Severe SOPH syndrome due to a novel NBAS mutation in a 27-year-old woman-Review of this pleiotropic, autosomal recessive disorder: Mystery solved after two decades.

Autosomal recessive SOPH syndrome was first described in the Yakuts population of Asia by Maksimova et al. in 2010. It arises from biallelic pathogenic variants in the NBAS gene and is characterized by severe postnatal growth retardation, senile facial appearance, small hands and feet, optic atrophy with loss of visual acuity and color vision, and normal intelligence (OMIM #614800). The presence of Pelger-Hüet anomaly in this disorder led to its name as an acronym for Short stature, Optic nerve atrophy, and Pelger-Hüet anomaly. Recent publications have further contributed to the characterization of this syndrome through additional phenotype-genotype correlations. We review the clinical features described in these publications and report on a 27-year-old woman with dwarfism with osteolysis and multiple skeletal problems, minor anomalies, immunodeficiency, diabetes mellitus, and multiple secondary medical problems. Her condition was considered an unknown autosomal recessive disorder for many years until exome sequencing provided the diagnosis by revealing a founder disease-causing variant that was compound heterozygous with a novel pathogenic variant in NBAS. Based on the major clinical features of this individual and others reported earlier, a revision of the acronym is warranted to facilitate clinical recognition.

Main prophylactic measures in bariatric endoscopy. Spanish Expert Recommendations Guideline.

Bariatric endoscopy (BE) encompasses a number of techniques -some consolidated, some under development- aiming to contribute to the management of obese patients and their associated metabolic diseases as a complement to dietary and lifestyle changes. To date different intragastric balloon models, suture systems, aspiration methods, substance injections and both gastric and duodenal malabsorptive devices have been developed, as well as endoscopic procedures for the revision of bariatric surgery. Their ongoing evolution conditions a gradual increase in the quantity and quality of scientific evidence about their effectiveness and safety. Despite this, scientific evidence remains inadequate to establish strong grades of recommendation allowing a unified perspective on prophylaxis in BE. This dearth of data conditions leads, in daily practice, to frequently extrapolate the measures that are used in bariatric surgery (BS) and/or in general therapeutic endoscopy. In this respect, this special article is intended to reach a consensus on the most common prophylactic measures we should apply in BE. The methodological design of this document was developed while attempting to comply with the following 5 phases: Phase 1: delimitation and scope of objectives, according to the GRADE Clinical Guidelines. Phase 2: setup of the Clinical Guide-developing Group: national experts, members of the Grupo Español de Endoscopia Bariátrica (GETTEMO, SEED), SEPD, and SECO, selecting 2 authors for each section. Phase 3: clinical question form (PICO): patients, intervention, comparison, outcomes. Phase 4: literature assessment and synthesis. Search for evidence and elaboration of recommendations. Based on the Oxford Centre for Evidence-Based Medicine classification, most evidence in this article will correspond to level 5 (expert opinions without explicit critical appraisal) and grade of recommendation C (favorable yet inconclusive recommendation) or D (inconclusive or inconsistent studies). Phase 5: External review by experts. We hope that these basic preventive measures will be of interest for daily practice, and may help prevent medical and/or legal conflicts for the benefit of patients, physicians, and BE in general.

Gastric serrated adenoma.

A 51 years-old male with several family history of gastric cancer, who was studied one year before for dyspepsia. A new gastroscopy was done that objectified in the greater curvature, a sessile polyp with slightly depressed center and a villous crypt pattern with Narrow Band Imaging. The histopathology study shown a horizontalization of the basal glands and basal dysplasia, compatible with serrated adenoma. A 51 year-old male with a family history of gastric cancer was studied for one year due to dyspepsia. A new gastroscopy was performed that identified a sessile polyp with a slightly depressed center and a villous crypt pattern in the greater curvature via narrow band imaging. The histopathology study showed horizontal basal glands and basal dysplasia, which was compatible with serrated adenoma.

Racial differences in neighborhood disadvantage, inflammation and metabolic control in black and white pediatric type 1 diabetes patients.

BACKGROUND: Racial variation in the relationship between blood glucose and hemoglobin A1c (HbA1c) complicates diabetes diagnosis and management in racially mixed populations. Understanding why HbA1c is persistently higher in blacks than whites could help reduce racial disparity in diabetes outcomes. OBJECTIVE: Test the hypothesis that neighborhood disadvantage is associated with inflammation and poor metabolic control in a racially mixed population of pediatric type 1 diabetes patients. METHODS: Patients (n = 86, 53 white, 33 black) were recruited from diabetes clinics. Self-monitored mean blood glucose (MBG) was downloaded from patient glucose meters. Blood was collected for analysis of HbA1c and C-reactive protein (CRP). Patient addresses and census data were used to calculate a concentrated disadvantage index (CDI). High CDI reflects characteristics of disadvantaged neighborhoods. RESULTS: HbA1c and MBG were higher (p < 0.0001) in blacks [10.4% (90.3 mmol/mol), 255 mg/dL] than whites [8.9% (73.9 mmol/mol), 198 mg/dL). CDI was higher in blacks (p < 0.0001) and positively correlated with HbA1c (r = 0.40, p = 0.0002) and MBG (r = 0.35, p = 0.0011) unless controlled for race. CDI was positively associated with CRP by linear regression within racial groups. CRP was not different between racial groups, and was not correlated with MBG, but was positively correlated with HbA1c when controlled for race (p = 0.04). CONCLUSIONS: Neighborhood disadvantage was associated with inflammation and poor metabolic control in pediatric type 1 diabetes patients. Marked racial differences in potential confounding factors precluded differentiation between genetic and environmental effects. Future studies should recruit patients matched for neighborhood characteristics and treatment regimen to more comprehensively assess racial variation in HbA1c.

Differences in Red Blood Cell Indices Do Not Explain Racial Disparity in Hemoglobin A1c in Children with Type 1 Diabetes.

We assessed the association of erythrocyte indices on mean blood glucose-independent racial disparity in hemoglobin A1c (HbA1c) in youth with type 1 diabetes. Blacks still had higher HbA1c after adjustment for mean blood glucose, red blood cell indices, age, and sex. Such differences need to be taken into account when interpreting HbA1c in Black patients.

Low serum levels of vitamin D significantly increase the risk of death in older adults with hip fractures: a prospective cohort.

OBJECTIVE: to evaluate the relationship between 25(OH)D3 levels and fatal outcome in patients over 60 years of age undergoing surgical repair of hip fractures. METHODS: prospective cohort of patients undergoing surgical repair of hip fractures. At admission, 25(OH)D3 levels were measured, among other parameters. Patients were followed for at least 1 year, and incident mortality was recorded. RESULTS: 209 patients were included in the study, with a mean age of 79.5 ± 7.6 years among survivors and 80.7 ± 8.2 years among those who died in the first postoperative year (p=0.346). The 25(OH)D3 levels of survivors were significantly higher than those of patients who died (p=0.003). After adjusting for confounding variables, 25(OH)D3 levels below 12.5ng/mL were significant risk factors regardless of mortality (adjusted OR: 7.6; 95% CI: 2.35 to 24.56). CONCLUSIONS: our data show that serum 25(OH)D3 levels below 12.5ng/mL significantly and independently increased the risk of mortality in the first year after surgical repair of low-energy hip fracture in patients over 60 years of age in the geographic region where this study was conducted. Low albumin also showed a significant association with mortality in these patients. All other factors had no significant associations.

Virilizing para-adrenocortical adenoma associated with idiopathic-acquired generalized anhidrosis in an adolescent girl.

Adrenocortical tumors are rare in childhood and adolescence. Virilization, alone or in combination with signs of overproduction of other adrenal hormones, is the most common clinical presentation. Here we report an unusual case of an African-American female adolescent presenting with idiopathic acquired generalized anhidrosis, dysregulation of body temperature, absence of adult body odor and dry skin in the face of a virilizing para-adrenocortical adenoma. Virilization signs regressed soon after removal of the tumor, but normalization of the 3alpha-androstenediol glucuronide (3alpha-AG) took longer compared to other measurable androgens; accompanied by anhidrosis. The association of remitting anhidrosis with normalized levels of 3alpha-AG suggests it might be a possible mechanism for anhidrosis. High 3alpha-AG levels might implicate the increased peripheral conversion of weak pro-androgens with different biochemical structure. We recommend obtaining 3alpha-AG beside other androgens in virilized patients with atypical dermatological symptoms in the face of hyperandrogenism.

[Utility of infliximab therapy in severe enterorrhagia associated with Crohn's disease. Report of three cases]. / Utilidad del tratamiento con infliximab en la enterorragia severa asociada a la enfermedad de Crohn. Experiencia de tres casos.

Severe lower gastrointestinal (GI) bleeding is an infrequent complication in Crohn's disease. We report the cases of three patients with Crohn's disease, localized in distinct areas, who developed severe enterorrhagia requiring multiple transfusions. All three patients responded favorably to infliximab administration, which resolved the life-threatening hemorrhages and avoided emergency surgical resection, which had seemed inevitable. Based on this clinical experience and a review of the literature comparing infliximab with other pharmacological options, we believe that this drug should be the treatment of choice in patients with Crohn's disease who develop severe lower gastrointestinal bleeding. This strategy can, in some cases, avoid surgery if the bleeding stops due to rapid healing of the deep mucosal lesions causing the hemorrhagic episode.

Low birth weight is not associated with type 2 diabetes in African American children in New Orleans.

OBJECTIVES: We sought to determine if low birth weight (LBW) occurs more frequently in African American children with type 2 diabetes (T2D), and if patients with LBW differ metabolically. STUDY DESIGN: We collected birth weight, anthropometric and metabolic data from African American children with T2D born in New Orleans from clinic charts. Comparable birth weight data from all African American infants born in New Orleans were obtained from Louisiana state vital statistics. RESULTS: In African American patients with T2D, 14.3% had LBW compared to 13.9% in the reference population (z = 0.997, p = 0.33). There was no difference between LBW and non-LBW patients with regard to body mass index (BMI) at diagnosis, presenting insulin, c-peptide, glucose levels, or HbA1c one year post diagnosis. CONCLUSIONS: African American children with T2D were not enriched with LBW individuals. LBW patients were not anthropometrically or metabolically different from non-LBW T2D patients. Thus prenatal factors may not be the driving force in the development of T2D in African American children.

The relationship of insulin secretion and GAD65 antibody levels at diagnosis on glycemic control in type 2 diabetes.

OBJECTIVE: To determine if pretreatment insulin and C-peptide levels together with antibody status are predictive of HbAlc levels before and during therapy in obese African-American youth with type 2 diabetes. METHODS: Records of African-American patients with clinical diagnosis of type 2 diabetes were retrospectively analyzed. Insulin, C-peptide, blood glucose, HbA1c and islet autoantibodies at diagnosis were recorded. These variables were compared with HbA1c levels during therapy. RESULTS: Eight of 45 patients were islet autoantibody positive. There was no difference in age, Body Mass Index z-score, insulin, C-peptide, glucose or HbAlc levels between antibody positive or negative patients. Insulin (r = -0.45, p < 0.01 n=45) and C-peptide (r = -0.59, p < 0.001, n=36) were correlated with HbA1c at diagnosis but not during therapy. CONCLUSIONS: Higher insulin levels were associated with lower HbA1c at presentation but not during therapy. Antibody status was not associated with differences in insulin, C-peptide levels or HbAlc level.

Proteomic analysis of the venom from the fish eating coral snake Micrurus surinamensis: novel toxins, their function and phylogeny.

The protein composition of the soluble venom from the South American fish-eating coral snake Micrurus surinamensis surinamensis, here abbreviated M. surinamensis, was separated by RP-HPLC and 2-DE, and their components were analyzed by automatic Edman degradation, MALDI-TOF and ESI-MS/MS. Approximately 100 different molecules were identified. Sixty-two components possess molecular masses between 6 and 8 kDa, are basically charged molecules, among which are cytotoxins and neurotoxins lethal to fish (Brachidanios rerio). Six new toxins (abbreviated Ms1-Ms5 and Ms11) were fully sequenced. Amino acid sequences similar to the enzymes phospholipase A2 and amino acid oxidase were identified. Over 20 additional peptides were identified by sequencing minor components of the HPLC separation and from 2-DE gels. A functional assessment of the physiological activity of the six toxins was also performed by patch clamp using muscular nicotinic acetylcholine receptor assays. Variable degrees of blockade were observed, most of them reversible. The structural and functional data obtained were used for phylogenetic analysis, providing information on some evolutionary aspects of the venom components of this snake. This contribution increases by a factor of two the total number of alpha-neurotoxins sequenced from the Micrurus genus in currently available literature.

Hemoglobin A1c, frequency of glucose testing and social disadvantage: Metrics of racial health disparity in youth with type 1 diabetes.

INTRODUCTION: Black youth with type 1 diabetes (T1D) have higher HbA1c than whites. To understand HbA1c differences, we examined the relationship of psycho-social factors and glucose testing with HbA1c. METHODS: Glucose tests per day (BGs/d) and mean blood glucose (MBG) were calculated from meter data of youth self-identified as black (n = 33) or white (n = 53) with T1D. HbA1c, family income, insurance status, concentrated disadvantage (CDI), psychological depression (DSC), mother educational attainment (MEA), and insulin delivery method (IDM) data was were analyzed. RESULTS: Black patients had significantly higher HbA1c, MBG and disadvantage measures compared to whites. BGs/d correlated with HbA1c, MBG, age and CDI. Race (p < 0.0158), age (p < 0.0001) and IDM (p < 0.0036) accounted for 50% of the variability (R2 = 0.5, p < 0.0001) in BGs/d. Regardless of age, black patients had lower BGs/d than whites. MBG (p < 0.0001) and BGs/d (p < 0.0001) accounted for 61% of the variance in HbA1c (p < 0.0001). CONCLUSIONS: BGs/d is easily assessed and closely associated with HbA1c racial disparity. BGs/d is intricately linked with greater social disadvantage. Innovative management approaches are needed to overcome obstacles to optimal outcomes.

Enteral Feeding as an Adjunct to Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Withholding enteral feedings during hypothermia lacks supporting evidence. OBJECTIVES: We aimed to determine if minimal enteral nutrition (MEN) during hypothermia in patients with hypoxic-ischemic encephalopathy was associated with a reduced duration of parenteral nutrition, time to full oral feeds, and length of stay, but would not be associated with increased systemic inflammation or feeding complications. METHODS: We performed a pilot, retrospective, matched case-control study within the Florida Neonatal Neurologic Network from December 2012 to May 2016 of patients who received MEN during hypothermia (n = 17) versus those who were not fed (n = 17). Length of stay, feeding-related outcomes, and brain injury identified by MRI were compared. Serum inflammatory mediators were measured at 0-6, 24, and 96 h of life by multiplex assay. MRI were scored using the Barkovich system. RESULTS: MEN subjects had a reduced length of hospital stay (mean 15 ± 11 vs. 24 ± 19 days, p < 0.05), days receiving parenteral nutrition (7 ± 2 vs. 11 ± 6, p < 0.05), and time to full oral feeds (8 ± 5 vs. 18 ± 18, p < 0.05). MEN was associated with a significantly reduced serum IL-12p70 at 24 and 96 h (p < 0.05). Brain MRI scores were not significantly different between groups. CONCLUSION: MEN during hypothermia was associated with a reduced length of stay and time to full feeds, but did not increase feeding complications or systemic inflammation.