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1.
Isr Med Assoc J ; 25(11): 752-756, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37980621

RESUMO

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.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Humanos , Estudos Retrospectivos , Registros Eletrônicos de Saúde , Ultrassonografia , Fígado/diagnóstico por imagem
2.
Clin Microbiol Infect ; 28(12): 1644-1648, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35843565

RESUMO

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.


Assuntos
COVID-19 , Vacinas Virais , Humanos , Feminino , Imunoglobulina G , Vacinas de Produtos Inativados , Vacina BNT162 , Anticorpos Antivirais , Estudos de Coortes , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinas de mRNA
3.
JACC Heart Fail ; 10(1): 41-49, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34969496

RESUMO

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).


Assuntos
Insuficiência Cardíaca , Doença Aguda , Assistência ao Convalescente , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Hospitalização , Humanos , Alta do Paciente , Prognóstico , Fala
4.
J Clin Med ; 10(15)2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34362065

RESUMO

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.

5.
Harefuah ; 160(8): 520-526, 2021 Aug.
Artigo em Hebraico | MEDLINE | ID: mdl-34396728

RESUMO

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.


Assuntos
Assistência ao Convalescente , Doença Pulmonar Obstrutiva Crônica , Progressão da Doença , Feminino , Seguimentos , Hospitalização , Humanos , Masculino , Alta do Paciente , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia
6.
Am J Disaster Med ; 16(1): 35-41, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954973

RESUMO

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.


Assuntos
COVID-19 , Atenção à Saúde , Hospitais , Humanos , Pandemias , SARS-CoV-2
7.
PLoS One ; 16(4): e0239240, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33882062

RESUMO

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.


Assuntos
Células Epiteliais Alveolares/metabolismo , Isoformas de Proteínas/metabolismo , Trocador 1 de Sódio-Hidrogênio/metabolismo , Células A549 , Animais , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Regulação para Baixo/fisiologia , Humanos , Intestinos/fisiologia , Rim/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Sódio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo
8.
Rambam Maimonides Med J ; 12(2)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33576732

RESUMO

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.

9.
Am J Disaster Med ; 15(3): 159-167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33270207

RESUMO

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.


Assuntos
Tratamento Farmacológico da COVID-19 , Pandemias , Hospitais , Humanos , Israel , Líbano , Pacientes , SARS-CoV-2
10.
Isr J Health Policy Res ; 9(1): 66, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33234151

RESUMO

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.


Assuntos
Atenção à Saúde/organização & administração , Hospitalização/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Centros de Atenção Terciária/organização & administração , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais de Ensino/organização & administração , Humanos , Incidência , Israel , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga de Trabalho
11.
mSphere ; 5(2)2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350099

RESUMO

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.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/patogenicidade , Portador Sadio/microbiologia , Disbiose/microbiologia , Infecções por Enterobacteriaceae/fisiopatologia , Intestinos/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Carbapenêmicos/farmacologia , Estudos de Coortes , Infecções por Enterobacteriaceae/microbiologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal , Humanos , Intestinos/microbiologia , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Filogenia , RNA Ribossômico 16S/genética , Adulto Jovem
12.
COPD ; 16(1): 18-24, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30947556

RESUMO

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.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Sumários de Alta do Paciente Hospitalar , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Doença Aguda , Idoso , Broncodilatadores/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Progressão da Doença , Prescrições de Medicamentos , Feminino , Humanos , Influenza Humana/prevenção & controle , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Pneumonia Pneumocócica/prevenção & controle , Encaminhamento e Consulta , Abandono do Hábito de Fumar , Exacerbação dos Sintomas , Vacinação
13.
J Med Genet ; 55(11): 779-784, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29875123

RESUMO

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.


Assuntos
Proteínas de Transporte/genética , Estudos de Associação Genética , Homozigoto , Proteínas de Membrana/genética , Mutação de Sentido Incorreto , Fenótipo , Enteropatias Perdedoras de Proteínas/diagnóstico , Enteropatias Perdedoras de Proteínas/genética , Adulto , Substituição de Aminoácidos , Biomarcadores , Biópsia , Proteínas de Transporte/química , Biologia Computacional/métodos , Consanguinidade , Feminino , Humanos , Recém-Nascido , Masculino , Proteínas de Membrana/química , Modelos Moleculares , Linhagem , Conformação Proteica , Enteropatias Perdedoras de Proteínas/metabolismo , Relação Estrutura-Atividade , Adulto Jovem
14.
PLoS One ; 13(3): e0193725, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29513729

RESUMO

BACKGROUND: A recently published, large prospective study showed unexpectedly high prevalence of acute pulmonary embolism (APE) among patients hospitalized for syncope. In such a case, a high incidence of recurrent pulmonary embolism is expected among patients who were discharged without APE workup. OBJECTIVES: To determine the incidence of symptomatic APE among patients hospitalized for a first episode of syncope and discharged without APE workup or anticoagulation. METHODS: This retrospective cohort study included patients hospitalized at Rambam Health Care Campus between January 2006 and February 2017 with a primary admission diagnosis of syncope, who were not investigated for APE and were not taking anticoagulants. The patients were followed up for up to three years after discharge. The occurrence of venous thromboembolism (VTE) during the follow-up period was documented. RESULTS: The median follow-up duration was 33 months. 1,126 subjects completed a three-year follow-up. During this period, 38 patients (3.38%) developed VTE, 17 (1.51%) of them had APE. The cumulative incidence of VTE and APE was 1.9% (95% CI 1.3%-2.5%) and 0.9% (95% CI 0.4%-1.3%) respectively. Only seven subjects developed APE during the first year of follow-up. The median times from the event of syncope to the development of APE and VTE were 18 and 19 months respectively. CONCLUSIONS: The cumulative incidence of VTE during a three-year follow-up period after an episode of syncope is low. In the absence of clinical suspicion, a routine diagnostic workup for APE in patients with syncope cannot be recommended.


Assuntos
Embolia Pulmonar/complicações , Embolia Pulmonar/epidemiologia , Síncope/complicações , Síncope/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Síncope/terapia
15.
Respir Med ; 136: 1-7, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29501240

RESUMO

BACKGROUND: Acute exacerbation of COPD (AECOPD) is one of the leading causes for hospitalization and readmission in developed countries. No laboratory indices were consistently found to be associated with readmission risk. Recent evidence attests that red blood cell distribution width (RDW), conveys important information for short and long term prognosis in a variety of medical conditions. Prognostic usefulness of RDW in patients with AECOPD has not been investigated. OBJECTIVE: To evaluate the usefulness of RDW in predicting early adverse outcomes in patients hospitalized due to AECOPD. METHODS: Patients hospitalized for AECOPD between 2011 and 2013 were revised. Clinical and laboratory parameters were noted. Participants were followed to determine the incidence of readmission due to AECOPD, readmission from any cause and composite end point of readmission or death during 60 days after discharge. RESULTS: 539 patients were included in the study. The 60-day overall readmission rate was 26.35%, of that, 41.55% were due to AECOPD. The Presence of heart failure, pH below 7.35 at discharge and abnormal RDW were associated with the composite endpoint. The negative predictive value of normal RDW was 80.12%. CONCLUSION: Increased RDW is an independent negative prognostic factor associated with adverse outcomes after hospitalization due to AECOPD.


Assuntos
Índices de Eritrócitos/fisiologia , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Aguda , Idoso , Área Sob a Curva , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Readmissão do Paciente/estatística & dados numéricos , Prognóstico , Doença Pulmonar Obstrutiva Crônica/mortalidade , Estudos Retrospectivos
16.
Harefuah ; 156(10): 663-665, 2017 Oct.
Artigo em Hebraico | MEDLINE | ID: mdl-29072388

RESUMO

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.


Assuntos
Alvéolos Pulmonares/metabolismo , Edema Pulmonar/metabolismo , Humanos , Pulmão , Mucosa Respiratória
18.
J Crit Care ; 42: 117-122, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28719839

RESUMO

OBJECTIVES: Sepsis is a multifactorial syndrome with increasing incidence of morbidity and mortality. Identification of outcome predictors is therefore essential. Recently, elevated brain natriuretic peptide (BNP) levels have been observed in patients with septic shock. Little information is available concerning BNP levels in patients with critical illness, especially with sepsis. Therefore, this study aims to evaluate the role of BNP as a biomarker for long-term mortality in patients with sepsis. METHODS: We studied 259 patients with sepsis and absence of heart failure. BNP levels were obtained for all patients. A long-term survival follow-up was done, and survival was evaluated 90days after admission, and during the subsequent 60months of follow-up. RESULTS: Eighty-two patients died during the 90-day follow-up (31.7%), 53 died in the index hospitalization (20.5%). On multivariate analysis models, elevated values of BNP were a strong predictor of in-hospital mortality, 90-day and 60-month mortality in patients with sepsis. BNP was a better prognostic predictor than the Sepsis-related Organ Failure Assessment (SOFA) score for 90-day mortality, and a better predictor for 60-month mortality in low risk groups. CONCLUSION: In the population of hospitalized patients with sepsis, BNP is a strong independent predictor of short- and long-term mortality.


Assuntos
Peptídeo Natriurético Encefálico/metabolismo , Sepse/mortalidade , Idoso , Biomarcadores/metabolismo , Cuidados Críticos , Feminino , Seguimentos , Mortalidade Hospitalar , Humanos , Masculino , Escores de Disfunção Orgânica , Prognóstico , Sepse/sangue , Choque Séptico/sangue , Choque Séptico/mortalidade
20.
Curr Drug Saf ; 12(1): 7-9, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27659942

RESUMO

Herein, we report a 70-year-old male patient, with recurrent multiple hepatic abscesses, that was admitted to the internal medicine department for treatment of Carbapenem Resistant Escherichia Coli (CRE) bacteremia. The patient was treated with Tigecycline; few days later, he developed "Disseminated Intravascular Coagulation (DIC)" like coagulation study abnormality that seemed to be related to Tigecycline treatment. Upon discontinuing it, the DIC-like condition was resolved. Tigecycline should be considered as a possible etiological factor in patients with DIC-like, and this therapy should be withdrawn immediately in suspected cases.


Assuntos
Antibacterianos/efeitos adversos , Coagulação Intravascular Disseminada/induzido quimicamente , Coagulação Intravascular Disseminada/diagnóstico , Minociclina/análogos & derivados , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Idoso , Coagulação Intravascular Disseminada/complicações , Humanos , Masculino , Minociclina/efeitos adversos , Índice de Gravidade de Doença , Trombocitopenia/complicações , Tigeciclina
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