Retained bullets and lead toxicity: a systematic review.

INTRODUCTION: Lead toxicity secondary to retained bullet(s) (RB) after a penetrating gunshot wound is a rare but likely underdiagnosed condition, given the substantial number of firearm injuries in the United States. There is currently no consensus on the indications for surveillance, chelation, or surgical intervention. OBJECTIVE: The purpose of our review is to summarize the literature on systemic lead toxicity secondary to RBs to help guide clinicians in the management of these patients. METHODOLOGY: The primary literature search was conducted in Medline (PubMed), EMBASE, Cochrane, and CENTRAL using the following MESH terms: "chelation" and "lead poisoning" or "lead toxicity" or "lead" and "bullet" or "missile" or "gunshot", or "bullet". RESULTS: The search identified 1,082 articles. After exclusions, a total of 142 articles were included in our final review, the majority of which were case reports. Several factors appear to increase the risk of developing lead toxicity including the location of the RB, the presence of a fracture or recent trauma, number of fragments, hypermetabolic states, and bullet retention duration. Particularly, RBs located within a body fluid compartment like an intra-articular space appear to be at a substantially higher risk of developing lead toxicity. Even though patients with lead toxicity from RBs will have similar symptoms to patients with lead toxicity from other sources, the diagnosis of lead poisoning may occur months or years after a gunshot wound. Symptomatic patients with high blood lead levels (BLLs) tended to improve with a combination of chelation and surgical removal of RBs. CONCLUSIONS: We suggest surveillance with serial BLLs should be performed. Patients with intra-articular RBs appear to be at increased risk of lead toxicity and if possible, early surgical removal of the RBs is warranted, especially given that signs of toxicity are vague, and patients may not have access to follow-up. Long-term chelation should not be used as a surgical alternative and management should be multidisciplinary.

Clinical outcome of massive acetaminophen overdose treated with standard-dose N-acetylcysteine.

BACKGROUND: Recent recognition of "massive" acetaminophen (APAP) overdoses has led to the question of whether standard dosing of N-acetylcysteine (NAC) is adequate to prevent hepatoxicity in these patients. The primary aim of this study was to evaluate the clinical outcome for patients with massive APAP overdose who received standard intravenous NAC dosing of 300 mg/kg over 21 h. METHODS: This was a single-center retrospective cohort study conducted by chart review of APAP overdoses reported to a regional poison center from 1 January 2010 to 31 December 2019. Massive APAP overdose was defined by single, acute overdose resulting in an APAP concentration exceeding 300 mcg/mL at 4 h post-ingestion. Standard univariate statistical analysis was conducted to describe the cohort, and a multivariate logistic model was utilized to calculate adjusted odds ratios for risk of hepatoxicity. RESULTS: 1425 cases of APAP overdose were reviewed. 104 cases met the inclusion criteria of massive APAP overdose. Overall, 79 cases (76%) had no acute liver injury or hepatotoxicity, and 25 (24%) developed hepatoxicity. Nine percent (n = 4) of cases receiving NAC within 8 h developed hepatotoxicity. Crude odds for hepatoxicity was 5.5-fold higher for cases who received NAC after 8 h. CONCLUSIONS: Standard NAC dosing received within 8 h prevented hepatoxicity in 91% (n = 40) of cases in our series of massive APAP overdoses. Additional data is needed to determine the clinical outcomes of massive APAP overdose using current intravenous NAC dosing.

Heparan sulfate proteoglycan modulation of Wnt5A signal transduction in metastatic melanoma cells.

Heparan sulfate proteoglycans (HSPGs) are important modulators for optimizing signal transduction of many pathways, including the Wnt pathways. We demonstrate that HSPG glycosaminoglycan levels increased with increasing metastatic potential of melanoma cells. Previous studies have demonstrated that Wnt5A increases the invasiveness of melanoma cells. We further demonstrate that HSPGs potentiate Wnt5A signaling, since enzymatic removal of the HSPG backbone resulted in a decrease in cellular Wnt5A levels, an increase in secreted Wnt5A in cell media, a decrease in downstream signaling, and ultimately, a decrease in invasiveness. Specifically, syndecan 1 and syndecan 4 expression correlated to Wnt5A expression and melanoma malignancy. Knockdown of syndecan 1 or 4 caused decreases in cell invasion, which could be restored by treating the cells with recombinant Wnt5A. These data indicate that syndecan 1 and 4 correlate to increased metastatic potential in melanoma patients and are an important component of the Wnt5A autocrine signaling loop, the activation of which leads to increased metastasis of melanoma.