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Introduction: Convolutional Neural Network (CNN) systems in healthcare are influenced by unbalanced datasets and varying sizes. This article delves into the impact of dataset size, class imbalance, and their interplay on CNN systems, focusing on the size of the training set versus imbalance-a unique perspective compared to the prevailing literature. Furthermore, it addresses scenarios with more than two classification groups, often overlooked but prevalent in practical settings., Methods: Initially, a CNN was developed to classify lung diseases using X-ray images, distinguishing between healthy individuals and COVID-19 patients. Later, the model was expanded to include pneumonia patients. To evaluate performance, numerous experiments were conducted with varied data sizes and imbalance ratios for both binary and ternary classifications, measuring various indices to validate the model's efficacy., Results: The study revealed that increasing dataset size positively impacts CNN performance, but this improvement saturates beyond a certain size. A novel finding is that the data balance ratio influences performance more significantly than dataset size. The behavior of three-class classification mirrored that of binary classification, underscoring the importance of balanced datasets for accurate classification., Conclusions: This study emphasizes the fact that achieving balanced representation in datasets is crucial for optimal CNN performance in healthcare, challenging the conventional focus on dataset size. Balanced datasets improve classification accuracy, both in two-class and three-class scenarios, highlighting the need for data-balancing techniques to improve model reliability and effectiveness., Motivation: Our study is motivated by a scenario with 100 patient samples, offering two options: a balanced dataset with 200 samples and an unbalanced dataset with 500 samples (400 healthy individuals). We aim to provide insights into the optimal choice based on the interplay between dataset size and imbalance, enriching the discourse for stakeholders interested in achieving optimal model performance., Limitations: Recognizing a single model's generalizability limitations, we assert that further studies on diverse datasets are needed.

Background: Waning immunity after the coronavirus disease 2019 (COVID-19) vaccinations creates the constant need of boosters. Predicting individual responses to booster vaccines can help in its timely administration. We hypothesized that the humoral response to the first two doses of the BNT162b2 vaccine can predict the response to the booster vaccine., Methods: A prospective cohort of hospital health care workers (HCW) that received three doses of the BNT162b2 vaccine. Participants completed serological tests at 1 and 6 months after the second vaccine dose and 1 month after the third. We analyzed predictive factors of antibody levels after the booster using multivariate regression analyses., Results: From 289 eligible HCW, 89 (31%) completed the follow-up. Mean age was 48 (±10) and 46 (52%) had daily interaction with patients. The mean (±standard deviation) antibody level 1 month after the second vaccine was 223 (±59) AU/ml, and 31 (35%) had a rapid antibody decline (>50%) in 6 months. Low antibody levels 1 month after the second vaccine and a rapid antibody decline were independent predictors of low antibody levels after the booster vaccine., Conclusions: The characteristics of the humoral response to COVID-19 vaccinations show promise in predicting the humoral response to the booster vaccines., (© The Author(s) 2023. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

COVID-19 vaccination and acute infection result in cellular and humoral immune responses with various degrees of protection. While most studies have addressed the difference in humoral response between vaccination and acute infection, studies on the cellular response are scarce. We aimed to evaluate differences in immune response among vaccinated patients versus those who had recovered from COVID-19. This was a prospective study in a tertiary medical centre. The vaccinated group included health care workers, who had received a second dose of the BNT162b2 vaccine 30 days ago. The recovered group included adults who had recovered from severe COVID-19 infection (<94% saturation in room air) after 3-6 weeks. Serum anti-spike IgG and cytokine levels were taken at entry to the study. Multivariate linear regression models were applied to assess differences in cytokines, controlling for age, sex, BMI, and smoking status. In total, 39 participants were included in each group. The mean age was 53 ±14 years, and 53% of participants were males. Baseline characteristics were similar between the groups. Based on multivariate analysis, serum levels of IL-6 (β=-0.4, p<0.01), TNFα (β=-0.3, p=0.03), IL-8 (β=-0.3, p=0.01), VCAM-1 (β=-0.2, p<0.144), and MMP-7 (β=-0.6, p<0.01) were lower in the vaccinated group compared to the recovered group. Conversely, serum anti-spike IgG levels were lower among the recovered group (124 vs. 208 pg/mL, p<0.001). No correlation was identified between antibody level and any of the cytokines mentioned above. Recovered COVID-19 patients had higher cytokine levels but lower antibody levels compared to vaccinated participants. Given the differences, these cytokines might be of value for future research in this field.

Background: The concept of remission on biological treatment has been suggested as a therapeutic target for patients with severe asthma, composed of 1. no chronic use of systemic steroids, 2. no exacerbations, 3. minimal symptoms, and 4. optimized lung function, for a significant time. However, the criteria for remission are not clearly defined., Objective: Our objective was to compare different criteria for remission in subjects receiving biologicals for severe asthma., Methods: A cross-sectional study of adult subjects who receive a stable regimen of a biological for severe asthma for at least 6-months. We compared the proportion of subjects who fulfilled different specific criteria in the four domains, as well as those who achieved different composite outcome measures of clinical remission., Results: Of 39 subjects, 28 were females (71.8%), mean age 60.4. Twelve were current or past smokers (30.8%). Twelve had prior different biological treatment (30.8%), and 3/39 had more than one previous treatment (7.7%). Current biological included mepolizumab 12/39 (30.8%), dupilumab 11/39 (28.2%), benralizumab 10/39 (25.6%), omalizumab 5/39 (12.8%), reslizumab 1/39 (2.6%). Different specific criteria were achieved in 39-80% of subjects, being highest for no chronic steroid use and lowest for symptoms control and lung function. Overall remission was obtained by 20-41%, depending on definition, with significant variability in agreement between different sets of remission criteria (Cohen's kappa 0.33-0.89)., Conclusion: Clinical remission is achievable in real-world severe asthmatics on biological therapies. The core criteria for remission should be better defined., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ori Wand reports a relationship with GlaxoSmithKline that includes: consulting or advisory and speaking and lecture fees. Ori Wand reports a relationship with AstraZeneca that includes: consulting or advisory and speaking and lecture fees. Ori Wand reports a relationship with Boehringer Ingelheim Ltd that includes: speaking and lecture fees. Ori Wand reports a relationship with Sanofi that includes: speaking and lecture fees. Ori Wand reports a relationship with Kamada Ltd that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Infections with B.1.1.529 (Omicron) variants of SARS-CoV-2 became predominant worldwide since late 2021, replacing the previously dominant B.1.617.2 variant (Delta). While those variants are highly transmissible and can evade vaccine protection, population studies suggested that outcomes from infection with Omicron variants are better compared with Delta. Data regarding prognosis of maintenance hemodialysis (MHD) patients infected with Omicron versus Delta variants, however, are scarce., Methods: This retrospective cohort study includes all patients with end-stage kidney disease treated with MHD in Meir Medical Center, Kfar-Saba, Israel, that were diagnosed with SARS-CoV-2 infection between June 2021 and May 2022., Results: Twenty-six subjects were diagnosed with the Delta variant and 71 with Omicron. Despite comparable age between groups and higher mean vaccine doses prior to the infection among the Omicron group (p &lt; 0.001), SARS-CoV-2 infection severity was significantly worse among MHD infected with the Delta variant: 50% developed severe or critical COVID-19 versus 5% in the Omicron group (p &lt; 0.001). Over half of MHD infected with Omicron (57%) were asymptomatic during their illness. The 30-day mortality rate for the whole cohort was 5.2%. It was significantly higher among MHD in the Delta group than in the Omicron group (5/26, 19.2% vs. 0/71, p &lt; 0.001), as was the 90-day mortality rate (5/26, 19.2% vs. 3/71, 4.2%, p = 0.02)., Conclusions: Infection with the SARS-CoV-2 Delta variant was associated with worse outcomes compared with Omicron, among subjects on MHD. However, despite mild disease among vaccinated MHD patients, infection with Omicron variant was still associated with the significant 90-day mortality rate., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Medical follow-up of symptomatic patients after acute Coronavirus Disease 2019 (COVID-19) results in major burdens on patients and healthcare systems. The value of serological markers as part of this follow-up remains undetermined. We aimed to evaluate the clinical implications of serological markers for follow-up of acute COVID-19. For this purpose, we conducted an observational cohort study of patients 3 months after acute COVID-19. Participants visited a respiratory-clinic between October 2020 and March 2021, and completed pulmonary function tests (PFTs), serological tests, symptom-related questionnaires, and chest CT scans. Overall, 275 patients were included at a median of 82 days (IQR 64-111) post infection. 162 (59%) patients had diffusing capacity for carbon monoxide corrected for hemoglobin (DLCOc) below 80%, and 69 (25%) had bilateral chest abnormalities on CT scan. In multivariate analysis, anti-S levels were an independent predictor for DLCOc (β = - 0.14, p = 0.036). Anti-S levels were also associated with severe COVID-19 and older age, and correlated with anti-nucleocapsid (r = 0.30, p < 0.001) and antibodies to receptor binding domain (RBD, r = 0.37, p < 0.001). Other serological variables were not associated with clinical outcomes. In conclusion, symptomatic patients 3-months after COVID-19 had high respiratory symptomatic burden, in which anti-S levels were significantly associated with previous severe COVID-19 and DLCOc., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Respiratory sequela after acute COVID-19 is common and requires medical follow-up. Considering its vast economic impact, there is still no consensus regarding the mid-term follow-up plan after recovery., Objective: To evaluate the necessity of a close pulmonary follow-up schedule after acute COVID-19 and its related investigations., Methods: A prospective cohort study including adult patients after acute COVID-19 pneumonia. Patients were invited or referred to a 3- and 6-month follow-up visits at a large pulmonary institute in a tertiary center. Before each visit, patients completed demographic and clinical questionnaires, pulmonary function tests (PFTs), and chest CT scans., Results: 168 patients were included after completing both visits (medians of 80 and 177 days). Their mean age was 58 ± 15 and 52% recovered from severe or critical COVID-19. Between the two visits, there was no change in DLCOc (mean 73 ± 18 %predicted in both visits) and FVC (mean 90 ± 16 vs. 89 ± 16 %predicted). The COPD assessment tool and modified Medical Research Council scale had inverse correlations with the DLCOc, and similarly did not change between the visits. Occupational exposures were the only factor associated with a change in DLCOc during follow-up (3% decrease, p = 0.04). An improvement in chest CT findings at the second visit was not associated with a change in PFTs., Conclusions: Most clinical variables did not change during a close follow-up schedule in the first six months after acute COVID-19. Such a follow-up plan does not appear necessary and should be personalized to limit excessive costs and resources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and objectives : Vascular calcification is an integral part of atherosclerosis and has been reported to be an independent risk factor for cardiovascular diSsease. Intra Cranial Arterial Calcifications (ICAC) in maintenance hemodialysis (MHD) is highly prevalent. Materials and Methods : The aim of this retrospective study was to assess the predictors and outcomes of ICAC in MHD patients compared to a control group without kidney disease. A blinded neuroradiologist graded ICAC in brain imaging (computerized tomography) of MHD patients. Age- and sex-matched patients with normal kidney function served as the control group. Results : A total of 280 patients were included in the cohort; 140 of them were MHD patients with a mean ICAC score of 2.3 ± 0.2 versus a mean ICAC score of 1.4 ± 0.2 in the control group ( p < 0.01). More than 90% of hemodialysis patients in our study had some degree of ICAC. Lower albumin and higher phosphorus and CRP levels were associated with increased ICACs. The multivariate analysis model for predictors of 1-year mortality demonstrated an increased odds ratio for mortality as the ICAC score increased. Conclusions: ICAC is very prevalent among MHD patients and results not simply from passive deposition of calcium and phosphate but rather from complex and active processes involving inflammation and structural changes in blood vessels. ICAC independently predicted all-cause mortality and may help with risk stratification of this high-risk population.

Background and Objectives: Highly effective vaccines against severe acute respiratory syndrome virus 2 have been developed and administered worldwide. However, protection from coronavirus disease 2019 is not absolute and an optimal vaccination regimen needs to be established. This study assessed the clinical efficacy of the coronavirus disease 2019 vaccine among dialysis patients receiving 3 or 4 doses of vaccine., Design, Setting, Participants, and Measurements: This retrospective study was conducted using the electronic database of Clalit Health Maintenance Organization in Israel. Chronic dialysis patients treated with either hemodialysis or peritoneal dialysis during the coronavirus disease 2019 pandemic were included. We compared clinical outcomes of patients who had received three or four doses of the severe acute respiratory syndrome virus 2 vaccine., Results: This study included 1,030 patients on chronic dialysis, with a mean age of 68 ± 13 years. Among them, 502 patients had received 3 doses of the vaccine and 528 received 4 doses. Severe acute respiratory syndrome virus 2 infection rates, severe COVID-19 that resulted in hospitalizations, COVID-19-related mortality and all-cause mortality rates were lower among chronic dialysis patients who received a fourth dose of vaccine as compared to those who received only 3 doses (after controlling for age, sex and comorbidities). Despite lower mortality rates observed with the Omicron variant, the fourth dose was significantly associated with reduced COVID-19-related mortality (1.7% vs. 3.8%, p = 0.04). Odds ratio for COVID-19-related mortality was 0.44 with 95% CI 0.2-0.98., Conclusions: As seen in the general population and with previous vaccine boosters, the fourth dose of the BNT162b2 vaccine reduced rates of severe COVID-19-related hospitalization and mortality among chronic dialysis patients. Further studies are needed to establish the optimal regimens of vaccination for patients on chronic dialysis., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: COVID-19 vaccinations have a central role in decreasing severe SARS-CoV-2 disease complications. This study investigated the long-term humoral immune response to BNT162b2 vaccine among hemodialysis (HD) versus peritoneal dialysis (PD) patients, and their relative risk for COVID-19 infection., Methods: This prospective, observational study included maintenance HD and PD patients who had received at least two BNT162b2 vaccine doses. Levels of antibodies targeting SARS-CoV-2 spike protein were measured 6 and 12 months after the first vaccine dose, and 2-3 weeks after the third and fourth vaccine doses. Patients were divided according to dialysis modality (HD or PD). Humoral response was evaluated at different time points among different vaccine regimens (two vs. three vs. four doses of vaccine). An adjusted multivariate model was used to assess cumulative risk for SARS-CoV-2 infection., Results: Eighty-seven HD and 36 PD patients were included. Among them, 106 (86%) received at least three vaccine doses. Both HD and PD patients demonstrated marked increases in humoral response 2-3 weeks after the third dose (mean anti-S antibody increased from 452 ± 501 AU/mL to 19,556 ± 14,949 AU/mL, p < 0.001). By 6 months after the third dose, antibody titers had declined significantly (mean anti-S antibody 9841 ± 10,493 AU/mL, p < 0.001). HD patients had higher risk for SARS-CoV-2 infection than PD patients (OR 4.4 [95% CI 1.4-13.6], p = 0.006). In multivariate analysis, the most important predictor for SARS-CoV-2 infection was dialysis modality., Conclusion: This study found a high antibody response rate after the third and fourth doses of BNT162b2 vaccine among dialysis patients. Hemodialysis as dialysis modality is an important predictor of COVID-19 infection, despite similar humoral responses to vaccine in peritoneal dialysis., (© 2023 The Authors. Seminars in Dialysis published by Wiley Periodicals LLC.)

Background and objectives : Dyslipidemia is one of the most important modifiable risk factors in the pathogenesis of cardiovascular disease in the general population, but its importance in the hemodialysis (HD) population is uncertain. Materials and Methods : This retrospective cohort study includes HD patients hospitalized due to acute coronary syndrome (ACS) in the period 2015-2020 with lipid profile data during ACS. A control group with preserved kidney function was matched. Risk factors for 30-day and 1-year mortality were assessed. Results : Among 349 patients included in the analysis, 246 were HD-dependent ("HD group"). HD group patients had higher prevalence of diabetes, hypertension, and heart disease than the control group. At ACS hospitalization, lipid profile and chronic statin treatment were comparable between groups. Odds ratios for 30-day mortality in HD vs. control group was 5.2 (95% CI 1.8-15; p = 0.002) and for 1-year, 3.4 (95% CI 1.9-6.1; p <0.001). LDL and LDL < 70 did not change 30-day and 1-year mortality rates in the HD group ( p = 0.995, 0.823, respectively). However, survival after ACS in HD patients correlated positively with nutritional parameters such as serum albumin (r = 0.368, p < 0.001) and total cholesterol (r = 0.185, p < 0.001), and inversely with the inflammatory markers C-reactive protein (CRP; r = -0.348, p < 0.001) and neutrophils-to-lymphocytes ratio (NLR; r = -0.181, p = 0.019). Multivariate analysis demonstrated that heart failure was the only significant predictor of 1-year mortality (OR 2.8, p = 0.002). LDL < 70 mg/dL at ACS hospitalization did not predict 1-year mortality in the HD group. Conclusions : Despite comparable lipid profiles and statin treatment before and after ACS hospitalization, mortality rates were significantly higher among HD group. While malnutrition-inflammation markers were associated with survival of dialysis patients after ACS, LDL cholesterol was not. Thus, our study results emphasize that better nutritional status and less inflammation are associated with improved survival among HD patients.

Hypersensitivity pneumonitis (HP) is a heterogeneous interstitial lung disease (ILD) that may be difficult to confidently diagnose. Recently, the 2020 ATS/JRS/ALAT HP diagnostic guidelines were published, yet data validating their performance in real-life settings are scarce. We aimed to assess the diagnostic performance of the HP guidelines compared to the gold-standard multidisciplinary discussion (MDD). For this purpose, we included consecutive ILD patients that underwent diagnostic bronchoscopy between 2017 and 2020 in three large medical centers. Four diagnostic factors (antigen exposure history, chest computed tomography pattern, bronchoalveolar lavage lymphocyte count, and histology results) were used to assign guidelines-based HP diagnostic confidence levels for each patient. A sensitivity analysis was performed, with MDD diagnosis as the reference standard. Overall, 213 ILD patients were included, 45 (21%) with an MDD diagnosis of HP. The guidelines' moderate (≥70%) confidence threshold produced optimal performance with 73% sensitivity for HP, 89% specificity, and a J-index of 0.62. The area under the receiver operating characteristic curve (AUC) for a correct guidelines-based diagnosis was 0.86. The guidelines had better performance for non-fibrotic than fibrotic HP (AUC 0.92 vs. 0.82). All diagnostic factors, except bronchoalveolar lavage lymphocyte count, were independent predictors for MDD diagnosis of HP in a multivariate analysis. In conclusion, the HP guidelines exhibited a good diagnostic performance compared to MDD diagnosis in real-life setting.

Background: While it appears not to affect healthy aviators' hearts, there are scarce data regarding the impact of high-performance flights on aviators with mitral valve prolapse (MVP)., Methods: A retrospective, comparative cohort study of military aviators with MVP. Subjects were categorized to either high-performance (jet fighter) or low-performance (transport and helicopter) aviators. The primary outcomes were the rates of mitral interventions and of adverse cardiovascular events since being an aircrew candidate and up to the end of flying career. Additional outcomes were echocardiographic measurements and the cumulative proportion of mitral valve interventions over time., Results: Of 33 male aviators with MVP, 18 were high-performance aviators. On average, follow-up started at age 18.5 years and lasted 27.8 ± 10.1 years. Baseline characteristics were similar between the study groups. Aviators of high-performance aircraft had increased rates of mitral valve surgery (33 % vs. 0, p = 0.021), MVP-related complications (39 % vs. 6.7 %, p = 0.046), and a higher incidence of mitral valve repair over time (p = 0.02). High-performance flight was associated with increased intraventricular septum thickness (IVS, 9.7 mm vs 8.9 mm, p = 0.015) and IVS index (p = 0.026) at the last echocardiographic assessment. High-performance aviators tended to develop worsening severity of mitral regurgitation., Conclusions: High-performance flight may be associated with an increased risk for valvular deterioration and need for mitral surgery in aviators with MVP., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: A third dose of the BNT162b2 SARS-CoV-2 vaccine leads to a significant increase in antibody levels, however, concerns regarding the long-term persistence of this response exist. We assessed the humoral response for one year following vaccination., Methods: A prospective study among immunocompetent healthcare workers (HCW) who received three doses of BNT162b2. anti-spike antibody titers were measured at six predefined timepoints, from before the second vaccine dose, and up to one year afterwards, which is 4-6 months after the third dose. HCW with a history of SARS-CoV-2 infection were excluded., Results: Seventy-six HCW had all the six serological measurements. Antibody titers significantly increased shortly following the third vaccine dose, and while declining, remained higher from all previous measurements for up to six months., Conclusions: A third dose of BNT162b2 leads to a profound humoral response, which remains significantly higher than previous measurements, even after 6 months., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Interstitial lung disease (ILD) evaluation often requires lung biopsy for definite diagnosis. In recent years, transbronchial cryobiopsy (TBCB) emerged as a procedure with higher diagnostic yield than transbronchial forceps biopsy (TBFB), especially for fibrotic ILDs. Nonetheless, studies comparing these modalities in non-fibrotic ILDs and for specific ILD diagnoses are scarce., Objectives: The aim of this study was to evaluate the diagnostic yield and safety of TBCB and TBFB in patients with fibrotic and non-fibrotic ILDs., Method: An observational retrospective multicenter study including patients with ILD diagnosis by multidisciplinary discussion that underwent TBCB or TBFB between 2017 and 2021. Chest CT scans were reviewed by a chest radiologist. Biopsy specimens were categorized as diagnostic (with specific histological pattern), nondiagnostic, or without lung parenchyma. Nondiagnostic samples were reassessed by a second lung pathologist. TBCB and TBFB diagnostic yields were analyzed by multivariate regression. Procedural complications were evaluated as well., Results: 276 patients were included, 116 (42%) underwent TBCB and 160 (58%) TBFB. Fibrotic ILDs were present in 148 patients (54%). TBCB diagnostic yield was 78% and TBFB 48% (adjusted odds ratio [AOR] 4.2, 95% CI: 2.4-7.6, p &lt; 0.01). The diagnostic yield of TBCB was higher than TBFB among patients with fibrotic ILD (AOR 3.8, p &lt; 0.01), non-fibrotic ILD (AOR 5.8, p &lt; 0.01), and across most ILD diagnoses. TBCB was associated with higher risk for significant bleeding (10% vs. 3%, p &lt; 0.01), but similar risk for pneumothorax., Conclusions: Diagnostic yield of TBCB was superior to that of TBFB for both fibrotic and non-fibrotic ILDs, and across most diagnoses., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objective: To review the medical literature regarding chylothorax associated with sarcoidosis., Methods: A literature review of all reported cases of sarcoidosis-associated chylothorax, we included a novel case report to the analysis., Results: Of sixteen cases included in the study, 10 were women (62.5%), mean age 47±17years. In 6 subjects (37.5%) chylothorax was part of the initial presentation of sarcoidosis. Four subjects (25%) additionally suffered from lymphedema and chylous ascites, and one from chylous ascites only. Thoracic lymphadenopathy was reported for 13/16 subjects (81.3%) and lung parenchymal disease in 8/16 (50%). Compression of the thoracic duct was considered as a causative factor in 10 cases (62.5%). One case was attributed to granulomatous pleural inflammation, one to generalized lymphangiectasia, and no specific causative factors were identified in 4 remaining cases (25%). Overall mortality rate was 18.8% (3/16 subjects). Of note, all the subjects treated with corticosteroids survived., Conclusions: Since the association of sarcoidosis with chylothorax is exceedingly rare, alternative etiologies should be pursued even when chylothorax develops in a subject with preexisting sarcoidosis. However, the possibility of sarcoidosis should be entertained when other etiologies for a newly diagnosed chylothorax are ruled out. A multidisciplinary approach is required for optimal management, both for elucidating the diagnosis and for employing therapy, which could be multimodal. A trial of immunosuppressive therapy with corticosteroids should be considered.

Chronic kidney disease is associated with an increased risk for cardiovascular and bleeding events. Data regarding the effectiveness and risks of aspirin therapy for primary prevention in the high-risk group of patients with chronic kidney disease are scant and controversial. This retrospective study included patients with chronic kidney disease. Participants were divided according to aspirin use. Outcomes included non-fatal cardiovascular events, major bleeding events and all-cause mortality. Among 10,303 patients, 2169 met the inclusion criteria and 1818 were included after 1:1 propensity-score matching. Our final cohort included patients with mean age of 73.4 ± 11.6 years, estimated glomerular filtration rate of 31.5 ± 10.5 ml/min/1.73m 2 with follow up of 4.9 ± 1.5 years. There were no significant differences in all-cause mortality and bleeding events (odds ratio = 1.03, confidence interval [0.62, 1.84], p = .58 and odds ratio = 1.09, confidence interval [0.65, 1.72], p = .87 respectively). The incidence of cardiovascular events was higher in aspirin users versus non-users on univariate analysis (p < 0.01) and was comparable after controlling for possible risk-factors (OR = 1.05, CI [0.61, 3.14], p = .85). Chronic aspirin use for primary prevention of cardiovascular disease was not associated with lower mortality, cardiovascular events or increased bleeding among patients with chronic kidney disease. Those results were unexpected and should prompt further research in this field., (© 2022. The Author(s).)

Maintenance hemodialysis (MHD) patients have impaired immunological responses to pathogens and vaccines. In this study, we compared the humoral response to HBV and COVID-19 vaccines in a cohort of MHD patients. Demographic and clinical characteristics of vaccine responders and non-responders were also compared, and the association between the humoral responses to both vaccines was evaluated. The cohort included 94 MHD patients who were vaccinated at least once for HBV and twice for COVID-19. Among the 94 patients, 28 (29.8%) did not develop protective titers to HBV. Hypertension, coronary heart disease, and heart failure were more common in non-responders. Among MHD patients, 85% had positive IgG anti-spike SARS-CoV-2 levels 6 months after two doses of BNT162b2 (Pfizer/Biotech) vaccine. Age and immunosuppressive therapy were the main predictors of humoral response to COVID-19 vaccine. We did not find any association between non-responders to HBV and non-responders to COVID-19 vaccine. There was no difference in IgG anti-spike titers between HBV responders and non-responders (505 ± 644 vs. 504 ± 781, p = 0.9) Our results suggest that reduced humoral response to hepatitis B is not associated with reduced response to COVID-19 vaccine. Different risk-factors were associated with poor immune response to HBV and to COVID-19 vaccines.

Introduction: Arterial calcification is an integral component of active atherosclerosis and is an independent risk factor for cardiovascular disease. Atherosclerosis is a systemic, life-threating disease that may occur at different sites and in various clinical presentations. Intracranial and valvular calcifications are common among dialysis patients and have been associated with poor cardiovascular outcomes. The aim of this study was to assess the clinical impact of valvular and intracranial arterial calcifications on mortality among chronic hemodialysis patients., Methods: A blinded neuroradiologist graded intracranial calcifications (ICC) of all hemodialysis patients who underwent brain computerized tomography (CT) from 2015 to 2017 in our institution. Valvular calcifications were assessed by echocardiography. Only hemodialysis patients with available echocardiography and brain CT were included., Findings: This study included 119 patients (mean age 70.6 ± 12.6 years, 57.1% men, and mean dialysis vintage 25.8 ± 42.6 months). Among the cohort, 19 (16%) had no cardiac or brain calcifications and 65 (54.6%) had both valvular and intracranial calcifications. Considering the patients with no calcification as the reference group yielded adjusted odds ratios for all-cause mortality of 3.68 (95%CI 1.55-8.75) among patients with any brain calcifications, p = 0.002. While valvular calcifications alone did not increase the 1-year mortality rate, ICC was the most important predictor of all-cause 1-year mortality in the study cohort., Discussion: We found an independent association between ICC and the risk of death among hemodialysis patients. Assessing ICC may contribute to the risk stratification of hemodialysis patients. These calcifications are no less important than valvular calcifications., (© 2022 The Authors. Hemodialysis International published by Wiley Periodicals LLC on behalf of International Society for Hemodialysis.)

The CHA 2 DS 2 -VASc score incorporates several comorbidities which have prognostic implications in COVID-19. We assessed whether a modified score (M-R 2 CHA 2 DS 2 -VASc), which includes pre-admission kidney function and male sex, could be used to classify mortality risk among people hospitalized with COVID-19. This retrospective study included adults admitted for COVID-19 between March and December 2020. Pre-admission glomerular filtration rate (GFR) was calculated based on serum creatinine and used for scoring M-R 2 CHA 2 DS 2 -VASc. Participants were categorized according to the M-R 2 CHA 2 DS 2 -VASc categories as 0-1 (low), 2-3 (intermediate), or ≥ 4 (high), and according to initial COVID-19 severity score. The primary outcome was 30-day mortality rates. Secondary outcomes were mortality rates over time, and rates of mechanical ventilation, hemodynamic support, and renal replacement therapy. Eight hundred hospitalizations met the study criteria. Participants were 55% males, average age was 65.2 ± 17 years. There were similar proportions of subjects across the M-R 2 CHA 2 DS 2 -VASc categories. 30-day mortality was higher in those in higher M-R 2 CHA 2 DS 2 -VASc category and with severe or critical COVID-19 at admission. Subjects in the low, intermediate, and high M-R 2 CHA 2 DS 2 -VASc categories had 30-day mortality rates of 4.7%, 17% and 31%, respectively (p < 0.001). Higher category was also associated with increased need for mechanical ventilation and renal replacement therapy. All-cause 90-day mortality remained significantly associated with M-R 2 CHA 2 DS 2 -VASc. The M-R 2 CHA 2 DS 2 -VASc score is associated with 30-day mortality rates among patients hospitalized with COVID-19, and adds predictive value when combined with initial COVID-19 severity., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Background: SARS-CoV-2 is a novel human pathogen causing Coronavirus Disease 2019 that has caused widespread global mortality and morbidity. Since health workers in Israel were among the first to be vaccinated, we had a unique opportunity to investigate the post-vaccination level of IgG anti-S levels antibodies (Abs) and their dynamics by demographic and professional factors. Methods: Prospective Serological Survey during December 2020−August 2021 at Barzilai Medical Center among 458 health care workers (HCW) followed for 6 months after the second BNT162b2 vaccine dose. Results: Antibody levels before the second dose, and 30, 90 and 180 days after were 57.1 ± 29.2, 223 ± 70.2, 172.8 ± 73.3 and 166.4 ± 100.7 AU/mL, respectively. From GEE analysis, females had higher Abs levels (β = 26.37 AU/mL, p = 0.002). Age was negatively associated with Abs, with a 1.17 AU/mL decrease for each additional year (p < 0.001). Direct contact with patients was associated with lower Abs by 25.02 AU/mL (p = 0.009) compared to working with no such contact. The average decline rate overall for the study period was 3.0 ± 2.9 AU/mL per week without differences by demographic parameters and was faster during the first 3 months after vaccination than in the subsequent 3 months. Conclusions: All demographic groups experienced a decline in Abs over time, faster during the first 3 months. Findings of overall Abs lower in males, workers with direct contact with patients, and older workers, should be considered for policy-making about choosing priority populations for additional vaccine doses in hospital settings.

Introduction: Breakthrough COVID-19 may occur in vaccinated people, and may result from declining vaccine effectiveness or highly transmittable SARS-CoV-2 variants, such as the B.167.2 (delta) variant. We investigated risk factors and outcomes for infection with the delta variant among vaccinated hemodialysis patients., Methods: Patients on maintenance hemodialysis who received two doses of the BNT162b2 (Pfizer-BioNTech) vaccine were analysed according to having developed COVID-19 (study group) or not (control group), in a retrospective, observational, comparative study. We compared risk-factors for developing breakthrough COVID-19 and assessed clinical outcomes, including 30-day mortality rates., Results: Twenty-four cases of breakthrough SARS-CoV-2 infection were compared to 91 controls without infection. Breakthrough infection was associated with chronic immunosuppressive treatment, hematological malignancies, and low antibody levels against SARS-CoV-2 spike protein. All COVID-19 cases occurred at least 5 months after vaccination, and most were caused by the B.1.617.2 variant (at least 23/24 cases). COVID-19 was categorized as severe or critical disease in 11/24 patients (46%), and 54% required hospitalization and COVID-19-directed treatment. The source of infection was nosocomial in 6/24 cases (25%), and healthcare-related in 3/24 (12.5%). Mortality rate was 21%. Overall mortality was significantly higher in patients who developed COVID-19 than in controls (odds ratio for all-cause mortality 7.6, 95% CI 1.4-41, p = 0.002)., Conclusions: Breakthrough COVID-19 with the B.1.617.2 variant can occur in vaccinated hemodialysis patients and is associated with immunosuppression and weaker humoral response to vaccination. Infections may be nosocomial and result in significant morbidity and mortality., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Introduction: While there is evidence of the presence of the coronavirus in the kidneys and resultant acute kidney injury (AKI), information on the effect of chronic kidney disease (CKD) on COVID-19 outcomes and its pathogenesis is currently lacking., Methods: This retrospective, observational study evaluated the outcomes of all consecutive patients hospitalized during COVID-19 outbreaks in Meir Medical Center. Serum creatinine level was assessed before hospitalization ("baseline serum creatinine") and at admission, as well as minimum and maximum serum creatinine levels during hospitalization., Results: Among 658 patients, 152 had eGFR < 60 ml/min (termed the CKD group), 506 patients served as controls. Patients in the CKD group were older, with higher prevalence of hypertension, diabetes mellitus and atherosclerosis. Disease severity and clinical presentation of CKD group were comparable to that of control group. Odds ratio for AKI was 5.8 (95%CI 3.8-8.7; p < 0.001) in CKD group vs. control group and 3.4 (95%CI 1.1-10.8) for renal replacement therapy (p < 0.026). Among the CKD group, 32.2% died after COVID-19 infection versus 14.8% of the controls (p < 0.001). Mortality increased as CKD stage increased (14.8% in controls, 29.6% in CKD stage 3, and 39.3% in CKD stages 4 and 5, p < 0.001)., Conclusion: Despite comparable disease severity at presentation, patients with CKD had significantly more AKI events and required more renal replacement therapy during hospitalization than control patients did. Mortality increased as CKD stage increased., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Background: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a frequently used method for obtaining tissue samples for the diagnosis of various respiratory conditions, including lung cancer staging. In most cases, EBUS-TBNA is performed under moderate sedation (MS). However, in cases of respiratory compromised patients, if this procedure is performed, it is conducted under general anesthesia (GA)., Objectives: To assess the diagnostic yield of EBUS-TBNA among respiratory compromised patients., Methods: Data of consecutive patients (n=191) who underwent EBUS-TBNA at our medical center between January 2019 and December 2019 were retrospectively analyzed. Respiratory compromised patients underwent GA and patients without respiratory compromise were mostly moderately sedated (MS). Characteristics, diagnostic yield, and complication rates were compared., Results: Diagnostic yield was similar between the two sedation modes (89% in GA group and 78% in the MS group, P = 0.11). The number of total samples obtained per procedure was significantly higher in the GA vs. the MS group (4.1 ± 2.1 vs. 2.1 ± 1.33, P < 0.01). The overall complication rate was 13% and 20.9% in the GA vs. the MS groups, respectively (P = 0.14), with the most frequent complication being minor bleeding. Interestingly, while the number of brushings, bronchoalveolar lavage, and endobronchial biopsy were similar, the percent of subjects who underwent transbronchial biopsy was significantly higher in the GA group (49% vs. 24.2%, P < 0.01)., Conclusions: EBUS-TBNA performed under GA among respiratory compromised patients is safe and has similar diagnostic yield to that of patients without a respiratory compromise.

Introduction: Coronavirus disease is associated with increased morbidity and mortality in maintenance hemodialysis (MHD) patients. Recent breakthrough infection in vaccinated people has led some authorities to recommend a booster dose for patients fully vaccinated 5-8 months ago. We aimed to assess the humoral response of MHD patients following a booster dose with the BNT162b2 vaccine., Methods: The study included 102 MHD patients vaccinated with 2 doses of the BNT162b2 (Pfizer-BioNTech) vaccine. A third dose (booster) was recommended to all MHD patients in our center and was given to those who opted to receive it, resulting in a booster group and a control group that did not receive the booster. Previous exposure was excluded by testing for the presence of the anti-nucleocapsid antibody (SARS-CoV-2) or positive PCR. We assessed the humoral response before and after the booster dose., Results: Of 66 patients in the booster group, 65 patients (98.5%) developed a positive antibody response, from 472.7 ± 749.5 to 16,336.8 ± 15,397.3, as compared to a sustained decrease in the control group (695.7 ± 642.7 to 383.6 ± 298.6), p < 0.0001. No significant adverse effects were reported. Prior antibody titers were positively correlated to IgG levels following the booster dose. There was a significant association between malnutrition-inflammation markers and the humoral response., Conclusions: Almost all MHD patients developed a substantial humoral response following the booster dose, which was significantly higher than levels reported for MHD patients following administration of 2 doses alone. Further studies and observations are needed to determine the exact timing and dosing schedule., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

The optimal SARS-CoV-2 vaccination schedule in dialysis patients and the potential need for a fourth vaccine dose are debatable. We prospectively assessed the humoral responses to three and four doses of BNT162b2 among dialysis patients. The study included 106 dialysis patients; 60 (56.6%) and 46 (43.4%) received 3 and 4 vaccine doses, respectively. Anti-spike (anti-S) antibody titers significantly increased after the third vaccine dose, followed by a decline, yet still remained higher than all previous measurements. The fourth vaccine dose led to another profound rise in anti-S titers. The absolute increase following the fourth dose correlated with response to the third dose. Infection risk however was similar between patients vaccinated with three or four doses., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that causes scarring of the lungs. The disease is associated with the usual interstitial pneumonia pattern, which was not yet fully recapitulated by an animal model. Therefore, the disease is considered 'human specific'. miRNA-608 is a primate specific miRNA with many potential targets, such CdC42 and Interlukin-6 (IL-6) that were previously implicated in IPF pathology., Objective: To test miR-608 expression and its targets in IPF patient samples., Methods: RNA was extracted from Formalin fixed paraffin embedded tissue sections (N = 18). miRNA-608 and Cdc42 and IL-6 levels were analyzed by qPCR. Acetylcholinesterase (AChE) is another target of miRNA-608. Its' rs17228616 allele has a single-nucleotide polymorphism causing weakened miR-608 interaction (C2098A). Thus, DNA was extracted from whole blood samples from 56 subjects with fibrosing interstitial lung disease and this region was sequenced for assessment of rs17228616 allele polymorphism., Results: miR-608 is significantly overexpressed in IPF samples in comparison with controls (p < 0.05). Cdc42 and IL-6 levels were lower in the IPF patient samples compared with control samples (p < 0.001 and p < 0.05, respectively). The frequency of the rs17228616 minor A-allele was 17/56 (30.4%) with all patients being heterozygous. This result is significant vs. the published Israeli cohort of healthy individuals, which reported 17% prevalence of this allele in healthy control volunteers (p = 0.01, OR = 2.1, CI 95% [1.19-3.9])., Conclusion: miR-608 is overexpressed in IPF patients. While the exact mechanism remains to be discovered, it could potentially promote fibrotic disease.