Mathys (Netherlands)

ABSTRACT Background Inborn errors of immunity (IEI), or primary immune disorders (PID), predispose individuals to infections, autoimmunity, inflammation, allergy, and malignancy. Malignancies are a major cause of morbidity and mortality in IEI/PID patients, with poorer outcomes compared to the general population. Objectives This European Society for Immunodeficiencies Registry (ESID-R) study aimed to determine the frequency and types of malignancies in IEI/PID patients and to assess clinical management approaches across Europe. Methods Descriptive analyses were performed on malignancy data within each IEI category. Additionally, an ESID-R survey (05/2022–03/2024) collected data on management strategies and challenges. Results Of 19,959 IEI/PID patients, 1,783 (8.9%) developed malignancies, of whom 27.1% presented malignancy as first manifestation of IEI/PID. A total of 1,210 malignancies were specified; B-cell non- Hodgkin lymphoma was most common (24.2%). Detailed malignancy–IEI/PID association maps are provided. Predominantly antibody deficiencies accounted for 59.1% of malignancy cases, with a higher median age at first malignancy (43.6 years) compared to other categories, e.g ., combined immunodeficiencies with syndromic or associated features (11.7 years). Survey findings revealed oncological treatment was modified due to IEI/PID in 21.5% of cases, with assumed negative impacts of IEI/PID on complications and outcomes (in 27.4% and 30.7%, respectively). IEI/PID influenced transplant decisions in 16.5% of cases. Management practices like interdisciplinary decision finding and guideline availability were recorded. Conclusion This study provides comprehensive epidemiological data on malignancies in IEI/PID, highlighting the need for tailored screening and management. Survey results emphasize the real-world challenges and support the development of IEI/PID-specific oncologic surveillance guidelines and treatment strategies. Clinical Implications Overall, ca. 9% of IEI/PID patients develop malignancies —often as first presentation and highly varying between IEI/PID categories— most commonly B-cell non-Hodgkin lymphoma. High oncological treatment modification rates highlight the need for IEI/PID-specific cancer surveillance and interdisciplinary management strategies. Capsule Summary This large ESID-R study quantifies malignancy burden in IEI/PID, identifies disease-specific patterns, and reveals management modifications and challenges, underscoring the urgent need for dedicated oncologic surveillance guidelines and tailored treatment strategies in this vulnerable population. Abstract Figure

Optimal treatment duration is unknown in metastatic renal cell carcinoma (mRCC) responding to immune checkpoint inhibitors (ICPIs). Prolonged treatment can lead to late toxicity, burden for day clinics and financial impact. This multicenter retrospective study included mRCC patients responding to ipilimumab/nivolumab in first-line or nivolumab in later lines, who were treated for at least 21 months and did not stop for toxicity. Progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) were modeled non- and semi-parametrically. The effect of elective ICPI discontinuation (i.e. treatment interruption at the clinician's discretion) between 21 and 25 months on PFS was assessed by a causal inference approach using artificial censoring along with inverse probability of censoring weighting. Ninety-five patients were included with a median follow-up of 62.1 (95% confidence interval [CI]: 57.3-67.5) months. Fifty-four received ipilimumab/nivolumab, whereas 41 patients received nivolumab, for a median treatment duration of 33.8 (95% CI: 28.5-39.6) months. Fifty-seven patients discontinued ICPIs electively. Three-year PFS after discontinuation was 57.1% (95% CI: 34.3-95.1), 3-year OS 67.5% (95% CI: 37.0-100.0), and 3-year CSS 90.0% (95% CI: 73.2-100.0). Fifteen (15.8%) patients discontinued ICPIs between 21 and 25 months. Compared to 80 patients who were treated longer, they had more often a metachronous metastatic pattern (p=0.048) and a complete response (p=0.045). Elective ICPI stop between 21 and 25 months did not significantly impact the hazard for progression/death (adjusted HR 1.08, 95% CI: 0.64-1.84, p=0.766). Among mRCC patients responding to ICPI, elective therapy discontinuation approximately 24 months after initiation does not appear to compromise outcomes compared to continuing therapy.

Breast cancer-related lymphedema (BCRL) remains a significant burden despite conservative treatments like complex decongestive therapy (CDT). Surgical interventions, such as lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT), have emerged as effective alternatives. This study evaluated the effectiveness of LVA or VLNT, or both, combined with CDT compared with CDT alone in reducing upper-limb volume in patients with BCRL. This prospective controlled study included 92 patients with BCRL divided into 4 groups: LVA ( n = 30), VLNT ( n = 15), LVA + VLNT ( n = 13), and CDT control ( n = 34). Limb volumes were measured preoperatively and 1 year postoperatively. Volume differential change, expressed as the percentage relative interlimb difference, was calculated for each group. The mean volume differential changes were -6.21% ± 5.76 for LVA, -9.61% ± 12.03 for VLNT, -7.00% ± 6.56 for LVA + VLNT, and +3.23% ± 6.83 for CDT control. Statistical analysis revealed significant reductions in limb volume for all surgical groups compared with the CDT control group ( P < 0.0001 for LVA, P < 0.0001 for VLNT, and P < 0.0001 for LVA + VLNT). In patients with chronic BCRL, surgical interventions (LVA, VLNT, and LVA + VLNT) combined with CDT significantly reduced limb volume compared with CDT alone. These findings highlight the potential of these surgical options, combined with CDT, in the effective management of lymphedema.

Abstract Study question Which clinical and biological factors contribute to the risk of pregnancy loss and the likelihood of live birth in pre-implantation genetic testing for aneuploidy (PGT-A)? Summary answer Adenomyosis and delayed embryo development significantly affect live birth rate (LBR) following euploid blastocyst transfer, while artificial endometrial preparation is associated with increased pregnancy loss. What is known already Embryo selection by PGT-A is intended to improve reproductive outcomes per transfer. While selecting euploid blastocysts does not improve cumulative LBR, PGT-A aims to reduce the time to pregnancy and lower the risk of pregnancy loss. However, despite genetic selection, many euploid embryos still fail to implant or result in non-viable pregnancies. Multiple factors, including maternal and paternal characteristics, as well as clinical and laboratory variables contribute to these outcomes. The relative importance of these factors may differ depending on the clinical indication for PGT-A. Study design, size, duration This retrospective cohort study includes patients who underwent frozen embryo transfer (FET) of a euploid embryo following intracytoplasmic sperm injection (ICSI) with trophectoderm biopsy (day 5/6) and PGT-A in a single tertiary university hospital between 2017 and 2023. Patients with additional testing for monogenic diseases or structural rearrangements were excluded. Participants/materials, setting, methods A total of 375 patients undergoing 533 FET cycles following PGT-A for specific clinical indications, including recurrent pregnancy loss (RPL), recurrent implantation failure (RIF) and advanced maternal age. Transfers were performed in either a natural (n = 248) or artificial cycle (n = 285). Cycle monitoring included serial hormonal and ultrasound assessments. Ultrasound-guided single embryo transfer was performed once endometrial thickness was deemed sufficient. Ovulation triggering and/or luteal phase support was prescribed at the discretion of the treating physician. Main results and the role of chance Following euploid blastocyst transfer, biochemical pregnancy rate was 69.0%, LBR was 51.2% and early pregnancy loss (EPL) rate was 18.5%. When considering only the first FET per patient (n = 375), biochemical pregnancy rate was 73.3%, LBR reached 56.3% and EPL rate was 17.3%. Univariate and multivariate analyses were conducted with GEE to adjust for multiple transfers per patient, with a sub-analysis performed on the first cycle of each patient. Multivariate logistic regression identified delayed embryo development, reflected in day 6 transfers, as significantly associated with lower LBR compared to day 5 (OR 0.55, 95%CI 0.34-0.90, p = 0.017). Additionally, the presence of adenomyosis was linked to reduced LBR (OR 0.42, 95% CI 0.22-0.79, p = 0.007). Importantly, the type of endometrial preparation (natural versus artificial) did not significantly influence LBR. Conversely, considering only first embryo transfer cycles, the rate of pregnancy loss per clinical pregnancy was significantly lower for natural cycle compared to artificial cycle FET (10% [11/114] vs. 24% [33/140]; p = 0.003, OR 2.3, 95% CI 1.3-4.2). A history of ≥ 2 pregnancy losses did not significantly influence live birth outcomes (p = 0.49), nor did we observe an association between LBR and the number of pregnancy losses when treated as a continuous variable. Limitations, reasons for caution The primary limitation is the retrospective design, which carries an inherent risk of bias. Patient heterogeneity and varying indications for PGT-A may have influenced both treatment decisions and success rates. Additionally, greater standardization in defining RIF and RPL would have enhanced data consistency. Wider implications of the findings Our findings highlight the impact of adenomyosis on live birth rates, emphasizing the need for subtype classification and refined treatment strategies. Additionally, the association between endometrial preparation and EPL provides clinicians with essential insights for optimizing FET management. Trial registration number No

Artificial Intelligence (AI) is reshaping preoperative preparation for both patients and surgeons in plastic surgery, offering innovative tools that improve efficiency, precision, and outcomes. This manuscript examines the growing role of AI in preoperative patient education, surgeon preparation, and clinical workflows, and provides an overview of its main domains of impact. AI-powered tools show great promise in consultations, providing personalized, clear patient education, simplifying administrative tasks such as drafting consultation letters, and enhancing communication. For surgeons, AI can support preoperative planning with reinforcement learning, advanced imaging algorithms, and virtual simulations. These technologies assist in accurate surgical decision making, as seen in deep inferior epigastric artery perforator (DIEP) flap breast reconstruction, where AI may be able to reduce perforator analysis times while maintaining precision. In aesthetic surgery, AI-driven 3D imaging and generative algorithms enable realistic postoperative simulations, improving communication and helping patients set realistic expectations. From a patient communication perspective, AI promotes patient-centered care by simplifying medical jargon, making information more accessible, and fostering better understanding and adherence. Despite challenges such as ethical considerations, data security, and algorithmic bias, AI’s integration into preoperative workflows highlights its potential to improve patient and surgeon experiences. By enhancing patient education, refining surgical strategies, and optimizing preparation, AI is redefining how care is delivered in plastic surgery, aiming for better patient satisfaction and outcomes. Collaboration among clinicians, engineers, and ethicists remains crucial to ensure the responsible use of AI, balancing innovation with the core values of medical care.

Traumatic brain injury (TBI) is a leading cause of mortality and long-term disability, with its pathophysiology encompassing both primary mechanical damage and secondary neuroinflammatory, metabolic, and biochemical alterations. These complex mechanisms contribute to the observed heterogeneous clinical outcomes, including neuroendocrine dysfunctions, post-traumatic seizures, and disorders of consciousness (DoC). Thyroid hormones (THs) play essential roles in synaptic plasticity, neurogenesis and neuronal homeostasis, and the hypothalamic-pituitary-thyroid (HPT) axis has recently emerged as a potential acute and chronic modulator of neurological and functional recovery following TBI, thereby hinting at the potential involvement of THs in post-TBI outcomes. While evidence suggests that alterations in the HPT axis may influence susceptibility to seizures, progression of DoC, and rehabilitation outcomes, an increased blood-brain barrier permeability in concert with dysregulated deiodinase activity and expanding oxidative stress have all been proposed as mechanisms linking THs to post-TBI neurological complications. This review aims to summarize current evidence on the potential role of the thyrotropic axis in neurological and rehabilitation outcomes following TBI.

Benign hepatocellular lesions are frequent findings in abdominal imaging, with focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) being the two principal entities. Although they share overlapping imaging features, their clinical implications differ substantially. Accurate differentiation is crucial, as FNH requires no treatment, whereas HCA carries risks of hemorrhage and malignant transformation.

To monitor fetal size and identify predictors for birthweight in women with gestational diabetes (GDM) and normal glucose tolerance (NGT). Cohort study of 1843 women universally screened for GDM, with routine ultrasounds each trimester. Women with GDM and NGT were categorized in subgroups by birthweight centile. Of the total cohort, 231 (12.5%) women were diagnosed with GDM. Fetal size, incidence of large-for-gestational age (LGA: 12.3% of GDM vs. 12.9% of NGT, p = 0.822) and small-for-gestational age (SGA) neonates (4.8% of GDM vs. 5.1% of NGT, p = 0.886) were similar between GDM and NGT. GDM women with LGA neonates were more insulin resistant at baseline and had more often estimated fetal weight (EFW) ≥ P90 on the 28-33 weeks ultrasound (p = 0.033) than those with AGA (appropriate-for-gestational age) neonates. Compared to NGT women with AGA neonates, those with LGA neonates were more often obese and multiparous, had higher fasting glycemia, a worse lipid profile, and higher insulin resistance between 24 -28 weeks, with more often excessive gestational weight gain. On the 28-33 weeks ultrasound, abdominal circumference ≥ P95 had a high positive predictive value for LGA neonates in GDM (100%), whereas, in both GDM and NGT, EFW ≥ P90 and ≤ P10 had a high negative predictive value for LGA and SGA neonates (> 88%), respectively. There were no differences in fetal size throughout pregnancy nor in LGA incidence between GDM and NGT women. EFW centile at 28-33 weeks correlated well with birthweight. This indicates that GDM treatment is effective and targeted ultrasound follow-up is useful. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT02036619. Registration date: January 15, 2014. https://clinicaltrials.gov/ct2/show/NCT02036619 .