Citations

Background Socioeconomic status (SES) is an important predictor for outcomes of chronic diseases. However, it is often unavailable in clinical data. We sought to determine whether an individual housing-based SES index termed HOUSES can influence the likelihood of multiple chronic conditions (MCC) and hospitalisation in a community population. Methods Participants were residents of Olmsted County, Minnesota, aged >18 years, who were enrolled in Mayo Clinic Biobank on 31 December 2010, with follow-up until 31 December 2011. Primary outcome was all-cause hospitalisation over 1 calendar-year. Secondary outcome was MCC determined through a Minnesota Medical Tiering score. A logistic regression model was used to assess the association of HOUSES with the Minnesota tiering score. With adjustment for age, sex and MCC, the association of HOUSES with hospitalisation risk was tested using the Cox proportional hazards model. Results Eligible patients totalled 6402 persons (median age, 57 years; 25th–75th quartiles, 45–68 years). The lowest quartile of HOUSES was associated with a higher Minnesota tiering score after adjustment for age and sex (OR (95% CI) 2.4 (2.0 to 3.1)) when compared with the highest HOUSES quartile. Patients in the lowest HOUSES quartile had higher risk of all-cause hospitalisation (age, sex, MCC-adjusted HR (95% CI) 1.53 (1.18 to 1.98)) compared with those in the highest quartile. Conclusions Low SES, as assessed by HOUSES, was associated with increased risk of hospitalisation and greater MCC health burden. HOUSES may be a clinically useful surrogate for SES to assess risk stratification for patient care and clinical research.

Background and Purpose— The ABC/2 score estimates intracerebral hemorrhage (ICH) volume, yet validations have been limited by small samples and inappropriate outcome measures. We determined accuracy of the ABC/2 score calculated at a specialized reading center (RC-ABC) or local site (site-ABC) versus the reference-standard computed tomography–based planimetry (CTP). Methods— In Minimally Invasive Surgery Plus Recombinant Tissue-Type Plasminogen Activator for Intracerebral Hemorrhage Evacuation-II (MISTIE-II), Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR-IVH) and CLEAR-III trials. ICH volume was prospectively calculated by CTP, RC-ABC, and site-ABC. Agreement between CTP and ABC/2 was defined as an absolute difference up to 5 mL and relative difference within 20%. Determinants of ABC/2 accuracy were assessed by logistic regression. Results— In 4369 scans from 507 patients, CTP was more strongly correlated with RC-ABC ( r 2 =0.93) than with site-ABC ( r 2 =0.87). Although RC-ABC overestimated CTP-based volume on average (RC-ABC, 15.2 cm 3 ; CTP, 12.7 cm3), agreement was reasonable when categorized into mild, moderate, and severe ICH (κ=0.75; P <0.001). This was consistent with overestimation of ICH volume in 6 of 8 previous studies. Agreement with CTP was greater for RC-ABC (84% within 5 mL; 48% of scans within 20%) than for site-ABC (81% within 5 mL; 41% within 20%). RC-ABC had moderate accuracy for detecting ≥5 mL change in CTP volume between consecutive scans (sensitivity, 0.76; specificity, 0.86) and was more accurate with smaller ICH, thalamic hemorrhage, and homogeneous clots. Conclusions— ABC/2 scores at local or central sites are sufficiently accurate to categorize ICH volume and assess eligibility for the CLEAR-III and MISTIE III studies and moderately accurate for change in ICH volume. However, accuracy decreases with large, irregular, or lobar clots. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: MISTIE-II NCT00224770; CLEAR-III NCT00784134.

AbstractBackgroundMerkel cell carcinoma (MCC) is a rare, aggressive, often cutaneous malignancy. The incidence has been estimated from national registries in the USA and elsewhere, and data indicate variations depending on the region studied. The objective of this study was to determine the incidence of MCC in Olmsted County (MN, USA).MethodsUsing the Rochester Epidemiology Project, which contains health records for all the residents of Olmsted County, we retrospectively reviewed the records for all cases of MCC from 1976 to 2011.ResultsThe overall annual age‐ and sex‐adjusted incidence of MCC in Olmsted County during 1976–2011 was 0.35 per 100,000 person‐years (95% CI, 0.14–0.57). The incidence tended to be higher among men than women with 0.69 per 100,000 (95% CI, 0.24–1.14) and 0.10 per 100,000 (95% CI, 0–0.24), respectively.ConclusionsThese data are within the range of previous MCC incidence reports, and the incidence of MCC in Olmsted County is consistent with rates reported in the remainder of the USA.

ObjectiveThe Lymphatic Malformation Function (LMF) instrument is a preliminary parent‐report assessment designed to measure outcomes in children with cervicofacial lymphatic malformation (LM). This study aimed to assess the measurement properties of the LMF, refine it, test criterion validity, and evaluate the test‐retest reliability.Study DesignCross‐sectional.SettingTwo pediatric tertiary referral centers.SubjectsParents of 60 children from 6 months to 15 years old with cervicofacial LM.MethodsParents were recruited via mail and online. The LMF was administered on paper or online initially and again within 21 days. Response distributions and interitem correlations were examined for item reduction. Exploratory factor analysis was conducted on retained items. Cronbach’s α, Spearman correlation, and intraclass correlation (ICC) coefficients were calculated to test internal consistency, criterion validity (compared to stage), and test‐retest reliability, respectively.ResultsOne item was removed due to a floor effect. The response scale was collapsed from a 5‐point scale to a 3‐point scale due to skewness. Six items were discarded due to redundancy (interitem correlations >0.7); 2 items were discarded due to factor loadings <0.4. Exploratory factor analysis revealed a 2‐factor structure explaining 84% of variance, and the domains Signs and Impacts had good internal consistency (all Cronbach’s α >0.80 and <0.90), significant association with stage (P <. 05), and good overall test‐retest reliability (ICC, 0.82).ConclusionThe LMF has been refined into a 12‐item, 2‐domain instrument measuring LM‐specific signs and impacts with internal consistency, criterion validity, and test‐retest reliability.

Purpose Less than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma. Patients and Methods Gene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate-thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables. Results ITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false-negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk). Conclusion The addition of cell adhesion–linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis.

Frozen section pathology is routinely used for margin assessment of non‐melanoma skin cancer ( NMSC ). Frozen section can also be used for the primary diagnosis of several skin lesions. Limited data exist on the accuracy of frozen section in the diagnosis of NMSC . We performed a retrospective chart review of 300 cases in which frozen section diagnoses were compared with permanent section diagnoses of NMSC . Frozen section and permanent section pathology were concordant 83.3% of the time, with the highest concordance rates noted for basal cell carcinoma (145/153, 95%). Our results show a high level of concordance between frozen section and corresponding permanent section pathology diagnosis for NMSC . The rapidity of frozen section tissue processing and pathology reporting makes this technique useful in dermatologic practice for immediate diagnosis and management of NMSC . Further studies should explore strategies to decrease or eliminate discrepancies between frozen and permanent section diagnosis.

Objectives To assess whether HOUSES (HOUsing-based index of socioeconomic status (SES)) is associated with risk of and mortality after rheumatoid arthritis (RA). Design We conducted a population-based case–control study which enrolled population-based RA cases and their controls without RA. Setting The study was performed in Olmsted County, Minnesota. Participants Study participants were all residents of Olmsted County, Minnesota, with RA identified using the 1987 American College of Rheumatology criteria for RA from 1 January 1988, to 31 December 2007, using the auspices of the Rochester Epidemiology Project. For each patient with RA, one control was randomly selected from Olmsted County residents of similar age and gender without RA. Primary and secondary outcome measure The disease status was RA cases and their matched controls in relation to HOUSES as an exposure. As a secondary aim, post-RA mortality among only RA cases was an outcome event. The associations of SES measured by HOUSES with the study outcomes were assessed using logistic regression and Cox models. HOUSES, as a composite index, was formulated based on a summed z-score for housing value, square footage and number of bedrooms and bathrooms. Results Of the eligible 604 participants, 418 (69%) were female; the mean age was 56±15.6 years. Lower SES, as measured by HOUSES, was associated with the risk of developing RA (0.5±3.8 for controls vs −0.2±3.1 for RA cases, p=0.003), adjusting for age, gender, calendar year of RA index date, smoking status and BMI. The lowest quartile of HOUSES was significantly associated with increased post-RA mortality compared to higher quartiles of HOUSES (HR 1.74; 95% CI 1.10 to 2.74; p=0.017) in multivariate analysis. Conclusions Lower SES, as measured by HOUSES, is associated with increased risk of RA and mortality after RA. HOUSES may be a useful tool for health disparities research concerning rheumatological outcomes when conventional SES measures are unavailable.

Abstract IL10 is attributed with immune-suppressive and anti-inflammatory properties, which could promote or suppress cancer in the gastrointestinal tract. Loss of IL10 exacerbates colonic inflammation, leading to colitis and cancer. Consistent with this, transfer of IL10-competent regulatory T cells (Treg) into mice with colitis or hereditary polyposis protects against disease, while IL10-deficient mice are predisposed to polyposis with increased colon polyp load. Little is known about the protective or pathogenic function of IL10 in cancers of the small intestine. We found CD4+ T cells and CD4+ Foxp3+ Tregs to be the major sources of IL10 in the small intestine and responsible for the increase in IL10 during polyposis in the APCΔ468 mouse model of hereditary polyposis. Targeted ablation of IL10 in T cells caused severe IL10 deficiency and delayed polyp growth. However, these polyps progressively lost cytotoxic activity and eventually progressed to cancer. Several observations suggested that the effect was due to the loss of IFNγ-dependent immune surveillance. IL10-incompetent CD4+ T cells failed to secrete IFNγ when stimulated with polyp antigens and were inefficient in T-helper-1 (TH1) commitment. By contrast, the TH17 commitment was unaffected. These findings were validated using mice whose T cells overexpress IL10. In these mice, we observed high intra-polyp cytotoxic activity and attenuation of polyposis. Thus, expression of IL10 by T cells is protective and required for immune surveillance in the small intestine. Cancer Immunol Res; 3(7); 806–14. ©2015 AACR.

AbstractBackgroundPatients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or non‐Hodgkin lymphoma (NHL) are at increased risk for the development of skin malignancies.ObjectivesThis study was conducted to estimate the incidences of rare skin malignancies in patients with CLL/SLL or NHL.MethodsPatients with a diagnosis of CLL/SLL or NHL recorded in the Surveillance, Epidemiology and End Results (SEER) database during 1992–2007 were identified. Diagnoses of specific skin malignancies were identified from SEER files.ResultsDuring 1992–2007, a total of 128,674 patients with first diagnoses of CLL/SLL or NHL were recorded in SEER; 4743 were excluded because follow‐up data were unavailable. Among the remaining 123,931 patients, 28,964 had CLL/SLL and 94,967 had NHL. Standardized incidence ratios (SIRs) for invasive malignant melanoma, Merkel cell carcinoma, malignant fibrous histiocytoma, dermatofibrosarcoma protuberans, Kaposi's sarcoma, and sebaceous carcinoma were 2.3, 8.2, 3.6, 2.5, 2.9, and 1.4, respectively, in CLL/SLL patients and 1.6, 3.2, 1.5, 1.3, 17.6, and 0.8, respectively, in NHL patients. When invasive melanoma was stratified by patient age and sex, the highest SIR (17.8) was found in men aged 0–49 years with CLL (P < 0.001).ConclusionsPatients with CLL/SLL or NHL have a higher risk for the subsequent development of rare skin cancers. Given the more aggressive nature of these malignancies in this setting, regular monitoring for the development and prompt treatment of cutaneous malignancy is prudent in patients with NHL and particularly in patients with CLL. Regular use of sun protection may decrease the morbidity associated with skin cancer in this immunosuppressed population.