Cadavers play an irreplaceable role in anatomy education, offering unique opportunities for hands-on learning and the internalization of ethical values. While large language models (LLMs) are increasingly utilized in medical education, their perspectives on the moral status of cadavers remain underexplored. This study examined the responses of four LLMs-ChatGPT, Gemini, DeepSeek, and Copilot-regarding the concept, significance, and ethical responsibilities toward cadavers. A thematic analysis was conducted based on the AI-generated responses. Three main themes emerged: (1) The Meaning of the Cadaver, where all LLMs preferred the term "donor," reflecting respect for the body's human origin and voluntary contribution to science; (2) The Importance of the Cadaver, emphasizing its educational superiority over models and simulations due to realism, anatomical variation, and ethical learning; and (3) Attitudes and Responsibilities, where LLMs expressed moral, ethical, legal, and academic responsibilities, highlighting respect, non-maleficence, and professional conduct. LLMs also acknowledged that donor-related terminology and background knowledge influence learners' attitudes. Large language models attribute moral value to cadavers based on their human origin and educational role. While not granting full personhood, they support respectful and ethically guided engagement. These findings suggest that LLMs, when integrated into medical education, may reinforce ethical awareness and serve as potential tools for promoting professional identity formation.
The co-occurrence of mirror-image dextrocardia and tetralogy of Fallot (TOF) is a rare congenital condition. Reoperative multivalve surgery in such patients, especially after repaired TOF, presents exceptional challenges due to the mirrored cardiac anatomy and altered surgical field. This case highlights the surgical strategy for concomitant tricuspid, mitral, and pulmonary valve replacement in this unique setting. A 14-year-old male patient with a history of corrected TOF and mirror-image dextrocardia presented with progressive heart failure due to severe regurgitation of the tricuspid, mitral, and pulmonary valves. Preoperative imaging confirmed the complex anatomy, with the atria positioned posteriorly, rendering the atrioventricular valve orifices near-vertical during surgery. The patient successfully underwent triple valve replacement under cardiopulmonary bypass. Key technical adaptations were made to select the valve model and position. The postoperative course was uneventful, with significant symptomatic and echocardiographic improvement at discharge and during the two-month and six-month follow-up. This case demonstrates that concomitant triple valve replacement is feasible in patients with mirror-image dextrocardia and a history of TOF repair, despite the profound technical challenges posed by the anatomical distortions. Success hinges on meticulous preoperative planning using advanced imaging and the development of an individualized surgical approach. This report provides a valuable reference for managing such complex, high-risk reoperations in the setting of congenital situs inversus.
The occipital interhemispheric transtentorial approach (OITT) is widely used for accessing lesions in the pineal region. Although reports are scarce, this approach can also be successfully applied to superior cerebellar lesions, involving the quadrangular lobule. We describe the OITT approach for cerebellar quadrangular lobe lesions, providing relevant anatomy, surgical technique, and key technical considerations. Gross total resection can be achieved while preserving normal brain tissue and functionOITT is a safe and low-morbidity route for lesions within the cerebellar quadrangular lobe, as it uses a natural anatomical corridor, avoids manipulation of eloquent areas, and minimizes injury to normal brain tissue.
Endocrine disorders in pediatric patients often involve a variety of imaging modalities as part of a diagnostic workup or disease surveillance. This pictorial essay and review of the literature highlights adrenal and reproductive system imaging findings related to endocrine-related diseases. This review includes descriptions of normal adrenal gland anatomy and imaging characteristics, as well as the clinical presentations and diagnostic imaging of congenital adrenal hyperplasia and of benign and malignant adrenal masses. Additionally, normal reproductive tract development and puberty will be covered, followed by an overview of Müllerian anomalies, 46,XY gonadal dysgenesis, and polycystic ovarian syndrome. Differential diagnostic considerations, appropriate imaging protocols, and clinical management strategies will be discussed.
Coronary computed tomography angiography (CCTA) is emerging as a valuable adjunct for chronic total occlusion (CTO) percutaneous coronary intervention (PCI), particularly for lesions in which angiography incompletely defines procedural anatomy. In this systematic review, the authors evaluated the role of CCTA in CTO diagnosis, lesion characterization, prediction of guidewire crossing and procedural success, and procedural guidance. CCTA provides a detailed assessment of key features that directly influence CTO PCI strategy and outcomes. Randomized and observational data suggest that preprocedural CCTA can improve procedural planning, increase technical success in complex lesions, and support safer and more efficient CTO PCI through fluoroscopic co-registration and other real-time guidance applications. These findings highlight the clinical value of CCTA as a tool that can enhance case selection, optimize crossing strategy, and improve procedural success in contemporary CTO PCI.
Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder that imposes significant personal and societal burdens. Traditional diagnostic approaches, which rely on behavioral assessments, are susceptible to subjectivity and variability, underscoring the need for objective and automated diagnostic tools. This study develops an ADHD-specific, biologically informed multi-stream deep learning framework for pediatric brain MRI classification, in which a Vision Transformer (ViT) and an Enhanced Convolutional Neural Network (ECNN) are integrated with Raw MRI, Phase Spectrum Transform (PST), and Quantile Histogram Equalization with Denoising (QHED) representations to capture complementary global and local neuroanatomical characteristics. The architecture leverages complementary modeling capacities by combining global contextual representations from ViT with localized discriminative features extracted by ECNN across a biologically informed multi-stream preprocessing strategy, including Raw MRI to preserve global anatomy, Phase Spectrum Transform (PST) to highlight cortical boundary irregularities, and Quantile Histogram Equalization with Denoising (QHED) to enhance subtle gray-white matter contrasts. Experimental evaluations conducted on a stratified pediatric MRI dataset demonstrated that the proposed ViT+ECNN model achieved a classification accuracy of 99.4%, precision of 99.3%, recall of 99.5%, and an F1-score of 0.99, substantially outperforming standalone ViT and ECNN configurations. These findings indicate that hybrid transformer-convolutional models can substantially enhance diagnostic accuracy and offer a promising approach for supporting early identification and intervention in ADHD.
Severe scoliosis with prior corrective spinal surgery poses significant anesthetic challenges in obstetric patients due to altered spinal anatomy and potential respiratory compromise. Conventional neuraxial or general anesthesia may be risky, making alternative approaches necessary for safe cesarean delivery. The Taylor paramedian technique provides an effective option by bypassing distorted midline anatomy. A 35-year-old primigravida (G1P0) at 37±1 week's gestation with surgically corrected thoracolumbar scoliosis and restrictive pulmonary disease, complicated by bronchopneumonia, was admitted for cesarean delivery. Preanesthetic assessment revealed limited cervical mobility, restricted mouth opening, and challenging spinal landmarks. Initial midline puncture at L3-L4 failed, so a paramedian Taylor approach at L5-S1 using anatomical landmarks was performed. Intrathecal 12 mg plain 0.5% bupivacaine with 20 µg fentanyl achieved complete sensory and motor block. Maternal hemodynamics remained stable with normal oxygenation. Cesarean section was completed uneventfully, delivering a healthy neonate weighing 3 kg with Apgar scores 8 and 9. Postoperative recovery was smooth, and the patient was discharged on day 3. Paramedian Taylor spinal anesthesia is a safe and effective alternative in parturients with severe scoliosis and restrictive pulmonary disease. Individualized planning, technical expertise, and careful execution allow complete sensomotor block, minimize respiratory risk, and ensure successful cesarean delivery in high-risk patients.
Isolated locoregional recurrence of pancreatic adenocarcinoma occurs in 25-50% of cases after surgical resection and has limited treatment options. Data on ablative stereotactic body radiation therapy (SBRT) with daily online adaptation for this condition are limited. Our objective was to illustrate the efficacy and safety of adaptive radiation for isolated locoregional recurrences of pancreatic adenocarcinoma. This was a retrospective cohort study of 46 patients treated with adaptive 5-fraction SBRT for isolated locoregional recurrence of pancreatic adenocarcinoma after surgical resection between 2015-2024. Kaplan-Meier curves with log-rank analysis and Cox regression were conducted to assess oncologic outcomes including locoregional recurrence-free survival, distant metastasis-free survival, and overall survival. Variables of clinical significance including biologically effective dose, planning target volume, and receipt of salvage chemotherapy in conjunction with salvage radiation were assessed. Local failure was defined by RECIST criteria. Toxicities were assessed using CTCAE v5.0 criteria. Radiation dose median was 50 Gy in 5 fractions. Seven patients had prior radiation and 27 patients received chemotherapy as part of their salvage treatment. The median duration of chemotherapy was 3.9 months. 46 patients were treated with a median age of 65, the majority were White and male. Median time to local recurrence from initial diagnosis was 20 months. Online adaptation was performed for 91% of fractions. Median follow-up from recurrent diagnosis and end of salvage radiation was 14 and 10.4 months, respectively. One-year local control was 73%, and 1- and 2-year overall survival were 69% and 42%, respectively. Chemotherapy had a statistically significant effect on progression-free survival (HR 0.45, 95% CI 0.23-0.89, p = 0.02). No acute grade 3+ toxicities occurred but three late grade 3+ toxicities were documented. Adaptive SBRT permits high biologically effective dose in 5 fractions and results in local control concordant with conventionally fractionated salvage radiation for locoregionally recurrent PDAC after definitive surgery, even after prior radiation with a reasonable toxicity profile. Future work may combine adaptive radiation with coverage of extra-pancreatic neural tract anatomy and additional chemotherapy to improve outcomes.
Revision total elbow arthroplasty is technically demanding and carries a substantial risk of postoperative neurological complications because of scarring, altered anatomy, implant removal, and repeated humeral and ulnar exposure. The incidence, nerve distribution, and recovery profile of nerve injury after revision total elbow arthroplasty remain incompletely defined. This study aimed to systematically review the literature to define the incidence, recovery profile, and risk factors for nerve injury after revision TEA. A systematic review of the literature was performed in accordance with PRISMA guidance. Thirteen retrospective case series were included, comprising 282 revision total elbow arthroplasties in 271 patients. Random-effects meta-analysis of proportions was undertaken where the data permitted. The primary outcome was postoperative nerve injury following revision total elbow arthroplasty. Secondary outcomes included nerve type, recovery, secondary nerve-related procedures, infection, triceps insufficiency, metallosis, periprosthetic fracture, and re-revision. The pooled incidence of postoperative nerve injury was 22.3% (95% CI 16.3 to 29.6; I2 = 34.6%). The crude incidence was 60 of 282 revisions (21.3%, 95% CI 16.6 to 26.5). The ulnar nerve was involved in 66.7% of all nerve injuries, the radial nerve in 31.7%, and the median nerve in 1.7%. No significant difference in pooled nerve-injury incidence was identified between studies published before 2010 and those published from 2010 onwards (22.9% vs 21.4%, p = 0.837). Recovery reporting was heterogeneous; among injuries with numerically extractable outcomes, 85.4% improved partially or completely (95% CI 72.2 to 93.9). Secondary nerve-related procedures were reported in seven studies. Pooled complication estimates were 10.2% for infection, 13.6% for triceps insufficiency, 25.5% for metallosis, 15.9% for periprosthetic fracture, and 14.0% for re-revision. Postoperative nerve injury is a common and clinically important complication of revision total elbow arthroplasty, affecting approximately one in five cases. The ulnar nerve is most frequently involved, although radial nerve injury accounts for a substantial proportion of cases. Many neuropathies improve during follow-up, but persistent deficits and the need for secondary nerve-related procedures are not uncommon. Future studies should adopt standardised neurological definitions and reporting to improve comparability and guide preventive surgical strategies.
Early detection of pancreatic cancer is crucial for survival, but detecting smalllesions remains challenging. Intraductal Ultrasound (IDUS) using intracardiac echocardiography (ICE) catheters for B-mode and Shear-Wave Elastography (SWE) potentially offers improved visualization and characterization of small tumors. This study assesses the feasibility of IDUS using ICE catheters to detect and visualize periampullary tumors in surgically resected specimens. In this two-phase ex-vivo feasibility study, 25 pancreatic specimens were included, of which the first 10 were used to establish and standardize the imaging protocol, followed by technical feasibility evaluation in the remaining 15 specimens. Catheters were introduced into the pancreatic duct, common bile duct, or positioned extraductally to enable tumor visualization with B-mode imaging and shear-wave elastography (SWE). Tumor visualization rates, catheter insertion success, SWE measurements in normal and tumor tissue, and image quality were assessed. ICE catheter insertion was successful in 12 of 15 specimens; unsuccessful access was primarily related to large tumor size (>4 cm) or unidentifiable ductal anatomy following surgical resection. However, extraluminal imaging successfully visualized tumors in one of these cases. Median shear-wave speed and elastic modulus for normal pancreatic parenchyma were 1.58 m/s and 7.6 kPa, respectively. SWE measurements in tumor tissue were suboptimal, likely due to ex-vivo tissue variability and catheter strain during repeated use. IDUS with ICE is feasible for qualitative B-mode visualization of periampullary tumors and enables SWE assessment of pancreatic parenchyma in an ex-vivo setting. Reliable elastography of tumor tissue remained challenging, indicating the need for further technical refinement and in-vivo validation.
Endotracheal intubation is performed by health care providers from different training backgrounds and in diverse locations. The first pass failure rate has been reported to be variable, and complications can arise from multiple intubation attempts. This is a hypothesis-generating descriptive analysis of first pass endotracheal intubation failure performed by a critical care transport team. Secondary outcomes included patient and procedural factors associated with failure. This is a retrospective chart review of adults (≥18 years) intubated by a critical care transport service between January 2017 and June 2024. One intubation attempt was defined as the insertion of the laryngoscope past the lips. First pass failure was defined as failure to place an endotracheal tube through the vocal cords on the first intubation attempt. There were 388 patients intubated with 54 first pass failures (13.9%). Multiple reasons for failure were cited in 20 first pass intubation failures (37.0%). The most common reasons for failure were desaturation during intubation (7; 13.0%); contamination with blood, secretions, emesis, or foreign bodies (23; 42.6%); and anatomy (33; 61.1%). There was an association between first pass failure and retrospectively documented predicted difficult airway (adjusted odds ratio, 2.96; 95% confidence interval, 1.57-5.56). First pass failure occurred in 13.9% of intubations. This descriptive analysis serves as a starting point for further quality improvement work that includes a systematic review of intubations with objective data (ie, video-recorded laryngoscopy) and the use of an airway failure taxonomy to describe errors.
Oleanolic acid (OA) is a natural anti-inflammatory triterpenoid. This study investigates its therapeutic potential against rheumatoid arthritis (RA), a chronic autoimmune condition characterized by inflammatory activity, and explores the novel mechanism of gut microbiota modulation in a rat model. The anti-arthritic effect of OA was assessed in collagen-induced arthritis (CIA) in rats following oral or intravenous administration. Arthritis severity, joint pathology, and mesenteric Th17/Treg cell frequencies were evaluated. The role of gut microbiota was investigated using 16S rRNA sequencing and antibiotic ablation. Oral, but not intravenous, OA administration significantly alleviated arthritis and joint damage in CIA rats, indicating a gastrointestinal-dependent mechanism. Therapeutically, oral OA modulated gut microbiota by reducing Prevotella abundance and restored immune balance by decreasing Th17 and increasing Treg cell frequencies. This protective effect was abolished by co-treatment with antibiotics, confirming gut microbiota-dependency. Taken together, our findings show that the improvement in CIA after oral administration of OA is mainly due to changes in the structure and function of the gut microbiota. This study, therefore, suggests that OA is a promising therapeutic candidate for RA, based on its ability to restore the intestinal microenvironment.
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Serum ferritin and iron have high inter-individual variability and inflammatory sensitivity, limiting its diagnostic value in several clinical settings. The Reticulocyte Subpopulation Analysis may indicate iron availability during erythropoiesis in real time. This study investigated the associations between reticulocyte parameters and various hematological and iron-related biomarkers in Iron Deficiency Anemia. In this retrospective study, 150 patients with IDA (Iron Deficiency Anemia) were included (146 females, 97.3%; 23 pregnant, 15.8%; 12 on iron treatment, 8.0%), RET-He, LFR/MFR/HFR, and IRF were correlated with iron markers. Associations between anemia severity and treatment status were examined using Spearman correlation, Kruskal-Wallis, and Mann-Whitney U analyses. While other reticulocyte indices exhibited minor connections, RET-He showed strong positive correlations with ferritin (r=0.430, p<0.001), serum iron (r=0.364, p<0.001), and transferrin saturation (r=0.350, p<0.001 A significant decrease in RET-He was seen in mild anemia (24.6 pg) and severe anemia (15.2 pg, p<0.001). RET-He was marginally reduced (p=0.0750) while serum iron and transferrin saturation were considerably lower in iron-treated subjects (p=0.0023). Reticulocyte and iron characteristics did not correlate with age (p>0.05). A sensitive, independent biomarker of iron status, RET-He measures functional iron availability during erythropoiesis. Strong correlation and severity-stratified discrimination support in populations where inflammation confounds ferritin interpretation, RET-He inclusion into iron deficient diagnostic methods. Prospective studies are needed to establish clinical thresholds and validate RET-He in chronic renal disease, inflammatory conditions, and pregnancy-related iron metabolism.
Bone remodelling is essential for maintaining skeletal integrity by preserving the balance between bone formation and resorption, with excessive osteoclast activity contributing to osteoporosis. Osteocytes act as central regulators of osteoclastogenesis through mechanically sensitive paracrine signals, yet the influence of osteoblasts and their mesenchymal precursors remains less defined. Extracellular vesicles (EVs) have recently emerged as mediators of bone cell communication, although their role in osteoclast regulation are still underexplored. This study demonstrates that mesenchymal-derived bone cells inhibit osteoclastogenesis through an EV-dependent mechanism shaped by their differentiation stage and mechanical environment. Mechanically stimulated osteocyte-derived EVs showed the strongest anti-catabolic response. Notably, we identify miR-150-5p as a mechano-responsive miRNA enriched within osteocyte EVs, capable of inducing a dose-dependent reduction in osteoclastogenesis. Transcriptomic analyses reveal that EV treatment and miR-150-5p delivery induce substantial transcriptional changes in osteoclast precursors, including downregulation of shared target genes linked to bone remodelling. Overall, we highlight mechanically activated osteocytes as key regulators of osteoclastogenesis through an EV-mediated mechanism, in which miR-150-5p represents a promising candidate contributor within the broader EV cargo landscape, highlighting their potential for future cell-free therapeutic strategies.
Propofol is a widely employed intravenous general anesthetic that can induce neurotoxic effects on neurons. Previous research has indicated dysregulation of miR-140-3p in the hippocampal tissues of propofol-treated mice. This research was designed to investigate the function and underlying mechanism of miR-140-3p in propofol-induced neurotoxicity. To simulate propofol-induced neurotoxicity, human SH-SY5Y cells and mice were treated with propofol. Commercial kits were used to measure LDH, MDA, SOD, GSH-Px, and BDNF levels. Cells were transfected with miR-140-3p mimics, inhibitor, or BACE1 overexpression plasmids. Gene expression was assessed by RT-qPCR, cell viability by CCK-8, and apoptosis by flow cytometry. Dual-luciferase and RIP assays confirmed that miR-140-3p targets BACE1. The results confirmed that as the concentration of propofol increased, miR-140-3p levels were progressively downregulated, while BACE1 was correspondingly upregulated. Upregulation of miR-140-3p rescued propofol-treated SH-SY5Y cells from cytotoxicity, as evidenced by enhanced viability, suppressed apoptosis, and ameliorated oxidative stress. Consistently, miR-140-3p overexpression also attenuated propofol-induced neurotoxicity in vivo. Furthermore, BACE1 was confirmed to be a direct target of miR-140-3p through experimental validation, and this post-transcriptional repression was shown to mediate the observed neuroprotection. miR-140-3p attenuates propofol-induced neurotoxicity via BACE1 in vitro and in vivo, providing new insights and a potential biomarker for managing propofol-associated neurotoxicity.
BACKGROUND The incidence of breast cancer is high among women, with a significant proportion of cases being familial. However, the driver genes for breast cancer can differ across families. CASE REPORT Our patient was a 37-year-old woman diagnosed with triple-negative breast cancer (TNBC) by pathology, revealing invasive ductal carcinoma of the outer upper quadrant of the breast, WHO grade 3. The maximum diameter of the microscopic invasive cancer was approximately 0.5 cm. No definite vascular tumor thrombus or nerve invasion was observed. Some (30-90%) of the tumor cells disappeared, and the remaining tumor cells showed degeneration, interstitial sclerosis, scattered lymphocyte infiltration, and hemosiderin deposition. No cancer was found in the nipple and base resection margins, or in the other quadrants. The chemotherapy response was classified as grade III according to the MP (Miller and Payen classification) scoring system. Blood samples were collected from affected family members. Whole-exome sequencing (WES) and bioinformatics analyses were used to identify potential driver genes, followed by Sanger sequencing for validation, which ultimately confirmed the pathogenic gene and the underlying mechanism in this family. CONCLUSIONS A series of analyses suggested that the co-occurrence of heterozygous deletions in BRCA1 and OBSCN was the main cause of breast cancer in this family. The simultaneous association of 2 genes with the occurrence of breast cancer was discovered for the first time in this family, which could help guide disease prevention for family.
Pulp necrosis in immature permanent teeth arrests root development and compromises long-term prognosis. This study aimed to develop a multifunctional scaffold integrating structural biomimicry, mechanical matching, and sustained growth factor release for orderly root regeneration. A poly(ε-caprolactone) (PCL) conical scaffold was fabricated via melt electrowriting (MEW) combined with mechanical winding. Bone morphogenetic protein‑2 (BMP‑2)-loaded microspheres were prepared and physically incorporated into the scaffold. The scaffold surface was modified with collagen. Human dental pulp stem cells (hDPSCs) were cultured on the scaffold to evaluate proliferation, adhesion, and osteogenic differentiation. The scaffold exhibited a trilayer "collagen-microsphere-PCL" architecture with mechanical compatibility (elastic modulus: 22.5 MPa; fracture strength: 5.29 MPa; elongation: 441.59%). Microspheres (2.86 ± 0.45 μm) showed a gradient distribution and sustained release (70-75% over 90 days). In vitro, the scaffold promoted hDPSC adhesion and proliferation and significantly enhanced osteogenic differentiation with elevated alkaline phosphatase activity, upregulated the expression of osteogenic-related genes, and increased protein levels. The scaffold integrates structural support, controlled growth factor delivery, and a bioactive interface, offering a promising strategy for root development in immature permanent teeth. By enabling physiological root development, the scaffold addresses a critical unmet need, offering a viable alternative to conventional root canal therapy.
The treatment landscape for relapsed or refractory diffuse large B-cell lymphoma has changed profoundly with the introduction of novel drug classes, some approved solely on the basis of single-arm early-phase trials. We aimed to evaluate antitumour activity and safety outcomes across drug classes in early-phase trials in relapsed or refractory diffuse large B-cell lymphoma since 2000. We did a systematic review and meta-analysis of phase 1-2 trials. We searched PubMed, Embase.com, Web of Science and Wiley/Cochrane Library from database inception to May 9, 2025. We included English-language studies published between Jan 1, 2000, and May 9, 2025, enrolling adults aged 18 years or older with relapsed or refractory diffuse large B-cell lymphoma treated with experimental agents alone or combined with CD20-antibodies; trials including other B-cell malignancies were eligible if diffuse large B-cell lymphoma-specific responses could be extracted. Trials restricted to highly-selected subgroups, supportive-care, administration-routes, country-specific approvals, and conference abstracts were excluded. Two investigators independently extracted summary data. The primary outcomes were objective response rate and complete response rate, and were pooled using random-effects generalised linear mixed models. Adverse events were secondary outcomes. Prespecified subgroup analyses evaluated drug class and publication period. The study was registered with PROSPERO, CRD42023394451. We identified 2797 citations, of which 1824 unique records remained after removal of duplicates. 132 trials including 7786 patients were eligible for analysis. 3375 (43%) of 7786 patients were female and 4411 (57%) were male. Objective response rate was 30·5% (95% CI 26·0-35·5, I2=84·7%) and complete response rate 14·3% (11·5-17·7, I2=82·2%). Response rates varied across drug classes, with the highest objective response rate or complete response rate for cellular therapies (70·0%, 95% CI 61·0-77·0 and 51·0%, 95% CI 43·0-59·0), followed by bispecific antibodies (46·0%, 38·0-53·0 and 30·0%, 24·0-36·0) and antibody-drug conjugates (40·0%, 32·0-47·0 and 18·0%, 13·0-24·0). Objective response rate increased over time, from 16·6% (95% CI 9·0-29·0) in 2000-08 to 36·8% (30·0-45·0) in 2018-25. The overall rate of dose-limiting-toxicities or discontinuations was 6·0% (95% CI 4·7-7·6). The rate of grade 3-4 adverse events was 61·5% (95% CI 54·2-68·3), treatment-related-mortality was 0·6% (0·4-1·0), and non-relapse-mortality was 3·6% (2·9-4·5). Treatment-related mortality remained below 1% over time. Since the year 2000, early-phase trials in relapsed or refractory diffuse large B-cell lymphoma have shown more than a doubling of response rates, driven primarily by cellular and bispecific antibody therapies, while maintaining low treatment-related mortality. These results provide risk-benefit trends in early-phase trials and define contemporary benchmarks for clinicians, investigators and regulators. None.
Hepatopulmonary hydatidosis (HPH) is a clinically relevant presentation of hepatic cystic echinococcosis (CE) in which pulmonary involvement is present at the time of diagnosis. Reliable identification of patients at risk remains challenging, and indiscriminate thoracic imaging may lead to unnecessary investigations. This study aimed to identify hepatic predictors associated with concomitant pulmonary involvement and to develop a simple risk stratification model to support selective thoracic imaging. We conducted a retrospective cohort study of patients with confirmed hepatic CE followed at a single tertiary center. Cyst activity was classified according to the World Health Organization (WHO) staging system, and anatomical distribution was assessed using a segment-based classification. Multivariable logistic regression was performed to identify predictors of HPH. A point-based clinical risk score (HepatoMAP) was derived by combining cyst activity and anatomical distribution. Model discrimination and calibration were assessed using receiver operating characteristic (ROC) analysis, bootstrap validation, and calibration plots. Among 292 patients, 23 (7.8%) had hepatopulmonary hydatidosis (HPH) at initial diagnosis. Active cysts (WHO CE1-2) were strongly associated with HPH (91.3% in HPH vs. 33.2% in hepatic-only disease, p < 0.001) and remained the only independent predictor in multivariable analysis. The HepatoMAP score demonstrated good discrimination (AUC 0.83) with good calibration (bootstrap-corrected slope 0.97). No cases of HPH were observed in patients with low-risk scores (0-1 points), whereas HPH occurred predominantly in patients with scores ≥ 3. In hepatic CE, concomitant pulmonary involvement at baseline was strongly associated with cyst activity and showed a structured but non-independent relationship with segmental topography. The HepatoMAP score showed promising rule-out characteristics in this cohort and may support more selective use of thoracic imaging. Prospective external validation is required before routine clinical implementation.