Potential Adverse Events Reported With the Janus Kinase Inhibitors Approved for the Treatment of Rheumatoid Arthritis Using Spontaneous Reports and Online Patient Reviews

The aim of this study was to analyze the potential adverse events (AEs) caused by Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, and upadacitinib, used to treat rheumatoid arthritis using spontaneous AE reports from the FDA (FAERS) and interpreting them in correlation with those from Korea (KAERS) and an online patient review (WebMD). Potential AEs were identified based on a disproportionality analysis using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and the information component (IC). A total of 23,720 reports were analyzed from FAERS database, of which 91.5% were reports on tofacitinib. Potentially important medical AEs related to infections were reported frequently, as well as thromboembolism-related AEs. The AEs, such as malignancy, interstitial lung diseases, myocardial infarction, and gastrointestinal disorder, also reported. In an online patient review report, the ineffectiveness of the drug and gastrointestinal AEs were frequently reported. Infection with baricitinib and symptoms related to pain or edema due to upadacitinib were the main discomfort experienced by patients. In conclusion, the results of this study highlight the possible safety issues associated with JAK inhibitors. Routine clinical observations and further research using various real-world databases are needed.

Effect of Mentha aquatica L. Extract on Bloating Symptom of Irritable Bowel Syndrome Disease: A Double-Blind Randomized, Placebo-Controlled Study

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that causes abdominal pain, distension, change of bowel habit, bloating, constipation, diarrhea, and mucus discharge along with stools. Although the disease causes long-term and agonizing pain, no ideal cure has been found for it so far. This study aimed to investigate the efficacy and compliance of Mentha aquatica L. extract for the treatment of bloating caused by IBS. This double-blind, randomized, placebo-controlled trial study was conducted in Tooba gastroenterology clinic in Sari, Iran, during 2019 (from January to May). A total of 104 patients with IBS in the age range of 20-80 years were randomly divided into two parallel groups of herbal medicine (MAC-330) and placebo. Study period consisted of a 4 weeks of administration, and 2 weeks of follow-up. IBS-associated symptoms including severity of bloating (as primary outcome) and frequency of defecation and abdominal pain were evaluated using a questionnaire before treatment, 1, 2 and 4 weeks after beginning treatment and 2 weeks after stopping treatment. There were no significant differences between the two groups in terms of their baseline characteristics (p > 0.05). The severity of bloating was significantly reduced in the both groups at fourth week (p < 0.030) and 2 weeks after stopping intervention (sixth week) (p < 0.026). The frequency of defecation has increased with the onset of the intervention until the fourth week of the treatment which was not significant. The abdominal pain reduced during the 4 weeks’ intervention, but it was not significant. Based on the obtained results, MAC-330 could not be used as an effective treatment for patients with IBS in short time; however, it reduces the abdominal bloating and pain in these patients, especially in the long-term use.

Transcriptomic Signatures Associated With Gray Matter Volume Changes in Patients With Functional Constipation

Functional constipation, which belongs to the functional gastrointestinal disorder (FGID), is a common disease and significantly impacts daily life. FGID patients have been progressively proven with functional and structural alterations in various brain regions, but whether and how functional constipation affects the brain gray matter volume (GMV) remains unclear; besides, which genes are associated with the GMV changes in functional constipation is largely unknown. On account of the structural MRI image from the 30 functional constipation patients and 30 healthy controls (HCs), GMV analysis showed that functional constipation patients had significantly decreased GMV in the right orbital prefrontal cortex (OFC), left precentral gyrus (PreG), and bilateral thalamus (THA). Correlation analysis showed that the self-rating depressive scale, patient assessment of constipation quality of life (PAC-QOL), and Wexner constipation scores were negatively correlated with GMV of the OFC and negative correlations between PAC-QOL score and GMV of the bilateral THA. Based on the Allen Human Brain Atlas, a cross-sample spatial correlation was conducted and found that 18 genes’ expression values showed robust correlations with GMV changes in functional constipation patients. These outcomes highlight our recognition of the transcriptional features related to GMV changes in functional constipation and could be regarded as candidates to detect biological mechanisms of abnormality in functional constipation patients.

Scutellariae Radix and Citri Reticulatae Pericarpium Mixture Regulate PPARγ/RXR Signaling in Reflux Esophagitis

Objective. Gastroesophageal reflux disease (GERD) is a gastrointestinal disorder in which stomach contents reflux into the esophagus, causing complications such as mucosal damage. GERD is a very common disease and is on the rise worldwide. The aim of this study was to assess the impact of a Scutellariae Radix and Citri Reticulatae Pericarpium mixture (SC) on esophageal mucosal injury in rats with chronic acid reflux esophagitis (CARE). Methods. After inducing reflux esophagitis through surgery, the group was separated and the drug was administered for 2 weeks: normal rats (Normal, n = 8), CARE-induced rats were treated with distilled water (Control, n = 8), CARE-induced rats were treated with vitamin E 30 mg/kg body weight (VitE, n = 8), CARE-induced rats were treated with SC 100 mg/kg body weight (SC100, n = 8), and CARE-induced rats were treated with SC 200 mg/kg body weight (SC200, n = 8). Results. SC treatment significantly reduced the degree of esophageal mucosal damage, significantly reduced levels of MDA and MPO, and inhibited the activation of the NF-κB inflammatory pathway by activating the PPARγ/RXR pathway. In addition, SC treatment significantly regulated the expression of arachidonic acid-related proteins (COX-1, COX-2, and PGE2) and modulated the MMP/TIMP proteins in reflux esophagitis. Conclusion. Consequently, SC improved the damage to the esophageal mucosa. Also, the anti-inflammatory effects of the SC suggested the inhibition of NF-κB pathway through the activation of the PPARγ/RXR pathway, thereby reducing the expression of inflammation-related cytokines.

Cyclic Vomiting Syndrome in Pediatric Patients: A Review of Therapeutics

Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder that can present quite a challenge to clinicians caring for children with this complex disease. Different therapeutic interventions are recommended for prophylaxis and acute abortive therapy for a CVS attack. The aim of this review is to summarize therapeutic treatment recommendations from the 2008 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHN) Consensus Statement on the Diagnosis and Management of Cyclic Vomiting Syndrome and discuss studies contemporary to this expert recommendation. After an extensive search of medical databases, 8 studies that evaluated therapeutic treatments for CVS were identified. Amitriptyline and cyproheptadine remain the standard of care for prophylaxis. Nutritional supplements such as carnitine and coenzyme Q10 have shown efficacy in decreasing episodes and severity in small studies with high tolerability among patients. The combination of ondansetron and sumatriptan are recommended for abortion of an acute vomiting episode, but other agents such as aprepitant and sedative agents can be considered when vomiting is refractory to initial treatments.

The low-FODMAP diet as an effective tool for managing irritable bowel syndrome – an assessment of adult patients’ knowledge of dietary guidelines

Background. Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder that is driven by the gutbrain axis and affects 1-20% of the population. Most patients note that various foods elicit abdominal symptoms, and they eliminate these products from their diets. A diet that is low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) is currently one of the mainstays in IBS treatment. Objective. The aim of this study was to assess the knowledge of IBS patients about the disease, treatment and the principles of the low-FODMAP diet that can alleviate gastrointestinal symptoms. Material and methods. The participants were adults diagnosed with IBS, the inclusion criteria were: absence of comorbidities requiring an elimination diet, age over 18 years, and consent to participate in the study. The respondents filled out an anonymous questionnaire containing questions about the IBS diagnosis, disease history and treatment, as well as 45 questions assessing the participants’ knowledge about the low-FODMAP diet. Results. In 28% of the cases, IBS was diagnosed by a general practitioner; in nearly 40% of the cases – by a gastroenterology specialist; in 10% of the cases – by a dietitian, whereas the remaining respondents had arrived at the diagnosis independently or with the help of support groups for IBS patients. After diagnosis, only every fourth respondent sought treatment in a gastroenterology clinic. In the studied population, 237 of the respondents had followed to the low-FODMAP diet, and the differentiating factors were sex (p=0.002), place of residence (city with a population higher than 100,000 vs. rural area; p=0.0001) and education (university vs. vocational school p=0.0043). Respondents who had been recently diagnosed with IBS (less than 12 months vs. more than 12 months before the study) were more likely to follow the FODMAP diet. Conclusions. The surveyed population was characterized by high levels of knowledge about the low-FODMAP diet, but many respondents did not strictly comply with dietary guidelines, in particular the duration of each dietary phase. Age was significantly correlated with the respondents’ knowledge, and the participants’ familiarity with low-FODMAP guidelines decreased with age. Nutritional consultations did not significantly improve the respondents’ knowledge about the low-FODMAP diet.

Gut Microbiome and Its Role in the Pathophysiology of Irritable Bowel Syndrome

Irritable bowel syndrome is the most common functional gastrointestinal disorder, affecting up to 9% individuals globally. Although the etiology of this syndrome is likely heterogenous, it presents with its hallmark symptoms of abdominal pain and altered intestinal motility. Moreover, it is considered to be a disorder of the gut-brain interaction, and the microbiome has often been implicated as a central player in its pathophysiology. Patients with irritable bowel syndrome display altered composition and function of the gut microbiota compared to healthy controls. Microbiome directed therapies, such as probiotics, antibiotics and fecal microbiome transplantation, appear to be beneficial for both gut symptoms and psychiatric comorbidities. This review aims to recapitulate the available literature on the microbiome contribution to the pathophysiology and symptoms presentation of irritable bowel syndrome, as well as the current literature on microbiome-targeted treatments for this disease.

Case Report: Clostridium neonatale Bacteremia in a Preterm Neonate With Necrotizing Enterocolitis

Necrotizing enterocolitis is a life-threatening acquired gastrointestinal disorder among preterm neonates and is associated with a high mortality rate and long-term neurodevelopmental morbidity. No etiologic agent has been definitively established; nonetheless, the most implicated bacteria include members of the Clostridium genus. We reported here on a case of Clostridium neonatale bacteremia in a preterm neonate with necrotizing enterocolitis, providing more information regarding the potential role of this bacterium in pathogenesis of necrotizing enterocolitis. We emphasized the sporulating form of C. neonatale that confers resistance to disinfectants usually applied for the hospital environmental cleaning. Further works are needed to establish the causal relationship between the occurrence of NEC and the isolation of C. neonatale, with promising perspectives in terms of diagnostic and therapeutic management.

Relationship Functioning and Gut Microbiota Composition Among Older Adult Couples: Feasibility of Data Collection

An emerging area of research extends work on couple functioning and physical health to gut health, a critical marker of general health and known to diminish with age. As a foray into this area, we conducted a pilot study to determine feasibility of data collection (questionnaires and a stool sample) among older adult couples. Participants were recruited from the community using a variety of methods including social media. Among 41 persons responding with interest across recruitment sources, 32 were contacted for screening. Inclusion criteria were: age 60+, marriage or cohabiting partnership, and English speaking/understanding. Exclusion criteria were a gastrointestinal disorder, receiving enteric nutrition, use of antibiotics (past month), cancer treatment (past 6 months), and a +COVID-19 diagnosis (past 2 months). Among 31 eligible couples, 30 consented. All 60 participants completed questionnaires and provided a stool sample using DNAgenotek’s OMR-200 collection kit, chosen for its ease and because samples can be stored at room temperature for 60 days. Sample characteristics were: M (SD) age = 66.57 (4.78); 53.3% female; 91.7% White; 1.7% Latinx; and 78.3% college-educated. 2 couples were same-sex. 43% reported at least one health condition and 25% reported use of a proton pump inhibitor (which can affect the gut microbiome), though none daily. Relational well-being was moderate-high on average per measures of dyadic adjustment and intimacy. Despite original plans to recruit couples in-person from a retirement community, remote operations were feasible via online assessment and study-coordinated shipping, a necessary yet fruitful shift due to the SARS-CoV-2 pandemic.