The Impact of a Clinical Decision Support System on the Utilization Pattern of Liver Ultrasound Examination.

BACKGROUND: In the past decade, numerous new imaging and laboratory tests have been implemented that significantly contribute to improved medical diagnostic capabilities. However, inappropriate utilization, which occurs on a large scale, has significant ramifications for both patient care and health systems. OBJECTIVES: To assess the impact of a novel clinical decision support system (CDSS) applied to our electronic medical records on abdominal ultrasonography utilization pattern. METHODS: We conducted a retrospective cohort study comparing patterns of abdominal ultrasound utilization in cases of liver enzyme elevation, with and without CDSS, between February and May in 2017 (before CDSS implementation) and during the same months in 2018 (after CDSS implementation). The following parameters were collected: number of tests ordered according to the guidelines, tests with a diagnostic value, and order forms completed with any data or a diagnostic question. The comparison was conducted using chi-square test. RESULTS: Of 152 abdominal ultrasound tests, 72 were ordered in the pre-implementation period and 80 in the post-implementation period. The system failed to reach statistical significance regarding the rates of ordered tests according to the guidelines and/or tests with a diagnostic value. However, the use of the CDSS had a statistically significant impact regarding completing the order form with data, including a specific diagnostic question. CONCLUSIONS: The effect of the system on the efficiency of test utilization was partial. However, our findings strongly suggested that CDSS has the potential to promote proper usage of complementary technologies.

[ASSIMILATING PROMS DURING AND POST-HOSPITALIZATION OF COPD PATIENTS DUE TO DISEASE EXACERBATION MAY IMPROVE THEIR CLINICAL FOLLOW-UP - A CLINICAL, PROSPECTIVE, OBSERVATIONAL STUDY].

BACKGROUND: Chronic obstructive pulmonary disease (COPD) exacerbations necessitating hospitalization are known to have a negative impact on post-discharge clinical outcomes. In the present study, we evaluated the potential benefits in applying Patient-Reported-Outcome-Measures (PROMS) in order to better these patients' post-hospitalization prognostication. METHODS: This was a prospective, observational study. RESULTS: Ninety-nine COPD patients were recruited (aged 9.7±73 years, 61.6% males). All patients filled two separate PROMS (EXACT & PROMIS GLOBAL 10) while 69 of them also filled a second battery of PROMS within 3 months post discharge. The median follow-up time was 14.3 months. The patients' characteristics found to have a statistically significant association with increased risk for 90-days re-hospitalization were: permanent use of oxygen at home [55.2% vs. 32.8%, p=0.045]; significant change in the dyspnea score of the EXACT [54(40-71) vs. 38(11-60), OR=1.115; 95CI 1.006-1.236, p=0.038] and significant change in the cough and sputum, score section of the EXACT [0 (-19-25) vs. -14 (-31-0), OR=1.095; 95CI 1.011-1.187, p=0.027]. Patients' characteristics found to have a statistically significant association with increased risk for 90-days mortality were: age [83±8.43 vs. 72.46±9.53, p=0.047], diagnosis of pneumonia during index hospitalization [60% vs. 14.9%, P=0.034] and low ALT blood activity [10IU (5.5-13.8) vs. 17IU (13-22.8), p=0.016]. Significant change in the EXACT score was associated with increased risk of long-term mortality [-3 (-8.8-9.5) vs. -9 (-21.5-0), OR=1.047; CI95% 1.005-1.091, p=0.03]. CONCLUSIONS: Assimilating PROMS, during and post-hospitalization due to COPD exacerbation could improve our prediction for negative clinical outcomes, both short- and long-term. This may offer better therapeutic interventions in the future. We recommend usage of the EXACT as part of the post-discharge follow-up of COPD patients.

Establishing the role of PLVAP in protein-losing enteropathy: a homozygous missense variant leads to an attenuated phenotype.

BACKGROUND: Intestinal integrity is essential for proper nutrient absorption and tissue homeostasis, with damage leading to enteric protein loss, that is, protein-losing enteropathy (PLE). Recently, homozygous nonsense variants in the plasmalemma vesicle-associated protein gene (PLVAP) were reported in two patients with severe congenital PLE. PLVAP is the building block of endothelial cell (EC) fenestral diaphragms; its importance in barrier function is supported by mouse models of Plvap deficiency. OBJECTIVE: To genetically diagnose two first-degree cousins once removed, who presented with PLE at ages 22 and 2.5 years. METHODS: Family-based whole exome sequencing was performed based on an autosomal recessive inheritance model. In silico analyses were used to predict variant impact on protein structure and function. RESULTS: We identified a rare homozygous variant (NM_031310.2:c.101T>C;p.Leu34Pro) in PLVAP, which co-segregated with the disease. Leu34 is predicted to be located in a highly conserved, hydrophobic, α-helical region within the protein's transmembrane domain, suggesting Leu34Pro is likely to disrupt protein function and/or structure. Electron microscopy and PLVAP immunohistochemistry demonstrated apparently normal diaphragm morphology, predicted to be functionally affected. CONCLUSIONS: Biallelic missense variants in PLVAP can cause an attenuated form of the PLE and hypertriglyceridaemia syndrome. Our findings support the role of PLVAP in the pathophysiology of PLE, expand the phenotypic and mutation spectrums and underscore PLVAP's importance in EC barrier function in the gut.

Clinical Decision Support System: A Pragmatic Tool to Improve Acute Exacerbation of COPD Discharge Recommendations.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with significant mortality, morbidity and increased risk for further exacerbations. Therefore, appropriate measures for prevention of further exacerbations should be initiated before discharge. Unfortunately, this opportunity for treatment review and change in disease course is often missed. We designed a decision support tool to automatically generate discharge recommendations for COPD patients based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report. A pre- and post-intervention study was conducted including data from 24 months before and 18 months after the implementation of the tool. The rate of adherence of the discharge recommendations to the report was measured. Overall, 536 patients were included in the pre-intervention cohort and 367 in the intervention cohort. Demographic and clinical features were similar between the two groups. After introduction of the tool, the percentage of patients discharged with long-acting medications increased from 42% to 84%, recommendations for smoking cessation increased from 32% to 91%, for vaccination from 13% to 92%, and for follow-up visit in a pulmonology clinic from 72% to 98%. Of the patients given prescriptions for long-acting bronchodilators, 54% purchased these after discharge versus 20% of the patients without such prescriptions. Decision-support tools can significantly improve adherence to guidelines among patients discharged after hospitalization due to Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) and potentially improve their clinical course.

[THE CELLULAR MECHANISMS OF LUNG EDEMA CLEARANCE: DOES THE ALVEOLAR EPITHELIUM PLAY A ROLE?]

INTRODUCTION: Pulmonary edema develops as a result of either alteration in the hydrostatic and oncotic pressure gradients across the pulmonary circulation and the lung interstitium or due to increased lung permeability. Alveolar fluid clearance is important in keeping the airspaces free of edema. This process is carried out via the alveolar epithelial active transport of Na+ across the alveolo-capillary barrier mostly by apical Na+ channels and basolateral Na,K-ATPases. Several pharmacologic agents such as catecholamines, vasopressin and gene therapy interventions have currently been found to stimulate the active Na+ transport and lung edema clearance. While others such as amiloride, ouabain, high tidal volume ventilation, hyperoxia and sepsis decrease the rate of alveolar fluid clearance. In conclusion, this review discusses the mechanisms and signal pathways by which the alveolar epithelium impacts lung edema clearance.

Vasopressin-2 receptor antagonist attenuates the ability of the lungs to clear edema in an experimental model.

In the last two decades, the role of the alveolar active sodium transport was extensively studied and was found to play a crucial role in regulating alveolar fluid clearance (AFC), and thus in keeping the airspaces free of edema. The recent development of highly selective nonpeptide vasopressin-receptor antagonists gives us a rare chance to explore the role of vasopressin in the pathogenesis of lung edema. Therefore, the present study examined the involvement of vasopressin in modulating the ability of the lung to clear edema. Vasopressin enhanced the rate of lung edema clearance by 30% as compared with untreated control rats (from 0.49 ± 0.02 to 0.64 ± 0.02 ml/h), whereas V(2) receptor antagonists significantly decreased the ability of the lung to clear water (from 0.64 ± 0.02 to 0.31 ± 0.06 ml/h; P < 0.0001). In contrast, V(1) receptor antagonist did not change the rate of AFC. The administration of ouabain (a Na,K-ATPase inhibitor) and amiloride (a Na(+) channel blocker) inhibited the stimulatory effects of vasopressin (from 0.64 ± 0.02 to 0.22 ± 0.02 ml/h [P < 0.0001] and from 0.64 ± 0.017 to 0.23 ± 0.02 ml/h [P < 0.0001], respectively). Vasopressin significantly increased Na,K-ATPase protein abundance in the basolateral membranes of the alveolar epithelial cells via V(2) receptor activation. We report a novel role of the vasopressin pathway in AFC. This observation indicates a beneficial role of vasopressin in AFC by up-regulating active sodium transport.

Outcome of Pneumocystis jirovecii pneumonia diagnosed by polymerase chain reaction in patients without human immunodeficiency virus infection.

BACKGROUND AND OBJECTIVE: Pneumonia caused by Pneumocystis jirovecii (PCP) in patients without human immunodeficiency virus (HIV) infection is associated with high mortality. The diagnosis of PCP at our institution is based on detection of DNA using a polymerase chain reaction (PCR) assay. The aim of this study was to describe the clinical manifestations, outcomes and factors associated with mortality due to PCP, as diagnosed by PCR, in patients without HIV infection. METHODS: Over a 6-year period, all HIV-negative immunocompromised patients suspected of having an opportunistic pulmonary infection underwent diagnostic bronchoscopy. A multigene PCR assay that detects Pneumocystis jirovecii DNA was used for the diagnosis of PCP. Patients were considered to have PCP if they had underlying immunodeficiency, compatible signs and symptoms, abnormal radiological findings, and Pneumocystis jirovecii DNA was detected in a bronchoalveolar lavage fluid sample. Data was collected retrospectively. RESULTS: PCP was diagnosed in 58 patients. The underlying conditions included haematological malignancies (60.3%), solid tumours (17.2%) and immunosuppressive treatment (22.4%). The most common clinical features in patients with PCP were fever (94.6%), dyspnoea (67.2%) and cough (36.2%). The overall in-hospital mortality was 17.2% (10/58). Mortality was associated with co-infections, high lactate dehydrogenase levels, female gender, and higher pneumonia severity index and acute physiology and chronic health evaluation III scores. CONCLUSIONS: In this study, the mortality of HIV-negative patients with PCP was low compared with previous reports. We hypothesize that this finding resulted from the increased sensitivity of a PCR-based assay, as compared with traditional methods, for the diagnosis of PCP in HIV-negative patients.

Characterization of pulmonary venous hypertension patients with reactive pulmonary hypertension as compared to proportional pulmonary hypertension.

BACKGROUND: Patients with pulmonary venous hypertension (PVH) secondary to left heart disease can be further classified according to their hemodynamic profile: pulmonary hypertension (PH) in proportion to the pulmonary capillary wedge pressure (PCWP) and PH out of proportion to the PCWP or reactive PH. Currently, there are no measures that enable prediction of the development of reactive PH in patients with left heart disease. OBJECTIVES: In this study, we aim to characterize PVH patients with reactive PH as compared to proportional PH in an attempt to create a distinct profile for patients with left heart disease carrying a high risk for the development of reactive PH. METHODS: Thirty-three PVH patients with reactive PH and 29 PVH patients with proportional PH were analyzed retrospectively over a 6-year period. Clinical, laboratory, echocardiographic and hemodynamic parameters were noted and compared between subgroups. RESULTS: There was no significant difference between PVH patients with reactive and proportional PH with regard to gender, age (65.91 ± 11.9 vs. 66.69 ± 10.5 years) and body surface area (1.89 ± 0.24 vs. 1.9 ± 0.23 m(2)). Prevalence of the metabolic syndrome components was similar in both groups. Interestingly, PCWP was similar in both groups, as were the structural and functional parameters of the left heart. CONCLUSIONS: PVH patients with reactive PH have a similar profile as patients with proportional PH; consequently, the evolution of reactive PH is unpredictable. Therefore, it is imperative that physicians maintain a high index of suspicion for the development of reactive PH even in the early stage of heart disease.

Preliminary prospective explanatory observation on the impact of 3-month steroid therapy on the objective measures of sleep-disordered breathing.

BACKGROUND: Excess endogenous steroids are a risk factor for obstructive sleep apnea (OSA). The role of exogenous steroids in this setup is not known. In this study, we prospectively looked at the consequences of a 3-month steroid treatment on the objective measures of sleep-disordered breathing. METHODS: Patients scheduled for long-term steroids treatment underwent two sleep studies, the first before initiation and the second after 3 months of steroid therapy. Their weight and neck girth were measured. Correlations between the changes in the body weight, neck girth, and cumulative steroids dose to apnea/hypopnea index (AHI) change were examined. A group of untreated mild OSA patients (n = 23) served as control. RESULTS: Seventeen patients, five males and 12 females, mean age 52.4 ± 12.6 years, were studied. Fifteen patients increased their mean AHI by 56% from 9.8 ± 11.8 to 15.4 ± 15.8, p = 0.004. This increment was significantly higher when compared to the control group. Body weight and neck girth changes and cumulative steroid dose were not correlated to the AHI increment (Spearman's correlation coefficient r = 0.18 and p = 0.49, r = -0.23 and p = 0.37, r = -0.17 and p = 0.51, respectively). CONCLUSIONS: We found that the objective measures of sleep-disordered breathing worsened after the 3-month steroid treatment. Future studies to define pertinent mechanisms and clinical relevance are warranted.

Association between IgG antibody levels and adverse events after first and second Bnt162b2 mRNA vaccine doses.

OBJECTIVES: This study sought to correlate the SARS-CoV-2 IgG antibody response level to the BNT162b2 (Pfizer BioNTech) mRNA vaccine after the first and second doses with the reported adverse events. METHODS: This cohort study examined the adverse events profiles of people vaccinated with BNT162b2 in our institute between late 2020 and May 2021. Adverse events, age, and sex were reported using an electronic questionnaire, and their SARS-CoV-2 IgG antibody levels were retrieved from the hospital database. RESULTS: Between 20 December 2020 and 31 May 2021, the adverse events questionnaire was completed by 9700 individuals who received the first vaccine dose and 8321 who received the second dose. After the first and second doses, the average antibody levels were 62.34 AU/mL (mean 4-373) and 188.19 AU/mL (mean 20-392), respectively. All of the adverse events, except local pain, were more common after the second vaccine dose. Multivariate analysis showed that after the first vaccine dose, female sex and younger age (but not IgG titres) were associated with a higher probability of adverse events (OR 2.377, 95% CI, 1.607-3.515, p = 0.000; OR 0.959, 95% CI, 0.944-0.977, p £0.000; OR 1.002, 95% CI, 0.995-1.008, p £0.601; respectively); however, all three parameters were associated with the incidence of adverse events after the second dose (OR 2.332, 95% CI, 1.636-3.322, p = 0.000; OR 0.984, 95% CI, 0.970-0.999, p £0.039; OR 1.004, 95% CI, 1.001-1.007, p £0.022; respectively). DISCUSSION: Adverse events are significantly more common after the second BNT162b2 vaccine dose than after the first dose. We found an association between sex, age, and SARS-CoV-2 IgG antibody titre with the incidence of adverse events.

Remote Speech Analysis in the Evaluation of Hospitalized Patients With Acute Decompensated Heart Failure.

OBJECTIVES: This study assessed the performance of an automated speech analysis technology in detecting pulmonary fluid overload in patients with acute decompensated heart failure (ADHF). BACKGROUND: Pulmonary edema is the main cause of heart failure (HF)-related hospitalizations and a key predictor of poor postdischarge prognosis. Frequent monitoring is often recommended, but signs of decompensation are often missed. Voice and sound analysis technologies have been shown to successfully identify clinical conditions that affect vocal cord vibration mechanics. METHODS: Adult patients with ADHF (n = 40) recorded 5 sentences, in 1 of 3 languages, using HearO, a proprietary speech processing and analysis application, upon admission (wet) to and discharge (dry) from the hospital. Recordings were analyzed for 5 distinct speech measures (SMs), each a distinct time, frequency resolution, and linear versus perceptual (ear) model; mean change from baseline SMs was calculated. RESULTS: In total, 1,484 recordings were analyzed. Discharge recordings were successfully tagged as distinctly different from baseline (wet) in 94% of cases, with distinct differences shown for all 5 SMs in 87.5% of cases. The largest change from baseline was documented for SM2 (218%). Unsupervised, blinded clustering of untagged admission and discharge recordings of 9 patients was further demonstrated for all 5 SMs. CONCLUSIONS: Automated speech analysis technology can identify voice alterations reflective of HF status. This platform is expected to provide a valuable contribution to in-person and remote follow-up of patients with HF, by alerting to imminent deterioration, thereby reducing hospitalization rates. (Clinical Evaluation of Cordio App in Adult Patients With CHF; NCT03266029).

Sepsis impairs alveolar epithelial function by downregulating Na-K-ATPase pump.

Widespread vascular endothelial injury is the major mechanism for multiorgan dysfunction in sepsis. Following this process, the permeability of the alveolar capillaries is augmented with subsequent increase in water content and acute respiratory distress syndrome (ARDS). Nevertheless, the role of alveolar epithelium is less known. Therefore, we examined alveolar fluid clearance (AFC) using isolated perfused rat lung model in septic rats without ARDS. Sepsis was induced by ligating and puncturing the cecum with a 21-gauge needle. AFC was examined 24 and 48 h later. The expression of Na-K-ATPase proteins was examined in type II alveolar epithelial cells (ATII) and basolateral membrane (BLM). The rate of AFC in control rats was 0.51 ± 0.02 ml/h (means ± SE) and decreased to 0.3 ± 0.02 and 0.33 ± 0.03 ml/h in 24 and 48 h after sepsis induction, respectively (P < 0.0001). Amiloride, significantly decreased AFC in sepsis; conversely, isoproterenol reversed the inhibitory effect of sepsis. The alveolar-capillary barrier in septic rats was intact; therefore the finding of increased extravascular lung water in early sepsis could be attributed to accumulation of protein-poor fluid. The expression of epithelial sodium channel and Na-K-ATPase proteins in whole ATII cells was not different in both cecal ligation and puncture and control groups; however, the abundance of Na-K-ATPase proteins was significantly decreased in BLMs of ATII cells in sepsis. Early decrease in AFC in remote sepsis is probably related to endocytosis of the Na-K-ATPase proteins from the cell plasma membrane into intracellular pools, with resultant inhibition of active sodium transport in ATII cells.

Idiopathic pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension: can we be certain?

Idiopathic pulmonary arterial hypertension (IPAH) is an isolated small-vessel disease comprising vasoconstriction, remodeling and thrombosis of small pulmonary arteries. However, there is evidence that IPAH does not respect anatomic boundaries and might extend into large vessels such as large central thrombi. On the other hand, chronic thromboembolic pulmonary hypertension (CTEPH) represents a distinct category of pulmonary hypertension as it is thought to be due to an occlusion of the major pulmonary arteries following a thromboembolic event. However, it is currently evident that in most patients there is a concomitant small-vessel disease. The involvement of both small and large vessels in both IPAH and CTEPH, together with a high incidence of silent thromboembolic events, might create difficulties in identifying the true cause of pulmonary hypertension. An accurate diagnosis of the cause determines the management and prognosis. Patients with CTEPH can potentially be offered curative surgery in the form of pulmonary endarterectomy; however, oxygen, vasodilators, anticoagulation, and lung transplantation are more feasible options for IPAH.

Association of Low Alanine Aminotransferase Values with Extubation Failure in Adult Critically Ill Patients: A Retrospective Cohort Study.

BACKGROUND: Liberation from mechanical ventilation is a cardinal landmark during hospitalization of ventilated patients. Decreased muscle mass and sarcopenia are associated with a high risk of extubation failure. A low level of alanine aminotransferase (ALT) is a known biomarker of sarcopenia. This study aimed to determine whether low levels of ALT are associated with increased risk of extubation failure among critically ill patients. METHODS: This was a retrospective single-center cohort study of mechanically ventilated patients undergoing their first extubation. The study's outcome was extubation failure within 48 h and 7 days. Multivariable logistic and Cox regression were performed to determine whether ALT was an independent predictor of these outcomes. RESULTS: The study included 329 patients with a median age of 62.4 years (IQR 48.1-71.2); 210 (63.8%) patients were at high risk for extubation failure. 66 (20.1%) and 83 (25.2%) failed the extubation attempt after 48 h and 7 days, respectively. Low ALT values were more common among patients requiring reintubation (80.3-61.5% vs. 58.6-58.9%, p < 0.002). Multivariable logistic regression analysis identified ALT as an independent predictor of extubation failure at 48 h and 7 days. ALT ≤ 21 IU/L had an adjusted hazard ratio (HR) of 2.41 (95% CI 1.31-4.42, p < 0.001) for extubation failure at 48 h and ALT ≤ 16 IU/L had adjusted HR of 1.94 (95% CI 1.25-3.02, p < 0.001) for failure after 7 days. CONCLUSIONS: Low ALT, an established biomarker of sarcopenia and frailty, is an independent risk factor for extubation failure among hospitalized patients. This simple laboratory parameter can be used as an effective adjunct predictor, along with other weaning parameters, and thereby facilitate the identification of high-risk patients.

Career Trajectory of Physicians Following a Fellowship Program: A Descriptive Study.

INTRODUCTION: A clinical and/or research fellowship abroad has become a prevalent choice among Israeli physicians. However, the influence of fellowship programs on the career path is unclear. We evaluated the role of physicians returning from fellowship in the organizational hierarchy and their professional and academic status. METHODS: This was a retrospective, descriptive, cross-sectional study of physicians who completed a survey after accomplishing a fellowship. The survey included questions about the physicians' attitudes toward the program, programs' details, and the physicians' current academic, professional, and administrative status. Information about scientific publications was also collected. RESULTS: Of the 106 physicians receiving the questionnaire, 101 responded. The majority completed a two-year fellowship in North America. Forty percent participated in an integrated program (research and clinical), and 40% participated in clinical programs. Subjectively, the physicians attributed a significant value to the fellowship and positively recommend it. Most of the physicians held managerial positions, academic appointments, and had generated significant research. DISCUSSION: The subjective perspective of all physicians participating in the study was that attending a fellowship program had a positive impact on their careers. Objectively, the accomplishment of a fellowship program empowered the studied physicians to become scholars, senior executives, and opinion leaders in their professional field.

Hospital solution for COVID-19 isolation facility.

OBJECTIVE: In response to the coronavirus disease 2019 (COVID-19) pandemic, the Israeli government strategy initially focused on containment. The Ministry of Health mandated isolation of COVID-19 patients in hospitals and instructed healthcare institutions to make necessary arrangements. As the second Israeli hospital to establish a COVID-19 department, this article describes our experience in its rapid establishment, while maintaining normal medical center activities. SETTING: Establishing the COVID-19 department involved planning, set-up, and implementations phases, each one based on knowledge available regarding the pandemic and established medical standards for isolation and protection of patients and staff. Wherever possible, new innovative technologies were utilized to provide maximum protection for both patients and staff, together with special online training that was developed for medical teams. RESULTS: A COVID-19 department was successfully established on the hospital campus, remote from other ongoing patient activities. A novel methodology of disease-adapted medicine was implemented successfully among the department's medical staff, who underwent training tailored to expected clinical scenarios. The COVID-19 department is receiving patients, with no contamination of medical personnel to date. A recent survey of COVID-19 patients revealed a very high patient satisfaction rate. CONCLUSION: Based on the experience described herein and lessons learned, the hospital is preparing for a potential large-scale COVID-19 wave, aimed at full readiness through utilization of a fortified underground emergency hospital to treat up to 900 COVID-19 patients, and establishment of versatile in-hospital infrastructure for quick conversion from standard conditions to COVID-19 appropriate conditions.

Identification, localization and expression of NHE isoforms in the alveolar epithelial cells.

Na+/H+ exchangers (NHEs), encoded by Solute Carrier 9A (SLC9A) genes in human, are ubiquitous integral membrane ion transporters that mediate the electroneutral exchange of H+ with Na+ or K+. NHEs, found in the kidney and intestine, play a major role in the process of fluid reabsorption together via Na+,K+-ATPase pump and Na+ channels. Nevertheless, the expression pattern of NHE in the lung and its role in alveolar fluid homeostasis has not been addressed. Therefore, we aimed to examine the expression of NHE specific isoforms in alveolar epithelial cells (AECs), and assess their role in congestive heart failure (CHF). Three NHE isoforms were identified in AEC and A549 cell line, at the level of protein and mRNA; NHE1, NHE2 and mainly NHE8, the latter was shown to be localized in the apical membrane of AEC. Treating A549 cells with angiotensin (Ang) II for 3, 5 and 24 hours displayed a significant reduction in NHE8 protein abundance. Moreover, the abundance of NHE8 protein was downregulated in A549 cells that were treated overnight with Ang II. NHE8 abundance in whole lung lysate was increased in rats with 1-week CHF compared to sham operated rats. However, lower abundance of NHE8 was observed in 4-week CHF group. In conclusion, we herein show for the first time, the expression of a novel NHE isoform in AEC, namely NHE8. Notably, Ang II decreased NHE8 protein levels. Moreover, NHE8 was distinctly affected in CHF rats, probably depending on the severity of the heart failure.

Delayed discharges from a tertiary teaching hospital in Israel- incidence, implications, and solutions.

OBJECTIVES: The Israeli health system is facing high workloads with average occupancy in certain hospital wards of around 100%. Since there is a shortage of hospitalization beds in institutions for continuous, long-term care, transferring patients from the general hospitals' wards is often delayed. This situation has many significant ramifications, to the waiting patients themselves, to other patients who are waiting to be treated and to the entire organization. In this study, we describe the phenomenon of the "detained patients" - its extent, characteristics, significance, and possible solutions. MATERIALS AND METHODS: Rambam Health Care Campus is a tertiary medical center serving the population of the northern part of Israel. In recent years, the hospital management documents data regarding the "detained patients". We reviewed hospital data of detained patients over a period of nine months. The data concerning adult patients awaiting transfer to an institution for continuous care, between May 2019 and January 2020, were obtained retrospectively from the computerized database of the social service. RESULTS: During the study period, 12,723 adult patients were discharged. Of those, 857 patients (6.74%) were transferred to one of the facilities providing prolonged institutional care. For that group of patients, median inpatient waiting time from the decision to discharge until the transfer was 8 days (IQR 6-14), translating to 10,821 waiting days or 1202 hospitalization days per month. These hospitalization days account for 9.35% of the total hospitalization days during the study period. The "detained patients" were hospitalized in internal medicine wards (32%), orthopedic (30%), and neurology/neurosurgery (26%) departments. At any given moment, about 40 hospitalized patients were waiting for long-term care facilities. CONCLUSIONS: Health-care systems must adapt to the current patients' case-mix to achieve optimal utilization of hospital beds and maximal operational efficiency. The number of long-term care beds should be increased, the coordination between general hospitals, health maintenance organizations and long-term facilities improved, and patients that may require long term care after the acute phase of their illness should be early identified and addressed. Meanwhile, establishment of organic units for waiting patients and reorganization of the hospital structure should be considered.

Intestinal Dysbiosis in Carriers of Carbapenem-Resistant Enterobacteriaceae.

Infection with carbapenem-resistant Enterobacteriaceae (CRE) has become an important challenge in health care settings and a growing concern worldwide. Since infection is preceded by colonization, an understanding of the latter may reduce CRE infections. We aimed to characterize the gut microbiota in CRE carriers, assuming that microbiota alterations precede CRE colonization. We evaluated the gut microbiota using 16S rRNA gene sequencing extracted of fecal samples collected from hospitalized CRE carriers and two control groups, hospitalized noncarriers and healthy adults. The microbiota diversity and composition in CRE-colonized patients differed from those of the control group participants. These CRE carriers displayed lower phylogenetic diversity and dysbiotic microbiota, enriched with members of the family Enterobacteriaceae Concurrent with the enrichment in Enterobacteriaceae, a depletion of anaerobic commensals was observed. Additionally, changes in several predicted metabolic pathways were observed for the CRE carriers. Concomitantly, we found higher prevalence of bacteremia in the CRE carriers. Several clinical factors that might induce changes in the microbiota were examined and found to be insignificant between the groups. The compositional and functional changes in the microbiota of CRE-colonized patients are associated with increased risk for systemic infection. Our study results provide justification for attempts to restore the dysbiotic microbiota with probiotics or fecal transplantation.IMPORTANCE The gut microbiota plays important roles in the host's normal function and health, including protection against colonization by pathogenic bacteria. Alterations in the gut microbial profile can potentially serve as an early diagnostic tool, as well as a therapeutic strategy against colonization by and carriage of harmful bacteria, including antibiotic-resistant pathogens. Here, we show that the microbiota of hospitalized patients demonstrated specific taxa which differed between carriers of carbapenem-resistant Enterobacteriaceae (CRE) and noncarriers. The difference in the microbiota also dictates alterations in microbiome-specific metabolic capabilities, in association with increased prevalence of systemic infection. Reintroducing specific strains and/or correction of dysbiosis with probiotics or fecal transplantation may potentially lead to colonization by bacterial taxa responsible for protection against or depletion of antibiotic-resistant pathogens.

Israeli underground hospital conversion for treating COVID-19 patients.

OBJECTIVE: This paper describes how a large academic medical center solved the challenges of war preparedness and subsequently adapted them for the COVID-19 pandemic. SETTING: A 1,000-bed academic medical center in Northern Israel has faced two extreme challenges since 2006: operating under missile attack during the 2006 Second Lebanon War, and rapid establishment of a scalable infrastructure for COVID-19 patients. The first challenge led to construction of a dual-use facility: a parking lot during peacetime, and a fully functioning fortified underground emergency hospital (FUEH) in times of emergency. Several drills have confirmed readiness for various scenarios including conventional and unconventional warfare, and treating isolated patients during the Ebola and SARS threats. RESULTS: The hospital achieved preparedness for patient care during the COVID-19 pandemic, including all facilities and personnel, including infrastructure, laboratories, and innovations, to maintain standard patient care and separate COVID-19 treatment facilities. The hospital's second challenge represented by the COVID-19 pandemic led to adaptation of the FUEH as a key strategic facility in Northern Israel for treating hundreds of COVID-19 patients. Each solution was supported by innovations targeted for specific purposes and needs. CONCLUSIONS: The function and unique mechanisms used to leverage use of a dual facility was proven viable for several emergency conditions, including the COVID-19 pandemic. Infrastructure and technological flexibility is essential when planning for handling different emergencies situations.