Birth in the Operating Room for Immediate Cardiac Surgery: A Rare but Effective Strategy.

Background: With significant advancements in fetal cardiac imaging, patients with complex congenital heart disease (CHD) carrying a high risk for postnatal demise are now being diagnosed earlier. We sought to assess an interdisciplinary strategy for delivering these children in an operating room (OR) adjacent to a cardiac OR for immediate surgery or stabilization. Methods: All children prenatally diagnosed with CHD at risk for immediate postnatal hemodynamic instability and cardiogenic shock who were delivered in the operating room (OR) between 2012 and 2023 in which the senior author was consulted were included. Results: Eight patients were identified. Six (75%) patients were operated on day-of-life zero, all requiring obstructed total anomalous pulmonary venous return (TAPVR) repair. Of these six patients, 2 (33%) required a simultaneous Norwood procedure, 2 (33%) required pulmonary artery unifocalization and modified Blalock-Taussig-Thomas shunt, and 2 (33%) patients had repair of obstructed mixed TAPVR. The remaining 2 patients potentially planned for immediate surgery had nonimmune hydrops fetalis and went into cardiogenic shock at 12 and 72 hours postnatally, requiring a novel Norwood procedure with left-ventricular exclusion for severe aortic/mitral valve insufficiency. The median ventilation and inpatient durations were 19 [IQR: 11-26] days and 41 [IQR: 32-128] days, respectively. Three(38%) patients required one or more in-hospital reoperations. Subsequent staged procedures included Glenn (n = 5), Fontan (n = 3), biventricular repair (n = 2), ventricular assist device placement (n = 1), and heart transplant (n = 1). Median follow-up was 5.7 [IQR:1.3-7.8] years. The five-year postoperative survival was 88% (n = 7/8). Conclusion: While children with these diagnoses have historically had poor survival, the strategy of birth in the OR adjacent to a cardiac OR where emergent surgery is planned is a potentially promising strategy with excellent clinical outcomes. However, this is a high-resource strategy whose feasibility in any program requires thoughtful assessment.

Outcomes in Children Who Undergo Post-cardiotomy ECMO: A Report from the STS-CHSD.

BACKGROUND: Children who undergo cardiac surgery may require post-cardiotomy extracorporeal membrane oxygenation (ECMO). Although morbidities are considerable, our understanding of outcome determinants is limited. We evaluated associations between patient and peri-operative factors with outcomes. METHODS: The STS Congenital Heart Surgery Database was queried for patients <18yo who underwent post-cardiotomy ECMO from 1/2016-6/2021. PRIMARY OUTCOME: survival to hospital discharge. SECONDARY OUTCOME: survival without neurologic injury. Logistic regression for binary outcomes and competing risk analysis for survival were used to identify the most important predictors. Variables were selected by stepwise procedure using entry level p=0.35. Those with p≤0.1 were kept in the final model. RESULTS: A total of 3,181 patients were supported with post-cardiotomy ECMO during the same hospitalization as cardiac surgery: (A) intra-operative initiation of ECMO, n=1206; (B) early post-operative (≤48 hours), n=936; (C) late post-operative (>48 hours), n=1039. Most common primary procedure of index operation was the Norwood procedure. 57% intra-op survived to discharge, versus 59% early post-op and 42% late post-op group (χ2 (2) = 64, p<0.0001, V = 0.14). In all groups, post-op septicemia, cardiac arrest, and new neurologic injury had the strongest association with mortality, while post-operative reintubation and unplanned non-cardiac reoperation were associated with higher survival. CONCLUSIONS: Multiple risk factors impact survival in children who undergo cardiac surgery and post-cardiotomy ECMO. ECMO initiated >48 hours after surgery is associated with the poorest outcomes. This is the first step in creating a predictive tool to educate clinicians and families regarding expectations in this high-risk population.

Kinetics of Renin Concentrations in Infants Undergoing Congenital Cardiac Surgery.

BACKGROUND: Elevated renin has been shown to predict poor response to standard vasoactive therapies and is associated with poor outcomes in adults. Similarly, elevated renin was associated with mortality in children with septic shock. Renin concentration profiles after pediatric cardiac surgery are unknown. The purpose of this study was to characterize renin kinetics after pediatric cardiac surgery. METHODS: Single-center retrospective study of infants who underwent cardiac surgery with cardiopulmonary bypass (CPB) utilizing serum samples obtained in the perioperative period to measure plasma renin concentrations (pg/mL). Time points included pre-bypass and 1, 4, and 24 h after initiation of CPB. RESULTS: Fifty patients (65% male) with a median age 5 months (interquartile range (IQR) 3.5, 6.5) were included. Renin concentrations peaked 4 h after CPB. There was a significant difference in preoperative and 4 h post-CPB renin concentration (4 h post-CPB vs preoperative: mean difference 100.6, 95% confidence interval (CI) 48.9-152.4, P < .001). Median renin concentration at 24 h after CPB was lower than the preoperative baseline. CONCLUSIONS: We describe renin kinetics in infants after CPB. Future studies based on these data can now be performed to evaluate the associations of elevated renin concentrations with adverse outcomes.

An evaluation of the outcomes associated with peritoneal catheter use in neonates undergoing cardiac surgery: A multicenter study.

Objective: The study objective was to determine if intraoperative peritoneal catheter placement is associated with improved outcomes in neonates undergoing high-risk cardiac surgery with cardiopulmonary bypass. Methods: This propensity score-matched retrospective study used data from 22 academic pediatric cardiac intensive care units. Consecutive neonates undergoing Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 3 to 5 cardiac surgery with cardiopulmonary bypass at centers participating in the NEonatal and Pediatric Heart Renal Outcomes Network collaborative were studied to determine the association of the use of an intraoperative placed peritoneal catheter for dialysis or passive drainage with clinical outcomes, including the duration of mechanical ventilation. Results: Among 1490 eligible neonates in the NEonatal and Pediatric Heart Renal Outcomes Network dataset, a propensity-matched analysis was used to compare 395 patients with peritoneal catheter placement with 628 patients without peritoneal catheter placement. Time to extubation and most clinical outcomes were similar. Postoperative length of stay was 5 days longer in the peritoneal catheter placement cohort (17 vs 22 days, P = .001). There was a 50% higher incidence of moderate to severe acute kidney injury in the no-peritoneal catheter cohort (12% vs 18%, P = .02). Subgroup analyses between specific treatments and in highest risk patients yielded similar associations. Conclusions: This study does not demonstrate improved outcomes among neonates with placement of a peritoneal catheter during cardiac surgery. Outcomes were similar apart from longer hospital stay in the peritoneal catheter cohort. The no-peritoneal catheter cohort had a 50% higher incidence of moderate to severe acute kidney injury (12% vs 18%). This analysis does not support indiscriminate peritoneal catheter use, although it may support the utility for postoperative fluid removal among neonates at risk for acute kidney injury. A multicenter controlled trial may better elucidate peritoneal catheter effects.

A 2023 International Survey of Clinical Practice Patterns in the Management of Graves' Disease: A Decade of Change.

CONTEXT: Over the past several decades, there have been indications of potential shifts in the diagnostic strategies, treatment, and monitoring of patients with Graves´ disease (GD). OBJECTIVE: To evaluate current practices in managing GD and compare them to previous surveys. DESIGN: We used a global survey of endocrinologists to assess diagnosis, monitoring and treatment in a typical patient with GD, as well as treatment variation in five different clinical scenarios. SETTING: Online survey. PARTICIPANTS: Members of various endocrine societies worldwide. INTERVENTION: None. MAIN OUTCOME: Shifts in the management of GD. RESULTS: 1252 respondents from 85 countries completed the survey. Methods used to diagnose an uncomplicated GD case have changed over the past decade, reflecting increased use of TRAb and reciprocal decreases in nuclear medicine studies. The preferred mode of therapy for uncomplicated GD was antithyroid drugs (ATDs) by 91.5% of respondents, radioactive iodine (RAI) therapy by 7%, and thyroidectomy by 1.5%. Compared with previous surveys, the use of RAI as a first-line choice decreased in all geographic regions. The U.S. had the sharpest decline in the selection of initial therapy with RAI, decreasing from 69% in 1990 to 11.1% in 2023. In patients with persistent TRAb positivity after 18 months, 68.7% of respondents would continue the use of ATDs. After a relapse of GD, resumption of ATDs was selected by 59.9% of respondents. In patients with active TED or planning pregnancy, ATDs were the first choice (67.5% and 72.8%, respectively), and thyroidectomy emerged as the second choice (22.9% and 15.6%, respectively). CONCLUSIONS: Paradigm shifts have occurred in the management of uncomplicated GD and its variants, as well as the response to persistent and recurrent hyperthyroidism.

Contemporary Trends in Cardiac Surgical Care for Trisomy 13 and 18 Patients Admitted to Hospitals in the United States.

OBJECTIVE: To assess rates of cardiac surgery and the clinical and demographic features that influence surgical vs nonsurgical treatment of congenital heart disease (CHD) in patients with trisomy 13 (T13) and trisomy 18 (T18) in the United States. STUDY DESIGN: A retrospective study was performed using the Pediatric Health Information System. All hospital admissions of children (<18 years of age) with T13 and T18 in the United States were identified from 2003 through 2022. International Classifications of Disease (ICD) codes were used to identify presence of CHD, extracardiac comorbidities/malformations, and performance of cardiac surgery. RESULTS: Seven thousand one hundred thirteen patients were identified. CHD was present in 62% (1625/2610) of patients with T13 and 73% (3288/4503) of patients with T18. The most common CHD morphologies were isolated atrial/ventricular septal defects (T13 40%, T18 42%) and aortic hypoplasia/coarctation (T13 21%, T18 23%). Single-ventricle morphologies comprised 6% (100/1625) of the T13 and 5% (167/3288) of the T18 CHD cohorts. Surgery was performed in 12% of patients with T13 plus CHD and 17% of patients with T18 plus CHD. For all cardiac diagnoses, <50% of patients received surgery. Nonsurgical patients were more likely to be born prematurely (P < .05 for T13 and T18). The number of extracardiac comorbidities was similar between surgical/nonsurgical patients with T13 (median 2 vs 2, P = .215) and greater in surgical vs nonsurgical patients with T18 (median 3 vs 2, P < .001). Hospital mortality was <10% for both surgical cohorts. CONCLUSIONS: Patients with T13 or T18 and CHD receive surgical palliation, but at a low prevalence (≤17%) nationally. Given operative mortality <10%, opportunity exists perhaps for quality improvement in the performance of cardiac surgery for these vulnerable patient populations.

Hyperthyroidism.

Thyrotoxicosis causes a variety of symptoms and adverse health outcomes. Hyperthyroidism refers to increased thyroid hormone synthesis and secretion, most commonly from Graves' disease or toxic nodular goitre, whereas thyroiditis (typically autoimmune, viral, or drug induced) causes thyrotoxicosis without hyperthyroidism. The diagnosis is based on suppressed serum concentrations of thyroid-stimulating hormone (TSH), accompanied by free thyroxine and total or free tri-iodothyronine concentrations, which are raised (overt hyperthyroidism) or within range (subclinical hyperthyroidism). The underlying cause is determined by clinical assessment, detection of TSH-receptor antibodies and, if necessary, radionuclide thyroid scintigraphy. Treatment options for hyperthyroidism include antithyroid drugs, radioactive iodine, and thyroidectomy, whereas thyroiditis is managed symptomatically or with glucocorticoid therapy. In Graves' disease, first-line treatment is a 12-18-month course of antithyroid drugs, whereas for goitre, radioactive iodine or surgery are preferred for toxic nodules or goitres. Evidence also supports long-term treatment with antithyroid drugs as an option for patients with Graves' disease and toxic nodular goitre.

Thyroiditis After Parathyroidectomy.

Various clinical manifestations of thyroiditis after parathyroidectomy have been reported in the literature, ranging from mild symptoms to tachyarrhythmias and myocardial infarction. We report 2 cases of post-parathyroidectomy thyroiditis. Both patients had primary hyperparathyroidism and underwent parathyroidectomy for a solitary parathyroid adenoma. They subsequently developed symptoms of hyperthyroidism, including palpitations and heat intolerance. Laboratory investigations demonstrated a suppressed TSH level with elevated free T4 levels and low uptake on thyroid radioiodine scan, confirming the diagnosis of thyroiditis. The patients were managed conservatively, and their symptoms gradually resolved with normalization of thyroid hormone levels. A review of 27 cases reported to date reveals that this condition is mostly attributed to manipulation of the thyroid during parathyroid surgery. It occurs more frequently in patients who undergo 4-gland parathyroidectomy for secondary or tertiary hyperthyroidism and is self-limited within a few weeks. The case reports highlight the importance of recognizing thyroiditis as a potentially underrecognized complication of parathyroid surgery. Further research is warranted to better understand the underlying pathophysiology and to establish potential risk factors for its development post-parathyroidectomy.

Utility of a pharmacist-managed Anticoagulation Program in patients with congenital heart disease.

BACKGROUND: Warfarin remains the preferred anticoagulant for many patients with CHD. The complexity of management led our centre to shift from a nurse-physician-managed model with many providers to a pharmacist-managed model with a centralized anticoagulation team. We aim to describe the patient cohort managed by our Anticoagulation Program and evaluate the impact of implementation of this consistent, pharmacist-managed model on time in therapeutic range, an evidence-based marker for clinical outcomes. METHODS: A single-centre retrospective cohort study was conducted to evaluate the impact of the transition to a pharmacist-managed model to improve anticoagulation management at a tertiary pediatric heart centre. The percent time in therapeutic range for a cohort managed by both models was compared using a paired t-test. Patient characteristics and time in therapeutic range of the program were also described. RESULTS: After implementing the pharmacist-managed model, the time in therapeutic range for a cohort of 58 patients increased from 65.7 to 80.2% (p < .001), and our Anticoagulation Program consistently maintained this improvement from 2013 to 2022. The cohort of patients managed by the Anticoagulation Program in 2022 included 119 patients with a median age of 24 years (range 19 months-69 years) with the most common indication for warfarin being mechanical valve replacement (n = 81, 68%). CONCLUSIONS: Through a practice change incorporating a collaborative, centralized, pharmacist-managed model, this cohort of CHD patients on warfarin had a fifteen percent increase in time in therapeutic range, which was sustained for nine years.

Peritoneal catheters in neonates undergoing complex cardiac surgery: a multi-centre descriptive study.

BACKGROUND: The use of peritoneal catheters for prophylactic dialysis or drainage to prevent fluid overload after neonatal cardiac surgery is common in some centres; however, the multi-centre variability and details of peritoneal catheter use are not well described. METHODS: Twenty-two-centre NEonatal and Pediatric Heart Renal Outcomes Network (NEPHRON) study to describe multi-centre peritoneal catheter use after STAT category 3-5 neonatal cardiac surgery using cardiopulmonary bypass. Patient characteristics and acute kidney injury/fluid outcomes for six post-operative days are described among three cohorts: peritoneal catheter with dialysis, peritoneal catheter with passive drainage, and no peritoneal catheter. RESULTS: Of 1490 neonates, 471 (32%) had an intraoperative peritoneal catheter placed; 177 (12%) received prophylactic dialysis and 294 (20%) received passive drainage. Sixteen (73%) centres used peritoneal catheter at some frequency, including six centres in >50% of neonates. Four centres utilised prophylactic peritoneal dialysis. Time to post-operative dialysis initiation was 3 hours [1, 5] with the duration of 56 hours [37, 90]; passive drainage cohort drained for 92 hours [64, 163]. Peritoneal catheter were more common among patients receiving pre-operative mechanical ventilation, single ventricle physiology, and higher complexity surgery. There was no association with adverse events. Serum creatinine and daily fluid balance were not clinically different on any post-operative day. Mortality was similar. CONCLUSIONS: In neonates undergoing complex cardiac surgery, peritoneal catheter use is not rare, with substantial variability among centres. Peritoneal catheters are used more commonly with higher surgical complexity. Adverse event rates, including mortality, are not different with peritoneal catheter use. Fluid overload and creatinine-based acute kidney injury rates are not different in peritoneal catheter cohorts.

Balloon atrial septostomy versus left atrial cannulation for left heart decompression in children with dilated cardiomyopathy and myocarditis on extracorporeal membrane oxygenation: An ELSO registry analysis.

INTRODUCTION: In children with myocarditis or dilated cardiomyopathy (DCM) on extracorporeal membrane oxygenation (ECMO) for cardiogenic shock, it is often necessary to decompress the left heart to minimize distension and promote myocardial recovery. We compare outcomes in those who underwent balloon atrial septostomy (BAS) versus direct left atrial (LA) drainage for left heart decompression in this population. METHODS: Retrospective study of the Extracorporeal Life Support Organization (ELSO) multicenter registry of patients ≤ 18 years with myocarditis or DCM on ECMO who underwent LA decompression. Descriptive and univariate statistics assessed association of patient factors with decompression type. Multivariable logistic regression sought independent associations with outcomes. RESULTS: 369 pediatric ECMO runs were identified. 52% myocarditis, 48% DCM, overall survival 74%. 65% underwent BAS and 35% LA drainage. Patient demographics including age, weight, gender, race/ethnicity, diagnosis, pre-ECMO pH, mean airway pressure, and arrest status were similar. 89% in the BAS group were peripherally cannulated onto ECMO, versus 3% in the LA drainage group (p < .001). On multivariable analysis, LA drainage (OR 3.96; 95% CI, 1.47-10.711; p = .007), renal complication (OR 2.37; 95% CI, 1.41-4.01; p = .001), cardiac complication (OR 3.14; 95% CI, 1.70-5.82; p < .001), and non-white race/ethnicity (OR 1.75; 95% CI, 1.04-2.94; p = .035) were associated with greater odds of mortality. There was a trend toward more episodes of pulmonary hemorrhage in BAS (n = 17) versus LA drainage group (n = 3), p = .08. Comparing only those with central cannulation, LA drainage group was more likely to be discontinued from ECMO due to recovery (72%) versus the BAS group (48%), p = .032. CONCLUSIONS: In children with myocarditis or DCM, there was a three times greater likelihood for mortality with LA drainage versus BAS for LA decompression. When adjusted for central cannulation groups only, there was better recovery in the LA drainage group and no difference in mortality. Further prospective evaluation is warranted.

A Near Real-Time Risk Analytics Algorithm Predicts Elevated Lactate Levels in Pediatric Cardiac Critical Care Patients.

BACKGROUND: Postoperative pediatric congenital heart patients are predisposed to develop low-cardiac output syndrome. Serum lactate (lactic acid [LA]) is a well-defined marker of inadequate systemic oxygen delivery. OBJECTIVES: We hypothesized that a near real-time risk index calculated by a noninvasive predictive analytics algorithm predicts elevated LA in pediatric patients admitted to a cardiac ICU (CICU). DERIVATION COHORT: Ten tertiary CICUs in the United States and Pakistan. VALIDATION COHORT: Retrospective observational study performed to validate a hyperlactatemia (HLA) index using T3 platform data (Etiometry, Boston, MA) from pediatric patients less than or equal to 12 years of age admitted to CICU (n = 3,496) from January 1, 2018, to December 31, 2020. Patients lacking required data for module or LA measurements were excluded. PREDICTION MODEL: Physiologic algorithm used to calculate an HLA index that incorporates physiologic data from patients in a CICU. The algorithm uses Bayes' theorem to interpret newly acquired data in a near real-time manner given its own previous assessment of the physiologic state of the patient. RESULTS: A total of 58,168 LA measurements were obtained from 3,496 patients included in a validation dataset. HLA was defined as LA level greater than 4 mmol/L. Using receiver operating characteristic analysis and a complete dataset, the HLA index predicted HLA with high sensitivity and specificity (area under the curve 0.95). As the index value increased, the likelihood of having higher LA increased (p < 0.01). In the validation dataset, the relative risk of having LA greater than 4 mmol/L when the HLA index is less than 1 is 0.07 (95% CI: 0.06-0.08), and the relative risk of having LA less than 4 mmol/L when the HLA index greater than 99 is 0.13 (95% CI, 0.12-0.14). CONCLUSIONS: These results validate the capacity of the HLA index. This novel index can provide a noninvasive prediction of elevated LA. The HLA index showed strong positive association with elevated LA levels, potentially providing bedside clinicians with an early, noninvasive warning of impaired cardiac output and oxygen delivery. Prospective studies are required to analyze the effect of this index on clinical decision-making and outcomes in pediatric population.

Outcomes of Extracorporeal Life Support in Children with Meningococcal Septicemia: A Retrospective Cohort Study.

Meningococcal disease is associated with high mortality despite aggressive antibiotic therapy and intensive care support. Patients may develop refractory hypotension and acute respiratory distress syndrome in which extracorporeal membrane oxygenation (ECMO) could serve as a life-saving rescue therapy. However, there is limited data regarding the outcomes of ECMO support in the setting of meningococcal disease. This retrospective analysis of prospectively collected data from Extracorporeal Life Support Organization registry (1989-2019) enrolled children (29 days-18 years old) with Neisseria meningitidis infection receiving ECMO for any support type and mode. A total of 122 patients underwent a single course of ECMO support, equating to 122 ECMO runs. The overall survival-to-discharge rate was 46.7%. Patients receiving pulmonary venovenous (VV) ECMO had the highest survival-to-discharge of 85.7%, while those receiving venoarterial (VA) ECMO for pulmonary indications had a survival of 32.4%. Patients receiving VA ECMO support for cardiac indications had a survival-to-discharge rate of 60.9%. Those needing extracorporeal cardiopulmonary resuscitation (ECPR) had a poor survival (14.3%). Hemorrhagic complications were common, occurring in 43.4% of patients, but not found to be associated with mortality (complication was present in 47.7% of deceased and 38.6% of survivors, p = 0.31). Multivariable logistic regression analysis revealed that neurologic complications were associated with increased odds of mortality (odds ratio: 44.11; 95% confidence interval: 4.95-393.08). ECMO can be utilized as rescue therapy in children with refractory cardiopulmonary failure in setting of meningococcemia. Patients who require pulmonary VV or cardiac ECMO have the best ECMO outcomes. However, the use of ECMO in those suffering cardiac arrest (ECPR) should be undertaken with caution.

Advocacy at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

The Origin of Antithyroid Drugs.

Background: When the antithyroid drugs were discovered in the early 1940s, they were immediately recognized as a revolutionary new treatment for hyperthyroidism. Although much has been learned about their mechanism of action and clinical utility, they continue to be used today in much the same way as they have been since their introduction. Summary: In 1995, Dr. Clark Sawin gave an address on the history of antithyroid drug development at the 11th International Thyroid Congress in Toronto, Ontario, Canada. In his review, Dr. Sawin recounted the original observations by Drs. Julia and Cosmo Mackenzie and Curt Richter at the Johns Hopkins University School of Medicine, and how their work ultimately led to Dr. Edwin (Ted) B. Astwood's seminal 1943 report on the use of thiourea and thiouracil in the Journal of the American Medical Association. He also described the development of propylthiouracil and methimazole as less toxic alternatives. He concluded his remarks by noting the often-serendipitous pathway of drug development and the role of pharmaceutical companies in the process. Conclusions: Antithyroid drugs remain a cornerstone of thyroid therapeutics. It is informative to review the process by which they came into use, as this is a seminal part of the history of thyroid disease in the 20th century. This knowledge may also spark additional research leading to new pharmacotherapies for patients with hyperthyroidism.

A Phase 1b, Open-Label Study to Evaluate the Safety and Tolerability of the Putative Remyelinating Agent, Liothyronine, in Individuals with MS.

Thyroid hormones are essential during developmental myelination and may play a direct role in remyelination and repair in the adult central nervous system by promoting the differentiation of oligodendrocyte precursor cells into mature oligodendrocytes. Since tri-iodothyronine (T3) is believed to mediate the majority of important thyroid hormone actions, liothyronine (synthetic T3) has the potential to induce reparative mechanisms and limit neurodegeneration in multiple sclerosis (MS). We completed a phase 1b clinical trial to determine the safety and tolerability of ascending doses of liothyronine in individuals with relapsing and progressive MS. A total of 20 people with MS were enrolled in this single-center trial of oral liothyronine. Eighteen participants completed the 24-week study. Our study cohort included mostly women (11/20), majority relapsing MS (12/20), mean age of 46, and baseline median EDSS of 3.5. Liothyronine was tolerated well without treatment-related severe/serious adverse events or evidence of disease activation/clinical deterioration. The most common adverse events included gastrointestinal distress and abnormal thyroid function tests. No clinical thyrotoxicosis occurred. Importantly, we did not observe a negative impact on secondary clinical outcome measures. The CSF proteomic changes suggest a biological effect of T3 treatment within the CNS. We noted changes primarily in proteins associated with immune cell function and angiogenesis. Liothyronine appeared safe and was well tolerated in people with MS. A larger clinical trial will help assess whether liothyronine can promote oligodendrogenesis and enhance remyelination in vivo, limit axonal degeneration, or improve function.

A tribute to Ernest L. Mazzaferri, MD and the lasting impact that he had on thyroid cancer care ten years after his death.

This viewpoint highlights the contributions of Dr. Ernest Mazzaferri, a prominent figure in the field of thyroid cancer care, who made significant contributions to the diagnosis and treatment of this disease. Dr. Mazzaferri's first paper on thyroid cancer, published in 1977, established fundamental principles that remain fundamental to differentiated thyroid cancer management. He was an advocate of total thyroidectomy and of postoperative radioiodine therapy and contributed to improving thyroid fine needle aspiration techniques. Dr. Mazzaferri's leadership in developing guidelines for the management of thyroid cancer and thyroid nodules has been influential and widely accepted. His groundbreaking work established a systematic and data-driven approach to the diagnosis and treatment of thyroid cancer that continues to shape the field of thyroid cancer care today. This Viewpoint reflects on his lasting impact ten years after his death.

Exogenous nitric oxide delivery protects against cardiopulmonary bypass-associated acute kidney injury: Histologic and serologic evidence from an ovine model.

OBJECTIVE: Several human studies have associated nitric oxide administration via the cardiopulmonary bypass circuit with decreased incidence of cardiopulmonary bypass-associated acute kidney injury, but histopathologic and serologic evidence of nitric oxide efficacy for acute kidney injury attenuation are lacking. METHODS: By using a survival ovine model (72 hours), acute kidney injury was induced by implementing low-flow cardiopulmonary bypass for 2 hours, followed by full-flow cardiopulmonary bypass for 2 hours. The nitric oxide cohort (n = 6) received exogenous nitric oxide through the cardiopulmonary bypass circuit via the oxygenator, and the control group (n = 5) received no nitric oxide. Serial serologic biomarkers and renal histopathology were obtained. RESULTS: Baseline characteristics (age, weight) and intraoperative parameters (cardiopulmonary bypass time, urine output, heart rate, arterial pH, and lactate) were equivalent (P > .10) between groups. Postoperatively, urine output, heart rate, respiratory rate, and peripheral arterial saturation were equivalent (P > .10) between groups. Post-cardiopulmonary bypass creatinine elevations from baseline were significantly greater in the control group versus the nitric oxide group at 16, 24, and 48 hours (all P < .05). Histopathologic evidence of moderate/severe acute kidney injury (epithelial necrosis, tubular slough, cast formation, glomerular edema) occurred in 60% (3/5) of the control group versus 0% (0/6) of the nitric oxide group. Cortical tubular epithelial cilia lengthening (a sensitive sign of cellular injury) was significantly greater in the control group than in the nitric oxide group (P = .012). CONCLUSIONS: In a survival ovine cardiopulmonary bypass model, nitric oxide administered with cardiopulmonary bypass demonstrated serologic and histologic evidence of renal protection from acute kidney injury. These results provide insight into 1 potential mechanism for cardiopulmonary bypass-associated acute kidney injury and supports continued study of nitric oxide via cardiopulmonary bypass circuit for prevention of acute kidney injury.