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Introduction: Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food and Drug Administration (FDA)-approved three-bag protocol in which each bag has a unique concentration and infusion duration. Recently, simplified, off-label two-bag NAC infusion protocols have become more common. The purpose of this review is to summarize the effectiveness and safety of two-bag NAC.Methods: We undertook a comprehensive search of PubMed, EMBASE, and MEDLINE from inception to December 13, 2022, for articles describing human acetaminophen poisonings treated with two-bag NAC, defined as any regimen involving two discrete infusions in two separate bags. Outcomes included effectiveness (measured by incidence of liver injury); incidence of non-allergic anaphylactoid reactions (NAAR); gastrointestinal, cutaneous, and systemic reactions; treatments for NAARs; incidence of NAC-related medication errors; and delays or interruptions in NAC administration.Results: Twelve articles met final inclusion, 10 of which compared two-bag NAC to the three-bag regimen. Nine articles evaluated the two-bag/20-hour regimen, a simplified version of the FDA-approved three-bag regimen in which the traditional first and second bags are combined into a single four-hour infusion. Nine articles assessed comparative effectiveness of two-bag NAC in terms of liver injury, most commonly assessed for by incidence of hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1,000 international units per liter). No difference in liver injury was observed between two-bag and three-bag regimens. Of nine articles comparing incidence of NAARs, eight demonstrated statistically fewer NAARs with two-bag regimens, and one showed no difference. In seven articles evaluating treatment for NAARs (antihistamines, corticosteroids, epinephrine), all showed that patients received fewer medications for NAARs with two-bag NAC. Three articles evaluated NAC-related medication errors; two demonstrated no difference, while one study evaluating only children showed fewer errors with two-bag NAC. Two studies evaluated delays and/or interruptions in NAC infusions; both favored two-bag NAC.Conclusion: For patients with acetaminophen poisoning, two-bag NAC regimens appear to have similar outcomes to the traditional three-bag regimen in terms of liver injury. Two-bag NAC regimens are associated with fewer adverse events and fewer treatments for those events than the three-bag regimen and fewer interruptions in antidotal therapy.

Here, we report that the LynB splice variant of the Src-family kinase Lyn exerts a dominant immunosuppressive function in vivo, whereas the LynA isoform is uniquely required to restrain autoimmunity in female mice. We used CRISPR-Cas9 gene editing to constrain lyn splicing and expression, generating single-isoform LynA knockout (LynAKO) or LynBKO mice. Autoimmune disease in total LynKO mice is characterized by production of antinuclear antibodies, glomerulonephritis, impaired B cell development, and overabundance of activated B cells and proinflammatory myeloid cells. Expression of LynA or LynB alone uncoupled the developmental phenotype from the autoimmune disease: B cell transitional populations were restored, but myeloid cells and differentiated B cells were dysregulated. These changes were isoform-specific, sexually dimorphic, and distinct from the complete LynKO. Despite the apparent differences in disease etiology and penetrance, loss of either LynA or LynB had the potential to induce severe autoimmune disease with parallels to human systemic lupus erythematosus (SLE).

Background: Proper diagnosis in primary care is crucial due to the large number of skin cancer diagnoses each year and its associated growing economic burden. Understanding how primary care providers can be best trained in dermoscopy is instrumental in helping primary care providers differentiate benign and malignant cutaneous lesions so that appropriate action can be taken (eg, biopsy/referral to dermatology or reassurance). Objective: To assess the success of concise dermoscopy training among primary care providers. Design: A cohort study was conducted in primary care at Mayo Clinic, Rochester, including primary care physicians, nurse practitioners, and physician assistants in internal medicine and family medicine. Diagnostic accuracy was measured on standardized testing through image-based recognition and in clinical practice through observation of referral and biopsy patterns both before and after dermoscopy education, focused on the TADA plus method. Results: Forty-three primary care providers completed the image-based recognition tests, with significant improvement in mean score measured after dermoscopy training workshop (20%). Among the thirteen primary care providers who continued to use dermoscopy in clinical practice, a significant improvement (31%) in mean clinical diagnostic accuracy was observed comparing 1 year of practice data before versus after dermoscopy training. Conclusion: Improvement in diagnostic accuracy with utilization of the TADA plus method translates into clinical practice. Therefore, training primary care providers in dermoscopy may improve the dermatologic care patients receive in primary care, especially in rural or medically underserved areas where access to dermatology is limited. [ABSTRACT FROM AUTHOR]

Objectives: Recovery from traumatic brain injury (TBI) is extremely difficult to predict, with TBI severity usually demonstrating weak predictive validity for functional or other outcomes. A possible explanation may lie in the statistical phenomenon called suppression, according to which a third variable masks the true association between predictor and outcome, making it appear weaker than it actually is. Age at injury is a strong candidate as a suppressor because of its well-established main and moderating effects on TBI outcomes. We tested age at injury as a possible suppressor in the predictive chain of effects between TBI severity and functional disability, up to 10 years post-TBI. Setting: Follow-up interviews were conducted during telephone interviews. Participants: We used data from the 2020 NDILRR Model Systems National Dataset for 4 successive follow-up interviews: year 1 (n = 10,734), year 2 (n = 9174), year 5 (n = 6,201), and year 10 (n = 3027). Design: Successive cross-sectional multiple regression analyses. Main Measures: Injury severity was operationalized using a categorical variable representing duration of posttrauma amnesia. The Glasgow Outcomes Scale--Extended (GOS-E) operationally defined functioning. Sociodemographic characteristics having significant bivariate correlations with GOS-E were included. Results: Entry of age at injury into the regression models significantly increases the association between TBI severity and functioning up to 10 years post-TBI. Conclusions: Age at injury is a suppressor variable, masking the true effect of injury severity on functional outcomes. Identifying the mediators of this suppression effect is an important direction for TBI rehabilitation research. [ABSTRACT FROM AUTHOR]

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