Assessing the impact of blood alcohol concentration on the rate of in-hospital mortality following traumatic motor vehicle crash injury: A matched analysis of the National Trauma Data Bank

Background

The purpose of this study was to compare the outcomes of trauma patients who were injured in a motor vehicle crash and tested positive for alcohol upon hospital arrival versus those who tested negative.

Factors Associated with Reoperation in Breast-Conserving Surgery for Cancer: A Prospective Study of American Society of Breast Surgeon Members

Background

More than 20% of patients undergoing initial breast-conserving surgery (BCS) for cancer require reoperation. To address this concern, the American Society of Breast Surgeons (ASBrS) endorsed 10 processes of care (tools) in 2015 to be considered by surgeons to de-escalate reoperations. In a planned follow-up, we sought to determine which tools were associated with fewer reoperations.

Methods

A cohort of ASBrS member surgeons prospectively entered data into the ASBrS Mastery^® registry on consecutive patients undergoing BCS in 2017. The association between tools and reoperations was estimated via multivariate and hierarchical ranking analyses.

Results

Seventy-one surgeons reported reoperations in 486 (12.3%) of 3954 cases (mean 12.7% [standard deviation (SD) 7.7%], median 11.5% [range 0–32%]). There was an eightfold difference between surgeons in the 10th and 90th percentile performance groups. Actionable factors associated with fewer reoperations included routine planned cavity side-wall shaves, surgeon use of ultrasound (US), neoadjuvant chemotherapy, intra-operative pathologic margin assessment, and use of a pre-operative diagnostic imaging modality beyond conventional 2D mammography. For patients with invasive cancer, ≥ 24% of those who underwent reexcision did so for reported margins of < 1 or 2 mm, representing noncompliance with the SSO-ASTRO margin guideline.

Conclusions

Although ASBrS member surgeons had some of the lowest rates of reoperation reported in any registry, significant intersurgeon variability persisted. Further efforts to lower rates are therefore warranted. Opportunities to do so were identified by adopting those processes of care, including improved compliance with the SSO-ASTRO margin guideline, which were associated with fewer reoperations.

     

A synthetic peptide targeting the BH4 domain of Bcl-2 induces apoptosis in multiple myeloma and follicular lymphoma cells alone or in combination with agents targeting the BH3-binding pocket of Bcl-2

Bcl-2 inhibits apoptosis by two distinct mechanisms but only one is targeted to treat Bcl-2-positive malignancies. In this mechanism, the BH1-3 domains of Bcl-2 form a hydrophobic pocket, binding and inhibiting pro-apoptotic proteins, including Bim. In the other mechanism, the BH4 domain mediates interaction of Bcl-2 with inositol 1,4, 5-trisphosphate receptors (IP₃Rs), inhibiting pro-apoptotic Ca²⁺ signals. The current anti-Bcl-2 agents, ABT-263 (Navitoclax) and ABT-199 (Venetoclax), induce apoptosis by displacing pro-apoptotic proteins from the hydrophobic pocket, but do not inhibit Bcl-2-IP₃R interaction. Therefore, to target this interaction we developed BIRD-2 (Bcl-2 IP₃ Receptor Disruptor-2), a decoy peptide that binds to the BH4 domain, blocking Bcl-2-IP₃R interaction and thus inducing Ca²⁺-mediated apoptosis in chronic lymphocytic leukemia, multiple myeloma, and follicular lymphoma cells, including cells resistant to ABT-263, ABT-199, or the Bruton’s tyrosine kinase inhibitor Ibrutinib. Moreover, combining BIRD-2 with ABT-263 or ABT-199 enhances apoptosis induction compared to single agent treatment. Overall, these findings provide strong rationale for developing novel therapeutic agents that mimic the action of BIRD-2 in targeting the BH4 domain of Bcl-2 and disrupting Bcl-2-IP₃R interaction.     

Intravenous methylprednisolone versus therapeutic plasma exchange for treatment of anti‐n‐methyl‐d‐aspartate receptor antibody encephalitis: A retrospective review

Introduction : Anti‐N‐methyl‐d ‐aspartate (NMDA) receptor antibody encephalitis is an increasingly recognized form of autoimmune encephalitis. Conventional treatments include therapies such as corticosteroids, intravenous immunoglobulin (IVIg), and/or therapeutic plasma exchange (TPE). Although TPE is regularly used for treatment of anti‐NMDA receptor antibody encephalitis, the American Society for Apheresis has given it a category III recommendation only. Earlier administered immunotherapies in tumor‐negative patients may facilitate faster recoveries, but it remains unclear whether or not TPE is superior to steroids and/or IVIG. Methods : We retrospectively evaluated 10 of 14 patients that received steroids and TPE with modified Rankin scores and subjectively assessed the point of largest sustained improvement in all 14 patients. Results : In the patients that received both steroids and TPE at our institution during the same hospitalization (only 10 of 14 patients), 7/10 patients after TPE had improved with the modified Rankin score versus 3/10 patients after steroids. The average modified Rankin score improvement after steroids in this group was ?0.1 as compared with 0.4 after TPE. Based on subjective chart review analysis during which all 14 patients were assessed, the largest sustained improvement occurred immediately following the third–fifth exchange in 9/14 patients, whereas only 2/14 patients appeared to have had significant benefit immediately following steroids. Conclusions : This is compelling preliminary data that suggests that corticosteroids may not be as effective compared to steroids followed by TPE. Given the importance of time‐sensitive treatment, more formal studies may illuminate the ideal first‐line treatment for anti‐NMDA receptor antibody encephalitis. J. Clin. Apheresis 30:212–216, 2015. © 2015 Wiley Periodicals, Inc.     

The abscopal effect: a sense of DNA damage is in the air

Tumor metastasis is a singularly important determinant of survival in most cancers. Historically, radiation therapy (RT) directed at a primary tumor mass was associated infrequently with remission of metastasis outside the field of irradiation. This away-from-target or “abscopal effect” received fringe attention because of its rarity. With the advent of immunotherapy, there are now increasing reports of abscopal effects upon RT in combination with immune checkpoint inhibition. This sparked investigation into underlying mechanisms and clinical trials aimed at enhancement of this effect. While these studies clearly attribute the abscopal effect to an antitumor immune response, the initial molecular triggers for its onset and specificity remain enigmatic. Here, we propose that DNA damage–induced inflammation coupled with neoantigen generation is essential during this intriguing phenomenon of systemic tumor regression and discuss the implications of this model for treatment aimed at triggering the abscopal effect in metastatic cancer.     

Sex- or Gender-specific Differences in the Clinical Presentation,Outcome, and Treatment of SARS-CoV-2

This review describes the sex and gender differences in COVID-19 presentation, treatment, and outcomes. We discuss the differences between the sexes in susceptibility to infection, the role of sex chromosomes on the body's immunologic response and the influence of hormones on the body's response to the virus. Additionally, the sex differences in clinical and laboratory presentation, complications of infection and outcomes, as well as differences in response to treatment and prevention are reviewed.     

Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

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