Ebola Virus Glycoprotein Strongly Binds to Membranes in the Absence of Receptor Engagement.

Ebola virus (EBOV) is an enveloped virus that must fuse with the host cell membrane in order to release its genome and initiate infection. This process requires the action of the EBOV envelope glycoprotein (GP), encoded by the virus, which resides in the viral envelope and consists of a receptor binding subunit, GP1, and a membrane fusion subunit, GP2. Despite extensive research, a mechanistic understanding of the viral fusion process is incomplete. To investigate GP-membrane association, a key step in the fusion process, we used two approaches: high-throughput measurements of single-particle diffusion and single-molecule measurements with optical tweezers. Using these methods, we show that the presence of the endosomal Niemann-Pick C1 (NPC1) receptor is not required for primed GP-membrane binding. In addition, we demonstrate this binding is very strong, likely attributed to the interaction between the GP fusion loop and the membrane's hydrophobic core. Our results also align with previously reported findings, emphasizing the significance of acidic pH in the protein-membrane interaction. Beyond Ebola virus research, our approach provides a powerful toolkit for studying other protein-membrane interactions, opening new avenues for a better understanding of protein-mediated membrane fusion events.

Disparities in Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Prescription and Dispensing in the Israeli Population-A Retrospective Cohort Study.

OBJECTIVE: To describe disparities in prescribing and dispensing sodium-glucose cotransporter 2 inhibitors (SGLT2i) in Israel. RESEARCH DESIGN AND METHODS: This was a population-based retrospective cohort study of adults with type 2 diabetes eligible for SGLT2i treatment from 2017 to 2023. The primary outcome was the time between initial eligibility and the first prescription of SGLT2i. RESULTS: Among 32,742 eligible patients, only 53% were prescribed SGLT2i. Multivariable analyses, adjusting for death as a competing risk, revealed delays in prescription were associated with older age, Arab or Bedouin ethnicity, neoplasms, acute kidney failure, falls, previous hospitalization, urinary tract infections, and dementia. Factors associated with shorter time intervals to prescription were sex (men), medium/high socioeconomic status, and residing in an intermediate or central area of Israel. CONCLUSIONS: Disparities in drug prescription exist, even in a country with universal health coverage. Addressing these disparities requires improvements in health care systems, education, and alert systems to overcome barriers to evidence-based interventions.

Sex Differences in the Diagnosis, Management, and Outcomes of Suspected Non-ST-Elevation Acute Coronary Syndromes Meeting Rapid Rule-Out Criteria.

(1) Background: patients who meet current rapid rule-out criteria for myocardial infarction (MI) are considered low risk, yet their management remains nebulous, especially among women. We aimed to examine sex differences in the diagnosis, management, and outcomes of patients meeting the rapid rule-out criteria. (2) Methods: by simulating application of the rapid rule-out MI criteria, we analyzed consecutively triaged men and women with suspected NSTE-ACS who had high-sensitivity cardiac troponin T (hs-cTnT) values that met criteria (n = 11,477), in particular, those who were admitted (n = 3775). (3) Results: men constituted ~55% of triaged patients who met the rule-out criteria, whether admitted or discharged. Men were more likely to be admitted (33.7% vs. 31.9%, p = 0.04), more commonly with hs-cTnT values between level of detection (LOD, 5 ng/ml) and the 99th percentile (59.4% of all admissions vs. 40.5% for women), whereas women were more likely to be admitted with values < level of blank (LOB, 3 ng/mL; 22.9% vs. 9.2% for men). Thirty-day mortality (1 man and 1 woman) and in-hospital MI (9 men vs. 1 woman) were uncommon among admitted patients, yet resource utilization during 3-4 hospitalization days was substantial for both sexes, with men undergoing coronary angiography (6.8% vs. 2.9%) and revascularization (3.4% vs. 1.1%) more commonly. Long-term survival for both men and women, whether admitted or discharged, was significantly worse for hs-cTnT values between LOD and the 99th percentile, even after adjusting for age and cardiovascular comorbidities. (4) Conclusions: reporting actual hs-cTnT values < 99th percentile allows for better risk stratification, especially for women, possibly closing the sex gap.

The prevalence of masked hypertension in patients with lone atrial fibrillation: a cross sectional analytical study.

Atrial fibrillation (AF) is prevalent in individuals with essential hypertension (HTN). Masked hypertension occurs in up to 15% of the general population and is associated with adverse clinical outcome. The aim of the current study was to evaluate the prevalence of masked hypertension in apparently normotensive individuals with lone AF. A cross sectional analytical study performed at the Rabin Medical Center included all patients > 18 years who visited the emergency department (ED) in the years 2018-2021 with idiopathic AF, had normal blood pressure (BP) values during their ED visit and did not have a history of hypertension or current use of anti-hypertensives. Ambulatory blood pressure monitoring (ABPM) was performed in all eligible patients within 30 days from ED visit. Data collected included information from the ED visit and data extracted from the monitoring device. A total of 1258 patients were screened for eligibility, of which 40 were included in the analysis. The average age was 53.4 ± 16 years, 28 patients (70%) were males. Overall, 18 individuals (46%) had abnormal BP values according to the 2017 ACC/AHA guidelines for the diagnosis of hypertension. Of these, 12 had abnormal 24-h BP average (≥ 125/75 mmHg), one had isolated daytime abnormal average (≥ 130/80 mmHg) and 11 had isolated night time abnormal average (≥ 110/65 mmHg). Masked hypertension is prevalent in patients with lone AF without a diagnosis of HTN and performing ABPM in such individuals should be strongly considered.

Safety and efficacy of non-insulin therapy in non-critically ill hospitalized patients with type 2 diabetes mellitus.

INTRODUCTION: Clinical guidelines recommend insulin as the mainstay of therapy for hospitalized patients with diabetes mellitus. The aim of the current study is to evaluate safety and efficacy of non-insulin anti-hyperglycemic therapy in hospitalized patients. MATERIALS AND METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) examining treatment of hospitalized patients with type 2 diabetes with insulin vs non-insulin therapy. We searched PubMed and the Cochrane Library for RCTs published from inception to November 30, 2022. Primary outcomes were 30-day mortality and hypoglycemic events during hospitalization. This meta-analysis includes two parts, the first is a comparison between insulin and non-insulin therapy and the second is a comparison between insulin only and a combination of insulin+non-insulin therapy. RESULTS: A total of 14 randomized control studies and 1570 patients were included. There was a lower incidence of 30-day mortality in the insulin+non-insulin group compared with the insulin group without statistical significance, RR 0.64 (95%CI 0.30-1.35). Hypoglycemic events were significantly lower with the non-insulin therapies compared to insulin therapy, RR 0.23 (95%CI 0.09-0.55). Mean daily glucose levels were significantly lower in the insulin+non-insulin group compared to the insulin group by 10.83 mg/dL (95%CI -14.78-(-6.87)). CONCLUSIONS: Non-insulin either with or without insulin, results in lower rates of hypoglycemia. Non-insulin+insulin is more effective than insulin alone in reducing blood glucose levels. Non-insulin-based therapy is safe and effective for control of hyperglycemia. Insulin combined with non-insulin drugs seems to be the preferred treatment option for the majority of hospitalized patients with type 2 DM in the non-critical care setting.

Suspected Non-ST-elevation acute coronary syndrome meeting rapid rule-out criteria: resource utilization, diagnostic yield, and clinical outcomes of hospital admission.

AIMS: Many patients with suspected non-ST-elevation (NSTE) acute coronary syndromes (ACS) are admitted, even those with initial high-sensitivity cardiac troponins (hs-cTn) values who meet rapid rule-out criteria for myocardial infarction (MI). We examined the clinical outcomes, resource utilization, and diagnostic yield of suspected NSTE-ACS patients, who presented with hs-cTnT values meeting these criteria but were nevertheless hospitalized. METHODS AND RESULTS: Applying the 2020 European Society of Cardiology (ESC) rapid rule-out MI criteria, we identified consecutive patients with an initial value of hs-cTnT <5 ng/L or an initial value of ≥5 ng/L but <14 ng/L (99th percentile) and a small increment in a subsequent test, who were nevertheless admitted. The majority (85.4%) of patients presented to the emergency department (ED) with suspected NSTE-ACS had an initial hs-cTnT <99th percentile. We examined 3775 admitted patients out of 11 477 patients who were triaged and met MI rule-out criteria. Only 0.32% (12 patients) of admitted patients experienced index MI or overall death within 30 days. Resource utilization in terms of ED stay, hospital stay, noninvasive and invasive tests was substantial, yet revascularization was uncommon (2.5%). Multivariate adjustment for age, gender, and baseline cardiovascular risk factors demonstrates similar survival of admitted vs. discharged patients (P = 0.88). Initial hs-cTnT even below the 99th percentile provided a prognostic stratification for long term mortality. CONCLUSION: Our findings support a policy of ED discharge of suspected NSTE-ACS patients meeting rapid MI rule-out criteria and subsequent ambulatory evaluation, sparing resource-consuming admissions. In-hospital and ensuing prognosis were better with lower initial hs-cTnT values.

Glucose variability is a marker for COVID-19 severity and mortality

ABSTRACT Objective: We aimed to investigate the association between glucose coefficient of variation (CV) and mortality and disease severity in hospitalized patients with coronavirus disease-19 (COVID-19). Subjects and methods: Retrospective cohort study in a tertiary center of patients with COVID-19 admitted to designated departments between March 11th, 2020, and November 2nd, 2020. We divided patients based on quartiles of glucose CV after stratification to those with and without diabetes mellitus (DM). Main outcomes were length of stay and in-hospital mortality. Results: The cohort included 565 patients with a mean age of 67.71 ± 15.45 years, and 62.3% were male. Of the entire cohort, 44.4% had DM. The median glucose CV was 32.8% and 20.5% in patients with and without DM, respectively. In patients with DM, higher glucose CV was associated with a longer hospitalization in the unadjusted model (OR = 2.7, 95% CI [1.3,5.6] for Q4), and when adjusted for age, sex, comorbidities, and laboratory markers, this association was no longer statistically significant (OR = 1.3, 95% CI [0.4,4.5] for Q4). In patients with and without DM, higher glucose CV was associated with higher rates of in-hospital mortality in the unadjusted model, but adjustment for comorbidities and laboratory markers eliminated the association (OR = 0.5, 95% CI [0.1,3.4] for Q4 in patients with DM). Conclusion: Higher glucose CV was associated with increased in-hospital mortality and length of stay, but this association disappeared when the adjustment included laboratory result data. Glucose CV can serve as a simple and cheap marker for mortality and severity of disease in patients with COVID-19.

Glucose variability is a marker for COVID-19 severity and mortality.

Objective: We aimed to investigate the association between glucose coefficient of variation (CV) and mortality and disease severity in hospitalized patients with coronavirus disease-19 (COVID-19). Subjects and Methods: Retrospective cohort study in a tertiary center of patients with COVID-19 admitted to designated departments between March 11th, 2020, and November 2nd, 2020. We divided patients based on quartiles of glucose CV after stratification to those with and without diabetes mellitus (DM). Main outcomes were length of stay and in-hospital mortality. Results: The cohort included 565 patients with a mean age of 67.71 ± 15.45 years, and 62.3% were male. Of the entire cohort, 44.4% had DM. The median glucose CV was 32.8% and 20.5% in patients with and without DM, respectively. In patients with DM, higher glucose CV was associated with a longer hospitalization in the unadjusted model (OR = 2.7, 95% CI [1.3,5.6] for Q4), and when adjusted for age, sex, comorbidities, and laboratory markers, this association was no longer statistically significant (OR = 1.3, 95% CI [0.4,4.5] for Q4). In patients with and without DM, higher glucose CV was associated with higher rates of in-hospital mortality in the unadjusted model, but adjustment for comorbidities and laboratory markers eliminated the association (OR = 0.5, 95% CI [0.1,3.4] for Q4 in patients with DM). Conclusion: Higher glucose CV was associated with increased in-hospital mortality and length of stay, but this association disappeared when the adjustment included laboratory result data. Glucose CV can serve as a simple and cheap marker for mortality and severity of disease in patients with COVID-19.

Re-Admission of COVID-19 Patients Hospitalized with Omicron Variant-A Retrospective Cohort Study.

In accordance with previous publications, re-admission rates following hospitalization of patients with COVID-19 is 10%. The aim of the current study was to describe the rates and risk factors of hospital re-admissions two months following discharge from hospitalization during the fifth wave due to the dominant Omicron variant. A retrospective cohort study was performed in Rabin Medical Center, Israel, from November 2021 to February 2022. The primary outcome was re-admissions with any diagnosis; the secondary outcome was mortality within two months of discharge. Overall, 660 patients were hospitalized with a diagnosis of COVID-19. Of the 528 patients discharged from a primary hospitalization, 150 (28%) were re-admitted. A total of 164 patients (25%) died throughout the follow-up period. A multi-variable analysis determined that elevated creatinine was associated with a higher risk of re-admissions. Rates of re-admissions after discharge during the Omicron wave were considerably higher compared to previous waves. A discharge plan for surveillance and treatment following hospitalization is of great importance in the management of pandemics.

Current use of D-dimer for the exclusion of venous thrombosis in hospitalized patients.

D-dimer assay's utility for excluding venous thromboembolism (VTE) in hospitalized patients is debatable. We aimed to assess the current use of D-dimer as a diagnostic tool for excluding VTE in hospitalized patients and examine a mandatory age-adjusted D-dimer (AADD) threshold for diagnostic imaging. Retrospective cohort study between 2014 to 2019 that included patients from medical and surgical wards with a positive AADD result drawn during their hospitalization. The outcomes were determining a D-dimer threshold requiring further evaluation and assessing the prognostic value of D-dimer in predicting clinically relevant VTE in hospitalized patients. The cohort included 354 patients, 56% of them underwent definitive diagnostic imaging, and 7.6% were diagnosed with VTE after a positive AADD within 90 days of follow-up. Mortality rates were higher in patients diagnosed with VTE (33.3% vs. 15.9%, p = 0.03). Patients with pneumonia and other infectious etiologies were less likely to be further evaluated by definitive imaging (p = 0.001). Patients with a respiratory complaint (p = 0.02), chest pain (p < 0.001), or leg swelling (p = 0.01) were more likely to undergo diagnostic imaging. Patients with D-dimer levels > X2 the AADD were at increased risk of VTE [OR 3.87 (1.45-10.27)]. At 90 days of follow-up, no excess mortality was observed for patients without diagnostic evaluation following elevated AADD. D-dimer may be used in hospitalized patients to exclude VTE using the traditional AADD thresholds, with a high negative predictive value. D-dimer levels > X2 the AADD usually mandates further diagnostic imaging, while lower levels, probably do not require additional workup, with a sensitivity of almost 80% and no excess mortality.

T-Lymphoblastic Leukemia/Lymphoma and Thymoma: A Case Report and Review of the Literature of a Rare Association.

The co-occurrence of thymoma and T-lymphoblastic lymphoma/leukemia is an extremely rare but previously reported association that poses a diagnostic and therapeutic challenge. We describe a 67-year-old patient with long-standing untreated B1 thymoma that presented with constitutional symptoms and a painless soft tissue mass on the right chest wall. Pathological analysis of the biopsy from the mass demonstrated T-lymphoblastic leukemia/lymphoma. The patient went through a complicated course, was refractory to several lines of therapy, and eventually underwent allogeneic hematopoietic stem cell transplantation in complete remission from a matched related donor. The association between thymoma and malignant neoplasms has been described in the literature, most notably with colorectal adenocarcinoma and thyroid cancer. Thymoma-associated leukemia is, however, extremely unusual, with limited reports in the literature. Distinguishing between thymoma and leukemia can be challenging and often requires meticulous diagnostic efforts. For patients with a past history of thymoma, awareness of this particular association should be bared in mind to allow earlier diagnosis and therapy.

Outcome of Elderly Patients with Venous Thromboembolism Treated with Direct Oral Anticoagulants-A Retrospective Cohort Study.

INTRODUCTION: Randomized controlled trials that compared direct oral anticoagulants (DOACs) to vitamin K antagonists (VKA) for the treatment of venous thromboembolism (VTE), demonstrated both efficacy and safety of DOACs. The aim of the current study was to compare DOACs to VKA for the treatment of VTE in the elderly, in a real-life setting. METHODS: A retrospective cohort study was performed in Rabin Medical Center encompassing a 7-year period. Hospitalized patients >65 years, with a diagnosis of VTE discharged with DOACs or VKA were included. The primary outcome was a composite of all-cause mortality, major bleeding, recurrent VTEs and hospitalizations throughout the follow-up period of one year. RESULTS: A total of 603 patients were included in the final analysis. The mean age was 79.6 ± 8.5 years. The primary composite outcome occurred in 74.6% and 56.7% of the patients in the VKA group and DOACs group, respectively, hazard ratio 0.59, 95% confidence interval 0.46 to 0.76, in favor of the DOACs group. In a matched cohort analysis, the results were the same as the original analysis. CONCLUSION: In the elderly population, treatment of VTE with DOACs was associated with a lower rate of the composite outcome. DOACs are safe and effective for elderly patients with VTE.

Risk-factors for re-admission and outcome of patients hospitalized with confirmed COVID-19.

Burden of COVID-19 on Hospitals across the globe is enormous and has clinical and economic implications. In this retrospective study including consecutive adult patients with confirmed SARS-CoV-2 who were admitted between 3/2020 and 30/9/20, we aimed to identify post-discharge outcomes and risk factors for re-admission among COVID-19 hospitalized patients. Mortality and re-admissions were documented for a median post discharge follow up of 59 days (interquartile range 28,161). Univariate and multivariate analyses of risk factors for re-admission were performed. Overall, 618 hospitalized COVID-19 patients were included. Of the 544 patient who were discharged, 10 patients (1.83%) died following discharge and 50 patients (9.2%) were re-admitted. Median time to re-admission was 7 days (interquartile range 3, 24). Oxygen saturation or treatment prior to discharge were not associated with re-admissions. Risk factors for re-admission in multivariate analysis included solid organ transplantation (hazard ratio [HR] 3.37, 95% confidence interval [CI] 2.73-7.5, p = 0.0028) and higher Charlson comorbidity index (HR 1.34, 95% CI 1.23-1.46, p < 0.0001). Mean age of post discharge mortality cases was 85.0 (SD 9.98), 80% of them had cognitive decline or needed help in ADL at baseline. In conclusion, re-admission rates of hospitalized COVID-19 are fairly moderate. Predictors of re-admission are non-modifiable, including baseline comorbidities, rather than COVID-19 severity or treatment.

Detection of occult atrial fibrillation with 24-hour ECG after cryptogenic acute stroke or transient ischaemic attack: A retrospective cross-sectional study in a primary care database in Israel.

BACKGROUND: Ischaemic stroke or cerebrovascular accident (CVA) due to occult atrial fibrillation (AF) may cause severe morbidity and mortality. Diagnosing occult AF can be challenging and there is no consensus regarding the optimal duration of screening. A 24-hour Holter electrocardiogram (ECG) is frequently employed to detect occult AF following ischaemic CVA. OBJECTIVES: Demonstration of occult AF detection rate using a 24-hour Holter ECG in a primary care setting with descriptive analyses of independent variables to compare AF detected and non-detected patients. METHODS: This retrospective cross-sectional study utilised primary care data and included patients 50 years and older with a new CVA or transient ischaemic attack (TIA) diagnosis followed by a 24-hour Holter examination within 6 months, between 01 January 2013 and 01 June 2019. The analyses included descriptive statistics comparing demographics and clinical characteristics in patients who had AF or Atrial Flutter (AFL) detection to those who did not. RESULTS: Out of 5015 eligible patients, 66 (1.3%) were diagnosed with AF/AFL, with a number needed to screen of 88.5. Compared with those without AF/AFL detection, those diagnosed were older (75.42 ± 7.89 vs. 69.89 ± 9.88, p = 0.050), had a higher prevalence of hypertension (80.3% vs. 66.8%, p = 0.021) and chronic kidney disease (CKD) (71.2% vs. 44.2%, p < 0.001). CONCLUSION: 24-hour Holter has a low AF/AFL detection rate. Older persons and those with hypertension or CKD are more likely to be detected with AF/AFL using this method.

A Randomized Clinical Trial of Linagliptin vs. Standard of Care in Patients Hospitalized With Diabetes and COVID-19.

Objective: To assess the effect of linagliptin vs. standard therapy in improving clinical outcomes in patients hospitalized with diabetes and coronavirus disease 2019 (COVID-19). Materials and Methods: We did an open-label, prospective, multicenter, randomized clinical trial in 3 Israeli hospitals between October 1, 2020, and April 4, 2021. Eligible patients were adults with type 2 diabetes mellitus and a diagnosis of COVID-19. A total of 64 patients, 32 in each group, were randomized to receive linagliptin 5 mg PO daily throughout the hospitalization or standard of care therapy. The primary outcome was time to clinical improvement within 28 days after randomization, defined as a 2-point reduction on an ordinal scale ranging from 0 (discharged without disease) to 8 (death). Results: The mean age was 67 ± 14 years, and most patients were male (59.4%). Median time to clinical improvement was 7 days (interquartile range (IQR) 3.5-15) in the linagliptin group compared with 8 days (IQR 3.5-28) in the standard of care group (hazard ratio, 1.22; 95% CI, 0.70-2.15; p = 0.49). In-hospital mortality was 5 (15.6%) and 8 (25.0%) in the linagliptin and standard of care groups, respectively (odds ratio, 0.56; 95% CI, 0.16-1.93). The trial was prematurely terminated due to the control of the COVID-19 outbreak in Israel. Conclusions: In this randomized clinical trial of hospitalized adult patients with diabetes and COVID-19 who received linagliptin, there was no difference in the time to clinical improvement compared with the standard of care. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04371978.

Use of proton pump inhibitors is associated with lower rates of first-time ischemic stroke in community-dwelling elderly.

AIM: Data on cardiovascular outcomes in elderly using proton pump inhibitors (PPI) are scant. We aimed to test the association between PPI use and the occurrence of first-time ischemic stroke (FTIS) among elderly. METHODS: The electronic database of a centrally located district branch of a large health maintenance organization in Israel was retrospectively screened (2002-2016) for community-dwelling individuals (≥65-95 years) for demographics and co-morbidities. Follow-up was until FTIS, death or end of study. Findings were analyzed by PPI use and occurrence of FTIS. RESULTS: 29,639 subjects (without history of stroke and use of antiplatelet aggregation drugs) mean age of 82.2 ± 5.5 years (range: 65-95 years, 38% male) were analyzed: 8,600 (29%) used PPIs. Mean follow up was 10.58 years (SD ± 5.44). Similar total and annual occurrence rates of FTIS were depicted in PPI users and non-users (20.9% vs. 21% and 2% vs. 2.1%, respectively). On a Cox regression analysis, upon adjustment for age, gender and cardiovascular disease related risk factors, PPI use was significantly associated with lower rates of FTIS (HR 0.73, 95% C.I. 0.69-0.77, p < 0.001). The risk for FTIS was significantly lower in subjects using PPI at any dose and for any time period compared to non-users (HR 0.9, 95% C.I. 0.85-0.96 for 7-48 yearly prescriptions and HR 0.51, 95% C.I. 0.46-0.55 for ≥49 yearly prescriptions). CONCLUSIONS: PPI use was associated with lower rates of FTIS in community-dwelling elders. Prospective large-scale studies are needed to fully elucidate the effect of PPI in this aging population.

Post-transplant diabetes mellitus: incidence, predicting factors and outcomes.

PURPOSE: To identify predictors and evaluate outcomes of posttransplant diabetes mellitus (PTDM) and to investigate the effect of treatment modalities on outcomes. METHODS: The database of a tertiary medical center was searched for all adult patients without prior diabetes who underwent lung, liver, or heart transplantation between January 1, 2012 and June 30, 2018. Patients in whom PTDM (defined as HbA1C ≥ 6.5% at least 3 months post transplantation) developed during follow-up (mean 3.32 years) were identified. Risk factors for PTDM, determined by regression analysis and clinical outcomes [all-cause mortality, severe infections, graft loss, and major adverse cardiovascular events (MACE)], were compared between those who developed PTDM and those who did not; in the former, insulin-based therapy was compared with non-insulin regimen. RESULTS: The cohort included 281 transplant recipients: 158 lung, 109 liver, and 14 heart. PTDM was diagnosed in 60 (21.35%) patients at a mean of 11.3 ± 12.89 months post transplantation. The only significant independent risk factor for PTDM was age (HR 1.028, 95% CI = 1.002-1.054, P = 0.0314). PTDM was associated with higher rates of severe infections (HR 2.565, 95% CI = 1.626-4.050, P < 0.0001), MACE (HR 1.856, 95% CI = 1.013-3.401, P = 0.0454) and death (HR 1.840, 95% CI = 1.024-3.304, P = 0.0413). Recipients treated with insulin-based regimens had a higher risk of severe infections (HR 2.579, 95% CI = 1.640-4.055, P < 0.0001), MACE (1.925, 95% CI = 1.074-3.451, P = 0.0278) and death (HR 1.960, 95% CI = 1.071-3.586, P = 0.0291). CONCLUSIONS: PTDM is associated with increased mortality and poor outcomes in lung, liver, and heart transplant recipients. Early identification and aggressive treatment of PTDM and its associated cardiometabolic risk factors may improve outcomes.

Pheochromocytoma: Positive predictive values of mildly elevated urinary fractionated metanephrines in a large cohort of community-dwelling patients.

The diagnostic utility of different thresholds of elevated urinary fractionated metanephrine (UFM) for pheochromocytoma-paraganglioma (PPGL) was evaluated in 10 164 community-dwelling subjects (2012-2017). Levels were ≥1.5× the upper normal limit (UNL) in 276 subjects (2.7%) and ≥2×UNL in 138 (1.4%). PPGL was subsequently diagnosed in 59 (mean age 51.9 ± 14.3, 64% female); 58 (98.3%) with UFM ≥ 2×UNL. Positive predictive values (PPV) were 42% for UFM ≥ 2×UNL, 55% for UFM ≥ 2.5×UNL, and 69% for UFM ≥ 3×UNL. The main reason for PPGL screening (52.5%) was adrenal incidentaloma. Mean (median) metanephrine/normetanephrine levels were 6.7 ± 9×UNL (3 × UNL) and 6.1 ± 8.9×UNL (2.5 × UNL). Six patients (10.2%) had an extra-adrenal tumor (one malignant paraganglioma); one had bilateral pheochromocytoma. Only one patient presented with the "classic triad" (headache, palpitations, sweating). In conclusion, after excluding obvious reasons for false-positive results, thorough diagnostic assessment for PPGL is justified in all subjects with UFM ≥ ×2UNL. The PPV of milder UFM elevations is very low.

Lowering the upper limit of serum alanine aminotransferase levels may reveal significant liver disease in the elderly.

This study sought to determine the prevalence of significant liver disease in those subjects with serum alanine aminotransferase levels in the range between the current and the newly suggested upper limit of normal (termed the delta range). The files of the previous study subjects (who underwent at least one alanine aminotransferase measurement in 2002 and followed to 2012) were reviewed for a diagnosis of chronic liver disease; aspartate aminotransferase/platelet ratio index, FIB-4 and alanine aminotransferase/aspartate aminotransferase ratio were used to evaluate liver fibrosis. The prevalence of significant liver disease, by diagnoses and fibrosis scores was compared between subjects with alanine aminotransferase levels in the delta range (men, 42-45 IU/L; women, 26-34 IU/L) and in the newly suggested normal range (men, 15-42 IU/L; women, 10-26 IU/L). The cohort included 49,634 subjects (41% male, mean age 83±6 years) of whom 2022 were diagnosed with chronic liver disease including 366 with cirrhosis. Compared to subjects with alanine aminotransferase levels in the newly suggested normal range, subjects with alanine aminotransferase levels in the delta range had a significantly higher rate of chronic liver disease (men, 15.3% vs. 4.9%; women, 7.8% vs. 3.3%) and of cirrhosis specifically (men, 4.2% vs. 0.9%; women, 1.5% vs. 0.4%) and also had higher mean fibrosis scores (P <0.001 for all). Lowering the current upper limit of normal of serum alanine aminotransferase may help to identify elderly patients at risk of significant liver disease.

Structural and Functional Echocardiographic Changes Following Kidney Transplantation: The Role of Allograft Function.

BACKGROUND: Kidney transplantation is associated with early improvement in cardiac function and structure; however, data on cardiac adaptation and its relation to kidney allograft function remain sparse. OBJECTIVES: To investigate the relationship between post-transplant kidney function and echocardiographic measures in patients with normal/preserved pre-transplant cardiac structure and function. METHODS: The study included 113 patients who underwent kidney transplantation at a single tertiary medical center from 2000 to 2012. The patients were evaluated by echocardiography before and after transplantation, and the relation between allograft function and echocardiographic changes was evaluated. Echocardiography was performed at a median of 510 days after transplantation. RESULTS: The post-transplantation estimated glomerular filtration rate (eGFR) was directly correlated with left ventricular (LV) systolic function and inversely correlated with LV dimensions, LV wall thickness, left atrial diameter, and estimated systolic pulmonary arterial pressure. In patients with significant allograft dysfunction (eGFR ≤ 45 ml/min), LV hypertrophy worsened, with no improvement in LV dimensions. In contrast, in patients with preserved kidney function, there was a significant reduction in both LV diameter and arterial pulmonary systolic pressure. CONCLUSIONS: Our results show that in kidney transplant recipients, allograft function significantly affects cardiac structure and function. Periodic echocardiographic follow-up is advisable, especially in patients with kidney graft dysfunction.