Tirzepatide-Induced Gastrointestinal Manifestations: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis determine how frequently and how seriously gastrointestinal manifestations affect people with type 2 diabetes mellitus on tirzepatide. Tirzepatide is a recently developed drug that attempts to enhance type 2 diabetics' ability to regulate their blood sugar levels and promote weight reduction. Despite its potential benefits, clinical trials have revealed that the medication may lead to gastrointestinal side effects, including nausea, vomiting, decreased appetite, dyspepsia, constipation, and diarrhea. These side effects may negatively affect the drug's efficacy and patient tolerance. A comprehensive search of electronic databases such as PubMed, Web of Science, and Cochrane Library, was conducted to find pertinent studies reporting on the frequency and severity of gastrointestinal symptoms in type 2 diabetes patients receiving tirzepatide. This systematic review follows the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Study selection, data extraction, and quality assessment were performed. Six randomized controlled trials with a total of 4,586 patients were included. Most patients received tirzepatide to regulate their blood sugar levels and promote weight reduction, and the comparators were placebo, glucagon-like peptide one receptor agonists drugs, and insulin degludec. The dose of tirzepatide was 5mg, 10mg, and 15mg weekly. The incidence rate of nausea in patients who receive tirzepatide was 20.43%, while the incidence rate in the comparators was 10.47%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 2.90; 95% CI, 1.89 to 4.44; P ≤ 0.00001). The incidence rate of vomiting in patients who receive tirzepatide was 9.05%, while the rate in the comparators was 4.86%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 2.69; 95% CI, 1.67 to 4.36; P ≤ 0.0001). The incidence rate of constipation in patients who receive tirzepatide was 2.54%, while the rate in the comparators was 0.856%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 3.08; 95% CI, 1.83 to 5.20; P ≤ 0.0001). The incidence rate of decreased appetite in patients who receive tirzepatide was 9.64%, while the rate in the comparators was 2.88%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 5.04; 95% CI, 3.01 to 8.45; P ≤ 0.00001). The incidence rate of diarrhea in patients who receive tirzepatide was 16.24%, while the rate in the comparators was 8.63%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 2.07; 95% CI, 1.60 to 2.68; P ≤ 0.00001). The incidence rate of dyspepsia in patients who receive tirzepatide was 7.13%, while the rate in the comparators was 3.31%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 2.52; 95% CI, 1.58 to 4.01; P ≤ 0.0001). Tirzepatide usage is linked to a significant prevalence of gastrointestinal symptoms, including nausea, constipation, decreased appetite, dyspepsia, diarrhea, and vomiting, in people with type 2 diabetes. These findings may influence clinical decision-making and patient counseling on the use of tirzepatide and have significant implications for the medication's tolerance and efficacy. To find ways to reduce these negative effects and improve therapy for type 2 diabetes patients, more research is required.

Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review.

BACKGROUND: Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most common complication of IEIs and children can acquire coronavirus disease 2019 (COVID-19) even when protective measures are taken. OBJECTIVES: To estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with IEIs and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with IEIs with COVID-19 illness. METHODS: For this systematic review, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline for studies on the development of COVID-19 in children with IEIs, published from December 1, 2019 to February 28, 2023, with English language restriction. RESULTS: Of the 1095 papers that were identified, 116 articles were included in the systematic review (73 case report, 38 cohort 4 case-series and 1 case-control studies). Studies involving 710 children with IEIs with confirmed COVID-19 were analyzed. Among all 710 IEIs pediatric cases who acquired SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 119, 16.8%), intubated and placed on mechanical ventilation (n = 87, 12.2%), suffered acute respiratory distress syndrome (n = 98, 13.8%) or died (n = 60, 8.4%). Overall, COVID-19 in children with different IEIs patents resulted in no or low severity of disease in more than 76% of all included cases (COVID-19 severity: asymptomatic = 105, mild = 351, or moderate = 88). The majority of children with IEIs received treatment for COVID-19 (n = 579, 81.5%). Multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 in children with IEIs occurred in 103 (14.5%). Fatality in children with IEIs with COVID-19 was reported in any of the included IEIs categories for cellular and humoral immunodeficiencies (n = 19, 18.6%), immune dysregulatory diseases (n = 17, 17.9%), innate immunodeficiencies (n = 5, 10%), bone marrow failure (n = 1, 14.3%), complement deficiencies (n = 1, 9.1%), combined immunodeficiencies with associated or syndromic features (n = 7, 5.5%), phagocytic diseases (n = 3, 5.5%), autoinflammatory diseases (n = 2, 3%) and predominantly antibody deficiencies (n = 5, 2.5%). Mortality was COVID-19-related in a considerable number of children with IEIs (29/60, 48.3%). The highest ICU admission and fatality rates were observed in cases belonging to cellular and humoral immunodeficiencies (26.5% and 18.6%) and immune dysregulatory diseases (35.8% and 17.9%) groups, especially in children infected with SARS-CoV-2 who suffered severe combined immunodeficiency (28.6% and 23.8%), combined immunodeficiency (25% and 15%), familial hemophagocytic lymphohistiocytosis (40% and 20%), X-linked lymphoproliferative diseases-1 (75% and 75%) and X-linked lymphoproliferative diseases-2 (50% and 50%) compared to the other IEIs cases. CONCLUSION: Children with IEIs infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the immunocompetent pediatric populations. Underlying immune defects does seem to be independent risk factors for severe SARS-CoV-2 infection in children with IEIs, a number of children with SCID and CID were reported to have prolonged infections-though the number of patients is small-but especially immune dysregulation diseases (XLP1 and XLP2) and innate immunodeficiencies impairing type I interferon signalling (IFNAR1, IFNAR2 and TBK1).

Distribution of corneal densitometry in different grades of keratoconus.

Purpose: To evaluate the use of Scheimpflug tomography in corneal densitometry (CD) in comparing the stages of keratoconic eyes. Methods: Keratoconic (KC) corneas (stages 1-3 classified according to the topographic parameters) were examined using the Scheimpflug tomographer (Pentacam, Oculus) using the CD software. CD was measured over three different depths (anterior stromal layer [120 µm], posterior stromal layer [60 µm], and middle stromal layer between these two layers), and concentric annular zones (0.0 to 2.0, 2.0 to 6.0, 6.0 to 10.0, and 10.0 to 12.0 mm diameter area). Results: The study participants were divided into three groups: keratoconus (KC) stage 1 (KC1) with 64 participants, keratoconus stage 2 (KC2) with 29 participants, and keratoconus stage 3 (KC3) with 36 participants. Comparing CD of all three layers (anterior, central, and posterior) of the cornea over different circular annuli (0-2, 2-6, 6-10, and 10-12 mm) revealed a significant difference in the 6-10 mm annulus between all groups and in all layers (P = 0.3, 0.2, and 0.2, respectively). Area under curve (AUC) was done. It revealed that the central layer showed the highest specificity (93.8%) in comparing KC1 and KC2, whereas CD in the anterior layer between KC2 and KC3 had the highest specificity (86.2%). Conclusion: CD showed increased values in the anterior corneal layer and in the annulus 6-10 mm more than other locations in all stages of KC.

Etiology of Pediatric Uveitis in a Tertiary Pediatric Eye Hospital in Egypt.

PURPOSE: To report the causes of childhood-onset uveitis in a tertiary pediatric ophthalmology hospital in Egypt. METHODS: Retrospective study of the medical records of all uveitis patients following up at a tertiary pediatric ophthalmology hospital in Egypt from January 2017 to December 2020. RESULTS: The present study included 388 patients. The most common anatomical category was intermediate uveitis (30.4%), and around half of these children had pars planitis. This was followed by panuveitis (25.5%), posterior uveitis (23.5%), and anterior uveitis (20.6%), in decreasing frequency. Juvenile idiopathic arthritis, toxoplasmosis, and Vogt-Koyanagi-Harada syndrome were the most common causes of anterior uveitis, posterior uveitis, and panuveitis respectively. Cataract (40.5%), glaucoma (33.8%), and cystoid macular edema (31.6%) were the most frequent ocular complications. CONCLUSION: The present report provides the relative prevalence of the different anatomical types of uveitis, as well as their main causes in a cohort of Egyptian patients with childhood-onset uveitis.

Urinary Bladder Traversed by Peritoneal Dialysis Catheter and Discovered Accidently During Living Donor Kidney Transplant: A Case Report and Review of the Literature.

Peritoneal dialysis is a well-established renal replacement therapy for end-stage renal disease. Insertion of a peritoneal dialysis catheter has inherent complication risks. We present a case of a triple-cuff peritoneal dialysis catheter that traversed the urinary bladder on its way to its final destination and was discovered 3 months later during living donor kidney transplant. We observed a 22-year-old male patient on peritoneal dialysis who was admitted for living related kidney transplant. Intraoperatively, we discovered that the well-functioning peritoneal dialysis catheter was inserted through the urinary bladder. Diagnostic intraoperative cystogram and cystoscopy were conducted. Open removal of the peritoneal dialysis catheter and repair of entry and exit sites were performed. The postoperative course was uneventful, and the patient was discharged 11 days postoperatively with a functioning graft. Bladder catheterization before peritoneal dialysis catheter insertion, even in low-risk patients, is mandatory, to avoid bladder perforation. In addition to the case report, we reviewed the pertinent literature.

Pattern of Uveitis Associated with Behçet's Disease in an Egyptian Cohort.

PURPOSE: To report the clinical experience of uveitis associated with Behçet's disease in a cohort of Egyptian patients. METHODS: The present study is a retrospective analysis of the medical charts of patients with Behçet's disease, who were referred to a tertiary eye care center in Egypt between June 2010 and June 2018. RESULTS: The current study included 1301 eyes of 681 patients with Behçet's disease. The mean age of the patients at the time of referral was 27.2 ± 3.9 years. Panuveitis was the most common presentation. About 28% of all involved eyes had a final visual acuity <20/200, by the last follow-up visit. CONCLUSION: Behçet's disease is an important cause of uveitis in Egypt, and despite the fact that the prognosis of Behçet's uveitis has globally improved in recent years, the visual outcome in Egypt is still not favorable especially in case of delayed referral to tertiary centers.

Mouse monoclonal antibody towards e1 specific epitope blocks viral entry and intracellular viral replication in vitro.

We characterized viral neutralization by a murine monoclonal antibody (mAb315) developed against conserved E1 specific epitope aa 315-323 at pre- and post-binding steps of infection into Huh7 cells. Detection of native virus in infected Huh7 cells by mAb315 were demonstrated by immunostaining. Inhibitions of viral entry by three different concentrations of mAb315 were measured by intracellular amplification of HCV RNA post infection. HCV RNA positive sera from 24 patients were used to infect Huh7 cell line in absence or presence of mouse monoclonal antibody produced in Balb/c mice or culture supernatant of mouse hybrid cells. Monoclonal Ab mAb315 could detect synthetic peptide p315 adsorbed on peripheral human lymphocytes by flow cytometry and showed high immuno reactivity to E1 viral antigen in infected Huh7 cells by immunostaining. Antibody-mediated neutralization assays demonstrated the ability of mAb315 to block HCV binding/entry to target cells at 0.73 mg/mL ascitic fluid or 250 µg/mL culture supernatant of mouse hybrid cells. Sixteen of 24 infected sera could infect Huh7 cells (67%). Binding/entry of HCV was completely blocked by mAb315 in 11/16 cases (69%). These findings suggest that mAb315 can induce HCV neutralization in vitro, which makes it a candidate for developing HCV therapeutic antibodies.