Paediatric gastrointestinal disorders in SARS-CoV-2 infection: Epidemiological and clinical implications

The coronavirus disease 2019 (COVID-19) pandemic is a threat worldwide for individuals of all ages, including children. Gastrointestinal manifestations could be the initial presenting manifestation in many patients, especially in children. These symptoms are more common in patients with severe disease than in patients with non-severe disease. Approximately 48.1% of patients had a stool sample that was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA. Children typically form 1%-8% of all laboratory-confirmed cases of SARS-CoV-2. Gastrointestinal manifestations of COVID-19 in children are not rare, with a prevalence between 0 and 88%, and a wide variety of presentations, including diarrhoea, vomiting, and abdominal pain, can develop before, with or after the development of respiratory symptoms. Atypical manifestations such as appendicitis or liver injury could also appear, especially in the presence of multisystem inflammatory disease. In this review, we discussed the epidemiology of COVID-19 gastrointestinal diseases in children as well as their implications on the diagnosis, misdiagnosis, prognosis, and faecal-oral transmission route of COVID-19 and the impact of gastrointestinal diseases on the gut microbiome, child nutrition, and disease management.     

Application of the American College of Cardiology (ACC/AHA) 2017 Guideline for the Management of Hypertension in Adults and Comparison with the 2014 Eighth Joint National Committee Guideline

ObjectivesThis study aims to compare the 2017-ACC/AHA hypertension guideline with 2014-JNC-8 guideline in regard to the number of patients who are eligible for treatment and to determine the physicians’ adherence and the financial impact of implementing the new guideline.MethodsA cross-sectional observational study was conducted on adult patients who attended the hospital outpatient setting in UAE during January 1, 2018 till February 28, 2018. Adults who are diagnosed with hypertension and those with blood pressure (BP) levels based on two or more readings obtained on two or more different occasions were screened for inclusion into this study and cardiovascular diseases (CVD) risk was calculated. The two guidelines were compared with respect to the number of patients diagnosed with hypertension and eligible for treatment. Results were extrapolated to the UAE population. Financial impact of applying the 2017-ACC/AHA guideline was also evaluated.ResultsIn comparison with the JNC-8, the 2017-ACC/AHA guideline would increase the proportion of patients diagnosed with hypertension among UAE adults from 40.8% to 76.3% and the number of UAE adults recommended for antihypertensive medications would rise from 2.42 million (32.1%) to 4.71 million (62.5%). Among UAE adults, almost 4.42 million (58.6%) and 0.76 million (10.1%) would have BP above the target according to the 2017-ACC/AHA and JNC-8 guidelines, respectively. The expected increase in the cost of anti-hypertension medications prescribed for the new labeled cases according to 2017-ACC/AHA but not JNC-8 would reach 1.8 billion AED/year. For those who were recommended for antihypertensive medications, who had BP above target, the additional cost would reach 3.5 billion AED/year.ConclusionsThe current study reveals marked increase in the proportion of patients diagnosed with hypertension in concordance with the 2017-ACC/AHA guideline. This is also will be associated with almost double the number of UAE adults recommended for antihypertensive medications. The poor compliance with the 2017-ACC/AHA reflects the concern regarding the increase risk of adverse events.     

Impaired contractile responses and altered expression and phosphorylation of Ca2+ sensitization proteins in gastric antrum smooth muscles from ob/ob mice

Diabetic gastroparesis is a common complication of diabetes, adversely affecting quality of life with symptoms of abdominal discomfort, nausea, and vomiting. The pathogenesis of this complex disorder is not well understood, involving abnormalities in the extrinsic and enteric nervous systems, interstitial cells of Cajal (ICCs), smooth muscles and immune cells. The ob/ob mouse model of obesity and diabetes develops delayed gastric emptying, providing an animal model for investigating how gastric smooth muscle dysfunction contributes to the pathophysiology of diabetic gastroparesis. Although ROCK2, MYPT1, and CPI-17 activities are reduced in intestinal motility disorders, their functioning has not been investigated in diabetic gastroparesis. We hypothesized that reduced expression and phosphorylation of the myosin light chain phosphatase (MLCP) inhibitory proteins MYPT1 and CPI-17 in ob/ob gastric antrum smooth muscles could contribute to the impaired antrum smooth muscle function of diabetic gastroparesis. Spontaneous and carbachol- and high K⁺-evoked contractions of gastric antrum smooth muscles from 7 to 12 week old male ob/ob mice were reduced compared to age- and strain-matched controls. There were no differences in spontaneous and agonist-evoked intracellular Ca²⁺ transients and myosin light chain kinase expression. The F-actin:G-actin ratios were similar. Rho kinase 2 (ROCK2) expression was decreased at both ages. Basal and agonist-evoked MYPT1 and myosin light chain 20 phosphorylation, but not CPI-17 phosphorylation, was reduced compared to age-matched controls. These findings suggest that reduced MLCP inhibition due to decreased ROCK2 phosphorylation of MYPT1 in gastric antrum smooth muscles contributes to the antral dysmotility of diabetic gastroparesis.     

Chest radiography requirements for patients with asymptomatic COVID-19 undergoing coronary artery bypass surgery: Three case reports

BACKGROUNDThe coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2, represents a major challenge to health care systems both globally and regionally, with many opting by cancelling elective surgeries. Cardiac operations in patients diagnosed with COVID-19 have been imperative due to their emergency nature, critical condition of patients awaiting cardiac surgery, and accumulated number of cardiac surgical interventions throughout the last months.CASE SUMMARYHere we describe three COVID-19 positive cases who underwent coronary surgery, on an urgent basis. We did not experience worsening of the patients’ clinical condition due to COVID-19 and therefore a routine post-operative chest X-ray (CXR) was not required. None of the health care providers attending the patients endured cross infection. Further trials would be needed in order to confirm these results.CONCLUSIONWhile the pandemic has adversely hit the health systems worldwide, cardiac surgical patients who concomitantly contracted COVID-19 may undergo a smooth post-operative course as a routine post-operative CXR may not be required.     

A new variant of type II von Willebrand disease with aberrant multimeric structure of plasma but not platelet von Willebrand factor (type IIF)

A patient with a lifelong bleeding disorder was diagnosed as having Type II von Willebrand disease. The larger multimers of von Willebrand factor were absent from her plasma but present in platelets. A high- resolution electrophoretic technique was used to study the complex structure of individual von Willebrand factor multimers. In normal plasma, each multimer could be resolved into five bands: a more intense central one and four less intense, two moving faster and two slower than the central band. In normal platelets, each multimer could also be resolved into five bands. The central one had a mobility similar to that in plasma, whereas the four satellite bands had a mobility that differed from that of the corresponding plasma bands. In the patient, platelet von Willebrand factor antigen content and ristocetin cofactor activity were normal, and von Willebrand factor showed the same structure of individual multimers as seen in normal platelets. On the other hand, plasma von Willebrand factor antigen and ristocetin cofactor activity were decreased, and the structure of individual von Willebrand factor multimers was different from that of normal plasma and similar to that seen in normal and patient's platelets. After infusion of 1-deamino-8-D-arginine vasopressin, the largest von Willebrand factor multimers, as well as new satellite bands with a mobility similar to those in normal plasma, appeared in the patient plasma, and the levels of von Willebrand factor antigen and ristocetin cofactor activity became normal. Yet no relevant change in the prolonged bleeding time was observed. This new variant of von Willebrand disease, therefore, is characterized by the presence of a dysfunctional von Willebrand factor molecule that exhibits unique structural abnormalities in plasma but appears to be normal in platelets. The designation of Type IIF is proposed for this type of von Willebrand disease in accordance with the terminology that has been previously used.     

Radioactive choline metabolism in guinea pig gallbladder

Acetylcholine may be released from gallbladder intrinsic nerves in response to cholecystokinin stimulation. This study characterized metabolites of [¹⁴C]choline produced in the gallbladder and released during incubation, with or without cholecystokinin-octapeptide. Radiolabeled [¹⁴C]choline was applied to the mucosal or muscle surface of intact guinea pig gallbladders in an organ bath. After radiolabeling, gallbladders were incubated with or without the contractile agonist cholecystokinin-octapeptide. Metabolites of [¹⁴C]choline were identified in gallbladder tissue and incubation buffers using HPLC and thin-layer chromatography. The major metabolites of [¹⁴C]choline were betaine and phosphocholine. [¹⁴C]Phosphocholine was incorporated slowly into [¹⁴C]phosphatidylcholine. [¹⁴C]Choline was released into buffers during incubation. [¹⁴C]Acetylcholine constituted less than 1% of radiolabel in the gallbladder. There was no identifiable [¹⁴C]acetylcholine released in buffers. Cholecystokinin-octapeptide did not affect choline metabolism. These studies showed that choline in the gallbladder is metabolized along pathways similar to those in the liver. Gallbladders released mostly choline, rather than acetylcholine, even during hormonally induced contraction.This project was supported by the Research and Development Office of the Department of Veterans Affairs.     

Association of granulocyte-macrophage colony-stimulating factor with the crystalloid granules of human eosinophils

We have previously shown that normal-density human peripheral blood eosinophils transcribe and translate mRNA for granulocyte-macrophage colony-stimulating factor (GM-CSF) and that the intracellular distribution was granular as assessed by light microscopy immunocytochemistry. The present study was conducted to confirm this apparent association between GM-CSF and the crystalloid granule using a subcellular fractionation method for human eosinophils and immunogold electron microscopy (EM). Highly purified (> 99%, by negative selection using anti-CD16 immunomagnetic microbeads) human peripheral blood eosinophils were obtained from four asthmatic subjects (not taking systemic medication), homogenized and density fractionated (5 x 10(7) cells/subject) on linear Nycodenz gradients. Twenty-four fractions were collected from each cell preparation and analyzed for marker enzyme activities as well as total protein. Dot blot analysis with specific monoclonal antibodies (MoAbs) was used to detect the eosinophil granule proteins major basic protein (MBP) and eosinophil cationic protein (ECP). An anti-CD9 MoAb was used as an eosinophil plasma membrane marker. Lactate dehydrogenase (LDH) was used as a cytosolic marker. Immunoreactivity for GM-CSF was detected by a specific enzyme-linked immunosorbent assay using a polyclonal antihuman GM-CSF antibody and confirmed by dot blot. GM-CSF coeluted with the cellular fractions containing granule markers (MBP, ECP, eosinophil peroxidase, hexosaminidase, and arylsulphatase), but not those containing cytoplasm (LDH+) or membrane (CD9+) markers. EM examination of pooled fractions associated with the peak of GM-CSF immunoreactivity confirmed that they contained crystalloid and small granules, but not plasma membrane. In addition, quantification, using immunogold labeling with an anti/GM-CSF MoAb, indicated preferential localization of gold particles over the eosinophil granule cores of intact cells. Thus, our results indicate that GM-CSF resides as a granule-associated, stored mediator in unstimulated human eosinophils.