Muslim Women and Disparities in Cancer Diagnosis: A Retrospective Study.

Muslim women often find their religious customs at odds with their healthcare needs, such as regular gynecological check-ups and cervical cancer screenings, especially before marriage. Religious beliefs may also affect beliefs about gender roles, illness, and death, affecting seeking healthcare services. This retrospective study explored the differences in care-seeking related to cancer between Muslim women and the general female population at the Virginia Commonwealth University in the United States between 2010 and 2019. There were major differences in insurance status between the two cohorts. Muslim women were less likely to have government-sponsored health insurance and were much more likely to be uninsured than non-Muslim women. We also found that preventable female cancers were more prevalent among Muslim women than among non-Muslim women and was also diagnosed at more advanced stages.

Liver disease and other comorbidities in Wolcott-Rallison syndrome: different phenotype and variable associations in a large cohort.

BACKGROUND: Wolcott-Rallison syndrome (WRS) is caused by recessive EIF2AK3 mutations and characterized by early-onset diabetes and skeletal dysplasia. Hepatic dysfunction has been reported in 60% of patients. AIMS: To describe a cohort of WRS patients and discuss the pattern and management of their liver disease. METHODS: Detailed phenotyping and direct sequencing of EIF2AK3 gene were conducted in all patients. RESULTS: Twenty-eight genetically confirmed patients (67% male; mean age 4.6 years) were identified. 17 different EIF2AK3 mutations were detected, of which 2 were novel. The p.S991N mutation was associated with prolonged survival and p.I650T with delayed onset. All patients presented before 25 months with diabetes with variation in the frequency and severity of 10 other features. Liver disease, first manifested as non-autoimmune hepatitis, was the commonest extra-pancreatic feature identified in 85.7% (24/28). 22/24 had at least one episode of acute hepatic failure which was the cause of death in all deceased patients (13/28). One child was treated by liver transplantation and had no liver disease and better diabetes control for the following 6 years. CONCLUSIONS: Liver disease in WRS is more frequent than previously described and carries high mortality. The first experience with liver transplantation in WRS is encouraging.

Differentiating the roles of STAT5B and STAT5A in human CD4+ T cells.

STAT5A and STAT5B are highly homologous proteins whose distinctive roles in human immunity remain unclear. However, STAT5A sufficiency cannot compensate for STAT5B defects, and human STAT5B deficiency, a rare autosomal recessive primary immunodeficiency, is characterized by chronic lung disease, growth failure and autoimmunity associated with regulatory T cell (Treg) reduction. We therefore hypothesized that STAT5A and STAT5B play unique roles in CD4(+) T cells. Upon knocking down STAT5A or STAT5B in human primary T cells, we found differentially regulated expression of FOXP3 and IL-2R in STAT5B knockdown T cells and down-regulated Bcl-X only in STAT5A knockdown T cells. Functional ex vivo studies in homozygous STAT5B-deficient patients showed reduced FOXP3 expression with impaired regulatory function of STAT5B-null Treg cells, also of increased memory phenotype. These results indicate that STAT5B and STAT5A act partly as non-redundant transcription factors and that STAT5B is more critical for Treg maintenance and function in humans.

Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy.

BACKGROUND & AIMS: Homozygous loss of function mutations in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) cause severe infantile (very early onset) inflammatory bowel disease (IBD). Allogeneic hematopoietic stem cell transplantation (HSCT) was reported to induce sustained remission in 1 patient with IL-10R deficiency. We investigated heterogeneity among patients with very early onset IBD, its mechanisms, and the use of allogeneic HSCT to treat this disorder. METHODS: We analyzed 66 patients with early onset IBD (younger than 5 years of age) for mutations in the genes encoding IL-10, IL-10R1, and IL-10R2. IL-10R deficiency was confirmed by functional assays on patients' peripheral blood mononuclear cells (immunoblot and enzyme-linked immunosorbent assay analyses). We assessed the therapeutic effects of standardized allogeneic HSCT. RESULTS: Using a candidate gene sequencing approach, we identified 16 patients with IL-10 or IL-10R deficiency: 3 patients had mutations in IL-10, 5 had mutations in IL-10R1, and 8 had mutations in IL-10R2. Refractory colitis became manifest in all patients within the first 3 months of life and was associated with perianal disease (16 of 16 patients). Extraintestinal symptoms included folliculitis (11 of 16) and arthritis (4 of 16). Allogeneic HSCT was performed in 5 patients and induced sustained clinical remission with a median follow-up time of 2 years. In vitro experiments confirmed reconstitution of IL-10R-mediated signaling in all patients who received the transplant. CONCLUSIONS: We identified loss of function mutations in IL-10 and IL-10R in patients with very early onset IBD. These findings indicate that infantile IBD patients with perianal disease should be screened for IL-10 and IL-10R deficiency and that allogeneic HSCT can induce remission in those with IL-10R deficiency.

Costello syndrome and hyperinsulinemic hypoglycemia.

Costello syndrome is characterized by mental retardation, loose skin, coarse facies, skeletal abnormalities, cardiovascular abnormalities (congenital heart defects, cardiomyopathy, rhythm disturbances), and predisposition to neoplasia. Endocrine abnormalities including growth hormone deficiency, adrenal insufficiency, glucose intolerance, parathyroid adenoma with hyperprolactinemia and hypoglycemia have been described. Hypoglycemia has been documented due to growth hormone and cortisol deficiency. We report on two patients with Costello syndrome and persistent hyperinsulinemic hypoglycemia and review the endocrine manifestations of Costello syndrome. Both patients required diazoxide therapy to stop the unregulated insulin secretion and maintain normoglycemia. The mechanism of persistent hyperinsulinism in patients with Costello syndrome is unclear.

Acute pyelonephritis and renal scarring in Kuwaiti children: a follow-up study using 99mTc DMSA renal scintigraphy.

The aim of this study was to determine the prevalence of renal scarring in a group of Kuwaiti Arab children with their first documented acute pyelonephritis (APN). Eighty-two Kuwaiti Arab children (10 males and 72 females) who had abnormal (99m)Tc DMSA renal scan findings of acute pyelonephritis were prospectively studied with the same imaging modality 6 months after treatment to identify those who developed renal scarring. A micturition cystourethrogram (MCUG) was performed for all of the children 1 month after diagnosis. Children were divided into 3 age groups (<2 years, 2-5 years and above 5 years). The follow-up DMSA renal scans 6 months after diagnosis revealed normalization of renal changes in 56% (46 patients), much improvement with residual renal abnormality in 6% (5 patients), and persistent parenchymal defects in 38% (31 patients). Vesicoureteric reflux (VUR) was found in 32% of children (26/82) and the majority were between grade I and III. Thirteen of those with VUR (50%) developed renal scars on follow-up. Fifty-three percent of the scarred kidneys (19/36) were drained by non-refluxing ureters. In this study, children older than 2 years had less VUR yet were more susceptible to APN and to the development of renal scars. Girls were more prone to developing APN and renal scarring than boys. This work shows that APN is a serious cause for renal scarring in our patients, particularly if associated with other risk factors such as recurrent infections and the female sex.

Vesicoureteric reflux in Kuwaiti children with first febrile urinary tract infection.

The prevalence of vesicoureteric reflux (VUR) in children with urinary tract infection (UTI) varies among different racial groups. The purpose of this study was to determine the frequency of VUR and associated renal changes in a group of Arab Kuwaiti children with their first documented febrile UTI and to compare our findings with those reported from other racial groups. One hundred and seventy-four children (38 males and 136 females) fulfilled the study criteria and were divided into three age groups (<1 year, 1-5 years, and >5 years). Patients in each group had both micturating cystourethrography (MCUG) and 99m-Tc-dimercaptosuccinic acid (DMSA) renal scan after diagnosis. VUR was detected in 39 children (22%). Two-thirds of cases had mild reflux (grade I and II). Females ( n=32) had more reflux than males ( n=7) (24% vs. 18%). Sixty-three patients (36%) had abnormal (DMSA) renal scans (acute pyelonephritis [AP] or renal scars). Of these, 79% were children below 5 years. Abnormal DMSA scans were found in 4 of 38 males (11%) versus 59 of 136 females (43%). Abnormal scans in children with VUR were seen in 1 of 7 males (14%) versus 19 of 32 females (59%). In total, the combination of abnormal scan with VUR occurred in 1 of 38 males (3%) and in 19 of 136 females (14%), whereas abnormal scan without demonstrable VUR was seen in 3 of 38 males (8%) versus 40 of 136 females (29%). Our data showed that the frequency of VUR in Arab Kuwaiti children with febrile UTI is midway between Caucasian and other racial groups. In this study, males had a lower-risk profile than females, the latter having a higher rate of reflux as well as a higher rate of abnormal DMSA scans, irrespective of demonstrable VUR.