Citations

Abstract Introduction/Aims Intracellular congophilic inclusions within muscle fibers, although nonspecific, are one of the pathological hallmarks of sporadic inclusion body myositis (sIBM). Extracellular amyloid deposits in muscle, on the other hand, are the canonical findings of amyloid myopathies, which occur with or without systemic amyloidosis. Methods We reviewed the muscle biopsy database (1998–2020) to identify sIBM patients with extracellular amyloid deposits. Clinical and laboratory data were reviewed. Results We identified five sIBM patients (three clinicopathologically defined and two clinically defined) with extracellular amyloid deposits in muscle. Mean age at diagnosis was 74.8 y (range, 68–84 y). All patients had a typical sIBM pattern of weakness without associated sensory or autonomic symptoms. None had electrophysiological evidence of peripheral neuropathy. Only one patient had a monoclonal gammopathy (immunoglobulin M‐lambda, IgM‐λ) with normal bone marrow biopsy. This patient with monoclonal gammopathy and three other patients underwent abdominal fat pad aspirate and were negative for amyloid. Cardiac evaluation was unrevealing in the four patients tested. Three patients without monoclonal gammopathy had normal transthyretin gene sequencing and inconclusive mass spectrometry‐based analysis. The patient with monoclonal gammopathy died of pneumosepsis 5 y after diagnosis and autopsy revealed multi‐organ transthyretin amyloidosis. Discussion Detection of extracellular amyloid deposition in muscle should trigger an aggressive search for systemic amyloidosis independently from other associated myopathological abnormalities. Amyloid subtyping is crucial for early therapy and mortality prevention. An isolated monoclonal gammopathy should not halt a search for non‐hematological causes of systemic amyloidosis.

Abstract Background: Prostate cancer is the most common cancer among men. Monitoring of patient-reported outcomes (PROs) can enhance provider-patient communication, promote better decision-making, and improve survival. Geospatial factors, namely rurality and neighborhood socioeconomic deprivation, could influence the experience across cancer treatment, thus impacting PROs and survival. This study examined associations of rurality, neighborhood socioeconomic deprivation (Area Deprivation Index [ADI]) with cancer treatment-related PROs and survival in men with prostate cancer. Methods: Data from men with prostate cancer in the trial NRG Oncology/RTOG 0415 were analyzed. In this trial, 1092 men were randomized to receive conventional radiotherapy (RT) or hypofractionated RT. Patients had Gleason scores of 2-6 and prostate-specific antigen of <10 ng/mL. Rurality was categorized as urban vs rural using Rural-Urban Continuum Codes via patient zip codes. Neighborhood socioeconomic deprivation was assessed by the ADI calculated via the American Community Survey by patient zip codes. The Expanded Prostate Cancer Index Composite (EPIC) measures cancer-specific quality of life (QOL); Hopkins Symptom Checklist measures anxiety and depression; EuroQoL-5 Dimension (EQ-5D) VAS and Index scores assess general health. All PROs were measured at baseline before and 6, 12, 24 and 60 months after RT. Overall survival (OS) and disease-free survival (DFS) were assessed using Cox proportional hazards models. Mixed effects models and generalized estimating equations were used to analyze PROs. Results: We analyzed 751 patients with complete data. Patients from the ADI 25% most deprived neighborhoods (vs. the other 75% of neighborhoods) were more likely to be non-white, unmarried and from rural areas. At baseline, patients from the most deprived areas had worse EPIC bowel score (P=0.011), worse sexual score (P=0.042) and worse hormonal score (P=0.015); patients from the most deprived areas had worse self-care (P=0.04) and more pain (P=0.047). Patients from rural areas had worse EPIC urinary score (P=0.03) and sexual score (P=0.003). Longitudinal analyses showed that ADI 25% most deprived areas (β=4.05, P=0.001) and rural areas (β=-5.70, P=0.003) were associated with worse EQ-5D VAS score. Compared to the 75% less deprived neighborhoods and urban, the ADI 25% most deprived neighborhoods and rural areas respectively had 47% (HR=1.466, P=0.033) and 93% (HR=1.925, P=0.026) relative increase in risk of recurrence or death (DFS). No differences were seen in OS. Conclusions: Patients with prostate cancer from the most deprived neighborhoods and rural areas had low QOL at baseline, poor general health and DFS. Interventions should target populations from socioeconomic deprived neighborhoods and rural areas to improve patient access to supportive care services and DFS. Citation Format: Jinbing Bai, Stephanie L. Pugh, Ronald Eldridge, Katherine Yeager, Qi Zhang, W Robert Lee, Amit B. Shah, Ian S. Dayes, David P. D'Souza, Jeff M. Michalski, Jason A. Efstathiou, John M. Longo, Thomas M. Pisansky, Jordan M. Maier, Sergio L. Faria, Anand B. Desai, Samantha A. Seaward, Howard M. Sandler, Mary E. Cooley, Deborah W. Bruner. Rurality and neighborhood socioeconomic deprivation associated with patient-reported outcomes andsurvivalin men with prostate cancer in NRG RTOG 0415 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2528.

AbstractBackgroundWe sought to evaluate the association between vitamin D deficiency and the severity of coronavirus disease 2019 (COVID‐19) infection.MethodsMultiple databases from 1 January 2019 to 3 December 2020 were searched for observational studies evaluating the association between vitamin D deficiency and severity of COVID‐19 infection. Independent reviewers selected studies and extracted data for the review. The main outcomes of interest were mortality, hospital admission, length of hospital stay and intensive care unit admission.ResultsSeventeen observational studies with 2756 patients were included in the analyses. Vitamin D deficiency was associated with significantly higher mortality (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.50–4.05; 12 studies; hazard ratio [HR]: 4.11, 95% CI: 2.40–7.04; 3 studies), higher rates of hospital admissions (OR: 2.18, 95% CI: 1.48–3.21; 3 studies) and longer hospital stays (0.52 days; 95% CI: 0.25–0.80; 2 studies) as compared to nonvitamin D deficient status. Subgroup analyses based on different cut‐offs for defining vitamin D deficiency, study geographic locations and latitude also showed similar trends.ConclusionsVitamin D deficiency is associated with greater severity of COVID‐19 infection. Further studies are warranted to determine if vitamin D supplementation can decrease the severity of COVID‐19.

Introduction: Genetic studies of early-onset disease have been an effective strategy to identify novel pathways and drug targets relevant to later-onset disease. Few studies have investigated the role of common genetic variation in the etiology of early-onset ischemic stroke (IS). Methods: We performed a GWAS meta-analysis of 38 studies from 10 countries, comprised of 5,847 IS cases of European ancestry under age 60 and 32,533 controls. Results: We identified two genome-wide significant (p< 5 x 10 -8 ) loci (see Figure). The ABO locus has previously been associated with venous thrombosis and ischemic stroke in predominantly older adults, but the effect size of our top SNP (OR 1.18; p = 9.1 x 10 -12 ) is larger than the effect size for this same SNP in MEGASTROKE (OR: 1.05; p = 6.5 x 10 -5 ). The lead SNP at the BCL7A/MLXIP locus is a novel GWAS finding for stroke (OR 1.14, 95% CI 1.08-1.19; p = 1.7 x 10 -8 ) and is noteworthy because of prior reports linking SNPs in these genes to BMI and blood pressure. Conclusions: We identified a novel locus that is near variants associated with BMI and blood pressure. Further studies are needed to confirm this locus, examine subtype specificity, and determine its function. The larger effect size observed at the ABO in this early-onset IS sample compared to older-onset IS samples is consistent with a larger role for prothrombotic mechanisms in early-onset IS.

Degeneration of the thymus and severe contraction of the T‐cell repertoire with aging suggest that immune homeostasis in old age could be mediated by distinct effectors. Therefore we examined receptors expressed on T cells as they undergo senescence in vitro , and those displayed by circulating T cells during normal chronologic aging. Monitoring of T cells driven to senescence showed de novo induction of CD56, the prototypic receptor of NK cells. Analysis of fresh T cells in blood showed an age‐dependent induction of CD56. These unusual T cells expressed high levels of Bcl2, p16, and p53, and had limited, or completely lost, ability to undergo cell division; properties consistent with senescence. CD56 cross‐linking without TCR ligation on CD56 + T cells resulted in extensive protein phosphorylation, NFκB activation, and Bax down‐regulation. CD56 cross‐linking was also sufficient to drive production of various humoral factors. These data indicate that the immunologic environment in old age is functionally distinct, rather than a dysfunctional version of that seen at a young age. In view of the reported inefficiencies of TCR‐driven immunity with aging, elicitation of TCR‐independent immune cascades by CD56 + T cells provide new avenues for the development of alternative strategies to enhance protective immunity in the elderly. [Supported by NIH grants R01‐AG022379, R01‐AG023629, P20‐CA103730, and T35‐AG026778].

Background: Guidelines recommend involvement of palliative care (PC) for patients with cardiovascular (CV) disease and their families. Little is known about the current integration of PC and CV services. Research Objectives: Our national survey aimed to describe current practices and to identify benefits, challenges, and barriers with collaboration. Methods: Qualitative content analysis of open-response questions in an investigator-developed electronic survey study of CV and PC providers (MDs, NPs, PAs, and other allied health) using email listservs, social media, and crowdsourcing. Frequencies were tabulated using SAS statistical software. Results: Of 134 respondents, most were physicians (n=56, 57%) or advanced practice RNs or PAs (n=37, 28%), from 52 U.S. institutions, representing 33 states. The most common care for which PC was integrated were mechanical circulatory support, advanced heart failure, and heart transplantation; the least common care for which PC was integrated were TAVR, ECMO, and pulmonary hypertension. Integrated practice (n=80, 61%), PC identification of goals of care (n=20, 15%) and PC aid in patient/family communication (n=15, 11%) were the most commonly identified as positives in current practice. PC provider workforce (n=22, 16%), underutilization of PC referrals (n=20, 15%), late disease PC referral (n=19, 14%), and fundamental knowledge deficit of specialty scope (n=18, 14%) were most frequently identified as challenges. Other barriers specifically noted were underdeveloped health infrastructure and limited allocated resources (n=23,17%) and mis-/negative perception of services (n=15, 11%). Conclusion: PC and CV collaboration occurs for a high proportion of CV patients and is viewed as overwhelming positive, despite the challenges of limited PC specialists availability, underdeveloped healthcare infrastructure, limited understanding of specialty practice, and late referrals. Priorities includes increasing PC provider availability, expanding knowledge of PC services, educating providers on models of collaboration, and improving institutional support.

Persons with metabolic syndrome could benefit from improved fruit consumption and reduced caloric intake. A cranberry fruit containing reduced titratable acidity was developed and used to create a 27% reduced calorie cranberry juice (RCCBJ) containing less added sugar (74 Cal/240 ml) relative to the 110 Cal/240 ml industry standard cranberry juice (CBJ). Subjects were recruited for metabolic syndrome (n=18; 53 16 years; BMI=34.4 ± 3.9) and their metabolic response to CBJ and RCCBJ was evaluated in single cross‐over fashion. Plasma glucose for CBJ at 0‐, 30‐, 60‐, and 120‐min was 105.6±12.3, 149.5±22.6, 127.9±30.3, and 98.6±14.6 (mg/dl). Plasma glucose for RCCBJ was 104.6±13.3, 140.3±22.5, 116.0±27.23, and 100.4±13. Plasma insulin for CBJ at 0‐, 30‐, 60‐, and 120‐ min was 10.21±5.1, 41.5±22.6, 30.3±19.7, and 12.0± (µIU/ml). Plasma insulin for RCCBJ was 12.2±8.4, 34.8±21.6, 20.7±13.9, and 12.3±9.8. For CBJ and RCCBJ plasma glucose and insulin significantly increased relative to baseline at 30‐ and 60‐min. At 60 min RCCBJ glucose and insulin were significantly less than CBJ. Plasma adiponectin and glucagon like peptide‐1 responses were also measured for CBJ and RCCBJ at 0‐, 30‐, 60‐, and 120‐min. Reduced acidity cranberry fruit was associated with RCCBJ containing 33% fewer calories and a beneficial metabolic response in persons with metabolic syndrome.

ABSTRACTLarge‐scale studies have not addressed the knowledge level of US resident physicians regarding osteoporosis management. We gauged the knowledge level of family medicine, internal medicine, and obstetrics and gynecology resident physicians regarding osteoporosis management. In 2019, we sent an anonymous survey via e‐mail to all program directors of Accreditation Council for Graduate Medical Education–accredited residency programs in family medicine, internal medicine, and obstetrics and gynecology for distribution to resident physicians. Knowledge items assessed osteoporosis screening, diagnosis, and treatment. We received responses from 182 family medicine, 275 internal medicine, and 122 obstetrics and gynecology programs. Of 582 resident physician respondents, 31% were family medicine residents, 47% were internal medicine residents, and 21% were obstetrics and gynecology residents. Although 77% of respondents correctly selected the T‐score threshold for the diagnosis of osteoporosis among persons aged 50 years and older (−2.5), only 20% of respondents correctly identified minimal‐trauma hip fracture as being diagnostic of osteoporosis. One‐third of respondents correctly identified which medications were demonstrated in clinical trials to decrease hip fracture risk. Fifteen percent of respondents correctly identified that denosumab and alendronate are associated with osteonecrosis of the jaw; and 40% of respondents correctly identified that decline in bone density is more rapid after discontinuation of denosumab than after discontinuation of bisphosphonates. Less than half of resident physicians knew that bisphosphonate‐associated atypical femoral fractures are duration‐dependent. One‐quarter of respondents felt not at all prepared to manage osteoporosis. In this nationwide survey of resident physicians, knowledge regarding osteoporosis diagnosis and treatment was poor, with a striking lack of knowledge regarding the two most serious adverse effects of osteoporosis pharmacotherapy (osteonecrosis of the jaw and atypical femoral fractures). The undertreatment of osteoporosis is unlikely to improve without increased education of resident physicians. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

OBJECTIVE Scoliosis is common in patients with Chiari malformation type I (CM-I)–associated syringomyelia. While it is known that treatment with posterior fossa decompression (PFD) may reduce the progression of scoliosis, it is unknown if decompression with duraplasty is superior to extradural decompression. METHODS A large multicenter retrospective and prospective registry of 1257 pediatric patients with CM-I (tonsils ≥ 5 mm below the foramen magnum) and syrinx (≥ 3 mm in axial width) was reviewed for patients with scoliosis who underwent PFD with or without duraplasty. RESULTS In total, 422 patients who underwent PFD had a clinical diagnosis of scoliosis. Of these patients, 346 underwent duraplasty, 51 received extradural decompression alone, and 25 were excluded because no data were available on the type of PFD. The mean clinical follow-up was 2.6 years. Overall, there was no difference in subsequent occurrence of fusion or proportion of patients with curve progression between those with and those without a duraplasty. However, after controlling for age, sex, preoperative curve magnitude, syrinx length, syrinx width, and holocord syrinx, extradural decompression was associated with curve progression > 10°, but not increased occurrence of fusion. Older age at PFD and larger preoperative curve magnitude were independently associated with subsequent occurrence of fusion. Greater syrinx reduction after PFD of either type was associated with decreased occurrence of fusion. CONCLUSIONS In patients with CM-I, syrinx, and scoliosis undergoing PFD, there was no difference in subsequent occurrence of surgical correction of scoliosis between those receiving a duraplasty and those with an extradural decompression. However, after controlling for preoperative factors including age, syrinx characteristics, and curve magnitude, patients treated with duraplasty were less likely to have curve progression than patients treated with extradural decompression. Further study is needed to evaluate the role of duraplasty in curve stabilization after PFD.