Eur J Gastroenterol Hepatol. 2025 Jun 18. doi: 10.1097/MEG.0000000000003022. Online ahead of print.

ABSTRACT

Vedolizumab is a humanized antiintegrin α4β7 mAb, selective for the intestine, used in the treatment of moderate to severe inflammatory bowel disease. Safety studies show that vedolizumab has a 31% risk of serious adverse events, but reports of hepatotoxicity are rare. Previous case descriptions show that the lesion is mainly cholestatic or mixed, but hepatocellular lesion can also occur. We report a case of vedolizumab-associated hepatotoxicity in a patient with ulcerative colitis who had no previous liver disease. After starting treatment with vedolizumab, the patient presented elevated transaminases and canalicular in a cholestatic pattern, with normal liver imaging. Due to the suspicion of underlying hepatopathies such as primary sclerosing cholangitis and autoimmune hepatitis (AIH), a biopsy was performed, which showed a lymphocytic inflammatory infiltrate with lymphoid aggregates and eosinophils and plasma cells, as well as interface activity with 'spill-over' of lymphocytes to the parenchyma, which was interpreted as a lesion secondary to the drug. Discontinuation of vedolizumab led to a gradual improvement in liver tests. The case highlights the importance of monitoring liver tests in patients being treated with vedolizumab and the need to differentiate drug hepatotoxicity from other liver diseases.

PMID:40530502 | DOI:10.1097/MEG.0000000000003022

BMJ Case Rep. 2025 Jun 16;18(6):e264962. doi: 10.1136/bcr-2025-264962.

ABSTRACT

Atezolizumab is an immune checkpoint inhibitor that targets PDL-1 (programmed death ligand-1) on the tumour cells and inactivates it. The addition of this drug to chemotherapy has led to survival benefits in the treatment of small cell lung cancer-extensive stage (SCLC-ES). However, these excellent outcomes may be marred by the development of immune-mediated adverse events (irAEs). The pathophysiology of these irAEs is not well defined, and as a result, they are less understood as an entity. In addition to this, the highly non-specific presentation and unawareness among treating physicians may lead to delays in diagnosis and subsequently affect patient outcomes. Immunotherapy-induced myositis is one such rare irAE.Herein, we present a case of a male in his early 70 s undergoing treatment for SCLC-ES, who initially presented with non-specific symptoms and grade four transaminitis and was subsequently diagnosed with atezolizumab-related myositis after comprehensive evaluation. The patient was managed successfully and has an ongoing response more than 6 months after stopping immunotherapy and 18 months since initial diagnosis. This case report aims to address the knowledge gap regarding this irAE with insights on diagnosis and management.

PMID:40527534 | DOI:10.1136/bcr-2025-264962

Drug Dev Res. 2025 Jun;86(4):e70118. doi: 10.1002/ddr.70118.

ABSTRACT

β-glucuronidase (βG) is a critical enzyme involved in the hydrolysis of glucuronide conjugates, significantly influencing drug metabolism, detoxification processes, and enterohepatic circulation. Although essential for maintaining physiological homeostasis, dysregulated βG activity has been implicated in diverse pathological conditions, including drug-induced toxicity, inflammation, and hormone-dependent cancers. Specifically, microbial βG expressed by gut microbiota can reactivate glucuronide-conjugated drugs, leading to adverse reactions through increased drug toxicity and reduced therapeutic efficacy. Consequently, inhibition of βG has emerged as an attractive therapeutic approach to reduce chemotherapy-induced toxicity, gastrointestinal complications, and metabolic disorders. This review systematically examines recent progress in the discovery, characterization, and optimization of βG inhibitors, focusing on natural products, synthetic molecules, and microbiome-targeted agents. Structure-activity relationship analyses reveal crucial functional groups and chemical modifications necessary for enhancing inhibitor potency, selectivity, and bioavailability. In addition, contemporary advances in βG inhibitor evaluation through enzyme kinetics, molecular docking simulations, high-throughput screening, and preclinical animal models are discussed, alongside essential pharmacokinetic parameters, including absorption, distribution, metabolism, excretion, and potential drug-drug interactions. Furthermore, emerging approaches such as microbiome modulation, CRISPR-based enzyme engineering, and combination therapies are explored. Despite promising preclinical outcomes, significant challenges remain regarding clinical translation, such as selectivity, bioavailability, and regulatory compliance. Ultimately, this review highlights future opportunities in precision medicine, emphasizing personalized βG inhibitor development to optimize therapeutic safety and effectiveness across various disease states.

PMID:40522235 | DOI:10.1002/ddr.70118

Ann Pharmacother. 2025 Jun 16:10600280251345079. doi: 10.1177/10600280251345079. Online ahead of print.

ABSTRACT

BACKGROUND: Levetiracetam administration via intravenous push (IVP) may improve outcomes in status epilepticus (SE) by decreasing time to administration. However, there is a paucity of literature describing the safety of IVP administration of higher loading doses used for early management of SE.

OBJECTIVE: The purpose of this evaluation was to investigate the safety of high-dose IVP levetiracetam.

METHODS: This was a retrospective, single-arm cohort study conducted at an academic medical center. Patients were included if they received IVP levetiracetam ≥3000 mg. The primary outcome was a composite of clinically significant adverse events (AEs) within 1-hour post-administration of levetiracetam: hypotension, hypertension, bradycardia, tachycardia, arrhythmia, and/or injection site reaction.

RESULTS: A total of 140 patients met inclusion criteria, receiving a median levetiracetam dose of 4000 mg (interquartile range [IQR] = 3000, 4500). Seventeen (12.1%) patients experienced a clinically significant AE. The most common clinically significant AE was hypotension (9.2% [10/109]), followed by tachycardia (3.6% [4/112]), arrhythmia (1.8% [2/112]), hypertension (0.9% [1/109]), and injection site reaction (0.7% [1/140]). Eighty percent [8/10] of patients who experienced clinically significant hypotension were on at least 1 medication with potential confounding hemodynamic effects.

CONCLUSION AND RELEVANCE: In this retrospective, single-arm analysis, high-dose (≥3000 mg) IVP levetiracetam was relatively well-tolerated but associated with a higher rate of clinically significant hypotension than has been reported in the previous literature, although several confounding factors may have contributed to this outcome. Our findings support the continued use of high-dose IVP levetiracetam with appropriate hemodynamic monitoring; hemodynamic effects should be further explored in future studies.

PMID:40522137 | DOI:10.1177/10600280251345079

Front Pharmacol. 2025 May 30;16:1586368. doi: 10.3389/fphar.2025.1586368. eCollection 2025.

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the food effect on the pharmacokinetics of TQB3616 capsule in Chinse healthy subjects.

METHODS: The subjects were randomly allocated to two distinct sequences in a 1:1 ratio. During each treatment periods, subjects ingested a single oral dose of 180 mg TQB3616 capsule administered with 240 mL of warm water under fasted and fed conditions. To avoid carryover effects, a 19 days washout period was strictly implemented between treatment periods. Blood samples were collected in accordance with the study protocol, and the plasma concentration of TQB3616 was measured using a fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Safety evaluations were performed continuously throughout the duration of the trial.

RESULTS: Following the administration of TQB3616 capsules under both fasted and fed conditions, the geometric mean ratios of Cmax, AUC0-t, and AUC0- ∞ for TQB3616 in the fed state compared to the fasted state were 148.04%, 145.06%, and 143.13%, respectively. The corresponding 90% confidence intervals (CIs) were 101.23%-216.51%, 117.68%-178.83%, and 116.46%-175.91%, none of which fell within the conventional bioequivalence range of 80.00%-125.00%. A total of 81 adverse events (AEs) were reported among 16 subjects, with 77 events deemed related to the drug. Among the 77 drug-related adverse events, two cases were grade II, with the rest being grade I. Notably, there were no serious adverse events, deaths, or unexpected serious reactions.

CONCLUSION: A pharmacokinetic study conducted on healthy volunteers, who received a single 180 mg dose of TQB3616 capsules under fasting and fed conditions, demonstrated clinically significant effects of food on the drug's bioavailability. Compared with fasted, postprandial administration delayed median Tmax by 1 h while increasing total systemic exposure and peak concentration. Additionally, postprandial dosing was associated with reduced incidence of gastrointestinal adverse reactions. These data support the recommendation that TQB3616 capsules be administered with food to maximize therapeutic bioavailability while improving gastrointestinal tolerability profile.

CLINICAL TRIAL REGISTRATION: http://www.chinadrugtrials.org.cn, identifier, CTR20210354; clinicaltrials.gov, identifier, NCT05344729.

PMID:40520159 | PMC:PMC12163317 | DOI:10.3389/fphar.2025.1586368

Front Immunol. 2025 May 29;16:1559275. doi: 10.3389/fimmu.2025.1559275. eCollection 2025.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are limited by immune-related adverse events (irAEs). This study aimed to assess peripheral T cell profiles to identify irAEs biomarkers and construct predictive models.

METHODS: In our study, we enrolled and followed 51 gastrointestinal cancer patients receiving anti-PD-1/PD-L1 therapies, with 22 developed irAEs (AE) and 29 didn't (NAE). We examined their peripheral blood using Olink technology, RNA-seq, and flow cytometry to explore the immunological characteristics of their circulating environment before and after early stages of ICIs treatment.

RESULTS: Our study discovered after early stages of ICIs treatment, a stronger upregulation of T cell activation genes, particularly Tfh-associated genes, was observed in AE patients. Flow cytometry result confirmed that AE patients exhibited elevated CD4+CXCR5-ICOS+ cells (p<0.01), CD4+CXCR5+ICOS+ cells (p<0.05) and Th1/Th2 ratio (p<0.05) after early stages. At baseline, AE patients had higher levels of serum inflammatory proteins including IL-12β, IL-15RA and CXCL9 (p<0.05). Higher peripheral Tfh (p<0.05), Tph (p<0.001) were also observed in the baseline flow cytometry result of AE patients compared to NAE patients. Based on these findings, predictive models for both irAEs and grade 2-4 irAEs were established, demonstrating good discriminatory ability.

CONCLUSION: This study demonstrates that high-dimensional immune profiling can uncover novel blood-based immune signatures associated with the risk and mechanism of severe irAEs are effective biomarkers for predicting irAEs at both baseline and early stages of ICIs treatment.

PMID:40519906 | PMC:PMC12163322 | DOI:10.3389/fimmu.2025.1559275

Rev Med Liege. 2025 May;80(5-6):315-322.

ABSTRACT

Immune checkpoint inhibitors (ICI) have revolutionized the treatment of solid tumors. However, they can induce immune-related adverse effects (irAEs) that can affect any organ. These irAEs are different from the side effects of traditional oncological treatments and require specific management. Given the increasing use of ICI, first-line care will increasingly need to manage these irAEs. This article aims to assist in the implementation of the guidelines for managing irAEs, with a particular focus on aspects related to first-line care.

PMID:40518884

Zhonghua Yu Fang Yi Xue Za Zhi. 2025 Jun 6;59(6):942-945. doi: 10.3760/cma.j.cn112150-20241129-00956.

ABSTRACT

The incidence rate of suspected adverse events following immunization (AEFI) after single administration of pentavalent recombinant rotavirus attenuated live vaccine (RV5) in Chaoyang District, Beijing City from 2019 to 2021 was 362.3 per 100 000 doses. The incidence rate of AEFI after simultaneous administration with oral polio vaccine (OPV), inactivated polio vaccine (IPV), hepatitis B vaccine (HBV), Haemophilus influenzae type b (Hib), and pneumococcal conjugate vaccine 13-valent (PCV13) was 239.3 per 100 000, 643.4 per 100 000, 346.8 per 100 000, 438.1 per 100 000, and 434.0 per 100 000, respectively. The specific incidence rates for common AEFI symptoms such as fever, local allergic rash, irritability, and vomiting under different vaccination regimens were as follows: RV5 alone (fever: 88.3 per 100 000, rash: 9.1 per 100 000, irritability: 100.5 per 100 000, vomiting: 83.3 per 100 000), RV5 and IPV simultaneous administration (fever: 239.4 per 100 000, rash: 104.7 per 100 000, irritability: 134.7 per 100 000, vomiting: 89.8 per 100 000), RV5 and OPV simultaneous administration (fever: 119.6 per 100 000, rash: 32.6 per 100 000, irritability: 32.6 per 100 000, vomiting: 32.6 per 100 000), RV5 and HBV simultaneous administration (fever: 111.0 per 100 000, rash: 69.4 per 100 000, irritability: 83.2 per 100 000, vomiting: 41.6 per 100 000), RV5 and Hib simultaneous administration (fever: 159.3 per 100 000, rash: 238.9 per 100 000, irritability: 0 per 100 000, vomiting: 39.8 per 100 000), and RV5 and PCV13 simultaneous administration (fever: 142.8 per 100 000, rash: 98.0 per 100 000, irritability: 126.0 per 100 000, vomiting: 25.2 per 100 000).

PMID:40518428 | DOI:10.3760/cma.j.cn112150-20241129-00956

Dermatol Ther (Heidelb). 2025 Jun 15. doi: 10.1007/s13555-025-01450-x. Online ahead of print.

ABSTRACT

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease. This study evaluated the efficacy and safety of xeligekimab (GR1501), a novel anti-interleukin-17A (anti-IL-17A) monoclonal antibody, in Chinese patients with moderate-to-severe plaque psoriasis.

METHODS: In this multicenter, randomized, double-blind, phase II trial, 199 patients were assigned (1:1:1:1) to receive placebo (n = 49) or xeligekimab 100 mg (n = 50), 150 mg (n = 49), or 200 mg (n = 51) every 4 weeks for 12 weeks. All participants then entered a 40-week extension receiving xeligekimab 200 mg every 4 or 8 weeks. The primary endpoint was a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) at week 12. Secondary endpoints included PASI 75, PASI 90 (≥ 90% improvement), and a static Physician's Global Assessment (sPGA) score of 0/1 (clear/almost clear) at week 52. Safety, pharmacokinetics (PK), and anti-drug antibodies (ADA) were also assessed.

RESULTS: At week 12, PASI 75 response rates for the 100, 150, and 200 mg groups were 86.0%, 89.8%, and 88.2%, respectively, versus 2.0% for placebo (P < 0.05). At week 52, PASI 75, PASI 90, and sPGA 0/1 response rates remained high in both 4-week (98.8%, 83.3%, 77.4%) and 8-week (92.9%, 83.3%, 78.6%) groups. No dose-dependent safety issues or ADA positivity were observed.

CONCLUSION: Xeligekimab demonstrated strong efficacy, sustained response, and favorable safety in patients with moderate-to-severe plaque psoriasis.

TRIAL REGISTRATION NUMBER: ChiCTR1800017956.

PMID:40517362 | DOI:10.1007/s13555-025-01450-x

Lancet Microbe. 2025 Jun 11:101126. doi: 10.1016/j.lanmic.2025.101126. Online ahead of print.

ABSTRACT

BACKGROUND: Clostridioides difficile infection is a common health-care-associated and community-acquired disease with few antibiotic treatment options. We aimed to assess the safety, efficacy, pharmacokinetics, and associated microbiome changes of ibezapolstat, an antibiotic that inhibits the PolC-type DNA polymerase III α subunit C, versus vancomycin for the treatment of C difficile infection in adults.

METHODS: This was a phase 2b, randomised, double-blind, active-controlled study conducted at 15 centres, primarily outpatient clinics and hospitals, in the USA. Adults aged 18-90 years, with signs and symptoms of C difficile infection and a positive toxin stool test were recruited. Participants were randomly assigned (1:1) with block assignment by study site using an interactive web response system to receive oral ibezapolstat (450 mg twice daily) or oral vancomycin (125 mg every 6 h) for 10 days. Masking was achieved by over-encapsulation of both study drugs (ibezapolstat and vancomycin) and placebo into identically sized capsules. Participants were excluded if they had received more than 24 h of treatment with oral vancomycin, fidaxomicin, or metronidazole for the current episode of C difficile infection before the first dose of study drug or any other antibacterial therapy within 48 h, had had more than three episodes of C difficile infection in the previous 12 months, or had had more than one previous episode in the past 3 months (excluding the current episode). The primary efficacy endpoint was initial clinical cure maintained for at least 48 h after the end of treatment. All individuals with C difficile infection who met inclusion and exclusion criteria, were randomly assigned, and were administered at least one dose of study drug were included in the efficacy analysis. The safety and tolerability of ibezapolstat was assessed in all individuals who were administered at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04247542.

FINDINGS: Between March 12, 2021, and Oct 27, 2023, 39 individuals were assessed for eligibility, 32 of whom were recruited and randomly assigned to ibezapolstat (n=18) or vancomycin (n=14). Two participants were excluded from the efficacy analysis: one participant in the ibezapolstat group withdrew consent before receiving the study drug and another was identified after random assignment as having an exclusion criterion. The primary efficacy analysis included 16 participants in the ibezapolstat group and 14 in the vancomycin group; 24 (80%) participants were female and six (20%) were male. 15 (94%) of 16 participants in the ibezapolstat group had initial clinical cure compared with 14 (100%) of 14 participants in the vancomycin group (treatment difference -6·3% [95% CI -30·7 to 19·4]; p=1·0). Ibezapolstat was well tolerated with a safety profile similar to vancomycin. No drug-related serious adverse events, drug-related treatment withdrawal, or treatment-related deaths occurred in either group.

INTERPRETATION: Ibezapolstat is a Gram-positive selective spectrum antibiotic that shows potential in the treatment of initial C difficile infection and prevention of recurrence. Further clinical development is warranted.

FUNDING: Acurx Pharmaceuticals.

PMID:40516571 | DOI:10.1016/j.lanmic.2025.101126

Oncologist. 2025 Jun 4;30(6):oyaf120. doi: 10.1093/oncolo/oyaf120.

ABSTRACT

BACKGROUND: While immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, they can trigger severe immune-related adverse events (irAEs). The safety and efficacy of ICI retreatment after severe irAEs remain poorly understood.

METHODS: We conducted a retrospective analysis of 1271 patients with malignancies treated with ICIs at a university hospital in Japan between September 2014 and June 2023. We evaluated the incidence and characteristics of severe irAEs, defined as grade ≥3, and the safety and efficacy of ICI retreatment.

RESULTS: Severe irAEs occurred in 222 patients (17.5%). Patients with single endocrinopathies were excluded, and 46 (28.4%) of the remaining 162 patients underwent ICI retreatment. Upon retreatment, 14 patients (30.4%) experienced recurrent or new grade ≥2 irAEs. One patient who experienced hepatotoxicity (grade 3) at initial ICI treatment developed a recurrence (grade 4). Regarding antitumor response, the objective response rate to retreatment was 28.3% (13/46), with 10.9% achieving complete and 17.4% partial response. The median duration of ICI administration after retreatment was 218 days (95% confidence interval [CI]: 84-399). At 1 year after retreatment, 15.4% (95% CI: 6.8-27.4) of patients discontinued due to irAEs, 44.4% (95% CI: 29.7-58.1) due to disease progression, 6.6% (95% CI: 1.7-16.3) completed planned treatment, and 33.4% (95% CI: 20.3-47.2) continued treatment.

CONCLUSIONS: ICI retreatment after severe irAEs demonstrated a manageable safety profile and promising efficacy, even in patients with grade ≥3 irAEs. ICI retreatment may be a viable option for patients with limited alternatives, particularly those showing favorable antitumor responses at initial treatment.

PMID:40515478 | DOI:10.1093/oncolo/oyaf120

Inquiry. 2025 Jan-Dec;62:469580251335805. doi: 10.1177/00469580251335805. Epub 2025 Jun 13.

ABSTRACT

Drug safety is a critical aspect of public health, yet traditional detection methods may miss rare or long-term side effects. Recently, machine learning (ML) techniques have shown promise in predicting drug-related side effects earlier in the development pipeline. The objective of this policy brief was to propose evidence-based policy options for using ML techniques to predict drug-related side effects. This policy brief was developed upon a previously published scoping review of relevant studies. A secondary analysis synthesized key barriers and opportunities relevant to policy development. Key findings revealed some challenges in data standardization, interpretability, and regulatory alignment. Moreover, the results highlighted the potential of explainable ML and cross-sector collaboration to improve prediction accuracy and fairness. Five policy recommendations were proposed: (1) establishing standardized data collection and secure protocol sharing; (2) funding ML model development and rigorous validation; (3) integrating ML into drug development pipelines; (4) increasing public awareness through targeted education; and (5) implementing fairness regulations to address bias. These recommendations require joint efforts from governments, regulatory bodies, pharmaceutical firms, and academia to be implemented in practice. While ML offers transformative potential for drug safety, its real-world implementation faces ethical, regulatory, and technical hurdles. Policies must ensure model transparency, promote equity, and support infrastructure for ML adoption. Through interdisciplinary coordination and evidence-based policymaking, stakeholders can responsibly advance ML use in drug development to enhance patient outcomes.

PMID:40514209 | DOI:10.1177/00469580251335805

Indian J Pharmacol. 2025 Mar 1;57(2):77-82. doi: 10.4103/ijp.ijp_88_23. Epub 2025 Jun 13.

ABSTRACT

INTRODUCTION: Deferasirox is a newer oral iron chelator which needs to be given for at least 1 year to see a significant decrease in serum ferritin level in thalassemia patients with chronic iron overload. This study aimed to assess the safety profile of branded generic deferasirox in pediatric thalassemia cases, as it has not been studied in eastern India, especially in real-world settings.

SUBJECTS AND METHODS: It was an observational hospital-based study in a government tertiary care teaching hospital where branded generic deferasirox is distributed free of cost to patients. One hundred and seventy-four patients were included. Safety assessment was done through active questioning about the symptoms starting after deferasirox therapy and through laboratory parameters and clinical examination.

RESULTS: Sixty percent of patients developed adverse drug reactions (ADRs) with deferasirox during the 1-year follow-up. ADRs were more common in males than females. The highest number of ADRs was related to the gastrointestinal and hepatobiliary system. The ADRs were either mild or moderate. Compliance and number of ADRs were found to be inversely correlated.

CONCLUSION: ADRs of deferasirox are acceptable looking at the benefits. Regular monitoring and management of ADRs will facilitate patient compliance. However, healthcare professionals need to be alert while prescribing this drug and report any ADR, even if it is not labeled. This study found increased serum lipase and mouth ulcer as adverse effects, which are not yet labeled. These can be signals for further analysis by regulatory authorities.

PMID:40509761 | DOI:10.4103/ijp.ijp_88_23

Int J Mol Sci. 2025 May 28;26(11):5188. doi: 10.3390/ijms26115188.

ABSTRACT

Food components and herbal substances can inhibit or enhance the therapeutic effects of drugs, thus influencing their efficacy and safety. As relatively little in known of these interactions, the aim of this review is to shed further light on the potentially dangerous influences that food and herbs may have on cytochrome P450 enzyme (CYP) and monoamine oxidase (MAO) activity in the first stage of drug biotransformation. The review includes documented cases in which such interactions have led to health complications in patients. For example, fruit juices, such as grapefruit juice, cranberry juice, and pomegranate juice, have been found to interact with drugs, and to particularly inhibit CYP450 activity, and commonly used herbs are known to inhibit (e.g., Astragalus membranous) or induce (e.g., Hypericum perforatum) CYP enzymes involved in drug metabolism. CYP is also induced by polycyclic aromatic hydrocarbons (PAHs), found in grilled meat and tobacco smoke. The paper also discusses the toxic effects of tyramine, present in inter alia blue cheese, resulting from interactions with MAO-metabolised drugs. Most importantly, while the quantity of food and herbs consumed plays a significant role in the described drug interactions, it is possible for toxic effects to be observed even after the consumption of relatively small amounts. Patients are encouraged to consult a healthcare provider about any potential drug interactions that may occur when starting a new medication.

PMID:40507996 | DOI:10.3390/ijms26115188

Cancer Control. 2025 Jan-Dec;32:10732748251347902. doi: 10.1177/10732748251347902. Epub 2025 Jun 12.

ABSTRACT

IntroductionThe Cancer and Aging Research Group (CARG) model predicts chemotherapy-related toxicities in older patients; however, its applicability has not been validated in Taiwanese patients. This study aims to validate the CARG model in older Taiwanese patients with solid tumors.MethodsPatients (N = 258) aged ≥65 years with solid tumors from a single medical center, slated for first-line chemotherapy, were recruited between 2018 and 2021, with follow-up until December 31, 2022. Patients were categorized into low- (N = 85), medium- (N = 117), and high- (N = 56) risk based on CARG. Validation of CARG involved receiver operating characteristic (ROC) curves. Individual CARG variables were analyzed using univariate analysis for their impact on toxicities and survival.ResultsToxicities of grades ≥3 were 38.8%, 44.4%, and 67.9% (P = .001) in the three ascending risk groups, and there were significant differences in both hematological (P = .002) and non-hematological (P < .001) toxicities. ROC was 0.631 (95% CI: 0.562-0.700), indicating satisfactory discrimination. One-year overall survival rates were 88.7%, 79.7%, and 63.8%, respectively, in ascending-risk groups, with high-risk groups showing decreased survival (P = .002). In the multivariate analysis, decreased hemoglobin, history of falls, and inability to walk one block remained significantly associated with toxicity. For overall survival, the inability to take medications was the only independent predictor.ConclusionThis prognostic study validated the CARG model in a heterogeneous solid tumor cohort in Taiwan. In addition to predicting both hematological and non-hematological toxicities, CARG could offer insights into patient survival among older individuals with cancer.

PMID:40504733 | DOI:10.1177/10732748251347902

Pediatr Surg Int. 2025 Jun 12;41(1):166. doi: 10.1007/s00383-025-06085-9.

ABSTRACT

PURPOSE: To evaluate real-world effectiveness of intrapleural fibrinolysis versus drainage alone or surgery, and to identify factors linked to prolonged hospitalisation in children with pleural empyema at a tertiary centre. We also aimed to provide regional baseline data to guide future care.

METHODS: We retrospectively reviewed records for all patients aged ≤ 14 years treated for pleural empyema et al. Jalila Children's Specialty Hospital, Dubai, from January 2021 to December 2024. Demographics, imaging, treatments, antibiotic use, and in-hospital outcomes were abstracted and summarised descriptively.

RESULTS: Thirty-five children (median age 4 years; 54% female) were included. All underwent ultrasound-guided tube thoracostomy, and 30 (86%) also received intrapleural alteplase. Four children needed surgical decortication and 1 child with lymphoma died. Median tube drainage was 6 days with fibrinolysis versus 8 days without. Median hospital stay was 11 days with fibrinolysis, 27 days without, and 13.5 days after surgery. Hospitalisation ≥ 15 days correlated with older age, omission of fibrinolysis, use of ≥ 4 antibiotics, and computed tomography imaging. No serious drug-related adverse events occurred.

CONCLUSION: Prompt tube thoracostomy combined with intrapleural alteplase is a safe, effective, and resource-efficient first-line therapy for paediatric empyema, shortening hospital stay and markedly reducing the need for surgery.

PMID:40504261 | DOI:10.1007/s00383-025-06085-9

Pharmacol Res Nat Prod. 2025;7:100252. doi: 10.1016/j.prenap.2025.100252. Epub 2025 May 5.

ABSTRACT

BACKGROUND: Airway inflammation plays a major role in the development and progression of chronic obstructive pulmonary disease (COPD). Quercetin, which has potent antioxidant and anti-inflammatory properties reduces lung inflammation in mice displaying COPD-like lung disease. Previously we showed that quercetin was safely tolerated up to 2000 mg/day. We conducted a pilot Phase II clinical trial to examine the effects of quercetin on inflammation in COPD patients.

METHODS: Fourteen COPD patients with ≥ 10 pack-year smoking history and CRP > 3.0 mg/L were randomized in 1:2 ratio to either placebo or quercetin 2000 mg/day for 6 months. Blood and bronchoalveolar lavage fluid (BALF) were collected at baseline and 6 months post-treatment. The reduction of inflammatory and oxidative stress biomarkers in BALF and blood were expressed as change from baseline. Safety of quercetin was assessed based on FEV1 and blood tests.

RESULTS: Plasma quercetin levels significantly increased after treatment in only quercetin group. The levels of IL-8, IL-1β, and 8-isoprostane in the BAL and serum SP-D were significantly different from baseline in patients treated with quercetin, but not placebo. The patient-reported disease symptoms showed lowering trend in quercetin-treated group. No study drug-related adverse events were observed as assessed by comprehensive metabolic panel and FEV1.

CONCLUSIONS: Oral treatment with quercetin was safely and well-tolerated by COPD patients. Quercetin treatment reduced some lung and serum inflammatory biomarkers in COPD. Further prospective studies are necessary to confirm the anti-inflammatory and antioxidant effects of quercetin in COPD patients and to determine if quercetin offers any clinical benefit.

PMID:40503179 | PMC:PMC12151252 | DOI:10.1016/j.prenap.2025.100252

Clin Breast Cancer. 2025 May 13:S1526-8209(25)00116-8. doi: 10.1016/j.clbc.2025.05.003. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: CDK 4/6 inhibitors with ET are the recommended choice as 1st-line therapy in HR+/HER2- MBC patients, however ET alone could remain an option for some of them. HERMIONE-7 is a multicenter, single-arm, Phase II study, aimed to evaluate Abemaciclib 150 mg BID + AIs, in patients who progressed on 1st line Fulvestrant.

MATERIALS AND METHODS: Primary aim was the efficacy of Abemaciclib + AIs in terms of Clinical Benefit Rate (CBR), secondary aims were Time to Progression (TTP), Overall Response Rate (ORR), duration of response (DOR), and safety.

RESULTS: From April 2020 to January 2022, we enrolled 31 patients. Median age was 72 years (range 47-86), 55% had < 2 comorbidities, mainly hypertension (12, 38.7%). Clinical Benefit Rate was 69% (95% CI, 49-85) and ORR was 21% (95%CI, 8-40). 1-year TTP and OS rates were 53.8% (95% CI, 38.6-74.9%) and 69.5% (95% CI, 54.8%-88.5%), respectively. Main adverse events remain diarrhea (80.6%), fatigue (54.8%) and nausea (35.5%), 3 patients (10.7%) had non drug-related fatal events.

CONCLUSIONS: HERMIONE-7 study showed that 2nd-line treatment with Abemaciclib + AIs is a feasible option in MBC patients who progressed on Fulvestrant in 1st-line setting and could be an alternative especially in terms of optimizing the cost-benefit ratio in some Countries.

PMID:40500613 | DOI:10.1016/j.clbc.2025.05.003

Exp Biol Med (Maywood). 2025 May 27;250:10555. doi: 10.3389/ebm.2025.10555. eCollection 2025.

ABSTRACT

Pharmacovigilance is essential for protecting patient health by monitoring and managing medication-related risks. Traditional methods like spontaneous reporting systems and clinical trials are valuable for identifying adverse drug events, but face delays in data access. Social media platforms, with their real-time data, offer a novel avenue for pharmacovigilance by providing a wealth of user-generated content on medication usage, adverse drug events, and public sentiment. However, the unstructured nature of social media content presents challenges in data analysis, including variability and potential biases. Advanced techniques like natural language processing and machine learning are increasingly being employed to extract meaningful information from social media data, aiding in early adverse drug event detection and real-time medication safety monitoring. Ensuring data reliability and addressing ethical considerations are crucial in this context. This review examines the existing literature on the use of social media data for drug safety analysis, highlighting the platforms involved, methodologies applied, and research questions explored. It also discusses the challenges, limitations, and future directions of this emerging field, emphasizing the need for ethical principles, transparency, and interdisciplinary collaboration to maximize the potential of social media in enhancing pharmacovigilance efforts.

PMID:40495881 | PMC:PMC12149966 | DOI:10.3389/ebm.2025.10555

Ann Fam Med. 2025 Jun 10:240383. doi: 10.1370/afm.240383. Online ahead of print.

ABSTRACT

PURPOSE: Prescribing cascades occur when one medication is used to treat adverse effects of another medication. Older adults with polypharmacy are at higher risk for this phenomenon. We examined the prevalence, magnitude, and effect modification of 9 prescribing cascades (ThinkCascades) among older community-dwelling adults in a national prescription database.

METHODS: We used prescription sequence symmetry analysis to examine prescriptions for ThinkCascades medications dispensed in primary care under the General Medical Services scheme in Ireland. Analyses were based on prescriptions dispensed between 2017 and 2020 among 533,464 adults aged 65 years or older. Incident users of both medications in each ThinkCascades dyad were included. We used an observation window of 365 days and examined other windows in sensitivity analyses. Adjusted sequence ratios (aSRs) took into account secular prescribing trends. We also conducted analyses stratified by sex, age, and individual index medication.

RESULTS: Five prescribing cascades had significant positive aSRs, indicating that the patient was more likely to receive the index medication before the marker medication. The largest signal was identified for the calcium channel blocker to diuretic cascade (prevalence, 2.6%; aSR = 1.93; 95% CI, 1.79-2.09). Positive signals were also identified for the α1-receptor blocker to vestibular sedative cascade (prevalence, 3.0%; aSR = 1.63; 95% CI, 1.46-1.81); the selective serotonin reuptake inhibitor/selective norepinephrine reuptake inhibitor to sleep medication cascade (prevalence, 2.5%; aSR = 1.54; 95% CI, 1.40-1.69); the antipsychotic to antiparkinsonian cascade (prevalence, 0.4%; aSR = 1.20; 95% CI, 1.00-1.43); and the benzodiazepine to antipsychotic cascade (prevalence, 3.2%; aSR = 1.15; 95% CI, 1.08-1.21).

CONCLUSIONS: To our knowledge, this study is the first to describe the prevalence of an expert consensus-based list of prescribing cascades, ThinkCascades, in a national population of older adults, and it identified 5 clinically relevant prescribing cascades. These findings highlight prescribing cascades as an important underresearched area contributing to complex polypharmacy among older people living with multimorbidity.

PMID:40494622 | DOI:10.1370/afm.240383