Citations

The spleen is a commonly encountered specimen in surgical pathology. However, little is known about the incidence, morphologic pattern, and clinical features of spleens involved by amyloidosis. We retrospectively identified 69 spleen amyloid cases typed using a proteomics-based method between 2008 and 2020. The frequency of amyloid types, clinicopathologic features, and distribution of amyloid deposits were assessed. Four amyloid types were detected: immunoglobulin light chain (AL) (N=30; 43.5%); leukocyte chemotactic factor 2 amyloidosis (ALECT2) (N=30; 43.5%); amyloid A (AA) (N=8; 11.6%); and fibrinogen alpha (AFib) (N=1; 1.4%). The splenic amyloid showed 5 distinct distribution patterns: (1) diffuse pattern, exhibited by most AL cases; (2) red pulp pattern, exhibited by most ALECT2 cases; (3) multinodular pattern, seen in subsets of AA and AL-kappa cases; (4) mass-forming pattern, seen in the AFib case; and (5) vascular only, seen in a subset of AA cases. Atraumatic splenic rupture was the most common reason for splenectomy in AL cases, while most ALECT2 spleens were removed incidentally during an unrelated abdominal surgery. Splenomegaly was significantly more common in AA spleens than in AL or ALECT2 spleens and was often the reason for splenectomy in this group. In conclusion, splenic amyloid may be underrecognized as it is often an incidental finding. Although, as expected, many of the spleens were involved by AL amyloidosis, ALECT2 emerged as another common spleen amyloid type. Although the spleen amyloid types exhibited characteristic distribution patterns, proteomics-based typing is warranted as some morphologic overlap still exists. Awareness of ALECT2 as a major spleen amyloid type is important for appropriate diagnostic workup and patient management.

The precision health era is likely to reduce and respond to antimicrobial resistance (AMR). Our stewardship and precision efforts share terminology, seeking to deliver the “right drug, at the right dose, at the right time.” Already, rapid diagnostic testing, phylogenetic surveillance, and real-time outbreak response provide just a few examples of molecular advances we dub “precision stewardship.” However, the AMR causal factors range from the molecular to that of global health policy. Mirroring the cross-sectoral nature of AMR science, the research addressing the ethical, legal and social implications (ELSI) of AMR ranges across academic scholarship. As the rise of AMR is accompanied by an escalating sense of its moral and social significance, what is needed is a parallel field of study. In this paper, we offer a gap analysis of this terrain, or an agenda for “the ELSI of precision stewardship.” In the first section, we discuss the accomplishments of a multi-decade U.S. national investment in ELSI research attending to the advances in human genetics. In the next section, we provide an overview of distinct ELSI topics pertinent to AMR. The distinctiveness of an ELSI agenda for precision stewardship suggests new opportunities for collaboration to build the stewardship teams of the future.

Abstract Background: There is mixed evidence about the relations of current versus past cancer with severe COVID-19 outcomes and how they vary by patient and cancer characteristics. Methods: Electronic health record data of 104,590 adult hospitalized patients with COVID-19 were obtained from 21 United States health systems from February 2020 through September 2021. In-hospital mortality and ICU admission were predicted from current and past cancer diagnoses. Moderation by patient characteristics, vaccination status, cancer type, and year of the pandemic was examined. Results: 6.8% of the patients had current (n = 7,141) and 6.5% had past (n = 6,749) cancer diagnoses. Current cancer predicted both severe outcomes but past cancer did not; adjusted odds ratios (aOR) for mortality were 1.58 [95% confidence interval (CI), 1.46–1.70] and 1.04 (95% CI, 0.96–1.13), respectively. Mortality rates decreased over the pandemic but the incremental risk of current cancer persisted, with the increment being larger among younger vs. older patients. Prior COVID-19 vaccination reduced mortality generally and among those with current cancer (aOR, 0.69; 95% CI, 0.53–0.90). Conclusions: Current cancer, especially among younger patients, posed a substantially increased risk for death and ICU admission among patients with COVID-19; prior COVID-19 vaccination mitigated the risk associated with current cancer. Past history of cancer was not associated with higher risks for severe COVID-19 outcomes for most cancer types. Impact: This study clarifies the characteristics that modify the risk associated with cancer on severe COVID-19 outcomes across the first 20 months of the COVID-19 pandemic. See related commentary by Egan et al., p. 3

COVID-19 mRNA vaccinations have recently been implicated in causing myocarditis. Therefore, the primary aim of this systematic review and meta-analysis was to investigate the clinical characteristics of patients with myocarditis following mRNA vaccination. The secondary aims were to report common imaging and laboratory findings, as well as treatment regimes, in these patients. A literature search was performed from December 2019 to June 2022. Eligible studies reported patients older than 18 years vaccinated with mRNA, a diagnosis of myocarditis, and subsequent outcomes. Pooled mean or proportion were analyzed using a random-effects model. Seventy-five unique studies (patient n = 188, 89.4% male, mean age 18–67 years) were included. Eighty-six patients had Moderna vaccines while one hundred and two patients had Pfizer-BioNTech vaccines. The most common presenting symptoms were chest pain (34.5%), fever (17.1%), myalgia (12.4%), and chills (12.1%). The most common radiologic findings were ST-related changes on an electrocardiogram (58.7%) and hypokinesia on cardiac magnetic resonance imaging or echocardiography (50.7%). Laboratory findings included elevated Troponin I levels (81.7%) and elevated C-reactive protein (71.5%). Seven patients were admitted to the intensive care unit. The most common treatment modality was non-steroid anti-inflammatory drugs (36.6%) followed by colchicine (28.5%). This meta-analysis presents novel evidence to suggest possible myocarditis post mRNA vaccination in certain individuals, especially young male patients. Clinical practice must therefore take appropriate pre-cautionary measures when administrating COVID-19 mRNA vaccinations.

OBJECTIVES: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19. DESIGN: Retrospective observational study. SETTING: Multicenter, international COVID-19 registry. Subjects: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19–1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03–1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81–0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20–1.56]; p < 0.0001). CONCLUSIONS: Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with significantly higher mortality in hospitalized COVID-19 patients.

Background: Black adults experience a disproportionately higher burden of cardiovascular risk factors and disease in comparison with White adults in the United States. Less is known about how sex-based disparities in cardiovascular mortality between these groups have changed on a national scale over the past 20 years, particularly across geographic determinants of health and residential racial segregation. Methods: We used CDC WONDER (Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research) to identify Black and White adults age ≥25 years in the United States from 1999 to 2019. We calculated annual age-adjusted cardiovascular mortality rates (per 100 000) for Black and White women and men, as well as absolute rate differences and rate ratios to compare the mortality gap between these groups. We also examined patterns by US census region, rural versus urban residence, and degree of neighborhood segregation. Results: From 1999 to 2019, age-adjusted mortality rates declined overall for both Black and White adults. There was a decline in age-adjusted cardiovascular mortality among Black (602.1 to 351.8 per 100 000 population) and White women (447.0 to 267.5), and the absolute rate difference (ARD) between these groups decreased over time (1999: ARD, 155.1 [95% CI, 149.9–160.3]; 2019: ARD, 84.3 [95% CI, 81.2–87.4]). These patterns were similar for Black (824.1 to 526.3 per 100 000) and White men (637.5 to 396.0; 1999: ARD, 186.6 [95% CI, 178.6–194.6]; 2019: ARD, 130.3 [95% CI, 125.6–135.0]). Despite this progress, cardiovascular mortality in 2019 was higher for Black women (rate ratio, 1.32 [95% CI, 1.30–1.33])— especially in the younger (age <65 years) subgroup (rate ratio, 2.28 [95% CI, 2.23–2.32])—as well as for Black men (rate ratio, 1.33 [95% CI, 1.32–1.34]), compared with their respective White counterparts. There was regional variation in cardiovascular mortality patterns, and the Black-White gap differed across rural and urban areas. Cardiovascular mortality rates among Black women and men were consistently higher in communities with high levels of racial segregation compared with those with low to moderate levels. Conclusions: During the past 2 decades, age-adjusted cardiovascular mortality declined significantly for Black and White adults in the United States, as did the absolute difference in death rates between these groups. Despite this progress, Black women and men continue to experience higher cardiovascular mortality rates than their White counterparts.

AbstractBackgroundTwo studies that examined the interaction between HLA‐DRB1 and smoking in Parkinson's disease (PD) yielded findings in opposite directions.ObjectiveTo perform a large‐scale independent replication of the HLA‐DRB1 × smoking interaction.MethodsWe genotyped 182 single nucleotide polymorphism (SNPs) associated with smoking initiation in 12 424 cases and 9480 controls to perform a Mendelian randomization (MR) analysis in strata defined by HLA‐DRB1.ResultsAt the amino acid level, a valine at position 11 (V11) in HLA‐DRB1 displayed the strongest association with PD. MR showed an inverse association between genetically predicted smoking initiation and PD only in absence of V11 (odds ratio, 0.74, 95% confidence interval, 0.59–0.93, PInteraction = 0.028). In silico predictions of the influence of V11 and smoking‐induced modifications of α‐synuclein on binding affinity showed findings consistent with this interaction pattern.ConclusionsDespite being one of the most robust findings in PD research, the mechanisms underlying the inverse association between smoking and PD remain unknown. Our findings may help better understand this association. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Background: The COVID-19 pandemic has led to increased burnout and staff turnover for health care providers (HCPs). The purpose of this pilot study was to evaluate the safety and acceptability of a Stress Resilience Program (SRP) for reducing perceived stress and improving resilience among HCPs during a pandemic. Method: Of the 12 HCPs expressing interest in the study, 10 were enrolled in this study. Participants attended three in-person visits (consent/screen, baseline, and end-of-study). The SRP consisted of education related to resilience enhancement and a breathing device ( BreatherFit®) for combined respiratory muscle training (cRMT). Participants completed 4 weeks of cRMT and applied situational breathing strategies as needed. Outcomes measured were changes in stress (PSS-10), resilience (BRS), depression (PRIME-MD), and sleep (PSQI and Ōura Ring®). Findings: The majority of participants were male (60%) and White (60%) with an average age of 39.7 years. Changes from baseline to end-of-treatment indicated a positive trend with significant stress reduction (−3.2 ± 3.9, p = .028) and nonsignificant depression reduction (−0.5 ± 0.7, p = .05). Resilience was high at baseline and continued to stay high during the study with a nonsignificant increase at end-of-study (+0.07 ± 0.7, p = .77). No changes in overall sleep scores were noted. All participants agreed the study was worthwhile, 80% indicated they would repeat the experience, while 90% indicated they would recommend the study to others. Conclusion/Application to Practice: Because of its size and portability, SRP is an easily applicable and promising option for reducing stress among HCPs during a high-stress period, such as a pandemic. Larger studies are needed.

AbstractAcute lymphoblastic leukemia (B‐ALL) with intrachromosomal amplification of chromosome 21 (iAMP21‐ALL) represents a recurrent high‐risk cytogenetic abnormality and accurate identification is critical for appropriate clinical management. Identification of iAMP21‐ALL has historically relied on fluorescence in situ hybridization (FISH) using a RUNX1 probe. Current classification requires ≥ five copies of RUNX1 per cell and ≥ three additional copies of RUNX1 on a single abnormal iAMP21‐chromosome. We sought to evaluate the performance of the RUNX1 probe in the identification of iAMP21‐ALL. This study was a retrospective evaluation of iAMP21‐ALL in the Mayo Clinic and Children's Oncology Group cohorts. Of 207 cases of iAMP21‐ALL, 188 (91%) were classified as “typical” iAMP21‐ALL, while 19 (9%) cases were classified as “unusual” iAMP21‐ALL. The “unusual” iAMP21 cases did not meet the current definition of iAMP21 by FISH but were confirmed to have iAMP21 by chromosomal microarray. Half of the “unusual” iAMP21‐ALL cases had less than five RUNX1 signals, while the remainder had ≥ five RUNX1 signals with some located apart from the abnormal iAMP21‐chromosome. Nine percent of iAMP21‐ALL cases fail to meet the FISH definition of iAMP21‐ALL demonstrating that laboratories are at risk of misidentification of iAMP21‐ALL when relying only on the RUNX1 FISH probe. Incorporation of chromosomal microarray testing circumvents these risks.

Background: Restoring touch perception for individuals with upper extremity limb loss is an ambitious task. It is important to understand how persons with upper limb loss think this would be best achieved. Methods: An anonymous online survey was developed to obtain data from prosthetic users. Participants ranked the perceived acceptability and effectiveness of noninvasive sensory feedback to areas of intact sensation not typically involved in sensory feedback (i.e., the arm). The focus was on 4 main types of haptic information—object contact, proprioception, surface texture, and grasp force—as well as how best to convey those senses with various stimuli. The users were asked to grade themselves in certain tasks and then analyze which tasks would be improved with sensory feedback. Associations were explored between demographic characteristics and interest in sensory feedback. Results: Nationally, prostheses providers sent more than 2000 email invitations to the online survey and received 142 unique responses. Responses indicated interest in sensory feedback through prosthetic limbs by individuals with upper limb loss. The most popular pairing of haptic information with sensory substitution was grasp force paired with gentle vibration. Tasks that most persons taking the survey agreed would benefit from sensory feedback were zipping a jacket, tying shoes, buttoning a shirt, and using a cup. No difference was observed in interest between sex and employment status, but a significant decrease (P = .004) was seen in interest among participants with more years of prosthetic use. Discussion: The results from this national survey of upper extremity prosthetic users can be used to help guide the development of noninvasive sensory feedback options.