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Corrigendum to “Hormonal factors predictive of fertility in patients with breast cancer interrupting adjuvant endocrine therapy to attempt pregnancy in POSITIVE trial” [The Breast 83 (2025) 104547]
Get PDFAssisted reproductive technology; Breast cancer; Ovarian reserveTécnicas de reproducción asistida; Cáncer de mama; Reserva ováricaTecnologia de reproducció assistida; Càncer de mama; Reserva ovàric
Matching-Adjusted Indirect Comparison of Sotorasib Versus Adagrasib in Previously Treated Advanced/Metastatic Non-Small Cell Lung Cancer Harboring KRAS G12C Mutation
Get PDFNon-small cell lung cancer; Progression-free survival; Treatment-related adverse eventCáncer de pulmón de células no pequeñas; Supervivencia libre de progresión; Evento adverso relacionado con el tratamientoCàncer de pulmó de cèl·lules no petites; Supervivència lliure de progressió; Esdeveniment advers relacionat amb el tractamentIntroduction: Sotorasib and adagrasib are the only treatments approved in the USA and Europe for advanced/metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC). In the absence of head-to-head trials, a matching-adjusted indirect comparison (MAIC) was conducted to assess the relative efficacy and safety of sotorasib versus adagrasib using phase 3 trials.
Methods: Patient-level data from CodeBreaK 200 were reweighted to match the baseline characteristics reported in KRYSTAL-12. The analysis evaluated progression free-survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE). Age, sex, region, prior treatment, brain metastases, and liver metastases were selected for adjustment in the primary analysis per clinical guidance, using an unanchored approach (no common comparator). We conducted sensitivity analyses including additional covariates or anchoring the analysis via common comparator (docetaxel). Additional subgroup analysis was performed in patients with baseline brain metastases, assessing systemic PFS.
Results: Following adjustment, the reweighted patient characteristics from CodeBreaK 200 and KRYSTAL-12 were well balanced. In the primary analysis, sotorasib and adagrasib showed similar efficacy: PFS (HR [hazard ratio] 0.93; 95% confidence interval [CI] 0.70-1.22; p = 0.589) and ORR (odds ratio 0.86; 95% CI 0.53-1.38; p = 0.524). Among patients with brain metastases, sotorasib demonstrated a 39% reduced risk of progression compared with adagrasib (HR 0.61; 95% CI 0.38-0.98; p = 0.040). Sotorasib also demonstrated a more favorable safety profile than adagrasib, with lower odds of TRAEs, TRAEs leading to dose reduction or dose interruption, and all eight individual TRAEs evaluated. Sensitivity analyses supported the robustness of base-case results.
Conclusion: In this MAIC, sotorasib and adagrasib showed comparable efficacy in previously treated advanced KRAS G12C-mutated NSCLC. Among patients with baseline brain metastases, PFS point estimates favored sotorasib. Sotorasib also demonstrated a favorable overall safety profile. These findings may help inform payer decisions and clinical practice in the treatment of KRAS G12C-mutated NSCLC.This study was funded by Amgen, Inc. The journal’s Rapid Service Fee was funded by Amgen Inc
Access to kidney transplantation and re-transplantation from childhood to adulthood: long-term data from the ERA Registry
Get PDFKidney transplantation; Paediatric; Re-transplantationTrasplantament renal; Pediatria; RetrasplantamentTrasplante renal; Pediatría; RetrasplanteBackground and hypothesis
Knowledge regarding access to first kidney transplantation (KT) and subsequent KT in patients commencing kidney replacement therapy (KRT) in childhood is limited.
Methods
Using European Renal Association (ERA) Registry data, we investigated European patients who started KRT below 20 years of age between 1978 and 2019. Access and determinants to first, second, and third KT were assessed using multivariable Cox regression.
Results
Totals of 12 623, 4077, and 1186 patients were included while awaiting first, second, and third KT, at median ages of 13.8 (IQR: 7.5–17.4), 20.9 (IQR: 16.5–26.1), and 26.6 (IQR: 20.3–32.8) years, respectively. During the study period, overall access was 87.8%, 72.7%, and 60.5% for first, second, and third KT, respectively, and median time to each KT was 0.9 (IQR: 0.2–2.1), 1.9 (0.6–4.5), and 2.6 (IQR: 1.0–5.3) years. Younger age at KRT initiation (aHR 0-4 vs. 10–14 years: 0.54; 95%CI: 0.51–0.57) and female sex (HR: 0.94; 95%CI: 0.90–0.98) were associated with lower access to first KT. KT candidates between 15 and 19 years had lower access to first and second KT (aHR: 0.69; 95%CI: 0.66–0.73, and aHR: 0.70; 95%CI: 0.61–0.81) compared to 10–14 year-olds. Compared to CAKUT, glomerulonephritis patients had lower access to KT (aHR: 0.75; 95%CI: 0.71–0.80 for first, aHR: 0.89; 95%CI: 0.81–0.98 for second, and aHR: 0.80; 95%CI: 0.66–0.97 for third KT). Similarly, patients with primary renal diseases with high risk of recurrence, had lower chances of receiving a first and second KT (aHR: 0.80; 95%CI: 0.76–0.85 for first, aHR: 0.86; 95%CI: 0.78–0.95 for second KT). Access to re-transplantation was also higher with previous pre-emptive KT and previous graft survival exceeding 5 years.
Conclusion
Our study highlights KT access disparities particularly for females, the youngest recipients, high-risk age (15–19 years), and diseases with recurrence risk. Notably, pre-emptive transplants and enduring previous grafts offer advantages regarding re-transplantation.The ERA Registry is funded by the European Renal Association (ERA). S.D.M. reports to be the Director or NIHR Great Ormond Street Hospital Clinical Research Facility. A.P.J.d.V. reports receiv- ing consulting fees from Hansa, Sanofi, Takeda, Neovii, Astellas, Sandoz; is a member of the Steering Committee Renal Lifecycle Trial; being past chair of the Dutch Kidney Transplant Advisory Committee and board member of the Dutch Nephrology Associ- ation Board member Nefrovisie. S.S.S. reports receiving consult- ing fees from Novo Nordisk and support from Amicus Therapeu- tics for attending meetings/and or travel; and is board member of Nordic Kidney Group and Scandiatransplant. T.J. reports receiv- ing grants from Lastentautien tutkimussäätiö (Foundation for Pe- diatric Research); support for attending meetings/and or travel from Helsinki and Uusimaa Heath District; and being a board member of the Scandiatransplant council. M.S. reports receiving consulting fees from Hansa Biopharma and Vfor Pharma; and payment for lectures from Otsuka. M.A. reports receiving grants from Slovenian Research and Innovation Agency; payments for lectures from Astellas Pharma, Chiesi, Astra Zeneca, Takeda, No- vartis, Bayer, and Boehringer Ingelheim; and support for attend- ing meetings/and or travel from Chiesi. L.A.P. reports receiving grants from Kidney Research UK, Academy of Medical Sciences and National Institute for Health and Care Research; support for attending meetings through a paid role at UK Kidney Associa- tion/UK Renal Registry; and being a UK Renal Registry Paediatric Research Lead. S.M. reports being the Chair of Scottish Renal Reg- istry, Public Health Scotland. R.P. reports support for the present manuscript from Landspitali University Hospital and University of Iceland; and receiving grants from The University of Iceland Re- search Fund Research and Landspitali University Hospital Science Fund; being the President of the Icelandic Society of Transplan- tation and a board member of the Icelandic Society of Internal Medicine. A.O. reports receiving grants from Sanofi and is Director of the Catedra Mundipharma-UAM of diabetic kidney disease and the Catedra Astrazeneca-UAM of chronic kidney disease and elec- trolytes; consultancy or speaker fees or travel support from Ad- viccene, Alexion, Astellas, Astrazeneca, Amicus, Amgen, Bioporto, Boehringer Ingelheim, Fresenius Medical Care, GSK, Bayer, Sanofi- Genzyme, Sobi, Menarini, Mundipharma, Kyowa Kirin, Lilly, Free- line, Idorsia, Chiesi, Otsuka, Novo-Nordisk, Sysmex and Vifor Fre- senius Medical Care Renal Pharma and Spafarma; is a board mem- ber of ERA Council and SOMANE; and has stock options in Telara Pharma. V.S.S. reports having support for the present manuscript from European Renal Association. J.H. reports receiving consult- ing fees from Alnylam pharmaceuticals; is a board member of DSMB RCT Obirins (obinutuzumab vs rituximab in nephrotic syn- drome) and ESPN Council. K.J.J. reports having support for the present manuscript from European Renal Association; and receiv- ing a grant from the European Society for Paediatric Nephrology. All other co-authors declare that they have no relevant financial interests
Antirheumatic drugs in reproduction, pregnancy, and lactation: a systematic literature review informing the 2024 update of the EULAR recommendations
Get PDFFármacos antirreumáticos; Reproducción; EmbarazoAntirheumatic drugs; Reproduction; PregnancyFàrmacs antireumàtics; Reproducció; EmbaràsObjectives
This study aimed to summarise and update evidence to inform the 2024 update of the European Alliance of Associations for Rheumatology recommendations for the use of antirheumatic drugs in reproduction, pregnancy, and lactation.
Methods
A systematic literature review (SLR) was performed, including keywords on reproduction, adverse pregnancy outcomes (APOs), and lactation. Two appraised SLRs were the basis for the SLR on drug safety in men. If sufficient data were available, a meta-analysis was performed on maternal drug exposure and the risk of APOs.
Results
Of 6680 screened articles, 255 were included in the final analysis. In pregnancy, most evidence was available for biologic disease-modifying antirheumatic drugs (bDMARDs). Meta-analyses with adjusted risk estimates did not reveal APOs or serious infant infections to be associated with tumour necrosis factor inhibitor (TNFi) use. Data on non-TNFi bDMARDs did not raise concerns. In bDMARD-exposed infants, no serious adverse effects to rotavirus live vaccination were reported. Safety of Bacille Calmette–Guérin vaccination in TNFi-exposed infants could be a concern in the first 6 months of life. Regarding oral glucocorticoids, the SLR and meta-analysis using adjusted risk estimates found a dose-dependent association with an increased risk of preterm birth. Nonsteroidal anti-inflammatory drug use could reversibly reduce fecundability. Concerning lactation, available data on various bDMARDs was reassuring. In male patients, available evidence on methotrexate and most other drugs did not reveal adverse effects on sperm quality or birth outcomes. Cyclophosphamide remains the only drug that causes a dose-dependent irreversible infertility.
Conclusions
This SLR provides up-to-date evidence to guide the 2024 update of the European Alliance of Associations for Rheumatology recommendations for the use of antirheumatic drugs in reproduction, pregnancy, and lactation.This work was supported by the European League Against Rheumatism as project QoC012
Sharp increase in the incidence and severity of invasive Streptococcus pyogenes infections in children after the COVID-19 pandemic (2019-2023): A nationwide multicenter study
Get PDFChildren; Group A streptococcus; OutbreakNiños; Estreptococo del grupo A; BroteInfants; Estreptococ del grup A; BroteObjectives
A global surge in pediatric invasive group A streptococcal infection (iGAS) was reported after autumn 2022. This study analyzed the epidemiology and severity of iGAS in Spain, comparing two periods; P1: pre-outbreak (January 2019-September 2022) versus P2: outbreak (October 2022-July 2023).
Methods
Children ≤16 years with iGAS enrolled in the Spanish PedGAS-net (2019-2023), were included. Bacterial isolates were analyzed for emm typing, antibiotic susceptibility, and whole genome sequencing. Multivariate analysis identified risk factors for PICU admission and mortality.
Results
558 cases were included; 307 (55.1%) were male, with a median age of 43.9 months (IQR:19.3-84.1). There were significantly more iGAS in P2 (35.7 vs. 4.5 cases/month, P < 0.001), with higher PICU admissions (51.3% vs. 30.8%, P < 0.001). Pneumonia was the most common syndrome (32.3%), with pleural effusion in 58.3%. Of the 130 samples available for emm-typing, the most frequent were emm1 (56.1%) and emm12 (27.1%). 245 (43.9%) required PICU admission. Factors associated with PICU were streptococcal toxic shock syndrome (STSS), pneumonia, necrotizing fasciitis, acute kidney failure, and previous consultation before diagnosis. The emm1 (especially M1UK) increased PICU risk. 11 children (2.0%) died. STSS, sepsis, and central nervous system infection were associated with mortality.
Conclusion
In Spain, pediatric iGAS cases sharply increased during 2022-2023, with a remarkable increase in severity. Epidemiological surveillance of iGAS remains crucial.This work was partially funded by the Centro de Investigación Biotecnológica en Red de Enfermedades Infecciosas (CIBERINFEC: IM23/INFEC/3)
Iron Deficiency Is Associated With Impaired Myocardial Reperfusion in ST‐Segment–Elevation Myocardial Infarction: Influence of the Definition Used
Get PDFAcute myocardial infarction; Iron deficiency; ReperfusionInfarto agudo de miocardio; Deficiencia de hierro; ReperfusiónInfart agut de miocardi; Deficiència de ferro; ReperfusióBackground
The role of iron deficiency (ID) in ST‐segment–elevation myocardial infarction (STEMI) remains unclear. This study aimed to assess whether ID is associated with impaired myocardial reperfusion in STEMI and whether this association is affected by ID definition.
Methods
We included 942 consecutive patients with STEMI successfully treated with primary percutaneous coronary intervention. ID was defined either as recommended by international guidelines or, alternatively, as ferritin <100 ng/mL, transferrin saturation <20%, or serum iron ≤13 μmol/L. In 595 patients, serum soluble transferrin receptor levels were measured. Impaired myocardial reperfusion was defined as lack of ST‐segment resolution ≥50% 60 to 90 minutes after percutaneous coronary intervention.
Results
ID prevalence varied across these definitions. Impaired reperfusion was present in 12.7% of patients without ID and 41.0% of those with ID defined by transferrin saturation <20% (P<0.001). This association was less pronounced for serum iron ≤13 μmol/L, weaker for guideline criteria, and absent for high (≥1.59 mg/L) soluble transferrin receptor levels or low ferritin. Transferrin saturation <20%, but not ferritin‐based criteria, was associated with poorer clinical course and left ventricular function and higher in‐hospital mortality and remained an independent predictor of impaired reperfusion after adjusting for baseline predictors and anemia.
Conclusions
ID defined by transferrin saturation <20% is strongly related to impaired ST resolution and predicts a worse in‐hospital outcome in patients with STEMI treated with primary percutaneous coronary intervention. The association of other ID criteria with myocardial reperfusion or with the clinical course is weaker or absent. The potential preventive or therapeutic strategies targeting ID in STEMI warrant further investigation.This study was funded by Instituto de Salud Carlos III, Spain, through the projects AES PI16/00232 and AES PI23/00068 and the research network CIBERCV (CB16/11/00479), both co‐funded by European Regional Development Fund, and by the Sociedad Española de Cardiología y Fundación Española del Corazón (SEC/FEC‐INV‐BAS 23/11)
Sleep and Risk of Multiple Sclerosis: Bridging the Gap Between Inflammation and Neurodegeneration via Glymphatic Failure
Get PDFMultiple sclerosis; Neurodegeneration; SleepEsclerosis múltiple; Neurodegeneración; DormirEsclerosi múltiple; Neurodegeneració; DormirEpidemiological studies identified insufficient and poor-quality sleep as independent risk factors for multiple sclerosis (MS). The glymphatic system, active during slow-wave sleep, clears brain waste through perivascular astrocytic aquaporin-4 (AQP4) channels. The presence of antigens induces a transient, physiological lowering of glymphatic flux as a first step of an inflammatory response. A possible hypothesis linking infection with the Epstein-Barr virus, a well identified causal step in MS, and the development of the disease is that mechanisms such as poor sleep or less functional AQP4 polymorphisms may sustain glymphatic flow reduction. Such chronic glymphatic reduction would trigger a vicious circle in which the persistence of antigens and an inflammatory response maintains glymphatic dysfunction. In addition, viral proteins that persist in demyelinated plaques can depolarize AQP4, further restricting waste elimination and sustaining local inflammation. This review examines the epidemiological evidence connecting sleep and MS risk, and the mechanistic findings showing how poor sleep and other glymphatic modulators heighten inflammatory signaling implicated in MS pathogenesis. Deepening knowledge of glymphatic functioning in MS could open new avenues for personalized prevention and therapy.GS-B receives support from grant CP23/00039, funded by the Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union/FSE+ and the MCIN/AEI/10.13039/501100011033, through project PID2020-119556RA-I00
Update on the Prevalence, Incidence, Mortality, and Trends in Treatment of Inflammatory Bowel Disease in a Population-Based Registry in Catalonia Between 2017 and 2023
Get PDFEpidemiology; Psychological endpoints; Quality of life; Socio-economicalEpidemiología; Criterios de valoración psicológicos; Calidad de vida; SocioeconómicosEpidemiologia; Criteris d'avaluació psicològics; Qualitat de vida; SocioeconòmicThe prevalence of inflammatory bowel disease (IBD) is increasing worldwide, while the incidence is tending to stabilize. Moreover, the use of biological treatments is increasing; some studies suggest that surgeries and hospitalizations are decreasing instead. Methods: A population-based, retrospective cohort study was conducted using data from the Catalan Health Surveillance System (CHSS). All patients diagnosed with IBD were included between 2017 and 2023. Crude incidence and prevalence rates were calculated for the Catalan population. Data on pharmacological therapy, surgical procedures, hospitalizations, and mortality were analyzed. Trends in age-sex-adjusted rates were also estimated, and logistic regression was used to calculate the adjusted mortality odds ratio (OR). Data for Crohn's disease (CD) and ulcerative colitis (UC) were analyzed separately. Results: The number of prevalent IBD cases rose from 28,752 in 2017 to 41,423 in 2023. Despite incidence rates remaining stable (30.8 in 2017 and 29.9 per 100,000 inhabitants in 2023), prevalence rates increased (386.9 and 510.9 per 100,000 inhabitants, respectively). The use of biologics significantly increased (from 13.5% in 2017 to 21.0% in 2023), particularly ustekinumab and vedolizumab. In parallel, a decline in the use of immunosuppressants was observed. IBD-related surgeries and hospitalizations decreased during the study period, particularly among CD patients. Mortality remained low but was higher among IBD patients compared to the general population. Conclusions: The incidence of IBD in Catalonia has stabilized, while its prevalence continues rising, suggesting a transition to Stage 3 (compounding prevalence). The use of biological treatments is increasing steadily, whereas rates of surgeries and hospitalizations are consistently decreasing.This study was supported by CIBERehd
Pharmacokinetics of Isavuconazole During Extracorporeal Membrane Oxygenation Support in Critically Ill Patients: A Case Series
Get PDFAntifungal therapy; Critical care; PharmacokineticsTeràpia antifúngica; Cures intensives; FarmacocinèticaTerapia antifúngica; Cuidados intensivos; FarmacocinéticaBackground/objectives: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients, but may significantly alter the pharmacokinetics (PK) of antifungals. Data on plasma concentrations of Isavuconazole (IsaPlasm) in ECMO patients are limited. Our objective is to evaluate Isavuconazole exposure and variability in critically ill COVID-19 patients receiving ECMO.
Methods: We conducted a pharmacokinetic analysis of Isavuconazole in critically ill patients receiving Veno-Venous ECMO for respiratory support. Plasma concentrations were measured using therapeutic drug monitoring (TDM) at multiple time points, including sampling before and after the membrane oxygenator. PK parameters-Area Under Curve (AUC0-24), Minimum Plasma Concentration (Cmin), Elimination Half-Life (T1/2), volume of distribution (Vd), and clearance (CL)-were estimated and compared with published data in non-ECMO populations.
Results: Five patients were included. The median AUC0-24 was 227.3 µg·h/mL (IQR 182.4-311.35), higher than reported in non-ECMO patients. The median Vd was 761 L (727-832), suggesting extensive peripheral distribution and potential drug sequestration in the ECMO circuit. CL was increased (1.6 L/h, IQR 1.5-3.4). Two patients with recently replaced ECMO circuits exhibited significant drug loss across the membrane. Obesity and hypoalbuminemia were identified as factors associated with altered drug exposure.
Conclusions: Isavuconazole pharmacokinetics show marked variability in critically ill ECMO patients. Increased AUC and Vd, along with reduced clearance, highlight the need for individualized dosing
To heal or harm: A systematic review of the role of fluoroquinolones in periprosthetic joint infections
Get PDFFluoroquinolones; Periprosthetic joint infections; EfficacyFluoroquinolones; Infeccions articulars periprotètiques; EficàciaFluoroquinolonas; Infecciones articulares periprotésicas; EficaciaBackground
Fluoroquinolones (FQs) are currently recommended for the treatment of periprosthetic joint infections (PJIs) caused by staphylococci and Gram-negative bacteria (GNB) in patients undergoing debridement, antibiotics and implant retention (DAIR). In recent decades, reports of serious adverse events associated with FQ use have led to official regulatory recommendations for their restricted use. This review aims to describe the evidence for, and discuss the risks and benefits of, FQ use for PJI.
Methods
A comprehensive search of MEDLINE and EMBASE up to October 2024 was conducted using pre-defined criteria to identify studies addressing (i) the efficacy of FQs in treating staphylococcal and GNB-PJI, and (ii) serious adverse events associated with FQs. A narrative synthesis of the results was performed.
Results
No randomized controlled trials were identified. A total of 19 retrospective studies were reviewed to assess the efficacy of FQs in treating staphylococcal and GNB-PJI, though the sample sizes in these studies were relatively small. Fifty-seven studies, mostly large retrospective epidemiological cohorts, were found evaluating adverse events associated with FQ treatment.
Conclusions
There is evidence supporting the use of FQ monotherapy for GNB-PJI and FQ combined with rifampin for staphylococcal PJIs following DAIR over other antimicrobial regimens. There is evidence that FQs are associated with an increased risk of tendinopathy, prolonged QTc interval, peripheral neuropathy and dysglycaemia, however the absolute risk is low. When FQs are used in the treatment of PJIs, an individualized risk assessment and close monitoring during treatment are recommended.S.T. is supported by the Research committee of Region Värmland (LIVFOU) and by grants from the Swedish state under the ALF agreement between the Swedish government and the county councils (Region Örebro County, Sweden OLL-967677). B.Y. is supported by the National institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC)