Search Results (170)

Nodal T-follicular helper cell lymphomas comprise a biologically similar but morphologically diverse family of T-cell neoplasms, including angioimmunoblastic T-cell lymphoma, nodal T-follicular helper cell lymphoma, follicular-type, and nodal TFH lymphoma, not otherwise specified. Despite recurrent molecular alterations involving RHOA, IDH2, TET2, and DNMT3A, the diagnosis of TFH lymphomas remains challenging because of their mimicry of other lymphoid neoplasms and reactive lymphadenopathy. A key pitfall is confusion with classical Hodgkin lymphoma, as admixed Epstein–Barr virus-positive large B-cells with Reed–Sternberg cell-like morphology and immunophenotype can be found in TFH lymphomas. Similarly, follicular-type TFH lymphoma is often misclassified as follicular B-cell lymphoma unless T-cell lineage is investigated by immunophenotyping and the absence of BCL2 or BCL6 rearrangement is established. The ‘not otherwise specified’ category should be reserved for cases with proven T-follicular helper immunophenotype but lacks definitive angioimmunoblastic or follicular architecture. Comparing current frameworks, 5th edition of the World Health Organization classification permits rare CD4/CD8 double negative cases, while International Consensus Classification requires CD4 positivity. Some of these distinctions may appear taxonomic as all T-follicular helper T-cell lymphoma subtypes share molecular alterations, prognosis, and treatment approach. However, these classifications are meaningful from the perspective of a histopathologic diagnosis as a wrong diagnosis may lead to ineffective treatment approach. Accurate recognition of these lymphomas prevents misclassification, avoids inappropriate regimens, and ensures eligibility for proper clinical trials. A structured approach integrating morphology, multiparameter immunohistochemistry, flow cytometry, and molecular testing provides the best safeguard against diagnostic pitfalls and refines classification across subtypes. Full article

Background/Objectives: Cardiovasc{Citation}ular disease accounts for 50% of chronic kidney disease (CKD) mortality, yet fewer than 40% of patients achieve guideline LDL-cholesterol (LDL-C) targets on statins. Injectable lipid-lowering therapies (ILLTs)—PCSK9 inhibitors and inclisiran—offer 50–70% LDL-C reductions but lack comprehensive CKD-specific evidence synthesis. This systematic review evaluated ILLT efficacy, safety, and implementation across kidney function stages including dialysis. Methods: Following PROSPERO registration (CRD42024612594), we searched MEDLINE, Embase, Cochrane Library, CINAHL, and Google Scholar (1995–August 2025). Two reviewers independently screened studies using PICOS criteria: adults with CKD stages G3-G5, dialysis, or transplant recipients receiving injectable lipid therapies. Primary outcomes were LDL-C percentage change and major adverse cardiovascular events. Quality was assessed using NIH tools. Given heterogeneity, we performed narrative synthesis following SWiM guidance. Results: Eight studies (n = 28,013) met the criteria. The FOURIER trial demonstrated that evolocumab achieved 58–59% LDL-C reductions across kidney function strata (interaction p = 0.77) with preserved cardiovascular benefit (HR 0.82–0.89). Absolute risk reduction was greater in advanced CKD (2.5% vs. 1.7%), reflecting higher baseline rates. Pharmacokinetic studies showed no eGFR-exposure correlation requiring dose adjustment; evolocumab was not removed by haemodialysis. Inclisiran achieved a 67–80% PCSK9 reduction and a 35–58% LDL-C reduction across renal groups, with twice-yearly maintenance dosing. Both classes reduced non-HDL-C (45–50%), apoB (40–45%), and lipoprotein(a) (20–25%). Safety was favourable, with mild injection-site reactions (< 5%); no renal decline signals emerged. Conclusions: Evidence for injectable lipid-lowering therapies in CKD are driven largely by a single large post hoc subgroup analysis (FOURIER) and small phase 1–2 PK/PD studies, with minimal dialysis representation and no transplant data. These agents appear to provide substantial LDL-C reductions across CKD stages G3–G5 without dose adjustment, but cardiovascular and renal outcome data in advanced CKD and dialysis remain limited and should be interpreted cautiously. Full article

Background/Objectives: Influenza, RSV, and SARS-CoV-2 co-circulate and evolve under immune and therapeutic pressures, complicating decision-making for both vaccine formulation and antiviral use. Fragmented, pathogen-specific sequencing approaches limit cross-virus comparability. Methods: We applied a standardized, multiplexed, amplicon-based next-generation sequencing (NGS) workflow to 34 diagnostic specimens (Ct < 35) positive for influenza A/B, RSV-A/B, or SARS-CoV-2. Sequencing libraries were generated and run on an Illumina MiSeq platform (2 × 250 bp). Although the wet-lab workflow is standardized across pathogens, consensus generation and annotation utilized two different analysis environments: Geneious Prime for influenza and MicrobioChek for RSV and SARS-CoV-2. Quality metrics included genome breadth and depth of coverage. Results: Near-complete genomes (mean coverage ≥98%) were recovered for all samples. Influenza A(H1N1)pdm09 sequences clustered in clade 6B.1A; A(H3N2) clustered in subclade 3C.2a1b.2a.2; and influenza B belonged to the Victoria lineage V1A.3a.2. RSV sequences were assigned to Nextclade clades A.D.5.1, A.D.1.10, A.D.2.1, and A.D.3 (RSV-A) and to B.D.4.1.3 and B.D.E.1 (RSV-B), consistent with the ON1 (RSV-A) and BA (RSV-B) genotypes prevalent in recent seasons. Clinically relevant mutations included changes in the influenza HA site and neuraminidase substitutions, RSV F-protein polymorphisms, and spike protein substitutions associated with recent Omicron sublineages (L455F/S, F456L) in SARS-CoV-2. Conclusions: A unified amplicon–NGS approach yields harmonized genomic data across respiratory viruses, enabling timely detection of antigenic drift and resistance markers while supporting integrated, cross-pathogen surveillance. Full article

During hemorrhagic procedures, autotransfusion is one of the main strategies for patient blood management. While conventional cell savers only concentrate red blood cells due to the centrifugation method, the innovative same™ autotransfusion medical device (i-SEP, Nantes, France), based on a hollow-fiber filtration technology, has the ability to preserve red blood cells along with the majority of platelets. Background/Objectives: The present study aimed at comparing the functionality of preserved platelets in the clot formation by using Quantra^® and/or ROTEM^® Point-Of-Care coagulation tests, after blood treatment for autotransfusion with either a standard centrifugation-based system (Xtra^® device, LivaNova, London, UK), or the filtration-based same™ device. Methods: First, coagulation was assessed in an in vitro experiment, where human blood samples were used to obtain ten treated blood products by each autotransfusion device that were evaluated with or without supplementation of plasma poor or rich in platelets. Then, to confirm the potential clinical benefit of the platelet preservation in a surgical context, coagulation was studied in vivo using a massive surgical hemorrhagic model on eight minipigs per device. Samples were collected after reinfusion steps and during a 6 h post-operative follow-up. Results: Both in vitro and in vivo, the same™ device consistently retained more platelets compared to the Xtra^® device. This enhanced preservation resulted in significantly stronger clot formation, likely due to higher platelet concentration and superior functional integrity. Conclusions: These findings highlight the potential clinical benefit of same™-recovered platelets for improving hemostasis during hemorrhagic surgery. Full article

Background: Pulmonary rehabilitation (PR) is increasingly used across the lung-cancer care pathway, but the scope, effectiveness, and optimal delivery of programmes remain variably reported. Objective: To examine the effectiveness of PR in adults undergoing lung cancer surgery across preoperative perioperative, and post operating settings. Methods: We conducted a narrative synthesis of studies evaluating PR interventions in patients undergoing lung cancer resection. Eligible designs included randomised, non-randomised trials and observational studies published between 2021 and 2025. Interventions were classified by timing (preoperative, perioperative, postoperative) and by completeness of PR content. Full PR was defined as programmes including structured exercise training, at least one respiratory-specific component, and structured education and/or supportive interventions. Outcomes of interest included postoperative pulmonary complications (PPCs), length of stay (LOS), functional capacity, ventilatory function, symptoms and health-related quality of life (HRQoL). Results: Across perioperative phases, PR was feasible and safe, with consistent improvements in functional capacity and patient-reported outcomes. Preoperative PR reliably improved presurgical fitness with reductions in PPCs and LOS most evident in supervised and physiologically targeted programmes. Perioperative PR integrated within enhanced recovery pathways supported early mobilisation and respiratory recovery. Postoperative PR accelerated recovery of exercise capacity, respiratory symptoms, and HRQoL beyond expected natural recovery. Programmes classified as Full PR demonstrated more consistent and broader benefits across outcome domains compared with Partial PR. Substantial heterogeneity in intervention design and outcome measurement was observed. Conclusions: Pulmonary rehabilitation is an effective, multidimensional intervention across the surgical lung cancer continuum. Comprehensive, multimodal programmes appear to confer the greatest clinical benefit. Standardisation of PR content and outcome measurement is needed to strengthen evidence synthesis and guide implementation in perioperative lung cancer care. Full article

Glutamine metabolism has emerged as one of the most critical bioenergetic and biosynthetic programs sustaining leukemic cell growth, survival, stemness and therapeutic resistance. In both acute and chronic leukemias, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), malignant cells display a strong dependency on extracellular glutamine to support mitochondrial respiration, anabolic biosynthesis and redox homeostasis. This dependency is reinforced by oncogenic signaling networks, post-transcriptional metabolic regulation and microenvironmental adaptation within the bone marrow niche. Therapeutic strategies targeting glutamine utilization, including glutaminase inhibition, transporter blockade and enzymatic glutamine depletion, have demonstrated robust antileukemic activity in preclinical models, and early clinical efforts have begun to explore glutamine-directed interventions in myeloid neoplasms. However, metabolic plasticity, microenvironment-derived nutrient buffering and systemic toxicity remain significant limitations to clinical translation. This review provides a detailed synthesis of the biochemical framework of glutamine metabolism in leukemia, the molecular mechanisms enforcing glutamine addiction, the downstream functional consequences on proliferation, redox balance and leukemic stem cell biology, the current landscape of therapeutic strategies and emerging directions aimed at overcoming resistance and improving clinical efficacy. Full article

Breast cancer remains the most frequently diagnosed cancer in women worldwide, with outcomes strongly dependent on stage at detection. Conventional imaging modalities such as mammography, ultrasound and MRI are limited by reduced sensitivity in dense breasts, radiation exposure, high cost and restricted availability in low-resource settings. This review critically examines microwave imaging (MWI) as a non-invasive, radiation-free and an emerging resource-efficient breast imaging modality that exploits dielectric contrast between healthy and malignant breast tissues. We first summarise experimental and clinical evidence on breast dielectric properties and their implications for numerical phantoms and device design. We then review passive, active (tomographic and radar-based) and hybrid MWI systems, including key clinical prototypes such as SAFE, MammoWave, MARIA and Wavelia, and analyse associated image-reconstruction algorithms from classical inverse scattering to advanced beamforming, Huygens-based methods and AI based reconstruction. Finally, we discuss outstanding challenges—tissue heterogeneity, calibration, hardware constraints and computational complexity—and identify future directions including AI-assisted reconstruction, multimodal hybrid imaging and large-scale clinical validation needed to translate MWI into routine breast cancer screening and diagnosis. Full article

Background/Objectives: Diabetic Foot Ulceration (DFU) is one of the most debilitating and costly complications of diabetes mellitus, representing a significant cause of morbidity, disability, and healthcare burden worldwide. Refractory non-healing ulcers that fail to respond to conventional therapies require novel adjuvant treatment modalities. This clinical audit aimed to evaluate the long-term clinical outcomes of an autologous, bioactive platelet-rich fibrin (PRF) matrix combined with topical gentamicin in patients with chronic, non-healing DFUs. Methods: A retrospective observational audit was conducted, involving eleven patients with refractory DFUs who underwent adjunctive treatment with a PRF matrix (Arthrozheal^®) and co-applied gentamicin. Patients were followed at three-week intervals using standardised wound imaging (Silhouette^® 3D) to assess healing parameters. Long-term follow-up data, evaluating healing durability and complications, is presented. Results: All patients completed the treatment protocol, with significant reductions in mean wound area (87.9%), perimeter, depth, and volume (all p < 0.05). Epithelialised tissue increased from 24.7% to 82.8%. At 12 months, 81.8% of patients maintained complete ulcer healing. Two patients experienced complications: one ulcer recurrence requiring surgical debridement and one unrelated amputation due to osteomyelitis. Conclusions: The combination of autologous PRF matrix and gentamicin demonstrated promising results in promoting sustained healing of refractory DFUs with minimal complications. These findings support further investigation in larger, controlled studies to validate this biologic-antimicrobial approach as a safe, effective, and durable therapy for complex diabetic wounds. Full article

Background/Objectives: Mesenchymal stem cells (MSCs) are deemed to be a highly safe model for autologous and allogeneic cellular therapy, owing to their inherent lack of HLA-DR expression, immunomodulatory properties, homing ability, and plasticity allowing differentiation into different cell types. The interest in activating autophagic signaling in MSCs has recently grown due to its significant potential in maintaining stemness, enhancing paracrine signaling, and providing therapeutic benefits for cancer and neurodegenerative diseases. This study aimed to explore the impact of autophagy induction on enhancing the therapeutic potential of MSCs by maintaining their plasticity and to assess different induction agents. Methods: In this study, MSCs were first extracted from the fat tissue of Sprague–Dawley (SD) rats and characterized phenotypically and molecularly by their positive expression of stemness markers CD29, CD106, and CD44, and their negative expression of hematopoietic surface markers CD14, CD34, and CD45, using a flow cytometry approach. Isolated MSCs were then treated separately with two FDA-approved autophagy inducers: Lithium Chloride and Trehalose, following assessment of autophagy activity. Results: Treated MSCs showed significant increases in autophagic activity at both the transcriptional and translational levels. The successful induction of autophagy in MSCs was confirmed through the elevated expression of autophagy-related genes such as ATG3, ATG13, ATG14, P62, and ULK1. These data were confirmed by the significant upregulation in LC3 protein expression and the formation of autophagosomes, which was detected using a transmission electron microscope. Furthermore, the expression of Oct4, Sox2, and Nanog genes was significantly enhanced after treatment with Trehalose and Lithium Chloride compared with untreated control MSCs which may indicate an upregulation of pluripotency. Meanwhile, Lithium Chloride and Trehalose did not significantly induce cellular apoptosis, indicated by the Bax/Bcl-2 expression ratio, and significantly decreased the expression of the antioxidant markers SOD and GPx. Conclusions: Treatment of MSCs with Trehalose and, in particular, Lithium Chloride significantly activated autophagic signaling, which showed a profound effect in enhancing cells’ pluripotency, reinforcing the usage of treated MSCs for autologous and/or allogenic cellular therapy. However, further in vivo studies for activating autophagy in cellular grafts should be conducted before their use in clinical trials. Full article

Background/Objectives: Pilates is a form of exercise that benefits people with bodily pain and movement limitations. The Clinical Pilates method assesses a patient through history taking and exercise testing to identify the patient’s problem side and directional preference. This study is a technical report of two case studies to evaluate the feasibility of the Clinical Pilates conceptual framework for the management of neck and shoulder musculoskeletal conditions. Methods: A conceptual framework on the use of the diagnostic bullseye for neck and shoulder movements are presented. To illustrate the application of the framework, two independent case studies with neck and shoulder pain were interpreted. These cases were assessed for upper and lower quadrant movement preferences using the Clinical Pilates method. Patient self-reported outcome measures included the pain numeric rating scale (/10), patient-specific functional scale (/10), and shoulder pain and disability index (%). Results: In both case studies, the clinical outcomes improved by more than 50% from the baseline. These improvements showed that the conceptualized framework is feasible for use among individuals with neck and musculoskeletal conditions. Conclusions: The neck and shoulder diagnostic bullseyes developed provide an extension from existing lower quadrant diagnostic bullseye. The feasibility of the Clinical Pilates method for neck and shoulder conditions was illustrated in the two case studies. Full article

A 57-year-old man presented with fever and progressive odynophagia three days after a suspected fish bone impaction. Laboratory tests revealed leukocytosis (17,400/µL) and an elevated C-reactive protein level (8.93 mg/dL). Initial chest radiography was unremarkable, ruling out pneumomediastinum. Contrast-enhanced computed tomography (CT) of the neck revealed focal thickening of the cervical esophageal wall, along with a low-attenuation collection and mild fat stranding surrounding the esophagus. Also, extraluminal air was absent. These findings supported the diagnosis of intramural abscess rather than free perforation. Upper endoscopy revealed a submucosal bulging lesion with a pinpoint mucosal defect that was actively draining pus, consistent with a contained intramural collection. Water-soluble contrast esophagogram confirmed smooth passage without extravasation, obstruction, or the double-lumen sign. The patient received bowel rest, intravenous piperacillin/tazobactam, and close observation. Symptoms and inflammatory markers improved, and follow-up CT confirmed the resolution of the intramural collection. Esophageal intramural abscesses develop when an infection spreads within the submucosa after a mucosal breach. In East Asia, this often occurs due to fish bone impaction. Early CT enables the differentiation of esophageal intramural abscess from perforation or dissection and guides the selection of conservative, rather than interventional, management. Full article

Takotsubo syndrome (TTS), popularly known as “broken heart syndrome”, is a type of reversible but not benign acute heart failure condition of unknown etiology, usually triggered by physical or emotional stress, affecting primarily elderly women. Recently a subtype of TTS, triggered by positive/pleasant emotions, has been identified (“happy heart syndrome”) with affected patients showing the same complications, including in-hospital and long-term mortality, as the patients afflicted with the “broken heart syndrome”. There is a need to increase the awareness of physicians, other medical providers, our patients, and the general public about the existence of “happy heart syndrome”. Full article

Background/Objectives: Bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) are the gold standard to measure fat mass, but they are unavailable in regular consultations. Relative Fat Mass (RFM) and Pediatric Relative Fat Mass (pRFM) equations are calculated using DXA images in adults and children, but they have not been correlated with BIA. Methods: A longitudinal prospective study was conducted with 531 children from a public school followed over one year; sex, age, weight, height, waist circumference and fat mass percentage were recorded. We calculated body mass index Z-score (Z-BMI), body mass index percentile (Pc BMI), waist-to-height ratio (WHtR), and RFM-pRFM to diagnose Overweight (Ow)/Obesity (Ob). We used descriptive statistics, Pearson’s correlation, sensitivity and specificity, 95% CI, and ROC curves; SPSS version 22 was used. Results: Adiposity was found in 34.5%, 33.2%, 21.5% and 43.5% of children using Z-BMI, Pc BMI, WHtR, and BIA, respectively; excluding children younger than 8 years old, the frequency of adiposity was 51.5% by RFM-pRFM. The highest correlation was between RFM-pRFM and BIA (0.84, p < 0.000). Of the total measurements of each visit considered as normal weight using Z-BMI, 21.5% had adiposity using BIA, and the proportion of girls underdiagnosed was twice that of boys. Conclusions: RFM-pRFM had the highest correlation with BIA but Z-BMI, Pc BMI, and WHtR are also helpful. It is important to consider that 21.5% of children with apparent normal weight present adiposity. Full article

Central sensitization of pain (CSP) is defined as the “increased responsiveness of nociceptive neurons in the central nervous system (CNS) to normal or subthreshold afferent input” The primary objective of this study is to compare the prevalence of CSP between patients presenting with foot and ankle conditions and those presenting with low back pain. Materials and Methods: A cross-sectional study was conducted comparing a cohort of patients with a first consultation for foot and ankle disorders to another cohort with a first consultation for lumbar spine pain at the same institution. Demographic variables, pain duration, main diagnosis, and a series of questionnaires assessing pain and disability were collected. The Central Sensitization Inventory (CSI) was administered to determine the presence of CSP within the groups. Statistical analyses were performed using STATA. Results: A total of 195 patients presenting with foot/ankle conditions and 252 patients with low back pain were included. Among the foot/ankle cohort, 16.4% (95% CI, 10.92–21.9%) were classified as having CSP, compared to 22.2% (95% CI, 16.85–27.6%) in the lumbar pain cohort. The difference in CSP prevalence between groups was not statistically significant (difference 5.79%, Chi² = 2.357, p = 0.125). However, the difference in mean scores on Part A of the CSI was statistically significant (31.82 ± 13.88 vs. 25.20 ± 14.31, z = 4.237, p < 0.001). Among foot/ankle pathologies, plantar fasciitis showed the highest prevalence of CSP (21.9%), followed by hallux valgus (18.8%). A significant association was observed between CSP and higher levels of pain and disability. Female patients demonstrated a higher prevalence of CSP. Conclusions: Patients with low back pain exhibited higher CSI scores and a greater prevalence of central sensitization compared with those with foot and ankle disorders. Recognizing these mechanisms may help clinicians tailor more effective, multidisciplinary treatment strategies. Full article

Introduction: Current treatments for patients with stage III non-small-cell lung cancer (NSCLC) are not sufficiently personalized, resulting in suboptimal outcomes and high mortality rates. The Developing Circulating and Imaging Biomarkers Towards Personalized Radiotherapy in Lung Cancer (VIGILANCE) study employs innovative health technologies to collect a range of clinical data and features. This includes longitudinal analyses of cell-free and circulating tumor DNA from blood samples and radiomic features extracted from standard-of-care imaging. Additionally, patient-reported outcome measures will be collected to capture patients’ symptoms and quality of life. This will provide invaluable insight into the patient experience during and after radiotherapy. We aim to evaluate whether the data, including patient-reported outcomes, can serve as biomarkers to refine treatment strategies, improve post-treatment follow-up and provide patients with realistic outcome predictions. Key endpoints include the following: (1) assessing whether baseline ctDNA status and its early on-treatment dynamics can identify patients with radioresistant disease who could benefit from treatment intensification; (2) determining whether post-radiotherapy ctDNA clearance can predict benefit from consolidation durvalumab, potentially sparing ctDNA-negative patients from unnecessary immunotherapy; and (3) developing integrated models combining novel ctDNA and radiomic biomarkers to distinguish between radiation fibrosis and tumor recurrence and to predict survival. We adopt a pragmatic approach by recruiting patients receiving standard-of-care treatments in a real-world setting. In addition, most of the clinical data is already routinely collected in our center, except for the blood tests for cell-free and circulating tumor DNA analysis. Methods and analysis: This is a single-center, prospective, exploratory, longitudinal, follow-up study, recruiting patients with stage III NSCLC undergoing standard-of-care curative-intent radiotherapy (with or without systemic therapy). Data collection spans from baseline to during radiotherapy and is extended up to 1 year following radiotherapy. The longitudinal analysis aims to describe and characterize dynamic changes in the collected features and assess their utility as prognostic and response biomarkers. Trial registration number: NCT06086574. Full article