To assess the impact of resilience, the ability to withstand and bounce back from adversity, on measures of well-being, self-reported stress, and mental health diagnoses.
This study was a ...cross-sectional survey of participants seen at an executive health practice at Mayo Clinic, Rochester, Minnesota, from January 2012 through September 2016. Participants completed an anonymous survey that included demographic information and 3 validated survey instruments-the 10-item Connor-Davidson Resilience Scale (CD-RISC), the 12-item Linear Analogue Self-Assessment Scale (LASA), and the 14-item Perceived Stress Scale (PSS). Self-reported history of mental health diagnoses was also collected. CD-RISC scores were used to stratify participants into lower (<30), medium (30-34), or higher (≥35) resilience categories. Participants' LASA scores, PSS scores, and self-reported mental health diagnoses were compared among resilience categories.
Of the 2,027 eligible participants, 1,954 met the study inclusion criteria as currently employed corporate-sponsored executive or business professionals (self-designated) who completed the CD-RISC survey. Most participants (62.5%) were aged 40 to 59 years. The majority were male (78.3%), white (95.3%), educated (86.2%), and in a committed relationship (89.7%). Among participants, 41.7% reported higher resilience, 34.3% had medium resilience, and 24.0% had lower resilience. The quality of life and overall LASA scores were positively associated with higher resilience (P < .001). PSS scores and self-reported mental health diagnoses were negatively associated with higher resilience (P < .001). These associations remained significant after adjusting for patient characteristics.
In this cross-sectional survey of a large cohort of corporative executives, the lower-resilience cohort had a 4-fold higher prevalence of depression and an almost 3-fold higher prevalence of anxiety compared with the higher-resilience cohort. High resilience was positively associated with well-being and negatively associated with perceived stress. Our findings suggest that higher resilience in the executive workplace environment is associated with better mental health, reduced stress, and greater well-being.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background & Aims Pancreatobiliary cancer is detected by fluorescence in situ hybridization (FISH) of pancreatobiliary brush samples with UroVysion probes, originally designed to detect bladder ...cancer. We designed a set of new probes to detect pancreatobiliary cancer and compared its performance with that of UroVysion and routine cytology analysis. Methods We tested a set of FISH probes on tumor tissues (cholangiocarcinoma or pancreatic carcinoma) and non-tumor tissues from 29 patients. We identified 4 probes that had high specificity for tumor vs non-tumor tissues; we called this set of probes pancreatobiliary FISH. We performed a retrospective analysis of brush samples from 272 patients who underwent endoscopic retrograde cholangiopancreatography for evaluation of malignancy at the Mayo Clinic; results were available from routine cytology and FISH with UroVysion probes. Archived residual specimens were retrieved and used to evaluate the pancreatobiliary FISH probes. Cutoff values for FISH with the pancreatobiliary probes were determined using 89 samples and validated in the remaining 183 samples. Clinical and pathologic evidence of malignancy in the pancreatobiliary tract within 2 years of brush sample collection was used as the standard; samples from patients without malignancies were used as negative controls. The validation cohort included 85 patients with malignancies (46.4%) and 114 patients with primary sclerosing cholangitis (62.3%). Samples containing cells above the cutoff for polysomy (copy number gain of ≥2 probes) were classified as positive in FISH with the UroVysion and pancreatobiliary probes. Multivariable logistic regression was used to estimate associations between clinical and pathology findings and results from FISH. Results The combination of FISH probes 1q21, 7p12, 8q24, and 9p21 identified cancer cells with 93% sensitivity and 100% specificity in pancreatobiliary tissue samples and were therefore included in the pancreatobiliary probe set. In the validation cohort of brush samples, pancreatobiliary FISH identified samples from patients with malignancy with a significantly higher level of sensitivity (64.7%) than the UroVysion probes (45.9%) ( P < .001) or routine cytology analysis (18.8%) ( P < .001), but similar specificity (92.9%, 90.8%, and 100.0% respectively). Factors significantly associated with detection of carcinoma, in adjusted analyses, included detection of polysomy by pancreatobiliary FISH ( P < .001), a mass by cross-sectional imaging ( P < .001), cancer cells by routine cytology (overall P = .003), as well as absence of primary sclerosing cholangitis ( P = .011). Conclusions We identified a set of FISH probes that detects cancer cells in pancreatobiliary brush samples from patients with and without primary sclerosing cholangitis with higher levels of sensitivity than UroVysion probes. Cytologic brushing test results and clinical features were independently associated with detection of cancer and might be used to identify patients with pancreatobiliary cancers.
Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive ...autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients with multiple system atrophy, including a patient with visual hallucinations. Further, the presence of Lewy body-like inclusions in neocortex, but not hippocampal alpha-synuclein pathology, was associated with cognitive impairment (P = 0.002). However, several cases had the presence of isolated Lewy body-like inclusions at atypical sites (e.g. thalamus, deep cerebellar nuclei) that are not typical for Lewy body-spectrum disease. Finally, interregional correlations (rho ≥ 0.6) in pathologic glial and neuronal lesion burden suggest shared mechanisms of disease progression between both discrete anatomic regions (e.g. basal forebrain and hippocampus) and cell types (neuronal and glial inclusions in frontal cortex and white matter, respectively). These findings suggest that in addition to glial inclusions, neuronal pathology plays an important role in the developmental and progression of multiple system atrophy.
Prognostic significance of histological anaplasia and BRAF V600E mutation were retrospectively evaluated in 74 patients with pleomorphic xanthoastrocytoma (PXA). Median age at diagnosis was 21.5 ...years (31 pediatric, 43 adult) and median follow‐up 7.6 years. Anaplasia (PXA‐AF), defined as mitotic index ≥ 5/10HPF and/or presence of necrosis, was present in 33 cases. BRAF V600E mutation was detected in 39 (of 60) cases by immunohistochemical and/or molecular analysis, all negative for IDH1 (R132H). Mitotic index ≥ 5/10HPF and necrosis were associated with decreased overall survival (OS; P = 0.0005 and P = 0.0002, respectively). In all cases except two, necrosis was associated with mitotic index ≥ 5/10HPF. Patients with BRAF V600E mutant tumors had significantly longer OS compared with those without BRAF V600E mutation (P = 0.02). PXA‐AF patients, regardless of age, had significantly shorter OS compared with those without (P = 0.0003). Recurrence‐free survival was significantly shorter for adult PXA‐AF patients (P = 0.047) only. Patients who either recurred or died ≤3 years from diagnosis were more likely to have had either PXA‐AF at first diagnosis (P = 0.008) or undergone a non‐gross total resection procedure (P = 0.004) as compared with patients who did not. This study provides further evidence that PXA‐AF behaves more aggressively than PXA and may qualify for WHO grade III “anaplastic” designation.
BACKGROUND:We hypothesized that pulmonary venous hypertension in heart failure (HF) leads to predominate remodeling of pulmonary veins and that the severity of venous remodeling is associated with ...the severity of pulmonary hypertension (PH) in HF.
METHODS:Patients with HF (n=108; 53 preserved and 55 reduced ejection fraction) with PH (HF-PH; pulmonary artery systolic pressure PASP ≥40 mm Hg) were compared to normal controls (n=12) and patients with primary pulmonary veno-occlusive disease (PVOD; n=17). In lung specimens from autopsy (control, HF-PH, and 7 PVOD) or surgery (10 PVOD), quantitative histomorphometry was performed in all analyzable arteries (n=4949), veins (n=7630), and small indeterminate vessels (IV; n=2168) to define percent medial thickness (arteries) and percent intimal thickness (%IT) (arteries, veins, and IV) relative to external diameter.
RESULTS:The average arterial percent medial thickness (control, 6.9; HF-PH, 11.0; PVOD, 15.0), arterial %IT (control, 4.9; HF-PH, 14.9; PVOD, 31.1), venous %IT (control, 14.0; HF-PH, 24.9; PVOD, 43.9), and IV %IT (control, 10.6; HF-PH, 25.8; PVOD, 50.0) in HF-PH were higher than controls (P<0.0001 for all) but lower than PVOD (P≤0.005 for all). PASP (mm Hg) was lower in HF-PH (median, 59 interquartile range, 50–70) than in PVOD (median, 91 interquartile range, 82–103). PASP correlated with arterial percent medial thickness (r=0.41) and arterial %IT (r=0.35) but more strongly with venous %IT (r=0.49) and IV %IT (r=0.55) (P<0.0001 for all). Associations between PASP and venous or IV %IT remained significant after adjusting for arterial percent medial thickness and %IT and did not vary by HF type. In patients with right heart catheterization (30 HF-PH, 14 PVOD), similar associations between the transpulmonary gradient and pulmonary vascular remodeling existed, with numerically stronger associations for venous and IV %IT. Although the PASP was slightly higher in patients with HF-PH with right ventricular dysfunction, pulmonary vascular remodeling was not more severe. Pulmonary vascular remodeling severity was associated with reductions in the diffusing capacity of the lungs.
CONCLUSIONS:In HF, PH is associated with global pulmonary vascular remodeling, but the severity of PH correlates most strongly with venous and small IV intimal thickening, similar to the pattern observed in PVOD. These findings expand our understanding of the pathobiology of PH in HF.
Angiosarcoma (AS) is the most common cardiac sarcoma with differentiation, and is poorly characterized from a molecular genetic standpoint. Prognosis remains poor, owing to several factors including ...aggressive tumor biology, poor response to adjuvant therapy, and lack of targeted therapy. The clinical, pathologic and molecular cytogenetic features were studied in ten cardiac AS surgically resected at Mayo Clinic (1994–2015) using a whole genome single nucleotide polymorphism based platform (OncoScan). Mean patient age was 47.8 years, male:female ratio was 1:1.5, and overall median survival was 5.2 months. The most common location was the right atrium (n = 7), with one case each occurring in the epicardium, pericardium, and right ventricle. No patients had received thoracic irradiation. The most common morphology was spindle cell (n = 8), with one case each of epithelioid and biphasic. ERG was the most sensitive vascular marker, with diffuse immunoreactivity in all cases. Several recurrent (present in at least 3 cases) aberrations were identified including trisomies in chromosomes 4, 8, 11, 17, 20, as well as 1q+, and homozygous deletion of CDKN2. Patients who received adjuvant therapy had longer overall survival than those who did not (median 13.4 vs 3.2 months; P = .0283). There were no significant associations between tumor location, histology, immunohistochemical findings, cytogenetic profile, and clinical outcome, however there was a trend towards improved overall survival in patients with tumors harboring 1q + (median 31.8 vs 3.7 months, P = .06). This study confirms recurrent cytogenetic aberrations in cardiac AS, some of which may have prognostic or predictive implications.
A distinct subset of thoracic sarcomas with undifferentiated rhabdoid morphology and SMARCA4 inactivation has recently been described, and potential targeted therapy for SMARC-deficient tumors is ...emerging. We sought to validate the clinicopathological features of SMARCA4-deficient thoracic sarcomas. Clinicopathological information was gathered for 40 undifferentiated thoracic tumors with rhabdoid morphology (mediastinum (n=18), lung (n=14), pleura (n=8)). Thymic carcinomas (n=11) were used as a comparison group. Immunohistochemistry included BRG1 (SMARCA4), BRM (SMARCA2), INI-1 (SMARCB1), pan-cytokeratin, desmin, NUT, S-100 protein, TTF1, CD34, and SOX2. BRG1 loss was present in 12 of 40 rhabdoid thoracic tumors (30%): 7 of 18 in mediastinum (39%), 2 of 8 in pleura (25%), and 3 of 14 in lung (21%). All BRG1-deficient tumors tested for BRM (n=8) showed concomitant loss. All thymic carcinomas showed retained BRG1 and INI-1. Morphologically, tumors with BRG1 loss showed sheets of monotonous ovoid cells with indistinct cell borders, abundant eosinophilic cytoplasm, and prominent nucleoli. Scattered areas with rhabdoid morphology (ie, eccentric nuclei, dense eosinophilic cytoplasm, discohesion) were present in all the cases. SMARCA4/BRG1-deficient sarcomas showed rare cells positive for cytokeratin in 10 cases (83%). One showed rare TTF1-positive cells. All were negative for desmin, NUT, and S-100 protein. CD34 was positive in three of five (60%) BRG1-deficient tumors tested. SOX2 was positive in all four BRG1-deficient tumors tested, and negative in all seven tested cases with retained BRG1. SMARCA4/BRG1-deficient sarcomas occurred at median age of 59 years (range 44-76) with male predominance (9:3) and had worse 2-year survival compared with BRG1-retained tumors (12.5% vs 64.4%, P=0.02). SMARCA4-deficient thoracic sarcomas can be identified based on their distinctive high-grade rhabdoid morphology, and the diagnosis can be confirmed by immunohistochemistry. Identification of these tumors is clinically relevant due to their aggressive behavior, poor prognosis, and potential targeted therapy.
Despite improvements in mortality rates over the past several decades, cardiovascular (CV) disease remains the leading cause of death for African-Americans (AAs). Innovative approaches through mobile ...health (mHealth) interventions have the potential to support lifestyle change for CV disease prevention among AAs. We aimed to translate a behavioral theory-informed, evidence-based, face-to-face health education program into an mHealth lifestyle intervention for AAs. We describe the design and development of a culturally relevant, CV health and wellness digital application (app) and pilot testing using a community-based participatory research (CBPR) approach with AA churches.
This mixed methods study used a 4-phase iterative development process for intervention design with the AA community. Phase 1 included focus groups with AA community members and church partners (n = 23) to gain insight regarding potential app end user preferences. In Phase 2, the interdisciplinary research team synthesized Phase 1 input for preliminary app design and content development. Phase 3 consisted of a sequential 3-meeting series with church partners (n = 13) for iterative app prototyping (assessment, cultural tailoring, final review). Phase 4, a single group pilot study among AA church congregants (n = 50), assessed app acceptability, usability, and satisfaction.
Phase 1 focus groups indicated general and health-related apps preferences: multifunctional, high-quality graphics/visuals, evidence-based, yet simple health information and social networking capability. Phase 2 integrated these preferences into the preliminary app prototype. Phase 3 feedback was used to refine the app prototype for pilot testing. Phase 4 pilot testing indicated high app acceptability, usability, and satisfaction.
This study illustrates integration of formative and CBPR approaches to design a culturally relevant, mHealth lifestyle intervention to address CV health disparities among AAs. Given the positive app perceptions, our study supports the use of an iterative development process by others interested in implementing an mHealth lifestyle intervention for racial/ethnic minority communities.
Clinicaltrials.gov NCT03084822.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVE:To 1) determine, using contemporary recombinant antigen–based assays, the aquaporin-4 (AQP4)–immunoglobulin G (IgG) detection rate in sequential sera of patients assigned a clinical ...diagnosis of neuromyelitis optica (NMO) but initially scored negative by tissue-based indirect immunofluorescence (IIF) assay; and 2) evaluate the impact of serostatus on phenotype and outcome.
METHODS:From Mayo Clinic records (2005–2011), we identified 163 patients with NMO; 110 (67%) were seropositive by IIF and 53 (33%) were scored seronegative. Available stored sera from 49 “seronegative” patients were tested by ELISA, AQP4-transfected cell-based assay, and in-house fluorescence-activated cell sorting assay. Clinical characteristics were compared based on final serostatus.
RESULTS:Thirty of the 49 IIF-negative patients (61%) were reclassified as seropositive, yielding an overall AQP4-IgG seropositivity rate of 88% (i.e., 12% seronegative). The fluorescence-activated cell sorting assay improved the detection rate to 87%, cell-based assay to 84%, and ELISA to 79%. The sex ratio (female to male) was 1:1 for seronegatives and 9:1 for seropositives (p < 0.0001). Simultaneous optic neuritis and transverse myelitis as onset attack type (i.e., within 30 days of each other) occurred in 32% of seronegatives and in 3.6% of seropositives (p < 0.0001). Relapse rate, disability outcome, and other clinical characteristics did not differ significantly.
CONCLUSIONS:Serological tests using recombinant AQP4 antigen are significantly more sensitive than tissue-based IIF for detecting AQP4-IgG. Testing should precede immunotherapy; if negative, later-drawn specimens should be tested. AQP4-IgG–seronegative NMO is less frequent than previously reported and is clinically similar to AQP4-IgG–seropositive NMO.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, coronavirus disease 2019 (COVID-19), is an emergent cause of mortality worldwide. Cardiac ...complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of individuals with COVID-19 undergoing postmortem evaluation is provided, with 4 aims: (1) describe the pathological spectrum of the myocardium; (2) compare with an alternate viral illness; (3) investigate angiotensin-converting enzyme 2 expression; and (4) provide the first description of the cardiac findings in patients with cleared infection.
Study cases were identified from institutional files and included COVID-19 (n=15: 12 active, 3 cleared), influenza A/B (n=6), and nonvirally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An angiotensin-converting enzyme 2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction.
Male sex was more common in the COVID-19 group (
=0.05). Nonocclusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls) and were more common in the active COVID-19 cohort (
=0.006). Four active COVID-19 cases showed focal myocarditis, whereas 1 case of cleared COVID-19 showed extensive disease. Arteriolar angiotensin-converting enzyme 2 endothelial expression was lower in COVID-19 cases than in controls (
=0.004). Angiotensin-converting enzyme 2 myocardial expression did not differ by disease category, sex, age, or number of patient comorbidities (
=0.69,
=1.00,
=0.46,
=0.65, respectively). SARS-CoV-2 immunohistochemistry showed nonspecific staining, whereas ultrastructural examination and droplet digital polymerase chain reaction were negative for viral presence. Four patients (26.7%) with COVID-19 had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations.
This detailed histopathologic, immunohistochemical, ultrastructural, and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury. Moreover, myocarditis is present in 33.3% of patients with active and cleared COVID-19 but is usually limited in extent. Histological features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.
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