Citations

Purpose A major concern with sublobar resection (SR) for non–small-cell lung cancer (NSCLC) is high local recurrence (LR). Adjuvant brachytherapy may reduce LR This multicenter randomized trial compares SR to SR with brachytherapy (SRB). Patients and Methods High-risk operable patients with NSCLC ≤ 3 cm were randomly assigned to SR or SRB. The primary end point was time to LR, where LR included recurrence at the staple line (local progression), in the primary tumor lobe away from the staple line, and in ipsilateral hilar nodes. The trial was designed to have a 90% power to detect a hazard ratio (HR) of 0.315 in favor of SRB, using a one-sided type I error rate of 0.05 with a sample size of 100 eligible patients in each arm. Results Two hundred twenty-four patients were randomly assigned; 222 patients were evaluable for intent-to-treat analysis. Median age was 71 years (range, 49 to 87 years). No differences were found in baseline characteristics. Median follow-up time was 4.38 years (range, 0.04 to 5.59 years). There was no difference in time to LR (HR, 1.01; 95% CI, 0.51 to 1.98; log-rank P = .98) or in the types of LR. Local progression occurred in only 17 (7.7%) of 222 patients. In patients with potentially compromised margins (margin < 1 cm, margin-to-tumor ratio < 1, positive staple line cytology, wedge resection, nodule size > 2.0 cm), SRB did not reduce LR, although trends favored the SRB arm. This was most marked in 14 patients with positive staple line cytology (HR, 0.22; P = .24). Three-year overall survival rates were similar for patients in the SR (71%) and SRB (71%) arms (P = .97). Conclusion Brachytherapy did not reduce LR after SR. This finding may have been related to closer attention to parenchymal margins by surgeons participating in this study.

ABSTRACT We describe a case of shoulder hemiarthroplasty infection with Desulfovibrio legallii . Antimicrobial susceptibilities of 36 Desulfovibrio isolates are presented. Metronidazole and carbapenems exhibited reliable activity, although piperacillin-tazobactam did not. Eleven previous cases of Desulfovibrio infection are reviewed; most arose from a gastrointestinal tract-related source.

ABSTRACT We describe a case of chronic tenosynovitis in the hand of a 58-year-old cattle farmer. Surgical biopsy specimens grew Mycobacterium arupense . The patient responded to surgery and antimicrobial therapy based on in vitro susceptibility testing. The antimicrobial susceptibility profiles of the isolate from this patient and 39 additional clinical isolates are presented.

Abstract Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients can be a good model for studying human diseases and for future therapeutic regenerative medicine. Current initiatives to establish human iPSC (hiPSC) banking face challenges in recruiting large numbers of donors with diverse diseased, genetic, and phenotypic representations. In this study, we describe the efficient derivation of transgene-free hiPSCs from human finger-prick blood. Finger-prick sample collection can be performed on a “do-it-yourself” basis by donors and sent to the hiPSC facility for reprogramming. We show that single-drop volumes of finger-prick samples are sufficient for performing cellular reprogramming, DNA sequencing, and blood serotyping in parallel. Our novel strategy has the potential to facilitate the development of large-scale hiPSC banking worldwide.

ABSTRACT Objectives To determine whether α‐synuclein dinucleotide repeat (REP1) genotypes are associated with survival in Parkinson's disease (PD). Methods Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium provided REP1 genotypes and baseline and follow‐up clinical data for cases. The primary outcome was time to death. Cox proportional hazards regression models were used to assess the association of REP1 genotypes with survival. Results Twenty‐one sites contributed data for 6,154 cases. There was no significant association between α‐synuclein REP1 genotypes and survival in PD. However, there was a significant association between REP1 genotypes and age at onset of PD (hazard ratio: 1.06; 95% confidence interval: 1.01‐1.10; P value = 0.01). Conclusions In our large consortium study, α‐synuclein REP1 genotypes were not associated with survival in PD. Further studies of α‐synuclein's role in disease progression and long‐term outcomes are needed. © 2014 International Parkinson and Movement Disorder Society

ABSTRACTA 75-year-old man was diagnosed with probableCampylobacter jejuniprosthetic knee infection after a diarrheal illness. Joint aspirate and operative cultures were negative, but PCR of prosthesis sonicate fluid was positive, as was stool culture. Nineteen additional cases ofCampylobacterprosthetic joint infection reported in the literature are reviewed.

Abstract Integrative genomics has the potential to uncover relevant loci, as clinical outcome and response to chemotherapies are most likely not due to a single gene (or data type) but rather a complex relationship involving genetic variation, mRNA, DNA methylation, and copy number variation. In addition to this complexity, many complex phenotypes are thought to be controlled by the interplay of multiple genes within the same molecular pathway or gene set (GS). To address these two challenges, we propose an integrative gene set analysis approach and apply this strategy to a cisplatin (CDDP) pharmacogenomics study involving lymphoblastoid cell lines for which genome-wide SNP and mRNA expression data was collected. Application of the integrative GS analysis implicated the role of the RNA binding and cytoskeletal part GSs. The genes LMNB1 and CENPF, within the cytoskeletal part GS, were functionally validated with siRNA knockdown experiments, where the knockdown of LMNB1 and CENPF resulted in CDDP resistance in multiple cancer cell lines. This study demonstrates the utility of an integrative GS analysis strategy for detecting novel genes associated with response to cancer therapies, moving closer to tailored therapy decisions for cancer patients.

Renal leiomyosarcoma is a very rare tumor that clinically and radiographically mimics more common renal malignancies. The infrequency of the condition makes it very difficult to diagnose. A 70-year-old male smoker presented with months of hematuria, right-sided flank pain, and weight loss. Imaging revealed a 3.8-centimeter renal mass that had characteristics similar to renal cell carcinoma. Initial biopsy of the mass was negative for malignancy. Two months later, subsequent imaging revealed what appeared to be metastatic bone lesions. Again, a biopsy of one of the lesions was negative for malignancy. Subsequent ureteral pyeloscopy, ureteroscopic renal pelvis biopsy, and brush cytology were negative for malignancy as well. The decision was made to perform nephrectomy for the removal of the mass. Pathologic analysis revealed renal leiomyosarcoma. This case illustrates the difficulty in diagnosing renal leiomyosarcoma. Repeated pathologic sampling was negative because of the tumor heterogeneity. Prompt diagnosis and treatment are very significant as surgical resection at an early stage offers the best prognosis.

Objective: To summarize the pharmacology, development, and clinical application of sorafenib, a specific tyrosine kinase and vascular growth factor inhibitor, for the treatment of renal cell carcinoma (RCC). Data Sources: Clinical literature, including both primary studies and review articles, was obtained by searching MEDLINE (1966–May 2006), using the search terms BAY 43-9006, sorafenib, renal cell carcinoma, and tyrosine kinase inhibitor. Additional information was supplied by the manufacturer, Bayer HealthCare Pharmaceuticals. Study Selection and Data Extraction: Review articles, abstracts, and clinical studies related to sorafenib were analyzed. An evaluation of the research exploring sorafenib as a potential therapy for RCC was conducted. Relevant information was then selected and is reviewed in this article. Data Synthesis: Knowledge of the cellular abnormalities that can cause solid tumors has led to the development of medications that block these pathways. Sorafenib is an oral tyrosine kinase inhibitor that both blocks the Raf kinase pathway and inhibits vascular growth factors. Phase I and II trials have demonstrated that sorafenib has activity against RCC. Dermatologic reactions (rash, desquamation), fatigue, and hypertension have been the most commonly seen treatment-related adverse events. Sorafenib received FDA approval in December 2005 for treatment of advanced RCC. Conclusions: Sorafenib is a novel oral tyrosine kinase inhibitor effective in the treatment of RCC.