Ital J Dermatol Venerol. 2025 Jun 5. doi: 10.23736/S2784-8671.25.08147-2. Online ahead of print.

ABSTRACT

Gender medicine has been achieving increasing importance. Gender differences in disease depend on hormonal status and may involve functions of the skin, immune responses and metabolic pathways, and have to do also with indications and response to treatments. Psoriasis is a common chronic inflammatory immune-mediated disease. The prevalence of psoriasis in the population is balanced between males and females, but early onset psoriasis is slightly more prevalent in males, with the latter suffering from a more severe disease. In general, male and female patients receive identical drugs at equivalent dosages. However, females receive systemic treatments less frequently compared to males. Males are more satisfied with their psoriasis treatment and respond better to biologics. Females have a significant higher rate of adverse events and drug-related discontinuation rate compared to males. About conventional systemic treatments for psoriasis during pregnancy, only cyclosporine is suggested when the benefits exceed the potential side effects, whereas methotrexate is contraindicated during pregnancy and lactation and in the three months before fatherhood and motherhood. Among the biologics, only certolizumab pegol is considered safe in pregnant patients, as it does not cross the maternal-placental barrier. Therefore, it is important to consider a gender perspective in the treatment of psoriasis, including her willingness to procreate. This is a narrative review highlighting the challenges that the healthcare dermatologists may face regarding management of psoriasis in female patients.

PMID:40470625 | DOI:10.23736/S2784-8671.25.08147-2

Front Cell Infect Microbiol. 2025 May 21;15:1570382. doi: 10.3389/fcimb.2025.1570382. eCollection 2025.

ABSTRACT

OBJECTIVES: This study aimed to analyze the clinical characteristics and genetic features of children with adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine. The goal was to improve understanding of this condition, provide insights into early diagnosis and intervention, and support stratified management.

METHODS: Clinical data of 35 children hospitalized at Kunming Children's Hospital between January 2014 and June 2024 with complete records and diagnosed with BCG vaccine adverse reactions were collected. Cases were classified into two groups: disseminated BCG disease (BCG-D) and BCG-itis. Children with primary immunodeficiency (PID) were further divided into severe combined immunodeficiency (SCID) and non-SCID groups. Clinical characteristics, immunological profiles, genetic backgrounds, and outcomes were compared between the groups.

RESULTS: Among the 35 cases, 25 were male, and 10 were female, with a median age of onset of 2 months (1-4 months). Eight cases (22.9%) were diagnosed with BCG-D, while 27 cases (77.1%) were classified as BCG-itis. Sixteen cases (45.7%) were confirmed to have PID, including SCID (7 cases, 20.0%), chronic granulomatous disease (6 cases, 17.1%), Mendelian susceptibility to mycobacterial disease (2 cases, 5.7%), and fas associated via death domain (FADD) gene mutation (1 case, 2.6%). Compared to the BCG-itis group, the BCG-D group exhibited significantly higher rates of fever, hepatosplenomegaly, elevated white blood cell counts, neutrophil counts, and C-reactive protein (CRP) levels, along with lower red blood cell counts and hemoglobin levels (p<0.05). Similarly, the SCID group showed significantly lower age, lymphocyte counts, IgM levels, CD3, CD4, and CD8 cell ratios, but higher CD19 cell ratios and mortality rates compared to the non-SCID group (p<0.05). Twenty-seven (77.1%) cases were discharged after improvement, and eight children (22.9%) succumbed to the condition, including six with SCID gene mutations (representing 85.7% of the total SCID cases), one with an interleukin 12 receptor subunit beta 1(IL12RB1) mutation, and one who was not genetically tested but diagnosed with disseminated BCG disease.

CONCLUSIONS: In children presenting with adverse reactions to the BCG vaccine, the presence of fever, hepatosplenomegaly, elevated neutrophil levels, and CRP should prompt evaluation for disseminated BCG disease and assessment of immunological status. Early identification of underlying PID, particularly SCID, is crucial, given the high mortality and poor prognosis associated with the condition, necessitating timely interventions.

PMID:40470261 | PMC:PMC12133749 | DOI:10.3389/fcimb.2025.1570382

Front Cell Infect Microbiol. 2025 May 21;15:1584950. doi: 10.3389/fcimb.2025.1584950. eCollection 2025.

ABSTRACT

OBJECTIVE: To compare and analyze the efficacy and safety of different antifungal drug treatment regimens for patients with invasive pulmonary aspergillosis (IPA) in the intensive care unit (ICU).

METHODS: We retrospectively collected the clinical data of patients with IPA in the ICU in two grade-A tertiary hospitals from January 2019 to January 2024 using the HIS system and compared the clinical efficacy, incidence of adverse drug reactions (ADRs), and all-cause mortality at discharge among different antifungal treatments, such as voriconazole alone, caspofungin alone, and a combination of voriconazole plus caspofungin.

RESULTS: A total of 151 patients were enrolled, including 129 in the monotherapy group (with 92 in the voriconazole subgroup and 37 in the caspofungin subgroup) and 22 in the voriconazole plus caspofungin combination group. Aspergillus fumigatus was the most common pathogenic fungus in patients with IPA, followed by Aspergillus flavus. In terms of clinical efficacy, monotherapy and combination therapy were equally effective (P=0.618), and the efficacy of voriconazole or caspofungin alone and that of voriconazole combined with caspofungin in the treatment of IPA was equivalent (P=0.630). In terms of safety, the total incidence of ADRs in the combination therapy group was greater than that in the monotherapy group, but the difference was not statistically significant (P=0.109). The two groups were also equally safe in terms of causing renal dysfunction, liver dysfunction, visual abnormalities, and hypokalemia. However, compared with the monotherapy group, the combination therapy group exhibited a significantly greater incidence of pancytopenia (P=0.013, P=0.004). The all-cause mortality in the combination therapy group was significantly greater than that in the monotherapy group (P=0.027, P=0.009).

CONCLUSIONS: Voriconazole is still the preferred treatment for critically ill patients with IPA, and caspofungin has good clinical efficacy and safety and can effectively replace voriconazole for these patients. However, the combination treatment with voriconazole and caspofungin did not improve the all-cause mortality rate of critically ill patients with IPA, is associated with increased total ADR and pancytopenia incidence and is not recommended as an initial treatment plan.

PMID:40470260 | PMC:PMC12133850 | DOI:10.3389/fcimb.2025.1584950

Acta Oncol. 2025 Jun 4;64:742-750. doi: 10.2340/1651-226X.2025.43366.

ABSTRACT

BACKGROUND: Precision cancer medicine (PCM) is key to advancing cancer treatment beyond the standard of care. We performed an explorative clinical trial, MEGALiT, to investigate the feasibility, safety, and clinical benefit of genomics-based PCM in advanced cancer.

METHODS: MEGALiT recruited adult patients with advanced solid tumors refractory to standard treatment. Tumor DNA from newly acquired biopsies or ctDNA were analyzed for alterations targetable with the PD-L1 inhibitor atezolizumab, the MEK inhibitor cobimetinib, the mTOR inhibitor everolimus, or the PARP-inhibitor niraparib. Any other 'in study' treatment was left to the discretion of the physician.

RESULTS: Outcome data are reported for 153 patients. The median age was 65 years and the most common diagnoses were colorectal, prostate, and ovarian cancer. The median time from study inclusion to the Molecular Tumor Board was 35 days for tumor sampling by biopsy and 21 days by ctDNA. Of the 44 patients allocated to a study drug, 38 started treatment. The median follow-up was 1.9 years. Of the patients on a study drug and evaluable for tumor response, 6% (2/32) had partial remission, and 25% (8/32) had disease control at 16 weeks. Median overall survival for patients starting a study drug was longer, 7.4 months, compared to 2.7 months for the 61 untreated patients (HR 0.43; log-rank p < 0.0001), but shorter than for the 50 patients receiving treatment of physician's choice, 11.8 months (HR 0.55; log-rank p = 0.012). No significant procedure- or drug-related severe adverse events were observed.

INTERPRETATION: Genomics-guided treatment selection in advanced cancer is feasible and safe. However, evidence of patient benefit warrants further investigation.

PMID:40468525 | DOI:10.2340/1651-226X.2025.43366

Cancer Res Commun. 2025 Jun 1;5(6):973-980. doi: 10.1158/2767-9764.CRC-24-0631.

ABSTRACT

The Centers for Medicare & Medicaid Services Hospital Outpatient Quality Reporting Program's OP-35 rule penalizes health systems that have a higher-than-expected rate of emergency department (ED) visits or inpatient admissions for 10 potentially preventable conditions within 30 days of receiving chemotherapy. Identifying patients at risk for toxicities and resultant acute care could lead to reducing the rate of such events, improving patient care, and reducing costs. We identified patients with cancer seen in the ED at our institution between January 1, 2018, and December 31, 2021, for one of the OP-35 toxicities who had received chemotherapy within the previous 30 days and analyzed demographic factors using zero-truncated Poisson regression. We further analyzed comorbid conditions for risk factors by matching by demographics and cancer type a cohort of patients without ED visits due to OP-35 events. A total of 1,618 patients were identified. The most frequent events were pain, sepsis, and fever. Thirty-nine percent had two or more visits during the study, and among those patients, the most frequent cancer types were gastrointestinal (32%) and breast (22%) cancers. Race, age, and sex were associated with an increased risk of events. In the matched cohort analysis, five comorbidities were statistically significant (P < 0.05) with event risk: history of coagulopathy/pulmonary emboli, myocardial infarction, cardiac arrhythmias, depression, and weight loss (concordance = 0.58). Forty-seven percent of patients with an event had at least one of these five comorbidities. Future interventions may concentrate on resources to monitor patients based on the risk assessment established in this study.

SIGNIFICANCE: Cardiovascular comorbidities, cancer cachexia, and depression were associated with increased risk for ED visits due to OP-35 events throughout cancer treatment. Future interventions may concentrate on resources to monitor patients based on the risk assessment established in this real-world data study.

PMID:40464592 | DOI:10.1158/2767-9764.CRC-24-0631

J Drugs Dermatol. 2025 Jun 1;24(6):617-620. doi: 10.36849/JDD.8590.

ABSTRACT

BACKGROUND: Periorificial dermatitis (POD) is a facial skin rash often found in the oral commissures and nasolabial folds, and around the eyes. Treatment options include topical metronidazole and azelaic acid, and oral tetracycline-class antibiotics. While the broad-spectrum antibiotics are efficacious, they can lead to adverse gastro-intestinal (GI) symptoms, negatively impact gut flora, and lead to antibiotic resistance. Narrow-spectrum tetracyclines, such as sarecycline, have a low potential for promoting bacterial resistance and GI issues.

OBJECTIVE: The main objective of this study is to demonstrate sarecycline&rsquo;s efficacy and safety in treating POD. It was hypothesized that subjects with POD given a 4-week course of sarecycline would have improvement in their POD and tolerate the medication well.

METHODS: This was a single-center, prospective, pilot study to evaluate the efficacy, safety, and tolerability of sarecycline for the treatment of POD with once-daily dosing over 4 consecutive weeks. Subjects were evaluated using the PODSI score at weeks 0, 2, and 4.

RESULTS: All 9 subjects who completed the study had shown improvement in POD with no reported drug-related adverse events. All subjects were female, and the mean age was 41 years old.

CONCLUSION: Sarecycline may be an appropriate novel treatment option for POD and should be explored further in a larger population study capturing this data. Furthermore, there is a need for more large-scale clinical studies evaluating treatment options for POD, with a focus on the impacts of antibiotic resistance and its implications on public health.

CITATION: Swenson K, Graber E. A single-center pilot study to evaluate the efficacy, safety, and tolerability of sarecycline for treating periorificial dermatitis. J Drugs Dermatol. 2025;24(6):617-620. doi:10.36849/JDD.8590.

PMID:40465502 | DOI:10.36849/JDD.8590

Drug Ther Bull. 2025 Jun 3:dtb-2025-000023. doi: 10.1136/dtb.2025.000023. Online ahead of print.

NO ABSTRACT

PMID:40461176 | DOI:10.1136/dtb.2025.000023

Drug Ther Bull. 2025 Jun 3;63(6):85-93. doi: 10.1136/dtb.2025.000019.

ABSTRACT

Methylphenidate and lisdexamfetamine are recommended as first-line pharmacological treatment options for adults with attention deficit hyperactivity disorder (ADHD). Formulations of methylphenidate can generally be classified into three groups according to their duration of action: one group lasts 12 hours, another group lasts 8 hours and the immediate-release group lasts 3-4 hours. Patients are usually able to substitute brands with one of the equivalent release profiles without significant problems. Lisdexamfetamine is a prodrug which has a slow onset and long duration (approximately 12 hours), ensuring minimal potential for abuse compared with its active metabolite dexamfetamine. Second-line treatments such as atomoxetine are also available for those who cannot tolerate or do not respond to methylphenidate or lisdexamfetamine. In the UK, ADHD has been previously managed largely in tertiary clinics, but many cases could be managed by appropriately trained clinicians in secondary or primary care (as already happens in some countries), with great benefit for patients and job satisfaction for clinicians.

PMID:40461172 | DOI:10.1136/dtb.2025.000019

Drug Ther Bull. 2025 Jun 3:dtb-2025-000018. doi: 10.1136/dtb.2025.000018. Online ahead of print.

NO ABSTRACT

PMID:40461177 | DOI:10.1136/dtb.2025.000018

Basic Clin Pharmacol Toxicol. 2025 Jul;137(1):e70063. doi: 10.1111/bcpt.70063.

ABSTRACT

Prescribing cascades occur when an adverse drug reaction (ADR) to one medication is treated with additional medication. Most literature focusses on this simplistic singular concept of one medication followed by another. However, ADRs in clinical practice may appear less straightforward, making prescribing cascades difficult to identify and deprescribe. More insight is needed into the real-world complexity of prescribing cascades, since they may negatively impact both patients and the healthcare system. This article aims to provide exemplary cases of the real-world complexity of prescribing cascades and explores strategies to identify, mitigate and prevent them. The real-world cases discussed highlight the multifaceted nature of prescribing cascades in clinical practice. They show several factors contributing to the challenges in recognizing ADRs and preventing prescribing cascades, including misinterpretation of ADRs, fragmented healthcare systems and accumulation of pharmacological effects and comorbidities within an individual patient. Several strategies are recommended to improve identification, mitigation and prevention of prescribing cascades. Although educating patients and healthcare providers (HCPs) can help bridge the knowledge gap, additional strategies are needed. Implementing supportive tools to deprescribe, enhanced communication among HCPs and patients regarding ADRs and rationale for medication changes, and monitoring patients for ADRs are considered the most promising strategies.

PMID:40457590 | DOI:10.1111/bcpt.70063

Neurol Ther. 2025 Jun 2. doi: 10.1007/s40120-025-00752-8. Online ahead of print.

ABSTRACT

Omaveloxolone is approved for the treatment of Friedreich ataxia (FA) in patients aged ≥ 16 years and is under clinical development for pediatric patients. In the MOXIe study, alanine and aspartate aminotransferase (ALT and AST) elevations were among the most common treatment-emergent adverse events (TEAEs) in the omaveloxolone arm and were mild to moderate, generally asymptomatic, transient, and reversible; no patients who received omaveloxolone had laboratory abnormalities that met the Hy's law criteria. Omaveloxolone labels (US and EU) provide guidance for monitoring and managing these elevations. Here, practical use considerations, from experience-based opinions of four FA experts and a hepatologist via semi-structured interviews, are presented. Prior to omaveloxolone initiation, assessment of baseline ALT, AST, and total bilirubin is recommended per label. During treatment, ALT, AST, and total bilirubin should be monitored monthly for the first 3 months and periodically thereafter per label. Reduced frequency of patient monitoring after 3 months is suggested if aminotransferase levels remain normal. Per label, omaveloxolone should be temporarily discontinued if aminotransferases increase to > 5 × the upper limit of normal (ULN) or > 3 × ULN with other evidence of liver dysfunction. Stemming from real-world practical considerations wherein patients are followed up less frequently than in the trial setting, treatment interruption when aminotransferases increase to ≥ 3 × ULN without other signs of hepatic impairment may be considered. When aminotransferase elevations stabilize or resolve, omaveloxolone may be reinitiated with an appropriate increased frequency of monitoring of liver function per label. We propose patients who pause treatment may have testing repeated after 2 weeks, while those with resolving aminotransferase elevations may reinitiate omaveloxolone with stepwise dose titrations and testing every 2 weeks for ≈ 3 months. Use considerations herein may inform decisions on monitoring and managing ALT and AST elevations, which potentially help to encourage the treatment adherence needed to achieve the slowing of FA progression seen in MOXIe.Graphical abstract available for this article.

PMID:40455368 | DOI:10.1007/s40120-025-00752-8

N Engl J Med. 2025 May 31. doi: 10.1056/NEJMoa2503119. Online ahead of print.

ABSTRACT

BACKGROUND: On the basis of phase 2 studies, trastuzumab deruxtecan was approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric cancer or gastroesophageal junction adenocarcinoma who had previously received trastuzumab-based therapy. Ramucirumab plus paclitaxel is also a standard second-line treatment option regardless of HER2 status.

METHODS: We conducted an international, randomized, phase 3 trial comparing second-line trastuzumab deruxtecan at a dose of 6.4 mg per kilogram of body weight with ramucirumab plus paclitaxel in patients with HER2-positive metastatic gastric cancer or gastroesophageal junction adenocarcinoma confirmed on tumor biopsy conducted after the patient had progression while receiving trastuzumab-based therapy. The primary end point was overall survival. Secondary end points included progression-free survival, confirmed objective response (complete or partial response lasting ≥4 weeks), disease control, duration of response, and safety.

RESULTS: Among 494 patients who had undergone randomization, overall survival was significantly longer with trastuzumab deruxtecan than with ramucirumab plus paclitaxel (median, 14.7 vs. 11.4 months; hazard ratio for death, 0.70; 95% confidence interval, 0.55 to 0.90; P = 0.004). Significant results were also seen with regard to progression-free survival (hazard ratio for disease progression or death, 0.74; 95% CI, 0.59 to 0.92) and confirmed objective response (in 44.3% of the patients in the trastuzumab deruxtecan group vs. 29.1% of those in the ramucirumab-paclitaxel group). The incidence of drug-related adverse events of any grade was 93.0% with trastuzumab deruxtecan and 91.4% with ramucirumab plus paclitaxel; the incidence of drug-related adverse events of grade 3 or higher was 50.0% and 54.1%, respectively. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 13.9% of the patients who received trastuzumab deruxtecan (grade 1 or 2 in 33 patients and grade 3 in 1) and in 1.3% of those who received ramucirumab plus paclitaxel (grade 3 in 2 patients and grade 5 in 1).

CONCLUSIONS: Trastuzumab deruxtecan led to significantly longer overall survival than ramucirumab plus paclitaxel among patients with HER2-positive metastatic gastric cancer or gastroesophageal junction adenocarcinoma. Adverse events were common in both groups. Events of interstitial lung disease or pneumonitis with trastuzumab deruxtecan, a known risk, were mainly low-grade. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Gastric04 ClinicalTrials.gov number, NCT04704934.).

PMID:40454632 | DOI:10.1056/NEJMoa2503119

Surg Case Rep. 2025;11(1):25-0104. doi: 10.70352/scrj.cr.25-0104. Epub 2025 May 28.

ABSTRACT

INTRODUCTION: The use of immune checkpoint inhibitors (ICIs) as neoadjuvant therapies for locally advanced and resectable non-small cell lung cancer is increasing. As a result, immune-related adverse events (irAEs) may be observed before surgery and may require preoperative intervention. We report the case of a patient with destructive thyroiditis induced by neoadjuvant ICI treatment, in which surgical resection was performed after steroid treatment.

CASE PRESENTATION: A 74-year-old woman was diagnosed with slow-growing squamous cell carcinoma of the right upper lobe during treatment for another disease. Imaging studies revealed a small nodule suggestive of pulmonary metastasis in the right upper lobe and hilar lymph node metastasis. The patient was initially diagnosed with primary lung cancer of the right upper lobe (cT3N1M0, Stage IIIA, TNM Classification, 8th edition), and neoadjuvant nivolumab combined with chemotherapy was planned every 3 weeks for three cycles. After the first cycle, the patient experienced drug-induced kidney injury. Nivolumab and chemotherapy were discontinued, and surgical resection was planned. However, a laboratory analysis on the day before surgery revealed elevated free triiodothyronine and free thyroxine, and decreased thyroid-stimulating hormone. Subsequent examination led to a diagnosis of destructive thyroiditis due to irAEs, and surgery was postponed. Dexamethasone was administered orally for 1 week, and once the thyroid function showed consistent improvement, a thoracoscopic right upper lobectomy was performed. The patient progressed without any other complications after surgery.

CONCLUSIONS: This report highlights a case of preoperative destructive thyroiditis secondary to irAEs. In patients receiving preoperative ICIs therapy, routine blood tests, including thyroid function tests, are recommended as part of preoperative assessment. In this case, the patient underwent lobectomy safely following steroid administration. The optimal timing of surgery in patients with preoperative ICI-induced destructive thyroiditis requires further investigation.

PMID:40454085 | PMC:PMC12127077 | DOI:10.70352/scrj.cr.25-0104

Front Oncol. 2025 May 16;15:1567317. doi: 10.3389/fonc.2025.1567317. eCollection 2025.

ABSTRACT

BACKGROUND: Drug-induced interstitial lung disease (DIILD) is a serious complication of cancer treatment that is primarily treated with corticosteroids. However, effective standardized regimens for corticosteroid-refractory DIILD have not been established. Cyclophosphamide (CPA) is an immunosuppressant that is potentially effective against DIILD, but supporting evidence is limited, particularly for diseases induced by novel chemotherapeutic drugs. In this study, we examined the efficacy and safety of CPA in corticosteroid-refractory DIILD caused by various anticancer drugs.

METHODS: We retrospectively reviewed the medical records of patients who underwent CPA therapy for corticosteroid-refractory DIILD at the National Cancer Center Hospital East between January 2013 and October 2023. Corticosteroid-refractory DIILD was defined as cases of DIILD classified as grade ≥3 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, in which no improvement was observed within 48 hours after initiating corticosteroid therapy. The primary endpoint was 30-day survival post-CPA. The secondary endpoints included radiological improvements and changes in oxygen supplementation.

RESULTS: Fifteen patients (median age 73 years; 80% male) were included in the analysis. Patients were classified into molecular-targeted drugs (MT; 20%, 3/15), MT + cytotoxic drugs (33%, 5/15), immune checkpoint inhibitors (ICI) ± cytotoxic drugs (27%, 4/15), and cytotoxic drugs alone (20%, 3/15) groups. The overall 30-day survival rate was 47% (7/15). Improvement of oxygen demand allowed 20% (3/15) of patients to discontinue oxygen supplementation. CPA demonstrated drug class-dependent efficacy: highest in the MT group (67% survival, 2/3), less benefit in the cytotoxic drugs alone group (0% survival, 0/3). Adverse events included grade 3 anemia (n=2), grade 4 neutropenia (n=1), and grade 2 cytomegalovirus infection (n=1), with no treatment-related deaths.

CONCLUSION: CPA exhibited potential efficacy for corticosteroid-refractory DIILD, particularly in patients with MT-induced DIILD, with manageable toxicity. The differential responses based on drug category suggest tailored approaches to DIILD management may be warranted. These findings may contribute to optimizing the management of severe DIILD during cancer treatment.

PMID:40452849 | PMC:PMC12122744 | DOI:10.3389/fonc.2025.1567317

Cureus. 2025 May 1;17(5):e83302. doi: 10.7759/cureus.83302. eCollection 2025 May.

ABSTRACT

This systematic review and meta-analysis evaluated the efficacy and safety of tegoprazan compared to proton pump inhibitors (PPIs) in the treatment of erosive esophagitis (EE). A comprehensive literature search was conducted across multiple electronic databases from inception to 25 March 2025. Randomized controlled trials comparing tegoprazan with PPIs in patients with endoscopically confirmed EE were included. Primary outcomes were healing rates and safety profiles. Four randomized controlled trials comprising 963 patients were included. Meta-analysis revealed comparable healing rates between tegoprazan and PPIs (RR: 1.03, 95% CI: 0.97-1.10), with no significant differences observed at both four weeks (RR: 1.05, 95% CI: 0.96-1.16) and eight weeks (RR: 1.01, 95% CI: 0.96-1.06). Safety analyses demonstrated similar profiles between treatments, with no significant differences in treatment-emergent adverse events (RR: 0.93, 95% CI: 0.73-1.35), drug-related adverse events (RR: 0.93, 95% CI: 0.51-1.69), or serious adverse events (RR: 1.07, 95% CI: 0.12-9.29). Symptom relief was comparable between groups across all studies, with tegoprazan showing consistent efficacy, regardless of CYP2C19 genotype. Most patients had mild to moderate EE (LA grades A and B), limiting conclusions about efficacy in severe cases. This first meta-analysis directly comparing tegoprazan with PPIs suggests that tegoprazan is an effective and safe alternative to PPIs for EE treatment. Its efficacy independent of CYP2C19 polymorphism represents a potential advantage. However, limitations include the small number of studies, predominantly Asian populations, and relatively short follow-up periods. Further research is needed to assess long-term outcomes and efficacy in diverse populations.

PMID:40452708 | PMC:PMC12126153 | DOI:10.7759/cureus.83302

Can J Psychiatry. 2025 Jun 2:7067437251342279. doi: 10.1177/07067437251342279. Online ahead of print.

ABSTRACT

ObjectivesTo compare the short-term safety and efficacy of centanafadine, an investigational treatment, versus long-acting controlled-release methylphenidate hydrochloride (methylphenidate, Foquest®) among adult patients with attention-deficit/hyperactivity disorder (ADHD), using matching-adjusted indirect comparison (MAIC).MethodsThis anchored MAIC used pooled individual patient data (IPD) from two centanafadine trials (NCT03605680, NCT03605836) and published aggregate data from one methylphenidate trial (NCT02139124). Using propensity scores, IPD from the centanafadine trials were reweighted to match the aggregate baseline characteristics of the methylphenidate trial. Safety and efficacy outcomes were compared at Week 4. Safety outcomes were the rates of adverse events reported by ≥5% of patients in any treatment group in either trial with an incidence twice that of the placebo. The efficacy outcome was the mean change from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS)/ADHD Rating Scale-5 (ADHD-RS-5) score at Week 4.ResultsAfter matching, no significant differences in baseline characteristics were observed across trials. Relative to methylphenidate, centanafadine exhibited a better safety profile, with a significantly lower risk of insomnia (risk difference in percentage points: -9.46 points) and initial insomnia (-4.68 points). There was no significant difference in efficacy across treatments as measured by the mean change from baseline in AISRS/ADHD-RS-5 score.ConclusionsIn this MAIC, centanafadine was associated with a lower risk of insomnia and comparable (i.e., nondifferent) efficacy compared to methylphenidate at Week 4. Information on the comparative safety and efficacy of ADHD treatments in the adult population will help inform personalized treatment decisions given the range of treatment options with varying attributes.

PMID:40452389 | DOI:10.1177/07067437251342279

Oncologist. 2025 Jun 2:oyaf163. doi: 10.1093/oncolo/oyaf163. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: The prognosis of biliary tract cancers (BTC) after radical resection is still unsatisfactory. However, the clinical value of adjuvant therapy remains controversial. This retrospective study aimed to evaluate the clinical value of adjuvant chemotherapy and adjuvant chemoimmunotherapy in patients with BTC after radical resection.

METHODS: Data from BTC patients who underwent radical resection were retrospectively obtained from Hunan Provincial People's Hospital between January 2020 and July 2024. Patients were divided into observation group, adjuvant chemotherapy group and adjuvant chemoimmunotherapy group according to the treatment received by the patient after surgery. Survival curves were determined by the Kaplan-Meier method. The COX proportional hazards regression model was used to determine independent prognostic risk factors. The adjuvant chemotherapy group and adjuvant chemoimmunotherapy group were analyzed by propensity score matching at 1:1 ratio.

RESULTS: A total of 219 patients with BTC were reenrolled in this study, with 108 cases of iCCA, 39 cases of pCCA, 15 cases of DCCA and 57 cases of GBC. 87 patients (39.73%) received surgery alone, 69 patients (31.51%) received postoperative adjuvant chemotherapy, 63 patients (28.77%) received postoperative adjuvant chemoimmunotherapy. There was no different significance for median recurrence-free survival (RFS) in three groups (13.20 months vs 20.40 months vs 19.68 months) (P =0.195). The median overall survival (OS) was the longest in the chemoimmunotherapy group (29.20 months vs 31.5 months vs 43.27 months) (P=0.003). After PSM, there was no difference in median RFS in two adjuvant groups (22.03 months vs 19.87 months) (P =0.350). The median OS was longer in the chemoimmunotherapy group (45.27 months vs 29.40 months) (P =0.015). In Cox analysis, lymph node metastasis, differentiation, and adjuvant treatment were the independent predictor of OS in patients with BTC. The most common adverse events were of any grade of hematologic toxicity. No drug-related deaths occurred in either group.

CONCLUSIONS: The safety of chemoimmunotherapy was acceptable and could significantly prolong the overall survival of BTC. These data provided a basis for an additional prospective clinical trial to evaluate the efficacy of chemoimmunotherapy in adjuvant therapy for BTC.

PMID:40452387 | DOI:10.1093/oncolo/oyaf163

Atherosclerosis. 2025 May 26:120229. doi: 10.1016/j.atherosclerosis.2025.120229. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) have a favourable efficacy and safety profile. Advancing age may pose challenges such as increasing drug toxicity, polypharmacy, and comorbidities. This study aims to assess whether the efficacy and safety of PCSK9 mAbs are comparable between patients ≥70 years versus patients <70 years.

METHODS: In a prospective registry of all consecutive patients who started PCSK9 mAbs as part of routine care in a university medical center-based lipid clinic, data was collected on LDL cholesterol levels, side effects, and discontinuation. Data on efficacy and safety (reported side effects and discontinuation) were stratified for patients ≥70 and < 70 years.

RESULTS: Of the 474 patients (median age 59 [51-66] years, 51 % men) who started a PCSK9 mAb, 70 patients were ≥70 years (15 %). After 6 months, relative and absolute LDL cholesterol reduction was similar across age groups (relative decrease: 58 % [48-70] vs 59 % [44-71], p = 0.99; mean (SD) absolute decrease 2.4 (0.8) vs 2.4 (1.2) mmol/L, p = 0.90). A comparable proportion of patients ≥70 years compared to those <70 years achieved European and Dutch guideline-recommended goals (36 % vs 46 %, p = 0.18, and 54 % vs 62 %, p = 0.26, respectively). Efficacy outcomes were similar after 12 and 24 months follow-up. Reported side effects and discontinuation of PCSK9 mAbs were comparable across age groups.

CONCLUSIONS: Efficacy and safety of PCSK9 mAbs are comparable for patients ≥70 years and patients <70 years in a real-world study.

PMID:40450473 | DOI:10.1016/j.atherosclerosis.2025.120229

BMC Cancer. 2025 Jun 1;25(1):979. doi: 10.1186/s12885-025-14391-7.

ABSTRACT

BACKGROUND: Wilms' tumor (WT) is a common renal malignancy in children. Although certain patient groups exhibit high survival rates, those experiencing recurrence, metastasis, or chemoresistance face significant challenges. The identification of reliable prognostic markers is essential for adapting treatment strategies to enhance survival rates and reduce chemotherapy-related adverse events (CRAEs).

METHODS: This study included patients diagnosed with WT at our institution. Inflammatory biomarkers were measured from pre-treatment blood tests, and their associations with event-free survival (EFS) and overall survival (OS) were evaluated using Kaplan-Meier and Cox regression analyses. The relationship between biomarkers and CRAEs was examined through logistic regression.

RESULTS: Multifactorial Cox regression analysis identified tumor stage (HR = 4.68, 95% CI: 1.58-13.87, p = 0.005), pan-immune-inflammation value (PIV) (HR = 3.94, 95% CI: 1.80-8.60, p < 0.001), and neutrophil-to-lymphocyte ratio (NLR) (HR = 0.40, 95% CI: 0.18-0.90, p = 0.027) as independent prognostic factors for EFS. Multivariate Cox regression revealed that stage IV (HR = 12.24, 95% CI: 1.56-95.85, p = 0.017) and PIV levels exceeding 246.4 (HR = 5.50, 95% CI: 2.13-14.19, p < 0.001) were significant predictors for OS. Additionally, high PIV (OR 2.32, 95% CI: 1.15-4.67, p = 0.018) independently predicted the occurrence of CRAEs.

CONCLUSION: WT patients with higher PIV levels showed significant associations with poorer EFS, worse OS, and an increased likelihood of developing CRAEs during treatment.

PMID:40452012 | DOI:10.1186/s12885-025-14391-7

Diabetes Metab. 2025 May 30:101668. doi: 10.1016/j.diabet.2025.101668. Online ahead of print.

ABSTRACT

AIMS: Limited data are available on the effectiveness of pharmacological treatments for diabetes secondary to disorders of the exocrine pancreas (DEP). This study evaluated the real-world effectiveness and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors in individuals with DEP.

METHODS: A retrospective cohort study was conducted using data from the Korean National Health Insurance Service database. Data on 66,120 individuals with DEP who initiated glucose-lowering drugs (GLDs) between September 2014 and December 2022 were analyzed. Patients initiating SGLT2 inhibitors were matched 1:1 with patients initiating other GLDs using propensity-score matching. The effectiveness outcomes included major adverse cardiovascular events (MACEs), heart failure, end-stage kidney disease (ESKD), and all-cause mortality. The safety outcomes included hypoglycemia, diabetic ketoacidosis, genital infections, urinary tract infections, fractures, and pancreatitis.

RESULTS: After matching, 4,128 SGLT2 inhibitor-other GLD user pairs were included in the analysis, with a mean follow-up of 2.3 years. Compared with use of other GLDs, use of SGLT2 inhibitors was associated with a significantly lower risk of MACE (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.51-0.93), hospitalization for heart failure (HR: 0.70; 95% CI: 0.51-0.95), ESKD (HR: 0.19; 95% CI: 0.06-0.61), and all-cause mortality (HR: 0.38; 95% CI: 0.27-0.53). SGLT2 inhibitor use was associated with a reduced risk of urinary tract infections (HR: 0.87; 95% CI: 0.78-0.96) and pancreatitis (HR 0.71; 95% CI 0.58-0.87).

CONCLUSIONS: SGLT2 inhibitors were associated with a reduced risk of adverse cardiorenal outcomes and all-cause mortality and were safely used in patients with DEP.

PMID:40451328 | DOI:10.1016/j.diabet.2025.101668