Citations

Introduction: Tissue biopsies are needed to establish a diagnosis of systemic AL amyloidosis. Biopsy can be obtained from an involved organ with suspected amyloid deposition (target biopsy) or from sites in which amyloid commonly deposits (surrogate biopsy). The choice of biopsy site depends on institutional and physician preference. Two commonly used sites for surrogate biopsies are abdominal fat pad and bone marrow. The present systematic review and meta-analysis aims to evaluate the diagnostic test accuracy of fat pad and bone marrow biopsies as surrogate biopsy sites in the diagnosis of AL amyloidosis. Methods: As part of the ASH AL Amyloidosis Diagnostic Guideline, we performed systematic reviews for seven prioritized PICO questions related to the screening, diagnosis and organ involvement evaluation of AL amyloidosis. We conducted electronic searches on PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception until January 2024. Two reviewers independently and in duplicate performed title and abstract screening and full text article screening on LASER AI, with conflicts resolved by a third reviewer. Studies were eligible if they included patients that had a fat pad sample or bone marrow biopsy and a target organ biopsy for suspicion of AL amyloidosis allowing for the calculation of diagnostic test accuracy measures. Diagnostic test accuracy measures of interest were sensitivity, specificity, positive and negative predictive value. Statistical analysis was performed on OpenMeta[Analyst]. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence. Results: After deduplication, we retrieved 29,237 studies.. 20 studies with 2955 patients reporting on bone marrow biopsy, 25 with 4702 patients on fat pad sampling were included. The pooled sensitivity for bone marrow biopsy was 55.1% (95% CI 45.8-64.0, I2 = 94%) (Certainty of evidence: Low ⨁⨁◯◯), For fat pad sampling sensitivity was 76.6% (95% CI 72.1-80.8, I2 = 84.2%) (Certainty of evidence: Moderate ⨁⨁⨁◯). Among the included studies, 1 evaluated the sensitivity of fat pad sampling and bone marrow biopsy combined and found it to be 89%. No included studies evaluated specificity for bone marrow biopsy or fat pad sample. Conclusion: Combination of fat pad and bone marrow biopsy together significantly improve sensitivity for amyloid detection compared to either fat pad sampling or bone marrow biopsy alone.

Abstract Patient-reported outcomes (PROs) are associated with treatment outcomes in multiple myeloma (MM) in the clinical trial setting. However, most PRO tools are time consuming, which hinders use in routine practice. Our institution incorporated a “Hematology Patient-Reported Symptom Screen” (HPRSS), a 3-item questionnaire for fatigue, pain, and quality of life (QOL). The main objective of this study was to evaluate the impact of these symptoms on progression-free survival (PFS) and overall survival (OS) in a real-world cohort of patients with newly diagnosed MM. This retrospective study included patients with MM diagnosed between April 2011 and December 2017, seen at Mayo Clinic (Rochester, MN), who completed the HPRSS. Patients rated their symptoms on a scale from 0 to 10. Clinically relevant symptoms were defined as scores ≥5 for pain and fatigue, and ≤5 for QOL. At diagnosis, 735 patients had scores for all domains. The median follow-up was 8.1 years. Age was associated with increased odds of fatigue and decreased QOL. Female sex and comorbidities were associated with fatigue and pain. Higher disease stage, anemia, lytic lesions, and increased plasma cell burden were associated with fatigue, pain, and decreased QOL. Clinically relevant fatigue, pain, and decreased QOL were associated with decreased PFS and OS. On multivariate analysis including age, International Staging System III, high-risk cytogenetics, and postinduction transplantation, fatigue and decreased QOL were independently associated with decreased OS. A composite HPRSS score stratified patients into 3 groups with distinct OS. Patient-reported symptoms are prognostic in patients with newly diagnosed MM. The prognostic values of fatigue and decreased QOL are independent of age, disease stage, and transplant status.

INTRODUCTION: This study investigates seasonal variations in eosinophilic esophagitis (EoE)-related emergency department visits among adults. METHODS: We analyzed the National Emergency Department Sample (2016–2021), identifying adult patients with EoE using ICD-10 codes. Generalized additive models assessed seasonal patterns. RESULTS: Among 18,791 EoE-related emergency department visits, a significant seasonal variation was observed, peaking in summer and nadiring in winter. This pattern was consistent across all US regions. CONCLUSION: Seasonal dietary habits and social behaviors likely contribute to EoE exacerbations. Healthcare providers should emphasize management strategies during high-risk periods, particularly summer months and weekends.

Background: Invasive management strategies for myocardial infarction (MI) and multivessel coronary artery disease (MV-CAD) include complete revascularization (successful revascularization of all coronary artery lesions or segments ≥1.5 mm in diameter with ≥50% diameter stenosis) and incomplete revascularization (including culprit-only revascularization). However, non-culprit lesion management strategy in elderly patients remains ambiguous due to a lack of representation of this cohort in randomized trials (RCTs) and higher cardiovascular complication risks. Methods: We performed a meta-analysis comparing clinical outcomes of elderly individuals (age ≥65 years) with MI and MV-CAD submitted to complete vs. incomplete (including culprit-only) percutaneous coronary intervention (PCI). The outcomes of interest were all-cause death, cardiovascular mortality, recurrent MI, and any revascularization. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model. Results: Thirteen studies (3 RCTs, 1 post hoc analysis of previous RCT, and 9 observational studies) with a total of 12,289 patients were included. Complete revascularization (CR) was performed in 5,232 patients, while 7,057 patients underwent incomplete revascularization (IR). The mean age was 80.46 years for CR and 80.73 years for IR and the mean durations of follow-ups ranged from 12-78 months. As compared to IR, the CR group was associated with significantly lower risk of all-cause mortality (OR 0.59, 95% CI 0.49 to 0.71, p<0.0001) (Figure 1), cardiovascular mortality (OR 0.56, 95% CI 0.40 to 0.77, p=0.0005), recurrent MI (OR 0.62, 95% CI .47 to 0.81, p=0.0005) (Figure 2), and any revascularization (OR 0.47, 95% CI 0.26 to 0.86, p=0.01). Conclusion: Among elderly patients with MI and MV-CAD, CR is associated with a lower risk of all-cause mortality, cardiovascular mortality, recurrent MI, and any revascularization.

Background: Ambiguity surrounds invasive management of non-ST-segment elevation myocardial infarction (NSTE-MI) in older adults (≥70 years), and the number of elderly patients undergoing invasive treatment in clinical practice remains relatively low. Data comparing the efficacy of invasive versus conservative medical management for NSTEMI in this population is conflicting due to the under-representation or exclusion of the older population from randomized controlled trials (RCTs). Methods: We performed a meta-analysis of RCTs to evaluate the long-term outcomes of invasive versus conservative medical strategies in older patients with NSTEMI. Random effects meta-analysis was conducted to estimate the odds ratio (OR) with 95% CI for the individual endpoints of all-cause mortality, cardiovascular (CV) mortality, recurrent myocardial infarction (MI), unplanned revascularization, and readmission for cardiovascular causes. Results: A total of nine RCTs with 4,336 patients (Invasive: 2,368; Control: 1,968) with median follow-ups ranging from 6-63.6 months were included. Compared with a conservative strategy, an invasive strategy was associated with a significantly decreased risk of recurrent MI (OR 0.62, 95% CI 0.47-0.81; p<0.001) (Figure 1) and unplanned revascularization (OR 0.38, 95% CI 0.25-0.56; p<0.001). There was no difference in all-cause mortality (OR 0.81, 95% CI 0.39-1.35; p=0.42) (Figure 2), CV mortality (OR 0.72, 95% CI 0.43-1.23; p=0.23), or readmission for cardiovascular causes (OR 1.21, 95% CI 0.63-2.33; p=0.57) between invasive and conservative management strategies. Conclusion: In older patients ≥70 years old with NSTE-MI, an invasive strategy reduced the risk of recurrent MI and revascularization when compared with conservative management. However invasive strategy did not offer any benefit in mortality or cardiac-cause related readmission over conservative management.

Abstract Most TERT promoter (TERTp) clinically relevant sequence variants in CNS tumors are the canonical C228T and C250T mutations. Non-canonical TERTp mutations have been reported mainly in non-CNS tumors. We describe 12 CNS tumors with non-canonical TERTp variants interpreted as clinically relevant. Using clinical targeted NGS panels (2020-2024), we detected c.-100_-79dup (n=2), c.-92_-91insGGCGGCCCCGCCCCTTCCTTTC (n=1), c.-118_-117insTCCCCGGCCCAGCCCCTTCCGGG (n=1), c.-123_-76dup (n=1), c.-110_-89dup (n=2), and c.-57A&gt;C (n=5). Most cases had chromosomal microarray (n=11) and/or methylation array data analyzed using the NCI/Bethesda v.2 classifier (n=9). All non-canonical TERTp variants occurred at a variant allele frequency suggestive of somatic clonal origin (mean, 34%; range, 18-46), and in adults (mean age, 60 years; range, 36-88). Except for the c.-57A&gt;C variant, all non-canonical TERTp variants occurred in tumors with histological and/or molecular diagnostic features of glioblastoma, IDH-wildtype (GBM), often epigenetically aligning to this tumor type. All five tested cases matched to superfamily glioblastoma (score ≥ 0.9), with three to class GBM_RTK_I (&gt;0.9 in 2, 0.86 in 1) and two to GBM_RTK_II (&gt;0.9). The size and sequence of such variants suggest that these may be functionally equivalent to canonical mutations or generate favorable TERTp activation motif conformations like previously reported activating duplications. The c.-57A&gt;C variant is a well-established oncogenic mutation observed in other cancer types but has not been reported in CNS tumors. We describe five cases with the c.-57A&gt;C variant: one GBM matching to methylation class GBM_MES_TYP (0.99); two oligodendroglioma, IDH-mutant and 1p/19q-codeleted, one of which had methylation data matching to class O_IDH (0.99); one diffuse glioma, IDH-mutant, which was partially 1p/19q-codeleted and matched to class O_IDH (0.99); and one anaplastic meningioma, aligning to superfamily meningioma (0.99)/MNG_MAL (0.79). Our findings show that non-canonical TERTp variants typically occur in tumor types that often harbor TERTp canonical mutations, expanding the spectrum of TERTp clinically relevant variants that are molecular biomarkers in CNS tumors.

BACKGROUND Despite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive 10 or more years after standard treatment. METHODS We evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared with mid-term (MTS; 5–7.99 years; n = 433) and short-term survivors (STS; 2–4.99 years; n = 416). Primary tumor samples were immunostained and scored for intraepithelial and intrastromal densities of 10 immune-cell subsets (including T cells, B cells, plasma cells, myeloid cells, PD-1 + cells, and PD-L1 + cells) and epithelial content. RESULTS Positive associations with LTS compared with STS were seen for 9 of 10 immune-cell subsets. In particular, the combination of intraepithelial CD8 + T cells and intrastromal B cells showed near 5-fold increased odds of LTS compared with STS. All of these associations were stronger in tumors with high epithelial content and/or the C4/Differentiated molecular subtype, despite immune-cell densities generally being higher in tumors with low epithelial content and/or the C2/Immunoreactive molecular subtype. CONCLUSION The tumor microenvironment of HGSC LTS is distinguished by the intersection of T and B cell coinfiltration, high epithelial content, and C4/differentiated molecular subtype, features which may inspire new approaches to immunotherapy. FUNDING Ovarian Cancer Research Program (OCRP) of the Congressionally Directed Medical Research Program (CDMRP), U.S. Department of Defense (DOD); American Cancer Society; BC Cancer Foundation; Canada’s Networks of Centres of Excellence; Canadian Cancer Society; Canadian Institutes of Health Research; Cancer Councils of New South Wales, Victoria, Queensland, South Australia, and Tasmania, Cancer Foundation of Western Australia; Cancer Institute NSW; Cancer Research UK; Deutsche Forschungsgesellschaft; ELAN Funds of the University of Erlangen-Nuremberg; Fred C. and Katherine B. Andersen Foundation; Genome BC; German Cancer Research Center; German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research; Instituto de Salud Carlos III; Mayo Foundation; Minnesota Ovarian Cancer Alliance; Ministerio de Economía y Competitividad; Medical Research Council (MRC); National Center for Advancing Translational Sciences; National Health and Medical Research Council of Australia (NHMRC); Ovarian Cancer Australia; Peter MacCallum Foundation; Sydney West Translational Cancer Research Centre; Terry Fox Research Institute; The Eve Appeal (The Oak Foundation); UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; University of Pittsburgh School of Medicine; U.S. National Cancer Institute of the National Institutes of Health; VGH & UBC Hospital Foundation; Victorian Cancer Agency.

Objective Epilepsy surgery is vital in managing of children with drug-resistant epilepsy. Noninvasive and invasive testing modalities allow for evaluation and treatment of children with drug-resistant epilepsy. Evidence-based algorithms for this process do not exist. This study examines expert response to a vignette of pediatric nonlesional epilepsy to assess associations in evaluation and treatment choices. Methods We analyzed annual report data and an epilepsy practice survey reported in 2020 from 135 pediatric epilepsy center directors in the United States. Characteristics of centers along with noninvasive and invasive testing and surgical treatment strategies were collected. Multivariable logistic regression modeling was performed. Results The response rate was 100% with 135 responses included in the analyses. Most used noninvasive testing modalities included Neuropsychology evaluation (90%), interictal brain fluorodeoxyglucose-positron emission tomography (85%), and functional magnetic resonance imaging (MRI) (72%) with nearly half obtaining genetic testing. Choosing functional MRI was associated with stereo electroencephalography (EEG) ( P = .025) and selecting Wada with subdural grid/strips ( P = .038). Directors from pediatric-only centers were more likely to choose stereo EEG as opposed to combined centers ( P = .042). Laser interstitial thermal therapy was almost 7 times as likely to be chosen as a treatment modality compared with open resection in dedicated pediatric centers (OR 6.96, P = .002). Significance In a vignette of nonlesional childhood drug-resistant epilepsy, epilepsy center directors’ patterns of noninvasive testing, invasive testing, and treatment were examined. Management choices were associated with pediatric versus combined pediatric/adult center characteristics. Expert opinions demonstrated equipoise in evaluation and management of children with drug-resistant epilepsy and the need for evidence-based management strategies.