Segmentation of Glomeruli Within Trichrome Images Using Deep Learning.

INTRODUCTION: The number of glomeruli and glomerulosclerosis evaluated on kidney biopsy slides constitute standard components of a renal pathology report. Prevailing methods for glomerular assessment remain manual, labor intensive, and nonstandardized. We developed a deep learning framework to accurately identify and segment glomeruli from digitized images of human kidney biopsies. METHODS: Trichrome-stained images (n = 275) from renal biopsies of 171 patients with chronic kidney disease treated at the Boston Medical Center from 2009 to 2012 were analyzed. A sliding window operation was defined to crop each original image to smaller images. Each cropped image was then evaluated by at least 3 experts into 3 categories: (i) no glomerulus, (ii) normal or partially sclerosed (NPS) glomerulus, and (iii) globally sclerosed (GS) glomerulus. This led to identification of 751 unique images representing nonglomerular regions, 611 images with NPS glomeruli, and 134 images with GS glomeruli. A convolutional neural network (CNN) was trained with cropped images as inputs and corresponding labels as output. Using this model, an image processing routine was developed to scan the test images to segment the GS glomeruli. RESULTS: The CNN model was able to accurately discriminate nonglomerular images from NPS and GS images (performance on test data: Accuracy: 92.67% ± 2.02% and Kappa: 0.8681 ± 0.0392). The segmentation model that was based on the CNN multilabel classifier accurately marked the GS glomeruli on the test data (Matthews correlation coefficient = 0.628). CONCLUSION: This work demonstrates the power of deep learning for assessing complex histologic structures from digitized human kidney biopsies.

An active-learning laboratory on immunizations.

OBJECTIVE: To implement and evaluate an active-learning laboratory activity to teach pharmacy students about influenza, pneumococcal, and shingles vaccines. DESIGN: The laboratory session was divided into 6 immunization stations: 3 stations on influenza including a pediatrics station, and 1 station each for pneumococcal, shingles, and anaphylaxis. ASSESSMENT: Although 118 of 123 (95.9%) students had completed an immunization training certificate prior to attending the laboratory, the average score on a pre-assessment to measure immunization knowledge and confidence was 56%. The post-assessment score was 87.4%. Students' confidence improved by 18.7% to 51.2% in each of the 5 areas assessed. Most respondents rated the activity overall as good or excellent on a post-activity evaluation. CONCLUSION: An active-learning approach to teaching immunizations allowed students to gain knowledge in simulated real-world experiences and reinforced key concepts on influenza, pneumococcal, and shingles vaccines.

Management of chronic nonmalignant pain: a needs assessment in an internal medicine resident continuity clinic.

INTRODUCTION: The authors hypothesized that Internal Medicine (IM) residents experience a lack of preparation, confidence, and reward when managing patients with chronic nonmalignant pain (CNMP) in their continuity clinic and that they exhibit deficiencies in CNMP management practices, particularly when opioids are prescribed. METHODS: As part of a quality improvement project in the IM resident continuity clinic, the authors performed a needs assessment through a self-administered resident questionnaire and a retrospective chart review. RESULTS: Fifty-seven percent of respondents rated their CNMP preparation as "fair" or "poor," 89 percent reported that their experience was "much less" or "somewhat less" rewarding than managing patients with other chronic conditions, and 58 percent reported that CNMP management "negatively" or "very negatively" affected their view of primary care as a career. Twenty-eight charts of patients receiving opioids during a 1-year study period were reviewed. Although residents were likely to document pain diagnoses (93 percent) and pain scores (82 percent) as well as utilize medication agreements (82 percent), they were less likely to document illicit substance use (39 percent), document legal history (32 percent), or obtain prior medical records (39 percent). Few urine drug screens were ordered (18 percent) and 25 percent of patients had fewer than four face-to-face visits during the year. DISCUSSION: The questionnaire indicated that IM residents lack preparation in managing CNMP, which results in lack of confidence and reward. The chart review revealed management practice deficiencies in risk assessment and prescription drug misuse monitoring. As a result, the authors have implemented curricular interventions, integrated a pain clinic within the continuity clinic, optimized residency program clinic scheduling, and developed tools for consistency in management practices.

Fibromyalgia: diagnosis and management for the primary healthcare provider.

Fibromyalgia is a disorder of chronic generalized musculoskeletal pain affecting 2% of the general population, with an increased frequency in women. Clinical diagnosis relies on history and research-supported tender point criteria. As in other chronic pain syndromes, a multidimensional approach optimizes treatment response. Empirical data and consensus support the use of nonpharmacological modalities, such as education, aerobic exercise, and cognitive behavioral therapy, in the management of fibromyalgia. Evidence-supported pharmacological interventions include tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, alpha-2-delta ligands, and other serotonergic-noradrenergic analgesic agents, such as tramadol. This paper offers the primary healthcare provider a systematic approach to the diagnosis of fibromyalgia and management strategies based on available evidence, consensus, and empirical data.

New therapeutic options for the management of diabetes.

OBJECTIVE: To review new hypoglycemic and antihyperglycemic agents recently approved for the treatment of type 1 and type 2 diabetes mellitus. DATA SOURCES: A MEDLINE search of articles published from 1966 to March 2006 was conducted to identify English-language literature available on the newer therapies approved for the treatment of diabetes. Search terms used were: Byetta, exenatide, insulin detemir, NN304, Exubera inhaled insulin, Levemir, pramlintide, Symlin, AC137, AC0137, and Tripro-Amylin. These articles, abstracts, and data provided by the pharmaceutical manufacturers were reviewed to identify pertinent data. Additional references were obtained from the bibliographies of these publications. STUDY SELECTION: Randomized, English-language studies investigating safety or efficacy data on these newer agents with a focus on human studies. DATA EXTRACTION: These hypoglycemic and antihyperglycemic agents were reviewed with regard to background information, pharmacokinetic and pharmacodynamic data, relevant clinical studies, U.S. Food and Drug Administration-approved indications, dosing and administration, contraindications, drug interactions, adverse effects, storage, cost, availability, and role in therapy. DATA SYNTHESIS: Over the last decade, management options for the treatment of diabetes have exploded. Among these are the incretin mimetics, amylin analogs, insulin analogs, and inhaled insulin. Short-term studies demonstrate that each of these therapies may offer specific advantages such as improved glycemia, convenience, and/or weight loss. Continued study of the incretin mimetics, amylin analogs, and inhaled insulin will be needed to verify long-term safety and efficacy of these agents. CONCLUSIONS: These agents with novel mechanisms of action and a new insulin-delivery device offer patients and clinicians additional options that improve glycemic and nonglycemic factors while addressing some of the concerns of older agents. Longer term studies will help providers weigh the benefits, adverse effects, cost, and unknown long-term risks of these medications.

Aspergillus fumigatus triggers inflammatory responses by stage-specific beta-glucan display.

Inhalation of fungal spores (conidia) occurs commonly and, in specific circumstances, can result in invasive disease. We investigated the murine inflammatory response to conidia of Aspergillus fumigatus, the most common invasive mold in immunocompromised hosts. In contrast to dormant spores, germinating conidia induce neutrophil recruitment to the airways and TNF-alpha/MIP-2 secretion by alveolar macrophages. Fungal beta-glucans act as a trigger for the induction of these inflammatory responses through their time-dependent exposure on the surface of germinating conidia. Dectin-1, an innate immune receptor that recognizes fungal beta-glucans, is recruited in vivo to alveolar macrophage phagosomes that have internalized conidia with exposed beta-glucans. Antibody-mediated blockade of Dectin-1 partially inhibits TNF-alpha/MIP-2 induction by metabolically active conidia. TLR-2- and MyD88-mediated signals provide an additive contribution to macrophage activation by germinating conidia. Selective responsiveness to germinating conidia provides the innate immune system with a mechanism to restrict inflammatory responses to metabolically active, potentially invasive fungal spores.