To evaluate the efficacy and safety of adjunctive perampanel (PER) in young children with drug-resistant epilepsy (DRE) aged 7-46 months, and to identify predictors of treatment response in real-world clinical practice. We conducted a nonrandomized, open-label, single-arm, self-controlled real-world study at the Children's Hospital of Chongqing Medical University between December 2020 and August 2024. Eighty-seven children with DRE received PER as adjunctive therapy to existing antiseizure medications (ASMs). The primary endpoint was the responder rate (≥ 50% reduction in seizure frequency) at 3, 6, 9, and 12 months. Secondary endpoints included seizure freedom, treatment retention, and treatment-emergent adverse events (TEAEs). Responder rates were 39.5%, 46.9%, 43.2%, and 44.4% at 3, 6, 9, and 12 months, respectively. Responder rates were 50.0% in Dravet syndrome, 50.0% in Lennox-Gastaut syndrome, and 34.8% in infantile epileptic spasms syndrome. Children with genetic etiologies had a 51.7% responder rate, including 60.0% in those with SCN1A variants. Multivariable logistic regression identified perinatal brain injury as an independent predictor of favorable response, while concomitant use of three ASMs predicted poorer outcomes. Treatment retention rates were 87.4%, 69.0%, 59.8%, and 55.2% at 3, 6, 9, and 12 months. TEAEs occurred in 23.0% of patients, most commonly somnolence (11.5%) and irritability/aggressive behavior (9.2%); 4.6% discontinued due to TEAEs. Adjunctive PER demonstrated clinically meaningful efficacy and a favorable safety profile in young children with DRE, supporting its potential role as a broad-spectrum ASM in this age group.
Appendiceal goblet cell adenocarcinoma (GCA) is an uncommon malignancy that has been described under various names and grading schemes. The 5th Edition of the World Health Organization (WHO) Classification of Digestive System Tumours provides a three-tiered system for grading these neoplasms, but the reproducibility of this classification scheme has not been studied. We scanned 58 H&E-stained slides from 20 GCA and circulated the whole-slide images among seven pathologists with interest in appendiceal pathology. They evaluated each slide for the presence of 15 histological patterns defined by the WHO as criteria for low-grade (n = 5) and high-grade (n = 10) GCA. Cases were also evaluated for the presence of extracellular mucin. Participants also reported the percentage of high-grade features in each whole slide image and each case. Interobserver variability was assessed statistically. All seven observers agreed on the WHO grade for four of the 20 cases (20%; one grade 1, three grade 3). Using Fleiss's kappa statistic, overall agreement for cases was fair at 0.29 (95% confidence interval [CI]: 0.14-0.44), and pairwise agreement between observers ranged from 0.00 to 0.82 (median = 0.13). Gwet's agreement coefficient ranged from 0.10 to 0.87 (median = 0.28), while overall agreement was 0.36 (95% CI: 0.17-0.54). There was significant variability with respect to assessing the presence of individual features. The best agreement was seen for extracellular mucin (neutral feature, κ = 0.43) and tumour sheets (high-grade feature, κ = 0.41), whereas the worst agreement was seen for mild architectural disarray/tubular fusion (low-grade feature, κ = 0.05) and necrosis (high-grade feature, κ = 0.07). We conclude that interobserver agreement for grading GCA using the three-tiered WHO 5th Edition classification system is fair at best. A validated two-tiered system (i.e. low- versus high-grade) may be more reproducible.
Dolutegravir (DTG) plus lamivudine (3TC) is one of the preferred treatment regimens for HIV, yet evidence remains limited for people living with HIV (PLWH) with high baseline viral load. This study aims to evaluate the effectiveness of DTG/3TC in treatment-naive PLWH with baseline viral load > 500,000 copies/mL in China. In this real-world multicenter cohort study, PLWH with baseline viral load (VL) > 500,000 copies/mL who initiated DTG/3TC were recruited across 18 clinical sites in China. Matched participants from the same sites with lower baseline VL were also included as a control group. Participants were followed for 48 weeks. The primary endpoint was virological suppression (HIV-1 RNA < 50 copies/mL) at week 48 using the US Food and Drug Administration snapshot algorithm. Of the 375 PLWH enrolled, 150 were classified into the high VL group and 225 into the low VL group. Baseline median HIV-1 RNA was 5.99 and 5.07 log10 copies/mL, respectively. At week 48, virologic suppression was achieved in 88.0% (95% CI 82.8-93.2%) of the high VL group and 92.0% (95% CI 87.9-96.2%) of the low VL group (P = 0.233); 7.5% and 4.0% of participants in the high and low VL groups had plasma HIV-1 RNA ≥ 50 copies/mL, respectively. Median CD4 increases from baseline to week 48 were 153.5 and 147.0 cells/μL in the high and low VL groups, respectively (P = 0.408). Safety profiles were comparable, with one grade 3 adverse event in each group. DTG/3TC showed favorable virological and safety outcomes in treatment-naive PLWH with baseline HIV-1 RNA > 500,000 copies/mL, suggesting that it may be a viable option for PLWH with high baseline viral load. Chinese Clinical Trial Registry: ChiCTR2300074854.
Since real-world data lack information on treatment assignment (usually the only information available is treatment prescription/administration) and early outcomes can happen in advanced cancer, some design choices may introduce immortal time due to selection or due to treatment strategy misclassification. To illustrate design choices that would biassedly introduce immortal time and propose unbiased alternatives, using as a case study the estimation of the effects of different monoclonal antibody (mAb) sequencing strategies on overall survival in colorectal cancer patients. We specified a target trial to estimate the effect on overall survival of initiating mAb within 8 weeks of starting first line chemotherapy versus initiating mAb with second line chemotherapy. The first biased design choice would be requiring the initiation of second line chemotherapy for eligibility. This was avoided by aligning eligibility with the initiation of first line chemotherapy. The second biased design choice would be excluding from the first line mAb strategy those who die during the grace period without starting mAb. This was avoided separately via cloning, censoring and weighting and by sequential emulation. There were 1014 eligible patients in GEMCAD 1401. The CCW approach estimated a 4-year survival difference (second-first line mAb) of 4.3% (95% CI) (-3.3%; 10.0%) and a risk ratio (RR) of 0.95 (0.88; 1.04). Sequential trial emulation estimated a survival difference of -2.8% (-7.5%; 1.2%) and a RR of 1.04 (0.98; 1.10). Biased analyses that introduced immortal time estimated an implausible early survival benefit for mAb initiation with second-line (6-month RR of 0.13 (0.03; 0.28)). Our results are compatible with no effect on survival by mAb sequencing. Misalignment of time zero, treatment assignment, and eligibility introduced immortal time.
Mirikizumab (MIRI), an IgG4 monoclonal antibody targeting IL-23 p19, was recently licensed for ulcerative colitis (UC). Most available data come from the pivotal trials, but real-life data are scant. We aimed to evaluate the effectiveness and safety of MIRI in a real-world setting. UC patients from 12 centres of the SN-IBD were prospectively enrolled. The primary endpoints were clinical response, steroid-free remission (SFR), and reduction of urgency at week 12 and at week 24. As secondary endpoint, the need for prolonged induction was considered. All patients received 3 infusions at monthly intervals of 300 mg MIRI; in case of inadequate response, the induction period was prolonged. Urgency was determined by means of the Urgency Numerical Rating Scale (UNRS). One hundred and five patients were included. Previous failures to 2 or more lines of advanced therapies were present in 74% of patients. At week 12, 24% of patients achieved a clinical response and 53% achieved SFR. At week 24 (n = 71), the rates were 20% and 68%, respectively. The median urgency score decreased from 6 at baseline to 2 at week 12 and to 1 at week 24 (p < 0.001, both). Prolonged induction was necessary to half of patients. Adverse events were reported in 5% of patients. Treatment failures occurred in 14 patients (13%). Our real-life study confirmed the short-term effectiveness and safety of MIRI in patients with UC especially in relieving bowel urgency. The flexible induction schedule allows an additional gain in response and remission.
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, often associated with significant disability. As treatment options increase, comparative effectiveness data for disease-modifying therapies (DMTs) are essential. This study evaluated treatment switching, healthcare resource utilization, and cost outcomes among US patients with MS (PwMS) treated with cladribine tablets (CladT) vs. fingolimod (FTY), dimethyl fumarate (DMF), and teriflunomide (TER) during a 4-year follow-up period. This retrospective study used claims data from the Komodo Healthcare Map (4/1/2018-3/31/2024). Adult PwMS with ≥ 1 claim for CladT, FTY, DMF, and TER were included. Index date was the first claim date for the respective DMT. Continuous enrollment for 12 months pre-index and 48 months post-index was required. Cohorts were balanced using propensity score weighting and 4-year outcomes were assessed using generalized linear and Cox proportional hazards models. Overall, 3038 PwMS were included: CladT (n = 140), FTY (n = 454), DMF (n = 1465), and TER (n = 979). In the weighted cohorts, mean age was 48 years, and 74-77% were female. Treatment switching during a 4-year follow-up period was lower for CladT (11%), vs. FTY (42%), DMF (57%), and TER (42%) cohorts. CladT showed lower all-cause medical costs per patient per year (PPPY): $13,377 vs. FTY (adjusted mean difference [AMD] $10,073; 95% confidence interval (CI) $5006-15,148), DMF (AMD $12,013; 95% CI $7490-16,706), and TER (AMD $9917; 95% CI $6558-13,997) cohorts. All-cause total costs PPPY were lower with CladT ($53,007) vs. FTY (AMD $14,140; 95% CI $7181-22,021) and TER (AMD $6652; 95% CI $567-12,395) cohorts, but similar to DMF cohort (AMD $4472; 95% CI - $2011, $11,111). PwMS treated with CladT had significantly fewer treatment switches and lower all-cause medical costs vs. FTY, DMF, and TER. Total healthcare costs were lower vs. FTY and TER but similar to DMF.
暂无摘要（点击查看详情）
Patients with end-stage renal disease (ESRD) on dialysis face a high risk of sudden cardiac death, but traditional transvenous implantable cardioverter-defibrillators (TV-ICD) carry risks of central venous stenosis and infection. Subcutaneous implantable cardioverter-defibrillators (S-ICD) provide an extravascular alternative, though comparative outcomes in dialysis patients remain limited. This study evaluated ESRD patients on hemodialysis who underwent S-ICD or TV-ICD implantation between January 2000 and March 2026 using the TriNetX global health network. A 1:1 propensity score matching (PSM) was utilized across 81 clinical covariates. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to assess long-term outcomes, including infectious complications, dialysis access revisions, and mortality. Following PSM, 456 matched pairs (N = 912) of ESRD patients on dialysis were identified. There were no significant differences between the S-ICD and TV-ICD cohorts regarding the composite outcome of sepsis, bacteremia, or transvenous lead extraction (53.5% vs. 55.1%; p = 0.268). All-cause mortality (58.7% vs. 60.4%; p = 0.747) and hospitalization rates (87.9% vs. 85.4%; p = 0.874) were also similar between the groups. However, S-ICD was associated with higher rates of composite open and endovascular dialysis access revision (39.1% vs. 25.8%; p = 0.001), percutaneous dialysis access intervention (p = 0.002), and dialysis access surgery (p = 0.021). S-ICD and TV-ICD demonstrated similar rates of infectious complications, hospitalization, and all-cause mortality in ESRD patients. S-ICD implantation was associated with higher rates of dialysis access revisions and interventions. Device selection should remain individualized, guided by anatomy, access planning, and clinical context.
暂无摘要（点击查看详情）
The MOONBEAM retrospective cohort study examined epidemiology, treatment patterns, and outcomes in patients with endometrial cancer (EC) in France. Data were obtained from the National Healthcare Database System (SystèmeNational desDonnées deSanté) from 2016-2021. Patients first hospitalized for EC or with first inscription on the Long-Term Disease list during the study period formed an incident EC cohort. A second cohort comprising patients with initial metastatic and/or recurrent EC was also analyzed. Endpoints included annual incidence and prevalence of EC, baseline characteristics, treatment patterns, overall survival (OS), and time to next treatment or death (TTNTD). Of 60,083 patients in the incident EC cohort (median follow-up 2.0 years; median age 70 years), 23,060 met criteria for the initial metastatic and/or recurrent EC cohort (median follow-up 1.2 years; median age 71 years). Sociodemographic characteristics and comorbidities were similar between cohorts. In first line, 45.3% of the incident EC cohort and 7.4% of the metastatic/recurrent cohort underwent surgery alone, while 5.2% and 31.2%, respectively, received chemotherapy. Chemotherapy alone was the most frequent intervention in both cohorts. Median OS and TTNTD from index date were both not reached in the incident EC cohort, and 2.3 and 1.1 years, respectively, in the metastatic/recurrent EC cohort. At 2 years of follow-up, 21% of patients in the incident EC cohort and 37% in the metastatic/recurrent EC cohort had switched to second-line treatment. The MOONBEAM study highlights the need for improved first-line treatments for metastatic and/or recurrent EC.
Obesity affects 15%-40% of adults with Crohn's disease (CD) and is associated with worse outcomes. GLP-1 receptor agonists (GLP-1RAs) have pleiotropic anti-inflammatory effects, yet their clinical impact in CD with comorbid obesity is incompletely characterized. We evaluated whether GLP-1RA initiation was associated with mortality, health care utilization, and TNF inhibitor use as a proxy measure of treatment intensity. Retrospective new-user cohort study using the TriNetX Global Collaborative Network (162 organizations, 2015-2024). Adults (≥ 18 years) with CD and obesity without prior GLP-1RA exposure were included. Nonusers received calendar-time-matched index dates to minimize immortal time bias. Propensity score matching (1:1) incorporated > 30 covariates including comorbidities, CD treatment intensity proxies, and inflammatory markers. Outcomes were assessed at 1 year (days 1-365 post-index) and 5 years (days 1-1,825 post-index); both time windows were analyzed as fixed horizons under an intention-to-treat framework using separate TriNetX query runs. Patients were censored at last recorded EHR encounter or study end (2024). Due to database constraints, detailed longitudinal exposure data (adherence, discontinuation, agent switching) were not available. Among 10,550 GLP-1RA users and 108,944 nonusers, 9,766 pairs were matched at 1 year and 9,320 at 5 years (the latter representing a subset of the base population with sufficient follow-up). After matching, covariates were well-balanced (all SMDs < 0.1 except BMI by design). At 1 year, GLP-1RA initiation was associated with lower mortality (0.7% vs. 4.2%; RR 0.17, 95% CI 0.13-0.22), hospitalization (10.0% vs. 24.7%; RR 0.40, 95% CI 0.38-0.43), ED visits (18.9% vs. 25.3%; RR 0.75, 95% CI 0.71-0.79), and TNF inhibitor use (7.1% vs. 10.9%; RR 0.65, 95% CI 0.60-0.72); corticosteroid rates were similar (RR 1.00, 95% CI 0.96-1.03). At 5 years, all utilization associations were sustained; corticosteroid use was modestly lower (RR 0.91, 95% CI 0.89-0.94). E-value for 1-year mortality upper CI: 8.56; healthy-user bias cannot be excluded. In adults with CD and obesity, GLP-1RA initiation was associated with lower health care utilization and lower TNF inhibitor use at 1 and 5 years; the latter should not be interpreted as evidence of reduced treatment escalation given inability to distinguish new initiation from continuation. The observed mortality difference is unlikely to reflect a true causal effect and should be treated as hypothesis-generating. These findings support GLP-1RA metabolic safety in this population and warrant prospective evaluation.
Men with castration-resistant prostate cancer (CRPC) who have a pre-existing history of cardiovascular disease (CVD) or other comorbidities are often excluded from clinical trials involving oral androgen receptor pathway inhibitors (ARPi). In this study, we compared all-cause and prostate cancer-specific mortality among CRPC patients, with and without a pre-existing history of CVD, receiving ARPi compared to chemotherapy. Men with CRPC were identified using the Surveillance, Epidemiology, and End Results-Medicare Linked Database from 2004 to 2015. Patients were grouped into two analytical cohorts by drug use. Inverse probability treatment weights (IPTW)-adjusted Cox models and Fine-Gray subdistribution hazards models were used to evaluate associations between ARPi and chemotherapy, and between ENZ and AA for all-cause mortality and cancer-specific mortality separately. The study cohort included 1438 men with CRPC. Nearly 54.4% of patients had a pre-existing history of CVD. Patients with a pre-existing history of CVD had a higher incidence of all-cause and prostate cancer-specific mortality compared to patients without a history of CVD (all-cause mortality: 69.7% vs. 59.3%, prostate cancer-specific mortality: 56.0% vs. 49.5%, respectively). In the pre-existing history of CVD cohort, the IPTW-adjusted Cox model showed a significantly lower all-cause mortality in patients who received APRi, enzalutamide, and abiraterone, versus chemotherapy (IPTW-adjusted hazard ratio [AHR], 0.56; 95% Confidence Interval [CI], 0.48-0.64; p-value < 0.001). Further, the IPTW-adjusted competing risk model showed significantly lower prostate cancer-specific mortality in patients who received ARPi compared with those who received chemotherapy (IPTW-AHR, 0.48; 95% CI, 0.41 to 0.57; p-value < 0.001). In the without pre-existing history of CVD cohort, the adjusted Cox model showed significantly lower all-cause mortality in patients who received APRi than those who received chemotherapy (IPTW-AHR, 0.49; 95% CI, 0.41-0.60; p-value < 0.001). Whereas the IPTW-adjusted competing risk model showed significantly lower prostate cancer-specific mortality in patients who received ARPi compared with those who received chemotherapy (IPTW-AHR, 0.52; 95% CI, 0.42-0.64; p-value < 0.001). In this population-based cohort of older men with castration-resistant prostate cancer, treatment with oral androgen receptor pathway inhibitors was associated with lower estimated risks of all-cause and prostate cancer-specific mortality compared with chemotherapy in patients with and without pre-existing CVD. These findings add real-world comparative effectiveness evidence for patient populations not well represented in randomized clinical trials; however, given the observational design and limitations of administrative data, residual confounding and unmeasured clinical differences may have influenced the results. Prostate cancer that no longer responds to hormone therapy is called castration‐resistant prostate cancer (CRPC). Two commonly used treatments for CRPC are oral androgen receptor pathway inhibitors (ARPis), which are pills, and chemotherapy, which is given by infusion. Many older men with CRPC also have cardiovascular disease (CVD) (such as heart disease or prior stroke), but these patients are often underrepresented in clinical trials. In this study, we used national Medicare data linked with cancer registry records to examine survival outcomes among 1438 older men with CRPC who received either ARPis or chemotherapy between 2012 and 2014. About half of the patients had pre‐existing CVD. After accounting for differences in patient characteristics between treatment groups, men who received ARPis had lower overall mortality and lower prostate cancer–specific mortality compared with those who received chemotherapy. These patterns were similar among patients with and without CVD. Because this was an observational study using administrative data, unmeasured differences between groups may still have influenced the results. Nonetheless, the findings provide real‐world evidence to help inform treatment decisions for older men with advanced prostate cancer.
From a historical perspective, long non-coding RNAs (lncRNAs) represent a relatively short story. However, this story has many plot lines, thrills, twists, and turns that altogether form quite a long saga of its own. lncRNAs stay at the forefront of a recent paradigm shift from a protein-only world to the mysterious RNA world, the enormous complexity of which we are only beginning to appreciate. Here, we review the most enigmatic aspect of lncRNAs, their coding ability in the context of whole-cell regulation. What peptides do lncRNAs encode as true translons? What is the mechanism of their translation? What roles do these ncRNA-encoded peptides (ncPEPs) play during differentiation and development and in distinct pathologies? Do these ncPEPs contribute to the already known regulatory roles of lncRNAs? Shouldn't we coin the coding subset of lncRNAs its apt name: cryptic long non-coding RNAs (crpt-lncRNAs) for their cryptic coding capacity? These and other questions concerning these current winners of the spotlight in molecular biology, which await resolution, are discussed so that molecular history can be rewritten once again.
Artificial intelligence (AI)-powered large language models (LLMs) are increasingly used as adjunctive tools in education, research, and patient care. This systematic review aimed to investigate the current literature on the applications, performance, and ethical considerations regarding the use of artificial intelligence (AI), including large language models (LLM) in plastic and reconstructive surgery. A comprehensive search of PubMed, Scopus, and Cochrane Library was conducted by two independent investigators for studies published in English in peer-reviewed journals reporting findings about applications (education, clinical decision-making, research process), ethical and practical challenges (bias, data privacy, and accountability), and performance of LLMs in facial plastic and reconstructive surgery practice. PRISMA statements and PICOTS frameworks were used for conducting the search and summarizing the literature findings. Twenty-one studies met inclusion criteria, including 11 examining practical uses of ChatGPT and other LLMs, 8 evaluating performance on medical and surgical tasks, and 7 assessing ethical issues and potential limitations. Based on several performance tools, LLMs demonstrated moderate-to-high accuracy, ranging from 54.96% to 77.3%, for generating operative notes, improving patient communication, and conducting literature synthesis. The following concerns were identified in the literature: risk of hallucination or misinformation, lack of data protection compliance, and insufficient transparency. More robust evidence-based longitudinal investigations are needed to establish not only safety and effectiveness but also real-world feasibility. LLMs report promising application results in plastic and reconstructive surgery, particularly for educational and administrative purposes. The use of LLMs in plastic and reconstructive surgical practice remains limited by the lack of evidence-based longitudinal investigations and unclear data protection and ethical frameworks.
Clinical translation in glioma and glioblastoma remains inefficient despite advances in computational drug discovery. An underrecognized contributor to this gap is structural degradation of clinical registry metadata. We analyzed the complete set of 2.357 glioma-related clinical trial records available in the WHO ICTRP registry at the time of extraction (3 January 2026). A deterministic Python-based validation pipeline was developed to normalize phase and study-type annotations while distinguishing technical voids, methodological non-applicability, and structurally inconsistent entries. Two quantitative indices were introduced: the Reporting Gap ([Formula: see text]), reflecting phase metadata completeness, and the Maturity Ratio ([Formula: see text]), describing the balance between early and late translational stages. Phase annotation showed substantial structural degradation, with large fractions of records lacking machine-interpretable phase labels, whereas study-type fields demonstrated high completeness but severe terminological fragmentation. This asymmetry indicates a systemic mismatch between real-world research designs and the classical phase ontology. Consequently, clinically relevant evidence remains invisible to algorithms, which may lead to biased AI-based translational evaluation. The results suggest that semantic validation of registry metadata is a critical prerequisite for robust integration of clinical data into computational drug development cycles.
The acquisition of advanced dental skills typically necessitates extensive practical training. Currently, immersive reality (IR) represents an innovative approach that combines the physical and virtual worlds, providing an optimal learning experience for students. Despite the potential significance of immersive reality (IR) technology in dental education, the impact remains under-studied. This systematic review aimed to provide a thorough review of the benefits of IR technology in dental education. Searches were conducted in PubMed, Embase, and Cochrane databases covering the years 2014 to 2025. The studies selected for inclusion focused on the effects and benefits of using immersive reality technology in dental training, comparing it to traditional dental training methods. Two independent researchers reviewed the selected studies, concentrating on aspects such as training duration, procedural time and errors, and the enhancement of knowledge and skills. 13 studies were included. The main findings indicated that IR technology in dental education reduced procedural time and shortened training durations, decreasing errors while contributing to knowledge and skills development. Overall, these findings collectively provide strong evidence of the benefits of IR technology in dental education. Integrating immersive reality into dental education offers a beneficial approach to support student engagement and skill development for future clinical practice. PROSPERO CRD42024617799.
Diabetes mellitus is a chronic metabolic disorder characterised by impaired glucose homeostasis, resulting in persistent hyperglycaemia. Accurate and prompt diagnosis is essential for early intervention and prevention of long-term complications. Fasting blood glucose levels have traditionally been central to the diagnosis and monitoring of diabetes mellitus. However, growing evidence highlights the clinical relevance of non-fasting glucose measures, including postprandial glucose, random plasma glucose, and glycated haemoglobin (HbA1c) levels. Practical challenges, safety concerns, and evolving insights into glucose physiology have prompted renewed interest in flexible and context-driven approaches to glucose testing. This narrative review examines the physiological basis of fasting and non-fasting glucose regulation and critically evaluates their roles in diabetes screening, diagnosis, and monitoring. It also discusses the strengths and limitations of measuring fasting blood glucose, oral glucose tolerance, HbA1c, random plasma glucose, postprandial glucose, and continuous glucose monitoring. Special attention is given to pre-analytical and practical considerations, patient safety, and the ability of non-fasting measures to capture early metabolic dysfunction and real-world glycaemic exposure. This article reviews evidence supporting the prognostic value of postprandial hyperglycaemia and the expanding role of non-fasting monitoring tools. Non-fasting glucose testing offers substantial advantages in terms of accessibility, safety, and clinical relevance, and is well-suited for population screening and routine diabetes monitoring. Fasting glucose testing remains essential for specific diagnostic and research applications, particularly when strict metabolic standardisation is required. A context-driven framework that prioritises non-fasting approaches while reserving fasting tests for targeted indications provides a balanced and patient-centred strategy for contemporary diabetes care.
We report a pooled analysis of real-world data of adult patients from two European registries of defibrotide use (DEFIFrance and EBMT Post-Authorization Safety Study [EBMT PASS]) to provide insights into the duration of defibrotide therapy to achieve resolution of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) symptoms by severity. Overall, 275 defibrotide-treated adults with VOD/SOS post-hematopoietic cell transplantation (HCT) were included (severe VOD/SOS, n = 215; nonsevere VOD/SOS, n = 60). Median time from the start of defibrotide treatment to VOD/SOS resolution was 18.5 and 16.5 days in patients with severe and nonsevere VOD/SOS, respectively. Among patients with VOD/SOS resolution, symptoms resolved after >21 days in 31% (n = 40/128) and 32% (n = 14/44) with severe and nonsevere VOD/SOS, respectively. In all patients with VOD/SOS resolution independent of severity (n = 174), the Kaplan-Meier-estimated survival at Day 100 post-HCT was 82% (95% confidence interval [CI]: 75%, 87%); this was 78% (95% CI: 70%, 84%) and 91% (95% CI: 78%, 96%) in patients with severe and nonsevere VOD/SOS, respectively. Serious treatment-emergent adverse events of interest occurred in 31% of patients with VOD/SOS resolution. This pooled analysis supports the utility of defibrotide treatment for VOD/SOS and highlights that treatment may often need to be continued beyond 21 days to achieve resolution.
Accurately distinguishing between healthy and diseased states is fundamental to clinical diagnostics. This paper introduces the Harmonic Fowlkes-Mallows (HFM) index, a novel and robust metric for assessing diagnostic accuracy and identifying optimal cut-off points. The proposed HFM index integrates performance across both positive and negative classes by combining the traditional Fowlkes-Mallows Index (FM) with the proposed Negative Fowlkes-Mallows Index (NFM), using a weighted harmonic mean. Unlike conventional measures such as the F1-score or Youden Index, HFM provides a more comprehensive evaluation of classification performance by simultaneously addressing sensitivity and specificity. Additionally, it incorporates a tunable β parameter to adjust for asymmetries in class importance. Through simulation studies, the HFM index demonstrates strong performance in binary classification tasks and proves effective in selecting optimal decision thresholds. To further demonstrate its practical utility, we apply the HFM index to real-world breast cancer data and compare its performance with other diagnostic accuracy measures.