Multicenter Study Research Articles

Exploring ischemic core growth rate and endovascular therapy benefit in large core patients.

After stroke onset, ischemic brain tissue will progress to infarction unless blood flow is restored. Core growth rate measures the infarction speed from stroke onset. This multicenter cohort study aimed to explore whether core growth rate influences benefit from the reperfusion treatment of endovascular thrombectomy in large ischemic core stroke patients. It identified 134 patients with large core volume >70 mL assessed on brain perfusion image within 9 hours of stroke onset. Of 134 patients, 71 received endovascular thrombectomy and 63 did not receive the treatment. Overall, poor outcomes were frequent, with 3-month severed disability or death rate at 56% in treatment group and 68% in no treatment group (p = 0.156). Patients were then stratified by core growth rate. For patients with 'ultrafast core growth' of >70 mL/hour, rates of poor outcome were especially high in patients without endovascular thrombectomy (n = 13/14, 93%) and relatively lower in patients received the treatment (n = 12/20, 60%, p = 0.033). In contrast, for patients with core growth rate <70 mL/hour, there was not a large difference in poor outcomes between patients with and without the treatment (55% vs. 61%, p = 0.522). Therefore, patients with 'ultrafast core growth' might stand to benefit the most from endovascular treatment.

Efficacy and Safety of Pioglitazone Add-on in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin and Dapagliflozin: A Multicenter, Randomized, Double-blind, and Placebo-Controlled Study

PurposeThe purpose of this study was to determine the efficacy and safety profile of pioglitazone compared with placebo (PBO) in patients with type 2 diabetes (T2D) inadequately controlled with metformin and dapagliflozin. MethodsIn this prospective, multicenter, randomized, double-blind, PBO-controlled trial, 366 patients with T2D who did not meet glycemic targets (7.0% ≤ glycosylated hemoglobin [HbA1c] ≤ 10.5%), despite treatment with metformin ≥1000 mg and dapagliflozin 10 mg, received either a PBO, 15 mg of pioglitazone daily (PIO15), or 30 mg of pioglitazone daily (PIO30). The primary end point was the mean change in HbA1c from baseline at 24 weeks across the groups. FindingsFor the 366 participants (PBO, n = 124; PIO15, n = 118; PIO30, n = 124), the mean age was 55.6 years and mean duration of diabetes was 8.7 years, with a baseline HbA1c of 7.9%. After 24 weeks, HbA1c reduced significantly in the PIO15 and PIO30 groups from baseline, with intergroup differences of −0.38% and −0.83%, respectively, compared with the PBO group. The proportion of patients with HbA1c levels <7% was significantly higher in the PIO15 and PIO30 groups than in the PBO group. The adverse event rates did not significantly differ across the groups, indicating favorable safety profiles for triple combination therapy using metformin, dapagliflozin, and pioglitazone. ImplicationsThe addition of pioglitazone as a third oral antidiabetic medication is an appropriate option for patients with T2D inadequately controlled with metformin and dapagliflozin based on the resulting significant efficacy in glycemic control and favorable safety profile. ClinicalTrials.gov identifier: NCT04885712.

Impact of Serum Indoxyl Sulfate on One-Year Adverse Events in Chronic Kidney Disease Patients with Heart Failure

Background/Objectives: Indoxyl sulfate, a uremic toxin, is associated with mortality and cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to evaluate the prognostic implications of serum indoxyl sulfate levels in patients with heart failure and CKD. Methods and Results: This was a prospective multicenter observational study. Overall, 300 patients with chronic heart failure with a previous history of hospitalization and an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m2 or less (CKD stage G3b to G5) without dialysis were analyzed. The primary outcome assessed in a time-to-event analysis from the measurement of indoxyl sulfate was a composite of all-cause death, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Clinical events were followed-up to one year after indoxyl sulfate measurement. The median patient age was 75 years, and 57% of the patients were men. We divided the cohort into low and high indoxyl sulfate categories according to a median value of 9.63 mg/mL. The primary outcome occurred in 27 of 150 patients (18.0%) in the low indoxyl sulfate group and 27 of 150 patients (18.0%) in the high indoxyl sulfate group (hazard ratio, 1.00; 95% confidence interval, 0.58 to 1.70, p = 0.99). In the post hoc exploratory analyses, the results were consistent across age, sex, body mass index, left ventricular ejection fraction, eGFR, and N-terminal pro b-type natriuretic peptide. Conclusions: Among heart failure patients with CKD stages G3b to 5G, serum indoxyl sulfate concentrations were not significantly associated with the subsequent occurrence of cardiovascular events.

Decompressive craniectomy in symptomatic intracerebral hemorrhage after ischemic stroke: a multicenter retrospective cohort study.

Symptomatic intracerebral hemorrhage (sICH) after stroke is a devastating neurological complication. Current guidelines support a "possible benefit" of decompressive craniectomy (DC) for large supratentorial sICH with significant mass effect. The authors conducted a retrospective study of 8 comprehensive stroke centers. They included all patients who sustained an sICH after acute ischemic stroke (AIS), as defined by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), from January 2016 to December 2020. They compared patients who underwent DC to those who were treated with standard medical treatment to measure functional outcome at 90 days, primarily as defined by the modified Rankin Scale (mRS) and secondarily by the Glasgow Outcome Scale-Extended (GOS-E). Eighty-five patients were identified, 26 of whom (30.5%) underwent DC. Patients who underwent DC were younger (58 years [DC] vs 76 years [no DC], p < 0.001). No patient with a previous history of cancer underwent DC (n = 14, p = 0.004). Twenty-five patients (96.2%) in the DC group underwent thrombectomy versus 54 (91.5%) in the non-DC group (p = 0.443). Patients who underwent DC had a longer ICU stay (median [IQR] 240 [38-408] hours vs 24 [5-96] hours in non-DC patients, p = 0.002). At 90 days, 3 patients (4.1%) had obtained an mRS score of 0-2 and 10 patients (11.7%) an mRS score of 0-3. Patients who had improved functional outcome were younger (mRS score, OR 1.06, 95% CI 1.01-1.10, p = 0.012). Patients with a history of cancer had worse 90-day mRS scores (OR 8.49, 95% CI 1.54-159, p = 0.046). The rate of in-hospital mortality or discharge to hospice was significantly higher in the non-DC cohort (10 [38.5%] patients in the DC cohort vs 38 [64.4%] in the non-DC cohort, p = 0.026). Ninety days later, patients who underwent DC were more likely to have improved outcome (mRS mean rank 30.0 vs 40.0, p = 0.027). In multivariable analysis, history of cancer (OR 12.2, 95% CI 1.26-118, p = 0.031) and older age (OR 1.07, 95% CI 1.02-1.13, p = 0.011) increased the odds of worse mRS outcomes while DC did not (OR 1.34, 95% CI 0.357-5.03, p = 0.665). DC after sICH did not improve functional outcome at 90 days according to multivariable analysis, although younger age and absence of previous cancer history were associated with improved outcomes.

The Dangers of Distracted Driving: A substudy of Patient Perception Data from the DRIVSAFE Observational Study.

To determine how fracture clinic patients perceive the dangers of distracted driving. Design: Analysis of patient perception subset data from the original DRIVSAFE study; a large, multi-center cross-sectional study, surveying fracture clinic patients about distracted driving. Four level 1 Canadian trauma center fracture clinics. English-speaking patients with a valid Canadian driver's license and a traumatic musculoskeletal injury sustained in the past six months. Primary outcome was patients' safety ratings of driving distractions. As per the original DRIVSAFE study, patients were categorized as distraction-prone or distraction-averse using their questionnaire responses and published crash-risk odds ratios (OR). A regression analysis was performed to identify associations with unsafe driving perceptions. The study included 1378 patients, 749 (54.3%) male and 614 (44.6%) female. The average age was 45.8 years old ± 17.0 (range 16-87). Sending electronic messages was perceived as unsafe by 92.9% (1242/1337) of patients, while reading them was seen as unsafe by 81.2% (1086/1337). Approximately three-quarters of patients viewed making (78.9%, 1061/1344) and accepting (74.8%, 998/1335) calls on handheld mobile phones as unsafe. However, 31.0% (421/1356) of patients believed they had no differences in their driving ability when talking on the phone while 13.1% (175/1340) reported no driving differences when texting. Younger age (OR, 0.93 [95% CI 0.90-0.96], p<0.001), driving experience (OR, 1.06 [95% CI 1.02-1.09], p<0.001), and distraction-prone drivers (OR, 3.79 [95% CI 2.91-4.94], p<0.001) were associated with unsafe driving perceptions. There is a clear association between being prone to distractions and unsafe driving perceptions, with distraction-prone drivers being 3.8 times more likely to perceive driving distractions as safe. This information could potentially influence the appropriate delivery and content of future educational efforts to change the perception of driving distractions and thereby reduce distracted driving. Level III. See Instructions for Authors for a complete description of levels of evidence.

Outcomes and safety of atezolizumab plus bevacizumab in the treatment of hepatocellular carcinoma: treatment prognosis and comparison with tyrosine kinase inhibitors in a French multicenter matched real-life study.

The combination of atezolizumab plus bevacizumab (Atz/Bev) has radically changed the treatment strategy for advanced hepatocellular carcinoma (HCC) but raises questions. Our objectives were to determine survival outcomes and safety in a real-life multicenter French cohort, to investigate the on-treatment prognostic value of the bioinflammatory RECA score, and to perform a matched comparison with patients who previously received tyrosine kinase inhibitors (TKIs). A retrospective analysis of 109 consecutive patients enrolled from September 2020 to January 2023 and a post matched comparison with a TKI cohort (n = 79) by the propensity score matching method. The Atz/Bev population was mainly nonviral disease patients (69%) with Child-Pugh grade A (90%), performance status 0/1 (90%), and Barcelona Clinic Liver Cancer stage B (38%) or stage C (62%) classification. After a median follow-up of 6.5 months (3.6-11.7), overall survival (OS) was 13.0 (5.1-28.7) months. OS was independently associated with metastasis, increased alkaline phosphatase, and serum bilirubin levels. Treatment-related adverse events were reported in 78% of patients, mostly grade 1 or 2. The RECA score clearly revealed two different prognosis groups after three cycles. No difference in OS was observed after matching between sequential treatment with TKIs and Atz/Bev. This real-life study highlights the importance of liver function when using Atz/Bev combination and the necessity of identifying predictive markers of response to HCC therapies. Our findings suggest a change in practices, with a marked proportion of intermediate stages, and support the on-treatment prognostic value of an inflammatory score.

Anti-CD19 CAR-T cell therapy in elderly patients: multicentric real-world experience from GETH-TC/GELTAMO

CAR-T cell therapy is approved for the treatment of relapsed/refractory (R/R) large B cell lymphoma (LBCL). However, elderly patients might not be candidates for this therapy due to its toxicity, and criteria for candidate selection are lacking. Our aim was to analyze efficacy and toxicity results of CAR-T cell therapy in the population of 70 years and older as compared to those obtained in younger patients in the real-world setting. A multicentric retrospective study was performed including patients with R/R aggressive LBCL who received commercial CAR-T cell therapy with either tisagenlecleucel or axicabtagene ciloleucel within Spanish GETH-TC/GELTAMO centers between 2019 and 2023. As of August 2023, 442 adult patients with aggressive LBCL underwent apheresis for CAR-T cell therapy as third or subsequent line and had follow-up data. Of 412 infused patients, 71 (17%) were 70 years or older. Baseline characteristics, product selection and characteristics at apheresis (including disease status, Ann Arbor stage, R-IPI, bulky disease, LDH and ECOG) were comparable between groups. Median time from both approval to infusion and apheresis to infusion did not differ. No differences were found between groups in overall and complete response rates at one and three months. With a median follow-up of 12.2 months (range 1-44), 12-month progression-free survival (PFS) and overall survival (OS) were comparable between groups (35.2% in <70y vs. 35.9% in ≥70y (p= p=0.938) and 51.1% and 52.1% (p= p=0.885), respectively). Age ≥70 years did not affect PFS (HR 0.98, p=0.941) and OS (HR 0.97, p=0.890) in the univariate and multivariate analysis. Cytokine release syndrome (CRS) was observed in 82% patients in <70y and 84.5% in ≥70y (p=0.408). Grade ≥3 CRS was more frequent in the older group (5% vs. 15%, p=0.002). In the multivariate analysis, age ≥70y was associated with an increased risk of grade ≥3 CRS (OR 3.7, p=0.013). No differences were observed in terms of overall neurotoxicity (35% vs. 42%, p=0.281) or grade ≥3 (12% vs. 17%, p=0.33). The proportion of patients with infections, admission to intensive care unit within the first month and non-relapse mortality were similar between both groups. CAR-T cell therapy in patients older than 70 years showed similar efficacy than that observed in younger patients in the real-world setting. However, age ≥70 years was an independent risk factor for grade 3-4 CRS. Need of additional strategies to reduce toxicity in this population should be addressed in future studies.

Determinants of non-union after standard plate fixation for combined radial and ulnar fractures in adults

Treatment of mid-shaft fractures of both forearm bones in adults typically consists of individual plate fixation of each bone according to AO principles. The primary objective of this multicentre retrospective study was to identify predictive and prognostic factors of failed bone union after internal fixation with a standard plate in adults.130 mid-shaft fractures of both forearms occurred in 92 men and 38 women, who had a mean age of 35.1 years were reviewed; 42 were open: 31 were Gustilo type I, 10 were type II and 1 was type III. All patients underwent ORIF using a direct approach over the supinator crest for the ulnar fracture and using an anterior approach at the level of the radial fracture by dynamic compression plate in 90 cases and a limited-contact dynamic compression plate in 40 cases, all with 3.5 mm diameter screws.The radiographs from all patients were reviewed after a minimum follow-up of 12 months: primary union of both forearm bones occurred in 121 of the 130 cases after a mean of 4.6 months (±2.6). 104 patients were reviewed clinically with a minimum follow-up of 12 months and a mean of 36 months (±21.7). According to Tscherne-Oestern classification, 79 % of patients had a very good outcome, 6 % had a good outcome, 10 % had a fair outcome and 5 % had a poor outcome Non-union occurred in 9 patients (one septic): 4 times at both fracture sites, 4 times at the ulna only and once at the radius only. The mean age was higher in the patients with non-union: 46.4 years versus 34.2 (P = 0.08). Smoking, alcoholism, associated head trauma, presence of pre-operative nerve deficit and open fracture did not appear to be risk factors for non-union. The type of plate used and the number of screws placed on either side of the fracture site had no effect on union.This patient series had a similar non-union rate to the one reported in other published studies, likely because the technical rules were followed. A lack of statistical power probably prevented us from identifying prognostic factors for bone union.

Characterization of omalizumab updosing patterns and predictive factors in chronic spontaneous urticaria: A prospective multicentric observational study.

Limited information is available on the use of omalizumab (OMA) updosing since its introduction as a second-line therapy in chronic spontaneous urticaria (CSU) in 2014. Practical guidelines from health authorities are lacking, and the specific characteristics of patients requiring higher doses remain unknown. Our objectives were to characterize the patterns of OMA updosing (defined as changes in dose and/or injection intervals), to identify the predictive factors associated with updosing, and to improve CSU management. We conducted a prospective, multicentric, real-life observational study, including patients diagnosed with CSU and starting OMA. The data were collected at 0, 3, 6, and 9 months. The primary endpoint was the frequency of OMA updosing at 3 months. The secondary endpoints included an analysis of updosed patients' profile, and an assessment of OMA efficacy and safety. We included 153 patients. Twenty percent of patients were updosed at 3 months, and 27% in total during the 9-month follow-up. Practitioners mainly chose to increase the frequency of injections (66%). At baseline, the updosed patients were more likely to have more severe CSU (UCT < 4, p < 0.030), a lower lymphocyte count (<2000/mm3, p = 0.037), and low IgE levels (<70 UI/mL, p = 0.024). The side effects of OMA were not more frequent after updosing. One in five patient underwent updosing within just 3 months. OMA updosing is frequent in particular in cases of severe disease and low IgE blood levels.

Prospective multicenter study to validate the Gastrointestinal Dysfunction Score (GIDS) in intensive care patients: Study protocol for Part A of the international GUTPHOS study

BackgroundWhile gastrointestinal (GI) dysfunction is commonly encountered among critically ill patients, a uniform prospectively validated scoring system is lacking. The present study aims to validate the recently developed Gastrointestinal Dysfunction Score (GIDS) in a multicenter, prospective cohort of consecutive adult patients admitted to intensive care units (ICU). MethodsGUTPHOS is a prospective, multicenter, non-interventional cohort study in which at least 1400 consecutive adult patients (age ≥18 years) admitted to the ICU will be monitored daily for abdominal signs and symptoms of GI dysfunction. The previously developed GIDS constructed from these signs and symptoms will be tested in relation to mortality and duration of ICU dependency and parenteral nutrition (PN) dependency. Between January and June 2024, each participating clinical site will include 50-120 consecutive patients over an eight-week period. Study data will be collected in three phases: baseline data upon ICU admission, daily observations throughout a maximum of 7 days in ICU or until discharge, and a follow-up period of 90 days. The primary outcomes are 28- and 90-day all-cause mortality. Secondary outcomes include ICU and hospital mortality, ICU and hospital length of stay, days alive and free of ICU by day 28 and day 90, days alive and free of hospital by day 28 and day 90, and days alive and free of organ support and PN dependency by day 28. DiscussionThe GUTPHOS study will be the first worldwide, multicenter, prospective, observational cohort study to validate the GIDS in adult patients admitted to ICUs against 28- and 90-day mortality. The availability of a validated tool will allow its use in interventional studies that are currently hindered by the lack of a validated measurement tool for GI dysfunction. Clinical trial registryNCT05909722

Genetic testing for primary aldosteronism in SPAIN: Results from the SPAIN-ALDO Registry and review of the literature.

To determine the rate of genetic testing for familial hyperaldosteronism (FH) in the SPAIN-ALDO Registry and to describe the clinical characteristics of patients with FH. In addition, a literature review of reports of FH cases was performed. A retrospective multicenter study of primary aldosteronism (PA) in patients followed in 35 Spanish tertiary hospitals (SPAIN-ALDO Registry). Twenty-five of the 855 patients (3%) with PA included in the registry underwent genetic testing for FH, with complete results available in only 24 patients. However, we found that there were 57 patients who met the criteria for performing a genetic study of PA. Only 8 out of these 57 patients were genetically tested (14.0%), while the reasons to perform a genetic study in the remaining 9 genetically studied cases were quite heterogeneous. A positive result for FH was found only in one case for FH type III (KCNJ5 pathogenic variant). A systematic review of the literature was performed and identified a total of 25 articles reporting 246 patients with FH type I; 12 articles reporting 72 patients with FH type II; 14 articles reporting 29 cases of FH type III and 3 articles reporting 12 patients with FH type IV. The genetic study of familial hyperaldosteronism is often scarce in real-world clinical practice, as 86% of patients with criteria to undergo genetic study were not evaluated in our cohort. Nevertheless, FH is an uncommon cause of PA, representing only 0.2% of cases in the SPAIN-ALDO Registry, although its prevalence may be as high as 4% among suspected cases might be studied.

Serious injuries of Lisfranc joint: A retrospective multicenter study of 141 patients

IntroductionLisfranc joint injuries are common and often underdiagnosed. They occur during trauma of various mechanisms, high or low energy. Their management is difficult because of the wide spectrum of lesions and the management of associated lesions, particularly in the emergency stage. Their surgical treatment remains controversial. Therefore, the objective of this study was to evaluate and compare the management of Lisfranc injuries and to study their clinical, functional and radiologic evolution. We also wanted to assess the consequences of these lesions on the patient's quality of life. Material and methodsThis was a retrospective multicenter study of 141 patients over 16 years at the time of the trauma. The patients included had presented a Lisfranc injury from January 2010 to June 2018. The epidemiological characteristics, the type of osteosynthesis, and the immediate and radiographic results at the last follow-up were collected. Functional assessment was analyzed by telephone review using the SF12, FAAM and AOFAS scores. ResultsAn associated M2 base fracture was found in almost 50 % of cases. A closed reduction and fixation was made in 25 % of cases. There was 69 % pins fixation. The reduction was not anatomical in 1/3 of the cases and was more difficult to achieve with an associated fracture. The FAAM score was statistically superior in the patients with internal fixation by screws compared to the treatment by pins. We found 18 % early complications. At least 1 year after the injury, C2M2 osteoarthritis was found in 45 % of patients. DiscussionContrary to what is recommended in the literature, this study reported a high rate of osteosynthesis by pins whereas screws and plates were more recommended. Open reduction was also recommended and was the strategy of choice in this study. An M2 fracture was often associated with Lisfranc dislocations. The quality of reduction was essential and was better with open reduction and screw fixation.

Towards multicenter β-amyloid PET imaging in mouse models: A triple scanner head-to-head comparison

β-amyloid (Aβ) small animal PET facilitates quantification of fibrillar amyloidosis in Alzheimer's disease (AD) mouse models. Thus, the methodology is receiving growing interest as a monitoring tool in preclinical drug trials. In this regard, harmonization of data from different scanners at multiple sites would allow the establishment large collaborative cohorts and may facilitate efficacy comparison of different treatments. Therefore, we objected to determine the level of agreement of Aβ-PET quantification by a head-to-head comparison of three different state-of-the-art small animal PET scanners, which could help pave the way for future multicenter studies. Within a timeframe of 5 ± 2 weeks, transgenic APPPS1 (n = 9) and wild-type (WT) (n = 8) mice (age range: 13-16 months) were examined three times by Aβ-PET ([18F]florbetaben) using a Siemens Inveon DPET, a MedisonanoScan PET/MR, and a MedisonanoScan PET/CT with harmonized reconstruction protocols. Cortex-to-white-matter 30-60 min p.i. standardized uptake value ratios (SUVRCTX/WM) were calculated to compare binding differences, effect sizes (Cohen's d) and z-score values of APPPS1 relative to WT mice. Correlation coefficients (Pearson's r) were calculated for the agreement of individual SUVR between different scanners. Voxel-wise analysis was used to determine the agreement of spatial pathology patterns. For validation of PET imaging against the histological gold standard, individual SUVR values were subject to a correlation analysis with area occupancy of methoxy‑X04 staining. All three small animal PET scanners yielded comparable group differences between APPPS1 and WT mice (∆PET=20.4 % ± 2.9 %, ∆PET/MR=18.4 % ± 4.5 %, ∆PET/CT=18.1 % ± 3.3 %). Voxel-wise analysis confirmed a high degree of congruency of the spatial pattern (Dice coefficient (DC)PETvs.PET/MR=83.0 %, DCPETvs.PET/CT=69.3 %, DCPET/MRvs.PET/CT=81.9 %). Differences in the group level variance of the three scanners resulted in divergent z-scores (zPET=11.5 ± 1.6; zPET/MR=5.3 ± 1.3; zPET/CT=3.4 ± 0.6) and effect sizes (dPET=8.5, dPET/MR=4.5, dPET/CT=4.1). However, correlations at the individual mouse level were still strong between scanners (rPETvs.PET/MR=0.96, rPETvs.PET/CT=0.91, rPET/MRvs.PET/CT=0.87; all p ≤ 0.0001). Methoxy-X04 staining exhibited a significant correlation across all three PET machines combined (r = 0.76, p < 0.0001) but also at individual level (PET: r = 0.81, p = 0.026; PET/MR: r = 0.89, p = 0.0074; PET/CT: r = 0.93, p = 0.0028). Our comparison of standardized small animal Aβ-PET acquired by three different scanners substantiates the possibility of moving towards a multicentric approach in preclinical AD research. The alignment of image acquisition and analysis methods achieved good overall comparability between data sets. Nevertheless, differences in variance of sensitivity and specificity of different scanners may limit data interpretation at the individual mouse level and deserves methodological optimization.

Novel method of iliac accessory rods for rod fracture prevention in adult deformity surgery: a case series of 82 patients with outcomes and complications.

Primary rod fracture after surgery for adult spinal deformity (ASD) is a leading cause of revision, with recent prospective multicenter fracture rates reported at 11%-14% by 2 years. Consequently, the addition of supplemental rods has been explored to reduce fractures. Here the authors describe their experience with a novel iliac accessory rod technique in which each accessory rod anchors to an independent iliac bolt caudally via lateral connector, and attaches to the primary rod rostrally via side-to-side connector. This retrospective, single-center case series included patients who underwent thoracolumbar/lumbar fusion for ASD between March 2019 and August 2023. Data on baseline demographics, radiographic parameters, surgical characteristics, complications, rod fracture, and revision rates were collected. Paired, 2-tailed t-tests were used to compare pre- and postoperative radiographic outcomes. Rod fracture rates were compared to prior investigations via chi-square goodness of fit testing. The technique for iliac accessory rod placement is described. The study consisted of 82 patients (mean age 66 years, 51% female, 26% with prior fusion) with a median follow-up of 2 years (IQR 28-104 weeks). A total of 50 patients (61%) had ≥ 2-year follow-up. Each surgery involved an average of 4 posterior column osteotomies and 8 segments. Iliac accessory rods were cobalt chromium and were placed bilaterally in 87% of constructs. Postoperative alignment improved significantly in the following parameters: maximum coronal Cobb angle, fractional curve, sagittal vertical axis, lumbar lordosis, thoracic kyphosis, and pelvic incidence to lumbar lordosis mismatch (p < 0.001 for all comparisons). Of 50 patients with ≥ 2-year follow-up, rod fracture occurred in 1 (2.0%), which was incidentally found and required no intervention. The present rod fracture rate was significantly lower than the authors' historically reported institutional rate of 21% for traditional dual-rod constructs, and the 11%-14% reported in recent prospective multicenter studies that used traditional and supplemental rod constructs (p < 0.05 for all comparisons). Reoperation occurred in 12 patients (14.6%); 7 (8.5%) for proximal junctional kyphosis and 5 (6.1%) for wound complication. Here the authors describe their experience with a novel iliac accessory rod technique to prevent rod fracture in patients undergoing surgery for ASD. The 2-year rod fracture rate (2.0%) in this study is significantly lower than the authors' historical dual-rod fracture rate, and other prospective multicenter investigations. Future studies with longer follow-up are needed to determine the durability of this technique.

Diagnostic MRI Score to Differentiate Susac Syndrome from Primary Angiitis of the Central Nervous System and Multiple Sclerosis.

Susac syndrome (SuS), multiple sclerosis (MS), and primary angiitis of the central nervous system (PACNS) present diagnostic challenges due to overlapping clinical features. We aimed to enhance diagnostic precision by developing the SPAMS (SuS, PACNS, MS) score, a practical radiological tool. This multicenter study included 99 patients (43 SuS, 37 MS, 19 PACNS) from South American countries. Relevant MRI features were identified through an elastic-net model determined key variables. The SPAMS score assigned 2 points for snowball lesions, 1 point for spokes-like lesions, or if there are more than 4 lesions in the corpus callosum, corpus callosum involvement, or cerebellar involvement. It subtracted 1 point if gadolinium-enhancing lesions or 4 points if Dawson's fingers are present. Bootstrapping validated the optimal cutoff at 2 points, exhibiting a diagnostic performance of area under the curve = 0.931, sensitivity = 88%, specificity = 89%, positive predictive value = 88%, negative predictive value = 89%, and accuracy = 88%. When specific MRI findings coexisted, the SPAMS score differentiated SuS from MS and PACNS. Access to MRI and standard protocol sequences makes it a valuable tool for timely diagnosis and treatment, potentially preventing disability progression and severe clinical outcomes. ANN NEUROL 2024.

Bone-Active Drugs in Pre-Menopausal Women with Breast Cancer Under Hormone Deprivation Therapies.

Bone health management in pre-menopausal women with breast cancer (BC) under hormone-deprivation therapies (HDTs) is often challenging, and the effectiveness of bone-active drugs is still unknown. This retrospective multicenter study included 306 premenopausal women with early BC undergoing HDTs. Bone mineral density (BMD) and morphometric vertebral fractures (VFs) were assessed 12 months after HDTs initiation and then after at least 24 months. After initial assessment, bone-active drugs were prescribed in 77.5% of women (151 denosumab 60 mg/6 months, 86 bisphosphonates). After 47.0±20.1 months, new VFs were found in 16 women (5.2%). VFs risk was significantly associated with obesity [OR 3.87, p=0.028], family history of hip fractures or VFs (OR 3.21, p=0.040], chemotherapy-induced menopause (OR 6.48, p<0.001), pre-existing VFs (OR 25.36, p<0.001), baseline T-score ≤-2.5 SD at any skeletal site (OR 4.14, p=0.036) and changes at lumbar and total hip BMD (OR 0.94, p=0.038 and OR 0.88, p<0.001, respectively). New VFs occurred more frequently in women untreated compared to those treated with bone-active drugs (14/69, 20.8% vs. 2/237, 0.8%; p<0.001) and the anti-fracture effectiveness remained significant after correction for BMI (OR 0.033; p<0.001), family history of fractures (OR 0.030; p<0.001), chemotherapy-induced menopause (OR 0.04; p<0.001) and pre-existing VFs (OR 0.014; p<0.001). Pre-menopausal women under HDTs are at high risk of VFs in relationship with high BMI, densitometric diagnosis of osteoporosis, pre-existing VFs and family history of osteoporotic fractures. VFs in this setting might be effectively prevented by bisphosphonates or denosumab.

Blood Pressure Fluctuation During 72 Hours After Endovascular Therapy and Prognosis in Acute Ischemic Stroke Patients.

Our study aimed to investigate the relationship between fluctuations in different blood pressure (BP) components within 72 hours following endovascular therapy (EVT) and the prognosis of acute ischemic stroke (AIS) patients. This prospective multicenter study included 283 AIS patients who underwent EVT and had available BP data. The primary outcome was the ordinal modified Rankin Scale (mRS) score evaluated at 90 days. The secondary outcome was a combination of death and major disability, defined as an mRS score of 3 to 6 within 3 months. After adjusting for imbalanced variables, the highest tertile of systolic blood pressure (SBP) fluctuation had an odds ratio (OR) of 1.747 (95% confidence interval [CI]=1.031-2.961; p for trend=0.035) for the primary outcome and 1.889 (95% CI=1.015-3.516; p for trend=0.039) for the secondary outcome, respectively. Fluctuations in diastolic blood pressure (DBP) (OR=1.914, 95% CI=1.134-3.230, p for trend=0.015) and mean arterial pressure (MAP) (OR=1.759, 95% CI=1.026-3.015, p for trend=0.039) were only associated with the primary outcome. The multivariate-adjusted restricted cubic spline analyses supported these findings. Furthermore, the fluctuations in both SBP and MAP exhibited the significant discriminatory capability in predicting the prognosis, comparable to their mean values. Our study revealed that larger fluctuations in SBP, DBP, and MAP within 72 hours after EVT were associated with a higher risk of poor clinical outcomes within 3 months in AIS patients. Controlling BP fluctuations may be valuable for improving the prognosis in patients undergoing EVT. How will this change clinical practice?It provides physicians a new approach to directly monitor BP fluctuations over an extended observation period in AIS patients after EVT in routine clinical practice.What does it mean for the clinicians?These results underscore the importance of giving equal attention to controlling long-term BP fluctuations, in addition to managing mean BP, as a means to improve the prognosis of AIS patients after EVT.What is the innovation behind the study?This study systematically evaluated the association between fluctuations in different blood pressure components and clinical outcomes in AIS patients over an extended period following EVT.

Predictors for reintervention and survival during long-term follow-up after TEVAR for descending thoracic aortic aneurysm

BackgroundSeveral studies have reported short- and intermediate-term outcomes after TEVAR for descending thoracic aortic aneurysm (DTAA), however, reports on long-term (10 years) outcomes are sparse. Therefore, the aim of this study was to analyze predictors impacting long-term outcome following thoracic endovascular aortic repair (TEVAR) for DTAA. Materials and methodsDatabases from four academic institutions were reviewed and consecutive cases of TEVAR for DTAA between 1999 and 2021 were included in this retrospective multicenter study (Case series). Ethical approval from Institutional review board was obtained and patient demographics, treatment data as well as follow-up information were retrieved and analyzed. Results305 patients (mean age 72±10 years) treated with TEVAR for degenerative DTAA with mean aortic diameter of 64mm were identified. Altogether 445 endografts were implanted via femoral access (93%) with a technical success of 94%. Operative mortality, stroke rate and rate of spinal cord ischemia were 6% (5% for intact, 12% for ruptured DTAA), 4% and 3%, respectively. Kaplan-Meier estimates for overall survival rates were 76%, 59% and 34% at 1, 5 and 10 years and freedom from reintervention rates were 84%, 73% and 58% at 1, 5 and 10 years, respectively. In multivariate analysis, ASA grade 3-5 and non-elective case were identified as predictors for death, wheres as fusiform DTAA, proximal landing zone 2 and hypertension but not device generation were predictive for reintervention. ConclusionThis is to date the largest study reporting long-term (10 years) outcome on TEVAR for DTAA. We found acceptable rates for long-term survival and freedom-from reintervention that were independent of endovascular device generation.

Prospective multicenter study to describe the prevalence, outcomes, and management of phosphate disorders in intensive care patients: Study protocol for Part B of the international GUTPHOS study

BackgroundAberrations in blood phosphate (Pi) levels, whether presenting as hypo- or hyperphosphatemia, appear to be associated with clinical complications and adverse outcomes in patients admitted to an intensive care unit (ICU). However, the prevalence of Pi disorders and the association with subsequent factors and organ failures leading to death in ICU patients are poorly described. Despite endeavors to understand the etiology and treatment of low Pi levels from systematic reviews and meta-analyses, the literature lacks comprehensive guidance for managing hypophosphatemia. Hyperphosphatemia, on the other hand, appears to be associated with higher mortality among critically ill patients, yet its prevalence among ICU patients, particularly following phosphate repletion, remains unknown. The present study aims to investigate the prevalence of Pi abnormalities upon ICU admission and their incidence during the first week of ICU stay, the factors associated with Pi alterations, and the effect of phosphate repletion on the normalization of Pi levels, and its associations with clinical outcomes. MethodsThis multicentre, prospective, non-interventional cohort study will include at least 1000 consecutive adult ICU patients (≥18 years) as part B of the GUTPHOS study. Sites are eligible if an anticipated minimal inclusion of 50 eligible patients during eight weeks from January 2024 until June 2024 and daily phosphate measurements during the first seven days of ICU stay are expected. All consecutive adult patients admitted to a participating ICU during the recruitment period, lasting up to eight weeks, or up to 120 patients if enrollment reaches that limit earlier, will be included. Study parameters include study site characteristics, patient demographics, daily assessment of Pi levels, Pi-related treatment, feeding details, renal replacement therapy details, the incidence of refeeding-associated hypophosphatemia and administered medication (during the first seven calendar days of ICU stay). There will be a follow-up period of a maximum of 90 days to document 28- and 90-day all-cause mortality as the primary outcome. Multiple logistic regression will be used to assess independent associations with mortality in addition to Receiver Operating Characteristics curves to identify cut-off Pi values associated with mortality and overcorrection. Linear mixed models will be conducted to assess Pi treatment effects. Subgroup analyses will be performed based on Pi abnormalities observed during ICU admission, categorized as normo-, hypo-, hyper-, or mixed, along with its severity (mild, moderate, or severe). DiscussionThe GUTPHOS study will be the first multicentre, prospective observational cohort study to investigate the prevalence, management practices, and consequent outcomes associated with Pi abnormalities during the first week of ICU admission. Its results may bridge the current evidence gap in repletion protocols while establishing the groundwork for a subsequent randomized controlled trial.

Periprosthetic fracture around total knee arthroplasty: What are the advantages of minimal-invasive surgery?

ObjectivesPeriprosthetic femur fractures after total knee arthroplasty in older adults are mostly treated by internal fixation. Members of the GETRAUM (French Orthopedic Trauma Society) sought to compare two surgical techniques – conventional open surgery and minimally invasive surgery – with the aim of analyzing the patients’ functional recovery. We hypothesized that a minimally invasive technique would produce better early functional outcomes with recovery of independence. Materials and MethodsThis retrospective multicenter study of patients treated between 2009 and 2015 consisted of 90 fractures with a follow-up of 1 year. Demographic, preoperative data and the characteristics of fractures, type of fixation and the surgeon's experience level were collected. The endpoints were the Parker Mobility score, Katz ADL, place of residence at the time of fracture and at 6 months and one-year follow-up. All complications and one-year mortality during the follow up were searched. ResultsAt 6 months follow-up, the minimally invasive technique contributed to significantly better functional recovery as measured by the Parker (p < 0.05) and Katz scores (p < 0.05). However, there were no differences in these scores at one-year follow-up. The complication rate was 31% at one year follow-up. Mortality rate was 12 % (11 patients). ConclusionOur hypothesis was confirmed, as there was a difference between techniques that impacted functional recovery and independence, but only in the early postoperative phase. A minimally invasive technique appears to be beneficial in the short term for distal femur fractures after total knee arthroplasty but must be evaluated in a comparative and prospective study to fully confirm its reliability.