Acute Kidney Injury and Hair-Straightening Products: A Case Series.

RATIONALE & OBJECTIVE: Keratin-based hair-straightening treatment is a popular hair-styling method. The majority of keratin-based hair-straightening products in Israel contain glycolic acid derivatives, which are considered safe when used topically. Systemic absorption of these products is possible, and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe acute kidney injury (AKI) following use of hair-straightening treatment in Israel during the past several years. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 26 patients from 14 medical centers in Israel who experienced severe AKI and reported prior treatment with hair-straightening products in 2019-2022. FINDINGS: The 26 patients described had a median age of 28.5 (range, 14-58) years and experienced severe AKI following a hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients experienced a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies, which demonstrated intratubular calcium oxalate deposition in 6 and microcalcification in tubular cells in 1. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in 4 cases. Three patients required temporary dialysis. LIMITATIONS: Retrospective uncontrolled study, small number of kidney biopsies. CONCLUSIONS: This series describes cases of AKI with prior exposure to hair-straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential underrecognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.

A multidisciplinary nephrogenetic referral clinic for children and adults-diagnostic achievements and insights.

BACKGROUND: Genetic kidney diseases contribute a significant portion of kidney diseases in children and young adults. Nephrogenetics is a rapidly evolving subspecialty; however, in the clinical setting, increased use of genetic testing poses implementation challenges. Consequently, we established a national nephrogenetics clinic to apply a multidisciplinary model. METHODS: Patients were referred from different pediatric or adult nephrology units across the country if their primary nephrologist suspected an undiagnosed genetic kidney disease. We determined the diagnostic rate and observed the effect of diagnosis on medical care. We also discuss the requirements of a nephrogenetics clinic in terms of logistics, recommended indications for referral, and building a multidisciplinary team. RESULTS: Over 24 months, genetic evaluation was completed for a total of 74 unrelated probands, with an age range of 10 days to 72 years. The most common phenotypes included congenital anomalies of the kidneys and urinary tract, nephrotic syndrome or unexplained proteinuria, nephrocalcinosis/nephrolithiasis, tubulopathies, and unexplained kidney failure. Over 80% of patients were referred due to clinical suspicion of an undetermined underlying genetic diagnosis. A molecular diagnosis was reached in 42/74 probands, yielding a diagnostic rate of 57%. Of these, over 71% of diagnoses were made via next generation sequencing (gene panel or exome sequencing). CONCLUSIONS: We identified a substantial fraction of genetic kidney etiologies among previously undiagnosed individuals which influenced subsequent clinical management. Our results support that nephrogenetics, a rapidly evolving field, may benefit from well-defined multidisciplinary co-management administered by a designated team of nephrologist, geneticist, and bioinformatician. A higher resolution version of the Graphical abstract is available as Supplementary information.

The Relationship between Hypertension and Cancer.

BACKGROUND: Hypertension and cancer are both common due to the aging of the population and the advances in medical treatment which result in increased survival of cancer patients today. More patients with cancer; therefore, present with hypertension, which is attributed to different factors, including genetics and age as well as the type of tumor and cancer-related treatments. Given the increased cardiovascular and mortality risk related to hypertension, it is important to appropriately identify and treat hypertension, particularly in the population of vulnerable cancer patients. In this article we discuss the epidemiology, different etiologies, and approaches to the management of hypertension in cancer patients.

Critical Stepwise Decline of Antibodies against SARS-CoV-2 among Chronic Hemodialysis Patients 180 Days Post Comirnaty Vaccine.

BACKGROUND: The reduced immune response of maintenance hemodialysis patients to coronavirus disease 2019 (COVID-19) vaccines is a major concern. OBJECTIVES: To analyze the late (6 months after full vaccination) antibody response and compare it to early post-vaccination titer. METHODS: We conducted a multicenter prospective study of 13 hemodialysis units in Israel. RESULTS: We demonstrated that the low titers observed among ESRD patients 2-3 months after vaccination with the Comirnaty vaccine (median 63.8 AU/ml) declined to critically lower values 6 months after full vaccination. (Mediananti S antibodies, 31 AU/ml). Seropositivity significantly declined among hemodialysis patients from 89% to 74% (P < 0.0001), although it did not significantly change among controls. CONCLUSIONS: We recommend all patients on hemodialysis receive a booster COVID-19 vaccine 6 months after the second dose.

History of Childhood Kidney Disease and Risk of Adult End-Stage Renal Disease.

BACKGROUND: The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease (ESRD) among adolescents who had normal renal function and a history of childhood kidney disease. METHODS: We conducted a nationwide, population-based, historical cohort study of 1,521,501 Israeli adolescents who were examined before compulsory military service in 1967 through 1997; data were linked to the Israeli ESRD registry. Kidney diseases in childhood included congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease; all participants included in the primary analysis had normal renal function and no hypertension in adolescence. Cox proportional-hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease. RESULTS: During 30 years of follow-up, ESRD developed in 2490 persons. A history of any childhood kidney disease was associated with a hazard ratio for ESRD of 4.19 (95% confidence interval [CI], 3.52 to 4.99). The associations between each diagnosis of kidney disease in childhood (congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease) and the risk of ESRD in adulthood were similar in magnitude (multivariable-adjusted hazard ratios of 5.19 [95% CI, 3.41 to 7.90], 4.03 [95% CI, 3.16 to 5.14], and 3.85 [95% CI, 2.77 to 5.36], respectively). A history of kidney disease in childhood was associated with younger age at the onset of ESRD (hazard ratio for ESRD among adults <40 years of age, 10.40 [95% CI, 7.96 to 13.59]). CONCLUSIONS: A history of clinically evident kidney disease in childhood, even if renal function was apparently normal in adolescence, was associated with a significantly increased risk of ESRD, which suggests that kidney injury or structural abnormality in childhood has long-term consequences.

The opposing trends of body mass index and blood pressure during 1977-2020; nationwide registry of 2.8 million male and female adolescents.

BACKGROUND: Elevated blood pressure among adolescents has been shown to be associated with future adverse cardiovascular outcomes and early onset diabetes. Most data regarding systolic and diastolic blood pressure trends are based on surveys of selected populations within 10-20-year periods. The goal of this study was to characterize the secular trend of blood pressure given the rising prevalence of adolescent obesity. METHODS: This nationwide population-based study included 2,785,515 Israeli adolescents (41.6% females, mean age 17.4 years) who were medically evaluated and whose weight, height and blood pressure were measured, prior to mandatory military service between 1977 and 2020. The study period was divided into 5-year intervals. Linear regression models were used to describe the P for trend along the time intervals. Analysis of covariance was used to calculate means of blood pressure adjusted for body mass index. RESULTS: During the study period, the mean body mass index increased by 2.1 and 1.6 kg/m2 in males and females, respectively (P for trend < 0.001 in both sexes). The mean diastolic blood pressure decreased by 3.6 mmHg in males and by 2.9 mmHg in females (P < 0.001 in both sexes). The mean systolic blood pressure increased by 1.6 mmHg in males and decreased by 1.9 mmHg in females. These trends were also consistent when blood pressure values were adjusted to body mass index. CONCLUSION: Despite the increase in body mass index over the last four decades, diastolic blood pressure decreased in both sexes while systolic blood pressure increased slightly in males and decreased in females.

[CLINIC BLOOD PRESSURE MONITORING AS A PREDICTOR OF MASKED HYPERTENSION].

INTRODUCTION: Masked hypertension is strongly linked to morbidity and mortality. The phenomenon poses a challenge to physicians due to the difficult diagnosis. Recent studies have shown that the incidence may occur in 8.8% -16.6% of the population and up to 30.4% among people with borderline blood pressure. OBJECTIVES: To examine the prevalence of masked hypertension in the Israeli population and the clinic blood pressure status as a predictor of masked hypertension. METHODS: Interviewees were randomly recruited from among passers-by at Assuta Hospital in Ashdod. Those who were found to have normal and normal-high blood pressure ranges were included in the study. Ambulatory blood pressure monitoring was performed, and anthropometric measures were assessed. A statistical analysis compared groups according to their blood pressure clinical and ambulatory blood pressure categories. RESULTS: A total of 35 participants were included in this research. Masked hypertension was found among 35.3% of patients with normal range blood pressure and 27.7% of those in the borderline range. Significant differences were found between the normotensive group and the masked hypertension group in BMI, waist circumference, and clinical category of clinic diastolic blood pressure. CONCLUSIONS: A third of those with in-clinic normal blood pressure suffer from masked hypertension. Borderline in-clinic diastolic blood pressure is significantly associated with masked hypertension. DISCUSSION: This study presents higher masked hypertension rates than previously reported, the difference may be explained by differences in the nature and the lifestyle of the study population. The high incidence of the phenomenon indicates the need for further investigation of patients with in-clinic normal and borderline blood pressure.

[IMPLEMENTING AMBULATORY BLOOD PRESSURE MONITORING (ABPM) IN THE PRIMARY CLINIC].

BACKGROUND: Hypertension (HTN) is the leading reversible risk factor for cardiovascular morbidity and all-cause mortality. Screening is currently based on office blood pressure measurement (OBPM) - a method that is neither sensitive nor specific in detecting true HTN. Home blood pressure monitoring, which is often used to confirm and follow-up the diagnosis of HTN, is limited in its ability to detect certain blood pressure (BP) patterns that are harmful, and not covered by Israeli health insurers. Over the last two decades, the alternative and gold standard - 24 hours ambulatory blood pressure monitoring (ABPM) has become cheap and easy to use, but it is virtually nonexistent in primary care clinics. METHODS: This research aims to assess the clinical and distributional benefits of operating an ABPM in the primary clinic, without utilising any additional external resources besides the ABPM monitor, which was borrowed for this purpose from the regional Israeli Defense Force's Medical Corps (IDFMC) health-care center. All service-members in a medium sized Israeli Air Force (IAF) airbase were screened for HTN using OBPM. Inclusion criteria were BP over 130/85 at least once during the past two years or a personal or family history of HTN. Exclusion criteria were any antihypertensive medication taken over the past 6 months, renal dysfunction or secondary HTN. RESULTS: A total of 2167 patients were screened, of whom 64 (2.9%) met selection criteria. Of these, 56 (87.5%) responded to our invitation and performed full OBPM on three separate occasions. During an 8 weeks long lease 46 of 47 (96.4%) available slots were utilized - 2.19 times more efficient than the regional clinic average utilization rate. Of 18 patients who have been diagnosed with HTN in the past, 13 (72.2%) met the criteria on OBPM but only 6 (46.1%) of these were confirmed as having HTN on ABPM. The positive predictive value (PPV) of abnormally high BP on OBPM for the diagnosis of HTN on ABPM averaged 41.3%. The negative predictive value (NPV) of normal OBPM was 80% and 83.4%, for patients diagnosed in the past with HTN or having risk factors (obesity and family history), respectively. CONCLUSIONS: The therapeutic, prognostic and economic implications of the diagnosis of HTN necessitate the utilization of an accurate diagnostic tool. Recent advancements, making ABPM affordable and easy to use, combined with the immediate and dramatic clinical implications witnessed when ABPM was used in our clinic, necessitate a closer look at the need to make ABPM available at the primary clinic.

[CATHETER-BASED RENAL DENERVATION FOR THE TREATMENT OF HYPERTENSION].

INTRODUCTION: Hypertension is a significant risk factor for cardiovascular morbidity and mortality. Despite a large variety of pharmacological treatment options, many patients remain uncontrolled. Medical inertia and patients' non-adherence to medications are the main reasons for lack of control. Experimental evidence shows that increased renal sympathetic nerve activity increases blood pressure and surgical denervation lowers blood pressure. In studies published between the years 2010-2013, radiofrequency endovascular ablation of renal sympathetic nerves (RDN) seemed to produce antihypertensive effects. However, a randomized sham-control study failed to prove active treatment-specific benefit. One of the main reasons for failure was the small number of ablations in each procedure. In recent years, technological progress has been made with the possibility to quadruple the number of ablation sites and extend them to the branches of the main renal arteries. Small sham-controlled studies were conducted in patients with grade 1-2 hypertension, either untreated or treated with up to three drugs. At three to six months follow-up, modest yet significant decrease of blood pressure was found, both in office and ambulatory measurements. Data from the Global SYMPLICITY Registry, which collects data from consecutive patients undergoing RDN with Medtronic radiofrequency ablation catheters, most of them with resistant hypertension, also showed significant improvement in blood pressure. However, in the absence of a control group, these real-life results should be interpreted with caution. Selection criteria of patients more likely to benefit from RDN have not been defined and will be discussed in the current review. In summary, RDN is a promising new treatment for hypertension. Randomized sham-controlled studies with a longer follow-up are still needed to confirm long-lasting treatment-specific effects and to show cardiovascular protection and safety.

[RESISTIVE INDEX - A POSSIBLE SUBTLE INDEX OF KIDNEY DYSFUNCTION IN PRE-HYPERTENSIVE PATIENTS].

INTRODUCTION: The phenomenon of "masked hypertension" is a diagnostic challenge for physicians. The renal resistance index is a radiological index that expresses damage to the renal blood vessels. The literature regarding the relationship between the renal resistance index and primary kidney disease (as a cause of hypertension) or kidney disease as a result of hypertension is low and limited. OBJECTIVES: The aim of this study is to examine the reliability of the renal resistive index as a means of detecting masked hypertension. METHODS: Respondents were recruited at random, those who were found within normal and normal-high blood pressure ranges were included in the study. A renal ultrasound and ambulatory blood pressure monitoring were performed, and anthropometric measures were assessed. A statistical analysis compared groups according to their blood pressure clinical category and the presence of masked hypertension versus normal. RESULTS: No significant difference was found between the study groups in the renal resistance indices. CONCLUSIONS: The renal resistive index is not an appropriate tool for assessing the presence of masked hypertension in patients with in-clinic pre-hypertension. DISCUSSION: The results of the study were consistent with previous studies that question the clinical use of the renal resistive index. There is no room for using the renal resistive index as a tool to assess the likelihood of masked hypertension in patients with in-clinic pre-hypertension.

[HYPERTENSION IN A PATIENT WITH AN ADEQUATELY TREATED COARCTATION OF THE AORTA - WHAT IS THE REASON FOR UNCONTROLLED HYPERTENSION?]

INTRODUCTION: A 35 year old patient, who had a successful surgical repair of coarctation of the aorta in early childhood, was referred for investigation regarding the cause for resistant hypertension. He underwent a full workup which was negative. Due to elevated renin levels his medications were altered with corresponding normalization of the renin levels. Symptomatic palpitations subsided after stopping treatment with a calcium channel blocker (lercanidipine), which implies reflex tachycardia secondary to lercanidipine. After all the investigations and interventions were performed, it appears that the etiology of resistant hypertension in his case is secondary to the coarctation, in spite of prior successful therapeutic interventions.

[COVID-19, THE KIDNEY AND HYPERTENSION].

INTRODUCTION: COVID-19, is a new corona virus of the Beta Coronavirus genus which originated in bats. The virus first emerged in China in December 2019 and has rapidly spread since to other areas worldwide. The World Health Organization (WHO) has therefore recently declared it as the source of a pandemic. The disease caused by the virus manifests in most cases as a lower respiratory tract infection leading to fever, cough and dyspnea, while more severe cases can led to respiratory failure and/or multi organ failure. COVID-19 enters the human cell using the ACE2, an enzyme abundant in renal tubular epithelial cells. Theoretically, this may be significant in several ways: acute kidney injury (AKI) as well as proteinuria and/or microhematuria could be associated with the penetration of COVID-19 into the cells. Moreover, medications based on RAAS inhibition, such and ACE inhibitors and ARBs, upregulate the enzyme ACE2 and could therefore hypothetically explain the high prevalence of hypertension and diabetes reported as previous diagnoses in severe cases. In the setting of chronic kidney disease, the risk of infection with COVID-19 is not clear at this time. However, hemodialysis patients represent a unique group of patients, mostly elderly and immunocompromised, for whom dialysis is a life-saving treatment which cannot be stopped. Hence, the COVID-19 pandemic has presented a complex medical and logistic challenge for the medical staff in hospital and community based dialysis units.

Adolescent overweight and obesity and the risk for pancreatic cancer among men and women: a nationwide study of 1.79 million Israeli adolescents.

BACKGROUND: There is growing concern regarding the impact of adolescent obesity on adult health. The objective of this study was to evaluate the association between body mass index (BMI) in late adolescence and the incidence of pancreatic cancer during adulthood. METHODS: The authors analyzed a cohort of 1087,358 Israeli Jewish men and 707,212 Jewish women who underwent a compulsory physical examination between ages 16 and 19 years from 1967 to 2002. Pancreatic cancer incidence through December 31, 2012 was identified by linkage to the national cancer registry. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer according to the US Centers for Disease Control and Prevention (CDC) BMI percentiles at baseline. RESULTS: Over a median 23 year follow-up, 551 incident cases of pancreatic cancer cases occurred (423 men; 128 women). Compared with normal weight (5th to-<85th percentile), obesity (≥95th percentile) was associated with an increased risk of cancer among both men (HR, 3.67; 95% confidence interval [CI], 2.52-5.34) and women (HR, 4.07; 95% CI, 1.78-9.29). Among men, compared with low-normal BMI (≥5th to <25th percentile), high-normal BMI (≥75th to <85th percentile) and overweight (85th to 95th percentile) also were associated with a higher risk for cancer(high-normal BMI: HR, 1.49; 95% CI, 1.05-2.13; overweight: HR, 1.97; 95% CI, 1.39-2.80). The estimated population-attributable fraction because of overweight and obesity was 10.9% (95% CI, 6.1%-15.6%). CONCLUSIONS: Men and women who were obese or overweight as adolescents are at an increased risk for subsequent pancreatic cancer.

Body-Mass Index in 2.3 Million Adolescents and Cardiovascular Death in Adulthood.

BACKGROUND: In light of the worldwide increase in childhood obesity, we examined the association between body-mass index (BMI) in late adolescence and death from cardiovascular causes in adulthood. METHODS: We grouped data on BMI, as measured from 1967 through 2010 in 2.3 million Israeli adolescents (mean age, 17.3±0.4 years), according to age- and sex-specific percentiles from the U.S. Centers for Disease Control and Prevention. Primary outcomes were the number of deaths attributed to coronary heart disease, stroke, sudden death from an unknown cause, or a combination of all three categories (total cardiovascular causes) by mid-2011. Cox proportional-hazards models were used. RESULTS: During 42,297,007 person-years of follow-up, 2918 of 32,127 deaths (9.1%) were from cardiovascular causes, including 1497 from coronary heart disease, 528 from stroke, and 893 from sudden death. On multivariable analysis, there was a graded increase in the risk of death from cardiovascular causes and all causes that started among participants in the group that was in the 50th to 74th percentiles of BMI (i.e., within the accepted normal range). Hazard ratios in the obese group (≥95th percentile for BMI), as compared with the reference group in the 5th to 24th percentiles, were 4.9 (95% confidence interval [CI], 3.9 to 6.1) for death from coronary heart disease, 2.6 (95% CI, 1.7 to 4.1) for death from stroke, 2.1 (95% CI, 1.5 to 2.9) for sudden death, and 3.5 (95% CI, 2.9 to 4.1) for death from total cardiovascular causes, after adjustment for sex, age, birth year, sociodemographic characteristics, and height. Hazard ratios for death from cardiovascular causes in the same percentile groups increased from 2.0 (95% CI, 1.1 to 3.9) during follow-up for 0 to 10 years to 4.1 (95% CI, 3.1 to 5.4) during follow-up for 30 to 40 years; during both periods, hazard ratios were consistently high for death from coronary heart disease. Findings persisted in extensive sensitivity analyses. CONCLUSIONS: A BMI in the 50th to 74th percentiles, within the accepted normal range, during adolescence was associated with increased cardiovascular and all-cause mortality during 40 years of follow-up. Overweight and obesity were strongly associated with increased cardiovascular mortality in adulthood. (Funded by the Environment and Health Fund.).

Renal glucosuria is associated with lower body weight and lower rates of elevated systolic blood pressure: results of a nationwide cross-sectional study of 2.5 million adolescents.

BACKGROUND: Gene coding mutations found in sodium glucose co-transporters (SGLTs) are known to cause renal glucosuria. SGLT2 inhibitors have recently been shown to be effective hypoglycemic agents as well as possessing cardiovascular and renal protective properties. These beneficial effects have to some extent, been attributed to weight loss and reduced blood pressure. The aim of the current study was to evaluate the prevalence of renal glucosuria amongst a large cohort of Israeli adolescents and to investigate whether renal glucosuria is associated with lower body weight and lower blood pressure values. METHODS: Medical and socio-demographic data were collected from the Israeli Defense Force's conscription center's database. A cross-sectional study to evaluate the association between conscripts diagnosed as overweight [BMI percentiles of ≥ 85 and < 95 and obesity (≥ 95 BMI percentile)] and afflicted with renal glucosuria was conducted. In addition, we assessed the association of renal glucosuria with elevated diastolic and systolic blood pressure. Multinomial regression models were used. RESULTS: The final study cohort comprised 2,506,830 conscripts of whom 1108 (0.044%) were diagnosed with renal glucosuria, unrelated to diabetes mellitus, with males twice as affected compared to females. The adjusted odds ratio for overweight and obesity was 0.66 (95% CI 0.50-0.87) and 0.62 (95% CI 0.43-0.88), respectively. Adolescents afflicted with renal glucosuria were also less likely to have an elevated systolic blood pressure of 130-139 mmHg with an adjusted odds ratio of 0.74 (95% CI 0.60-0.90). CONCLUSIONS: Renal glucosuria is associated with lower body weight and obesity as well as with lower rates of elevated systolic blood pressure.

Adolescent obesity and adult male breast cancer in a cohort of 1,382,093 men.

Male breast cancer (MBC) accounts for 1% of all breast cancer. Adult obesity and tallness are risk factors for MBC, but the role of adolescent fatness is largely unknown. We aimed to assess the association between body mass index (BMI) in adolescence and the incidence of MBC in a large cohort of 16- to 19-year-old Israeli males. 1,382,093 Jewish Israeli males aged 16-19 who underwent anthropometric measurements, a general intelligence test (GIT) and other examinations during 1967-2011, were followed up to December 31, 2012 for MBC incidence. Cox proportional hazards models assessed the association between adolescent BMI (as WHO BMI categories and as age-specific CDC percentiles) and time to MBC diagnosis, adjusting for sociodemographic covariates. Of 100 MBC cases diagnosed during 29,386,233 person-years of follow-up, 97 were included in multivariable analyses. Compared to "healthy" BMI (18.5-24.9 kg/m2 ) and adjusted for year of birth, country of origin and GIT score, higher adolescent BMI was associated with higher MBC risk: hazard ratio (HR) = 2.01 (95% confidence interval [CI] 1.14-3.55, p = 0.015) in overweight (25.0 ≤ BMI < 30.0 kg/m2 ) adolescents; and HR = 4.97 (95%CI 2.14-11.53, p = 0.0002) in obese (BMI ≥ 30.0 kg/m2 ) adolescents. When CDC age-specific BMI percentiles were assessed results were similar and statistically significant for obesity. In addition, low (vs. high) GIT score (HR = 4.76, 95%CI 1.96-12.50, p = 0.001) and European (vs. west-Asian) origin (HR = 1.99, 95%CI 1.19-3.34, p = 0.009) were independent predictors of MBC. Measured adolescent overweight and obesity are associated with increased risk of MBC, suggesting a modifiable risk factor potentially allowing for early intervention. The novel association with cognitive function should be further explored.

Risk factors associated with gastroenteropancreatic neuroendocrine tumors in a cohort of 2.3 million Israeli adolescents.

We investigated whether obesity and sociodemographic factors at adolescence are associated with incident gastroenteropancreatic neuroendocrine tumors (GEP-NET).Our cohort included 2.3 million Israeli adolescents examined at ages 16 to 19 years between 1967 and 2010. The baseline database included sex, country of birth, residential socioeconomic status (SES), body-mass index (BMI) and height. Participants were followed through linkage with the National Cancer Registry up to 2012. We identified 221 cases of GEP-NET (66 pancreatic, 52 gastric, 39 rectal, 27 appendiceal, 23 small bowel and 14 colonic). Immigration from the Former Soviet Union (FSU) was associated with the risk of small bowel and rectal NET's, [Hazard Ratio (HR) 4.79, 95% Confidence Interval (CI) 1.37-16.76 and 3.43, 95% CI 1.20-9.83, respectively].Height >75th percentile and BMI ≥ 85th percentile were associated with increased risk of gastric NET (HR 2.25 95% CI 1.14-4.42 and HR 2.38, 95% CI 1.19-4.75, respectively). Female sex was associated with appendiceal NET (HR 2.30, 95% CI 1.06-4.96) while male gender was associated with an increased risk for NET of the small bowel [HR 4.72 (95% CI 1.10-20.41)].In conclusion, our findings suggest different risk factor associations with the various GEP-NETS: immigrants from the FSU were at increased risk for small bowel and rectal NET; increased height and weight were associated with the risk of gastric NET and females were at increased risk for appendiceal NET. Further focus on the FSU population is indicated in addition to studies verifying the association of BMI and height with gastric NET.

Body mass index at adolescence and risk of noncardia gastric cancer in a cohort of 1.79 million men and women.

BACKGROUND: This study assessed adolescent predictors of noncardia gastric cancer (NCGC) with a focus on the body mass index (BMI) in late adolescence. METHODS: This study analyzed a cohort of 1,087,358 Israeli Jewish males and 707,212 Israeli Jewish females who underwent a compulsory physical examination between the ages of 16 and 19 years from 1967 to 2002. By linkage to the national cancer registry, participants were followed for NCGC through December 31, 2012. With a median follow-up of 23 years, 515 NCGC cases occurred (379 men and 136 women), and the median age was 47.0 years (interquartile range, 39.3-53.4 years). Multivariate-adjusted Cox regression was used to estimate hazard ratios (HRs) for NCGC according to the US Centers for Disease Control and Prevention BMI percentiles at the baseline (normal weight, 5th to <85th percentile; overweight, 85th to <95th percentile; and obesity, ≥95th percentile) as well as the country of birth, residential socioeconomic status (SES), and education. RESULTS: In comparison with normal weight, adolescent obesity, but not overweight, was associated in both men and women with the risk of subsequent NCGC (unadjusted HR, 1.95; 95% confidence interval [CI], 1.25-3.06; adjusted HR, 1.78; 95% CI, 1.12-2.83). Immigration from the former Soviet Union (FSU), a low education level, and a low residential SES were also associated with the risk for NCGC with adjusted HRs of 2.67 (95% CI, 1.86-3.83), 1.85 (95% CI, 1.53-2.25), and 1.48 (95% CI, 1.13-1.93), respectively. CONCLUSIONS: The findings suggest that adolescent obesity, but not overweight, is associated with an increased risk for NCGC. Immigration from the FSU, a low residential SES, and a low education level are also significantly associated with the risk for NCGC. Cancer 2018;124:356-63. © 2017 American Cancer Society.

Increasing Prevalence of Nephrolithiasis in Association with Increased Body Mass Index in Children: A Population Based Study.

PURPOSE: Epidemiological studies demonstrate an association of increased body mass index and risk of kidney stone formation in adults. We conducted a population based pediatric study to examine the epidemiology of nephrolithiasis in Israeli children during a 30-year period, and to determine body mass index distribution during the same period. MATERIALS AND METHODS: We accessed data from the compulsory medical evaluations of 17-year-old military service candidates in Israel before their enlistment during 1980 to 2013. Candidates for the army with a history of stone disease were compared to those without such a history. RESULTS: Of 1,908,893 candidates 1,691 reported a history of nephrolithiasis, yielding an average prevalence rate of 88.6 per 100,000. During 1980 to 1995 the average reported prevalence of nephrolithiasis was 69 cases per 100,000. From 1995 onward the reported prevalence increased by an average of 6% yearly, reaching 120 per 100,000 during 2010 to 2012. This increased prevalence was observed for males and females but was more prominent among males. Mean ± SD body mass index of stone formers was higher than that of controls (22.7 ± 3.5 vs 22.1 ± 3.9 kg/m2, p <0.001). The trend of increasing body mass index among male candidates during 1995 to 2012 parallels the trend of increasing nephrolithiasis during these years. The odds ratio for nephrolithiasis in candidates with body mass index 30 or greater kg/m2 was 1.7 (range 1.4 to 2.1) compared to candidates with a body mass index of 18.5 to 24.9 kg/m2. CONCLUSIONS: This large, population based study documents an increasing prevalence of nephrolithiasis in children. The possible association of this finding with the increase in body mass index during the same period warrants further investigation.

Sex-specific associations between adolescent categories of BMI with cardiovascular and non-cardiovascular mortality in midlife.

CONTEXT: Most studies linking long-term consequences of adolescent underweight and obesity are limited to men. OBJECTIVE: To assess the sex-specific association of adolescent BMI with cardiovascular- and non-cardiovascular-related mortality in young adulthood and midlife. SETTING: A nationwide cohort. PARTICIPANTS: 927,868 women, 1,366,271 men. INTERVENTIONS: Medical examination data at age 17, including BMI, were linked to the national death registry. MAIN OUTCOMES: Death attributed to cardiovascular (CVD) and non-CVD causes. RESULTS: During 17,346,230 women-years and 28,367,431 men-years of follow-up, there were 451 and 3208 CVD deaths, respectively, and 6235 and 22,223 non-CVD deaths, respectively. Compared to low-normal BMI (18.5-22.0 kg/m2), underweight women had a lower adjusted risk for CVD mortality (Cox hazard ratio (HR) = 0.68; 95% CI 0.46-0.98) in contrast to underweight men (HR = 0.99; 0.88-1.13). The latter were at higher risk for non-CVD mortality (HR = 1.04; 1.00-1.09), unlike underweight women (HR = 1.01; 0.93-1.10). Findings, which persisted when the study sample was limited to those with unimpaired health, were accentuated for the obese with ≥ 30 years follow-up. Both sexes exhibited similarly higher risk estimates already in the high-normal BMI range (22.0 ≤ BMI < 25.0 kg/m2) with overall no interaction between sex and BMI (p = 0.62). Adjusted spline models suggested lower BMI values for minimal mortality risk among women (16.8 and 18.2 kg/m2) than men (18.8 and 20.0 kg/m2), for CVD and non-CVD death, respectively. CONCLUSIONS: Underweight adolescent females have favorable cardiovascular outcomes in adulthood. Otherwise the risk patterns were similar between the sexes. The optimal BMI value for women and men with respect to future CVD outcomes is within or below the currently accepted low-normal BMI range.