Spectrum of germline pathogenic variants in Brazilian hereditary breast/ovarian cancer cases.

PURPOSE: To define the spectrum of germline pathogenic variants (PVs) and copy number variant (CNV) in cancer susceptibility genes to the burden of breast and ovarian cancer (BC, OvC) in high-risk Brazilians in Minas Gerais with health insurance, southeast Brazil, undergoing multigene panel testing (MGPT). METHODS: Genotyping eligible individuals with health insurance in the Brazilian healthcare system for Hereditary Breast and Ovarian Cancer Syndrome to undergo molecular testing for 44 or 141-gene panels, a decision that was insurance driven. RESULTS: Overall, 701 individuals clinically defined as high BC/OvC risk, underwent MGPT from 1/2021 to 10/2022, with ~ 50% genotyped with a 44-gene panel and the rest with a 141-gene panel. Overall, 16.4% and 22.6% of genotyped individuals harbored PVs using 44-gene and the 141 gene panel, respectively. The most frequently mutated genes were: BRCA2 (3.7%); BRCA1 (3.6%) and monoallelic MUTYH (3.1%). CONCLUSION: The rate of PVs detected in high-risk individuals in this study was twice the 10% threshold used in Brazilian health guidelines. MGPT doubled the detection rate of PVs in cancer susceptibility genes in high-risk individuals compared with BRCA1/BRCA2 genotyping alone. The spectrum of PVs in Southern Brazil is diverse, with few recurring variants such as TP53 (0.6%), suggesting regional founder effects. The use of MGPT in hereditary cancer in Minas Gerais significantly increased the detection rate of P/LPVs compared to existing guidelines and should be considered as the primary genotyping modality in assessing hereditary cancer risk in Brazil.

Screening for pancreatic cancer in high-risk individuals using MRI: optimization of scan techniques to detect small lesions.

Pancreatic cancer has a dismal prognosis in the general population. However, early detection and treatment of disease in high-risk individuals can improve survival, as patients with localized disease and especially patients with lesions smaller than 10 mm show greatly improved 5-year survival rates. To achieve early detection through MRI surveillance programs, optimization of imaging is required. Advances in MRI technologies in both hardware and software over the years have enabled reliable detection of pancreatic cancer at a small size and early stage. Standardization of dedicated imaging protocols for the pancreas are still lacking. In this review we discuss state of the art scan techniques, sequences, reduction of artifacts and imaging strategies that enable early detection of lesions. Furthermore, we present the imaging features of small pancreatic cancers from a large cohort of high-risk individuals. Refinement of MRI techniques, increased scan quality and the use of artificial intelligence may further improve early detection and the prognosis of pancreatic cancer in a screening setting.

The Spanish Familial Pancreatic Cancer Registry (PANGENFAM): a decade follow-up of individuals at high-risk for pancreatic cancer.

The Spanish Familial Pancreatic Cancer Registry (PANGENFAM) was established in 2009 and aims to characterize the genotype and phenotype of familial pancreatic cancer (FPC). Furthermore, an early detection screening program for pancreatic ductal adenocarcinoma (PDAC) is provided to healthy high-risk individuals from FPC and hereditary pancreatic cancer families (first-degree relatives). This article describes our experience over the last 10 years in high-risk screening. Hereditary and familial pancreatic cancer families were identified through the oncology and gastroenterology units. High-risk individuals underwent annual screening with endoscopic ultrasound (EUS) and magnetic resonance (MRI) from age 40 or 10 years younger than the youngest affected family member. Results: PANGENFAM has enrolled 290 individuals from 143 families, including 52 PDAC cases and 238 high-risk individuals. All high-risk individuals eligible for screening were offered to enter the surveillance program, with 143 currently participating. Pancreatic abnormalities were detected in 94 individuals (median age 53 years (29-83), with common findings including cystic lesions and inhomogeneous parenchyma. Imaging test concordance was 66%. Surgical intervention was performed in 4 high-risk individuals following highly suspicious lesions detected by imaging. PANGENFAM is a valuable resource for science innovation, such as biobanking, with clinical and imaging data available for analysis. For high-risk families, it may offer a potential for early diagnosis. Collaboration with other national and international registries is needed to increase our understanding of the disease biology and to standardize criteria for inclusion and follow-up, optimizing cost-effectiveness and efficacy.

The role of endoscopic ultrasound in the detection of pancreatic lesions in high-risk individuals.

Individuals at high risk of developing pancreatic ductal adenocarcinoma are eligible for surveillance within research programs. These programs employ periodic imaging in the form of magnetic resonance imaging/magnetic resonance cholangiopancreatography or endoscopic ultrasound for the detection of early cancer or high-grade precursor lesions. This narrative review discusses the role of endoscopic ultrasound within these surveillance programs. It details its overall strengths and limitations, yield, burden on patients, and how it compares to magnetic resonance imaging. Finally, recommendations are given when and how to incorporate endoscopic ultrasound in the surveillance of high-risk individuals.

Aspects and outcomes of surveillance for individuals at high-risk of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths and is associated with a poor prognosis. The majority of these cancers are detected at a late stage, contributing to the bad prognosis. This underscores the need for novel, enhanced early detection strategies to improve the outcomes. While population-based screening is not recommended due to the relatively low incidence of PDAC, surveillance is recommended for individuals at high risk for PDAC due to their increased incidence of the disease. However, the outcomes of pancreatic cancer surveillance in high-risk individuals are not sorted out yet. In this review, we will address the identification of individuals at high risk for PDAC, discuss the objectives and targets of surveillance, outline how surveillance programs are organized, summarize the outcomes of high-risk individuals undergoing pancreatic cancer surveillance, and conclude with a future perspective on pancreatic cancer surveillance and novel developments.

Prediction of brain age in individuals with and at risk for alcohol use disorder using brain morphological features.

Brain age measures predicted from structural and functional brain features are increasingly being used to understand brain integrity, disorders, and health. While there is a vast literature showing aberrations in both structural and functional brain measures in individuals with and at risk for alcohol use disorder (AUD), few studies have investigated brain age in these groups. The current study examines brain age measures predicted using brain morphological features, such as cortical thickness and brain volume, in individuals with a lifetime diagnosis of AUD as well as in those at higher risk to develop AUD from families with multiple members affected with AUD (i.e., higher family history density (FHD) scores). The AUD dataset included a group of 30 adult males (mean age = 41.25 years) with a lifetime diagnosis of AUD and currently abstinent and a group of 30 male controls (mean age = 27.24 years) without any history of AUD. A second dataset of young adults who were categorized based on their FHD scores comprised a group of 40 individuals (20 males) with high FHD of AUD (mean age = 25.33 years) and a group of 31 individuals (18 males) with low FHD (mean age = 25.47 years). Brain age was predicted using 187 brain morphological features of cortical thickness and brain volume in an XGBoost regression model; a bias-correction procedure was applied to the predicted brain age. Results showed that both AUD and high FHD individuals showed an increase of 1.70 and 0.09 years (1.08 months), respectively, in their brain age relative to their chronological age, suggesting accelerated brain aging in AUD and risk for AUD. Increased brain age was associated with poor performance on neurocognitive tests of executive functioning in both AUD and high FHD individuals, indicating that brain age can also serve as a proxy for cognitive functioning and brain health. These findings on brain aging in these groups may have important implications for the prevention and treatment of AUD and ensuing cognitive decline.

The Italian registry of families at risk for pancreatic cancer (IRFARPC): implementation and evolution of a national program for pancreatic cancer surveillance in high-risk individuals.

Screening programs for early detection and treatment of pancreatic cancer (PC) and its precursor lesions are increasingly implemented worldwide to reduce disease-specific lethality. Given the relatively low prevalence of the disease, the ideal target of such approaches is an enriched cohort of individuals harboring a lifetime risk of developing PC significantly higher compared to the general population, given either a substantial aggregation of PC cases in their family (i.e. familial pancreatic cancer) or a genomic landscape enriched with pathogenic variants associated with pancreatic carcinogenesis (i.e. mutation carriers). In Italy, a national registry for the census and surveillance of high-risk individuals for PC was launched in 2015, enrolling some 1200 subjects as of today. In this perspective, the scientific background, multi-level structure, and evolution of IRFARPC are outlined, as well as its long-term results, future developments, and areas for improvement.

Profiles and Findings of Population-Based Esophageal Cancer Screening With Endoscopy in China: Systematic Review and Meta-analysis.

BACKGROUND: Population-based esophageal cancer (EC) screening trials and programs have been conducted in China for decades; however, screening strategies have been adopted in different regions and screening profiles are unclear. OBJECTIVE: We performed a meta-analysis to profile EC screening in China by positivity rate, compliance rate, and endoscopy findings, aiming to provide explicit evidence and recommendations for EC screening programs. METHODS: English (PubMed, Embase) and Chinese (China National Knowledge Infrastructure, Wanfang) language databases were systematically searched for population-based EC screening studies in the Chinese population until December 31, 2022. A meta-analysis was performed by standard methodology using a random-effects model. Pooled prevalence rates were calculated for three groups: high-risk areas with a universal endoscopy strategy, rural China with a risk-stratified endoscopic screening (RSES) strategy, and urban China with an RSES strategy. Positive cases included lesions of severe dysplasia, carcinoma in situ, intramucosal carcinoma, submucosal carcinoma, and invasive carcinoma. RESULTS: The pooled positivity rate of the high-risk population was higher in rural China (44.12%) than in urban China (23.11%). The compliance rate of endoscopic examinations was the highest in rural China (52.40%), followed by high-risk areas (50.11%), and was the lowest in urban China (23.67%). The pooled detection rate of positive cases decreased from 1.03% (95% CI 0.82%-1.30%) in high-risk areas to 0.48% (95% CI 0.25%-0.93%) in rural China and 0.12% (95% CI 0.07%-0.21%) in urban China. The pooled detection rate of low-grade intraepithelial neoplasia (LGIN) was also in the same order, being the highest in high-risk areas (3.99%, 95% CI 2.78%-5.69%), followed by rural China (2.55%, 95% CI 1.03%-6.19%) and urban China (0.34%, 95% CI 0.14%-0.81%). Higher detection rates of positive cases and LGIN were observed among males than among females and at older ages. The pooled early detection rate was 81.90% (95% CI 75.58%-86.88%), which was similar to the rates in high-risk areas (82.09%), in rural China (80.76%), and in urban China (80.08%). CONCLUSIONS: Under the current screening framework, a higher screening benefit was observed in high-risk areas than in other regions. To promote EC screening and reduce the current inequality of screening in China, more focus should be given to optimizing strategies of high-risk individual assessment and surveillance management to improve compliance with endoscopic examination. TRIAL REGISTRATION: PROSPERO CRD42022375720; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=375720.

Hereditary pancreatic cancer.

Pancreatic cancer is one of the deadliest malignancies. Therefore, there is an urgent need to detect pancreatic cancer in an earlier stage to improve outcomes. A variety of hereditary cancer syndromes have been associated with an increased risk of developing pancreatic cancer, and these individuals may benefit from surveillance programs. Surveillance programs have shown potential to improve outcomes, but have important risks such as overtreatment. In this review we will discuss the definitions and epidemiology of hereditary pancreatic cancer, recommendations for genetic testing and participation in surveillance. Important aspects are differences in surveillance strategies, target lesions, and potential benefits and harms of surveillance. Lastly we will highlight future directions for research and improvement of care for individuals at high-risk of pancreatic cancer.

Surgical management of familial pancreatic cancer: a systematic review of the literature.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the third most common cause of cancer-related mortality. The fact that the vast majority of patients with PDAC are diagnosed at an advanced stage highlights the need of early diagnosis. As hereditary factors are associated with approximately 5% of all PDAC cases, a screening programme to these high-risk individuals (HRI) has been proposed. The aim of screening methods is to identify selected group of patients with morphological abnormalities at an early stage, in order to be treated promptly. In this study, we evaluate the surgical outcomes and the appropriateness of pancreatic resection in HRIs who were selected for screening. METHODS: A systematic literature search of the PubMed, Embase, and Cochrane databases was performed. The clinicopathological features were recorded and evaluated. RESULTS: Six studies were selected for data collection. A total number of 77 patients were identified. Twenty-one patients had a germline mutation, with CDKN2A being the most prominent one (15.6%). Distal pancreatectomy was the most common surgical procedure (42.8%), followed by pancreaticoduodenectomy (33.8%). The mean disease-free survival was 23.6 months and tumour recurrence occurred in 9 patients (11.7%). Disease-specific mortality was 17.8%, while overall mortality was 19.5%. The most frequently reported postoperative diagnosis was PDAC (28 cases, 38.9%), followed by IPMN (23 cases, 31.9%), whereas high-grade PanIN lesions were found in 13 patients (18.1%). CONCLUSION: High-risk individuals for pancreatic cancer, who are eventually operated may have a relatively uneventful postoperative course, however the oncological outcomes are comparable to the general population.

Colorectal cancer screening participation among citizens not recommended to be screened: a cohort study.

BACKGROUND: Guidelines on colorectal cancer (CRC) screening recommend screening of average-risk adults only. In addition, screening of individuals with active inflammatory bowel disease (IBD) might result in too many false-positive cases. However, the organisers of CRC screening programmes are often uninformed of whom to exclude due to an elevated CRC risk or active IBD. It is therefore unknown how often high-risk individuals (i.e. individuals with a previous diagnosis of CRC or polyps associated with hereditary CRC syndromes and certain patient groups with a diagnosis of inflammatory bowel disease (IBD) or multiple polyps) and individuals with active IBD participate in CRC screening following invitation. MATERIALS AND METHODS: We used data from the first two years of the Danish CRC screening programme (2014-2015). Information on invitations, participations and FIT test results were obtained from the national screening database, while information on previous CRC, hereditary CRC syndromes, IBD or multiple polyps diagnoses were obtained from the Danish Cancer Registry and the Danish Patient Register. Screening participation rates and FIT-positive rates were calculated and compared for high-risk invitees, invitees having IBD and an average risk group of remaining invitees not diagnosed with colorectal polyps in 10 years preceding the invitation. RESULTS: When invited to CRC screening, 28-48% of high-risk residents (N: 29; 316; 5584) and 55% of residents with IBD (N: 2217; 6927) chose to participate. The participation rate was significantly higher (67%) among residents without previous colorectal disease, i.e. the average risk group (N = 585,624). In this average group 6.7% of the participants had a positive FIT test. The proportion of positive FIT results was higher among all disease groups (7.7-14.8%), though not statistically significant for participants with prior CRC diagnosis and participants with high-risk IBD. CONCLUSION: When high-risk residents and residents with IBD receive an invitation to CRC screening, many participate despite being recommended not to. The screening program was not intended for these groups and further research is needed as several of these groups have a higher rate of positive screening result than the average risk population.

The Impact of Risk Factor Control on Health-Related Quality of Life in Individuals with High Cardiovascular Disease Risk: A Cross-sectional Study Based on EQ-5D Utility Scores in Inner Mongolia, China.

OBJECTIVES: To assess the impact of cardiovascular disease (CVD) risk factor control on health-related quality of life (HRQoL), as well as the other influencing factors of HRQoL among high CVD risk individuals. METHODS: From 2015 to 2017, residents of six villages or communities in Inner Mongolia, selected using a multi-stage stratified cluster random sampling method, were invited to complete a questionnaire and undergo physical examination and laboratory testing. We selected participants whose predicted 10-year risk for CVD exceeded 10% as those with high CVD risk. HRQoL in individuals with high CVD risk was investigated based on the EuroQol-5 Dimension (EQ-5D) scale. The Chinese utility value integral system was used to calculate EQ-5D utility scores, and the Tobit regression model was used to analyze the influencing factors of HRQoL among individuals with high CVD risk. RESULTS: Of 13,359 participants with high CVD risk, 65.63% reported no problems in any of the five dimensions; the most frequently reported difficulty was pain/discomfort. The median utility score was 1.000 (0.869, 1.000). Participants with hypertension, and uncontrolled glycemic and blood lipids had lower HRQoL. In addition, sex, age, living environment, education level, household income, and medical insurance were influencing factors of HRQoL. CONCLUSION: Sex, age, living environment, education level, household income, medical insurance, hypertension, and whether glycemic and blood lipids control or not are related to HRQoL of high CVD risk individuals.

Familial pancreatic cancer: who should be considered for genetic testing?

BACKGROUND: Determining how many female patients who underwent breast imaging meet the eligibility criteria for genetic testing for familial pancreatic cancer (FPC). METHODS: A total of 42,904 patients seen at the Newton-Wellesley Hospital between 2007 and 2009 were retrospectively reviewed. The first four categories were based on pancreatic cancer-associated syndromes: (1) hereditary breast and ovarian cancer (HBOC), (2) Lynch syndrome (LS), (3) familial atypical multiple mole melanoma (FAMMM), and (4) family history of FPC (FH-FPC). PancPRO (5) and MelaPRO (6) categories were based on risk scores from Mendelian risk prediction tool. RESULTS: Exactly 4445 of 42,904 patients were found to be in at least one of the six risk categories. About 5.7% of patients were classified as being at high risk for HBOC, 2.3% as being at high risk for LS, 0.1% as being at high risk for FAMMM, 0.1% as being at high risk for FH-FPC, 2.7% as being at high risk based on PancPRO, and 0.2% as being at high risk based on MelaPRO. CONCLUSION: About 10.4% of the female patients were classified as being at high risk for FPC. This finding emphasizes the importance of applying criteria to the general population, in order to ensure that individuals with high risk are identified early.

Chinese Consensus for Pancreatic Cancer Screening and Surveillance in High ⁃ risk Individuals (2021, Nanjing) / 胃肠病学

Pancreatic cancer is highly malignant with low 5‑year survival rate because it is hard to be diagnosed in early stage. So far, a standardized screening strategy of early pancreatic cancer has not been achieved in China. Based on updated research evidence, a total of 26 recommendations are proposed for screening aims, high ‑ risk individuals, initial screening age, follow ‑ up interval, monitoring methods and timing of operation. Chinese consensus for early pancreatic cancer screening and surveillance is finally formulated.

Prevalence and treatment of high cardiovascular disease risk in Inner Mongolia, China.

Early identification of individuals with high risk is crucial to preventing cardiovascular disease (CVD). We aimed to determine the prevalence of high CVD risk in Inner Mongolia and to analyze the treatment of major risk factors among individuals with high CVD risk. We selected 70,380 participants aged 35-75 years in Inner Mongolia between 2015 and 2017 using multistage stratified sampling. All participants completed a questionnaire and their blood pressure, blood glucose and lipid levels, height, weight and waist circumference were measured. Participants without a history of CVD were defined as high CVD risk if the predicted 10-year risk for CVD exceeded 10%. We assessed rates of high CVD risk and the prevalence and treatment of major risk factors among individuals with high CVD risk. After excluding participants with previous CVD, 68,083 participants remained. The overall prevalence of high CVD risk was 24.96%. The age- and sex-standardized rate of high CVD risk was 22.92%. Among high-risk participants, the prevalence of risk factors was hypertension (91.9%), dyslipidemia (54.1%), obesity (34.6%), diabetes (27.6%), and smoking (24.5%); clustering of these risk factors was common. The percentage of high-risk individuals taking antihypertensive drugs was 45.94% in those with hypertension; 27.99% of those with diabetes took hypoglycemic drugs and only 5.01% of those with dyslipidemia took lipid-lowering drugs. Control rates of hypertension, diabetes, and dyslipidemia were 1.20%, 4.43%, and 2.78%, respectively. Therefore, the prevalence of high CVD risk was elevated in Inner Mongolia, and treatment and control rates were low.

Guidelines on management of pancreatic cysts detected in high-risk individuals: An evaluation of the 2017 Fukuoka guidelines and the 2020 International Cancer of the Pancreas Screening (CAPS) consortium statements.

BACKGROUND: Objectives: Pancreatic cysts are frequently detected in high-risk individuals (HRI) undergoing surveillance for pancreatic cancer. The International Cancer of the Pancreas Screening (CAPS) Consortium developed consensus recommendations for surgical resection of pancreatic cysts in HRI that are similar to the Fukuoka guidelines used for the management of sporadic cysts. We compared the performance characteristics of CAPS criteria for pancreatic cyst management in HRI with the Fukuoka guidelines originally designed for the management of cysts in non-HRI. METHODS: Using prospectively collected data from CAPS studies, we determined for each patient with resected screen-detected cyst(s) whether Fukuoka guidelines or CAPS consensus statements would have recommended surgery. We compared sensitivity, specificity, PPV, NPV, and Receiver Operator Characteristics (ROC) curves of these guidelines at predicting the presence of high-grade dysplasia or invasive cancer in pancreatic cysts. RESULTS: 356/732 HRI had ≥ one pancreatic cyst detected; 24 had surgery for concerning cystic lesions. The sensitivity, specificity, PPV, and NPV for the Fukuoka criteria were 40%, 85%, 40%, and 85%, while those of the CAPS criteria were 60%, 85%, 50%, 89%, respectively. ROC curve analyses showed no significant difference between the Fukuoka and CAPS criteria. CONCLUSIONS: In HRI, the CAPS and Fukuoka criteria are moderately specific, but not sufficiently sensitive for detecting advanced neoplasia in cystic lesions. New approaches are needed to guide the surgical management of cystic lesions in HRI.

Impaired Sensorimotor Gating Using the Acoustic Prepulse Inhibition Paradigm in Individuals at a Clinical High Risk for Psychosis.

Many robust studies have investigated prepulse inhibition (PPI) in patients with schizophrenia. Recent evidence indicates that PPI may help identify individuals who are at clinical high risk for psychosis (CHR). Selective attention to prepulse stimulus can specifically enhance PPI in healthy subjects; however, this enhancement effect is not observed in patients with schizophrenia. Modified PPI measurement with selective attentional modulation using perceived spatial separation (PSS) condition may be a more robust and sensitive index of PPI impairment in CHR individuals. The current study investigated an improved PSSPPI condition in CHR individuals compared with patients with first-episode schizophrenia (FES) and healthy controls (HC) and evaluated the accuracy of PPI in predicting CHR from HC. We included 53 FESs, 55 CHR individuals, and 53 HCs. CHRs were rated on the Structured Interview for Prodromal Syndromes. The measures of perceived spatial co-location PPI (PSCPPI) and PSSPPI conditions were applied using 60- and 120-ms lead intervals. Compared with HC, the CHR group had lower PSSPPI level (Inter-stimulus interval [ISI] = 60 ms, P < .001; ISI = 120 ms, P < .001). PSSPPI showed an effect size (ES) between CHR and HC (ISI = 60 ms, Cohen's d = 0.91; ISI = 120 ms, Cohen's d = 0.98); on PSSPPI using 60-ms lead interval, ES grade increased from CHR to FES. The area under the receiver operating characteristic curve for PSSPPI was greater than that for PSCPPI. CHR individuals showed a PSSPPI deficit similar to FES, with greater ES and sensitivity. PSSPPI appears a promising objective approach for preliminary identification of CHR individuals.

Italian registry of families at risk of pancreatic cancer: AISP Familial Pancreatic Cancer Study Group.

Pancreatic cancer is one of the main causes of cancer-related death worldwide, with a survival rate around 9%. In Italy 13,500 new cases of pancreatic cancer occurred in 2019. It is estimated that at least 5% have a hereditary background. Surveillance is advisable for healthy individuals with specific genetic syndromes with or without family history of pancreatic cancer or members of families with multiple cases of pancreatic cancer, irrespective of genetic syndromes. In 2010 the Italian Association for the Study of the Pancreas (AISP) defined criteria to include individuals in such surveillance programs with the first-round results published in 2019. In order to include other categories at high-risk and increase the diagnostic yield of surveillance, these criteria have recently been modified. The present position paper presents the updated criteria of the Italian Registry of Families at Risk of Pancreatic Cancer (IRFARPC) with their diagnostic yield calculation. Also, AISP priority projects concerning: (a) increasing awareness of citizens and primary care physicians through a dedicated App; (b) increasing access to germline testing to personalize surveillance; (c) measuring psychological impact of surveillance; (d) investigating the role of risk-modifiers and (e) evaluating the cost-effectiveness and ability to save lives of the program are briefly presented.

Altered structural connectivity and cytokine levels in Schizophrenia and Genetic high-risk individuals: Associations with disease states and vulnerability.

BACKGROUND: Alterations of white matter (WM) integrity have been observed in both schizophrenia (SZ) and individuals at genetic high risk for SZ (GHR-SZ); however, the molecular mechanisms underlying WM disruption remain unclear. Cytokines are chemical messengers of the immune system that are closely related to inflammation and neurogenesis in the brain. This study aimed to identify abnormalities in WM integrity, cytokine levels, and their association in SZ and GHR-SZ. METHODS: A total of 355 participants (126 with SZ, 99 GHR-SZ, and 130 healthy controls [HCs]) were recruited. All participants underwent diffusion tensor imaging and blood samples were obtained from 113 participants within 24 h of imaging. RESULTS: In SZ, there was decreased fractional anisotropy(FA) in the genu and body of the corpus callosum (GCC/BCC), anterior corona radiata, anterior and posterior limbs of the internal capsule (ALIC/PLIC), superior fronto-occipital fasciculus, external capsule, and fornix, and elevated IL-6 levels. In both SZ and GHR-SZ, decreased FA in the splenium of the corpus callosum (SCC), posterior corona radiate (PCR), and posterior thalamic radiation (PTR) was observed, and elevated leptin levels were present. Additionally, the IL-6 levels were negatively correlated with FA in the GCC and ALIC in SZ, and leptin levels were negatively correlated with the SCC, PCR, and PTR in SZ and GHR-SZ. CONCLUSIONS: Abnormal WM integrity in SZ may reflect the state of disease and is associated with increased IL-6 levels. In addition, these leptin-associated WM integrity abnormalities in both SZ and GHR-SZ may reflect a genetic vulnerability to SZ.

Use of the Whole Child Assessment to identify children at risk of poor outcomes.

BACKGROUND: Screening for Adverse Childhood Experiences (ACEs) in pediatric patients has the potential to prevent poor health outcomes associated with ACEs. Only a limited number of tools screen for all ten ACEs in all pediatric age groups, and none of these have demonstrated robust validity to date. OBJECTIVE: In order to evaluate the validity of the Whole Child Assessment, we examined associations between poor outcomes in pediatric patients and responses to questions about exposure to and risk of ACEs. METHODS: This cross-sectional study used medical record data from 499 children ages 5-11 years old who received care at one of two university-affiliated clinics in California. All Child-ACE measures were included on the Whole Child Assessment, which caregivers completed when they brought their child to a well-child visit. Medical charts were reviewed for current diagnoses and problems, current or past history of any developmental delay, and health care utilization. RESULTS: Compared to lower risk patients (0-1 reported ACE exposure), patients with 2 or more reported exposures were statistically significantly more likely to experience sadness, anger, sleep problems, bullying, school problems, and enuresis. The directionality of effects and the number of statistically significant associations improved when adding questions about risk of ACEs to the total Child-ACE score. CONCLUSION: We found strong relationships between Child-ACEs reported on the Whole Child Assessment and odds of poor child health and psychosocial outcomes in pediatric patients age 5-11 years old, which supports the validity of using the Whole Child Assessment at well-child visits.