Heroin Overdose Complicated by Compartment Syndrome, Rhabdomyolysis, and Acute Renal Failure.

The opioid-abuse epidemic is a problem that continues to persist world-wide. As such, appropriately evaluating and treating such patients is crucial, especially when considering the various complications that may arise. In rare cases, opioid overdoses can be complicated by compartment syndrome, rhabdomyolysis, and acute renal failure. All three of these complications can result in life threatening emergencies. We present a case of a 38-year-old male who was brought to the emergency department after reportedly being found lying on the ground for an unknown period of time from suspected heroin overdose. He was initially treated with 2 milligrams (mg) of intramuscular naloxone en route via emergency medical services with appropriate response. Shortly after arrival to the emergency department, the patient complained of severe right lower extremity pain, paresthesia and paralysis. Patient developed acute lower extremity compartment syndrome that was further complicated by rhabdomyolysis and acute renal failure. While emergency medicine physicians are familiar with the common complications of heroin overdose including mental status changes, respiratory depression and gastrointestinal symptoms, they must also be familiar with the less common ones. Notably, acute compartment syndrome. Compartment syndrome is ultimately a clinical diagnosis and warrants emergent surgical consultation. Every patient presenting to the emergency department warrants a complete, thorough physical examination to evaluate for any and all life-threatening conditions, regardless of the presenting complaint.

Mast Cell Activation in the Systemic Sclerosis Esophagus.

INTRODUCTION: Previously, we discovered similar esophageal gene expression patterns in patients with systemic sclerosis (SSc) and eosinophilic esophagitis (EoE) where eosinophil/mast cell-targeted therapies are beneficial. Because SSc and EoE patients experience similar esophageal symptoms, we hypothesized that eosinophil/mast cell-directed therapy may potentially benefit SSc patients. Herein, we determine the association between esophageal mast cell quantities, gene expression and clinical parameters in order to identify SSc patients who may benefit from eosinophil/mast cell-directed therapy. METHODS: Esophageal biopsies from SSc patients and healthy participants were stained for tryptase, a mast cell marker, and associations with relevant clinical parameters including 24h esophageal pH testing were assessed. Intra-epithelial mast cell density was quantified by semi-automated microscopy. Microarray data were utilized for functional and gene set enrichment analyses and to identify intrinsic subset (IS) assignment, an SSc molecular classification system that includes inflammatory, proliferative, limited and normal-like subsets. RESULTS: Esophageal biopsies from 40 SSc patients (39 receiving proton pump inhibition) and eleven healthy participants were studied. Mast cell numbers in both the upper esophagus (rs = 0.638, p = 0.004) and the entire (upper + lower) esophagus (rs = 0.562, p = 0.019) significantly correlated with acid exposure time percentage. The inflammatory, fibroproliferative, and normal-like ISs originally defined in skin biopsies were identified in esophageal biopsies. Although esophageal mast cell numbers in SSc patients and healthy participants were similar, gene expression for mast cell-related pathways showed significant upregulation in the inflammatory IS of SSc patients compared to patients classified as proliferative or normal-like. DISCUSSION: Esophageal mast cell numbers are heterogeneous in SSc patients and may correlate with acid exposure. Patients with inflammatory IS profiles in the esophagus demonstrate more tryptase staining. Mast cell targeted therapy may be a useful therapeutic approach in SSc patients belonging to the inflammatory IS, but additional studies are warranted.

Mycophenolate Mofetil Treatment of Systemic Sclerosis Reduces Myeloid Cell Numbers and Attenuates the Inflammatory Gene Signature in Skin.

Fewer than half of patients with systemic sclerosis demonstrate modified Rodnan skin score improvement during mycophenolate mofetil (MMF) treatment. To understand the molecular basis for this observation, we extended our prior studies and characterized molecular and cellular changes in skin biopsies from subjects with systemic sclerosis treated with MMF. Eleven subjects completed ≥24 months of MMF therapy. Two distinct skin gene expression trajectories were observed across six of these subjects. Three of the six subjects showed attenuation of the inflammatory signature by 24 months, paralleling reductions in CCL2 mRNA expression in skin and reduced numbers of macrophages and myeloid dendritic cells in skin biopsies. MMF cessation at 24 months resulted in an increased inflammatory score, increased CCL2 mRNA and protein levels, modified Rodnan skin score rebound, and increased numbers of skin myeloid cells in these subjects. In contrast, three other subjects remained on MMF >24 months and showed a persistent decrease in inflammatory score, decreasing or stable modified Rodnan skin score, CCL2 mRNA reductions, sera CCL2 protein levels trending downward, reduction in monocyte migration, and no increase in skin myeloid cell numbers. These data summarize molecular changes during MMF therapy that suggest reduction of innate immune cell numbers, possibly by attenuating expression of chemokines, including CCL2.

Multiple hepatocellular adenomas presenting in a male 8 years post-pancreaticoduodenectomy for islet cell tumor of the pancreas.

We report the case of a 29-year-old male who presented with vague right upper quadrant pain, 8 years following a pancreaticoduodenectomy for a symptomatic pancreatic islet cell tumor. Subsequent imaging revealed multiple lesions in the right lobe of the liver. A diagnosis of metastatic disease could not be out ruled and hence a formal resection was performed. A formal retrospective review of case notes, preoperative imaging, operative notes, subsequent histology as well as a review of the current literature using the Medline, CINAHL, and EMBASE databases was performed. Histologic analysis showed these lesions to be hepatocellular adenomas. We highlight in this case the importance of preoperative imaging and workup, discuss hepatocellular adenomas in males and hypothesize as to the underlying pathophysiology in this particular case based on the available evidence.