Citations

Abstract Diabetes engenders the loss of pancreatic β-cell mass and/or function, resulting in insulin deficiency relative to the metabolic needs of the body. Diabetic care has traditionally relied on pharmacotherapy, exemplified by insulin replacement to target peripheral actions of the hormone. With growing understanding of the pathogenesis of diabetic disease, alternative approaches aiming at repair and restoration of failing β-cell function are increasingly considered as complements to current diabetes therapy regimens. To this end, emphasis is placed on transplantation of exogenous pancreas/islets or artificial islets, enhanced proliferation and maturation of endogenous β cells, prevention of β-cell loss, or fortified renewal of β-like-cell populations from stem cell pools and non-β-cell sources. In light of emerging clinical experiences with human embryonic stem cells and approval of the first in-human trial with induced pluripotent stem cells, in this study we highlight advances in β-cell regeneration strategies with a focus on pluripotent stem cell platforms in the context of translational applications.

AbstractHobnail hemangioma (HH), initially termed targetoid hemosiderotic hemangioma, is a rare, often solitary lesion classically characterized by a central brown or violaceous papulonodule surrounded at times by an ecchymotic halo. This lesion is typically found on the trunk or limbs of children or young to middle‐aged adults. Numerous case reports have found HHs to have a reproducible histologic appearance. Although the exact histogenesis of these lesions is unknown, multiple recent immunohistochemical studies suggest a lymphatic origin of these lesions. We present six cases of children with HHs with classic histology but with variability in their clinical appearance. Because the clinical presence of a targetoid halo is inconsistent and the hobnail phenomenon is not specific, we favor the designation of superficial hemosiderotic lymphovascular malformation instead of HH or targetoid hemosiderotic hemangioma as a more unifying term for this rare clinical entity. By eliminating confounding terminologies (in this case, incorporation of “hemangioma” in the name of this entity), we also hope to encourage a swifter change in practice to move away from erroneous diagnostic considerations.

Depression symptoms contribute to significant morbidity and health care utilization. The aim of this study was to determine the impact of symptom improvement (to remission) on outpatient clinical visits by depressed primary care patients. This study was a retrospective chart review analysis of 1733 primary care patients enrolled into collaborative care management (CCM) or usual care (UC) with 6-month follow-up data. Baseline data (including demographic information, clinical diagnosis, and depression severity) and 6-month follow-up data (Patient Health Questionnaire scores and the number of outpatient visits utilized) were included in the data set. To control for individual patient complexity and pattern of usage, the number of outpatient visits for 6 months prior to enrollment also was measured as was the presence of medical comorbidities. Multiple logistic regression analysis demonstrated that clinical remission at 6 months was an independent predictor of outpatient visit outlier status (>8 visits) (odds ratio [OR] 0.609, confidence interval (CI) 0.460–0.805, P <0.01) when controlling for all other independent variables including enrollment into CCM or UC. The OR of those patients not in remission at 6 months having outpatient visit outlier status was the inverse of this at 1.643 (CI 1.243–2.173). The most predictive variable for determining increased outpatient visit counts after diagnosis of depression was increased outpatient visits prior to diagnosis (OR 4.892, CI 3.655–6.548, P <0.01). In primary care patients treated for depression, successful treatment to remission at 6 months decreased the likelihood of the patient having more than 8 visits during the 6 months after diagnosis. ( Population Health Management 2014;17:180–184)

Abstract The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95% confidence interval (CI), 1.22–1.64; P = 5.7 × 10−6], rs791587 (HR, 1.36; 95% CI, 1.17–1.57; P = 6.2 × 10−5), rs2476491 (HR, = 1.40; 95% CI, 1.19–1.64; P = 5.6 × 10−5), and rs10795763 (HR, 1.35; 95% CI, 1.17–1.57; P = 7.9 × 10−5), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95% CI, 0.54–0.82; P = 9.3 × 10−5) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cancer. Cancer Immunol Res; 2(4); 332–40. ©2014 AACR.

Significance Cancer cells reprogram their metabolism for optimal growth and survival. AMPK-activated protein kinase (AMPK) is a key energy sensor that controls many metabolic pathways including metabolic reprogramming. However, its role in cancer is poorly understood. Some studies claim that it has a tumor suppressor role while others show its protumor role. Two AMPK-activating compounds (including metformin, now in many clinical trials) are widely used to suppress cancer cell proliferation. We found that AMPK is abundantly expressed in high-grade gliomas and, in contrast to popular belief, these two AMPK activators suppressed glioma cell proliferation through unique AMPK-independent mechanisms.

Background: The expertise required for proper electroencephalography (EEG) setup can make the 10-20 array unwieldy in the hospital setting. There may be a role for an EEG array with reduced leads to improve the efficiency of inpatient practice. Methods: Clips from 100 EEG records, 50 ictal and 50 non-ictal, in adult inpatients from January 1, 2007, to January 1, 2012, were retrospectively reviewed and selected for digital lead reduction and blind review. Two epileptologists reviewed these tracings and documented the presence of seizures and severe disturbance of background. The reduced array included 7 leads spanning the scalp. Three different montages were available. Sensitivity and specificity of the reduced array were calculated using the formal EEG report as the comparison standard. Results: For the detection of any seizure, the reduced array EEG had a sensitivity of 70% and specificity of 96%. Sensitivity for identifying encephalopathic patterns was 62% and specificity was 86%. Focal seizures were more readily identified by the reduced array (20 of 25) than were generalized ictal patterns (13 of 25). Conclusion: The reduced electrode array was insufficiently sensitive to seizure detection. Reducing EEG leads might not be a preferred means of optimizing hospital EEG efficiency.

Background: The inclusion of mental health issues in the evaluation of multimorbidity generally has been as the presence or absence of the condition rather than severity, complexity, or stage. The hypothesis for this study was that clinical outcome of the depression 6 months after enrollment into collaborative care management would have a role in predicting future complexity of care tier. Methods: This study was a retrospective chart review of 1894 primary care patients who were diagnosed with major depressive disorder or dysthymia as of December 2012. Multiple logistic regression analysis was used to test the independent associations between each variable and the odds of being included in the higher tiers (HT) group. Results: Age (odds ratio [OR] = 1.022, confidence interval [CI] = 1.013-1.030, P < .001), female gender (OR = 1.380, CI = 1.020-1.868, P = .037), being married (OR = 0.730, CI = 0.563-0.947, P = .018), and the presence of comorbidities (1, OR = 1.986, CI = 1.485-2.656, P < .001; ≥2, OR = 4.678, CI = 3.242-6.750, P < .001) were independently associated with future HT levels. The presence of persistent depressive symptoms (PHQ-9 ≥10) at 6 months conferred 2.280 (CI = 1.673-3.107, P < .001) times likely odds of HT level compared with clinical remission at 6 months. Conclusion: Patients with the diagnosis of major depression or dysthymia had greater odds of complex tier levels in the future, if depression was not treated to remission by 6 months. This study demonstrated the importance of the goal of significant improvement (ie, remission) of depression symptoms by 6 months (especially those older patients with more comorbidity) from entering into the higher complexity tiers.