Gut microbiome shifts in people with type 1 diabetes are associated with glycaemic control: an INNODIA study.

AIMS/HYPOTHESIS: The gut microbiome is implicated in the disease process leading to clinical type 1 diabetes, but less is known about potential changes in the gut microbiome after the diagnosis of type 1 diabetes and implications in glucose homeostasis. We aimed to analyse potential associations between the gut microbiome composition and clinical and laboratory data during a 2 year follow-up of people with newly diagnosed type 1 diabetes, recruited to the Innovative approaches to understanding and arresting type 1 diabetes (INNODIA) study. In addition, we analysed the microbiome composition in initially unaffected family members, who progressed to clinical type 1 diabetes during or after their follow-up for 4 years. METHODS: We characterised the gut microbiome composition of 98 individuals with newly diagnosed type 1 diabetes (ND cohort) and 194 autoantibody-positive unaffected family members (UFM cohort), representing a subgroup of the INNODIA Natural History Study, using metagenomic sequencing. Participants from the ND cohort attended study visits within 6 weeks from the diagnosis and 3, 6, 12 and 24 months later for stool sample collection and laboratory tests (HbA1c, C-peptide, diabetes-associated autoantibodies). Participants from the UFM cohort were assessed at baseline and 6, 12, 18, 24 and 36 months later. RESULTS: We observed a longitudinal increase in 21 bacterial species in the ND cohort but not in the UFM cohort. The relative abundance of Faecalibacterium prausnitzii was inversely associated with the HbA1c levels at diagnosis (p=0.0019). The rate of the subsequent disease progression in the ND cohort, as assessed by change in HbA1c, C-peptide levels and insulin dose, was associated with the abundance of several bacterial species. Individuals with rapid decrease in C-peptide levels in the ND cohort had the lowest gut microbiome diversity. Nineteen individuals who were diagnosed with type 1 diabetes in the UFM cohort had increased abundance of Sutterella sp. KLE1602 compared with the undiagnosed UFM individuals (p=1.2 × 10-4). CONCLUSIONS/INTERPRETATION: Our data revealed associations between the gut microbiome composition and the disease progression in individuals with recent-onset type 1 diabetes. Future mechanistic studies as well as animal studies and human trials are needed to further validate the significance and causality of these associations.

Genitourinary cancer and family: The reverberating psychological and cardiovascular effects of a genitourinary cancer diagnosis on first-degree relatives and spouses.

BACKGROUND: The psychological and cardiovascular health impacts on family members of patients who have been diagnosed with cancer have not been well characterized. The purpose of this study is to determine whether a family member's cancer diagnosis influences the risk of psychological illness and cardiovascular disease in first-degree relatives and spouses of patients affected by cancer. METHODS: This retrospective cohort analysis evaluated the risk of psychological illness and cardiovascular disease in first-degree relatives and spouses of patients diagnosed with a genitourinary cancer between 1990 and 2015 compared to relatives of those not diagnosed with a genitourinary cancer. The Utah Population Database was used and familial linkage was determined. Follow-up included 1-, 3-, and 5-year intervals. Patients residing outside of Utah and first-degree relatives and spouses with psychological or cardiovascular disease diagnosed before a family member's cancer diagnosis were excluded. RESULTS: A total of 49,284 patients with a genitourinary cancer were identified with 77,938 first-degree relatives and spouses. A matched control group included 246,775 patients with 81,022 first-degree relatives and spouses. Via Cox proportional hazards models, a 10% increased risk of developing a psychological illness (hazard ratio [HR], 1.10; 95% CI, 1.00-1.20) and a 28% increased risk of developing cardiovascular disease (HR, 1.28; 95% CI, 1.17-1.41) at 1 year after a family member's cancer diagnosis were found. CONCLUSIONS: This study provides population-level evidence to support the hypothesis that cancer diagnoses will lead to adverse health outcomes for family members of patients with cancer. Increased clinical attention and support are needed to reduce the harm to families caused by cancer.

The frequency of colorectal lesions in the first-degree relatives of patients with colorectal lesions among PERSIAN Guilan Cohort Study population (PGCS).

BACKGROUND: This study aimed to investigate the frequency of colorectal lesions in the first-degree relatives of patients with colorectal lesions among the Prospective Epidemiological Research Studies in Iran (PERSIAN )Guilan Cohort Study (PGCS) population. METHODS: In this cross-sectional study, 162 first-degree relatives with a history of colorectal lesions were randomly selected from 52 participants in PGCS. All subjects underwent total colonoscopy by a gastroenterologist, and a pathologist evaluated colorectal biopsies. Also, individuals' demographic information, clinical data, and dietary habits were recorded. RESULTS: The mean age of the participants was 56.55 ± 7.04. Of 86 colon polyps, 52 neoplastic and 34 non-neoplastic polyps were observed in 56 patients (34.6%). Individuals with age > 60 years had 3.29-fold increased odds of developing colorectal polyps (OR = 3.29, 95% CI: 1.13-9.56, P = 0.029). The smokers were 2.73 times more susceptible to developing colorectal polyps than non-smokers (OR = 2.73, 95% CI: 1.24-6.02, P = 0.013). Moreover, consumption of vegetables more than three times per day was associated with decreased OR of colorectal polyp development (OR = 0.43, CI: 0.19-0.98, P = 0.045). CONCLUSIONS: Considering the high prevalence of neoplastic colorectal polyps among the first-degree relatives of patients with colorectal lesions, early screening is recommended for individuals with a family history of colorectal lesions.

Gyrification of the medial and lateral orbitofrontal cortex in first-degree relatives of patients with obsessive-compulsive disorder.

Gyrification patterns reflect early neurodevelopment and could be highly heritable. While some discrepant results have been reported, the most consistent finding was that patients with obsessive-compulsive disorder showed altered gyrification patterns in the orbitofrontal cortex. Nevertheless, no study has investigated the alterations in gyrification in unaffected first-degree relatives of patients with obsessive-compulsive disorder. We measured local gyrification by the FreeSurfer software in 23 unaffected first-degree relatives of patients with obsessive-compulsive disorder and 52 healthy control participants. We explored differences in the local gyrification index using vertex-wise whole-brain analysis and a region of interest-based approach in the medial and lateral orbitofrontal cortex. There was no significant difference in the local gyrification index between the 2 groups in the vertex-wise whole-brain analysis. Region of interest analyses showed that, compared with healthy controls, first-degree relatives showed significantly reduced local gyrification index in the left medial and lateral orbitofrontal cortex. A negative correlation was observed between the reduced local gyrification index in lateral orbitofrontal cortex and the subclinical anxiety scores of first-degree relatives. Our results showed that first-degree relatives of patients with obsessive-compulsive disorder had an altered local gyrification index in the orbitofrontal cortex. Especially, reduced local gyrification index in lateral orbitofrontal cortex associated with subclinical anxiety symptom could be a potential neurodevelopmental marker for the illness onset.

Functional connectivity between pre-supplementary motor area and inferior parietal lobule associated with impaired motor response inhibition in first-degree relatives of patients with obsessive-compulsive disorder.

Previous studies have suggested that specific fronto-striatal circuits are associated with impaired motor response inhibition in patients with obsessive-compulsive disorder (OCD) and their relatives. However, no study has investigated the underlying resting-state network associated with motor response inhibition in the unaffected first-degree relatives of patients with OCD. We measured motor response inhibition using stop-signal task, and obtained resting-state fMRI in 23 first-degree relatives and 52 healthy control participants. We explored the group differences in the functional network from seed regions-of-interest (ROIs) associated with motor response inhibition abilities. We used the inferior frontal gyrus (IFG) and pre-supplementary motor area (pre-SMA) as seed-ROIs. A significant group difference was observed in functional connectivity between the pre-SMA and inferior parietal lobule. In the relative group, reduced functional connectivity between these areas was associated with a longer stop-signal reaction time. Additionally, relatives showed significantly greater functional connectivity between the IFG and SMA, precentral, and postcentral areas. Our results could provide new insights into the resting-state neural activity of the pre-SMA underlying impaired motor response inhibition of unaffected first-degree relatives. In addition, our results suggested that relatives have an altered connectivity of the sensorimotor region, similar to that of patients with OCD shown in previous literature.

Osteopontin, osteoprotegerin and musculoskeletal ultrasound findings in first-degree relatives of rheumatoid arthritis: potential markers of preclinical disease.

BACKGROUND: First-degree relatives (FDRs) of rheumatoid arthritis (RA) patients are known to have increased risk of developing the disease. The detection of altered bone metabolism in FDRs could be a predictor of the disease. Musculoskeletal ultrasound (MSUS) is known for its ability to detect subclinical joint inflammation in RA, but changes in FDRs are not yet described. We aimed to study serum Osteopontin (OPN) and Osteoprotegerin (OPG) levels in FDRs of RA patients as markers of altered bone metabolism in relation to clinical, laboratory and musculoskeletal ultrasound (MSUS) findings. METHODS: Fifty-five individuals were included, 20 had definite RA, 25 were first degree relatives (FDRs) of RA patients, and 10 healthy controls. Clinical evaluation for joint swelling/tenderness was performed for all. ESR, CRP, rheumatoid factor (RF), anti-citrullinated antibodies (ACPA), OPN, OPG, and Musculoskeletal ultrasound (MSUS) by the US7 score were evaluated. RESULTS: Osteoprotegerin was significantly higher in RA (143.89 pg/ml ± 365.47) than in FDRs (22.23 pg/ml ± 65.73; p = 0.009) and controls (6.20 pg/ml ± 12.43; p = 0.003). OPN was also higher in RA (3.66 ng/ml ± 4.20) than in FDRs (1.97 ng/ml ± 1.04) and controls (2.81 ng/ml ± 1.31), though not significant (p = 0.102). Eight of 25 FDRs (32%) had arthralgia without clinical arthritis and 17/25 (68%) were asymptomatic. FDRs with arthralgia had significantly higher ESR and CRP levels than asymptomatic FDRs (9.82 mm/h ± 4.13; p = 0.003, and 3.93 mg/l ± 3.58; p = 0.003). Osteoprotegerin was higher in FDRs than in controls, and also in those with arthralgia (51.55 pg/ml ± 114.68) than in those without (8.44 pg/ml ± 9.67), though without significant difference. OPN was higher in FDRs with arthralgia (2.09 ng/ml ± 1.19) than in asymptomatic (1.70 ng/ml ± 0.55), also without significant difference. Pathologic findings by US7 were detected in 10/25 (40%) FDRs, of which three (12%) had arthralgia and seven (28%) were asymptomatic. CONCLUSIONS: The raised OPG and lower OPN in FDRs than in controls reflect an altered bone metabolism which could precede clinical disease phase. OPN and OPG could serve as markers of altered preclinical bone metabolism in FDRs of RA. US7 score might be a useful screening tool to identify 'at-risk' individuals.

Family screening for bicuspid aortic valve and aortic dilatation: a meta-analysis.

AIMS: International guidelines recommend screening of first-degree relatives (FDR) of people with bicuspid aortic valves (BAVs). However, the prevalence of BAV and of aortic dilatation amongst family members is uncertain. METHODS AND RESULTS: A systematic review and meta-analysis of original reports of screening for BAV. Databases including MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to December 2021 using relevant search terms. Data were sought on the screened prevalence of BAV and aortic dilatation. The protocol was specified prior to the searches being performed, and standard meta-analytic techniques were used. Twenty-three observational studies met inclusion criteria (n = 2297 index cases; n = 6054 screened relatives). The prevalence of BAV amongst relatives was 7.3% [95% confidence interval (CI) 6.1%-8.6%] overall and per family was 23.6% (95% CI 18.1%-29.5%). The prevalence of aortic dilatation amongst relatives was 9.4% (95% CI 5.7%-13.9%). Whilst the prevalence of aortic dilatation was particularly high in relatives with BAV (29.2%; 95% CI 15.3%-45.1%), aortic dilatation alongside tricuspid aortic valves was a more frequent finding, as there were many more family members with tricuspid valves than BAV. The prevalence estimate amongst relatives with tricuspid valves (7.0%; 95% CI 3.2%-12.0%) was higher than reported in the general population. CONCLUSION: Screening family members of people with BAV can identify a cohort substantially enriched for the presence of bicuspid valve, aortic enlargement, or both. The implications for screening programmes are discussed, including in particular the substantial current uncertainties regarding the clinical implications of aortic findings.

Effects of interventions on the screening behavior in female first-degree relatives of breast cancer patients: A systematic review.

BACKGROUND: Women are more likely to develop breast cancer if their first-degree relatives (FDRs) have the disease, but they are often unaware of their individual risk and conduct screening behaviors. OBJECTIVE: This study aimed to evaluate the effectiveness of interventions in increasing breast self-examination, clinical breast examination, and mammography rates in FDRs of breast cancer patients. METHODS: We selected randomized clinical trials and quasi-experimental studies in eight databases. Interventions in each study were categorized as "promising", or "non-promising" according to whether they led to a positive change in screening behaviors. Interventions were also coded using the Behavioral Change Techniques (BCTs) Taxonomy and a promise ratio calculated for each. BCTs with a promise ratio ≥2 was classified as "promising". RESULTS: Thirteen studies with 21 different BCTs were included. The most frequent BCTs were "Prompts/cues", "Credible source", and "Instructions on how to perform the behavior". Seven BCTs had a promise ratio of ≥2 and the four most promising were "Information about health consequences" (promise ratio = 6), "Problem solving" (promise ratio = 4), "Demonstration of the behavior" (promise ratio = 4), and "Adding objects to the environment" (promise ratio = 4). CONCLUSIONS: This review indicated an overall weak use of theory, and an insufficient description of several interventions to support the assessment of how specific BCTs were activated.

Association of inflammatory bowel disease in first-degree relatives with risk of colorectal cancer: A nationwide case-control study in Sweden.

This study aims to assess the association between inflammatory bowel disease (IBD) history in first-degree relatives (FDRs) and colorectal cancer (CRC) risk. We conducted a nationwide case-control study in Sweden among 69 659 CRC cases and 343 032 non-CRC controls matched on age, sex, birth year and residence county. Through linkage of multi-generation register and the nationwide ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, we ascertained IBD diagnoses among parents, full siblings and offspring of the index individuals. Odds ratios (ORs) of CRC associated with IBD family history were calculated using conditional logistic regression. 2.2% of both CRC cases (1566/69659) and controls (7676/343027) had ≥1 FDR with IBD history. After adjusting for family history of CRC, we observed no increased risk of CRC in FDRs of IBD patients (OR, 0.96; 95%CI, 0.91-1.02). The null association was consistent according to IBD subtype (Crohn's disease or ulcerative colitis), number of FDRs with IBD (1 or ≥ 2), age at first IBD diagnosis in FDRs (<18, 18-39, 40-59 or ≥60 years), maximum location/extent of IBD or FDR relation (parent, sibling or offspring). The null association remained for early-onset CRC (diagnosed at age <50 years). In conclusion, IBD history in FDRs was not associated with an increased risk of CRC. Our findings suggest that extra screening for CRC may not be needed in the offspring, siblings or parents of IBD patients, and strengthen the theory that it is the actual inflammation or atypia of the colon in IBD patients that confers the increased CRC risk.

Familial coaggregation of MASLD with hepatocellular carcinoma and adverse liver outcomes: Nationwide multigenerational cohort study.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD) is the fastest growing cause of hepatocellular carcinoma (HCC) worldwide. However, whether family members of individuals with MASLD also share an increased risk of developing HCC is unknown. METHODS: This nationwide multigenerational cohort study involved family members of all Swedish adults diagnosed with biopsy-proven MASLD (1969-2017), and matched general population comparators. Using the Swedish Multi-generation Register, we identified 38,018 first-degree relatives (FDRs: parents, siblings, offspring) and 9,381 spouses of patients with MASLD, as well as 197,303 comparator FDRs and 47,572 comparator spouses. We used Cox proportional hazards models to calculate adjusted hazard ratios (aHRs) for HCC, major adverse liver outcomes (cirrhosis, decompensated liver disease or liver transplantation), liver-related mortality, extrahepatic cancer, and non-liver-related mortality. RESULTS: Over a median of 17.6 years, the rate of the primary outcome HCC was higher in MASLD FDRs vs. comparator FDRs (13 vs. 8/100,000 person-years [PY]; aHR 1.80, 95% CI 1.36-2.37). The HCC risk was further increased in FDRs of individuals with liver fibrosis/cirrhosis (aHR 2.14, 95% CI 1.07-4.27; PHeterogeneity = 0.03). MASLD FDRs also had higher rates of major adverse liver outcomes (73 vs. 51/100,000 PY; aHR 1.52, 95% CI 1.36-1.69) and liver-related mortality (20 vs. 11/100,000 PY; aHR 2.14, 95% CI 1.67-2.74). MASLD FDRs with any concomitant chronic liver condition experienced accelerated progression of liver disease (aHR 1.47, 95% CI 1.29-1.67). MASLD spouses were at higher risks of major adverse liver outcomes (86 vs. 74/100,000 PY; aHR 1.23, 95% CI 1.01-1.51) and liver-related mortality (25 vs. 19/100,000 PY; aHR 1.93, 95% CI 1.15-3.23), but not of HCC (aHR 1.43, 95% CI 0.87-2.35). CONCLUSIONS: There is distinct familial clustering of adverse liver-related outcomes in families of individuals with biopsy-proven MASLD, with higher relative risks of HCC, progressive liver disease, and liver-related mortality, but absolute risks are low. IMPACT AND IMPLICATIONS: Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly termed NAFLD) clusters in families with high genetic susceptibility and shared environmental risk factors, but the risks of developing hepatocellular carcinoma and other major liver-related outcomes in family members of individuals with MASLD are largely unknown. This large nationwide multigenerational cohort study involving family members (first-degree relatives and spouses) of individuals with biopsy-proven MASLD and of matched general population comparators found slightly increased risks of hepatocellular carcinoma in first-degree relatives, and of developing cirrhosis and liver-related mortality in all family members of individuals with biopsy-proven MASLD. The findings of this study provide large-scale evidence to inform clinical practice guidelines for recommendations on the early identification of individuals at higher risk of liver-related morbidity and mortality.

A potential role for chlamydial infection in rheumatoid arthritis development.

OBJECTIVES: To assess the relationship between self-reported and serologic evidence of prior chlamydial infection, rheumatoid arthritis (RA)-related autoantibodies and risk of RA-development. METHODS: This is a nested study within a prospective Swiss-based cohort including all first-degree relatives of RA patients (RA-FDR) who answered a question on past chlamydial infections. Primary outcome was systemic autoimmunity associated with RA (RA-autoimmunity) defined as positivity for anti-citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF). Secondary outcomes were high levels of RA-autoimmunity, RA-associated symptoms and RA-autoimmunity, and subsequent seropositive RA diagnosis. We conducted a nested case-control analysis by measuring the serological status against Chlamydia trachomatis' major outer membrane protein. We replicated our analysis in an independent United States-based RA-FDR cohort. RESULTS: Among 1231 RA-FDRs, 168 (13.6%) developed RA-autoimmunity. Prevalence of self-reported chlamydial infection was significantly higher in individuals with RA-autoimmunity compared with controls (17.9% vs 9.8%, OR = 2.00, 95%CI: 1.27-3.09, p < 0.01). This association remained significant after adjustments (OR = 1.91, 95%CI: 1.20-2.95). Stronger effect sizes were observed in later stages of RA development. There was a similar trend between a positive C. trachomatis serology and high levels of RA-autoimmunity (OR = 3.05, 95% CI: 1.10-8.46, p= 0.032). In the replication cohort, there were significant associations between chlamydial infection and RF positivity and incident RA, but not anti-CCP positivity. CONCLUSIONS: Self-reported chlamydial infections are associated with elevated RA-autoimmunity in at risk individuals. The differing association of chlamydial infections and ACPA/RF between cohorts will need to be explored in future studies but is consistent with a role of mucosal origin of RA-related autoimmunity.

A meta-analysis on the uncinate fasciculus in depression.

Aberrant microstructure of the uncinate fasciculus (UNC), a white matter (WM) tract implicated in emotion regulation, has been hypothesized as a neurobiological mechanism of depression. However, studies testing this hypothesis have yielded inconsistent results. The present meta-analysis consolidates evidence from 44 studies comparing fractional anisotropy (FA) and radial diffusivity (RD), two metrics characterizing WM microstructure, of the UNC in individuals with depression (n = 5016) to healthy individuals (n = 18 425). We conduct meta-regressions to identify demographic and clinical characteristics that contribute to cross-study heterogeneity in UNC findings. UNC FA was reduced in individuals with depression compared to healthy individuals. UNC RD was comparable between individuals with depression and healthy individuals. Comorbid anxiety explained inter-study heterogeneity in UNC findings. Depression is associated with perturbations in UNC microstructure, specifically with respect to UNC FA and not UNC RD. The association between depression and UNC microstructure appears to be moderated by anxiety. Future work should unravel the cellular mechanisms contributing to aberrant UNC microstructure in depression; clarify the relationship between UNC microstructure, depression, and anxiety; and link UNC microstructure to psychological processes, such as emotion regulation.

Socio-economic functioning in patients with bipolar disorder and their unaffected siblings - results from a nation-wide population-based longitudinal study.

BACKGROUND: Few studies have reported real-life data on socio-economic functioning in patients with bipolar disorder and their unaffected first-degree relatives. METHODS: We used Danish nation-wide population-based longitudinal register linkage to investigate socio-economic functioning in 19 955 patients with bipolar disorder, their 13 923 siblings and 20 sex, age and calendar-matched control individuals from the general population. Follow-up was from 1995 to 2017. RESULTS: Patients with a diagnosis of bipolar disorder had lower odds of having achieved the highest educational level [OR 0.75 (95% confidence interval (CI) 0.73-0.77)], being employed [OR 0.16 (95% CI 0.159-0.168)], having achieved the 80% highest quartile of income [OR 0.33 (95% CI 0.32-0.35)], cohabitating [OR 0.44 (95% CI 0.43-0.46)] and being married [OR 0.54 (95% CI 0.52-0.55)] at first contact to hospital psychiatry as inpatient or outpatient compared with control individuals from the general population. Similarly, siblings to patients with bipolar disorder had a lower functioning within all five socio-economic areas than control individuals. Furthermore, patients and partly siblings showed substantially decreased ability to enhance their socio-economic functioning during the 23 years follow-up compared to controls. CONCLUSIONS: Socio-economic functioning is substantially decreased in patients with bipolar disorder and their siblings and does not improve during long-term follow-up after the initial hospital contact, highlighting a severe and overlooked treatment gap.

Familial clustering of nonalcoholic fatty liver disease in first-degree relatives of adults with lean nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: The heritability of nonalcoholic fatty liver disease (NAFLD) in lean individuals is undetermined. This familial aggregation study aimed to evaluate familial linkage for NAFLD and the risk of NAFLD among first-degree relatives of probands with lean NAFLD. METHODS: This study prospectively recruited cohorts of probands with lean NAFLD, probands with obese NAFLD, and lean probands with non-NAFLD and their respective first-degree relatives. A total of 257 participants were evaluated for liver steatosis, defined by the controlled attenuation parameter ≥288 dB/m2 , metabolic characteristics, and the PNPLA3, TM6SF2, and MBOAT7 polymorphisms. RESULTS: The prevalence of NAFLD in first-degree relatives of lean NAFLD probands (39.9%) was similar to that in the obese NAFLD group (36.9%) and was significantly higher than in lean persons without NAFLD (19.1%). First-degree relatives of probands with NAFLD who were male, and had central obesity, hypertriglyceridaemia, insulin resistance, and the PNPLA3 rs738409C>G allele had a significantly higher prevalence of NAFLD. After multivariable adjustment for gender, metabolic characteristics, and the PNPLA3 rs738409C>G allele, first-degree relatives of probands with lean NAFLD (odds ratio [OR], 5.13; 95% CI, 1.77-14.86) and obese NAFLD (OR, 3.20; 95% CI, 1.14-8.99) exhibited an increased risk of NAFLD compared with those of lean controls without NAFLD. CONCLUSIONS: Our well-phenotype cohorts revealed familial clustering of NAFLD and higher risks of NAFLD in first-degree relatives of probands with lean or obese NAFLD. The findings encourage clinicians caring for NAFLD patients to be more vigilant for NAFLD in their family members.

Long-term risk of cancer among the first-degree relatives of epithelial ovarian cancer patients: A cohort study with 48 years of follow up.

INTRODUCTION: The long-term risk of cancer among first-degree relatives of ovarian cancer patients, especially their offspring, is of apparent clinical importance. Risks caused by known inherited factors such as BRCA1 or BRCA2 pathogenic variants are well established, but these account for only about 15% of ovarian cancer cases. Less is known about the possible familial risks of sporadic ovarian cancers. MATERIAL AND METHODS: Using registry data, we conducted a retrospective cohort study with a total of 6501 first-degree relatives of 559 epithelial ovarian cancer patients. We studied the occurrence of overall cancer and cancer in specific sites known or suspected to be associated with ovarian cancer (breast, cervix, colon, endometrium, lung and trachea, skin melanoma, ovary, pancreas, prostate, rectum, and stomach). RESULTS: The overall number of cancers was not increased among the first-degree relatives of epithelial ovarian cancer patients during the up to 48 years of follow up. Among female relatives, the standardized incidence ratio for ovarian cancer was 1.92 (95% CI 1.27-2.79), mostly explained by a 2.30-fold (95% CI 1.46-3.45) risk among the patients' sisters. There was a decreasing trend in the standardized incidence ratio for ovarian cancer among patients' sisters by increasing age of the index patient. CONCLUSIONS: In our study cohort, we did not observe an increase in the overall cancer risk among the first-degree relatives of epithelial ovarian cancer patients in comparison with the general population. The risk for ovarian cancer, however, was increased. Current recommendations suggest prophylactic removal of the fallopian tubes and ovaries only with identified inherited risk factors. Our results emphasize the role of genetic counseling and testing, particularly in young ovarian cancer patients and their close female relatives.

Olfactory identification ability among schizophrenia patients, their first-degree relatives and healthy subjects.

OBJECTIVE: Olfactory impairments, including identification, have been reported in patients with schizophrenia, while few studies have examined the olfactory function of unaffected first-degree relatives of patients with schizophrenia, and the sample sizes of first-degree relatives were relatively small. Here, we investigated olfactory identification ability among patients with schizophrenia, first-degree relatives and healthy controls (HCs) using relatively large sample sizes at a single institute. METHODS: To assess olfactory identification ability, the open essence odorant identification test was administered to 172 schizophrenia patients, 75 first-degree relatives and 158 healthy controls. Differences in olfactory identification and correlations between olfactory ability and clinical variables were examined among these participants. RESULTS: We found a significant difference in olfactory identification ability among the diagnostic groups (p = 7.65 × 10-16). Schizophrenia patients displayed lower olfactory identification ability than first-degree relatives (Cohen's d = -0.57, p = 3.13 × 10-6) and healthy controls (d = -1.00, p = 2.19 × 10-16). Furthermore, first-degree relatives had lower olfactory identification ability than healthy controls (d = -0.29, p = 0.039). Olfactory identification ability moderately and negatively correlated with the duration of illness (r = -0.41, p = 1.88 × 10-8) and negative symptoms (r = -0.28, p = 1.99 × 10-4) in schizophrenia patients, although the correlation with the duration of illness was affected by aging (r = -0.24). CONCLUSIONS: Our results demonstrated that schizophrenia patients have impaired olfactory identification ability compared with first-degree relatives and healthy controls, and the impaired olfactory identification ability of first-degree relatives was intermediate between those in schizophrenia patients and healthy controls. Olfactory identification ability was relatively independent of clinical variables. Therefore, olfactory identification ability might be an intermediate phenotype for schizophrenia.

Dimensional characteristics of persistent negative symptoms in schizophrenia and their relationships with schizotypy in first-degree relatives.

PURPOSE OF THE ARTICLE: Schizophrenia with persistent negative symptoms (PNS) may have different characteristics regarding negative symptom dimensions and heritability patterns. This study aimed to investigate the dimensional characteristics of PNS and their relationships with schizotypal features in first-degree relatives (FDRs). MATERIALS AND METHODS: The study included 142 patients, 142 FDRs, and 71 healthy controls (HC). Patients were evaluated with the Positive and Negative Symptom Scale (PANSS), Brief Negative Symptom Scale (BNSS), Calgary Depression Scale for Schizophrenia (CDSS), and Simpson-Angus Scale (SAS). Schizotypy Personality Questionnaire was applied to FDR and HC groups. Clinical symptoms were compared between primary-PNS, secondary-PNS, and non-PNS groups. In addition, schizotypy scores were compared between FDRs and HCs. Then, the relationship between the symptoms of the patients in the PNS group and the schizotypy scores of their relatives was evaluated by multiple regression analysis. RESULTS: All negative symptom dimension scores were similar in primary-PNS and secondary-PNS and lowest in non-PNS. PNS-FDR had higher in all schizotypy scores than non-PNS-FDR and HC, except for lack of close friends and social anxiety. In the PNS group, positive symptom severity and PANSS experiential deficit scores significantly predicted positive and negative schizotypy scores in relatives. Negative schizotypy was associated with asociality. CONCLUSIONS: The PNS is likely a subtype in which the genetic basis of negative symptoms is stronger and is associated with genetic abnormalities shared by positive and negative schizotypy dimensions in relatives. Family-based genetic studies will be beneficial in enlightening the genetic etiology of PNS.

The prevalence and risk factors of kidney disease in first degree relatives of patients with ESRD treatment - single center study.

OBJECTIVE: To determine the prevalence and risk factors of kidney disease in first degree relatives of patients undergoing treatment for end-stage renal disease. METHODS: The prospective, cross-sectional study was conducted at the Sindh Institute of Urology and Transplantation, Karachi, from May 1 to July 31, 2021, and comprised patients undergoing treatment for end-stage renal disease at the pre-transplant out-patients clinic, and their first degree relatives. Risk factors of chronic kidney disease, including age, gender, body mass index, hypertension, diabetes mellitus, and the causes of index cases were investigated alongside proteinuria, haematuria and estimated glomerular filtration rate. Diagnosis was made according to the criteria of the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative. The participants were divided chronic kidney disease group 1, and healthy group 2. The risk factors were compared between the groups. Data was analysed using SPSS 22. RESULTS: Of the 1,406 subjects assessed, 266(19%) were ESRD patients; 175(65.8%) males and 91(34.2%) females with mean age 34.04±11.19 years. 1,140(81%) first degree relatives of these 266 ESRD patient were assessed; 595(52.2%) males and 545(47.8%) females with mean age 36.78±13.76 years. Among the relatives, 146 (12.8%) had chronic kidney disease out of which 54 (4.7%) were already aware of their underlying disease. Older age, hypertension and diabetes mellitus were among the risk factors for chronic kidney disease (p<0.05), while gender was not significantly different between groups 1 and 2 (p>0.05). The relatives of index cases with underlying stone disease were at higher risk of haematuria 39(22.4%), whereas the relatives of index cases with chronic glomerulonephritis were at higher risk of proteinuria 67(28.03%) compared to index cases of other kinds (p<0.05). CONCLUSIONS: Screening in the high-risk population might help to identify early chronic kidney disease patients for making suitable interventions to prevent disease progression.

Factors affecting colonoscopy screening among first-degree relatives of colorectal cancer patients: A mixed-method systematic review.

BACKGROUND: First-degree relatives (FDRs) of colorectal cancer (CRC) patients have a higher risk of developing CRC than the general population. Ensuring that these at-risk populations receive colonoscopy screening is an effective strategy for reducing the increased risk, but the rates remain low. Colonoscopy screening behavior is influenced by factors at multiple levels. However, most previous reviews failed to review them and their interactions systematically. AIMS: To explore factors influencing FDRs' colonoscopy screening behavior according to the ecological model. METHOD: A mixed-method systematic review was performed in accordance with The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. A comprehensive literature search was conducted using eight bibliographic databases (Medline, EMBASE, PubMed, the Cochrane Library, Scopus, China National Knowledge Infrastructure, Wan Fang Data, and China Biology Medicine) for the period from January 1995 to February 2023. The Joanna Briggs Institute critical appraisal checklists were applied to assess studies qualities. A convergent integrated approach was used for data synthesis and integration. RESULTS: In total, 24 articles reporting on 23 studies were included. Only one study was rated low quality, and the other 22 studies were rated moderate to high quality. The findings revealed that certain factors and their interactions affected FDRs' colonoscopy screening behaviors according to the ecological model, including misconceptions about CRC and colonoscopy, concerns about the procedure, perceived susceptibility to developing CRC, health motivation, fear of CRC, fatalism, the recommendation from CRC patients, and recommendations from physicians, colonoscopy schedules, cancer taboo, health insurance and cost of colonoscopy. LINK EVIDENCE TO ACTION: Family communication-centered multilevel interventions are recommended to promote colonoscopy screening behavior among FDRs of CRC patients.

Breast Cancer Worry in U.S. Female First-degree Relatives: Moderating Role of Daily Spiritual Experiences.

Female first degree relatives of breast cancer patients experience worry because of their own increased breast cancer risk. The aim in the present study was to examine the role of daily spiritual experiences as a potential protective factor against breast cancer worry. We hypothesized that daily spiritual experiences would moderate the relationship between relatives' stage of disease and breast cancer worry. Sixty-three mothers, daughters or sisters of breast cancer survivors completed surveys assessing relative's disease characteristics and their own demographics, fear of breast cancer, and daily spiritual experiences. All participants were living in the midwestern United States. Results showed that daily spiritual experiences moderated the relationship between stage of disease and breast cancer worry. Low scores on daily spiritual experiences were associated with more worry when relatives had advanced disease, and high scores on daily spiritual experiences was associated with less worry when relatives had advanced disease. Findings suggest the need to focus on this population when providing support services to families of patients.