HLA investigation in ICI-induced T1D and isolated ACTH deficiency including meta-analysis.

OBJECTIVE: Widespread use of immune checkpoint inhibitors (ICIs) in cancer treatment has led to an increase in the number of reported cases of immunotherapy-related endocrinopathies. This study aimed to analyze and compare human leukocyte antigen (HLA) signatures associated with ICI-induced type 1 diabetes (ICI-T1D) and isolated adrenocorticotropic hormone deficiency (ICI-IAD) in patients with both conditions. METHODS: HLA signatures were examined for their frequencies of occurrence in 22 patients with ICI-T1D without concurrent IAD, including 16 patients from nationwide reports (ICI-T1D group) and 14 patients with ICI-IAD without concurrent T1D (ICI-IAD group). The HLA signatures were also compared for their respective frequencies in 11 patients with ICI-T1D and ICI-IAD, including eight from nationwide reports (ICI-T1D/IAD group). RESULTS: In the ICI-T1D group, HLA-DRB1*09:01-DQB1*03:03 and DQA1*03:02, which are in linkage disequilibrium with DRB1*09:01-DQB1*03:03 and DRB1*13:02-DQB1*06:04, were susceptible to ICI-T1D, whereas DRB1*15:02-DQB1*06:01 was protective against ICI-T1D. In the ICI-IAD group, DPB1*09:01, C*12:02-B*52:01, and DRB1*15:02-DRB1*06:01, which are in strong linkage disequilibrium, were associated with susceptibility to ICI-IAD. Moreover, DRB1*15:02-DRB1*06:01 was not detected in the ICI-T1D/IAD group. CONCLUSIONS: This study revealed specific HLA signatures associated with ICI-T1D and ICI-IAD. Moreover, HLA-DRB1*15:02-DRB1*06:01, an ICI-IAD-susceptible HLA haplotype, coincides with the ICI-T1D-protective HLA haplotype, suggesting that the presence of DRB1*15:02-DRB1*06:01 may protect against the co-occurrence of T1D in patients with ICI-IAD.

Impact of visitation restrictions on the mental health of family caregivers during the COVID-19 pandemic: A mixed methods study.

AIM: To examine the mental health conditions of family caregivers residing away from their loved ones who experienced visitation restrictions during the coronavirus disease 2019 pandemic. DESIGN: A mixed-methods design applying the Kessler Scale-10 for the quantitative measurement of psychological distress and an open-ended question for qualitative analysis. METHODS: The participants were recruited from care facilities between February and September 2021. This cross-sectional study included 197 family caregivers who were utilizing formal residential care services for their loved ones. Using thematic analyses, open-ended responses regarding the impact of visitation restrictions were coded. These themes were then examined to determine thematic patterns across caregiver characteristics. RESULTS: Thirteen themes were identified regarding the impact of visitation restrictions. Many participants reported primary harmful effects as follows: 'inability to confirm the type of care and lifestyle assistance provided to an older relative' and 'difficulty communicating with an older relative because of the inability to converse face-to-face'. Younger age, being employed, poor sleep, poor relationship quality with the care recipient and experiencing harmful effects from the visitation restrictions were associated with psychological distress. CONCLUSION: Our findings suggest that to maintain positive mental health after a care transition, it is important for family caregivers to take part in the care of their loved ones and ensure information sharing between the care recipient's family and institution. IMPACT: These findings suggest that both residents and family caregivers living outside facilities may feel distressed due to separation. Therefore, institutional care staff needs to consider how to adjust facility procedures or communication with family caregivers. PATIENT OR PUBLIC CONTRIBUTION: The comments obtained from the participants in this survey helped to shape the study design and are expected to contribute to the further development of quality facility care.

HLA analysis of immune checkpoint inhibitor-induced and idiopathic isolated ACTH deficiency.

PURPOSE: Isolated adrenocorticotropic hormone deficiency is a rare disease; however, since immune check point inhibitors (ICIs) have become widely used, many more cases have been reported. In this study, we compared the human leukocyte antigen (HLA) signatures between ICI-induced isolated adrenocorticotropic hormone deficiency (IAD) and idiopathic IAD (IIAD). DESIGN AND METHODS: Clinical features and HLA frequencies were compared among 13 patients with ICI-induced IAD, 8 patients with IIAD, and healthy controls. HLA frequencies of healthy controls were adopted from a HLA database of Japanese population. RESULTS: Age and body mass index were higher, while the rate of weight loss was lower, in patients with ICI-induced IAD than in those with IIAD. No HLA alleles had a significantly higher frequency in patients with ICI-induced IAD than in healthy controls, whereas the frequencies of HLA-DRB1*09:01, HLA-DQA1*03:02, and DQB1*03:03 were significantly higher in patients with IIAD than in healthy controls. CONCLUSIONS: ICI-induced IAD and IIAD were different in terms of HLA frequencies. There were no specific HLAs related to ICI-induced IAD, whereas several HLAs in strong linkage disequilibrium were associated with IIAD. This might suggest that the two diseases have different pathological mechanisms. HLAs unique to IIAD may be helpful in predicting its pathophysiology.

A survey of surgically resected pituitary incidentalomas and a comparison of the clinical features and surgical outcomes of non-functioning pituitary adenomas discovered incidentally versus symptomatically.

Pituitary tumors are discovered either incidentally by imaging studies (incidentalomas) or via evaluation of certain clinical symptoms (symptomatic tumors). In this study, we first surveyed patients with incidentalomas who underwent surgery. Cases included 62.3% non-functioning adenomas (NFPAs), 14.5% functioning adenomas, and 13.8% Rathke's cleft cysts. Next, we compared the clinical features and surgical outcomes of 145 patients whose preoperative diagnosis was NFPA (incidentalomas [n = 79] vs. symptomatic tumors [n = 66]). The patients with incidentalomas were older (59.9 vs. 55.3 years, p < 0.05) and had smaller tumors compared with the patients with symptomatic tumors (mean maximum diameter: 23.1 vs. 27.5 mm, p < 0.01). The main reason for undergoing imaging studies was headache (n = 25) in the incidentaloma group and visual disturbance (n = 46) in the symptomatic tumor group. The incidence of preoperative pituitary hormone deficiencies was lower in the incidentaloma than symptomatic tumor group (growth hormone deficiency: 37.7% vs. 66.7%, p < 0.01; gonadotropin deficiency: 19.0% vs. 39.4%, p < 0.01; adrenocorticotropic hormone deficiency: 3.8% vs. 18.2%, p < 0.01; thyroid stimulating hormone deficiency: 6.3% vs. 12.1%, p = 0.25). Postoperative pituitary function was better preserved in the incidentaloma than symptomatic tumor group (no deficiency: 58.2% vs. 28.8%, p < 0.01). The difference in postoperative complications between groups was not statistically significant (incidentalomas vs. symptomatic tumors: 21.5% vs. 19.7%, p = 0.84). In conclusion, incidentalomas were detected while smaller size and lower incidence of hormone deficiency than symptomatic tumors, and the pituitary hormones were also preserved after surgery. It is important to observe incidentalomas carefully and to judge whether to operate appropriately before they become symptomatic tumors.

Association between social support and place of delivery: a cross-sectional study in Kericho, Western Kenya.

BACKGROUND: An estimated 358,000 maternal deaths still occur worldwide each year. The place of delivery is of great significance to the reduction of maternal mortality. Moreover, socio-economic factors, cultural traits, and local customs are associated with health-seeking behavior. This study aimed to explore determinants of association between social support and place of delivery. METHODS: This cross-sectional study was conducted from September to November 2011 at Sosiot Health Center, Kericho West District, Kenya. Participants were 303 mothers who brought their babies to the health center for immunization within their first year of life. Women underwent a structured interview using a questionnaire on demographic characteristics and their experiences of delivery including place of delivery and social support. RESULTS: The proportion of deliveries at health facilities was significantly higher in unmarried than married women (93% and 78%, respectively; P = 0.008). Unmarried women whose mothers supported them in housework and whose sisters helped them fetch water were more likely to deliver at health facilities (P = 0.002 and 0.042, respectively) than those without this support. However, married women whose husbands supported them in farming and whose neighbors helped them fetch water were less likely to deliver at health facilities (P = 0.003 and 0.021, respectively) than those without this support. Married women who were advised to deliver at a health facility by their mother-in-law or health staff were more likely to deliver at health facilities (P = 0.015 and 0.022, respectively) than those who did not receive this advice. Multivariate analysis revealed that married women were more likely to deliver at health facilities if they were highly educated (odds ratio [OR] = 2.5); had financial capability (OR = 4.3); had medical insurance (OR = 4.2); were primiparous (OR = 3.5); did not have the support of sisters-in-law for fetching water (OR = 2.2); or were advised to deliver at a health facility by family or neighbors (OR = 2.5). CONCLUSIONS: Promotion of delivery at health facilities requires approaches that consider women's social situation, since factors influencing place of delivery differ for married and unmarried women.