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Background Bronchial stenosis is a common complication following lung transplantation. We evaluated long-term associations of the use of self-expandable metal stents (SEMSs) with lung function tests, patient safety, and survival. Methods A retrospective chart review of 582 lung transplantations performed at our institution between January 2002 and January 2018. Fifty-four patients with SEMSs (intervention group) were matched one-to-one to patients without SEMSs (control group) using propensity score matching for age, sex, the year, and type of transplantation (unilateral/bilateral), and underlying disease. Data regarding long-term lung function and survival were compared between the groups. Results During a median follow-up of 54.8 months, the difference in survival between the study groups was not statistically significant (p = 0.2). Following 5, 7.5 and 10 years, values of mean forced expiratory volume in 1 second (FEV1) were comparable between patients with and without SEMSs as follows: 59.5 versus 62.6% (p = 0.2), 55.9 versus 55.0% (p = 0.4), and 63.5 versus 61.9% (p = 0.3), respectively. In the intervention group, a significant increase in the mean FEV1 was observed in 60 days after stent insertion (from 41.9 ± 12.8 to 49.5 ± 16.7% days, p Conclusion SEMS insertion is associated with a positive sustained effect on lung function, without increasing long-term mortality. Thus, airway stenosis after lung transplantation can be safely and successfully treated using endobronchial metal stenting, with tight bronchoscopic follow-up and maintenance.

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.

Background: The prognostic significance of amino-terminal pro-brain natriuretic peptide (NT-proBNP) in lung transplant candidates has not been investigated. Methods: The study was designed as a retrospective single-center investigation. Data regarding various baseline characteristics and all-cause mortality were collected in 172 lung transplant candidates placed in waiting list during November 2017−August 2018. The associations of NT-proBNP levels with baseline characteristics and mortality were analyzed. Results: NT-proBNP values correlated positively with age, forced vital capacity, mean pulmonary artery pressure (MPAP) and pulmonary capillary wedge pressure, while negatively with diffusing lung capacity for carbon monoxide and cardiac index. The optimal cut-off of NT-proBNP for prediction of MPAP levels ≥35 mmHg was 251 pg/ml; with 65.2% sensitivity, 89.3% specificity, 51.7% positive predictive value and 93.6% negative predictive value. On median follow-up period lasting 1.9 years, 81 patients underwent lung transplantation, 31 died waiting for donation, and 60 were alive and still waiting for the transplantation. There was a significantly higher risk of cumulative mortality in waitlisted lung transplant candidates with NT-proBNP level ≥450 vs.

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.

Rationale: In the past few years there are growing reports of non-tuberculosis mycobacterial (NTM) infections in patients with silicosis. Methods: This was a retrospective observational single-center study, in which we reviewed the medical reports of 120 patients with silicosis for whom bronchoalveolar lavage or sputum culture were performed in order to diagnose NTM between the years: 2013-2019. Results: We found 11/120 patients with NTM infections. The average patients age was 49 years old, all of whom were males who have been exposed to Cesar stone as part of their occupation. The main presenting symptoms were cough for 1-12 weeks. The NTM bacteria that were detected were: M. kansasii, M. abscessus, M. intracellulare, M. fortuitum and M. xenopi. 4 out of the 11 patients with silicosis died until the end of the follow up. On high resolution CT the main finding was cavitary lesions. Conclusions: It is important to keep in mind NTM infections in every patient with silicosis who presented with a pulmonary infection which does not respond to a standard antibiotic therapy.

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: Leukocytosis (white blood cell count >12 000/µL) in the delayed postoperative period (4-7 days) after lung transplantation is due to diverse etiologies. We aimed to describe the etiologies of delayed postoperative leukocytosis in lung transplant recipients and to evaluate the association of leukocytosis causes with short-term survival. Methods: A retrospective chart review of 274 lung transplantations performed in our institution during 2006 to 2013. Results: Delayed postoperative leukocytosis was seen in 159 (58.0%) of lung transplant recipients. In 57 (35.8%) of them, the etiology of the leukocytosis was not identified. The etiologies of leukocytosis that were identified were infection (n = 39), second surgery, acute rejection (n = 12), primary graft dysfunction (n = 3), multiple etiologies (n = 17), and other causes (n = 10). On multivariate analysis, delayed postoperative leukocytosis was one of the variables that most significantly associated with decreased survival in the entire sample (hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.01-2.29, P = .040). On additional analysis for mortality assessing each leukocytosis subgroup, the data were acute graft rejection (HR = 8.21, 95% CI: 4.09-16.49, P < .001), second surgery (HR = 2.05, 95% CI: 1.08-3.90, P = .020), primary graft dysfunction (HR = 2.72, 95% CI: 0.65-11.33, P = .169), other causes (HR = 1.30, 95% CI: 0.47-3.62, P = .620), and unknown etiology (HR = 0.94, 95% CI: 0.54-1.62, P = .800). Conclusions: Delayed post-lung transplant leukocytosis is a poor prognostic sign, especially when attributed to acute graft rejection, infection, and multiple etiologies. In the absence of an identifiable etiology, it can be attributed to postoperative reactive stress, is not associated with increased mortality, and likely does not warrant further diagnostic investigation.

Purpose: Orthostatic hypotension (OH) is a common disorder, especially among hospitalised patients. Classic OH is defined as occurring 3 or less minutes of orthostatic stress, and delayed OH as occurring after 3 min of stress. We aimed to compare clinical characteristics and prognosis between inpatients with classic vs. delayed OH. Methods: We performed a retrospective analysis of data from 358 inpatients, aged ≥60 years, who were evaluated for the occurrence of OH at the initial phase of ambulation in four previous prospective studies in our department. Demographic, clinical and prognostic data were compared between patients with (n = 191) vs. without (n = 167) OH, classic (n = 138) vs. delayed (n = 53) OH and seated (n = 115) vs. standing (n = 76) OH. Results: Demographic characteristics, duration of bed rest, the main reasons for admission and the use of offending medications were comparable between the delayed and classic OH groups. Mean maximal postural diastolic (p p = .063) blood pressure falls were higher among patients with classic v. delayed OH. No statistically significant difference between the patients with classic and delayed OH were observed in the occurrence of OH-related symptoms (62.3 vs. 69.8%, p = .42). During a median follow-up of 5.5 years, no statistically significant differences in survival were observed between patients with vs. without OH (p = .14), classic vs. delayed OH (p = .68) and seated vs. standing OH (p = .067). On multivariate analysis, these variables remained not significantly associated with decreased survival. Conclusions: Among inpatients, delayed OH is associated with a lesser magnitude of orthostatic blood pressure fall than classic OH. However, rates of symptomatic OH and long-term mortality were comparable between the groups. Thus, among hospitalised patients, delayed OH should be considered as posing the same severity as classic OH.

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.

INTRODUCTION Exertional desaturation is a cardinal manifestation of idiopathic pulmonary fibrosis (IPF) which raises concerns for serious complications. OBJECTIVES To evaluate the safety of clinically significant desaturation (CSD) during exercise and to assess whether abnormal electrocardiographic (ECG) changes are associated with mortality and hospitalizations in patients with IPF. METHODS Thirty-four IPF patients (68 ± 8 years, 35% women) underwent maximal cycle cardiopulmonary exercise testing (CPET) using 12-lead ECG and pulse oximetry (SpO2 ) and were followed up to 40 months. CSD was considered as SpO2

Background: Lifestyle behaviors are not well-characterized in idiopathic pulmonary fibrosis (IPF). Objectives: To assess the association between lifestyle behaviors and clinical outcomes in patients with IPF. Methods: A total of 34 IPF patients (median age 68 years) were assessed for daily sitting and weekly walking times using the International Physical Activity Questionnaire by in-person interview at baseline, and they were followed up for up to 40 months. Cox proportional hazard analysis was conducted for cardiorespiratory-related hospitalizations and mortality as outcomes. Results: Fifty percent of all patients were hospitalized, and 32% died during the follow-up period. Sitting and walking times were associated with hospitalizations and mortality in IPF. Compared to patients who reported a sitting time of p trend = 0.036) for hospitalization and of 4.6 and 21.2 (p trend = 0.018) for mortality, respectively. Compared to patients walking p trend = 0.022) and a 62 and 86% reduced risk for mortality (p trend = 0.018), respectively. The risk for mortality was further reduced with a combination of shorter sitting and extended walking times. Conclusions: Shorter daily sitting and longer weekly walking times were associated with reduced hospitalization and mortality risks in patients with IPF. These findings suggest a clinical importance of assessing lifestyle behaviors in a comprehensive evaluation and prognostication of IPF patients. The results underscore potential clinical benefits of reducing sedentary behaviors among IPF patients; however, this warrants further investigation.

Background Mucormycosis is a rare infection in lung transplant recipients (LTR). Our objective was to better define the clinical presentation and optimal management of this frequently lethal infection. Methods A systematic review of the literature was performed to identify all published cases of mucormycosis in LTR using PubMed/MEDLINE. These cases were analyzed together with a new case series from our clinic. Results Literature search yielded 44 articles matching the inclusion criteria, describing 121 cases. Six additional cases were identified from our clinic. Data regarding infection site and outcome were available for a total of 53 patients. The lungs were the most common site of infection (62%), followed by rhinocerebral and disseminated disease. Most cases (78%) developed in the first post-transplant year, with over 40% of them in the first month. Additional risk factors for mucormycosis were identified in over half of the patients. Surgical debridement was uncommon in pulmonary infection (9%). Posaconazole therapy was used in 35% of cases, mostly in combination with amphotericin B. Overall mortality was 32% but varied according to site of infection. Conclusion Mucormycosis in LTRs tends to be an early post-surgical infection, associated with additional risk factors and intensified immunosuppressive states, and most often affects the lungs, where surgical debridement is rarely feasible. Posaconazole as first-line therapy should be further explored.

Background: Platelet distribution width (PDW) has demonstrated clinical significance in populations with specific disorders; its prognostic significance in internal medicine wards has not been investigated. Methods: Demographic, clinical and laboratory data were collected prospectively for 1036 internal medicine inpatients. The primary outcome was 90-day mortality, secondary outcomes were: treatment with mechanical ventilation, prolonged hospital stay, in-hospital death, and all-cause mortality following discharge. Data were assessed according to PDW values on admission ≤16.7% (group A) and >16.7% (group B). Results: Compared to group A patients (n = 273), group B patients (n = 763) were more likely to be older, admitted for cardio-cerebrovascular disorder, to present with comorbidities, to be mechanically ventilated, to have prolonged hospital stay and to die during the current hospitalization. The respective 90-day and total (median follow-up of 5 months) mortality rates were significantly higher in group B (13.2% and 16.3%) than in group A (6.6% and 9.5%), P

This pilot study aimed to compare physiological responses between cycle cardiopulmonary exercise tests (CPETs) and 6-min walk tests (6MWTs) and to assess their prognostic value among patients with idiopathic pulmonary fibrosis (IPF).Thirty-four patients with IPF (68 ± 8 yr) underwent CPETs and 6MWTs and were followed up for 40 mo. Differences, levels of agreement, and relative risks for mortality were analyzed between measured and estimated peak responses for the 2 tests.Compared with the CPET, oxygen uptake ((Equation is included in full-text article.)O2), heart rate (HR), and the nadir of SpO2 were lower during the 6MWT, whereas work rate (WR) was higher. Mean differences were as follows: (Equation is included in full-text article.)O2 =-1.9 mL/kg/min, 95% CI, -1.1 to -2.7, P.001; HR =-9 beats/min, 95% CI, -4 to -14, P = .002; SpO2 =-6%, 95% CI, -4 to -7, P.001; and WR = 9 W/min, 95% CI, 3 to 16, P = .008. Interclass correlations ranged from 0.84 to 0.90 and both tests demonstrated prognostic value for mortality.Significant differences and variation in peak physiological responses were observed between cycle CPETs and 6MWTs in patients with IPF. However, good agreement was evident, suggesting that both tests provide value for clinical and research settings. Future studies should compare the physiological responses between treadmill CPETs and 6MWTs for prognostic utility in IPF.

Orthostatic hypotension (OH) is a common and clinically important disorder. Published papers vary regarding the definitions of OH and methodologies of evaluation. Moreover, substantial gaps in the skills and knowledge required for assessment of OH have been reported by clinicians. We aimed to provide current information regarding the definition, classification and evaluation of OH.We performed a comprehensive search of medical databases, using the following keywords: "postural hypotension" or "orthostatic hypotension", combined with: "definition", "classification", "diagnosis", "evaluation" or "meaning". We selected for this review the most relevant recent publications and key papers in the field, published in the English language.Current data regarding definitions, classification and the evaluation of OH are reviewed. The various aspects of OH assessment are extensively discussed. Considerable discrepancies exist between the published guidelines regarding the methodology of OH diagnosing. We propose an algorithm for OH evaluation and a standardized protocol for bedside determination of OH by healthcare providers.Correct assessment of OH is essential for its accurate diagnosis. The methodology of OH evaluation has not been sufficiently standardized. We emphasize the clinical importance of the uniform investigation of OH, according to the current guidelines for OH definition and meaning.

We investigated outcomes of patients hospitalized with community-acquired pneumonia (CAP) according to the changes in red cell distribution width (RDW).For 980 adults, clinical characteristics, outcomes during hospitalization for CAP (transfer to the intensive care unit, treatment with mechanical ventilation, prolonged hospital stay, and death), and all-cause mortality following discharge were compared: according to RDW changes versus stable RDW during hospitalization, and according to normal (≤14.7 %) versus high (14.7 %) RDW values on admission/discharge.RDW changes (n = 386) during hospitalization were associated with more severe clinical and laboratory characteristics than stable RDW (n = 594). Changes in RDW strongly predicted poor in-hospital outcomes (p 0.001). The respective 30, 90-day, and total (median follow-up 54 months) mortality rates were significantly higher (9.8, 16.0 and 43.5 %) among patients with RDW changes, compared to 4.0, 7.6 and 30.5 % among those with stable RDW (p 0.001 for all comparisons). RDW changes, as well as high RDW (each 1 % increment) on admission and discharge, were powerful predictors of mortality (the respective relative risks 1.41, 1.13, and 1.15, and 95 % confidence intervals 1.13-1.74, 1.08-1.19, and 1.10-1.21).RDW changes during hospitalization for CAP are common and associated with a severe clinical profile. Time-dependent RDW changes strongly predict poor in-hospital outcomes and increased short- and long-term mortality. Repeated RDW determinations during hospitalization for CAP may provide useful prognostic information.

Most studies of orthostatic hypotension (OH) have focused on community-dwelling and institutionalized patient populations. Less is known about OH in hospitalized patients. Moreover, a comprehensive review of OH in internal medicine wards has not been published in the English literature. Our purpose is to provide current information regarding OH in internal medicine inpatients.A comprehensive search of medical databases was performed for potentially relevant articles, using the following keywords: postural or orthostatic hypotension, with the combination of hospitalization or internal medicine. Inclusion criteria were: population of patients hospitalized for acute disorders in internal medicine or geriatric wards with a sample size of ≥50 and publication as an original full-length article in the English language. Data from 14 selected studies are reviewed, including: pathophysiology, evaluation, prevalence, manifestations, risk factors, prognosis, and management.OH is a common and often symptomatic disorder in elderly internal medicine patients. The prevalence of OH in this population ranges from 22-75%. There are substantial discrepancies between the studies reviewed regarding definitions and means of evaluating OH. OH in internal medicine wards is largely non-neurogenic and multifactorial. The main predisposing factors for OH are prolonged bed rest, hypertension, and heart failure. OH in internal medicine wards is managed mainly with non-pharmacologic interventions, and is frequently reversible.In internal medicine inpatients, OH warrants attention because this disorder is common, potentially dangerous, and treatable. In the hospital setting, OH should be routinely assessed on ambulation, following the current guidelines for OH definition and meaning.

To assess the prognostic value of the 8-foot-up-and-go test (8-FUGT) in pilot cohort of patients with idiopathic pulmonary fibrosis (IPF). Thirty-four patients with IPF (68 ± 8 years) underwent 8-FUGT at baseline and were followed for up to 40 months. Receiver operating characteristics and age-adjusted Cox hazard ratios (HR) were analyzed for 8-FUGT, hospitalizations, and mortality. Correlation coefficients were determined between 8-FUGT and other exercise tests. 8-FUGT ≥ 6.9 s was found to be associated with hospitalization (sensitivity = 77%, specificity = 76%, p = 0.03) and mortality (sensitivity = 91%, specificity = 70% p = 0.008) in patients with IPF. Categorical models demonstrated that 8-FUGT ≥ 6.9 s was associated with 14.1- (p

Non-cystic fibrosis bronchiectasis (NCFBr) is a major cause of morbidity due to frequent infectious exacerbations. We analyzed the influence of patient age and bronchiectasis location on the bacterial profile of patients with NCFBr. This retrospective cohort study included 339 subjects diagnosed with an infectious exacerbation of NCFBr during the 9-year period between January 2006 and December 2014. Bronchoalveolar lavage (BAL) cultures and high-resolution computed tomography scans (HRCT) were utilized to characterize the location of the bronchiectasis and bacteriologic pathogenic profile. In univariate logistic regression, the frequency of Haemophilus influenzae was higher in patients aged ≤64 years (OR = 0.969, p 0.0001, 95 % CI 0.954-0.983), whereas the frequency of Pseudomonas aeruginosa (OR = 1.027, p = 0.008, 95 % CI 1.007-1.048) and Enterobacteriaceae (OR = 1.039, p = 0.01, 95 % CI 1.009-1.069) were significantly higher in patients aged64 years. The lobar distribution of bronchiectasis in the subjects was 25.9 % in the right middle lobe (RML), 20.7 % in the right lower lobe (RLL), 20.4 % in the left lower lobe (LLL), 13.8 % in the lingula, 13 % in the right upper lobe (RUL), and 6.2 % in the left upper lobe (LUL). In the lower lobes, H. influenzae was the dominant species isolated, whereas in the RUL it was P. aeruginosa and in the LUL it was non- tuberculous mycobacterium (NTM). H. influenzae was more prevalent in younger patients, whereas P. aeruginosa, Enterobacteriaceae and NTM predominated in older patients. Different pathogens were associated with different lobar distributions. The RML, RLL and LLL showed a greater tendency to develop bronchiectasis than other lobes.

BACKGROUND Lung transplant (LTx) recipients suffer from high rates of malignancy. Exposure to immunosuppressive medication such as tacrolimus has been proposed as a risk factor for tumorigenesis. We hypothesized that chronically high levels of tacrolimus would be associated with risk of malignancy. MATERIAL AND METHODS The study was performed in a transplant center in Israel, with a nested case-control design. Cases were LTx recipients who were diagnosed with any solid or hematological malignancy except non-melanoma skin cancer. Controls were tumor-free during their entire follow-up after LTx and had at least the same follow-up time as their matched case. Controls were matched to cases by age and type of transplant received (single/double). Tacrolimus levels were extracted and analyzed for median drug level and also integrated over time (area under the curve - AUC-tacrolimus). RESULTS We reviewed 412 LTx recipients in our registry. Thirty-nine cases of malignancy were diagnosed and 160 controls were matched, giving a crude tumor incidence rate of 26/100 000/year. Lung cancers were the commonest diagnosis. Cases and controls were well matched by age, smoking status, and LTx type. Median tacrolimus levels were 11.0 ng/ml and 11.3 ng/ml in cases and controls, respectively (p=0.88). The median log (AUC-tacrolimus) was 9.4 in the cases and 9.5 in the controls (p=0.59). CONCLUSIONS In this nested case-control study, exposure to tacrolimus was similar in tumor cases and non-tumor controls. These data, based on a cohort with modest size, suggest either that tumorigenesis in LTx recipients is unrelated to tacrolimus exposure or that levels in these patients are above an unknown threshold at which the dose-response effect is saturated.

Studies in lung transplantation demonstrate that the ancestry and gender dissimilarities of donor-recipients lead to a decrease in survival of the recipient.To evaluate the survival of lung transplant recipients in Israel based on whether the donors and recipients are of Jewish or Arab ancestry as well as survival based on gender match or mismatch.We performed a retrospective observational cohort study of 345 lung transplant recipients at the Rabin Medical Center, Petah Tikva, Israel between January 1997 and January 2013. We compared the survival of lung transplant recipients in two ancestry categories: ancestry matched (Jewish donors to Jewish recipients or Arab donors to Arab recipients) and ancestry mismatched (Jewish donors to Arab recipients and vice versa). We also compared the survival among the four gender donor and recipient combinations (male to male, female to female, male to female, and female to male).Survival analysis revealed no significant differences between the two ancestry groups (P = 0.51) and among the four gender combinations (P = 0.58). On Cox multivariate analysis, younger donor age was the only significant parameter for longer survival (hazards ratio 1.025, 95% confidence interval 1.012-1.037).Gender and ancestry mismatches in these two Israeli populations do not appear to alter the clinical outcomes following lung transplantation.

Purpose To investigate clinical characteristics and the prognostic significance of a prolonged international normalized ratio (INR) without obvious cause or anticoagulant treatment, in elderly inpatients. Methods Demographic, clinical, and laboratory data, in-hospital death and 30 day-mortality were prospectively registered for 100 consecutive patients aged ≥75 years admitted to an internal medicine ward for a variety of acute medical disorders, and compared according to normal (≤1.15) and prolonged (>1.15) INR on admission. Exclusion criteria were: anticoagulant therapy, disseminated intravascular coagulopathy, acute bleeding, liver disease, active malignant disorder, and known coagulopathy. Results Prolonged INR was found in 52% of patients. Patients with prolonged INR tended more likely to present with dementia and pressure sores than patients with normal INR. Moreover, patients with prolonged INR more often needed assisted feeding and presented lower mean levels of serum albumin on admission. In-hospital (21.2% vs. 6.2%) and 30-day (32.7% vs. 6.2%) mortality rates were significantly higher in patients with prolonged INR than those with normal INR. On stepwise logistic regression analysis, prolonged INR strongly predicted 30-day mortality (P = 0.004, relative risk 1.67, 95% confidence interval 1.07–2.60). Conclusions Prolonged INR without obvious cause or anticoagulant treatment is common among elderly patients admitted to an internal medicine ward, and is associated with a severe clinical profile. Prolonged INR is a powerful predictor of 30-day mortality. Assessment of INR my improve risk stratification for elderly inpatients.

Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal interstitial lung disease associated with cardiovascular impairments which compromise exercise tolerance and worsen prognosis. Aim To examine the effect of participating in supervised exercise training (ET) program on cardiovascular function in patients with IPF. Design A randomized controlled study. Setting Outpatient hospital. Population Thirty-two IPF patients (68±8 years). Methods An ET group (N.=15) participated in a 12-week twice a week 60-minute supervised exercise program while a control group (N.=17) received usual care. At baseline and after the 12-week intervention all patients underwent resting echocardiography, cardiopulmonary exercise testing and N-terminal pro-brain natriuretic peptide (NT-proBNP) assessments. Results The ET group significantly improved peak values of exercise cardiovascular indexes while the control group showed a trend of deterioration in the outcomes. The mean difference between the groups (95% CI) for circulatory power was 638 mLO2/kg/min/mmHg (95% CI: 197-1080) (P=0.006), cardiac power output 0.3 W (95% CI: 0.1 to 0.6) (P=0.041), and stroke work 312 mL/beat/mmHg (95% CI: 52-573) (P=0.02). No significant differences between groups were detected in most echocardiography measures and NT-proBNP. Changes in exercise cardiovascular indexes showed significant correlation with improvements in functional capacity, dyspnea and quality of life among ET group. Conclusions Participation in supervised ET program can improve exercise cardiovascular function in patients with IPF, however resting cardiac evaluations seem to be less sensitive to detect such changes. Clinical rehabilitation impact These findings underscore the utility of supervised ET for cardiovascular enhancement which may also be clinically beneficial in reducing the cardiovascular morbidity and mortality in IPF patients.

The prognostic significance of platelet count (PC) changes during hospitalization for community-acquired pneumonia (CAP) has not been investigated. For 976 adults, clinical data during hospitalization for CAP and all-cause mortality following discharge were compared according to ΔPC (PC on discharge minus PC on admission): groups A (declining PC, ΔPC 50 × 109/l), and according to the presence of thrombocytopenia, normal PC, and thrombocytosis on admission/discharge. Groups A, B, and C comprised 7.9%, 46.5%, and 45.6% of patients, respectively. On hospital admission/discharge, thrombocytopenia, normal PC, and thrombocytosis were observed in 12.8%/6.4%, 84.1%/84.4%, and 3.1%/9.2% of patients, respectively. The respective 90-day, 3-year, and total (median follow-up of 54 months) mortality rates were significantly higher: in group A (40.3%, 63.6%, and 72.7%), compared to groups B (12.3%, 31.5%, and 39.0%) and C (4.9%, 17.3%, and 25.4%), p < 0.001; and in patients with thrombocytopenia at discharge (27.4%, 48.4%, and 51.6%), compared to those with normal PC (10.2%, 26.9%, and 35.4%) and thrombocytosis (8.9%, 17.8%, and 24.4%) at discharge (p < 0.001). Mortality rates were comparable among groups with thrombocytopenia, normal PC, and thrombocytosis at admission (p = 0.6). In the entire sample, each 100 × 109/l increment of ΔPC strongly predicted lower mortality (p < 0.001, relative risk 0.73, 95% confidence interval 0.64-0.83). In conclusion, PC changes are common among CAP inpatients. Rising PC throughout hospitalization is a powerful predictor of better survival, while declining PC predicts poor outcome. Evaluation of PC changes during hospitalization for CAP may provide useful prognostic information.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that manifests in hypoxemia, inactivity, and poor prognosis. This study aimed to assess the prognostic role of physical activity (PA) and exertional desaturation (ED) with mortality in IPF. At baseline, 34 IPF patients (68 (50–81) years) were interviewed using the International Physical Activity Questionnaire (IPAQ), and SpO2 was assessed pre to post 6-min walking test (∆SpO2). Patients were prospectively followed up for 40 months. Receiver operating characteristics curve analysis determined cut-off points associated with mortality, and Cox proportional hazard ratio (HR) were conducted. Thresholds for increased mortality risk in IPF patients were determined as IPAQ ≤ 417 metabolic equivalent task (METS)-min/week, p = 0.004 (HR; 9.7, CI 95% (1.3–71.9), p = 0.027), and ∆SpO2 ≥ 10%, p = 0.002, (HR; 23.3, CI 95% (1.5–365), p = 0.025). This study demonstrated a significant association of PA and ED with mortality in IPF patients. The findings emphasize the clinical importance of PA and ED assessments to aid in IPF risk stratification, prognosis prediction, and in providing early appropriate treatments, such as pulmonary rehabilitation, PA consultation, oxygen supplementation, and lung transplantation referral. These results underscore that even low levels of PA corresponding to 100–105 min/week were associated with a reduced mortality risk and better survival in IPF.

Background: Lung abscesses are commonly treated with antibiotics. However, some patients fail to respond and may require percutaneous catheter drainage or surgical intervention. Bronchoscopic drainage (BD) of lung abscesses emerged as a therapeutic alternative in selected patients. Objective: To describe our experience with 15 patients who underwent BD at our center during 2006-2016. Methods: Patients underwent flexible bronchoscopy. Under fluoroscopic guidance, a pigtail catheter was introduced into the abscess cavity, its correct position being confirmed by the injection of contrast medium. The catheter remained in place for a few days and was flushed repeatedly with antibiotics. Results: Fifteen patients (9 males; median age 59 years) underwent 16 BD procedures. A pigtail catheter was successfully inserted and pus was drained from the abscess cavity in 13 procedures (81%) conducted in 12 patients, leading to rapid clinical improvement in 10 of them; resolution of fever occurred a median of 2 days (range Conclusion: BD of lung abscesses was achieved in 13 out of 16 procedures, leading to rapid improvement in the majority of patients. This work adds to the existing literature in establishing this procedure as an acceptable therapeutic alternative in selected patients who fail to respond to antibiotics, especially those with an airway obstruction or a fairly central lung abscess.

Purpose. The aim of this study was to evaluate the sensitivity of pleural C-reactive protein (CRP) biomarker levels in identifying parapneumonic effusions.Methods. A single-center, retrospective review of 244 patients diagnosed with pleural effusions was initiated among patients at the Rabin Medical Center, Petah Tikva, Israel, between January 2011 and December 2013. The patients were categorized into 4 groups according to their type of pleural effusion as follows: heart failure, malignant, post-lung transplantation, and parapneumonic effusion.Results. The pleural CRP levels significantly differentiated the four groups (p<0.001) with the following means: parapneumonic effusion,5.38±4.85 mg/dL; lung transplant,2.77±2.66 mg/dL; malignancy,1.19±1.51 mg/dL; and heart failure,0.57±0.81 mg/dL. The pleural fluid CRP cut-off value for differentiating among parapneumonic effusions and the other 3 groups was 1.38 mg/dL. The sensitivity, specificity, positive predictive value, and negative predictive value were 84.2%, 71.5%, 37%, and 95%, respectively. A backward logistic regression model selected CRP as the single predictor of parapneumonic effusion (OR = 1.59, 95% CI = 1.37–1.89).Conclusions. Pleural fluid CRP levels can be used to distinguish between parapneumonic effusions and other types of exudative effusions. CRP levels < 0.64 mg/dL are likely to indicate a pleural effusion from congestive heart failure, whereas levels ≥ 1.38 mg/dL are suggestive of an infectious etiology.

In Israel, where the "Do not resuscitate code" and "advanced directives" are not yet universally practiced, physicians are frequently 'forced' to mechanically ventilate patients despite an upfront unfavorable prognosis. Due to the shortage of intensive care unit (ICU) beds, patients are mostly hospitalized in general medicine wards.To differentiate between patients with particularly grim prognoses and those with good prognoses, in order to inform the potential decision-making process regarding whether or not to offer aggressive medical care.This retrospective study included all mechanically ventilated patients hospitalized exclusively in one of the six general internal medicine wards at the Assaf Harofeh Medical Center during 2009-2010. Demographic and ventilation-related data, laboratory values and main medical diagnoses were correlated to in-hospital mortality.The study group comprised 437 patients with a median age of 83 years. Mortality was 72%. Initiation of mechanical ventilation out of the hospital or in the emergency room improved outcome. Age, anemia, leukocytosis and renal failure correlated negatively to outcome. In-hospital mortality was 80% in patients after in-hospital resuscitation, 90% in patients ventilated due to infections, but 50% in patients ventilated for cardiac or respiratory failure.The prognosis of mechanically ventilated patients can be foreseen, which could help in deciding whether aggressive life support would be in the interest of the patient.

Nocardiosis is an opportunistic infection caused by the Gram-positive weakly acid-fast, filamentous aerobic Actinomycetes. The lungs are the primary site of infection mainly affecting immunocompromised patients. In rare circumstances even immunocompetent hosts may also develop infection. Diagnosis of pulmonary nocardiosis is usually delayed due to nonspecific clinical and radiological presentations which mimic fungal, tuberculous, or neoplastic processes. The present report describes a rare bronchoscopic presentation of an endobronchial nocardial mass in a 55-year-old immunocompetent woman without underlying lung disease. The patient exhibited signs and symptoms of unresolving community-acquired pneumonia with a computed tomography (CT) scan that showed a space-occupying lesion and enlarged paratracheal lymph node. This patient represents the unusual presentation of pulmonaryNocardia beijingensisas an endobronchial mass. Pathology obtained during bronchoscopy demonstrated polymerase chain reaction (PCR) confirmation of nocardiosis. Symptoms and clinical findings improved with antibiotic treatment. This patient emphasizes the challenge in making the diagnosis of pulmonary nocardiosis, especially in a low risk host. A literature review presents the difficulties and pitfalls in the clinical assessment of such an individual.

Background: Rabbit antithymocyte globulin (rATG) therapy has been shown to be beneficial in lung transplant recipients as induction therapy for treating acute lung rejection; however, its role in chronic lung rejection has been reported only rarely. We evaluated the effectiveness of rATG therapy in slowing the progression of chronic lung allograft dysfunction (CLAD) syndrome. Methods: We conducted a retrospective review of 25 lung transplant patients with CLAD who received rATG therapy in the Pulmonary Institute of Rabin Medical Center, Israel, between May 2005 and February 2016. Response to treatment was divided into 2 categories: stabilization, defined as a halting of the decline of forced expiratory volume in 1 second (FEV1) for >= 6 months after rATG therapy, and deterioration, defined as showing a continued decline in FEV1. Results: Of 25 subjects, 8 (32%) were categorized as part of the stabilization group and 17 (68%) were categorized as showing continued deterioration. The stabilization group was older (61 +/- 8 vs 44 +/- 19 years) and showed longer survival rate after rATG therapy (930 +/- 385 vs 414 +/- 277 days). The stabilization group also demonstrated a lower mean white blood cell count (7.9 +/- 1.8 vs 8.5 +/- 2.9 x 10(9) cells/L) and lymphocyte count (0.37 +/- 0.1 vs 0.55 +/- 0.3 x 10(9) cells/L) during rATG treatment. The stabilization group also demonstrated a higher FEV1 after lung transplantation (91% +/- 21% vs 75% +/- 15.4%), at the beginning of rATG therapy (51% +/- 11% vs 39% +/- 9.6%) and at 6 months after rATG therapy follow-up (51% +/- 9.1% vs 28% +/- 7.6%). Conclusions: rATG was effective in stabilizing rejection progression in approximately one-third of our patients with CLAD. rATG therapy should be considered early in the course of CLAD. Randomized, controlled studies should be considered to confirm these findings.