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Barak Pertzov,1,2 Maysaa Soliman,2 Yael Shostak,1,2 Moshe Heching,1,2 Dror Rosengarten,1,2 Gabriel Izbicki,3,4,* Mordechai Reuven Kramer1,2,* 1Pulmonary Division, Rabin Medical Center, Petach Tikva, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Pulmonary Institute, Shaare Zedek Medical Center, Jerusalem, Israel; 4Hebrew University-Hadassah Medical School, Jerusalem, Israel*These authors contributed equally to this workCorrespondence: Barak PertzovPulmonary Division, Rabin Medical Center, Petach Tikva, IsraelTel +972-3-9377221/3Fax +972-3-9242091Email pertzovb@gmail.comBackground: Lung volume reduction with endobronchial coils treatment (ECT), for patients with severe emphysema, has shown modest improvement in exercise capacity and lung functions in clinical trials, yet the benefit of this procedure is still unclear.Methods: We conducted a multicenter retrospective cohort study including all patients who underwent ECT in Israel and a propensity score matched control group of patients with chronic obstructive pulmonary disease (COPD) that were treated with usual care. The primary outcome was six-minute walk test distance (6MWTD), secondary outcomes were lung function tests and patient survival.Results: Overall, 46 patients were included in the ECT group. Their mean 6MWTD at baseline and at 6 and at 24 months post procedure was 331.0± 101.4, 372.9± 76.8 and 338.8± 104.8, respectively (overall P=0.04, pairwise comparison: baseline to 6 months (P=0.1), baseline to 24 months (P=1.0)). Mean FEV1 values at baseline and at 6 and at 24 months post procedure were 0.86± 0.38, 0.92± 0.37 and 0.82± 0.36 liters, respectively (overall P=0.003, pairwise comparison: baseline to 6 months (P=0.04), baseline to 24 months (P=0.75)). The median 6MWTD for the ECT and control groups at 24 months were 333.0 (262.5– 390) and 280 (210– 405), respectively (P=0.16). There was no difference in overall survival (P=0.84). Heterogenous emphysema was a significant predictor of treatment success in univariate analysis (p=0.004).Conclusion: Lung volume reduction with endobronchial coils may improve the exercise capacity and FEV1 of COPD patients. However, the majority of the effect was diminished after 24 months. The current state of evidence does not support regulatory approval of ECT and warrant its use only after consideration of the benefit-harm ratio in a highly selected patient population.Keywords: emphysema, endobronchial coils, lung volume reduction, six-minute walk, residual volume, FEV1, survival

OBJECTIVE To study the outcome of men with macroprolactinoma following cabergoline treatment based on tumour size. DESIGN Retrospective cohort study. METHODS The study included 94 men, divided into three groups according to adenoma diameter: 10-19 mm (Group A, n = 36); 20-39 mm (Group B, n = 41); or ≥40 mm (Group C, giant prolactinomas, n = 17). Patients were followed for a mean of 7.5 years with sellar magnetic resonance imaging, visual fields and hormone measurements. RESULTS Mean baseline prolactin was 767, 2090 and 24,806 ng/ml in Groups A, B and C, respectively (p

Indirect calorimetry (IC)-guided nutrition might positively affect the clinical outcome of critically ill patients. In this systematic review and meta-analysis, our objective was to assess the benefit of isocaloric nutrition guided by IC, compared to hypocaloric nutrition, for critically ill patients admitted to the intensive care unit (ICU). We performed a systematic review of all randomized controlled trials published through January 2021, assessing the benefit of isocaloric nutrition guided by IC. The primary outcome was 28-day all-cause mortality. Secondary outcomes were ICU and 90-day all-cause mortality, rate of nosocomial infections, and adverse events. Four trials evaluating 1052 patients were included. Patients treated with isocaloric nutrition had a lower 28-day mortality rate (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.63–0.99, P = 0.04). No between-group difference was found in ICU and 90-day mortality (RR 0.92, 95% CI 0.68–1.23, P = 0.56 and RR 0.88, 95% CI 0.72–1.07; P = 0.2, respectively) and in the rate of nosocomial infections (RR 1.15, 95% CI 0.77–1.72, P = 0.51). A pooled analysis of studies that evaluated the benefit of isocaloric nutrition guided by IC, for critically ill patients in the ICU, has shown reduced 28-day mortality. However, there was no difference in 90-day mortality and nosocomial infection rate.

Alpha 1 antitrypsin (A1AT) is the major human blood serine protease inhibitor. Transmembrane serine protease 2 (TMPRSS2), which is crucial for SARS-CoV-2 cell entry, is inhibited by A1AT. Therefore, we hypothesized that individuals with diminished levels of A1AT may be more prone to SARS-CoV-2 infection and severe COVID-19 disease. Our aim in this study was to evaluate the level of A1AT in hospitalized COVID-19 patients in comparison to hospitalized patients with non-COVID-19 pneumonia.We conducted an observational prospective study between October 2020 and April 2021 in Rabin Medical Centre in Israel. A1AT levels were measured from the routine serum samples of hospitalized patients with COVID-19 and non-COVID-19 pneumonia (control group). The primary outcome was A1AT level, secondary outcomes were clinical outcomes and predictors of morality.Overall, 145 patients were included in the study, 98 in the COVID-19 group and 47 in the control group. The median A1AT level was 222 mg/dL (interquartile range (IQR) 188-269) and 258 mg/dL (IQR 210-281) in the COVID-19 and control groups, respectively (Patients admitted due to severe COVID-19 had lower A1AT levels in comparison to patients admitted due to non-COVID pneumonia. This observation may suggest an association between mildly diminished A1AT and higher risk of SARS-CoV-2 infection with severe COVID-19 disease.

AIMS: To assess the short-term immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in a population of heart transplant (HTx) recipients. A prospective single-centre cohort study of HTx recipients who received a two-dose SARS-CoV-2 mRNA vaccine (BNT162b2, Pfizer-BioNTech). METHODS AND RESULTS: Whole blood for anti-spike IgG (S-IgG) antibodies was drawn at days 21-26 and at days 35-40 after the first vaccine dose. Geometric mean titres (GMT) ≥50 AU/mL were interpreted positive. Included were 42 HTx recipients at a median age of 61 [interquartile range (IQR) 44-69] years. Median time from HTx to the first vaccine dose was 9.1 (IQR 2.6-14) years. Only 15% of HTx recipients demonstrated the presence of positive S-IgG antibody titres in response to the first vaccine dose [GMT 90 (IQR 54-229) AU/mL]. Overall, 49% of HTx recipients induced S-IgG antibodies in response to either the first or the full two-dose vaccine schedule [GMT 426 (IQR 106-884) AU/mL]. Older age [68 (IQR 59-70) years vs. 46 (IQR 34-63) years, P = 0.034] and anti-metabolite-based immunosuppression protocols (89% vs. 44%, P = 0.011) were associated with low immunogenicity. Importantly, 36% of HTx recipients who were non-responders to the first vaccine dose became S-IgG seropositive in response to the second vaccine dose. Approximately a half of HTx recipients did not generate S-IgG antibodies following SARS-CoV-2 two-dose vaccine. CONCLUSIONS: The generally achieved protection from SARS-CoV-2 mRNA vaccination should be regarded with caution in the population of HTx recipients. The possible benefit of additive vaccine should be further studied.

Background Central airway obstruction and fistula are treated with a tracheobronchial Y stent. In the currently used self‐expandable metal Y stents, the delivery system is 8 mm in diameter and requires either a 9 mm tracheal tube or rigid bronchoscope to enable airway control during insertion. In this study we present a novel technique of laryngeal mask airway (LMA) assisted Y stent insertion, enabling airway control during deployment of the Y stent. Methods All procedures using LMA in assisting Y stent insertions between 2014–2020 were reviewed. Data collected included demographics, clinical diagnosis and disease characteristics, indication, procedural success rates, clinical outcome and survival. Results A total of 10 patients with a median age of 61.5 years (range 37–73) underwent LMA assisted Y stent insertion. Indications for stent insertion were malignant disease with central airway obstruction or fistula. In all cases airway patency was achieved leading to improvement of symptoms and performance status. No procedural complications were reported. The median survival was 4.5 weeks (range: 2–26). Conclusions LMA assisted Y stent insertion enables airway control during the procedure. In comparison to silicone Y stent insertion, the procedure is less cumbersome, shorter in duration and does not require the use of general anesthesia or rigid bronchoscopy. Key points Significant findings of the study LMA assisted Y stent insertion enables airway control during the implantation of metallic self‐expanding Y stent. The procedure does not require the use of general anesthesia or rigid bronchoscopy. What this study adds In this study we present the technique and outcomes of LMA assisted Y stent insertion. This method of Y stent insertion provides an additional treatment option for patients with central airway obstruction and fistula., LMA assisted Y stent insertion enables airway control during the implantation of metallic self‐expanding Y stent. The procedure does not require the use of general anaesthesia or rigid bronchoscopy.

Introduction: Reports regarding the external validity of randomized controlled trials (RCTs) are scarce. We aimed to assess the population external validity of an investigator-initiated RCT on the duration of antibiotics for the treatment of Gram-negative bacteremia by comparing patients included in the RCT to patients that were not included in the trial. Methods: Hospitalized patients with Gram-negative bacteremia were recruited into an RCT and randomized to receive 7 or 14 days of covering antibiotic therapy in Israel and Italy from 2013 to 2017. In a concomitant observational study, RCT participants were compared with patients who fulfilled the inclusion criteria but were not included in the trial due to participation in other trials, discharge before approached by researchers, refusal to participate, or unwillingness of the treating physician to allow participants’ recruitment. Results: Six hundred and four RCT patients were compared with 613 nonincluded patients. Almost 50% of nonincluded patients (288/613) were dependent on others for activities of daily living at baseline compared to 37.7% of RCT participants (228/604). Dementia was nearly 2-fold more frequent in nonincluded patients than those included (5.9% [36/613] versus 3.6% [22/604], p = 0.07). Patients who were not included in the RCT were more likely to acquire their infection in the hospital (53.3% [327/613] versus 29.1% [176/604], p < 0.001). The primary composite outcome of mortality, clinical failure, readmissions, or extended hospitalization at 90 days occurred in 353 of 613 nonincluded patients (57.6%) compared to 299 of 604 RCT participants (49.6%), p = 0.005. However, on multivariate analysis noninclusion in the RCT was not an independent risk factor for clinical failure and mortality. Conclusions: RCTs, even with broad eligibility criteria, do not represent the whole spectrum of patients and leave out a population with more severe illness for whom the evidence is lacking.

Background Patients with interstitial lung disease (ILD) are at high risk of severe COVID-19 infection. Additionally, their anti-inflammatory and antifibrotic treatment may cause immunosuppression. Nevertheless, their ability to mount an adequate immune response to messenger RNA SARS-CoV-2 vaccines was not evaluated. Therefore, we aimed to evaluate the humoral response after the BNT162b2 vaccine among idiopathic pulmonary fibrosis (IPF) patients treated with antifibrotic therapy and among non-IPF ILD patients treated with anti-inflammatory therapy. Methods We conducted an observational prospective cohort study to evaluate the level of anti-spike (S-IgG) antibodies after two doses of the BNT162b2 vaccine in patients with ILD. The cohort included 40 patients with idiopathic pulmonary fibrosis (IPF) treated with anti-fibrotic therapy and 29 patients with non-IPF ILD treated with anti-inflammatory therapy. For S-IgG titer measurement, one serology test was drawn from all patients 4–6 months after the second vaccine dose. In addition a control group matched for age and sex was created from a healthy control cohort of 107 patients. The study was conducted in Rabin Medical Center (Israel) between June and August 2021. Results All patients in the anti-fibrotic arm were seropositive (40/40), corresponding to the matched control group (P = 1.0). The anti-fibrotic arm had a significantly lower median antibody titer in comparison to the matched control group (361.10 [IQR, 207–811] AU/ml vs. 820.75 [IQR, 459–1313] AU/ml; P Conclusion IPF patients treated with antifibrotic therapy mount an adequate immune response after 2 doses of the BNT162b2 vaccine, and maintain a 100% seropositivity rate 4–6 months after vaccination. However, their antibody titer was reduced in comparison to a healthy control group. Among patients with non-IPF ILD treated with anti-inflammatory therapy, 48% were seronegative 4–6 months after the second vaccine dose. Moreover, treatment with rituximab caused significant immunosuppression, even in comparison to other anti-inflammatory treatments.

Objectives Data are limited regarding the clinical significance of nontuberculous mycobacteria pulmonary infections among lung transplant recipients. We investigated the incidence and characteristics of pulmonary nontuberculous mycobacteria infection in ourlung transplant patient population. Materials and methods We obtaineddata of the patients who underwent lung transplant in our center from January 1997 to March 2019. Results Of 690 patients, nontuberculous mycobacteria were identified in 58 patients (8.4%) over a median follow-up of 3 years. Types of species were as follows: Mycobacterium simiae (n = 24), avium complex (n = 12), abscessus (n = 9), fortuitum (n = 6), chelonae (n = 2), szulgai (n = 1), kansasii (n = 1), lentiflavum (n = 1), and undefined mycobacteria (n = 2). When we compared infections in the early versus late period posttransplant (before and after 6 months), infections with Mycobacterium simiae (16 vs 8 incidents) and Mycobacterium fortuitum (5 vs 1 incident) were more often observed within the early period, whereas most Mycobacterium abscessus (7 vs 1 incident) and Mycobacterium avium complex (9 vs 3 incidents) were observed in the later period. The median forced expiratory volume in 1 second overtime did not differ significantly between patients with and without nontuberculous mycobacteria infection (P = .29). Nontuberculous mycobacteria acquisition was significantly associated with decreased survival (relative risk of 2.41, 95% CI, 1.70-3.43; P ⟨ .001). Conclusions The nontuberculous mycobacteria species isolated varied according to the time elapsed since transplant. Among lung transplant recipients, nontuberculous mycobacteria infection was associated with increased mortality but not with lung dysfunction.

The interleukin 5 (IL-5) pathway is an important component in the pathophysiology of severe eosinophilic asthma. Mepolizumab is a monoclonal antibody that targets the IL-5 pathway. Clinical trials showed efficacy of Mepolizumab in patients with severe eosinophilic asthma. However, reports on experience with treatment in a real-world cohort are limited.Evaluation of the efficacy and safety of Mepolizumab for treatment of severe eosinophilic asthma in a real-world cohort of patients.A clinical prospective observational trial included all patients18 years treated with Mepolizumab between March 2016 to March 2019 at Rabin Medical Center. The composite primary outcome measures evaluated: increase in FEV1 by≥ 200 ml and/or decrease in exacerbation rate of ≥50% and/or cessation of oral corticosteroids (OCS) treatment or ≥50% decrease in dosage. Also evaluated: blood eosinophil count, adverse events and quality of life.Of 61 patients, 50 (82.0%) achieved the primary outcome. The number of patients who suffered from frequent exacerbations decreased from 52 (85.2%) to 8 (13.1%) (Treatment with mepolizumab was well tolerated and significantly lowered the exacerbation rate and OCS dependence in a real-world cohort of severe eosinophilic asthma patients. Response to therapy was within six months and treatment effect was sustained over time.

BackgroundGram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited.MethodsThis was a randomized, multicenter, open-label, noninferiority trial. Inpatients with gram-negative bacteremia, who were afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 days (intervention) or 14 days (control) of covering antibiotic therapy. Patients with uncontrolled focus of infection were excluded. The primary outcome at 90 days was a composite of all-cause mortality; relapse, suppurative, or distant complications; and readmission or extended hospitalization (>14 days). The noninferiority margin was set at 10%.ResultsWe included 604 patients (306 intervention, 298 control) between January 2013 and August 2017 in 3 centers in Israel and Italy. The source of the infection was urinary in 411 of 604 patients (68%); causative pathogens were mainly Enterobacteriaceae (543/604 [90%]). A 7-day difference in the median duration of covering antibiotics was achieved. The primary outcome occurred in 140 of 306 patients (45.8%) in the 7-day group vs 144 of 298 (48.3%) in the 14-day group (risk difference, –2.6% [95% confidence interval, –10.5% to 5.3%]). No significant differences were observed in all other outcomes and adverse events, except for a shorter time to return to baseline functional status in the short-course therapy arm.ConclusionsIn patients hospitalized with gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was noninferior to 14 days. Reducing antibiotic treatment for uncomplicated gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention.Clinical Trials RegistrationNCT01737320.

Background Capnography waveform contains essential information regarding physiological characteristics of the airway and thus indicative of the level of airway obstruction. Our aim was to develop a capnography-based, point-of-care tool that can estimate the level of obstruction in patients with asthma and COPD. Methods Two prospective observational studies conducted between September 2016 and May 2018 at Rabin Medical Center, Israel, included healthy, asthma and COPD patient groups. Each patient underwent spirometry test and continuous capnography, as part of, either methacholine challenge test for asthma diagnosis or bronchodilator reversibility test for asthma and COPD routine evaluation. Continuous capnography signal, divided into single breaths waveforms, were analyzed to identify waveform features, to create a predictive model for FEV1 using an artificial neural network. The gold standard for comparison was FEV1 measured with spirometry. Measurements and main results Overall 160 patients analyzed. Model prediction included 32/88 waveform features and three demographic features (age, gender and height). The model showed excellent correlation with FEV1 (R = 0.84), R2 achieved was 0.7 with mean square error of 0.13. Conclusion In this study we have developed a model to evaluate FEV1 in asthma and COPD patients. Using this model, as a point-of-care tool, we can evaluate the airway obstruction level without reliance on patient cooperation. Moreover, continuous FEV1 monitoring can identify disease fluctuations, response to treatment and guide therapy. Trial registration clinical trials.gov, NCT02805114. Registered 17 June 2016, https://clinicaltrials.gov/ct2/show/NCT02805114

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., The LungVision fluoroscopy‐based navigation and guidance technology for bronchoscopic biopsy of peripheral pulmonary nodules is safe and effective.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. The IPF-conditioned matrix (IPF-CM) system enables the study of matrix–fibroblast interplay. While effective at slowing fibrosis, nintedanib has limitations and the mechanism is not fully elucidated. In the current work, we explored the underlying signaling pathways and characterized nintedanib involvement in the IPF-CM fibrotic process. Results were validated using IPF patient samples and bleomycin-treated animals with/without oral and inhaled nintedanib. IPF-derived primary human lung fibroblasts (HLFs) were cultured on Matrigel and then cleared using NH4OH, creating the IPF-CM. Normal HLF-CM served as control. RNA-sequencing, PCR and western-blots were performed. HIF1α targets were evaluated by immunohistochemistry in bleomycin-treated rats with/without nintedanib and in patient samples with IPF. HLFs cultured on IPF-CM showed over-expression of ‘HIF1α signaling pathway’ (KEGG, p &lt, 0.0001), with emphasis on SERPINE1 (PAI-1), VEGFA and TIMP1. IPF patient samples showed high HIF1α staining, especially in established fibrous tissue. PAI-1 was overexpressed, mainly in alveolar macrophages. Nintedanib completely reduced HIF1α upregulation in the IPF-CM and rat-bleomycin models. IPF-HLFs alter the extracellular matrix, thus creating a matrix that further propagates an IPF-like phenotype in normal HLFs. This pro-fibrotic loop includes the HIF1α pathway, which can be blocked by nintedanib.

Idiopathic pulmonary fibrosis (IPF) has poor prognosis. Anti-fibrotic treatment has been shown to slow disease progression. Lung transplantation (LTx) offers a survival benefit. The 5-year survival after LTx in IPF is between 40 and 50.To evaluate which IPF patients have better prognosis following LTx.A retrospective study was conducted with all IPF patients who had undergone LTx in the Rabin Medical Center between 2010 and 2018. We collected data on pre-evaluation of pulmonary function tests, echocardiographic and right heart catherization, and anti-fibrotic treatments. The Kaplan-Meier method was used for survival analysis.Among148 patients who underwent LTx, 58 were double LTx (DLT) and 90 single LTx (SLT). Mean age was 58.07 ± 9.78 years; 104 males and 44 females. DLT patients had significantly lower survival rates than SLT in the short and medium term after LTx. Patients with saturation above 80% after the 6-minute walk test (6MWT) had higher survival rates. Patients over 65 years of age had a lower survival rates. Those with pulmonary hypertension (PHT) above 30 mmHg had a poorer prognosis with lower survival rates.IPF patients with higher mean PHT, older age (65 years), and desaturation following 6MWT had lower survival rates following LTx. DLT may decrease survival rate compared to SLT just for the short and medium period of time after LTx. These results may lead to better selection of IPF patient candidates for LTx. Additional studies are warranted for choosing which patients will have better prognosis after LTx.

Objective To identify risk factors for functional decline after hospitalization for Gram-negative bacteremia. Patients and methods A prospective cohort study based on a randomized controlled trial conducted between January 1, 2013 and August 31, 2017 in Israel and Italy. Hospitalized patients with Gram-negative bacteremia who survived until day 90 and were not bedridden at baseline were included. The primary end point was functional decline at 90 days. Results Five hundred and nine patients were included. The median age of the cohort was 71 years (interquartile range [IQR], 60–80 years), 46.4% (236/509) were male and 352 of 509 (69%) patients were independent at baseline. Functional decline at 90 days occurred in 24.4% of patients (124/509). In multivariable analysis; older age (odds ratio [OR], 1.03; for an one-year increment, 95% confidence interval [CI] 1.01–1.05), functional dependence in instrumental activities of daily living at baseline (OR, 4.64; 95% CI 2.5–8.6), low Norton score (OR, 0.87; 95% CI 0.79–0.96) and underlying comorbidities: cancer (OR, 2.01; 95% CI 1.14–3.55) and chronic pulmonary disease (OR, 2.23 95% CI 1.12–4.42) and longer length of hospital stay (OR 1.09; for one-day increment, 95% CI 1.04–1.15) were associated with functional decline. Appropriate empirical antibiotic treatment was associated with lower rates of functional decline within 90 days (OR, 0.4; 95% CI 0.21–0.78). Conclusions Patients surviving bloodstream infections have poor long term trajectories after clinical recovery and hospital discharge. This has vast implications for patients, their family members and health policy makers.

Indirect calorimetry (IC)-guided nutrition might positively affect the clinical outcome of critically ill patients. In this systematic review and meta-analysis, our objective was to assess the benefit of isocaloric nutrition guided by IC, compared to hypocaloric nutrition, for critically ill patients admitted to the intensive care unit (ICU). We performed a systematic review of all randomized controlled trials published through January 2021, assessing the benefit of isocaloric nutrition guided by IC. The primary outcome was 28-day all-cause mortality. Secondary outcomes were ICU and 90-day all-cause mortality, rate of nosocomial infections, and adverse events. Four trials evaluating 1052 patients were included. Patients treated with isocaloric nutrition had a lower 28-day mortality rate (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.63-0.99, P = 0.04). No between-group difference was found in ICU and 90-day mortality (RR 0.92, 95% CI 0.68-1.23, P = 0.56 and RR 0.88, 95% CI 0.72-1.07; P = 0.2, respectively) and in the rate of nosocomial infections (RR 1.15, 95% CI 0.77-1.72, P = 0.51). A pooled analysis of studies that evaluated the benefit of isocaloric nutrition guided by IC, for critically ill patients in the ICU, has shown reduced 28-day mortality. However, there was no difference in 90-day mortality and nosocomial infection rate.

Background: Malignancy after lung transplantation is an important cause of morbidity and mortality and is associated with the intensity and cumulative dose of immunosuppressive drugs. There is some evidence that the use of mammalian target of rapamycin (mTOR) inhibitors may reduce the risk of malignancy in kidney transplant recipients. Aims: To compare the effect of everolimus on the incidence of new malignancies, as well as the rate of acute rejection, CMV infection and overall survival between lung transplant recipients who were treated with an everolimus/calcineurin inhibitors (CNI)-based regimen versus CNI-based regimen. Methods: A single center retrospective cohort study including all transplanted patients treated with everolimus for >7 months from 1998-2019. Propensity score matching was used to select a similar control group. Results: 142 lung transplant recipients and matched controls were included. The incidence of malignancies was not significantly different between groups (RR 0.75, CI 0.34-1.67, P=0.48). However, a survival benefit was demonstrated in the everolimus group compared to the control group. In addition, the rate of acute rejection events was lower in the everolimus group (RR 0.31, CI 0.15-0.63, P=0.001). There were also less CMV infection episodes in the everolimus group (8.4%) compared to the control group (16.9%) (P=0.07). Conclusions: Whereas our study did not show a significant difference in the incidence of malignancies among the two groups of lung transplant recipients, our results suggest that treatment with everolimus may prolong survival and decrease the rates of acute rejection and CMV infection episodes.

OBJECTIVES We evaluated associations of endobronchial stenting with airway bacterial colonization, the antimicrobial resistance profile, hospitalizations for pneumonia and survival in lung transplant recipients. METHODS This is a retrospective single-centre study of 582 recipients of lung transplant during 2002–2018. We compared outcomes of 57 patients (9.7%) who received endobronchial stents (intervention group) to a control group of 57 patients without stents who were matched one to one for age, sex, year of transplantation, unilateral/bilateral transplantation and underlying disease. RESULTS For the intervention compared to the control group, airway colonization was more common for Pseudomonas (86% vs 35%, P CONCLUSIONS Lung transplant recipients with endobronchial stents were more likely to be colonized with pathologic bacteria and having pneumonia; however, stent placement was not associated with increased long-term mortality with appropriate stent maintenance.

Background: The interleukin 5 (IL-5) pathway is an important component in the pathophysiology of severe eosinophilic asthma. Mepolizumab is a monoclonal antibody that targets the IL-5 pathw...

Background Invasive aspergillosis is a significant cause of morbidity and mortality in lung transplant recipients (LTRs). Early diagnosis may improve outcome, yet is challenging. We assessed the diagnostic yield of a routine, comprehensive, prospectively employed Aspergillus screening strategy in LTRs. Methods During a 6-month period, all bronchoalveolar lavage (BAL) samples (including post-transplant surveillance) obtained from LTRs at our center were routinely tested for Aspergillus PCR, galactomannan (GM), and fungal culture. Invasive aspergillosis (IA) was defined using EORTC/MSG and ISHLT criteria for proven and probable aspergillosis. Results Ninety-five consecutive BAL samples were tested. PCR, GM, and fungal culture were positive in 28.4%, 30.6%, and 7.4%, respectively. Five cases of IA (two proven, three probable) were identified. Fungal culture failed to detect 40% of IA cases, which were detected by a positive PCR and/or GM. However, the majority of positive PCR samples represented colonization (59.3%). Sensitivity of PCR, GM, and culture for IA was 80%, 60%, and 60%, respectively, and specificity was 74%, 71%, and 96%. Conclusions In LTRs, a routine prospectively employed screening strategy in which all BAL samples were screened for Aspergillus PCR and GM, detected aspergillosis cases that were otherwise missed by a false-negative fungal culture, but resulted in more cases of colonization being detected. Clinical judgment is thus warranted to avoid unnecessary treatment of colonization.

BackgroundPatients with idiopathic pulmonary fibrosis (IPF) have significantly higher incidence of lung cancer (LC) relative to the general population. There is a further increase in LC incidence in patients with IPF subsequent to lung transplant, specifically in patients with IPF undergoing single lung transplant.ObjectivesTo examine the incidence and characteristics of LC in patients with IPF during follow-up and after lung transplantation (LTX).MethodsWe conducted a retrospective analysis of all patients with IPF diagnosed with LC in Rabin Medical Center, Israel, over an 11-year period. We compared the characteristics of transplanted patients with IPF diagnosed with LC to patients with IPF who did not undergo lung transplant. Data were accessed from database registries using the words ‘fibrosis’, ‘lung-cancer’ and ‘lung-transplantation’. Demographic parameters included age, gender and smoking history (pack years). Clinical-pathological parameters included lapse in time from IPF diagnosis to LC, type of malignancy, affected pulmonary lobe, and stage at diagnosis, oncological treatment and survival.ResultsBetween 2008 and 2018, 205 patients with IPF underwent lung transplantation at our medical centre. Double LTX was performed in 83 and single LTX in 122 cases. Subsequently, 15 (12.3%) single LTX patients were diagnosed with LC during the study period. During the same period, of 497 non-transplanted patients with IPF followed in our centre, 45 (9.1%) were diagnosed with LC. In all 15 transplanted patients with IPF, LC was diagnosed exclusively in the native fibrotic lung. LC incidence was higher in the transplanted as compared with the non-transplanted group, but this difference did not reach statistical significance (OR=0.7, 95% CI 0.38 to 1.32, p=0.28). At LC diagnosis, the non-transplanted group was older than the transplanted group with average age of 67.7 versus 60.8 years, respectively (p=0.006). Both groups showed male predominance. In both groups, LC was primarily peripheral, lower lobe predominant and most frequently squamous cell carcinoma. The median survival time after LC diagnosis was 4 months in the transplanted group and 11 months in the non-transplanted group (p=0.19). Multivariate analysis showed improved survival in the non-transplanted group among those patients who received oncological treatment.ConclusionChest CT should be performed regularly in order to evaluate IPF patients for potential LC. Single lung transplant IPF patients face an increased risk of post-transplant LC in the native fibrotic lung. Where practicable, IPF patients should be prioritised for double lung transplant.

There is clinical significance to a delay in response time for detecting desaturation by pulse oximetry. Our aim in this study was to compare the response time of the reflectance and transmittance saturation probes during fiberoptic bronchoscopy (FOB) under monitored anesthesia care. A prospective study included 104 patients scheduled for FOB. Patients were monitored with transmittance (finger) and reflectance (ear) oximetry probes. The response time was evaluated during desaturation and resaturation. We also acquired blood tests for arterial oxygen saturation to assess the agreement with the oximetry probes. Ninety patients had a desaturation episode during FOB and were included in the final analysis. Mean time difference between the reflectance ear probe (reference probe) and transmittance finger probe for the detection of desaturation (SpO2 = 90%) was + 36 s (CI 27.0–45.0, P

Background: A diagnostic lung biopsy may be required in some cases of fibrotic interstitial lung diseases (ILD). Transbronchial cryobiopsy has been suggested as a possible alternative to surgical lung biopsy. However, previous estimates of its diagnostic yield were not validated compared to the definitive diagnosis in explanted lungs. Objectives: We aimed to assess the diagnostic accuracy of cryobiopsy in fibrotic ILD patients who subsequently had lung transplantation. Methods: All 197 patients who underwent lung transplantation at our Center due to fibrotic ILD from January 2010 to May 2018, were screened for the presence of a pre-transplant cryobiopsy. Fourteen patients who underwent cryobiopsy before transplantation were identified. Two expert lung pathologists blindedto the explant diagnoses, independently examined these cryobiopsy specimens to decide if they match guideline criteria for usual interstitial pneumonia (UIP) pattern or an alternative diagnosis. The primary measure was the diagnostic accuracy of cryobiopsy to detect or refute a UIP pattern, as compared to the final explant diagnosis. Results: Median time between cryobiopsy and transplantation was 1.4 years. All 14 cryobiopsy samples contained adequate alveolar tissue. The explant diagnosis of 13/14 patients was UIP. The two pathologists correctly diagnosed or refuted UIP in the cryobiopsy specimen in 12/14 cases (85.7%) and 11/14 cases (78.6%), respectively. The level of diagnostic agreement between pathologists was good (kappa 0.59, p = 0.016). Conclusions: Compared to the final explant diagnosis, transbronchial cryobiopsy had high diagnostic accuracy and good inter-observer agreement for UIP pattern. These findings support a potential diagnostic role for cryobiopsy in experienced centers.

Background During cardiopulmonary exercise testing (CPET), Idiopathic Pulmonary Fibrosis (IPF) patients do not reach their direct maximum voluntary ventilation (MVV) and have deranged gas exchange. Their exercise limitation is therefore attributed to a pulmonary vascular mechanism. Methods We studied two cohorts (derivation and validation) of IPF patients with lung function testing and CPET. Maximal ventilation at exercise (VEpeak) was compared to direct MVV by Bland-Altman analysis. Results In the derivation cohort (n = 101), direct MVV over-estimated VEpeak by a factor of 1.51, driven by respiratory rate during MVV that was 1.99 times higher at rest as compared to VEpeak at exercise. The formula (FEV1 × 20.1) + 15.4 was shown to predict VEpeak (r2 = 0.56) in the derivation cohort. In the validation cohort of 78 patients, VEpeak was within a factor of 1.27 (6.8 l/min) of predicted according to the novel formula. According to the novel prediction formula the majority of patients (58%) in the entire cohort have VEpeak within 85% of their predicted MVV, which would indicate a mechanical respiratory limitation to exercise. Conclusion Estimation of direct MVV performed at rest leads to significant over-estimation of the breathing reserve in IPF patients. This may lead to over-diagnosis of pulmonary vascular limitation in these patients. Expected maximal ventilation at exercise may be accurately predicted indirectly by an IPF-specific formula.