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Women with multiple comorbidities have competing health needs that may delay screening for early detection of breast cancer. Our objective was to determine associations between physical functioning and frailty with risk of locally-advanced breast cancer (BC). We conducted a retrospective cohort study of women 65 years and older diagnosed with first primary stage I-III BC using the Surveillance, Epidemiology and End Results Medicare Health Outcome Survey Data Resource. Physical health-related quality of life was measured using Veterans RAND 12 Item Health Survey scales within two years before diagnosis; frailty was determined by calculating deficit-accumulation frailty index (DAFI) scores. Multivariable modified Poisson regression models were used to estimate rate ratios (RR) and 95% confidence intervals (CI) for risk of locally-advanced (stage III) versus early-stage (I-II) BC. Among 2411 women with a median age of 75 years at BC diagnosis, 2189 (91%) were diagnosed with incident stage I-II BC and 222 (9%) were diagnosed at stage III. Compared to women with early-stage disease, women with locally-advanced BC had lower physical component scores (37.8 vs. 41.4) and more classified as pre-frail or frail (55% vs. 50%). In multivariable models, frailty was not associated with increased risk of locally-advanced disease. However, worse physical function subscale scores (lowest vs. upper quartile; RR = 1.56, 95% CI 1.04–2.34) were associated with risk of locally-advanced BC. Breast cancer screening among non-frail older women should be personalized to include women with limited physical functioning if the benefits of screening and early detection outweigh the potential harms. • Older women have competing health needs that may delay early detection of breast cancer. • Women with locally-advanced disease had lower health-related quality of life prior to diagnosis. • Worse physical functioning was associated with risk of locally-advanced breast cancer. [ABSTRACT FROM AUTHOR]

• We report two patients with mainly heart-confined Sanfilippo A syndrome, SAS. • Heart-SAS may disclose some gross finding of thin right ventricle. • Early recognition and cardiac transplantation are essential for patients with cardiac involvement. To report two unusual presentations of mucopolysaccharidosis type III (Sanfilippo syndrome) and provide evidence for the cardiac involvement. We report two siblings with cardiac involvement that were diagnosed in childhood with Sanfilippo A Syndrome (SAS). All patients' diagnosis was confirmed by the excess of heparan sulfate in the urine and the reduction of heparan sulfamidase protein activity. The heart specimens were studied. We report two sibling patients (15-years-old female and 12-years-old female) occurring in sisters both with onset in childhood with no neurological, ophthalmic, hepatic symptoms or coarsening of features as classically described. Both patients underwent bilateral hip arthroplasty in their early 30's. The older sister had an orthotopic heart transplant because of end-stage heart failure of her cardiomyopathy at the age of 45. She is alive and well. The youngest sister died due to heart failure before a transplantation took place. In the two siblings a thin right ventricular free wall was seen, which triggered the differential diagnosis with arrhythmogenic right ventricular cardiomyopathy or lamin A/C cardiomyopathy. Early recognition of solitary or mainly cardiac involvement is essential for patients with mucopolysaccharidosis type III (SAS). [ABSTRACT FROM AUTHOR]

Objectives: Allograft vascular tissue is important in the repair of complex structural lesions of the heart and great vessels, but induces a deleterious immune response that might shorten the effective lifespan of the tissue and sensitize the recipient. We hypothesized that decellularizing allograft vascular tissue reduces the host allogeneic immune response. Methods: Allograft ovine pulmonary artery patches were decellularized, cryopreserved, and implanted into the descending thoracic aorta. The humoral immune response was measured by means of flow cytometry at regular intervals over 6 months. Graft histology, immunohistochemistry, and calcification were assessed after 4 weeks or 6 months. Results: Leukocyte infiltration was reduced in decellularized grafts. A trend toward decreased in-patch calcification was observed in the decellularized group (7.6 ± 4.3 vs 40.0 ± 15.9 mg of calcium/mg of protein, P = .107). Decellularization reduced IgG antibody binding to donor splenocytes (9.8% ± 3.3% vs 57.8% ± 13.7% [control value], P = .010), as assessed by means of flow cytometry. All cytokines examined were detected in nondecellularized tissues after 4 weeks but not at 6 months, indicating complete graft rejection at that time. In contrast, transforming growth factor β1 and interleukin 10 were the only prominent cytokines in all decellularized grafts at 4 weeks after transplantation. Conclusions: Decellularization of allograft vascular tissue minimized the recipient cellular immune response and eliminated the production of anti-donor antibodies in recipients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Animal and human studies suggest that C-reactive protein (CRP) may be inversely associated with serum insulin-like growth factor-I (IGF-I) concentrations. However, most human studies have not controlled adequately for confounding factors, particularly nutritional intake. This population-based study examined whether CRP is inversely associated with IGF-I and IGFBP-3 concentrations. Methods: In cross-sectional analysis, multivariable linear regression with adjustment for age, BMI, smoking status, alcohol intake, and nutritional factors was used to relate log CRP, the independent variable, to IGF-I and IGFBP-3 in a sample of black (n =364) and white men (n =486) separately by race. Results: Only black men had positive findings: log CRP was significantly associated with IGF-I (β =−13.1ng/ml, p =0.02) and the difference in mean IGF-I concentrations between the highest and lowest quartiles of CRP was 26ng/ml. There was a statistically significant interaction between log CRP and smoking status (p =0.02); the regression coefficient for IGF-I predicted from log CRP was significant in smokers (β =−39.8ng/ml, p =0.0001), but not in non-smokers. The difference in mean IGF-I concentrations between highest and lowest quartiles of CRP was 100ng/ml for black smokers. There were no associations for IGFBP-3. Conclusions: In our study, CRP levels are inversely associated with IGF-I concentrations in black male smokers; however, the causal nature of the association is unclear and should be studied further. [Copyright &y& Elsevier]

Abstract: No studies have examined the associations of vitamin D and calcium intake with mammographic breast density in Hispanic women. Using the Southwest Food Frequency Questionnaire, we investigated these associations in a sample of 99 Hispanic women from the Chicago Breast Health Project Phase II Pilot Study. Using cutpoints based on recommended daily allowances, we classified women according to their intake status as low, medium, or high and compared adjusted mean percent density and dense area across the intake groups. Mean percent densities were 22.0%, 20.3%, and 9.6%, respectively, in the low, medium, and high intake groups for dietary vitamin D (P = .009). Inverse associations also were observed when the analysis was stratified by menopausal status. Total dense area was weakly and inversely associated with intake of dietary vitamin D (P = .1). There were no other meaningful associations. These results support previous findings of inverse associations between dietary vitamin D and breast density. [Copyright &y& Elsevier]

Abstract: Recent studies have demonstrated that stem cells derived from adult hematopoietic tissues are capable of trans-differentiation into non-hematopoietic cells, and that the culture in microgravity (g) may modulate the proliferation and differentiation. We investigated the application of g to human umbilical cord blood stem cells (CBSC) in the induction of vascular endothelial phenotype expression and cellular proliferation. CD34+ mononuclear cells were isolated from waste human umbilical cord blood samples and cultured in simulated g for 14 days. The cells were seeded in rotary wall vessels (RWV) with or without microcarrier beads (MCB) and vascular endothelial growth factor was added during culture. Controls consisted of culture in 1G. The cell cultures in RWV were examined by inverted microscopy. Cell counts, endothelial cell and leukocyte markers performed by flow-cytometry and FACS scan were assayed at days 1, 4, 7 and at the termination of the experiments. Culture in RWV revealed significantly increased cellular proliferation with three-dimensional (3D) tissue-like aggregates. At day 4, CD34+ cells cultured in RWV bioreactor without MCB developed vascular tubular assemblies and exhibited endothelial phenotypic markers. These data suggest that CD34+ human umbilical cord blood progenitors are capable of trans-differentiation into vascular endothelial cell phenotype and assemble into 3D tissue structures. Culture of CBSC in simulated g may be potentially beneficial in the fields of stem cell biology and somatic cell therapy. [Copyright &y& Elsevier]

PURPOSE: To investigate the association between alcohol consumption and the risk of non-Hodgkin''s lymphoma (NHL) and to examine whether the association is modified by a family history of hematolymphoproliferative cancer (HLPC).METHODS: Data on white men from two population-based case-control studies of NHL conducted in Iowa/Minnesota and Kansas were pooled for this analysis. Information on alcohol consumption, family history of HLPC, and other factors was obtained by interviewing 792 cases and 2193 controls or, if deceased, their next-of-kin. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).RESULTS: There was no clear association between NHL and the use of alcohol, beer, hard liquor, or wine. The relationship, however, may differ according to a family history of HLPC. Alcohol use was not associated with the risk of NHL in men without a family history of HLPC (ORs = 0.8 and 0.9 for men consuming alcohol ⩽ median and > median, respectively), the presence of a family history in the absence of alcohol use was associated with a slightly increased risk (OR = 1.4; 95% CI 0.8–2.5), whereas risks of NHL among men with a positive family history were 2.1 (CI 1.0–4.7) for men consuming alcohol ⩽ median (13.7 g/day) and 2.8 (1.3–5.9) for men consuming alcohol greater than median.CONCLUSIONS: The present data found no clear association between alcohol consumption and the risk of NHL among men without a family history of HLPC, whereas alcohol intake was associated an elevated risk in men with a positive family history. The finding of effect modification of the alcohol-NHL association by a family history of HLPC is novel and requires confirmation. [Copyright &y& Elsevier]

• We report on a family with Carney complex harboring left atrial myxomas. • Carney complex includes skin lesions, cardiac myxoma, and endocrine disorders. • Approximately 1% of patients with cardiac myxoma have Carney complex with autosomal dominant inheritance. • In Carney complex, cardiac myxomas do not necessarily occur at fossa ovalis. • Early recognition is essential for patients with cardiac involvement. Carney syndrome is an autosomal dominant complex involving endocrinopathy, mucocutaneous hyperpigmentation, and different tumors, including cardiac myxomas. We report on a single family with several members affected with Carney syndrome. Family and individual medical histories were investigated in several Canadian provinces. The histology slides were also reviewed. Four family members (two young women, both sisters, their mother, and maternal grandmother) were found to harbor Carney syndrome. Everyone was presented with multiple and recurrent atrial myxomas of the heart, requiring multiple open cardiac surgeries. Breast myxomas and cutaneous hyperpigmentation were also revealed in one of the sisters and their mother. Interestingly, genetic testing was positive for the female family members and negative for the father and brother. We cannot rule out that the brother may have had a new mutation or harboring a mosaic. The young woman's brother did not have cardiac myxoma but developed a unilateral Sertoli cell tumor of testis. Carney syndrome is a rare complex multisystemic genetic disorder, including multiple and recurrent cardiac myxomas. We strongly suggest that reporting familial Carney syndrome is still critical in the 21st century to augment the awareness of this situation among clinicians and pathologists. [ABSTRACT FROM AUTHOR]

Introduction: Racial disparities in diagnosis, treatment and survival in Black patients with Parkinson's disease (PD) compared to White patients have not been well studied, largely due to limited number of studies and information on Black patients in healthcare systems. Studying racial disparities and identifying underlying factors in large populations are important to understand PD and improve care.Methods: We retrospectively identified PD patients on both races from 1/1/2006 to 10/31/2017 and compared demographics, socioeconomic status (educations, incomes and insurances), comorbidities (all categories, including mood, cognition and psychosis), treatment (medications for parkinsonism and major non-motor symptoms, and frequency and locations of healthcare) and survival, and identified factors associated with medication usage and survival.Results: We retrospectively studied 2033 PD patients, of whom 725 were Black. Black patients lacked male predominance, were 4 years older at first diagnosis here, more likely to smoke and live in a low education and income community, and possessed limited insurances compared to White patients. Black patients also had more comorbidities and were more likely to receive care through emergency or inpatient service, but less likely to be on medications for parkinsonism and mood disorders. Race, age, smoking status, insurance type, frequency and locations of healthcare and comorbidities were associated with medication usage. Black race, older age, inpatient admission and malignancy were associated with increased risk of death.Conclusion: We revealed racial disparities in diagnosis, treatment and survival, and factors associated with medication usage and survival in the largest reported Black PD cohort from a single center. [ABSTRACT FROM AUTHOR]

Subcellular dysfunction and impaired metabolism derived from the complex interaction of cytokines and mediators with cellular involvement are on the basis of the cardiovascular response to sepsis. The lethal consequences of an infection are intimately related to its ability to spread to other organ sites and the immune system of the host. About one century ago, William Osler (1849–1919), a Canadian physician, remarkably defined the sequelae of the host response in sepsis: “ except on few occasions, the patient appears to die from the body’s response to infection rather than from it. ” Cardiac dysfunction has received considerable attention to explain the heart failure in patients progressing from infection to sepsis, but our understanding of the processes remains limited. In fact, most concepts are linked to a mechanical concept of the sarcomeric structure, and physiological data seems to be often disconnected. Cytokines, prostanoids, and nitric oxide release are high direct impact factors, but coronary circulation and cardiomyocyte physiology also play a prominent role in modulating the effects of monocyte adhesion and infiltration. Damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) are involved in the host response. The identification of microRNAs, as well as the cyclic activation of the inflammatory cascade, has further added complexity to the scene. In this review, we delineate the current concepts of cellular dysfunction of the cardiomyocyte in the setting of sepsis and consider potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: We investigated occupational risk of multiple myeloma (MM) in a pooled analysis of five international case-control studies. Methods: We calculated the odds ratio and its 95% confidence interval for selected occupations with unconditional regression analysis in 1959 MM cases and 6192 controls, by pooling study-specific risks using random-effects meta-analysis. Exposure to organic solvents was assessed with a job-exposure matrix (JEM). Results: Gardeners and nursery workers combined, most likely exposed to pesticides, showed a 50% increase in risk (OR= 1.50, 95% CI 0.9-2.3), while other farming jobs did not. Metal processors (OR = 1.55,95% CI 0.9-2.3), female cleaners (OR = 1.32,95% CI 1.0-1.8), and high level exposure to organic solvents (OR = 1.38, 95% CI 0.96-1.8) also showed moderately increased risks. Conclusions: Additional case-control studies of MM aetiology are warranted to further investigate the nature of the repeatedly reported increase in MM risk in several occupational groups. [ABSTRACT FROM AUTHOR]

Abstract: To investigate the association between sun exposure and risk of non-Hodgkin lymphoma (NHL) by histologic subtypes and to explore whether or not vitamin D intake modify sun–NHL association, we analysed data from a population-based, case–control study conducted in Nebraska between 1999 and 2002. Information on sun exposure during the spring, summer, fall and winter was collected from 387 cases and 535 controls by telephone interview. We found no association between seasonal sun exposure and risk of NHL. Vitamin D intake was also not associated with NHL risk, nor does it modify the sun–NHL association. In contrast, total hours of sun exposure was inversely associated with the risk of NHL (odds ratio (OR)=0.7 comparing >30h/week to <14h/week, 95% confidence interval (CI)=0.5–1.1). Sun exposure was associated with a lower risk of NHL among farmers (OR=0.8, 0.5–1.3 for 14–30h/week; OR=0.6, 0.3–0.9 for >30h/week; p-trend=0.02), but not among non-farmers. Total hours of sun exposure was also inversely associated with risk of diffuse large B-cell lymphoma and T-cell lymphoma. In conclusion, our data suggest that total hours of sun exposure is associated with a lower risk of NHL, and the inverse association is not modified by vitamin D intake, is stronger among farmer, and may vary by subtypes. [Copyright &y& Elsevier]

Summary: Androgen receptor (AR) CAG repeat length (RL) might modify the relationship between endogenous testosterone (T) and depressive symptoms in men on average over age 50 years. We hypothesized that CAG RL modifies the association between T and depressive symptoms in 525 black and 721 white men under age 40 years participating in the CARDIA Male Hormone Study. We assessed cross-sectional associations of quartiles of total and bioavailable T and tertiles of CAG RL with depressive symptoms, defined as Center for Epidemiologic Studies Depression Scale (CES-D) score ⩾16, in 1995–1996. The interaction of CAG RL and total T on depressive symptoms was statistically significant for blacks, whites, and both groups combined. In the combined analysis, the odds ratios (OR) (95% confidence intervals (CI)) across the quartiles of total T were 1.00, 0.17 (95% CI=0.07–0.43), 0.31 (95% CI=0.14–0.70), and 0.49 (95% CI=0.22–1.09) for the shortest RL group. The interaction of CAG RL and bioavailable T on depressive symptoms was statistically significant for black men only, and nonsignificant in a combined analysis. For black men in the shortest RL group, the ORs for the quartiles of bioavailable T were 1.00, 0.41 (95% CI=0.16–1.05), 0.10 (95% CI=0.03–0.38), and 0.35 (95% CI=0.14–0.90). In other CAG groups, there were no relationships of total or bioavailable T with depressive symptoms. CAG RL might modify the association between endogenous total and bioavailable T and depressive symptoms in younger black men. Clinical trials assessing the effects of T replacement therapy on depressive symptoms in hypogonadal men should consider including CAG RL in their design and/or analysis. [Copyright &y& Elsevier]

Summary: Background: Previous epidemiological studies of the relation between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) have been inconsistent, probably because of small sample sizes of individual studies that result from stratification by NHL subtype and type of alcoholic beverage. We aimed to assess the role of alcohol consumption in NHL with sufficient sample size to analyse by both type of alcoholic beverage and disease subtype. Methods: We obtained original data from nine case-control studies from the USA, UK, Sweden, and Italy in the International Lymphoma Epidemiology Consortium (InterLymph), yielding a pooled study population of 15 175 individuals (6492 cases and 8683 controls). We derived odds ratios (OR) and 95% CI from unconditional logistic regression models, controlling for study centre and other confounding factors. Heterogeneity between studies was assessed by comparison of results from joint fixed-effects logistic regression and two-stage random-effects logistic regression, and by calculation of Wald χ2 statistics. Findings: People who drank alcohol had a lower risk of NHL than did non-drinkers (OR 0·83 [95% CI 0·76–0·89]). Compared with non-drinkers, risk estimates were lower for current drinkers than for former drinkers (0·73 [0·64–0·84] vs 0·95 [0·80–1·14]), but risk did not decrease with increasing alcohol consumption. The protective effect of alcohol did not vary by beverage type, but did change with NHL subtype. The lowest risk estimates were recorded for Burkitt''s lymphoma (0·51 [0·33–0·77]). Interpretation: People who drink alcoholic beverages might have a lower risk of NHL than those who do not, and this risk might vary by NHL subtype. Further study designs are needed to determine whether confounding lifestyle factors or immunomodulatory effects of alcohol explain this association. [Copyright &y& Elsevier]

Isolated cardiac metastasis from a primary liposarcoma of noncardiac origin is a rare occurrence. A patient who presented with biventricular failure and constrictive hemodynamics years after successful resection of a primary liposarcoma of the thigh is described. Extensive cardiac encasement by tumor was suspected on diagnostic imaging. Hemodynamic instability and multiorgan failure necessitated urgent exploratory sternotomy. The patient died intraoperatively. Extensive metastatic sarcoma limited to the heart was confirmed during surgical procedure. This case suggests that in clinical and pathological investigation of a cardiac mass, knowledge of previous extracardiac involvement with soft tissue sarcoma is essential. [Copyright &y& Elsevier]