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Sato, Ayaka; Sumimoto, Takahiro; Tanaka, Ryota; Tatsuta, Ryosuke; Yoshikawa, Naoki; Itoh, Hiroki
doi: 10.1007/s00228-026-04110-xpmid: 42298206
PurposeThis study investigated the association between anamorelin (ANAM) treatment and longitudinal changes in renal function in patients with cancer cachexia.MethodsThis retrospective, single-centre, observational cohort study reviewed electronic medical records of patients diagnosed with cancer cachexia. Renal function parameters—including blood urea nitrogen (BUN), serum creatinine, and estimated glomerular filtration rate (eGFR)—were compared between patients treated with ANAM and those not receiving ANAM. Propensity score matching was applied to adjust for baseline imbalance in patient characteristics. Renal deterioration was defined as ≥ 10% increase in BUN or ≥ 10% serum creatinine, or ≥ 10% decrease in eGFR. Cox proportional hazards models were applied to BUN, serum creatinine, and eGFR deterioration, respectively.ResultsAfter propensity score matching, ANAM treatment was associated with significantly greater improvements in serum creatinine and eGFR over an 8-week period compared with non-ANAM treatment. Multivariable Cox regression analyses demonstrated that ANAM use was independently associated with a reduction in risk of ≥ 10% increase in serum creatinine and ≥ 10% decrease in eGFR. Longitudinal analyses revealed improvements in renal function markers in the early phase after initiation of ANAM, followed by a gradual return toward baseline levels.ConclusionANAM treatment was associated with improvements in renal function markers and a lower risk of renal function deterioration in patients with cancer cachexia. These findings suggest that ANAM may potentially confer renoprotective effects in addition to its established therapeutic benefits for cachexia.
Kurt, İlker; Koçak, Esen Gül; Şen, Meliha; Mete, Bilgül; Aygün, Gökhan; Özdemir, Özkan; Günver, Mehmet Güven; Dikmen, Yalım; Tabak, Ömer Fehmi; Uydeş Doğan, B. Sönmez; Pala Kara, Zeliha
doi: 10.1007/s00228-026-04103-wpmid: 42310132
PurposeVancomycin therapeutic drug monitoring is essential for optimizing efficacy and reducing the risk of vancomycin-associated acute kidney injury (VA-AKI). Although recent guidelines recommend the ratio of area under the curve over 24 h to minimum inhibitory concentration (AUC24/MIC)–based monitoring over trough concentration-based monitoring, differences between AUC24/MIC estimation methods (e.g., pharmacokinetic equations and Bayesian approaches) may influence therapeutic classification in clinical practice. In addition, pharmacogenetic factors contributing to interindividual variability in vancomycin exposure remain incompletely characterized.MethodsThis prospective, single-center cohort study included adult patients who received intravenous vancomycin for at least 72 h between June 2024 and April 2025. Vancomycin trough and peak plasma concentrations were measured using an enzyme-linked immunosorbent assay. AUC24/MIC values were calculated using pharmacokinetic equation and Bayesian method. Agreement in therapeutic classification between trough concentration–based and AUC24/MIC-based monitoring was assessed. Associations between the rs2789047 genetic variant and relevant parameters were also evaluated.ResultsThirty-six patients were included, of whom 38.9% developed VA-AKI. Despite strong correlations between trough concentration and AUC24/MIC values (r = 0.84–0.87), substantial discordance in therapeutic classification was observed, with agreement rates of 63.9% for pharmacokinetic equation-based and 66.7% for Bayesian-based compared with trough concentration-based monitoring. In contrast, pharmacokinetic equation-based and Bayesian-based methods demonstrated strong concordance (86.1%). Higher trough concentrations and AUC24/MIC values were significantly associated with VA-AKI (p < 0.001). Carriers of rs2789047 A-allele exhibited higher trough concentrations and reduced elimination rates.ConclusionTrough concentration-based monitoring frequently misclassified vancomycin exposure compared with AUC24/MIC–based approaches. Pharmacogenetic variability may further influence vancomycin exposure.
Cruz, Artur Macedo; Lima, Bruna Carolyne Venancio; de Ferreira, José Erivelton Souza Maciel; Teles, Rian Brito
doi: 10.1007/s00228-026-04095-7pmid: 42265474
BackgroundIn recent years, metabolic therapies originally developed to treat systemic metabolic disorders have been investigated as potential therapeutic strategies for Metabolic dysfunction-associated steatohepatitis (MASH).ObjectiveThis study aimed to critically evaluate recent clinical evidence on emerging metabolic therapies, particularly sodium-glucose cotransporter-2 (SGLT2) inhibitors and incretin-based agents, examining their effects on hepatic and metabolic outcomes and, when available, histological endpoints, as well as safety in patients with MASH.MethodsA systematic review of clinical studies evaluating metabolic therapies in patients with MASH or metabolically associated fatty liver disease was conducted. Randomized clinical trials and other relevant clinical studies investigating SGLT2 inhibitors, incretin-based therapies, and other emerging metabolic agents were included. Outcomes of interest comprised metabolic parameters, hepatic outcomes related to steatosis and disease activity, and histological endpoints when available.ResultsTwelve clinical studies were included. In trials with histological endpoints, semaglutide achieved steatohepatitis resolution without worsening of fibrosis in 62.9% versus 34.3% with placebo in a phase 3 trial (p < 0.001), while a phase 2 trial reported NASH resolution in 59% versus 17% with placebo (p < 0.001), without significant fibrosis improvement (43% versus 33%; p = 0.48). Tirzepatide achieved MASH resolution without worsening of fibrosis in 44–62% of patients versus 10% with placebo (p < 0.001 for all doses), and fibrosis improvement in 51–55% versus 30%. Among SGLT2 inhibitors, dapagliflozin achieved MASH improvement without worsening of fibrosis in 53% versus 30% (p = 0.006), MASH resolution in 23% versus 8% (p = 0.01), and fibrosis improvement in 45% versus 20% (p = 0.001). Overall, metabolic therapies improved body weight, hepatic steatosis, glycemic parameters, and disease activity, but evidence for durable fibrosis regression and long-term liver-related outcomes remains heterogeneous.ConclusionEmerging metabolic therapies show promising effects on metabolic and hepatic outcomes in patients with MASH. Incretin-based therapies appear to exert particularly robust effects on body weight reduction and steatohepatitis resolution, whereas SGLT2 inhibitors may provide complementary metabolic, cardiometabolic, and hepatic benefits. Nevertheless, fibrosis-related effects remain less consistent across studies, and future trials with paired histological endpoints, longer follow-up, and clinically meaningful liver-related outcomes are needed.
Penninx, B. M. F.; Hollak, C. E. M.; Tas, S. W.; Timmers, L.; de Visser, S. J.; van Kempen, Z. L. E.
doi: 10.1007/s00228-026-04097-5pmid: 42265224
PurposeAfter the marketing authorisation of biologicals, uncertainty often remains regarding their real-world effectiveness, safety, and rational use. This study investigates how frequently the recommended use of biologicals changes post-authorisation, and who funds the studies leading to these changes.MethodsBiologicals receiving a positive opinion for adult indications by the Committee for Medicinal Products for Human use (CHMP) between 2006 and 2010 were identified. For each indication, we compared the initial and current Summary of Product Characteristics (SmPC), as well as current SmPC and European clinical guidelines, to identify discrepancies in start and stop criteria, dosage, and administration frequency. We assessed whether discrepancies led to increased or decreased use of the biological and whether this was associated with the sponsor type of supporting publications.FindingsSmPC changes, driven by Marketing Authorisation Holder (MAH)-sponsored studies, were found in 47% of identified indication-biological combinations: 41% led to increased use, 29% to decreased use, and 29% were neutral. Guideline-SmPC discrepancies, mostly supported by publicly sponsored studies, were identified in 75% of cases, with most discrepancies (86%) recommending decreased use. Publications sponsored by public healthcare stakeholders were associated with decreased use, as compared to publications sponsored by the MAH (p < 0.05, OR 28·2, 95% CI 4·8–166·1).ConclusionRecommendations for the use of biologicals often evolve post-authorisation. MAH-sponsored studies tend to support increased use, whereas guideline recommendations, typically based on publicly sponsored studies, more often favor restriction. Rational use of biologicals requires timely evidence generation and should ideally lead to amendments in SmPC’s.
Liao, Jiahao; Li, Xiaomeng; Li, Guowei
doi: 10.1007/s00228-026-04092-wpmid: 42271082
BackgroundCisplatin-based chemotherapy is the standard of care for muscle-invasive and advanced bladder cancer, but its significant toxicity renders approximately 30–50% of patient ineligible. Carboplatin is widely used as a substitute; however, its comparative efficacy and safety remain controversial due to fragmented and inconsistent evidence. This meta-analysis aims to compare survival outcomes, response rates, and toxicity profiles between carboplatin- and cisplatin-based regimens.MethodsWe conducted a systematic review and meta-analysis following PRISMA guidelines (PROSPERO: CRD420251249371). MEDLINE, Embase, Cochrane Library, and Web of Science were searched from inception to December 2025 for studies comparing carboplatin-based versus cisplatin-based chemotherapy and restricting study populations to patients with bladder cancer only. This strict selection criterion was applied intentionally to ensure homogeneity. Outcomes included overall survival (OS), cancer-specific survival (CSS), objective response rate (ORR), pathological complete response (pCR) and adverse events (AEs). Risk of bias was assessed using RoB 2 (RCTs) and ROBINS-I (observational studies). Data were pooled using random-effects models. Heterogeneity was quantified using I² statistics.ResultsEleven studies (2 RCTs, 9 cohort studies; n = 2,543 patients) were included. Compared to cisplatin-based regimens, carboplatin-based regimens were associated with worse OS (HR = 1.30, 95% CI: 1.11–1.52; I² = 47%) and CSS (HR = 1.79, 95% CI: 1.39–2.32; I² = 16%). This survival disadvantage was pronounced in palliative settings (OS: HR = 1.27; 95% CI, 1.08–1.50; I² = 0%; CSS: HR = 1.79; 95% CI, 1.16–2.77; I² = 0%) but not significant in neoadjuvant settings (OS: HR = 1.15; 95% CI, 0.97–1.37; I² = 26%; CSS: HR = 1.86; 95% CI, 0.93–3.69; I² = 70%; pCR: RR = 0.92; 95% CI, 0.70–1.22; I² = 0%). Carboplatin is associated with significantly lower gastrointestinal toxicity (RR = 0.30; 95% CI, 0.15–0.62; I² = 0%). No significant differences were observed in hematologic toxicity (RR = 1.27; 95% CI, 0.37–4.30; I² = 75%) or grade 3–4 adverse events (RR = 0.61; 95% CI, 0.24–1.55; I² = 87%).ConclusionsBased largely on observational studies, this study suggests that cisplatin is associated with better survival than carboplatin in bladder cancer, particularly in palliative setting. In the neoadjuvant setting, no significant difference was found while this does not imply equivalence. Carboplatin offers lower gastrointestinal toxicity and remains an option for cisplatin-ineligible patients. However, our strict selection excluded pivotal studies enrolling mixed urothelial carcinoma limits generalizability to the broader urothelial cancer population. A less strict selection that included such studies might alter effect estimates. Future RCTs with broader inclusion criteria are needed to confirm our findings.
Bruun, Lina Dorthea; Andersen, Geir Øystein; Myhre, Peder Langeland; Halvorsen, Sigrun; Kringen, Marianne Kristiansen; Hansen, Charlotte Holst; Molden, Espen; Øie, Erik
doi: 10.1007/s00228-026-04091-xpmid: 42271119
PurposeTo investigate the association between β1-adrenergic receptor (ADRB1) polymorphisms on cardiovascular events in patients treated with metoprolol after acute myocardial infarction (AMI).MethodsPatients hospitalized for AMI (n = 1584) who were treated with metoprolol at discharge were genotyped for the ADRB1 variants Arg389Gly and Ser49Gly. The association between the ADRB1 variants and major adverse cardiovascular events (MACE) and cardiovascular death were assessed by the Cox proportional hazards model, using both a dominant and a codominant genetic model, as well as by haplotype copy number.ResultsAfter three years of follow-up, MACE occurred in 105 and cardiovascular death in 47 patients. Gly389 homozygotes (n = 105, 11 events; hazard ratio [HR] 2.02 [1.01, 4.02], p = 0.046), but not heterozygotes (n = 588, 45 events, HR 1.40 [0.90, 2.13], p = 0.12) were at increased risk of MACE, compared with Arg389 homozygotes (n = 891, 49 events). The risk was not significantly different when all Gly389 carriers were merged (p = 0.052). No primary events occurred in Gly49 homozygotes (n = 28); however, when merged with Gly49 heterozygous carriers (n = 383, 6 events) we found a numerical, but not statistically significant difference in cardiovascular deaths relative to Ser49 homozygotes (n = 1173, 41 events) (p = 0.07). The Arg389Ser49 haplotype was not associated with a primary outcome.ConclusionIn post-AMI patients treated with metoprolol, Gly389 homozygotes, but not heterozygotes were associated with an increased risk of MACE compared with Arg389 homozygotes. Our observations raise the possibility of a protective association of the Gly49 variant on cardiovascular death, but this hypothesis requires validation in larger, future studies.Graphical Abstract[graphic not available: see fulltext]
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