Glycated albumin (GA), the product of nonenzymatic glycation of serum albumin, reflects the mean glucose levels over the preceding approximately 2 weeks, bridging the gap between daily self-monitoring of blood glucose and the roughly 3-month window covered by glycated hemoglobin (HbA1c) measurement. First quantified in the early 1980s, GA was long overshadowed by HbA1c, but at present, interest has revived for two reasons. First, HbA1c assessment proves unreliable when the erythrocyte lifespan or hemoglobin glycation is perturbed, as in patients with renal failure, hemolytic anemia, hemoglobin variants, and iron deficiency. Second, continuous glucose monitoring has drawn attention to postprandial excursions and shortterm glucose variability that are not captured by HbA1c. This review revisits GA's biology, measurement, standardization, clinical utility, limitations, and evidence linking it to diabetic complications. Because it responds within 2 weeks to treatment and is markedly influenced by postprandial glucose excursions, GA supports early monitoring of therapy, and its ratio to HbA1c serves as an index of postprandial glycemia and insulin secretion. However, it must also be recognized that conditions that alter albumin turnover change GA levels independently of blood glucose levels. The prognostic value of GA is strongest in patients on maintenance hemodialysis, although recent studies in various cohorts and a meta-analysis have expanded situations in which GA measurement is of prognostic value. New measurement approaches, including finger-prick sampling, weekly home measurement, and noninvasive saliva and tear assays, point toward a renewed role for GA measurement in everyday glucose monitoring in individuals with diabetes.

Periprosthetic joint infection (PJI) remains one of the most serious complications following primary total knee arthroplasty (TKA), despite its relatively low incidence. Prevention requires addressing multiple interacting factors related to patient characteristics, microbial burden, antimicrobial prophylaxis, operative technique, and postoperative wound management. The objective of this review is to synthesize contemporary evidence on strategies for reducing infection risk in primary TKA, with particular emphasis on clinically actionable interventions, areas of controversy, and current evidence gaps. This narrative review integrated evidence from the source manuscript and its supporting evidence base, prioritizing TKA-specific systematic reviews, meta-analyses, randomized controlled trials, registry studies, large observational cohorts, clinical guidelines, and implementation studies. Evidence was evaluated according to study design, TKA relevance, consistency of findings, susceptibility to confounding, and applicability to current clinical practice. No de novo systematic search, formal risk-of-bias assessment, or meta-analysis was performed. Current evidence supports structured preoperative risk assessment and optimization, Staphylococcus aureus screening and decolonization, avoidance of intra-articular injections within three months before TKA when feasible, timely cefazolin-based systemic prophylaxis in patients without true contraindications, and stewardship-conscious antibiotic duration. Standardized antiseptic skin preparation and irrigation, efficient operative workflow, meticulous wound management, and early surveillance are also supported as components of a comprehensive prevention strategy. However, several controversies remain. Body mass index, glycemic control, nutritional status, anemia, and smoking are established risk markers, but evidence is insufficient to define universal thresholds for postponing surgery. Cefazolin remains the preferred prophylactic agent, although the optimal regimen for patients with true beta-lactam allergy or resistant-organism risk remains uncertain. Extended oral antibiotic prophylaxis may benefit selected high-risk patients but lacks sufficient evidence for routine use. Evidence regarding antibiotic-loaded bone cement and intraosseous antibiotic prophylaxis remains heterogeneous. Recent randomized evidence does not support routine intrawound vancomycin powder in primary TKA because it did not reduce infection and was associated with more minor wound complications. Persistent wound drainage also remains incompletely standardized in terms of escalation and surgical intervention. Infection prevention in primary TKA should be approached as a risk-stratified perioperative pathway rather than as a single intervention or universal checklist. Current evidence favors systematic host optimization, microbial-burden reduction, appropriate systemic prophylaxis, standardized antisepsis, efficient high-quality surgery, and structured wound surveillance, while selective use of controversial adjuncts should be guided by patient risk and local protocols. Future research should prioritize registry-nested randomized trials, standardized definitions of high-risk patients, procedure-specific outcomes, antimicrobial-stewardship measures, cost-effectiveness, and implementation studies evaluating complete perioperative prevention bundles.

To review the classification, epidemiology, etiology, prenatal diagnostic approach, and neurodevelopmental outcomes of fetal intracranial hemorrhage (ICH), and to provide clinicians with a practical, fetal-specific framework for investigating and counseling families facing this diagnosis. Narrative review of the current evidence on fetal ICH, encompassing intraventricular hemorrhage (IVH) and periventricular hemorrhagic infarction (PVHI), cerebellar hemorrhage, and extra-axial bleeding, with a primary focus on IVH as the most common presentation. The true prenatal incidence of fetal ICH is uncertain, with estimates of 0.5-1 per 10,000 pregnancies likely underestimating the true burden. Etiologies are diverse, including fetal-neonatal alloimmune thrombocytopenia (FNAIT), monogenic vasculopathies (notably COL4A1/COL4A2), congenital infection, fetal anemia, coagulopathy, and twin-related complications; however, a definitive cause is identified in fewer than half of cases even after complete workup, with a genetic etiology found in roughly 30% of fully investigated cases. Detailed neurosonography remains the primary diagnostic tool, with fetal MRI serving as an important adjunct for characterizing hemorrhage extent, associated parenchymal injury, and posterior fossa involvement. Outcomes vary substantially by hemorrhage grade, location, and laterality: low-grade IVH generally carries a favorable prognosis, while PVHI-for which the Bassan territorial classification aids prognostication-carries substantially higher rates of cerebral palsy, ventriculoperitoneal shunting, and cognitive impairment, particularly when extensive and bilateral. Existing prognostic data derive largely from small, heterogeneous neonatal cohorts using a grading system not designed for the fetal context, limiting the precision of individualized counseling. Fetal ICH is rare, etiologically heterogeneous, and variable in severity, and current evidence does not support precise individualized outcome prediction. A thorough, systematic evaluation and an interdisciplinary team approach are essential, with transparent communication about the inherent uncertainties forming the foundation of parental counseling.

Therapeutic goals in BCR::ABL1-negative myeloproliferative neoplasms (MPNs) are evolving to include biologically anchored measures of disease modification with control of blood counts, splenomegaly, and symptoms. Disease modification endpoints and their linkage to survival in MPNs were central to the framework of MPN Asia 2026, which took place in Seoul. This review summarizes key themes from MPN Asia 2026 and relevant recent literature, examining the evolving roles of molecular response and long-term clinical benefits within a broader disease-modification framework across polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF).

Multiple myeloma (MM) is a hematologic malignancy characterized by monoclonal plasma cell proliferation within the bone marrow. According to current International Myeloma Working Group (IMWG) criteria, true non-secretory multiple myeloma (NSMM) is defined by the absence of detectable monoclonal protein even on serum free light chain (FLC) assay, unlike oligosecretory multiple myeloma (OSMM), in which electrophoresis and immunofixation are negative but the FLC κ/λ ratio is pathological - making diagnosis particularly challenging by conventional techniques. The association of OSMM with an intracranial plasmacytoma is exceptional. We report the case of a 70-year-old hypertensive former smoker admitted for diffuse osteoarticular pain evolving over nine months, associated with gait disturbance and complete left oculomotor palsy. Laboratory workup revealed aregenerative anemia, thrombocytopenia, hyperleukocytosis with hyperlymphocytosis, and initially normal calcium (1.73 mmol/L), which secondarily worsened to 4.31 mmol/L during hospitalization. Serum/urine electrophoresis and immunofixation were negative, but FLC assay showed a pathological κ/λ ratio of 13.37, suggestive of OSMM. Bone marrow aspiration confirmed 75% dystrophic plasma cell infiltration. Whole-body magnetic resonance imaging (MRI) showed diffuse myelomatous infiltration with vertebral compression fractures, and orbito-cerebral MRI revealed an expansile clival lesion with bone lysis, invading the sella turcica, optic chiasm, carotid canal, and left cavernous sinus (360° carotid encasement), left petrous apex, and sphenoid sinus - for which chordoma, chondrosarcoma, bone metastasis, and lymphoma were excluded in favor of an intracranial plasmacytoma, based on convergent histological, marrow, and radiological findings. The patient was classified as International Staging System (ISS) stage I; cytogenetic testing could not be performed due to technical constraints and rapid clinical deterioration, limiting prognostic stratification (Revised-ISS (R-ISS) not calculable). Radiotherapy targeting the sphenoidal mass was initiated, combined with corticosteroid therapy and zoledronic acid for hypercalcemia; the neurological emergency and the patient's frailty led to favoring this local approach over standard systemic therapy. The clinical course was unfavorable, marked by septic shock due to a multidrug-resistant organism, leading to death before completion of radiotherapy. This case highlights the pivotal role of FLC assay in diagnosing OSMM when conventional techniques are negative, and the need for a multidisciplinary approach in cases of intracranial involvement. Biochemical (serial FLC) and radiological (brain MRI at three months, then every three to six months) follow-up remain recommended in the literature, as does high-performance liquid chromatography (HPLC), currently under validation for minimal residual disease detection - these points, however, remain general literature-based recommendations rather than conclusions drawn from our single observation.

Fanconi anemia (FA) is a rare inherited disorder of bone marrow failure that presents with progressive pancytopenia, multiple congenital abnormalities, and an increased predisposition to various malignancies. We describe a 19-year-old male who reported generalized weakness, shortness of breath on exertion, and a dry cough persisting for 1 month. He had undergone three blood transfusions within the preceding 3 months. Clinical examination revealed marked pallor without evidence of jaundice, cyanosis, clubbing, or lymphadenopathy. Laboratory investigations showed pancytopenia, while bone marrow biopsy demonstrated normocellular marrow with trilineage hematopoiesis and mild hemophagocytosis. Radiological assessment identified bilateral ectopic kidneys, and serum ferritin levels were significantly elevated (2753.93 ng/mL). These findings raised a strong clinical suspicion of FA, which was subsequently confirmed through comprehensive genetic testing. This case underscores the importance of considering FA in young adults with unexplained pancytopenia and congenital anomalies, highlighting the need for an integrated, multidisciplinary diagnostic and management approach.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2026 Clinical Practice Guideline for the Management of Anemia in Chronic Kidney Disease (CKD) provides an update of the 2012 version. Its scope includes anemia diagnosis and use of iron therapy, erythropoiesis-stimulating agents (ESAs), hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs), and red blood cell (RBC) transfusions to treat anemia in CKD.

Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome (CBMFS) primarily managed with corticosteroids and blood transfusions; however, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the sole curative option when these therapies fail or relapse occurs. We report the case of a 21-year-old woman diagnosed with DBA caused by an RPS19 mutation shortly after birth. Although she responded well to corticosteroid therapy until 18 years of age, discontinuation led to relapse and subsequent transfusion dependence, necessitating allogeneic transplantation. In the absence of a human leukocyte antigen (HLA)-matched donor, she underwent post-transplantation cyclophosphamide (PT-Cy)-based haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) at 21 years of age, utilizing her father as the donor. Myeloablative conditioning was performed using fludarabine, melphalan, and busulfan. For acute graft-versus-host disease (GVHD) prophylaxis, PT-Cy (50 mg/kg on days 3 and 4), tacrolimus, and mycophenolate mofetil were administered, resulting in successful neutrophil engraftment on day 16 post-transplantation. Although the patient developed acute GVHD (grade II), it resolved with corticosteroid therapy. Post-discharge, she was readmitted due to acute gastrointestinal GVHD (grade II), which improved after methylprednisolone administration. She was discharged on day 92 and achieved complete transfusion independence for the past 5 years, making this the first reported case of long-term survival following PT-Cy-based haplo-PBSCT for this condition. Including our patient, there are only four reported cases of allo-HSCT using PT-Cy for adult patients with DBA; notably, all patients survived without developing severe GVHD or infectious complications. Generally, transplant outcomes for DBA worsen with increasing age due to severe GVHD and organ damage secondary to long-term iron overload. Given that DBA is a non-malignant disease, meticulous attention must be paid to prevent unnecessary GVHD and graft failure. In adult patients with DBA, PT-Cy yielded successful engraftment and safety, with no incidence of severe GVHD, leading to long-term survival and minimal complications. These findings suggest that allo-HSCT utilizing PT-Cy remarkably expands donor options for congenital bone marrow failure syndromes. Consequently, this approach is expected to become a promising therapeutic strategy not only for hematologic malignancies but also for non-malignant disorders.

Sickle cell disease (SCD) presents substantial interindividual clinical variability that remains only partially explained by genotype, fetal hemoglobin (HbF), and co-inherited alpha-thalassemia. We investigated whether endogenous metabolites modulate the sickling tendency, independently of HbF. We analyzed 368 steady-state HbSS patients with oxygen gradient ektacytometry (Point of Sickling [PoS]) and untargeted metabolomics (DI-HRMS, 1309 metabolites). PoS was adjusted for HbF for ANOVA analysis (A-FDR p ≤ 0.05). Linear regression (lr) models were adjusted for HbF, age, alpha-thalassemia, Oxygenscan device, and hydroxyurea (lr-FDR p ≤ 0.05). 111 metabolites differed between adjusted-PoS groups, and 27 metabolites associated with PoS in lr. Seven metabolites overlapped across approaches. Increased sickling (higher PoS) positively correlated with glycolytic and pentose phosphate pathway intermediates, glyceraldehyde-3-phosphate (A-FDR <0.001), 2,3-DPG (A-FDR = 0.002; lr-FDR = 0.004), and ribulose-5-phosphate (A-FDR <0.001). RBC membrane remodeling markers, including carnitines (lr-FDR = 0.002), and oxidative stress and inflammation metabolites: glutathione disulfides (A-FDR = 0.001), acetylated citrulline (A-FDR < 0.001; lr-FDR = 0.009), spermidine (lr-FDR = 0.03), and acetylated tryptophan (A-FDR = 0.03; lr-FDR = 0.03), were also elevated in this group. Low PoS associated with downstream tryptophan metabolites (A-FDR < 0.001, 0.006), indicating inflammatory regulation. Overall, this study demonstrates that metabolic processes are associated with sickling tendencies independent of HbF, providing insights into SCD heterogeneity, identifying candidate metabolic pathways, and supporting current strategies to target glycolysis in SCD.

The molecular determinants of phenotypic severity in red cell enzymopathies are often obscured by the disconnect between coding sequence variants and their regulatory landscapes. Here we present a single-patient molecular case study that uses an integrative multi-omic approach-combining short-read WGS, PacBio HiFi long-read sequencing, native CpG methylation profiling, and Iso-Seq full-length transcriptomics-to characterize a severe, transfusion-dependent hemolytic anaemia. We identified a compound heterozygous state in the glucose-6-phosphate isomerase (GPI) gene, with no wild-type allele present. One allele (Haplotype 1) carried a missense variant (p.His191Arg); the other (Haplotype 2) carried a distinct missense variant, c.1414C>T (p.Arg472Cys), previously reported as biochemically unstable. Long-read phasing placed the two variants in trans. Allele-resolved transcript counts showed a directionally consistent but statistically non-significant trend toward higher expression of Haplotype 2 across two Iso-Seq replicates. Notably, the c.1414C>T transition abolishes a local CpG dinucleotide; in a small number of haplotype-2 reads spanning this position, the corresponding cytosine on the wild-type/Haplotype-1 background was methylated. We did not measure GPI protein abundance, enzymatic activity, or stability in this patient, and we do not establish that methylation at this site regulates GPI transcription. On the basis of these correlative observations in a single patient, we propose-as a hypothesis for future testing-that a coding variant might simultaneously perturb protein stability and disrupt a local epigenetic mark, and we outline the experiments required to test whether such a dual effect contributes to disease. This case illustrates the value of integrative long-read multi-omics for generating mechanistic hypotheses about variants of uncertain significance, while underscoring that causal claims require dedicated functional validation.