Differential Diagnosis of Acute Diarrhea

Acute diarrhea is a condition of increased water stool content, stool volume, and number of bowel movements that lasts less than 14 days. Mild diarrhea is usually self-limiting; however, undertreated moderate to severe diarrhea may cause severe dehydration and lead to hypovolemic shock. In order to prevent severe dehydration and treat patients appropriately, it is crucial for health care providers to determine the right diagnosis of patients with acute diarrhea. This article focuses on pathophysiology, general patient presentation, diagnostic tests and differential diagnosis lists of acute diarrhea to discuss which diagnosis should be made based on patient presentation and objective data.     

Polymerase Chain Reaction and Goldmann-Witmer Coefficient Testing in the Diagnosis of Infectious Uveitis in HIV-Positive and HIV-Negative Patients in South Africa

Purpose: To use polymerase chain reaction (PCR) and Goldmann-Witmer coefficient (GWC) calculation to diagnose infectious uveitis.

Methods: Prospective cross-sectional study.

Results: Twenty-seven of 106 patients had positive PCR and/or GWC results on aqueous humor (AH) sampling and 15 of 27 (55.6%) were HIV-positive. Patients with non-anterior uveitis (NAU) were more likely to be HIV+ (p = 0.005). More than 1 possible pathogen was identified in 9 of 27 patients of whom 7 were HIV+. The final clinical diagnosis was discordant with AH findings in 9 of 27 cases. A positive EBV PCR result was associated with a discordant diagnosis (p = 0.001). All cases of herpetic anterior uveitis (42.9% HIV+) tested PCR-/GWC+ while all cases of herpetic NAU tested PCR+/GWC- (83.3% HIV+). All rubella virus cases were PCR+/GWC+.

Conclusion: PCR is useful to diagnose herpetic NAU in HIV+ patients while GWC is useful to diagnose herpetic anterior uveitis.     

2019 novel coronavirus disease (COVID-19) in Taiwan: Reports of two cases from Wuhan,China

We reported two cases with community-acquired pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who returned from Wuhan, China in January, 2020. The reported cases highlight non-specific clinical presentations of 2019 novel coronavirus disease (COVID-19) as well as the importance of rapid laboratory-based diagnosis.     

Enteric anendocrinosis attributable to a novel Neurogenin-3 variant

Congenital diarrhea and enteropathies (CODEs) are a group of monogenic disorders that often present with severe diarrhea in the first weeks of life. Enteric anendocrinosis (EA), an extremely rare cause of CODE, is characterized by a marked reduction of intestinal enteroendocrine cells (EC). EA is associated with recessively inherited variants in Neurogenin-3 (NEUROG3) gene. Here we investigate a case of a male infant who presented with mysterious severe malabsorptive diarrhea since birth. Thorough clinical assessments and laboratory tests were successful to exclude the majority of differential diagnosis categories. However, the patient's diagnosis was not established until the genetic test using whole-exome sequencing (WES) was performed. We identified a novel homozygous missense disease-causing variant (DCV) in NEUROG3 (c.413C>G, p.Thr138Arg). Moreover, molecular dynamic simulation analysis showed that (p.Thr138Arg) led to a global change of the NEUROG3 orientation affecting its DNA binding capacity. To the best of our knowledge, this is the first time to apply WES to reach a differential diagnosis of patients with CODEs. Our study not only expands our knowledge about NEUROG3 variants and their clinical consequences but also proves that WES is a very effective tool for the diagnosis of CODEs. This might be of value in early diagnosis of diseases and prenatal CODEs detection.     

Collecting and evaluating convalescent plasma for COVID-19 treatment: why and how?

Plasma provided by COVID-19 convalescent patients may provide therapeutic relief as the number of COVID-19 cases escalates steeply worldwide. Prior findings in various viral respiratory diseases including SARS-CoV-related pneumonia suggest that convalescent plasma can reduce mortality, although formal proof of efficacy is still lacking. By reducing viral spread early on, such an approach may possibly downplay subsequent immunopathology. Identifying, collecting, qualifying and preparing plasma from convalescent patients with adequate SARS-CoV-2-neutralizing Ab titres in an acute crisis setting may be challenging, although well within the remit of most blood establishments. Careful clinical evaluation should allow to quickly establish whether such passive immunotherapy, administered at early phases of the disease in patients at high risk of deleterious evolution, may reduce the frequency of patient deterioration, and thereby COVID-19 mortality.     

In the Era of mRNA Vaccines,Is There Any Hope for HIV Functional Cure?

Over 36 million people worldwide are infected with HIV. Antiretroviral therapy (ART) has proven to be highly effective to prevent HIV-1 transmission, clinical progression and death. Despite this success, the number of HIV-1 infected individuals continues increasing and ART should be taken for life. Therefore, there are two main priorities: the development of preventive vaccines to protect from HIV acquisition and achieve an efficient control of HIV infection in the absence of ART (functional cure). In this sense, in the last few years, there has been a broad interest in new and innovative approaches such as mRNA-based vaccines. RNA-based immunogens represent a promising alternative to conventional vaccines because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. Some mRNA-based vaccines platforms against infectious diseases have demonstrated encouraging results in animal models and humans. However, their application is still limited because the instability and inefficient in vivo delivery of mRNA. Immunogens, design, immunogenicity, chemical modifications on the molecule or the vaccine delivery methods are all crucial interventions for improvement. In this review we, will present the current knowledge and challenges in this research field. mRNA vaccines hold great promises as part of a combined strategy, for achieving HIV functional cure.     

Systematic review of drug–drug interactions between rifamycins and anticoagulant and antiplatelet agents and considerations for management

Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%–74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3–5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%–67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.     

Disseminated trichosporonosis with atypical histologic findings in a patient with acute lymphocytic leukemia

We report a case of disseminated Trichosporon asahii in a patient on systemic antifungal therapy who presented with multiple cutaneous nodules suggestive of fungal infection. Histologic features resembled neutrophilic eccrine hidradenitis but staining with periodic acid‐Schiff and Gomori methenamine silver confirmed the clinical diagnosis. This case highlights the importance of maintaining suspicion for trichosporonosis and contextualizing histologic findings within the underlying clinical picture.