Citations

Goals: Our aim was to develop a scoring system to predict risk of microscopic colitis (MC), to identify patients at low risk, potentially avoiding unnecessary biopsies. Background: Patients with chronic diarrhea often undergo colonoscopy with biopsy, but few have histologic abnormalities. Study: We conducted a retrospective study of patients with chronic diarrhea and a macroscopically normal colonoscopy at our institution over a 9-month period. Multivariable logistic regression assessed the association between predictors and the presence of biopsy-proven MC. Results: The derivation cohort included 617 patients. Median age was 55.1 (39.6 to 68.1) years; 397 (64.3%) were female and 81 (13.1%) had MC. Age ≥55 years, duration of diarrhea ≤6 months, ≥5 bowel movements per day, body mass index <30 kg/m2, current smoking, and current use of selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitorss and non-steroidal anti-inflammatory drugs were independently associated with MC. A score of ≥10 points in our scoring system, yielded an area under the ROC curve (AUC) of 0.83 with a sensitivity of 93% and specificity of 49% in predicting which patients have MC. The negative predictive value (NPV) was 97.8% (95.0% to 99.1%). In the validation cohort, the scoring system performed similarly (AUC 0.79, sensitivity 91%, specificity 49%, NPV 97%). By avoiding biopsies in patients at low risk of having MC, costs associated with colon biopsies could be reduced by almost 43%. Conclusion: This scoring system including 7 clinical variables was able to identify patients unlikely to have MC, with excellent sensitivity, reasonable specificity, and a high NPV, translating into important potential cost savings.

If untreated, most children with severe combined immunodeficiency disorder (SCID) will die of complications of infection within the first 2 years of life. Early hematopoietic stem cell transplant (HSCT) is the current standard of care for this disease. Although potentially lifesaving, prognosis of HSCT in SCID is variable depending on a number of host and donor factors. Of the survivors, many develop secondary problems such as chronic graft-versus-host disease or even second malignancies. Posttransplant care is complex and requires great effort from parents to adhere to difficult treatment regimens. In this article, we address the difficult ethical question of what to do if parents choose not to have their child with SCID undergo HSCT but prefer palliative care.

Purpose To (1) evaluate long‐term outcomes of osteochondral allograft (OCA) with regard to clinical outcome scores, reoperation and failure rates, and (2) examine if certain factors predispose patients to worse outcomes. Methods A comprehensive review was performed with specific inclusion criteria for studies with long‐term outcomes after OCA. Studies reported on patient clinical scores such as Hospital for Special Surgery score, Knee Society Score (knee and function score), and Lysholm score. Reoperation and failure rates were recorded for each study. Modified Coleman Methodology Scores assessed study methodological quality. Results Five studies with a total of 291 patients (55% male, 45% female) and average age of 34.8 years (range, 15 to 69 years) were included. Of all lesions, 67% were on the femoral condyles, 29% on the tibial plateau, and 4% were patellofemoral. All scores (Knee Society Function Score, Knee Society Knee Score, and Lysholm score) have significant mean improvement from preoperative to final follow‐up. The mean postoperative Hospital for Special Surgery score was 84.1. The mean failure rate was 25% at 12.3 years with a reoperation rate of 36%. A total of 72% of the failures were conversion to total (68%) or unicompartmental (4%) knee arthroplasty and 28% involved graft removal, graft fixation, and graft revision. Patellofemoral lesions (83%) had a significantly higher reoperation rate than lesions involving the tibial plateau or the femoral condyles (34%, P = .01). Conclusions Overall, OCA demonstrated significant improvements in clinical outcome scores and good durability with successful outcomes in 75% of the patients at 12.3 years after surgery. Patellofemoral lesions are associated with decreased clinical improvement and more frequent reoperations. The orthopaedic literature is limited by heterogeneity in surgical technique, lesion and patient characteristics, and reporting of nonstandardized outcome measures. Level of Evidence Level IV, systematic review of Level II and IV studies.

AbstractSevere aortic stenosis and coronary artery disease often coexist. Coronary angiography (CA) and percutaneous coronary intervention (PCI) can be challenging in patients with prior transcatheter aortic valve implantation (TAVI). Depending on the type and position of the implanted valve, the procedure can be challenging or even unfeasible due to interference of diagnostic catheters and valve parts. The correct positioning of the TAVI prosthesis during TAVI was identified as an important factor with regard to the feasibility of subsequent CA or PCI. TAVI has been also associated with vascular, cerebrovascular and conduction complication. One is rare but life-threatening complication, coronary ostial obstruction. Coronary ostial obstruction can develop, especially if a safety check of more than 10 mm of coronary ostial height is not taken into consideration during TAVI. This complication can cause recurrent episodes of angina and can severely worsen the patient′s cardiac systolic function.

BACKGROUND. Variable response to chemotherapy in acute myeloid leukemia (AML) represents a major treatment challenge. Clinical and genetic features incompletely predict outcome. The value of clinical epigenetic assays for risk classification has not been extensively explored. We assess the prognostic implications of a clinical assay for multilocus DNA methylation on adult patients with de novo AML. METHODS. We performed multilocus DNA methylation assessment using xMELP on samples and calculated a methylation statistic (M-score) for 166 patients from UPENN with de novo AML who received induction chemotherapy. The association of M-score with complete remission (CR) and overall survival (OS) was evaluated. The optimal M-score cut-point for identifying groups with differing survival was used to define a binary M-score classifier. This classifier was validated in an independent cohort of 383 patients from the Eastern Cooperative Oncology Group Trial 1900 (E1900; NCT00049517). RESULTS. A higher mean M-score was associated with death and failure to achieve CR. Multivariable analysis confirmed that a higher M-score was associated with death ( P = 0.011) and failure to achieve CR ( P = 0.034). Median survival was 26.6 months versus 10.6 months for low and high M-score groups. The ability of the M-score to perform as a classifier was confirmed in patients ≤ 60 years with intermediate cytogenetics and patients who achieved CR, as well as in the E1900 validation cohort. CONCLUSION. The M-score represents a valid binary prognostic classifier for patients with de novo AML. The xMELP assay and associated M-score can be used for prognosis and should be further investigated for clinical decision making in AML patients.

In human myocarditis and its sequela dilated cardiomyopathy (DCM), the mechanisms and immune phenotype governing disease and subsequent heart failure are not known. Here, we identified a Th17 cell immunophenotype of human myocarditis/DCM with elevated CD4 + IL17 + T cells and Th17-promoting cytokines IL-6, TGF-β, and IL-23 as well as GM-CSF–secreting CD4 + T cells. The Th17 phenotype was linked with the effects of cardiac myosin on CD14 + monocytes, TLR2, and heart failure. Persistent heart failure was associated with high percentages of IL-17–producing T cells and IL-17–promoting cytokines, and the myocarditis/DCM phenotype included significantly low percentages of FOXP3 + Tregs, which may contribute to disease severity. We demonstrate a potentially novel mechanism in human myocarditis/DCM in which TLR2 peptide ligands from human cardiac myosin stimulated exaggerated Th17-related cytokines including TGF-β, IL-6, and IL-23 from myocarditic CD14 + monocytes in vitro, and an anti-TLR2 antibody abrogated the cytokine response. Our translational study explains how an immune phenotype may be initiated by cardiac myosin TLR ligand stimulation of monocytes to generate Th17-promoting cytokines and development of pathogenic Th17 cells in human myocarditis and heart failure, and provides a rationale for targeting IL-17A as a therapeutic option.

Abstract Prostate cancer is a biologically heterogeneous disease with variable molecular alterations underlying cancer initiation and progression. Despite recent advances in understanding prostate cancer heterogeneity, better methods for classification of prostate cancer are still needed to improve prognostic accuracy and therapeutic outcomes. In this study, we computationally assembled a large virtual cohort (n = 1,321) of human prostate cancer transcriptome profiles from 38 distinct cohorts and, using pathway activation signatures of known relevance to prostate cancer, developed a novel classification system consisting of three distinct subtypes (named PCS1–3). We validated this subtyping scheme in 10 independent patient cohorts and 19 laboratory models of prostate cancer, including cell lines and genetically engineered mouse models. Analysis of subtype-specific gene expression patterns in independent datasets derived from luminal and basal cell models provides evidence that PCS1 and PCS2 tumors reflect luminal subtypes, while PCS3 represents a basal subtype. We show that PCS1 tumors progress more rapidly to metastatic disease in comparison with PCS2 or PCS3, including PSC1 tumors of low Gleason grade. To apply this finding clinically, we developed a 37-gene panel that accurately assigns individual tumors to one of the three PCS subtypes. This panel was also applied to circulating tumor cells (CTC) and provided evidence that PCS1 CTCs may reflect enzalutamide resistance. In summary, PCS subtyping may improve accuracy in predicting the likelihood of clinical progression and permit treatment stratification at early and late disease stages. Cancer Res; 76(17); 4948–58. ©2016 AACR.

Introduction Under certain circumstances, e-consultations can substitute for a face-to-face consultation. A basic requirement for a successful e-consultation is that the e-consultant has access to important medical history and exam findings along with laboratory and imaging results. Knowing just what information the specialist needs to complete an e-consultation is a major challenge. This paper examines differences between specialties in their need for past information from laboratory, imaging and clinical notes. Methods This is a retrospective study of patients who had an internal e-consultation performed at an academic medical centre. We reviewed a random sample of e-consultations that occurred in the first half of 2013 for the indication for the e-consultation and whether the e-consultant reviewed data in the medical record that was older than one year to perform the e-consultation. Results Out of 3008 total e-consultations we reviewed 360 (12%) randomly selected e-consultations from 12 specialties. Questions on management (35.8%), image results (27.2%) and laboratory results (25%) were the three most common indications for e-consultation. E-consultants reviewed medical records in existence more than one year prior to the e-consultation 146 (40.6%) of the time with e-consultants in the specialties of endocrinology, haematology and rheumatology, reviewing records older than one year more than half the time. Labs (20.3%), office notes (20%) and imaging (17.8%) were the types of medical data older than one year that were reviewed the most frequently overall. Discussion Management questions appear to be the most common reason for e-consultation. E-consultants frequently reviewed historical medical data that is older than one year at the time of the e-consultation, especially in endocrinology, haematology and rheumatology specialties. Practices engaging in e-consultations that require transfer of data may want to include longer time frames of historical information for those specialties.