Uncertainties in the Absence of Data: Use of Pravastatin in Young Children

Learning Objective: Understand that, when risks and benefits of prevention are not fully known, physicians must provide patient decision makers with existing information such as the Number Needed to Treat and the Number Needed to Harm and leave the decision to those whom the intervention will affect

Short bowel syndrome: pathogenesis, clinical presentation and treatment

Aim of review. To present basic information on the short bowel syndrome (SBS) Summary. Patients with the SBS are quite rare in practice of a clinician and, as a rule, require multidisciplinary approach. Most frequently disease manifests by malabsorption signs: diarrhea, weight loss, macro - and micronutrients deficiency, meteorism and abdominal pain. Nevertheless the spectrum and severity of signs considerably vary among patients. The aim of review was to highlight features of pathogenesis, clinical manifestations and treatment of SBS after small intestinal resection for various reasons. Localization and volume of resection, presence of the background affection of the small intestine and other abdominal organs involved in digestion process and also adaptation capacity of the remaining part of the gut fragment are the basic factors that determine severity of SBS and prognosis of patients. Conclusion. SBS prophylaxis is feasible and, taking into account of high disability and mortality rates of such patients, is essential both at preoperative stage, and during surgical intervention. Even at following of all modern guidelines only stabilization of the state is available in part of the SBS patients, while improvement of remaining small intestinal segment function will be impossible. Small intestinal transplantation may be considered as alternative treatment approach in these patients. Key words: short bowel syndrome, malabsorbtion syndrome, diarrhea, rehabilitation, parenteral nutrition

Aerodynamic numerical calculations of air-cooled condensers and dry cooling towers at different wind velocities and multilevel configuration of sections

Multilevel configuration of heat exchange sections of air-cooled condensers and dry cooling towers with a multi-row arrangement are offered. Results of a research of the combined operation of fans and V-shaped heat exchangers by methods of numerical model operation at wind and without it for three-row sections are given. It is shown that in the presence of wind multilevel configuration of heat exchange sections has advantages over single-level configuration

Aerodynamic numerical calculations of air-cooled condensers and dry cooling towers at different wind velocities and multilevel configuration of sections

Multilevel configuration of heat exchange sections of air-cooled condensers and dry cooling towers with a multi-row arrangement are offered. Results of a research of the combined operation of fans and V-shaped heat exchangers by methods of numerical model operation at wind and without it for three-row sections are given. It is shown that in the presence of wind multilevel configuration of heat exchange sections has advantages over single-level configuration

Structure and Metabolic Activity of the Gut Microbiota in Diarrhea-Predominant Irritable Bowel Syndrome Combined with Functional Dyspepsia

Gut dysbiosis presents in many digestive diseases. The aim of this study is to investigate the composition of the gut microbiota and its metabolic activity in patients with diarrhea-predominant irritable bowel syndrome combined with functional dyspepsia (I + D). This study included 60 patients with I + D and 20 healthy controls. Gut microbiota composition was studied using 16S rRNA gene sequencing. The short-chain fatty acids (SCFAs) spectrum was determined via gas–liquid chromatography. Patients with I + D had an increase in the abundance of Holdemanella, Erysipelotrichaceae, Erysipelotrichales, Prevotellaceae, Agathobacter, Slackia, Lactococcus, Pseudomonadaceae, Stenotrophomonas, Xanthomonadaceae, Rhizobiaceae, Erysipelatoclostridiaceae, Lachnospiraceae, and other taxa in addition to a decrease in the abundance of Frisingicoccus, Ralstonia, Burkholderiaceae, Hungatella, Eisenbergiella, Parabacteroides, Peptostreptococcaceae, Merdibacter, Bilophila, Rikenellaceae, Tannerellaceae, Bacteroidaceae, and Flavonifractor in comparison to controls. Patients with I + D showed significantly higher total SCFA content in feces; increased absolute content of acetic acid, propionic acid, butyric acid, and isoacids; and a significant negative shift in the anaerobic index. The relative levels of the main SCFAs and isoacids in the patient group did not differ significantly from those in the control group. The fecal acetate and isoacid levels correlated with the severity of diarrhea. The fecal butyrate level correlated with the severity of flatulence

Effect of Rebamipide on the Intestinal Barrier, Gut Microbiota Structure and Function, and Symptom Severity Associated with Irritable Bowel Syndrome and Functional Dyspepsia Overlap: A Randomized Controlled Trial

Treatment of functional digestive disorders is not always effective. Therefore, a search for new application points for potential drugs is perspective. Our aim is to evaluate the effect of rebamipide on symptom severity, intestinal barrier status, and intestinal microbiota composition and function in patients with diarrheal variant of irritable bowel syndrome overlapping with functional dyspepsia (D-IBSoFD). Sixty patients were randomized to receive trimebutine (TRI group), trimebutine + rebamipide (T + R group), or rebamipide (REB group) for 2 months. At the beginning and end of the study, patients were assessed for general health (SF-36), severity of digestive symptoms (Gastrointestinal Symptom Rating and 7 × 7 scales), state of the intestinal barrier, and composition (16S rRNA gene sequencing) and function (short-chain fatty acid fecal content) of the gut microbiota. The severity of most digestive symptoms was reduced in the REB and T + R groups to levels similar to that observed in the TRI group. The duodenal and sigmoidal lymphocytic and sigmoidal eosinophilic infiltration was decreased only in the REB and T + R groups, not in the TRI group. Serum zonulin levels were significantly decreased only in the REB group. A decrease in intraepithelial lymphocytic infiltration in the duodenum correlated with a decrease in the severity of rumbling and flatulence, while a decrease in infiltration within the sigmoid colon correlated with improved stool consistency and decreased severity of the sensation of incomplete bowel emptying. In conclusion, rebamipide improves the intestinal barrier condition and symptoms in D-IBSoFD. The rebamipide effects are not inferior to those of trimebutine

Ofatumumab versus Teriflunomide in Multiple Sclerosis

BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known. METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume. RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups. CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.)