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Background: Children with IgA Vasculitis (IgAV) may develop renal complications, which can impact their long-term prognosis. This study aimed to build a machine learning model to predict renal damage in children with IgAV and analyze risk factors for IgA Vasculitis with Nephritis (IgAVN). Methods: 50 clinical indicators were collected from 217 inpatients at our hospital. Six machine learning algorithms—Logistic Regression, Linear Discriminant Analysis, K-Nearest Neighbor, Support Vector Machine, Decision Trees, and Random Forest—were utilized to select the model with the highest predictive performance. A simplified model was developed through feature importance ranking and validated by an additional cohort with 46 patients. Results: The random forest model had the highest accuracy, precision, recall, F1 score, and area under the curve, with values of 0.91, 0.98, 0.70, 0.79 and 0.94, respectively. The top 11 features according to the importance ranking were anti-streptolysin O, corticosteroids therapy, antihistamine therapy, absolute eosinophil count, immunoglobulin E, anticoagulant therapy, C-reactive protein, prothrombin time, age at onset, D-dimer, recurrence of rash ≥ 3 times. A simplified model using these features demonstrated optimal performance with an accuracy of 84.2%, a sensitivity of 89.4%, and a specificity of 82.5% in external validation. Finally, we provided a web tool based on the simplified model, whose code was published on https://github.com/mulanruo/IgAVN%5fPrediction. Conclusion: The model based on the random forest algorithm demonstrates good performance in predicting renal damage in children with IgAV, providing a basis for early clinical diagnosis and decision-making. [ABSTRACT FROM AUTHOR]

Background: Tranexamic acid (TXA) is commonly considered a safe drug to mitigate bleeding during and after various surgical settings among adults and children. In recent decades, anaphylaxis induced by TXA has been increasingly reported in adults. However, among pediatrics, there are fewer reported cases. Case presentation: We report a case of a 6-year-old female who experienced anaphylaxis after receiving intravenous TXA following unilateral cleft lip and palate repair surgery. She exhibited clinical symptoms involving the cardiovascular system, respiratory system, and skin. Following the administration of epinephrine, corticosteroid, and anti-histamine, the patient's symptoms were relieved. A few months after discharge, an intradermal test, yielded a positive result, confirming TXA as the culprit drug. Conclusion: Our report emphasizes the importance of considering anaphylaxis as a potential adverse reaction to TXA in pediatric patients, showing the criticality of rapid diagnosis and appropriate management for a successful outcome. [ABSTRACT FROM AUTHOR]

Texture and color enhancement imaging (TXI) may improve the visibility of gastric tumors and allow their early detection. However, few reports have examined the utility of TXI. Between June 2021 and October 2022, 56 gastric tumors in 51 patients undergoing endoscopic submucosal dissection at Fukuchiyama City Hospital were evaluated preoperatively using conventional white light imaging (WLI), narrow-band imaging (NBI), and TXI modes 1 and 2. The color differences of the tumors and surrounding mucosae were evaluated using the CIE 1976 L*a*b color space, Additionally, the visibility scores were scaled. Of the 56 gastric tumors, 45 were early gastric cancers, and 11 were adenomas. Overall, the color difference in TXI mode 1 was considerably higher compared to WLI (16.36 ± 7.05 vs. 10.84 ± 4.05; p < 0.01). Moreover, the color difference in early gastric cancers was considerably higher in TXI mode 1 compared to WLI, whereas no significant difference was found in adenomas. The visibility score in TXI mode 1 was the highest, and it was significantly higher compared to WLI. Regarding adenomas, the visibility score in TXI mode 1 was also significantly higher compared to that in WLI. TXI may provide improved gastric tumor visibility. [ABSTRACT FROM AUTHOR]

Cisplatin is the most commonly used platinum-based treatment for nasopharyngeal carcinoma (NPC). However, its clinical application is limited owing to its nephrotoxicity and gastrointestinal reactions. Proton pump inhibitors (PPIs) have been reported to increase nephrotoxicity risk in previous studies. We aimed to evaluate whether PPIs increase cisplatin-induced nephrotoxicity in patients with NPC. In total, 295 patients were included in this prospective cohort study: 145 in the PPIs group and 150 in the non-PPIs group. All patients underwent cisplatin-based induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy. The PPIs group received 40 mg of intravenous esomeprazole sodium for 7 days in each chemotherapy cycle. Chi-squared test and logistic regression analyses with odds ratios and 95% confidence intervals were applied to assess the association between PPIs and the risk of acute kidney injury (AKI). AKI incidence in the PPIs group was significantly higher than that in the non-PPIs group (P = 0.005). After adjusting for various confounders including demographic features, clinical features, and renal function indices, PPIs use was significantly associated with a higher AKI risk (odds ratio: 2.775; 95% confidence interval 1.280–6.020; P = 0.010). The incidences of acute and chronic kidney diseases were similar between both groups (P > 0.05), whereas the incidence of nausea was lower in the PPIs group than in the non-PPIs group (P = 0.029). This study has shown that PPIs use may increase the risk of cisplatin-induced acute nephrotoxicity in patients with NPC. [ABSTRACT FROM AUTHOR]

H. pylori infection is gaining increasing attention, but detailed investigations into its impact on gastric microbiota remain limited. We collected gastric mucosa samples from 47 individuals divided into three groups: 1. Group HP: patients with initial positive H. pylori infection (25 cases); 2. Group ck: H. pylori-negative patients (14 cases); 3. Group DiffHP: patients with refractory H. pylori infection (8 cases). The samples were analyzed using 16S rDNA sequencing and functional prediction with PICRUSt. Group HP showed differences in flora distribution and function compared to Group ck, while Group DiffHP overlapped with Group HP. The abundances of Aeromonas piscicola, Shewanella algae, Vibrio plantisponsor, Aeromonas caviae, Serratia marcescens, Vibrio parahaemolyticus, Microbacterium lacticum, and Prevotella nigrescens were significantly reduced in both Group DiffHP and Group HP compared to Group ck. Vibrio shilonii was reduced only in Group DiffHP compared to Group ck, while Clostridium perfringens and Paracoccus marinus were increased only in Group DiffHP. LEfSe analysis revealed that Clostridium perfringens and Paracoccus marinus were enriched, whereas Vibrio shilonii was reduced in Group DiffHP compared to Group ck at the species level. In individuals with refractory H. pylori infection, the gastric microbiota exhibited enrichment in various human diseases, organic systems, and metabolic pathways (amino acid metabolism, carbohydrate metabolism, transcription, replication and repair, cell cycle pathways, and apoptosis). Patients with multiple failed H. pylori eradication exhibited significant changes in the gastric microbiota. An increase in Clostridium perfringens and Paracoccus marinus and a decrease in Vibrio shilonii appears to be characteristic of refractory H. pylori infection. [ABSTRACT FROM AUTHOR]

The genomic characteristics of Peruvian patients with gastric adenocarcinoma from diverse socioeconomic backgrounds were examined in consideration of the possibility that patients from different socioeconomic backgrounds may be exposed to different risk factors. We conducted a prospective pilot study in two Peruvian cities (Lima and Ica). This study enrolled 15 patients from low socioeconomic status (LSES) and 15 patients from medium/high socioeconomic status (MHSES). The genomic profiling of gastric adenocarcinoma samples was done through the FoundationOne CDx platform. We compared the genomic characteristics and the need for targeted therapy and immunotherapy between LSES and MHSES. The genes with higher rates of alterations were TP53 (73.3% vs. 50.0%, P = 0.2635); CDH1 (26.7% vs. 28.6%, P = 1); CDKN2A (20.0% vs. 28.6%, P = 1); KRAS (33.3% vs. 7.1%, P = 0.1686); ARID1A (20.0% vs. 14.3%, P = 1); MLL2 (13.3% vs. 21.4%, P = 1) and SOX9 (33.3% vs. 0.0%, P = 0.0421) in LSES versus HMSES, respectively. There was no significant difference in tumor mutational burden (P = 0.377) or microsatellite status (P = 1). The LSES group had a higher need for targeted therapy or immunotherapy according to gene involvement and alterations. A significant genomic difference exists among patients with gastric adenocarcinoma of different socioeconomic status, which may result in a different need for targeted therapy and immunotherapy. [ABSTRACT FROM AUTHOR]

Proton pump inhibitor (PPI) use may be associated with renal dysfunction. Renal dysfunction in PPI users requires evaluation of development and progression risks simultaneously, using estimated glomerular filtration rate (eGFR) slope, which indicates changes in eGFR per year. To the best of our knowledge, no studies have evaluated eGFR slope in PPI users. This study investigated the association between PPI use and renal dysfunction using eGFR slope. A single-center cohort study was conducted using the health records data at Hamamatsu University Hospital in Japan. Participants were defined as first users of acid-suppressing drugs (PPIs or Histamine H2 receptor antagonists (H2RAs)) from 2010 to 2021 and continuously prescribed for ≥ 90 days. The H2RA group was used for the propensity-score matching (PSM) to the PPI group to minimize the effects of confounders. The eGFR slope was estimated using a linear mixed effects model. Participants were stratified by baseline eGFR and age, respectively, as subgroup analyses. A total of 4,649 acid-suppressing drug users met the inclusion criteria, including 950 taking H2RAs and 3,699 PPIs. After PSM, 911 patients were assigned to each group. The eGFR slopes of the PPI and H2RA users were -4.75 (95% CI: -6.29, -3.20) and -3.40 (-4.38, -2.42), respectively. The difference between the groups was not significant. Significant declines in eGFR were observed with PPIs with baseline eGFR ≥ 90 and age < 65. PPI use for ≥ 90 days may hasten eGFR decline compared to H2RA use, especially in patients with eGFR ≥ 90 or age < 65. [ABSTRACT FROM AUTHOR]

The plant health status is determined by the interplay of plant-pathogen-microbiota in the rhizosphere. Here, we investigate this tripartite system focusing on the pathogen Fusarium oxysporum f. sp. lycopersici (FOL) and tomato plants as a model system. First, we explore differences in tomato genotype resistance to FOL potentially associated with the differential recruitment of plant-protective rhizosphere taxa. Second, we show the production of fusaric acid by FOL to trigger systemic changes in the rhizosphere microbiota. Specifically, we show this molecule to have opposite effects on the recruitment of rhizosphere disease-suppressive taxa in the resistant and susceptible genotypes. Last, we elucidate that FOL and fusaric acid induce changes in the tomato root exudation with direct effects on the recruitment of specific disease-suppressive taxa. Our study unravels a mechanism mediating plant rhizosphere assembly and disease suppression by integrating plant physiological responses to microbial-mediated mechanisms in the rhizosphere. The phytotoxin fusaric acid produced by the phytopathogen Fusarium oxysporum f. sp. lycopersici results in a differential assembly of the rhizosphere microbiota of resistant and susceptible genotypes with implication for disease suppression. [ABSTRACT FROM AUTHOR]

Purpose: Somatostatin receptor antagonists have shown promising performance for imaging neuroendocrine neoplasms. However, there is a lack of studies exploring the diagnostic performance of SSTR antagonists or comparing them with agonists in a large cohort of patients with NENs. This study aimed to retrospectively review all SSTR antagonist PET/CT scans conducted at Peking Union Medical College Hospital since November 2018 in patients with confirmed or suspected NENs. Methods: Four types of SSTR antagonists were utilized, including [68Ga]Ga-NODAGA-LM3, [68Ga]Ga-DOTA-LM3, [68Ga]Ga-NODAGA-JR11, and [68Ga]Ga-DOTA-JR11. The reference standard was based on a combination of histopathology, clinical evaluation, imaging results, and follow-up. Patient-based sensitivity, specificity, and accuracy were evaluated. The SUVmax and tumor-to-liver ratio (TLR) of the hottest lesions was recorded and compared between antagonists and [68Ga]Ga-DOTATATE. Results: A total of 622 antagonist scans from 549 patients were included in the analysis. The patient-level sensitivity, specificity, and accuracy of antagonist imaging (all tracers combined) were 91.0% (443/487), 91.9% (57/62), and 91.1% (500/549), respectively. In 181 patients with a comparative [68Ga]Ga-DOTATATE PET/CT scan, the patient-level sensitivity, specificity, and accuracy were 87.5% (147/168), 76.9% (10/13), and 86.7% (157/181), respectively. For the hottest lesions, SSTR antagonists all tracers combined demonstrated an overall comparable SUVmax to [68Ga]Ga-DOTATATE (40.1 ± 32.5 vs. 39.4 ± 23.8, p = 0.772). While [68Ga]Ga-NODAGA-LM3 showed significantly higher uptake than [68Ga]Ga-DOTATATE (57.4 ± 38.5 vs. 40.0 ± 22.8, p<0.001), [68Ga]Ga-NODAGA-JR11 (39.7 ± 26.5 vs. 34.3 ± 23.9, p = 0.108) and [68Ga]Ga-DOTA-LM3 (38.9 ± 32.1 vs. 37.2 ± 22.1, p = 0.858) showed comparable uptake to [68Ga]Ga-DOTATATE, and [68Ga]Ga-DOTA-JR11 showed lower uptake (28.9 ± 26.1 vs. 44.0 ± 25.7, p = 0.001). All antagonists exhibited significantly higher TLR than [68Ga]Ga-DOTATATE (12.1 ± 10.8 vs. 5.2 ± 4.5, p<0.001). Conclusion: Gallium-68 labeled SSTR antagonists could serve as alternatives to SSTR agonists for imaging of NENs. Among various antagonists, [68Ga]Ga-NODAGA-LM3 seems to have the best imaging profile. [ABSTRACT FROM AUTHOR]

The Montreal consensus recognizes chronic cough as an extra-esophageal manifestation of gastroesophageal reflux disease. We performed a meta-analysis to assess the effects of acid-suppressive medications in adults with non-specific chronic cough. The protocol was registered on PROSPERO (CRD42022368769). Placebo-controlled randomized trials evaluating the impact of acid-suppressive medications on persistent cough were included. The systematic search was performed on the 1st of November 2022 in three databases. A random-effects model was used for the calculations. The effect size was the standardized mean difference (SMD) with 95% confidence interval (CI). A total number of 11 double-blinded placebo-controlled randomized trials were included in the meta-analysis. Data showed that compared to placebo, PPIs decreased the severity of cough (SMD 0.33; CI 0.05; 0.61). Therapeutic response was not different in patients with non-specific chronic cough only, compared to those with laryngopharyngeal reflux. Prolonged treatment durations did not result in greater symptomatic improvement, with SMD 0.33 (CI − 0.22; 0.88), 0.31 (CI − 1.74; 2.35), 0.32 (CI − 0.29; 0.93) and 0.34 (CI − 0.16; 0.85), following 4, 6, 8 and 12 weeks of treatment, respectively. The pooled analysis of the improvement in quality of life with PPIs found an SMD of 0.39 (CI − 0.51; 1.29). PPIs mildly decrease the severity of non-specific chronic cough, irrespective of treatment duration. [ABSTRACT FROM AUTHOR]

Over the past couple of decades, the incidence of breast cancer (BC) has significantly increased among females in comparison to other cancer types. In medicinal terminology, the susceptibility to BC is mainly centered around three hormonal receptors: estrogen (ER), progesterone (PR), and human epidermal growth receptor (HER2). Notably, estrogen- dependent breast cancer has a considerable female demographic, making it treatable with hormonal drugs and less intensive immunotherapy. Conversely, the narrative delves into the ominous type of cancer known as triple-negative breast cancer (TNBC). The orientation of all three receptors falls in a negative direction, which is ineffective for treatments that rely on hormonal or antagonist medicaments. Therefore, the only option available to tackle this type of cancer is chemotherapy, which causes toxicity within the body, is highly expensive, and is non-targeted. To counter this challenge, researchers have pioneered nano-based drug delivery systems (NDDS) owing to their innumerable merits and scientific development. NDDS mainly involves polymeric nanoparticles, liposomes, and dendrimers. This review comprehensively details the advancements in nanoinduced targeted drug delivery systems, with a focus on surface modification techniques for active targeting, enhanced drug release, and improved pharmacokinetics. Critical analysis extends to preclinical and clinical studies, revealing the potential of nano-drug delivery systems in TNBC to surpass traditional therapies, with promising heightened efficacy and reduced side effects. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is a life-threatening disease predominantly affecting premature and very low birth weight infants resulting in inflammation and necrosis of the small bowel and colon and potentially leading to sepsis, peritonitis, perforation, and death. Numerous research efforts have been made to better understand, treat, and prevent NEC. This review explores a variety of factors involved in the pathogenesis of NEC (prematurity, low birth weight, lack of human breast milk exposure, alterations to the microbiota, maternal and environmental factors, and intestinal ischemia) and reports treatment modalities surrounding NEC, including pain medications and common antibiotic combinations, the rationale for these combinations, and recent antibiotic stewardship approaches surrounding NEC treatment. This review also highlights the effect of early antibiotic exposure, infections, proton pump inhibitors (PPIs), and H2 receptor antagonists on the microbiota and how these risk factors can increase the chances of NEC. Finally, modern prevention strategies including the use of human breast milk and standardized feeding regimens are discussed, as well as promising new preventative and treatment options for NEC including probiotics and stem cell therapy. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) stage and tissue differentiation affect treatment efficacy and prognosis, highlighting the importance of understanding the risk factors that affect these parameters. Therefore, this study analyzed risk factors affecting the GC stage and differentiation and the relationships between the cancer site and the sex and age of the patient. We collected clinical data from 6961 patients with GC, including sex, age, endoscopic lesion location, and pathological differentiation. Patients were grouped based on GC stage (early or advanced), differentiation (well or poorly differentiated), and lesion site (upper stomach [cardia and fundus], middle stomach [gastric body], and lower stomach [gastric antrum]). Differences in sex, age, location, stage, and degree of differentiation were assessed based on these groupings. Univariate analysis revealed that the disease location and differentiation significantly differed based on the GC stage (P < 0.05), whereas sex, age, site, and stage significantly differed based on GC differentiation (P < 0.05). A multivariate analysis confirmed these factors as independent risk factors affecting GC. Moreover, lesion sites significantly differed between sexes (P < 0.05) and among age groups (P < 0.05). Although the effects of family history, lifestyle, and Helicobacter pylori infection status of the patients were not considered, this single-center retrospective study established independent risk factors for GC. Trial registration ChiCTR2200061989. [ABSTRACT FROM AUTHOR]

Acute gastric bleeding (AGB) is a common and potentially serious complication in patients with gastrointestinal disorders. Nursing interventions play a critical role in the management of acute gastric bleeding, but their impact on clinical outcomes is not well understood. The aim of this retrospective analysis was to evaluate the impact of nursing interventions on clinical outcomes in patients with acute gastric bleeding. A retrospective review of medical records was conducted for 220 patients with acute gastric bleeding who were admitted to the hospital between February 2022 and February 2023. Patients were divided into two groups based on whether or not they received nursing interventions during their hospital stay. Clinical outcomes, including length of hospital stay, blood transfusion requirements, and mortality rates, were compared between the two groups using descriptive statistics and logistic regression analysis. Of the 220 patients included in the study, 168 (76.4%) received nursing interventions during their hospital stay. Patients who received nursing interventions had a significantly shorter length of hospital stay (mean = 7.2 days, SD = 2.1) compared to those who did not receive nursing interventions (mean = 10.5 days, SD = 3.4, p < 0.001). Additionally, the 90-day mortality rate was lower in the group receiving professional nursing interventions (4.2% vs. 15.4%, p = 0.010). Fewer patients who received nursing interventions required blood transfusions (33.3% vs. 65.2%, p < 0.001) and mortality rates were lower (6.7% vs. 20.8%, p = 0.04). Multivariate logistic regression analysis suggested that professional nursing intervention was a protective factor for postoperative rebleeding in patients with gastric hemorrhage (OR 0.727, 95% CI 0.497–0.901, P < 0.001). The results of this retrospective analysis suggest that nursing interventions are associated with improved clinical outcomes in patients with acute gastric bleeding. The implementation of nursing interventions, such as individualized care plans, monitoring and evaluation, and patient education, should be encouraged to optimize patient outcomes in this population. Further research is needed to identify the most effective nursing interventions and to evaluate their cost-effectiveness. [ABSTRACT FROM AUTHOR]

The interaction of genetic, epigenetic, and environmental factors underlies the pathogenesis of allergic diseases. Allergic rhinitis and atopic bronchial asthma are closely related and often concurrent allergic airway diseases. The chronic recurrent course of these diseases establishes the importance of further and more profound studies of the mechanisms underlying the development of these pathologies. Histamine is one of the most significant inflammatory mediators secreted during allergic reactions. The aim of the research was to study the role of polymorphic variants of the AOC1, HRH2, HRH3, ALDH7A1, ADCYAP1, HNMT, PSAP, and SCG3 genes involved in the histamine metabolism in the development of different endophenotypes of the allergic airway diseases in individuals living in the Republic of Bashkortostan. DNA samples of 358 individuals with allergic airway diseases of different ethnicity (Russians—165, Tatars—143, Bashkirs—50) and 200 controls with unweighted heredity in allergic diseases (Russians—75, Tatars—83, Bashkirs—42). Genotyping of polymorphic variants was performed by real-time PCR and PCR-RFLP analysis. It was revealed that the rs104979793*CC genotype and the rs104979793*C allele of the AOC1 gene were associated with allergic airway diseases and asthma with concomitant allergic rhinitis in Russians. A significant increase in total IgE level was revealed in Russian patients with allergic airway diseases with the rs1049793*CC genotype of the AOC1 gene compared to carriers of the rs1049793*CG and rs1049793*GG genotypes. The association of the C allele of the rs17525472 polymorphic variant localized near the SCG3 gene with allergic rhinitis in Russians was established. The results revealed that AOC1 and SCG3 genes involved in the metabolism of histamine are related to the development of different endophenotypes of allergic airway tract diseases in children. [ABSTRACT FROM AUTHOR]

The objective of this study was to clarify the long-term prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma with additional copies of MALT1. In this multicenter retrospective study, we enrolled 145 patients with gastric MALT lymphoma who underwent fluorescence in situ hybridization (FISH) analysis to detect t(11;18) translocation. The patient cohort was divided into three groups: Group A (n = 87), comprising individuals devoid of the t(11;18) translocation or extra MALT1 copies; Group B (n = 27), encompassing patients characterized by the presence of the t(11;18) translocation; and Group C (n = 31), including patients with extra MALT1 copies. The clinical outcomes in each cohort were collected. Over the course of a mean follow-up of 8.5 ± 4.2 years, one patient died of progressive MALT lymphoma, while 15 patients died due to etiologies unrelated to lymphoma. The progression or relapse of MALT lymphoma was observed in 11 patients: three in Group A, two in Group B, and six in Group C. In Groups A, B, and C, the 10-year overall survival rates were 82.5%, 93.8%, and 86.4%, respectively, and the 10-year event-free survival rates were 96.1%, 96.0%, and 82.9%, respectively. The event-free survival rate in Group C was significantly lower than that in Group A. However, no differences were observed in the 10-year event-free survival rates among individuals limited to stage I or II1 disease (equivalent to excluding patients with stage IV disease in this study, as there were no patients with stage II2), with rates of 98.6%, 95.8%, and 92.3% for Groups A, B, and C, respectively. In conclusion, the presence of extra copies of MALT1 was identified as an inferior prognostic determinant of event-free survival. Consequently, trisomy/tetrasomy 18 may serve as an indicator of progression and refractoriness to therapeutic intervention in patients with gastric MALT lymphoma, particularly stage IV gastric MALT lymphoma. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) resistance is the most important risk factor for eradication failure. However, in most regions, antibiotic resistance rates of H. pylori in patients with different types of gastric mucosal lesions are still unclear. An 8-year clinical retrospective cohort study involving 2847 patients was performed. In this study, we first summarized and compared the resistance status of H. pylori in different years, ages, sexes, and gastric diseases. The resistance profiles of amoxicillin (AMX), clarithromycin (CLR), levofloxacin (LVX) and furazolidone (FR) and their changing trends in the clinic were described. Then, multiple antibiotic resistance in different gastric diseases and years were described and compared. The relationship between proton pump inhibitor (PPI) medication history and antibiotic resistance in H. pylori was also explored. Finally, an antibiotic resistance risk model was constructed for clinical resistance risk prediction. The overall resistance rates of AMX, CLR, LVX and FR in gastric diseases were 8.18%, 38.11%, 43.98%, and 13.73%, respectively. The mono resistance, double resistance, triple resistance, and quadruple resistance rates were 30.17%, 25.96%, 6.46%, and 0.63%, respectively. Compared with the period from 2014 to 2016, the rates of mono-resistance and multiple resistance all showed relatively downward trends in the past 5 years. Factors including age, sex, type of gastric lesions and recent PPI treatment history are associated with the antibiotic resistance rate of H. pylori. Atrophic gastritis is an important clinical feature of high-risk antibiotic resistance in H. pylori-infected patients. Patients with atrophic gastritis have higher risk of resistant strains infection. In this study, our data provide the association between antibiotic resistance of H. pylori and gastritis pattern, which indicate the higher risk of resistant strain infection if the patients with atrophic gastritis, PPI history and older age. [ABSTRACT FROM AUTHOR]

Gelsolin (GSN) is an important actin-binding protein. The current studyidentified the potential role of GSN in Gastric cancer (GC) tumorigenesis and prognosis using bioinformatic analysis. The TCGA, GTEx, and GEO databases were used to gain clinicopathological data on GC patients. Expression of GSN across cancers was evaluated. Kaplan–Meier analyses were conducted to evaluatethe prognostic value of GSN, while the association between GSN expression and clinical characteristics in gastric carcinoma was evaluated using the UALCAN database. The potential diagnostic value of GSN was assessed by the construction of ROC curves. The putative underlying cellular mechanisms were investigated by GO and KEGG pathway enrichment analyses. The GSN mRNA was validated by RT-qPCR. GSN mRNA and protein expression were lower in gastric carcinoma tissue than in noncancerous tissue. GO and KEGG enrichment analyses revealed that GSN plays a key regulatory role in actin binding and capping and thec-erbB/EGFR and PI3K/Akt signaling pathways. GSN has a high diagnostic significance, and low GSN expression is associated with shorter overall survival (OS) in gastric carcinoma. GSN expression was a risk factor for the progression-free interval in patients with gastric carcinoma. We observed that the OS rate of patients with higher GSN expression levels was longer, and GSN had significant predictive value for the clinical outcome of GC. GSN expression is involved in the tumorigenesis of gastric carcinoma progression and may regard as a putative diagnostic and prognostic biomarker for gastric carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: Acid suppressive therapy using histamine H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) can be utilized for the prevention of gastrointestinal bleeding (GIB) among patients with cardiovascular disease receiving dual antiplatelet therapy (DAPT). However, emerging data suggests underlying associations between PPI or H2RA use and cardiovascular disease incidence, progression, and mortality. This review explores the history of acid suppressive therapies and their use in cardiovascular disease patients and the growing evidence in support of H2RA use. Recent Findings: PPIs were originally championed as better than H2RAs for preventing GIB events in cardiovascular disease patients on DAPT therapy, but there is evidence to suggest that drug-drug interactions between clopidogrel and PPIs may translate to worse cardiovascular outcomes. Studies demonstrating PPI superiority in the setting of DAPT were also limited due to small sample sizes and high levels of bias. Consequently, there is renewed interest in H2RAs for patients on DAPT with some data demonstrating similar or improved clinical outcomes over PPI therapy. Additionally, studies have discovered a possible role for H2RAs in the management of heart failure (HF) incidence, symptoms, and mortality. Summary: Studies comparing H2RAs and PPIs in patients on DAPT have demonstrated mixed results for cardiovascular and GIB outcomes, with several studies being underpowered and limited by biases. Recent clinical and pre-clinical studies now support the noninferiority of H2RAs for major outcomes and even utility in HF. These findings suggest that H2RAs may warrant reconsideration as an acid suppressive therapy over PPIs for patients on DAPT or with HF. [ABSTRACT FROM AUTHOR]

Obesity and type 2 diabetes mellitus (T2DM) is an alarming problem globally and a growing epidemic. Metabolic surgery has been shown to be successful in treating both obesity and T2DM, usually after other treatments have failed. This study aims to compare Roux-Y gastric bypass and sleeve gastrectomy in determining early diabetic outcomes in obese Malaysian patients with T2DM following surgery. A total of 172 obese patients with T2DM who were assigned to either laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) were analysed up to a year post-procedure. The patients' T2DM severity were stratified using the Individualized Metabolic Surgery (IMS) score into mild, moderate and severe. Remission rates of diabetes were compared between surgical techniques and within diabetic severity categories. T2DM remission for patients who underwent either surgical technique for mild, moderate or severe disease was 92.9%, 56.2% and 14.7% respectively. Both surgical techniques improved T2DM control for patients in the study. Comparing baseline with results 1 year postoperatively, median HbA1c reduced from 7.40% (IQR 2.60) to 5.80% (IQR 0.80) (p < 0.001), mean total antidiabetic medications use reduced from 1.48 (SD 0.99) to 0.60 (SD 0.86) [p < 0.001], insulin usage reduced from 27.9 to 10.5% (p < 0.001), and T2DM control improved from 27.9 to 82% (p < 0.001). The patients had a median excess BMI loss of 69.4% (IQR 34%) and 53.2% (IQR 36.0%) for RYGB and SG respectively (p = 0.016). At one year following surgery, there is no difference between LRYGB and LSG in terms of diabetic remission. LSG is not inferior to LRYGB in terms of early diabetic outcomes. Milder T2DM shows a better response. LSG is a simpler procedure with a lower risk profile and should be considered as an early treatment option for obese patients with T2DM. [ABSTRACT FROM AUTHOR]

Portal hypertension often precedes the development of advanced fibrosis in patients with Metabolic dysfunction-associated steatotic liver disease (MASLD) and may accelerate disease progression to cirrhosis. We aimed to evaluate whether prioritization tools accurately predict survival in patients with MASLD and clinically significant portal hypertension (CSPH). We retrospectively identified patients diagnosed with esophageal or gastric varices (EGV). Laboratory results, endoscopy reports and outcomes of patients with MASLD were compared to patients with advanced stage chronic liver disease (CLD) of other etiologies. During the study period 326 patients were diagnosed with EGV. 88 (26.9%) had MASLD, 113 (34.6%) viral hepatitis (VH), 63 (19.3%) alcoholic liver disease (ALD) and 62 (19%) both VH and ALD (VHALD). EGV bleeding events were significantly more frequent in patients with MASLD (36.3%), compared to VH (28.3%), ALD (30.1%) and VHALD (25.8%), respectively (p < 0.01). Mean Model for End-Stage Liver Disease (MELD)-Na score surrounding 1 year of first event of EGV bleeding was significantly lower in MASLD patients compared to all other etiologies (p = 0.02). At a MELD-Na score of 11–20, cumulative survival rate was significantly lower in MASLD patients compared to all other etiologies (log rank p < 0.01). MASLD patients present with EGV bleeding at lower MELD-Na scores compared to other etiologies of CLD. MELD-Na score may therefore underestimate disease severity and risk of death in patients with MASLD and CSPH. [ABSTRACT FROM AUTHOR]

This manuscript aims to critically evaluate the current evidence regarding adverse cardiovascular effects associated with proton pump inhibitors (PPIs) in patients with coronary artery disease (CAD). It also provides guidance for the selection of the most appropriate PPI within the context of cardiovascular polypharmacy and emphasizes the importance of establishing consensus among clinicians on the need to prescribe PPIs with limited cytochrome P450 (CYP450) enzyme inhibition to reduce the risk of drug interactions. PPIs are among the most widely used drugs for the treatment of gastroesophageal reflux disease (GERD) and the prevention of gastrointestinal (GI) bleeding. The manuscript reports the proceedings from the first practice recommendations meeting on the cardiovascular compatibility of PPIs in an Indian setting. A panel of eight Indian experts in cardiology and gastroenterology reviewed 14 consensus statements. Available literature was searched and summarized, and after multiple rounds of review, consensus was achieved for these statements. Based on the available evidence, the consensus panel highlights that a PPI with minimal drug–drug interaction (DDI) is recommended, especially in patients requiring clopidogrel or polypharmacy. Rabeprazole appears to be a good option in cases where co-prescription is indicated, owing to its optimal acid suppression and minimal drug interaction profile. [ABSTRACT FROM AUTHOR]

Background: With rising worldwide population aging, the number of homebound individuals with multimorbidity is increasing. Improvement in the quality of home medical care (HMC), including medications, contributes to meeting older adults' preference for "aging in place" and securing healthcare resources. Objective: To evaluate the changes in drug prescriptions, particularly potentially inappropriate medications (PIMs), among older adults receiving HMC in recent years, during which measures addressing inappropriate polypharmacy were implemented, including the introduction of clinical practice guidelines and medical fees for deprescribing. Design: A cross-sectional study. Participants: Using data from the national claims database in Japan, this study included older adults aged ≥ 75 years who received HMC in October 2015 (N = 499,850) and October 2019 (N = 657,051). Main Measures: Number of drugs, prevalence of polypharmacy (≥ 5 regular drugs), major drug categories/classes, and PIMs according to Japanese guidelines were analyzed. Random effects logistic regression models were used to evaluate the differences in medications between 2015 and 2019, considering the correlation within individuals who contributed to the analysis in both years. Key Results: The number of drugs remained unchanged from 2015 to 2019 (median: 6; interquartile range: 4, 9). The prevalence of polypharmacy also remained unchanged at 70.0% in both years (P = 0.93). However, the prescription of some drugs (e.g., direct oral anticoagulants, new types of hypnotics, acetaminophen, proton pump inhibitors, and β-blockers) increased, whereas others (e.g., warfarin, vasodilators, H2 blockers, acetylcholinesterase inhibitors, and benzodiazepines) decreased. Among the frequently prescribed PIMs, benzodiazepines/Z-drugs (25.6% in 2015 to 21.1% in 2019; adjusted odds ratio: 0.52) and H2 blockers (11.2 to 7.3%; 0.45) decreased, whereas diuretics (23.8 to 23.6%; 0.90) and antipsychotics (9.7 to 10.5%; 1.11) remained unchanged. Conclusions: We observed some favorable changes but identified some continuous and new challenges. This study suggests that continued attention to medication optimization is required to achieve safe and effective HMC. [ABSTRACT FROM AUTHOR]

Purpose: We present the results of an open-label, phase I/II study evaluating the safety and efficacy of the novel somatostatin receptor (SSTR) antagonist [177Lu]Lu-satoreotide tetraxetan in 40 patients with previously treated, progressive neuroendocrine tumours (NETs), in which dosimetry was used to guide maximum administered activity. Methods: This study was conducted in two parts. Part A consisted of 15 patients who completed three cycles of [177Lu]Lu-satoreotide tetraxetan at a fixed administered activity and peptide amount per cycle (4.5 GBq/300 µg). Part B, which included 25 patients who received one to five cycles of [177Lu]Lu-satoreotide tetraxetan, evaluated different administered activities (4.5 or 6.0 GBq/cycle) and peptide amounts (300, 700, or 1300 μg/cycle), limited to a cumulative absorbed radiation dose of 23 Gy to the kidneys and 1.5 Gy to the bone marrow. Results: Median cumulative administered activity of [177Lu]Lu-satoreotide tetraxetan was 13.0 GBq over three cycles (13.1 GBq in part A and 12.9 GBq in part B). Overall, 17 (42.5%) patients experienced grade ≥ 3 treatment‑related adverse events; the most common were lymphopenia, thrombocytopenia, and neutropenia. No grade 3/4 nephrotoxicity was observed. Two patients developed myeloid neoplasms considered treatment related by the investigator. Disease control rate for part A and part B was 94.7% (95% confidence interval [CI]: 82.3–99.4), and overall response rate was 21.1% (95% CI: 9.6–37.3). Conclusion: [177Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three cycles, has an acceptable safety profile with a promising clinical response in patients with progressive, SSTR-positive NETs. A 5-year long-term follow-up study is ongoing. Trial registration: ClinicalTrials.gov, NCT02592707. Registered October 30, 2015. [ABSTRACT FROM AUTHOR]

This study aims to investigate the impact of antithrombotic agents and proton-pump inhibitors (PPIs) on fecal immunochemical test (FIT). PubMed, EMBASE, Web of Science, Cochrane Central, and Google Scholar were searched from inception until September 3, 2023. Studies comparing the diagnostic performance of FIT between medicine users and non-users in average-risk colorectal cancer screening populations were included. Pooled sensitivity, specificity, and positive predictive values (PPVs) for advanced neoplasia (AN) of FIT were compared by reporting pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a random-effects model. Twenty-two studies enrolling 5,572,367 individuals were included. For aspirin, pooled sensitivity and specificity for AN were 57.2% and 88.4% in users versus 60.2% and 93.2% in non-users; while pooled ORs were 1.49 (95% CI 0.89–2.48, P = 0.13) and 0.72 (95% CI 0.62–0.83, P < 0.001), respectively. In subgroup analysis, there was no difference in sensitivity and specificity between the two groups at the cutoff of 20 μg Hb/g (P = 0.57 and 0.29, respectively) but a significantly lower specificity in users compared with non-users at lower cutoffs (P < 0.001). Moreover, a significantly lower PPVAN in users compared with non-users was observed after matching age and sex confounders (P = 0.001). Warfarin had no significant influence on PPVAN of FIT (P = 0.43). PPIs were associated with a significantly lower PPVAN in users (P < 0.001). Aspirin use was associated with lower specificity and PPV of FIT. Aspirin discontinuation before FIT to reduce false-positive results should be interpreted with caution given concerns about cardiovascular events. Increasing cutoff values of FIT in aspirin users may be another possible approach. Additionally, warfarin withdrawal before FIT is unnecessary but PPIs withdrawal before FIT is recommended to reduce false-positive results. [ABSTRACT FROM AUTHOR]

Introduction: Ranitidine, a histamine H2-receptor antagonist (H2RA), is indicated in the management of gastric acid-related disorders. In 2020, the European Medicines Agency (EMA) recommended suspension of all ranitidine-containing medicines in the European Union (EU) due to the presence of N-nitrosodimethylamine (NDMA) impurities, which were considered to be carcinogenic. The aim of this study was to investigate the impact of regulatory intervention on use patterns of ranitidine-containing medicines and their therapeutic alternatives. Objectives: The aim was to study drug utilisation patterns of ranitidine and report discernible trends in treatment discontinuation and switching to alternative medications. Methods: This retrospective, population-based cohort study was conducted using primary care records from six European countries between 2017 and 2023. To explore drug utilisation patterns, we calculated (1) incident use of ranitidine, other H2RAs, and other alternative drugs for the treatment of gastric ulcer and/or gastric bleeding; (2) ranitidine discontinuation; and (3) switching from ranitidine to alternative drugs (H2RAs, proton-pump inhibitors [PPIs], and other medicinal products for acid-related disorders). Results: During the study period, 385,273 new ranitidine users were observed, with most users being female and aged 18–74 years. Ranitidine was the most commonly prescribed H2RA in the pre-referral period (September 2017–August 2019), with incidence rates between 0.8 and 9.0/1000 person years (PY). A steep decline to 0.3–3.8/1000 PY was observed in the referral period (September 2019–March 2020), eventually dropping to 0.0–0.4/1000 PY in the post-referral period (April 2020–March 2022). Switching from ranitidine to alternative drugs increased in the post-referral period, with the majority of patients switching to PPIs. Discontinuation of ranitidine use ranged from 270 to 380/1000 users in 2017 and decreased over time. Conclusions: Ranitidine was commonly used prior to referral, but it was subsequently discontinued and replaced primarily with PPIs. [ABSTRACT FROM AUTHOR]

Ergometrine (6aR,9R)-N-((S)-1-hydroxypropan-2-yl)-7-methyl-4,6,6a,7,8,9-hexa-hydro-indolo-[4,3-fg]chinolin-9-carboxamide or lysergide acid β-ethanolamide or ergonovine) activates several types of serotonin and histamine receptors in the animal heart. We thus examined whether ergometrine can activate human serotonin 5-HT4 receptors (h5-HT4R) and/or human histamine H2 receptors (hH2R) in the heart of transgenic mice and/or in the human isolated atrium. Force of contraction or beating rates were studied in electrically stimulated left atrial or spontaneously beating right atrial preparations or spontaneously beating isolated retrogradely perfused hearts (Langendorff setup) of mice with cardiac specific overexpression of the h5-HT4R (5-HT4-TG) or of mice with cardiac specific overexpression of the hH2R (H2-TG) or in electrically stimulated human right atrial preparations obtained during cardiac surgery. Western blots to assess phospholamban (PLB) phosphorylation on serine 16 were performed. Ergometrine exerted concentration- and time-dependent positive inotropic effects and positive chronotropic effects in atrial preparations starting at 0.3 µM and reaching a plateau at 10 µM in H2-TGs (n = 7). This was accompanied by an increase in PLB phosphorylation at serine 16. Ergometrine up 10 µM failed to increase force of contraction in left atrial preparations from 5-HT4-TGs (n = 5). Ten micrometer ergometrine increased the force of contraction in isolated retrogradely perfused spontaneously beating heart preparations (Langendorff setup) from H2-TG but not 5-HT4-TG. In the presence of the phosphodiesterase inhibitor cilostamide (1 µM), ergometrine at 10 µM exerted positive inotropic effects in isolated electrically stimulated human right atrial preparations, obtained during cardiac surgery, and these effects were eliminated by 10 µM of the H2R antagonist cimetidine but not by 10 µM of the 5-HT4R antagonist tropisetron. Furthermore, ergometrine showed binding to human histamine H2 receptors (at 100 µM and 1 mM) using HEK cells in a recombinant expression system (pKi < 4.5, n = 3). In conclusion, we suggest that ergometrine is an agonist at cardiac human H2Rs. [ABSTRACT FROM AUTHOR]

The treatment modality of gastric adenocarcinoma (GCA) depends on the stage of the disease at the clinical presentation. Long delays are probably an unfavorable factor for the patient's prognosis. A prospective longitudinal, study involving 145 consecutive GCA was conducted at the National Hospital of Sri Lanka (NHSL). The overall delay (in weeks) was recorded for each patient and divided into four periods-patient, endoscopy, pathology and treatment. The median and Interquartile Range (IQR) duration of delays were calculated and differences were explored with chi square test and Mann Whitney U test Survival analysis was done with Kaplan Meier technique and Cox regression. The median duration of delays for patient, endoscopy, histology reporting delay, other histology delay (specimen transfer delay and report receipt delay) and treatment were 18 (IQR 14–27), 2 (IQR 2–3), 3 (IQR 2–3), 2 (IQR 1–2) and 6 (IQR 4–8) weeks respectively. Delayed patient presentation to hospital was associated with significant adverse median survival 16 (IQR 11.5–22.5) weeks versus 20 (IQR 16–27.5) weeks, p = 0.004. Delay in initiating treatment was associated with significantly lower median survival 04 (IQR 4–6) weeks versus 06 (IQR 4–8) weeks, p = 0.003. Over 60% of both proximal and distal GCA presented at an advanced radiological stage (stage III/IV). The Kaplan Meier analysis showed that the higher hazard function was associated with a higher tumour stage and undergoing chemotherapy. Age of the patient and the treatment modality were significant predictors of the survival. Patient delay and delay in initiation of definitive treatment are the most important factors that adversely affect the outcomes of GCA. Public health interventions aiming to shorten the patient delay time with proper referral for specialist care would play an important role. Also, it is important to minimize these preventable delays and there should be time limits in producing the histopathology report and to establish online portals of hospital and laboratory information systems for easy access of histology reports in future. [ABSTRACT FROM AUTHOR]

Gastro-esophageal reflux disease (GERD) can cause erosive esophagitis (EE) and compromise the quality of life (QoL). We examined differences in symptom severity and QoL according to EE severity grade. A follow-up study was conducted among GERD patients at the Nazareth Hospital in Israel. Patients underwent a baseline gastroscopy in 2014–2020 during which the EE grade was determined using the Los Angeles classification. Follow-up telephone interviews were conducted during 2019–2020 with a mean time interval of 18.9 months (SD = 14.9) after the baseline gastroscopy to assess GERD symptoms using the Reflux disease questionnaire (RDQ) and QoL using the GERD QoL questionnaire. The patients were interviewed in their native language (Arabic or Hebrew). Overall, 149 (66.4% males) patients were included; 50 had EE grades C/D and 99 had grades A/B. The mean age at baseline and follow-up was 44.6 years (SD = 15.1) and 46.2 years (SD = 14.9), respectively. Cronbach's alpha was 0.928 and 0.855 for the RDQ and QoL questionnaires, respectively. Patients with EE C/D grades had more severe symptoms than patients with EE A/B grades (P = 0.05), especially in regurgitation scores (P = 0.03). Females had more severe symptoms (overall) than males (adjusted OR = 2.34; 95% CI 1.12–4.90). Patients with the more severe esophagitis EE C/D group (adjusted OR = 1.98; 95% CI 0.93–4.24) and those who used PPIs treatment (adjusted OR = 2.19; 95% CI 0.95–5.01) reported more severe GERD symptoms. The number of schooling years was significantly associated with better QoL score (beta coefficient 1.33, P = 0.005) but not EE grade or GERD symptoms. Follow-up endoscopy conducted among 22 patients with EE grades C/D showed that 13 (59.1%) of these patients had normal endoscopic findings, 6 patients (27.3%) had a grade A EE, 1 patient (4.5%) had grade B, and 2 (9.1%) remained with grade C EE. The Arabic and Hebrew versions of the RDQ and QoL questionnaires were highly reliable. GERD symptoms severity was more profound among patients with more severe esophagitis. No significant association between EE grade and QoL; this negative result might be due to the improvement in esophagitis endoscopic findings among patients with C/D grade. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the fifth most frequent malignancy worldwide and has a high mortality rate related to late diagnosis. Although the gold standard for the GC diagnosis is endoscopy with biopsy, nonetheless, it is not cost-effective and is invasive for the patient. The Human leukocyte antigen G (HLA-G) molecule is a checkpoint of the immune response. Its overexpression in cancer is associated with immune evasion, metastasis, poor prognosis, and lower overall survival. We evaluate the plasma levels of soluble HLA-G, (sHLA-G) in patients with GC and benign gastric pathologies using an ELISA test. A higher concentration of sHLA-G in patients with GC than in those with benign pathologies, higher levels of plasma sHLA-G in women with GC compared with men and significant differences in the sHLA-G levels between the benign gastric pathologies evaluated, was our main findings. As no significant differences were found between the GC assessed stages in our study population, we suggest that sHLA-G is not an adequate marker for staging GC, but it does have diagnostic potential. In addition to providing information on the potential of sHLA-G as a diagnostic marker for GC, our study demonstrate that HLA-G molecules can be found in the membrane of exosomes, which highlights the need to perform studies with a larger number of samples to explore the functional implications of HLA-G positive exosomes in the context of gastric cancer, and to determine the clinical significance and possible applications of these findings in the development of non-invasive diagnostic methods. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) can reduce the risk of upper gastrointestinal bleeding (UGIB) in patients who are taking oral anticoagulants. This study aimed to identify the association between NOACs with PPI cotherapy and UGIB. This retrospective cohort analysis included patients over the age of 18 years who were using NOACs between 2013 and 2020. NOAC categories, concomitant medications, endoscopic findings, the HAS-BLED score and the Charlson Comorbidity Index score were recorded. Using Poisson regression models, the relationship between UGIB events and risk factors was analyzed. Throughout a mean follow-up of 29.5 months, 14 (5.1%) individuals experienced UGIB. The incidence of UGIB was greater in patients receiving NOACs without PPIs (2.7 [1.26–5.60] per 1000) than in those receiving NOACs with PPIs (1.3 [0.61–2.67] per 1000). Patients receiving NOACs with PPIs had a 79.2% lower incidence of UGIB than patients receiving NOAC monotherapy (RR 0.208, 95% CI 0.061–0.706; p = 0.012). Female sex and the HAS-BLED score were associated with UGIB (RR 5.043; 95% CI 1.096–23.20; p = 0.038; RR 2.024; 95% CI 1.095–3.743; p = 0.024, respectively). Patients receiving NOAC and PPI cotherapy had a lower incidence of UGIB than those receiving NOACs alone, and female sex was a risk factor for UGIB in NOAC-treated patients. [ABSTRACT FROM AUTHOR]

The mechanism of metachronous recurrence (MR) after performing endoscopic treatment for early gastric adenocarcinoma (GAC) and eradicating Helicobacter pylori (H. pylori) is unknown. To elucidate the mechanism and risk factors of MR, we analyzed gene expression at multiple locations of the gastric mucosa. We selected each five patients with MR and without MR (control), after early GAC treatment and eradication of H. pylori. Mucosal tissue was collected from four sites in the stomach of each patient as biopsy specimens for mRNA sequencing, gene set enrichment analysis, and microRNA (miRNA) sequencing. We also performed correlation analysis and target prediction on pathways. As a result, endoscopically, the MR group had more intestinal metaplasia and enlarged folds. A total of 384 mRNAs presented changes in expression and 31 gene sets were enriched in the MR group. Immune-related pathways were enriched in the entire stomach, and the IFN-α response had the highest enrichment score. Additionally, 32 miRNAs revealed changes in their expression. Correlation analysis and target prediction with genes in the gene set of IFN-α response revealed that 10 miRNA–mRNA pairs presented a significant correlation. Immune-related pathways with miRNAs in the gastric mucosa after H. pylori eradication may be a risk factor for MR. [ABSTRACT FROM AUTHOR]

Histamine receptors play a pivotal role in various physiological functions (ranging from allergic responses to memory and sleep regulation), hence representing important drug targets. While second-generation antihistamines have successfully been used in rodents and humans, testing their effects in non-traditional animal models furthers our understanding of their physiological activity and facilitates the development of novel drug candidates. Here, we examined the effects of the first-generation antihistaminic drug chloropyramine and the second-generation drugs loratadine and cetirizine, at concentrations of 1, 5, and 10 mg/L, on adult zebrafish behavior in the novel tank test. All three drugs significantly altered zebrafish locomotor activity, decreasing the distance traveled and average velocity, as well as increasing low acceleration frequency. Chloropyramine (5 and 10 mg/L) and loratadine (1, 5, and 10 mg/L) also significantly reduced top entries compared to the control. Additionally, chloropyramine (5 mg/L) increased the total duration of top entries, whereas loratadine (10 mg/L) reduced this behavior compared to controls. Overall, chloropyramine and loratadine exhibited a sedative effect typical of antihistamines, whereas cetirizine solely reduced locomotor activity without affecting other patterns of fish behavior. Thus, cetirizine demonstrated the least side effects on the central nervous system among the studied drugs, making it the optimal and safest choice among antihistamines. [ABSTRACT FROM AUTHOR]

Pharmacoencephalography (pharmaco-EEG) is a prominent instrument for the pharmacological screening of new psychoactive molecules. This experimental approach has not remained a vestige of neurobiological studies, and can be used successfully to complete today's research objectives. The development and rise to universal use of machine learning techniques opens up novel prospects for the use of pharmaco-EEG data to solve the problems of classification and prognosis. We have previously shown that naïve Bayes classifier (NBC) combined with principal component analysis (PCA) can be used to differentiate between antipsychotic and sedative drug effects as well as to distinguish among the antipsychotics' effects. In the present study, we evaluated the possibility to employ this method to assess the dose-dependency of antipsychotic effects. The experiments were carried out in white outbred male rats with chronically implanted electrocorticographic electrodes. As the agents of interest, we chose two drugs with antipsychotic activity, chlorpromazine and promethazine, in three doses each (0.1, 1, 10 mg/kg and 0.5, 5 and 20 mg/kg, respectively). The training set, used as a reference to determine the pharmacological effects of the agents of interest, included the D2-dopamine receptor blocker haloperidol, M-cholinergic receptor blocker tropicamide, H1-histamine receptor blocker chloropyramine, the sedative dexmedetomidine, and the anxiolytic phenazepam. We have shown that the lowest chlorpromazine dose (0.1 mg/kg) can be characterized as antipsychotic with a marked histaminolytic effect, while the highest one (10 mg/kg) exhibits predominantly antipsychotic activity with a cataleptogenic effect. All three doses demonstrated anticholinergic activity, which increased with the dose. For promethazine, we observed a clear dose-dependent shift from antipsychotic action to cataleptogenic, alongside a notable antimuscarinic effect of all doses. None of promethazine doses showed any resemblance to chloropyramine, which probably indicates its anti-dopaminergic and antimuscarinic effects being able to mask its H1-antihistamine effect in the used dose range. In summary, our results demonstrate that NBC combined with PCA can be used to determine the dose-dependency of antipsychotic agents' effects based on their impact on electrocorticogram parameters. Further development of this method as well as expansion of psychotropic agent electropharmacogram library would allow for more precise prediction of pharmacological activity of the agents of interest. [ABSTRACT FROM AUTHOR]

Background: The anti-HER2 antibody trastuzumab is a standard treatment for gastric carcinoma with HER2 overexpression, but not all patients benefit from treatment with HER2-targeted therapies due to intrinsic and acquired resistance. Thus, more precise predictors for selecting patients to receive trastuzumab therapy are urgently needed. Methods: We applied mass spectrometry-based proteomic analysis to 38 HER2-positive gastric tumor biopsies from 19 patients pretreated with trastuzumab (responders n = 10; nonresponders, n = 9) to identify factors that may influence innate sensitivity or resistance to trastuzumab therapy and validated the results in tumor cells and patient samples. Results: Statistical analyses revealed significantly lower phosphorylated ribosomal S6 (p-RPS6) levels in responders than nonresponders, and this downregulation was associated with a durable response and better overall survival after anti-HER2 therapy. High p-RPS6 levels could trigger AKT/mTOR/RPS6 signaling and inhibit trastuzumab antitumor efficacy in nonresponders. We demonstrated that RPS6 phosphorylation inhibitors in combination with trastuzumab effectively suppressed HER2-positive GC cell survival through the inhibition of the AKT/mTOR/RPS6 axis. Conclusions: Our findings provide for the first time a detailed proteomics profile of current protein alterations in patients before anti-HER2 therapy and present a novel and optimal predictor for the response to trastuzumab treatment. HER2-positive GC patients with low expression of p-RPS6 are more likely to benefit from trastuzumab therapy than those with high expression. However, those with high expression of p-RPS6 may benefit from trastuzumab in combination with RPS6 phosphorylation inhibitors. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are used in cancer immunotherapy; however, they can lead to immune-related adverse events (irAEs) through immune function of patients. Therefore, this meta-analysis aimed to assess the concomitant effect of acid suppressants (ASs) on ICIs, including several subgroup analyses. Methods: We identified related studies and generated the forest plot. The primary endpoint was defined as the change in progression free survival (PFS) and overall survival (OS) with or without ASs administration. We also evaluated the effect of ASs on the incidence of irAEs. Results: The total hazard ratio (HR) of ASs on PFS with ICI treatment was 1.39 and the 95% confidence interval (95% CI) was 1.21–1.59 (Z: p < 0.00001). Moreover, the total HR of ASs on OS was 1.40 and the 95% CI was 1.21–1.61 (Z: p < 0.00001), suggesting that ASs reduced ICI's therapeutic effect. The total odds ratio (OR) for evaluating the effect of ASs on irAEs was 1.23 with a 95% CI of 0.81–1.88 (Z: p = 0.34). However, ASs significantly worsened acute kidney injury (AKI) (total OR 2.10; 95% CI 1.74–2.53 (Z, p < 0.00001)). Furthermore, although proton pump inhibitors (PPIs) reduced ICI's therapeutic effect, histamine H2-receptor antagonists (H2RAs) did not affect OS. Conclusions: It was shown that ASs, especially PPIs, reduced ICI's therapeutic effect, while H2RAs had no effect, and ASs did not affect irAEs; however, it is a risk factor for ICIs-induced AKI. [ABSTRACT FROM AUTHOR]

Purpose: An international shortage of ranitidine led to adjustments in premedication regimens for paclitaxel-based chemotherapy in early October 2019. In this study, we implemented and evaluated an anti-allergic protocol without histamine-2 antagonists (H2As) and aimed to assess the risk of hypersensitivity reactions (HSRs) to the different premedication regimens used. Methods: We conducted a single-center observational retrospective study of paclitaxel administrations (7173 administrations in 831 patients). Between January 2019 and December 2020, all allergies reported were recorded. A mixed logistic regression model was implemented to predict the risk of allergy at each injection and to account for repeated administration per patient. Results: A total of 27 HSRs occurred in 24 patients. No protective effect was observed for H2A when comparing paclitaxel injections with H2A premedication versus without H2A (OR = 1.12, p = 0.84). There was also no significant difference in risk of HSR for famotidine versus ranitidine (OR = 0.79, p = 0.78). However, the risk of HSRs was significantly lower for paclitaxel injections with corticosteroids than for those without (OR = 0.08, p = 0.03). In addition, the risk of HSR was significantly higher for the first, second, or third paclitaxel injections than for the subsequent injections (OR = 10.1, p < 0.001). Conclusion: We did not find substantial evidence of an increased risk of HSR due to the absence of H2A in the premedication protocols for paclitaxel. Thus, in contrary to the existing literature on paclitaxel, our findings support the use of a premedication protocol without H2A. [ABSTRACT FROM AUTHOR]

Purpose: Vertical sleeve gastrectomy (VSG) evolved in the early 2000s into the standalone weight loss procedure we see today. While numerous studies highlight VSG's durability for weight loss, and improvements co-morbidities such as type 2 diabetes mellitus and cardiovascular disease, patients with gastroesophageal reflux disease (GERD) have been counseled against VSG due to the concern for worsening reflux symptoms. When considering anti-reflux procedures, VSG patients are unable to undergo traditional fundoplication due to lack of gastric cardia redundancy. Magnetic sphincter augmentation lacks long-term safety data and endoscopic approaches have undetermined longitudinal benefits. Until recently, the only option for patients with a history of VSG with medically refractory GERD has been conversion to roux en Y gastric bypass (RNYGB), however, this poses other risks including marginal ulcers, internal hernias, hypoglycemia, dumping syndrome, and nutritional deficiencies. Given the risks associated with conversion to RNYGB, we have adopted the ligamentum teres cardiopexy as an option for patients with intractable GERD following VSG. Methods: A retrospective chart review was conducted of patients who had prior laparoscopic or robotic VSG and subsequently GERD symptoms refectory to pharmacological management who underwent ligamentum teres cardiopexy between 2017 and 2022. Pre-operative GERD disease burden, intraoperative cardiopexy characteristics, post-operative GERD symptomatology and changes in H2 blocker or PPI requirements were reviewed. Results: Of the study's 60 patients the median age was 50 years old, and 86% were female. All patients had a diagnosis of GERD through pre-operative assessments and were taking antisecretory medication. Of the 36 patients who have completed their one year follow up, 81% of patients had either a decrease in dosage or cessation of the antisecretory medication at one year following ligamentum teres cardiopexy. Conclusion: Ligamentum teres cardiopexy is a viable alternative to RNYGB in patients with a prior vertical sleeve gastrectomy with medical refractory GERD. [ABSTRACT FROM AUTHOR]

Background: Obesity is an epidemic, with its accompanying medical conditions putting patients at increased risk of postoperative complications. For patients undergoing elective surgery, preoperative weight loss provides an opportunity to decrease complications. We sought to evaluate the safety and efficacy of an intragastric balloon in achieving a body mass index (BMI) < 35 kg/m2 prior to elective joint replacement or hernia repair. Methods: Retrospective review of all patients who had intragastric balloon placement at a level 1A VA medical center from 1/2019 to 1/2023. Patients who had a scheduled qualifying procedure (knee/hip replacement or hernia repair) and had a BMI > 35 kg/m2 were offered intragastric balloon placement to achieve 30-50lbs (13–28 kg) weight loss prior to surgery. Participation in a standardized weight loss program for 12 months was required. Balloons were removed 6 months after placement, preferentially concomitant with the qualifying procedure. Baseline demographics, duration of balloon therapy, weight loss and progression to qualifying procedure were recorded. Results: Twenty patients completed intragastric balloon therapy and had balloon removal. Mean age 54 (34–71 years), majority (95%) male. Mean balloon duration was 200 ± 37 days. Mean weight loss was 30.8 ± 17.7lbs (14.0 ± 8.0 kg) with an average BMI reduction of 4.4 ± 2.9. Seventeen (85%) patients were successful, 15 (75%) underwent elective surgery and 2 (10%) were no longer symptomatic after weight loss. Three patients (15%) did not lose sufficient weight to qualify or were too ill to undergo surgery. Nausea was the most frequent side effect. One (5%) patient was readmitted within 30 days for pneumonia. Discussion: Intragastric balloon placement resulted in an average 30lbs (14 kg) weight loss over 6 months allowing more than 75% of patients to undergo joint replacement or hernia repair at an optimal weight. Intragastric balloons should be considered in patients requiring 30–50lbs (13–28 kg) weight loss prior to elective surgery. More study is needed to determine the long-term benefit of preoperative weight loss prior to elective surgery. [ABSTRACT FROM AUTHOR]

Background: Severe obesity is a relative contraindication for renal transplantation, therefore bariatric surgery is an important option as a pre-kidney transplant weight loss strategy. However, comparative data regarding postoperative outcomes of laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB) in patients with or without ESRD on dialysis are scarce. Methods: Patients between 18- and 80-year-old who underwent LSG and RYGB were included. To determine the outcomes of patient who underwent bariatric surgery with ESRD on dialysis, a 1:4 PSM was performed between the patients with ESRD on dialysis and those without renal disease. The PSM analyses in both groups were performed using 20 preoperative characteristics. Then 30-day postoperative outcomes were assessed. Results: The operative time and postoperative-LOS were significantly longer in ESRD patients on dialysis compared to those with no renal disease either for LSG (82.37 ± 40.42 vs. 73.62 ± 38.65; P < 0.001, 2.22 ± 3.01 vs. 1.67 ± 1.90; P < 0.001) or for LRYGB (129.13 ± 63.20 vs. 118.72 ± 54.16; P = 0.002, 2.53 ± 1.74 vs. 2.00 ± 1.68; P < 0.001). In the LSG cohort (2137 vs. 8495 matched cases), patients with ESRD on dialysis showed significant increase in mortality (0.7% vs 0.3%; P = 0.019), unplanned ICU admission (3.1% vs 1.3%; P < 0.001), blood transfusions (2.3% vs 0.8%; P 0.001), readmissions (9.1% vs. 4.0%; P < 0.001), reoperations (3.4% vs. 1.2%; P < 0.001), interventions (2.3% vs. 1.0%; P = 0.006). In the LRYGB group (443 vs. 1769 matched cases), patients with ESRD on dialysis showed a significantly higher need for unplanned ICU admission (3.8% vs. 1.4%; P = 0.027), readmissions (12.4% vs. 6.6%; P = 0.011), and interventions (5.2% vs. 2.0%; P = 0.050). Conclusion: Bariatric surgery is a safe procedure for patients with ESRD on dialysis to help them get a kidney transplant. Even though this group experienced a higher incidence of postoperative complications compared to those without kidney disease, the absolute complication rates are low and not associated with bariatric-specific complications. Therefore, ESRD should not be perceived as contraindications to bariatric surgery. [ABSTRACT FROM AUTHOR]

Background: Gastroesophageal reflux disease (GERD) is a possible side effect of sleeve gastrectomy (SG). However, procedure selection for patients with GERD and risk factors for morbidity after bypass surgeries is complex. For patients with a preoperative GERD diagnosis, literature related to worsening postoperative symptoms is discordant. Objective: This study evaluated the effects of SG on patients with pre-operative GERD confirmed through pH testing. Setting: University Hospital, United States. Methods: This was a single-center case-series. SG patients with preoperative pH testing were compared based on DeMeester scoring. Preoperative demographics, endoscopy results, need for conversion surgery, and changes in gastrointestinal quality of life (GIQLI) scores were compared. Two-sample independent t-tests assuming unequal variances were used for statistical analysis. Results: Twenty SG patients had preoperative pH testing. Nine patients were GERD positive; median DeMeester score 26.7 (22.1–31.15). Eleven patients were GERD negative, with a median DeMeester score of 9.0 (4.5–13.1). The two groups had similar median BMI, preoperative endoscopic findings and use of GERD medications. Concurrent hiatal hernia repair was performed in 22% of GERD positive vs. 36% of GERD negative patients, (p = 0.512). Two patients in the GERD positive cohort required conversion to gastric bypass (22%), while none in the GERD negative cohort did. No significant postoperative differences were noted in GIQLI, heartburn, or regurgitation symptoms. Conclusion: Objective pH testing may allow the differentiation of patients who would be higher risk for need for conversion to gastric bypass. For patients with mild symptoms, but negative pH testing, SG may represent a durable option. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA) are commonly used medications in neonates and infants for the treatment of gastroesophageal reflux disease (GERD), especially in neonatal intensive care units (NICUs). A literature review was conducted to evaluate the efficacy and safety of histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) in preterm neonates, term neonates, and infants. A total of 27 studies were included in this review. Antacid medications in studies have consistently shown positive pharmacodynamic effects, including increasing gastric pH, reducing the reflux index, and reducing the number of acidic reflux events. The benefit found in placebo-controlled trials are limited exclusively to these surrogate outcomes. The actual clinically salient outcomes which H2RAs and PPIs are used for, such as reduction in GERD symptoms, especially irritability and improved feed tolerance and weight gain, have consistently shown no clinical benefit. H2RAs and PPIs appear to be extremely well tolerated by the neonatal and infant populations, which would mimic our experience with these medications in our unit. The available data from large, retrospective cohort and case-control studies paint a much more concerning picture regarding the potential for an increased risk in the development of allergies, anaphylactic reactions, necrotizing enterocolitis (NEC), other nosocomial infections, and lower respiratory tract infections. Given the risks associated with and lack of clinical effectiveness of both H2RAs and PPIs, use of these medications should be limited to specific clinical situations. Further studies are required to determine whether antacid pharmacologic therapy might benefit certain neonates and infants, such as those with complex medical issues. [ABSTRACT FROM AUTHOR]

Background and Objective: Migraine is a neurological disorder characterized by episodes of moderate-to-severe headache. The emergence of drugs derived from monoclonal antibodies specific for the calcitonin gene has brought forth a therapeutic option for patients in whom the traditional treatments have failed. This study aimed to evaluate the clinical effectiveness of calcitonin gene-related peptide antibodies in the prevention of migraine through a systematic review and meta-analysis of observational cohort studies. Methods: A literature search for evidence was performed in electronic databases for observational studies that evaluated adult patients with migraine receiving calcitonin gene-related peptide receptor antagonists (e.g. erenumab, fremanezumab, galcanezumab and eptinezumab) and reported effectiveness outcomes (mean reduction in monthly migraine/headache days, and proportion of patients with 50% or greater reduction in migraine/headache days). Results: During the screening process, 47 records were included for data extraction and qualitative and quantitative analyses. The overall rate of patients with a reduction of at least 50% of mean monthly migraine days was 54% (95% CI 49–59%), and overall mean monthly migraine reduction was about 7.7 days (95% CI 8.4–7.0 days). Regarding the outcome ≥ 50% reduction in mean monthly headache reduction, the overall rate of patients with a reduction of at least 50% was 57% (95% CI 48–64%), and the overall mean monthly headache reduction was approximately 8.8 days (95% CI 10.1–7.5 days). Subgroup analyses considering the drug treatment used and type of migraine were consistent with previous results. Conclusions: The use of calcitonin gene-related peptide antibodies in real-world studies to prevent migraine demonstrates promising effectiveness outcomes, in agreement with those reported in previously published randomized clinical trial reports. [ABSTRACT FROM AUTHOR]

Background: Drug shortages are a complex global challenge, and few studies have analyzed quantitative data on their impacts. In September 2019, detection of a nitrosamine impurity in ranitidine led to recalls and shortages. Aims: We investigated the extent of the ranitidine shortage and its impacts on acid suppression drug utilization in Canada and the United States (US). Methods: We conducted an interrupted time series analysis of acid suppression drug purchases in Canada and the US from 2016 through 2021 using IQVIA's MIDAS database. We used autoregressive integrated moving average models to determine the impact of the shortage on purchasing rates for ranitidine, other histamine-2 receptor antagonists (H2RAs), and proton pump inhibitors (PPIs). Results: Prior to the recalls, 20,439,915 ranitidine units were purchased monthly in Canada and 189,038,496 in the US on average. After the recalls started in September 2019, purchasing rates decreased for ranitidine (Canada p = 0.0048, US p < 0.0001) and increased for non-ranitidine H2RAs (Canada p = 0.0192, US p = 0.0534). One month into the recalls, purchasing rates dropped by 99% (Canada) and 53% (US) for ranitidine and increased by 128.3% (Canada) and 37.3% (US) for non-ranitidine H2RAs. PPI purchasing rates did not change significantly in either country. Conclusions: The ranitidine shortage led to immediate and sustained shifts in H2RA utilization in both countries, potentially affecting hundreds of thousands of patients. Our results emphasize the need for future studies of the clinical and financial implications of the shortage, and the importance of ongoing work to mitigate and prevent drug shortages. [ABSTRACT FROM AUTHOR]

Background: As a novel antineoplastic drug, immune checkpoint inhibitors (ICIs) are associated with a spectrum of autoimmune-related side effects, including acute kidney injury (AKI). Understanding the risk factors for immune-associated acute kidney injury will inform future symptom management measures to reduce this risk. This study aims to identify the risk factors for ICIs-AKI in cancer patients through a systematic review and meta-analysis. Methods: The systematic search was conducted in The Cochrane Library, Pubmed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Database. The related studies published since the establishment of the database to Aug 22, 2022, were screened, data was extracted following the inclusion and exclusion criteria, and the quality of the selected studies was assessed by Newcastle–Ottawa Scale (NOS). The above was performed independently by the two reviewers. The estimated pooled odds ratios (ORs) for risk factors of developing ICIs-AKI were conducted by random-effects meta-analysis. Results: A total of 8 publications, including 5267 patients, were included. Meta-analysis results showed that extrarenal immune-related adverse events (irAEs), therapy with the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), male, hypertension, pre-existent use of a diuretic, and a proton pump inhibitor (PPI) were significantly correlated to ICIs-AKI. Conclusions: We identified extrarenal irAEs, CTLA-4 treatments, males, hypertension, previous use of diuretics, and PPIs are essential predictors of ICIs-AKI. These findings are helpful for healthcare providers to monitor ICIs-AKI for management and timely interventions. [ABSTRACT FROM AUTHOR]

In this paper, a data set of [3H] diazepam derivatives was analyzed using various computational methods: molecular docking/dynamic simulations, and QSAR analysis. The main aims of these studies are to understand the binding mechanisms by which benzodiazepines allosterically modulate GABAA receptor α1β2γ2 subtypes, from inducing neuronal inhibition at lower doses to the anesthetic effect at higher doses, and also, to define the structural requirements that contribute to improving the response of GABAA/α1β2γ2 receptor to benzodiazepine drugs. The results of the molecular docking study allowed selecting Ro12-6377 and proflazepam as the best modulators for the four binding sites simultaneously. Subsequently, the stability of the selected complexes was investigated by performing molecular dynamics simulation. The latter confirmed the features of both modulators to exert direct effects on the chloride-channel lining residues. Pharmacokinetics and drug-likeness profile were assessed through in silico tool. Furthermore, a QSAR analysis was conducted using an improved vemolecular dynamics simulations proposed byrsion of PLS regression. The goodness of fit and the predictive power of the resulting PLS model were estimated according to internal and external validation parameters: R2 = 0.632, R2adj = 0.584, F = 12.806; p-value = 6.2050e − 07, Q2loo = 0.639, and Q2F3 = 0.813. Clearly, the obtained results ensure the predictive ability of the developed QSAR model for the design of new high-potency benzodiazepine drugs. [ABSTRACT FROM AUTHOR]

Biosurfactants are attracting much interest due to their potential application as therapeutic agents in the medical and cosmetic field. Previous studies have demonstrated that biosurfactant such as sophorolipid (SL) exhibits immunomodulatory effects. In this article, we found the potential of sophorolipid for inhibiting histamine-induced itch and preliminarily explored its molecular basis. First, behavioral tests indicated that SL can remit the histamine-induced scratching behaviors of mice. Second, SL can suppress the the calcium influx induced by histamine, HTMT and VUF8430 in HaCaT cells. RT-PCR analysis showed that the histamine-induced upregulation of mRNA levels of phospholipase Cγ1, 1,4,5-trisphosphate receptor (IP3R), and protein kinase Cα can be inhibted by SL, suggesting that SL may impede the PLC/IP3R signaling pathway activated by histamine. In further tests, the capsaicin-induced calcium influx can also be inhibited by SL. The immunofluorescence and molecular docking analysis indicated that SL acts as an inhibitor of transient receptor potential vanilloid-1 (TRPV1) activation to decrease calcium influx against stimuli. In summary, these results revealed that SL may inhibit histamine-induced itch by decreasing PLC/IP3R signaling pathway activation and modulating TRPV1 activity. This paper indicates that SL can be a useful treatment for histamine-dependent itch. [ABSTRACT FROM AUTHOR]

Cetirizine, a metabolite of hydroxyzine and derivative of piperazine, belongs to a family of antihistamines, which is effective second-generation histamine H1-receptor antagonist with antiallergic properties, showing prominent substitute to other 'non-sedating' antihistamines, and helps in treatment of physical urticaria and allergic asthma. Fast disintegration of prescription 'over-the-counter' standard Cetirizine tablets might generate early "burst-released" kinetics, resulting in significant drug absorption and a higher serum concentration. So, it is enviable to design a drug delivery system for Cetirizine which delivers drug in body in controlled fashion. In this study, a single system was developed that included the benefits of both nanoparticles and microspheres for continual delivery of Cetirizine via a simple emulsification process. Initially, PEG C-Dot was formulated, and then Cetirizine drug was dissolved in PEG C-Dot, which was then encapsulated in PLA microspheres to form drug-conjugated C-Dot-encapsulated microspheres, which were characterized using UV–Vis spectroscopy, photoluminescence spectroscopy, Zeta potential, and FESEM techniques. In addition, FESEM images exhibited a uniform spherical morphology for the PLA microspheres. Cell viability of the nanocomposite was evaluated in normal HEK293 human embryonic cells by MTT assay. The aim of study was to optimize process parameters for uniformity on size, shape, and surface morphology of microspheres. Furthermore, optimized parameters were used to synthesize drug-conjugated C-Dot-encapsulated microspheres for controlled drug delivery. This study showed that engineered drug-conjugated C-Dot-encapsulated microspheres had excellent cell viability and imaging effects against HEK293 cell lines. These findings provide a novel platform for controlled drug delivery of Cetirizine and could pave the way for cancer therapy medications in future. [ABSTRACT FROM AUTHOR]

Objective and methods: IL-33 is present in endothelial, epithelial, and fibroblast-like cells and released upon cell injury. IL-33 reportedly induces mast-cell degranulation and is involved in various diseases, including allergic diseases. So, IL-33-related diseases seem to overlap with histamine-related diseases. In addition to the release from mast cells, histamine is newly formed by the induction of histidine decarboxylase (HDC). Some inflammatory and/or hematopoietic cytokines (IL-1, IL-3, etc.) are known to induce HDC, and the histamine produced by HDC induction is released without storage. We examined the involvement of HDC and histamine in the effects of IL-33. Results: A single intraperitoneal injection of IL-33 into mice induced HDC directly and/or via other cytokines (including IL-5) within a few hours in various tissues, particularly strongly in hematopoietic organs. The major cells exhibiting HDC-induction were mast cells and c-kit+ cells in the bone marrow. HDC was also induced in non-mast cells in non-hematopoietic organs. HDC, histamine, and histamine H4 receptors (H4Rs) contributed to the suppression of IL-33-induced eosinophilia. Conclusion: IL-33 directly and indirectly (via IL-5) induces HDC in various cells, particularly potently in c-kit+ cells and mature mast cells, and the newly formed histamine contributes to the negative regulation of IL-33-induced eosinophilia via H4Rs. [ABSTRACT FROM AUTHOR]

Background: Sepsis is marked by elevated histamine, which is a vasodilator that increases vascular permeability. Although human studies are lacking, murine models of sepsis have indicated potential protective effects of histamine 2 receptor antagonist administration (H2RAs). Objective: To assess any association between H2RA use in sepsis-3 patients admitted to the ICU and mortality, mechanical ventilation, length of stay, and markers of renal, liver, and lung dysfunction. Design: Retrospective cohort study. Setting: Intensive care units of the Beth Israel Deaconess Medical Center (BIDMC) accessed via the MIMIC-IV database spanning an 11-year period from 2008 to 2019. Patients (or participants): A total of 30,591 patients met the inclusion criteria for sepsis-3 on admission (mean age 66.49, standard deviation 15.92). Main measures: We collected patient age, gender, ethnicity, comorbidities (contained within the Charlson comorbidity index), SOFA score, OASIS score, APS III score, SAPS II score, H2RA use, creatinine, BUN, ALT, AST, and P/F ratios. Primary outcomes were mortality, mechanical ventilation, and ICU length of stay. Key results: A total of 30,591 patients met inclusion criteria over the 11-year sample period. The 28-day in hospital mortality rate was significantly lower among patients who received an H2RA (12.6% vs 15.1%, p < 0.001) as compared to those who did not receive an H2RA. Patients receiving an H2RA had significantly lower adjusted odds of mortality (0.802, 95% CI 0.741–0.869, p < 0.001), but significantly higher adjusted odds of invasive mechanical ventilation (4.426, 95% CI 4.132–4.741, p < 0.001) and significantly higher ICU LOS (3.2 days vs. 2.4 days, p < 0.001) as compared to the non-H2RA group. H2RA use was also associated with decreased severity of acute respiratory distress syndrome (ARDS) and lower serum creatinine. Conclusion: Among patients hospitalized in the ICU for sepsis, the use of an H2RA was associated with significantly lower odds of mortality, decreased severity of ARDS, and a lower incidence of renal insufficiency. [ABSTRACT FROM AUTHOR]