Gastrointestinal Adverse Reactions Research Articles

#1579 The effectiveness and safety of sucroferric oxyhydroxide in the treatment of hyperphosphatemia in dialysis patients: a systematic review

Abstract Background and Aims Hyperphosphatemia is an independent prognostic factor for mortality in dialysis patients. The most widely used phosphate binders are sevelamer and lanthanum carbonate. Poor compliance may be due to high pill burden and gastrointestinal adverse reactions. Some previous studies on sucroferric oxyhydroxide showed a potential reduction of phosphorus levels and pill burden. This study aims to determine the effectiveness and safety profile of sucroferric oxyhydroxide in the control of hyperphosphatemia in dialysis-dependent patients. Method A systematic search was conducted in the Cochrane Library, MEDLINE, TRIP Database, and ClinicalTrials.gov until Jan 8, 2024. All randomized controlled trials on the use of sucroferric oxyhydroxide for the treatment of hyperphosphatemia in adult dialysis patients were included. The comparator groups considered were sevelamer or lanthanum. The outcomes of interest were post-treatment serum phosphorus level, the change of serum phosphorus level from baseline, hemoglobin level, ferritin level, transferrin saturation level, adverse events, serious adverse events, and all-cause mortality. Two authors independently searched for articles, screened the articles for inclusion, and appraised the articles using the REVMAN risk of bias table. The GRADE was used to assess the certainty of evidence. In case of a disagreement, the two authors discussed until a consensus was reached. If a consensus was not reached, an independent third-party reviewer was consulted. Meta-analysis was conducted using Review Manager 5.4.1 software. Results We included 7 RCTs represented by 11 records and a total of 2031 adult dialysis patients with hyperphosphatemia. The usual dose of sucroferric oxyhydroxide is 750 mg-3000 mg/day. Sucroferric oxyhydroxide reduces serum phosphorus levels comparable to that of sevelamer (MD = −0.03 mmol/L, 95% CI −0.10 to 0.03, I2 49%) and of lanthanum (MD = −0.02 mmol/L, 95% CI −0.36 to 33, I2 0%). The decrease in serum phosphorus level from the baseline is also comparable with sevelamer (MD = −0.06 mmol/L, 95% CI −0.13 to 0.00, I2 59%). Sucroferric oxyhydroxide significantly reduces the daily number of tablet intake (MD = −7.09 tablets/day, 95% CI −10.45 to −3.73, p-value < 0.0001, I2 = 99%) compared to sevelamer. The use of sucroferric oxyhydroxide shows significantly higher hemoglobin level (MD = 1.15; 95% CI 0.92 to 1.39, p-value < 0.0001, I2 = 0%), higher transferrin saturation level (MD = 8.33; 95% CI 6.06 to 10.59, p-value < 0.0001, I2 = 0%) and higher ferritin level (MD = 64.16; 95% CI 31.64 to 96.68, p-value 0.0001) compared with the use of sevelamer. Pooled analysis on sucroferric oxyhydroxide showed no significant differences in adverse events (RR = 1.05, 95% CI 0.95 to 1.17, I2 = 47%); serious adverse events (RR = 1.11, 95% CI 0.84 to 1.47, I2 = 0%) and all-cause mortality (RR = 0.94; 95% CI 0.38 to 2.31, I2 = 0%) compared to sevelamer. The most common adverse events reported were nausea, diarrhea, abdominal discomfort, fecal discoloration, and hyperphosphatemia. Conclusion Sucroferric oxyhydroxide is comparable with sevelamer and lanthanum in decreasing serum phosphorus levels. It is also associated with higher hemoglobin, ferritin, and transferrin saturation levels compared with the sevelamer group. Since there are no significant differences in the risks of adverse events, serious adverse events, and all-cause mortality, the decrease in pill burden with sucroferric oxyhydroxide may help improve patient compliance.

Imatinib-induced ulcerative colitis.

Imatinib, a tyrosine kinase inhibitor, is the first-line therapy for patients with KIT mutation in gastrointestinal stromal tumor (GIST). Nausea, vomiting, diarrhea, dyspepsia and abdominal pain are common gastrointestinal adverse reactions of imatinib, but imatinib-induced ulcerative colitis (UC) is rarely reported. We presented a case of UC induced by imatinib in a 56-year-old male patient who experienced this adverse event after 5 years of imatinib 400 mg/d treatment following GIST resection. The patient's diarrhea and bloody stools showed significant improvement following the discontinuation of imatinib therapy and administration of antidiarrheal medications. Then, imatinib was restarted at a daily dosage of 400 mg. UC is a rare adverse event associated with imatinib. Physicians should consider the possibility of UC induced by imatinib when patients present with diarrhea and bloody stool after receiving imatinib treatment. This case offered objective evidence of UC induced by imatinib.

Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials

Introduction: FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3 inhibitors are in clinical trials, and some have been applied in clinic. However, the safety, efficacy and pharmacodynamics of these FLT3 inhibitors have not been systemically analyzed before.Methods: We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023.Results: Our results showed the most common adverse events (AEs) were gastrointestinal adverse reactions, including diarrhea, hand-foot syndrome and nausea, while the most common hematological AEs were febrile neutropenia, anemia, and thrombocytopenia. Based on the published data, the mean overall survival (OS) and the mean progression-free survival (PFS) were 9.639 and 5.905 months, respectively. The incidence of overall response rate (ORR), complete remission (CR), partial response (PR), and stable disease (SD) for all these FLT3 inhibitors was 29.0%, 8.7%, 16.0%, and 42.3%, respectively. The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration (Tmax) in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life (T1/2) range was highly variable, from 6.8 to 151.8 h.Discussion: FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication.

Gastrointestinal adverse reaction to food (GARF) and endoscopic confocal laser endomicroscopy (eCLE).

Gastrointestinal adverse reaction to food (GARF) is reported frequently in the general population and even more in patients with disorders of the gut brain axis. However, there is a significant difference between self-reported and objective proven GARF. The aim of the study was to characterize a mucosal correlate of GARF by endoscopic confocal laser endomicroscopy (eCLE) with duodenal food challenge (DFC). In an observational and proof of concept study we evaluated 71 patients with disorders of the gut brain axis without (group I, n=19) and with (group II, n=52) GARF by eCLE and DFC. Spontaneous and food induced transfer of fluorescein into duodenal lumen was detected 10 minutes following intravenously application of fluorescein and 10 minutes after DFC. According to Rom IV, the patients (group I/II) could be classified as irritable bowel syndrome (IBS) 32%/31%, functional abdominal pain without changes in bowel movement 47 %/48 %, functional abdominal bloating/distension 0 %/10 %, functional diarrhea 5 %/ 2 %, and unspecified functional bowel disorder 16 %/10 %, respectively. 21 %/27 % of the patients responded with a fluorescein leakage into the duodenal lumen before and 74 %/69 % following to DFC. Frequency rank order of food components that induced a response were soy (55.5 %/60 %), wheat (60 %/45.5 %), egg (35.7 %/8.3), milk (30 %/18.2 %) and yeast (10 %/6.6 %), respectively. Histology of duodenal biopsies, number, form and distribution of intraepithelial lymphocytes and mucosal mast cells as well as mast cell function were normal. Overall, 14 %/79 % reported main symptom benefit following a food exclusion therapy according to eCLE and DFC that was significant different between the groups. The results of our study indicate that eCLE with DFC is a technique to clinically evaluate patients with disorders of the gut brain axis and GARF resulting in a high proportion of patients reporting symptom benefit upon food exclusion dietary advice focussed on the results of eCLE.

Integrated models of population pharmacokinetics and exposure response to optimize dosage regimen for anaprazole sodium in duodenal ulcer

Anaprazole sodium enteric-coated tablet is a novel proton pump inhibitor which has been approved for the treatment of duodenal ulcer. The aim of this study is to provide reliable information for the design of an optimal dosage regimen. Population pharmacokinetics and exposure-response models were integrated to evaluate the pharmacokinetic parameters and covariates of Anaprazole and its metabolite M21-1, and subsequently provided dosage suggestions based on clinical trials and simulation data. A pharmacokinetic model incorporating two-compartment for the parent drug and one-compartment for the metabolite, with both first-order and zero-order mixed absorption was used to describe the pharmacokinetics of Anaprazole and M21-1. Age emerged as a significant covariate affecting the elimination rate constant of M21-1, with clearance decreasing as age advances. No correlation was observed between the pharmacokinetics of Anaprazole or M21-1 and the adverse reactions under the current dosages. BMI might be the influence factor of the mild gastrointestinal adverse reactions. Meanwhile, Anaprazole had a good healing rate (94.0 %) in duodenal ulcer patients and the exposure-response analysis indicated that the cured results were not influenced by the exposure parameters of parent drug or metabolite. In conclusion, the drug is safe when dosing between 20 and 100 mg once a day.

Efficacy and Safety of Oral Supplementation with Liposomal Iron in Non-Dialysis Chronic Kidney Disease Patients with Iron Deficiency.

Iron deficiency is common in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Oral iron supplementation is recommended in these patients, but it is associated with a higher incidence of gastrointestinal adverse reactions. Liposomal iron therapy has been proposed as a new iron formulation, improving iron bioavailability with less side effects; however, few data are available in patients with NDD-CKD. We designed a single-arm pilot study to evaluate the efficacy of liposomal iron administered for six months in correcting iron deficiency (defined as serum ferritin < 100 ng/mL and/or transferrin saturation < 20%) in patients with NDD-CKD stages 1-5. The primary endpoints were the achievement of serum ferritin ≥ 100 ng/mL and transferrin saturation ≥ 20%. Secondary outcomes were hemoglobin (Hb) changes and the safety of liposomal iron. The efficacy population included 34/38 patients, who completed at least one visit after baseline. Liposomal iron increased the achievement of transferrin saturation targets from 11.8% at baseline to 50.0% at month 6 (p = 0.002), while no significant correction of serum ferritin (p = 0.214) and Hb was found (p = 0.465). When patients were stratified by anemia (Hb < 12 g/dL in women and Hb < 13 g/dL in men), a significant improvement of transferrin saturation was observed only in anemic patients (from 13.3 ± 5.8% to 20.2 ± 8.1%, p = 0.012). Hb values slightly increased at month 6 only in anemic patients (+0.60 g/dL, 95%CI -0.27 to +1.48), but not in those without anemia (+0.08 g/dL, 95%CI -0.73 to +0.88). In patients taking at least one dose of liposomal iron (safety population, n = 38), the study drug was discontinued in eight patients due to death (n = 2), a switch to intravenous iron (n = 2), and the occurrence of side effects (n = 4). The use of liposomal iron in patients with NDD-CKD is associated with a partial correction of transferrin saturation, with no significant effect on iron storage and Hb levels.

Effect of Transarterial Chemotherapy on the Structure and Function of Gut Microbiota in New Zealand White Rabbits.

The gut microbiota (GM) are closely related to hepatocellular carcinoma (HCC) occurrence and development. Furthermore, patients with HCC who have received transcatheter arterial chemoembolization (TACE) treatment often experience adverse gastrointestinal reactions, which may be related to changes in the GM caused by the chemotherapeutic drugs used in TACE. Therefore, we conducted animal experiments to investigate these changes. We analyzed changes in the GM of New Zealand white rabbits treated with hepatic arterial chemotherapy by measuring the levels of serological and colonic tissue markers. Simultaneously, we evaluated the correlation between the GM and these markers to explore the mechanism by which chemotherapy affects the GM. Following transarterial chemotherapy with epirubicin, the Firmicutes abundance decreased, whereas that of Proteobacteria increased. The relative abundance of beneficial bacteria, such as Muribaculaceae, Enterococcus, Ruminococcus, and Clostridia, decreased in the experimental group compared with those in the control group. However, the relative abundance of harmful bacteria, such as Bacteroides and Escherichia (Shigella), was higher in the experimental group than in the control group. Following chemotherapy, the GM of rabbits showed a dynamic change over time, first aggravating and then subsiding. The changes were most notable on the fourth day after surgery and recovered slightly on the seventh day. The changes in the host's GM before and after arterial chemotherapy are evident. Hepatic arterial chemotherapy induces dysbiosis of the intestinal microbiota, disrupts intestinal barrier function, damages the integrity of the intestinal mucosa, increases intestinal permeability, facilitates excessive passage of harmful substances through the gut-liver axis communication between the liver and intestine, and triggers activation of inflammatory pathways such as LPS-TLR-4-pSTAT3, ultimately leading to an inflammatory response. This study provides a theoretical basis for combining TACE with targeted GM intervention to treat HCC and reduce adverse gastrointestinal reactions.

Aspirin Caused Intestinal Damage through FXR and ET-1 Signaling Pathways.

Aspirin is a non-steroidal, anti-inflammatory drug often used long term. However, long-term or large doses will cause gastrointestinal adverse reactions. To explore the mechanism of intestinal damage, we used non-targeted metabolomics; farnesoid X receptor (FXR) knockout mice, which were compared with wild-type mice; FXR agonists obeticholic acid (OCA) and chenodeoxycholic acid (CDCA); and endothelin-producing inhibitor estradiol to explore the mechanisms of acute and chronic intestinal injuries induced by aspirin from the perspective of molecular biology. Changes were found in the bile acids taurocholate acid (TCA) and tauro-β-muricholic acid (T-β-MCA) in the duodenum, and we detected a significant inhibition of FXR target genes. After additional administration of the FXR agonists OCA and CDCA, duodenal villus damage and inflammation were effectively improved. The results in the FXR knockout mice and wild-type mice showed that the overexpression of endothelin 1 (ET-1) was independent of FXR regulation after aspirin exposure, whereas CDCA was able to restore the activation of ET-1, which was induced by aspirin in wild-type mice in an FXR-dependent manner. The inhibition of ET-1 production could also effectively protect against small bowel damage. Therefore, the study revealed the key roles of the FXR and ET-1 pathways in acute and chronic aspirin-induced intestinal injuries, as well as strategies on alleviating aspirin-induced gastrointestinal injury by activating FXR and inhibiting ET-1 overexpression.

Enteric-coated Mycophenolate Sodium therApy versus cyclophosphamide for induction of Remission in Microscopic PolyAngiitis (EMSAR-MPA trial): study protocol for a randomised controlled trial

IntroductionSeveral studies have demonstrated that mycophenolate mofetil (MMF) may be an excellent alternative to cyclophosphamide (CYC) or rituximab for the induction of remission in non-life-threatening anti-neutrophil cytoplasmic antibodies associated vasculitis...

Clinical characteristics and risk factors analysis of 505 cases of infusion reactions in a tertiary hospital.

Background: The clinical characteristics and risk factors of infusion reactions (IRs) are inadequately described in clinical practice due to underreported cases. In the present study, we reported the current status of IRs based on an in-hospital pharmacovigilance database of a tertiary care hospital. Methods: Our study conducted a retrospective analysis of drug-induced IRs recorded at an in-hospital pharmacovigilance center between January 2015 to December 2019. The descriptive statistical analysis encompassed main causative agents, clinical manifestations, organ/system involvement and outcome. The severity of IRs was assessed with reference to the CTCAE version 5.0 criteria and we investigated risk factors associated with severe IRs. Results: During the study period, a total of 505 cases of inpatient drug-induced IRs were detected, of which 79.2% (400 cases) were classified as general IRs and 20.8% (105 cases) were categorized as severe IRs. The primary drugs responsible for these reactions were antibiotics (23%, 116 cases), with piperacillin sodium-sulbactam sodium being the most prevalent, followed by antineoplastic agents (18.4%, 93 cases) and traditional Chinese medicine injections (TCMIs) (12.9%, 65 cases). The administration of cefoperazone - sulbactam, mannatide, Shenqi Fuzheng, elemene, and diterpene ginkgolides meglumine resulted in a higher incidence of critical IRs. Among all cases of IRs, 43.2%, 41.2%, and 23.4% showed signs and symptoms of circulation, skin mucosa, and respiratory organs/systems, respectively. 9.1% of cases experienced systemic damage, while 7.1% and 5.9% of cases reported neurological and gastrointestinal related adverse reactions, respectively. The multivariate analysis revealed that alcohol consumption (OR = 2.389%, 95% CI 1.141-5.002, p = 0.021), age over 65 (OR = 1.814%, 95% CI 1.052-3.127, p = 0.032) and the utilization of contrast media (OR = 4.072%, 95% CI 1.903-8.713, p < 0.001) were identified as risk factors for the development of severe IRs. Conclusion: Understanding the clinical characteristics of IRs helps to implement effective pharmaceutical monitoring and appropriate preventive measures for susceptible populations with risk factors.

Glucagon-like Peptide-1 Receptor Agonists Associated Gastrointestinal Adverse Events: A Cross-Sectional Analysis of the National Institutes of Health All of Us Cohort.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used diabetes and obesity medications but have been associated with gastrointestinal (GI) adverse events. However, real-world evidence on comparative GI adverse reaction profiles is limited. This study aimed to evaluate GI adverse events among GLP-1 RA users and compare semaglutide, dulaglutide, liraglutide, and exenatide safety regarding the GI adverse reaction profile. This retrospective cross-sectional analysis utilized real-world data on 10,328 adults with diabetes/obesity in the National Institutes of Health All of Us cohort. New GLP-1 RA users were identified, and GI adverse events were examined. Logistic regression determined factors associated with GI adverse events. The mean age of the study population was 61.4 ± 12.6 years, 65.7% were female, 51.3% were White, and they had a high comorbidity burden. Abdominal pain (57.6%) was the most common GI adverse event, followed by constipation (30.4%), diarrhea (32.7%), nausea and vomiting (23.4%), GI bleeding (15.9%), gastroparesis (5.1%), and pancreatitis (3.4%). Dulaglutide and liraglutide had higher rates of abdominal pain, constipation, diarrhea, and nausea and vomiting than semaglutide and exenatide. Liraglutide and exenatide had the highest pancreatitis (4.0% and 3.8%, respectively). Compared to semaglutide, dulaglutide and liraglutide had higher odds of abdominal pain, and nausea and vomiting. They also had higher odds of gastroparesis than semaglutide. No significant differences existed in GI bleeding or pancreatitis risks between the GLP-1 RAs. In this real-world cohort, GI adverse events were common with GLP-1 RAs. Differences in GI safety profiles existed between agents, with exenatide appearing safer than other GLP-1 RAs, except for gastroparesis. These findings can inform GLP-1 RA selection considering GI risk factors. Further studies are needed to evaluate the causal relationship and GLP-1 RA safety with concomitant medication use.

Tirzepatide as a novel effective and safe strategy for treating obesity: a systematic review and meta-analysis of randomized controlled trials.

To systematically evaluate the efficacy and safety of a new hypoglycemic drug, tirzepatide, for treating obesity based on indicators such as BMI, waist circumference, and body weight. A search formula was written using search terms such as "tirzepatide," "overweight," and "obesity." A comprehensive search was conducted on databases such as PubMed, Cochrane Library, Embase, and Web of Science using a computer. Random controlled trial (RCT) literature was selected based on inclusion and exclusion criteria. After extracting the data, literature bias risk assessment and meta-analysis were conducted using RevMan 5.4 software. The search deadline is from the establishment of each database to May 2023. A total of 12 randomized controlled trials were included, with a total of 11,758 patients. Meta analysis results showed that compared with the glucagon like peptide-1 receptor agonist (GLP-1 RAs), placebo and insulin groups, tirzepatide could significantly reduce the BMI (body mass index) of patients [MD = -1.71, 95% CI (-2.46, -0.95), p < 0.00001], [MD = -3.99, 95% CI (-3.69, -2.45), p < 0.00001], [MD = -4.02, 95% CI (-4.72, -3.31), p < 00.00001]. In terms of decreasing waist circumference, tirzepatide has a more significant advantage [MD = -4.08, 95% CI (-5.77, -2.39), p < 0.00001], [MD = -7.71, 95% CI (-10.17, -5.25), p < 0.00001], [MD = -9.15, 95% CI (-10.02, -8.29), p < 0.00001]. In the analysis of body weight, tirzepatide showed a more significant reduction effect compared to the control group [MD = -5.65, 95% CI (-7.47, -3.82), p < 0.001], [MD = -10.06, 95% CI (-12.86, -7.25), p < 0.001], [MD = -10.63, 95% CI (-12.42, -8.84), p < 0.001]. In comparison with placebo, tirzepatide had a prominent advantage in weight loss ≥20% and ≥25% [RR = 30.43, 95% CI (19.56, 47.33), p < 0.00001], [RR = 37.25, 95% CI (26.03, 53.30), p < 0.00001]. Subgroup analysis showed a dose-dependent therapeutic effect. In terms of safety, compared with the placebo and insulin groups, the incidence of gastrointestinal adverse reactions was markedly higher in the tirzepatide group, slightly higher to the GLP-1 RAs group. The hypoglycemic (<70 mg/dL) risk of tirzepatide was slightly higher to that of placebo and GLP-1 RAs, but significantly lower than that of the insulin group [RR = 0.46, 95% CI (0.36, 0.58), p < 0.001]. The incidence of other adverse events, including pancreatitis, cholecystitis, major adverse cardiovascular events-4, hypersensitivity reactions, and neoplasms did not show significant statistical differences compared to the control group (p > 0.05). Tirzepatide, as a weight loss drug, significantly reduces BMI, waist circumference and body weight while gastrointestinal adverse reactions need to be vigilant. Overall, its efficacy is significant and its safety is high.

Efficacy and safety of Yangxue Qingnao Granules in treatment of migraine: A systematic review and meta-analysis.

Yangxue Qingnao Granules (YXQN) is a Chinese patent medicine that has been commonly used in the clinical treatment of migraine. To assess the efficacy and safety of YXQN alone for the treatment of migraine. We searched 10 databases to identify relevant randomized controlled trials (RCTs) published before September 2022. Two review authors independently searched and screened the literature, extracted the data, and assessed the methodological quality of the studies using criteria from ROB 2.0, and analyzed the data using Review Manager 5.4 software. A total of 12 RCTs including 767 participants with migraine met the selection criteria. We divided these studies into comparisons of YXQN with placebo, routine treatment drugs, and other Chinese patent medicines. The meta-analysis showed the following: (1) Efficacy: The YXQN group outperformed the placebo group [relative risk (RR) = 0.29, 95% confidence interval (95%CI): 0.15-0.43, P < 0.00001], routine treatment group (RR = 0.18, 95%CI: 0.09-0.27, P < 0.0001), and Chinese patent medicine group (RR = 0.27, 95%CI: 0.13-0.41, P < 0.001); (2) frequency of headache: There was a significant difference between YXQN vs placebo [mean difference (MD) = -1.25, 95%CI: -1.60 to -0.90, P < 0.00001], routine treatment drugs (MD = -0.85, 95%CI: -1.15 to -0.56, P < 0.00001), and Chinese patent medicine (MD = -0.91, 95%CI: -1.35 to -0.46, P < 0.0001); (3) headache duration: We found great heterogeneity between studies, with no differences between YXQN and placebo (MD = -0.61, 95%CI: -1.53 to -0.31, P = 0.19) and routine treatment drugs (MD = -0.22, 95%CI: -0.89 to 0.46, P < 0.53). YXQN was more effective than other Chinese patent medicines in reducing headache duration (MD = -1.24, 95%CI: -1.70 to -0.77, P < 0.00001); and (4) headache severity: There was no significant difference between YXQN vs placebo (MD = -1.67, 95%CI: -3.52 to 0.19, P = 0.08), routine treatment drugs (MD = -0.53, 95%CI: -2.02 to 0.96, P = 0.68), and other Chinese patent medicines (MD = -0.49, 95%CI: -2.83 to 1.85, P = 0.68). Mild gastrointestinal adverse reactions were reported in three cases. This study revealed that YXQN is effective and safe for treatment of migraine.

Interaction of antituberculosis drugs with food

The peculiarities of the development and evolution of tuberculosis require a rich and varied diet to restore the nutritional status, reduce the incidence of gastrointestinal adverse reactions and increase adherence to treatment. Food can modify the pharmacokinetic parameters (Cmax, AUC, Tmax) and thus influence the effectiveness of antituberculosis drugs or contribute to the development of resistance. Rifampicin and isoniazid need to be taken on an empty stomach. Food does not significantly influence the pharmacokinetic parameters of pyrazinamide and ethambutol. Calcium-rich products will decrease the absorption of fluoroquinolones. Acidic drinks reduce the absorption and Cmax of cycloserine/terizidone and increase the absorption of paraaminosalicylic acid. Pharmacodynamic interaction can be observed when isoniazid is combined with products containing tyramine and histamine, with increased manifestations of adverse reactions.

ВСТРЕЧАЕМОСТЬ АЛЛЕЛЕЙ И ГЕНОТИПОВ ПО АЛЛЕЛЬНЫМ ВАРИАНТАМ CYP2С9*2 И CYP2С9*3 СРЕДИ БОЛЬНЫХ С БОЛЕВЫМ СИНДРОМОМ, ПРИНИМАВШИХ НЕСТЕРОИДНЫЕ ПРОТИВОВОСПАЛИТЕЛЬНЫЕ СРЕДСТВА

Abstract. Introduction. The most clinically significant polymorphic markers of the CYP2C9 gene are the amino acid substitutions of CYP2C9*2. One of the human cytochrome P450 types, i.e., cytochrome CYP2C19, is essential to the metabolism of some drugs, including proton pump inhibitors. Genetic polymorphism of СУР2С19 has some pronounced interindividual differences. Significance of genetic polymorphism is detected where the occurrence of variant alleles exceeds 1% in the population. Aim of the study was to improve the principles of pharmacotherapy with nonsteroidal anti-inflammatory drugs, as related to the frequency of alleles and genotypes on the allelic variants of CYP2С9*2 and CYP2С9*3 in pain syndrome patients taking nonsteroidal anti-inflammatory drugs. Materials and Methods. The study included 69 patients with pain syndrome. Association between being the carrier of genotypes on the CYP2С9*2 and CYP2С9*3 alleles and developing gastropathies as reactions to administering anti-inflammatory drugs was investigated by conducting a prospective case-control study. Molecular genetic testing was performed based on the Laboratory of Medical Genetics of the Research Institute of Hematology and Blood Transfusion at the Ministry of Health of the Republic of Uzbekistan. Results and Discussion. No statistically significant differences were found in the frequencies of the CYP2C9 and CYP2C19 alleles between the groups of patients with and without adverse gastrointestinal reactions to administering nonsteroidal anti-inflammatory drugs or proton pump inhibitors. Conclusions. Our findings allow us to suggest that being a carrier of the allelic CYP2C9*2 and CYP2C9*3 variants should be considered as a gastropathy risk factor of using nonsteroidal anti-inflammatory drugs. It can be assumed that, to reduce the risk of adverse reactions developed in the patients of this category to nonsteroidal anti-inflammatory drugs, the latter ones need a concomitant administration with proton pump inhibitors. It is necessary to continue studying the frequencies of the alleles and genotypes on allelic CYP2С9*2 and CYP2С9*3 variant sin pain syndrome patients taking nonsteroidal anti-inflammatory drugs.

Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta-analysis including the 2-year STEP 5 trial.

To explore the safety and efficacy of subcutaneous semaglutide 2.4 mg, administered once a week in non-diabetic overweight or obese individuals. A thorough search was performed of various databases including PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrials.gov, CNKI and Wanfang from their inception up to April 11, 2023. Our aim was to identify randomized controlled trials (RCTs) that compared the efficacy of semaglutide administered once weekly with placebo in overweight or obese adults. Through a review of the literature, data were extracted from relevant studies and assessed for quality, and a meta-analysis was conducted using RevMan 5.4.1 software. Six RCTs comprising 3962 overweight or obese individuals were identified. The findings indicated that, in comparison to the placebo group, semaglutide caused a significant and sustainable reduction in the percentage of body weight (BW; mean difference [MD]: -11.80% [95% confidence interval {CI} -12.93, -10.68]; P < 0.00001) as well as a decrease in absolute BW (MD: -12.2 kg [95% CI -13.3, -11.1]; P < 0.00001), body mass index (MD: -4.5 kg/m2 [95% CI -4.9, -4.1]; P < 0.00001) and waist circumference (MD:-9.4 cm [95% CI -10.1, -8.8]; P < 0.00001). Moreover, it achieved a higher proportion of patients who experienced weight loss exceeding 5%, 10%, 15% and 20%. Furthermore, semaglutide showed significant efficacy in controlling blood pressure, blood sugar levels, C-reactive protein levels, and lipid profiles. In terms of safety, the most common adverse effects following semaglutide treatment were gastrointestinal adverse reactions (risk ratio: 1.49 [95% CI 1.38, 1.60]; P < 0.00001), which were generally mild to moderate in severity and temporary. In overweight or obese non-diabetic individuals, semaglutide had a remarkable and sustained weight loss effect that was well tolerated and safe.

The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

Association of ABCB1 Polymorphisms with Efficacy and Adverse Drug Reactions of Valproic Acid in Children with Epilepsy.

Genetic polymorphisms in ATP-binding cassette subfamily B member 1 (ABCB1, also known as MDR1) have been reported to be possibly associated with the regulation of response to antiseizure medications. The aim of this study was to investigate the association of ABCB1 polymorphisms with the efficacy of and adverse drug reactions to valproic acid among Chinese children with epilepsy. A total of 170 children from southern China with epilepsy treated with valproic acid for more than one year were recruited, including 61 patients with persistent seizures and 109 patients who were seizure-free. Two single nucleotide polymorphisms of ABCB1, rs1128503 and rs3789243, were genotyped using the Sequenom MassArray system. The two single nucleotide polymorphisms of ABCB1 were found to be significantly associated with treatment outcomes of valproic acid in children with epilepsy. Carriers with the TT genotype of ABCB1 rs1128503 were more inclined to exhibit persistent seizures after treatment with valproic acid (p = 0.013). The CC genotype of rs3789243 was observed to be a potential protective factor for valproic acid-induced gastrointestinal adverse drug reactions (p = 0.018), but possibly increased the risk of valproic acid-induced cutaneous adverse drug reactions (p = 0.011). In contrast, the CT genotype of rs3789243 was associated with a lower risk of valproic acid-induced cutaneous adverse drug reactions (p = 0.011). Haplotype analysis showed that CC haplotype carriers tended to respond better to valproic acid treatment (p = 0.009). Additionally, no significant association was found between ABCB1 polymorphisms and serum concentrations of valproic acid. This study revealed that the polymorphisms and haplotypes of the ABCB1 gene might be associated with the treatment outcomes of valproic acid in Chinese children with epilepsy.

Efficacy and safety of Xiang-Sha-Liu-Jun-Zi (XSLJZ) for treatment of Semaglutide-induced gastrointestinal side effects: Study protocol for a multicentre, randomized, open-label trial

Background: Semaglutide is a newly approved glucagon-like peptide 1 receptor agonist(GLP-1 RA), significantly reducing HbA1c and body weight. However, it is associated with an increased incidence of gastrointestinal adverse events. Xiang-Sha-Liu-jun-Zi (XSLJZ), is a classic traditional Chinese medicine (TCM) formula with the effects of modulating gastrointestinal disturbance. This study aims to evaluate the clinical efficacy and safety of the XSLJZ for treatment of Semaglutide-induced gastrointestinal side effects. Methods: This is a multicentre, randomized, open-label trial. The trial included a run-in period within 2 weeks, a 4-week treatment period, and another 4 weeks after the end of the experimental phase. Patients who have Gastrointestinal Adverse Reactions during the run-in period will be randomly divided (1:1) into 2 groups. The primary outcome measures were changes in scores on the Gastrointestinal System Rating Scale(GSRS), the duration of individual gastrointestinal adverse events. The secondary outcomes were TCM syndrome score, changes in glycaemic excursions, homeostatic model assessment 2-B (HOMA2-B)and homeostatic model assessment 2-insulin resistance(HOMA2-IR), glucagon, C-peptide, plasma lipids, Anthropometric parameters: body weight, body mass index, waist-hip circumference, waist-hip ratio. Discussion: The results of this trial will provide initial evidence for the use of XSLJZ as an alternative and complementary intervention to manage Semaglutide-induced gastrointestinal side effects.

Effectiveness and safety of Pingxiao capsule as adjuvant therapy in treatment of breast cancer: a systematic review and Meta-analysis.

To systematically review the effectiveness and safety of Pingxiao capsule adjuvant chemotherapy in the treatment of breast cancer. A total of 8 databases including the Cochrane Library, PubMed, EMBASE, Engineering Index, Chinese Biomedical Literature Database, Wanfang database, China National Knowledge Infrastructure Database, and China Science and Technology Journal Database were searched for the Randomized Controlled Trials (RCTs) of Pingxiao capsule combined with chemotherapy in the treatment of breast cancer published before June 2022. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias. R language was used for estimating risks of bias of included studies, data analysis, and plotting. A total of 15 RCTs involving 1272 patients were included in this study. Meta-analysis results indicated that compared with chemotherapy alone, Pingxiao capsule combined with chemotherapy could significantly improve breast cancer patients' objective response rate of breast cancer patients [rate ratio () = 1.35, 95% confidence interval () (1.12, 1.63), = 0.0017], the disease control rate [=1.16, 95% (1.08, 1.25), < 0.0001], the quality of life [ =1.42, 95% (1.16, 1.74), = 0.007], and the level of the immune cells [CD3+: standardized mean difference () =1.42, 95% (0.76, 2.09), < 0.001; CD4+: =1.18, 95% (0.70, 1.66), < 0.001]. In addition, Pingxiao capsule combined with chemotherapy can also significantly reduce CD8+ level ( < 0.0001) and reduce the symptoms of decreased white blood cell count [ = 0.62, 95% (0.39, 0.85), < 0.0001], and the occurrence of adverse reactions such as gastrointestinal adverse reactions and limb pain ( < 0.05). Pingxiao capsule can significantly improve the efficacy of chemotherapy, the quality of life and immune function of patients, and reduce the clinical side effects caused by chemotherapy. However, high-quality randomized clinical trials with large samples are required for further verification of these results.