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Atopic dermatitis and the risk of osteoporosis and fractures: a meta-analysis of cohort studies.
BACKGROUND: This meta-analysis aims to evaluate the risk of osteoporosis and fractures in patients with atopic dermatitis (AD) by synthesizing data from cohort studies. We also provide a comprehensive analysis of fracture risks across different severities of AD and anatomical sites. METHODS: Following the PRISMA 2020 guidelines, a systematic search was conducted in PubMed, Embase, and the Cochrane Library up to May 30, 2025. Studies that investigated the relationship between AD and osteoporosis or fractures were included in the analysis. Data extraction and screening were performed independently by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was applied, alongside sensitivity and subgroup analyses. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: Ten cohort studies, involving 368 to over 2 million AD patients, were included. NOS scores ranged from 7 to 8, indicating generally high study quality. The pooled analysis revealed a 56% increased risk of osteoporosis (OR = 1.56, 95% CI: 1.14-2.13; I2 = 99.9%, p < 0.0001) and an 8% increased risk of all-cause fractures (OR = 1.08, 95% CI: 1.05-1.10; I2 = 82.1%, p < 0.0001) in AD patients. Subgroup analyses demonstrated a progressive increase in fracture risk with the severity of AD. Specific risks were significantly higher for vertebral fractures (OR = 1.14, 95% CI: 1.08-1.20; I2 = 67.3%, p = 0.009) and lower limb fractures (OR = 1.11, 95% CI: 1.08-1.13; I2 = 65.0%, p = 0.014). Sensitivity analyses confirmed the robustness of these findings, and no significant publication bias was detected (p = 0.316). CONCLUSION: AD is associated with an increased risk of osteoporosis and fractures, particularly among patients with severe AD and those experiencing vertebral or lower limb fractures. These findings highlight the importance of targeted bone health monitoring in the clinical management of AD patients.Registration: (PROSPERO: CRD420251066550).
Association between fruit and vegetable intake and risk of depression: A systematic review and meta-analysis of prospective cohort studies.
Depression is a leading cause of global disability, and identifying modifiable lifestyle factors is a public health priority. We conducted a systematic review and dose-response meta-analysis of prospective cohort studies examining the association between fruit and vegetable intake and incident depression. PubMed, Web of Science, Scopus, Embase, and Google Scholar were searched through November 2025. Data on study characteristics, dietary assessment, outcomes, effect estimates, and covariates were independently extracted by two reviewers. Random-effects models were used to calculate pooled relative risks (RRs), and linear and non-linear dose-response relationships were assessed. Heterogeneity was evaluated using I2, and evidence certainty was rated with GRADE. Thirteen cohorts with 385,449 participants and 26,592 depression cases were included. Highest versus lowest combined fruit and vegetable intake was associated with a 37% lower risk of depression (RR: 0.63; 95% CI: 0.50, 0.80). Each 200 g/day increase corresponded to a 16% risk reduction (RR: 0.84; 95% CI: 0.74-0.94). Separate analyses showed that fruit and vegetable intake reduced depression risk by 16% and 12%, respectively, with a non-linear dose-response for vegetables. These findings indicate that higher consumption of fruits and vegetables is associated with lower depression risk, supporting dietary strategies as a potential approach for mental health prevention. However, given the observational nature of the included studies, these results should be interpreted with caution, as residual confounding may partially account for the observed associations. Registration: This study was registered at PROSPERO (CRD420261279998).
HYPNOSA: Study protocol for a prospective observational cohort of patients with obstructive sleep apnea.
BACKGROUND: Obstructive Sleep Apnea (OSA) is a common chronic disease that affects more than 20% of the adult population. One of the most frequent and characteristic symptoms of OSA is excessive daytime sleepiness (EDS). This symptom is typically treated in patients with OSA with the application of continuous positive airway pressure (CPAP), the gold-standard treatment for this disease. In some patients who are adequately treated with CPAP, residual excessive daytime sleepiness (REDS) persists. The prevalence, associations, and outcomes associated with REDS remain poorly understood. METHODS: Multicenter, prospective, observational cohort study including 1000 patients. Participants will undergo a sleep study for the diagnosis of obstructive sleep apnea (OSA), 24-h ambulatory blood pressure monitoring, clinical assessment, quality-of-life questionnaires, Epworth Sleepiness Scale, and collection of biochemical variables and biological samples. Patients with OSA will receive standard care, and those prescribed continuous positive airway pressure (CPAP) will be monitored for treatment adherence. OSA patients will be assessed at baseline and at 6, 12, and 24 months. DISSCUSION: We aim to establish a prospective observational cohort of patients with obstructive sleep apnea (OSA) treated with CPAP, with and without REDS. The HYPNOSA project will create the largest available registry of patients with OSA and REDS using real-world data, providing accurate prevalence estimates and long-term outcomes. Biological samples will be analyzed to assess the role of specific biomarkers. TRIAL REGISTRATION: Registered at ClinicalTrials.gov. Identifer: NCT06514482.
Population-level impact of HPV vaccination: a global systematic review of ecological, cross-sectional, and cohort studies.
BACKGROUND: Human papillomavirus (HPV) causes approximately 4.5% of cancers globally, with the highest burden in low- and middle-income countries (LMICs). Since their introduction in 2006, HPV vaccination programs have led to substantial declines in HPV-related outcomes, although impact varies across settings. RESEARCH DESIGN AND METHODS: We conducted a systematic review to evaluate the population-level impact of HPV vaccination on HPV infection, cervical intraepithelial neoplasia grade 2 or higher (CIN2+), genital warts, invasive cervical cancer (ICC), and oropharyngeal cancer (OPC), and examined the influence of coverage, age at initiation, and vaccine type. The review followed PRISMA 2020. RESULTS: Of 13,549 records screened, 63 were included: 9 assessed HPV infection, 24 on CIN2+, 25 on genital warts, and 7 on ICC. Greatest reductions were observed in settings with at least 70% coverage and early vaccination prior to sexual debut, typically achieved through school-based programs. Reported declines ranged from 58-100% for HPV infection, 30-88% for CIN2+, 60-90% for genital warts, and 70-88% for ICC. CONCLUSIONS: HPV vaccination offers strong protection, especially when delivered early and at high coverage within schools. Expanding access and prioritizing underserved populations are essential to achieving global cancer prevention goals. Limitations include heterogeneity across designs, outcome definitions, and follow-up.
Aneurysmal subarachnoid hemorrhage care in a middle-income public healthcare system: A real-world neurocritical care cohort.
BACKGROUND AND PURPOSE: Although aneurysm treatment capacity has expanded worldwide, outcomes after aneurysmal subarachnoid hemorrhage (aSAH) remain strongly influenced by neurocritical care (NCC) delivery, referral pathways, and access to specialized treatment. Contemporary data describing real-world aSAH care in resource-limited healthcare systems remain scarce. We aimed to characterize treatment patterns, NCC delivery, complications, and outcomes in a large Brazilian public referral center. METHODS: This retrospective cohort study included consecutive adults with confirmed aSAH admitted between June 2018 and March 2022 to a high-volume Brazilian tertiary referral center. Only patients admitted within five days of symptom onset were included. Demographic, clinical, radiological, treatment, complication, and outcome data were extracted from institutional records. Primary outcomes were in-hospital mortality and 3-month functional outcome assessed by the modified Rankin Scale (mRS). RESULTS: Seventy-four patients were included. Disease severity was high, with 45% presenting WFNS grades 4-5, 73% modified Fisher grade 4 hemorrhage, and 64% hydrocephalus. Endovascular treatment was performed in 73% of cases, and median time from admission to aneurysm treatment was 1 day. Despite early treatment capability, only 28% of patients were admitted to an ICU within 48 h, while 38% never received ICU care. Delayed cerebral ischemia occurred in 43%, radiologic vasospasm in 58%, ventriculitis in 22%, and infectious complications in 57%. External ventricular drainage was required in 42%, and vasoactive drugs were used in 85%. In-hospital mortality was 42%, and 66% had unfavorable 3-month outcomes (mRS 4-6). CONCLUSIONS: This real-world cohort highlights the substantial neurocritical care burden of aSAH in a middle-income public healthcare system. Despite timely access to definitive aneurysm treatment, patients experienced frequent neurological and systemic complications, emphasizing that contemporary aSAH care extends well beyond aneurysm occlusion.
Revisiting somatosensory evoked potentials in motor neuron diseases: neurophysiological insights from a large cohort.
OBJECTIVE: To systematically investigate Somatosensory Evoked Potential (SEP) abnormalities in a large cohort of patients with Motor Neuron Disease (MND), and to explore their relationship with Motor Evoked Potentials (MEPs) and clinical phenotypes. METHODS: We retrospectively analyzed 267 patients with confirmed MND who underwent standardized SEPs and transcranial magnetic stimulation. Patients were divided into pure/predominant Upper Motor Neuron (UMN) and pure/predominant Lower Motor Neuron/Amyotrophic Lateral Sclerosis (LMN/ALS) groups. SEP abnormalities were assessed using internal normative data, including prolonged latencies, reduced amplitudes, and increased N20-P25 amplitudes. MEPs were classified semi-quantitatively as normal or abnormal by independent raters. RESULTS: At least one SEP abnormality was detected in 75 % of patients, with no significant differences between the UMN and LMN/ALS groups. Increased N20-P25 amplitudes were observed in both phenotypes, suggesting widespread sensory cortical hyperexcitability across the MND spectrum. In contrast, abnormal MEPs were significantly more frequent in UMN patients (p < 0.001). No significant association was found between SEP abnormalities and MEP findings. Upper- and lower-limb SEP latencies were strongly correlated (all p < 0.001), whereas increased SEP amplitudes did not correlate with latency abnormalities. CONCLUSIONS: SEP abnormalities are highly prevalent in MND and appear largely independent from corticospinal dysfunction. Increased SEP amplitudes likely reflect primary cortical sensory hyperexcitability rather than impaired sensory conduction. SIGNIFICANCE: These findings support the concept of MND as a multisystem network disorder that involves sensory cortical circuits and highlight the role of SEPs in the diagnostic workup.
Non-motor symptoms and healthcare utilization before diagnosis of myasthenia gravis: a nationwide cohort study.
BACKGROUND: Non-motor symptoms have been reported prior to myasthenia gravis (MG) diagnosis. However, the temporal patterns of non-motor symptoms and healthcare utilization before MG diagnosis remain unclear. METHODS: We conducted a retrospective, population-based cohort study using the Korean National Health Insurance Service (KNHIS) database from 2011 to 2021. Incident MG cases were identified using the International Classification of Diseases, Tenth and Rare Intractable Disease codes. Individuals younger than 20  years or with missing health screening data were excluded. Each MG case was matched 1:10 by age, sex, and index date to controls. Non-motor symptoms and healthcare utilization were defined using operational criteria derived from KNHIS claims data. Rate ratios (RRs) and 95 % confidence intervals (CIs) were estimated across four prespecified intervals (0-1, 1-2, 2-5, and 5-10  years) before MG diagnosis. RESULTS: We included 8,355 MG patients and 83,550 controls (mean age, 53.7  years; male, 44 %). MG patients had higher rates of any non-motor symptoms over 10  years(RR 1.34; 95 % CI 1.30-1.39), with the sharpest increase in the year before diagnosis. Depression, anxiety, migraine, constipation, and insomnia consistently showed higher RRs across all intervals. Hospitalizations (RR 1.66; 95 % CI 1.61-1.71) and outpatient clinic visits (RR 1.10; 95 % CI 1.04-1.17) were consistently higher across 10  years, peaking during the 0-1 year before MG diagnosis. CONCLUSION: Non-motor symptoms and healthcare utilization increased years before MG diagnosis. Earlier recognition of these symptom patterns may facilitate timelier evaluation for MG and improve diagnostic pathways.
Oxymetazoline hydrochloride nasal spray for nasal function recovery after endoscopic transsphenoidal pituitary adenectomy: a propensity score-matched cohort study.
OBJECTIVE: To evaluate whether short-term adjunctive oxymetazoline hydrochloride nasal spray is associated with improved early nasal recovery after endoscopic transnasal transsphenoidal surgery for pituitary adenoma. METHODS: This single-center retrospective propensity score-matched cohort study included adults undergoing first-time endoscopic transnasal transsphenoidal surgery between January 2021 and December 2024. Patients receiving oxymetazoline hydrochloride 0.05% nasal spray plus routine saline irrigation were compared with those receiving saline irrigation alone. The primary outcome was longitudinal change in Nasal Obstruction Symptom Evaluation (NOSE) score from postoperative baseline to weeks 1, 2, and 4. Secondary outcomes included endoscopic nasal findings, nasal comfort, responder-defined NOSE improvement, and short-term safety outcomes. RESULTS: Among 860 eligible patients, 630 remained after 1:1 propensity score matching, with 315 patients in each group. Baseline covariates and postoperative pre-intervention nasal status were well balanced. Adjunctive oxymetazoline was associated with lower NOSE scores and modestly more favorable endoscopic findings and nasal comfort during early follow-up, although the absolute between-group differences were small and attenuated by week 4. Responder analyses based on ≥ 30% NOSE score reduction showed no statistically significant between-group differences. Major postoperative nasal complications were comparable between groups. Potentially drug-related adverse reactions occurred in 55 patients in the oxymetazoline group (17.5%), mainly mild local symptoms, and no serious drug-related adverse events or treatment discontinuations were documented. CONCLUSIONS: Short-term adjunctive oxymetazoline combined with routine saline irrigation was associated with modest early nasal recovery benefits after endoscopic transnasal transsphenoidal surgery. Its use should remain cautious, selective, and time-limited, pending prospective confirmation of clinical benefit and long-term safety.
Endovascular treatment after stroke beyond 24 h vs 6-24 h: a propensity score-matched cohort study.
BACKGROUND: Endovascular thrombectomy (EVT) is the standard treatment for acute ischemic stroke due to anterior circulation large vessel occlusion (LVO) within 6-24 h. However, the safety and feasibility of EVT for anterior circulation strokes beyond 24 h remain uncertain. METHODS: We conducted a retrospective cohort study of consecutive patients with anterior circulation LVO who underwent EVT at Changhai Hospital from 2018 to 2023. Patients were stratified into late (6-24 h) and very late (>24 h) windows. Propensity score matching (PSM) was performed to adjust for baseline imbalances, including age, sex, NIHSS, ASPECTS, occlusion location, perfusion parameters, and vascular risk factors. The primary outcome was functional independence (modified Rankin Scale [mRS] ≤ 2) at 3 months. Secondary outcomes included successful reperfusion (TICI 2b-3) and symptomatic intracranial hemorrhage (sICH). RESULTS: Among 1043 screened patients, 429 patients with anterior circulation LVO were included after exclusions, comprising 373 in the late window and 56 in the very late window. PSM yielded 42 matched pairs. Compared with the late window group, the very late window group showed no statistically significant differences in functional independence (54.8% vs. 57.1%; OR = 0.908, 95% CI 0.382-2.153, p = 0.830), successful reperfusion (88.1% vs. 92.9%; OR = 1.800, 95% CI 0.481-7.096, p = 0.460), sICH (2.4% vs. 9.5%; OR = 0.232, 95% CI 0.012-1.652, p = 0.200), intraprocedural complications (26.2% vs. 19.0%; OR = 1.508, 95% CI 0.540-4.362, p = 0.440), or postoperative complications (33.3% vs. 35.7%; OR = 0.900, 95% CI 0.363-2.219, p = 0.820). CONCLUSIONS: In this selected, single-center cohort of anterior circulation LVO patients undergoing EVT, treatment initiated beyond 24 h appeared to have comparable effectiveness and safety to treatment initiated within 6-24 h. Definitive evidence requires confirmation from adequately powered randomized controlled trials.
Chronic neurological diseases with acute respiratory failure in a real-life cohort: insights into ICU and long-term survival-A retrospective study.
BACKGROUND: Patients with chronic neurological diseases (CND) are at increased risk of pulmonary complications that often require ICU admission. This study aimed to identify clinical factors associated with ICU mortality and long-term survival in patients with CND who developed acute respiratory failure (ARF). METHODS: This retrospective cohort study was conducted in a level III respiratory ICU. Patients with pre-existing CND admitted to the ICU with ARF were included. ICU mortality was analyzed using multivariable logistic regression. Long-term survival after ICU discharge was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. Mortality timing was further characterized using hazard function analysis. RESULTS: A total of 220 patients were included; the most common neurological diagnoses were dementia (37.3%), stroke (22.7%), and amyotrophic lateral sclerosis (14.1%). ICU mortality was 33.6%. Higher APACHE II scores were independently associated with increased ICU mortality (OR 1.076 per point increase; 95% CI 1.029-1.126; p < 0.001). Long-term survival differed significantly by post-discharge respiratory support strategy, with Kaplan-Meier analysis demonstrating more favorable survival patterns among patients receiving home non-invasive mechanical ventilation (NIMV) (p = 0.003). In Cox regression analysis, age, home NIMV, and feeding modality at discharge were independently associated with long-term outcomes. Survival analyses revealed an early clustering of deaths within the first months after ICU discharge, particularly among patients with dementia. CONCLUSIONS: In patients with CND, acute physiological severity was the main determinant of ICU mortality, whereas long-term survival after ICU discharge was poor, with deaths clustering within the first months thereafter. Post-discharge respiratory support and nutritional management should be individualized according to the expected clinical trajectory and patient values.
Approaches to observational study designs and analytical options to evaluate the safety of multi-dose vaccines: a systematic review.
INTRODUCTION: Observational studies require careful considerations when evaluating the safety of multidose vaccines. We reviewed design and analytical approaches in observational studies evaluating the safety of multidose vaccines in the post-licensure phase. METHODS: EMBASE, MEDLINE, Web of Science, and Scopus (2018-2022) were searched for hypothesis-testing studies evaluating the safety of multidose vaccines. Key features from frequently used designs were extracted. RESULTS: Among 123 eligible studies, cohort (46%) and self-controlled case series (SCCS)/self-controlled risk interval (SCRI) (40%) followed by case-control (12%) were the most common designs, and 15% of studies used multiple designs. Among cohort studies evaluating multiple doses, vaccination date (36%) and cohort entry with time-updated exposure status (32%) were frequent approaches used to define time zero. Twenty-eight percent of cohort studies did not report time zero; all but one evaluated COVID-19 vaccine effect on post-delivery and fertility-related outcomes. For SCCS/SCRI, 64% of studies accounted for event-dependent exposures, mainly by including pre-exposure periods (53%) and modified SCCS model (48%), while 20% employed multiple correction strategies. Among studies using multiple designs, 68% reached consistent conclusions. CONCLUSIONS: SCCS/SCRI and cohort designs dominate multidose vaccine safety studies. Clear reporting on time zero in pregnancy and fertility-related cohort studies, and on addressing event-dependent exposures in SCCS/SCRI studies is needed, along with guidance on interpreting results from multiple designs.
Evaluation of intravenous sedation in dental implant surgeries: A prospective cohort study.
PURPOSE: This study aimed to evaluate the impact of intravenous sedation on patient-centered outcomes during implant and bone augmentation surgeries. METHOD: A prospective observational cohort study included 40 patients undergoing placement of ≥3 implants, with or without bone augmentation. Patients underwent surgery under either intravenous sedation (n = 20) or local anesthesia alone (n = 20), according to routine clinical decision-making and patient preference. The sedation group received intravenous sedation with a multimodal regimen comprising remimazolam, dexmedetomidine, alfentanil, and low-dose esketamine, whereas the control group received local anesthesia only. Patient-reported outcome measures, hemodynamic parameters (SBP, DBP, HR, SpO2), postoperative pain (0-10 scale), and OHRQoL (OHIP-14) were recorded from baseline through 7 days post-surgery. RESULTS: Intravenous sedation was associated with significantly lower intraoperative pain (0.5 [IQR: 0∼2.75] vs. 3.25 ± 2.40, p = 0.003), anxiety (1 [IQR: 0∼2.75] vs. 4 [IQR: 3∼6], p = 0.001), and experienced discomfort (2 [IQR: 1∼3.75] vs. 4.15 ± 2.16, p = 0.016), and shortened perceived treatment duration (2.90 ± 2.34 vs. 5 [IQR: 4∼5], p = 0.020). Early postoperative pain was lower in the sedation group from Days 1-4 (p = 0.003-0.010). Hemodynamic parameters were more stable under sedation, with lower SBP (116.42 ± 13.32 vs. 144.11 ± 17.42 mmHg, p < 0.001), DBP (73.21 ± 10.28 vs. 82.37 ± 11.03 mmHg, p = 0.012), and HR (71.00 [IQR: 62.50∼79.25] vs. 85.00 ± 10.72 bpm, p = 0.021). OHRQoL scores favored the sedation group in swallowing, diet, malaise, and daily activities, particularly during the first three postoperative days (p=0.006-0.040). CONCLUSION: Intravenous sedation may enhance the patient experience during implant and/or bone augmentation procedures by reducing intraoperative pain and anxiety, improving hemodynamic stability, and promoting better early-postoperative recovery and OHRQoL. These findings suggest that intravenous sedation provides a safe and effective alternative for implant dentistry surgery, particularly for anxious or pain-sensitive individuals.
PGR expression as a pharmacogenomic companion biomarker to GENE70-derived genomic risk in ER-positive/HER2-negative breast cancer.
BACKGROUND: The biology of the estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancers is heterogeneous even when they are categorized by their risk via genomics. Transcriptomic PGR expression reflects endocrine pathway activity and may provide complementary biological information within established GENE70-derived genomic-risk categories. Whether this molecular marker improves the biological interpretation of genomic-risk stratification beyond conventional clinicopathological assessment remains uncertain. OBJECTIVES: The aim of this study was to determine whether transcriptomic PGR expression provides complementary biological and prognostic information within reconstructed GENE70-derived genomic-risk categories and refines the characterization of endocrine-related tumour biology in ER-positive/HER2-negative breast cancer. METHODS: This study analysed publicly available transcriptomic and clinical data from three cohorts: METABRIC (discovery cohort), GSE96058/SCAN-B cohort (validation cohort) and TCGA-BRCA cohort (molecular validation cohort). The GENE70-derived genomic-risk score was reconstructed for each cohort using matched genes. Cox regression, Kaplan-Meier analysis and subgroup comparisons were used to assess relationships between PGR expression, clinicopathologic variables, molecular features and survival outcomes. RESULTS: Across the three independent cohorts, low transcriptomic PGR expression was consistently associated with higher GENE70-derived genomic risk, increased MKI67 expression, reduced ESR1 expression and enrichment of the Luminal B subtype. Survival findings differed between cohorts. In the discovery METABRIC cohort, transcriptomic PGR expression showed heterogeneous associations with survival, particularly within GENE70-derived high-risk subgroups, whereas the external GSE96058/SCAN-B validation cohort demonstrated consistent associations between low PGR expression and poorer overall survival in both the overall ER-positive/HER2-negative population and GENE70-derived high-risk subgroups. CONCLUSION: These findings suggest that transcriptomic PGR provides complementary biological and prognostic information within GENE70-derived genomic-risk categories. However, because treatment response was not evaluated in the present study, the findings should not be interpreted as evidence of predictive or pharmacogenomic utility and prospective studies incorporating treatment-response analyses are required before such applications can be established.
ALID score for treatment-effect heterogeneity of adjunctive low-voltage area ablation in persistent atrial fibrillation: A post hoc analysis of SUPPRESS-AF.
BACKGROUND: In persistent atrial fibrillation (AF), the incremental benefit of adjunctive low-voltage area (LVA) ablation beyond pulmonary vein isolation (PVI) remains inconsistent. OBJECTIVE: To examine whether a simple clinical score characterizes treatment-effect heterogeneity of adjunctive LVA ablation among patients with mapped LVA > 5 cm2 and to perform an exploratory supportive analysis in an independent randomized cohort. METHODS: In this post-hoc analysis of SUPPRESS-AF, which included patients with persistent AF and mapped LVA > 5 cm2 after PVI, four variables-age ≥ 75 years, left atrial diameter > 44 mm, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and absence of diabetes-were combined into the ALID score (0-4). Patients were stratified into low (0-1), intermediate (2), and high (3-4) score groups. Because EARNEST-PVI did not use LVA-guided ablation or select patients based on mapped LVA, it was analyzed as an exploratory supportive cohort rather than as an external validation cohort. RESULTS: In SUPPRESS-AF (n = 336), a significant treatment-by-score interaction was observed (P < 0.001). Adjunctive LVA ablation was associated with increased recurrence in the low-score stratum (HR 3.92; 95% CI 1.50-10.20) and reduced recurrence in the high-score stratum (HR 0.48; 95% CI 0.26-0.86). In EARNEST-PVI (n = 494), a qualitatively similar interaction pattern was observed for additional ablation beyond PVI (interaction P = 0.029), although the ablation strategy differed from LVA-guided ablation. CONCLUSIONS: Among patients with persistent AF and mapped LVA >5 cm2, the ALID score identified heterogeneity in response to adjunctive LVA ablation. These hypothesis-generating findings require prospective validation before clinical implementation.
Randomized phase-II trial of surufatinib plus FOLFOX/FOLFIRI versus FOLFOXIRI as second-line therapy for metastatic colorectal cancer.
BACKGROUND: Second-line treatment for metastatic colorectal cancer (mCRC) typically involves oxaliplatin- or irinotecan-based doublet chemotherapy with or without anti-angiogenic antibodies. Triplet regimens such as FOLFOXIRI have demonstrated synergy and improved efficacy as first-line therapy. Surufatinib, an oral multi-kinase inhibitor targeting VEGFR1-3, FGFR1, and CSF-1R, may enhance chemotherapy efficacy. We evaluated surufatinib combined with doublet (FOLFOX/FOLFIRI) versus triplet (FOLFOXIRI) chemotherapy as second-line treatment for mCRC. PATIENTS AND METHODS: This multicentre, open-label, randomized phase-II trial used Simon's minimax two-stage design. Eligible patients had mCRC progressing on or within 6 months after first-line doublet chemotherapy. Patients were randomized 1:1 to surufatinib 250 mg once daily plus either mFOLFOX6/FOLFIRI (doublet cohort, selected based on prior regimen) or FOLFOXIRI (triplet cohort). The primary endpoint was objective response rate (ORR). RESULTS: From September 2021 to November 2023, 57 patients were randomized (28 per cohort after one withdrawal). In the doublet cohort, ORR was 35.7% (95% CI: 18.6-55.9), median progression-free survival (PFS) was 5.4 months (95% CI: 3.8-7.0), and median overall survival (OS) was 19.0 months (95% CI: 9.2-28.8). In the triplet cohort, ORR was 39.3% (95% CI: 21.5-59.4), median PFS was 5.8 months (95% CI: 3.3-8.2), and median OS was 10.9 months (95% CI: 6.0-15.8). Grade ≥3 treatment-emergent adverse events occurred more frequently in the triplet (71.4%) versus doublet (57.1%) cohort, with higher rates of treatment delays (89.3% versus 72.0%) and discontinuations (25.0% versus 14.3%). CONCLUSIONS: Surufatinib plus doublet chemotherapy showed encouraging antitumor activity and acceptable tolerability in second-line mCRC, warranting further evaluation in a larger randomized trial. In contrast, surufatinib plus triplet chemotherapy was associated with increased toxicity, more frequent treatment delays or discontinuations, and shorter overall survival; this combination is not recommended for further investigation in this setting.ClinicalTrials.gov: NCT04734249Date of registration: January 31, 2021.
Retrosigmoid craniotomy surgical guide: The way forward for precise exposure of the transverse-sigmoid sinuses.
INTRODUCTION: The retrosigmoid craniotomy is the workhorse approach to the cerebellopontine angle. Accurate localisation of the transverse-sigmoid junction (TSJ) is key for optimised exposure and cerebellar retraction. Various methods, both anatomical and navigational, have been used but with suboptimal results. We utilised a 3D-printed retrosigmoid surgical guide in an attempt to overcome this and report our early outcomes and experiences in the design, production and utilisation of the guide. METHODS: This is a prospective cohort study of the patients with retrosigmoid craniotomies performed using the surgical guides. Patient demographics and diagnoses, along with the accuracy of the planned burrhole and craniotomy, need for craniotomy extension, presence of venous sinus injury, set-up time, and cost were reported. RESULTS: There were ten cerebellopontine angle cases in which the surgical guides were utilised, three petrous meningiomas, two trigeminal neuralgias, two metastasis, and three other tumours. The planned burrhole and craniotomy were precise in all cases with accurate exposure of the TSJ and no requirement for craniotomy extension. The mean set up time was 3.9 min, and the mean cost of the surgical guides was USD 470.90. One elderly patient had an intraoperative transverse sinus injury related to adherent dura that was planned for exposure. CONCLUSION: The 3D-printed surgical guide is a potential solution to the rapid, precise and consistent identification of the TSJ when performing a retrosigmoid craniotomy. We present our early experience and discuss nuances in the designing, production, and intraoperative phases to optimise the precision of this guide. We suggest two methods to avoid sinus injury in elderly patients: either to plan the craniotomy to the edge of the sinus, or to plan sinus exposure but to use burr drills rather than the osteotome, as in our case, to expose the sinus.
Development and validation of a comprehensive prognostic model for 28-day ICU mortality in non-traumatic subarachnoid hemorrhage: an analysis based on the MIMIC-IV database.
BACKGROUND: Due to the complex pathophysiology of non-traumatic subarachnoid hemorrhage (SAH), accurate risk prediction remains a challenge. Our aim is to develop and validate a comprehensive prognostic model that integrates demographic characteristics, vital signs, laboratory parameters, and more, to provide clinical decision-making support in real-world practice. METHODS: We conducted a retrospective cohort study of 785 Non-traumatic subarachnoid hemorrhage patients. The cohort was randomly divided into a training set (n = 549) and a validation set (n = 236). Feature selection was performed using LASSO regression, followed by backward stepwise Cox regression for optimization. A nomogram was constructed based on independent predictive factors, and model performance was assessed using discrimination, calibration, and decision curve analysis. To prevent immortal-time bias, all predictors were anchored to a fixed early (first-24-hour) measurement window, treatment variables were modelled as binary indicators rather than cumulative exposures, and a five-model sensitivity analysis with baseline-severity adjustment was performed. RESULTS: The development of our model followed a systematic approach: first, 15 potential predictive factors were selected via LASSO regression, which were then refined to 12 independent predictors using backward stepwise Cox regression. The final predictive factors included: Ventilation, AHT, Nimodipine 60 mg, Age, SAPS.II, Input amount, Calcium total, Platelet count, White blood cells, Anion gap, pH, and Chloride. The integrated model demonstrated excellent predictive ability for 7-day, 14-day, and 21-day mortality in both the training set (AUC: 0.972, 0.934, 0.898) and the validation set (AUC: 0.968, 0.948, 0.911). Calibration curves and decision curve analysis confirmed the model's reliability and clinical utility across different time points. We constructed a nomogram for individualized risk prediction. Univariate Kaplan-Meier survival analysis demonstrated significant stratification of survival outcomes by each predictor, while restricted cubic spline analysis revealed non-linear relationships between continuous variables and mortality risk. Random survival forest analysis identified the top three predictive factors (Nimodipine 60 mg, Ventilation, AHT) and compared them with our full 12-variable model, confirming superior performance of the integrated model at all time points. At the 28-day primary endpoint, the model achieved a time-dependent AUC of 0.898 (training) and 0.904 (validation); after restricting predictors to the early baseline window, the leakage-controlled model retained good discrimination (validation C-index 0.803). CONCLUSIONS: Our ICU 28-day mortality prognosis model demonstrated robust performance in predicting ICU 28-day mortality in non-traumatic subarachnoid hemorrhage. The model, through the nomogram, provides individualized risk assessment, aiding clinical decision-making and patient stratification.