Gastrointestinal coronavirus disease 2019: epidemiology, clinical features, pathogenesis, prevention, and management.

INTRODUCTION: The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019. Some authors reported pieces of evidence that patients with SARS-CoV-2 infection could have direct involvement of the gastrointestinal tract, and in symptomatic cases, gastrointestinal symptoms (diarrhea, nausea/vomiting, abdominal pain) could be very common. AREA COVERED: In this article, we reviewed current-published data of the gastrointestinal aspects involved in SARS-CoV-2 infection, including prevalence and incidence of specific symptoms, the presumptive biological mechanism of GI infection, prognosis, clinical management, and public health-related concerns on the possible risk of oral-fecal transmission. EXPERT OPINION: Different clues point to direct virus infection and replication in mucosal cells of the gastrointestinal tract. In vitro studies showed that SARS-CoV-2 could enter into the gastrointestinal epithelial cells by the Angiotensin-Converting enzyme two membrane receptor. These findings, coupled with the identification of viral RNA found in stools of patients, clearly suggest that direct involvement of the gastrointestinal tract is very likely. This can justify most of the gastrointestinal symptoms but also suggest a risk for an oral-fecal route for transmission, additionally or alternatively to the main respiratory route.

Intra-operative hypotensive episodes may be associated with post-operative esophageal anastomotic leak.

This study aims to report the hypotensive episodes (HEs) during esophagectomy and their influence on the occurrence of anastomotic leak. Eighty-four patients underwent esophagectomy with gastric pull-up. Pre-, intra-, and post-operative data were prospectively collected. HEs were defined by systolic pressure decreasing more than 30 % of the basal value for more than 5 min. Nineteen patients had intra-operative HEs (22.6 %). HEs were significantly more frequent in patients undergoing prone esophagectomy (P = 0.001) and those with an epidural catheter (EC) (P = 0.04) used during surgery. Among them, 15 were treated with vasopressors. There were six severe post-operative anastomotic leaks, which required surgery; leaks were significantly more common in patients with intra-operative HEs (21 vs 3.1 %; P = 0.02), especially those treated with vasopressive agents (20 vs 0 %; P = 0.008). Intra-operative use of EC can, in certain conditions, significantly influence gastric blood flow due to HEs. A higher incidence of severe leak occurred in patients experiencing intra-operative HEs. Several factors can lead to intra-operative HEs, and the perioperative use of an EC should be carefully evaluated.

Volume and outcomes after esophageal cancer surgery: the experience of the Region of Lombardy-Italy.

Surgical procedures for cancer of the esophagus are complex operations, with considerable perioperative morbidity and mortality that require high use of resources. Recent reports indicate better results with centralization of these procedures, referring patients to high-volume dedicated hospitals. The aim of this study was to analyze the results of resective surgery for cancer of the esophagus and cardia performed in hospitals of the Region of Lombardy over the period 2005-2011, in terms of volume of operations, 30-day postoperative mortality, and length of hospitalization. The results showed a significant relation between reduction of mortality rate and number of resections performed in intermediate- and high-volume centers. In the Region of Lombardy there is an inverse relation between volume of esophagectomies in the single hospital, length of postoperative hospital stay, and postoperative 30-day mortality. Centralization of care on a regional level and standardized clinical pathways of diagnosis and care at single healthcare organizations and professionals should be implemented to improve clinical results in patients affected by esophageal and cardia cancer.

Percutaneous transhepatic biliary drainage and occlusion balloon in the management of duodenal stump fistula.

BACKGROUND: Duodenal stump fistula (DSF) after gastrectomy is a complication with a high mortality rate. We report a series of patients with postoperative DSF treated with percutaneous transhepatic biliary drainage and occlusion balloon (PTBD-OB). The aim of this study is to explore the feasibility and efficacy of PTBD-OB in the treatment of DSF. PATIENTS AND METHODS: Six patients developing DSF underwent PTBD-OB because of high DSF output and because medical and surgical management was unsuccessful. In these patients, an occlusion balloon was percutaneously inserted into the common bile duct and a biliary drain was positioned above the balloon to obtain external drainage of bile. RESULTS: In all cases, percutaneous access to the biliary tree was achieved. Patients maintained the PTBD-OB for a median of 43 days. In all patients, DSF output decreased after PTBD-OB placement from a median of 500 to 100 ml/day (p = 0.02). The DSF resolved in three patients and three patients died of sepsis, but in two of them, death was related to other digestive fistulas that developed before PTBD-OB placement. CONCLUSIONS: This paper presents the first published series on DSF management with PTBD-OB and shows that it is a feasible and safe procedure which reduces DSF output.

Frequencies of promoter pentanucleotide (TTTTA)n of CYP11A gene in European and North African populations.

The present work attempts to determine the distribution of CYP11A (TTTTA)n genotype and allele frequencies in 10 European and North African populations. This polymorphism has been associated with hyperandrogenism by several association studies. To our knowledge, this is the first study investigating the ethnic variation of this polymorphism. DNA was extracted from 868 whole-blood samples with the standard phenol-chloroform technique, and PCR reactions were carried out using fluorescent primers as described previously. PCR products were analyzed by an ABI 3,730 DNA Analyzer. A total of six alleles were identified, ranging from 220 bp (4 repeats [4R]) to 250 bp (10R). The most frequent allelic fragment size in all populations was 4R, with frequencies ranging from 47.9% (Sicily) to 62.8% (Tuscany and Germany). Allelic frequencies showed high heterogeneity between analyzed populations. We detected a significant gradient for alleles 4R and 8R. In this study, we report the allele frequency distribution of CYP11A (TTTTA)n showing a north-south geographic gradient. This result could be useful for epidemiological studies about hyperandrogenism.

Italian isolates today: geographic and linguistic factors shaping human biodiversity.

We briefly review the current status of anthropological and genetic studies of isolated populations and of their micro-evolutionary and biomedical applications, with particular emphasis on European populations. Thereafter, we describe the ongoing collaborative research project "Isolating the Isolates: geographic and cultural factors of human genetic variation" regarding Italian extant geographical and/or linguistic isolates, aimed at overcoming the limitations of previous studies regarding geographical coverage of isolates, number and type of genetic polymorphisms under study and suitability of the experimental design to investigate gene-culture coevolutionary processes. An interdisciplinary sampling approach will make it possible to collect several linguistic isolates and their geographic neighbours from Trentino, Veneto, Friuli, Tuscany, Sardinia and Calabria. This will be coupled with a shared genotyping strategy based on mitochondrial and Y-chromosomal polymorphisms. The results will be analyzed with a focus on the role of geographical and cultural factors in shaping human biodiversity. The aims of the project go beyond the simple reconstruction of the genetic structure and history of the examined groups. In fact, the study will also include an assessment for future bio-medical studies and the development of genetic and bio-demographic databases. Ethical and educational aspects are also foreseen by the project, by using informed consents together with disseminating activities in loco, completed by the creation of a dedicated web site for both scientific and public audiences.

Human CHIT1 gene distribution: new data from Mediterranean and European populations.

A 24 bp duplication in the CHIT1 gene (H allele) is associated with a deficiency in the activity of chitotriosidase, an enzyme with the capability to hydrolyse chitin. A recent study in European and two sub-Saharan populations suggested a relationship between the presence of the mutation, improved environmental conditions, and the disappearance of parasitic diseases, including Plasmodium falciparum malaria. This result was not supported by the high frequency of the 24 bp duplication in a sample from Taiwan, an area with high malaria endemicity until 40 years ago. In this study, we analysed the frequency variability of the H allele in Mediterranean populations and its internal variability in Sardinia (Italy) with respect to malaria, which had been endemic on the island until its eradication during 1946-1950. The pattern of H frequency distributions is not consistent with the hypothesis of selective pressures acting on CHIT1 gene. The Moran's index coefficient and correlogram seem to indicate, indeed, that allele distribution was determined by random factors. The pattern of frequency distribution suggests a possible Asiatic origin of the H allele, but it could be possible also that the mutant allele had diffused out of Africa, and was subsequently lost from African populations.

Insulin sensitivity in patients with primary aldosteronism: a follow-up study.

CONTEXT: The relationship between aldosterone and glucose metabolism is poorly understood, and there is substantial disparity among findings of studies that have examined glucose tolerance and insulin sensitivity in patients with primary aldosteronism. OBJECTIVE: The objective of the study was to determine the outcome of glucose tolerance and insulin sensitivity in patients with primary aldosteronism after treatment. DESIGN: This was a prospective study of patients who received a diagnosis of primary aldosteronism and were followed up for an average period of 5.7 yr (range, 3-9 yr). SETTING: The study was conducted at a university referral center. PATIENTS: A consecutive sample of 47 patients with tumoral or idiopathic aldosteronism was followed up after either surgical or medical treatment. Patients with primary aldosteronism were compared with 247 patients with essential hypertension with the same severity and duration of disease and 102 normotensive subjects. MAIN OUTCOME MEASURES: Short- and long-term changes in glucose tolerance and insulin sensitivity were measured. RESULTS: After adjustment for age, gender, and body mass index, patients with primary aldosteronism had greater homeostasis model assessment index (P < 0.05) and plasma insulin response to an oral glucose load (P < 0.05) and lower quantitative insulin sensitivity check index (P < 0.01) than normotensive controls. Changes in insulin sensitivity were significantly greater in essential hypertension than primary aldosteronism, and this difference was confirmed by assessment with the hyperinsulinemic-euglycemic clamp (P < 0.01). Treatment of primary aldosteronism decreased blood pressure significantly, and during the initial 6 months of follow-up, parameters of insulin sensitivity were restored to normal. Analysis of subsequent follow-up showed nonsignificant changes in glucose metabolism parameters in both adrenalectomized and spironolactone-treated patients. CONCLUSIONS: Insulin resistance is present in patients with tumoral and idiopathic aldosteronism, but the defect appears less severe than in patients with essential hypertension. Treatment with surgery or aldosterone antagonists restores rapidly and persistently normal sensitivity to insulin.

Abnormalities of glucose metabolism in patients with early renal failure.

Abnormalities of glucose metabolism and hyperinsulinemia have been demonstrated in patients with end-stage renal disease and may contribute to the development of atherosclerotic complications in these patients. In the present study, we investigated the stage of renal failure in which abnormalities of glucose metabolism develop and whether these abnormalities were associated with an increased prevalence of cardiovascular events in patients with early renal failure. In 321 untreated essential hypertensive patients, we assessed renal function by measuring 24-h creatinine clearance, urinary protein excretion, and microalbuminuria; we assessed cardiovascular status by clinical and laboratory tests; and we measured plasma glucose, insulin, and C-peptide levels at fasting and after a 75-g oral glucose load. To evaluate insulin sensitivity, a hyperinsulinemic-euglycemic clamp was performed in a subgroup of 104 patients. Patients with creatinine clearance < 30 ml.min(-1).1.73 m(-2), severe hypertension, BMI < 30 kg/m(2), and diabetes or family history of diabetes were excluded. Hypertensive patients were found to be hyperinsulinemic when compared with 92 matched normotensive subjects. Early renal failure (creatinine clearance < 90 ml.min(-1).1.73 m(-2)) caused by hypertensive nephrosclerosis was detected in 116 of 321 patients. Analysis of patients with varying degrees of renal function impairment demonstrated increased plasma glucose and insulin response to oral glucose load, decreased fasting glucose-to-insulin ratio, and reduced sensitivity to insulin only in those patients with creatinine clearance < 50 ml.min(-1).1.73 m(-2). Parameters of glucose metabolism were not correlated with creatinine clearance and microalbuminuria. Prevalence of atherosclerotic cardiovascular events was significantly related to reduction of creatinine clearance, but parameters of glucose metabolism were comparable in patients with and without evidence of atherosclerotic damage. Thus, in patients with hypertensive nephrosclerosis and early impairment of glomerular filtration, alterations of glucose metabolism become evident only when creatinine clearance is < 50 ml.min(-1).1.73 m(-2) and are not related to microalbuminuria and cardiovascular complications.