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DOAJ Open Access 2026
Pleural Metastases From Acral Lentiginous Melanoma Diagnosed by Medical Thoracoscopy

Ad Rian Chong, Khai Lip Ng, Nai‐Chien Huan et al.

ABSTRACT Acral lentiginous melanoma (ALM) with pleural metastases is rare and under‐recognised. We report an 86‐year‐old woman with progressive dyspnoea and pleuritic chest pain. 18 months ago, she was diagnosed with stage IIC ALM of the right heel, and was treated with wide local excision, but she declined adjuvant therapy. Imaging demonstrated a large left pleural effusion with diffuse pleural thickening, pulmonary mass, and hepatic metastases. Brownish pleural fluid, along with thoracoscopic identification of multiple pigmented nodules, led to a histologically confirmed diagnosis. Talc pleurodesis was performed for symptom control, and best supportive care was pursued. This case highlights the diagnostic value of medical thoracoscopy in identifying pleural melanoma metastases and emphasises the need to consider melanoma recurrence when pigmented effusions are encountered.

Diseases of the respiratory system
DOAJ Open Access 2026
Developmental dynamics of bronchioalveolar stem cells revealed by dual-reporter lineage tracing

Yuanshu Li, Jiaqi Liu, Shuilian Chi et al.

Abstract Bronchioalveolar stem cells (BASCs), located at the bronchioalveolar duct junction (BADJ), contribute to adult lung regeneration after injury, yet their role during postnatal lung morphogenesis remains poorly characterized. In this study, we showed that BASCs first emerged at birth and persisted throughout the postnatal saccular stage with stable localization and abundance. To trace their fate, we generated a Sftpc DreER knock-in mouse and combined it with Scgb1a1 CreER and dual-reporter H11 LSL − ZsG_RSR−tdT mice to establish a dual recombinase-mediated lineage tracing system (BASC-Tracer). Using this system, we observed that BASCs expanded postnatally and migrated into both alveolar and airway compartments. In the alveoli, they lost SCGB1A1 expression and differentiated into AT2 and AT1 cells to drive alveolar maturation, whereas in the airways, they lost SFTPC expression and gave rise to club cells. Furthermore, we employed a hyperoxia-induced bronchopulmonary dysplasia model to assess the injury response of BASCs during lung development. We found that hyperoxic exposure markedly suppresses BASC regenerative capacity. Finally, spatial transcriptomic analysis revealed that BASCs reside within a distinct BADJ-associated niche, characterized by a unique repertoire of signaling ligands that distinguishes this niche from those of AT2 and club cells. Together, these findings delineate the dynamic behavior of BASCs during lung development and provide spatial characterization of their niche.

Diseases of the respiratory system
DOAJ Open Access 2025
USP18 confers protection against allergic asthma by suppressing CCL8 production in alveolar type II epithelial cells

Huihui Zhang, Zhi Rao, Xiaoke Liu et al.

Abstract Background Alveolar epithelial type II (AT2) cells participate in epithelial repair and lung immune defense, while the detailed molecular mechanisms through which AT2 cells regulate inflammatory immune responses in asthma remain unclear. Ubiquitin-specific peptidase 18 (USP18) has been implicated in immune regulation, but its role in asthma pathogenesis is not fully understood. Methods USP18 expression in AT2 cells was analyzed in both mouse models of allergic asthma and asthmatic patients. Functional studies were conducted using USP18 knockout mice, AT2 cell-specific chemokine (C-C motif) ligand 8 (CCL8) knockdown, and exogenous CCL8 treatment. Th2 responses, eosinophil recruitment, and chemokine production were assessed. Mechanistic investigations focused on USP18-mediated regulation of SOCS1 stability and downstream ERK-STAT3 signaling. Results USP18 is increased in AT2 cells from both mouse models of asthma and asthmatic patients, and played a protective role in the progression of allergic asthma by suppressing Th2 responses and reducing CCL8 production. Notably, USP18 deficiency causes increased CCL8 in AT2 cells, which in turn recruits Th2 cells and eosinophils, thereby exacerbating allergic asthma. Consistently, CCL8 treatment induced asthmatic inflammation and knocking down CCL8 in AT2 cells of USP18 knockout mice alleviates asthma symptoms. Mechanistically, USP18 stabilizes SOCS1 by inhibiting its ubiquitination and degradation, leading to reduced CCL8 production through the ERK-STAT3 signaling pathway in a negative feedback loop. Conclusions Overall, these findings reveal a previously unrecognized role for USP18 in regulating CCL8 production during asthma progression, highlighting USP18 and CCL8 as potential therapeutic targets for asthma treatment.

Diseases of the respiratory system
DOAJ Open Access 2025
Prevalence of insomnia in health care workers during coronavirus disease 2019 pandemic: a cross sectional study

Eman A.A. Ali, Marwa I. Mohammed, Amina M.A. El-Maksoud et al.

Background In December 2019, a highly infectious critical acute respiratory syndrome caused by coronavirus disease 2019 (COVID-19) virus developed in Wuhan, China. The health care workers (HCWs) were subjected to increased workload, physical exhaustion, improper personal protective equipment and dangerous of nosocomial infection. HCWs are, as a result, liable for mental health troubles, such as fear, anxiety, depression, and insomnia. Patients and methods This was a cross–sectional study conducted on HCWs in Mansoura University Hospital within the period from August to December 2020 to assess the prevalence of insomnia throughout COVID-19 Pandemic. We comprised HCWs (they were physicians, nursing specialists, nursing technicians, Lab technicians, and technical radiologists) who dealt COVID-19 patients. HCWs on anti-psychotic drugs interfering with sleep rhythm were ruled out. Results This study was conducted on 427 HCWs with mean age 30.59±5.19 years, majority of studied HCWs were females (76.8%). The majority of HCWs were physicians (71.4%). The prevalence of insomnia among studied HCWs was 78.7%. 60.7% of HCWs had anxiety and 95.3% had depression. There was a statistically significant positive correlation between insomnia total score and fatigue total score and Epworth sleepiness scale. Conclusion From this study, we could conclude that during COVID-19 pandemic there was high prevalence of insomnia among HCWs, most of them with subthreshold to moderate insomnia.

Diseases of the respiratory system
DOAJ Open Access 2024
Job-related factors associated with tobacco use among Chinese food delivery riders: A cross-sectional survey

Chen Li, Dan Wu, Christopher Bullen et al.

Introduction Food delivery drivers represent a rapidly growing occupational group in China in recent years. Their unique work patterns such as a complex work environment and high time-pressure may subject them to more severe tobacco use issues compared to other professions. This study aims to investigate the prevalence of tobacco use within this group and examine the underlying reasons behind it. Methods A cross-sectional, multistage sampling design was conducted to select 1879 food delivery riders from Guangzhou and Shenzhen. A self-administered questionnaire was used to collect the data from August to December 2022. Chisquared analysis and binary logistic regression analysis, adjusted for factors including gender, education level, type of employment, alcohol use, job-related uncertainty stress, and emotional exhaustion, were used to explore the key factors associated with smoking among this occupational group. Results Altogether, 65.5% of individuals in this sample were smokers, with 69.5% among males and 26.2% among females. Factors found to be significantly associated with smoking behavior were male sex (AOR=5.48; 95% CI: 3.74–8.02), education level of junior high school or lower (AOR=1.60; 95% CI: 1.21–2.11), education level of senior high school (AOR=1.52; 95% CI: 1.18–1.95), full-time job (AOR=1.39; 95% CI: 1.18–1.80), alcohol use (AOR=3.91; 95% CI: 3.14–4.87), moderate level of job-related uncertainty stress (AOR=0.58; 95% CI: 0.42–0.81), high level of emotional exhaustion (AOR=1.57; 95% CI: 1.17–2.10) and moderate level of emotional exhaustion (AOR=1.52; 95% CI: 1.00–2.30). Conclusions Demographic factors like gender, education level, job type, and substance use should be considered in designing smoking cessation campaigns for this group. Improving work conditions, reducing emotional exhaustion, and managing stress may also reduce smoking and enhance the well-being of these riders.

Diseases of the respiratory system, Neoplasms. Tumors. Oncology. Including cancer and carcinogens
DOAJ Open Access 2023
Regenerative and translational medicine in COPD: hype and hope

Lucas Pires Guarnier, Lincoln Gozzi Moro, Francislaine Aparecida dos Reis Lívero et al.

COPD is a common, preventable and usually progressive disease associated with an enhanced chronic inflammatory response in the airways and lung, generally caused by exposure to noxious particles and gases. It is a treatable disease characterised by persistent respiratory symptoms and airflow limitation due to abnormalities in the airways and/or alveoli. COPD is currently the third leading cause of death worldwide, representing a serious public health problem and a high social and economic burden. Despite significant advances, effective clinical treatments have not yet been achieved. In this scenario, cell-based therapies have emerged as potentially promising therapeutic approaches. However, there are only a few published studies of cell-based therapies in human patients with COPD and a small number of ongoing clinical trials registered on clinicaltrials.gov. Despite the advances and interesting results, numerous doubts and questions remain about efficacy, mechanisms of action, culture conditions, doses, timing, route of administration and conditions related to homing and engraftment of the infused cells. This article presents the state of the art of cell-based therapy in COPD. Clinical trials that have already been completed and with published results are discussed in detail. We also discuss the questions that remain unanswered about cell-based regenerative and translational medicine for COPD.

Diseases of the respiratory system
S2 Open Access 2022
Lymph Node Involvement in Early-Stage Cervical Cancer: Is Lymphangiogenesis a Risk Factor? Results from the MICROCOL Study

M. Tantari, S. Bogliolo, M. Morotti et al.

Simple Summary The prognosis of cervical cancer is significantly influenced by lymph node involvement. The lymphatic system is the primary way of metastasis for cervical carcinoma, and lymph-vascular space invasion (LVSI) is considered the most important risk factor for pelvic lymph node metastasis (PLNM). Previous studies have not clarified the correlation between lymphangiogenesis and an increased risk of metastasis and tumor recurrence. The evaluation and identification of several markers of lymphangiogenesis may identify patients with high risk of PLNM. Our findings suggest that the lymphatic spread does not required the proliferation of new lymphatic endothelial cells. These results emphasize the importance of pre-existing peritumoral lymphatic vessels in the metastatic process in early cervical cancer. Abstract Background: In patients with cervical cancer, the presence of tumoral lymph-vascular space invasion (LVSI) is the main risk factor for pelvic lymph node metastasis (PLNM). The objective of this study was to evaluate the presence of several markers of lymphangiogenesis in early-stage cervical cancer and their correlation with PLNM and tumoral recurrence. Materials and Methods: Seventy-five patients with early-stage cervical carcinoma underwent sentinel lymph node (SLN) sampling in association with complete pelvic lymph node dissection. Primary tumors were stained with the following markers: Ki67, D2-40, CD31 and VEGF-C. A 3-year follow-up was performed to evaluate the disease-free survival. Results: Overall, 14 patients (18.6%) had PLNM. Positive LVSI was seen in 29 patients (38.6%). There was a significant correlation between LVSI evidenced by H/E staining and PLNM (p < 0.001). There was no correlation between high Ki67, CD31, D2-40, and VEGF-C staining with PLNM or tumor recurrence. Conclusions: Our data support that lymphatic spread does not require the proliferation of new lymphatic endothelial cells in early-stage cervical cancer. These results emphasize the importance of pre-existing peritumoral lymphatic vessels in the metastatic process in early cervical cancer. None of the markers of lymphangiogenesis and proliferation assessed in this study were predictive of PLNM or recurrence.

17 sitasi en Medicine
S2 Open Access 2022
Age- and Sex-Matched Normal Leukocyte Subset Ranges in the General Population Defined with the EuroFlow Lymphocyte Screening Tube (LST) for Monoclonal B-Cell Lymphocytosis (MBL) vs. Non-MBL Subjects

I. Criado, Wendy G Nieto, Guillermo Oliva-Ariza et al.

Simple Summary Assessment of the status of the immune system in both health and disease requires robust and reliable reference ranges for the different blood leukocyte (sub)populations that take into consideration factors that might influence their distribution, such as age, sex, ethnicity and the presence vs. absence of low-count monoclonal B-cell lymphocytosis with a chronic-lymphocytic-leukemia-like phenotype (MBLlo). It should be noted that despite MBLlo being highly prevalent in the general population and being associated with immune impairment, MBLlo individuals have not been previously excluded in the definition of normal leukocyte ranges. Here, we provide reference cell-count ranges for the major leukocyte populations identified in blood using an optimized and fully validated 8-color flow-cytometry antibody combination based on the largest (n = 706) cohort reported to date of Caucasian adult donors from the general population, grouped by age and sex, and highlight the altered immune profiles associated with MBLlo (622 non-MBL and 84 MBLlo subjects). Abstract Reference ranges of blood-circulating leukocyte populations by, e.g., age and sex, are required for monitoring immune-cell kinetics. Most previous reports in which flow cytometry has been used to define the reference ranges for leukocyte counts included a limited number of donors and/or cell populations and/or did not consider age and sex simultaneously. Moreover, other factors not previously considered in the definition of normal ranges, such as the presence of chronic-lymphocytic-leukemia (CLL)-like low-count monoclonal B-cell lymphocytosis (MBLlo), might also be associated with an altered distribution of leukocytes in blood in association with an immunodeficiency and increased risk of infection and cancer. Here, we established reference cell-count ranges for the major populations of leukocytes in blood of non-MBL and MBLlo adult Caucasians matched by age and sex using the EuroFlow Lymphocyte Screening Tube (LST). A total of 706 Caucasian adult donors—622 non-MBL and 84 MBLlo—were recruited from the general population. Among non-MBL donors, the total leukocyte, neutrophil, basophil dendritic cell and monocyte counts remained stable through adulthood, while the absolute numbers of T- and B-cell populations and plasma cells decreased with age. The number of eosinophils and NK-cell increased over time, with clear differences according to sex for certain age ranges. In MBLlo subjects, few differences in the absolute cell counts by age (vs. non-MBL) were observed, and MBLlo men and women showed similar trends to non-MBL subjects except for the B-cell count drop observed in >70 y-men, which was more pronounced in MBLlo vs. non-MBL controls. Building robust age- and sex-matched reference ranges for the most relevant immune-cell populations in the blood of non-MBL donors is essential to appropriately identify an altered immune status in different clinical settings and highlight the altered immune-cell profiles of MBLlo subjects.

11 sitasi en Medicine
S2 Open Access 2022
Biopsychosocial Response to the COVID-19 Lockdown in People with Major Depressive Disorder and Multiple Sclerosis

S. Siddi, I. Giné-Vázquez, R. Bailón et al.

Background: Changes in lifestyle, finances and work status during COVID-19 lockdowns may have led to biopsychosocial changes in people with pre-existing vulnerabilities such as Major Depressive Disorders (MDD) and Multiple Sclerosis (MS). Methods: Data were collected as a part of the RADAR-CNS (Remote Assessment of Disease and Relapse Central Nervous System) programme. We analyzed the following data from long-term participants in a decentralized multinational study: symptoms of depression, heart rate (HR) during the day and night; social activity; sedentary state, steps and physical activity of varying intensity. Linear mixed-effects regression analyses with repeated measures were fitted to assess the changes among three time periods (pre, during and post-lockdown) across the groups, adjusting for depression severity before the pandemic and gender. Results. Participants with MDD (N=255) and MS (N=214) were included in the analyses. Overall, depressive symptoms remained stable across the three periods in both groups. Lower mean HR and HR variation were observed between pre and during lockdown during the day for MDD and during the night for MS. HR variation during rest periods also decreased between pre-and post-lockdown in both clinical conditions. We observed a reduction of physical activity for MDD and MS upon the introduction of lockdowns. The group with MDD exhibited a net increase in social interaction via social network apps over the three periods. Conclusions: Behavioral response to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDD and MS.

9 sitasi en Medicine
S2 Open Access 2022
SARS-CoV-2 Antibody Response against Mild-to-Moderate Breakthrough COVID-19 in Home Isolation Setting in Thailand

P. Mongkolsucharitkul, A. Surawit, S. Pumeiam et al.

Background: In December 2021, Omicron replaced Delta as the dominant coronavirus disease 2019 (COVID-19) variant in Thailand. Both variants embody diverse epidemiological trends and immunogenicity. We investigated whether Delta and Omicron patients’ biological and clinical characteristics and immunogenicity differed post-COVID-19 infection. Methods: This retrospective cohort study investigated the clinical outcomes and laboratory data of 5181 patients with mild-to-moderate COVID-19 (Delta, 2704; Omicron, 2477) under home isolation. We evaluated anti-receptor-binding domain immunoglobulin G (anti-RBD IgG) and surrogate viral neutralizing (sVNT) activity in 495 individuals post-COVID-19 infection during the Delta pandemic. Results: Approximately 84% of all patients received favipiravir. The median cycle threshold (Ct) values were lower for Omicron patients than Delta patients (19 vs. 21; p < 0.001), regardless of vaccination status. Upper respiratory tract symptoms were more frequent with Omicron patients than Delta patients. There were no significant associations between Ct and Omicron symptoms (95% confidence interval 0.98–1.02). A two-dose vaccine regimen reduced hospital readmission by 10% to 30% and death by under 1%. Anti-RBD IgG and sVNT against Delta were higher among older individuals post-COVID-19 infection. Older individuals expressed anti-RBD IgG and sVNT for a more extended period after two-dose vaccination than other age groups. Conclusions: After a full vaccination course, breakthrough mild-to-moderate Delta and Omicron infections have limited immunogenicity. Prior infections exert reduced protection against later reinfection or infection from novel variants. However, this protection may be sufficient to prevent hospitalization and death, particularly in countries where vaccine supplies are limited.

4 sitasi en Medicine
S2 Open Access 2022
Timing and Outcomes of Noninvasive Ventilation in 307 ARDS COVID-19 Patients: An Observational Study in an Italian Third Level COVID-19 Hospital

Nardi Tetaj, P. Piselli, S. Zito et al.

Background and Objectives: Background: Coronavirus disease 2019 (COVID-19) is a novel cause of Acute Respiratory Distress Syndrome (ARDS). Noninvasive ventilation (NIV) is widely used in patients with ARDS across several etiologies. Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, its use has grown significantly in hospital wards. However, there is a lack of evidence to support the efficacy of NIV in patients with COVID-19 ARDS. Materials and Methods: We conducted an observational cohort study including adult ARDS COVID-19 patients admitted in a third level COVID-center in Rome, Italy. The study analyzed the rate of NIV failure defined by the occurrence of orotracheal intubation and/or death within 28 days from starting NIV, its effectiveness, and the associated relative risk of death. The factors associated with the outcomes were identified through logistic regression analysis. Results: During the study period, a total of 942 COVID-19 patients were admitted to our hospital, of which 307 (32.5%) presented with ARDS at hospitalization. During hospitalization 224 (23.8%) were treated with NIV. NIV failure occurred in 84 (37.5%) patients. At 28 days from starting NIV, moderate and severe ARDS had five-fold and twenty-fold independent increased risk of NIV failure (adjusted odds ratio, aOR = 5.01, 95% CI 2.08–12.09, and 19.95, 95% CI 5.31–74.94), respectively, compared to patients with mild ARDS. A total of 128 patients (13.5%) were admitted to the Intensive Care Unit (ICU). At 28-day from ICU admission, intubated COVID-19 patients treated with early NIV had 40% lower mortality (aOR 0.60, 95% CI 0.25–1.46, p = 0.010) compared with patients that underwent orotracheal intubation without prior NIV. Conclusions: These findings show that NIV failure was independently correlated with the severity category of COVID-19 ARDS. The start of NIV in COVID-19 patients with mild ARDS (P/F > 200 mmHg) appears to increase NIV effectiveness and reduce the risk of orotracheal intubation and/or death. Moreover, early NIV (P/F > 200 mmHg) treatment seems to reduce the risk of ICU mortality at 28 days from ICU admission.

3 sitasi en Medicine
DOAJ Open Access 2022
Risk prediction for Obstructive Sleep Apnea prognostic in Obese patients referred for bariatric surgery

Adriana Fontes Hora, Lara Maris Nápolis, Débora Strose Villaça et al.

ABSTRACT Objectives (i) To assess the anthropometric measurements, along with the clinical characteristics and quality of life profiles of the studied patients; (ii) To determine the occurrence and severity of Obstructive Sleep Apnea (OSA), using polysomnography; and (iii) To identify the best anthropometric and clinical indicators to predict OSA in obese patients who are candidates for bariatric surgery. Methods a prospective observational study conducted in a private clinic, using consecutive sampling of patients eligible for bariatric surgery with a BMI ≥ 40, or with a BMI of ≥ 35 kg/m² accompanied by comorbidities associated with obesity. Results Sixty patients were initially selected, of whom 46 agreed to take part in the preoperative evaluation. OSA was observed in 76% of patients, 59% of whom had moderate-to-severe OSA, with a predominance of men in these groups. Among the variables suggesting statistical difference between groups, waist-to-hip ratio (WHR) was the only clinical factor associated with scores the apnea hypopnea index (AHI) ≥ 15, with a cut-off value of 0.95. The results showed that patients scoring above 0.95 are three times more likely to have moderate-to-severe apnea. Conclusion The best risk factor for the prognostic of moderate-to-severe OSA was presenting a WHR score with a cut-off value of 0.95 or above.

Diseases of the respiratory system
DOAJ Open Access 2022
The potential role of interleukin (IL)‐25/IL‐33/thymic stromal lymphopoietin (TSLP) on the pathogenesis of idiopathic pulmonary fibrosis

Xuefeng Xu, Huaping Dai, Jinglan Zhang

Abstract Objectives Interleukin (IL)‐25, IL‐33, and thymic stromal lymphopoietin (TSLP) are the important drivers for excessive type‐2 immunity. It has been well elucidated that IL‐25/IL‐33/TSLP plays an important role in allergic airway inflammation and remodeling, whereas their roles in idiopathic pulmonary fibrosis (IPF) still remained largely unclear. Herein, the aim of the review is to discuss the potential role and mechanism of IL‐25/IL‐33/TSLP on IPF by literature analysis and summary. Data source We have done a literature search using the following terms: (“idiopathic pulmonary fibrosis” OR “IPF” OR “lung fibrosis”) and (TSLP or “thymic stromal lymphopoietin” or IL‐25 OR IL‐17E OR IL‐33) from the database of PubMed published in English up to July 2018. Study selection We have totally found 58 articles by using the retrieval terms mentioned above. By careful title and abstract reading, 10 original research articles of high quality were enrolled for the full text reading and analysis. Two additional relevant studies were also included during the course of literature readings. Results IL‐25/IL‐33/TSLP and their corresponding receptors, that is, IL‐17BR/ST2L/TSLPR, are shown to be up‐regulated both in IPF patients and bleomycin (BLM)‐induced lung fibrosis mice model. IL‐25 may promote lung fibrosis by activating IL‐17BR+fibroblast and IL‐17BR+ILC2 (type 2 innate lymphoid cell). Full length (fl)‐IL‐33, as a transcription factor mainly in the cell nucleus, mediated non‐atopic lung inflammation and fibrosis by modulating expressions of several pro‐fibrotic mediators, including transforming growth factor (TGF)‐b1. By contrast, mature (m)‐IL‐33 potentiates lung fibrosis by recruiting ST2L+M2 macrophages and ST2L+ILC2 to enlarge type 2 immunity. TSLP was shown to directly promote CCL2 expression in primary human lung fibroblasts (pHLFs). Conclusion IL‐25/IL‐33/TSLP contributes to non‐allergic lung fibrosis by mediating persistent abnormal epithelial‐mesenchymal crosstalk. IL‐25/IL‐33/TSLP may serve the promising novel target for the treatment of IPF.

Diseases of the respiratory system
DOAJ Open Access 2022
Underrepresentation of women in randomized controlled trials: a systematic review and meta-analysis

Vered Daitch, Adi Turjeman, Itamar Poran et al.

Abstract Background Although regulatory changes towards correcting the underrepresentation of women in randomized controlled trials (RCTs) occurred (National Institutes of Health 1994), concerns exist about whether an improvement is taking place. In this systematic review and meta-analysis, we aimed to assess the inclusion rates of women in recent RCTs and to explore the potential barriers for the enrollment of women. Methods RCTs published in 2017 examining any type of intervention in adults were searched in PubMed and Cochrane Library. The following predefined medical fields were included: cardiovascular diseases, neoplasms, endocrine system diseases, respiratory tract diseases, bacterial and fungal infections, viral diseases, digestive system diseases, and immune system diseases. Studies were screened independently by two reviewers, and an equal number of studies was randomly selected per calendric month. The primary outcome was the enrollment rate of women, calculated as the number of randomized women patients divided by the total number of randomized patients. Rates were weighted by their inverse variance; statistical significance was tested using general linear models (GLM). Results Out of 398 RCTs assessed for eligibility, 300 RCTs were included. The enrollment rate of women in all the examined fields was lower than 50%, except for immune system diseases [median enrollment rate of 68% (IQR 46 to 81)]. The overall median enrollment rate of women was 41% (IQR 27 to 54). The median enrollment rate of women decreased with older age of the trials’ participants [mean age of trials’ participants ≤ 45 years: 47% (IQR 30–64), 46–55 years: 46% (IQR 33–58), 56–62 years: 38% (IQR 27–50), ≥ 63 years: 33% (IQR 20–46), p < 0.001]. Methodological quality characteristics showed no significant association with the enrollment rates of women. Out of the 300 included RCTs, eleven did not report on the number of included women. There was no significant difference between these studies and the studies included in the analysis. Conclusions Women are being inadequately represented, in the selected medical fields analyzed in our study, in recent RCTs. Older age is a potential barrier for the enrollment of women in clinical trials. Low inclusion rates of elderly women might create a lack of crucial knowledge in the adverse effects and the benefit/risk profile of any given treatment. Factors that might hinder the participation of women should be sought and addressed in the design of the study.

Medicine (General)
S2 Open Access 2021
Gender-Based Differences by Age Range in Patients Hospitalized with COVID-19: A Spanish Observational Cohort Study

C. Josa-Laorden, A. Crestelo-Vieitez, María del Mar García Andreu et al.

There is some evidence that male gender could have a negative impact on the prognosis and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of the present study was to compare the characteristics of coronavirus disease 2019 (COVID-19) between hospitalized men and women with confirmed SARS-CoV-2 infection. This multicenter, retrospective, observational study is based on the SEMI-COVID-19 Registry. We analyzed the differences between men and women for a wide variety of demographic, clinical, and treatment variables, and the sex distribution of the reported COVID-19 deaths, as well as intensive care unit (ICU) admission by age subgroups. This work analyzed 12,063 patients (56.8% men). The women in our study were older than the men, on average (67.9 vs. 65.7 years; p < 001). Bilateral condensation was more frequent among men than women (31.8% vs. 29.9%; p = 0.007). The men needed non-invasive and invasive mechanical ventilation more frequently (5.6% vs. 3.6%, p < 0.001, and 7.9% vs. 4.8%, p < 0.001, respectively). The most prevalent complication was acute respiratory distress syndrome, with severe cases in 19.9% of men (p < 0.001). In men, intensive care unit admission was more frequent (10% vs. 6.1%; p < 0.001) and the mortality rate was higher (23.1% vs. 18.9%; p < 0.001). Regarding mortality, the differences by gender were statistically significant in the age groups from 55 years to 89 years of age. A multivariate analysis showed that female sex was significantly and independently associated with a lower risk of mortality in our study. Male sex appears to be related to worse progress in COVID-19 patients and is an independent prognostic factor for mortality. In order to fully understand its prognostic impact, other factors associated with sex must be considered.

17 sitasi en Medicine
DOAJ Open Access 2021
Profile of Patients With Respiratory Failure at Pediatric Intensive Care Unit (PICU) Dr. Soetomo General Hospital

Cindy Aprilia Eka Prasanty, Arina Setyaningtyas, Arie Utariani

Introduction: Respiratory failure is the respiratory system’s inability to maintain its gas exchange functions, oxygenation, and carbon dioxide elimination. Infant and children are more susceptible to develop respiratory failure. Respiratory failure can also be caused by several diseases/conditions, which is a common reason for pediatrics to be admitted to the intensive care unit. Objective: This study aims to describe patients’ demographic and clinical profile with respiratory failure at the PICU of Dr. Soetomo General Hospital, Surabaya. Materials and Methods: This is a prospective study with the descriptive method using the medical records of patients with respiratory failure who were admitted to the PICU from September 2019 to February 2020 and had arterial BGA data (PaCO2, PaO2), which were examined in the PICU or resuscitation room before the patients were admitted to the PICU. Results: This study showed that out of 35 patients, 24 (68.6%) were female, 19 (54.3%) were <1 year old, and 20 (57.1%) had normal nutritional status. Type I (hypoxemic) and type II (hypercapnic) respiratory failures were found in 13 patients (37.1%), respectively. The most common clinical signs were fever in 26 patients (74.3%), shortness of breath in 24 patients (68.6%), and chest retraction in 24 patients (68.6%). The primary diagnosis that commonly occurred was respiratory system disorders in 15 patients (42.9%). The other diagnosis that mainly occurred was nutrition and metabolic disorders of 19 patients (54.3%). The patients' outcome was that 24 patients were survived (68.6%), and ten patients died (28.6%). Conclusions: Various clinical signs and diagnoses can be found in patients with respiratory failure at PICU. The most common respiratory failure types are type I (hypoxemic) and type II (hypercapnic) respiratory failure.

DOAJ Open Access 2021
Clinicoradiopathological features among mediastinal masses

R Sridhar, R Narasimhan, L Sundararajan et al.

Background: The mediastinum is a place where various benign and malignant diseases usually manifest as mass and present as interesting diagnostic challenge. The purpose of this study was to describe clinical features, radiological, and pathological information of mediastinal masses to help have an organized approach to diagnosis of mediastinal masses. Patients and Methods: This was a prospective, descriptive cross-sectional study conducted over a period of 1 year at our hospital after obtaining ethical committee clearance. Patients with mediastinal masses fulfilling the inclusion criteria were enrolled in the study. Patient's clinical history, radiological features, techniques used to obtain specimens, and cyto-histopathology results from data collected in our total study population were analyzed. Results: A total of 73 patients with mediastinal masses were included. Thirty-three of them (45.2%) were malignant and 32 (43.8%) were nonmalignant masses. The masses were commonly located in the middle compartment (n = 42 [57.5%]), followed by anterior compartment (20 [27.4%]), posterior compartment (8 [11%]), and multicompartment (3 [4.1%]). Among middle mediastinal masses, infectious masses were 14 (33.3%), followed by 11 (26.2%) malignant masses. Anterior mediastinal masses were predominantly malignant in nature (90%). Nature of mass was inconclusive in eight (11%) patients. Conclusion: Clinical history, anatomical position, and imaging characteristics allow the correct diagnosis in many cases when it is combined with histopathology. The newer endoscopic techniques such as endoscopic ultrasound-guided fine-needle aspiration or biopsy are generally preferred in view of lesser complications and ease compared to more invasive surgical procedures for mediastinal mass evaluation.

Diseases of the respiratory system
S2 Open Access 2020
Pathway mapping of leukocyte transcriptome in influenza patients reveals distinct pathogenic mechanisms associated with progression to severe infection

Y. Zerbib, E. Jenkins, M. Shojaei et al.

Influenza infections produce a spectrum of disease severity, ranging from a mild respiratory illness to respiratory failure and death. The host-response pathways associated with the progression to severe influenza disease are not well understood. To gain insight into the disease mechanisms associated with progression to severe infection, we analyzed the leukocyte transcriptome in severe and moderate influenza patients and healthy control subjects. Pathway analysis on differentially expressed genes was performed using a topology-based pathway analysis tool that takes into account the interaction between multiple cellular pathways. The pathway profiles between moderate and severe influenza were then compared to delineate the biological mechanisms underpinning the progression from moderate to severe influenza. 107 patients (44 severe and 63 moderate influenza patients) and 52 healthy control subjects were included in the study. Severe influenza was associated with upregulation in several neutrophil-related pathways, including pathways involved in neutrophil differentiation, migration, degranulation and neutrophil extracellular trap (NET) formation. The degree of upregulation in neutrophil-related pathways were significantly higher in severely infected patients compared to moderately infected patients. Severe influenza was also associated with downregulation in immune response pathways, including pathways involved in antigen presentation such as CD4+ T-cell co-stimulation, CD8+ T cell and Natural Killer (NK) cells effector functions. Apoptosis pathways were also downregulated in severe influenza patients compare to moderate and healthy controls. These findings showed that there are changes in gene expression profile that may highlight distinct pathogenic mechanisms associated with progression from moderate to severe influenza infection.

22 sitasi en Medicine

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