Utilization Patterns of Perioperative Neuromuscular Blockade Reversal in the United States: A Retrospective Observational Study From the Multicenter Perioperative Outcomes Group.

BACKGROUND: Following the introduction of sugammadex to the US clinical practice, scarce data are available to understand its utilization patterns. This study aimed to characterize patient, procedure, and provider factors associated with sugammadex administration in US patients. METHODS: This retrospective observational study was conducted across 24 Multicenter Perioperative Outcomes Group institutions in the United States with sugammadex on formulary at the time of the study. All American Society of Anesthesiologists (ASA) physical status I-IV adults undergoing noncardiac surgery from 2014 to 2018 receiving neuromuscular blockade (NMB) were eligible. The study established 3 periods based on the date of first documented sugammadex use at each institution: the presugammadex period, 0- to 6-month transitional period, and 6+ months postsugammadex period. The primary outcome was reversal using sugammadex during the postsugammadex period-defined as 6 months after sugammadex was first utilized at each institution. A multivariable mixed-effects logistic regression model controlling for institution was developed to assess patient, procedure, and provider factors associated with sugammadex administration. RESULTS: A total of 934,798 cases met inclusion criteria. Following the 6-month transitional period, sugammadex was used on average in 40.0% (95% confidence interval [CI], 39.8-40.2) of cases receiving NMB. Multivariable analysis demonstrated sugammadex use to be associated with train-of-four count of 0-1 (adjusted odds ratio = 4.06; 95% CI, 33.83-4.31) or 2 (2.45; 2.29-2.62) vs 3-4 twitches before reversal; the amount of NMB administered (3.01; 2.88-3.16) for the highest effective dose 95 quartile compared to the lowest quartile; advanced age (1.83; 1.71-1.95) compared to age <41; male sex (1.36; 1.32-1.39) compared to female sex; major thoracic surgery (1.26; 1.13-1.39); congestive heart failure (1.17, 1.07-1.28); and ASA III or IV (1.13; 1.10-1.16) versus ASA I or II. CONCLUSIONS: Our data demonstrate broad early clinical adoption of sugammadex following Food and Drug Administration approval. Sugammadex is used preferentially in cases with higher degrees of NMB before reversal and in patients with greater burden of comorbidities and known risk factors for residual blockade or pulmonary complications.

Considerations for Integration of Perioperative Electronic Health Records Across Institutions for Research and Quality Improvement: The Approach Taken by the Multicenter Perioperative Outcomes Group.

Use of the electronic health record (EHR) has become a routine part of perioperative care in the United States. Secondary use of EHR data includes research, quality, and educational initiatives. Fundamental to secondary use is a framework to ensure fidelity, transparency, and completeness of the source data. In developing this framework, competing priorities must be considered as to which data sources are used and how data are organized and incorporated into a useable format. In assembling perioperative data from diverse institutions across the United States and Europe, the Multicenter Perioperative Outcomes Group (MPOG) has developed methods to support such a framework. This special article outlines how MPOG has approached considerations of data structure, validation, and accessibility to support multicenter integration of perioperative EHRs. In this multicenter practice registry, MPOG has developed processes to extract data from the perioperative EHR; transform data into a standardized format; and validate, deidentify, and transfer data to a secure central Coordinating Center database. Participating institutions may obtain access to this central database, governed by quality and research committees, to inform clinical practice and contribute to the scientific and clinical communities. Through a rigorous and standardized approach to ensure data integrity, MPOG enables data to be usable for quality improvement and advancing scientific knowledge. As of March 2019, our collaboration of 46 hospitals has accrued 10.7 million anesthesia records with associated perioperative EHR data across heterogeneous vendors. Facilitated by MPOG, each site retains access to a local repository containing all site-specific perioperative data, distinct from source EHRs and readily available for local research, quality, and educational initiatives. Through committee approval processes, investigators at participating sites may additionally access multicenter data for similar initiatives. Emerging from this work are 4 considerations that our group has prioritized to improve data quality: (1) data should be available at the local level before Coordinating Center transfer; (2) data should be rigorously validated against standardized metrics before use; (3) data should be curated into computable phenotypes that are easily accessible; and (4) data should be collected for both research and quality improvement purposes because these complementary goals bolster the strength of each endeavor.

Predictors of operative failure in parathyroidectomy for primary hyperparathyroidism.

INTRODUCTION: Many adjuncts guide surgical decision making in parathyroidectomy, yet their independent associations with outcome are poorly characterized. We examined a broad range of perioperative factors and used multivariate techniques to identify independent predictors of operative failure (persistent disease) after parathyroidectomy. METHODS: This was a retrospective review of 2239 patients with primary hyperparathyroidism who underwent parathyroidectomy at a single-center from 1999 to 2014. We used multivariate logistic regress to measure associations between multiple perioperative factors and an operative failure (persistent hypercalcemia). RESULTS: Operative failure was identified in 67 patients (3.0%). The following variables were independently associated with operative failure on multivariate analysis: IOPTH criteria met (protective, OR = 0.22, P < 0.001), preoperative calcium (risk factor, OR = 2.27 per unit increase, P < 0.001), weight of excised gland(s) (protective, OR = 0.70 per two-fold increase, P = 0.003), and preoperative PTH (protective, OR = 0.55 per two-fold increase, P = 0.008). CONCLUSION: In addition to the well-established IOPTH criteria, we suggest that consideration of the above independent perioperative risk factors may further inform surgical decision-making in parathyroidectomy.

Long-Term Outcomes of Kidney Transplant Recipients with Bladder Dysfunction: A Single-Center Study.

BACKGROUND: Long-term outcomes of kidney transplantation recipients with bladder dysfunction or prior bladder surgery are not well characterized. MATERIAL AND METHODS: Electronic records of 1753 recipients of kidney-alone transplant between January 2000 and December 2008 were reviewed. We found that 1652 recipients had normal bladder function, 80 had bladder dysfunction, and 21 had bladder substitute or urinary diversion. Kaplan-Meier survival curves and multivariable regression modeling were performed to determine survival outcomes. RESULTS: Kaplan-Meier graft survival (p=.11) and patient survival (p=.18) were lower in recipients with bladder surgery but not statistically significant. Multivariate analysis demonstrated inferior graft survival (HR 3.57, 95% CI 1.06-12.1, p =0.04) and a trend towards inferior patient survival (HR 3.19, 95% CI .71-14.5, p=0.13) in reci-pients with bladder surgery. The major cause of graft failure was chronic rejection for normal function (17.1%) and bladder dysfunction (28.5%), and infection for bladder surgery (28.5%). Post-operative urinary infectious and surgical complications were higher in recipients with bladder dysfunction (35%) and substitutes (52.3%) compared with normal function (12.8%). CONCLUSIONS: Kidney transplant recipients with prior bladder surgery have an increased risk of graft failure and an increased risk of infectious urinary complications. These risks should be considered in recipient selection and post-transplant management.

Preconception counseling, fertility, and pregnancy complications after abdominal organ transplantation: a survey and cohort study of 532 recipients.

BACKGROUND: Pregnancy after solid organ transplant is a significant priority for transplant recipients but how patients report being counseled is unknown. METHODS: We performed a single-center retrospective cohort study and telephone survey of female patients ages 18-49 at the time of kidney, pancreas, or liver transplant from 2000 to 2012 (n = 532). Data on pregnancy counseling, fertility, and maternal, fetal- and transplant-specific outcomes were collected. Multivariate Cox models assessed the impact of pregnancy on graft-specific outcomes. RESULTS: The survey response rate was 29% (n = 152). One-third (n = 51) of women were actively counseled against pregnancy by one or more providers. A total of 17 pregnancies occurred among nine patients (5.9%), with 47% live births, 47% early embryonic demises, 5.9% stillbirths. Of live births, 50% were premature. Gestational complications, including diabetes, hypertension, and preeclampsia were present in 88% of mothers. Pregnancy after transplant was associated with higher rates of acute rejection than nulliparous transplant recipients (33% vs. 5.6%, p = 0.07) but did not significantly affect graft survival (HR = 1.00, 95% CI 0.99-1.01), after stratifying by organ and adjusting for clinical factors. CONCLUSION: This study suggests that transplant patients are being counseled against pregnancy despite acceptable risks of complications and no specific effects on long-term graft function.

Neddylation plays an important role in the regulation of murine and human dendritic cell function.

Posttranslational protein modifications (PTMs) are necessary for cells to function properly. The role of PTMs in regulating immune responses, specifically those mediated by dendritic cells (DCs), which are critical for both innate and adaptive immunity, is not well understood. Utilizing multiple but complementary approaches, we determined the role of an important but less understood type of PTM, namely, neddylation, in regulating DC functions. Inhibition of neddylation suppressed the release of proinflammatory cytokines by DCs in response to Toll-like receptor, nucleotide oligomerization domain-like receptor, and noninfectious CD40L stimulation. These effects were more profound than those mediated by the proteasome inhibitor bortezomib or a commonly used antiinflammatory agent, dexamethasone. Targeting neddylation also suppressed the ability of DCs to stimulate murine allogeneic T cells in vitro and in vivo and human allogeneic T-cell responses in vitro. Mechanistic studies demonstrated that inhibition of neddylation reduced both canonical and noncanonical nuclear factor-κB (NF-κB) activity. Neddylation inhibition prevented the degradation of inhibitor-κB and thus reduced the translocation and activation of NF-κB, but without perturbation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Thus, blocking neddylation could be a novel strategy for mitigating immune-mediated disease processes.