Follow-up Data Research Articles

INNV-14. OUTCOMES OF PATIENTS WITH ISOCITRATE DEHYDROGENASE-MUTANT WHO GRADE 4 ASTROCYTOMA TREATED WITH TUMOR TREATING FIELDS (TTFIELDS) THERAPY: A REAL-WORLD ANALYSIS

Abstract BACKGROUND Tumor Treating Fields (TTFields) therapy is approved for the treatment of patients with newly diagnosed glioblastoma, based on the EF-14 study which demonstrated improvement in progression free survival and overall survival (OS). EF-14 included patients with the isocitrate dehydrogenase (IDH) mutation (IDHmut), which has since been reclassified as IDHmut WHO grade 4 astrocytoma (Astrocytoma IDHmut/G4) and confers a more favorable prognosis than IDH wild type. However, large real-world datasets are lacking. Here, we report real-world outcomes of patients with Astrocytoma IDHmut/G4 treated with TTFields in the US. METHODS Utilizing electronic health records from the xCures real-world data platform, patients with newly diagnosed Astrocytoma IDHmut/G4 receiving TTFields in the US from January 1 to December 31, 2019 were analyzed and IDH-mut status was confirmed. Survival was analyzed based on IDH-mut status and TTFields usage, with patients categorized into 2 usage groups (minimum 30 days treatment): high (≥50%) and low (<50%) usage. RESULTS Among 1285 patients with known IDH status, 82 had an IDH-mut and were included. The median (range) age of patients was 40.6 (21–75) years, with the majority being men (n=58/71%) and with methylguanine-methyltransferase-promoter methylation (n=48/59%). Median TTFields therapy duration and usage were 9.4 months and 76.8%, respectively. OS at 2 and 4 years was 66% (95% CI: 56–77%) and 44% (34–57%), respectively. Patients with high TTFields usage had increased OS compared to low usage (HR: 0.53 [0.28–1.02], P=0.057, n=80). Among 22 patients with a minimum 4 years of survival, 5 were still on therapy as of the data cutoff. CONCLUSIONS These findings demonstrate the utility of the xCures platform in systematically assessing outcomes for a rare glioma subtype in the real-world setting, and suggests that patients with Astrocytoma IDHmut/G4 may benefit from TTFields therapy. Additional patient follow-up and correlative data will be presented.

QOL-07. LONG-TERM FOLLOW-UP OF PHYSICAL FUNCTION AND SOCIAL CONDITIONS IN CENTRAL NERVOUS SYSTEM GERM CELL TUMORS

Abstract BACKGROUND This paper presents an analysis of iving and social conditions from a long-term follow-up of Phase II clinical trial for central nervous system germ cell tumors conducted between 1995 and 2003. METHODS A retrospective analysis was performed on 228 cases, including 161 germinomas, 66 non-germinomas, and 1 mature teratoma, over a median follow-up of 222 months. There were 56 recurrences and 39 deaths recorded. The analysis at the final follow-up included final educational level, employment status, activities of daily living (ADLs), marital and parental status, and hormone replacement therapy. The study targeted 157 cases with more than 10 years of follow-up data. RESULTS At 20 years post-treatment, survival rates were 91% for germinomas and 65% for non-germinomas. At the last follow-up, ages ranged from 19 to 58 years (median 36 years). The Karnofsky Performance Status (KPS) was 80 or higher in 118 cases, 70 in 7 cases, and 60 or lower in 32 cases. Educational achievements were: elementary school in 1 case, middle school in 8, high school in 52, university in 45, and graduate school in 2. Employment status showed 37 unemployed, 4 in school, 23 part-time, 80 full-time, and 2 homemakers. Childbirth was reported in 16 men (18%) and 4 women (16%). The frequency of a KPS≧80 at the final follow-up was higher in initial germinoma cases than in non-germinoma cases (80 vs 62%, p=0.04), and was also higher in cases without recurrence (83 vs 47%, p<0.0001). Only the proportion of growth hormone supplementation showed a significant correlation with KPS (≧80: 19% vs <80: 3%, p=0.03). CONCLUSION Long-term social outcomes are favorable for germinoma patients without recurrence, while non-germinoma patients who have recurred and survived face tougher conditions, indicating significant treatment impacts. Managing treatment intensity and ensuring comprehensive long-term follow-up are crucial.

Learning curve and long-term outcomes of minimally invasive correction and fusion for adolescent idiopathic scoliosis.

Retrospective analysis. This study sought to report the long-term outcomes of patients that underwent minimally invasive surgery (MIS) correction for Adolescent Idiopathic Scoliosis (AIS) in terms of radiographic, clinical, and patient-reported outcomes. Furthermore, we examined the learning curve of MIS technique over the course of 13years. Both MIS and open techniques are used to surgically address AIS. MIS techniques are purported to preserve the midline spinal musculature and to decrease estimated blood loss (EBL) and hospital length of stay (LOS). Data were collected at a single tertiary care center of all consecutive AIS patients undergoing deformity surgery from January 2008 to October 2021. Demographic, clinical, and radiographic data were collected at various intervals. Descriptive and inferential analyses were conducted. 70 AIS patients were included in the study. Mean patient age was 16.2years of which 95.7% were female, with a mean BMI of 21.7. The majority of the patients were Lenke type 1A (60%) followed by Lenke 1B (18.6%) with mean preop Cobb angle as 52.2°. The mean follow-up was approximately 6years with 35.7% of our cohort meeting the long-term follow-up landmark (> 5years, 2-11). The mean number of spinal levels treated was 9.3 with mean ASA score of 1.7. Overall, mean EBL was 151cc with mean OR of 308min. The mean LOS was 3.94days with postop Day 1 as the initiation of ambulation. Overall, the percent correction at the last visit was significantly greater than preop (Cobb: 77.6%, p < 0.05). Mean loss of correction on follow-ups was less than 5º. The overall revision rate was 2.9%. At 2years postop, 98.6% (69/70) of the patients achieved fusion with 100% (24/24) at 5years, and 96% (24/25) beyond the 5-year mark. Surgeon's technical proficiency in performing MIS for the treatment of AIS corrections was achieved after 23 cases. Based on our cohort's 2-11year follow-up data, we conclude that MIS provides an effective treatment option for AIS reconstruction. Our study indicates that MIS can achieve adequate deformity correction and positive long-term clinical outcomes as indicated by Cobb angle, VAS, ODI, and SRS-22r scores during follow-ups. If the individual goals of AIS surgery can be achieved, consideration should be given to less-invasive techniques. IV.

Long-term safety and tolerability of hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: Results from the ADVANCE-CIDP 3 trial.

Hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) consists of subcutaneous human immunoglobulin G (IgG) 10% with recombinant human hyaluronidase (rHuPH20) and can be administered at the same dose and interval as intravenous IgG (IVIG). fSCIG recently received US approval as maintenance therapy for adults with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and European approval for adults and children with CIDP after stabilization with IVIG. ADVANCE-CIDP 3 (NCT02955355) was an open-label long-term extension of the Phase 3 double-blind randomized placebo-controlled ADVANCE-CIDP 1 study (NCT02549170) that examined fSCIG safety and efficacy as maintenance CIDP therapy. Primary outcomes were safety, tolerability, and immunogenicity. Efficacy was an exploratory outcome. The study provided 220 patient-years of follow-up data from 85 patients. Median (range) exposure was 33 (0-77) months. Patients received fSCIG every 4 weeks (88.2%) or every 3 weeks (11.8%). Median (range) 4-weekly IgG dose equivalent was 64.0 (28.0-200.0) g. Mean (standard deviation) infusion duration was 135.5 (62.8) minutes. Most adverse events (AEs) were mild or moderate and self-limiting. Of the 1406 AEs, only 48 were severe and 30 were serious. fSCIG-related AEs (n = 798) included infusion site reactions such as pain, redness, and pruritus. Three infusions (0.1%) were reduced in rate, interrupted, or stopped due to intolerability. Relapse occurred in 10 of 77 patients (13.0%); annual relapse rate was 4.5%. An anti-rHuPH20 antibody titer ≥1:160 was detected in 14 of 84 patients (16.7%); patients who tested positive (≥1:160) had similar relapse rates versus those who tested negative (16.7% vs. 12.3%, respectively). ADVANCE-CIDP 3 demonstrated favorable fSCIG long-term safety and tolerability consistent with its established safety profile, and a low relapse rate, supporting use as maintenance CIDP treatment.

Inflammatory stress determines the need for chemotherapy in patients with HER2-positive esophagogastric adenocarcinoma receiving targeted and immunotherapy.

Anti-PD-1, trastuzumab, and chemotherapy are used in the treatment of patients with advanced HER2-positive esophagogastric adenocarcinoma (EGA), but long-term survival remains limited. Herein, we report extended follow-up data from the INTEGA trial (NCT03409848), which investigated the efficacy of the anti-PD-1 nivolumab, trastuzumab, and FOLFOX chemotherapy (FOLFOX arm) in comparison to a chemotherapy-free regimen involving nivolumab, trastuzumab, and the anti-CTLA-4 ipilimumab (Ipi arm) in the first-line setting for advanced disease. The 12-month overall survival (OS) showed no statistical difference between the arms, with 57% OS (95% CI: 41%-71%) in the Ipi arm and 70% OS (95% CI: 54%-82%) in the FOLFOX arm. Crossing of the survival curves indicated a potential long-term benefit for some patients within the Ipi arm, but early progressors in the Ipi arm underlined the need for biomarker-guided strategies to optimize treatment selection. To this end, metabolomic and cytokine analysis demonstrated elevated levels of normetanephrine, cortisol, and interleukin 6 (IL-6) in immunotherapy-unresponsive patients in the Ipi arm, suggesting a role for systemic inflammatory stress in modulating antitumor immune responses. Patients with this signature also showed an increased neutrophil-to-lymphocyte ratio (NLR) that persisted in the Ipi arm, but not in the FOLFOX arm, and strongly correlated with survival. Furthermore, a low NLR characterized patients benefiting from immune- and targeted therapy without the need for additional chemotherapy. This data suggests that patient selection based on inflammatory stress-driven immune changes could help to customize first-line treatment in patients with advanced HER2-positive EGA to potentially improve long-term survival.

Comparison of robot-assisted versus fluoroscopically guided treatment of atlantoaxial dislocation in combination with high-riding vertebral artery: a preliminary study

BackgroundRobotic-assisted surgery has emerged as an innovative approach widely adopted in the field of orthopedics. However, its application specifically for managing atlantoaxial dislocation with a high-riding vertebral artery (AAD-HVA) remains underreported in the existing literature.ObjectiveTo compare the perioperative outcomes of robotic-assisted (RA) and fluoroscopic-guided free-hand (FH) techniques for atlantoaxial dislocation in combination with a high-riding vertebral artery (AAD-HVA).Study designThis was a retrospective study.SettingThis research was performed at a single department of spine surgery.MethodsData from patients who underwent atlantoaxial internal fixation between July 2018 and January 2022 at our hospital were retrospectively analyzed. Among the cases, 14 were performed using free-hand (FH) techniques and 11 utilized robotic-assisted (RA) techniques. Data collected included case notes, imaging records, and follow-up data. The reliability of screw placement was evaluated based on the Gertzbein and Robbins scores, while treatment outcomes were assessed using the Japanese Orthopaedic Association (JOA) score, visual analog scale (VAS), neck disability index (NDI), and postoperative complication rate.ResultsBaseline patient characteristics were comparable between the FH and RA groups. The mean blood loss was markedly lower in the RA group (157.3 ± 49.7 ml) compared to the FH group (290.0 ± 110.3 ml) (p = 0.03). Although the average operative time was slightly higher in FH group than in RA group, this disparity did not achieve statistical significance (p = 0.7588). Moreover, the radiation exposure dose was remarkably higher in FH group (32.7 ± 4.4 mGy) than in RA group (23.0 ± 3.2 mGy) (p < 0.0001). The percentage of clinically acceptable screw placement was slightly lower in FH group (87.5%) than in RA group (97.8%), but the observed variance was not statistically meaningful (p = 0.3669). Furthermore, the differences in JOA, VAS, and NDI scores between the FH and RA groups were not statistically significant. Additionally, no obvious differences were found in clinical outcomes or complications related to screw implantation between the two groups.LimitationsThis study has inherent limitations as it was retrospective in nature and conducted at a single center.ConclusionRobotic-assisted surgery for AAD-HVA patients offers a minimally invasive approach, reduced bleeding and lower radiation exposure compared with traditional free-hand surgery.

Per-oral endoscopic myotomy: a multi-centre New Zealand experience.

Per-oral endoscopic myotomy (POEM) is an established treatment for achalasia. We aim to review outcomes of all POEM cases performed in New Zealand for achalasia. A retrospective review of all POEM procedures performed in the five hospitals offering POEM between November 2015 and December 2022 was undertaken. The primary outcome was clinical success, defined as Eckardt score ≤3. Secondary outcomes included procedural complications. One hundred and sixty-six index and four redo POEM procedures were performed by seven clinicians. Ninety-six (58%) were male and mean age was 49.6 years (standard deviation [SD] 19.2 years). Eighty-three (50%) had a previous achalasia intervention. Median length of hospital stay was 1 day (interquartile range [IQR] 1-2 days). Median pre-POEM Eckardt score was 8 (IQR 6-9) and improved to 0 (IQR 0-2) at 6 months (p<0.001). Technical success was achieved in 164 (99%). Clinical success was achieved in 124 (93%) at 6 months and sustained to 12 months in 37/42 (88%) of these patients with follow-up data. Clinical success was achieved in 92% who underwent any prior intervention. There were five reported complications: tunnel leak (three), significant pain (one) and pneumothorax (one). One tunnel leak required thoracotomy for empyema debridement, all other complications were managed conservatively. Forty-seven (31%) reported symptomatic reflux after POEM. This first review of all POEM procedures performed in New Zealand for achalasia demonstrates high 6-month clinical success and safety for the management of achalasia.

An Artificial Intelligence Approach for Test-Free Identification of Sarcopenia.

The diagnosis of sarcopenia relies extensively on human and equipment resources and requires individuals to personally visit medical institutions. The objective of this study was to develop a test-free, self-assessable approach to identify sarcopenia by utilizing artificial intelligence techniques and representative real-world data. This multicentre study enrolled 11 661 middle-aged and older adults from a national survey initialized in 2011. Follow-up data from the baseline cohort collected in 2013 (n = 9403) and 2015 (n = 10 356) were used for validation. Sarcopenia was retrospectively diagnosed using the Asian Working Group for Sarcopenia 2019 framework. Baseline age, sex, height, weight and 20 functional capacity (FC)-related binary indices (activities of daily living = 6, instrumental activities of daily living = 5 and other FC indices = 9) were considered as predictors. Multiple machine learning (ML) models were trained and cross-validated using 70% of the baseline data to predict sarcopenia. The remaining 30% of the baseline data, along with two follow-up datasets (n = 9403 and n = 10 356, respectively), were used to assess model performance. The study included 5634 men and 6027 women (median age = 57.0 years). Sarcopenia was identified in 1288 (11.0%) individuals. Among the 20 FC indices, the running/jogging 1 km item showed the highest predictive value for sarcopenia (AUC [95%CI] = 0.633 [0.620-0.647]). From the various ML models assessed, a 24-variable gradient boosting classifier (GBC) model was selected. This GBC model demonstrated favourable performance in predicting sarcopenia in the holdout data (AUC [95%CI] = 0.831 [0.808-0.853], accuracy = 0.889, recall = 0.441, precision = 0.475, F1 score = 0.458, Kappa = 0.396 and Matthews correlation coefficient = 0.396). Further model validation on the temporal scale using two longitudinal datasets also demonstrated good performance (AUC [95%CI]: 0.833 [0.818-0.848] and 0.852 [0.840-0.865], respectively). The model's built-in feature importance ranking and the SHapley Additive exPlanations method revealed that lifting 5 kg and running/jogging 1 km were relatively important variables among the 20 FC items contributing to the model's predictive capacity, respectively. The calibration curve of the model indicated good agreement between predictions and actual observations (Hosmer and Lemeshow p = 0.501, 0.451 and 0.374 for the three test sets, respectively), and decision curve analysis supported its clinical usefulness. The model was implemented as an online web application and exported as a deployable binary file, allowing for flexible, individualized risk assessment. We developed an artificial intelligence model that can assist in the identification of sarcopenia, particularly in settings lacking the necessary resources for a comprehensive diagnosis. These findings offer potential for improving decision-making and facilitating the development of novel management strategies of sarcopenia.

Actionable Variants of Unknown Significance in Inherited Arrhythmogenic Syndromes: A Further Step Forward in Genetic Diagnosis

Background/Objectives: Inherited arrhythmogenic syndromes comprise a heterogenic group of genetic entities that lead to malignant arrhythmias and sudden cardiac death. Genetic testing has become crucial to understand the disease etiology and allow for the early identification of relatives at risk; however, it requires an accurate interpretation of the data to achieve a clinically actionable outcome. This is particularly challenging for the large number of rare variants obtained by current high-throughput techniques, which are mostly classified as of unknown significance. Methods: In this work, we present a new algorithm for the genetic interpretation of the remaining rare variants in order to shed light on their potential clinical implications and reduce the burden of unknown significance. Results: Our study illustrates the potential utility of our individualized comprehensive stepwise analyses focused on the rare variants associated with IAS, which are currently classified as ambiguous, to further determine their trends towards pathogenicity or benign traits. Conclusions: We advocate for personalized disease-focused population frequency data and family segregation analyses for all rare variants that remain ambiguous to further clarify their role. The current ambiguity should not influence medical decisions, but a potential deleterious role would suggest a closer clinical follow-up and frequent genetic data review for a more personalized clinical approach.

Barriers and facilitators to implementation of a national antimicrobial stewardship toolkit for inpatient settings

Abstract Introduction Antimicrobial stewardship (AMS) is vital for combating antimicrobial resistance (AMR). The updated 2023 "Start Smart Then Focus" (SSTF) national antimicrobial stewardship (AMS) toolkit1, designed for inpatient settings, supports optimising prescribing of antimicrobials. Aim This project was designed to identify the barriers and facilitators to implementing the national toolkit to improve patient outcomes and reduce AMR. Method An online training workshop was conducted for healthcare professionals across England, focusing on the SSTF toolkit. Before the workshop, participants completed a survey that included consent and gathered information on their roles, familiarity with AMS principles, current practices, and perceived barriers and facilitators to AMS implementation. This information in this survey was used to form basis for the workshop and it was helpful in developing content appropriate for the target audience, which will be delivered during the session. The workshop included discussions on knowledge mobilisation, behavioural science using the COM-B model, and SSTF implementation case studies. Participants engaged in breakout sessions to identify implementation challenges at their organisations. Post-workshop surveys collected feedback on learning outcomes. Collaboration with NHS England AMS leads and UKHSA behavioural scientists was integral. The NHS Health Research Authority tool confirmed the project did not require ethical approval as the surveys were service evaluation. Data were analysed using descriptive statistics for quantitative responses and thematic analysis for qualitative feedback, tailoring workshop content to address specific needs. Results The workshop attracted 57 out of 71 (80%) registered healthcare professionals, including pharmacists (n=45), doctors(n=3), and nurses(n=4). Post-workshop surveys received a 28%(n=16) response rate. Feedback was positive, with 14 out of 16 (88%) of participants expressing high satisfaction. Highlights included SSTF development, e-prescribing implementation, and sessions on barriers and facilitators.Key barriers identified were lack of time, competing priorities, data complexity, insufficient organisational support, and limited resources3. Facilitators included engaging microbiology consultants and the ePMA team, raising awareness through AMS ward rounds, and embedding the SSTF toolkit into guidelines and education. Participants suggested further support from UKHSA and NHSE, including more teaching sessions, workshops, educational materials, and e-learning resources. Practical tools like posters, lanyard cards, infographics, and virtual sessions were recommended to reinforce implementation. The survey responses were analysed using descriptive statistics for quantitative data, such as satisfaction ratings, and thematic analysis for qualitative feedback. This analysis evaluated the workshop's impact on participants' understanding and readiness to implement the toolkit and provided insights for enhancing future training activities. Discussion/Conclusion The workshop identified key facilitators and barriers to SSTF implementation. While the toolkit offers a comprehensive framework for AMS, overcoming barriers requires a multifaceted approach involving education, stakeholder engagement, and continuous support. Clearer role definitions and improved support structures are essential. Limitations include limited participant representation and reliance on self-reported data, which may introduce bias. The study lacks long-term follow-up data to assess sustained impact, and feedback might be influenced by personal experiences or organisational culture, affecting generalisability. Future studies could expand participant diversity, incorporate longitudinal assessments, and explore additional AMS aspects.

Long-term health outcomes of COVID-19 in ICU- and non-ICU-treated patients up to 2 years after hospitalization: a longitudinal cohort study (CO-FLOW)

BackgroundMany patients hospitalized for COVID-19 experience long-term health problems, but comprehensive longitudinal data up to 2 years remain limited. We aimed to (1) assess 2-year trajectories of health outcomes, including comparison between intensive care unit (ICU) treated and non-ICU-treated patients, and (2) identify risk factors for prominent health problems post-hospitalization for COVID-19.MethodsThe CO-FLOW multicenter prospective cohort study followed adults hospitalized for COVID-19 at 3, 6, 12, and 24 months post-discharge. Measurements included patient-reported outcomes (a.o., recovery, symptoms, fatigue, mental health, sleep quality, return to work, health-related quality of life [HRQoL]), and objective cognitive and physical tests. Additionally, routine follow-up data were collected.Results650 patients (median age 60.0 [IQR 53.0–67.0] years; 449/650 [69%] male) surviving hospitalization for COVID-19 were included, of whom 273/650 (42%) received ICU treatment. Overall, outcomes improved over time. Nonetheless, 73% (322/443) of patients had not completely recovered from COVID-19, with memory problems (274/443; 55%), concentration problems (259/443; 52%), and dyspnea (251/493; 51%) among most frequently reported symptoms at 2 years. Moreover, 61% (259/427) had poor sleep quality, 51% (222/433) fatigue, 23% (102/438) cognitive failures, and 30% (65/216) did not fully return to work. Objective outcome measures showed generally good physical recovery. Most outcomes were comparable between ICU- and non-ICU-treated patients at 2 years. However, ICU-treated patients tended to show slower recovery in neurocognitive symptoms, mental health outcomes, and resuming work than non-ICU-treated patients, while showing more improvements in physical outcomes. Particularly, female sex and/or pre-existing pulmonary disease were major risk factors for poorer outcomes.Conclusions73% (322/443) of patients had not completely recovered from COVID-19 by 2 years. Despite good physical recovery, long-term neurocognitive complaints, dyspnea, fatigue, and impaired sleep quality persisted. ICU-treated patients showed slower recovery in neurocognitive and mental health outcomes and resumption of work. Tailoring long-term COVID-19 aftercare to individual residual needs is essential. Follow-up is required to monitor further recovery.Trial registration: NL8710, registration date 12-06-2020.

Impact of cervical kyphosis on segmental motion and symptomatic adjacent segment degeneration: a long-term follow-up data of more than 5 years.

This study was performed to assess the impact of cervical kyphosis on the locations of average center of rotation (COR) of each level preoperatively and to investigate whether uncorrected cervical kyphosis increases the incidence of symptomatic adjacent segment degeneration (ASD) after anterior cervical decompression and fusion (ACDF). We retrospectively analyzed all patients surgically treated for cervical myelopathy, radiculopathy, or deformity at a single institution from 2012 to 2018. They were divided into cervical kyphosis and cervical lordosis cohorts. Propensity score matching was performed. Preoperative cervical segmental and postoperative adjacent segment CORs were measured. Development of symptomatic ASD in all patients was assessed after > 5 years of follow-up. Among 412 patients with cervical lordosis and 47 patients with S-type cervical kyphosis, we established 37 matched pairs before and after surgery. In total, 368 COR locations were measured. Uncorrected kyphosis was identified in seven patients. The CORs of the cervical spine were located farther forward and upward in the cervical kyphosis group than in the control group (p < 0.05). At 1-year visit after ACDF, the locations of the adjacent COR showed no significant differences between the cervical postoperative lordosis group and control group. The incidence of symptomatic ASD was significantly higher in the uncorrected kyphosis group than in the corrected kyphosis group (42.9% vs. 2.5%, p = 0.001) and lordosis group (42.9% vs. 1.9%, p < 0.001). Cervical kyphosis can impact the locations of COR and increase the incidence of symptomatic ASD. Kyphosis correction is needed during ACDF in patients with cervical kyphosis.

Chronic Subdural Hematomas—A Retrospective Analysis of the Internal Architecture and Evaluation of Risk Factors for Recurrences After Surgical Therapy

Background: Chronic subdural hematoma (CSDH) is increasingly common due to the aging population and widespread use of anticoagulant and antiplatelet medications. The objective of this study is to examine the internal composition of CSDH and explore potential risk factors associated with its recurrence. Methods: This retrospective study analyzed data from 189 patients who underwent surgery in our department between 2014 and 2018. Recorded data included demographics, clinical information, details of surgical interventions, computer tomography (CT) scans, neurological assessments, and follow-up data. The outcome was evaluated clinically and through CT follow-up conducted 4–12 weeks post-surgery. CT scans measured various parameters, including hematoma thickness, hyperdense regions, chronic components, and membrane presence. Results: Patients after the evacuation of CSDH were significantly more common males (66.1%, p &gt; 0.001) had a significantly higher BMI (p &lt; 0.001, 61.6%), arterial hypertension (p &lt; 0.001, 68.3%), and the intake of anticoagulant therapy (p &lt; 0.001, 58%). The recurrence rate was 18.6% after 4 weeks and 2.1% after 8–12 weeks. After uni- and multivariable analysis, the initial hemispheric type (p = 0.019, HR: 3.191; p = 0.012, HR: 3.810) and the increasing preoperative midline shift in CT (p = 0.028, HR: 1.114; p = 0.041, HR: 1.107) were found as independent predictors for recurrence. Overall, outcomes were favorable with a modified Rankin scale (mRS) of 0–2 at discharge (72%), after 4 (89.7%) and 12 (87%) weeks. Conclusion: According to our data, increasing midline shift before surgery and initial hemispheric type of hematoma were independent predictors of recurrence. Most patients achieved an excellent outcome with a low-risk profile.

Alloplastic Vascular Grafts for Venous Interposition in Pancreatic Surgery: Readily Available and Reliable.

To investigate patency and clinical outcomes of alloplastic and other venous interposition graft materials in pancreatic surgery. Vascular pancreatic surgery is increasingly performed for locally advanced pancreatic neoplasms. Different than other centers, we prefer to use alloplastic vascular graft materials for superior mesenteric vein and portal vein interposition in pancreatic surgery. Advantages are off-the-shelf availability at any customizable length, different diameters, and ring-enforcement but proposed concerns are their thrombogenicity and fatal complications. Patients who underwent elective pancreatic resections with mesoportal venous interposition grafts (ISGPS type 4) between 2003-2022 were identified from the institutional pancreatectomy registry. Alloplastic vascular grafts imply synthetic materials, either based on polytetrafluorethylene (PTFE) or polyethylene terephthalate (PET). Surgical details, clinicopathological, and follow-up data were analyzed. The patients were followed for graft patency by cross-sectional imaging. In this study, 201 patients with venous interposition grafts were included (23% simultaneous arterial resections). Total pancreatectomy (41%) and pancreatoduodenectomy (35%) were the most frequent procedures. Vascular graft materials were alloplastic in 180 patients (83% PTFE and 17% PET) with a median diameter of 10mm and a median length of 33mm (measurement by CT scan). Patency rates among all graft materials at 7-, 30-, and 90-days were 99%, 93%, and 87%. Alloplastic grafts demonstrated superior patency over other materials (hazard ratio 2.7, P=0.009), and PTFE reached a 1-year patency of 78%. The all-cause 90-day mortality rate was 10%. No graft infection occurred. Alloplastic venous vascular grafts are safe and readily available tools in pancreatic surgery, especially for long-segmental mesoportal venous reconstructions.

Predicting post-COVID-19 condition in children and young people up to 24 months after a positive SARS-CoV-2 PCR-test: the CLoCk study

BackgroundPredicting which children and young people (CYP) are at the highest risk of developing post-COVID-19 condition (PCC) could improve care pathways. We aim to develop and validate prediction models for persistent PCC up to 24 months post-infection in CYP.MethodsCYP who were PCR-positive between September 2020 and March 2021, with follow-up data up to 24-months post-infection, were analysed. Persistent PCC was defined in two ways, as PCC at (a) 3, 6, 12 and 24 months post-infection (N = 943) or (b) 6, 12 and 24 months post-infection (N = 2373). Prediction models were developed using logistic regression; performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping; the final model was adjusted for overfitting.ResultsWhile 24.7% (233/943) of CYP met the PCC definition 3 months post-infection, only 7.2% (68/943) continued to meet the PCC definition at all three subsequent timepoints, i.e. at 6, 12 and 24 months. The final models predicting risk of persistent PCC (at 3, 6, 12 and 24 months and at 6, 12 and 24 months) contained sex (female), history of asthma, allergy problems, learning difficulties at school and family history of ongoing COVID-19 problems, with additional variables (e.g. older age at infection and region of residence) in the model predicting PCC at 6, 12 and 24 months. Internal validation showed minimal overfitting of models with good calibration and discrimination measures (optimism-adjusted calibration slope: 1.064–1.142; C-statistic: 0.724–0.755).ConclusionsTo our knowledge, these are the only prediction models estimating the risk of CYP persistently meeting the PCC definition up to 24 months post-infection. The models could be used to triage CYP after infection. CYP with factors predicting longer-term symptomology, may benefit from earlier support.

Association of High-Sensitivity C-Reactive Protein (hs-CRP) with Weight Loss After Sleeve Gastrectomy and Roux-en-Y Gastric Bypass at 10 Years: A Secondary Analysis of the SLEEVEPASS Randomized Clinical Trial.

Severe obesity is associated with a low-grade chronic inflammation, and high-sensitivity C-reactive protein (hs-CRP) is a marker that can be used to evaluate chronic inflammation status. Metabolic bariatric surgery (MBS) is shown to decrease hs-CRP level, but long-term results are scarce, and association with weight loss outcomes is undetermined. This study aims to evaluate chronic inflammation in patients with obesity using hs-CRP, and its association with long-term weight loss outcomes after laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). The long-term follow-up data of SLEEVEPASS (ClinicalTrials.gov NCT00793143) randomized clinical trial (RCT) was used. Hs-CRP was measured at baseline, and at 6months, 1, 3, 5, 7, and 10years after surgery, and the association with weight and weight loss outcomes were analyzed. Hs-CRP at baseline was available for 59 out of 240 (24.6%) patients. In the whole study population, the nadir hs-CRP (mean estimate 1.14mg/ml, 95% CI 0.87-1.49) was achieved at 3years after surgery with a statistically significant difference to baseline (p = 0.003). No statistically significant difference was seen between LSG and LRYGB in hs-CRP change over time (operation*time interaction p = 0.540). Higher hs-CRP correlated with higher BMI at baseline (Spearman correlation 0.282, p = 0.030) and at 10years (Spearman correlation 0.490, p = 0.001). At 10years, a greater percentage total weight loss (%TWL) correlated with lower hs-CRP level (Spearman correlation - 0.558, p < 0.001). Baseline hs-CRP (Spearman correlation - 0.152, p = 0.299) and hs-CRP change in first 6months postoperatively (Spearman correlation 0.167, p = 0.254) did not correlate statistically significantly with %TWL at 10years. MBS decreases hs-CRP also at long-term follow-up with weight loss as the driving force. Neither baseline hs-CRP nor hs-CRP change at 6months were feasible as a predictive marker for long-term outcomes.

Clinicopathological Analysis of a European Cohort of MYOD1 Mutant Rhabdomyosarcomas in Children and Young Adults.

Patients with PAX3/7-FOXO1 fusion-negative rhabdomyosarcomas (fnRMS) harbouring the rare L122R MYOD1 mutation have significantly poorer prognosis than other fnRMS. We undertook a detailed clinicopathological evaluation of a cohort of patients with MYOD1 mutated fnRMS in order to improve risk stratification and treatment options. Histological, mutational and clinical data from a cohort of patients with MYOD1 mutant RMS treated in Europe were analysed. Thirty-two cases with mutant MYOD1 RMS were identified from patients enrolled in sequential European rhabdomyosarcoma clinical trials from 1992 to 2022 (n = 22) and non-trial cohorts (n = 10). Thirty cases had the recurrent L122R missense mutation, one case harboured a K124E mutation and one case had a truncating mutation (S63X). Increased MyoD1 and reduced MYF4 immunostaining were consistent features of MYOD1L122R-mutated RMS. Applying the risk stratification of the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 trial, among 20 localised RMS cases that could be assigned a risk category, one was Very High Risk, 13 were High Risk and six were Standard Risk. Eight patients had distant metastases at diagnosis. Of the 25 patients with adequate clinical follow-up data, 15/25 (60%) patients had an event at a median time of 9months (12/15 included failure of local control) and 13/25 (52%) died of disease. This MYOD1 mutant cohort demonstrates increased MYOD and reduced MYF4 immunostaining, high risk of local failure and poor survival in agreement with other studies. Increased treatment intensity and improved local control should be considered for these patients.

Update of prognosis and characteristics of chronic obstructive pulmonary disease in a real-world setting: a 5-year follow-up analysis of a multi-institutional registry

BackgroundWe conducted a prospective observational study to elucidate the long-term prognosis and management of chronic obstructive pulmonary disease (COPD) in clinical practice in Japan in the mid-2010s.MethodsThis prospective cohort study included 29 facilities. Data from 427 patients clinically diagnosed with COPD, enrolled between September 2013 and April 2016, were analyzed. Interstitial pneumonia was excluded through a central multidisciplinary discussion. Follow-up data were collected for up to 5 years after patient registration.ResultsAt the time of registration, 53 patients clinically diagnosed with COPD did not have airflow limitation (AFL). In the cohort with AFL (n = 374), 232 patients completed a 5-year follow-up, while 49 patients died during the 1576.6 person-years of observation. The mean age was 71.7 years with an overall 5-year survival rate of 85.4%. Stratified by % forced expiratory volume in one second (FEV1), survival rates were 93.6% in the mild and moderate AFL group, 82.5% in the severe AFL group, and 66.1% in the very severe AFL group. The prognosis of the subpopulation without AFL was poor with a 5-year survival of 81.6%. This subpopulation exhibited respiratory symptoms, low vital capacity and total lung capacity, and emphysematous changes.ConclusionsOur study presents the 5-year survival and real-world clinical practice scenario of a prospective cohort of patients clinically diagnosed with COPD in Japan in the mid-2010s. The survival rates of our cohort were numerically better than the Japanese cohort in the 1990s, regardless of the high median age of this cohort. Overall, 12.4% of the patients in this cohort with no AFL at registration exhibited respiratory symptoms and distinct spirometric patterns, and had a poor prognosis.

Minimal disease activity and associated factors in patients with psoriatic arthritis: cross-sectional study from a single center

IntroductionPsoriatic arthritis (PsA) is a heterogeneous disease with various manifestations such as dactylitis, enthesitis, spondylitis, and skin involvement. Minimal disease activity (MDA) has been successfully used in daily clinical practice and is considered a reasonable treatment target in patients with PsA. In this study, we aimed to evaluate the MDA status and associated factors in patients with PsA in our tertiary referral clinic.Material and methodsThis cross-sectional study included patients who met the CASPAR classification criteria and had at least 6 months of follow-up data between 2001 and 2021. Patients who met at least 5 of 7 criteria (tender joint count ≤ 1/68, swollen joint count ≤ 1/66, Psoriasis Area Severity Index [PASI] ≤ 1, Visual Analogue Scale [VAS] ≤ 15, patient global VAS ≤ 20, Health Assessment Questionnaire-Disability Index [HAQ-DI] ≤ 0.5, and enthesitis number ≤ 1) were considered to achieve MDA.ResultsData from 172 patients (61% female) were analyzed and included in the study. While most patients had polyarticular involvement (33.7%), mono-oligoarthritis was present in 30.2%, mixed type in 26.2%, isolated distal interphalangeal arthritis in 5.8%, isolated spondylitis in 2.9%, and arthritis mutilans in 1.2%. Overall, 95 (55.2%) of the patients were observed at MDA, which was lower in tumor necrosis factor inhibitor (TNFi) users compared to only conventional synthetic disease-modifying antirheumatic drug users. In univariate analysis, MDA was associated with higher patient age, longer psoriasis duration, late-onset PsA, and continued use of first TNFi. In multivariate analysis, higher patient age, late-onset PsA, and higher continuation rate of first TNFi were associated with MDA.ConclusionsIn the study, more than half of our patients achieved MDA status. A higher MDA rate was associated with a higher continuation rate at first-line TNFi treatment. The relatively large po­pulation who could not reach MDA status in our study indicates an unmet need for monitoring and treatment of PsA.

Appraisal of six sigma in pre-analytical phase of clinical biochemistry laboratory

Objectives: The aim of the study is to measure the performance of pre-analytical phase of a clinical biochemistry laboratory using sigma metrics and the six sigma scale. Materials and Methods: The study included documented data of blood sample rejection from March 2023 to February 2024 and follow-up data from March 2024 to August 2024. International Federation of Clinical Chemistry and Laboratory Medicine developed Quality Indicators (QIs) used are QI-9 Wrong tubes; QI-10 Hemolyzed samples; QI-11 Clotted samples; QI-12 Insufficient samples; QI-14 Damaged samples in transport; and QI-15 Mislabeled samples. Based on “Six Sigma Quality Design and Control” established by Dr. Westgard, the sigma metric was calculated for the above-mentioned QIs. Statistical analysis: Obtained data were entered and analyzed using Microsoft Excel 2021. Results: Out of 162,380 received samples, 547 samples were rejected as not satisfied with the sample acceptance criteria. The most common pre-analytical error in the observed QIs is hemolyzed samples (458), followed by insufficient sample volume (55). The Sigma score of QI-10 was determined to be 4.81, whereas QI-9, QI-11, QI-12, and QI-15 were well maintained and graded excellent. Following training sessions, the follow-up month revealed a sigma score of 4.98 for QI-10. Conclusions: Six sigma metrics are a competent means to measure the performance of pre-analytical QIs in a clinical biochemistry laboratory. The observed QIs were effectively managed (&gt;4 σ).