An Unusual Case of Hemothorax in an Ehlers-Danlos Syndrome Patient Following Sildenafil Use.

Ehlers-Danlos syndrome is a disorder of collagen production that affects the connective tissues of the body. It can cause several conditions and severely affect patients' quality of life and activities of daily living. Here, we present an unusual case of hemothorax in a patient with Ehlers-Danlos syndrome after sildenafil use. This manifested in shortness of breath and cough and prompted the patient to visit the emergency room. The hemothorax was treated surgically, and the patient recovered well. Sildenafil was initially prescribed via a telemedicine service without in-person consultation. It is important that physicans perform a thorough history and physical examination prior to prescribing medications to patients, especially those at risk for complications.

Exploring Models of Exposure to Primary Care Careers in Training: a Narrative Review.

Multiple models of clinical exposure to primary care exist within undergraduate medical education (UME) and graduate medical education (GME). In this narrative review, we explore the evidence behind these different models of exposure, their alignment with positive promoters of primary care careers, and the pros and cons of each. Without positive exposure to primary care during training, sustaining the future primary care work force becomes increasingly challenging. Here, we explore multiple models of clinical exposure in UME, including longitudinal integrated clerkships, primary care tracks, and primary care clerkships. Within GME, we will review the impact of primary care tracks, Area Health Education Centers, block scheduling models, and continuity clinic scheduling models. The goal of this narrative review is to allow educators to think broadly and intentionally about the array of models to develop positive primary care experiences and perceptions in training, ultimately sustaining the primary care workforce.

RAGE contributes to allergen driven severe neutrophilic airway inflammation via NLRP3 inflammasome activation in mice.

Background: Asthma is a major public healthcare burden, affecting over 300 million people worldwide. While there has been great progress in the treatment of asthma, subsets of patients who present with airway neutrophilia, often have more severe disease, and tend to be resistant to conventional corticosteroid treatments. The receptor for advanced glycation endproducts (RAGE) plays a central role in the pathogenesis of eosinophilic asthma, however, it's role in neutrophilic asthma remains largely uninvestigated. Methods: A mouse model of severe steroid resistant neutrophilic airway disease (SSRNAD) using the common fungal allergen Alternaria alternata (AA) was employed to evaluate the effects of genetic ablation of RAGE and pharmacological inhibition of the NLRP3 inflammasome on neutrophilic airway inflammation. Results: AA exposure induced robust neutrophil-dominant airway inflammation and increased BALF levels of Th1/Th17 cytokines in wild-type mice, which was significantly reduced in RAGE-/- mice. Serum levels of IgE and IgG1 were increased similarly in both wild-type and RAGE-/- mice. Pharmacological inhibition of NLRP3 blocked the effects of AA exposure and NLRP3 inflammasome activation was RAGE-dependent. Neutrophil extracellular traps were elevated in the BALF of wild-type but not RAGE-/- mice and an atypical population of SiglecF+ neutrophils were identified in the BALF. Lastly, time-course studies found that RAGE expression promoted sustained neutrophil accumulation in the BALF of mice in response to AA.

Novel MEAF6-SUZ12 fusion in ossifying fibromyxoid tumor with unusual features.

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain differentiation that has the capacity for local recurrence and metastasis. Many OFMTs, including typical, atypical, and malignant tumors, have demonstrated recurrent gene fusions. The fusion partners reported to date share a common core function in that they play either a direct or indirect role in processes influencing histone modification. Herein, we report an OFMT with unusual morphology and non-specific immunoprofile harboring a novel MEAF6-SUZ12 fusion. A 34-year-old male presented with a slowly growing mass in the right antecubital fossa. Excision demonstrated a 6.9 cm partially encapsulated, tan-white, lobulated, and calcified lesion. Microscopic evaluation demonstrated cytologically bland spindle to ovoid cells arranged in a haphazard manner within a fibromyxoid background containing dense collagen, often with sclerotic nodules, and randomly distributed ossification. The tumor cells were diffusely positive for CD34 while essentially negative for S100, desmin, MUC4, SOX10, AE1/3, SMA, and EMA. Next-generation sequencing studies (sarcoma gene fusion next-generation sequencing panel with subsequent Sanger confirmation) performed on formalin-fixed paraffin-embedded tissue detected a fusion product between MEAF6 exon 4 (NM_001270875) and SUZ12 exon 2 (NM_001321207.1). The proposed mechanism of pathogenesis in OFMT, namely epigenetic dysregulation, is reinforced by the fact that both of these partner genes are involved in histone modification.