Novel subtype of obesity influencing the outcomes of sleeve gastrectomy: Familial aggregation of obesity.

BACKGROUND: Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy (SG) between patients with familial aggregation of obesity (FAO) and patients with sporadic obesity (SO) have not been elucidated. AIM: To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO. METHODS: A total of 193 patients with obesity who underwent SG were selected. Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity (1SO vs 1FAO, 2SO vs 2FAO). The baseline characteristics, weight loss outcomes, prevalence of obesity-related comorbidities and incidence of major surgery-related complications were compared between groups. RESULTS: We defined FAO as the presence of two or more first-degree relatives with obesity. Patients with FAO did not initially show significant differences in baseline data, short-term postoperative weight loss, or obesity-related comorbidities when compared to patients with SO preoperatively. However, distinctions between the two groups became evident at the two-year mark, with statistically significant differences in both percentage of total weight loss (P = 0.006) and percentage of excess weight loss (P < 0.001). The FAO group exhibited weaker remission of type 2 diabetes mellitus (T2DM) (P = 0.031), hyperlipidemia (P = 0.012), and non-alcoholic fatty liver disease (NAFLD) (P = 0.003) as well as a lower incidence of acid reflux (P = 0.038). CONCLUSION: FAO patients is associated with decreased mid-to-long-term weight loss outcomes; the alleviation of T2DM, hyperlipidemia and NAFLD; and decreased incidence of acid reflux postoperatively.

Relationship Between Family History and Quality of Life in Patients with Psoriasis: A Cross-Sectional Study from China.

Purpose: The purpose of this study was to investigate the comprehensive impact of family history of psoriasis, lesion size, disease severity, and the possibility of joint involvement on patients' quality of life(QoL). Patients and Methods: Data from 5961 patients with psoriasis recruited from 440 hospitals throughout China were analyzed. The effects of family history of psoriasis, Body Surface Area(BSA), Psoriasis Area and Severity Index(PASI), and Psoriasis Epidemiology Screening Tool(PEST) on their Dermatology Life Quality Index(DLQI) were studied using a moderated chained mediated effects test. Results: A total of 912 patients (15.30%) had a family history of psoriasis, and 5071 patients (85.10%) had plaque psoriasis. In patients with plaque psoriasis, the variables of family history, PASI, PEST, and DLQI were positively correlated with each other. Additionally, in patients with other types of psoriasis, PASI was positively correlated with PEST and DLQI. Age was positively correlated with PASI and PEST and negatively correlated with DLQI in patients with plaque psoriasis; their Body Mass Index(BMI) and disease duration were in positive correlation with PASI and PEST. The mediation effect of PASI and PEST between family history and DLQI was remarkable in patients with plaque psoriasis and not in those with other types of psoriasis. BSA moderated the association between family history and PASI in patients with plaque psoriasis. Conclusion: PASI and PEST play a chain mediating role in the relationship between family history and DLQI in patients with plaque psoriasis, and high levels of BSA increase the ability of family history to positively predict PASI in plaque psoriasis, thereby affecting the patient's QoL.

Impact of Family History and Germline Genetic Risk Single Nucleotide Polymorphisms on Long-Term Outcomes of Favorable-Risk Prostate Cancer.

PURPOSE: Family history and germline genetic risk single nucleotide polymorphisms (SNPs) have been separately shown to stratify lifetime risk of prostate cancer. Here, we evaluate the combined prognostic value of family history of prostate and other related cancers and germline risk SNPs among patients with favorable-risk prostate cancer. MATERIALS AND METHODS: A total of 1367 participants from the prospective Health Professionals Follow-up Study diagnosed with low- or favorable intermediate-risk prostate cancer from 1986 to 2017 underwent genome-wide SNP genotyping. Multivariable Cox regression was used to estimate the association between family history, specific germline risk variants, and a 269 SNP polygenic risk score with prostate cancer‒specific death. RESULTS: Family history of prostate, breast, and/or pancreatic cancer was observed in 489 (36%) participants. With median follow-up from diagnosis of 14.9 years, participants with favorable-risk prostate cancer with a positive family history had a significantly higher risk of prostate cancer‒specific death (HR 1.95, 95% CI 1.15-3.32, P = .014) compared to those without any family history. The rs2735839 (19q13) risk allele was associated with prostate cancer‒specific death (HR 1.81 per risk allele, 95% CI 1.04-3.17, P = .037), whereas the polygenic risk score was not. Combined family history and rs2735839 risk allele were each associated with an additive risk of prostate cancer‒specific death (HR 1.78 per risk factor, 95% CI 1.25-2.53, P = .001). CONCLUSIONS: Family history of prostate, breast, or pancreatic cancer and/or a 19q13 germline risk allele are associated with an elevated risk of prostate cancer‒specific death among favorable-risk patients. These findings have implications for how family history and germline genetic risk SNPs should be factored into clinical decision-making around favorable-risk prostate cancer.

Familial clustering of unexplained heart failure - A Danish nationwide cohort study.

AIMS: To determine whether a family history of unexplained heart failure (HF) in first-degree relatives (children or sibling) increases the rate of unexplained HF. METHODS AND RESULTS: Using Danish nationwide registry data (1978-2017), we identified patients (probands) diagnosed with first unexplained HF (HF without any known comorbidities) in Denmark, and their first-degree relatives. All first-degree relatives were followed from the HF date of the proband and until an event of unexplained HF, exclusion diagnosis, death, emigration, or study end, whichever occurred first. Using the general population as a reference, we calculated adjusted standardized incidence ratios (SIR) of unexplained HF in the three groups of relatives using Poisson regression models. We identified 55,110 first-degree relatives to individuals previously diagnosed with unexplained HF. Having a family history was associated with a significantly increased unexplained HF rate of 2.59 (95%CI 2.29-2.93). The estimate was higher among siblings (SIR 6.67 [95%CI 4.69-9.48]). Noteworthy, the rate of HF increased for all first-degree relatives when the proband was diagnosed with HF in a young age (≤50 years, SIR of 7.23 [95%CI 5.40-9.68]) and having >1 proband (SIR of 5.28 [95%CI 2.75-10.14]). The highest estimate of HF was observed if the proband was ≤40 years at diagnosis (13.17 [95%CI 8.90-19.49]. CONCLUSION: A family history of unexplained HF was associated with a two-fold increased rate of unexplained HF among first-degree relatives. The relative rate was increased when the proband was diagnosed at a young age. These data suggest that screening families of unexplained HF with onset below 50 years is indicated.

Impact of a family history of mental disorders on the characteristics of patients with early psychosis.

AIM: Children of parents with psychiatric illness have a higher risk of developing psychiatric disorders. This is particularly the case for psychoses and the evolution of these disorders could likely differ. The aim of this study was to study the impact of a first-degree and second-degree family history of psychiatric disorders (FHPD) on the characteristics of patients with early psychosis in a specialized programme. METHOD: This research is a prospective study based on 408 patients aged 18-35 years enrolled in the Treatment and Early Intervention in Psychosis Program (TIPP) with a three-years follow-up. Various characteristics were compared between patients with first-degree-FHPD and those without, then between patients with 2nd degree-FHPD and those without. The influence of the number of parents with first or second degree FHPD on clinical characteristics was also studied. RESULTS: Our results showed an influence of FHPD on the characteristics of patients presenting a first episode of psychosis. Over the 3 years of follow-up, patients with at least one second-degree relative showed more negative and depressive symptoms and poorer general functioning than patient who did not. The number of parents with first or second degree FHPD was also negatively associated with several clinical variables. CONCLUSION: The results of this study confirm the existence of a distinct premorbid profile and a different evolution in patients with FHPD, which is not limited to first-degree relatives. This suggests the importance of specific needs that should be addressed during treatment.

Family history and gastric cancer incidence and mortality in Asia: a pooled analysis of more than half a million participants.

BACKGROUND: The family history of gastric cancer holds important implications for cancer surveillance and prevention, yet existing evidence predominantly comes from case-control studies. We aimed to investigate the association between family history of gastric cancer and gastric cancer risk overall and by various subtypes in Asians in a prospective study. METHODS: We included 12 prospective cohorts with 550,508 participants in the Asia Cohort Consortium. Cox proportional hazard regression was used to estimate study-specific adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between family history of gastric cancer and gastric cancer incidence and mortality, then pooled using random-effects meta-analyses. Stratified analyses were performed for the anatomical subsites and histological subtypes. RESULTS: During the mean follow-up of 15.6 years, 2258 incident gastric cancers and 5194 gastric cancer deaths occurred. The risk of incident gastric cancer was higher in individuals with a family history of gastric cancer (HR 1.44, 95% CI 1.32-1.58), similarly in males (1.44, 1.31-1.59) and females (1.45, 1.23-1.70). Family history of gastric cancer was associated with both cardia (HR 1.26, 95% CI 1.00-1.60) and non-cardia subsites (1.49, 1.35-1.65), and with intestinal- (1.48, 1.30-1.70) and diffuse-type (1.59, 1.35-1.87) gastric cancer incidence. Positive associations were also found for gastric cancer mortality (HR 1.30, 95% CI 1.19-1.41). CONCLUSIONS: In this largest prospective study to date on family history and gastric cancer, a familial background of gastric cancer increased the risk of gastric cancer in the Asian population. Targeted education, screening, and intervention in these high-risk groups may reduce the burden of gastric cancer.

Cardiovascular Risk Factors Among First-Degree Relatives of Patients with Premature Cardiovascular Disease in Malta. Baseline Findings from the CRISO Project.

Purpose: A family history of premature atherosclerotic cardiovascular disease (ASCVD) confers a greater risk of developing ASCVD. However, the prevalence of ASCVD risk factors among asymptomatic Maltese adults with parental or fraternal history of premature ASCVD is unknown. The study aimed to evaluate and compare their risk with the general population. Patients and Methods: Posters to market the project were distributed in cardiac rehabilitation areas. Patients with premature cardiovascular disease facilitated recruitment by informing their relatives about the project. Medical doctors and cardiac rehabilitation nurses referred first-degree relatives. Posters were put up in community pharmacies, and an explanatory video clip was shared on social media for interested individuals to contact researchers. Those eligible were enrolled in a preventive cardiology lifestyle intervention. Their data were compared with the risk in the general population. Results: Many first-degree relatives had a suboptimal risk profile, with 60% (N = 89) having a total cholesterol level of >5.0 mmol/L; 54% having a low-density lipoprotein-cholesterol level of >3 mmol/L; 70.5% being overweight/obese, with 62% having a waist circumference greater than the recommended values; 34.8% having hypertension; 56.2% being inadequately adherent to the Mediterranean diet; 62% being underactive, with 18% being sedentary; and 25.8% being smokers. First-degree relatives had significantly higher proportions of underactive lifestyle (p = 0.00016), high body mass index (>25kg/m2) (p = 0.006), and systolic blood pressure (p = 0.001) than the general population, with 30% having metabolic syndrome. Conclusion: This study determined the prevalence of lifestyle, biochemical, physiological, and anthropometric cardiovascular risk factors among asymptomatic first-degree relatives of Maltese patients with premature ASCVD. First-degree relatives had considerable prevalences of an underactive lifestyle, hypertension, and obesity, suggesting better screening and early risk factor intervention are needed to modify their risk of ASCVD.

This study was done to evaluate factors that can increase the risk of heart disease in siblings and offspring of Maltese patients who developed atherosclerotic cardiovascular disease (ASCVD) at a young age. Relatives were invited to meetings during which a risk evaluation was performed. The researchers found that relatives had a high prevalence of cardiometabolic risk factors, meaning they were at increased risk of developing the disease. The researchers have concluded that reducing the risk of ASCVD in individuals at increased risk requires developing and testing potentially sustainable risk factor modification strategies.

[Analysis of clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues].

Objective: To explore the clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues. Methods: A retrospective analysis was performed according to different data types. An independent sample t-test, Mann-Whitney U test, chi-square test, or Fisher's exact probability method were used. Chronic hepatitis B patients followed up for four years were collected from the follow-up case database of the Department of Infectious Diseases of Zhongshan Third Hospital from January 2009 to December 2018 and were divided into two groups, A and B, with 87 and 145 cases respectively, according to the duration of HBeAg-negativity≤ 3 and persistent positivity >3 years. Statistical analysis was conducted on the age, gender, family history, baseline, follow-up visit duration, liver function, and other data among the two patient groups. Results: There were no statistically significant differences in gender, age, family history of liver cirrhosis, family history of liver cancer, liver cirrhosis condition before treatment, fatty liver disease combined condition before treatment, baseline HBsAg, anti-HBc, alanine aminotransferase, albumin, or total bilirubin between the two groups of patients (P > 0.05). HBV DNA and HBeAg were significantly higher in group B than those in group A at baseline, with P≤0.001. Aspartate aminotransferase and γ-glutamyl transferase were significantly higher in group A than those in group B at baseline. The proportion of family history of hepatitis B was significantly higher in group B (69.0%) than that in group A (50.6%) among the two groups of patients, and the difference was statistically significant (P = 0.005). The proportion of mothers with hepatitis B was significantly higher in group B (25.5%) than in group A (11.5%), P = 0.010. During the treatment process, the HBV DNA quantification was significantly higher in group B than that in group A at 0.5 and 1 years (P≤0.002). The proportion of HBV DNA <100IU/ml was also significantly different at six months and one year (χ(2)=30.327, P < 0.001 and χ(2)=11.779, P = 0.001). The HBsAg level was higher in group B than that of group A in the second and fourth years, P < 0.05. During the entire treatment process, the HBeAg level was significantly higher in group B than that in group A (P < 0.001). A total of seven cases developed liver cirrhosis or cancer during follow-up, including three cases in group A and four cases in group B (P > 0.05). Conclusion: HBeAg-positive patients with chronic hepatitis B have persistent HBeAg positivity when treated with long-term nucleos(t)ide analogues. Accordingly, a greater proportion of this kind of patient family and mothers have a remarkable history of hepatitis B and a reduced HBV DNA relapse rate in the early stages (within a year or less).

A Study of Hypertension and Related Biophysical and Health-related Lifestyle Behaviors in Patients Suffering from Schizophrenia.

Background: Schizophrenia is a life-shortening disease. The standardized mortality ratio has been higher than that of the general population, and it has doubled what it was 3-4 decades ago. This rise is mostly attributed to the increased cardiovascular risk associated with high second-generation antipsychotic (SGA) use. Evidence from the first-generation antipsychotic (FGA) era shows a lower prevalence of hypertension (HTN) but data regarding SGAs is scarce. Purpose: The purpose of the study was to assess the prevalence of HTN and related factors using standardized methodology in patients with schizophrenia on treatment with SGAs. Methods: A cross-sectional study through convenient sampling was done. Blood pressure, anthropometry, physical activity, and health-related lifestyle factors were assessed using the standard World Health Organization (WHO) methodology of cardiovascular survey methods and the Global Physical Activity Questionnaire (GPAQ) version 2. The prevalence of HTN, obesity, inadequate physical activity, and other demographic and clinical correlates like antipsychotic use, duration of illness, and family history of non-communicable diseases (NCDs) were studied. Results: The prevalence of HTN is 20.50%, and it increases with age. SGAs with the use of a single agent are the most common. In total, 45.50% of persons with schizophrenia have a positive family history of a NCD; 22.00% and 07.50% are current tobacco and alcohol users, respectively; and 70% have abdominal obesity, and 54% have generalized obesity. Waist circumference, obesity, and family history of NCDs are significant correlates of HTN. A family history of NCDs is the most significant predictor. Conclusion: The prevalence of HTN is lower than that of the general population despite the high prevalence of SGA use, obesity, and inadequate physical activity.

Association Between Family History in Patients with Primary Gout and Left Ventricular Diastolic Function: A Cross-Sectional Study.

Objective: This study aimed to employ echocardiography for measuring the markers of left ventricular (LV) diastolic function to investigate the effects of family history of gout on the LV diastolic function in patients with primary gout. Methods: Two hundred and eighty-four patients with primary gout who visited the Department of Rheumatology and Immunology of the First Affiliated Hospital of Chengdu Medical College from September 2020 to July 2022 were selected and their family history of gout, general information, and laboratory markers were recorded. Parameters of LV diastolic function were measured via echocardiography. The correlation between family history and LV diastolic function markers was analyzed using univariate and multivariate regression and the receiver operating characteristic (ROC) curve analyses. Results: LV diastolic function parameters, peak early mitral diastolic velocity (E)/peak late mitral diastolic velocity (A), and early septal mitral annulus diastolic motion velocity (Sepe'), early lateral mitral annulus diastolic motion velocity (Late') and their mean (e'), were significantly lower in patients with familial primary gout, while left atrial volume index (LAVI) and E/e' were markedly elevated in patients with sporadic primary gout. In patients with family history, the proportion of grade ≥2 LV diastolic insufficiency was distinctly higher than that in patients without family history (41.6% vs 12.3%). Even after adjusting for confounding variables, LAVI, E/A, Sepe', Late', e', E/e' were obviously associated with family history of gout. The area under ROC of family history combined with SUA level for identifying grade ≥2 LV diastolic insufficiency in patients with primary gout was 0.872 (P<0.05). Conclusion: Family history of gout was closely related to echocardiographic LV diastolic function parameters in patients with gout, what is more, family history of gout combined with SUA level was found to be a valuable indicator for discriminating grade ≥2 LV diastolic insufficiency in patients with primary gout.

Visual Field and Optical Coherence Tomography Parameters With and Without Positive Family History of Glaucoma.

BACKGROUND: To evaluate the Retinal Nerve Fiber Layer and Ganglion Cell Complex thickness using Spectral Domain Optical Coherence Tomography with and without positive family history of Primary Open Angle Glaucoma and its relation to visual field. METHODS: Total 120 eyes with each subjects with positive family history of Primary Open Angle Glaucoma (Group I, n=30) and healthy subjects without positive family history of Primary Open Angle Glaucoma (Group II, n=30) undergone complete ophthalmic evaluation with Retinal Nerve Fiber Layer, Ganglion Cell Complex and VF obtained from Spectral Domain Optical Coherence Tomography RTVue-100 and Humphrey visual field respectively .The measurements were analyzed and compared among two groups using independent-t test by using SPSS version 23.The relationship of Retinal Nerve Fiber Layer with visual field were evaluated with correlation analysis. RESULTS: There were 75 patients included in the study.nasal, temporal RNFL and average Ganglion Cell Complex was significantly lower and thinner in Group I with mean difference of -8.53±2.30 µm (p<0.001), -7.35±3.34 µm (p<0.001), -8.52±3.58µm (p<0.001),-11.87±2.24µm (p<0.001), -5.31±1.95µm (p<0.001) and -8.05±1.52µm (p<0.001) respectively. Correlation plot with Retinal Nerve Fiber Layer thickness as predictor of Mean Deviation and Pattern Standard Deviation indicated statistically significant degree of determination in Group I (r=0.455 and r=0.623, p<0.001 and p<0.001). CONCLUSIONS: The Optical Coherence Tomography and visual field Parameters are lower in group I and used as an early predictor, diagnosis, monitoring and management.

Joint Association of Lipoprotein(a) and a Family History of Coronary Artery Disease with the Cardiovascular Outcomes in Patients with Chronic Coronary Syndrome.

AIM: No data are currently available regarding the association between Lp(a) and the cardiovascular outcomes in patients with coronary artery disease (CAD) according to their family history (FHx) of CAD. This study aimed to evaluate the significance of Lp(a) in predicting major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome (CCS) with or without FHx. METHODS: A total of 6056 patients with CCS were enrolled. Information on FHx was collected, and the plasma Lp(a) levels were measured. All patients were followed up regularly. The independent and joint associations of Lp(a) and FHx with the risk of MACEs, including cardiovascular death, nonfatal myocardial infarction, and stroke, were analyzed. RESULTS: With over an average of 50.35±18.58 months follow-up, 378 MACEs were recorded. A Cox regression analysis showed an elevated Lp(a) level to be an independent predictor for MACEs in patients with [hazard ratio (HR): 2.77, 95% confidence interval (CI): 1.38-5.54] or without FHx (HR: 1.35, 95% CI: 1.02-1.77). In comparison to subjects with non-elevated Lp(a) and negative FHx, patients with elevated Lp(a) alone were at a nominally higher risk of MACEs (HR: 1.26, 95% CI: 0.96-1.67), while those with both had the highest risk (HR: 1.93, 95% CI: 1.14-3.28). Moreover, adding Lp(a) to the original model increased the C-statistic by 0.048 in subjects with FHx (p=0.004) and by 0.004 in those without FHx (p=0.391). CONCLUSIONS: The present study is the first to suggest that Lp(a) could be used to predict MACEs in CCS patients with or without FHx; however, its prognostic significance was more noteworthy in patients with FHx.

Exploring determinants of sex and family history-based disparity in type 2 diabetes mellitus prevalence among clinical patients.

BACKGROUND: Type 2 diabetes mellitus represents a multifaceted disorder characterized by intricate pathophysiological mechanisms, encompassing diminished insulin secretion, augmented hepatic glucose production, and heightened insulin resistance. This study aims to assess the sex (Male and Female only) and family history-based differences in the prevalence of T2DM and explore the determinants contributing to this disparity among clinical patients. SUBJECTS AND METHODS: The study encompassed a diverse pool of clinical patients, encompassing both individuals with diabetes and those without the condition, who had previously sought medical attention for clinical checkups at healthcare centers. The collected data included essential parameters such as blood pressure, weight, height, smoking habits, educational background, and physical activity levels. To ensure methodological rigor and data accuracy, blood pressure measurements adhered to the stringent guidelines set forth by the World Health Organization. RESULTS: Participants of the present study reported diabetes, among which notable findings emerged regarding health indicators. It was observed that the prevalence of high blood pressure, obesity, and high blood cholesterol exhibited a statistically significant increase among the female participants, underscoring the sex-based disparities in these health parameters. The male population aged 60 or older, the presence of a family history of DM accentuated this risk, resulting in a striking 3.1 times higher prevalence compared to females, who exhibited a 2.4 times higher risk (OR = 2.4, p = 0.0008). This intriguing relationship between diabetes and cholesterol levels was not limited to sex. Both male (OR = 2.47) and female (OR = 2.1) diabetes patients displayed highly significant associations with cholesterol levels. The risk of T2DM was significantly associated with triglycerides in both sexes (1.58 times higher in males, and 1.71 times higher in females). CONCLUSIONS: The significance of hypertension as a comorbidity in T2DM, highlighting sex-specific associations and the potential impact of a family history of diabetes on blood pressure. Our findings emphasize the importance of considering lipid profiles, obesity, and their sex-specific associations when assessing and managing diabetes risk. Comprehensive diabetes care should include strategies for lipid control, weight management, and cardiovascular risk reduction, tailored to the individual's sex and specific risk profile.

Association between low-dose aspirin and the risk of gastric cancer and adenoma according to a family history of gastric cancer.

This study aimed to evaluate the association between low-dose aspirin use and the risk of GC and gastric adenoma according to a family history of GC. We conducted a population-based study of 7,596,003 participants screened for GC between 2013 and 2014. Aspirin users and non-users were matched in a 1:1 ratio through propensity score matching (PSM). After PSM, 51,818 participants with a family history of GC and 359,840 without a family history of GC were analyzed (mean follow-up periods: 4.9 ± 0.8 and 4.8 ± 0.8 years, respectively). In patients with a family history of GC, aspirin use was significantly associated with a reduced risk of GC (adjusted hazard ratio [aHR]=0.80; 95 % confidence interval [CI]=0.65-0.995) and gastric adenoma (aHR=0.81; 95% CI=0.69-0.94). In those without a family history of GC, aspirin use was associated with a reduced risk of gastric adenoma (aHR = 0.92; 95 % CI = 0.86-0.98), but not with that of GC (aHR = 0.99; 95 % CI = 0.90-1.08). Low-dose aspirin use was associated with a reduced risk of gastric adenoma, regardless of a family history of GC, and may play a role in the early stages of gastric carcinogenesis. However, the association between aspirin and GC was only observed in those with a family history of GC.

The Role of Demographic and Clinical Factors in Germline Mutation Testing for Patients with Primary Hyperparathyroidism.

INTRODUCTION: Guidelines recommending genetic counseling in primary hyperparathyroidism (PHPT) vary. To further delineate current recommendations, this study examined genetic counseling referral patterns and rates of mutations in surgical patients with PHPT. PATIENTS AND METHODS: A single-institution review was performed of adult patients who underwent parathyroidectomy for presumed sporadic PHPT. Genetic testing indications of hypercalcemia onset ≤ 40 years, multigland disease (MGD), family history (FHx) of PHPT, or other clinical indications suspicious for a PHPT-related endocrinopathy were examined by demographics and mutation detection rates. RESULTS: Genetic counseling was performed in 237 (37.9%) of 625 patients. Counseling was discussed but not performed in 121 (19.4%) patients. No evidence was noted of genetic referral discussion in the remaining 267 (42.7%). Of these groups, patients who received genetic counseling were youngest, p < 0.001 [median age 55.3 (IQR 43.2, 66.7) years]. The majority of patients with indications of age ≤ 40 years (65.7%), FHx (78.0%), and other clinical indications (70.7%) underwent genetic counseling, while most with MGD (57.0%) did not. Eight mutations were detected in 227 patients (3.5%). Mutations included: MEN1 (n = 2), CDC-73 (n = 4), and CASR (n = 2). Detection was most common in patients with FHx (4/71, 5.6%), then age ≤ 40 years (3/66, 4.5%), and other clinical indications (3/80, 3.8%). No mutations were identified in 48 patients tested solely for MGD. CONCLUSIONS: Most patients with onset of hypercalcemia age ≤ 40 years, positive FHx, or other clinical concerns underwent genetic counseling, while most with MGD did not. As no germline mutations were identified in patients with MGD alone, further investigation of MGD as a sole indication for genetic counseling may be warranted.

Family history of substance problems among African Americans: Associations with drug use, drug use disorder, and prescription drug misuse.

A family history of substance problems is a well-known risk factor for substance use and use disorders; however, much of this research has been conducted in studies with predominantly White subjects. The aim of this study was to examine the associations between family history density of substance problems and drug use, risk for drug use disorder, and prescription drug misuse in a sample of African American adults. Results indicate that family history density of substance problems increased the risk for all drug outcomes in the full sample. However, when subgroup analyses by gender were conducted, family history was not a risk factor among men for prescription drug misuse.

Germline Cancer Susceptibility in Individuals with Melanoma.

BACKGROUND: Prior studies have estimated a small number of individuals with melanoma (2-2.5%) have germline cancer predisposition, yet a recent twin study suggested melanoma has the highest hereditability among cancers. OBJECTIVE: To determine the incidence of hereditary melanoma and characterize the spectrum of cancer predisposition genes that may increase the risk of melanoma. METHODS: 400 individuals with melanoma and personal or family history of cancers underwent germline testing of >80 cancer predisposition genes. Comparative analysis of germline data was performed on 3 additional oncologic and dermatologic datasets. RESULTS: Germline pathogenic/likely pathogenic (P/LP) variants were identified in 15.3% (61) individuals with melanoma. Most variants (41, 67%) involved genes considered unrelated to melanoma (BLM, BRIP1, CHEK2, MLH1, MSH2, PMS2, RAD51C). A third (20, 33%) were in genes previously associated with familial melanoma (BAP1, BRCA2, CDKN2A, MITF, TP53). Nearly half (30, 46.9%) of P/LP variants were in HRD genes. Validation cohorts demonstrated P/LP rates of 10.6% from an unselected oncologic cohort, 15.8% from a selected commercial testing cohort and 14.5% from a highly selected dermatologic study. LIMITATIONS: Cohorts with varying degrees of selection, some retrospective. CONCLUSION: Germline predisposition in individuals with melanoma is common, with clinically actionable findings diagnosed in 10.6% to 15.8%.

Associations Between Family History of Alcohol and/or Substance Use Problems and Frontal Cortical Development From 9 to 13 Years of Age: A Longitudinal Analysis of the ABCD Study.

Background: Previous investigations that have examined associations between family history (FH) of alcohol/substance use and adolescent brain development have been primarily cross-sectional. Here, leveraging a large population-based sample of youths, we characterized frontal cortical trajectories among 9- to 13-year-olds with (FH+) versus without (FH-) an FH and examined sex as a potential moderator. Methods: We used data from 9710 participants in the Adolescent Brain Cognitive Development (ABCD) Study (release 4.0). FH+ was defined as having ≥1 biological parents and/or ≥2 biological grandparents with a history of alcohol/substance use problems (n = 2433). Our primary outcome was frontal cortical structural measures obtained at baseline (ages 9-11) and year 2 follow-up (ages 11-13). We used linear mixed-effects models to examine the extent to which FH status qualified frontal cortical development over the age span studied. Finally, we ran additional interactions with sex to test whether observed associations between FH and cortical development differed significantly between sexes. Results: For FH+ (vs. FH-) youths, we observed increased cortical thinning from 9 to 13 years across the frontal cortex as a whole. When we probed for sex differences, we observed significant declines in frontal cortical thickness among boys but not girls from ages 9 to 13 years. No associations were observed between FH and frontal cortical surface area or volume. Conclusions: Having a FH+ is associated with more rapid thinning of the frontal cortex across ages 9 to 13, with this effect driven primarily by male participants. Future studies will need to test whether the observed pattern of accelerated thinning predicts future substance use outcomes.

The interaction of perfluoroalkyl acids and a family history of diabetes on arthritis: analyses of 2011-2018 NHANES.

Whether a family history of diabetes (FHD) and exposure to perfluoroalkyl acids (PFAAs) are correlated with an increased risk of developing arthritis remains unclear. This cross-sectional study was conducted to explore the correlations between FHD or exposure to PFAAs and arthritis as well as their interaction using the National Health and Nutrition Examination Survey (NHANES). In total, 6,194 participants aged ≥ 20 years from the 2011-2018 NHANES were enrolled. PFAAs are a cluster of synthetic chemicals, including perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA) and perfluorohexane sulfonic acid (PFHxS). FHD was evaluated using self-reported questionnaires. Arthritis was classified into three types, rheumatoid arthritis (RA), osteoarthritis (OA), and others, which were diagnosed using questionnaires. Generalized linear models (GLMs) were used to test the correlation between FHD and arthritis. To examine the joint effects of PFAAs and FHD on arthritis, interaction terms were applied in the GLM. Arthritis incidence was 26.7% among all participants. FHD was associated with both RA [OR = 1.70 (95% CI: 1.15-2.50)] and other types of arthritis [OR = 1.62 (95% CI: 1.21-2.16)]. However, the relationship between FHD and OA was not significant after adjustment (P = 0.18). Interaction outcomes indicated that higher PFDA levels increased the association between FHD and arthritis. FHD is associated with an increased incidence of arthritis, which may be increased by PFDA. Given the heavy burden of arthritis, preventive measures for arthritis and reduction of PFAAs exposure for patients with FHD are required.

Impact of bladder cancer family history on the prognosis of patients with non-muscle invasive bladder cancer treated with Bacillus Calmette-Guerin (BCG).

BACKGROUND: To evaluate the impact of having first-degree relatives (FDR) with bladder cancer (BC) among non-muscle invasive bladder cancer (NMIBC) patients treated with Bacillus Calmette - Guérin (BCG) on their oncological outcomes. METHODS: The National Phase II BCG/Interferon (IFN) trial database from 125 sites in the U.S.A. (1999-2001) and multi-institutional databases from France (FR) and Lebanon (LB) (2000-2021) were queried for NMIBC patients treated with BCG. Cox regression models were used to evaluate the effect of BC family history on tumor recurrence and progression in their relatives. RESULTS: There were 867 patients in the U.S.A. cohort and 1232 patients in the FR/LB cohort. Almost 8% of patients in both cohorts had FDR with BC. Patients in the FR/LB cohort were more likely to have carcinoma in situ tumors (CIS) (41% vs. 24%, p < 0.01). Having FDR with BC was not significantly associated with tumor recurrence or progression in the U.S.A. cohort. Conversely, on multivariable analysis FDR history was significantly associated with a 2.10 times increased risk of recurrence (p < 0.01) and a 3.01 times increased risk of progression (p < 0.01) in the FR/LB cohort. CONCLUSION: A family history of BC could have an important impact on the response to BCG.