Citations

Objective Although robotic technology has addressed many of the limitations of traditional videoscopic surgery, robotic surgery has not gained widespread acceptance in the general thoracic community. We report our initial robotic surgery experience and propose a structured, competency-based pathway for the development of robotic skills. Methods Between December 2008 and February 2012, a total of 79 robot-assisted pulmonary, mediastinal, benign esophageal, or diaphragmatic procedures were performed. Data on patient characteristics and perioperative outcomes were retrospectively collected and analyzed. During the study period, one surgeon and three residents participated in a triphasic, competency-based pathway designed to teach robotic skills. The pathway consisted of individual preclinical learning followed by mentored preclinical exercises and progressive clinical responsibility. Results The robot-assisted procedures performed included lung resection (n = 38), mediastinal mass resection (n = 19), hiatal or para-esophageal hernia repair (n = 12), and Heller myotomy (n = 7), among others (n = 3). There were no perioperative mortalities, with a 20% complication rate and a 3% readmission rate. Conversion to a thoracoscopic or open approach was required in eight pulmonary resections to facilitate dissection (six) or to control hemorrhage (two). Fewer major perioperative complications were observed in the later half of the experience. All residents who participated in the thoracic surgery robotic pathway perform robot-assisted procedures as part of their clinical practice. Conclusions Robot-assisted thoracic surgery can be safely learned when skill acquisition is guided by a structured, competency-based pathway.

Recent advances in the burgeoning field of genome engineering are accelerating the realization of personalized therapeutics for cardiovascular disease. In the postgenomic era, sequence-specific gene-editing tools enable the functional analysis of genetic alterations implicated in disease. In partnership with high-throughput model systems, efficient gene manipulation provides an increasingly powerful toolkit to study phenotypes associated with patient-specific genetic defects. Herein, this review emphasizes the latest developments in genome engineering and how applications within the field are transforming our understanding of personalized medicine with an emphasis on cardiovascular diseases.

Background Biomarkers have many distinct purposes, and depending on their intended use, the validation process varies substantially. Purpose The goal of this article is to provide an introduction to the topic of biomarkers, and then to discuss three specific types of biomarkers, namely, prognostic, predictive, and surrogate. Results A principle challenge for biomarker validation from a statistical perspective is the issue of multiplicity. In general, the solution to this multiplicity challenge is well known to statisticians: pre-specification and replication. Critical requirements for prognostic marker validation include uniform treatment, complete follow-up, unbiased case selection, and complete ascertainment of the many possible confounders that exist in the context of an observational sample. In the case of predictive biomarker validation, observational data are clearly inadequate and randomized controlled trials are mandatory. Within the context of randomization, strategies for predictive marker validation can be grouped into two categories: retrospective versus prospective validation. The critical validation criteria for a surrogate endpoint is to ensure that if a trial uses a surrogate endpoint, the trial will result in the same inferences as if the trial had observed the true endpoint. The field of surrogate endpoint validation has now moved to the multi-trial or meta-analytic setting as the preferred method. Conclusions Biomarkers are a highly active research area. For all biomarker developmental and validation studies, the importance of fundamental statistical concepts remains the following: pre-specification of hypotheses, randomization, and replication. Further statistical methodology research in this area is clearly needed as we move forward.

ObjectiveTo identify new genetic associations with juvenile and adult dermatomyositis (DM).MethodsWe performed a genome‐wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1,178) and controls (n = 4,724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single‐nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM.ResultsCompared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS‐level significance (P < 5 × 10–8) at 80 genotyped SNPs. An analysis of 141 non‐MHC SNPs previously associated with autoimmune diseases showed that 3 SNPs linked with 3 genes were associated with DM, with a false discovery rate (FDR) of <0.05. These genes were phospholipase C–like 1 (PLCL1; rs6738825, FDR = 0.00089), B lymphoid tyrosine kinase (BLK; rs2736340, FDR = 0.0031), and chemokine (C‐C motif) ligand 21 (CCL21; rs951005, FDR = 0.0076). None of these genes was previously reported to be associated with DM.ConclusionOur findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non‐MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches.

Objective To investigate aspects of juvenile dermatomyositis (DM), including disease characteristics and treatment, through a national multicenter registry. Methods Subjects meeting the modified Bohan and Peter criteria for definite juvenile DM were analyzed from the cross‐sectional Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry between 2010 and 2012 from 55 US pediatric rheumatology centers. Demographics, disease characteristics, diagnostic assessments, and medication exposure data were collected at enrollment. Results A total of 384 subjects met the criteria for analysis. At enrollment, the median Childhood Myositis Assessment Scale score was 51 (interquartile range [IQR] 46–52), the median Childhood Health Assessment Questionnaire score was 0 (IQR 0–0.5), and the median physician and subject global assessment scores were 1 (IQR 0–2) and 1 (IQR 0–3), respectively, out of a maximum of 10. Of the diagnostic assessments, magnetic resonance imaging was more likely than electromyography or muscle biopsy to show abnormalities. A total of 329 subjects had ≥2 diagnostic studies performed, and >34% of these subjects reported ≥1 negative study. Ninety‐five percent had been treated with corticosteroids and 92% with methotrexate, suggesting that these medications were almost universally prescribed for juvenile DM in the US. Conclusion In 2 years, the ongoing CARRA Registry has collected clinical data on 384 children with juvenile DM and has the potential to become one of the largest juvenile DM cohorts in the world. More research is needed about prognostic factors in juvenile DM, and differences in therapy based on manifestations of disease need to be explored by practitioners. This registry provides the infrastructure needed to advance clinical and translational research and represents a major step toward improving outcomes of children with juvenile DM.

Objective Diffuse alveolar hemorrhage (DAH) is an uncommon complication of primary antiphospholipid syndrome (APS). We aimed to describe the clinical characteristics, treatment, and outcomes of primary APS–associated DAH in a single center. Methods We conducted a retrospective review of all adults with primary APS–associated DAH evaluated at Mayo Clinic over a 15‐year period. DAH was defined as bilateral pulmonary infiltrates and bronchoalveolar lavage (BAL) fluid documenting progressively bloody returns and/or the presence of >20% hemosiderin‐laden macrophages. Patients with other causes of DAH were excluded. Results Eighteen patients were identified (median age 43 years). Capillaritis was present in surgical lung biopsy samples of 3 patients. BAL differential cell counts revealed predominantly neutrophils. All patients were treated initially with glucocorticoids. Cyclophosphamide (CYC) was used in 8 patients; complete remission was achieved in 3 patients treated with CYC alone and in 1 patient receiving combination therapy with rituximab (RTX). RTX was used in 9 patients; 2 patients achieved remission with RTX alone, whereas 3 patients required combination therapy with CYC or mycophenolate mofetil (MMF). No patient achieved complete remission while receiving single therapy with MMF, azathioprine, or plasma exchange. Intravenous gamma globulin therapy was administered in 5 patients; no patient achieved control of the disease. Six patients died, all because of complications related to uncontrolled DAH or its therapy. Conclusion We present the largest case series of primary APS–associated DAH reported in the literature. DAH carries a very poor prognosis and therapeutic options are limited. Immunosuppression with either CYC or RTX is associated with the highest likelihood of remission induction and should be considered early.

ABSTRACTIntroduction: The hallmark clinical presentation of inclusion‐body myositis (IBM) is slowly progressive weakness that characteristically affects the quadriceps and finger and wrist finger flexor muscles. Facial weakness can also occur, but it is typically mild and not a prominent finding. Methods: We describe the clinical features, laboratory investigations, and muscle biopsy findings in a 58‐year old man who presented with a 6‐year history of marked progressive symmetrical facial weakness. Examination also showed shoulder abduction and hip extensor weakness. Results: The patient's serum creatine kinase level was 655 U/L, and electromyography showed fibrillation potentials and myopathic motor unit potentials. A biopsy specimen of the left biceps muscle was pathognomonic for IBM. Conclusions: This patient did not have a typical presentation for IBM but rather fulfilled the pathological criteria for IBM. To our knowledge, facial diplegia has not been reported previously as a presenting manifestation of IBM. Muscle Nerve 49: 287–289, 2014