Role of Central Nervous System Glucagon-Like Peptide-1 Receptors in Enteric Glucose Sensing

OBJECTIVE—Ingested glucose is detected by specialized sensors in the enteric/hepatoportal vein, which send neural signals to the brain, which in turn regulates key peripheral tissues. Hence, impairment in the control of enteric-neural glucose sensing could contribute to disordered glucose homeostasis. The aim of this study was to determine the cells in the brain targeted by the activation of the enteric glucose-sensing system

Changing trends in mortality among solid organ transplant recipients hospitalized for COVID-19 during the course of the pandemic

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020–June 19, 2020) and late 2020 (June 20, 2020–December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p <.001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46–0.98, p =.016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p <.001 and 50/571 [8.8%] vs. 213/402 [52.2%], p <.001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p <.001 and 73/571 [12.8%] vs. 5/402 [1.2%], p <.001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study

COVID-19 in hospitalized lung and non-lung solid organ transplant recipients: A comparative analysis from a multicenter study

Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID-19) may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID-19 to compare mortality by 28 days between hospitalized LTR and non-lung SOTR. Multivariable logistic regression models were used to assess comorbidity-adjusted mortality among LTR vs. non-lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with COVID-19, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non-lung SOTR (p =.02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p =.032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0–2.6, p =.04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0–11.3, p =.05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID-19, LTR had higher mortality than non-lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality

Quantification of cells expressing the thyrotropin receptor in extraocular muscles in thyroid associated orbitopathy.

BACKGROUND/AIM: Thyroid associated orbitopathy (TAO) and Graves' disease (GD) have an autoimmune pathogenesis, possibly related to the thyrotropin receptor (TSHR). The aim of this study was to determine whether TSHR immunoreactivity is correlated with disease severity or serum TSHR antibody (TRAB) levels. METHODS: Orbital tissues from 30 patients with TAO were compared with those of 20 patients with strabismus and four with non-thyroid orbital inflammation. TSHR was detected by immunohistochemistry and TRAB were measured by radioreceptor assay. RESULTS: No TSHR immunoreactivity was detected in the 24 control orbital tissues, whereas in all TAO biopsies elongated fibroblast-like cells, expressing TSHR, were present. These cells were located between the muscle cells, which were separated by oedema in the acute phase but fibrous tissue in the chronic phase of disease. Semi-thin sections showed numerous mast cells present in the chronic phase and in close contact with adipocytes. The number of TSHR immunostained cells was high in early disease, decreased with disease duration, and was positively correlated with TRAB levels at the onset of TAO. CONCLUSION: TSHR immunoreactivity was demonstrated specifically in TAO orbits which highlights the importance of TRAB early in the pathogenesis.Journal Articleinfo:eu-repo/semantics/publishe

MRI features of combined hepatocellular- cholangiocarcinoma versus mass forming intrahepatic cholangiocarcinoma

Abstract Background Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare primary liver tumor, which has overlapping imaging features with mass forming intra-hepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). Previous studies reported imaging features more closely resemble ICC and the aim of our study was to examine the differential MRI features of cHCC-CC and ICC with emphasis on enhancement pattern observations of gadolinium enhanced MRI. Methods Institutional review board approval with consent waiver was obtained for this retrospective bi-centric study. Thirty-three patients with pathologically proven cHCC-CC and thirty-eight patients with pathologically proven ICC, who had pre-operative MRI, were identified. MRI images were analyzed for tumor location and size, T1 and T2 signal characteristics, the presence/absence of: cirrhosis, intra-lesional fat, hemorrhage/hemosiderin, scar, capsular retraction, tumor thrombus, biliary dilatation, degree of arterial enhancement, enhancement pattern, pseudocapsule and washout. Associations between MRI features and tumor type were examined using the Fisher’s exact and chi-square tests. Results Strong arterial phase enhancement and the presence of: washout, washout and progression, intra-lesional fat and hemorrhage were all strongly associated with cHCC-CC (P < 0.001). While cHCC-CC had a varied enhancement pattern, the two most common enhancement patterns were peripheral persistent (n = 6) and heterogeneous hyperenhancement with washout (n = 6), compared to ICC where the most common enhancement patterns were peripheral hypoenhancement with progression (n = 18) followed by heterogeneous hypoenhancement with progression (n = 14) (P < 0.001). Conclusion The cHCC-CC enhancement pattern seems to more closely resemble HCC with the degree of arterial hyperenhancement and the presence of washout being valuable in differentiating cHCC-CC from ICC. However the presence of washout and progression, in the same lesion or a predominantly peripheral /rim hyperenhancing mass were also seen as important features that should alert the radiologist to the possibility of a cHCC-CC

Genome, environment, microbiome and metabolome in autism (GEMMA) study design: Biomarkers identification for precision treatment and primary prevention of autism spectrum disorders by an integrated multi-omics systems biology approach

Autism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service availability. However, this is not sufficient to explain this epidemiological phenomenon. Research points to a possible link between ASD and intestinal microbiota because many children with ASD display gastro-intestinal problems. Current large-scale datasets of ASD are limited in their ability to provide mechanistic insight into ASD because they are predominantly cross-sectional studies that do not allow evaluation of perspective associations between early life microbiota composition/function and later ASD diagnoses. Here we describe GEMMA (Genome, Environment, Microbiome and Metabolome in Autism), a prospective study supported by the European Commission, that follows at-risk infants from birth to identify potential biomarker predictors of ASD development followed by validation on large multi-omics datasets. The project includes clinical (observational and interventional trials) and pre-clinical studies in humanized murine models (fecal transfer from ASD probands) and in vitro colon models. This will support the progress of a microbiome-wide association study (of human participants) to identify prognostic microbiome signatures and metabolic pathways underlying mechanisms for ASD progression and severity and potential treatment response

Changing trends in mortality among solid organ transplant recipients hospitalized for COVID-19 during the course of the pandemic.

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p \u3c .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46-0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p \u3c .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p \u3c .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p \u3c .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p \u3c .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study