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Abstract Background Right middle lobe (RML) syndrome is a recurrent or chronic obstruction of the RML causing atelectasis of the right middle lobe due to mechanical and nonmechanical etiologies. The consequences of untreated RML syndrome range from chronic cough to post‐obstructive pneumonia and bronchiectasis. We report here our bronchoscopy experience in patients with RML syndrome. Methods We conducted a retrospective study of adult patients who underwent bronchoscopy for RML syndrome at Rabin Medical Center from 2008 through 2022. Demographic data and medical history, bronchoscopy findings and procedures, and follow‐up results were collected. Results A total of 66 patients (57.6% male, mean age 63 ± 13 years) underwent bronchoscopy for RML syndrome during the study period. Bronchoscopy revealed a mechanical etiology in 49 (74.2%) cases, including endobronchial mass (21, 31.8%) and external compression (7, 10.6%). Malignancy was identified in 20 (30.3%) cases. In 62 patients (93.9%), the bronchoscopy resulted in partial or complete reopening of the RML bronchus. The therapeutic bronchoscopic procedures were balloon dilatation (19), laser ablation (17), mechanical debridement (12), endobronchial stent insertion (11), and cryoablation (6). Conclusions Malignancy was identified as the etiology of RML syndrome in approximately 25% of cases, suggesting bronchoscopy should be performed in every case of RML atelectasis. To our knowledge, this is the first reported series of endobronchial stenting of the RML bronchus in the context of RML syndrome.

Background. DISH is a systemic condition characterized by ligamentous ossification of at least four contiguous thoracic vertebrae. Prior studies have shown an association between DISH and cardiovascular morbidity. Objective. To investigate the association between DISH, cardiovascular risk factors, and MACE (myocardial infarction, ischemic stroke, and CV mortality) in patients who underwent coronary angiography between 5/2014 and 4/2015 in Ha’Emek Medical Center through 7 years of retrospective follow-up. Methods. Two cohorts were studied retrospectively and were defined according to the status of the coronary artery as diagnosed in angiography at enrolment (obstructive vs. nonobstructive coronary heart disease). For the retrospective analysis, we added the status of DISH (according to Resnick’s criteria) and defined four cohorts as follows: CHD and DISH (group 1), CHD and no DISH (group 2), no CHD and DISH (group 3), and no CHD and no DISH (group 4). The four groups were followed up retrospectively for a median period of 7 years. Association between DISH and cardiovascular outcomes was studied. Results. 198 patients were included in the study. 100 of them had CHD, and 98 were without significant CHD. At enrolment, DISH was present in 44 patients of CHD group and in 35 of non-CHD (p=0.28 age and sex adjusted). Through the follow-up period, the presence of DISH was not found to be associated with death from any cause, cardiovascular death, ischemic stroke, and MACE. Within the group of non-CHD, there were two additional MI events in DISH (group 3) which was found to be statistically significant. Conclusion. Among patients with high burden of cardiovascular risk factors undergoing coronary angiography, the presence of DISH was not associated with an increased incidence of MACE.

Abstract Background Adequate tissue sampling is fundamental for establishing a definitive diagnosis, assessing prognosis and tailoring therapy. Each of the methods for obtaining tissue (e.g., endoscopic, image guidance and surgical biopsies) results in a different diagnostic yield and complication rate profile. Objectives Present feasibility, and assess safety and efficacy of freehand transthoracic ultrasound‐guided core‐needle biopsies (USGNB) of thoracic lesions performed by pulmonologist. Methods A retrospective analysis study of ultrasound‐guided core‐needle biopsies of thoracic lesions performed at the Pulmonary Institute of Rabin Medical Center was conducted from September 2020 to October 2021. All core‐needle biopsies were performed under local anesthesia with guidance of Mindray TE7 2019 US system. Procedural variables including complications and pathological diagnostic yield were the primary end point. IRB 0671‐21‐RMC. Results In total 91 biopsy procedures were analyzed in38 females and 53 males, average age 71.1 years. Twenty‐three (25.3%) cases were lung lesions, 7 (7.7%) – mediastinal, 13 (14.3%) – chest wall, 27 (29.7%) – pleural, and 21 (23.1%) supraclavicular lesions. Average lesion size was 51.6 mm, the largest in the mediastinum and the smallest in supraclavicular locations (97.7mm and 28.0 mm, respectively). Overall pathological diagnostic yield was 90%, highest success in chest wall (100%) and lowest in mediastinal biopsies (71.4%). We had only one complication –hemothorax resolved by chest tube drainage‐ accounting for only 1.1% complication rate. Conclusion Safety and efficacy were demonstrated in freehand US‐guided core‐needle biopsy of thoracic lesions performed by pulmonologists. We suggest thoracic ultrasound and USG‐CNB be part of training and clinical practice in interventional pulmonology.

Abstract Background The diagnostic yield of endobronchial ultrasound‐transbronchial needle aspiration (EBUS‐TBNA) from mediastinal lymph nodes ranges from 66%–89%. However, in many cases cytologic material is not sufficient for full molecular evaluation. A novel method of transcarinal cryobiopsy aims to provide bronchoscopically obtained, larger specimen samples from mediastinal lymph nodes. We aimed to assess the efficacy and safety of transcarinal EBUS‐guided lymph node cryobiopsy. Methods Patients referred for EBUS‐TBNA, based on abnormal mediastinal clinical and radiographic findings, were enrolled into this prospective interventional study between July 2020 and August 2021. All EBUS‐TBNA procedures were performed using ProCore 22G needle (Cook Medical) to create, both a transcarinal tract for the cryoprobe and to obtain TBNA samples. For EBUS guided transcarinal cryobiopsy, we used flexible 1.1 mm or 1.7 mm cryoprobe inserted into the working channel of the EBUS scope and into the target subcarinal lymph node. Results Twenty‐four patients with male predominance 2:1 and mean age of 60.12 ± 10.16 years were enrolled. All target lymph nodes had hypoechoic, homogenic consistency with demarcated borders, without central structures. Cryobiopsy provided pathological diagnosis in 20 cases (83.33%), with 1.1 mm cryoprobe in 14 and with 1.7 mm cryoprobe in 6 cases. In one case each, pathology was provided by TBNA or by cryoprobe alone. No immediate or late complications were encountered during the procedures. Conclusion Transcarinal EBUS guided lymph node cryobiopsy following EBUS‐TBNA proved to be efficient with a high diagnostic yield and can be considered safe, because no immediate or late complications occurred.

Abstract Background The LungVision system is a novel augmented‐fluoroscopy‐based real‐time navigation and guidance technology for bronchoscopy that can be integrated with any standard biopsy tool, including the cryoprobe, to enable real‐time visualization and localization of pulmonary nodules. Objectives To evaluate the diagnostic yield and safety among patients undergoing peripheral pulmonary nodule biopsy with the LungVision system. Methods This prospective, single‐center study was conducted at Rabin Medical Center in Israel. All patients that underwent peripheral pulmonary nodule biopsy with the LungVision system from January 2016 to August 2020 were included. All procedures were performed under moderate sedation. The primary outcome was tissue diagnosis by either identification of malignant cells or benign diagnosis. Secondary outcomes were safety and the added value of cryobiopsy. Results Sixty‐three procedures were performed during the study period. Median lesion size (interquartile range) was 25.0 mm (18–28 mm). The diagnostic yield overall was 27/33 (81.8%) and for lesions smaller than 20 mm was 13/18 (72.2%). In nine cases the transbronchial cryobiopsy showed tissue with malignant cells that were not found in any other biopsy material taken with other sampling tools. One patient was treated with a chest tube for a pneumothorax. No other major complications were reported. Conclusions The LungVision system showed good feasibility and safety for peripheral pulmonary nodule biopsy. The system is compatible with all biopsy tools, including the cryoprobe. Randomized controlled trials are needed to accurately ascertain its diagnostic yield.

Abstract Cell therapy using induced pluripotent stem cell‐derived neurons is considered a promising approach to regenerate the injured spinal cord (SC). However, the scar formed at the chronic phase is not a permissive microenvironment for cell or biomaterial engraftment or for tissue assembly. Engineering of a functional human neuronal network is now reported by mimicking the embryonic development of the SC in a 3D dynamic biomaterial‐based microenvironment. Throughout the in vitro cultivation stage, the system's components have a synergistic effect, providing appropriate cues for SC neurogenesis. While the initial biomaterial supported efficient cell differentiation in 3D, the cells remodeled it to provide an inductive microenvironment for the assembly of functional SC implants. The engineered tissues are characterized for morphology and function, and their therapeutic potential is investigated, revealing improved structural and functional outcomes after acute and chronic SC injuries. Such technology is envisioned to be translated to the clinic to rewire human injured SC.

Background. Carboxyhemoglobin (COHb) is a complex formed by the binding of carbon monoxide to hemoglobin in blood. Higher COHb levels have been associated with poor prognosis in a variety of pulmonary disorders. However, little is known regarding the prognostic significance of COHb among individuals with chronic obstructive pulmonary disease (COPD) exacerbation. Methods. In a retrospective study, we evaluated associations of venous COHb levels on hospital admission with the need for invasive mechanical ventilation, in-hospital mortality, and rehospitalization, among 300 patients hospitalized for COPD exacerbation in internal medical wards. Results. Rates of in-hospital death and 1-year recurrent hospitalizations were 11.0% and 59.6%, respectively. COHb levels were not significantly associated with in-hospital mortality (OR = 0.82, P=0.25, 95% CI 0.59–1.15) or with 1-year rehospitalizations (OR = 0.91, P=0.18, 95% CI 0.79–1.04). The mean COHb level did not differ significantly between patients who needed invasive mechanical ventilation and those who were not invasively mechanically ventilated during the current hospitalization (2.01 ± 1.42% vs. 2.19 ± 1.68%, P=0.49). Conclusions. Among patients hospitalized with COPD exacerbation in internal medicine wards, COHb levels on admission were not associated with invasive mechanical ventilation treatment, rehospitalizations, or mortality.

Abstract Background Exercise training (ET) has beneficial effects on multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the intensity‐dependent effects of ET on the systemic immune system in EAE remain undefined. Objective (1) To compare the systemic immune modulatory effects of moderate versus high‐intensity ET protocols in protecting against development of EAE; (2) To investigate whether ET affects autoimmunity selectively, or causes general immunosuppression. Methods Healthy mice performed moderate or high‐intensity treadmill running programs. Proteolipid protein (PLP)‐induced transfer EAE was utilized to examine ET effects specifically on the systemic immune system. Lymph node (LN)‐T cells from trained versus sedentary donor mice were transferred to naïve recipients and EAE severity was assessed, by clinical assessment and histopathological analysis. LN‐T cells derived from donor trained versus sedentary PLP‐immunized mice were analyzed in vitro for proliferation assays by flow cytometry analysis and cytokine and chemokine receptor gene expression using real‐time PCR. T cell‐dependent immune responses of trained versus sedentary mice to the nonautoantigen ovalbumin and susceptibility to Escherichia coli‐induced acute peritonitis were examined. Results High‐intensity training in healthy donor mice induced significantly greater inhibition than moderate‐intensity training on proliferation and generation of encephalitogenic T cells in response to PLP‐immunization, and on EAE severity upon their transfer into recipient mice. High‐intensity training also inhibited LN‐T cell proliferation in response to ovalbumin immunization. E. coli bacterial counts and dissemination were not affected by training. Interpretation High‐intensity training induces superior effects in preventing autoimmunity in EAE, but does not alter immune responses to E. coli infection.

Abstract Generation of thick vascularized tissues that fully match the patient still remains an unmet challenge in cardiac tissue engineering. Here, a simple approach to 3D‐print thick, vascularized, and perfusable cardiac patches that completely match the immunological, cellular, biochemical, and anatomical properties of the patient is reported. To this end, a biopsy of an omental tissue is taken from patients. While the cells are reprogrammed to become pluripotent stem cells, and differentiated to cardiomyocytes and endothelial cells, the extracellular matrix is processed into a personalized hydrogel. Following, the two cell types are separately combined with hydrogels to form bioinks for the parenchymal cardiac tissue and blood vessels. The ability to print functional vascularized patches according to the patient's anatomy is demonstrated. Blood vessel architecture is further improved by mathematical modeling of oxygen transfer. The structure and function of the patches are studied in vitro, and cardiac cell morphology is assessed after transplantation, revealing elongated cardiomyocytes with massive actinin striation. Finally, as a proof of concept, cellularized human hearts with a natural architecture are printed. These results demonstrate the potential of the approach for engineering personalized tissues and organs, or for drug screening in an appropriate anatomical structure and patient‐specific biochemical microenvironment.