O2 concentration, HIF-1α is hydroxylated by the prolyl hydroxylase (PHD). The ubiquitin ligase VHL targets HIF-1α-OH for polyubiquitinylation and proteosomal degradation. Similarly, hydroxylation of the transient receptor potential channel (TRP) by PHD, and asparaginyl hydroxylase FIH targeting TRP-OH for ubiquitinylation and proteosomal degradation, contribute to homeostasis. (b) Ang II can contribute to hypoxia through binding to AT1R, which initiates signaling events including activation of reactive oxygen species (ROS) by mitochondria. Under hypoxia, HIF-1α translocates to the cell nucleus where it forms heterodimers with the HIF-β subunit and binds to the hypoxia response element (HRE) in the promoter of hypoxia-inducible genes, recruiting histone acetyltransferases CREB Binding Protein (CBP)/p300 to modulate hypoxia-inducible genes expression. For more details, see reference [<a href="#B65-jcm-12-02445" class="html-bibr">65</a>]. Full article ">Figure 3
Representative list of cellular genes upregulated by HIF-1. HIF-1α is considered a ‘master regulator’ type of transcription factor capable of controlling the expression of a multitude of genes grouped under the heading of hypoxia-inducible genes α (the list is not exhaustive and grows continuously). The consensus DNA sequence for HIF-1α/HIF-1β binding is common for many genes upregulated during hypoxia. It is worth noting that several genes involved in the RAS, in the development and functioning of the vascular system (which modulate vascular tone or promote angiogenesis), and in erythropoiesis, belong to this list. Full article ">Figure 4
Proposed model of signaling in SARS-CoV-2-induced silent hypoxia. In order to simplify the representation of the signaling pathways, the effects of Ang II have been summarized on a single cell, but several different cell types are involved in the process of ‘silent hypoxia’ and can therefore respond in a specific way to Ang II stimulation. When SARS-CoV-2 is present, the binding of SARS-CoV-2 to ACE2 leads to the dysfunction of ACE2, reduced hydrolysis of Ang II, and increased levels of Ang II. Under this condition, Ang-(1-7) is not sufficient to counterbalance the activity of Ang II. The binding of Ang II to the AT1R activates a signaling cascade that contributes to the lowering of intracellular oxygen and a reduction in the hydroxylation of HIF-1α by PHD. Under these conditions, HIF-1α translocates to the cell nucleus, forms heterodimers with the HIF-1α, and controls the expression of hypoxia-inducible genes. This leads to the upregulation of the ACE1 gene, which contributes to further increases in Ang II, the increased expression of TRPA1, and to the modulation of expression of various genes. In addition, chronic HIF triggers the downregulation of the ACE2 gene and the activation of ADAM17, which leads to the cleavage of the ACE2, the release of soluble ACE2 (sACE2), and S1/sACE2 complexes formation. Finally, there is a decrease in nitric oxide (NO) bioavailability, since O2- inactivates NO. Full article ">Figure 5
Physiologic mechanisms governing the control of breathing. Peripheral chemical and mechanical sensory receptors are involved in the control of breathing and the sensation of dyspnea. Peripheral chemoreceptors located in the aortic arch and the carotid arteries act as sensors for both O2 tension and CO2 tension. Pulmonary alveolar walls receptors include joint receptors and stretch receptors. Chemoreceptors in the central and peripheral airways act as irritant sensors. Mechanoreceptors located on the ribs provide information regarding displacement, while muscle tendons provide information regarding tension development. Muscle spindles provide integrated information. The central nervous system integrates these signals and governs breathing (neurons that regulate breathing are widely dispersed in the central cortex, the hypothalamus, the limbic/paralimbic system, pons, and medulla). In moderate hypoxemia, patients respond with intense cardiovascular response (e.g., increased tachycardia, cardiac output, and systemic arterial blood pressure) and accelerated breathing. In contrast, profound hypoxemia (SaO2 below 50%) is associated with cardiovascular collapse that results in loss of consciousness, bradycardia, and shock. The ‘hypoxic spillover’ corresponds to sudden deterioration in both oxygen saturation and cardiovascular compensation. For more details, see reference [<a href="#B149-jcm-12-02445" class="html-bibr">149</a>]. Full article ">

15 pages, 1733 KiB

Open AccessReview

Management of Statin Intolerant Patients in the Era of Novel Lipid Lowering Therapies: A Critical Approach in Clinical Practice

by Giosiana Bosco, Francesco Di Giacomo Barbagallo, Salvatore Spampinato, Lorena Lanzafame, Antonino Di Pino, Salvatore Piro, Francesco Purrello and Roberto Scicali

J. Clin. Med. 2023, 12(6), 2444; https://doi.org/10.3390/jcm12062444 - 22 Mar 2023

Cited by 12 | Viewed by 4992

Abstract

Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym [...] Read more.

Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym SAMS (Statin-Associated Muscle Side Effects). These side effects are responsible for statin treatment discontinuation that results in increased cardiovascular risk. The National Lipid Association (NLA) has recently provided an updated definition of statin intolerance, and a distinction between complete and partial statin intolerance has been reported. The evaluation of symptom severity and the presence of muscle damage biomarker alterations make it essential to adopt a patient-centered approach aimed at obtaining a personalized therapeutic strategy. Firstly, it could be useful to administer a different statin, reduce the dosage or adopt an alternate dosage regimen. However, some patients are unable to tolerate any statin at every dosage, or despite taking statins at the maximum tolerated dose, they fail to achieve the recommended LDL-C target, and thus it is necessary to introduce a non-statin hypolipidemic treatment. Ezetimibe, proprotein-convertase subtilisin/kexin type 9 (PCSK9) inhibitors such as monoclonal antibodies (alirocumab and evolocumab) or RNA messenger silencing (inclisiran), bempedoic acid or nutraceuticals are non-statin lipid-lowering therapies that could be used as an alternative or in addition to statins to achieve an early and sustained LDL-C reduction in clinical practice. In this review, we evaluated SI management focusing on non-statin lipid lowering therapies and their implications in lipid lowering approaches in clinical practice. Full article

(This article belongs to the Special Issue Dyslipidemia and Cardiovascular Disease)

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14 pages, 700 KiB

Open AccessArticle

Cross Sectional and Case-Control Study to Assess Time Trend, Gender Differences and Factors Associated with Physical Activity among Adults with Diabetes: Analysis of the European Health Interview Surveys for Spain (2014 & 2020)

by Carlos Llamas-Saez, Teresa Saez-Vaquero, Rodrigo Jiménez-García, Ana López-de-Andrés, David Carabantes-Alarcón, José J. Zamorano-León, Natividad Cuadrado-Corrales, Napoleón Pérez-Farinos and Julia Wärnberg

J. Clin. Med. 2023, 12(6), 2443; https://doi.org/10.3390/jcm12062443 - 22 Mar 2023

Cited by 3 | Viewed by 1889

Abstract

(1) Background: We aim to assess the time trend from 2014 to 2020 in the prevalence of physical activity (PA), identify gender differences and sociodemographic and health-related factors associated with PA among people with diabetes, and compare PA between people with and without [...] Read more.

(1) Background: We aim to assess the time trend from 2014 to 2020 in the prevalence of physical activity (PA), identify gender differences and sociodemographic and health-related factors associated with PA among people with diabetes, and compare PA between people with and without diabetes. (2) Methods: We conducted a cross-sectional and a case–control study using as data source the European Health Interview Surveys for Spain (EHISS) conducted in years 2014 and 2020. The presence of diabetes and PA were self-reported. Covariates included socio-demographic characteristics, health-related variables, and lifestyles. To compare people with and without diabetes, we matched individuals by age and sex. (3) Results: The number of participants aged ≥18 years with self-reported diabetes were 1852 and 1889 in the EHISS2014 and EHISS2020, respectively. The proportion of people with diabetes that had a medium or high frequency of PA improved from 48.3% in 2014 to 52.6% in 2020 (p = 0.009), with 68.5% in 2014 and 77.7% in 2020 being engaged in two or more days of PA (p < 0.001). Males with diabetes reported more PA than females with diabetes in both surveys. After matching by age and gender, participants with diabetes showed significantly lower engagement in PA than those without diabetes. Among adults with diabetes, multivariable logistic regression showed confirmation that PA improved significantly from 2014 to 2020 and that male sex, higher educational level, and better self-rated health were variables associated to more PA. However, self-reported comorbidities, smoking, or BMI > 30 were associated to less PA. (4) Conclusions: The time trend of PA among Spanish adults with diabetes is favorable but insufficient. The prevalence of PA in this diabetes population is low and does not reach the levels of the general population. Gender differences were found with significantly more PA among males with diabetes. Our result could help to improve the design and implementation of public health strategies to improve PA among people with diabetes. Full article

(This article belongs to the Special Issue Clinical Epidemiology of Diabetes and Its Complications)

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15 pages, 1690 KiB

Open AccessArticle

Cryoballoon-Induced Circumferential Pulmonary Vein Fibrosis, Assessed by Late Gadolinium-Enhancement Cardiac Magnetic Resonance Imaging, and Its Correlation with Clinical Atrial Fibrillation Recurrence

by Moshe Rav Acha, Oholi Tovia-Brodie, Yoav Michowitz, Feras Bayya, Fauzi F. Shaheen, Shalom Abuhatzera, Aharon Medina, Michael Glikson and Arik Wolak

J. Clin. Med. 2023, 12(6), 2442; https://doi.org/10.3390/jcm12062442 - 22 Mar 2023

Cited by 3 | Viewed by 1605

Abstract

Background: Prior studies evaluating post-atrial fibrillation (AF) ablation pulmonary vein (PV) ostial gaps via magnetic resonance imaging (MRI) have shown circumferential PV fibrosis in a minority of patients, and their correlation with AF recurrence was weak. These studies were mostly based on radio-frequency [...] Read more.

Background: Prior studies evaluating post-atrial fibrillation (AF) ablation pulmonary vein (PV) ostial gaps via magnetic resonance imaging (MRI) have shown circumferential PV fibrosis in a minority of patients, and their correlation with AF recurrence was weak. These studies were mostly based on radio-frequency AF ablations. Aim: We aimed to assess cryoballoon ablation-induced PV fibrosis via MRI and its correlation with AF recurrence. Methods and Results: This was a prospective study of consecutive patients with symptomatic AF who underwent pre- and post-ablation MRI to assess baseline and ablation-induced fibrosis, respectively. Post-ablation PV gaps were assessed by new semi-quantitative visual analysis assisted by computerized ADAS analysis. AF recurrence monitored via multiple ECGs and event monitoring at 6 and 12 months post ablation. Nineteen patients with 80 PVs were included, age 56 ± 11, with paroxysmal and persistent AF in 17/19 and 2/19 patients, respectively. Baseline MRI showed minimal LA fibrosis. All patients underwent successful cryoballoon PV electrical isolation. Post-ablation MRI revealed circumferential PV fibrosis among 63/80 (78.8%) PVs and partial fibrosis with major gaps among 17/80 (21.2%) PVs. AF recurred within one year in 5/9 (55.5%) patients with partial PV fibrosis, while no AF recurred among the 10 patients in whom all PVs had circumferential fibrosis (p < 0.01). Similarly, there were significantly more PVs without circumferential fibrosis (due to major gaps) among patients with AF recurrence as compared with patients without AF recurrence (42.9% vs. 13.5%; p < 0.01). Conclusion: Cryoballoon AF ablation results in circumferential PV fibrosis in the majority of PVs, as assessed by a new clinically relevant MRI-LGE analysis. Significant correlation was found between major PV gaps on post-ablation MRI and AF recurrence, suggesting that MRI might have the ability to predict AF recurrence. Full article

(This article belongs to the Topic Improving Diagnosis and Treatment in Heart Failure and Myocarditis)

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12 pages, 682 KiB

Open AccessArticle

Can Alterations in Cerebrovascular CO₂ Reactivity Be Identified Using Transfer Function Analysis without the Requirement for Carbon Dioxide Inhalation?

by Shigehiko Ogoh, Hironori Watanabe, Shotaro Saito, James P. Fisher and Erika Iwamoto

J. Clin. Med. 2023, 12(6), 2441; https://doi.org/10.3390/jcm12062441 - 22 Mar 2023

Viewed by 1831

Abstract

The present study aimed to examine the validity of a novel method to assess cerebrovascular carbon dioxide (CO₂) reactivity (CVR) that does not require a CO₂ inhalation challenge, e.g., for use in patients with respiratory disease or the elderly, etc. [...] Read more.

The present study aimed to examine the validity of a novel method to assess cerebrovascular carbon dioxide (CO₂) reactivity (CVR) that does not require a CO₂ inhalation challenge, e.g., for use in patients with respiratory disease or the elderly, etc. In twenty-one healthy participants, CVR responses to orthostatic stress (50° head-up tilt, HUT) were assessed using two methods: (1) the traditional CO₂ inhalation method, and (2) transfer function analysis (TFA) between middle cerebral artery blood velocity (MCA V) and predicted arterial partial pressure of CO₂ (PaCO₂) during spontaneous respiration. During HUT, MCA V steady-state (i.e., magnitude) and MCA V onset (i.e., time constant) responses to CO₂ inhalation were decreased (p < 0.001) and increased (p = 0.001), respectively, indicative of attenuated CVR. In contrast, TFA gain in the very low-frequency range (VLF, 0.005–0.024 Hz) was unchanged, while the TFA phase in the VLF approached zero during HUT (−0.38 ± 0.59 vs. 0.31 ± 0.78 radians, supine vs. HUT; p = 0.003), indicative of a shorter time (i.e., improved) response of CVR. These findings indicate that CVR metrics determined by TFA without a CO₂ inhalation do not track HUT-evoked reductions in CVR identified using CO₂ inhalation, suggesting that enhanced cerebral blood flow response to a change in CO₂ using CO₂ inhalation is necessary to assess CVR adequately. Full article

(This article belongs to the Section Vascular Medicine)

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The relationship between middle cerebral artery mean blood velocity (MCA Vmean) and predicted partial pressure of carbon dioxide (PaCO2) (A) and the average of the magnitude response of cerebrovascular CO2 reactivity (CVR) during supine and 50° head-up tilt (HUT) conditions (B) the bar and opened circles represent average and individual values, respectively (n = 21; 13 men and 8 women). The p-value represents the paired t-test analyses between supine and 50° HUT. Full article ">Figure 2
The response of middle cerebral artery mean blood velocity (MCA Vmean) to 5% CO2 inhalation in a representative participant (A) and the average of the time response of cerebrovascular CO2 reactivity (CVR) during supine and 50° head-up tilt (HUT) conditions (B): the bar and opened circles represent average and individual values, respectively (n = 21; 13 men and 8 women). The p-value represents the Wilcoxon matched-pairs signed-ranks analyses between supine and 50° HUT. τ, time constant, as an index of time response of CVR. Full article ">Figure 3
Cross-spectral analysis of the entire spectrum from 0 to 0.30 Hz during supine and 50° head-up tilt (HUT) conditions during spontaneous respiration without CO2 inhalation. The group-averaged transfer function phase (A), gain (B) and coherence function (C) between spontaneous changes in predicted partial pressure of arterial carbon dioxide (PaCO2) and middle cerebral artery mean blood velocity (MCA Vmean) during supine and 50° HUT conditions are shown (n = 21; 13 men and 8 women). The dash-dotted and solid lines represent the TFA parameters at supine and 50° HUT, respectively. Full article ">

17 pages, 1689 KiB

Open AccessArticle

Distinct Sleep Alterations in Alcohol Use Disorder Patients with and without Korsakoff’s Syndrome: Relationship with Episodic Memory

by Alice Laniepce, Shailendra Segobin, Claire André, Françoise Bertran, Céline Boudehent, Najlaa Lahbairi, Angéline Maillard, Alison Mary, Laurent Urso, François Vabret, Nicolas Cabé, Anne-Lise Pitel and Géraldine Rauchs

J. Clin. Med. 2023, 12(6), 2440; https://doi.org/10.3390/jcm12062440 - 22 Mar 2023

Viewed by 2152

Abstract

Alcohol Use Disorder (AUD) results in sleep disturbances that may have deleterious impacts on cognition, especially on memory. However, little is known about the sleep architecture in patients with Korsakoff’s syndrome (KS). This study aims at characterizing sleep disturbances in KS compared to [...] Read more.

Alcohol Use Disorder (AUD) results in sleep disturbances that may have deleterious impacts on cognition, especially on memory. However, little is known about the sleep architecture in patients with Korsakoff’s syndrome (KS). This study aims at characterizing sleep disturbances in KS compared to AUD without KS and at specifying the relationships with cognitive impairments. Twenty-nine AUD patients (22 without KS and 7 with KS) and 15 healthy controls underwent a neuropsychological assessment and a polysomnography. The severity of sleep-disordered breathing and sleep fragmentation was similar in AUD and KS patients compared to controls. Sleep architecture differed between both patient groups: the proportion of slow-wave sleep was reduced in AUD patients only, while a lower proportion of rapid-eye movement (REM) sleep was specifically observed in KS patients. The proportion of REM sleep correlated with the severity of episodic memory deficits when AUD and KS were examined together. These data provide evidence for both similarities and specificities regarding sleep alterations in AUD patients with and without KS. They also indicate that altered sleep architecture may contribute to the pathophysiology of alcohol-related memory disorders. Full article

(This article belongs to the Special Issue Wernicke's Encephalopathy and Korsakoff's Syndrome)

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12 pages, 1559 KiB

Open AccessArticle

Evaluation of Kidney Donor Risk Index/Kidney Donor Profile Index as Predictor Tools of Deceased-Donor Kidney Transplant Outcomes in a Greek Cohort

by Maria Darema, Diamanto Athanasopoulou, Ioannis Bellos, Ioanna Tsoumbou, Angeliki G. Vittoraki, John Bokos, Smaragdi Marinaki and Ioannis N. Boletis

J. Clin. Med. 2023, 12(6), 2439; https://doi.org/10.3390/jcm12062439 - 22 Mar 2023

Cited by 1 | Viewed by 2853

Abstract

The Kidney Donor Risk Index (KDRI) and Kidney Donor Profile Index (KDPI) have been developed to assess deceased-donor graft quality, although validation of their utility outside the USA remains limited. This single-center retrospective cohort study evaluated the ability of KDRI and KDPI to [...] Read more.

The Kidney Donor Risk Index (KDRI) and Kidney Donor Profile Index (KDPI) have been developed to assess deceased-donor graft quality, although validation of their utility outside the USA remains limited. This single-center retrospective cohort study evaluated the ability of KDRI and KDPI to predict transplant outcomes in a Greek cohort. The efficacy of KDRI, KDPI, and donor’s age in predicting death-censored graft failure was primarily assessed. Overall, 394 donors and 456 recipients were included. Death-censored graft survival was significantly worse with increasing KDRI (hazard ratio—HR: 2.21, 95% confidence intervals—CI: 1.16–4.22), KDPI (HR: 1.01, 95% CI: 1.00–1.02), and donor’s age (HR: 1.03, 95% CI: 1.00–1.05). The unadjusted discriminative ability was similar for KDPI (C-statistic: 0.54) and donor’s age (C-statistic: 0.52). The KDPI threshold of 85 was not predictive of graft failure (p-value: 0.19). Higher KDPI was linked to delayed graft function and worse kidney function, but not among expanded-criteria donor transplantations. No significant association was found between KDRI, KDPI, and patient survival. In conclusion, increasing KDRI and KDPI are linked to worse graft function, although their ability to discriminate long-term graft failure remains limited. Full article

(This article belongs to the Special Issue Recent Advances of Kidney Transplantation)

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13 pages, 1208 KiB

Open AccessArticle

The Associations between Insomnia Severity and Health Outcomes in the United States

by François-Xavier Chalet, Paul Saskin, Ajay Ahuja, Jeffrey Thompson, Abisola Olopoenia, Kushal Modi, Charles M. Morin and Emerson M. Wickwire

J. Clin. Med. 2023, 12(6), 2438; https://doi.org/10.3390/jcm12062438 - 22 Mar 2023

Cited by 8 | Viewed by 3993

Abstract

Little is known about the associations between insomnia severity, insomnia symptoms, and key health outcomes. Using 2020 United States National Health and Wellness Survey (NHWS) data, we conducted a retrospective, cross-sectional analysis to determine the associations between insomnia severity and a number of [...] Read more.

Little is known about the associations between insomnia severity, insomnia symptoms, and key health outcomes. Using 2020 United States National Health and Wellness Survey (NHWS) data, we conducted a retrospective, cross-sectional analysis to determine the associations between insomnia severity and a number of health outcomes germane to patients (health-related quality of life (HRQoL), employers and government (workplace productivity), and healthcare payers (healthcare resource utilization (HCRU)). The Insomnia Severity Index (ISI) questionnaire was used to evaluate overall insomnia severity. HRQoL was assessed using the physical and mental component summary scores of the Short Form-36v2 (SF-36v2) questionnaire, and health utility status was measured using the Short Form-6D (SF-6D) and EuroQoL-5D (EQ-5D) questionnaires. Workplace productivity was measured using the Work Productivity and Activity Impairment (WPAI) questionnaire. After adjusting for confounders, greater insomnia severity was significantly associated with worsened quality of life, decreased productivity, and increased HCRU in an apparent linear fashion. These findings have important implications for future research, including the need for specific assessment of insomnia symptoms and their impact on key health outcomes. Full article

(This article belongs to the Special Issue Insomnia Treatments: New Perspectives)

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9 pages, 1028 KiB

Open AccessArticle

Donor-Derived Cell-Free DNA for Kidney Allograft Surveillance after Conversion to Belatacept: Prospective Pilot Study

by Bilgin Osmanodja, Aylin Akifova, Michael Oellerich, Julia Beck, Kirsten Bornemann-Kolatzki, Ekkehard Schütz and Klemens Budde

J. Clin. Med. 2023, 12(6), 2437; https://doi.org/10.3390/jcm12062437 - 22 Mar 2023

Cited by 4 | Viewed by 1779

Abstract

Donor-derived cell-free DNA (dd-cfDNA) is used as a biomarker for detection of antibody-mediated rejection (ABMR) and other forms of graft injury. Another potential indication is guidance of immunosuppressive therapy when no therapeutic drug monitoring is available. In such situations, detection of patients with [...] Read more.

Donor-derived cell-free DNA (dd-cfDNA) is used as a biomarker for detection of antibody-mediated rejection (ABMR) and other forms of graft injury. Another potential indication is guidance of immunosuppressive therapy when no therapeutic drug monitoring is available. In such situations, detection of patients with overt or subclinical graft injury is important to personalize immunosuppression. We prospectively measured dd-cfDNA in 22 kidney transplant recipients (KTR) over a period of 6 months after conversion to belatacept for clinical indication and assessed routine clinical parameters. Patient and graft survival was 100% after 6 months, and eGFR remained stable (28.7 vs. 31.1 mL/min/1.73 m², p = 0.60). Out of 22 patients, 2 (9%) developed biopsy-proven rejection—one episode of low-grade TCMR IA and one episode of caABMR. While both episodes were detected by increase in creatinine, the caABMR episode led to increase in absolute dd-cfDNA (168 copies/mL) above the cut-off of 50 copies/mL, while the TCMR episode did show slightly increased relative dd-cfDNA (0.85%) despite normal absolute dd-cfDNA (22 copies/mL). Dd-cfDNA did not differ before and after conversion in a subgroup of 12 KTR with previous calcineurin inhibitor therapy and no rejection (12.5 vs. 25.3 copies/mL, p = 0.34). In this subgroup, 3/12 (25%) patients showed increase of absolute dd-cfDNA above the prespecified cut-off (50 copies/mL) despite improving eGFR. Increase in dd-cfDNA after conversion to belatacept is common and could point towards subclinical allograft injury. To detect subclinical TCMR changes without vascular lesions, additional biomarkers or urinary dd-cfDNA should complement plasma dd-cfDNA. Resolving CNI toxicity is unlikely to be detected by decreased dd-cfDNA levels. In summary, the sole determination of dd-cfDNA has limited utility in the guidance of patients after late conversion to belatacept. Further studies should focus on patients undergoing early conversion and include protocol biopsies at least for patients with increased dd-cfDNA. Full article

(This article belongs to the Special Issue Novel Insights in Renal Transplantation—Volume 2)

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11 pages, 666 KiB

Open AccessArticle

Inhaled Medications in Chronic Respiratory Diseases: Analysis of Real-Life Use in Puglia (Apulia), Italy

by Giulia Scioscia, Pasquale Tondo, Maria Grazia Cagnazzo, Anela Hoxhallari, Francesco Satriano, Giulio Rollo, Donato Cinquepalmi, Antonio Grieco, Maria Pia Foschino Barbaro and Donato Lacedonia

J. Clin. Med. 2023, 12(6), 2436; https://doi.org/10.3390/jcm12062436 - 22 Mar 2023

Cited by 1 | Viewed by 1499

Abstract

Background: Chronic respiratory diseases (CRDs) are common diseases with a heterogeneous distribution worldwide. Due to their impact on disability, weight assistance and pharmaceutical spending, they represent an important global burden for national health systems. However, few studies have investigated the use and consumption [...] Read more.

Background: Chronic respiratory diseases (CRDs) are common diseases with a heterogeneous distribution worldwide. Due to their impact on disability, weight assistance and pharmaceutical spending, they represent an important global burden for national health systems. However, few studies have investigated the use and consumption of inhaled drugs in real life in patients with CRDs. Objective: This study aimed to investigate the real-life consumption of health care resources of main CRDs through an analysis of the administrative databases of the local health authority (ASL) in the Puglia region (Italy). Methods: The present study is an observational study that longitudinally reviewed the administrative and health databases associated with patients’ consumption of health resources between 2017 and 2018. Results: The first important finding is a marked underestimation of the true incidence of CRDs despite the search for disease-specific exemption codes. Another important result is that the real-life consumption of inhaled drugs among these patients is well below the minimum acceptable values for adherence. The most commonly used inhaled drugs, for which at least one pack was withdrawn, were inhaled steroids (61.6%), followed by the ICS/LABA combination (43.7%) and LABAs (32.4%). However, less than one-third of patients (31%) withdrew at least three packages of ICS or ICS/LABA during the year, while the percentage was reduced to less than 15% for other combinations. Another alarming finding is that only 8.4% of patients taking CRDs drugs reported at least one spirometry during the study period. Conclusions: The wide availability of computerized systems may be an important tool for increasing therapeutic adherence and optimizing the resources of health systems in the diagnosis, treatment and management of patients with CRDs. Full article

(This article belongs to the Section Pulmonology)

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9 pages, 816 KiB

Open AccessArticle

Serum GDF-15 Levels Accurately Differentiate Patients with Primary Mitochondrial Myopathy, Manifesting with Exercise Intolerance and Fatigue, from Patients with Chronic Fatigue Syndrome

by Laura Bermejo-Guerrero, Carlos Pablo de Fuenmayor-Fernández de la Hoz, María Paz Guerrero-Molina, Paloma Martín-Jiménez, Alberto Blázquez, Pablo Serrano-Lorenzo, David Lora, Montserrat Morales-Conejo, Irene González-Martínez, Elena Ana López-Jiménez, Miguel A. Martín and Cristina Domínguez-González

J. Clin. Med. 2023, 12(6), 2435; https://doi.org/10.3390/jcm12062435 - 22 Mar 2023

Cited by 2 | Viewed by 3785

Abstract

Primary mitochondrial myopathies (PMM) are a clinically and genetically highly heterogeneous group that, in some cases, may manifest exclusively as fatigue and exercise intolerance, with minimal or no signs on examination. On these occasions, the symptoms can be confused with the much more [...] Read more.

Primary mitochondrial myopathies (PMM) are a clinically and genetically highly heterogeneous group that, in some cases, may manifest exclusively as fatigue and exercise intolerance, with minimal or no signs on examination. On these occasions, the symptoms can be confused with the much more common chronic fatigue syndrome (CFS). Nonetheless, other possibilities must be excluded for the final diagnosis of CFS, with PMM being one of the primary differential diagnoses. For this reason, many patients with CFS undergo extensive studies, including extensive genetic testing and muscle biopsies, to rule out this possibility. This study evaluated the diagnostic performance of growth differentiation factor-15 (GDF-15) as a potential biomarker to distinguish which patient with chronic fatigue has a mitochondrial disorder. We studied 34 adult patients with symptoms of fatigue and exercise intolerance with a definitive diagnosis of PMM (7), CFS (22), or other non-mitochondrial disorders (5). The results indicate that GDF-15 can accurately discriminate between patients with PMM and CFS (AUC = 0.95) and between PMM and patients with fatigue due to other non-mitochondrial disorders (AUC = 0.94). Therefore, GDF-15 emerges as a promising biomarker to select which patients with fatigue should undergo further studies to exclude mitochondrial disease. Full article

(This article belongs to the Section Clinical Neurology)

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14 pages, 4132 KiB

Open AccessArticle

Remineralization Potential of Three Restorative Glass Ionomer Cements: An In Vitro Study

by James Ghilotti, Icíar Fernández, José Luis Sanz, María Melo and Carmen Llena

J. Clin. Med. 2023, 12(6), 2434; https://doi.org/10.3390/jcm12062434 - 22 Mar 2023

Cited by 6 | Viewed by 2398

Abstract

The aim of this in vitro study was to evaluate the remineralizing ability of three glass ionomers on demineralized dentin with different thicknesses and time periods. Fifty third molars were obtained and were sectioned into 1-, 2-, and 3-mm thick slices (n = [...] Read more.

The aim of this in vitro study was to evaluate the remineralizing ability of three glass ionomers on demineralized dentin with different thicknesses and time periods. Fifty third molars were obtained and were sectioned into 1-, 2-, and 3-mm thick slices (n = 36 for each thickness). The specimens were demineralized with 18% EDTA for 2 h. From the glass ionomer cements (GICs) under study (Ketac Molar Aplicap, Equia Forte, or Riva Light Cure), 1 mm was placed over each slice, set, and preserved in PBS until observation after 1, 7, 14, and 28 days after placement. For each material, thickness, and time, three samples were prepared. Using Fourier Transform Infrared Spectrometry (FTIR), apatite formation was determined on the side opposite to that on which the material had been placed. By means of Energy Dispersive Spectroscopy (EDX), the changes in the Calcium/Phosphate (Ca/P) ratio were evaluated. These changes were compared between the different materials by means of a two-way ANOVA test, considering time and dentin thickness, for a significance level of p < 0.05. Results: FTIR showed a peak at 1420 cm⁻¹, evidencing the presence of carbonated hydroxyapatite in all the materials after 14 days, which indicates that a remineralization process occurred. Riva Light Cure showed the most homogeneous results at all depths at 28 days. The Ca/P ratio was maximum at 7 days in 2 mm of dentin for Riva Light Cure and Equia Forte HT (3.16 and 3.07; respectively) and for Ketac Molar at 14 days in 1 mm (3.67). All materials induced remineralization. Equia Forte achieved the greatest effect at 2 mm and Ketac Molar at 1 mm, whereas Riva Light Cure showed similar results at all depths. In terms of Ca/P ratio, Equia Forte and Riva Light Cure remineralized best at 2 mm, whereas for Ketac Molar, it was 1 mm. Carbonate apatite formation was higher at 24 h and 7 days for Ketac Molar, whereas it decreased at 14 days for Ketac Molar and peaked in Riva Light Cure and Equia Forte. Full article

(This article belongs to the Special Issue Management of Dental Caries)

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16 pages, 1546 KiB

Open AccessReview

The Role and Clinical Relevance of Osteopontin in Allergic Airway Diseases

by Yang Liu, Li Fu and Zheng Liu

J. Clin. Med. 2023, 12(6), 2433; https://doi.org/10.3390/jcm12062433 - 22 Mar 2023

Cited by 1 | Viewed by 2521

Abstract

The airway epithelium is exposed to numerous external irritants including infectious agents, environmental allergens, and atmospheric pollutants, releasing epithelial cytokines including thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 and initiating downstream type 2 (IL-4, IL-13, and IL-5) and IgE-driven pathways. These pathways trigger [...] Read more.

The airway epithelium is exposed to numerous external irritants including infectious agents, environmental allergens, and atmospheric pollutants, releasing epithelial cytokines including thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 and initiating downstream type 2 (IL-4, IL-13, and IL-5) and IgE-driven pathways. These pathways trigger the initiation and progression of allergic airway diseases, including chronic rhinosinusitis with nasal polyps (CRSwNP), allergic rhinitis (AR), and allergic asthma. However, the use of biological agents that target downstream cytokines, such as IL-5, IL-4, and IL-13 receptors and IgE, might not be sufficient to manage some patients successfully. Instead of blocking downstream cytokines, targeting upstream epithelial cytokines has been proposed to address the complex immunologic networks associated with allergic airway diseases. Osteopontin (OPN), an extracellular matrix glyco-phosphoprotein, is a key mediator involved in Th1-related diseases, including systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. Emerging evidence, including ours, indicates that epithelial-cell-derived OPN also plays an essential role in Th2-skewed airway diseases, including CRSwNP, AR, and allergic asthma involving the Th17 response. Therefore, we reviewed the current knowledge of epithelial-cell-derived OPN in the pathogenesis of three type-2-biased airway diseases and provided a direction for its future investigation and clinical relevance. Full article

(This article belongs to the Section Immunology)

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21 pages, 2795 KiB

Open AccessReview

The Optimal Management of Inflammatory Bowel Disease in Patients with Cancer

by Panu Wetwittayakhlang, Paraskevi Tselekouni, Reem Al-Jabri, Talat Bessissow and Peter L. Lakatos

J. Clin. Med. 2023, 12(6), 2432; https://doi.org/10.3390/jcm12062432 - 22 Mar 2023

Cited by 8 | Viewed by 3370

Abstract

Patients with inflammatory bowel disease (IBD) have an increased risk of cancer secondary to chronic inflammation and long-term use of immunosuppressive therapy. With the aging IBD population, the prevalence of cancer in IBD patients is increasing. As a result, there is increasing concern [...] Read more.

Patients with inflammatory bowel disease (IBD) have an increased risk of cancer secondary to chronic inflammation and long-term use of immunosuppressive therapy. With the aging IBD population, the prevalence of cancer in IBD patients is increasing. As a result, there is increasing concern about the impact of IBD therapy on cancer risk and survival, as well as the effects of cancer therapies on the disease course of IBD. Managing IBD in patients with current or previous cancer is challenging since clinical guidelines are based mainly on expert consensus. Evidence is rare and mainly available from registries or observational studies. In contrast, excluding patients with previous/or active cancer from clinical trials and short-term follow-up can lead to an underestimation of the cancer or cancer recurrence risk of approved medications. The present narrative review aims to summarize the current evidence and provide practical guidance on the management of IBD patients with cancer. Full article

(This article belongs to the Special Issue Clinical Advances in Inflammatory Bowel Disease)

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The risk of type-specific cancer associated with IBD therapies Note: a: 5-ASA has a protective effect for CRC; b: thiopurine has a protective effect for CRC and high-grade dysplasia; c: the increased risk was reported in meta-analyses and observational studies but not replicated in several studies, including RCTs, meta-analyses, and registry cohorts; d: the increased risk was reported in large population-based and case-control studies, but meta-analyses did not find an increased risk; e: insufficient data on the risk of lymphoma in IBD patients exposed to anti-TNF in combination with methotrexate. * Data on the risk of cancer in MTX alone were relatively limited, based on a small number of MTX-exposed patients and small numbers of cancer events. ** For vedolizumab, ustekinumab, and JAK inhibitors, long-term data are limited. No increased risk was reported with VDZ and UST exposures (excluding NMSC in UST). For JAK inhibitors, one safety RCT reported an increased risk of overall cancer, particularly lymphoma and lung cancer. Full article ">Figure 2
The risk of type-specific cancer associated with IBD therapies Management of IBD therapy in patients with a history of previous cancer (adapted from ECCO guideline 2015 [<a href="#B106-jcm-12-02432" class="html-bibr">106</a>]). Abbreviations: anti-TNF—anti-tumor necrosis factors; NMSC—non-melanoma skin cancer; JAK inhibitors—Janus kinase inhibitors. Full article ">Figure 3
The practical treatment algorithm for the management of IBD in patients with a previous history of cancer. Abbreviations: IBD—inflammatory bowel disease; anti-TNF—anti-tumor necrosis factors; MTX—methotrexate; VDZ—vedolizumab; UST—ustekinumab; 5-ASA—5-amino salicylic acid. Full article ">Figure 4
The practical treatment algorithm for the management of IBD in patients with active cancer. Abbreviations: IBD—inflammatory bowel disease; AZA—azathioprine; 6-MP—Mercaptopurine; CMT—chemotherapy; ICIs—immune checkpoint inhibitors; anti-TNF—anti-tumor necrosis factors; VDZ—vedolizumab. Full article ">Figure 5
Conceptual framework of decision-making for treatment of IBD in patients with cancer. Full article ">

12 pages, 1896 KiB

Open AccessArticle

Increased Access to Immunoglobulin Replacement Therapy for Patients with Primary Immunodeficiency in Poland Based on Clinical Usage Data of Immunoglobulin G over a 5-Year Period

by Ewa Więsik-Szewczyk, Marcin Ziętkiewicz, Anna Radziwilska-Muc and Karina Jahnz-Różyk

J. Clin. Med. 2023, 12(6), 2431; https://doi.org/10.3390/jcm12062431 - 22 Mar 2023

Cited by 2 | Viewed by 2353

Abstract

Owing to the rising popularity and demand for immunoglobulins (IgG), obtaining supplies and rationalizing IgG use have become challenging. Herein, IgG consumption in Poland was analyzed through total IgG use and number of patients reported to the National Health Fund between 1 January [...] Read more.

Owing to the rising popularity and demand for immunoglobulins (IgG), obtaining supplies and rationalizing IgG use have become challenging. Herein, IgG consumption in Poland was analyzed through total IgG use and number of patients reported to the National Health Fund between 1 January 2016 and 31 December 2020. Total IgG used within 5 years increased by 27.48%, IgG use/1000 inhabitants/year was 23.13 g (2016) and 29.61 g (2020). In 2020, 35.5 % of IgG used was for neurological conditions, 25% for primary immunodeficiencies (PID), and 39.3% for all other indications. Within 5 years, 1,121,168.75 g IgG was used in PID; the use increased by 72%, from 783 in 2016 to 1153 patients in 2020. The proportion of patients who received subcutaneous immunoglobulin (SCIG) replacement therapy (IgRT) increased to 78% (2020). Within 5 years, 1,783,534.81 g IgG was used in neurological drug programs (+42.44%) and 2,327,513.88 g (+1.25%) outside neurological indications and outside PID. The annual IgG amount decreased in adult anesthesiology and intensive care (−46%), internal medicine (−55%), pneumonology (−50%), pediatric clinical immunology (−50%), and gynecology and obstetrics (−48%) and increased in dermatology (+178%), rheumatology (+103%), and clinical transplantation (+82%). IgG use significantly increased in Poland, mostly owing to PID. Subcutaneous IgG administration is currently the most common mode of IgRT in PID patients. An increase in SCIG administration may be expected for other indications. Implementing evidence-based clinical guidelines is key to prioritizing and rationalizing IgG use for immunomodulatory indications and secondary immune deficiencies. Full article

(This article belongs to the Special Issue Immunodeficiency Diseases: Update of Concepts and Management Recommendations)

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12 pages, 900 KiB

Open AccessArticle

Durable Left Ventricular Assist Device Outflow Graft Obstructions: Clinical Characteristics and Outcomes

by Carli J. Peters, Robert S. Zhang, Mahesh K. Vidula, Jay Giri, Pavan Atluri, Michael A. Acker, Christian A. Bermúdez, Allison Levin, Kim Urgo, Joyce Wald, Jeremy A. Mazurek, Thomas C. Hanff, Lee R. Goldberg, Dinesh Jagasia and Edo Y. Birati

J. Clin. Med. 2023, 12(6), 2430; https://doi.org/10.3390/jcm12062430 - 22 Mar 2023

Cited by 3 | Viewed by 2100

Abstract

Purpose: We report on the clinical course and management of patients supported with durable implantable LVADs who developed outflow graft obstructions at a large academic center. Methods: We performed a retrospective review of patients receiving LVAD support from 2012 through 2020. Patients who [...] Read more.

Purpose: We report on the clinical course and management of patients supported with durable implantable LVADs who developed outflow graft obstructions at a large academic center. Methods: We performed a retrospective review of patients receiving LVAD support from 2012 through 2020. Patients who developed an outflow graft obstruction diagnosed by computed tomography angiography (CTA) or angiogram were identified, and patient characteristics and outcomes were reported. Results: Of the 324 patients supported by LVAD at our institution, 11 patients (3.4%) were diagnosed with outflow graft obstructions. The most common presentation was low flow alarms, which was present in 10/11 patients, and the remaining patient presented with lightheadedness. Patients had minimal LDH elevation with 8/11 presenting with less than 2-fold the upper limit of normal. Transthoracic echocardiograms were not diagnostic, but CTA enabled non-invasive diagnoses in 8/11 of the patients. Three patients with extrinsic compression of the outflow graft successfully underwent endovascular stent placement, and three patients with outflow cannula kinks received supportive care. Of the five patients diagnosed with intraluminal thromboses, one received a heart transplant, one underwent an outflow graft revision, and three received supportive care due to comorbidities. Conclusion: Outflow graft obstructions remain a rare, but serious complication. The true prevalence of this entity is likely underestimated due to the non-specific clinical presentation. CTA is a pivotal non-invasive diagnostic step. Patients with external compression were successfully treated with endovascular stenting. Full article

(This article belongs to the Section Cardiology)

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22 pages, 2337 KiB

Open AccessArticle

Identification of Clinical Response Predictors of Tocilizumab Treatment in Patients with Severe COVID-19 Based on Single-Center Experience

by Wiktor Schmidt, Katarzyna Pawlak-Buś, Barbara Jóźwiak and Piotr Leszczyński

J. Clin. Med. 2023, 12(6), 2429; https://doi.org/10.3390/jcm12062429 - 22 Mar 2023

Cited by 1 | Viewed by 2738

Abstract

Hyperinflammation in COVID-19 plays a crucial role in pathogenesis and severity; thus, many immunomodulatory agents are applied in its treatment. We aimed to identify good clinical response predictors of tocilizumab (TCZ) treatment in severe COVID-19, among clinical, laboratory, and radiological variables. We conducted [...] Read more.

Hyperinflammation in COVID-19 plays a crucial role in pathogenesis and severity; thus, many immunomodulatory agents are applied in its treatment. We aimed to identify good clinical response predictors of tocilizumab (TCZ) treatment in severe COVID-19, among clinical, laboratory, and radiological variables. We conducted a prospective, observational study with 120 patients with severe COVID-19 not improving despite dexamethasone (DEX) treatment. We used parametric and non-parametric statistics, univariate logistic regression, receiver operating characteristic (ROC) curves, and nonlinear factors tertile analysis. In total, 86 (71.7%) patients achieved the primary outcome of a good clinical response to TCZ. We identified forty-nine predictive factors with potential utility in patient selection and treatment monitoring. The strongest included time from symptom onset between 9 and 12 days, less than 70% of estimated radiological lung involvement, and lower activity of lactate dehydrogenase. Additional predictors were associated with respiratory function, vitamin D concentration, comorbidities, and inflammatory/organ damage biomarkers. Adverse events analysis proved the safety of such a regimen. Our study confirmed that using TCZ early in the hyperinflammatory phase, before severe respiratory failure development, is most beneficial. Considering the described predictive factors, employing simple and widely available laboratory, radiological, and clinical tools can optimize patient selection for immunomodulatory treatment with TCZ. Full article

(This article belongs to the Section Immunology)

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11 pages, 965 KiB

Open AccessArticle

Diagnostic Evaluation Using Salivary Gland Ultrasonography in Primary Sjögren’s Syndrome

by Yen-Fu Chen, Ao-Ho Hsieh, Yao-Fan Fang and Chang-Fu Kuo

J. Clin. Med. 2023, 12(6), 2428; https://doi.org/10.3390/jcm12062428 - 22 Mar 2023

Cited by 3 | Viewed by 2448

Abstract

The purpose of this study is to investigate the clinical manifestations in patients with early primary Sjögren’s syndrome (pSS) based on the severity score found by salivary gland ultrasonography. Thirty-five newly diagnosed patients with early pSS were enrolled and divided into mild (score [...] Read more.

The purpose of this study is to investigate the clinical manifestations in patients with early primary Sjögren’s syndrome (pSS) based on the severity score found by salivary gland ultrasonography. Thirty-five newly diagnosed patients with early pSS were enrolled and divided into mild (score 0–1) and severe (score 2–3) groups according to the salivary gland ultrasonography grade (SGUS) scores at baseline. Clinical evaluation, ESSPRI and ESSDAI index values, sicca symptoms of the mouth, salivary capacity, and serum autoantibodies and cytokines were investigated. The mean age of pSS patients at diagnosis was 49.9 ± 11.9 years, and the mean duration of sicca symptoms was 0.58 years. ESSPRI (EULAR Sjögren’s syndrome patient report index) and ESSDAI (EULAR Sjögren’s syndrome disease index) scores were 15.97 and 4.77, respectively. Clinical manifestations, including the low production of saliva and autoantibody production, such as antinuclear antibodies, rheumatoid factor, and anti-SSA antibody, were found. A higher prevalence of rheumatoid factor (p = 0.0365) and antinuclear antibody (p = 0.0063) and a higher elevation of total IgG (p = 0.0365) were found in the severe group than in the mild group. In addition, the elevated titer of IL-25 was detected in the severe group than in the mild group. This observation indicated that salivary gland ultrasonography grade (SGUS) scans may help physicians diagnose pSS and the elevated titer of IL-25 in patients may be implicated in the pathogenesis of pSS. Full article

(This article belongs to the Special Issue Sjögren’s Syndrome: An Update on Pathogenesis, Clinical Insights, and Treatment)

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10 pages, 3229 KiB

Open AccessArticle

Management of Pelvic Fracture Urethral Injury: Is Supracrural Urethral Rerouting (Step 4) Becoming Anecdotical or Does It Remain in Force?

by Christian Yepes, Maciej Oszczudlowski, Marco Bandini, Pankaj M. Joshi, Ahmed Alrefaey, Shreyas Bhadranavar, Francisco E. Martins and Sanjay B. Kulkarni

J. Clin. Med. 2023, 12(6), 2427; https://doi.org/10.3390/jcm12062427 - 22 Mar 2023

Cited by 2 | Viewed by 1713

Abstract

Webster described a step-based perineal approach for repairing the posterior urethra in patients with pelvic fracture urethral injury (PFUI). The higher the complexity of the step, the higher the morbidity for the patient and the lower the surgical outcomes. We evaluated the outcomes [...] Read more.

Webster described a step-based perineal approach for repairing the posterior urethra in patients with pelvic fracture urethral injury (PFUI). The higher the complexity of the step, the higher the morbidity for the patient and the lower the surgical outcomes. We evaluated the outcomes of anastomotic urethroplasty (especially Step 4 or higher) or substitution urethroplasty in patients with PFUI at our center. Between 2013 to 2021, we retrospectively collected data on patients with PFUI. Surgical procedures were categorized according to the Webster classification and rates of each step were reported. The success rate was defined as Qmax above 10 mL/s and no need for further treatment. In this period, 737 male patients with PFUI were surgically treated. Notably, 18.8%, 17.6%, 46%, 1.8%, and 5.6% of included patients received steps 1, 2, 3, and 4 and the abdominoperineal approach, respectively. In 68 (9.2%) patients, the substitution of urethroplasty with a pedicled preputial tube (PPT) was needed. The success rate was 69.2% in Step 4, 74.4% in the abdominoperineal approach, and 86.4% in PPT; however, recurrence-free survival was not significantly different between groups (p = 0.22). Step 4 perineal anastomotic urethroplasty represents a surgical option in the armamentarium of PFUI treatment. Indications should be carefully reviewed to improve patient selection and avoid surgical failure, stopping at the step which first gives a tension-free anastomosis. Full article

(This article belongs to the Special Issue New Trends in Urethral Reconstruction)

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10 pages, 1777 KiB

Open AccessArticle

One-Lung Ventilation during Rigid Bronchoscopy Using a Single-Lumen Endotracheal Tube: A Descriptive, Retrospective Single-Center Study

by Carolin Steinack, Helene Balmer, Silvia Ulrich, Thomas Gaisl and Daniel P. Franzen

J. Clin. Med. 2023, 12(6), 2426; https://doi.org/10.3390/jcm12062426 - 21 Mar 2023

Cited by 2 | Viewed by 1658

Abstract

Using one-lung ventilation (OLV) through a single-lumen endotracheal tube (SLT) in the untreated lung during rigid bronchoscopy (RB) and jet ventilation, high oxygenation can be guaranteed, whilst procedures requiring thermal energy in the other lung are still able to be used. This pilot [...] Read more.

Using one-lung ventilation (OLV) through a single-lumen endotracheal tube (SLT) in the untreated lung during rigid bronchoscopy (RB) and jet ventilation, high oxygenation can be guaranteed, whilst procedures requiring thermal energy in the other lung are still able to be used. This pilot study aimed to examine the bronchoscopy-associated risks and feasibility of OLV using an SLT during RB in patients with malignant airway stenosis. All consecutive adult patients with endobronchial malignant lesions receiving OLV during RB from 1 January 2017 to 12 May 2021 were included. We assessed perioperative complications in 25 RBs requiring OLV. Bleeding grades 1, 2, and 3 complicated the procedure in two (8%), five (20%), and five (20%) patients, respectively. The median saturation of peripheral oxygen remained at 94% (p = 0.09), whilst the median oxygen supply did not increase significantly from 0 L/min to 2 L/min (p = 0.10) within three days after the bronchoscopy. The 30-day survival rate of the patients was 79.1% (95% CI 58.4–91.1%), all of whom reported an improvement in subjective well-being after the bronchoscopy. OLV using an SLT during RB could be a new treatment approach for endobronchial ablative procedures without increasing bronchoscopy-associated risks, allowing concurrent high-energy treatments. Full article

(This article belongs to the Special Issue The Role of Interventional Pulmonology in Respiratory Diseases: From Diagnosis to Treatment)

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10 pages, 666 KiB

Open AccessArticle

Up to a 15-Year Survival Rate and Marginal Bone Resorption of 1780 Implants with or without Microthreads: A Multi Center Retrospective Study

by Ji-Hwan Oh, Se-Wook Pyo, Jae-Seung Chang and Sunjai Kim

J. Clin. Med. 2023, 12(6), 2425; https://doi.org/10.3390/jcm12062425 - 21 Mar 2023

Cited by 2 | Viewed by 2011

Abstract

The effect of microthreads at the implant neck on the amount of marginal bone resorption is controversial. This multicenter retrospective study compared the implant survival rate and amount of marginal bone resorption between two platform-switching internal connection implant systems with or without microthreads. [...] Read more.

The effect of microthreads at the implant neck on the amount of marginal bone resorption is controversial. This multicenter retrospective study compared the implant survival rate and amount of marginal bone resorption between two platform-switching internal connection implant systems with or without microthreads. Patient-related (age and sex), surgery-related (implant installation site, type, diameter, and length), and prosthesis-related (prosthesis type) data were collected from patient charts from the implant placement surgery to the final recall visit. A total of 1780 implants, including 1379 with microthreads and 401 without microthreads, were placed in 804 patients. For implants with and without microthreads, the longest follow-up period after prosthesis delivery was 15 and 6 years, respectively. Twenty implants failed during the 15-year follow-up period (98.8% survival rate) due to failed osseointegration, peri-implantitis, implant fractures, and non-functioning implants. The mean marginal bone loss was < 0.1 mm for both implant systems at the 1-year follow-up and 0.18 mm and 0.09 mm at the 4-year follow-up for implants with and without microthreads, respectively, without statistical significance. Microthreads did not significantly affect the amount of marginal bone loss or the implant survival rate for implants with an internal connection with a platform-switching design. Full article

(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)

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12 pages, 30928 KiB

Open AccessReview

Pathogenesis, Diagnosis and Management of Squamous Cell Carcinoma and Pseudoepithelial Hyperplasia Secondary to Red Ink Tattoo: A Case Series and Review

by Yasmina Rahbarinejad, Pedro Guio-Aguilar, Anh Ngoc Vu, Michael Lo, Christine McTigue, Alex Nirenberg and Warren M. Rozen

J. Clin. Med. 2023, 12(6), 2424; https://doi.org/10.3390/jcm12062424 - 21 Mar 2023

Cited by 2 | Viewed by 3521

Abstract

The increasing popularity of tattooing has paralleled an increase in associated cutaneous reactions. Red ink is notorious for eliciting cutaneous reactions. A common reaction is pseudoepitheliomatous hyperplasia (PEH), which is a benign condition closely simulating squamous cell carcinoma (SCC). Differentiating PEH from SCC [...] Read more.

The increasing popularity of tattooing has paralleled an increase in associated cutaneous reactions. Red ink is notorious for eliciting cutaneous reactions. A common reaction is pseudoepitheliomatous hyperplasia (PEH), which is a benign condition closely simulating squamous cell carcinoma (SCC). Differentiating PEH from SCC is challenging for pathologists and clinicians alike. The exact pathogenesis of these lesions secondary to red ink is not known, and there are no sources outlining diagnostic and treatment options and their efficacy. We present four study cases with different pathologies associated to red ink tattoos including lichenoid reaction, granulomatous reaction, PEH, and an SCC. Additionally, an extensive review of 63 articles was performed to investigate pathogenesis, diagnostic approaches, and treatment options. Hypotheses surrounding pathogenesis include but are not limited to the carcinogenic components of pigments, their reaction with UV and the traumatic process of tattooing. Pathogenesis seems to be multifactorial. Full-thickness biopsies with follow-up is the recommended diagnostic approach. There is no evidence of a single universally successful treatment for PEH. Low-dose steroids are usually tried following a step up in lack of clinical response. For SCC lesions, full surgical excision is widely used. A focus on clinicians’ awareness of adverse reactions is key for prevention. Regulation of the unmonitored tattoo industry remains an ongoing problem. Full article

(This article belongs to the Section Dermatology)

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Photograph taken immediately after tattoo was imprinted (a). Photograph taken six months after receiving the tattoo. Note the scaly, raised exophytic lesion in areas tattooed with red ink only while the black ink areas remain spared (b). Full article ">Figure 2
Skin biopsy at 12.5× magnification (a) showing orthokeratosis, hyperplastic squamous epithelium, papillomatous change and lichenoid inflammation at superficial dermis. At 100× magnification (b), tattoo pigment and lichenoid reaction is shown in the superficial dermis. Full article ">Figure 3
Eighteen months follow up with significant clinical improvement after management with six sessions of intra-lesional steroid injections and topical corticosteroid. The tattoo is no longer raised, scaly or pruritic. The tattoo is largely preserved with an acceptable aesthetic outcome. Full article ">Figure 4
Skin lesion affecting exclusively red-ink tattooed areas 6 months after initial tattoo was completed (a). Macroscopic appearance after deep shave biopsy was performed (b). Full article ">Figure 5
Histopathological photograph at 40× magnification (a) and 100× magnification (b) showing the features of the pseudoepitheliomatous hyperplasia (PEH) with haematoxylin eosin stain (H&E). Full article ">Figure 6
Macroscopic appearance after deep shave biopsy was performed. Full article ">Figure 7
Histological features of necrotising granulomatous reaction. Note the necrosis in the dermis, surrounding giant cells and some pigment. (a) low power; (b) high power. Full article ">Figure 8
Clinical photograph of two scaly lesions of the skin located in the red-inked areas of a multi-coloured tattoo of the left arm completed 13 years earlier. Full article ">

9 pages, 814 KiB

Open AccessArticle

A Cone Beam CT Study on the Correlation between Crestal Bone Loss and Periapical Disease

by Sari A. Mahasneh, Abeer Al-Hadidi, Fouad Kadim Wahab, Faleh A. Sawair, Mohammad Abdalla AL-Rabab’ah, Sarah Al-Nazer, Yara Bakain, Cosimo Nardi and Joanne Cunliffe

J. Clin. Med. 2023, 12(6), 2423; https://doi.org/10.3390/jcm12062423 - 21 Mar 2023

Cited by 4 | Viewed by 2373

Abstract

The aim of this study was to determine whether the degree of bone loss around teeth can be linked to the loss of vitality of adjacent teeth and periapical disease, which necessitates root canal treatments. Three hundred and twenty-one full maxilla cone-beam computed [...] Read more.

The aim of this study was to determine whether the degree of bone loss around teeth can be linked to the loss of vitality of adjacent teeth and periapical disease, which necessitates root canal treatments. Three hundred and twenty-one full maxilla cone-beam computed tomography scans were examined. The parameters investigated included the degree of crestal bone loss in relation to the cementoenamel junction, the presence/absence of apical periodontitis, and the presence/absence of root canal treatments. Out of the 2001 teeth examined, 696 (34.8%) showed evidence of crestal bone loss. The degree of crestal bone loss was classified as mild, moderate, or severe. A significant association (p < 0.001) was found between the presence of crestal bone loss around a tooth and root canal treatment of that tooth. It was found that it is more likely for teeth with crestal bone loss to be root canal treated compared to teeth with existing root canal treatment and healthy crestal bone levels. Furthermore, teeth with buccal or lingual crestal bone loss were significantly associated with a higher rate of periapical disease than teeth without crestal bone loss (p < 0.001). CBCT identified the severity of bone loss on all surfaces of the teeth, and the most common presentation was bone loss to the mid-root level. Teeth with crestal bone loss were significantly more likely to be associated with a higher rate of periapical disease. Teeth with crestal bone loss were more likely to be root treated than teeth with healthy crestal bone levels. Full article

(This article belongs to the Special Issue Current Topics in Endodontics)

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9 pages, 817 KiB

Open AccessArticle

A New Perspective for Potential Organ Damage Due to Iron-Mediated Oxidation in Thalassemia Major Patients

by Funda Eren, Ayça Koca Yozgat, Esra Firat Oğuz, Salim Neşelioğlu, Rıdvan Firat, Dilek Gürlek Gökçebay, Hüsniye Neşe Yarali, Namık Yaşar Özbek and Özcan Erel

J. Clin. Med. 2023, 12(6), 2422; https://doi.org/10.3390/jcm12062422 - 21 Mar 2023

Cited by 7 | Viewed by 1584

Abstract

Background: The aim of this study is to develop new perspectives to prevent or reduce potential organ damage due to iron-mediated oxidation in thalassemia major patients. Methods: Seventy patients were included in this study. Blood samples were taken from the patients before and [...] Read more.

Background: The aim of this study is to develop new perspectives to prevent or reduce potential organ damage due to iron-mediated oxidation in thalassemia major patients. Methods: Seventy patients were included in this study. Blood samples were taken from the patients before and after transfusion. Total thiol, native thiol, disulfide, disulfide/native thiol percentage ratio, ischemia modified albumin (IMA), total antioxidant status (TAS), total oxidant status (TOS), and ferroxidase levels were determined. Additionally, undepleted thiol level (UTL) was determined as a new parameter associated with organ damage. Results: After transfusion, the levels of native thiol, total thiol, disulfide, TAS, ferroxidase, and TOS were higher, while the IMA levels and disulfide/native thiol percent ratio were lower. Significant correlations were found between antioxidant and oxidant tests before and after transfusion. Additionally, a negative correlation was found between the TOS and UTL levels of the patients measured before the transfusion. Conclusion: In the present study, transfusion therapy increased both oxidation and the antioxidant levels. In addition, the term UTL has been introduced as a parameter that enables the determination of the oxidation level that may cause potential organ damage in transfusion-dependent thalassemia patients. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

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12 pages, 283 KiB

Open AccessReview

Obstructive Sleep Apnea and Right Ventricular Remodeling: Do We Have All the Answers?

by Marijana Tadic and Cesare Cuspidi

J. Clin. Med. 2023, 12(6), 2421; https://doi.org/10.3390/jcm12062421 - 21 Mar 2023

Cited by 3 | Viewed by 2121

Abstract

Obstructive sleep apnea (OSA) syndrome is a very important sleep-related breathing disorder related to increased cardiovascular and overall morbidity and mortality. It is associated with multisystemic target organ damage due to micro- and macrovascular changes, resulting in carotid and coronary atherosclerosis, increased arterial [...] Read more.

Obstructive sleep apnea (OSA) syndrome is a very important sleep-related breathing disorder related to increased cardiovascular and overall morbidity and mortality. It is associated with multisystemic target organ damage due to micro- and macrovascular changes, resulting in carotid and coronary atherosclerosis, increased arterial stiffness, retinal damage, microalbuminuria, and cardiac remodeling. The latter consists of left ventricular (LV) hypertrophy, as well as diastolic and systolic dysfunction. The increasing burden of evidence shows that OSA also induces right ventricular (RV) remodeling that is more difficult to diagnose, but may also contribute to cardiovascular morbidity and mortality in these patients. Conventional echocardiographic parameters for assessment of RV systolic and diastolic functions are often not sensitive enough to detect subclinical and subtle changes in the RV function. Data published over last decade showed that the RV function, particularly systolic, is impaired in OSA patients and related with its severity. However, the introduction of speckle tracking echocardiography and the particularly longitudinal strain enabled the earlier detection of functional and mechanical changes even when conventional echocardiographic parameters of RV systolic function remained unchanged. The 3D echocardiography provided the possibility to evaluate the entire RV, with its unique shape, and determine 3D RV ejection fraction, which is comparable with results obtained by cardiac magnetic resonance. The use of this modality also provided a new insight into RV systolic (dys)function in OSA patients. In addition to weight loss, which has been proven very helpful in OSA patients, the only approved therapeutic approach is continuous positive airway pressure (CPAP) therapy. It is very important to assess if this therapy induces any improvement in cardiac structure and function. Limited data on this topic show that RV longitudinal strain is a more sensitive parameter rather than other conventional RV indexes in the detection of improvement in RV systolic function and mechanics. The aim of this review article is to summarize the current understanding of RV structural, functional, and mechanical changes in patients with OSA. Furthermore, we sought to provide the current knowledge regarding the effect of CPAP therapy on RV reverse remodeling in OSA patients. Full article

(This article belongs to the Special Issue Obstructive Sleep Apnea with Cardiovascular, Metabolic and Mental Health Disorders)

10 pages, 479 KiB

Open AccessArticle

Epidemiology of Immune-Mediated Glomerulopathies before and after SARS-CoV-2 Vaccination: A Tertiary Referral Hospital Experience

by Jorge Iván Zamora, Marina López-Martínez, Marc Patricio Liebana, Juan Carlos Leon Román, Sheila Bermejo, Ander Vergara, Irene Agraz, Natalia Ramos Terrades, Maria Antonieta Azancot, Nestor Toapanta, Maria Alejandra Gabaldon and Maria José Soler

J. Clin. Med. 2023, 12(6), 2420; https://doi.org/10.3390/jcm12062420 - 21 Mar 2023

Viewed by 2073

Abstract

Background: Vaccination is a known trigger for the appearance of immune-mediated glomerulopathies (IMG). The appearance of IMG after SARS-CoV-2 vaccination with suspected causality has been described. Our aim is to analyze the incidence of IMG flares before and after SARS-CoV-2 vaccination in our [...] Read more.

Background: Vaccination is a known trigger for the appearance of immune-mediated glomerulopathies (IMG). The appearance of IMG after SARS-CoV-2 vaccination with suspected causality has been described. Our aim is to analyze the incidence of IMG flares before and after SARS-CoV-2 vaccination in our center. Methods: All persons with native kidney biopsy (KB) from January 2019 to March 2022 in our center were included in the study. We compared the incidence of IMG before and after the start of vaccination. We also collected information about whether the patients had received a SARS-CoV-2 vaccine or have suffered from COVID in the six weeks before the IMG. We also evaluated the analytical characteristics of the outbreaks. Results: A total of 386 KB were studied. Of them, 86/218 (39.4%) were IMG performed pre- and 85/168 (50.6%) post-SV (029). The incidence of idiopathic nephrotic syndrome (INS), studied separately, was also significantly increased post-vaccination (n = 18 (10.7%)) compared to pre-vaccination (n = 11 (5%)) (p = 0.036). There were no differences in the incidence of vasculitis or IgA nephropathy. Up to 17 (20%) flares occurred 6 weeks before SARS-CoV-2 vaccination and only 2 (2.4%) within the first 6 weeks after SARS-CoV-2 infection. Within those 17 flares, the most common diagnosis was IgAN (n = 5 (29.4%)); a total of 14 (82.4%) received an mRNA vaccine and 9 (52.9%) took place after the 1st vaccine dose. There were 13 cases of minimal change disease (MCD) with debut/recurrence pre-SV and 20 MCD with debut/recurrence post-SV (p = 0.002). Conclusions: The incidence of IMG, INS and MCD flares in our center increased significantly after SARS-CoV-2 vaccination. Importantly, 20% of IMG flares took place within the first 6 weeks after receiving a vaccine dose, with the first dose being the riskiest one and IgAN the most frequent diagnosis. Full article

(This article belongs to the Section Nephrology & Urology)

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12 pages, 286 KiB

Open AccessSystematic Review

Effect of Training Load on Post-Exercise Cardiac Biomarkers in Healthy Children and Adolescents: A Systematic Review of the Existing Literature

by Adamantia Papamichail, Emmanuel Androulakis, Andrew Xanthopoulos and Alexandros Briasoulis

J. Clin. Med. 2023, 12(6), 2419; https://doi.org/10.3390/jcm12062419 - 21 Mar 2023

Cited by 5 | Viewed by 1820

Abstract

Background: Postexercise release of cardiac biomarkers (cardiac troponins, cTn, and N-terminal pro b-type natriuretic peptide, NT-proBNP) is a well-known phenomenon in adults, although it remains unclear how it manifests in children. The aim of this review is to compare the pre-exercise with the [...] Read more.

Background: Postexercise release of cardiac biomarkers (cardiac troponins, cTn, and N-terminal pro b-type natriuretic peptide, NT-proBNP) is a well-known phenomenon in adults, although it remains unclear how it manifests in children. The aim of this review is to compare the pre-exercise with the post-exercise measurement of serum cardiac biomarkers, as well as to analyze their post-exercise release based on age, sex, and exercise intensity and duration. Methods: The terms troponin, football, swimmers, marathon, run, and exercise were used in a literature search at National Library of Medicine. The search was further refined by adding the keywords athletes, children, adolescents, and sport. Results: Fifteen pediatric studies and four studies with a mixed population of adults and children totaled 19 studies for the final analysis. In addition to them, some adult studies have been included for comparison. The kinetics of the cTn and NT-proBNP response after exercise have been the subject of our interest. While the impact of sport type, age, and sex has not yet been fully characterized, the existing data points to considerable impacts of sport intensity and duration on post-exercise biomarkers elevation. Most of the findings came from endurance sports, but the evidence is sparse. Furthermore, there is only limited data on women and less on young adults, African Caribbeans, and professional athletes. Conclusions: Both amateur and competitive athletes can exhibit post-exercise release of both cTn and NT-proBNP. This is transient and lacks pathological significance, in contrast with adult population, in which exercise-induced increases in in these biomarker levels may not always be benign. While NT-proBNP release is still primarily driven by activity duration, cTnT release is additionally affected by exercise intensity. To define individual ranges of normality for postexercise cTn and NT-proBNP elevation, the role of several confounders (age, sex, sport type/intensity etc.) remains to be further elucidated. Full article

(This article belongs to the Section Cardiovascular Medicine)

11 pages, 1299 KiB

Open AccessArticle

Features of Obstructive Sleep Apnea in Children with and without Comorbidities

by Eusebi Chiner, Jose N. Sancho-Chust, Esther Pastor, Violeta Esteban, Ignacio Boira, Carmen Castelló, Carly Celis, Sandra Vañes and Anastasiya Torba

J. Clin. Med. 2023, 12(6), 2418; https://doi.org/10.3390/jcm12062418 - 21 Mar 2023

Cited by 3 | Viewed by 1823

Abstract

Background: To compare the clinical and polysomnographic features of obstructive sleep apnea (OSA) in children with adenotonsillar hypertrophy (Group A) and comorbidities (Group B). Methods: A five-year prospective study using nocturnal polysomnography before and after treatment. Results: We included 168 patients: 121 in [...] Read more.

Background: To compare the clinical and polysomnographic features of obstructive sleep apnea (OSA) in children with adenotonsillar hypertrophy (Group A) and comorbidities (Group B). Methods: A five-year prospective study using nocturnal polysomnography before and after treatment. Results: We included 168 patients: 121 in Group A and 47 in Group B, with differences in age (6.5 ± 3 vs. 8.6 ± 4 years; p < 0.001), body mass index (BMI) (18 ± 4 vs. 20 ± 7 kg/m2; p < 0.05), neck circumference (28 ± 4 vs. 30 ± 5 cm; p < 0.05), and obesity (17% vs. 30%; p < 0.05). Group B patients were more likely to have facial anomalies (p < 0.001), macroglossia (p < 0.01), dolichocephaly (p < 0.01), micrognathia (p < 0.001), and prognathism (p < 0.05). Adenotonsillectomy was performed in 103 Group A patients (85%) and 28 Group B patients (60%) (p < 0.001). In B, 13 children (28%) received treatment with continuous positive airway pressure (CPAP) and 2 (4%) with bilevel positive airway pressure (BiPAP), compared with 7 in Group A (6%) (p < 0.001). Maxillofacial surgery was more common in Group B (p < 0.01). Clinical and polysomnography parameters improved significantly in both groups after therapeutic intervention, though Group A showed better results. Conclusions: Obesity and facial anomalies are more frequent in childhood OSA patients with comorbidities, who often require combination therapy, such as ventilation and surgery. Full article

(This article belongs to the Section Pulmonology)

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10 pages, 2019 KiB

Open AccessArticle

Prognostic Value of Absolute Lymphocyte Count in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab Plus Ipilimumab

by Kosuke Ueda, Naoyuki Ogasawara, Naoki Ito, Satoshi Ohnishi, Hiroki Suekane, Hirofumi Kurose, Tasuku Hiroshige, Katsuaki Chikui, Keiichiro Uemura, Kiyoaki Nishihara, Makoto Nakiri, Shigetaka Suekane and Tsukasa Igawa

J. Clin. Med. 2023, 12(6), 2417; https://doi.org/10.3390/jcm12062417 - 21 Mar 2023

Cited by 2 | Viewed by 1911

Abstract

Nivolumab and ipilimumab (NIVO + IPI) is standard therapy for patients with advanced renal cell carcinoma (RCC). Absolute lymphocyte count (ALC) is a valuable prognostic factor in patients with various cancers treated with immune checkpoint inhibitors. Herein, we determined the prognostic value of [...] Read more.

Nivolumab and ipilimumab (NIVO + IPI) is standard therapy for patients with advanced renal cell carcinoma (RCC). Absolute lymphocyte count (ALC) is a valuable prognostic factor in patients with various cancers treated with immune checkpoint inhibitors. Herein, we determined the prognostic value of pretreatment ALC in advanced RCC patients treated with NIVO + IPI as first-line therapy. Data from 46 advanced RCC patients treated with NIVO + IPI between September 2018 and August 2022 were retrospectively reviewed and analyzed. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with low than high ALC (PFS: p = 0.0095; OS: p = 0.0182). Multivariate analysis suggested that prior nephrectomy [hazard ratio (HR) = 3.854, 95% confidence interval (CI) = 1.433–10.359, p = 0.0075] and pretreatment ALC (HR = 2.513, 95% CI = 1.119–5.648, p = 0.0257) were independent factors for PFS. Our new prognostic ALNx model based on ALC and prior nephrectomy suggested that the poor-risk group was a predictor of significantly worse PFS (p < 0.0001) and OS (p = 0.0016). Collectively, the developed ALNx model may be a novel predictor of response in advanced RCC patients treated with NIVO + IPI. Full article

(This article belongs to the Section Oncology)

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10 pages, 256 KiB

Open AccessArticle

The Impact of Endometrioma on Embryo Quality in In Vitro Fertilization: A Retrospective Cohort Study

by Houjin Dongye, Yizheng Tian, Dan Qi, Yanbo Du and Lei Yan

J. Clin. Med. 2023, 12(6), 2416; https://doi.org/10.3390/jcm12062416 - 21 Mar 2023

Cited by 6 | Viewed by 1741

Abstract

The influence of endometrioma on oocyte and embryo competence is inconclusive. Furthermore, the benefits of surgical treatment remain uncertain. This study aimed to investigate the effect of endometrioma on oocyte and embryo quality from a morphological perspective and further explore whether surgery could [...] Read more.

The influence of endometrioma on oocyte and embryo competence is inconclusive. Furthermore, the benefits of surgical treatment remain uncertain. This study aimed to investigate the effect of endometrioma on oocyte and embryo quality from a morphological perspective and further explore whether surgery could contribute to improving oocyte and embryo competence. A total of 664 IVF cycles with endometrioma (538 cycles underwent surgeries) and 3133 IVF cycles from the control group were included. The propensity score matching was used to balance the baseline differences between groups. There was a lower MII oocyte rate (85.0% versus 87.8%, p < 0.001; 84.9% versus 87.6%, p = 0.001) and a similar good-quality embryos rate in women with endometrioma (and those who underwent surgeries) compared with control group. For women with endometrioma, the rates of blastocyst development (67.1% versus 60.2%; p = 0.013) and good blastocyst development (40.7% versus 35.2%; p = 0.049) were significantly higher in those who had undergone surgical treatment compared with those who had not, but the rates of MII oocytes (79.9% versus 87.7%; p < 0.001) and normal fertilization (55.2% versus 66.2%; p < 0.001) were lower. The study indicates that endometrioma, including its surgical treatment, compromises the oocyte maturity not the embryo quality at the cleavage stage; however, the surgery seems to contribute to improving blastocyst development. Full article

(This article belongs to the Special Issue Hot Topics in Reproductive Medicine Research)

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J. Clin. Med., Volume 12, Issue 6 (March-2 2023) – 361 articles

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