Mechanisms of thyrotropin receptor-mediated phenotype variability deciphered by gene mutations and M453T-knockin model.

The clinical spectrum of thyrotropin receptor-mediated (TSHR-mediated) diseases varies from loss-of-function mutations causing congenital hypothyroidism to constitutively active mutations (CAMs) leading to nonautoimmune hyperthyroidism (NAH). Variation at the TSHR locus has also been associated with altered lipid and bone metabolism and autoimmune thyroid diseases. However, the extrathyroidal roles of TSHR and the mechanisms underlying phenotypic variability among TSHR-mediated diseases remain unclear. Here we identified and characterized TSHR variants and factors involved in phenotypic variability in different patient cohorts, the FinnGen database, and a mouse model. TSHR CAMs were found in all 16 patients with NAH, with 1 CAM in an unexpected location in the extracellular leucine-rich repeat domain (p.S237N) and another in the transmembrane domain (p.I640V) in 2 families with distinct hyperthyroid phenotypes. In addition, screening of the FinnGen database revealed rare functional variants as well as distinct common noncoding TSHR SNPs significantly associated with thyroid phenotypes, but there was no other significant association between TSHR variants and more than 2,000 nonthyroid disease endpoints. Finally, our TSHR M453T-knockin model revealed that the phenotype was dependent on the mutation's signaling properties and was ameliorated by increased iodine intake. In summary, our data show that TSHR-mediated disease risk can be modified by variants at the TSHR locus both inside and outside the coding region as well as by altered TSHR-signaling and dietary iodine, supporting the need for personalized treatment strategies.

Utilization of machine learning to model the effect of blood product transfusion on short-term lung transplant outcomes.

The objective of this study was to identify the relationship between blood product transfusion and short-term morbidity and mortality following lung transplantation utilizing machine learning. Preoperative recipient characterstics, procedural variables, perioperative blood product transfusions, and donor charactersitics were included in the model. The primary composite outcome was occurrence on any of the following six endpoints: mortality during index hospitalization; primary graft dysfunction at 72 h post-transplant or the need for postoperative circulatory support; neurological complications (seizure, stroke, or major encephalopathy); perioperative acute coronary syndrome or cardiac arrest; and renal dysfunction requiring renal replacement therapy. The cohort included 369 patients, with the composite outcome occurring in 125 cases (33.9%). Elastic net regression analysis identified 11 significant predictors of composite morbidity: higher packed red blood cell, platelet, cryoprecipitate and plasma volume from the critical period, preoperative functional dependence, any preoperative blood transfusion, VV ECMO bridge to transplant, and antifibrinolytic therapy were associated with higher risk of morbidity. Preoperative steroids, taller height, and primary chest closure were protective against composite morbidity.

Intraoperative Hypoxia Independently Associated With the Development of Acute Kidney Injury Following Bilateral Orthotopic Lung Transplantation.

BACKGROUND: Acute kidney injury (AKI) is a common postoperative complication in bilateral orthotopic lung transplant (BOLTx) recipients, but the contribution of intraoperative variables is not well defined. The authors hypothesized that intraoperative hypotension as well as hypoxia and vasopressor use would be associated with the development of postoperative AKI after BOLTx in patients without pre-existing renal dysfunction. METHODS: The authors performed a retrospective analysis of patients undergoing BOLTx at a single center between 2013 and 2017. Intraoperative variables of hemodynamics included duration of mean arterial pressure <55, <60, and <65 mm Hg; duration of oxygen saturation <90%; and vasoactive-inotropic score (VIS). Associations between the occurrence of AKI and intraoperative hypotension, hypoxemia, and VIS were evaluated while controlling for significant confounding variables. RESULTS: AKI occurred in 177 (72%) of 245 patients in postoperative days 1-7. Notable significant differences in univariate analyses included cumulative mechanical support time, maximum VIS, peripheral oxygen saturation <90% for >15 min, total minutes oxygen saturation <90%, and surgery duration in minutes. There was no significant difference in intraoperative hypotension measured as a duration >15 min for mean arterial pressure <55, <60, or <65 mm Hg. Multivariate logistic regression revealed preoperative creatinine (Odds ratio [OR], 7.77; confidence interval [CI], 1.96-30.83; P = 0.004), surgery duration (OR, 1.004; CI, 1.002-1.007; P = 0.002), and oxygen saturation (OR, 2.06; CI, 1.01-4.24; P = 0.049) <90% for >15 min to be independently associated with AKI. CONCLUSIONS: This study revealed that >15 min of intraoperative hypoxia was independently associated with postoperative AKI after BOLTx.

The Year in Thoracic Anesthesia: Selected Highlights From 2020.

Selected highlights in thoracic anesthesia in 2020 include updates in the preoperative assessment and prehabilitation of patients undergoing thoracic surgery; updates in one-lung ventilation (OLV) pertaining to the devices used for OLV; the use of dexmedetomidine for lung protection during OLV and protective ventilation, recommendations for the care of thoracic surgical patients with coronavirus disease 2019; a review of recent meta-analyses comparing truncal blocks with paravertebral and thoracic epidural blocks; and a review of outcomes after initiating the enhanced recovery after surgery guidelines for lung and esophageal surgery.

The Year in Thoracic Anesthesia: Selected Highlights from 2019.

THIS special article is the 4th in an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief, Dr. Kaplan; the associate editor-in-chief, Dr. Augoustides; and the editorial board for the opportunity to expand this series, the research highlights of the year that specifically pertain to the specialty of thoracic anesthesia. The major themes selected for 2019 are outlined in this introduction, and each highlight is reviewed in detail in the main body of the article. The literature highlights in this specialty for 2019 include updates in the preoperative assessment and optimization of patients undergoing lung resection and esophagectomy, updates in one lung ventilation (OLV) and protective ventilation during OLV, a review of recent meta-analyses comparing truncal blocks with paravertebral catheters and the introduction of a new truncal block, meta-analyses comparing nonintubated video-assisted thoracoscopic surgery (VATS) with those performed using endotracheal intubation, a review of the Society of Thoracic Surgeons (STS) recent composite score rating for pulmonary resection of lung cancer, and an update of the Enhanced Recovery After Surgery (ERAS) guidelines for both lung and esophageal surgery.

Updated Retrospective Single-Center Comparative Analysis of Peripheral Nerve Block Complications Using Landmark Peripheral Nerve Stimulation Versus Ultrasound Guidance as a Primary Means of Nerve Localization.

OBJECTIVES: The purpose of this study was to perform an updated analysis of complications associated with upper and lower extremity peripheral nerve blocks (PNBs) performed with ultrasound (US) guidance versus the landmark approach. METHODS: We conducted a single-center retrospective cohort analysis to compare the incidence of PNB complications between the techniques. The primary outcome was local anesthetic systemic toxicity (LAST), whereas the secondary outcomes included short- and long-term nerve injuries. The current query included cases performed between 2012 and 2015. A combined analysis included data extending to 2006. The Statistical examination relied on the χ2 test. RESULTS: During this 4-year period, we performed 7789 US-guided and 498 landmark-guided blocks with no statistically significant difference in the incidence of nerve injury or LAST between the groups. Our 10-year analysis, however, revealed a significant increase (P < .01) in the rate of LAST with the landmark technique: 7 of 5932 versus 0 of 16,858 cases. The combined data also revealed a significant increase (P < .01) in short-term injuries associated with the landmark approach (30 of 5932 versus 33 of 16,858) but no significant difference in the incidence of long-term injuries. CONCLUSIONS: Our analysis supports a conclusion that the use of US guidance during PNBs leads to a significant reduction in the incidence of LAST, adding to growing evidence from similar investigations. The impact of US on the incidence of nerve injuries remains unclear, considering that the nature of transient deficits is thought to be multifactorial, and the frequency of lasting injuries did not differ significantly in this study.

Cost-effectiveness Analysis of Intraoperative Cell Salvage for Obstetric Hemorrhage.

BACKGROUND: Cost-effectiveness analyses on cell salvage for cesarean delivery to inform national and societal guidelines on obstetric blood management are lacking. This study examined the cost-effectiveness of cell salvage strategies in obstetric hemorrhage from a societal perspective. METHODS: Markov decision analysis modeling compared the cost-effectiveness of three strategies: use of cell salvage for every cesarean delivery, cell salvage use for high-risk cases, and no cell salvage. A societal perspective and lifetime horizon was assumed for the base case of a 26-yr-old primiparous woman presenting for cesarean delivery. Each strategy integrated probabilities of hemorrhage, hysterectomy, transfusion reactions, emergency procedures, and cell salvage utilization; utilities for quality of life; and costs at the societal level. One-way and Monte Carlo probabilistic sensitivity analyses were performed. A threshold of $100,000 per quality-adjusted life-year gained was used as a cost-effectiveness criterion. RESULTS: Cell salvage use for cases at high risk for hemorrhage was cost-effective (incremental cost-effectiveness ratio, $34,881 per quality-adjusted life-year gained). Routine cell salvage use for all cesarean deliveries was not cost-effective, costing $415,488 per quality-adjusted life-year gained. Results were not sensitive to individual variation of other model parameters. The probabilistic sensitivity analysis showed that at the $100,000 per quality-adjusted life-year gained threshold, there is more than 85% likelihood that cell salvage use for cases at high risk for hemorrhage is favorable. CONCLUSIONS: The use of cell salvage for cases at high risk for obstetric hemorrhage is economically reasonable; routine cell salvage use for all cesarean deliveries is not. These findings can inform the development of public policies such as guidelines on management of obstetric hemorrhage.

Impact of anesthesia on mortality during endovascular clot removal for acute ischemic stroke.

BACKGROUND: Endovascular clot retrieval is a technique available for removing intracranial arterial occlusions in acute ischemic stroke (AIS). This rescue therapy can be performed with moderate conscious sedation (CS) or general anesthesia (GA). The effect of GA on clinical outcome in AIS remains controversial. Therefore, we retrospectively investigated whether the use of CS or GA during endovascular intervention for AIS influenced outcomes. METHODS: Patients who underwent emergent endovascular intervention for intracranial arterial occlusion during the years 2006 to 2012 were included in this study. Statistical analysis using the Spearman ρ was performed to examine demographic data and clinical outcomes between patients in the GA and CS groups. Binary logistic regression was used to determine the predictors of mortality. RESULTS: A total of 109 patients fit the inclusion criteria. Among them, 35 patients had GA and 74 patients had CS. Patients needing intubation upon admission for airway protection were more likely to receive GA (P<0.001). The duration of the procedure and the time-to-revascularization from symptom onset were significantly longer in the GA group. Mortality was higher in the GA group compared with the CS group (40% vs. 22%, P=0.045). Multivariate analysis, controlled for confounding variables, identified GA and elevated postprocedure glucose level to be significant predictors of mortality. CONCLUSIONS: Larger prospectively randomized multicenter trials evaluating the effects of GA and CS on clinical and radiographic outcomes seems warranted.

Electroretinography during embolization of an ophthalmic arteriovenous fistula.

BACKGROUND: Intraoperative neuromonitoring (IONM) is used for real-time evaluation of neuronal tracts and reflexes in the anesthetized patient, when a neurologic exam is not possible. Changes in IONM signals forewarn of possible neurological deficit. This real-time feedback allows for immediate alterations in therapeutic technique by the treating physician. Transcranial visual evoked potentials are not reliable for evaluating the integrity of the prechiasmatic visual system. Electroretinography (ERG) has been used in animal models for monitoring retinal ischemia and can be used in humans as well to monitor for prechiasmatic ischemia of the retinae and optic nerves. CASE DESCRIPTION: We present a case where ERG signal amplitude and latency changed during ophthalmic arteriovenous fistula embolization, resulting in an intraprocedural decision to refrain from embolization of additional arterial pedicles to preserve vision. After awakening from general anesthesia, the patient had no deficits in visual acuity or field testing, but did complain of transient pain with eye movement that resolved the next day and worsened with episodes of blood pressure elevation. CONCLUSIONS: ERG may be helpful for detecting prechiasmatic ischemic changes during endovascular procedures and may provide early warning signs to the surgeon before the onset of permanent retinal damage. Further investigation is needed to assess the utility of ERG monitoring during the treatment of orbital and periorbital vascular lesions.