Citations

PURPOSE The multicenter, open-label, randomized phase 2 NCI-9944 study ( NCT02595892 ) demonstrated that addition of ATR inhibitor (ATRi) berzosertib to gemcitabine increased progression-free survival (PFS) compared to gemcitabine alone (hazard ratio [HR]=0.57, one-sided log-rank P = .044, which met the one-sided significance level of 0.1 used for sample size calculation). METHODS We report here the final overall survival (OS) analysis and biomarker correlations (ATM expression by immunohistochemistry, mutational signature 3 and a genomic biomarker of replication stress) along with post-hoc exploratory analyses to adjust for crossover from gemcitabine to gemcitabine/berzosertib. RESULTS At the data cutoff of January 27, 2023 (>30 months of additional follow-up from the primary analysis), median OS was 59.4 weeks with gemcitabine/berzosertib versus 43.0 weeks with gemcitabine alone (HR 0.79, 90% CI 0.52 to 1.2, one-sided log-rank P = .18). An OS benefit with addition of berzosertib to gemcitabine was suggested in patients stratified into the platinum-free interval ≤3 months (N = 26) subgroup (HR, 0.48, 90% CI 0.22 to 1.01, one-sided log-rank P =.04) and in patients with ATM-negative/low (N = 24) tumors (HR, 0.50, 90% CI 0.23 to 1.08, one-sided log-rank P = .06). CONCLUSION The results of this follow-up analysis continue to support the promise of combined gemcitabine/ATRi therapy in platinum resistant ovarian cancer, an active area of investigation with several ongoing clinical trials.

ObjectivesTo report an autoimmune paraneoplastic encephalitis characterized by immunoglobulin G (IgG) antibody targeting synaptic protein calmodulin kinase‐like vesicle‐associated (CAMKV).MethodsSerum and cerebrospinal fluid (CSF) samples harboring unclassified antibodies on murine brain‐based indirect immunofluorescence assay (IFA) were screened by human protein microarray. In 5 patients with identical cerebral IFA staining, CAMKV was identified as top‐ranking candidate antigen. Western blots, confocal microscopy, immune‐absorption, and mass spectrometry were performed to substantiate CAMKV specificity. Recombinant CAMKV‐specific assays (cell‐based [fixed and live] and Western blot) provided additional confirmation.ResultsOf 5 CAMKV‐IgG positive patients, 3 were women (median symptom‐onset age was 59 years; range, 53–74). Encephalitis‐onset was subacute (4) or acute (1) and manifested with: altered mental status (all), seizures (4), hyperkinetic movements (4), psychiatric features (3), memory loss (2), and insomnia (2). Paraclinical testing revealed CSF lymphocytic pleocytosis (all 4 tested), electrographic seizures (3 of 4 tested), and striking MRI abnormalities in all (mesial temporal lobe T2 hyperintensities [all patients], caudate head T2 hyperintensities [3], and cortical diffusion weighted hyperintensities [2]). None had post‐gadolinium enhancement. Cancers were uterine adenocarcinoma (3 patients: poorly differentiated or neuroendocrine‐differentiated in 2, both demonstrated CAMKV immunoreactivity), bladder urothelial carcinoma (1), and non‐Hodgkin lymphoma (1). Two patients developed encephalitis following immune checkpoint inhibitor cancer therapy (atezolizumab [1], pembrolizumab [1]). All treated patients (4) demonstrated an initial response to immunotherapy (corticosteroids [4], IVIG [2]), though 3 died from cancer.InterpretationCAMKV‐IgG is a biomarker of immunotherapy‐responsive paraneoplastic encephalitis with temporal and extratemporal features and uterine cancer as a prominent oncologic association. ANN NEUROL 2024;96:21–33

Background: Bar stabilization during minimally invasive pectus excavatum repair (MIRPE) is critical to avoid dislodgement. Multiple techniques are described including stabilizers, wires, and sutures. This retrospective study compared bar movement and outcomes between existing techniques and ZipFix™, a biocompatible cable tie. Methods: Patients ≤20 years of age who underwent MIRPE with ZipFix between January 2021 and September 2022 were compared with historical controls who underwent repair by same surgeons between January 2018 and December 2020 using stabilizers or polydioxanone suture (PDS). Demographics, clinical details, and outcomes were compared using Kruskal–Wallis and chi-square tests. Results: Of the 116 patients who underwent repair, 45 had bars secured with ZipFix (39%) and 71 (61%) were historical controls (35 stabilizer, 36 PDS). Median (interquartile range) age was 15 (14–16) years and Haller index was 3.9 (3.6–4.5). Nine (8%) patients required two bars. Haller index and use of second bar were comparable between stabilization techniques ( P > .05). In total, 49 patients (40%) reported any pain at 1 month and this was similar between stabilization techniques ( P = .45). Median bar movement was greater for bars secured with PDS than with ZipFix or stabilizers at 1 month (5.5 versus 2.3 versus 3.3°, P = .010) and last follow-up (6.5 versus 2.1 versus 3.6°, P < .001). One patient whose bar was secured with PDS required revision for dislodgement. Conclusion: Pectus bar stabilization with ZipFix is a safe alternative to metal stabilizers and both techniques are superior to suture stabilization alone. The use of ZipFix may be preferred given its lower cost and ease of use.

Abstract Background and Aims Non‐invasive tests (NITs) are underutilized for diagnosis and risk stratification in metabolic dysfunction‐associated steatotic liver disease (MASLD), despite good accuracy. This study aimed to identify challenges and barriers to the use of NITs in clinical practice. Methods We conducted a qualitative exploratory study in Germany, Italy, United Kingdom and United States. Phase 1 participants (primary care physicians, hepatologists, diabetologists, researchers, healthcare administrators, payers and patient advocates; n = 29) were interviewed. Phase 2 participants (experts in MASLD; n = 8) took part in a group discussion to validate and expand on Phase 1 findings. Finally, we triangulated perspectives in a hybrid deductive/inductive thematic analysis. Results Four themes hindering the use of NITs emerged: (1) limited knowledge and awareness; (2) unclear referral pathways for patients affected by liver conditions; (3) uncertainty over the value of NITs in monitoring and managing liver diseases; and (4) challenges justifying system‐level reimbursement. Through these themes, participants perceived a stigma associated with liver diseases, and primary care physicians generally lacked awareness, adequate knowledge and skills to use recommended NITs. We identified uncertainties over the results of NITs, specifically to guide lifestyle intervention or to identify patients that should be referred to a specialist. Participants indicated an ongoing need for research and development to improve the prognostic value of NITs and communicating their cost‐effectiveness to payers. Conclusions This qualitative study suggests that use of NITs for MASLD is limited due to several individual and system‐level barriers. Multi‐level interventions are likely required to address these barriers.

AbstractBackgroundThe COVID‐19 pandemic affected healthcare delivery across all specialties including apheresis. To describe the changes in apheresis service practices that occurred during the pandemic, the American Society for Apheresis (ASFA) Apheresis Medicine Attending Physician Subcommittee conducted a survey study.Study Design and MethodsA 32‐question survey was designed and distributed to 400 ASFA physician members on September 7, 2022. Attending physicians responded to questions about whether and how apheresis service practices changed during the COVID‐19 pandemic compared with the time period prior to the pandemic in terms of: (1) procedure types and volumes, (2) patient consultation workflow, and (3) the use of telemedicine. Descriptive analyses were reported as number and frequency of responses.ResultsThe survey response rate was 13.8% (55/400). Of these respondents, 96.4% (53/55) were attending physicians. The majority of respondents (42/53, 79.2%) indicated that the types of procedures performed during COVID‐19 compared to pre‐pandemic did not change. Most frequently for apheresis procedure volume, respondents reported: no change in their monthly inpatient volume (21/47, 44.7%) and a decrease in their monthly outpatient volume (28/46, 60.9%). Prior to COVID‐19, 75.0% (30/40) of respondents performed consultations at bedside for inpatients and 67.4% (29/43) performed consultations at bedside for outpatients. Bedside consultations decreased in both settings during the pandemic but were still most frequently performed by attending physicians. At the same time, the use of telemedicine increased for 15.4% of survey respondents during COVID‐19.ConclusionSome, but not all, respondents observed or made changes to their apheresis service during the COVID‐19 pandemic. A subset of changes, such as increased utilization of telemedicine, may persist.

Abstract Background Multimorbidity and functional limitation are associated with poor outcomes in heart failure (HF). However, the individual and combined effect of these on health‐related quality of life in patients with HF is not well understood. Methods Patients aged ≥30 years with two or more HF diagnostic codes and one or more HF‐related prescription drugs from four U.S. institutions were mailed a survey to measure patient‐centric factors including functional status (activities of daily living [ADLs]) and health‐related quality of life (PROMIS‐29 Health Profile). Patients with HF from January 1, 2013 to February 1, 2018 were included. Multimorbidity was defined as ≥2 non‐cardiovascular comorbidities; functional limitation as any limitation in at least one of eight ADLs. Patients were categorized into four groups by multimorbidity (Yes/No) and functional limitation (Yes/No). We dichotomized the PROMIS‐29 sub‐scale scores at the median and calculated odd ratios for the four multimorbidity/functional limitation groups. Results A total of 3330 patients with HF returned the survey (response rate 31%); 3020 completed the questions of interest and were retained. Among these patients (45% female; mean age 73 [standard deviation: 12] years), 29% had neither multimorbidity nor functional limitation, 24% had multimorbidity only, 22% had functional limitation only, and 25% had both. After adjustment, having functional limitation only was associated with higher anxiety (odds ratio [OR]: 3.44, 95% confidence interval [CI]: 2.66–4.45), depression (OR: 3.11, 95% CI: 2.39–4.06), and fatigue (OR: 4.19, 95% CI: 3.25–5.40); worse sleep (OR: 2.14, 95% CI: 1.69–2.72) and pain (OR: 6.73, 95% CI: 5.15–8.78); and greater difficulty with social activities (OR: 9.40, 95% CI: 7.19–12.28) compared with having neither. Results were similar for having both multimorbidity and functional limitation. Conclusion Patients with only functional limitation have similar poor health‐related quality of life scores as those with both multimorbidity and functional limitation, underscoring the important role that physical functioning plays in the well‐being of patients with HF.

Background/Objectives: Tuberculum sellae meningiomas (TSMs) constitute 5–10% of intracranial meningiomas, often causing visual impairment. Traditional microsurgical transcranial approaches (MTAs) have been effective, but the emergence of innovative surgical trajectories, such as endoscopic endonasal approaches (EEAs), has sparked debate. While EEAs offer advantages like reduced brain retraction, they are linked to higher cerebrospinal fluid leak (CSF leak) risk. This meta-analysis aims to comprehensively compare the efficacy and safety of EEAs and MTAs for the resection of TSMs, offering insights into their respective outcomes and complications. Methods: A comprehensive literature review of the databases PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted for articles published on TSMs treated with either EEA or MTA until 2024. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Meta-analysis was performed to estimate pooled event rates and assess heterogeneity. Fixed- and random-effects were used to assess 95% confidential intervals (CIs) of presenting symptoms, outcomes, and complications. Results: A total of 291 papers were initially identified, of which 18 studies spanning from 2000 to 2024 met the inclusion criteria. The exclusion of 180 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and a lack of details on method/results. The 18 studies comprised a total sample of 1093 patients: 444 patients who underwent EEAs and 649 patients who underwent MTAs for TSMs. Gross total resection (GTR) rates ranged from 80.9% for EEAs to 79.8% for MTAs. The rate of visual improvement was 86.6% in the EEA group and 65.4% in the MTA group. The recurrence rate in the EEA group was 6.9%, while it was 5.1% in MTA group. The postoperative complications analyzed were CSF leak, infections, dysosmia, intracranial hemorrhage (ICH), and endocrine disorders. The rate of CSF leak was 9.8% in the EEA group and 2.1% in MTA group. The rate of infections in the EEA group was 5.7%, while it was 3.7% in the MTA group. The rate of dysosmia ranged from 10.3% for MTAs to 12.9% for EEAs. The rate of ICH in the EEA group was 0.9%, while that in the MTA group was 3.8%. The rate of endocrine disorders in the EEA group was 10.8%, while that in the MTA group was 10.2%. No significant difference was detected in the rate of GTR between the EEA and MTA groups (OR 1.15, 95% CI 0.7–0.95; p = 0.53), while a significant benefit in visual outcomes was shown in EEAs (OR 3.54, 95% CI 2.2–5.72; p < 0.01). There was no significant variation in the recurrence rate between EEA and MTA groups (OR 0.92, 95% CI 0.19–4.46; p = 0.89). While a considerably increased chance of CSF leak from EEAs was shown (OR 4.47, 95% CI 2.52–7.92; p < 0.01), no significant difference between EEA and MTA groups was detected in the rate of infections (OR 1.92, 95% CI 0.73–5.06; p = 0.15), the rate of dysosmia (OR 1.25, 95% CI 0.31–4.99; p = 0.71), the rate of ICH (OR 0.61, 95% CI 0.20–1.87; p = 0.33), and the rate of endocrine disorders (OR 1.16, 95% CI 0.69–1.95; p = 0.53). Conclusions: This meta-analysis suggests that both EEAs and MTAs are viable options for TSM resection, with distinct advantages and drawbacks. The EEAs demonstrate superior visual outcomes in selected cases while GTR and recurrence rates support the overall effectiveness of MTAs and EEAs. Endoscopic endonasal approaches had a higher chance of CSF leaks, but there are no appreciable variations in other complications. These results provide additional insights regarding patient outcomes in the intricate clinical setting of TSMs.

Systemic vasculitides are a rare and complex group of diseases that can affect multiple organ systems. Clinically, presentation may be vague and non-specific and as such, diagnosis and subsequent management are challenging. These entities are typically classified by the size of vessel involved, including large-vessel vasculitis (giant cell arteritis, Takayasu’s arteritis, and clinically isolated aortitis), medium-vessel vasculitis (including polyarteritis nodosa and Kawasaki disease), and small-vessel vasculitis (granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis). There are also other systemic vasculitides that do not fit in to these categories, such as Behcet’s disease, Cogan syndrome, and IgG4-related disease. Advances in medical imaging modalities have revolutionized the approach to diagnosis of these diseases. Specifically, color Doppler ultrasound, computed tomography and angiography, magnetic resonance imaging, positron emission tomography, or invasive catheterization as indicated have become fundamental in the work up of any patient with suspected systemic or localized vasculitis. This review presents the key diagnostic imaging modalities and their clinical utility in the evaluation of systemic vasculitis.

Background: Breastfeeding has numerous health benefits for patients and their infants. There are inconsistencies in how anesthesia providers care for lactating patients undergoing anesthesia. Providers may be cautious and have patients “pump and dump” instead of following current evidence-based recommendations. Video-based education provides a novel reference for health care providers in their fast-paced work environments. This project evaluated the effectiveness of an online video module and resources accessed at the bedside for anesthesia providers caring for lactating patients. Materials and Methods: A preintervention survey was sent to anesthesia providers at a large academic institution to assess baseline knowledge of current recommendations for caring for lactating patients having anesthesia. A quick response code-linked video module and references were created and disseminated to all anesthesia providers. A postsurvey was sent to assess knowledge and satisfaction with the educational approach. Postsurvey data were compared with presurvey data. Results: All who watched the educational video found the education helpful to care for lactating patients undergoing surgery. In the posteducation group, 93% of providers selected the correct recommendation to continue breastfeeding or pumping after general anesthesia or sedation once the patient is awake and alert, compared with 48% in the pre-education group. After education, 92% would recommend preoperative feeding or pumping prior to transport to the operating room, compared with the 50% in the pre-education group. Conclusions: Video-based, just-in-time education is an effective way to deliver updated information to anesthesia providers. This format is conducive to just-in-time delivery, and there may be implications for other patient populations that present infrequently but require population-specific care.