Search Results (1,621)

In 2001, two enzyme-encoding genes were recognized in the fruit fly Drosophila melanogaster. The genetic material, labeled Dicer-1 and Dicer-2, encodes ribonuclease-type enzymes with slightly diverse target substrates. The human orthologue is DICER1. It is a gene, which has been positioned on chromosome 14q32.13. It contains 27 exons, which are linking the two enzyme domains. DICER1 is found in all organ systems. It has been proved that it is paramount in human development. The protein determined by DICER1 is a ribonuclease (RNase). This RNase belongs to the RNase III superfamily, formally known as ’endoribonuclease’. It has been determined that the function of RNase III proteins is set to identify and degrade double-stranded molecules of RNA. DICER1 is a vital “housekeeping” gene. The multi-domain enzyme is key for small RNA processing. This enzyme functions in numerous pathways, including RNA interference paths, DNA damage renovation, and response to viruses. At the protein level, DICER is also involved in several human diseases, of which the pleuro-pulmonary blastoma is probably the most egregious entity. Numerous studies have determined the full range of DICER1 functions and the corresponding relationship to tumorigenic and non-neoplastic diseases. In fact, genetic mutations (somatic and germline) have been detected in DICER1 and are genetically associated with at least two clinical syndromes: DICER1 syndrome and GLOW syndrome. The ubiquity of this enzyme in the human body makes it an exquisite target for nanotechnology-supported therapies and repurposing drug approaches. Full article

COVID-19, caused by the SARS-CoV-2 coronavirus, has significantly impacted global health, particularly among patients with obesity. This study evaluates the prevalence and effects of overweight and obesity on the clinical profiles and complications of COVID-19 patients admitted to a hospital in Northern Mato Grosso. We conducted a retrospective cohort study analyzing medical records of COVID-19 patients hospitalized from March 2020 to March 2021. Patients were classified into normal body weight, overweight, and obesity groups. Data were statistically analyzed using Kruskal–Wallis’s test and Dunn’s post-test (continuous variables) or by the chi-square test (χ²) (categorical variables). Among 145 ward records, 24.1% were normal body weight, 46.2% were overweight, and 29.7% were obese. In the intensive care unit, data from 243 patients indicated that 17.3% were normal body weight, 37.9% were overweight, and 44.9% were obese, highlighting a concerning prevalence of overweight/obesity. Chest computed tomography revealed that moderate pulmonary involvement (25–50%) was most frequent in the overweight group, while severe involvement (>50%) was predominant in the obesity group. The obesity group experienced more complications, including increased use of mechanical ventilation. Notably, in both settings, mortality rates were higher among patients with overweight and obesity. This study concludes that overweight and obesity significantly worsen COVID-19 outcomes. Full article

Paradoxical embolism occurs when a clot originates in the venous system and traverses through a pulmonary or intracardiac shunt into the systemic circulation, with a mortality rate of around 18%. The risk factors for arterial embolism and venous thrombosis are similar, but different disease entities can lead to a hypercoagulable state of the blood, including antithrombin III (AT III) deficiency. We report the case of a 43-year-old man with a massive central pulmonary embolism with a rider embolus and concomitant aortic arch embolism with involvement of the brachiocephalic trunk, bilateral subclavian and axillary arteries, and the right vertebral artery, followed by a secondary ischaemic stroke. The Pulmonary Embolism Response Team (PERT) consulted the patient on several occasions; he was treated initially with an intravenous infusion of unfractionated heparin under activation partial thromboplastin time (APTT) and AT III substitution. After several days of hospitalisation and the conversion of pharmacotherapy to oral anticoagulants, the patient was discharged home in a stable condition with recommendations for further follow-up in appropriate clinics. This case highlights the role of in-depth diagnostics for coagulation disorders in patients after pulmonary embolism, especially without known risk factors. Full article

Small-cell lung cancer (SCLC) is a recalcitrant form of cancer, representing 15% of lung cancer cases globally. SCLC is classified within the range of neuroendocrine pulmonary neoplasms, exhibiting shared morphologic, ultrastructural, immunohistochemical, and molecular genomic features. It is marked by rapid proliferation, a propensity for early metastasis, and an overall poor prognosis. The current conventional therapies involve platinum–etoposide-based chemotherapy in combination with immunotherapy. Nonetheless, the rapid emergence of therapeutic resistance continues to pose substantial difficulties. The genomic profiling of SCLC uncovers significant chromosomal rearrangements along with a considerable mutation burden, typically involving the functional inactivation of the tumor suppressor genes TP53 and RB1. Identifying biomarkers and evaluating new treatments is crucial for enhancing outcomes in patients with SCLC. Targeted therapies such as topoisomerase inhibitors, DLL3 inhibitors, HDAC inhibitors, PARP inhibitors, Chk1 inhibitors, etc., have introduced new therapeutic options for future applications. In this current review, we will attempt to outline the key molecular pathways that play a role in the development and progression of SCLC, together with a comprehensive overview of the most recent advancements in the development of novel targeted treatment strategies, as well as some ongoing clinical trials against SCLC, with the goal of improving patient outcomes. Full article

Introduction: Chronic obstructive pulmonary disease (COPD) has a diverse negative impact on patients, affecting them both physically and mentally. Psychosocial factors such as anxiety, depression, social isolation, and financial stress have been found to be positively associated with more exacerbations, hospital readmissions, poor adherence to medication, and lower quality of life among patients with COPD. However, healthcare professionals, who have a crucial role in diagnosing and managing COPD, often overlook these psychosocial factors of the disease, despite growing evidence suggesting their crucial role in improving disease outcomes. Consequently, this study will evaluate the effectiveness of a personalized individualized informational intervention on the quality of life, adherence, and psychosocial economic status of patients with COPD in healthcare settings of Greece. Methods: A prospective, mixed-methods design will be used, incorporating both quantitative data through questionnaires, including the Short Form (SF-12), Clinical COPD Questionnaire (CCQ), Test of Adherence to Inhalers (TAI), Patient Health Questionnaire (PHQ-4), Multidimensional Scale of Perceived Social Support (MSPSS), and Financial Ability Scale (FAS), alongside qualitative data with questions exploring themes such as general health perception, treatment adherence, mental status, socioeconomic status, and disease management. Participants will consist of patients receiving care at primary healthcare facilities and respiratory hospital departments in Crete, Greece. The intervention will involve providing structured information on social, financial, and psychological support services, along with psychosocial counseling over a six-month period. The impact of the intervention will be measured using validated tools to assess health status, quality of life, treatment adherence, mental health, and socioeconomic status before and after the intervention. Conversely, qualitative interviews will be conducted to gain deeper insights into the impact of the intervention. Finally, when the analyses of both data types are finalized, they will be triangulated to achieve convergence. This procedure entails the creation of a figure or illustration that demonstrates the convergence or divergence of both data types. Conclusions: The findings of this study are expected to highlight the importance of integrating an individualized informational intervention into the management of COPD. Thus, this study could guide healthcare professionals and policymakers in improving COPD care and patient outcomes. Full article

Objectives: We aimed to describe the cardiopulmonary function during exercise and the health-related quality of life (HRQoL) in patients with a history of COVID-19 pneumonia, stratified by chest computed tomography (CT) findings at baseline. Methods: Among 77 consecutive patients with COVID-19 who were discharged from the Pulmonology Ward between March 2020 and April 2021, 28 (mean age 54.3 ± 8.6 years, 8 females) agreed to participate to the current study. The participants were analyzed in two groups based on pulmonary involvement (PI) at baseline chest CT applying a threshold of 25%. A consequent artificial intelligence (AI)-guided total opacity score (TOS) was calculated in a subgroup of 22 patients. A cardiopulmonary exercise test (CPET) was conducted on average 8.4 (±1.9) months after discharge from the hospital. HRQoL was defined using the short-form (SF-36) questionnaire. The primary outcome was exercise intolerance that was defined as a peak oxygen uptake (V′O_2peak) < 80% predicted. Secondary outcomes were ventilatory limitation, defined as breathing reserve < 15%, circulatory limitation, defined as oxygen pulse predicted below 80%, and deconditioning, defined as exercise intolerance in the absence of ventilatory and circulatory limitations. Other secondary outcomes included the SF-36 domains. Results: In all, 15 patients had at least 25% PI (53.6%) at baseline chest CT. Exercise intolerance was observed in ten patients (35.7%), six due to deconditioning and four due to circulatory limitation; none had ventilatory limitation. AI-guided TOS was 30.1 ± 24.4% vs. 6.1 ± 4.8% (p < 0.001) at baseline, and 1.7 ± 3.0% vs. 0.2 ± 0.7% (nonsignificant) at follow-up in high and low PI groups, respectively. The physical functioning (PF) domain score of the SF-36 questionnaire was 66.3 ± 19.4 vs. 85.0 ± 13.1 in high and low PI groups, respectively (p = 0.007). Other SF-36 domains did not differ significantly between the groups. A high PI at baseline was inversely correlated with V′O_2peak (standardized β coefficient = −0.436; 95% CI −26.1; −0.7; p = 0.040) and with PF scores (standardized β coefficient −0.654; 95% CI −41.3; −7.6; p = 0.006) adjusted for age, sex, body mass index and lung diffusion capacity. Conclusions: One-third of participants experienced exercise intolerance eight months after COVID-19 pneumonia. A higher PI at baseline was significantly associated with exercise intolerance and PF. Notwithstanding, the radiological PI was resolved, and the exercise intolerance was mainly explained not by ventilatory limitation but by circulatory limitation and deconditioning. Full article

Chronic obstructive pulmonary disease (COPD) exacerbations are major contributors to morbidity and mortality, highlighting the need to better understand their molecular mechanisms to improve prevention, diagnosis, and treatment. This study investigated differential gene expression profiles and key biological processes in COPD exacerbations categorized based on sputum microbiome profiling. An observational study was performed on a cohort of 16 COPD patients, who provided blood and sputum samples during exacerbations, along with five stable-state samples as controls. Exacerbations were classified using 16S rRNA sequencing to analyze the sputum microbiota and multiplex PCR to detect respiratory viruses. Blood transcriptomic profiling was conducted using Oxford Nanopore technology, followed by differential gene expression and pathway enrichment analyses. A total of 768 regulated genes were identified across the exacerbation groups, with 35 shared genes associated with neutrophil activation. Bacterial exacerbations activated pathways related to phagocytosis and toll-like receptor signaling, while viral exacerbations were linked to pro-inflammatory responses and mitochondrial damage. Exacerbations of unknown origin showed activation of pathways involved in protozoan defense and neutrophilic asthma. Biomarkers such as IFITM3 and ISG15 for bacterial exacerbations, DEFA3 for viral, and CD47 for unknown-origin exacerbations were identified. These findings highlight distinct transcriptomic profiles and biological pathways in COPD exacerbations, emphasizing the central role of neutrophil-driven inflammation and identifying potential biomarkers for improved differential diagnosis and personalized management. Full article

Background/Objectives: The effects of ageing on the diaphragm are unclear. This study examined the association between ageing and diaphragm thickness, thickening fraction (TF), and diaphragm excursion (DE) as assessed by ultrasonography after adjusting for other factors. The relationship between these parameters and maximal inspiratory pressure (MIP) was also investigated. Methods: From 2022 to 2024, ambulatory and communicative adult volunteers and outpatients were recruited from four Japanese medical institutions. Each participant’s background factors (including height, weight, and underlying diseases) and pulmonary function test results were assessed. Diaphragm thickness, TF, and DE were evaluated using ultrasonography. Results: The study involved 230 individuals with a mean age of 55.5 years (older adults (65 years and over), n = 117; non-older adults, n = 113). In older adults, the diaphragm was thicker (2.1 vs. 1.7 mm, p < 0.001), and TF was lower (88.7% vs. 116.0%, p < 0.001), with no significant difference in DE. Multivariate linear regression analysis adjusted for sex, height, body mass index, and underlying diseases showed positive associations between age and diaphragm thickness (p = 0.001), but not with TF or DE. MIP was positively associated with DE (p < 0.001) but not with thickness or TF. Age was negatively associated with MIP, regardless of diaphragm thickness, TF, and DE (all p < 0.001). Conclusions: As the diaphragm thickens with age, neither thickness nor TF is associated with MIP; only DE is related to MIP. Additionally, ageing is negatively associated with MIP, independent of diaphragm thickness, TF, and DE. Diaphragm function should be assessed using DE rather than thickness or TF. Full article

Phosphodiesterase-4 (PDE4) is involved in the synthesis of inflammatory cytokines that mediate several chronic inflammatory disorders, including psoriasis and atopic dermatitis. In recent years, the therapeutic armamentarium in dermatology has expanded with the introduction of PDE4 inhibitors, both in oral and topical formulations. PDE4 inhibitors have gained increasing interest due to their remarkable safety record and ease of prescription, as evidenced by the recent influx of literature detailing its off-label uses. Apremilast was the first PDE4 inhibitor approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for psoriasis, psoriatic arthritis, and oral ulcers of Behcet’s disease. Off-label use has been reported in diverse dermatological conditions, including aphthous stomatitis, chronic actinic dermatitis, atopic dermatitis, cutaneous sarcoidosis, hidradenitis suppurativa, lichen planus, and discoid lupus erythematosus. Roflumilast is a PDE4 inhibitor that was approved by the FDA and the EMA as an oral treatment of chronic obstructive pulmonary disease. Since patent expiration, several generic formulations of oral roflumilast have become available, and various studies have documented its off-label use in psoriasis and other dermatological conditions such as hidradenitis suppurativa, recurrent oral aphthosis, nummular eczema, lichen planus, and Behçet’s disease. Topical roflumilast has received FDA approval for treatment of plaque psoriasis and seborrheic dermatitis. The favorable safety profile encourages its long-term use as an alternative to corticosteroids, addressing the chronic nature of many dermatological conditions. New oral PDE4 inhibitors are being developed, such as orismilast (LEO-32731), mufemilast (Hemay005), difamilast (OPA-15406) or lotamilast (E6005/RVT-501), among others. This narrative review provides a comprehensive synthesis of the pharmacology, clinical efficacy, safety profile, and practical considerations regarding the oral and topical use of PDE4 inhibitors in dermatology. Full article

Background: Hydrophilic polymer embolization (HPE) is a scarcely reported complication associated with endovascular procedures where the hydrophilic coating dislodges and disseminates to more distal vascular beds, leading to ischemic complications. The aim of this study is to assess the clinical outcomes associated with HPE in the literature and try to quantify it in a scoping manner. Methods: All reports with regard to HPE in the PubMed database where clinical data were available were included. Reports were excluded if no clinical data were available and only histopathological descriptions are available, if the language of the report was not in English, and if access could not be obtained to that specific report. Results: A total of 60 publications containing 111 patients were identified. The majority (N = 45, 75%) of the publications were “single-patient” case reports. An overwhelming minority of the reports reported underlying hypertension (N = 27, 45.0%) and ischemic heart disease (N = 28, 46.7%). The most common implicated procedures for HPE occurence were cardiac procedures (N = 28, 46.7%), intracranial procedures (N = 13, 21.7%) and aortic procedures (N = 10, 16.7%). Steroids were trialled in nine (15%) of the reports, mainly for HPE to the CNS (7/9), with no mortality in that specific group. However, HPE-related mortality, identified in 48/111 patients, was largely due to HPE with pulmonary and cardiac involvement (combined 36/48 of all deaths). Conclusions: HPE seems to be a rare occurrence, although low-quality evidence (mainly case reports) comprises most of the research on the subject. Fatal outcomes seem relatively common, and steroid therapy may be trialled in select cases. Further research, potentially through prospective registry studies may aid in providing more knowledge on HPE. Full article

Cystic echinococcosis (CE) is a neglected tropical parasitic disease linked with significant social and economic burdens worldwide. The scientific community has minimal information on echinococcosis in Romanian people, and hospital medical records are the only sources that may be used to investigate its status. A 7-year retrospective clinical study on pediatric patients with CE from Southeast Romania was performed, and 39 children and adolescents were included, aged 2–15 years old. They were hospitalized with cystic echinococcosis in the Pediatric Department and Pediatric Surgery Department of Constanta County Clinical Emergency Hospital “St. Apostle Andrew” between 1 January 2017 and 1 October 2024. Twenty-nine (74.36%) pediatric patients came from rural zones, and 10 (25.64%) had urban residences. In total, 28 children (71.79%) had contact with four different animals (dogs, goats, pigs, and sheep); only four were from urban zones, and they had contact only with dogs. Data regarding the length of hospital stay, cyst location, and complications were collected and analyzed. According to the medical files, the diagnosis was established using imaging techniques and serological tests for CE. IgE and IgG reported appreciable variations in correlation with all parameters, and significant differences (p < 0.05) were recorded. IgE levels considerably increased in cases of no animal contact, pulmonary involvement, complications, surgical treatment, and multiple hospitalizations. Moderate IgE values were recorded in cases of urban residences, pig and sheep contact, and hepatic involvement. The IgG concentration considerably increased with sheep contact and moderately increased in cases of rural zones, hepatic involvement, complications, and surgical treatment. The results show that incidental discovery, symptoms, complications, multiple dissemination, pulmonary involvement, and dog and pig contact increase the hospitalization time. Extensive data analysis supports our results. Our findings highlight the complexity of managing E. granulosus infections in children and evidence the importance of a multidisciplinary approach, combining early diagnostic tools, tailored medical therapy, and careful surgical intervention when necessary. Full article

Background/Objectives: Lung cancer is the primary cause of cancer-related deaths. Most patients are typically diagnosed at advanced stages. Low-dose computed tomography (LDCT) has been proven to reduce lung cancer mortality, but screening programs using LDCT are associated with a high number of false positives and unnecessary thoracotomies. It is therefore imperative that a certain diagnosis is refined, especially in cases of solitary pulmonary nodules that are difficult to technically access for an accurate preoperative diagnosis. Extracellular vesicles (EVs) involved in intercellular communication may be an innovative biomarker for diagnosis and therapeutic strategies in lung cancer, regarding their ability to carry tumor-specific cargo. The aim of the LUCEx study is to determine if extracellular vesicle cargoes from both lung tissue and blood could provide complementary information to screen lung cancer patients and enable personalized follow-up after the surgery. Methods: The LUCEx study is a prospective study aiming to recruit 600 patients with lung cancer and 50 control subjects (false positives) undergoing surgery after diagnostic imaging for suspected pulmonary nodules using computed tomography (CT) scans. These patients will undergo curative surgery at the Department of Thoracic Surgery of the Miguel Servet Hospital in Zaragoza, Spain, and will be followed-up for at least 5 years. At baseline, samples from both tumor distal lung tissue and preoperative peripheral blood will be collected and processed to compare the quantity and content of EVs, particularly their micro-RNA (miRNA) cargo. At the third and fifth years of follow-up, CT scans, functional respiratory tests, and blood extractions will be performed. Discussion: Extracellular vesicles and their miRNA have emerged as promising tools for the diagnosis and prognosis of several diseases, including cancer. The LUCEx study, based on an observational clinical cohort, aims to understand the role of these vesicles and their translational potential as complementary tools for imaging diagnosis and prognosis. Full article

Background and Clinical Significance: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune demyelinating disorder of the central nervous system, characterized by the presence of aquaporin-4 (AQP4) antibodies and a high relapse rate. We provide information about the diagnosis, unusual symptoms, and treatment of a paediatric patient with NMOSD. Case Presentation: A 14-year-old girl was hospitalized for weakness and paraesthesia of the lower limbs (LL). The patient underwent detailed investigations and was diagnosed with NMOSD and cryptogenic organizing pneumonia. Initial treatment with methylprednisolone and prednisone yielded a favourable response. Therapy with mycophenolate was initiated. However, the patient experienced two more relapses, prompting the use of rituximab therapy with a favourable outcome and a two-year relapse-free follow-up period. Conclusions: Patients with NMOSD may have multisystemic inflammation, including organs outside the central nervous system. Our case report highlights a case of NMOSD, pulmonary involvement, and unusual adverse reactions to rituximab. Full article

Combined therapies with Heat Shock Protein 90 (HSP90) inhibitors and Heat Shock Protein 70 (HSP70) inducers are gaining significant interest in cancer and cardiovascular research. Here, we tested the hypothesis that HSP90 inhibitors and HSP70 inducers, together, can block the development of pulmonary fibrosis. We exposed New Zealand White Rabbits to hydrochloric acid (HCl, 0.1 N, 1.5 mL/kg), one of the top five chemicals most commonly involved in accidental exposures and inhalation injuries worldwide, and treated animals with either the orally available HSP90 inhibitor TAS-116 (1.7 mg/kg 5x/week) or TAS-116 combined with the HSP70 inducer, geranylgeranyl acetone (GGA, 50 mg/kg, 3x/week). At 60 days post-HCl instillation, TAS and GGA treatment markedly reduced the degree of pulmonary fibrosis, lung dysfunction, and activation of profibrotic pathways. The use of HSP70 inducers may be a helpful tool to improve the profile of HSP90 inhibitors and reduce their minimal effective dose and side effects. Further investigation is required to explore the exact synergistic mechanism behind the antifibrotic profile of HSP90 inhibitors and HSP70 inducers. Full article

Chronic cough is a distressing and prevalent symptom in interstitial lung disease (ILD), significantly impairing quality of life (QoL) and contributing to disease progression, particularly in idiopathic pulmonary fibrosis (IPF). It is associated with physical discomfort, psychological distress, and social isolation and is often refractory to conventional therapies. The pathophysiology of cough in ILD is complex and multifactorial, involving neural hypersensitivity, structural lung changes, inflammatory processes, and comorbid conditions such as gastroesophageal reflux disease (GERD). Evaluating cough in ILD relies on subjective and objective tools to measure its severity, frequency, and impact on daily life, although standardization of these measures remains challenging. Management strategies span pharmacological interventions, including neuromodulators such as opiates, antifibrotic agents, pharmacologic and surgical GERD treatments, and non-pharmacological approaches like behavioral therapies, cough suppression techniques, and pulmonary rehabilitation and physiotherapy. Emerging treatments, such as P2X3 receptor antagonists and airway hydration therapies, offer promising avenues but require further investigation through robust clinical trials. This review aims to demonstrate the importance of addressing cough in ILD as a significant symptom and present objective and subjective methods of quantifying coughs, while providing insights into effective and emerging therapeutic options. By highlighting these potential therapies, we hope to guide healthcare practitioners in considering them through a thorough evaluation of benefits and risks on a case-by-case basis, with relevance both in the U.S. and internationally. Full article