Serum Orosomucoid Is Associated with Serum Adiponectin, Adipose Tissue Insulin Resistance Index, and a Family History of Type 2 Diabetes in Young Normal Weight Japanese Women.

INTRODUCTION: Adipose tissue (AT) expandability may be facilitated by adiponectin and suppressed by orosomucoid, and reduced AT expandability may be associated with first-degree relatives of type 2 diabetes. We tested the hypothesis that orosomucoid may be associated not only with adiponectin and adipose tissue insulin resistance but also with a family history of type 2 diabetes (FHD). Research Design and Methods. Anthropometric and metabolic variables, adipokines, and measures of inflammatory and insulin resistance were cross-sectionally investigated in 153 young normal weight Japanese women. Stepwise multivariate linear regression analyses were used to identify the most important determinants of orosomucoid. RESULTS: Orosomucoid was higher in women with positive (n = 57) compared to women with negative FHD and was associated positively with FHD (both p = 0.01). Orosomucoid also showed positive associations with fasting glucose (p < 0.001), free fatty acids (p = 0.001), and HbA1c (p = 0.007), whereas there was no association with fasting insulin and serum lipids. In addition, orosomucoid was associated inversely with adiponectin (p = 0.02) and positively with adipose tissue-insulin resistance index (AT-IR, the product of fasting insulin and free fatty acids; p = 0.001) but not with homeostasis model assessment-insulin resistance, leptin, and high-sensitivity C-reactive protein. In multivariate analyses, AT-IR (standardized ß, 0.22; p = 0.003), serum adiponectin (standardized ß, -0.163; p = 0.032), FHD+ (standardized ß, 0.178; p = 0.029), and HbA1c (standardized ß, 0.213; p = 0.005) emerged as independent determinants of orosomucoid and explained 15.2% of its variability. CONCLUSIONS: These results are the first to demonstrate that orosomucoid is associated not only with adipose tissue-insulin resistance and adiponectin but also with FHD.

Microsatellite instability is biased in Amsterdam II-defined Lynch-related cancer cases with family history but is rare in other cancers: a summary of 1000 analyses.

BACKGROUND: Microsatellite instability (MSI) is a key marker for predicting the response of immune checkpoint inhibitors (ICIs) and for screening Lynch syndrome (LS). AIM: This study aimed to see the characteristics of cancers with high level of MSI (MSI-H) in genetic medicine and precision medicine. METHODS: This study analyzed the incidence of MSI-H in 1000 cancers and compared according to several clinical and demographic factors. RESULTS: The incidence of MSI-H was highest in endometrial cancers (26.7%, 20/75), followed by small intestine (20%, 3/15) and colorectal cancers (CRCs)(13.7%, 64/466); the sum of these three cancers (15.6%) was significantly higher than that of other types (2.5%)(P < 0.0001). MSI-H was associated with LS-related cancers (P < 0.0001), younger age (P = 0.009), and family history, but not with smoking, drinking, or serum hepatitis virus markers. In CRC cases, MSI-H was significantly associated with a family history of LS-related cancer (P < 0.0001), Amsterdam II criteria [odds ratio (OR): 5.96], right side CRCs (OR: 4.89), and multiplicity (OR: 3.31). However, MSI-H was very rare in pancreatic (0.6%, 1/162) and biliary cancers (1.6%, 1/64) and was null in 25 familial pancreatic cancers. MSI-H was more recognized in cancers analyzed for genetic counseling (33.3%) than in those for ICI companion diagnostics (3.1%)(P < 0.0001). Even in CRCs, MSI-H was limited to 3.3% when analyzed for drug use. CONCLUSIONS: MSI-H was predominantly recognized in LS-related cancer cases with specific family histories and younger age. MSI-H was limited to a small proportion in precision medicine especially for non-LS-related cancer cases.

Risk factors for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a three-centric case-control study.

PURPOSE: Risk factors for sporadic GEP-NENs are still not well defined. To identify the main clinical risk factors represents the aim of this study performed by three Italian referral centers for NENs. METHODS: We performed a retrospective case-control study including 148 consecutive sporadic GEP-NENs and 210 age- and sex-matched controls. We collected data on clinical features, cancer family history and other potential risk factors. RESULTS: Mean age was 58.3 ± 15.8 years; 50% males, primary site was pancreas (50.7%), followed by ileum (22.3%). The 62.8% and 29.1% of cases were G1 and G2, respectively; the 40% had locally advanced or metastatic disease at diagnosis. Independent risk factors for GEP-NENs were: family history of non-neuroendocrine GEP cancer (OR 2.16, 95% CI 1.31-3.55, p = 0.003), type 2 diabetes mellitus (T2DM) (OR 2.5, 95% CI 1.39-4.51, p = 0.002) and obesity (OR 1.88, 95% CI 1.18-2.99, p = 0.007). In the T2DM subjects, metformin use was a protective factor (OR 0.28, 95% CI 0.08-0.93, p = 0.049). T2DM was also associated with a more advanced (OR 2.39, 95% CI 1.05-5.46, p = 0.035) and progressive disease (OR 2.47, 95% CI 1.08-5.34, p = 0.03). Stratifying cases by primary site, independent risk factors for pancreatic NENs were T2DM (OR 2.57, 95% CI 1.28-5.15, p = 0.008) and obesity (OR 1.98, 95% CI 1.11-3.52, p = 0.020), while for intestinal NENs family history of non-neuroendocrine GEP cancer (OR 2.46, 95% CI 1.38-4.38, p = 0.003) and obesity (OR 1.90, 95% CI 1.08-3.33, p = 0.026). CONCLUSION: This study reinforces a role for family history of non-neuroendocrine GEP cancer, T2DM and obesity as independent risk factors for GEP-NENs and suggests a role of metformin as a protective factor in T2DM subjects. If confirmed, these findings could have a significant impact on prevention strategies for GEP-NENs.

Cardiovascular Family History Increases the Risk of Disease Recurrence After a First Myocardial Infarction.

Background Family history of atherosclerotic cardiovascular disease (ASCVD) is easily accessible and captures genetic cardiovascular risk, but its prognostic value in secondary prevention is unknown. Methods and Results We followed 25 615 patients registered in SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) from their 1-year revisit after a first-time myocardial infarction during 2005 to 2013, until December 31, 2018. Data on relatives, diagnoses and socioeconomics were extracted from national registers. The association between family history and recurrent ASCVD was studied with Cox proportional-hazard regression, adjusting for risk factors and socioeconomics. A family history of ASCVD was defined as hospitalization due to myocardial infarction, angina with coronary revascularization, stroke, or cardiovascular death in ≥1 parent or full sibling, with early-onset defined as disease-onset before 55 years in men and 65 in women. The additional discriminatory value of family history to Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention was assessed with Harrell's C-index difference and reclassification was studied with continuous net reclassification improvement. Family history of early-onset ASCVD in ≥1 first-degree relative was present in 2.3% and was associated with recurrent ASCVD (hazard ratio [HR] 1.31; 95% CI, 1.17-1.47), fully adjusted for risk factors (HR, 1.22; 95% CI, 1.05-1.42). Early-onset family history improved the discriminatory ability of the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention, with Harrell's C improving 0.003 points (95% CI, 0.001-0.005) from initial 0.587 (95% CI, 0.576-0.595) and improved reclassification (continuous net reclassification improvement 2.1%, P<0.001). Conclusions Family history of early-onset ASCVD is associated with recurrent ASCVD after myocardial infarction, independently of traditional risk factors and improves secondary risk prediction. This may identify patients to target for intensified secondary prevention.

Determination of thresholds of risk in women at average risk of breast cancer to personalize the organized screening program.

In France, more than 10 million women at "average" risk of breast cancer (BC), are included in the organized BC screening. Existing predictive models of BC risk are not adapted to the French population. Thus, we set up a new score in the French Hérault region and looked for subgroups at a graded level of risk in women at "average" risk. We recruited a retrospective cohort of women, aged 50 to 60, who underwent the organized BC screening, and included 2241 non-cancer women and 527 who developed a BC during a 12-year follow-up period (2006-2018). The risk factors identified were high breast density (ACR BI-RADS grading)(B vs A: HR = 1.41, 95%CI [1.05; 1.9], p = 0.023; C vs A: HR = 1.65 [1.2; 2.27], p = 0.02 ; D vs A: HR = 2.11 [1.25;3.58], p = 0.006), a history of maternal breast cancer (HR = 1.61 [1.24; 2.09], p < 0.001), and socioeconomic difficulties (HR 1.23 [1.09; 1.55], p = 0.003). While early menopause (HR = 0.36 [0.13; 0.99], p = 0.003) and an age at menarche after 12 years (HR = 0.77 [0.63; 0.95], p = 0.047) were protective factors. We identified 3 groups at risk: lower, average, and higher, respectively. A low threshold was characterized at 1.9% of 12-year risk and a high threshold at 4.5% 12-year risk. Mean 12-year risks in the 3 groups of risk were 1.37%, 2.68%, and 5.84%, respectively. Thus, 12% of women presented a level of risk different from the average risk group, corresponding to 600,000 women involved in the French organized BC screening, enabling to propose a new strategy to personalize the national BC screening. On one hand, for women at lower risk, we proposed to reduce the frequency of mammograms and on the other hand, for women at higher risk, we suggested intensifying surveillance.

Predictors of Suicide Attempt Within 30 Days After First Medically Documented Suicidal Ideation in U.S. Army Soldiers.

OBJECTIVE: The authors sought to identify predictors of imminent suicide attempt (within 30 days) among U.S. Army soldiers following their first documented suicidal ideation. METHODS: Using administrative data from the Army Study to Assess Risk and Resilience in Servicemembers, the authors identified 11,178 active-duty Regular Army enlisted soldiers (2006-2009) with medically documented suicidal ideation and no prior medically documented suicide attempts. The authors examined risk factors for suicide attempt within 30 days of first suicidal ideation using logistic regression analyses, including sociodemographic and service-related characteristics, psychiatric diagnoses, physical health care visits, injuries, and history of family violence or crime perpetration or victimization. RESULTS: Among soldiers with first documented suicidal ideation, 830 (7.4%) attempted suicide, 46.3% of whom (N=387) attempted suicide within 30 days (rate, 35.4 per 1,000 soldiers). Following a series of multivariate analyses, the final model identified females (odds ratio=1.3, 95% CI=1.0, 1.8), combat medics (odds ratio=1.6, 95% CI=1.1, 2.2), individuals with an anxiety disorder diagnosis prior to suicidal ideation (odds ratio=1.3, 95% CI=1.0, 1.6), and those who received a sleep disorder diagnosis on the same day as the recorded suicidal ideation (odds ratio=2.3, 95% CI=1.1, 4.6) as being more likely to attempt suicide within 30 days. Black soldiers (odds ratio=0.6, 95% CI=0.4, 0.9) and those who received an anxiety disorder diagnosis on the same day as suicidal ideation (odds ratio=0.7, 95% CI=0.5, 0.9) were less likely. CONCLUSIONS: Suicide attempt risk is highest in the first 30 days following ideation diagnosis and is more likely among women, combat medics, and soldiers with an anxiety disorder diagnosis before suicidal ideation and a same-day sleep disorder diagnosis. Black soldiers and those with a same-day anxiety disorder diagnosis were at decreased risk. These factors may help identify soldiers at imminent risk of suicide attempt.

Review of Pediatric Neurologic History and Age-Appropriate Neurologic Examination in the Office.

The neurologic examination of an infant or child can be daunting, as they are unable to verbally communicate or follow directions. It starts with tailoring the pediatric neurologic history and examination to the child's specific age group. A good neurologic history obtained from the patient and parents is key to evaluating a pediatric patient. This article offers pearls on what information to ask the caregivers and patients, and salient aspects of a brief neurologic examination.

Neuroimaging for the Primary Care Provider: A Review of Modalities, Indications, and Pitfalls.

When evaluating a child with a potential neurologic or neurodevelopmental disorder, identifying indications for imaging and the correct imaging modality to order can be challenging. This article provides an overview of computed tomography, MRI, ultrasonography, and radiography with an emphasis on indications for use, pitfalls to be avoided, and recent advances. A discussion of the appropriate use of ionizing radiation, intravenous contrast, and sedation is also provided.

Infancy and Childhood Obesity Grade Predicts Weight Loss in Adulthood: The ONTIME Study.

We examined the relationships between intergenerational obesity, weight and size at birth, and obesity from infancy to adolescence with weight loss in response to a dietary intervention. We studied 4264 participants (3369 women; mean age 41.5 ± 12.9 years) of the ONTIME study. Participants followed a weight-loss treatment based on a Mediterranean diet. Associations between grandparental and parental obesity grade, birth weight and size, and obesity grade in infancy, childhood and adolescence with total weight loss in response to treatment were assessed, using multivariate linear regression models. A lower weight loss (kg) in response to treatment was found among participants who were obese during infancy (beta coefficient -2.13 kg; 95% CI, -3.96, -0.30; p = 0.023). Furthermore, obesity during infancy and also during childhood was associated with a slower weekly rate of weight loss during treatment (p < 0.05). In conclusion, obesity in infancy and in childhood impairs the weight-loss response to dietary treatments in adulthood. Tackling obesity throughout early life may improve the effectiveness of weight-loss interventions in adulthood.

Progression of Primary Angle Closure Suspect to Primary Angle Closure and Associated Risk Factors: The Handan Eye Study.

Purpose: To investigate the progression of angle closure from primary angle closure suspect (PACS) and associated risk factors over five years in rural Chinese adults. Methods: In this population-based cohort study, subjects aged ≥30 years old with unilateral or bilateral PACS at baseline of the Handan Eye Study who participated in the follow-up and had undergone baseline and follow-up gonioscopic examinations were included. The progression of angle closure was defined as the presence of primary angle closure (PAC)/primary angle-closure glaucoma (PACG) during the follow-up in subjects with PACS at baseline. Ocular data from the right eye were used for cases with bilateral PACS and unilateral PACS in the right eye at baseline. For those with unilateral PACS in the left eye at baseline, ocular data from the left eye were used. Demographic information, ocular conditions, personal history, and systemic comorbidities were compared between the progression and nonprogression groups. Univariate and multivariate logistic regression was performed to identify the baseline risk factors for progression of angle closure. Results: In total, 526 subjects (111 male, 415 female) with baseline PACS were finally enrolled. The overall progression of PACS to angle closure was 32 cases (31 PAC, 1 PACG). Logistic regression analysis identified narrower mean angle width (P < 0.001) to be associated with the progression. Conclusions: We report the progression from baseline PACS to PAC/PACG after five years. And baseline mean angle width was determined to be independent predictive risk factor for the progression of angle closure.

Determinants of Adherence to Diabetes Screening in Iranian Adults With a Positive Family History of Diabetes.

OBJECTIVES: Insufficient evidence exists regarding factors that affect screening adherence among people with a family history of diabetes, who comprise roughly half of all patients with diabetes. Therefore, we aimed to identify the determinants of diabetes screening adherence in adults with a family history of diabetes who had not yet been diagnosed with diabetes. METHODS: This cross-sectional study was conducted at selected urban primary healthcare facilities in Tehran, Iran. The study population was clinically non-diabetic adults above 20 years of age with a family history of diabetes in at least 1 first-degree relative. All eligible people identified on randomly-selected days of the month were invited to join the study. RESULTS: Among 408 participants, 128 (31.4%) had received a fasting blood glucose check during the last year. Using binary logistic regression, the independent predictors of screening adherence were knowledge of adverse effects of diabetes such as sexual disorders (odds ratio [OR], 3.05) and renal failure (OR, 2.73), the impact of family members' advice on receiving diabetes screening (OR, 2.03), recommendation from a healthcare provider to have a fasting blood glucose check (OR, 2.61), and intention to have a fasting blood glucose check within the next 6 months (OR, 2.85). Other variables that predicted screening adherence were age (OR, 1.05), job (being a housekeeper; OR, 3.39), and having a college degree (OR, 3.55). CONCLUSIONS: Knowledge of the adverse effects of diabetes, physicians' and healthcare providers' advice about the benefits of early disease detection, and family members' advice were independent predictors of screening adherence.

Impact of changing guidelines on genetic testing and surveillance recommendations in a contemporary cohort of breast cancer survivors with family history of pancreatic cancer.

Changing practice guidelines and recommendations have important implications for cancer survivors. This study investigated genetic testing patterns and outcomes and reported family history of pancreatic cancer (FHPC) in a large registry population of breast cancer (BC) patients. Variables including clinical and demographic characteristics, FHPC in a first or second-degree relative, and genetic testing outcomes were analyzed for BC patients diagnosed between 2010 and 2018 in the NYU Langone Health Breast Cancer Database. Among 3334 BC patients, 232 (7%) had a positive FHPC. BC patients with FHPC were 1.68 times more likely to have undergone genetic testing (p < 0.001), but 33% had testing for BRCA1/2 only and 44% had no genetic testing. Pathogenic germline variants (PGV) were identified in 15/129 (11.6%) BC patients with FHPC, and in 145/1315 (11.0%) BC patients without FHPC. Across both groups, updates in genetic testing criteria and recommendations could impact up to 80% of this cohort. Within a contemporary cohort of BC patients, 7% had a positive FHPC. The majority of these patients (56%) had no genetic testing, or incomplete testing by current standards, suggesting under-diagnosis of PC risk. This study supports recommendations for survivorship care that incorporate ongoing genetic risk assessment and counseling.

Individual differences in the associations between risk factors for alcohol use disorder and alcohol use-related outcomes.

BACKGROUND: Family history of alcohol use disorder; AUD (FH +) and impulsivity-related traits are known risk factors for problem drinking that have been investigated in predominately White samples. This cross-sectional study examined whether these risk factors vary by sex in the overall, majority White sample and in a Black subsample. METHOD: A model building regression procedure was used to investigate the combined effect of FH + and impulsivity-related traits on alcohol quantity, frequency, and problems by sex (overall sample: N = 757, 50% female, 73% White, agemean = 33.74, SD = 11.60; Black subsample: n = 138, 47% female, agemean = 33.60, SD = 9.87). RESULTS: Overall Sample. No sex differences were found in the compounding effects of FH + and impulsivity-related traits on alcohol outcomes. Males reported more physical, social, and overall alcohol-related problems than females. FH + was positively associated with all alcohol-related consequences. Poor self-regulation was the only trait associated with all alcohol outcomes. Black Subsample: A three-way interaction suggested a negative association between inhibition and frequency of alcohol use among FH + males only. A two-way interaction also suggested impulse control was associated with more interpersonal alcohol-related problems among males only. Main effects were also found in the expected direction such that higher impulsivity and FH + were associated with poorer alcohol outcomes. CONCLUSION: These findings suggest no sex differences in the overall sample in the interactive effects of established risk factors for AUD on alcohol outcomes, and that poor self-regulation may be key for personality-targeted alcohol prevention and intervention programs. Preliminary findings of sex differences in the Black subsample should be replicated. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Genetic susceptibility, family history of diabetes and healthy lifestyle factors in relation to diabetes: A gene-environment interaction analysis in Chinese adults.

AIMS/INTRODUCTION: To analyze the associations and interactions of the genetic susceptibility and family history of diabetes with lifestyle factors in relation to diabetes among Chinese adults. MATERIALS AND METHODS: We constructed a genetic risk score of 34 single-nucleotide polymorphisms in 11,596 participants from Songnan and Youyi communities, Baoshan District, Shanghai, China. We determined a healthy lifestyle by a normal body mass index (<24 kg/m2 ), adequate fruit and vegetable intake (≥4.5 cups/day), never smoked or quit smoking >1 year prior, sufficient physical activity (≥600 metabolic equivalent minutes per week), and a sleep duration of ≥6 to ≤8 h/day. Logistic regression models were used to examine the associations and interactions between heritability and lifestyle on diabetes. RESULTS: A healthier lifestyle was associated with a lower prevalence of diabetes within any heritable risk groups categorized by the genetic risk score and family history of diabetes. In the combined communities, the odds ratio (95% confidence interval) for diabetes associated with each additional healthy lifestyle factor was 0.83 (0.77-0.89) among participants with a low genetic risk score and 0.86 (0.81-0.91) among participants with a high genetic risk score (Pinteraction = 0.66). Similar interaction patterns of family history (Pinteraction = 0.15) and the combination of family history and the genetic risk score with healthy lifestyle (Pinteraction = 0.55) on diabetes were observed. CONCLUSIONS: A healthier lifestyle was associated with a significantly lower prevalence of diabetes regardless of heritable risk groups, highlighting the importance of adhering to a healthy lifestyle for diabetes prevention among the entire population.

US Childhood Asthma Incidence Rate Patterns From the ECHO Consortium to Identify High-risk Groups for Primary Prevention.

Importance: Asthma is the leading chronic illness in US children, but most descriptive epidemiological data are focused on prevalence. Objective: To evaluate childhood asthma incidence rates across the nation by core demographic strata and parental history of asthma. Design, Setting, and Participants: For this cohort study, a distributed meta-analysis was conducted within the Environmental Influences on Child Health Outcomes (ECHO) consortium for data collected from May 1, 1980, through March 31, 2018. Birth cohort data of children from 34 gestational weeks of age or older to 18 years of age from 31 cohorts in the ECHO consortium were included. Data were analyzed from June 14, 2018, to February 18, 2020. Exposures: Caregiver report of physician-diagnosed asthma with age of diagnosis. Main Outcome and Measures: Asthma incidence survival tables generated by each cohort were combined for each year of age using the Kaplan-Meier method. Age-specific incidence rates for each stratum and asthma incidence rate ratios by parental family history (FH), sex, and race/ethnicity were calculated. Results: Of the 11 404 children (mean [SD] age, 10.0 [0.7] years; 5836 boys [51%]; 5909 White children [53%]) included in the primary analysis, 7326 children (64%) had no FH of asthma, 4078 (36%) had an FH of asthma, and 2494 (23%) were non-Hispanic Black children. Children with an FH had a nearly 2-fold higher incidence rate through the fourth year of life (incidence rate ratio [IRR], 1.94; 95% CI, 1.76-2.16) after which the rates converged with the non-FH group. Regardless of FH, asthma incidence rates among non-Hispanic Black children were markedly higher than those of non-Hispanic White children during the preschool years (IRR, 1.58; 95% CI, 1.31-1.86) with no FH at age 4 years and became lower than that of White children after age 9 to 10 years (IRR, 0.67; 95% CI, 0.50-0.89) with no FH. The rates for boys declined with age, whereas rates among girls were relatively steady across all ages, particularly among those without an FH of asthma. Conclusions and Relevance: Analysis of these diverse birth cohorts suggests that asthma FH, as well as race/ethnicity and sex, were all associated with childhood asthma incidence rates. Black children had much higher incidences rates but only during the preschool years, irrespective of FH. To prevent asthma among children with an FH of asthma or among Black infants, results suggest that interventions should be developed to target early life.

Low Referral Rates for Genetic Assessment of Patients With Multiple Adenomas in United Kingdom Bowel Cancer Screening Programs.

BACKGROUND: Approximately 1 in 20 cases of colorectal cancer are caused by monogenic syndromes. Published guidelines recommend that patients with 10 or more adenomas be referred for genetic testing, based on evidence that colorectal cancer risk is associated with adenoma multiplicity. OBJECTIVE: The aim of this study was to determine adherence to guidelines on referral for genetic screening in patients with 10 or more adenomas. DESIGN: A cross-sectional study was performed of prospectively collected data from the UK Bowel Cancer Screening Programme between May 2007 and June 2018. Only histologically confirmed adenomas were included. Clinicopathological data were recorded from patient records, and referrals to clinical genetics services were ascertained. SETTING: Data were obtained from 3 centers in London, United Kingdom. PATIENTS: A total of 17,450 subjects underwent colonoscopy following an abnormal fecal occult blood test. MAIN OUTCOME MEASURES: We quantified patients with 10 or more adenomas and the proportion referred for genetic screening. RESULTS: The adenoma detection rate was 50.6% among 17,450 patients who underwent colonoscopy (8831 had 1 or more adenomas). Three hundred forty-seven patients (2.0%) had 10 or more adenomas. Patients with 10 or more adenomas were more likely to be male than those with fewer than 10 adenomas (76.9% vs 53.4%; p < 0.0001). A family history was collected in 37.8% of the multiple adenoma population. Of 347 patients with 10 or more adenomas, 28 (8.1%) were referred for genetic assessment. LIMITATIONS: All 3 screening centers were in a single city. No genetic outcome data were available to permit analysis of actual rates of inherited cancer syndromes in this population. CONCLUSIONS: In this study, almost 1 in 50 patients had 10 or more adenomas. Despite guidelines advising genetic testing in this group, referral rates are low. A referral pathway and management strategies should be established to address this patient population. See Video Abstract at http://links.lww.com/DCR/B630. TASAS BAJAS DE DERIVACIN PARA LA EVALUACIN GENTICA DE PACIENTES CON ADENOMAS MLTIPLES EN LOS PROGRAMAS DE DETECCIN DEL CNCER DE INTESTINO DEL REINO UNIDO: ANTECEDENTES:Aproximadamente uno de cada veinte casos de cáncer colorrectal son causados por síndromes monogénicos. Las pautas publicadas recomiendan que los pacientes con diez o más adenomas sean derivados para pruebas genéticas, basándose en la evidencia de que el riesgo de cáncer colorrectal está asociado con la multiplicidad de adenomas.OBJETIVO:El objetivo de este estudio fue determinar la adherencia a las guías de derivación para cribado genético en pacientes con diez o más adenomas.DISEÑO:Se realizó un estudio transversal de datos recolectados prospectivamente del Programa de Detección de Cáncer de Intestino del Reino Unido entre mayo de 2007 y junio de 2018. Solo se incluyeron los adenomas confirmados histológicamente. Los datos clínico-patológicos se registraron a partir de los registros de los pacientes y se determinaron las derivaciones a los servicios de genética clínica.AJUSTE ENTORNO CLINICO:Los datos se obtuvieron de tres centros en Londres, Reino Unido.PACIENTES:Un total de 17.450 17450 sujetos pacientes se sometieron a una colonoscopia después de una prueba de sangre oculta en heces anormal positiva.PRINCIPALES MEDIDAS DE RESULTADO VOLARACION:cuantificamos los pacientes con diez o más adenomas y la proporción remitida para cribado genético.RESULTADOS:La tasa de detección de adenomas fue del 50,6% entre 17.450 17450 pacientes que se sometieron a colonoscopia (8.831 8831 tenían uno o más adenomas). 347 pacientes (2,0%) tenían 10 o más adenomas. Los pacientes con 10 o más adenomas tenían más probabilidades de ser hombres que aquellos con menos de 10 adenomas (76,9% frente versus a 53,4%; p <0,0001). Se recogieron antecedentes familiares en el 37,8% de la población de adenomas múltiples. De 347 pacientes con 10 o más adenomas, 28 (8,1%) fueron remitidos para evaluación genética.LIMITACIONES:Los tres centros de detección se encontraban en una sola ciudad. No se disponía de datos de resultados genéticos que permitieran el análisis de las tasas reales de síndromes de cáncer hereditario en esta población.CONCLUSIONES:En este estudio, casi uno de cada cincuenta pacientes tenía diez o más adenomas. A pesar de las pautas que recomiendan las pruebas genéticas en este grupo, las tasas de derivación son bajas. Se debe establecer una vía de derivación y estrategias de manejo para abordar esta población de pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B630.

The contribution of Lynch syndrome to early onset malignancy in Ireland.

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant hereditary cancer syndrome responsible for 2-4% of hereditary colorectal cancers (CRC). Mismatch repair protein deficiency (dMMR) is a characteristic feature of LS. It has been associated with a poor response to standard chemotherapy in metastatic colorectal cancer (mCRC). There is currently no LS database to monitor trends of disease in Ireland. We aim to centralise LS data in Ireland to assess the burden of LS in Ireland and guide improvements in prevention and treatment of LS-associated cancer. METHODS: A retrospective review was carried out including all medical records for LS patients from two of the three cancer genetics clinics in Ireland between 2000 and 2018 was carried out. Clinicopathological data of probands (n = 57) and affected family members including demographics, mutation status, cancer diagnosis and outcome was recorded. Statistical analysis was carried out using SPSS software. RESULTS: Fifty-seven families including three-hundred and forty-five individuals affected by cancer were identified. The most common cancers recorded were colorectal (53%), breast (12%) and endometrial (10%). One-hundred and thirty-eight confirmed carriers were identified: 65 path_MLH1 (47%), 43 path_MSH2 (31%), 11 path_MSH6 (8%), 17 path_PMS2 (12%) and two path_EPCAM (1%). Cancer type varied significantly by gene. Median age of first diagnosis was 44.5 years (range 23-81). Half of all deceased patients (n = 11) in this group died within 2.5 years of first diagnosis. These deaths were directly related to cancer in 59% of cases. CONCLUSIONS: Under diagnosis of LS misses a powerful preventive and therapeutic opportunity. LS causes early onset dMMR cancer diagnoses with substantial societal impact. Implementation of ICBs into treatment policy for this small cohort of dMMR mCRC is an achievable therapeutic goal that may significantly improve survival. A prospective database for LS in Ireland is necessary to maximise prevention in this population.

Current and Past Infections of HBV Do Not Increase Mortality in Patients With COVID-19.

BACKGROUND AND AIMS: We compared risk of acute liver injury and mortality in patients with COVID-19 and current, past, and no HBV infection. APPROACH AND RESULTS: This was a territory-wide retrospective cohort study in Hong Kong. Patients with COVID-19 between January 23, 2020, and January 1, 2021, were identified. Patients with hepatitis C or no HBsAg results were excluded. The primary outcome was mortality. Acute liver injury was defined as alanine aminotransferase or aspartate aminotransferase ≥2 × upper limit of normal (ULN; i.e., 80 U/L), with total bilirubin ≥2 × ULN (i.e., 2.2 mg/dL) and/or international normalized ratio ≥1.7. Of 5,639 patients included, 353 (6.3%) and 359 (6.4%) had current and past HBV infection, respectively. Compared to patients without known HBV exposure, current HBV-infected patients were older and more likely to have cirrhosis. Past HBV-infected patients were the oldest, and more had diabetes and cardiovascular disease. At a median follow-up of 14 (9-20) days, 138 (2.4%) patients died; acute liver injury occurred in 58 (1.2%), 8 (2.3%), and 11 (3.1%) patients with no, current, and past HBV infection, respectively. Acute liver injury (adjusted HR [aHR], 2.45; 95% CI, 1.52-3.96; P < 0.001), but not current (aHR, 1.29; 95% CI, 0.61-2.70; P = 0.507) or past (aHR, 0.90; 95% CI, 0.56-1.46; P = 0.681) HBV infection, was associated with mortality. Use of corticosteroid, antifungal, ribavirin, or lopinavir-ritonavir (adjusted OR [aOR], 2.55-5.63), but not current (aOR, 1.93; 95% CI, 0.88-4.24; P = 0.102) or past (aOR, 1.25; 95% CI, 0.62-2.55; P = 0.533) HBV infection, was associated with acute liver injury. CONCLUSION: Current or past HBV infections were not associated with more liver injury and mortality in COVID-19.