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Ariel Melloul,1,2 Ophir Freund,1,2 Boaz Tiran,1,2 Tal Moshe Perluk,1,2 Netanel Golan,1,2 Eyal Kleinhendler,1,2 Evgeni Gershman,1,2 Avraham Unterman,1,2 Avishay Elis,2,3 Amir Bar-Shai1,2 1The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; 2Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Internal Medicine C, Rabin Medical Center, Petach Tikva, IsraelCorrespondence: Ophir Freund, The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel, Tel +972-545-305648, Email ophir068@gmail.comPurpose: Exacerbations of COPD (ECOPD) significantly impact disease progression and mortality. Visiting a respiratory specialist (RS) in proximity to the exacerbation may lead to prompt treatment and improved outcomes. We aimed to evaluate the association between an RS visit 30-days before admission and exacerbation outcomes.Patients and methods: The prospective study included subjects that were hospitalized with ECOPD between 2017 and 2019 in 13 medical centers. Pre-admission, in-hospital, and 30-day outcomes were assessed and compared between patients with and without a 30-day RS visit, using propensity score matching. A sub-group analysis was performed based on the reason for the RS visit (emergent vs regular follow-up).Results: Three hundred and forty-four subjects were included, and 105 (31%) had pre-admission RS visit (RS group). Before matching, indicators of severe COPD were prevalent in the RS group, while after matching there were no differences. RS visits were associated with pre-hospital initiation of short acting bronchodilators (50% vs 36%), antibiotics (30% vs 17%), and systemic steroids (38% vs 22%). The RS group had longer duration between first symptoms to hospital arrival (median 5 vs 3 days, p < 0.01) and shorter hospital length-of-stay (median 4 vs 5 days, p = 0.04). In-hospital and 30-days outcomes were similar between the groups. However, a non-emergent pre-hospital RS visit was associated with improved in-hospital and 30-day outcomes.Conclusion: Routine RS visits could lead to correct and early treatment for ECOPD with a potential for improved outcomes. These findings highlight the need for available specialists and higher awareness.Keywords: clinic, pulmonologist, bronchodilators, admission, diagnosis

Udi Shapira,1 Mor Krubiner,1 Michal Ehrenwald,1 Itzhak Shapira,1 David Zeltser,1 Shlomo Berliner,1 Ori Rogowski,1 Shani Shenhar-Tsarfaty,1 Amir Bar-Shai2 1Department of Internal Medicine C, D and E, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 2Division of Pulmonary Medicine, Barzilai Medical Center, Faculty of Health Sciences, Ben-Gurion University, Ashkelon, Israel Background: While chronic respiratory diseases are among the leading causes of mortality and morbidity worldwide, little is known about the effect of blood eosinophil levels on lung function trajectories among healthy individuals.Methods: We analyzed data of apparently healthy individuals (n=18,089) recruited for the Tel Aviv Medical Center Inflammation Survey. Blood eosinophil levels were compared between participants with normal and those with abnormal lung function. Multivariate regression was used to assess the OR of forced expiratory volume in 1 second (FEV1) deterioration according to baseline eosinophils in subjects with normal lung function (n=4,141) during a follow-up period of 4 years.Results: Participants with an abnormal, as opposed to a normal, pulmonary function test (PFT) (n=1,832, 10.1%) had significantly higher eosinophil levels, expressed as a percentage or count (2.99%±2.00% compared to 2.67%±1.88% and 0.2210e3/µL±0.163/µL compared to 0.1810e3/µL±0.183/µL, respectively; P

Avital Avriel,1 Dmitry Rozenberg,2 Yael Raviv,1 Dov Heimer,1 Amir Bar-Shai,3 Rachel Gavish,4 Jony Sheynin,5,6 Amos Douvdevani6 1Department of Medicine, Pulmonology Institute, Soroka Medical Center, Ben-Gurion University, Beer-Sheva, Israel; 2Division of Respirology, Department of Medicine, University Health Network, University of Toronto, Toronto, ON, Canada; 3Department of Medicine, Pulmonology Institute, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, 4Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel; 5Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA; 6Department of Clinical Biochemistry, Faculty of Health Sciences, Soroka Medical Center, Ben-Gurion University, Beer-Sheva, Israel Background: Chronic obstructive pulmonary disease exacerbations (COPDEs) are associated with increased morbidity and mortality. Cell-free DNA (cfDNA) is a novel biomarker associated with clinical outcomes in several disease states but has not been studied in COPD. The objectives of this study were to assess cfDNA levels during a COPDE, to evaluate the association of cfDNA with clinical parameters and to explore the prognostic implications of cfDNA levels on long-term survival.Methods: This was an observational study that assessed cfDNA levels in patients admitted to hospital for a COPDE. Plasma cfDNA levels of COPDE patients were compared to those of matched stable COPD patients and healthy controls. Multivariable and Cox regression analyses were used to assess the association of cfDNA levels with blood gas parameters and long-term survival.Results: A total of 62 patients (46 males, forced expiratory volume in 1 second [FEV1] 38%±13%) were included. The median cfDNA levels on admission for COPDE patients was 1,634 ng/mL (interquartile range [IQR] 1,016–2,319) compared to 781 ng/mL (IQR 523–855) for stable COPD patients, matched for age and disease severity, and 352 ng/mL (IQR 209–636) for healthy controls (P

Abstract Background Patient-reported interstitial lung disease (ILD) questionnaires are commonly used for the evaluation of ILD patients. However, research to test their performance is scarce. Methods This study aimed to assess the performance of the Chest Questionnaire in consecutive ILD patients presenting to a tertiary ILD center. The results of Chest Questionnaires routinely filled by patients were analyzed together with clinical and demographic data retrieved from the patients’ medical records. The ability of each questionnaire item to detect positive findings, such as environmental and occupational exposures, was examined relative to any additional findings detected by physician-acquired history. History was obtained by an experienced ILD pulmonologist who had access to the results of the questionnaire during the clinic visit. Results The final cohort for analysis included 62 patients. Shortness of breath frequency and duration were the questionnaire items with the lowest probability of being filled out by patients. The questionnaire performed well in identifying 96.2% of patients with a positive family history and 90.9% of patients with occupational exposures. However, exposures to mold or birds were frequently missed, self-reported by only 53.1% of exposed patients. Questionnaire’s performance was also lower for other exposures associated with ILD (48.3%). An ILD-related exposure was less likely to be identified by the questionnaire in males (p = 0.03), while age had no such effect. Conclusions The Chest Questionnaire performed well in several domains, while failing to detect some relevant exposures. Therefore, its use should be accompanied by careful history taking by the physician.

Background: Over the last few decades, the efficacy of biological therapies for COPD has been evaluated by different randomized controlled trials (RCTs). Still, the evaluation of real-world data and patient-reported outcome measures (PROMs) have not been performed in this field before. In the current work, we present a systematic literature review of the real-world data and PROMs of biological treatments for COPD. Methods: Three large databases (MEDLINE/PubMed, Scopus, and ScienceDirect) were utilized for the systematic literature review. Clinical studies (RCT, cohorts, case series/reports) assessing patients with COPD treated by any biological therapy were included. Results: The review resulted in twelve eligible studies (nine randomized controlled trials and three "real-world" case series/reports). The evaluation of PROMs in the included studies was mainly limited to the severity and burden of respiratory symptoms. Most biological therapies were associated with improved PROMs compared to the baseline, although not for the placebo. Dupilumab was the only biologic therapy with proven efficacy in RCT for both objective and subjective measures. One prior study reported patients' self-perceived drug effects, and none evaluated patients' perceived disease status. Only 25 patients were assessed in a real-world setting for all biologic therapies combined. Real-world data were retrospective in the form of case reports or series. Conclusions: There are limited data on patients' experience with biological therapies for COPD. While real-world data and PROMs are missing, biases such as a placebo effect must be considered, requiring their incorporation with objective outcomes from prospective controlled trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic graft vs. host disease (cGVHD) is a major complication that appears after allogeneic hematopoietic cell transplantation. As result, this has a significant and detrimental impact on both the quality of life and survival of patients after transplantation. In recent years, three novel therapies have been approved by the FDA for the management of cGVHD. To date, previous studies have not analyzed the effect of these novel drugs on other health-associated conditions such as metabolic syndrome, bone health, return to employment, mental health, and other para-medical outcomes. In this study, during three different time periods, we aimed to assess and highlight the association between novel advanced treatments for cGVHD and their impact on the quality of life of patients after allogeneic transplantation. Objectives—chronic graft vs. host disease (cGVHD) is associated with substantial morbidity and mortality. We aimed to analyze advances in treatment strategy and outcomes during the last decade due to the incorporation of novel immunosuppressive therapy (IST) drugs in the armamentarium. Methods—we retrospectively analyzed all patients > 18 years with cGVHD after their first hematopoietic cell transplantation (HCT) between 2012 and 2020 (n = 91), divided into three treatment periods: 2012–2014, 2015–2017, and 2018–2020 (groups 1, 2, and 3, respectively). Results—mean cumulative steroid dose and dose/total cGVHD-treatment days was lower in groups 2–3 compared to 1 (p = 0.008 and p = 0.042, respectively). The median IST-free survival was 79 (95%CI54–94) months, with more patients in group 3 (47% (95%CI 25–54%) discontinuing IST at 3 years, p = 0.1). Groups 2–3 compared to 1 had better glycemic control (p < 0.01), higher bone density (p = 0.06), and fewer cardiovascular events. The number of admissions/patient dropped from 0.7/year in group 1 to 0.24/year and 0.36/year in groups 2–3, respectively (p = 0.36). Employment reintegration was higher in groups 2–3 compared with 1 (p = 0.05) and so was earlier return to work (p = 0.01). There were no differences in survival outcomes. Conclusions—the incorporation of novel agents appears to be associated with reduced overall steroid burden, improved cGVHD control, and fewer long-term side effects. [ABSTRACT FROM AUTHOR]

Abstract Extracellular matrix (ECM) provides structural support for cell growth, attachments and proliferation, which greatly impact cell fate. Marine macroalgae species Ulva sp. and Cladophora sp. were selected for their structural variations, porous and fibrous respectively, and evaluated as alternative ECM candidates. Decellularization–recellularization approach was used to fabricate seaweed cellulose-based scaffolds for in-vitro mammalian cell growth. Both scaffolds were confirmed nontoxic to fibroblasts, indicated by high viability for up to 40 days in culture. Each seaweed cellulose structure demonstrated distinct impact on cell behavior and proliferation rates. The Cladophora sp. scaffold promoted elongated cells spreading along its fibers’ axis, and a gradual linear cell growth, while the Ulva sp. porous surface, facilitated rapid cell growth in all directions, reaching saturation at week 3. As such, seaweed-cellulose is an environmentally, biocompatible novel biomaterial, with structural variations that hold a great potential for diverse biomedical applications, while promoting aquaculture and ecological agenda.

During recent decades, bumble bees (Bombus terrestris) have continuously expanded their range in the Mediterranean climate regions of Israel. To assess their potential effects on local bee communities, we monitored their diurnal and seasonal activity patterns, as well as those of native bee species in the Judean Hills. We found that all bee species tend to visit pollen-providing flowers at earlier times compared to nectar-providing flowers. Bumble bees and honey bees start foraging at earlier times and colder temperatures compared to other species of bees. This means that the two species of commercially managed social bees are potentially depleting much of the pollen, which is typically non-replenished, before most local species arrive to gather it. Taking into consideration the long activity season of bumble bees in the Judean hills, their ability to forage at the low temperatures of the early morning, and their capacity to collect pollen at early hours in the dry Mediterranean climate, feral and range-expanding bumble bees potentially pose a significant competitive pressure on native bee fauna. Their effects on local bees can further modify pollination networks, and lead to changes in the local flora.

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.

Background The diagnosis of pulmonary arterial hypertension requires right heart catheterization (RHC) which is typically performed via proximal venous access (PVA). Antecubital venous access (AVA) is an alternative approach for RHC that can minimize complications, decrease procedural duration and allow for immediate patient recovery. A direct comparison between the two procedures in patients with pulmonary hypertension (PH) is lacking. Objectives To determine the feasibility, safety, and adoption rates of AVA-RHC as compared with ultrasound-guided PVA in a subpopulation of patients with PH. Methods All patients who underwent RHC for evaluation of PH between December 2014 and March 2017 at a single large academic medical center were included in this study. Demographic, procedural and outcomes data were retrieved from the medical records. Results In total, 159 RHC were included (124 AVA, 35 PVA). The duration of RHC was significantly shorter in the AVA compared with PVA group (53 (IQR 38–70) vs. 80 (IQR 56–95) min, respectively, p

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. [ABSTRACT FROM AUTHOR]