Thalassemia is one of the most common monogenic disorders in southern China, with the Hakka population exhibiting a distinct genetic profile. This study evaluated whether next-generation sequencing (NGS)-based universal screening offers advantages over traditional cascade screening in this specific population. We enrolled 91,857 reproductive-age individuals in Ganzhou, a high-prevalence Hakka region, comparing 37,500 participants who underwent traditional screening (2019-2021) with 54,357 who received NGS-based screening. NGS-based screening detected thalassemia carriers at a rate 4.74 times higher than traditional screening (15.05% vs. 3.18%), particularly identifying silent α-thalassemia and β++-thalassemia variants that were substantially under-detected by the traditional approach. Crucially, while traditional screening identified 98.7% of β‑high‑severity couples, it detected only 71.4% of α‑high‑severity couples and missed 28.6% of those at risk for Hb Bart's hydrops fetalis, as well as 32.7% of couples at risk for severe non‑deletional Hb H disease. Traditional screening cost only USD 3.90 per person (versus USD 21.00 for NGS) and provided faster results (6.40 vs. 13.06 days). NGS-based universal screening provides a more accurate assessment of thalassemia burden and genotype diversity, offering critical advantages for prevention programs. Although traditional cascade screening is more cost-effective, its limited sensitivity for α-thalassemia variants leads to substantial underdetection. These findings underscore the need to tailor screening protocols to local epidemiological and genetic characteristics.

Schwannoma is a benign, encapsulated, slow-growing tumor that arises from Schwann cells. Approximately 25%-45% of extracranial schwannomas occur in the head and neck region, accounting for 1%-8% of all neoplasms. However, involvement of the infraorbital nerve is exceptionally rare. This report describes the surgical management of an infraorbital nerve schwannoma using a transconjunctival approach with lateral canthotomy, and documents the clinical, functional and aesthetic outcomes at 12 months. A 32-year-old woman with a history of hypochromic microcytic anemia presented with a progressively enlarging mass in the right infraorbital region that had been present for four years, associated with mild paresthesia in the nasolabial region. The main reason for consultation was aesthetic concern due to facial protrusion. Physical examination revealed a firm, painless subcutaneous mass without local inflammatory signs. Contrast-enhanced computed tomography revealed a solid, lobulated lesion measuring approximately 60 mm in maximum diameter in the right infraorbital region. Imaging features suggested an origin from the infraorbital foramen and involvement of the corresponding nerve; there was no evidence of osteolysis. Fine-needle aspiration cytology (FNAC) suggested a mesenchymal neoplasm. Surgical excision was performed under general anesthesia via a transconjunctival approach with lateral canthotomy. The infraorbital nerve was identified and preserved intraoperatively. Histopathological examination confirmed a schwannoma, showing spindle-shaped cells with Verocay bodies. The patient had a favorable clinical course. At the 12-month follow-up, facial symmetry and preserved sensory function were confirmed, as was the absence of recurrence.

β-thalassemia comprises a clinically heterogeneous group of disorders in which anemia severity, transfusion exposure, iron loading, and organ complications vary widely among individuals. This structured narrative review summarizes practical applications of precision medicine in transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT), with explicit attention to which strategies apply to each clinical category. Literature indexed in PubMed and Scopus from 2000 to 2025 was reviewed using terms related to thalassemia, precision medicine, magnetic resonance imaging (MRI), chelation tailoring, next-generation sequencing (NGS), fetal hemoglobin (HbF) modifiers, luspatercept, mitapivat, hepcidin, gene therapy, gene editing, and artificial intelligence (AI). Evidence was synthesized descriptively because interventions, outcomes, and populations were heterogeneous, and no pooled meta-analysis was performed. In TDT, precision care is centered on individualized transfusion planning, extended red-cell antigen matching, MRI-guided cardiac and hepatic iron monitoring, organ-directed chelation intensification, and selection of disease-modifying or curative approaches. In NTDT, precision care emphasizes accurate phenotype classification, MRI liver iron concentration, because serum ferritin may underestimate iron burden, selective chelation, surveillance for NTDT-specific complications, and individualized use of agents that improve anemia. Personalized chelation should include deferiprone, either alone or in combination, when cardiac iron is increased. Comprehensive molecular diagnosis should include HBB together with HBA1 and HBA2 assessment, while secondary and tertiary modifiers help explain phenotypic variability and complication risk. Hepcidin and growth differentiation factor 15 (GDF-15) are discussed as investigational biomarkers; transferrin saturation is not recommended for routine iron-overload assessment in thalassemia. AI currently has its strongest role in screening and diagnosis, whereas risk-stratification models remain exploratory. Equitable implementation requires standardized TDT/NTDT pathways, regional MRI and genomics access, longitudinal registries, and multidisciplinary interpretation.

Acquired gastrointestinal vascular malformations not due to congenital disorders such as hereditary hemorrhagic telangiectasia are a common cause of chronic and acute hemorrhage, particularly in older adults. These lesions cause severe anemia, dependence on intravenous iron and/or red-cell transfusion, and recurring hospitalizations. Hemostatic procedures are temporizing and no standard treatment, including the somatostatin analogs, addresses the underlying angiogenic dysregulation driving vascular malformation formation and recurrence. Therefore, bevacizumab, an anti-VEGF-A monoclonal antibody, is a promising targeted therapeutic. In this observational cohort study, we analyzed 32 patients (median age 75 years, 44% female) with acquired gastrointestinal vascular malformations due to idiopathic angiodysplasia, chronic liver disease, or deficiencies of von Willebrand factor who were treated on a predefined institutional bevacizumab pathway. The median Hematologic Support Score (a composite endpoint integrating red-cell units transfused and elemental iron infused) improved from 15.04 (95% CI, 11.16-21.80) red-cell unit equivalents during 6 months pretreatment to 4.08 (4.00-8.00) during Months 1-6 of bevacizumab treatment (p < 0.001) and further to 0.00 (0.00-5.40) during months 7-12 (p < 0.001). Units of red cells transfused and quantity of elemental iron infused were analyzed independently; both significantly improved after bevacizumab initiation. Annualized hospitalization/ED visit rate improved from 3 (year before bevacizumab) to 1 (year after bevacizumab) (p = 0.01), and median hemoglobin improved by 3.1 g/dL after bevacizumab (p < 0.001). Proteinuria and hypertension occurred in 8 (25%) and 5 (16%) patients, respectively, leading to bevacizumab discontinuation in 3 (9%). In conclusion, bevacizumab is a novel, targeted therapeutic approach for acquired gastrointestinal vascular malformations that may be safe and effective.

This case describes a structured, multifactorial framework for interpreting tacrolimus therapeutic drug monitoring in a complex liver transplant recipient, with hypothesis-generating implications for clinical decision-making. This was a single-patient case report with serial therapeutic drug monitoring and longitudinal clinical follow-up. The clinical course of a 33-year-old male liver transplant recipient was documented in detail. During a 90-day hospitalization, the patient underwent two liver transplantations and experienced abnormal liver function, progressive anemia, and severe diarrhea, accompanied by marked fluctuations in tacrolimus trough concentrations (Ctac). Hematocrit (HCT)-corrected standardized concentrations (Cstd) were calculated using the formula Cstd = Cmeasured × (45/HCT[%]) as an interpretive aid for whole-blood Ctac during marked anemia. Across serial measurements in this single patient, tacrolimus whole-blood trough concentrations showed a positive descriptive association with HCT. Three distinct pharmacokinetic phases were identified: (1) early severe hepatic dysfunction, during which the expected CYP3A5 extensive-metabolizer phenotype appeared to be masked (peak C/D ratio: 7.70), likely attributable to compromised hepatic metabolic capacity; (2) recovery with markedly reduced HCT associated with apparently low whole-blood trough concentrations (nadir measured C: 3.2 ng/mL; corrected Cstd: 7.0 ng/mL) supporting cautious interpretation during severe anemia;and (3) inflammatory diarrhea associated with increased tacrolimus exposure (C/D ratio increased approximately 55%), possibly related to altered intestinal drug transporter and metabolic enzyme activity. Dose adjustments guided by the structured strategy successfully maintained drug exposure within the target range throughout the 90-day course without confirmed rejection episodes or severe tacrolimus-related toxicity. This case illustrates how a structured, multifactorial approach to tacrolimus therapeutic drug monitoring interpretation may assist clinical decision-making in complex post-liver-transplant settings. The proposed framework integrates pharmacological mechanisms with clinical evidence to address challenges in tacrolimus TDM interpretation. Prospective validation is required before the proposed framework can be recommended as a generalizable clinical strategy.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have rapidly expanded beyond the treatment of type 2 diabetes mellitus (T2DM) and obesity, with increasing relevance to dermatologic practice as more patients present while receiving these therapies. This medication class now includes oral formulations including oral semaglutide and the first non-peptide oral GLP-1RA, orforglipron as well as next-generation triple agonists such as retatrutide, which demonstrated up to 24.2% body weight reduction in phase 2 trials and a favorable body composition profile, with preferential fat over lean mass loss. Although GLP-1 RAs provide substantial metabolic and weight reduction benefits, their growing use has introduced a broad spectrum of systemic and cutaneous adverse effects that dermatologists must recognize and monitor. This review summarizes the current evidence regarding the safety profile of GLP-1RAs with emphasis on dermatologic implications and interdisciplinary monitoring considerations. Common adverse effects include gastrointestinal (GI) intolerance, nutritional deficiencies, gallbladder disease, pancreatitis, and loss of lean body mass. Other rarer potential side effects include anemia, neuropsychiatric, and sexual health effects. Emerging data also suggest associations with ophthalmologic complications, skeletal fragility in older adults, and alterations in body composition that may influence cosmetic and procedural outcomes. Dermatologic adverse events include alopecia, eczematous and hypersensitivity eruptions, bullous and pustular dermatoses, acneiform eruptions, hyperhidrosis, and significant facial volume loss ("Ozempic face"). Current evidence regarding GLP-1RA use in pregnancy remains limited and evolving, with recommendations generally advising discontinuation prior to conception. Given the increasing overlap between metabolic disease management and dermatologic care, dermatologists should understand contraindications, screening strategies, nutritional monitoring, and counseling considerations associated with GLP-1RA therapy. A multidisciplinary approach involving primary care physicians, endocrinologists, ophthalmologists, dietitians, and dermatologists is essential to optimize patient safety while maintaining the substantial therapeutic benefits of these medications.

In the current study, we genetically engineered Salmonella Typhimurium to serve a dual purpose in cancer immunotherapy, simultaneously inducing apoptosis and activating anti-cancer immune responses. Tumor-residing tryptophan auxotrophic Salmonella, featuring trpA and trpE deletions, selectively inhabits the tumor microenvironment, promoting tumor-targeted delivery of therapeutic antigens such as apoptin (an apoptosis inducer) and carcinoembryonic antigen (CEA; related to anti-cancer immunity), while minimizing off-target effects. The therapeutic strain had reduced endotoxic responses owing to a lack of pagL in its genome. Additionally, to enhance adaptation to the tumor microenvironment, the strain underwent consecutive passaging for over five generations, increasing its potency for tumor recognition and localization. A prokaryotic and eukaryotic dual-expression plasmid was developed by incorporating the complete apoptin open reading frame into the eukaryotic region and the CEA epitope collection associated with an MHC-II agonist peptide into the prokaryotic expression cassette. Each antigen was confirmed for successful expression at the intended sizes, with functional validation performed through in vitro cytotoxicity assessment. Mouse inoculation studies demonstrated that the Salmonella therapy significantly suppresses the progression of highly aggressive 4T1 breast cancer tumors as well as metastatic dispersion in lung, liver, and spleen tissues, fostering an anti-tumoral immune environment characterized by IFN-γ and CCL2 markers. This transformative approach to Salmonella-mediated cancer immunotherapy could pave the way for targeted treatments for immune-resistant cancers and hard-to-treat malignancies.

Anemia is a nearly universal complication of chronic kidney disease (CKD). While erythropoiesis-stimulating agents (ESAs) are the standard of care, they rarely induce acquired pure red cell aplasia (PRCA) via neutralizing anti-erythropoietin (anti-EPO) antibodies. Diagnosis is often delayed as clinical focus frequently shifts toward more common causes of acute anemia, such as hemorrhage. An 88-year-old male on maintenance hemodialysis presented with a precipitous hemoglobin drop to 6.8 g/dL. Investigation revealed replete hematinics but profound reticulocytopenia. After excluding occult gastrointestinal bleeding, hemolysis, and nutritional deficiencies, a bone marrow biopsy demonstrated isolated erythroid aplasia with preserved myeloid and megakaryocytic lineages, leading to a diagnosis of PRCA. Anti-EPO antibody testing was not performed, which limits definitive etiological confirmation. Due to the high risk of immunosuppression in an elderly patient and the limited accessibility of hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs), management was restricted to ESA cessation and supportive transfusions. This case highlights the diagnostic approach for severe anemia and the significance of profound reticulocytopenia in PRCA. The definitive hallmark remains the detection of circulating anti-EPO antibodies paired with a bone marrow study demonstrating near-total depletion of erythroid precursors, but preserved myeloid and megakaryocyte lineages. Management includes the permanent cessation of ESAs, immunosuppression to reduce circulating antibodies, and supportive blood transfusions. In chronic hemodialysis patients, early recognition of iatrogenic PRCA is essential to prevent the continued administration of potentially harmful ESAs and to facilitate a transition toward alternative therapies, such as HIF-PHIs.

Pancreatic cancer (PC) is a highly lethal malignancy. 4-10% are linked to inherited mutations in genes such as BRCA1/2, PALB2, ATM and mismatch repair (MMR) genes. Germline testing is essential to guide treatment decisions, yet delays remain common. Genetic testing models without pre-test assessment in a Hereditary Cancer Unit (HCU), have emerged as a strategy to improve earlier clinical decision-making. A retrospective, observational and descriptive study was conducted on 223 PC patients (55% male; average age 64 years) who underwent rapid germline genetic testing at Hospital General Universitario Gregorio Marañón (Madrid, Spain) between April 2019 and May 2024. Tests were ordered by oncologists with brief pre-test counseling, followed by a nurse-facilitated consent and peripheral blood collection. Post-test counseling in an HCU was offered for patients with variants of unknown significance (VUS) and pathogenic/likely pathogenic variants (PV), or upon physician or patient request. PV and VUS were identified in 32 (14.3%) and 82 (36.7%) patients, respectively. 50% of PV carriers did not meet familial PC criteria. Actionable mutations were detected in 14 (43.7%) of PV carriers, involving BRCA2 (6/32), PALB2 (1/32) and ATM (7/32). Treatment modifications occurred in 7/223 patients (3%), including PARP inhibitors or platinum-based regimens. Median time from the genetic test request to the results was 48 days (95% CI, 44-52). Mainstream genetic testing in PC is a viable approach to expedite results and facilitate precision oncology. Further studies are needed to evaluate long-term outcomes, cost-effectiveness and the psychosocial impact compared to traditional genetic counseling pathways.

Background/Objectives: Celiac disease (CD) is an immune-mediated enteropathy with gastrointestinal and extraintestinal manifestations. In primary care, recognition can be delayed when psychiatric symptoms, arthralgia, thyroid dysfunction, alcohol exposure, and liver-test abnormalities coexist. This case report describes a confounder-aware diagnostic approach to histologically confirmed CD in a patient with a multifactorial primary-care presentation. Methods: We report a single-patient, de-identified reflective case from routine family medicine practice, organized according to CARE case-report principles. Results: A woman in her early sixties with hypothyroidism and glaucoma presented with new low mood, anhedonia, somnolence, generalized anxiety, increased alcohol intake, poor appetite, weight loss, abdominal bloating, diarrhea, flatulence, and polyarthralgia. Initial investigations, including celiac serology obtained before gluten-free diet advice, showed mild anemia, marked hyperferritinemia, severe cholestatic and hepatocellular liver-test abnormalities, uncontrolled hypothyroidism, and strongly positive tissue transglutaminase IgA (>250 kIU/L; reference 0.0-14.9). Radiographs showed mild osteoarthritis and osteopenia without erosive arthropathy. Computed tomography excluded malignancy but showed severe diffuse hepatic steatosis and mild pancreatic atrophy. Mirtazapine was started at the index visit; after the initial laboratory results, gluten-free diet advice, alcohol-reduction counseling, and levothyroxine adjustment were undertaken. During the diagnostic episode, small-bowel biopsy demonstrated moderate-to-severe crypt hyperplastic villous atrophy with increased intraepithelial lymphocytes, and gastric biopsies showed no significant pathology; the histology was consistent with CD. Symptoms improved substantially. Longer-term objective follow-up showed persistent but improved celiac serology (tTG-IgA 49.4 kIU/L), normalization of thyroid-stimulating hormone, partial improvement in gamma-glutamyl transferase, which remained elevated, and a later iron-deficiency pattern with persistent anemia. Conclusions: This case supports targeted CD testing when anxiety or depressive symptoms occur alongside gastrointestinal symptoms, weight loss, arthralgia, hypothyroidism or documented thyroid autoimmunity, anemia, osteopenia, or liver-test abnormalities. Histology and repeat serology confirmed the diagnosis, but the psychiatric and hepatic manifestations still require cautious interpretation because hypothyroidism, alcohol exposure, steatotic liver disease, and simultaneous treatments also shaped the clinical course.

Postoperative complications following colorectal surgery-including anastomotic leak (AL), surgical site infection (SSI), perioperative haemorrhage and colovesical fistula-represent major causes of patient morbidity and mortality, prolonged hospitalisation, and healthcare expenditure. This review summarises contemporary evidence across two key domains of complication management-prevention and diagnosis-applied to four major complications (AL, SSI, perioperative haemorrhage, and colovesical fistula), drawn from a comprehensive literature review of recent randomised controlled trials, systematic reviews, meta-analyses, and prospective cohort studies. Preventive strategies discussed include optimisation of surgical techniques (minimally invasive and robotic approaches, indocyanine green perfusion assessment, self-expanding metal stent bridge-to-surgery, and negative pressure wound therapy), modification of patient factors where possible (obesity, anaemia, malnutrition, and immunosuppression), and system-level interventions including Enhanced Recovery After Surgery (ERAS) protocols, perioperative beta-blockade, prehabilitation, and structured quality improvement bundles. Diagnostic strategies have evolved to incorporate biomarker surveillance (CRP and procalcitonin), drain fluid pH analysis, CT imaging (including angiography), endoscopy, and novel digital health tools including wearable monitoring and mobile health applications. Reducing the risk of postoperative complications should involve a multidisciplinary, protocolised approach combining intraoperative technique optimisation with structured perioperative care bundles and close post-discharge surveillance, and centralisation to specialist colorectal surgical units.