Trends and Progress in Neuroendovascular Treatment in Japan: Japanese Registry of Neuroendovascular Therapy (JR-NET) 4. Main Report.

We reported the main results of the Japanese Registry of Neuroendovascular Therapy (JR-NET) 4, a nationwide surveillance of therapy (NET) in Japan from January 2015 to December 2019. JR-NET 4 registered consecutive patients who underwent NETs by Japan Society of Neuroendovascular Therapy (JSNET) -certified specialists. The primary endpoint was functional independence (mRS score of 0-2) at 30 days post-NET, with secondary endpoints focusing on technical success and major adverse events within 30 days.A total of 63,230 patients and 60,354 NET procedures from 166 participating centers were analyzed. During the study period, NET cases have consistently increased, with an increase in the proportion of elderly patients. A significant trend shift was observed in the distribution of NET procedures, with endovascular treatment for acute ischemic stroke that showed a dramatic increase in 5 years. This trend aligns with key randomized clinical trials from 2015 that presented the efficacy of this treatment. Clinical outcomes at 30 days posttreatment revealed that endovascular treatment for acute ischemic stroke and other NETs maintained safety and effectiveness despite varying prevalence of functional independence between target diseases. The study also observed a steady increase in emergency treatment cases, reflecting the increase in acute ischemic stroke, a time-sensitive medical condition.This comprehensive surveillance highlights the trend of NET practices in Japan, driven by clinical evidence and advancements in treatment devices. Although these findings were specific to Japan, they offer valuable insights into the broader trends in NETs and acute stroke care.

Clinical and radiological outcome following trauma-related reverse shoulder arthroplasty.

BACKGROUND: Reverse shoulder arthroplasty (RSA) is a frequently used therapy for complex proximal humeral fractures and posttraumatic disorders. The present study's purpose was to assess the clinical and radiological outcome of primary and secondary RSA, and to analyze the impact of refixation of the greater tuberosity (GT). PATIENTS AND METHODS: 28 patients with primary fracture RSA and 18 patients with RSA due to posttraumatic disorders were examined with a mean clinical follow-up of 2.5 ± 1.73 years. Operative details and radiographs were retrospectively reviewed. Additional analyses were performed for healed and non-healed GT in primary RSA. RESULTS: Patients with fracture RSA had higher Constant-Murley score (CMS) than secondary RSA without reaching significance (p = 0.104). No significant difference was present for the quality of life measured by the Short Form 36 (SF 36) and the range of motion. In primary RSA, 78.6% GT healed anatomically. Compared to non-healed GT, patients with healed GT had a significantly higher CMS (p = 0.011), external rotation (p = 0.026) and forward flexion (p = 0.083), whereas DASH score was lower without a significant difference (p = 0.268). SF 36 showed no significant difference. Patients with healed GT had a more neutral glenoid version (p = 0.009). CONCLUSION: Superior range of motion and clinical outcome scores were present for anatomically healed GT. Therefore, refixation of the tuberosities is recommended. Secondary RSA can result in inferior results compared to primary RSA, so patients need to be adequately informed.

Development of a Novel Statistical Model for Predicting Clinical Outcomes in Stroke Patients With Tandem Occlusions After Endovascular Therapy.

BACKGROUND: Tandem occlusions are intracranial large vessel occlusions (LVOs) with a concomitant ipsilateral extracranial internal carotid artery occlusion and can cause more severe stroke symptoms. AIM: To develop a simple, rigorously cross-validated novel tool to predict clinical outcomes following tandem occlusion in patients with acute LVO stroke, based on data that are easily available to clinicians. To have used machine learning approaches to utilize the available information from clinical and angiographic data to make predictive models able to distinguish between mortality versus survival and good (modified Rankin Scale (mRS) ≤ 2) versus unfavorable neurological outcomes (mRs ≥ 3) Materials and methods: Retrospective data from 87 consecutive patients with anterior circulation stroke and tandem occlusions who underwent mechanical thrombectomy and stenting between December 2009 and January 2020 were analyzed. Patients were stratified into three groups based on the location of their LVO, and these groups were compared using statistical tests. Predictive models were built and cross-validated 1000 times to estimate their predictive power, measured by accuracy and area under the receiver operating curve (AUROC). RESULTS: For distinguishing good outcome (mRS ≤ 2) versus poor outcome (mRS ≥ 3), the model comprised age, initial National Institute of Health Stroke Scale (NIHSS) score, Alberta Stroke Program Early CT Score (ASPECTS), NIHSS at 24 hours, NIHSS at discharge and intracranial haemorrhage and yielded an accuracy of 83% and the AUROC of 0.91. For mortality prediction, the model comprised age, initial NIHSS, intravenous thrombolysis, NIHSS at 24 hours and NIHSS at discharge and yielded an accuracy of 91% and an AUROC of 0.94. CONCLUSIONS: Models developed exhibit strong predictive performance and can distinguish between both the instances of survival versus mortality and good versus poor outcome with an aim to support clinicians in deciding on optimal management for these complex patients. The developed model will help identify those at risk of poorer outcomes and the prospective better selection of patients with acute ischaemic large vessel stroke secondary to tandem occlusions.

Anterolateral Dual Plate Fixation for Distal Metaphyseal-Diaphyseal Junction Fractures of the Humerus: Biomechanical Finite Element Analysis with Clinical Results.

Background: Distal metaphyseal-diaphyseal junction fractures of the humerus are a subset of injuries between humeral shaft fractures and distal intra-articular humerus fractures. A lack of space for distal fixation and the unique anatomy of concave curvature create difficulties during operative treatment. The closely lying radial nerve is another major concern. The aim of this study was to determine whether anterolateral dual plate fixation could be effective for a distal junctional fracture of the humerus both biomechanically and clinically. Methods: A right humerus 3-dimensional (3D) model was obtained based on plain radiographs and computed tomography data of patients. Two fractures, a spiral type and a spiral wedge type, were constructed. Three-dimensional models of locking compression plates and screws were constructed using materials provided by the manufacturer. The experiment was conducted by using COMSOL Multiphysics, a finite element analysis, solver, and simulation software package. For the clinical study, from July 2008 to March 2021, a total of 72 patients were included. Their medical records were retrospectively reviewed to obtain patient demographics, elbow range of motion, Disabilities of the Arm, Shoulder and Hand (DASH) scores, Mayo Elbow Performance Scores (MEPS), and hand grip strength. Results: No fracture fixation construct completely restored stiffness comparable to the intact model in torsion or compression. Combinations of the 7-hole and 5-hole plates and the 8-hole and 6-hole plates showed superior structural stiffness and stress than those with single lateral plates. At least 3 screws (6 cortices) should be inserted into the lateral plate to reduce the load effectively. For the anterior plate, it was sufficient to purchase only the near cortex. Regarding clinical results of the surgery, the range of motion showed satisfactory results in elbow flexion, elbow extension, and forearm rotation. The average DASH score was 4.3 and the average MEPS was 88.2. Conclusions: Anterolateral dual plate fixation was biomechanically superior to the single-plate method in the finite element analysis of a distal junctional fracture of the humerus model. Anterolateral dual plate fixation was also clinically effective in a large cohort of patients with distal junctional fractures of the humerus.

Association between procedural time and outcome in unsuccessful mechanical thrombectomy for acute ischemic stroke: analysis from the Italian Registry of Endovascular Treatment in Acute Stroke.

BACKGROUND: We aim to assess the association between procedural time and outcomes in patients in unsuccessful mechanical thrombectomy (MT) for anterior circulation acute stroke. METHODS: We conducted a cohort study on prospectively collected data from patients with M1 and/or M2 segment of middle cerebral artery occlusion with a thrombolysis in cerebral infarction 0-1 at the end of procedure. Primary outcome was 90-day poor outcome. Secondary outcomes were early neurological deterioration (END), symptomatic intracranial hemorrhage (sICH) according to ECASS II and sICH according to SITS-MOST. RESULTS: Among 852 patients, after comparing characteristics of favourable and poor outcome groups, logistic regression analysis showed age (OR: 1.04; 95%CI: 1.02-1.05; p < 0.001), previous TIA/stroke (OR: 0.23; 95%CI: 0.12-0.74; p = 0.009), M1 occlusion (OR: 1.69; 95%CI: 1.13-2.50; p = 0.01), baseline NIHSS (OR: 1.01; 95%CI: 1.06-1.13; p < 0.001) and procedural time (OR:1.00; 95% CI: 1.00-1.01; p = 0.003) as independent predictors poor outcome at 90 days. Concerning secondary outcomes, logistic regression analysis showed NIHSS (OR:0.96; 95%CI: 0.93-0.99; p = 0.008), general anaesthesia (OR:2.59; 95%CI: 1.52-4.40; p < 0.001), procedural time (OR: 1.00; 95% CI: 1.00-1.01; p = 0.002) and intraprocedural complications (OR: 1.89; 95%CI: 1.02-3.52; p = 0.04) as independent predictors of END. Bridging therapy (OR:2.93; 95%CI: 1.21-7.09; p = 0.017) was associated with sICH per SITS-MOST criteria whereas M1 occlusion (OR: 0.35; 95%CI: 0.18-0.69; p = 0.002), bridging therapy (OR: 2.02; 95%CI: 1.07-3.82; p = 0.03) and intraprocedural complications (OR: 5.55; 95%CI: 2.72-11.31; p < 0.001) were independently associated with sICH per ECASS II criteria. No significant association was found between the number of MT attempts and analyzed outcomes. CONCLUSIONS: Regardless of the number of MT attempts and intraprocedural complications, procedural time was associated with poor outcome and END. We suggest a deeper consideration of procedural time when treating anterior circulation occlusions refractory to MT.

Analysis of radiologic parameters and clinical outcomes in supramalleolar osteotomy for varus ankle osteoarthritis: A novel method for evaluating ankle alignment.

BACKGROUND: Solely relying on the tibial ankle surface (TAS) angle for determining the mechanical ankle axis might be insufficient. We introduce a novel method to determine the distance from the center of the talus to the tibial axis (TTD). This study aimed to investigate the association between clinical outcomes and radiological changes before and after supramalleolar osteotomy (SMO), including TAS angle, talar tilt (TT) angle, tibiotalar surface (TTS) angle and TTD. METHODS: Seventy patients who received SMO were enrolled. Radiological changes were measured using weight-bearing anteroposterior imaging. The percentage of talar center displacement (TTDP) was calculated as the difference between postoperative and preoperative TTD, divided by talar width (TW). Clinical assessments were performed using the American Orthopedic Foot and Ankle Society ankle-hindfoot (AOFAS) scale. Differences in the aforementioned indicators before and after the operation were analyzed. We defined ΔAOFAS, ΔTAS, ΔTT and ΔTTS as the difference between postoperative and preoperative values. RESULTS: ΔTTS correlated with ΔAOFAS (r = 0.40, p = 0.008), as did TTDP (r = 0.32, p = 0.035). No correlation was observed between ΔAOFAS and ΔTAS. In the comparison between groups, patients with a TTDP greater than 26.19 exhibited a significantly greater ΔAOFAS. The high intraclass correlation coefficient indicated good reliability of the novel method. CONCLUSION: Solely relying on the TAS angle for tibial correction was insufficient. We found TTD as a novel method to evaluate mechanical ankle joint axis. TTDP and ΔTTS both positively correlated with ΔAOFAS, indicating the usefulness of these radiologic parameters.

Assessing the predictive capability of machine learning models in determining clinical outcomes for patients with cervical spondylotic myelopathy treated with laminectomy and posterior spinal fusion.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is a prevalent degenerative condition resulting from spinal cord compression and injury. Laminectomy with posterior spinal fusion (LPSF) is a commonly employed treatment approach for CSM patients. This study aimed to assess the effectiveness of machine learning models (MLMs) in predicting clinical outcomes in CSM patients undergoing LPSF. METHODS: A retrospective analysis was conducted on 329 CSM patients who underwent LPSF at our institution from Jul 2017 to Jul 2023. Neurological outcomes were evaluated using the modified Japanese Orthopaedic Association (mJOA) scale preoperatively and at the final follow-up. Patients were categorized into two groups based on clinical outcomes: the favorable group (recovery rates ≥ 52.8%) and the unfavorable group (recovery rates < 52.8%). Potential predictors for poor clinical outcomes were compared between the groups. Four MLMs-random forest (RF), logistic regression (LR), support vector machine (SVM), and k-nearest neighborhood (k-NN)-were utilized to predict clinical outcome. RF model was also employed to identify factors associated with poor clinical outcome. RESULTS: Out of the 329 patients, 185 were male (56.2%) and 144 were female (43.4%), with an average follow-up period of 17.86 ± 1.74 months. Among them, 267 patients (81.2%) had favorable clinical outcomes, while 62 patients (18.8%) did not achieve favorable results. Analysis using binary logistic regression indicated that age, preoperative mJOA scale, and symptom duration (p < 0.05) were independent predictors of unfavorable clinical outcomes. All models performed satisfactorily, with RF achieving the highest accuracy of 0.922. RF also displayed superior sensitivity and specificity (sensitivity = 0.851, specificity = 0.944). The Area under the Curve (AUC) values for RF, Logistic LR, SVM, and k-NN were 0.905, 0.827, 0.851, and 0.883, respectively. The RF model identified preoperative mJOA scale, age, symptom duration, and MRI signal changes as the most significant variables associated with poor clinical outcomes in descending order. CONCLUSIONS: This study highlighted the effectiveness of machine learning models in predicting the clinical outcomes of CSM patients undergoing LPSF. These models have the potential to forecast clinical outcomes in this patient population, providing valuable prognostic insights for preoperative counseling and postoperative management.

The systemic immune-inflammation index at kasai portoenterostomy: related to clinical outcomes.

BACKGROUND: Systemic Immune-Inflammation Index (SII), known as an easy, economical and useful marker, correlates with the balance of inflammation and immune response. However, the usefulness of SII in biliary atresia (BA) remains unclear. Therefore, we evaluated the relationship of SII level and postoperative clinical outcomes of BA. METHODS: Retrospective review of 168 patients with BA was conducted with assessments of demographic information, histological findings, laboratory parameters, and clinical outcomes. The LASSO logistic regression analysis was established using the "glmnet" software package to explore the influencing factors related to native liver survival time. Numerical variables were dichotomized based on the receiver operating characteristic (ROC) curve and Youden index yielding the best performance of prediction. R software was used for statistical analysis. RESULTS: Overall, the 24 month native liver survival rate was 43.5% (73 cases) after Kasai portoenterostomy. LASSO logistic regression analysis show that preoperative malnutrition (OR = 0.032, 95%CI 0.001-0.424), gamma-glutamyltransferase (GGT, OR = 0.994, 95%CI 0.987-0.998), lymphocyte count (LY, OR = 2.426, 95%CI 1.467-4.604), SII (OR = 0.977, 95%CI 0.960-0.989), and liver fibrosis grading (LFG, reference: Grade 1, Grade 3, OR = 0.076, 95%CI 0.007-0.614) were the independent influencing factors for 24 month native liver survival. ROC curve analysis showed that the area under the curve of SII level (0.919) was larger than that of preoperative malnutrition (0.690), LFG (0.759), GGT (0.747), and Ly (0.773). A SII < 140.09 was found to be a significant marker in the prediction of 24-month native liver survival, with 90.41% sensitivity and 93.68% specificity. Furthermore, the rates of 24-month native liver survival (33.1% vs. 72.7%), jaundice clearance (46.8% vs. 75.0%), and good liver function recovery (46.8% vs. 65.9%) were lower in the SII ≥ 140.09 group than that in the SII < 140.09 group (all P < 0.05), but there was no difference in the occurrence of cholangitis (P > 0.05). CONCLUSION: Preoperative malnutrition, GGT, Ly, SII, and LFG were independent influencing factors for postoperative 24-month native liver survival of BA. The SII level, as a routine haematological marker, has better universality and simplicity and is related to clinical outcomes after Kasai portoenterostomy.

Establishment of a scoring model for predicting clinical outcomes in patients with unilateral primary aldosteronism after superselective adrenal artery embolization.

OBJECTIVE: Superselective adrenal arterial embolization (SAAE) is a potential alternative treatment for patients with unilateral primary aldosteronism (PA) who refuse unilateral adrenalectomy. Therefore, we aimed to establish a scoring model to differentiate between hypertensive remission after SAAE. METHODS: This prospective cohort study involved 240 patients who underwent SAAE for unilateral PA. Patients were randomly divided into a model training set and a validation set at a ratio of 7:3. The clinical outcome was a response to hypertension remission, defined as complete, partial, or absent success at 6 months after SAAE. Multivariate logistic regression was performed to identify independent parameters and develop a nomogram to predict clinical outcomes after SAAE. The discrimination, calibration efficacy, and clinical utility of the predictive model were assessed. RESULTS: Five independent predictors were identified: female sex, duration of hypertension, defined daily dose of antihypertensive medication, diabetes, and target organ damage. The above five independent predictors were put into a predictive model that was presented as a nomogram. Using bootstrapping for internal validation, the C-statistic for the predictive model was 0.866 (95% confidence interval [CI]: 0.834 to 0.898). In the validation cohort, the area under the curve (AUC) of the nomogram for predicting hypertension remission after SAAE was 0.809. CONCLUSION: The present model is the first nomogram-based score that specifically predicts hypertension remission after SAAE in patients with unilateral PA using conventional parameters. This is an effective risk stratification tool that can be used by clinicians for timely and tailored preoperative risk discussions.

Predicting Role of GFAP and UCH-L1 biomarkers in Spontaneous Subarachnoid Hemorrhage: a preliminary study to evaluate in the short-term their correlation with severity of bleeding and prognosis.

BACKGROUND: Spontaneous non-traumatic subarachnoid hemorrhage (sSAH) is a severe brain vascular accident. Glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) can be theoretically assayed to predict a patient's progression, picturing different aspects of clinical failure after sSAH. The study aims to: a) explore the correlation between sSAH blood volume and biomarkers variation; b) evaluate if these can be predictive of the neurogenic response after sSAH and be prognostic of patient outcome; c) establish eventual threshold levels of biomarkers to define patients' clinical outcome. METHODS: Blood volumetry at CT scan upon admission, GFAP and UCH-L1 were collected at 24 h, at 72 h, and after 7 days from hemorrhage. Trends and cut-off serum sampling were determined. Clinical outcome was assessed with mRS scale at 14 days. RESULTS: A strong correlation between GFAP and UCH-L1 and blood diffusion volume in all explored serum intervals related to unfavorable outcome. GFAP and UCH-L1 were very early predictors of unfavorable outcomes at 24 h from sSAH (p = 0.002 and 0.011 respectively). Threshold levels of UCH-L1 apparently revealed a very early, early and late predictor of unfavorable outcomes. CONCLUSION: GFAP and UCH-L1 represent a potential tool for prompt monitoring and customization of therapies in neurosurgical patients.

Individual participant data analysis comparing acute stroke patients with anterior versus posterior circulation dissections.

BACKGROUND: Cervical artery dissection (CAD) is a relevant etiology of transient ischemic attacks and strokes. Several trials explored the significance of specific antithrombotic treatments, i.e. oral anticoagulation (OAC) versus antiplatelet treatment (APT), on recurrent ischemic complications and clinical outcomes. As overall incidence rates of complications were low there is still controversy which antithrombotic treatment should be used. However, up to now there has been no systematic investigation among CAD-patients with ischemic stroke specifically comparing clinical course and outcome of patients with anterior versus posterior CAD. METHODS: We performed an individual participant data analysis of patients with CAD and ischemic stroke. Over a five-year period we pooled data from three sites (i.e. West China Hospital, Chengdu, China as well as Erlangen and Giessen University Hospitals, Germany) and enrolled patients with CAD-associated ischemic stroke. Patient demographics, clinical and in-hospital measures as well as radiological data were retrieved from institutional databases. Clinical follow-up was over 6 months and included data on recurrent ischemic strokes and hemorrhages as well as clinical functional outcome assessed by the modified Rankin Scale dichotomized into favourable (mRS=0-2) and unfavourable. RESULTS: A total of 203 patients with CAD were included of which n=112 had anterior and n=91 had posterior CAD. Patients with posterior CAD were younger (46.0 vs. 41.0 y; p<0.001) than patients with anterior CAD and showed less often arterial hypertension. (42.0 % vs. 28.6 %; p<0.048). Antithrombotic treatment with APT and OAC was similarily distributed among patients with anterior and posterior CAD and not significantly differently related to ischemic or hemorrhagic complications during follow-up (all p=n.s.). Main difference between Chinese and German patients were mode of antithrombotic treatment consisting predominantly of APT in China compared to OAC in Germany. Functional outcome overall was good, yet worse in patients with anterior CAD compared to posterior CAD (80.2 % favorable in anterior CAD vs. 92.2 % in posterior CAD (p=0.014). CONCLUSION: This study provides evidence that anterior and posterior CAD show baseline imbalances regarding age and comorbidity which may affect clinical outcome. There are no signals of superiority or harm of any specific mode of antithrombotic treatment nor relevant discrepancies in clinical outcome among Chinese and German CAD-associated stroke patients.

Clinical outcome assessments of disease burden and progression in late-onset GM2 gangliosidoses.

The late-onset GM2 gangliosidoses, comprising late-onset Tay-Sachs and Sandhoff diseases, are rare, slowly progressive, neurogenetic disorders primarily characterized by neurogenic weakness, ataxia, and dysarthria. The aim of this longitudinal study was to characterize the natural history of late-onset GM2 gangliosidoses using a number of clinical outcome assessments to measure different aspects of disease burden and progression over time, including neurological, functional, and quality of life, to inform the design of future clinical interventional trials. Patients attending the United States National Tay-Sachs & Allied Diseases Family Conference between 2015 and 2019 underwent annual clinical outcome assessments. Currently, there are no clinical outcome assessments validated to assess late-onset GM2 gangliosidoses; therefore, instruments used or designed for diseases with similar features, or to address various aspects of the clinical presentations, were used. Clinical outcome assessments included the Friedreich's Ataxia Rating Scale, the 9-Hole Peg Test, and the Assessment of Intelligibility of Dysarthric Speech. Twenty-three patients participated in at least one meeting visit (late-onset Tay-Sachs, n = 19; late-onset Sandhoff, n = 4). Patients had high disease burden at baseline, and scores for the different clinical outcome assessments were generally lower than would be expected for the general population. Longitudinal analyses showed slow, but statistically significant, neurological progression as evidenced by worsening scores on the 9-Hole Peg Test (2.68%/year, 95% CI: 0.13-5.29; p = 0.04) and the Friedreich's Ataxia Rating Scale neurological examination (1.31 points/year, 95% CI: 0.26-2.35; p = 0.02). Time since diagnosis to study entry correlated with worsening scores on the 9-Hole Peg Test (r = 0.728; p < 0.001), Friedreich's Ataxia Rating Scale neurological examination (r = 0.727; p < 0.001), and Assessment of Intelligibility of Dysarthric Speech intelligibility (r = -0.654; p = 0.001). In summary, patients with late-onset GM2 gangliosidoses had high disease burden and slow disease progression. Several clinical outcome assessments suitable for clinical trials showed only small changes and standardized effect sizes (change/standard deviation of change) over 4 years. These longitudinal natural history study results illustrate the challenge of identifying responsive endpoints for clinical trials in rare, slowly progressive, neurogenerative disorders where arguably the treatment goal is to halt or decrease the rate of decline rather than improve clinical status. Furthermore, powering such a study would require a large sample size and/or a long study duration, neither of which is an attractive option for an ultra-rare disease with no available treatment. These findings support the development of potentially more sensitive late-onset GM2 gangliosidoses-specific rating instruments and/or surrogate endpoints for use in future clinical trials.

Plasma neurofilament light chain as a biomarker for poor outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Neurofilament light chain (NfL), a biomarker reflecting neuro-axonal damage, may be useful in improving clinical outcome prediction after aSAH. We explore the robust and additional value of NfL to neurological and radiological grading scales in predicting poor outcome after aSAH. METHODS: In this prospective cohort study conducted in a single tertiary center, blood samples were collected of aSAH patients within 24 hours after ictus and before endovascular/surgical intervention. The primary endpoint was poor outcome at six months' follow-up. Receiver operating curves (ROC), area under the curve (AUC, 95% CI) and model-fit (Nagelkerke R2) were calculated for NfL, neurological grading scale (WFNS), modified Fisher, age and sex. A combined ROC and AUC were calculated for variables with an AUC≥0.70. RESULTS: A total of 66 (42%) had poor outcome. The AUC of NfL for poor outcome was 0.70 (0.62-0.78). Combining NfL and WFNS resulted in a slightly higher model-fit and not-significantly higher AUC for predicting poor outcome (R2 0.51; AUC 0.86, 0.80-0.92) compared to WFNS alone. When patients were stratified according to hemorrhage severity, median NfL [IQR] levels were significantly higher in poor grade (14 [7-32] pg/ml) than good grade patients (7 [5-14] pg/ml). Within poor grade patients, median NfL [IQR] levels were significantly higher in non-survivors (19 [11-36] pg/ml) than survivors (7 [6-13] pg/ml). CONCLUSION: In the entire aSAH cohort, plasma NfL has an acceptable predictive performance but does not improve clinical outcome prediction. However, NfL may have potential value in subgroups based on hemorrhage severity.

Effect of intraoperative cell salvage on coagulation function outcomes in patients with massive post-Cesarean section hemorrhage.

OBJECTIVE: To examine the impact of using intraoperative cell salvage (ICS) for the restoration of coagulation function in cases of massive Post-Cesarean Section Hemorrhage (PCSH). METHODS: A retrospective analysis was conducted on 60 cases of massive PCSH meeting inclusion criteria at Suqian Maternity and Children's Hospital from January 2020 to July 2022. Patients were divided into two groups: allogeneic blood transfusion group (Group A, n = 30) and ICS group (Group B, n = 30), based on transfusion methods. Blood parameters, coagulation function, and adverse reactions were assessed before (T0) and after (T1) transfusion. Patients were categorized into good prognosis (GP) and poor prognosis (PP) groups based on adverse reaction occurrence. Clinical profiles were compared between groups, and multivariate binary logistic regression analysis was employed to evaluate the factors that may affect the prognosis in women with PCSH. RESULTS: No significant differences in routine blood parameters were observed between groups at T0 and T1 (P>0.05). At T0, no significant differences in PT, APTT, TT, or FIB were found between groups (P>0.05). Both groups showed a reduction in PT, APTT, and TT values at T1 compared to T0, with Group B experiencing a more significant decrease than Group A (P<0.05). FIB increased in both groups at T1 compared to T0, with Group B demonstrating a higher increase than Group A (P<0.05). Both groups showed increased blood pressure at T1 compared to T0, with Group B showing a more pronounced elevation than Group A (P<0.05). The occurrence of adverse reactions was significantly lower in Group B (1/30, 3.33%) compared to Group A (7/30, 23.33%) (P<0.05). Logistic regression analysis identified FIB<1.52 g/L and HR<45.35 times/min as factors associated with increased risk of unfavorable outcome in women with PCSH. CONCLUSION: In patients experiencing significant PCSH, ICS may lead to better postoperative recovery of blood parameters, faster restoration of coagulation function, and reduced risk of adverse events compared to ABT. Moreover, early detection of coagulation function and blood gas indexes is crucial for clinicians to implement timely prevention and treatment measures.

Assessing the prognostic value of KRAS mutation combined with tumor size in stage I-II non-small cell lung cancer: a retrospective analysis.

Background: KRAS mutation status is a well-established independent prognostic factor in advanced non-small cell lung cancer (NSCLC), yet its role in early-stage disease is unclear. Here, we investigate the prognostic value of combining survival data on KRAS mutation status and tumor size in stage I-II NSCLC. Methods: We studied the combined impact of KRAS mutational status and tumor size on overall survival (OS) in patients with stage I-II NSCLC. We performed a retrospective study including 310 diagnosed patients with early (stage I-II) NSCLCs. All molecularly assessed patients diagnosed with stage I-II NSCLC between 2016-2018 in the Västra Götaland Region of western Sweden were screened in this multi-center retrospective study. The primary study outcome was overall survival. Results: Out of 310 patients with stage I-II NSCLC, 37% harbored an activating mutation in the KRAS gene. Our study confirmed staging and tumor size as prognostic factors. However, KRAS mutational status was not found to impact OS and there was no difference in the risk of death when combining KRAS mutational status and primary tumor size. Conclusions: In our patient cohort, KRAS mutations in combination with primary tumor size did not impact prognosis in stage I-II NSCLC.

Leveraging sensor-based functional outcomes to enhance understanding of the patient experience: challenges and opportunities.

INTRODUCTION: Sensor-based digital health technology (DHT) has emerged as a promising means to assess patient functioning within and outside clinical trials. Sensor-based functional outcomes (SBFOs) provide valuable insights that complement other measures of how a patient feels or functions to enhance understanding of the patient experience to inform medical product development. AREAS COVERED: This perspective paper provides recommendations for defining SBFOs, discusses the core evidence required to support SBFOs to inform decision-making, and considers future directions for the field. EXPERT COMMENTARY: The clinical outcome assessment (COA) development process provides an important starting point for developing patient-centered SBFOs; however, given the infancy of the field, SBFO development may benefit from a hybrid approach to evidence generation by merging exploratory data analysis with patient engagement in measure development. Effective SBFO development requires combining unique expertise in patient engagement, measurement and regulatory science, and digital health and analytics. Challenges specific to SBFO development include identifying concepts of interest, ensuring measurement of meaningful aspects of health, and identifying thresholds for meaningful change. SBFOs are complementary to other COAs and, as part of an integrated evidence strategy, offer great promise in fostering a holistic understanding of patient experience and treatment benefits, particularly in real-world settings.

FT4-to-FT3 ratio is a novel prognostic marker in subacute combined spinal cord degeneration patients.

Objectives: The FT4-to-FT3 ratio (FFR) variations in patients with subacute combined spinal cord degeneration (SCSD) as a potentially useful prognostic indicator are still unknown. This study aimed to investigate the changes of FFR as a potentially valuable prognostic predictor in patients with SCSD. Methods: This study included 144 consecutive SCSD patients who received standard diagnostic and therapeutic procedures between January 2015 and December 2021 and were admitted to the Department of Neurology at the First Affiliated Hospital of Bengbu Medical University. At the time of admission, we gathered data on all patients' demographics, daily routines, previous chronic conditions, medication histories, and other clinical details. For the purpose of measuring FFR, blood samples were specifically taken within 48 h of admission. The degree of neurological impairment of patients was assessed using the functional disability scale at the time of admission. At 6 months following discharge, the Modified Rankin Scale (mRS) was used to evaluate the clinical prognosis. To evaluate the relationship between the FFR and the risks of a poor outcome (mRS > 2), univariate and multivariate logistic regression analysis was utilized. The significance of the FT4/FT3 ratio in predicting the clinical outcomes in SCSD patients 6 months after discharge was assessed using the area under curve-receiver operating characteristic (AUC-ROC). Results: About 90 patients (62.5%) of the 144 patients had poor outcomes, while 54 (37.5%) had favorable outcomes. Higher FFR at admission was independently linked to higher odds of a poor outcome, according to a logistic analysis. With an optimized cutoff value of >2.843, the FFR exhibited the maximum accuracy for predicting a poor outcome, according to the AUC‒ROC curve (AUC 0.731, P < 0.001; sensitivity, 77.8%; specificity, 83.3%). FFR was identified as an independent predictor of poor outcomes by multivariate logistic regression (OR, 2.244; 95% CI, 1.74-2.90; P < 0.001). Conclusions: We discovered that in patients who had a bad result 6 months after discharge, the FFR had dramatically increased at the time of admission, providing a unique prognostic marker in patients with SCSD.

Epidemiology and Clinical impact of single and multi-viral respiratory infections in post-pandemic era.

Acute respiratory tract infections (ARI) are common diseases in children and adults and could cause severe infections in high-risk patients, like the immunocompromised and elderly, and are the leading cause of morbidity, hospitalization and mortality. This study aimed to explore the prevalence of respiratory viruses and the clinical impact of single- and multi-infection among hospitalized patients in various age groups. 3578 nasopharyngeal swabs (NPS) were analyzed for pathogen detection of acute respiratory tract infections. 930 out of 3578 NPS were diagnosed positive for at least one respiratory virus. The distribution of viral infections, prevalence and pathogen, differed significantly among age groups. Most RTI are observed in the age group over 65 years (50.6%) with a high SARS-CoV2 prevalence, following by group <5 years (25.6%), where the most frequently detected viruses were RSV, Rhinovirus, FluA-H3, MPV, and AdV. The co-infection rate also varies according to age and, in some cases, especially in older adults, could have severe clinical impact. This study emphasizes that it is important to know and analyze, in all age groups of hospitalized patients, the epidemiology of respiratory viruses, the prevalence of coinfections, and the clinical impact of various pathogens. Furthermore, in a clinical setting, the rapid diagnosis of respiratory infections by means of molecular tests is crucial not only to avoid hospital outbreaks, but also to allow early and optimal treatment to reduce morbidity and mortality.

Content Validity of the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) Instrument in Spinocerebellar Ataxia.

The functional Scale for the Assessment and Rating of Ataxia (f-SARA) assesses Gait, Stance, Sitting, and Speech. It was developed as a potentially clinically meaningful measure of spinocerebellar ataxia (SCA) progression for clinical trial use. Here, we evaluated content validity of the f-SARA. Qualitative interviews were conducted among individuals with SCA1 (n = 1) and SCA3 (n = 6) and healthcare professionals (HCPs) with SCA expertise (USA, n = 5; Europe, n = 3). Interviews evaluated symptoms and signs of SCA and relevance of f-SARA concepts for SCA. HCP cognitive debriefing was conducted. Interviews were recorded, transcribed, coded, and analyzed by ATLAS.TI software. Individuals with SCA1 and 3 reported 85 symptoms, signs, and impacts of SCA. All indicated difficulties with walking, stance, balance, speech, fatigue, emotions, and work. All individuals with SCA1 and 3 considered Gait, Stance, and Speech relevant f-SARA concepts; 3 considered Sitting relevant (42.9%). All HCPs considered Gait and Speech relevant; 5 (62.5%) indicated Stance was relevant. Sitting was considered a late-stage disease indicator. Most HCPs suggested inclusion of appendicular items would enhance clinical relevance. Cognitive debriefing supported clarity and comprehension of f-SARA. Maintaining current abilities on f-SARA items for 1 year was considered meaningful for most individuals with SCA1 and 3. All HCPs considered meaningful changes as stability in f-SARA score over 1-2 years, 1-2-point change in total f-SARA score, and deviation from natural history. These results support content validity of f-SARA for assessing SCA disease progression in clinical trials.

Case report: Transition from anti-CD20 therapy to inebilizumab for 14 cases of neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder of the central nervous system characterized by recurrent, disabling attacks that affect the optic nerve, spinal cord, and brain/brainstem. While rituximab, targeting CD20-positive B-cells, is used as an off-label therapy for NMOSD, some patients continue to exhibit breakthrough attacks and/or adverse reactions. Inebilizumab, a humanized and glycoengineered monoclonal antibody targeting CD19-positive B-cells, has been FDA approved for the treatment of NMOSD in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. Given the limited real-world data on the efficacy and safety of inebilizumab, especially in those transitioning from rituximab, a retrospective chart review was conducted on 14 NMOSD patients from seven centers. Of these, 71.4% (n = 10) experienced a combined 17 attacks during rituximab treatment, attributed to either breakthrough disease (n = 10) or treatment delay (n = 7). The mean duration of rituximab treatment was 38.4 months (3.2 years). Notably, no subsequent attacks were observed during inebilizumab treatment [mean duration of inebilizumab treatment was 19.3 months (1.6 years)], underscoring its potential as an effective treatment for NMOSD. Our data suggest that inebilizumab provides clinical benefit with effective disease control and a favorable safety profile for patients transitioning from rituximab.