In multiple sclerosis (MS) patients under therapy, the increase of serum glial fibrillary acidic protein (sGFAP) concentrations is associated with the course of 'progression in absence of relapse' (PIRA). While serum neurofilament light chain (sNfL) reflects both response as well as insufficient or lack of efficiency of disease-modifying therapies (DMT), the longitudinal course of sGFAP levels as a drug response marker for future PIRA in relation to specific types of DMT is less clear. We aimed to compare the predictive capacity of sGFAP and sNfL for PIRA and relapse activity and the longitudinal course in people with MS (PwMS) treated with fingolimod, based on Z scores derived from normative values. Overall, 420 PwMS under fingolimod treatment with follow-up of 9.1 years (interquartile range: 7.0-11.0) from the Swiss MS Cohort, contributing 2935 longitudinal serum samples, were included. A reference data set for sGFAP established from 4297 healthy controls across three European and North American cohorts was used to calculate Z scores. The longitudinal course and the predictive capacity of biomarkers for time to PIRA and relapse were assessed by Cox proportional hazards and linear mixed-effects models. In controls, sGFAP concentrations were 13.6% higher in females than males and increased exponentially with age. Altogether, 31.0% of PwMS experienced ≥1 PIRA event. Elevated sGFAP Z scores (>0.75) were associated with increased risk of PIRA [hazard ratio (HR): 1.64; 95% confidence interval (CI): 1.16-2.32; P = 0.006], while this was not the case for sNfL. Conversely, elevated sNfL predicted relapses (HR: 1.58; 95% CI: 1.13-2.23; P = 0.008), while sGFAP did not. Both biomarkers decreased under treatment: sGFAP by 0.19 Z score units (ZSU)/10 years (95% CI: -0.27 to -0.11; P < 0.001) and sNfL by 0.16 ZSU/10 years (95% CI: -0.27 to -0.06; P = 0.002). Serum GFAP remained elevated in PwMS with future PIRA events (estimate: 0.29; 95% CI: 0.07-0.50; P = 0.009); no such association was found for sNfL. Serum GFAP and sNfL Z scores provide complementary predictive capacity for PIRA and relapse risk. The decrease of sGFAP under fingolimod is a feature not observed with other types of DMT and may hint to a specific anti-neurodegenerative effect of Sphingosine-1-phosphate-receptor modulators on astrocytes.
The phase II GeparNuevo trial investigated whether adding durvalumab to neoadjuvant chemotherapy (NACT) only in patients with early triple-negative breast cancer cT1b-cT4a-d would improve pathologic complete response (pCR) rate and patient survival. Hundred and seventy-four patients were randomly assigned to receive durvalumab or placebo concurrently with nab-paclitaxel once per week and followed by dose-dense epirubicin and cyclophosphamide. With 86.4 months of median follow-up compared with the previously reported 43.7 months, durvalumab showed sustained significant improvements in long-term outcomes as defined by STEEP compared with placebo regarding not only invasive disease-free survival (iDFS; hazard ratio [HR], 0.56 [95% CI, 0.32 to 0.99]; stratified log-rank P = .0431), but also distant disease-free survival (DDFS; HR, 0.41 [95% CI, 0.21 to 0.80]; P = .0069) and overall survival (OS; HR, 0.33 [95% CI, 0.14 to 0.79]; P = .0085). All analyses were stratified by stromal tumor-infiltrating lymphocytes (sTILs) at baseline (low [≤10%], intermediate [11%-59%], high [≥60%]). In exploratory subgroup analysis, patients with nodal involvement at baseline demonstrated a greater iDFS benefit (HR, 0.33 [95% CI, 0.144 to 0.771]; P = .01; Pinteraction = 0.045). sTILs in residual disease (RD) could be assessed in 39/71 patients without pCR. Post hoc analyses by sTILs high (>10%) versus low (≤10%) in RD showed estimated 7-year iDFS rates of 92.3% (95% CI, 56.6 to 98.9) and 51.4% (95% CI, 29.2 to 69.7), respectively. Hence, adding durvalumab to dose-dense NACT without adjuvant continuation of checkpoint inhibition improved long-term survival outcomes, irrespective of the extent of pathologic response. This underscores the necessity to re-evaluate the adjuvant continuation of checkpoint inhibition.
OBJECTIVE:Evaluate long-term mortality and the role of causative pathogens in periprosthetic joint infection (PJI) following total hip arthroplasty (THA). METHODS:Retrospective nationwide cohort study of adults undergoing THA (2012-2022) using data from the Swiss Joint Registry, Center for Infection Prevention and civil registry. Primary outcome was up to 10-year survival with or without PJI. Adjusted hazard ratios (aHR) were estimated via Gompertz regression, controlling for sex, age, BMI, and ASA. Pathogen-specific mortality hazard was analyzed. RESULTS:Of 215,678 patients, 89,709 met inclusion criteria (51.3% women; median age 69 years). PJI occurred in 745 (0.8%) patients, 2 752 (3.1%) underwent aseptic revision. PJI was associated with increased mortality (aHR 2.15; 95% CI, 1.79-2.57; p<0.001) compared to no PJI/revision, aseptic revisions were not (aHR 0.92; 95% CI, 0.80-1.06; p=0.27). Pathogens associated with increased mortality included Enterobacterales (aHR 3.17; 95% CI, 2.09-4.83, p<0.001), Staphylococcus aureus (aHR 2.32; 95% CI, 1.65-3.27; p<0.001), Cutibacterium acnes (aHR 2.31; 95% CI, 1.20-4.45; p=0.01), and coagulase-negative staphylococci (aHR 1.65; 95% CI, 1.16-2.35; p=0.006). Streptococcal infections showed no significant association (aHR 1.24; 95% CI, 0.62-2.49; p=0.54). CONCLUSION:PJI following THA was associated with an approximately twofold increase in long-term mortality hazard. C. acnes presented an unexpectedly high mortality hazard.
Chronic back pain is highly prevalent and closely associated with opioid misuse, particularly in patients undergoing spine surgery. Optimizing opioid prescribing practices and advancing alternative treatment modalities is critical to reduce opioid-related morbidity and mortality. Despite their well-documented risks—including misuse, adverse effects, and detrimental impacts on postsurgical outcomes—opioids remain the most commonly prescribed analgesics for back pain. Spine surgery, meanwhile, is frequently followed by intense postoperative pain due to central sensitization, which often necessitates opioid use and complicates pain management. This review provides an overview of current literature on opioid prescribing trends and alternative therapies for patients undergoing spine surgery. Following spine surgery, non-opioid pharmacologic agents and nutraceuticals can enhance analgesia and reduce opioid consumption. While erector spinae plane blocks and neuraxial techniques offer transient pain relief, their efficacy is limited by duration and potential risks. Spinal cord stimulation may benefit selected patients with back pain, although its opioid-sparing effects remain uncertain. Opioid prescribing should be limited to breakthrough pain and integrated into structured tapering strategies. Optimizing postoperative analgesia in spine surgery requires a multimodal approach, interdisciplinary collaboration, and individualized prescribing—potentially guided by emerging tools such as pharmacogenomic testing.
The deltoid tuberosity index (DTI) value of 1.4 is the clinically relevant threshold for low local bone mineral density (BMD) of the proximal humerus. Since possible changes across the DTI threshold of 1.4 could influence treatment strategies for proximal humerus fractures, the purpose of this study was to find out whether and how the DTI values are affected by variable measurement positions. The correct measurement position for the DTI was determined on standard shoulder x-rays of 40 patients. Afterwards three observers placed lines on the inner and outer cortical bone contours. Analysis was performed with the R Statistical Package, the images were imported and converted to data frames. DTI was calculated at all levels from -25 to +25 mm (a total of 500 values) and plotted as line plots. 40 radiographs (32 female and 8 male patients) of acute proximal humerus fractures were analyzed. The median patient age was 72 years. The DTI decreased by 0.29 within the range of ± 25 mm. Within the range of ± 5 mm the DTI decreased by a mean of 0.07. That is equivalent to 91
