Proximal Tibiofibular Joint Reconstruction With a Semitendinosus Allograft for Chronic Instability.

Whereas acute proximal tibiofibular joint (PTFJ) dislocation may require urgent reduction, chronic or recurrent instability may initially be approached with conservative treatment. Indications for PTFJ reconstruction include persistent lateral knee pain and/or tibiofibular instability for which conservative treatment has failed. Owing to the low incidence of diagnosed isolated PTFJ instability, there is still no consensus regarding the optimal surgical treatment, with an array of options having been previously described. We describe the treatment of isolated PTFJ instability using an anatomic reconstruction with semitendinosus allograft for chronic instability.

Wikipedia: A Medical Student Educational Project to Edit Wikipedia in Preparation for Practicing Evidence-Based Pain Medicine.

OBJECTIVE: Wikipedia is commonly used to acquire information about various medical conditions such as chronic pain. Ideally, better online pain management content could reduce the burden of opioid use disorders. Our goal was to improve the quality of the content available on Wikipedia to make it more accurate and applicable to medical students and the general public while training medical students to practice evidence-based medicine and critically assess their sources of information. METHODS: An elective class in Neuroscience, Pain, and Opioids composed of 10 medical students met biweekly to discuss landmark and practice-changing research articles in the fields of acute pain, chronic pain, and opioid management. The professor chose Wikipedia articles relevant to this course. Three independent viewers analyzed the quality of citations, anecdotal medical content, and content value for both patients and medical professionals. As part of their coursework, students then edited the Wikipedia articles. RESULTS: Although some of the Wikipedia pain topic content (6.7% ± 2.0) was anecdotal, financially biased, or inconsistent with Western Medical Practice content, overall articles included primarily high-quality citations (85.6% ± 3.1). On a 0-5 Likert scale, students felt content would be moderately helpful for both medical students/professionals (3.4 ± 0.2) and laypersons (3.5 ± 0.2). Editing and adding citations was feasible, but novel material was often reverted. CONCLUSION: A significant amount of pain medicine content was relevant and amenable to student editing. Therefore, future use of this tactic could provide a unique opportunity to integrate evidence-based medicine into the medical curriculum and have a direct impact on the widely available medical information. Future refinement in the editorial process may also further improve online information.

The Clinical Utility of Additional Axillary and Velpeau Radiographs in the Evaluation of Suspected Shoulder Trauma.

OBJECTIVES: To investigate the clinical utility of additional axillary or Velpeau views in evaluating potential shoulder trauma after a standard radiograph series of anteroposterior, Grashey, and/or trans-scapular views. DESIGN: Retrospective study. SETTING: Level I academic medical center. PATIENTS: All patients in a 10-year span who received an initial shoulder radiograph series followed by additional axillary/Velpeau views within 24 hours. MAIN OUTCOME MEASUREMENTS: The clinical utility of the additional axillary/Velpeau views, including the final diagnosis and treatment plan, as ascertained through examination of radiology reports, progress notes, and radiograph images. RESULTS: A total of 271 cases were reviewed, with 35 patients being excluded from the final cohort because they received post-treatment radiographs to confirm a successful therapeutic outcome. The additional axillary/Velpeau views did not affect clinical decision making in 230 (97.5%) of the remaining 236 cases. All 6 patients whose care benefitted from the additional views carried the diagnosis of shoulder instability, accounting for 40% of this diagnostic group. The additional views confirmed an equivocal finding in 5 of these 6 cases and changed the diagnosis (demonstrating a posterior dislocation that was not evident on initial radiographs) and treatment plan (leading to a closed glenohumeral reduction procedure) in the other case. CONCLUSIONS: Additional axillary/Velpeau views of suspected shoulder trauma rarely led to a change in the final treatment plan, except in patients in which a definitive diagnosis of stability or instability could not be made based on initial radiographs. A cost/benefit analysis is required to weigh the cost of additional radiographs with the benefit of capturing infrequent yet serious dislocations (usually posterior). LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Lumbar discectomy is associated with higher rates of lumbar fusion.

BACKGROUND CONTEXT: Lumbar disc herniation affects more than 3 million people in the United States every year, and the rate of operation continually increases, particularly in patients 60 years or older (Taylor et al., 1994; Jordan et al., 2011). Surgical discectomy is a common treatment for lumbar disc herniation (Taylor et al., 1994; Atlas et al., 1996). One concern for this method is the risk of undergoing additional surgeries (Jordan et al., 2011; Österman et al., 2003; Lebow et al., 2011). There are very limited population-level studies that examine the rate of lumbar fusion after lumbar discectomy. Additionally, there is no study that examines the risk of undergoing lumbar fusion in patients who have undergone lumbar discectomies compared with the risk of lumbar fusion in the general population with no previous lumbar discectomy. PURPOSE: The present study aimed to calculate a more definitive rate of lumbar fusion after a lumbar discectomy procedure using a population-size study of more than 200,000 patients in the Truven Healthcare Analytics Marketscan Research Database who underwent discectomies. Additionally, the study aimed to compare the rate of lumbar fusion in patients who have undergone a lumbar discectomy to the rate of lumbar fusion in patients with no prior lumbar discectomy procedure. STUDY DESIGN/SETTING: This is a retrospective cohort study. PATIENT SAMPLE: The patients from both parts of the present study were extracted from the Truven Healthcare Analytics Marketscan Research Database. Ten-year fusion after discectomy rates: 223,291 patients who underwent discectomies from the years 2003 to 2015. Fusion rate comparison: 489,975 patients with a previous lumbar ICD-9 (International Classification of Diseases, Ninth Revision) diagnosis code who have also been enrolled in the database for at least 10 years. OUTCOME MEASURES: Ten-year fusion after discectomy rates: The proportion of patients who received a lumbar fusion up to 10 years after a lumbar discectomy. Fusion rate comparison: The proportion of patients who received a lumbar fusion after a lumbar discectomy compared with the proportion of patients who received a lumbar fusion with no previous lumbar discectomy. METHODS: Ten-year fusion after discectomy rates: The patients who had undergone discectomies were filtered in the Marketscan database via Current Procedural Terminology (CPT) codes specific for lumbar discectomy (63030, 63035). Patients who had a lumbar fusion before or concurrently with these indexed lumbar discectomy dates were removed from the index group. The group was then followed up every year up to 10 years after the initial indexed lumbar discectomy dates for reoperation involving a lumbar spinal fusion according to the lumbar fusion CPT codes (22533, 22558, 22612, 22630, 22632, 22633, 22634, 22534, 22585, 22614). Fusion rate comparison: Study population only included patients who had a previous lumbar ICD-9 diagnosis in the Marketscan database (7242, 72210, 72251, 72252, 72273, 72293, 7213, 72142, 72283, 72293, 7243, 72402, 72403, 7244, 7245, 7249). The patients were then separated into two arms: one with patients who had undergone lumbar discectomy after initial lumbar diagnosis and another with patients who had not undergone a lumbar discectomy procedure. Pearson chi-square test was used to assess significance when comparing the proportion of patients who receive lumbar fusion after lumbar discectomy with the proportion of patients who receive lumbar fusion without a prior lumbar discectomy in the general ICD-9 lumbar diagnosis population. RESULTS: For the 10-year trend of lumbar fusion rates after lumbar discectomy, the rate of fusion ranged from 1.69% (1-year time frame after discectomy) to 8.50% (10-year time frame after discectomy). When comparing the two cohorts in the second part of the present study, the fusion rates were 12.50% for the discectomy group and 4.19% for the non-discectomy group. The Pearson chi-square test reported a statistically significant difference between the fusion rates of the two groups (p<.0001, α=.05). We found that people who had a lumbar discectomy procedure were 2.97 (95% confidence interval [2.86, 3.10]) times more likely to undergo a lumbar fusion than those who with a lumbar diagnosis but had not undergone a lumbar discectomy in the past. CONCLUSIONS: Our study is the largest population study that explores the rate of lumbar fusion after an initial lumbar discectomy. To our knowledge, it is the first study that concludes that an initial lumbar discectomy is statistically associated with an increased likelihood of a patient undergoing a lumbar fusion in the future. We observed that patients who had previously undergone a lumbar discectomy were roughly three times more likely to undergo a lumbar fusion procedure than a patient with a lumbar diagnosis, but had not undergone a lumbar discectomy. Although not calculated, it stands to reason the difference would be even greater when comparing the discectomy population with a population without lumbar diagnoses. This finding can be an important supplement for the physician-patient discussion regarding expectations and potential for reoperation.

Multidimensional Assessment of the Host Response in Mechanically Ventilated Patients with Suspected Pneumonia.

Rationale: The identification of informative elements of the host response to infection may improve the diagnosis and management of bacterial pneumonia. Objectives: To determine whether the absence of alveolar neutrophilia can exclude bacterial pneumonia in critically ill patients with suspected infection and to test whether signatures of bacterial pneumonia can be identified in the alveolar macrophage transcriptome. Methods: We determined the test characteristics of alveolar neutrophilia for the diagnosis of bacterial pneumonia in three cohorts of mechanically ventilated patients. In one cohort, we also isolated macrophages from alveolar lavage fluid and used the transcriptome to identify signatures of bacterial pneumonia. Finally, we developed a humanized mouse model of Pseudomonas aeruginosa pneumonia to determine if pathogen-specific signatures can be identified in human alveolar macrophages. Measurements and Main Results: An alveolar neutrophil percentage less than 50% had a negative predictive value of greater than 90% for bacterial pneumonia in both the retrospective (n = 851) and validation cohorts (n = 76 and n = 79). A transcriptional signature of bacterial pneumonia was present in both resident and recruited macrophages. Gene signatures from both cell types identified patients with bacterial pneumonia with test characteristics similar to alveolar neutrophilia. Conclusions: The absence of alveolar neutrophilia has a high negative predictive value for bacterial pneumonia in critically ill patients with suspected infection. Macrophages can be isolated from alveolar lavage fluid obtained during routine care and used for RNA-Seq analysis. This novel approach may facilitate a longitudinal and multidimensional assessment of the host response to bacterial pneumonia.

Single-Cell Transcriptomic Analysis of Human Lung Provides Insights into the Pathobiology of Pulmonary Fibrosis.

Rationale: The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual cell populations during pulmonary fibrosis that are important for disease pathogenesis. Objectives: To determine whether single-cell RNA sequencing can reveal disease-related heterogeneity within alveolar macrophages, epithelial cells, or other cell types in lung tissue from subjects with pulmonary fibrosis compared with control subjects. Methods: We performed single-cell RNA sequencing on lung tissue obtained from eight transplant donors and eight recipients with pulmonary fibrosis and on one bronchoscopic cryobiospy sample from a patient with idiopathic pulmonary fibrosis. We validated these data using in situ RNA hybridization, immunohistochemistry, and bulk RNA-sequencing on flow-sorted cells from 22 additional subjects. Measurements and Main Results: We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to nonoverlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. We developed a web-based tool to explore these data. Conclusions: We generated a single-cell atlas of pulmonary fibrosis. Using this atlas, we demonstrated heterogeneity within alveolar macrophages and epithelial cells from subjects with pulmonary fibrosis. These results support the feasibility of discovery-based approaches using next-generation sequencing technologies to identify signaling pathways for targeting in the development of personalized therapies for patients with pulmonary fibrosis.

Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span.

Little is known about the relative importance of monocyte and tissue-resident macrophages in the development of lung fibrosis. We show that specific genetic deletion of monocyte-derived alveolar macrophages after their recruitment to the lung ameliorated lung fibrosis, whereas tissue-resident alveolar macrophages did not contribute to fibrosis. Using transcriptomic profiling of flow-sorted cells, we found that monocyte to alveolar macrophage differentiation unfolds continuously over the course of fibrosis and its resolution. During the fibrotic phase, monocyte-derived alveolar macrophages differ significantly from tissue-resident alveolar macrophages in their expression of profibrotic genes. A population of monocyte-derived alveolar macrophages persisted in the lung for one year after the resolution of fibrosis, where they became increasingly similar to tissue-resident alveolar macrophages. Human homologues of profibrotic genes expressed by mouse monocyte-derived alveolar macrophages during fibrosis were up-regulated in human alveolar macrophages from fibrotic compared with normal lungs. Our findings suggest that selectively targeting alveolar macrophage differentiation within the lung may ameliorate fibrosis without the adverse consequences associated with global monocyte or tissue-resident alveolar macrophage depletion.