Generating automated kidney transplant biopsy reports combining molecular measurements with ensembles of machine learning classifiers

We previously reported a system for assessing rejection in kidney transplant biopsies using microarray‐based gene expression data, the Molecular Microscope^® Diagnostic System (MMDx). The present study was designed to optimize the accuracy and stability of MMDx diagnoses by replacing single machine learning classifiers with ensembles of diverse classifier methods. We also examined the use of automated report sign‐outs and the agreement between multiple human interpreters of the molecular results. Ensembles generated diagnoses that were both more accurate than the best individual classifiers, and nearly as stable as the best, consistent with expectations from the machine learning literature. Human experts had ≈93% agreement (balanced accuracy) signing out the reports, and random forest‐based automated sign‐outs showed similar levels of agreement with the human experts (92% and 94% for predicting the expert MMDx sign‐outs for T cell–mediated (TCMR) and antibody‐mediated rejection (ABMR), respectively). In most cases disagreements, whether between experts or between experts and automated sign‐outs, were in biopsies near diagnostic thresholds. Considerable disagreement with histology persisted. The balanced accuracies of MMDx sign‐outs for histology diagnoses of TCMR and ABMR were 73% and 78%, respectively. Disagreement with histology is largely due to the known noise in histology assessments (ClinicalTrials.gov NCT01299168).     

Pyoderma gangrenosum: A case report of bilateral dorsal hand lesions and literature review of management

Pyoderma gangrenosum is a great masquerader in wound diagnosis and management. Frequently misdiagnosed as a necrotizing infection, the elusive nature of its etiology and pathogenesis has thwarted the establishment of a standardized management algorithm, leaving immunosuppressant therapies as the mainstay of treatment. The present report describes a 61-year-old woman presenting with temporally discrete bilateral dorsal hand lesions successfully managed with distinctive multimodality therapies. The initial lesion was managed under the auspices of a necrotizing process using a combination of hyperbaric oxygen therapy and skin grafting with a negative-pressure dressing, both individually demonstrated to be effective for prompt wound stabilization and coverage. A subsequent contralateral hand lesion was similarly managed as a necrotizing infection before a diagnosis of pyoderma gangrenosum was considered. Stabilization and eventual resolution was achieved using intravenous and topical steroids followed by hyperbaric oxygen therapy, again highlighting the benefits of multimodality therapy in the setting of pyoderma gangrenosum.     

Foreign service special care opportunity in SCDA

A foreign service clinic in Guatemala caring for patients with special needs was initiated by joining SCDA efforts with the Open Wide Foundation. The trip included five SCDA members: two AEGD residents and three support staff. Open Wide participants included the Executive Director, the Clinical Director in Guatemala, as well as two dentists, dental support staff, and Guatemalan dental students. Two physician anesthesiologists provided general anesthesia. Care adjuncts included general anesthesia, oral sedation, and medical stabilization. Lessons learned: (1) Conducting a dental clinic for patients with special needs is possible and relatively easy to accomplish, given a partnership with a foundation that agrees with and facilitates this service; (2) advance planning is required to maximize the service provided; (3) committed and flexible team members can accomplish a significant amount of care in a short period of time; and (4) limited but invaluable training of in‐country healthcare providers is possible. The Special Care Dentistry Association is long known for service and care delivery to patients with special needs by its members, and for its advocacy and organizational support for these activities. A foreign service opportunity in Guatemala, Central America, was sought out by members of the SCDA to further the outreach efforts of the organization, give members clinical experience in a foreign setting, and train in‐country providers to deliver care to patients with special needs. This was the first effort by SCDA members to host a clinic to deliver care specifically to patients with special needs outside of North America.     

Targeted Tissue and Cell-Free Tumor DNA Sequencing of Advanced Lung Squamous-Cell Carcinoma Reveals Clinically Significant Prevalence of Actionable Alterations

Background

Major guidelines do not recommend routine molecular profiling of lung squamous-cell carcinoma (LUSC) because the prevalence of actionable alterations is thought to be low. Increased utilization of next-generation sequencing (NGS), particularly with cell-free circulating tumor DNA, facilitates reevaluation of this premise.