Search

Helicobacter pylori infection is an important causative factor in a variety of gastrointestinal diseases, such as atrophic gastritis, peptic ulcer disease, and gastric cancer. Timely eradication treatment is conducive to maintaining the health of patients. With the increase of drug resistance in Helicobacter pylori, dual therapy with proton pump inhibitors combined with high-dose amoxicillin has gradually gained attention. Potassium- competitive acid blockers are new types of antacids that have a faster onset of action and a longer lasting acid suppression effect than traditional proton pump inhibitors, making it more suitable for dual therapy. In recent years, scholars have carried out a lot of exploration, improvement and verification of potassium-competitive acid blockers dual therapy, and this article reviews its research progress. [ABSTRACT FROM AUTHOR]

This document is a summary of a Cochrane review that examines the effectiveness of various medications in treating gastroesophageal reflux disease (GORD) in infants and older children. The review found very low-certainty evidence regarding the benefits of medications for symptom improvement in infants. For older children, there was also very low-certainty evidence that proton pump inhibitors (PPIs) may or may not improve GORD outcomes. The review calls for further research with longer follow-up periods and improved trial design. It also highlights the potential side effects and conflicts of interest associated with these medications. [Extracted from the article]

Simple Summary: Proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) are commonly used for acid reduction in patients with peptic ulcer disease or esophageal reflux. Previous studies have shown that acid-reducing agents (ARAs) might affect bevacizumab treatment. This study found that PPI use worsened the oncological outcomes in patients with metastatic colorectal cancer (mCRC) undergoing bevacizumab treatment. There was a negative dose–response relationship when compared to H2RA use. Physicians should consider the benefits and risks of long-term use of ARAs, especially PPIs, in mCRC patients treated with bevacizumab. Background: Approximately one-third of patients with advanced colorectal cancer (CRC) and treated with bevacizumab are prescribed proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs). However, there is limited data on the effects of PPIs and H2RAs in these patients. To investigate the oncological outcomes of PPI and H2RA use in CRC patients treated with bevacizumab, we performed a retrospective cohort study using the Taiwan National Health Insurance Research Database and Taiwan Cancer Registry Database from 2005 to 2020. Methods: In CRC patients treated with bevacizumab, the PPI users and H2RA users were matched with patients without acid-reducing agents (ARAs) by 1:4 propensity score matching. PPI users and H2RA users were matched with propensity scoring in a 1:1 ratio. We divided patients into 4 cumulative PPI dosage levels to assess the dose–response relationship. The primary endpoints were 5-year overall survival and cancer-specific survival. Results: Compared with ARA non-users, both H2RA users and PPI users were associated with reduced overall survival. PPI users were associated with more significant negative effects on overall survival. Compared with H2RA users, PPI users were associated with lower 5-year overall survival (aHR: 1.19, 95% CI: 1.09–1.31) and cancer-specific survival (aHR: 1.20, 95% CI: 1.09–1.31). A similar dose–response relationship was observed for PPI users in terms of 5-year overall survival and cancer-specific overall survival. Conclusions: Compared to H2AR use, PPI use was associated with dose-dependent poorer oncological outcomes in metastatic CRC patients treated with bevacizumab. [ABSTRACT FROM AUTHOR]

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]

Aims: The aims of this study were to measure the prevalence of polypharmacy and describe the prescribing of selected medications known for overuse in older people with polypharmacy in primary care. Methods: This was a multinational retrospective cohort study across six countries: Belgium, France, Germany, Italy, Spain and the UK. We used anonymized longitudinal patient‐level information from general practice databases hosted by IQVIA. Patients ≥65 years were included. Polypharmacy was defined as having 5–9 and ≥10 distinct drug classes (ATC Level 3) prescribed during a 6‐month period. Selected medications were: opioids, antipsychotics, proton pump inhibitors (PPI), benzodiazepines (ATC Level 5). We included country experts on the healthcare context to interpret findings. Results: Age and gender distribution was similar across the six countries (mean age 75–76 years; 54–56% female). The prevalence of polypharmacy of 5–9 drugs was 22.8% (UK) to 58.3% (Germany); ≥10 drugs from 11.3% (UK) to 28.5% (Germany). In the polypharmacy population prescribed ≥5 drugs, opioid prescribing ranged from 11.5% (France) to 27.5% (Spain). Prescribing of PPI was highest with almost half of patients receiving a PPI, 42.3% (Germany) to 65.5% (Spain). Benzodiazepine prescribing showed a marked variation between countries, 2.7% (UK) to 34.9% (Spain). The healthcare context information explained possible underreporting for selected medications. Conclusions: We have found a high prevalence of polypharmacy with more than half of the older population being prescribed ≥5 drugs in four of the six countries. Whilst polypharmacy may be appropriate in many patients, worryingly high usage of PPIs and benzodiazepines supports current efforts to improve polypharmacy management across Europe. [ABSTRACT FROM AUTHOR]

Previous studies found that histamine H2 receptor antagonists (H2RAs) had blood pressure lowering and cardioprotective effects, but the impact of H2RAs on the survival outcomes of critically ill patients with essential hypertension is still unclear. The aim of this study was to investigate the association of H2RAs exposure with all‐cause mortality in patients with essential hypertension based on Medical Information Mart for Intensive Care III database. A total of 17,739 patients were included, involving 8482 H2RAs users and 9257 non‐H2RAs users. Propensity score matching (PSM) was performed to improve balance between 2 groups that were exposed to H2RAs or not. Kaplan–Meier survival curves were used to compare the cumulative survival rates and multivariable Cox regression models were performed to evaluate the association between H2RAs exposure and all‐cause mortality. After 1:1 PSM, 4416 pairs of patients were enrolled. The results revealed potentially significant association between H2RAs exposure and decreased 30‐day, 90‐day, and 1‐year mortalities in multivariate analyses (HR = 0.783, 95% CI: 0.696‐0.882 for 30‐day; HR = 0.860, 95% CI: 0.778‐0.950 for 90‐day; and HR = 0.883, 95% CI: 0.811‐0.961 for 1‐year mortality, respectively). Covariate effect analyses showed that the use of H2RAs was more beneficial in essential hypertension patients with age ≥ 60, BMI ≥ 25 kg/m2, coronary arteriosclerosis, stroke, and acute kidney failure, respectively. In conclusion, H2RAs exposure was related to lower mortalities in critically ill patients with essential hypertension, which provided novel potential strategy for the use of H2RAs in essential hypertension patients. [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]

Aims Methods Results Conclusions Gastro‐oesophageal reflux is common in newborns, especially in premature infants. Treatment by medication is controversial as the drugs prescribed have not been consistently proven to be effective and are known to have adverse effects. This study sought to identify trends in the prescription of anti‐reflux medication in a large group of French neonatal units.Data on prescriptions of anti‐reflux treatments—proton pump inhibitors (PPIs), antacids, histamine‐2 receptor antagonists (H2RAs), and prokinetics—from 2014 to 2022 for infants with a corrected gestational age <45 weeks, were extracted from a prescription database (Logipren®) used by 63 French neonatal units, and then analysed.Of all infants recorded in the database during the study period (n = 152 743), 10.2% (n = 15 650) were prescribed anti‐reflux medication (95% confidence interval [CI] 10.0–10.4%), mainly as monotherapy (77.5%). The rate was higher in the subgroup of preterm infants born before 28 weeks of gestation (n = 9493) (20.6%, 95% CI 19.8–21.4%; n = 1956). PPIs were the most commonly prescribed anti‐reflux medications (6.9% of infants, 95% CI 6.8–7.0), followed by antacids (5.2%, 95% CI 5.1–5.3%), while H2RAs and prokinetics were rarely prescribed. Over the period, the prescription rate remained stable for PPIs, decreased for H2RAs (τ = −0.86, P = .02), and, among preterm infants born at gestational ages of 28–31 or 32–36 weeks, increased for antacids.Anti‐reflux medications were frequently prescribed by neonatal units, especially for extremely premature infants. Most of these prescriptions were for PPIs and antacids. [ABSTRACT FROM AUTHOR]

This article explores the potential misdiagnosis of diarrhea-predominant irritable bowel syndrome (IBS) as systemic mastocytosis (SM), a hematological condition characterized by abnormal mast cell proliferation. It provides an overview of SM and its diagnostic criteria, as well as the clinical features and histology of the disease. The article includes a case report of a patient initially diagnosed with refractory IBS-D who was later found to have SM, highlighting the challenges in diagnosing SM and the importance of awareness among healthcare professionals. The document also discusses the role of serum biomarkers in the diagnosis, treatment, and monitoring of SM, including well-known markers like serum tryptase and other biomarkers that are still being investigated. Treatment for SM is individualized and may involve medications to control symptoms and tyrosine kinase inhibitors. Early diagnosis is crucial and can be achieved through a high clinical index of suspicion. [Extracted from the article]

Aim: The use of vitamin K antagonists (VKAs) may increase the risk of peripheral arterial disease (PAD) because vitamin K is a strong inhibitor of medial arterial calcification. Type 2 diabetes (T2D) exposes patients to an increased risk of PAD. We examined how the use of VKAs modulates the risk of incident PAD in people with T2D. Materials and Methods: SURDIAGENE is a French cohort including 1468 patients with T2D with a prospective follow‐up from 2002 to 2015. The primary outcome of the current analysis was the first occurrence of PAD, a composite of lower‐limb amputation (LLA) or lower‐limb revascularization. LLA and lower‐limb revascularization were considered individually as secondary outcomes. Results: During a 7‐year median follow‐up, PAD occurred in 147 (10%) of the 1468 participants. The use of VKAs was not significantly associated with the risk of PAD [multivariable adjusted hazard ratio (HR) 1.42, 95% confidence interval (CI), 0.88‐2.31]. During the study period, LLA and lower‐limb revascularization occurred in 82 (6%) and 105 (7%) participants, respectively. The use of VKAs was significantly associated with increased risk of LLA [multivariable adjusted HR 1.90 (95% CI, 1.04‐3.47)], but not lower‐limb revascularization [multivariable adjusted HR 1.08 (95% CI, 0.59‐1.97)]. Conclusions: In this prospective study, we did not observe any excess risk of PAD requiring lower‐limb revascularization in people with type 2 diabetes using VKAs. However, our data suggest a high risk of LLA in VKA users. Further studies are required to confirm this observation. [ABSTRACT FROM AUTHOR]

Despite reliable evidence of adverse drug effects, the substantially increased prescription rates of proton pump inhibitors (PPIs) remain at a high level. This study analyzed the appropriateness of PPI prescriptions among residents of nursing homes in three regions of Germany. Baseline data of a cluster-randomized controlled trial were used to determine the prevalence of PPI prescriptions, the validity of indications, and the adequacy of the prescribed dosages according to 1. their drug approvals and 2. valid recommendation guidelines. Regression analyses were conducted to assess associated factors. A total of 437 residents in 37 nursing homes were included (mean age 83 ± 9.2 years, 72% women). The PPI prescription prevalence was 44% (n = 193). In 52/193 (27%) there was no adequate indication, and in 54 (39%) of 138 indicated PPI prescriptions it was overdosed. Yet, in only less than one-third (28%) of "adequate" prescriptions, the indication was according to the PPI approvals, whereas the majority (72%) were off-label indications in line with valid guideline recommendations. Non-indicated PPI prescription was associated with the total number of prescribed drugs (OR 1.32; 95% CI 1.18–1.62; p = 0.013). There were no associations with age, level of care dependency, cognitive impairment, prescription of psychotropic drugs, number of chronic diseases, number of physicians' consultations, or study region. To conclude, in 55%, the high prescription prevalence among residents was either not indicated or overdosed. In total, only 20% (39/193) of cases of PPI use complied with the approved indications. There is a need for quality control of 1. PPI administration in German nursing homes, and 2. of guideline recommendations expanding the off-label PPI use by 72% within the indication scale, predominantly from wide prescription for low-dose ASA. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a microvascular complication that frequently affects numerous patients diagnosed with diabetes. For the diagnosis of CKD, the guidelines recommend the identification of the urinary albumin/creatinine ratio and the determination of serum creatinine, based on which the estimated rate of glomerular filtration (eGFR) is calculated. Serum creatinine is routinely measured in clinical practice and reported as creatinine-based estimated glomerular filtration rate (eGFRcr). It has enormous importance in numerous clinical decisions, including the detection and management of CKD, the interpretation of symptoms potentially related to this pathology and the determination of drug dosage. The equations based on cystatin C involve smaller differences between race groups compared to GFR estimates based solely on creatinine. The cystatin C-based estimated glomerular filtration rate (eGFRcys) or its combination with creatinine (eGFRcr-cys) are suggested as confirmatory tests in cases where creatinine is known to be less precise or where a more valid GFR estimate is necessary for medical decisions. Serum creatinine is influenced by numerous factors: age, gender, race, muscle mass, high-protein diet, including protein supplements, and the use of medications that decrease tubular creatinine excretion (H2 blockers, trimethoprim, fenofibrate, ritonavir, and other HIV drugs). The low levels of creatinine stemming from a vegetarian diet, limb amputation, and conditions associated with sarcopenia such as cirrhosis, malnutrition, and malignancies may lead to inaccurately lower eGFRcr values. Therefore, determining the GFR based on serum creatinine is not very precise. This review aims to identify a new perspective in monitoring renal function, considering the disadvantages of determining the GFR based exclusively on serum creatinine. [ABSTRACT FROM AUTHOR]

The future of therapy for neurodegenerative diseases (NDs) relies on new strategies targeting multiple pharmacological pathways. Our research led to obtaining the compound AR71 [(E)-3-(3,4,5-trimethoxyphenyl)-1-(4-(3-(piperidin-1-yl)propoxy)phenyl)prop-2-en-1-one], which has high affinity for human H3R (Ki = 24 nM) and selectivity towards histamine H1 and H4 receptors (Ki > 2500 nM), and showed anti-inflammatory activity in a model of lipopolysaccharide-induced inflammation in BV-2 cells. The presented tests confirmed its antagonist/inverse agonist activity profile and good metabolic stability while docking studies showed the binding mode to histamine H1, H3, and H4 receptors. In in vitro tests, cytotoxicity was evaluated at three cell lines (neuroblastoma, astrocytes, and human peripheral blood mononuclear cells), and a neuroprotective effect was observed in rotenone-induced toxicity. In vivo experiments in a mouse neuropathic pain model demonstrated the highest analgesic effects of AR71 at the dose of 20 mg/kg body weight. Additionally, AR71 showed antiproliferative activity in higher concentrations. These findings suggest the need for further evaluation of AR71's therapeutic potential in treating ND and CNS cancer using animal experimental models. [ABSTRACT FROM AUTHOR]

Summary: Several professional societies have provided recommendations for prescribing medications for insomnia. None has provided an integrative analysis that concurrently quantifies safety and efficacy (e.g., risk–benefit ratios). This represents an important gap for informing clinician decision‐making. Accordingly, the aim of the present review is to provide such an analysis for five classes of sleep‐promoting medications. Adverse event data values were extracted from the most recent FDA‐approved package inserts and converted to an integer before being placebo‐adjusted and standardized as a rate per 1000 (AEr). Efficacy data, pre‐to‐post self‐reported data for active and placebo conditions were acquired from pivotal trials identified in "white papers" and systematic reviews/meta‐analyses. Weighted effect sizes were calculated for subjective sleep latency, wake time after sleep onset and total sleep time, and then were averaged by medication class for each sleep continuity variable. Overall efficacy was represented by a single variable, SWT (sleep latency + wake time after sleep onset + total sleep time). Risk–benefit was represented using a simple ratio value. For safety, it was found that melatonin receptor agonists had the lowest adverse event rate (AEr = 43.1), and non‐benzodiazepine benzodiazepine receptor agonists had the highest rate (AEr = 255.0). For efficacy, it was found that the pre‐to‐post placebo adjusted effect sizes were largest for benzodiazepines (effect size = 1.94) and smallest for melatonin receptor agonists (effect size = 0.109). For risk–benefit, histamine antagonist had the most favourable profile (risk–benefit = 69.5), while melatonin receptor agonist had the least favourable profile (risk–benefit = 395.7). Overall, the combined metric for risk–benefit suggests that treatment with a histamine antagonist is optimal and potentially represents the best first‐line therapy for the medical management of insomnia. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a common complication associated with treatment with tumour necrosis factor (TNF) antagonists and Janus kinase (JAK) inhibitors. However, there is uncertainty about the risk of TB relapse in patients with TB and comorbidities requiring treatment with these agents. To assess the risk of TB relapse in patients (re-)started on TNF antagonists or JAK inhibitors. Systematic review. PubMed and Cochrane Library databases until 11 December 2023. Randomized control trials, prospective and retrospective cohort studies, case reports and case series. Patients with current or previous TB who were (re-)started on TNF antagonists or JAK inhibitors. (Re-)introduction of TNF antagonists and JAK inhibitors. All studies meeting entry criteria were included regardless of quality. Categorical data are presented as frequencies and percentages. For non-normally distributed aggregated data, we calculated the pooled weighted median with 95% CI. For individual patient data, the median and interquartile range (IQR) were calculated. Of 5018 articles screened for eligibility, 67 publications reporting on 368 TB patients who (re-)initiated treatment with TNF antagonists for underlying diseases were included. The median age was 42.5 years (95% CI: 40.4–42.5) and the proportion of female patients was 36.6% (n = 74) of patients whose sex was reported. A total of 14 patients (3.8%, 95% CI: 2.1–6.3%) developed TB relapse after a median of 8.5 months (interquartile range, 6.8–14.8 months) following (re-)initiation of anti-TNF treatment. Furthermore, among 251 articles screened for eligibility, 11 reports on TB patients who were (re-)started on JAK inhibitors for underlying diseases were identified. The median age was 62 years (interquartile range, 48.5–68.5 years) and 45.5% (n = 5) were female. Only one patient (9.1%; 95% CI: 0.2–41.3%) had TB reactivation 10 months after starting treatment with ruxolitinib. In addition, 94 patients who were treated with TNF antagonists and two patients temporarily treated with JAK inhibitors for the prevention or treatment of paradoxical reactions were analysed. None of the publications reported microbiological failure or worsening of TB-related symptoms. (Re-)initiation of TNF antagonists and JAK inhibitors may be relatively safe in patients with current or previous TB and the need for further treatment of underlying diseases. [ABSTRACT FROM AUTHOR]

A physiologically‐based pharmacokinetic (PBPK) model for tipifarnib, which included mechanistic absorption, was built and verified by integrating in vitro data and several clinical data in healthy subjects and cancer patients. The final PBPK model was able to recover the clinically observed single and multiple‐dose plasma concentrations of tipifarnib in healthy subjects and cancer patients under several dosing conditions, such as co‐administration with a strong CYP3A4 inhibitor and inducer, an acid‐reducing agent (proton pump inhibitor and H2 receptor antagonist), and with a high‐fat meal. In addition, the model was able to accurately predict the effect of mild or moderate hepatic impairment on tipifarnib exposure. The appropriately verified model was applied to prospectively simulate the liability of tipifarnib as a victim of CYP3A4 enzyme‐based drug–drug interactions (DDIs) with a moderate inhibitor and inducer as well as tipifarnib as a perpetrator of DDIs with sensitive substrates of CYP3A4, CYP2B6, CYP2D6, CYP2C9, and CYP2C19 in healthy subjects and cancer patients. The effect of a high‐fat meal, acid‐reducing agent, and formulation change at the therapeutic dose was simulated. Finally, the model was used to predict the effect of mild, moderate, or severe hepatic, and renal impairment on tipifarnib PK. This multipronged approach of combining the available clinical data with PBPK modeling‐guided dosing recommendations for tipifarnib under several conditions. This example showcases the totality of the data approach to gain a more thorough understanding of clinical pharmacology and biopharmaceutic properties of oncology drugs in development. [ABSTRACT FROM AUTHOR]

Objective The ductus arteriosus normally closes after birth. Histamine 2 receptor antagonist (H 2 RA) has been associated with patent ductus arteriosus (PDA). We aimed to study the characteristics of term infants with PDA and their possible association with prenatal exposure to antacids—proton pump inhibitors (PPIs) and H 2 RA. Study Design This was a population-based matched case–control study of mothers registered at "Clalit" Health Maintenance Organization (HMO) and their infants born at "Soroka" University Medical Center (SUMC) between 2001 and 2018. Cases are defined as term infants born with PDA diagnosed by echocardiography and registered in the postdelivery discharge form. Each case was matched with four term newborns without PDA diagnosis. Exposure window was defined by the timing of first purchase of H 2 RA or PPI during pregnancy and based on information from a computerized medication database (Clalit HMO, SUMC). Results PDA was diagnosed in 1,884 term infants (4.9%). Characteristics included a significantly higher percentage of lack of prenatal care, cesarean section, in vitro fertilization, polyhydramnios, oligohydramnios, Apgar 1 minute <5, and prenatal exposure to H 2 RA (odds ratio [OR] 4.18) and PPIs (OR 3.50; all p < 0.001). PDA association with exposure window was similar in each trimester (1.5–2%) for both H 2 RA and PPI. Conclusion PDA incidence in term infants in our population was greater than previously reported. PPI and H 2 RA are both antiacids with different mechanisms of action. The similar OR for exposure to one as well as the other, and the lack of influence of the initial exposure period, are compatible with bias. Key Points Term newborns with PDA have different characteristics than newborns without PDA. Prenatal exposure to PPIs or H 2 RA is associated with greater risk of PDA in term newborns. The possible effect mechanism of PPIs on the ductus is unclear and understudied. [ABSTRACT FROM AUTHOR]

Transient receptor potential vanilloid 1 (TRPV1) was reported to be a putative target for recovery from chronic pain, producing analgesic effects after its inhibition. A series of drug candidates were previously developed, without the ability to ameliorate the therapeutic outcome. Starting from previously designed compounds, derived from the hybridization of antagonist SB-705498 and partial agonist MDR-652, we performed a virtual screening on a pharmacophore model built by exploiting the Cryo-EM 3D structure of a nanomolar antagonist in complex with the human TRPV1 channel. The pharmacophore model was described by three pharmacophoric features, taking advantage of both the bioactive pose of the antagonist and the receptor exclusion spheres. The results of the screening were implemented inside a 3D-QSAR model, correlating with the negative decadic logarithm of the inhibition rate of the ligands. After the validation of the obtained 3D-QSAR model, we designed a new series of compounds by introducing key modifications on the original scaffold. Again, we determined the compounds' binding poses after alignment to the pharmacophoric model, and we predicted their inhibition rates with the validated 3D-QSAR model. The obtained values resulted in being even more promising than parent compounds, demonstrating that ongoing research still leaves much room for improvement. [ABSTRACT FROM AUTHOR]

Background: Adverse effects of proton pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to evaluate whether PPI use increases the risks of these respiratory infections. Methods: The current study included 160,923 eligible participants at baseline who completed questionnaires on medication use, which included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Comparisons with H2RA users were tested. PPI use was associated with increased risks of developing influenza (HR 1.32, 95% CI 1.12–1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26–1.59). In contrast, the risk of COVID-19 infection was not significant with regular PPI use (HR 1.08, 95% CI 0.99–1.17), while the risks of severe COVID-19 (HR 1.19. 95% CI 1.11–1.27) and mortality (HR 1.37. 95% CI 1.29–1.46) were increased. However, when compared with H2RA users, PPI users were associated with a higher risk of influenza (HR 1.74, 95% CI 1.19–2.54), but the risks with pneumonia or COVID-19-related outcomes were not evident. Conclusions: PPI users are associated with increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared to non-users, while the effects on pneumonia or COVID19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required. Funding: This work is supported by the National Natural Science Foundation of China (82171698, 82170561, 81300279, 81741067, 82100238), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), the Guangdong Basic and Applied Basic Research Foundation (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People’s Hospital (DFJH201923, DFJH201803, KJ012019099, KJ012021143, KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL). [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]

Background: Although several small cohort studies have shown the utility of argon plasma coagulation (APC) in the treatment of gastric dysplasia, its clinical significance has not been established. This study aims to assess the efficacy of APC as a first line treatment for gastric dysplasia, and identify risk factors for residual dysplasia. Methods: A total of 179 cases of gastric dysplasia were treated with APC and have been followed-up with upper endoscopy within 1 year. The overall incidence and the characteristics of lesions with residual dysplasia in follow-up endoscopy were analyzed by logistic regression. Results: Among 179 lesions treated with APC, 171 (95.5%) lesions have achieved complete ablation in the follow-up endoscopy. Additional APC was applied for residual dysplasia, achieving complete ablation in 97.77% (175/179). The upper third location of the gastric dysplasia was significantly associated with residual dysplasia, while tumor size, horizontal location, macroscopic morphology and grade of dysplasia showed no significant associations with residual dysplasia following the initial APC. Conclusions: APC with meticulous follow-up can be recommended as a first line treatment in patients with gastric dysplasia. [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]

Key content: The perinatal period confers an elevated risk of both relapses and new onset of mental illness. Suboptimal treatment can have a profound impact on maternal mortality and morbidity, neonatal outcomes and longer term child development.Most psychotropic medication can be used safely in pregnancy, with some notable exceptions.While decisions on the use of psychotropic medications in pregnancy are often complex and should be multidisciplinary, it is imperative that obstetricians and gynaecologists familiarise themselves with current literature to provide evidence‐based counselling and care.Existing guidelines on the use of psychotropic medication are largely aimed at psychiatrists, and to date there has been a lack of concise, digestible information with a focus on core knowledge for obstetricians and gynaecologists.We summarise existing evidence on the use of antidepressants, antipsychotics, mood stabilisers and sedatives in the perinatal period. For each drug class we describe the teratogenicity, impact on pregnancy, breastfeeding and the newborn. Learning objectives: To be familiar with common psychotropic medication used in pregnancy and the postpartum period.To understand key evidence on the safety profile of psychiatric medication in the perinatal period and apply this to individualised counselling. [ABSTRACT FROM AUTHOR]

Background: To compare the effects of proton pump inhibitor (PPI) and histamine‐2 receptor antagonist (H2RA) use on the occurrence of acute kidney injury (AKI) in septic patients at high risk for developing stress ulcers. Methods: Using the Medical Information Mart for Intensive Care IV version 2.2 database, septic patients with high‐risk factors for stress ulcers (i.e., shock, coagulopathy, invasive mechanical ventilation, or chronic liver diseases) were included. Exposures included PPIs and H2RAs within 24 h of intensive care unit (ICU) admission or prior to ICU admission. The primary end point was severe sepsis‐associated AKI as defined by the Kidney Disease Improving Global Outcomes criteria stage 3 (KDIGO‐3). Propensity score matching (PSM) was performed to balance baseline characteristics. Multivariable Cox proportional hazards regression was used to estimate the effect size. Results: 4731 PPI users and 4903 H2RA users were included. After PSM, there were 1785 pairs exposed to PPIs and H2RAs. In the PSM cohort, the cumulative incident KDIGO‐3 rate was higher in the PPI group than in the H2RA group (log‐rank test, p = 0.009). Regression analyses showed that PPI exposure [adjusted hazard ratio 1.32, 95% confidence interval (CI) 1.11–1.58, p = 0.002] was associated with incident KDIGO‐3 compared with H2RA use. This association remained consistent in sensitivity analyses. Additionally, the PPI group had a higher need for kidney replacement therapy compared with the H2RA group (3.6% vs. 2.1%, P = 0.012). Conclusions: Among septic patients at high risk for developing stress ulcers, PPI exposure was associated with incident KDIGO‐3 AKI compared with H2RA use. [ABSTRACT FROM AUTHOR]

This article explores the benefits and challenges of conducting pragmatic trials using electronic health records (EHRs). Pragmatic trials are crucial for informing clinical practice when there is limited data available. EHRs offer advantages such as accessibility and the ability to enroll large numbers of patients quickly. However, there are unique challenges in conducting EHR-enabled trials, including potential biases and contamination of treatment groups. Real-time monitoring of enrollment and safety events is also difficult. Despite these challenges, EHR-enabled trials have shown promising results in various fields. The article emphasizes the importance of careful planning, monitoring, and validation of data in EHR-enabled trials to ensure accurate and reliable results. It also discusses the potential benefits and limitations of EHR-enabled trials in improving patient care. [Extracted from the article]

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal‐regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine‐induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p‐ERK in the spinal cord in a dry skin mouse model induced by acetone–ether–water (AEW). q‐PCR, Western blot, pharmacology and immunofluorescence were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c‐Fos and p‐ERK expression in the spinal cord neurons were increased and co‐labelled with GRPR‐positive neurons in AEW mice. Furthermore, H4R agonist 4‐methyhistamine dihydrochloride (4‐MH)induced itch. Both 4‐MH‐induced itch and the spontaneous itch in AEW mice were blocked by p‐ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p‐ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW‐induced dry skin mice. [ABSTRACT FROM AUTHOR]

Esophageal and gastric varices (EGV) bleeding is a dangerous side effect of liver cirrhosis. Ascites may affect the effectiveness of carvedilol in preventing EGV rebleeding. A retrospective analysis was done on patients with EGV bleeding who visited our gastroenterology department between January 1, 2015, and October 29, 2020, and were given carvedilol therapy again. Patients were classified based on whether they had ascites. The primary outcome was EGV rebleeding. A total of 286 patients were included, with a median follow‐up of 24.0 (19.0–42.0) months, comprising those without ascites (N = 155) and those with ascites (N = 131). The mean age of the patients was 55.15 ± 12.44 years, and 177 (61.9%) of them were men. There were 162 (56.6%) Child‐Pugh A grades. The etiology of cirrhosis included 135 (47.2%) cases of hepatitis B. After carvedilol therapy, the patient's portal vein diameter (DPV) was widened (p < 0.05), velocity of portal vein (VPV) was slowed (p = 0.001). During the 1‐year follow‐up, patients with ascites had a substantially higher rebleeding rate than patients without ascites, with 24 (18.3%) versus 13 (8.4%), respectively (p = 0.013). On univariate analysis, ascites was a risk factor for rebleeding (p = 0.015). The multivariate analysis remained significant after adjusting for age, gender, etiology of cirrhosis, and previous endoscopic treatment, with OR of 2.37 (95% CI: 1.12–5.04; p = 0.025). Ascites was a risk factor for EGV rebleeding in patients undergoing carvedilol therapy. After carvedilol therapy, the patient's DPV was widened and VPV was slowed. [ABSTRACT FROM AUTHOR]

Background: Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it is unclear which is the best treatment option for EE. Objectives: This study aimed to evaluate the comparative efficacy of P-CABs and PPIs for healing EE patients, seeking an appropriate treatment choice in the 4- or 8-week treatment and standard or double dose. Design: A systematic review and network meta-analysis. Data sources and methods: Relevant databases were searched to collect randomized controlled trials of PPIs and P-CABs in the treatment of EE up to 31 May 2023. Studies on standard or double-dose PPIs or P-CABs which were published in English and assessed 4- or 8-week healing effects in EE were included. A network meta-analysis was performed to evaluate the efficacy of the treatments under the frequentist framework. Sensitivity and subgroup analyses of patients with different baseline EE were also conducted. Results: In all, 34 studies involving 25,054 patients and 9 PPIs, 6 P-CABs, or placebo treatment interventions were included. The pooled 4-week healing rate was significantly statistically lower than the pooled 8-week healing rate for most treatments. Besides, the higher healing rate of double-dose treatment than standard-dose treatment was not observed in the initial treatment of most drugs. The main analysis only included studies conducted for both patients with and without severe EE at baseline, and the proportion of severe EE included in the study was >10%, Keverprazan 20 mg qd ranked best with a surface under the cumulative ranking curve (SUCRA) value of 84.7, followed by Ilaprazole 10 mg qd with a SUCRA value of 82.0, for the healing rate at 8 weeks. Sensitivity analysis showed that the results were robust. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, particularly for patients with severe EE. And the healing rate of Keverprazan 20 mg qd at 8 weeks ranked best in the subgroup without or with severe EE at baseline. Conclusion: This study showed that an 8-week treatment seemed more effective than the 4-week treatment for healing EE patients. The healing effect of Keverprazan (20 mg qd) ranked best in 8-week treatment, for both severe and non-severe EE patients. Trial registration: The study protocol was registered with INPLASY (registration number INPLASY2023120053). Plain language summary: A review and network meta-analysis of different medications for treating erosive esophagitis: potassium-competitive acid blockers and proton-pump inhibitors Why was the study done? Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are commonly used to treat Erosive esophagitis (EE) due to their good safety and tolerance. This study aimed to compare the effectiveness of P-CABs and PPIs in healing EE patients. We wanted to determine the best treatment choice in terms of the duration of treatment (4 or 8 weeks) and the dosage (standard or double-dose). What did the researchers do? The researchers searched relevant databases for randomized controlled trials that studied the use of PPIs and P-CABs in treating EE up until May 31, 2023. They included studies that evaluated the healing effects of standard or double-dose PPIs or P-CABs over a period of 4 or 8 weeks. A network meta-analysis was performed to compare the effectiveness of these treatments. They also conducted sensitivity analysis and subgroup analysis to examine the effects on patients with different levels of EE. What did the researchers find? The results showed that the healing rate after 4 weeks of treatment was significantly lower than the healing rate after 8 weeks for most treatments. Additionally, the higher healing rate observed with double-dose treatment compared to standard-dose treatment was not seen in the initial treatment of most drugs. In the main analysis, which included studies with patients both with and without severe EE at the beginning, Keverprazan 20mg qd was ranked as the most effective treatment with a healing rate of 84.7, followed by Ilaprazole 10mg qd with a healing rate of 82.0 at 8 weeks. The results were robust in sensitivity analysis. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, especially for patients with severe EE. What do the findings mean? Treating EE patients for 8 weeks was more effective than treating them for 4 weeks. Keverprazan (20mg once a day) with the 8-week treatment is the optimal method. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to estimate the prevalence of potentially inappropriate prescriptions (PIPs) in patients starting their first noninsulin antidiabetic treatment (NIAD) using two explicit process measures of the appropriateness of prescribing in UK primary care, stratified by age and polypharmacy status. Methods: A descriptive cohort study between 2016 and 2019 was conducted to assess PIPs in patients aged ≥45 years at the start of their first NIAD, stratified by age and polypharmacy status. The American Geriatrics Society Beers criteria 2015 was used for older (≥65 years) patients and the Prescribing Optimally in Middle‐age People's Treatments criteria was used for middle‐aged (45‐64 years) patients. Prevalence of overall PIPs and individual PIPs criteria was reported using the IQVIA Medical Research Data incorporating THIN, a Cegedim Database of anonymized electronic health records in the UK. Results: Among 28 604 patients initiating NIADs, 18 494 (64.7%) received polypharmacy. In older and middle‐aged patients with polypharmacy, 39.6% and 22.7%, respectively, received ≥1 PIP. At the individual PIP level, long‐term proton pump inhibitors (PPI) use was the most frequent PIP among older adults, and strong opioid without laxatives was the most frequent PIP in middle‐aged patients with polypharmacy (11.1% and 4.1%, respectively). Conclusions: This study revealed that patients starting NIAD treatment receiving polypharmacy have the potential for pharmacotherapy optimization. [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]

Gastric acid secretion is closely associated with the development and treatment of chronic gastritis, gastric ulcers, and reflux esophagitis. However, gastric acid secretion is affected by complex physiological and pathological factors, and real-time detection and control are complicated and expensive. A gastric delivery system for antacids and therapeutics in response to low pH in the stomach holds promise for smart and personalized treatment of stomach diseases. In this study, pH-responsive modular units were used to assemble various modular devices for self-regulation of pH and drug delivery to the stomach. The modular unit with a release window of 50 mm2 could respond to pH and self-regulate within 10 min, which is related to its downward floatation and internal gas production. The assembled devices could stably float downward in the medium and detach sequentially at specific times. The assembled devices loaded with antacids exhibited smart pH self-regulation under complex physiological and pathological conditions. In addition, the assembled devices loaded with antacids and acid suppressors could multi-pulse or prolong drug release after rapid neutralization of gastric acid. Compared with traditional coating technology, 3D printing can print the shell layer by layer, flexibly adjust the internal and external structure and composition, and assemble it into a multi-level drug release system. Compared with traditional coating, 3D-printed shells have the advantage of the flexible adjustment of internal and external structure and composition, and are easy to assemble into a complex drug delivery system. This provides a universal and flexible strategy for the personalized treatment of diseases with abnormal gastric acid secretion, especially for delivering acid-unstable drugs. [ABSTRACT FROM AUTHOR]

Background Allergies often present challenges in managing itch and the effects of histamine. Cooling agents that act via transient receptor potential melastatin 8 (TRPM8) agonism have shown potential in itch management. However, animal studies on itch have limitations, as animals cannot communicate subjective events and their fur-coated skin differs from that of humans. Human studies offer more direct and reliable information. Objectives To investigate the effects of a specific TRPM8 agonist gel (cryosim-1) on itch induced by various pruritogens in human skin. Methods Calcium imaging experiments determined the binding of cryosim-1 and histamine to their respective receptors. Thirty healthy volunteers underwent skin prick tests with pruritogens and a control vehicle. Itch and pain intensity were measured using a numerical rating scale (NRS) across 10 min. Participants were randomly assigned to pretreatments with vehicle or TRPM8 agonist gel. Tests were repeated at a later date, and skin moisture, transepidermal water loss and mechanical sensitivity were measured. Results The in vitro study confirmed that histamine is not a TRPM8 agonist and cryosim-1 does not act as an agonist or antagonist on the human histamine 1 receptor. The TRPM8 agonist gel significantly reduced the itch intensity for all pruritogens compared with the vehicle-only gel. It also reduced itch NRS and the integrated itch score. Mechanical sensitivity was also reduced. Conclusions The specific TRPM8 agonist gel effectively suppressed human skin itch induced by various pruritogens. These versatile actions suggest that cooling agents may be promising treatments for multiple forms of itch stimuli. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the treatment outcomes of proton-pump inhibitors (PPIs) in patients with contact granuloma (CG) and to investigate the parameters of 24 h combined dual channel pH/impedance (24 h pH/MII) monitoring, which are reliable for predicting the response to PPI of CG patients. : We reviewed the medical records of patients with CG who had been treated with PPIs and had completed more than 6 months of follow-up. We classified the patients into two groups (cured vs. persistent), according to their PPI treatment outcomes. Reflux events were categorized into three groups based on pharyngeal pH during reflux: 1) acid reflux (pH < 4), 2) weak acid reflux (4 < pH < 7), and 3) weak alkaline reflux (pH >7), as detected by a proximal probe. We compared the results of 24h-pH/MII between the two groups and used receiver operating characteristic curve (ROC) analysis to determine the cutoff values of significant parameters for predicting responses to PPIs. : Among 22 patients who completed at least 6 months of PPI treatment and follow-up, weak acid reflux events were more frequently observed in persistent group than in the cured group (p = 0.046), and the proportion of weak acid reflux was also higher in the persistent group (p = 0.031) than in the cured group. Reliable parameters predictive of a poor response to PPIs were a number of weak acid reflux events ≥ 11 (area under the curve [AUC], 0.775; p = 0.03) and a proportion of weak acid reflux events ≥ 56.7 % (AUC, 0.763; p = 0.038) in ROC analyses. : Weak acid reflux was identified as a significant factor associated with the treatment outcomes of PPIs in patients with CG. A number of weak acid reflux events ≥ 11 is considered to be the most reliable predictor of a poor response to PPIs in patients with CG. [ABSTRACT FROM AUTHOR]

Background: PCOS patients with unexpectedly low oocyte yield following conventional ovarian stimulation are referred to as suboptimal responders. However, identifying suboptimal responders presents a significant challenge within reproductive medicine and limited research exists on the occurrence of suboptimal response. This analysis aimed to develop a predictive model of suboptimal response during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments in PCOS patients. Methods: This retrospective study involved a cohort of 313 PCOS patients undergoing their first IVF/ICSI cycle from 2019 to 2022. Univariate logistic regression analyses, least absolute shrinkage, selection operator regression analysis, and recursive feature elimination were employed to identify relevant characteristics and construct predictive models. Moreover, a nomogram was constructed based on the best model. Receiver operating characteristic curves, decision curve analysis (DCA), and calibration curves were used to evaluate the model. Results: The predictors included in the model were age, Anti-Mullerian hormone, antral follicle count, and basal follicle-stimulating hormone. The area under the receiver operating characteristic curve (AUC) was 0.7702 (95% confidence interval 0.7157–0.8191). The AUC, along with the DCA curve and calibration curve, demonstrated a satisfactory level of congruence and discrimination ability. Conclusion: The nomogram effectively predicted the probability of suboptimal response in PCOS patients undergoing gonadotropin-releasing hormone antagonist protocol during IVF/ICSI treatment. [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]

Gastric perforation refers to the complete rupture of the gastric wall, leading to the extravasation of gastric contents into the thoracic cavity or peritoneum. Without timely intervention, the expulsion of gastric contents may culminate in profound discomfort, exacerbating the inflammatory process and potentially triggering perilous sepsis. In clinical practice, surgical suturing or endoscopic closure procedures are commonly employed. Magnetic-driven microswarms have also been employed for sealing gastrointestinal perforation. However, surgical intervention entails significant risk of bleeding, while endoscopic closure poses risks of inadequate closure and the need for subsequent removal of closure clips. Moreover, the efficacy of microswarms is limited as they merely adhere to the perforated area, and their sealing effect diminishes upon removal of the magnetic field. Herein, we present a Fe&Mg@Lard-Paraffin micromotor (LPM) constructed from a mixture of lard and paraffin coated with magnesium (Mg) microspheres and iron (Fe) nanospheres for sutureless sealing gastric perforations. Under the control of a rotating magnetic field, this micromotor demonstrates precise control over its movement on gastric mucosal folds and accurately targets the gastric perforation area. The phase transition induced by the high-frequency magnetothermal effect causes the micromotor composed of a mixed oil phase of lard and paraffin to change from a solid to a liquid phase. The coated Mg microspheres are subsequently exposed to the acidic gastric acid environment to produce a magnesium protonation reaction, which in turn generates hydrogen (H2) bubble recoil. Through a Mg-based micropower traction, part of the oil phase could be pushed into the gastric perforation, and it would then solidify to seal the gastric perforation area. Experimental results show that this can achieve long-term (>2 h) gastric perforation sealing. This innovative approach holds potential for improving outcomes in gastric perforation management. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are widely used in the long-term treatment of gastroesophageal reflux disease (GERD) and other upper gastrointestinal disorders, such as the healing of peptic ulcers and/or prophylactic treatment of peptic ulcers. PPIs are also widely used as symptomatic treatment in patients with functional dyspepsia. One of the adverse effects of the long-term use of PPI is rebound acid hypersecretion (RAHS), which can occur after the withdrawal of PPI therapy due to a compensatory increase in gastric acid production. Mechanisms of the RAHS have been well established. Studies have shown that pentagastrin-stimulated acid secretion after the discontinuation of PPIs increased significantly compared to that before treatment. In healthy volunteers treated with PPIs, the latter induced gastrointestinal symptoms in 40–50% of subjects after the discontinuation of PPI therapy but after stopping the placebo. It is important for practicing physicians to be aware and understand the underlying mechanisms and inform patients about potential RAHS before discontinuing PPIs in order to avoid continuing unnecessary PPI therapy. This is important because RAHS may lead patients to reuptake PPIs as symptoms are incorrectly thought to originate from the recurrence of underlying conditions, such as GERD. Mechanisms of RAHS have been well established; however, clinical implications and the risk factors for RAHS are not fully understood. Further research is needed to facilitate appropriate management of RAHS in the future. [ABSTRACT FROM AUTHOR]

Background: Although immune checkpoint blockade (ICB) therapy has proven to be extremely effective at managing certain cancers, its efficacy in treating pancreatic ductal adenocarcinoma (PDAC) has been limited. Therefore, enhancing the effect of ICB could improve the prognosis of PDAC. In this study, we focused on the histamine receptor H1 (HRH1) and investigated its impact on ICB therapy for PDAC. Methods: We assessed HRH1 expression in pancreatic cancer cell (PCC) specimens from PDAC patients through public data analysis and immunohistochemical (IHC) staining. The impact of HRH1 in PCCs was evaluated using HRH1 antagonists and small hairpin RNA (shRNA). Techniques including Western blot, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-PCR), and microarray analyses were performed to identify the relationships between HRH1 and major histocompatibility complex class I (MHC-I) expression in cancer cells. We combined HRH1 antagonism or knockdown with anti-programmed death receptor 1 (αPD-1) therapy in orthotopic models, employing IHC, immunofluorescence, and hematoxylin and eosin staining for assessment. Results: HRH1 expression in cancer cells was negatively correlated with HLA-ABC expression, CD8+ T cells, and cytotoxic CD8+ T cells. Our findings indicate that HRH1 blockade upregulates MHC-I expression in PCCs via cholesterol biosynthesis signaling. In the orthotopic model, the combined inhibition of HRH1 and αPD-1 blockade enhanced cytotoxic CD8+ T cell penetration and efficacy, overcoming resistance to ICB therapy. Conclusions: HRH1 plays an immunosuppressive role in cancer cells. Consequently, HRH1 intervention may be a promising method to amplify the responsiveness of PDAC to immunotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Endoscopic diagnosis is essential for predicting the curability of early gastric cancer (EGC; R0 resection) before treatment, but the relationship between ulcerative lesions and clinical outcomes remains unclear. We aimed to investigate the effect of proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) on the morphological changes of ulcerative EGCs and its relevance to the clinical outcomes. Methods: Altogether, 143 patients with differentiated ulcerative EGC that were resected by endoscopic submucosal dissection were retrospectively identified and divided into the following two cohorts depending on their PPI/P-CAB administration status: PPI/P-CAB (n = 76) and non-PPI/P-CAB (n = 67) cohorts. Furthermore, in each cohort, the patients were further divided into the improved and unimproved subgroups based on the ulcerative changes. Results: In the PPI/P-CAB cohort, the deep submucosal invasion and lymphovascular invasion rates were significantly higher in the unimproved subgroup than in the improved subgroup, resulting in a significantly lower R0 resection rate. Contrarily, no significant differences were found between the two subgroups in the non-PPI/P-CAB cohort. The significance of PPI/P-CAB administration was observed only in the ulcerative EGCs with open-type atrophy (R0 resection rate; improved vs. unimproved, 90.9% vs. 48.0%, p = 0.001). When the finding of improved ulcer with PPI/P-CAB administration was used as the indication of endoscopic resection in ulcerative EGCs with open-type atrophy, high sensitivity (78.9%) and accuracy (76.3%) rates for the curability were observed, which were higher than those of conventional endoscopic diagnosis alone (p = 0.021). Conclusion: PPI or P-CAB administration might contribute to the potential selection of ulcerative EGCs, enabling endoscopic curative resection. [ABSTRACT FROM AUTHOR]

Background: Chronic cough significantly impairs the quality of life. Although various studies focused on MNBI as assessed in the distal esophagus, scarce data are available on the clinical value of proximal measurements. Aim: To investigate the role of proximal MNBI in the workup of patients with chronic cough and its ability to predict PPI response. Methods: Demographic, clinical, endoscopy findings, impedance‐pH and HRM tracings from consecutive cough patients were evaluated. MNBI was calculated at proximal and distal esophagus. Results: One hundred and sixty four patients were included. In addition to traditional variables, when considering also the PSPW index or MNBI at 3 cm or 15 cm, the proportion of patients with pathological impedance‐pH monitoring significantly increased. 70/164 patients were responders, while 94 (57.3%) were non‐responder to double PPI dose (p < 0.05). Patients with pathologic MNBI at 3 cm and/or 15 cm as well as those with pathologic PSPW index were characterized by a significantly higher proportion of responders than that observed among patients with normal impedance‐pH variables (p < 0.001). The proportion of responders with pathological MNBI at 15 cm was significantly higher than the proportion of responders with pathological MNBI at 3 cm (82.8% vs. 64.3%, p < 0.05). At multivariable model, pathological MNBI at both 3 cm and 15 cm as well as PSPW index were associated with PPI responsiveness. The strongest association with PPI response was observed for MNBI at 15 cm. Conclusions: The assessment of MNBI at proximal esophagus increases the diagnostic yield of impedance‐pH monitoring and may represent a useful predictor of PPI responsiveness in the cumbersome clinical setting of suspected reflux‐related cough. [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]

BACKGROUND: With the introduction of H2 receptor antagonists and proton pump inhibitors, the incidence of elective surgery for peptic ulcer diseases have decreased, although complications of peptic ulcer such as perforation and bleeding have remained fairly constant. AIMS AND OBJECTIVES: To identify the risk factors that predict the morbidity and mortality in perforated Gastro duodenal ulcer and to assess postoperative complications in patients with Gastro duodenal ulcer perforation. MATERIALS AND METHODS: 50 patients who underwent surgery (simple closure with omental patch) and laparoscopic closure for perforated Gastro duodenal ulcer admitted in S.Nijalingappa medical college and H.S.K Hospital, Bagalkot were studied from December 2011 to June 2013 were included in the study group. The following factors were analyzed in terms of morbidity and mortality: age, gender, associated medical illness, chronic ingestion of NSAIDs, alcohol ingestion and smoking habits, pre operative shock, delay in surgery (>24 hours), site and size of ulcer perforation and type of peritoneal contamination. Postoperative complications like wound infection, wound dehiscence, intra-abdominal abscess pleural effusion, septicemia, respiratory infections and renal failure were assessed. RESULTS: There were 47 male and 3 female patients. Smoking (52%) and alcoholconsumption (48%) were risk factors in causation of Gastro duodenal ulcerperforation. There were 47 duodenal and 3 gastric ulcer perforations. Laparotomy and simple closure of perforation with omental patch was performed in 43 patients and laparoscopic closure in 7 patients. A total of 51 postoperative complications werepresent in 27 (48.3%) patients. Age = 65 years, associated medical illness, prolonguse of corticosteroid's, duration of perforation of more than 24 hours, werestatistically significant in determining postoperative complications. CONCLUSION: Gastro duodenal ulcer perforation is a frequent cause of acute abdomen in south India. Patient's age 65 years and more, associated medical illness, prolong use of drugs like NSAID's or Corticosteroid's, duration of perforation of more than 24 hours before surgery, presence of preoperative shock on admission, size of ulcer perforation and purulent peritoneal contamination are factors significantly associated with fatal outcomes in patients undergoing emergency surgery for perforated peptic ulcer. Therefore, proper resuscitation from shock and decreasing delay in surgery is needed to improve overall results. [ABSTRACT FROM AUTHOR]

Background and aims: Stress ulcer (SU) is a common complication in patients with acute ischemic stroke. The relationship of infarction location and the incidence of SU was unclear. Herein, we aim to investigate the association between ischemic insular damage and the development of SU. Methods: Data were retrieved from the SPARK study (Effect of Cardiac Function on Short‐Term Functional Prognosis in Patients with Acute Ischemic Stroke). We included the patients who had experienced an ischemic stroke within 7 days. The diagnosis of SU was based on clinical manifestations, including hematemesis, bloody nasogastric tube aspirate, or hematochezia. Evaluation of ischemic insular damage was conducted through magnetic resonance imaging. Cyclo‐oxygenase regression analysis and Kaplan–Meier survival curves were used to assess the relationship between ischemic insular damage and the occurrence of SU. Results: Among the 1357 patients analyzed, 110 (8.1%) developed SUs during hospitalization, with 69 (6.7%) experiencing infarctions in the anterior circulation. After adjusting for potential confounders, patients with ischemic insular damage exhibited a 2.16‐fold higher risk of developing SUs compared to those without insular damage (p =.0206). Notably, among patients with infarctions in the anterior circulation, those with insular damage had a 2.21‐fold increased risk of SUs (p =.0387). Moreover, right insular damage was associated with a higher risk of SUs compared to left insular damage or no insular damage (p for trend =.0117). Kaplan–Meier curves demonstrated early separation among groups, persisting throughout the follow‐up period (all p <.0001). Conclusions: This study identified a significant independent correlation between ischemic insular damage, particularly on the right side, and the development of SU during hospitalization, indicating the need to consider prophylactic acid‐suppressive treatment for patients with ischemic insular damage. [ABSTRACT FROM AUTHOR]

Although cases of late-onset localized rash after bee sting and localized cold urticaria after insect sting have been rarely reported, lateonset localized urticaria or recall urticaria after a wasp sting has not previously been reported as far as we are aware. A 24-year-old male patient was stung once in the neck by a wasp in October 2018. After 15 minutes, the patient developed dizziness, fainting, flushing and dyspnea that resolved in a few hours with the treatment administered in the emergency room. One week after this event, a wasp stung his right arm and he fainted within 5-10 minutes. The patient vomited and recovered in a few hours with the treatment provided in the emergency room. Approximately one month after the last wasp sting, skin lesions that were localized only to the right forearm and consistent with urticaria developed. There were no skin lesions in other parts of the body. While this complaint of the patient was under control with cetirizine 10 mg/day, it recurred every day if he did not use an antihistamine. This situation was not related to any trigger (cold, heat, drug use, etc.). The Vespula spp. (10 mcg/mL) skin prick test was positive and the wasp-specific IgE level was found to be 56.2 IU/mL (class5). Vespula spp. subcutaneous immunotherapy was started and the patient has been on maintenance therapy for two years. No side effects related to immunotherapy have been observed so far. However, localized urticaria on the right forearm still persists in the absence of antihistamine use. A very rare case of late onset chronic localized urticaria after a wasp sting is presented. Past history of wasp or bee stings should be questioned in cases of localized urticaria. [ABSTRACT FROM AUTHOR]

The article discusses the pharmacological management of narcolepsy in children and adolescents. It highlights the need for safe and effective treatments for young people with narcolepsy and mentions the European guidelines on the management of narcolepsy in adults and children. The article focuses on the efficacy and safety of pitolisant, a drug that has been approved by the European Medicine Agency for the treatment of narcolepsy in children and adolescents. It mentions a clinical trial that showed significant improvements in narcolepsy symptoms with pitolisant compared to a placebo. The article concludes by emphasizing the importance of early treatment for narcolepsy to prevent long-term consequences. [Extracted from the article]

Summary: Background: Proton pump inhibitors (PPI) are frequently used in patients with cirrhosis. Aims: This study aimed to determine whether PPI use is associated with the prognosis of cirrhotic patients. Methods: We conducted a multicentre retrospective cohort study involving 1485 patients who had experienced hepatic encephalopathy (HE) from 7 referral centres in Korea. The primary outcome was overall survival and secondary outcomes included the development of cirrhotic complications, including recurrent HE, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), and gastrointestinal bleeding. Patients treated with PPI with a mean defined daily dose (mDDD) ≥0.5 (high‐dose PPI group) were compared to those treated with PPI of an mDDD < 0.5 (No or low‐dose PPI group) for each outcome. Results: Among 1485 patients (median age, 61 years; male, 61%), 232 were assigned to the high‐dose PPI group. High‐dose PPI use was independently associated with a higher risk of death (adjusted HR [aHR] = 1.71, 95% confidence interval [CI] = 1.38–2.11, p < 0.001). This result was reproducible after propensity score‐matching (PSM) (aHR = 1.90, 95% CI = 1.49–2.44, p < 0.001). High‐dose PPI use was an independent risk factor of recurrent HE (before PSM: aHR = 2.04, 95% CI = 1.66–2.51, p < 0.001; after PSM: aHR = 2.16, 95% CI = 1.70–2.74, p < 0.001), SBP (before PSM: aHR = 1.87, 95% CI = 1.43–2.43, p < 0.001; after PSM: aHR = 1.76, 95% CI = 1.31–2.36, p = 0.002), HRS (before PSM: aHR = 1.48, 95% CI = 1.02–2.15, p = 0.04; after PSM: aHR = 1.47, 95% CI = 0.95–2.28, p = 0.09), and gastrointestinal bleeding (before PSM: aHR = 1.46, 95% CI = 1.12–1.90, p = 0.006; after PSM: aHR = 1.74, 95% CI = 1.28–2.37, p < 0.001). Conclusions: The use of high‐dose PPI was independently associated with increased risks of mortality and cirrhotic complications. [ABSTRACT FROM AUTHOR]