The direct effect of SARS-CoV-2 virus vaccination on human ovarian granulosa cells explains menstrual irregularities.

Following administration of the SARS-CoV-2 vaccine, many women worldwide reported short-term menstrual irregularities. Although menstrual bleeding, "the fifth vital sign", is experienced by more than 300 million people on any given day worldwide, these changes were only partially studied. Irregular periods are important well beyond fertility and the discomfort they impose; they are associated with the risk of cardiovascular morbidity, chronic diseases, and premature mortality. Pre-clinical examination of the vaccine polymeric envelope indicates its accumulation in the ovaries. The somatic endocrine cells of the ovarian follicle - the granulosa cells (GCs)-participate in the strict hypothalamic-pituitary-ovarian (HPO) feedback loop that governs the menstrual cycle via endocrine and paracrine regulators, as AMH and Inhibins. We aimed to unravel the direct effect of the COVID-19 vaccine on GCs and link their post-vaccine activity to changes in menstrual patterns. Human primary GCs exposed in-vitro to the Pfizer COVID-19 vaccine BNT162b2, demonstrated no change in their viability but altered mRNA transcripts, specifically of the regulatory key factors: InhibinB was upregulated, whereas AMH was downregulated. We further examined pre- and post-vaccination blood samples from individual women and found a 2-3 folds change in the post-vaccination FSH/InhibinB protein level ratio, compared to their pre-vaccination values. This altered expression of InhibinB could significantly impact the HPO axis in vaccinated women and may ultimately influence the endometrium cyclicity, manifested clinically by the commonly reported changes in menstrual bleeding patterns.

Cortisol Levels During First Admission Day Are Associated With Clinical Outcomes in Surgical Critically Ill Patients.

IMPORTANCE: To explore the correlation between cortisol levels during first admission day and clinical outcomes. OBJECTIVES: Although most patients exhibit a surge in cortisol levels in response to stress, some suffer from critical illness-related corticosteroid insufficiency (CIRCI). Literature remains inconclusive as to which of these patients are at greater risk of poor outcomes. DESIGN: A retrospective study. SETTING: A surgical ICU (SICU) in a tertiary medical center. PARTICIPANTS: Critically ill patients admitted to the SICU who were not treated with steroids. MAIN OUTCOMES AND MEASURES: Levels of cortisol taken within 24 hours of admission (day 1 [D1] cortisol) in 1412 eligible patients were collected and analyzed. Results were categorized into four groups: low (0-10 µg/dL), normal (10-25 µg/dL), high (25-50 µg/dL), and very high (above 50 µg/dL) cortisol levels. Primary endpoint was 90-day mortality. Secondary endpoints were the need for organ support (use of vasopressors and mechanical ventilation [MV]), ICU length of stay (LOS), and duration of MV. RESULTS: The majority of patients (63%) had high or very high D1 cortisol levels, whereas 7.6% had low levels and thus could be diagnosed with CIRCI. There were statistically significant differences in 90-day mortality between the four groups and very high levels were found to be an independent risk factor for mortality, primarily in patients with Sequential Organ Failure Assessment (SOFA) less than or equal to 3 or SOFA greater than or equal to 7. Higher cortisol levels were associated with all secondary endpoints. CIRCI was associated with favorable outcomes. CONCLUSIONS AND RELEVANCE: In critically ill surgical patients D1 cortisol levels above 50 mcg/dL were associated with mortality, need for organ support, longer ICU LOS, and duration of MV, whereas low levels correlated with good clinical outcomes even though untreated. D1 cortisol level greater than 50 mcg/dL can help discriminate nonsurvivors from survivors when SOFA less than or equal to 3 or SOFA greater than or equal to 7.

Relationship among sleep, work features, and SARS-cov-2 vaccine antibody response in hospital workers.

STUDY OBJECTIVES: Immunity is influenced by sleep and the circadian rhythm. Healthcare workers are predisposed to both insufficient sleep and circadian disruption. This study aimed to evaluate the relationship between sleep and work characteristics and the antibody response to the mRNA SARS-CoV-2 vaccine BNT162b2. METHODS: The authors' prospective cohort study ("COVI3") evaluated the effect of a third (booster) dose of the BNT162b2 vaccine. A subset of participants provided information on anthropometric measures, sleep, stress and work characteristics including shift work and number of work hours per week. Blood samples for anti-S1-RBD IgG antibody levels were obtained 21 weeks following receipt of the third dose of the vaccine. RESULTS: In total, 201 healthcare workers (73% women) were included. After adjustment for age, body mass index (BMI), shift work, smoking status, and perceived stress, short sleep duration (<7 h per night) was associated with lower anti-S1-RBD IgG levels (Odds ratio 2.36 [95% confidence interval 1.08-5.13]). Participants who performed shift work had higher odds of lower anti-S1-RBD IgG levels compared to those who did not work in shifts [odds ratio = 2.99 (95% confidence interval 1.40, 6.39)] after accounting for age, short sleep duration, BMI, smoking status and perceived stress. CONCLUSIONS: Shift work and self-reported short sleep duration were associated with a lower antibody response following a booster dose of the SARS-CoV-2 vaccine. These findings suggest that the efficacy of vaccination, particularly among healthcare workers, may be augmented by addressing both sleep and circadian alignment.

Kinetics of C-reactive protein during extracorporeal membrane oxygenation.

BACKGROUND: The exposure of blood to the artificial circuit during extracorporeal membrane oxygenation (ECMO) can induce an inflammatory response. C-reactive protein (CRP) is a commonly used biomarker of systemic inflammation. METHODS: In this retrospective observational study, we analyzed results of daily plasma CRP measurements in 110 critically ill patients, treated with ECMO. We compared CRP levels during the first 5 days of ECMO operation, between different groups of patients according to ECMO configurations, Coronavirus disease 2019 (COVID-19) status, and mechanical ventilation parameters. RESULTS: There was a statistically significant decrease in CRP levels during the first 5 days of veno-venous (VV) ECMO (173 ± 111 mg/L, 154 ± 107 mg/L, 127 ± 97 mg/L, 114 ± 100 mg/L and 118 ± 90 mg/L for days 1-5 respectively, p < 0.001). Simultaneously, there was a significant reduction in ventilatory parameters, as represented by the mechanical power (MP) calculation, from 24.02 ± 14.53 J/min to 6.18 ± 4.22 J/min within 3 h of VV ECMO initiation (p < 0.001). There was non-significant trend of increase in CRP level during the first 5 days of veno arterial (VA) ECMO (123 ± 80 mg/L, 179 ± 91 mg/L, 203 ± 90 mg/L, 179 ± 95 mg/L and 198 ± 93 for days 1-5 respectively, p = 0.126) and no significant change in calculated MP (from 14.28 ± 8.56 J/min to 10.81 ± 8.09 J/min within 3 h if ECMO initiation, p = 0.071). CONCLUSIONS: We observed a significant decrease in CRP levels during the first 5 days of VV ECMO support, and suggest that the concomitant reduction in ventilatory MP may have mitigated the degree of alveolar stress and strain that could have contributed to a decrease in the systemic inflammatory process.

Healthcare policy changes in an era of health workforce shortage.

In their recent IJHPR article, Wimpfheimer and colleagues outline the implications for the field of anesthesia of two major healthcare policy changes in Israel: The Yatziv Reform in licensing foreign medical graduates and the efforts to reduce residents' on-call shift duration. We argue that these reforms are necessary to strengthen the healthcare workforce and improve the quality of care in the long term, even though they may limit the availability of healthcare personnel for several years, particularly in the field of anesthesia. In this commentary, we examine the background to these policy changes, their likely impact on the medical workforce in Israel in general, and propose steps to reconcile these reforms with the global and national shortage of physicians. We urge policymakers to allocate the required resources and begin preparing for an era of continuous mismatch between physician supply and demand, which will necessitate creative solutions, increased reliance on technology, and the introduction of paramedical professionals to help offload tasks and better utilize the scarce physician workforce.

Two-hour indirect calorimetry measurement as a predictor of 24-hour energy expenditure in critically ill surgical patients: A longitudinal study.

BACKGROUND: Measuring energy expenditure (EE) by indirect calorimetry (IC) has become the gold standard tool for critically ill patients to define energy targets and tailor nutrition. Debate remains as to the optimal duration of measurements or the optimal time of day in which to perform IC. METHODS: In this retrospective longitudinal study, we analyzed results of daily continuous IC in 270 mechanically ventilated, critically ill patients admitted to the surgical intensive care unit in a tertiary medical center and compared measurements performed at different hours of the day. RESULTS: A total of 51,448 IC hours was recorded, with an average 24-h EE of 1523 ± 443 kcal/day. Night shift (00:00-8:00) was found to have significantly lower EE measurements (mean, 1499 ± 439 kcal/day) than afternoon (16:00-00:00; mean, 1526 ± 435 kcal/day) and morning (8:00-16:00; mean, 1539 ± 462 kcal/day) measurements (P < 0.001 for all). The bi-hourly time frame that most closely resembled the daily mean was 18:00-19:59, with a mean of 1521 ± 433 kcal/day. Daily EE measurements of the continuous IC at days 3-7 of admission showed a trend toward a daily increase in 24-h EE, but the difference was not statistically significant (P = 0.081). CONCLUSIONS: Periodic measurements of EE can differ slightly when performed at various hours of the day, but the error range is small and may not necessarily have a clinical impact. When continuous IC is not available, a 2-h EE measurement between 18:00 and 19:59 can serve as a reasonable alternative.

The price of internship through COVID-19: 1st year physicians report substantial mental health symptoms during the pandemic.

OBJECTIVES: To examine the prevalence of mental health symptoms among medical interns working for the first time as physicians in a large tertiary hospital in Israel during the 1st COVID year. METHODS: All interns who worked for at least 2 months during the 1st COVID year (March 2020-February 2021) at the Tel-Aviv Sourasky Medical Center (TASMC), a large tertiary general hospital in Israel were approached simultaneously during April-May 2021, and were requested to fill in an online survey. In each questionnaire, the interns were asked to refer to the worst time they endured the symptoms described. Included were all medical. Depression and anxiety symptoms, post-traumatic stress symptoms and Burnout measures were evaluated using validated questionnaires. Depressive/anxiety symptoms were defined as primary end measures. We assessed the association between depression and anxiety symptoms, and demographic, post-traumatic and burnout measures. RESULTS: 145 out of 188 interns completed the study (77% overall response rate). The mean age was 30.36 ± 2.97. Almost half the interns (47%) reported depression/anxiety symptoms. The high depression/anxiety group was characterized by a lower mean age (29.87 ± 2.93 vs. 30.92 ± 2.91, p = 0.041), higher post-traumatic symptoms (15.62 ± 13.32 vs. 3.63 ± 5.59, p < 0.0001) and higher scores in 2/3 burnout subscales - emotional exhaustion (5.09 ± 1.29 vs. 3.61 ± 1.38, p = 0.000001) and depersonalization (3.83 ± 1.71 vs. 2.94 ± 1.46, p = 0.002). 11.4% of interns in the full sample reported they used cannabis or alcohol as "self-medication". CONCLUSIONS: medical interns serving for their first year as physicians during the COVID pandemic, developed mental symptoms in alarming numbers. The findings point to a crucial need to implement active interventions to protect these doctors, so that they can safely embark on their medical careers, specifically in times of global health crises.

Short-Term Safety of Booster Immunization With BNT162b2 mRNA COVID-19 Vaccine in Healthcare Workers.

This study demonstrated a favorable short-term safety profile after a third dose of the BNT162b2 vaccine among healthcare workers (HCWs). There were more frequent local reactions and less systemic reactions compared to the second dose. The HCWs who reported reactions had higher prebooster titer of anti-S1 antibodies compared to those who reported no reactions.

Association of a Third Dose of BNT162b2 Vaccine With Incidence of SARS-CoV-2 Infection Among Health Care Workers in Israel.

Importance: Administration of a BNT162b2 booster dose (Pfizer-BioNTech) to fully vaccinated individuals aged 60 years and older was significantly associated with lower risk of SARS-CoV-2 infection and severe illness. Data are lacking on the effectiveness of booster doses for younger individuals and health care workers. Objective: To estimate the association of a BNT162b2 booster dose with SARS-CoV-2 infections among health care workers who were previously vaccinated with a 2-dose series of BNT162b2. Design, Setting, and Participants: This was a prospective cohort study conducted at a tertiary medical center in Tel Aviv, Israel. The study cohort included 1928 immunocompetent health care workers who were previously vaccinated with a 2-dose series of BNT162b2, and had enrolled between August 8 and 19, 2021, with final follow-up reported through September 20, 2021. Screening for SARS-CoV-2 infection was performed every 14 days. Anti-spike protein receptor binding domain IgG titers were determined at baseline and 1 month after enrollment. Cox regression with time-dependent analysis was used to estimate hazard ratios of SARS-CoV-2 infection between booster-immunized status and 2-dose vaccinated (booster-nonimmunized) status. Exposures: Vaccination with a booster dose of BNT162b2 vaccine. Main Outcomes and Measures: The primary outcome was SARS-CoV-2 infection, as confirmed by reverse transcriptase-polymerase chain reaction. Results: Among 1928 participants, the median age was 44 years (IQR, 36-52 years) and 1381 were women (71.6%). Participants completed the 2-dose vaccination series a median of 210 days (IQR, 205-213 days) before study enrollment. A total of 1650 participants (85.6%) received the booster dose. During a median follow-up of 39 days (IQR, 35-41 days), SARS-CoV-2 infection occurred in 44 participants (incidence rate, 60.2 per 100 000 person-days); 31 (70.5%) were symptomatic. Five SARS-CoV-2 infections occurred in booster-immunized participants and 39 in booster-nonimmunized participants (incidence rate, 12.8 vs 116 per 100 000 person-days, respectively). In a time-dependent Cox regression analysis, the adjusted hazard ratio of SARS-CoV-2 infection for booster-immunized vs booster-nonimmunized participants was 0.07 (95% CI, 0.02-0.20). Conclusions and Relevance: Among health care workers at a single center in Israel who were previously vaccinated with a 2-dose series of BNT162b2, administration of a booster dose compared with not receiving one was associated with a significantly lower rate of SARS-CoV-2 infection over a median of 39 days of follow-up. Ongoing surveillance is required to assess durability of the findings.

Association Between Vaccination With BNT162b2 and Incidence of Symptomatic and Asymptomatic SARS-CoV-2 Infections Among Health Care Workers.

IMPORTANCE: Randomized clinical trials have provided estimates of the effectiveness of the BNT162b2 vaccine against symptomatic SARS-CoV-2 infection, but its effect on asymptomatic infections remains unclear. OBJECTIVE: To estimate the association of vaccination with the Pfizer-BioNTech BNT162b2 vaccine with symptomatic and asymptomatic SARS-CoV-2 infections among health care workers. DESIGN, SETTING, AND PARTICIPANTS: This was a single-center, retrospective cohort study conducted at a tertiary medical center in Tel Aviv, Israel. Data were collected on symptomatic and asymptomatic SARS-CoV-2 infections confirmed via polymerase chain reaction (PCR) tests in health care workers undergoing regular screening with nasopharyngeal swabs between December 20, 2020, and February 25, 2021. Logistic regression was used to calculate incidence rate ratios (IRRs) comparing the incidence of infection between fully vaccinated and unvaccinated participants, controlling for demographics and the number of PCR tests performed. EXPOSURES: Vaccination with the BNT162b2 vaccine vs unvaccinated status was ascertained from the employee health database. Full vaccination was defined as more than 7 days after receipt of the second vaccine dose. MAIN OUTCOMES AND MEASURES: The primary outcome was the regression-adjusted IRR for symptomatic and asymptomatic SARS-CoV-2 infection of fully vaccinated vs unvaccinated health care workers. The secondary outcomes included IRRs for partially vaccinated health care workers (days 7-28 after first dose) and for those considered as late fully vaccinated (>21 days after second dose). RESULTS: A total of 6710 health care workers (mean [SD] age, 44.3 [12.5] years; 4465 [66.5%] women) were followed up for a median period of 63 days; 5953 health care workers (88.7%) received at least 1 dose of the BNT162b2 vaccine, 5517 (82.2%) received 2 doses, and 757 (11.3%) were not vaccinated. Vaccination was associated with older age compared with those who were not vaccinated (mean age, 44.8 vs 40.7 years, respectively) and male sex (31.4% vs 17.7%). Symptomatic SARS-CoV-2 infection occurred in 8 fully vaccinated health care workers and 38 unvaccinated health care workers (incidence rate, 4.7 vs 149.8 per 100 000 person-days, respectively, adjusted IRR, 0.03 [95% CI, 0.01-0.06]). Asymptomatic SARS-CoV-2 infection occurred in 19 fully vaccinated health care workers and 17 unvaccinated health care workers (incidence rate, 11.3 vs 67.0 per 100 000 person-days, respectively, adjusted IRR, 0.14 [95% CI, 0.07-0.31]). The results were qualitatively unchanged by the propensity score sensitivity analysis. CONCLUSIONS AND RELEVANCE: Among health care workers at a single center in Tel Aviv, Israel, receipt of the BNT162b2 vaccine compared with no vaccine was associated with a significantly lower incidence of symptomatic and asymptomatic SARS-CoV-2 infection more than 7 days after the second dose. Findings are limited by the observational design.

Adapting the Israeli national health insurance law to the 21st century- a report from the 19th Dead Sea Conference.

Passage of the National Health Insurance Law (NHIL) in 1995 marked a turning point in the history of the Israeli healthcare system, ensuring sustainable, high-quality medical care to all eligible Israeli residents. Over 100 amendments have been made to the law over the years, yet additional adaptations are required to ensure the law's relevance in years to come. In honor of the 25th anniversary of the passage of the law, the 19th annual Dead Sea Conference brought together prominent figures in the Israeli healthcare system for a discussion on "25 Years to the NHIL: Suggested Changes and Adaptations". Key topics discussed in the conference were regulatory aspects related to the healthcare system, administration of medical services, and financial aspects pertinent to the NHIL. The following meeting report summarizes the insights and recommendations from this conference.

Correction to: Lung ultrasound predicts clinical course and outcomes in COVID-19 patients.

The original article can be found online.

Lung ultrasound predicts clinical course and outcomes in COVID-19 patients.

PURPOSE: Information regarding the use of lung ultrasound (LUS) in patients with Coronavirus disease 2019 (COVID-19) is quickly accumulating, but its use for risk stratification and outcome prediction has yet to be described. We performed the first systematic and comprehensive LUS evaluation of consecutive patients hospitalized with COVID-19 infection, in order to describe LUS findings and their association with clinical course and outcome. METHODS: Between 21/03/2020 and 04/05/2020, 120 consecutive patients admitted to the Tel Aviv Medical Center due to COVID-19, underwent complete LUS within 24 h of admission. A second exam was performed in case of clinical deterioration. LUS score of 0 (best)-36 (worst) was assigned to each patient. LUS findings were compared with clinical data. RESULTS: The median baseline total LUS score was 15, IQR [7-20]. Baseline LUS score was 0-18 in 80 (67%) patients, and 19-36 in 40 (33%) patients. The majority had patchy pleural thickening (n = 100; 83%), or patchy subpleural consolidations (n = 93; 78%) in at least one zone. The prevalence of pleural thickening, subpleural consolidations and the total LUS score were all correlated with severity of illness on admission. Clinical deterioration was associated with increased follow-up LUS scores (p = 0.0009), mostly due to loss of aeration in anterior lung segments. The optimal cutoff point for LUS score was 18 (sensitivity = 62%, specificity = 74%). Both mortality and need for invasive mechanical ventilation were increased with baseline LUS score > 18 compared to baseline LUS score 0-18. Unadjusted hazard ratio of death for LUS score was 1.08 per point [1.02-1.16], p = 0.008; Unadjusted hazard ratio of the composite endpoint (death or need for invasive mechanical ventilation) for LUS score was 1.12 per point [1.05-1.2], p = 0.0008. CONCLUSION: Hospitalized patients with COVID-19, at all clinical grades, present with pathological LUS findings. Baseline LUS score strongly correlates with the eventual need for invasive mechanical ventilation and is a strong predictor of mortality. Routine use of LUS may guide patients' management strategies, as well as resource allocation in case of surge capacity.

Components of metabolic syndrome in patients with multiple myeloma and smoldering multiple myeloma.

BACKGROUND: The prevalences of diabetes mellitus and hypertension, both of which are components of metabolic syndrome, are known to be increased among patients with multiple myeloma (MM), but remain undetermined among patients with smoldering MM (SMM). METHODS: Changes in various components of metabolic syndrome were investigated during the follow-up of patients with either MM or SMM compared to healthy controls. The data of 153 patients (105 with MM and 48 with SMM) and 138 controls were accessed from our medical center's records between 2008 and 2015. We analyzed the patients' data at diagnosis (baseline) and after 1, 3, and 5 years of follow-up. RESULTS: Patients with SMM had a significantly higher prevalence of diabetes, hypertension, and dyslipidemia at baseline compared to controls. A multivariate Cox regression analysis revealed a higher risk to develop dyslipidemia after 1, 3, and 5 years of follow-up among the SMM patients. The MM patients had a higher risk to develop diabetes after 1 year, hypertension after 5 years, and dyslipidemia after 1, 3, and 5 years of follow-up. CONCLUSIONS: These data demonstrate that patients with SMM and those with MM are more prone to develop various components of metabolic syndrome, and they stress the importance of following-up metabolic syndrome components in both groups of patients.

The Role of Kidney Transplantation in Monoclonal Ig Deposition Disease.

INTRODUCTION: Monoclonal Ig deposition disease (MIDD) frequently leads to kidney failure, and a large proportion of these patients would greatly benefit from kidney transplantation. However, data on kidney transplantation outcomes in MIDD are limited. METHODS: This was a retrospective analysis of long-term renal outcomes of 23 patients with MIDD, including 6 patients who underwent kidney transplantation. RESULTS: The 1-, 5-, and 10-year overall survival (OS) from diagnosis were 95%, 78%, and 65%, respectively. Approximately half of the patients (n = 12) progressed to end-stage renal disease (ESRD) with a median time from diagnosis to ESRD of 3.4 years. The 1-, 5-, and 10-year renal survival from diagnosis were 77%, 48%, and 29% respectively. Renal response was observed only in 5 patients (22%), all of them after achieving hematologic complete response. Median OS from diagnosis was significantly better for those who underwent kidney transplantation versus those who remained on dialysis (19.8 years vs. 8.3 years, P = 0.016). Among patients who underwent kidney transplantation, the shortest survival from MIDD diagnosis was 13.7 years and the longest was 27.8 years. Of the 3 patients with kidney transplants who died, the time from the first kidney transplantation to death was 7.4, 18.8, and 20.4 years. Graft loss due to disease recurrence occurred at 4 months and 3.8 years after kidney transplantation in 2 patients who either were not treated or did not respond to treatment. CONCLUSION: As treatments for MIDD have dramatically improved, more patients are achieving sustained hematologic responses with longer patient and graft survival after kidney transplantation.

Hospitalization as an opportunity to correct errors in anticoagulant treatment in patients with atrial fibrillation.

AIMS: To assess whether hospitalization may assist in correcting errors in anticoagulant therapy among patients with atrial fibrillation (AF). METHODS: Our cohort included patients admitted to our institution with a history of AF between 2016 and 2018. We categorized patient's treatment upon admission and discharge as lacking (no treatment despite indication), inadequate (according to individual characteristics) or adequate. We assessed adequacy of treatment upon discharge and determined factors associated with correcting admission errors. RESULTS: Of 4427 patients admitted with a history of AF, the categorization to lacking, inadequate and adequate treatment was 1746 (39.4%), 1237 (27.9%) and 1444 (32.6%) patients, respectively. Of those with inadequate treatment, the most common types of errors were direct oral anticoagulant (DOAC) underdosing (n = 578; 46.7%), vitamin-K antagonists when DOAC was indicated (n = 258; 20.9%), DOAC despite contraindication to DOAC (n = 166; 13.4%) and DOAC overdosing (n = 124; 10%). Upon discharge 688 (18.6%, out of n = 3694) corrections but also 316 (8.6%) new mistakes were found. On multivariate logistic regression, the factors associated with correction of an error on admission were hospitalization due to AF (odds ratio [OR] 2.94 [2.39-3.61]), hospitalization in the neurologic or geriatric wards (OR 2.79 [2.04-3.80]), female sex (OR 1.34 [1.10-1.63]) and a history of stroke (OR 1.47 [1.17-1.86]), while the presence of a contraindication to DOAC decreased the chance of correction (OR 0.10 [0.06-0.18]). CONCLUSION: Hospitalization for any reason may contribute to correction of errors in AC treatment in patients with AF. Unfortunately, a significant portion of patients remains inadequately treated by both outpatient and inpatient providers.

Long term metabolic and renal outcomes of kidney donors compared to controls with excellent kidney function.

BACKGROUND: Only few studies of living kidney donors have included controls that were similarly healthy, including excellent kidney function. METHODS: In this study, we aimed to estimate long term metabolic and renal outcome in a cohort of 211 living donors compared to two control groups: paired-matched controls, and another control group of 2534 healthy individuals with excellent kidney function. RESULTS: Donors presented with higher estimated Glomerular Filtration Rate (eGFR): (97.6 ± 15.2 vs 96.1 ± 12.2 vs 94.5 ± 12.4 ml/min/1.73m2) and lower urine albumin to creatinine ratio (UACR) (4.3 ± 5.9 vs 5.9 ± 6.1 vs 6.1 ± 6.9 mg/g) for donors, matched controls and healthy controls, respectively (p <  0.001). In a mean follow up period of 5.5 for donors, donors presented with positive eGFR slopes during the first 3 years post donation, followed by negative slopes, compared to constantly negative slopes presented in the control group (p <  0.05). The variables related to the slope were being a donor, baseline eGFR, Body Mass Index (BMI) and age but not eGFR on the last day of follow-up or increased delta UACR. There was a significant increase in UACR in donors, as well as a higher rate of albuminuria, associated with a longer time since donation, higher pre-donation UACR and higher pre-donation BMI. Healthy controls had a lower BMI at baseline and gained less weight during the follow up period. Donors and controls had similar incidence of new onset diabetes mellitus and hypertension, as well as similar delta systolic and diastolic blood pressure. Donors were more likely to develop new onset metabolic syndrome, even after adjustment for age, gender and BMI. The higher incidence of metabolic syndrome resulted mainly from increased triglycerides and impaired fasting glucose criteria. However, prevalence of major cardiovascular events was not higher in this group. CONCLUSIONS: Donors are at increased risk to develop features of the metabolic syndrome in addition to the expected mild reduction of GFR and increased urine albumin excretion. Future studies are needed to explore whether addressing those issues will impact post donation morbidity and mortality.

The ability of the wide range CRP assay to classify individuals with low grade inflammation into cardiovascular risk groups.

BACKGROUND: High sensitivity C-reactive protein (hsCRP) has become a routine assessment tool to discriminate between patients at low, intermediate or high risk for cardiovascular events using the threshold values of 1 and 3mg/L, respectively. Over the past years, several studies have proposed the wide range C-reactive protein (wrCRP) as an alternative to the hsCRP in various clinical scenarios. However, the potential use of wrCRP in assessing the cardiovascular risk has not yet been evaluated. METHODS: Both wrCRP and hsCRP were evaluated in 15,780 apparently healthy individuals who underwent a routine annual checkup in the Tel Aviv Sourasky Medical Center. Individuals with CRP levels >5mg/L were excluded. Agreement between the two methods was observed using the Bland-Altman method and the concordance correlation coefficient. Deming regression was used to build a calibration equation. Reclassification of individuals' risk level was observed and Cohen's kappa was used to evaluate risk agreement. RESULTS: A high correlation (r=0.98) along with a significant difference (p<0.001) between hsCRP and wrCRP raised the need for calibration. A simple calibration equation (Adjusted wrCRP=0.3136+0.8803×wrCRP) led to high agreement which enabled 8.4% reclassification of the risk group. A change in the intermediate risk threshold value from 1 to 0.9mg/L led to an almost perfect agreement (kappa=0.87, p<0.001) and a low reclassification rate (7.6%), with under 0.05% of the population undergoing a major reclassification (from high to low risk or vice versa). CONCLUSIONS: In the era of limited financial resources, wrCRP assay may be used as a reasonable routine assay to evaluate the cardiovascular risk in patients undergoing a routine annual checkup.