Pattern of referral of sick Omani pilgrims from Omani medical mission during hajj 2019 (Preprint)

BACKGROUND Annually, in the month of Dhul hijjah, over 2 million Muslims travel to Saudi Arabia to perform Hajj. Hajj is the biggest mass gathering globally, which creates a significant influence on Hajjes' health. The Omani medical mission is the official delegation from the Omani government to Saudi Arabia to serve the Omani hajjees regarding their health issues. OBJECTIVE This study investigates the referral rate and pattern of diseases among hajjees referred by the Omani medical mission during Hajj 1440 H. METHODS We conducted a cross-sectional study at the Omani Medical missions in Makkah, Madinah, Mina, and Arafat. Data was collected via a predesigned form. All Omani pilgrims presenting to the mission who were referred to local hospitals were included. RESULTS The total number of cases was 5000, of which 106 (2.1%) were referred to local hospitals (21.2 per 1000 hajjees). The most common causes of referral were cardiovascular diseases (23.6%), followed by gastrointestinal disease (17.9%) and trauma (16.9%). Males comprised 60.1%. Their mean age was 47.3 years (SD ±11.27), with the highest referrals in the 51-60 years age group (30%). Over half (55.7%) had co-morbidities. Patients' mean time to reach the clinic was 8.87 min (SD ±6.41), with 65% arriving in 5 min or less. The mean time needed to reach the hospital by ambulance was 11.39 min (SD ±6.6), with 36% arriving within 5 min. Of the referrals, 42% were admitted into hospital. Hospitalization was significantly higher among patients with chest pain (P-value < 0.0057), diabetics (P-value < 0.0001), and patients with Heart Disease (P-value = 0.013). CONCLUSIONS The most common causes for referral of Hajjees from the Omani Medical Mission were cardiovascular diseases, gastrointestinal disease, and trauma. This information should assist the Omani government in planning their medical services in hajj season in future years.

Fecal microbiome profiles of neonatal dairy calves with varying severities of gastrointestinal disease

Gastrointestinal disease (GI) is the most common illness in pre-weaned dairy calves. Studies have associated the fecal microbiome composition with health status, but it remains unclear how the microbiome changes across different levels of GI disease and breeds. Our objective was to associate the clinical symptoms of GI disease with the fecal microbiome. Fecal samples were collected from calves (n = 167) of different breeds (Holstein, Jersey, Jersey-cross and beef-cross) from 4–21 d of age. Daily clinical evaluations assessed health status. Calves with loose or watery feces were diagnosed with diarrhea and classified as bright-sick (BS) or depressed-sick (DS) according to behavior. Calves with normal or semiformed feces and no clinical illness were classified as healthy (H). One hundred and three fecal samples were obtained from consistently healthy calves and 64 samples were from calves with diarrhea (n = 39 BS; n = 25 DS). The V3-V4 region of 16S rRNA gene was sequenced and analyzed. Differences were identified by a linear-mixed effects model with a negative binomial error. DS and Jersey calves had a higher relative abundance of Streptococcus gallolyticus relative to H Holstein calves. In addition, DS calves had a lower relative abundance of Bifidobacterium longum and an enrichment of Escherichia coli. Species of the genus Lactobacillus, such as an unclassified Lactobacillus, Lactobacillus reuteri, and Lactobacillus salivarius were enriched in calves with GI disease. Moreover, we created a model to predict GI disease based on the fecal microbiome composition. The presence of Eggerthella lenta, Bifidobacterium longum, and Collinsella aerofaciens were associated with a healthy clinical outcome. Although lactobacilli are often associated with beneficial probiotic properties, the presence of E. coli and Lactobacillus species had the highest coefficients positively associated with GI disease prediction. Our results indicate that there are differences in the fecal microbiome of calves associated with GI disease severity and breed specificities.

Development and Validation of a Novel Microbiome-Based Biomarker of Post-antibiotic Dysbiosis and Subsequent Restoration

Background: The human gut microbiota are important to health and wellness, and disrupted microbiota homeostasis, or “dysbiosis,” can cause or contribute to many gastrointestinal disease states. Dysbiosis can be caused by many factors, most notably antibiotic treatment. To correct dysbiosis and restore healthier microbiota, several investigational microbiota-based live biotherapeutic products (LBPs) are in formal clinical development. To better guide and refine LBP development and to better understand and manage the risks of antibiotic administration, biomarkers that distinguish post-antibiotic dysbiosis from healthy microbiota are needed. Here we report the development of a prototype Microbiome Health Index for post-Antibiotic dysbiosis (MHI-A).Methods: MHI-A was developed and validated using longitudinal gut microbiome data from participants in clinical trials of RBX2660 and RBX7455 – investigational LBPs in development for reducing recurrent Clostridioides difficile infections (rCDI). The MHI-A algorithm relates the relative abundances of microbiome taxonomic classes that changed the most after RBX2660 or RBX7455 treatment, that strongly correlated with clinical response, and that reflect biological mechanisms believed important to rCDI. The diagnostic utility of MHI-A was reinforced using publicly available microbiome data from healthy or antibiotic-treated populations.Results: MHI-A has high accuracy to distinguish post-antibiotic dysbiosis from healthy microbiota. MHI-A values were consistent across multiple healthy populations and were significantly shifted by antibiotic treatments known to alter microbiota compositions, shifted less by microbiota-sparing antibiotics. Clinical response to RBX2660 and RBX7455 correlated with a shift of MHI-A from dysbiotic to healthy values.Conclusion: MHI-A is a promising biomarker of post-antibiotic dysbiosis and subsequent restoration. MHI-A may be useful for rank-ordering the microbiota-disrupting effects of antibiotics and as a pharmacodynamic measure of microbiota restoration.

Predictive factors for the surgical treatment of necrotizing enterocolitis in preterm infants: a single-center retrospective study

Background Necrotizing enterocolitis (NEC) is a gastrointestinal disease that tends to occur in premature infants. Some features may be associated with an increased probability that preterm infants with NEC will require surgical treatment. This study aimed to identify the factors that increased the probability of surgical treatment in infants with NEC. Methods We retrospectively analyzed the data of premature infants with NEC who were hospitalized at The Affiliated Hospital of Qingdao University from April 2011 to April 2021. According to the treatments received, these patients were divided into medical NEC group and surgical NEC group. The perinatal characteristics, clinical manifestations, and laboratory values before the onset of NEC were subjected to univariate and multivariate analyses. Results A total of 623 preterm infants with NEC (> Bell’s stage I) were included in this study, including 350 (56%) who received surgical treatment and 273 (44%) who received conservative medical treatment. Multivariate analysis showed that lower gestational age (P = 0.001, odds ratio (OR) (95% CI) = 0.91[0.86–0.96]), early occurrence of NEC (P = 0.003, OR (95% CI) = 0.86 [0.77–0.95]), hemodynamically significant patent ductus arteriosus (P = 0.003, OR (95% CI) = 7.50 [2.03–28.47]), and low serum bicarbonate (P = 0.043, OR (95% CI) = 0.863 [0.749–0.995]) were associated with an increased probability of surgical treatment in preterm infants with NEC. Conclusions Our findings were applied to identify potential predictors for surgical treatment in preterm infants with NEC, which may facilitate early decisive management.

Terazosin Stimulates Pgk1 to Remedy Gastrointestinal Disorders

Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them, the most frequent diseases are gastric ulcer (GU) and ulcerative colitis (UC). DSS-induced UC and ethanol-stimulated GU models resemble the pathophysiology of human gastrointestinal disease. The current study was designed to explore the anti-oxidation, anti-inflammation, anti-cell death properties of terazosin, an α-adrenergic receptor antagonist, in vivo and in vitro. Our results indicate that terazosin dramatically activates Pgk1, and upregulates glycose metabolism, evidenced by the enhanced ATP production and higher LDH enzymatic activity. Also, terazosin significantly enhances p-AKT expression and inhibits NF-κB p65 activation through abrogating the phosphorylation of IKBα, as well as lowers Caspase-1 and GSDMD expression. The findings in this study demonstrate that terazosin exhibits anti-inflammatory effects by downregulating NF-κB-GSDMD signal pathway, along with enhancing glycolysis for gastrointestinal disease treatment. Meanwhile, we also find terazosin ameliorates ethanol-induced gastric mucosal damage in mice. Collectively, as a clinical drug, terazosin should be translated into therapeutics for gastrointestinal disease soon.

Health Problems Among Forcibly Displaced Myanmar Nationals (FDMNs) Admitted To The Medicine Ward of Cox’s Bazar Medical College Hospital

Background Forcibly displaced Myanmar nationals (FDMNs) or Rohingya refugees are one of the vulnerable groups suffering from different kinds of health problems but have been less reported yet. Therefore, the study was designed to delineate the health problems among FDMNs admitted to Cox’s Bazar Medical College Hospital. Methods This hospital-based cross-sectional study was conducted at the Medicine ward, Cox’s Bazar Medical College Hospital, for a six-month period following approval. Rohingya refugees who were admitted during the study period were approached for inclusion. Informed written consent was ensured prior to participation. A structured questionnaire was used during data collection. Collected information was recorded in case record form. A total of 290 subjects were interviewed. Analysis was performed using the statistical package for social science (SPSS) version 20. Results The mean age of the participants was 48.76±18.67 years (range: 16-91), with a clear male predominance (60.7%). Family size ranged 6-8. All of the participants reported at least one of the illnesses. Of all, 29.66% patients reported disease of the respiratory system, and 26.9% reported disease of the gastrointestinal disease and hepatobiliary system. Accidental injury or injury due to electrocution or thin falls or snake bites was present in 10.4% of the cases. Among the single most common diseases, COPD (20%) was the most frequently observed, and the rest of them were chronic liver disease (13.1%), pulmonary TB (5.5%), ischemic stroke (5.5%), CAP (4.1%), acute coronary syndrome (3.4%), thalassaemia (3.4%) and hepatocellular carcinoma (3.4%). Among the top 6 reported diseases, PTB was more common in elderly individuals (p=0.29). The disease pattern was similar across the sexes among the refugees except community acquisition pneumonia (CAP), which was commonly observed among males (p=.004). Considering different age groups, genitourinary problems were more common in males aged >60 years, and rheumatology and musculoskeletal problems were equally affected in females aged between 40-60 years. Conclusion COPD, CLD and CAP were the most prevalent diseases in FDMN patients who attended the medicine ward of Cox’s Bazar Medical College Hospital. Further exploration is warranted before any policy making and comprehensive plan.

Establishing the Molecular Diagnoses in a Cohort of 291 Patients With Predominantly Antibody Deficiency by Targeted Next-Generation Sequencing: Experience From a Monocentric Study

Predominantly antibody deficiencies (PAD) are a heterogeneous group of disorders characterized by dysfunctional antibody production, low immunoglobulin levels in serum and impaired vaccine responses. The clinical picture is variable, ranging from mild symptoms to severe complications, which may include autoimmunity, gastrointestinal disease, allergy, and malignancies. If left untreated, PAD patients are at risk of enduring disease progression, irreversible organ damage, and reduced life expectancy. A timely diagnosis has been shown to significantly improve disease prognosis. Here, we report on our experience using targeted gene panel sequencing by employing Agilent’s HaloPlex or SureSelect and Illumina’s MiSeq technologies in a cohort of 291 individuals who presented with low or absent immunoglobulin levels in combination with or without other clinical features. In total, we have detected over 57 novel or previously reported relevant mutations in ADA, ADA2, BTK, CTLA4, LRBA, NFKB1, NFKB2, PIK3CD, STAT3, and TNFRSF13B. Overall, a genetic diagnosis could be made in 24.7% of the investigated patients. The percentage of coverage for the targeted regions ranged from 90% to 98% in this study. Moreover, functional assays were performed on a defined group of the patients carrying candidate variants in CTLA4, LRBA, NFKB1 and BTK, which confirmed their deleterious effect on protein expression and/or function. This study reiterates that the immunological heterogeneity of predominantly antibody deficiencies may have a diverse genetic origin, although certain clinical features may hint towards a specific group of defects. Employing targeted sequencing panels proves to be a very time- and cost-efficient, yet reliable, method for the establishment of a genetic diagnosis in individuals with PAD. However, in case of negative panel results, or if functional testing reveals inconspicuous observations in patients with a clear indication for genetic testing, further work-up including whole exome or whole genome sequencing should be considered.

The Immuno-Modulation Effect of Macrophage-Derived Extracellular Vesicles in Chronic Inflammatory Diseases

As natural nanocarriers and intercellular messengers, extracellular vesicles (EVs) control communication among cells. Under physiological and pathological conditions, EVs deliver generic information including proteins and nucleic acids to recipient cells and exert regulatory effects. Macrophages help mediate immune responses, and macrophage-derived EVs may play immunomodulatory roles in the progression of chronic inflammatory diseases. Furthermore, EVs derived from various macrophage phenotypes have different biological functions. In this review, we describe the pathophysiological significance of macrophage-derived extracellular vesicles in the development of chronic inflammatory diseases, including diabetes, cancer, cardiovascular disease, pulmonary disease, and gastrointestinal disease, and the potential applications of these EVs.