Evaluation of Analgesic Practice Changes Following the Nuss Procedure in Pediatric Patients.

INTRODUCTION: Pectus excavatum repair by the Nuss procedure results in severe postoperative pain. Regional blocks and intercostal nerve cryoablation (INC) have emerged as potential strategies to manage analgesia. This study compares pain-related outcomes following these perioperative interventions. METHODS: We reviewed charts of patients <18 y who underwent the Nuss procedure at Duke Children's Hospital from July 2018 to June 2022. Patients were divided into three groups by analgesic strategy: no block, regional catheters, or INC, representing the chronologic change in our practice. The primary outcome was total and daily in-hospital opioid utilization measured by oral morphine equivalents (OMEs). Secondary outcomes included average daily pain scores, length of stay, opioid refills after discharge, and complications. RESULTS: Twenty-one patients were included and analyzed: no block (n = 6), regional catheters (n = 7), and INC (n = 8). INC-treated patients required significantly lower total postoperative, in-hospital OMEs (64 ± 47 [mean ± standard deviation]) than those with no block (270 ± 217, P = 0.04) or those with regional catheters (273 ± 176, P = 0.03). INC was associated with longer average operative times (161 ± 36 min) than no block (105 ± 21 min, P = 0.005) or regional catheters (90 ± 11 min, P < 0.001). INC-treated patients had shorter hospital length of stays (median 68 h) than those with regional catheters (median 74 h, P = 0.006). CONCLUSIONS: INC was associated with longer operative times but decreased in-hospital OMEs when compared to bilateral regional block catheters and multimodal analgesia alone.

What are the barriers to training residents in aortic root surgery?

BACKGROUND AND AIM OF THE STUDY: Aortic root surgery is a technically demanding procedure that is performed infrequently by most surgeons, with national mortality rates over 10%. The study aim was to identify the barriers to training residents in this operation. METHODS: By using univariate and multivariate logistic regression analysis, all consecutive adults (n = 356) undergoing aortic root reconstruction at The Mount Sinai Medical Center between 2007 and 2011 were retrospectively compared according to whether a resident or faculty surgeon performed the procedure. Surveys were then conducted to determine reasons why residents did not perform cases, and to evaluate outcomes of aortic root surgery performed by recent graduates of the program. RESULTS: Surgical techniques among patients included: root replacement (81%, n = 290) using homograft, composite bioprosthetic or mechanical valved conduits; Ross procedures (17%, n = 53); and other root surgery such as valve-sparing procedures (2%, n = 7). Residents performed 32% (n = 66/204) of cases when they were scrubbed. The incidence of mortality was lower for cases performed by residents (2%, n = 2) compared to faculty (4%, n = 12) (p=0.335), and no significant differences in cardiopulmonary bypass or cross-clamp times, early morbidity or late survival were observed. The most common reasons given why scrubbed residents did not perform cases were a mismatch between the skill of the resident and case complexity (46%, n = 94), followed by the faculty surgeon's preference (41%, n = 83). Recent program graduates had collectively performed 30 aortic root procedures independently as faculty surgeons, and with no mortality; however, most expressed a continued preference for more senior help on such cases. CONCLUSION: Residents can safely perform aortic root surgery under appropriate supervision. The greatest challenge involved in improving resident training in aortic root surgery lies in routinely matching resident skills with case complexity and teaching expertise.

Does payer status impact clinical outcomes after cardiac surgery? A propensity analysis.

BACKGROUND: Medicaid patients bear proportionately greater financial responsibility for the cost of outpatient care and medication than non-Medicaid patients. We hypothesized that this difference in provision of continuing care would be associated with adverse clinical outcomes after cardiac surgery. MATERIALS AND METHODS: In a retrospective cohort analysis, 5056 consecutive adult patients undergoing cardiac surgery at a single institution between 2005 and 2010 were divided according to payer status. Propensity scores were calculated using 16 preoperative and demographic variables for each patient, and 461 1:1 propensity score-matched pairs were analyzed. Patient socioeconomic position was determined using aggregate data derived from zip codes. The main outcome measures were early mortality, postoperative complications, and patient survival. RESULTS: In multivariate analysis, Medicaid was found to be an independent predictor of worse survival after cardiac surgery (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.2-3.7; P = .01). No significant difference was observed in operative mortality in the 2 groups. After propensity score matching and controlling for socioeconomic position, the only independent predictors of worse midterm survival were an ejection fraction = 30% (HR, 1.7; 95% CI, 1.1-2.7; P = .02) and a higher logistic EuroSCORE (HR, 1.03; 95% CI, 1.0-1.1; P = .02). CONCLUSIONS: Comorbidity and lower socioeconomic status appear to be more important predictors of late mortality after cardiac surgery than payer status, which does not have a significant impact on survival.

Exosomes mediate sensory hair cell protection in the inner ear.

Hair cells, the mechanosensory receptors of the inner ear, are responsible for hearing and balance. Hair cell death and consequent hearing loss are common results of treatment with ototoxic drugs, including the widely used aminoglycoside antibiotics. Induction of heat shock proteins (HSPs) confers protection against aminoglycoside-induced hair cell death via paracrine signaling that requires extracellular heat shock 70-kDa protein (HSP70). We investigated the mechanisms underlying this non-cell-autonomous protective signaling in the inner ear. In response to heat stress, inner ear tissue releases exosomes that carry HSP70 in addition to canonical exosome markers and other proteins. Isolated exosomes from heat-shocked utricles were sufficient to improve survival of hair cells exposed to the aminoglycoside antibiotic neomycin, whereas inhibition or depletion of exosomes from the extracellular environment abolished the protective effect of heat shock. Hair cell-specific expression of the known HSP70 receptor TLR4 was required for the protective effect of exosomes, and exosomal HSP70 interacted with TLR4 on hair cells. Our results indicate that exosomes are a previously undescribed mechanism of intercellular communication in the inner ear that can mediate nonautonomous hair cell survival. Exosomes may hold potential as nanocarriers for delivery of therapeutics against hearing loss.

Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines.

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Cisplatin is retained in the cochlea indefinitely following chemotherapy.

Cisplatin chemotherapy causes permanent hearing loss in 40-80% of treated patients. It is unclear whether the cochlea has unique sensitivity to cisplatin or is exposed to higher levels of the drug. Here we use inductively coupled plasma mass spectrometry (ICP-MS) to examine cisplatin pharmacokinetics in the cochleae of mice and humans. In most organs cisplatin is detected within one hour after injection, and is eliminated over the following days to weeks. In contrast, the cochlea retains cisplatin for months to years after treatment in both mice and humans. Using laser ablation coupled to ICP-MS, we map cisplatin distribution within the human cochlea. Cisplatin accumulation is consistently high in the stria vascularis, the region of the cochlea that maintains the ionic composition of endolymph. Our results demonstrate long-term retention of cisplatin in the human cochlea, and they point to the stria vascularis as an important therapeutic target for preventing cisplatin ototoxicity.