Citations

Abstract Objective To provide a comprehensive assessment of various fractionation schemes in radiation therapy for breast cancer, with a focus on side effects, cosmesis, quality of life, risks of recurrence, and survival outcomes. Design Systematic review and meta-analysis. Data sources Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (from inception to 23 October 2023). Study selection Included studies were randomised controlled trials focusing on conventional fractionation (CF; daily fractions of 1.8-2 Gy, reaching a total dose of 50-50.4 Gy over 5-6 weeks), moderate hypofractionation (MHF; fraction sizes of 2.65-3.3 Gy for 13-16 fractions over 3-5 weeks), and/or ultra-hypofractionation (UHF; schedule of only 5 fractions). Data extraction Two independent investigators screened studies and extracted data. Risk of bias and quality of evidence were assessed using the Cochrane Collaboration’s tool and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach, respectively. Data synthesis Pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity was analysed using Cochran’s Q test and I 2 statistic. Network meta-analysis was used to integrate all available evidence. Main outcome measures The pre-specified primary outcome was grade ≥2 acute radiation dermatitis and late radiation therapy related side effects; secondary outcomes included cosmesis, quality of life, recurrence, and survival metrics. Results From 1754 studies, 59 articles representing 35 trials (20 237 patients) were assessed; 21.6% of outcomes showed low risk of bias, whereas 78.4% had some concerns or high risk, particularly in outcome measurement (47.4%). The RR for grade ≥2 acute radiation dermatitis for MHF compared with CF was 0.54 (95% CI 0.49 to 0.61; P<0.001) and 0.68 (0.49 to 0.93; P=0.02) following breast conserving therapy and mastectomy, respectively. Hyperpigmentation and grade ≥2 breast shrinkage were less frequent after MHF than after CF, with RRs of 0.77 (0.62 to 0.95; P=0.02) and 0.92 (0.85 to 0.99; P=0.03), respectively, in the combined breast conserving therapy and mastectomy population. However, in the breast conserving therapy only trials, these differences in hyperpigmentation (RR 0.79, 0.60 to 1.03; P=0.08) and breast shrinkage (0.94, 0.83 to 1.07; P=0.35) were not statistically significant. The RR for grade ≥2 acute radiation dermatitis for UHF compared with MHF was 0.85 (0.47 to 1.55; P=0.60) for breast conserving therapy and mastectomy patients combined. MHF was associated with improved cosmesis and quality of life compared with CF, whereas data on UHF were less conclusive. Survival and recurrence outcomes were similar between UHF, MHF, and CF. Conclusions MHF shows improved safety profile, cosmesis, and quality of life compared with CF while maintaining equivalent oncological outcomes. Fewer randomised controlled trials have compared UHF with other fractionation schedules, but its safety and oncological effectiveness seem to be similar with short term follow-up. Given the advantages of reduced treatment time, enhanced convenience for patients, and potential cost effectiveness, MHF and UHF should be considered as preferred options over CF in appropriate clinical settings, with further research needed to solidify these findings. Systematic review registration PROSPERO CRD42023460249.

OBJECTIVES: The objectives of our systematic review and meta-analyses were to determine the diagnostic accuracy of central venous oxygen saturation (Scvo 2) in estimating mixed venous oxygen saturation (Svo 2) and cardiac index in critically ill patients. DATA SOURCES: A systematic search using MEDLINE, Cochrane Central Register of Controlled Trials, and Embase was completed on May 6, 2024. STUDY SELECTION: Studies of patients in the ICU for whom Scvo 2 and at least one reference standard test was performed (thermodilution and/or Svo 2) were included. DATA EXTRACTION: Individual patient data were used to calculate the pooled intraclass correlation coefficient (ICC) for Svo 2 and Spearman correlation for cardiac index. The Quality Assessment of Diagnostic Accuracy Studies-2 and Grading Recommendations Assessment, Development, and Evaluation tools were used for the risk of bias and certainty of evidence assessments. DATA SYNTHESIS: Of 3427 studies, a total of 18 studies with 1971 patients were identified. We meta-analyzed 16 studies (1335 patients) that used Svo 2 as a reference and three studies (166 patients) that used thermodilution as reference. The ICC for reference Svo 2 was 0.83 (95% CI, 0.75–0.89) with a mean difference of 2.98% toward Scvo 2. The Spearman rank correlation for reference cardiac index is 0.47 (95% CI, 0.46–0.48; p < 0.0001). CONCLUSIONS: There is moderate reliability for Scvo 2 in predicting Svo 2 in critical care patients with variability based on sampling site and presence of sepsis. There is limited evidence on the independent use of Scvo 2 in predicting cardiac index.

Abstract Despite extensive advances in cancer research, glioblastoma (GBM) still remains a very locally invasive and thus challenging tumor to treat, with a poor median survival. Tumor cells remodel their microenvironment and utilize extracellular matrix to promote invasion and therapeutic resistance. It is aimed here to determine how GBM cells exploit hyaluronan (HA) to maintain proliferation using ligand‐receptor dependent and ligand‐receptor independent signaling. Tissue engineering approaches are used to recreate the 3D tumor microenvironment in vitro, then analyze shifts in metabolism, hyaluronan secretion, HA molecular weight distribution, as well as hyaluronan synthetic enzymes (HAS) and hyaluronidases (HYAL) activity in an array of patient‐derived xenograft GBM cells. It is revealed that endogenous HA plays a role in mitochondrial respiration and cell proliferation in a tumor subtype‐dependent manner. A tumor‐specific combination treatment of HYAL and HAS inhibitors is proposed to disrupt the HA stabilizing role in GBM cells. Taken together, these data shed light on the dual metabolic and ligand – dependent signaling roles of hyaluronan in glioblastoma.

Abstract Background Smoldering multiple myeloma (SMM), an asymptomatic precursor of multiple myeloma (MM), carries a variable risk of progression to MM. There is little consensus on the efficacy or optimal timing of treatment in SMM. We systematically reviewed the landscape of all clinical trials in SMM. We compared the efficacy of treatment regimens studied in SMM to results from these regimens when used in newly diagnosed multiple myeloma (NDMM), to determine whether the data suggest deeper responses in SMM versus NDMM. Methods All prospective interventional clinical trials for SMM, including published studies, meeting abstracts, and unpublished trials listed on ClinicalTrials.gov up to April 1, 2023, were identified. Trial-related variables were captured, including treatment strategy and efficacy results. Relevant clinical endpoints were defined as overall survival (OS) and quality of life. Results Among 45 SMM trials identified, 38 (84.4%) assessed active myeloma drugs, while 7 (15.6%) studied bone-modifying agents alone. Of 18 randomized trials in SMM, only one (5.6%) had a primary endpoint of OS; the most common primary endpoint was progression-free survival (n = 7, 38.9%). Among 32 SMM trials with available results, 9 (28.1%) met their prespecified primary endpoint, of which 5 were single-arm studies. Six treatment regimens were tested in both SMM and NDMM; 5 regimens yielded a lower rate of very good partial response rate or better (≥VGPR) in SMM compared to the corresponding NDMM trial (32% vs 63%, 43% vs 53%, 40% vs 63%, 86% vs 89%, 92% vs 95%, and 94% vs 87%, respectively). Conclusion In this systematic review of all prospective interventional clinical trials in SMM, we found significant variability in trial design, including randomization status, primary endpoints, and types of intervention used. Despite the statistical limitations, comparison of treatment regimens revealed no compelling evidence that the treatment is more effective when introduced early in SMM compared to NDMM.

Abstract Background We evaluated the association of achieving endoscopic outcomes at week 12 of induction with improvements in clinical outcomes and quality of life (QoL) at week 52 of maintenance in patients with moderately to severely active Crohn’s disease (CD) treated with upadacitinib (UPA). Methods This post hoc analysis evaluated data from 2 phase 3 induction trials (NCT03345836 and NCT03345849) and 1 maintenance (NCT03345823) trial. Clinical responders to 12-week induction therapy with UPA who also received 52-week maintenance treatment with UPA were included. Endoscopic response, remission, healing, and ulcer-free endoscopy were assessed at week 12. Meaningful improvements in clinical and QoL outcomes were evaluated at week 52. Results A significantly greater proportion of patients who achieved an endoscopic response at the end of induction, compared with patients who did not, attained Crohn’s Disease Activity Index (CDAI) remission (52.0% vs 34.6%; P ≤ .01), corticosteroid-free CDAI remission (50.0% vs 30.9%), Inflammatory Bowel Disease Questionnaire remission (52.6% vs 30.3%), and meaningful improvements in Functional Assessment of Chronic Illness Therapy—Fatigue response (46.7% vs 25.9%), overall work impairment (47.1% vs 26.5%), and daily activity impairment (53.3% vs 34.1%) (all P &lt; .05) at week 52. Similar findings were observed for patients who achieved endoscopic remission, endoscopic healing, and ulcer-free endoscopy at the end of induction vs those who did not. Conclusions Early improvement in endoscopic outcomes after UPA induction treatment was associated with long-term meaningful improvements in clinical outcomes and QoL in patients with CD. Clinical Registration number U-EXCEED induction trial (NCT03345836), U-EXCEL induction trial (NCT03345849), and U-ENDURE maintenance trial (NCT03345823).

Study Design: A retrospective chart review. Objective: The authors aim to investigate the role of clinical and radiographic parameters in patients who underwent posterior cervical surgery, and their association with C5 palsy severity and time to recovery. Background: Postoperative C5 palsy affects 1%–30% of patients undergoing posterior decompression, with or without fusion. Causation and avoidance of this complication remain widely debated. Materials and Methods: A single institution review of patients who underwent posterior cervical spine surgery was focused on using specific Common Procedural Technology codes associated with the patient population of interest. Patients were excluded if they had inadequate pre and postoperative imaging, as well as a history of prior cervical spine surgery, concurrent anterior surgery, intradural pathology, spinal tumor, or spinal trauma. Radiographic measurements of the pre and postoperative images were completed with subsequent intraclass correlation coefficient analysis to confirm the precision of measurements. Results: Out of 105 total patients, 35 (33%) patients developed a C5 palsy. Twenty-four (69%) of those palsies completely resolved, with a median time to recovery of 8 months. Preoperative demographics and radiographic parameters demonstrated heterogeneity among those patients who did and did not have a resolution of palsy. Patients with increased change in C2–C7 lordosis (P = 0.011) after surgery were associated with decreased likelihood of recovery. Patients without a smoking history (P = 0.009) had an increased likelihood of recovering from C5 palsy. Conclusions: The degree of increased lordosis in the treatment of degenerative cervical disease plays a role in the rate of recovery from C5 palsy. This should be considered during preoperative planning in determining the amount of lordosis desired. In addition, patients without a smoking history were associated with a higher rate of recovery. Level of Evidence: Level IV.

The Human Factors (HF) track at the Annual Healthcare Distance Simulation Summit focuses on improving the effectiveness of distance simulation utilizing human factors principles. During this presentation, we will 1. review the work to-date of the HF track of the Distance Simulation Summit, 2. discuss current opportunities for collaboration between human factors practitioners and simulationists, and 3. introduce ideas for future work. The potential target audiences for this discussion are researchers and practitioners who are interested in or involved in distance simulation or simulation in healthcare generally, educators who want to learn how to use distance simulation effectively and efficiently, and healthcare professionals and students who want to enhance their skills and knowledge about distance simulation. The presentation will stimulate discussion and feedback from the audience, which can enrich the knowledge base and generate new research questions and directions for distance simulation.

Abstract Introduction: Current guidelines state the effectiveness of desmopressin to reduce hematoma expansion in antiplatelet-related intracerebral hemorrhage (ICH) is uncertain. This study sought to determine if desmopressin decreased hematoma expansion in ICH patients on antiplatelet agents. Methods: We conducted a multi-center, retrospective propensity-matched cohort study at 11 US emergency departments (ED) that participate in EMPHARM-NET. Adult patients ≥18 years with a primary diagnosis of spontaneous ICH on antiplatelets prior to admission from January 1, 2017 through May 1, 2021 were included. The primary endpoint was good or excellent hemostatic efficacy within the first 24 hours following ICH between patients that did and did not receive desmopressin. Brain imaging was reviewed using 3D-Slicer by blinded expert physicians. Results: Overall, 1408 patients were evaluated for inclusion. A total of 324 patients were included, of which 13.8% (n=45) received desmopressin and 86.1% (n=279) did not. After propensity matching, 35 patients receive desmopressin compared to 140 controls. Baseline hematoma volume (27.6 mL vs. 2.1 mL) and was significantly higher in the desmopressin group. The primary endpoint of good or excellent hemostatic efficacy was similar between groups (74.3% desmopressin group vs. 85% control group, -10.7% [-28.1% to 6.7%]). There was no difference in secondary outcomes. Conclusion: In this multicenter cohort, patients receiving desmopressin had higher baseline intraparenchymal hematoma volume, and did not appear to result in improved hemostatic efficacy relative to the control group. These results suggest against routine administration of desmopressin for antiplatelet-related ICH, though future study in a randomized trial design is necessary.

AbstractINTRODUCTIONWe evaluated preliminary feasibility of a digital, culturally‐informed approach to recruit and screen participants for the Alzheimer's Disease Neuroimaging Initiative (ADNI4).METHODSParticipants were recruited using digital advertising and completed digital surveys (e.g., demographics, medical exclusion criteria, 12‐item Everyday Cognition Scale [ECog‐12]), Novoic Storyteller speech‐based cognitive test). Completion rates and assessment performance were compared between underrepresented populations (URPs: individuals from ethnoculturally minoritized or low education backgrounds) and non‐URPs.RESULTSOf 3099 participants who provided contact information, 654 enrolled in the cohort, and 595 completed at least one assessment. Two hundred forty‐seven participants were from URPs. Of those enrolled, 465 met ADNI4 inclusion criteria and 237 evidenced possible cognitive impairment from ECog‐12 or Storyteller performance. URPs had lower ECog and Storyteller completion rates. Scores varied by ethnocultural group and educational level.DISCUSSIONPreliminary results demonstrate digital recruitment and screening assessment of an older diverse cohort, including those with possible cognitive impairment, are feasible. Improving engagement and achieving educational diversity are key challenges.Highlights A total of 654 participants enrolled in a digital cohort to facilitate ADNI4 recruitment. Culturally‐informed digital ads aided enrollment of underrepresented populations. From those enrolled, 42% were from underrepresented ethnocultural and educational groups. Digital screening tools indicate > 50% of participants likely cognitively impaired. Completion rates and assessment performance vary by ethnocultural group and education.