Identification of Clinical Drivers of Left Atrial Enlargement Through Genomics of Left Atrial Size.

BACKGROUND: Greater left atrial size is associated with a higher incidence of cardiovascular disease and mortality, but the full spectrum of diagnoses associated with left atrial enlargement in sex-stratified clinical populations is not well known. Our study sought to identify genetic risk mechanisms affecting left atrial diameter (LAD) in a clinical cohort. METHODS: Using Vanderbilt deidentified electronic health record, we studied 6163 females and 5993 males of European ancestry who had at least 1 LAD measure and available genotyping. A sex-stratified polygenic score was constructed for LAD variation and tested for association against 1680 International Classification of Diseases code-based phenotypes. Two-sample univariable and multivariable Mendelian randomization approaches were used to assess etiologic relationships between candidate associations and LAD. RESULTS: A phenome-wide association study identified 25 International Classification of Diseases code-based diagnoses in females and 11 in males associated with a polygenic score of LAD (false discovery rate q<0.01), 5 of which were further evaluated by Mendelian randomization (waist circumference [WC], atrial fibrillation, heart failure, systolic blood pressure, and coronary artery disease). Sex-stratified differences in the genetic associations between risk factors and a polygenic score for LAD were observed (WC for females; heart failure, systolic blood pressure, atrial fibrillation, and WC for males). By multivariable Mendelian randomization, higher WC remained significantly associated with larger LAD in females, whereas coronary artery disease, WC, and atrial fibrillation remained significantly associated with larger LAD in males. CONCLUSIONS: In a clinical population, we identified, by genomic approaches, potential etiologic risk factors for larger LAD. Further studies are needed to confirm the extent to which these risk factors may be modified to prevent or reverse adverse left atrial remodeling and the extent to which sex modifies these risk factors.

Epidemiological trend of suicide in north of Iran from 2011 to 2018 with a focus on joinpoint regression.

Background: Deaths due to potential suicide are preventable and this phenomenon is costly for the health care system and contradicts the values and cultural standards of an Islamic country. Methods: This study is a retrospective study. The research population includes all cases of suicide during the years 2011-2018 who were referred to the emergency department of Babol hospitals. The results were analyzed using SPSS v.23 and Joinpoint Trend Analysis software 4.9.0.0 to identify significant changes in the temporal trends of the outbreak. Results: The highest percentage of suicides occurred in summer (27.8%), on Saturdays (13%) and at night (53%). A total of 1.9% of the cases were commit suicides (leading to death). The highest frequency of suicide was shown in 1397 (21.2%) and the lowest in 1392 (5.1%) and was more common in women (68.2% vs. 31.8%). Suicide-related deaths was higher in the second four years (63.5%), but suicide rate was significantly higher in the first four years (2011-2014) and the mortality rate due to suicide was higher in men than women. Conclusion: Suicide attempts were higher in women than men but the death rate was higher in men which means that men attempt suicide more seriously than women. The model also predicted that suicide rates would rise in the coming years. For this reason, this important issue, along with a detailed analysis of the roots of suicidal ideation and preventive measures, should be considered by health officials and social institutions.

The genetic architecture of plasma kynurenine includes cardiometabolic disease mechanisms associated with the SH2B3 gene.

Inflammation increases the risk of cardiometabolic disease. Delineating specific inflammatory pathways and biomarkers of their activity could identify the mechanistic underpinnings of the increased risk. Plasma levels of kynurenine, a metabolite involved in inflammation, associates with cardiometabolic disease risk. We used genetic approaches to identify inflammatory mechanisms associated with kynurenine variability and their relationship to cardiometabolic disease. We identified single-nucleotide polymorphisms (SNPs) previously associated with plasma kynurenine, including a missense-variant (rs3184504) in the inflammatory gene SH2B3/LNK. We examined the association between rs3184504 and plasma kynurenine in independent human samples, and measured kynurenine levels in SH2B3-knock-out mice and during human LPS-evoked endotoxemia. We conducted phenome scanning to identify clinical phenotypes associated with each kynurenine-related SNP and with a kynurenine polygenic score using the UK-Biobank (n = 456,422), BioVU (n = 62,303), and Electronic Medical Records and Genetics (n = 32,324) databases. The SH2B3 missense variant associated with plasma kynurenine levels and SH2B3-/- mice had significant tissue-specific differences in kynurenine levels.LPS, an acute inflammatory stimulus, increased plasma kynurenine in humans. Mendelian randomization showed increased waist-circumference, a marker of central obesity, associated with increased kynurenine, and increased kynurenine associated with C-reactive protein (CRP). We found 30 diagnoses associated (FDR q < 0.05) with the SH2B3 variant, but not with SNPs mapping to genes known to regulate tryptophan-kynurenine metabolism. Plasma kynurenine may be a biomarker of acute and chronic inflammation involving the SH2B3 pathways. Its regulation lies upstream of CRP, suggesting that kynurenine may be a biomarker of one inflammatory mechanism contributing to increased cardiometabolic disease risk.

Genetic Thyrotropin Regulation of Atrial Fibrillation Risk Is Mediated Through an Effect on Height.

CONTEXT: A genetic predisposition to lower thyrotropin (TSH) levels is associated with increased atrial fibrillation (AF) risk through undefined mechanisms. OBJECTIVE: Defining the genetic mediating mechanisms could lead to improved targeted therapies to mitigate AF risk. METHODS: We used 2-sample mendelian randomization (MR) to test associations between TSH-associated single-nucleotide variations and 16 candidate mediators. We then performed multivariable mendelian randomization (MVMR) to test for a significant attenuation of the genetic association between TSH and AF, after adjusting for each mediator significantly associated with TSH. RESULTS: Four candidate mediators (free thyroxine, systolic blood pressure, heart rate, and height) were significantly inversely associated with genetically predicted TSH after adjusting for multiple testing. In MVMR analyses, adjusting for height significantly decreased the magnitude of the association between TSH and AF from -0.12 (SE 0.02) occurrences of AF per SD change in height to -0.06 (0.02) (P = .005). Adjusting for the other candidate mediators did not significantly attenuate the association. CONCLUSION: The genetic association between TSH and increased AF risk is mediated, in part, by taller stature. Thus, some genetic mechanisms underlying TSH variability may contribute to AF risk through mechanisms determining height occurring early in life that differ from those driven by thyroid hormone-level elevations in later life.

Immune checkpoint inhibitor-induced myositis, the earliest and most lethal complication among rheumatic and musculoskeletal toxicities.

BACKGROUND: In addition to restoring anti-tumor immune responses, immune checkpoint inhibitors (ICI) may also induce immune-related adverse events (irAE) that can affect any organ. We aim to determine the spectrum, timing, clinical features, and fatalities of rheumatic and musculoskeletal immune-related adverse events (RMS-irAE) associated with ICI. PATIENTS METHODS: We performed an observational, retrospective, pharmacovigilance study using the World Health Organization international pharmacovigilance database, VigiBase, from inception to January 2019. RMS-irAE reporting rate on ICI versus full database was performed using disproportionality analysis with computation of reporting-odds-ratios (ROR) and a Bayesian disproportional estimate (information component, IC). IC025 (lower end of the IC 95% credibility interval) >0 is deemed significant. RESULTS: We identified 1288 RMS-irAE significantly associated with ICI: polymyalgia rheumatica (n = 76, ROR = 14.6 [11.6-18.4], IC025 = 3.34), sarcoidosis (n = 94; ROR = 9.6 [7.9-11.9]; IC025 = 2.85), Sjogren's syndrome (n = 49; ROR = 6.9 [5.2-9.2]; IC025 = 2.24), myositis (n = 465; ROR = 4.9 [4.5-5.4]; IC025 = 2.12), arthritis (n = 606; ROR = 1.4 [1.3-1.5]; IC025 = 0.34) and scleroderma (n = 17; ROR = 2.0 [1.2-3.2]; IC025 = 0.17). Arthritis, myositis, and Sjogren's syndrome were over-reported in patients treated with ICI combination versus those treated with ICI monotherapy (ROR = 1.6-2.9, p < .05) and more frequently reported on anti-PD1/PDL1 monotherapy vs. anti-CTLA4 monotherapy (2.1-4.4, p < .05). Median time to onset occurred early for myositis (31 days [19.2-57.8]) and was the most delayed for scleroderma (395 days [323.8-457.2], p < .0001). The fatality rate for RMS-irAE ranged from 24% for myositis (n = 106/441) (up to 56.7% with concurrent myocarditis) to [0-6.7%] for other RMS-irAE (p < .0001). CONCLUSIONS: Clinicians should be aware of the spectrum of RMS-irAE. Myositis can be particularly life-threatening, particularly when associated with myocarditis.

Tyrosine Kinase Inhibitors in Leukemia and Cardiovascular Events: From Mechanism to Patient Care.

Targeted oncology therapies have revolutionized cancer treatment over the last decade and have resulted in improved prognosis for many patients. This advance has emanated from elucidation of pathways responsible for tumorigenesis followed by targeting of these pathways by specific molecules. Cardiovascular care has become an increasingly critical aspect of patient care in part because patients live longer, but also due to potential associated toxicities from these therapies. Because of the targeted nature of cancer therapies, cardiac and vascular side effects may additionally provide insights into the basic biology of vascular disease. We herein provide the example of tyrosine kinase inhibitors utilized in chronic myelogenous leukemia to illustrate this medical transformation. We describe the vascular considerations for the clinical care of chronic myelogenous leukemia patients as well as the emerging literature on mechanisms of toxicities of the individual tyrosine kinase inhibitors. We additionally postulate that basic insights into toxicities of novel cancer therapies may serve as a new platform for investigation in vascular biology and a new translational research opportunity in vascular medicine.

Evaluation of frequency of autoimmune hepatitis autoantibodies in children with type 1 diabetes / Frecuencia de anticuerpos de hepatitis autoinmune en niños con diabetes tipo I

Background: Diabetes mellitus type 1 (T1DM) is one of the childhood diseases with growing prevalence. Various accompanying autoimmune diseases were seen with type 1 diabetes. The most common autoimmune diseases with T1DM are autoimmune thyroiditis and celiac disease. In some reports, autoimmune hepatitis has been reported in association with DM-1. Objectives: The aim of this study was to evaluate autoimmune hepatitis autoantibodies in children with T1DM. Materials and methods: In this crosssectional study, 202 children with T1DM were evaluated (47.5% were males and 52.5% were girls). Liver enzymes, autoimmune hepatitis related autoantibodies such as anti-nuclear antibodies (ANA), anti-smooth muscle (ASMA) and anti liver and kidney microsomal antibodies (LKM-1) were measured. Liver ultrasound was done for participants and biopsy of liver was taken for children with increased echogenicity of the liver, hepatomegaly or elevated liver enzymes. Results analyzed by statistical software spss-16, Descriptive statistics and chi-square test, paired T-TEST. Level of less than 5% was considered statistically significant. Results: In 6 patients ANA and in 4 patients (2%) ASMA was positive,1 patient was ASMA positive but ANA negative. None of the patients were Anti LKM-1 positive. 3 patients had positive ANA and ASMA, and increased liver echogenicity on ultrasound simultaneously. Histological evaluation was showed that 2 patients had findings in favor of autoimmune hepatitis. Conclusion: Auto antibodies were positive in 10 cases. ANA was positive in 6 (2.97%) of all cases. ASMA was positive in 4 (1.98%) cases. Increased echogenicity was found in 3 cases. Histological evaluation showed 2 patients had biopsy confirmed autoimmune hepatitis. AIH-2 was not seen among our cases.

Antecedentes: La diabetes mellitus tipo 1 (DM1) es una de las enfermedades infantiles con mayor prevalencia. Se observaron varias enfermedades autoinmunes acompañantes con diabetes tipo 1. Las enfermedades autoinmunes más comunes con DM1 son la tiroiditis autoinmune y la enfermedad celíaca. En algunos reportes, se ha encontrado hepatitis autoinmune en asociación con DM-1. Objetivos: El objetivo de este estudio fue evaluar los autoanticuerpos de hepatitis autoinmunes en niños con DM1. Materiales y métodos: En este estudio transversal, se evaluaron 202 niños con DM1 (47,5% eran hombres y 52,5% eran niñas). Se midieron las enzimas hepáticas, los autoanticuerpos autoinmunes relacionados con la hepatitis, como los anticuerpos antinucleares (ANA), el músculo liso (ASMA) y los anticuerpos microsomales hepáticos y renales (LKM-1). Se realizó una ecografía hepática para los participantes y se tomó una biopsia del hígado para niños con mayor ecogenicidad del hígado, hepatomegalia o enzimas hepáticas elevadas. Los resultados fueron analizados por el software estadístico spss-16 usando estadística descriptiva y prueba de chi-cuadrado, T-TEST pareado. Se consideró estadísticamente significativo un nivel menor del 5%. Resultados: En 6 pacientes con ANA y en 4 pacientes (2%) ASMA fue positiva, 1 paciente fue ASMA positiva pero ANA negativa. Ninguno de los pacientes fue anti LKM-1 positivo. 3 pacientes tuvieron ANA y ASMA positivas, y aumentaron la ecogenicidad hepática en la ecografía simultáneamente. La evaluación histológica mostró que 2 pacientes tenían hallazgos a favor de la hepatitis autoinmune. Conclusión: Los autoanticuerpos fueron positivos en 10 casos. ANA fue positivo en 6 (2,97%) de todos los casos. La ASMA fue positiva en 4 (1,98%) casos. Se encontró mayor ecogenicidad en 3 casos. La evaluación histológica mostró que 2 pacientes tenían biopsia confirmada de hepatitis autoinmune. AIH-2 no fue visto entre nuestros casos.

Cardiovascular Toxicities Associated With Ibrutinib.

BACKGROUND: Ibrutinib has revolutionized treatment for several B-cell malignancies. However, a recent clinical trial where ibrutinib was used in a front-line setting showed increased mortality during treatment compared with conventional chemotherapy. Cardiovascular toxicities were suspected as the culprit but not directly assessed in the study. OBJECTIVES: The purpose of this study was to identify and characterize cardiovascular adverse drug reactions (CV-ADR) associated with ibrutinib. METHODS: This study utilized VigiBase (International pharmacovigilance database) and performed a disproportionality analysis using reporting odds ratios (ROR) and information component (IC) to determine whether CV-ADR and CV-ADR deaths were associated with ibrutinib. IC compares observed and expected values to find associations between drugs and adverse drug reactions using disproportionate Bayesian-reporting; IC025 (lower end of the IC 95% credibility interval) >0 is significant. RESULTS: This study identified 303 ibrutinib-associated cardiovascular deaths. Ibrutinib was associated with higher reporting of supraventricular arrhythmias (SVAs) (ROR: 23.1; 95% confidence interval: 21.6 to 24.7; p < 0.0001; IC025: 3.97), central nervous system (CNS) hemorrhagic events (ROR: 3.7; 95% confidence interval: 3.4 to 4.1; p < 0.0001; IC025: 1.63), heart failure (ROR: 3.5; 95% confidence interval: 3.1 to 3.8; p < 0.0001; IC025: 1.46), ventricular arrhythmias (ROR: 4.7; 95% confidence interval: 3.7 to 5.9; p < 0.0001; IC025: 0.96), conduction disorders (ROR: 3.5; 95% confidence interval: 2.7 to 4.6; p < 0.0001; IC025: 0.76), CNS ischemic events (ROR: 2.2; 95% confidence interval: 2.0 to 2.5; p < 0.0001; IC025: 0.73), and hypertension (ROR: 1.7; 95% confidence interval: 1.5 to 1.9; p < 0.0001; IC025: 0.4). CV-ADR often occurred early after ibrutinib administration. Importantly, CV-ADR were associated with fatalities that ranged from ∼10% (SVAs and ventricular arrhythmias) to ∼20% (CNS events, heart failure, and conduction disorders). Ibrutinib-associated SVA portends poor prognosis when CNS events occur concomitantly, with 28.8% deaths (15 of 52 cases). CONCLUSIONS: Severe and occasionally fatal cardiac events occur in patients exposed to ibrutinib. These events should be considered in patient care and in clinical trial designs. (Evaluation of Reporting of Cardio-vascular Adverse Events With Antineoplastic and Immunomodulating Agents [EROCA]; NCT03530215).

Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study.

BACKGROUND: Immune checkpoint inhibitors (ICI) produce durable antitumor responses but provoke autoimmune toxicities, including uncommon but potentially devastating neurologic toxicities. The clinical features, including the spectrum, timing, and outcomes, of ICI-induced neurologic toxicities are not well characterized. METHODS: We performed disproportionality analysis using Vigibase, the World Health Organization pharmacovigilance database, comparing neurologic adverse event (AE) reporting in patients receiving ICIs vs. the full database. Neurologic AEs were classified by group queries using Medical Dictionary for Regulatory Activities, between database inception to September 28, 2018. Associations between ICIs and neurologic AEs were assessed using reporting odds ratios (ROR) and information component (IC). IC compares observed and expected values to find associations between drugs and AEs using disproportionate Bayesian reporting; IC025 (lower end of the IC 95% credibility interval) > 0 is considered statistically significant. RESULTS: Among the full database, 18,518,994 AEs were reported, including 48,653 with ICIs. ICIs were associated with higher incidence of myasthenia gravis (0.47% of ICI reports vs. 0.04% of the full database, ROR 16.5 [95% CI 14.5-18.9]; IC025 3.31), encephalitis (0.51% vs. 0.05%, ROR 10.4 [95% CI 9.2-11.8]; IC025 3.15), peripheral neuropathy (1.16% vs. 0.67%, IC025 0.68), and meningitis (0.15% vs. 0.06%, ROR 3.1 [95% CI 2.5-3.9]; IC025 1.01). Myasthenia gravis and encephalitis were associated with anti-PD-1 whereas other neurologic AEs were associated with anti-CTLA-4. Myasthenia gravis was characterized by high fatality rates (~ 20%), early onset (median 29 days), and frequent concurrent myocarditis and myositis; whereas other neurologic AEs had lower fatality rates (6-12%), later onset (median 61-80 days), and were non-overlapping. CONCLUSIONS: ICIs produce a spectrum of distinct classes of neurologic AEs that can cause significant morbidity and mortality and tend to occur early and with class-specific associations.

Renin-Angiotensin-Aldosterone System Modulates Blood Pressure Response During Vascular Endothelial Growth Factor Receptor Inhibition.

OBJECTIVES: This study postulated that antihypertensive therapy with renin-angiotensin-aldosterone system (RAAS) inhibition may mitigate vascular endothelial growth factor inhibitor (VEGFi)-mediated increases in blood pressure more effectively than other antihypertensive medications in patients receiving VEGFi therapy. BACKGROUND: VEGFi therapy is commonly used in the treatment of cancer. One common side effect of VEGFi therapy is elevated blood pressure. Evidence suggests that the RAAS may be involved in VEGFi-mediated increases in blood pressure. METHODS: This retrospective cohort analysis was performed using a de-identified version of the electronic health record at Vanderbilt University Medical Center in Nashville, Tennessee. Subjects with cancer who were exposed to VEGFi therapy were identified, and blood pressure and medication data were extracted. Changes in mean systolic and diastolic blood pressure in response to VEGFi therapy in patients receiving RAAS inhibitor (RAASi) therapy before VEGFi initiation were compared with changes in mean systolic and diastolic blood pressure in patients not receiving RAASi therapy before VEGFi initiation. RESULTS: Mean systolic and diastolic blood pressure rose in both groups after VEGFi use; however, patients who had RAASi therapy before VEGFi initiation had a significantly lower increase in systolic blood pressure as compared with patients with no RAASi therapy (2.46 mm Hg [95% confidence interval: 0.7 to 4.2] compared with 4.56 mm Hg [95% confidence interval: 3.5 to 5.6], respectively; p = 0.034). CONCLUSIONS: In a real-world clinical population, RAASi therapy before VEGFi initiation may ameliorate VEGFi-mediated increases in blood pressure. Randomized clinical trials are needed to further our understanding of the role of RAASi therapy in VEGFi-mediated increases in blood pressure. (J Am Coll Cardiol CardioOnc 2019;1:14-23).

Evaluation of frequency of autoimmune hepatitis autoantibodies in children with type 1 diabetes.

BACKGROUND: Diabetes mellitus type 1 (T1DM) is one of the childhood diseases with growing prevalence. Various accompanying autoimmune diseases were seen with type 1 diabetes. The most common autoimmune diseases with T1DM are autoimmune thyroiditis and celiac disease. In some reports, autoimmune hepatitis has been reported in association with DM-1. OBJECTIVES: The aim of this study was to evaluate autoimmune hepatitis autoantibodies in children with T1DM. MATERIALS AND METHODS: In this crosssectional study, 202 children with T1DM were evaluated (47.5% were males and 52.5% were girls). Liver enzymes, autoimmune hepatitis related autoantibodies such as anti-nuclear antibodies (ANA), anti-smooth muscle (ASMA) and anti liver and kidney microsomal antibodies (LKM-1) were measured. Liver ultrasound was done for participants and biopsy of liver was taken for children with increased echogenicity of the liver, hepatomegaly or elevated liver enzymes. Results analyzed by statistical software spss-16, Descriptive statistics and chi-square test, paired T-TEST. Level of less than 5% was considered statistically significant. RESULTS: In 6 patients ANA and in 4 patients (2%) ASMA was positive,1 patient was ASMA positive but ANA negative. None of the patients were Anti LKM-1 positive. 3 patients had positive ANA and ASMA, and increased liver echogenicity on ultrasound simultaneously. Histological evaluation was showed that 2 patients had findings in favor of autoimmune hepatitis. CONCLUSION: Auto antibodies were positive in 10 cases. ANA was positive in 6 (2.97%) of all cases. ASMA was positive in 4 (1.98%) cases. Increased echogenicity was found in 3 cases. Histological evaluation showed 2 patients had biopsy confirmed autoimmune hepatitis. AIH-2 was not seen among our cases.

Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have substantially improved clinical outcomes in multiple cancer types and are increasingly being used in early disease settings and in combinations of different immunotherapies. However, ICIs can also cause severe or fatal immune-related adverse-events (irAEs). We aimed to identify and characterise cardiovascular irAEs that are significantly associated with ICIs. METHODS: In this observational, retrospective, pharmacovigilance study, we used VigiBase, WHO's global database of individual case safety reports, to compare cardiovascular adverse event reporting in patients who received ICIs (ICI subgroup) with this reporting in the full database. This study included all cardiovascular irAEs classified by group queries according to the Medical Dictionary for Regulatory Activities, between inception on Nov 14, 1967, and Jan 2, 2018. We evaluated the association between ICIs and cardiovascular adverse events using the reporting odds ratio (ROR) and the information component (IC). IC is an indicator value for disproportionate Bayesian reporting that compares observed and expected values to find associations between drugs and adverse events. IC025 is the lower end of the IC 95% credibility interval, and an IC025 value of more than zero is deemed significant. This study is registered with ClinicalTrials.gov, number NCT03387540. FINDINGS: We identified 31 321 adverse events reported in patients who received ICIs and 16 343 451 adverse events reported in patients treated with any drugs (full database) in VigiBase. Compared with the full database, ICI treatment was associated with higher reporting of myocarditis (5515 reports for the full database vs 122 for ICIs, ROR 11·21 [95% CI 9·36-13·43]; IC025 3·20), pericardial diseases (12 800 vs 95, 3·80 [3·08-4·62]; IC025 1·63), and vasculitis (33 289 vs 82, 1·56 [1·25-1·94]; IC025 0·03), including temporal arteritis (696 vs 18, 12·99 [8·12-20·77]; IC025 2·59) and polymyalgia rheumatica (1709 vs 16, 5·13 [3·13-8·40]; IC025 1·33). Pericardial diseases were reported more often in patients with lung cancer (49 [56%] of 87 patients), whereas myocarditis (42 [41%] of 103 patients) and vasculitis (42 [60%] of 70 patients) were more commonly reported in patients with melanoma (χ2 test for overall subgroup comparison, p<0·0001). Vision was impaired in five (28%) of 18 patients with temporal arteritis. Cardiovascular irAEs were severe in the majority of cases (>80%), with death occurring in 61 (50%) of 122 myocarditis cases, 20 (21%) of 95 pericardial disease cases, and five (6%) of 82 vasculitis cases (χ2 test for overall comparison between pericardial diseases, myocarditis, and vasculitis, p<0·0001). INTERPRETATION: Treatment with ICIs can lead to severe and disabling inflammatory cardiovascular irAEs soon after commencement of therapy. In addition to life-threatening myocarditis, these toxicities include pericardial diseases and temporal arteritis with a risk of blindness. These events should be considered in patient care and in combination clinical trial designs (ie, combinations of different immunotherapies as well as immunotherapies and chemotherapy). FUNDING: The Cancer Institut Thématique Multi-Organisme of the French National Alliance for Life and Health Sciences (AVIESAN) Plan Cancer 2014-2019; US National Cancer Institute, National Institutes of Health; the James C. Bradford Jr. Melanoma Fund; and the Melanoma Research Foundation.

A Case Report of Prolonged Apnea during ECT in a Patient with Suicidal Attempt by Organophosphorus Poison.

Organophosphorus pesticides have been used in some cases for suicidal attempts. Such poison can affect plasma cholinesterase activity. The case was a 47-year-old man hospitalized due to suicide attempt with swallowing agricultural poison. The patient, diagnosed with major depressive disorder (MDD), underwent treatment with electroconvulsive therapy (ECT). At the first ECT session, the patient developed apnea for 45 minutes following receiving 20 mg succinylcholine. The patient was intubated; after restoration of respiration depth and rate, the patient was extubated. Collectively, in cases with history of suicide attempts, taking organophosphorus pesticides should be warn for pre-ECT anesthesia.

Study of the normal internal organ weights in Tehran's population.

OBJECTIVE: Examine the normal adult internal organ weight and its relationship with body height, body weight, body mass index and age. MATERIALS AND METHODS: Prospective analysis of data from 1222 autopsies in Legal Medicine Organization of Iran from 1st January, 2007 to 1st September, 2008. All the subjects were adult residents of Tehran died from external causes and showed no pathological changes. RESULTS: The weight of the brain, heart, lungs, liver, spleen, pancreas, kidneys, thyroid gland, the pituitary gland, the suprarenal glands, testes, prostate, ovaries and the uterus were collected from 914 males and 308 females between 15 and 88 years. The weight of all the organs was correlated statistically with at least one external parameter with the exception of the pancreas in men, the uterus, the spleen and the thyroid in women. Organ weights decreased with age except for the heart and the prostate, and increased in relation to body height and/or BMI. Except for the brain, the organ weight showed a better statistical correlation with the BMI than the body height. CONCLUSION: These results can be used as standard organ weights to determine abnormal evidences in Forensic and Pathologic corpses. However such results have to be regularly updated by pathologists in order to keep organ weight as a good criterion used in postmortem diagnosis.