The American Society of Plastic Surgeons guidelines emphasize the need for additional evidence regarding perioperative glycemic control in patients with diabetes undergoing breast reduction surgery. This study evaluates the association between preoperative hemoglobin A1c (HbA1c) levels and postoperative complications in patients with diabetes undergoing reduction mammaplasty. A retrospective cohort study of the National Surgical Quality Improvement Program (NSQIP) database was performed, identifying patients diagnosed with diabetes who underwent breast reduction surgery from 2021 to 2023. Patients were stratified by preoperative HbA1c levels: well-controlled (HbA1c < 6.5
Gene therapy represents a paradigm shift in haemophilia management, offering the potential for sustained factor expression and freedom from prophylactic infusions. Two adeno-associated virus (AAV)-based gene therapies are now approved. Long-term follow-up data demonstrate remarkable durability, with 13-year results showing sustained reductions in annualized bleeding rates in patients with haemophilia B. Outcomes differ between haemophilia A and B: factor VIII levels in haemophilia A decline after peaking, whereas factor IX expression in haemophilia B remains more stable. Recent analyses confirm significant reductions in bleeding rates and treatment requirements, along with well-characterized safety profiles. Liver toxicity remains the primary safety concern, with transaminase elevations typically responding to corticosteroids. Rare adverse events include one reported case of inhibitor development and very few thrombotic events. Reported malignancies to date have not been associated with gene therapy. Current limitations include eligibility restrictions due to preexisting neutralizing antibodies, immune responses to AAV capsids, and variable patient outcomes. These challenges may contribute to slower adoption despite regulatory approval. Emerging approaches such as CRISPR-Cas9 gene editing, high-active factor variants, and novel delivery systems are under investigation. Key implementation issues include outcome-based reimbursement, hub-and-spoke treatment models, and ensuring equitable global access.
Purpose of reviewHospital-acquired anemia (HAA) is a common complication associated with adverse outcomes, including increased transfusion requirements and prolonged hospital length of stay. The precise etiology of HAA remains elusive, and preventive or therapeutic strategies are inconsistently applied or lacking altogether. This review summarizes current evidence on the incidence, underlying mechanism, clinical consequences, and available interventions for HAA.Recent findingsThe causes of HAA are multifactorial involving procedural or diagnostic blood loss, impaired erythropoiesis, coagulation abnormalities, nutritional deficiencies, and hemolysis. Measures such as small volume tubes and closed blood collection devices have proven safe and effective for reducing the volume of drawn blood. Recent studies suggest that the incidence of HAA can be diminished by implementing systematic, patient-centered approaches.SummaryHAA remains prevalent despite long-standing recognition of its clinical consequences. Although awareness has continuously increased, treatment and prevention strategies are still not widely established.
ABSTRACT:Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignant disease that remains a major clinical challenge, as relapsed and refractory disease is difficult to treat. Apoptosis evasion is a major feature of DLBCL. However, while the suppression of intrinsic apoptosis has long been recognized as a lymphoma-promoting event, the role of extrinsic apoptosis has remained poorly defined. In this study, we demonstrated at the genetic level that expression of cellular Fas-associated death domain protein-like IL-1β-converting enzyme-inhibitory protein (cFLIP), the most crucial, non-redundant inhibitor of extrinsic apoptosis, in B cells is necessary for the development of DLBCL in an autochthonous murine model. Indeed, B-cell-specific deletion of Cflar, the gene encoding for cFLIP, prevented lymphomagenesis mediated by oncogenic Myd88 and overexpression of BCL2. In human lymphoma cells, we showed that the absence of cFLIP sensitized activated B-cell-like (ABC)- but not germinal center B-cell-like (GCB)-DLBCL subtype cells to TRAIL- or lipopolysaccharide-induced, caspase-8-mediated apoptosis. Furthermore, we unveiled a cell death-independent role of cFLIP in the suppression of proinflammatory cytokines at the transcriptional level, selectively in the ABC subtype. These results indicate that the suppression of intrinsic apoptosis can support lymphomagenesis only if extrinsic apoptosis is properly controlled. Moreover, licensing extrinsic apoptosis through CFLAR deletion can efficiently promote death in DLBCL cells, despite the suppression of the intrinsic pathway. Overall, these data provide a rationale for the development of cFLIP inhibitors for the treatment of ABC-DLBCL and possibly other hematological cancers.
Abstract Background Although individual rare and complex diseases (RDs) affect small patient populations, together they impact an estimated 27–36 million people across the European Union. Addressing this major public health challenge has been a long-term priority for the European Union, leading to the establishment of the European Reference Networks (ERNs) in 2017. Main body ERNs are cross-border networks connecting clinical expert centres to share knowledge, improve and harmonise diagnosis and care for patients with rare and complex diseases. Since their inception, 24 ERNs have united 1,606 expert centres across 375 hospitals in all EU Member States and Norway. Their activities span multidisciplinary clinical collaboration, patient-centred governance, education and training, and the development of clinical guidelines. Over 4900 extremely rare or difficult cases have been discussed among experts without requiring the patients to travel abroad when expertise was not available in their own countries. A key factor for this success is the cross-border IT platform - known as the Clinical Patient Management System 2.0 - provided by the European Commission for medical discussions, which enables experts to share patient data, including medical images and lab results, in a secure and protected environment that is fully compliant with all relevant security and data privacy requirements. ERNs have demonstrated resilience in crises such as the COVID-19 pandemic and the war in Ukraine, providing rapid, coordinated responses to sustain care for vulnerable patient groups. The first formal evaluation in 2023 confirmed that more than 95% of member centres met quality standards, underscoring the networks’ maturity and effectiveness. Moving into the next phase, the Joint Action JARDIN (2024–2027) aims to integrate ERNs into national healthcare systems to ensure sustainability and equitable access to high-quality RD care. Conclusions ERNs exemplify European solidarity and innovation in healthcare, transforming how rare disease expertise is shared and applied across borders. Their continued integration into national systems will be pivotal to achieving a truly cohesive European Health Union that delivers improved outcomes for all patients with rare and complex diseases.
