Citations

Abstract The natural history of idiopathic pulmonary fibrosis (IPF) has been characterized as a steady, predictable decline in lung function over time. Recent evidence suggests that some patients may experience a more precipitous course, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF. This perspective is the result of an international effort to summarize the current state of knowledge regarding acute exacerbations of IPF. Acute exacerbations of IPF are defined as acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF. Proposed diagnostic criteria include subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The potential pathobiological roles of infection, disordered cell biology, coagulation, and genetics are discussed, and future research directions are proposed.

ABSTRACT Obesity is one of the major health problems of our times. Elucidating the signaling mechanisms by which high‐fat caloric diet induces obesity is critical for the understanding of this condition and for the development of therapeutic strategies for its treatment. Here, we demonstrate a novel role for protein CD38 as a regulator of body weight during a high‐fat diet. CD38 is a ubiquitous enzyme that catalyzes the synthesis of second messengers and has been implicated in the regulation of a wide variety of signaling pathways. We report that CD38‐deficient mice are pro‐tected against high‐fat diet‐induced obesity owing to enhanced energy expenditure. In fact, calorimetric studies indicate that CD38‐deficient animals have a higher metabolic rate compared to control mice. Analysis of the mechanism revealed that this resistance to diet‐induced obesity is mediated at least in part via a NAD‐dependent activation of SIRT‐PGC1α axis, a well‐established cascade, involved in the regulation of mito‐chondrial biogenesis and energy homeostasis. Thus, together these results identify a novel pathway regulating body weight and clearly show that CD38 is a nearly obligatory component of the cellular cascade that led to diet‐induced obesity.—Barbosa, M. T. P., Soares, S. M., Novak, C. M., Sinclair, D., Levine, J. A., Aksoy, P., Chini, E. N. The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet‐induced obesity. FASEB J. 21, 3629–3639 (2007)

The objective of this study was to assess the usefulness of a comparison of clinical failure and restenosis rates of endovascular procedures at 1 year in patients with peripheral arterial disease. The resulting comparison is presented as “clinical failure/restenosis coordinate.” The authors screened 171 papers describing the outcome of lower extremity angioplasty or stent placement. In 20 of them, authors reported detailed outcomes of interest, including baseline demographic measurements, location of arterial occlusive lesions, a measure of restenosis (measured by ankle-brachial indices, ultrasonography, or angiography), and clinical outcomes (mortality, repeat percutaneous transluminal angioplasty, or amputation). An overview of these 20 angioplasty papers was performed. Besides the usual meta-analyses of each end point separately, data were also plotted as coordinates of clinical failure versus restenosis. The clinical failure-to-restenosis coordinate was calculated and reported for percutaneous transluminal angioplasty of the aortoiliac and femoropopliteal distributions. Clinically reported outcomes in the literature were used to calculate the clinical failure/restenosis coordinate. This value was significantly different for various locations of the angioplasty and various baseline angiographic characteristics. A numeric coordinate pair of clinical failure and restenosis is identifiable in patients undergoing endovascular treatment of peripheral arterial disease. The varying coordinates may be important in elucidating the incidence and mechanisms of clinical failure after endovascular treatment. The coordinate reported in this article is hypothesis-generating about mechanisms of endovascular treatment failure. This coordinate is important in determining the role of restenosis in the clinical failure of endovascular therapy of peripheral arterial disease.

The purpose of this study was to review patellar tendon ruptures in athletes treated with surgical repair. Six pa tellar tendon ruptures in five athletic patients were iden tified at our institution between 1980 and 1990. All pa tients had operative debridement and primary repair of the ruptured patellar tendon using nonabsorbable su tures passed through patellar drill holes at an average of 2.5 days after injury. Personal interview, physical ex amination, roentgenographic evaluation, and isokinetic strength testing were performed at an average of 6 years after surgery. At final followup, no patient had complaints referable to the patellar tendon repair; all were able to achieve their premorbid levels of sports at an average of 18 months after injury. No patient thought that the surgically repaired knee was unstable or activity-limiting. All patients demonstrated full range of motion and strength equal to or greater than that of the noninjured side. One patient required an arthroscopic lateral release for lateral patellar facet pressure syn drome with an excellent result. No complications oc curred ; no other reoperations were required. Complete disruption of the patellar tendon is an uncommon injury in athletic individuals without predisposing medical con ditions. After acute operative repair and aggressive re habilitation, an excellent and enduring functional outcome can be expected.

Objectives The study goal was to report the oncologic outcomes of transoral laser microsurgery (TLM) in the treatment of squamous cell carcinoma of the supraglottic larynx. Study Design and Setting A two‐center prospective case series analysis. Results Thirty‐eight patients underwent TLM for previously untreated carcinoma of the supraglottic larynx between 1997 and 2005. Pathological T stages were T1 in 8 (21%), T2 in 14 (37%), T3 in 8 (21%), and T4 in 8 (21%). Twenty‐six patients (68%) had neck dissections. Thirteen patients (34%) received adjuvant radiotherapy. The mean follow‐up for all patients was 31 months. The 2‐year Kaplan‐Meier estimates for local control were 97%; locore‐gional control, 94%; disease‐specific survival, 80%; and overall survival, 85%. The overall functional laryngeal preservation rate was 79% (19 of 24). Conclusions TLM is a safe and effective treatment for cancer of the supraglottic larynx Significance TLM is an emerging strategy in the management of laryngeal cancer. © 2007 American Academy of Otolaryngology‐Head and Neck Surgery Foundation. All rights reserved.

Abstract Purpose: To detect insulin-like growth factor-IR (IGF-IR) on circulating tumor cells (CTC) as a biomarker in the clinical development of a monoclonal human antibody, CP-751,871, targeting IGF-IR. Experimental Design: An automated sample preparation and analysis system for enumerating CTCs (CellTracks) was adapted for detecting IGF-IR–positive CTCs with a diagnostic antibody targeting a different IGF-IR epitope to CP-751,871. This assay was used in three phase I trials of CP-751,871 as a single agent or with chemotherapy and was validated using cell lines and blood samples from healthy volunteers and patients with metastatic carcinoma. Results: There was no interference between the analytic and therapeutic antibodies. Eighty patients were enrolled on phase I studies of CP-751,871, with 47 (59%) patients having CTCs detected during the study. Before treatment, 26 patients (33%) had CTCs, with 23 having detectable IGF-IR–positive CTCs. CP-751,871 alone, and CP-751,871 with cytotoxic chemotherapy, decreased CTCs and IGF-IR–positive CTCs; these increased toward the end of the 21-day cycle in some patients, falling again with retreatment. CTCs were commonest in advanced hormone refractory prostate cancer (11 of 20). Detectable IGF-IR expression on CTCs before treatment with CP-751,871 and docetaxel was associated with a higher frequency of prostate-specific antigen decline by >50% (6 of 10 versus 2 of 8 patients). A relationship was observed between sustained decreases in CTC counts and prostate-specific antigen declines by >50%. Conclusions: IGF-IR expression is detectable by immunofluorescence on CTCs. These data support the further evaluation of CTCs in pharmacodynamic studies and patient selection, particularly in advanced prostate cancer.

The objective of this study is to present an algorithm for choosing graft materials for the reconstruction of severe caudal and/or dorsal septal cartilage abnormalities and to examine the long-term results obtained with these techniques. Retrospective review of 21 consecutive cases of caudal and/or dorsal septal reconstruction via the external approach using the algorithms is presented. The techniques used are carefully described. Patient survey at least 1 year after the initial procedure, rhinologic examination before and after the procedure, and photographic analysis of preoperative and postoperative views are presented. The graft choice algorithm presented helps the surgeon to consider appropriate graft choice alternatives before surgery.