Whole Blood Resuscitation for Injured Patients Requiring Transfusion: A Systematic Review, Meta-Analysis, and Practice Management Guideline from the Eastern Association for the Surgery of Trauma.

INTRODUCTION: Whole blood resuscitation has reemerged as a resuscitation strategy for injured patients. However, the effect of whole blood-based resuscitation on outcomes has not been established. The primary objective of this guideline was to develop evidence-based recommendations on whether whole blood should be considered in civilian trauma patients receiving blood transfusions. METHODS: An EAST working group performed a systematic review and meta-analysis utilizing the GRADE methodology. One PICO question was developed to analyze the effect of whole blood resuscitation in the acute phase on mortality, transfusion requirements, infectious complications, and ICU length of stay. English language studies including adult civilian trauma patients comparing in-hospital whole blood to component therapy were included. Medline, Embase, Cochrane CENTRAL, CINAHL Plus, and Web of Science were queried. GRADEpro was used to assess quality of evidence and risk of bias. The study was registered on PROSPERO (#CRD42023451143). RESULTS: A total of 21 studies were included. Most patients were severely injured and required blood transfusion, massive transfusion protocol activation, and/or a hemorrhage control procedure in the early phase of resuscitation. Mortality was assessed separately at the following intervals: early (i.e., ED, 3-, or 6-hour), 24-hour, late (i.e., 28- or 30-day), and in-hospital. On meta-analysis, whole blood was not associated with decreased mortality. Whole blood was associated with decreased 4-hour RBC (mean difference -1.82, 95% CI -3.12 to -0.52), 4-hour plasma (mean difference -1.47, 95% CI -2.94 to 0), and 24-hour RBC transfusions (mean difference -1.22, 95% CI -2.24 to -0.19) compared to component therapy. There were no differences in infectious complications or ICU length of stay between groups. CONCLUSION: We conditionally recommend WB resuscitation in adult civilian trauma patients receiving blood transfusions, recognizing that data are limited for certain populations, including women of childbearing age, and therefore this guideline may not apply to these populations. LEVEL OF EVIDENCE: Level III, Guidelines.

Genotype-Phenotype Correlations in TMPRSS3 (DFNB10/DFNB8) with Emphasis on Natural History.

BACKGROUND: Mutations in TMPRSS3 are an important cause of autosomal recessive non-syndromic hearing loss. The hearing loss associated with mutations in TMPRSS3 is characterized by phenotypic heterogeneity, ranging from mild to profound hearing loss, and is generally progressive. Clinical presentation and natural history of TMPRSS3 mutations vary significantly based on the location and type of mutation in the gene. Understanding these genotype-phenotype relationships and associated natural disease histories is necessary for the successful development and application of gene-based therapies and precision medicine approaches to DFNB8/10. The heterogeneous presentation of TMPRSS3-associated disease makes it difficult to identify patients clinically. As the body of literature on TMPRSS3-associated deafness grows, there is need for better categorization of the hearing phenotypes associated with specific mutations in the gene. SUMMARY: In this review, we summarize TMPRSS3 genotype-phenotype relationships including a thorough description of the natural history of patients with TMPRSS3-associated hearing loss to lay the groundwork for the future of TMPRSS3 treatment using molecular therapy. KEY MESSAGES: TMPRSS3 mutation is a significant cause of genetic hearing loss. All patients with TMPRSS3 mutation display severe-to-profound prelingual (DFNB10) or a postlingual (DFNB8) progressive sensorineural hearing loss. Importantly, TMPRSS3 mutations have not been associated with middle ear or vestibular deficits. The c.916G>A (p.Ala306Thr) missense mutation is the most frequently reported mutation across populations and should be further explored as a target for molecular therapy.

Effect of a pulmonary embolism response team on the management and outcomes of patients with acute pulmonary embolism.

OBJECTIVE: We aimed to evaluate the effects of a multidisciplinary pulmonary embolism (PE) response team (PERT) on the management and outcomes of patients with acute PE. METHODS: We retrospectively reviewed all patients presenting to our institution with a diagnosis of PE from July 2020 to April 2022. The primary outcome measures were in-hospital mortality, major bleeding events defined by the International Society on Thrombosis and Haemostasis, and use of catheter-directed interventions (CDIs). The secondary outcome measures included 30-day and 12-month mortality, hospital and intensive care unit (ICU) lengths of stay, vasopressor requirement, and cardiac arrest. Continuous variables were assessed using the Mann-Whitney U test and categorical variables using the χ2 or Fisher exact test, as appropriate. RESULTS: A total of 279 patients with acute PE were identified, of whom 79 (28%), 173 (62%), and 27 (10%) were considered to have low risk, intermediate risk, and high risk, respectively. The PERT was activated for 133 patients (47.7%). Saddle and main pulmonary artery embolisms (P < .001), right ventricular strain (P= .001), right ventricular dysfunction (P < .001), coexisting deep vein thrombosis (P < .001), and dyspnea as a presenting symptom (P = .008) were significantly associated with PERT activation. Patients evaluated by the PERT were more likely to undergo CDI (49% vs 27%; P < .001) across all risk groups and less likely to have an inferior vena cava filter placed (1% vs 5%; P = .04). PERT consultation showed numerical, but nonstatistically significant, trends toward reduced in-hospital (2% vs 5%; P = .2) and 30-day (2% vs 8%; P = .06) mortality but similar rates of 12-month mortality (7% vs 8%; P = .7). PERT activation was also associated with a trend toward reduced rates of major bleeding (2% vs 7%), cardiac arrest (2% vs 7%), and vasopressor requirement (9% vs 18%). PERT consultations decreased the median number of ICU days by one half; however, we did not observe any differences in the total hospital length of stay between the groups. CONCLUSIONS: At our institution, PERT consultations were associated with significantly higher usage of CDIs and improved clinical outcomes, including reduced mortality and a lower rate of major bleeding events. PERT consultations were also associated with fewer ICU days, suggesting a possible economic benefit for implementing PERTs, although further research is needed to confirm that conclusion.

Advanced Management of Severe Keloids.

Keloids negatively impact the health and quality of life of many affected dermatologic patients. Treating keloids is often difficult, and suboptimal responses are frequent. Fortunately, there are many treatment options available to the clinician that may lead to improved clinical outcomes. We present a review of currently available therapeutic options. Intralesional steroid injection remains the first-line treatment for keloids. Imiquimod, direct interferon therapy, or intralesional 5-flurouracil may alleviate the need for excessive corticosteroid therapy. Radiation and laser therapy are emerging therapeutic options that have demonstrated efficacy in reviewed studies. Given the unsatisfactory outcomes associated with pressure dressings, vitamin E, ablative laser, and surgical excision, these options should be avoided in keloid management. Further research is needed to evaluate the efficacy and recurrence associated with the reviewed therapeutics.