BMC Infect Dis. 2025 Feb 18;25(1):230. doi: 10.1186/s12879-025-10627-w.

ABSTRACT

BACKGROUND: Isavuconazole has been used to treat invasive fungal infections, however, it is unclear whether the efficacy of isavuconazole is superior to that of voriconazole. The purpose of this meta-analysis was to assess the efficacy and safety of isavuconazole compared to voriconazole in treating invasive fungal infections.

METHODS: Electronic databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, were searched to identify relevant studies. Studies evaluating the effect of isavuconazole in the treatment of patients with invasive fungal infections were included. Pooled rates of overall response, all-cause mortality, drug-related adverse events (AEs), and discontinuation due to drug-related AEs were calculated.

RESULTS: Seven studies involving 890 patients were included. Meta-analysis showed that there was no significant difference between isavuconazole and voriconazole in overall response (risk ratio [RR]: 1.02, 95% confidence interval [CI]: 0.83 to 1.25, p = 0.86) and all-cause mortality (RR: 0.95, 95% CI: 0.78 to 1.16, p = 0.61). However, isavuconazole had a significantly lower incidence of drug-related AEs (RR: 0.70, 95% CI: 0.61 to 0.81, p < 0.001) and discontinuation due to drug-related AEs (RR: 0.56, 95% CI: 0.39 to 0.82, p = 0.003) compared with voriconazole. Trial sequential analysis (TSA) confirmed that the difference between isavuconazole and voriconazole in discontinuation due to drug-related AEs need further valiadation, but the results of other outcomes were conclusive. < 0.001) and discontinuation due to drug-related AEs (RR: 0.56, 95% CI: 0.39 to 0.82, p = 0.003) compared with voriconazole. Trial sequential analysis (TSA) confirmed that the difference between isavuconazole and voriconazole in discontinuation due to drug-related AEs needs further validation, but the results of other outcomes were conclusive.

CONCLUSIONS: Our findings support the use of isavuconazole as the primary therapy for invasive fungal infections. More research is needed to compare the discontinuation rates of isavuconazole and voriconazole.

PMID:39966738 | DOI:10.1186/s12879-025-10627-w

Pathologie (Heidelb). 2025 Feb 18. doi: 10.1007/s00292-025-01418-w. Online ahead of print.

ABSTRACT

BACKGROUND: Besides reactions of the IgE-mediated immediate type, medicamentous therapies can cause a variety of different mucocutaneous adverse events. Exanthematous manifestations require a fast and certain diagnosis due to their extent, sometimes rapid progression, and mucous membrane or organ involvement.

OBJECTIVES: The spectrum of non-IgE-mediated exanthematic drug reactions is covered.

MATERIAL AND METHODS: The most relevant reactions are portrayed clinically and histopathologically.

RESULTS: Displayed are classical maculo-papular drug eruption, lichenoid drug reaction, acute generalized exanthematic pustulosis (AGEP), severe potentially life-threatening drug reactions such as Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) as well as generalized bullous fixed drug eruption (GBFDE), drug reaction with eosinophilia and systemic symptoms (DRESS), and some others.

CONCLUSIONS: Cutaneous drug-related side effects cover a broad spectrum. Important for the correct treatment is a reliable diagnosis. In the case of severe, life-threatening drug reactions, however, permanent discontinuation of the drug is essential.

PMID:39964515 | DOI:10.1007/s00292-025-01418-w

Oncologist. 2025 Feb 6;30(2):oyae320. doi: 10.1093/oncolo/oyae320.

ABSTRACT

BACKGROUND: The impact of concurrent proton pump inhibitors (PPIs) use on the prognosis of patients with breast cancer undergoing cyclin-dependent kinase inhibitors (CDKIs) treatment is currently uncertain. Considerable divergence exists regarding the clinical studies. In this study, we aim to perform a comprehensive analysis to evaluate the influence of concomitant PPI use on the effectiveness and adverse effects of CDKIs in patients with breast cancer.

METHODS: This study encompassed all pertinent clinical studies published up to the present, following the PRISMA guidelines. The study used hazard ratio (HR) or odds ratio (OR) as a summary statistic and used fixed or random effects models for pooled estimation.

RESULTS: This study incorporated 10 research articles involving 2993 participants. Among patients with breast cancer undergoing treatment with CDKIs, the simultaneous administration of PPIs was associated with a notable reduction in overall survival (HR = 2.00; 95% CI, 1.35-2.96). Nevertheless, no substantial correlation was observed between the simultaneous utilization of PPIs and the progression-free survival (PFS) of patients (HR = 1.30; 95% CI, 0.98-1.74). PFS did not change significantly when considering different drugs, treatment lines, or regions alone. Furthermore, the simultaneous administration of PPIs was found to result in a notable decrease in the incidence of grades 3/4 risk factors (OR = 0.63, 95% CI, 0.46-0.85).

CONCLUSION: The concurrent administration of PPIs did not result in significant alterations in the risk of disease advancement among patients with breast cancer undergoing CDKIs treatment. The utilization of PPIs led to a decrease in the adverse effects linked to the administration of CDKIs.

PMID:39963828 | DOI:10.1093/oncolo/oyae320

Eur Heart J Cardiovasc Pharmacother. 2025 Feb 17:pvaf014. doi: 10.1093/ehjcvp/pvaf014. Online ahead of print.

ABSTRACT

AIMS: Managing patients with atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF) is challenging. While sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) show cardiovascular benefits, the impact of combining these agents is unclear. This study evaluated whether adding GLP-1 RA to SGLT2i provides additional benefits in patients with both ASCVD and HF.

METHODS AND RESULTS: This retrospective observational study utilized the TriNetX database to analyze patients with ASCVD and HF who initiated GLP-1 RA with SGLT2i or SGLT2i alone from August 1, 2016, to September 30, 2024. A total of 2 797 317 patients were identified, with 96 051 patients meeting inclusion criteria. After propensity score matching (PSM), 5 272 patients in each group were analyzed. Primary outcomes included mortality or hospitalization within one year; secondary outcomes examined mortality, hospitalization, and heart failure exacerbation (HFE). Patients receiving GLP-1RA and SGLT2i therapies had significantly lower risk of mortality or hospitalization (HR 0.78; 95% CI 0.74-0.83), mortality (HR 0.72; 95% CI 0.62-0.84), hospitalization (HR 0.78; 95% CI 0.73-0.83), and HFE (HR 0.77; 95% CI 0.72-0.83) versus SGLT2i alone. Subgroup analyses showed consistent benefits in patients with HFpEF, HFrEF, patients with diabetes, obesity, chronic kidney disease, or those using semaglutide or dulaglutide, while liraglutide use showed a neutral effect. Drug-related side effects were monitored as safety outcomes, which showed no significant differences between groups.

CONCLUSIONS: In ASCVD and HF patients, adding GLP-1 RA to SGLT2i reduces one-year mortality and hospitalization, warranting further investigation in diverse settings.

PMID:39963713 | DOI:10.1093/ehjcvp/pvaf014

BMC Bioinformatics. 2025 Feb 17;26(1):54. doi: 10.1186/s12859-025-06053-z.

ABSTRACT

Adverse drug reactions (ADRs) are among the global public health events that seriously endanger human life and cause high economic burdens. Therefore, predicting the possibility of their occurrence and taking early and effective response measures is of great significance. Constructing a correlation matrix between drugs and their adverse reactions, followed by effective correlation data mining, is one of the current strategies to predict ADRs using accessible public data. Since the number of known ADRs in real-world data is far less than the number of their unknown counterparts, the drug-ADR association matrix is very sparse, which greatly affects the classification performance of machine learning methods. To effectively address the problem of sparsity, we proposed a novel weighted pseudo-labeling framework that mines potential unknown drug-ADR pairs by integrating multiple weighted matrix factorization (MF) models and treating them as pseudo-labeled drug-ADR pairs. Pseudo-labeled data is added to the training set, and the MF model is fine-tuned to improve the classification performance. To prevent overfitting to easily found pseudo-labels and improve the quality of pseudo-labels, a novel weighting approach for pseudo-labels was adopted. This paper reproduces the baselines under the same experimental conditions to evaluate the performance of the proposed method on sparse data from the Side Effect Resource (SIDER) database. Experimental results showed that our method outperformed other baselines in the Area Under Precision-Recall and F1-scores and still maintained the best performance in sparser scenarios. Furthermore, we conducted a case study, and the results showed that our proposed framework efficiently predicted ADRs in the real world.

PMID:39962381 | DOI:10.1186/s12859-025-06053-z

Pharmacoepidemiol Drug Saf. 2025 Feb;34(2):e70100. doi: 10.1002/pds.70100.

ABSTRACT

BACKGROUND: The use of real-world data is increasing to examine immune-related adverse event (irAE) incidence and risk factors in immune checkpoint inhibitor (ICI) users. We aimed to validate five case definition algorithms for irAE in a Johns Hopkins lung cancer registry.

METHODS: We conducted a retrospective cohort study using linked electronic health record (EHR) and cancer registry data from a large academic healthcare system. The Lung Immunotherapy irAE Monitoring Registry assesses irAEs in a group of patients treated for lung cancer at Johns Hopkins Medicine from 2013 to 2020. We used data from inpatient, outpatient, and emergency department encounters, including International Classification of Disease (ICD)-10 codes and medication administration records to classify the presence or absence of irAEs using five distinct algorithms. These algorithms included three that used both diagnosis (Dx) and medication (Rx) codes, one that used Rx codes only, and one that used Dx codes only, ranging from most numerous criteria (most stringent) to least numerous criteria (least stringent). We compared all five algorithms' performances against chart review-ascertained irAE status and reported sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and C-statistic (C-stat), with 95% confidence intervals (CI). We also explored algorithm performance by specific organ system toxicities and by Common Terminology Criteria for Adverse Events (CTCAE) severity.

RESULTS: The study cohort included 354 patients with ICI exposure for whom chart review-ascertained irAE status was available. A total of 89 (25.1%) experienced at least one irAE (38 pneumonitis, 12 arthritis, 12 colitis, 7 thyroiditis, and others). Across algorithm versions, Se ranged from 59.3% to 93.2% in descending order of algorithm stringency; Sp ranged from 21.0% to 77.6% in ascending order of algorithm stringency, and PPV ranged from 19.1% to 34.7%. The C-stat ranged from 0.57 (95% CI, 0.53-0.61) (Dx codes only) to 0.71 (0.64-0.77) (Rx codes only). For severe irAE (CTCAE Grade 3-5), all algorithms performed better than in the primary analysis, and four exceeded the threshold for usefulness as a measurement tool (maximum C-stat: 0.78 [0.71-0.85] [Rx codes only]). For severe tissue-specific toxicities, algorithmic detection of irAE pneumonitis, colitis, and hepatitis performed better than for the overall group of severe toxicities. Generally, the algorithm versions depicted a Se-Sp tradeoff depending on algorithm stringency.

CONCLUSION: In this validation study of five irAE case definition algorithms, a combination of ICD-10 codes and medication administration codes generally perform well to identify more severe irAE (CTCAE Grade 3-5), and severe pneumonitis, hepatitis, and colitis (common irAEs) among all possible irAE severity levels and sites. Medication codes alone perform well at identifying severe irAE, while the most stringent algorithm (mirroring guideline-recommended irAE treatment) has the highest Sp and PPV. Algorithms have utility for comparing the relative risk of irAE between regimens or patient subgroups.

PMID:39961795 | DOI:10.1002/pds.70100

J Biochem Mol Toxicol. 2025 Feb;39(2):e70172. doi: 10.1002/jbt.70172.

ABSTRACT

Cyclophosphamide (CYC) is one of the most potent antineoplastic drugs; however, hepatonephrotoxicity, observed following its use, remains one of its most severe side effects. Previous studies have reported that syringaldehyde (SYA), a flavonoid compound, exhibits anti-inflammatory and antioxidant properties. However, it is unclear whether SYA has any effects on hepatonephrotoxicity caused by the side effects of antineoplastic drugs. In the present research, we thoroughly evaluated the effects of SYA on cyclophosphamide-induced hepatonephrotoxicity in a mouse model, focusing on Nrf2/HO-1 pathway activation. In the present study, SYA (25 and 50 mg/kg, p.o.) and CYC (30 mg/kg, i.p.) were delivered to male mice for 10 days to induce hepatonephrotoxicity. SYA treatment alleviated the elevated levels of AST, ALT, BUN, and creatinine caused by CYC. It further suppressed lipid peroxidation by lowering MDA levels and enhanced antioxidant defense by elevating GSH, SOD, and CAT levels. Additionally, SYA increased the mRNA expression levels of HO-1, Nrf2, and Bcl-2, which had been reduced due to oxidative stress, inflammatory, and apoptotic pathways, while suppressing the elevated gene expression levels of NFκB, TNF-α, Bax, and Cas-3. Furthermore, SYA regulated the altered protein expression levels of Nrf2, Cas-3, Bax, and Bcl-2 induced by CYC. Microscopically, SYA also mitigated liver and kidney tissue damage caused by CYC. In conclusion, SYA significantly reduced CYC-induced hepatonephrotoxicity by inhibiting inflammation, oxidative stress, and apoptosis by employing the Nrf2/NFκB/HO-1 pathway. These findings indicate that SYA has the possibility as a treatment option agent in the case of prevention of liver and kidney damage.

PMID:39959927 | DOI:10.1002/jbt.70172

Am J Transl Res. 2025 Jan 15;17(1):685-692. doi: 10.62347/EHTT9544. eCollection 2025.

ABSTRACT

OBJECTIVE: This study aimed to assess the efficacy and safety of sacral nerve root magnetic stimulation (SNRMS) combined with solifenacin in female patients with overactive bladder (OAB) symptoms.

METHODS: A total of 183 female patients with OAB symptoms were prospectively randomized into 2 groups. Ninety-two patients in the combination group accepted SNRMS and solifenacin therapy and 91 patients serving as control accepted only solifenacin therapy. The lower urinary tract symptoms, OAB questionnaire (OAB-q) health-related quality of life (HRQoL), symptom bother score, and overactive bladder syndrome score (OABSS) were compared between the two groups at the end of the second, fourth, and eighth weeks.

RESULTS: The incidence of lower urinary tract symptoms, including urgency, frequent urination, and incontinence episodes, was significantly lower in the fourth and eighth weeks in patients of the combination treatment group than those in the solifenacin group (P < 0.05). The incidence of drug-related adverse events in the two groups was similar, with no statistically significant difference (P > 0.05). The OAB-q HRQoL score in the combination group was significantly higher than that in the solifenacin group between the fourth and eighth weeks (P < 0.05). Meanwhile, the OAB-q symptom bother score and OABSS were both lower in the combination group than those in the solifenacin group from the fourth to eighth weeks (P < 0.05).

CONCLUSIONS: The combination therapy of SNRMS and solifenacin demonstrated significant improvements over solifenacin monotherapy in reducing OAB symptoms in female patients, providing a higher QoL without increasing bothersome adverse effects.

PMID:39959226 | PMC:PMC11826160 | DOI:10.62347/EHTT9544

Liver Res. 2024 Oct 24;8(4):295-303. doi: 10.1016/j.livres.2024.10.001. eCollection 2024 Dec.

ABSTRACT

BACKGROUND AND AIMS: Antiviral therapy is essential for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). No data are available on the long-term prognosis or safety of tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), or entecavir (ETV) in treating HBV-ACLF globally. This study was conducted to investigate the long-term efficacy and safety of the three nucleos(t)ide analogs in the treatment of HBV-ACLF.

METHODS: In this prospective, real-world cohort study, patients with HBV-ACLF were assigned to the TAF, TDF, and ETV groups. A total of 199 patients completed the 144-week follow-up. After propensity score matching (PSM), 44 patients remained in each group for further analysis of survival status, incidence of hepatocellular carcinoma (HCC), virological response, and liver and renal function indicators.

RESULTS: In the original cohort, HCC developed in one patient in each group. No serious drug-related adverse events were observed. In the PSM cohort, the 144-week survival rates were 56.82%, 75.00%, and 59.09% in the TAF, TDF, and ETV groups, respectively (P = 0.118). When stratified into noncirrhosis and cirrhosis subgroups at baseline, the survival rate of the ETV group was slightly lower than that of the TAF and TDF group in noncirrhosis patients (P = 0.338), and the survival rate of the TAF group was slightly lower than that of the TDF and ETV group in cirrhosis patients (P = 0.052), but the differences were not statistically significant. The long-term overall survival rates in the TAF, TDF, and ETV groups were comparable. After 144 weeks, no significant difference in the virological response rate or liver or renal function indicators was found among the three groups, except for the level of aspartate aminotransferase, which was significantly higher in the TDF group than in the ETV group at week 144 (P = 0.001).

CONCLUSIONS: There were no significant differences in the survival rate, incidence of HCC, efficacy or safety associated with the use of these three nucleos(t)ide analogs in treating HBV-ACLF.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03920618.

PMID:39958923 | PMC:PMC11771274 | DOI:10.1016/j.livres.2024.10.001

Discoveries (Craiova). 2024 Dec 31;12(4):e201. doi: 10.15190/d.2024.20. eCollection 2024 Oct-Dec.

ABSTRACT

Lomotil (diphenoxylate-atropine) toxicity in the pediatric population remains a significant concern particularly in low and lower middle-income countries. This may result from accidental ingestion or inappropriate therapeutic administration which can lead to life threatening complications including respiratory and central nervous system depression. A 2-year-old child presented to the pediatric emergency room in an altered state of consciousness. Clinical examination revealed dry mucous membranes, and a prolonged capillary refill time with weak radial pulses. Keeping in view the one-day history of 10-12 episodes of acute onset loose, watery stools, patient was initially treated as a case of hypovolemic shock. With rehydration therapy, his perfusion improved. However, the Glasgow Coma Scale score remained 8, as was observed on initial presentation. Upon further probing, it was revealed by the parents that the child had been given Lomotil by a local general practitioner for unresolved watery diarrhea. Pinpoint pupils and slow shallow vesicular breathing confirmed this diagnosis of Lomotil overdose. Administration of 0.1mg/kg/dose Naloxone repeated once, completely reversed the toxic effects. The child was able to make a full recovery and was discharged the following day. This case highlights the importance of recognizing and managing diphenoxylate toxicity in children, emphasizing the need for increased clinical awareness. A lack of consensus regarding the toxic dose of this drug reveals a gap warranting further research and establishment of standardized guidelines to ensure accurate dosing and improved patient safety.

PMID:39958914 | PMC:PMC11830492 | DOI:10.15190/d.2024.20

Reg Anesth Pain Med. 2025 Feb 16:rapm-2024-105955. doi: 10.1136/rapm-2024-105955. Online ahead of print.

ABSTRACT

BACKGROUND/IMPORTANCE: Driving under the influence of drugs (DUID) refers to operating a vehicle after consuming drugs or medications other than alcohol that impair the ability to drive safely. There is no consensus on legal limits for drug intoxication while driving in the USA. Balancing the benefits of prescription medications, such as opioids, with traffic safety remains an ongoing public health challenge.

OBJECTIVE: This article examines DUID policy and provides recommendations for policy improvement and unification grounded in scientific evidence on opioid-related impairment and driving risks.

EVIDENCE REVIEW: A literature review of epidemiologic data, psychomotor effects, and public policy related to opioid use and driving was conducted. A total of 38 epidemiological studies, 21 studies on psychomotor effects, and pertinent laws and policies were reviewed.

FINDINGS: Epidemiological data reveal an increasing prevalence of opioid-positive drivers and an association between opioid use and elevated risk of motor vehicle collisions. Psychomotor studies show mixed results, with some indicating impairment in opioid users and others suggesting minimal effects on driving ability. State laws regarding DUID remain heterogeneous, with trends toward expanded testing powers, lower impairment thresholds, and limitations on prescription-based defenses. The lack of standardized opioid testing limits and inconsistent policy approaches across states hinder effective management of opioid-related impaired driving.

CONCLUSIONS: A balanced public health approach can reduce opioid-involved crashes through education, prevention, enhanced enforcement tools, and rehabilitation. In drafting future DUID laws, policymakers must analyze evolving opioid research when balancing the pain relief of opioids with public roadway safety.

PMID:39956556 | DOI:10.1136/rapm-2024-105955

Trop Med Int Health. 2025 Feb 16. doi: 10.1111/tmi.14091. Online ahead of print.

ABSTRACT

BACKGROUND: Drug-related adverse events cause poorer treatment outcomes amongst people with multi-drug-resistant tuberculosis, exacerbating a major global public health problem. The Harnessing new mHealth technologies to Strengthen the Management of Multi-Drug-Resistant Tuberculosis in Vietnam (V-SMART) trial tests whether a mobile health (mHealth) application (app) can optimise management of drug-related adverse events, within routine health services in Vietnam. Implementation of digital health within routine services is complex and driven by behaviour change as well as a range of health system factors. Understanding implementation is key to informing the evidence base for digital health prior to scale up, despite its potential appeal.

METHODS: Through a process evaluation of the V-SMART trial, we aim to (i) understand the multi-drug-resistant tuberculosis service delivery context and how trial procedures are implemented within services; (ii) describe 'dose' and 'reach' of the app; and (iii) understand health worker and patient perspectives of app implementation and identify areas for improvement. To achieve this, we will (i) conduct process maps (patient flow maps) to describe implementation of the mHealth intervention within routine multi-drug-resistant tuberculosis health services including adverse event management pathways at different levels of the health system; (ii) measure app usage by all participating health workers and people with multi-drug-resistant tuberculosis over time; and (iii) conduct a total of up to 45 semi-structured interviews in seven provinces, with people with multi-drug-resistant tuberculosis, health workers, and policymakers, to identify determinants of app uptake and suggestions for future person-centred app design. Interview topic guides are informed by the Theoretical Framework for Acceptability, Normalisation Process Theory, and the Tailored Implementation of Chronic Diseases framework respectively.

DISCUSSION: The process evaluation will strongly complement the parent trial impact evaluation, and the economic evaluation. Moreover, it will inform future tailored approaches to scaling up digital health as part of broader health system strengthening initiatives.

PMID:39956136 | DOI:10.1111/tmi.14091

Cell Rep Methods. 2025 Feb 24;5(2):100990. doi: 10.1016/j.crmeth.2025.100990. Epub 2025 Feb 14.

ABSTRACT

The need for a deeper understanding of adverse drug reaction (ADR) mechanisms is vital for improving drug safety and repurposing. This study introduces Drug Adverse Reaction Mechanism Explainer (DREAMER), a network-based framework that uses a comprehensive knowledge graph to uncover molecular mechanisms underlying ADRs and disease phenotypes. By examining shared phenotypes of drugs and diseases and their effects on protein-protein interaction networks, DREAMER identifies proteins linked to ADR mechanisms. Applied to 649 ADRs, DREAMER identified molecular mechanisms for 67 ADRs, including ventricular arrhythmia and metabolic acidosis, and emphasized pathways like GABAergic signaling and coagulation proteins in personality disorders and intracranial hemorrhage. We further demonstrate the application of DREAMER in drug repurposing and propose sotalol, ranolazine, and diltiazem as candidate drugs to be repurposed for cardiac arrest. In summary, DREAMER effectively detects molecular mechanisms underlying phenotypes, emphasizing the importance of network-based analyses with integrative data for enhancing drug safety and accelerating the discovery of novel therapeutic strategies.

PMID:39954672 | DOI:10.1016/j.crmeth.2025.100990

Pediatr Radiol. 2025 Feb 14. doi: 10.1007/s00247-025-06182-w. Online ahead of print.

ABSTRACT

Tuberculosis (TB) remains a significant public health concern despite preventive measures, such as the use of the Bacille Calmette-Guérin (BCG) vaccine, which reduces the risk and severity of early-life TB infection. The adverse effects of the BCG vaccine include infection by the live-attenuated organism, more commonly seen in the immunocompromised host. This pictorial review aims to outline the imaging spectrum of BCG-vaccine-related infections in immunocompromised pediatric patients, which can be localized (BCGitis) or disseminated (BCGosis). We illustrate the more common imaging findings, including lymphadenopathy and involvement of solid organs, as well as less frequently encountered sites, such as the lungs and gastrointestinal tract, emphasizing their distinct imaging patterns. Interpretation of these findings in the context of prior administration of the BCG vaccine not only helps in the diagnosis of BCG-vaccine-related infections and guiding timely management, but can also be an early indicator of an underlying immunodeficiency disorder, prompting comprehensive immunological investigation.

PMID:39953302 | DOI:10.1007/s00247-025-06182-w

Gan To Kagaku Ryoho. 2024 Dec;51(13):1587-1588.

ABSTRACT

Despite recent advances in chemotherapy with immune-checkpoint inhibitor(ICI), some patients may have to undergo surgery after the immune-related adverse events(irAE). We report here a case of a 61-year-old man who developed the irAE-related anastomotic stenosis after robotic gastrectomy for gastric cancer. Previously, he was diagnosed as double cancers of far-advanced hung cancer and gastric cancer. He was treated with ICI-based chemotherapy comprising CBDCA, PEM and pembrolizumab for lung cancer, and developed drug-induced pneumonia and dermatomyositis due to severe irAE. Stenosis was improved with steroid therapy. Until now, there has been no recurrence without symptoms in these 2 years.

PMID:39948933

Acta Anaesthesiol Scand. 2025 Mar;69(3):e14588. doi: 10.1111/aas.14588.

ABSTRACT

BACKGROUND: Remimazolam, a novel ultra-short-acting benzodiazepine, has gained popularity in various anesthetic applications due to its pharmacokinetic advantages. However, as its use increases, safety concerns also rise, necessitating thorough examination. Additionally, the limited reports on its side effects require a broader investigation to better understand the drug's safety profile.

METHODS: This observational study systematically investigated adverse drug events (ADEs) associated with remimazolam using the FAERS database from Q1 2020 to Q4 2023. The primary objective was to assess potential safety signals and provide comprehensive information for clinical and regulatory purposes.

RESULTS: A total of 67 cases and 161 ADEs were identified. The incidence of ADEs was higher in patients aged >45 years, particularly those >65 years. Intravenous general anaesthesia was the most common administration method. Notable ADE signals included serious events such as allergic reactions, respiratory and cardiac arrest, and vascular access occlusion.

CONCLUSION: Clinicians should be vigilant about potential allergic reactions to remimazolam, especially in older patients, and avoid off-label use until more data are available. Continuous monitoring of post-market surveillance data is essential for uncovering undetected ADEs and ensuring the safe use of remimazolam.

EDITORIAL COMMENT: This study analyzed adverse drug events (ADEs) associated with remimazolam using the FAERS database, identifying serious safety signals like allergic reactions, respiratory and cardiac arrests, and vascular access site occlusions, especially in older patients. The findings highlight the need for vigilant monitoring, cautious off-label use, and ongoing post-marketing surveillance.

PMID:39948627 | DOI:10.1111/aas.14588

Sci Rep. 2025 Feb 13;15(1):5322. doi: 10.1038/s41598-025-89632-7.

ABSTRACT

To explore and analyze the potential adverse event (AE) signals of trazodone, with reference to the safe clinical use of drugs. Based on the FDA Adverse Event Reporting System (FAERS), the AE data of trazodone were extracted from the first quarter of 2004 to the second quarter of 2024, and the extracted data were statistically analyzed using the method, to identify valid AE signals that met our judgment, compare them with those recorded in the authorized information for trazodone thereby identifying unexpected potential adverse reactions. A total of 5199 AE reports with trazodone as the main suspect were extracted, with a higher reported proportion of females (52.68%) than males (38.83%). Many reports (31.47%) did not provide age information, although for those reports with identifiable age data, the 50-60 years age group was the most common (14.20%), and the country of reporting was predominantly the United States (82.58%). A total of 179 significant AE signals were unearthed, with suicide, formulation toxicity, abnormal penile erection, insomnia, and cardiac and respiratory arrest reported with high frequency, which was not entirely consistent with the specification record. The study unearthed 156 new potential AEs on the basis of trazodone drug inserts and suggested precautions for overdosing and dose adjustment, which is conducive to safeguarding the safety of patients' medication.

PMID:39948419 | DOI:10.1038/s41598-025-89632-7

Cancer. 2025 Feb 15;131(4):e35766. doi: 10.1002/cncr.35766.

ABSTRACT

BACKGROUND: Older adults with advanced cancer are at higher risk of treatment-related toxicities, which can impair function. Relationships between clinician-rated and patient-reported toxicities with functional decline remain unclear.

METHODS: This secondary analysis of the GAP70+ trial aimed to evaluate the associations between clinician-rated (Clinician-rated common Terminology Criteria for Adverse Events [CTCAE]) and patient-reported toxicities (PRO-CTCAE) with changes in physical performance and functional outcomes in older adults receiving systemic therapy. Physical performance was measured using the Short Physical Performance Battery (SPPB; impairment: score ≤9). Functional capacity was assessed using activities of daily living (ADL) and instrumental ADL (IADL); impairment: any task difficulty. Toxicities were captured by CTCAE and PRO-CTCAE, which assess symptom severity and activity interferences. Generalized estimating equations evaluated the association of toxicity grades (0-1, 2, ≥3) within 3 months of treatment initiation with new functional impairments within 6 months.

RESULTS: Patients were age 70 to 96 years. At baseline, 82.9% had impaired SPPB, 51.5% had impaired IADL, and 27.4% had impaired ADL. Among patients without baseline impairments, 57.7%, 47.4%, and 31.0% developed new SPPB, IADL, and ADL impairments, respectively. No association was found between CTCAE toxicity and new SPPB impairment (p = .70), but higher PRO-CTCAE toxicity severity (p = .02) and interference (p = .02) were associated with new SPPB impairments. New IADL impairments were more common with higher grades of CTCAE (p = .02) severe PRO-CTCAE toxicities (p = .02).

CONCLUSION: These findings emphasize the need to assess both clinician-rated and patient-reported toxicities to understand and mitigate functional decline in older adults with advanced cancer.

PMID:39945245 | DOI:10.1002/cncr.35766

Cancers (Basel). 2025 Jan 27;17(3):437. doi: 10.3390/cancers17030437.

ABSTRACT

Objectives: The primary aim of this phase 1 trial is to establish the recommended phase 2 dose (RP2D) of tazemetostat given with a fixed dose of pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinomas (RM-HNSCCs). Methods: A 3 + 3 dose-escalation phase 1 design was used to assess three dose-levels of tazemetostat (400, 600, and 800 mg orally, twice daily) with pembrolizumab (200 mg intravenously). Cycle 1 was 35 days (tazemetostat days 1-35; pembrolizumab day 15). Subsequent cycles were 21 days (tazemetostat days 1-21; pembrolizumab day 1). Dose-limiting toxicity (DLT), assessed during cycle 1, was defined as study-drug-related grade 4 neutropenia or thrombocytopenia, grade 3 febrile neutropenia, or grade 3-4 non-hematologic adverse events (AEs). Patients had to have completed cycle 1 to be evaluable for the DLT assessment; otherwise, an equal number of additional patients were enrolled. The RP2D was defined as the highest dose level in which zero of three or less than or equal to one of six patients experienced a DLT. Results: Twelve patients were enrolled: three on 400 mg, three on 600 mg, and six on the 800 mg dose level of tazemetostat. Three patients on the 800 mg dose level did not complete cycle 1 and were not evaluable for DLT. In the other nine patients, DLTs did not occur during cycle 1. In all 12 patients, the most common AEs included anemia (10 patients), fatigue (eight), and hyponatremia (seven). Conclusions: Among the patients with RM-HNSCCs, the RP2D of tazemetostat was 800 mg and administered twice daily when given with pembrolizumab.

PMID:39941804 | DOI:10.3390/cancers17030437

Alzheimers Res Ther. 2025 Feb 12;17(1):40. doi: 10.1186/s13195-025-01681-2.

ABSTRACT

BACKGROUND: The importance of natural killer (NK) cells of the innate immune system in neurodegenerative disease has largely been overlooked despite studies demonstrating their ability to reduce neuroinflammation (thought to be mediated by the elimination of activated T cells, degradation of protein aggregates and secretion of anti-inflammatory cytokines). SNK01 is an autologous non-genetically modified NK cell product showing increased activity in vitro. We hypothesized that SNK01 can be safely infused to reduce neuroinflammation in Alzheimer's Disease (AD) patients.

METHODS: SNK01 was produced and characterized for its ability to eliminate activated T cells, degrade protein aggregates and secrete anti-inflammatory cytokines. In this phase 1 study, SNK01 was administered intravenously every three weeks for a total of 4 treatments using a 3 + 3 dose escalation design (1, 2 and 4 × 109 cells) in subjects with either mild, moderate, or severe AD (median CDR-SB 10.0). Cognitive assessments and cerebrospinal fluid biomarkers associated with protein aggregation, neurodegeneration and neuroinflammation including amyloid-β42 and 42/40, α-synuclein, total Tau, pTau217 and pTau181, neurofilament light, GFAP and YKL-40 analyses were performed at baseline, at 1 and 12 weeks after the last dose. The primary endpoint was safety; secondary endpoints included changes in cognitive assessments and biomarker levels.

RESULTS: In preclinical in vitro studies, SNK01 were able to uptake and degrade the protein aggregates of amyloid-β and α-synuclein, produce anti-inflammatory cytokines and eliminate activated T cells. In the phase 1 clinical study, eleven subjects were enrolled (10 evaluable). No drug-related adverse events were observed. Despite 70% of subjects being treated at relatively low doses of SNK01 (1 and 2 × 109 cells), 50-70% of all enrolled subjects had stable/improved CDR-SB, ADAS-Cog and/or MMSE scores and 90% had stable/improved ADCOMS at one-week after the last dose. SNK01 also appeared to have beneficial effects on protein aggregate levels and neuroinflammatory biomarkers in the cerebrospinal fluid, with decreases in pTau181 and GFAP appearing to be dose-dependent.

CONCLUSIONS: SNK01 was well tolerated and appeared to have clinical activity in AD while also having beneficial effects on cerebrospinal fluid protein and neuroinflammatory biomarker levels. A larger trial with a higher dosing/duration has been initiated in the USA in 2023.

TRIAL REGISTRATION: www.

CLINICALTRIALS: gov NCT04678453, date of registration: 2020-12-22.

PMID:39939891 | DOI:10.1186/s13195-025-01681-2