Human norovirus cultivation systems and their use in antiviral research.

Human norovirus (HuNoV) is a major cause of acute gastroenteritis and foodborne diseases, affecting all age groups. Despite its clinical needs, no approved antiviral therapies are available. Since the discovery of HuNoV in 1972, studies on anti-norovirals, mechanism of HuNoV infection, viral inactivation, etc., have been hampered by the lack of a robust laboratory-based cultivation system for HuNoV. A recent breakthrough in the development of HuNoV cultivation systems has opened opportunities for researchers to investigate HuNoV biology in the context of de novo HuNoV infections. A tissue stem cell-derived human intestinal organoid/enteroid (HIO) culture system is one of those that supports HuNoV replication reproducibly and, to our knowledge, is most widely distributed to laboratories worldwide to study HuNoV and develop therapeutic strategies. This review summarizes recently developed HuNoV cultivation systems, including HIO, and their use in antiviral studies.

Protective effects of sodium humate and its zinc and selenium chelate on the oxidative stress, inflammatory, and intestinal barrier damage of Salmonella Typhimurium-challenged broiler chickens.

The objective of this study was to investigate the protective effects and mechanisms of dietary administration of sodium humate (HNa) and its zinc and selenium chelate (Zn/Se-HNa) in mitigating Salmonella Typhimurium (S. Typhi) induced intestinal injury in broiler chickens. Following the gavage of 109 CFU S. Typhi to 240 broilers from 21-d to 23-d aged, various growth performance parameters such as body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), and feed ratio (FCR) were measured before and after infection. Intestinal morphology was assessed to determine the villus height, crypt depth, and chorionic cryptologic ratio. To evaluate intestinal barrier integrity, levels of serum diamine oxidase (DAO), D-lactic acid, tight junction proteins, and the related genes were measured in each group of broilers. An analysis was conducted on inflammatory-related cytokines, oxidase activity, and Nuclear Factor Kappa B (NF-κB) and Nuclear factor erythroid2-related factor 2 (Nrf2) pathway-related proteins and mRNA expression. The results revealed a significant decrease in BW, ADG, and FCR in S. typhi-infected broilers. HNa tended to increase FCR (P = 0.056) while the supplementation of Zn/Se-HNa significantly restored BW and ADG (P < 0.05). HNa and Zn/Se-HNa exhibit favorable and comparable effects in enhancing the levels of serum DAO, D-lactate, and mRNA and protein expression of jejunum and ileal tight junction. In comparison to HNa, Zn/Se-HNa demonstrates a greater reduction in S. Typhi shedding in feces, as well as superior efficacy in enhancing the intestinal morphology, increasing serum catalase (CAT) activity, inhibiting pro-inflammatory cytokines, and suppressing the activation of the NF-κB pathway. Collectively, Zn/Se-HNa was a more effective treatment than HNa to alleviate adverse impact of S. Typhi infection in broiler chickens.

Nanozyme-Enhanced Probiotic Spores Regulate the Intestinal Microenvironment for Targeted Acute Gastroenteritis Therapy.

Antibiotic therapeutics to combat intestinal pathogen infections often exacerbate microbiota dysbiosis and impair mucosal barrier functions. Probiotics are promising strategies, because they inhibit pathogen colonization and improve intestinal microbiota imbalance. Nevertheless, their limited targeting ability and susceptibility to oxidative stress have hindered their therapeutic potential. To tackle these challenges, Ces3 is synthesized by in situ growth of CeO2 nanozymes with positive charges on probiotic spores, facilitating electrostatic interactions with negatively charged pathogens and possessing a high reactive oxygen species (ROS) scavenging activity. Importantly, Ces3 can resist the harsh environment of the gastrointestinal tract. In mice with S. Typhimurium-infected acute gastroenteritis, Ces3 shows potent anti-S. Typhimurium activity, thereby alleviating the dissemination of S. Typhimurium into other organs. Additionally, owing to its O2 deprivation capacity, Ces3 promotes the proliferation of anaerobic probiotics, reshaping a healthy intestinal microbiota. This work demonstrates the promise of combining antibacterial, anti-inflammatory, and O2 content regulation properties for acute gastroenteritis therapy.

Gastrointestinal PCR panel results and antibiotic use in acute gastroenteritis cases: How appropriate are we in our usage?

BACKGROUND: We aimed to determine the pathogens detected by the Gastrointestinal (GI) PCR panel in patients with acute gastroenteritis (AGE), the evaluation of antibiotic use in these patients, and the investigation of the role of laboratory parameters in differentiating viral and bacterial etiologies. METHODS: The demographic characteristics, GI PCR panel results, laboratory investigations, antibiotic usage, and appropriateness of antibiotic treatment were investigated in AGE patients. RESULTS: A total of 175 adult patients with AGE and GI PCR panel results were included in the study. The most common pathogens were EPEC (24.6%) and C. difficile (18.3%). Among the 102 patients receiving antibiotic treatment, 34.3% were evaluated as inappropriate antibiotic use. WBC, CRP, procalcitonin, CRP/albumin ratio, and procalcitonin/albumin ratio were found to be significantly higher in cases with bacterial origin. CONCLUSIONS: The utilization of GI PCR panels in AGE patients has revolutionized the field of diagnostics by providing rapid and accurate identification of pathogens. In units without the possibility of GI PCR testing, CRP, procalcitonin, CRP/albumin ratio and procalcitonin/albumin ratio may be useful in the decision of antibiotic treatment.

Effects of probiotics in children with acute gastroenteritis: A systematic review and meta-analysis focusing on probiotics utilized in Japan.

BACKGROUND: Many randomized controlled trials and systematic reviews have evaluated the use of probiotics to treat acute infectious gastroenteritis. However, most probiotic species evaluated in previous large randomized controlled trials are unavailable in Japan. Our objective was to investigate the efficacy of probiotics utilized in Japan for acute gastroenteritis. METHODS: The inclusion criterion was a randomized controlled study that compared probiotics with a placebo to treat children younger than 18 years with acute infectious gastroenteritis. We excluded studies that did not contain the following species available in Japan: Bifidobacterium spp., Lactobacillus acidophilus, Enterococcus faecium, Clostridium butyricum, and Bacillus subtilis and studies in low- or lower-middle-income countries. We searched PubMed, CENTRAL, and Igaku Chuo Zasshi from their inception to November 27, 2022. After the risk of bias assessment, data on diarrhea duration, number of hospitalizations, length of hospital stay, and adverse effects were extracted. RESULTS: Fourteen studies were included in this meta-analysis. Diarrhea lasting longer than 48 h (7 articles, n = 878) was significantly lower in the probiotic group (risk ratio (RR) 0.70, 95 % confidence interval (CI) 0.59-0.83). The duration of diarrhea (14 articles; n = 1761) was 23.45 h (95 % CI 18.22-26.69) shorter in the probiotic group. Duration of hospitalization (6 articles; n = 971) was 17.73 h (95 % CI 6.9-28.56) shorter in the probiotic group. CONCLUSIONS: Although the certainty of evidence is very low, the use of probiotics for acute gastroenteritis in children may improve diarrhea approximately one day earlier. This study was registered with PROSPERO (CRD 42023405559).

Clinical Impact of Multiplex Molecular Diagnostic Testing in Children With Acute Gastroenteritis Presenting to an Emergency Department: A Multicenter Prospective Study.

BACKGROUND: Multiplex molecular diagnostic panels have greatly enhanced detection of gastrointestinal pathogens. However, data on the impact of these tests on clinical and patient-centered outcomes are limited. METHODS: We conducted a prospective, multicenter, stepped-wedge trial to determine the impact of multiplex molecular testing at 5 academic children's hospitals on children presenting to the emergency department with acute gastroenteritis. Caregivers were interviewed on enrollment and 7-10 days after enrollment to determine symptoms, risk factors, subsequent medical visits, and impact on family members. During the pre-intervention period, diagnostic testing was performed at the clinician's discretion . During the intervention period, multiplex molecular testing was performed on all children, with results available to clinicians. The primary outcome was return visits to a healthcare provider within 10 days of enrollment. RESULTS: Potential pathogens were identified by clinician-ordered tests in 19 of 571 (3.3%) in the pre-intervention period compared with 434 of 586 (74%) in the intervention period; clinically relevant pathogens were detected in 2.1% and 15%, respectively. In the multivariate model, the intervention was associated with a 21% reduction in the odds of any return visit (odds ratio, 0.79; 95% confidence interval, .70-.90) after adjusting for potential confounders. Appropriate treatment was prescribed in 11.3% compared with 19.6% during the intervention period (P = .22). CONCLUSIONS: Routine molecular multiplex testing for all children who presented to the ED with acute gastroenteritis detected more clinically relevant pathogens and led to a 21% decrease in return visits. Additional research is needed to define patients most likely to benefit from testing. Clinical Trials Registration. NCT02248285.

Listeria sepsis in a child.

In this case report, a previously healthy six-year-old presented with fever and altered mental status, and was found to have bacteremia with Listeria monocytogenes, acquired from premade fish balls. Invasive L. monocytogenes infection usually occurs in immunocompromised or newborns but may occasionally occur in healthy children with food-borne gastroenteritis. L. monocytogenes should be considered in patients with severe infection and symptoms of gastroenteritis, particularly since ceftriaxone, the Danish standard treatment for meningitis in children, does not cover L. monocytogenes.

Severe Immune-Related Enteritis after In Utero Exposure to Pembrolizumab.

Immune checkpoint blockade has become standard treatment for many types of cancer. Such therapy is indicated most often in patients with advanced or metastatic disease but has been increasingly used as adjuvant therapy in those with early-stage disease. Adverse events include immune-related organ inflammation resembling autoimmune diseases. We describe a case of severe immune-related gastroenterocolitis in a 4-month-old infant who presented with intractable diarrhea and failure to thrive after in utero exposure to pembrolizumab. Known causes of the symptoms were ruled out, and the diagnosis of pembrolizumab-induced immune-related gastroenterocolitis was supported by the results of histopathological assays, immunophenotyping, and analysis of the level of antibodies against programmed cell death protein 1 (PD-1). The infant's condition was successfully treated with prednisolone and infliximab.

Standardization of an antiviral pipeline for human norovirus in human intestinal enteroids demonstrates nitazoxanide has no to weak antiviral activity.

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis. In immunocompetent hosts, symptoms usually resolve within 3 days; however, in immunocompromised persons, HuNoV infection can become persistent, debilitating, and sometimes life-threatening. There are no licensed therapeutics for HuNoV due to a near half-century delay in its cultivation. Treatment for chronic HuNoV infection in immunosuppressed patients anecdotally includes nitazoxanide, a broad-spectrum antimicrobial licensed for treatment of parasite-induced gastroenteritis. Despite its off-label use for chronic HuNoV infection, nitazoxanide has not been clearly demonstrated to be an effective treatment. In this study, we standardized a pipeline for antiviral testing using multiple human small intestinal enteroid lines representing different intestinal segments and evaluated whether nitazoxanide inhibits replication of five HuNoV strains in vitro. Nitazoxanide did not exhibit high selective antiviral activity against any HuNoV strain tested, indicating it is not an effective antiviral for HuNoV infection. Human intestinal enteroids are further demonstrated as a model to serve as a preclinical platform to test antivirals against HuNoVs to treat gastrointestinal disease. Abstr.

Érase una vez una niña y su lindo gatito / Once upon a time there was a girl and her cute kitty

Introducción: Campylobacter es el principal patógeno de gastroenteritis transmitida por alimentos, ocurriendo generalmente por la ingesta de pollo mal cocinado, constituyendo otra importante fuente de infección los cachorros de animales domésticos. Caso clínico: escolar con gastroenteritis aguda con sospecha diagnóstica inicial de giardiasis por ambiente epidémico (gato doméstico). Se recoge coprocultivo en el que se detecta Campylobacter jejuni, prescribiéndose azitromicina, dado lo prolongado de la clínica. A lo largo del control evolutivo en el centro de salud la familia informa de que se ha solicitado nueva muestra de heces en el gato, dado persistencia de los síntomas pese a tratamiento con metronidazol. Finalmente, crece también Campylobacter jejuni en el coprocultivo de la mascota. Tras finalizar ambos el tratamiento antibiótico, permanecen asintomáticos. Como posible alimento sospechoso del origen del cuadro está el corazón de pollo no cocinado con el que alimentaban al gato de forma habitual. Conclusiones: ante un cuadro de gastroenteritis aguda es fundamental una adecuada anamnesis que incluya ambiente epidémico y alimentos sospechosos. En ocasiones las mascotas también constituyen una fuente de transmisión de la infección a nuestros pacientes. En este caso se sospecha la cadena de contaminación: corazón de pollo no cocinado-heces de gato doméstico-niña (AU)

Introduction: Campylobacter is a well-known food-borne pathogen that causes human gastroenteritis. The most common way for children to become infected with campylobacteriosis is through chicken that is not fully cooked, another important source of infection are domestic puppies.Case report: it is presented the case of an eight-year-old girl with acute gastroenteritis, the first diagnostic suspicion was giardiasis due to epidemic environment (domestic cat). A stool culture was collected in which Campylobacter jejuni was detected. Azithromycin was prescribed because of prolonged symptoms. Throughout the control in the health center, family reported that a new fecal sample has been requested from the cat due to the persistence of the symptoms despite treatment with metronidazole. Finally, Campylobacter jejuni also grew in the pet's stool culture. After both finished antibiotic treatment, they remained asymptomatic. The possible suspected infection source was the chicken heart with which the cat was regularly fed. Conclusions: the evaluation of the child with acute gastroenteritis begins with a careful history which includes epidemiological environment and suspicious food intake. Ocassionally, pets are also a source of transmission to our patients. In this case, the suspected contamination chain was: uncooked chicken heart- domestic cat faeces-girl. (AU)

Anti-infective treatment of gastro-intestinal tract infections in children.

Gastroenteritis is most often viral in origin and Rotavirus and Norovirus most frequently implicated in young children. Stool-based multiplex Polymerase Chain Reaction (PCR) can detect bacteria, viruses or parasites that may or may not be responsible for gastroenteritis (colonization). While the etiological profile of these digestive infections has greatly benefited from PCR, in the absence of underlying pathologies the presence of potential pathogens does not justify anti-infectious treatment. Indeed, very few bacterial causes require antibiotic treatment, apart from shigellosis, severe forms of salmonellosis and a few Campylobacter sp. infections. The development of antibiotic resistance in Salmonella sp., Shigella sp. and Campylobacter sp. is a cause for concern worldwide, limiting therapeutic options. The antibiotics proposed in this guide are in line with the joint recommendations of the European Society of Pediatric Infectious Diseases and the European Society of Pediatric Gastroenterology and Nutrition. Azithromycin is preferentially used to treat infections with Shigella sp. or Campylobacter sp. Ceftriaxone and ciprofloxacin are recommended for salmonellosis requiring antibiotic therapy. Empirical treatments without bacterial identification are not indicated except in cases of severe sepsis or in subjects at risk (e.g., sickle-cell disease). Metronidazole should be prescribed only for acute intestinal amebiasis after microbiological confirmation.

Racecadotril for the treatment of acute gastroenteritis in children received outpatient care in Qatar

Introduction: Acute gastroenteritis is a clinical syndrome often defined by increased stool frequency (eg, ≥3 loose or watery stools in 24 hours, also it is one of the most common causes of morbidity and mortality in children under 5 years in the developing world. Racecadotril is an antisecretory agent that can prevent fluid/electrolyte depletion from the bowel as a result of acute diarrhea without affecting intestinal motility. Research question or hypothesis: To investigate whether prescribing Racecadotril plus oral rehydrating solution in outpatient care helps to decrease the hospital revisit rate within 72 hours due to acute gastroenteritis in comparison with oral rehydrating solution alone. Study design: Retrospective cohort study. Methods: Pediatric patients aged 3 months to 14 years visited Al Wakra Pediatric emergency department due to acute gastroenteritis for outpatient care in the period between 1/1/2022 till 30/06/2022 were included. Case group was defined as patients who prescribed oral rehydrating solution plus Racecadotril upon their initial visit. Control group was defined as patients who prescribed only oral rehydrating solution upon their initial visit. Results: 2505 pediatric patients were included, 520 patients were enrolled in the control group, and 1985 patients were included in the case group. Most patients in both groups were 1 to 5 years old (67% in control group, and 59% in case group). The hospital revisit rate within 72 hours due to gastroenteritis was slightly less in case group 7.1% in comparison with 7.5% in control group (Relative risk 0.95, 95% CI 0.68 to 1.34). Most patients (88%) who revisited the hospital due to gastroenteritis within 72 hours showed no or mild signs of clinical dehydration in their initial visit (77% in control group, and 93% in case group) Conclusion: Racecadotril was found to have insignificant impact on hospital revisit rate in acute pediatric gastroenteritis managed at outpatient setting. (AU)

[Systematic review and Meta-analysis of efficacy and safety of Fengliao Changweikang prescription in treatment of acute gastroenteritis].

This study systematically evaluated the clinical efficacy and safety of Fengliao Changweikang prescription for treating acute gastroenteritis(AGE). The databases of CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library and two clinical trial registration platforms were retrieved from inception to August 30, 2022, to collect randomized controlled trial(RCT) on Fengliao Changweikang prescription treating AGE. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment according to pre-established inclusion and exclusion criteria. RevMan 5.4.1 was used for data analysis. Finally, 18 RCTs were included, involving 3 489 patients. Meta-analysis showed that compared with conventional western medicine, Fengliao Changweikang prescription improved the relief rate of abdominal pain(RR=1.27, 95%CI[1.17, 1.38],P<0.000 01); Fengliao Changweikang prescription + conventional western medicine increased the cure rate(RR=1.43, 95%CI[1.12, 1.82], P=0.004), shortened the duration of diarrhoea(RR=-1.65, 95%CI[-2.44,-0.86], P<0.000 1), abdominal pain(RR=-1.46, 95%CI[-2.00,-0.92], P<0.000 01), vomiting(RR=-2.16, 95%CI[-2.51,-1.81], P<0.000 01) and fever(RR=-2.61, 95%CI[-4.00,-1.23], P=0.000 2), down-regulated the level of interleukin-8(IL-8)(RR=-1.07, 95%CI[-1.26,-0.88], P<0.000 01), IL-6(RR=-8.24, 95%CI[-8.99,-7.49], P<0.000 01) and hypersensitive C-reactive protein(hs-CRP)(RR=-3.04, 95%CI[-3.40,-2.69], P<0.000 01) and recurrence of AGE(RR=0.20, 95%CI[0.05, 0.90], P<0.04). In conclusion, Fengliao Changweikang prescription was safe in clinical application. It was beneficial to alleviate the clinical symptoms of diarrhea, abdominal pain, vomiting, and fever, and down-regulate the levels of some serum inflammatory factors in AGE patients. However, considering that few high-quality studies have evaluated the efficacy and safety of Fengliao Changweikang prescription in treatment of AGE, further evidence is needed in the future.

Inhibitory effect of Ephedra herba on human norovirus infection in human intestinal organoids.

Human norovirus (HuNoV) is a major cause of acute gastroenteritis and foodborne diseases worldwide with public health concern, yet no antiviral therapies have been developed. In this study, we aimed to screen crude drugs, which are components of Japanese traditional medicine, ''Kampo'' to see their effects on HuNoV infection using a reproducible HuNoV cultivation system, stem-cell derived human intestinal organoids/enteroids (HIOs). Among the 22 crude drugs tested, Ephedra herba significantly inhibited HuNoV infection in HIOs. A time-of-drug addition experiment suggested that this crude drug more preferentially targets post-entry step than entry step for the inhibition. To our knowledge, this is the first anti-HuNoV inhibitor screen targeting crude drugs, and Ephedra herba was identified as a novel inhibitor candidate that merits further study.

Advances in the development of antivirals for rotavirus infection.

Rotavirus (RV) causes 200,000 deaths per year and imposes a serious burden to public health and livestock farming worldwide. Currently, rehydration (oral and intravenous) remains the main strategy for the treatment of rotavirus gastroenteritis (RVGE), and no specific drugs are available. This review discusses the viral replication cycle in detail and outlines possible therapeutic approaches including immunotherapy, probiotic-assisted therapy, anti-enteric secretory drugs, Chinese medicine, and natural compounds. We present the latest advances in the field of rotavirus antivirals and highlights the potential use of Chinese medicine and natural compounds as therapeutic agents. This review provides an important reference for rotavirus prevention and treatment.

Efficacy of single dose of phenytoin/fosphenytoin in benign convulsions with mild gastroenteritis.

BACKGROUND: This study evaluated the efficacy of a single dose of phenytoin/fosphenytoin (PHT) to control repetitive seizures in children with benign convulsions with mild gastroenteritis (CwG). METHODS: Children aged between 3 months and 5 years with CwG were retrospectively enrolled. Convulsions with mild gastroenteritis were defined as (a) seizures with acute gastroenteritis without fever or dehydration; (b) normal blood laboratory results; and (c) normal electroencephalography and brain imaging findings. Patients were divided into two groups according to whether or not intravenous PHT (10 mg/kg of phenytoin or phenytoin equivalents) was administered. Clinical manifestations and treatment efficacy were evaluated and compared. RESULTS: Ten of 41 children eligible for inclusion received PHT. Compared to children in the non-PHT group, those in the PHT group had a higher number of seizures (5.2 ± 2.3 vs. 1.6 ± 1.0, P < 0.001) and a lower serum sodium level (133.5 ± 3.2 mmol/L vs. 137.2 ± 2.6 mmol/L, P = 0.001). Initial serum sodium levels were negatively correlated with seizure frequency (r = -0.438, P = 0.004). In all patients, seizures were completely resolved with a single dose of PHT. There were no significant adverse effects from PHT. CONCLUSIONS: A single dose of PHT can effectively treat CwG with repetitive seizures. The serum sodium channel may play a role in seizure severity.

Predictors of Adherence to Short-Course Probiotics Among Children with Gastroenteritis who are Enrolled in a Clinical Trial.

BACKGROUND: To improve our understanding of adherence to discharge medications in the ED and within research trials, we sought to quantify medication adherence and identify predictors thereof in children with acute gastroenteritis (AGE). METHODS: We conducted a secondary analysis of a randomized trial of twice daily probiotic for 5 days. The population included previously healthy children aged 3-47 months with AGE. The primary outcome was patient-reported adherence to the treatment regimen, defined a priori as having received >70% of the prescribed doses. Secondary outcomes included predictors of treatment adherence and concordance between patient-reported adherence and the returned medication sachet counts. RESULTS: After excluding participants with missing data on adherence, 760 participants were included in this analysis: 383 in the probiotic arm (50.4%); and 377 in the placebo arm (49.6%). Self-reported adherence was similar in both groups (77.0% in probiotic versus 80.3% in placebo). There was good agreement between self-reported adherence and sachet counts (87% within limits of agreement (-2.9 to 3.5 sachets) on the Bland-Altman plots). In the multivariable regression model, covariates associated with adherence were greater number of days of diarrhea post-emergency department visit, and the study site; covariates negatively associated with adherence were age 12-23 months, severe dehydration and greater total number of vomiting and diarrhea episodes after enrolment. CONCLUSIONS: Longer duration of diarrhea and study site were associated with higher probiotic adherence. Age 12-23 months, severe dehydration and greater number of vomiting and diarrhea episodes post enrolment negatively predicted treatment adherence.

Defining a clinical prediction rule to diagnose bacterial gastroenteritis requiring empirical antibiotics in an emergency department setting: A retrospective review.

BACKGROUND: Gastroenteritis (GE) is a non-specific term for various pathologic states of the gastrointestinal tract. Infectious agents usually cause acute GE. At present, there are no robust decision-making rules that predict bacterial GE and dictate when to start antibiotics for patients suffering from acute GE to the emergency department (ED). We aim to define a clinical prediction rule to aid in the diagnosis of bacterial GE, requiring empirical antibiotics in adult patients presenting to the emergency department with acute GE. METHODS: A two-year retrospective case review was performed on all cases from July 2015 to June 2017 that included patients with acute GE symptoms referred to the ED, after which their stool cultures were performed. The clinical parameters analyzed included patient with comorbid conditions, physical examination findings, historical markers, point-of-care and radiographic tests and other laboratory work. We then used multi-variate logistic regression analysis on each group (bacterial culture-positive GE and bacterial culture-negative GE) to elucidate clinical criteria with the highest yield for predicting bacterial gastroenteritis (BGE). RESULTS: A total of 756 patients with a mean age of 52 years, 52% female and 48% male, respectively, were included in the study. On the basis of the data of these patients, we suggested using a scoring system to delineate the need for empirical antibiotics in patients with suspected bacterial GE based on six clinical and laboratory variables. We termed this the BGE score. A score 0 - 2 points suggests low risk (0.9%) of bacterial GE. A score of 3 - 4 points confers an intermediate risk of 12.0% and a score of 5 - 8 points confers a high risk of 85.7%. A cut-off of  ≥ 5 points may be used to predict culture-positive BGE with a 75% sensitivity and 75% specificity. The area under the receiver operating characteristic (AUROC) for the scoring system (range 0 - 8) was 0.812 (95% CI: 0.780-0.843) p-value < 0.001. CONCLUSION: We suggest using the BGE scoring system (cut-off ≥ 5 points) to delineate the need for empirical antibiotics in patients diagnosed with gastroenteritis. While this is a pilot study, which will require further validation with a larger sample size, our proposed decision-making rule will potentially serve to improve the diagnosis of BGE and thus reduce unnecessary prescription of antibiotics, which will in turn reduce antibiotic-associated adverse events and save on costs worldwide.

Advanced simulations and screening to repurposing a 3C protease inhibitor against the rupintrivir-resistant human norovirus-induced gastroenteritis.

Human norovirus (HuNoV) causes acute viral gastroenteritis in all age groups, and dehydration and severe diarrhea in the elderly. The World Health Organization reports ∼1.45 million deaths from acute gastroenteritis annually in the world. Rupintrivir, an inhibitory medicine against the human rhinovirus C3 protease, has been reported to inhibit HuNoV 3C protease. However, several HuNoV 3C protease mutations have been revealed to reduce the susceptibility of HuNoV to rupintrivir. The structural details behind rupintrivir-resistance of these single-point mutations (A105V and I109V) are not still clear. Hence, in this study, a combination of computational techniques were used to determine the rupintrivir-resistance mechanism and to propose an inhibitor against wild-type and mutant HuNoV 3C protease through structure-based virtual screening. Dynamic structural results indicated the unstable binding of rupintrivir at the cleft binding site of the wild-type and mutant 3C proteases, leading to its detachment. Our findings presented that the domain II of the HuNoV 3C protease had a critical role in binding of inhibitory molecules. Binding energy computations, steered molecular dynamics and umbrella sampling simulations confirmed that amentoflavone, the novel suggested inhibitor, strongly binds to the cleft site of all protease models and has a good structural stability in the complex system along the molecular dynamic simulations. Our in silico study proposed the selected compound as a potential inhibitor against the HuNoV 3C protease. However, additional experimental and clinical studies are required to corroborate the therapeutic efficacy of the compound.

Systematic review and Meta-analysis of efficacy and safety of Fengliao Changweikang prescription in treatment of acute gastroenteritis / 中国中药杂志

This study systematically evaluated the clinical efficacy and safety of Fengliao Changweikang prescription for treating acute gastroenteritis(AGE). The databases of CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library and two clinical trial registration platforms were retrieved from inception to August 30, 2022, to collect randomized controlled trial(RCT) on Fengliao Changweikang prescription treating AGE. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment according to pre-established inclusion and exclusion criteria. RevMan 5.4.1 was used for data analysis. Finally, 18 RCTs were included, involving 3 489 patients. Meta-analysis showed that compared with conventional western medicine, Fengliao Changweikang prescription improved the relief rate of abdominal pain(RR=1.27, 95%CI[1.17, 1.38],P<0.000 01); Fengliao Changweikang prescription + conventional western medicine increased the cure rate(RR=1.43, 95%CI[1.12, 1.82], P=0.004), shortened the duration of diarrhoea(RR=-1.65, 95%CI[-2.44,-0.86], P<0.000 1), abdominal pain(RR=-1.46, 95%CI[-2.00,-0.92], P<0.000 01), vomiting(RR=-2.16, 95%CI[-2.51,-1.81], P<0.000 01) and fever(RR=-2.61, 95%CI[-4.00,-1.23], P=0.000 2), down-regulated the level of interleukin-8(IL-8)(RR=-1.07, 95%CI[-1.26,-0.88], P<0.000 01), IL-6(RR=-8.24, 95%CI[-8.99,-7.49], P<0.000 01) and hypersensitive C-reactive protein(hs-CRP)(RR=-3.04, 95%CI[-3.40,-2.69], P<0.000 01) and recurrence of AGE(RR=0.20, 95%CI[0.05, 0.90], P<0.04). In conclusion, Fengliao Changweikang prescription was safe in clinical application. It was beneficial to alleviate the clinical symptoms of diarrhea, abdominal pain, vomiting, and fever, and down-regulate the levels of some serum inflammatory factors in AGE patients. However, considering that few high-quality studies have evaluated the efficacy and safety of Fengliao Changweikang prescription in treatment of AGE, further evidence is needed in the future.