Perioperative Management and Outcomes of Hyperthyroid Patients Unable to Tolerate Antithyroid Drugs.

BACKGROUND: Prior to thyroidectomy for hyperthyroidism, it is recommended that patients are managed with antithyroid drugs (ATDs) and rendered euthyroid to decrease the risk of thyroid storm. However, not all patients tolerate ATD and the risk of thyroid storm during thyroidectomy in these patients is unclear. Therefore, the aim of this study was to compare the management and outcomes of hyperthyroid patients that were on ATDs prior to surgery to those who were not. STUDY DESIGN: A prospectively maintained, single-institution database was queried for all hyperthyroid patients who were initially treated with ATDs and underwent thyroidectomy from January 1, 2012, to June 18, 2018. Patients were divided into two groups: (1) those on ATDs at surgery (ATD group) and (2) those who could not tolerate and stopped ATDs prior to surgery (no-ATD group). Demographic and clinical data were collected. Primary outcomes were readmissions/emergency department visits and postoperative complications within 30 days of thyroidectomy. RESULTS: Of the 248 patients, 231 were in the ATD group and 17 (7%) were in the no-ATD group. There were no mortalities or thyroid storm events in either group. There was no difference in Clavien-Dindo Grade 2 or 3 complications between the two groups. There were no ED visits or 30-day readmissions in the no-ATD group compared to 17 (7%) events in the ATD group (p = 1.0). CONCLUSION: While it is preferable to render patients euthyroid prior to thyroidectomy for hyperthyroidism, results of this study suggest that when patients cannot tolerate ATDs, it is possible to perform thyroidectomy without increased risk of thyroid storm or intra- and postoperative complications.

Pediatric Laparoscopic Common Bile Duct Exploration: An Opportunity to Decrease ERCP Complications.

BACKGROUND: Laparoscopic intraoperative cholangiogram (IOC) with common bile duct exploration (CBDE) and endoscopic retrograde cholangiopancreatography (ERCP) are two therapeutic techniques for choledocholithiasis. The preferred technique is unclear. MATERIALS AND METHODS: We identified subjects who underwent laparoscopic cholecystectomy (LC) and IOC/CBDE or ERCP from July 1, 2006, to December 31, 2016. We retrospectively reviewed 81 patients (≤ 18 y) who received these interventions for suspected choledocholithiasis. Main outcomes analyzed were success of intervention and complications. RESULTS: Of the 81 patients, 21 ERCPs and three endoscopic ultrasounds (EUSs) were performed before LC. Eighteen of 21 (85.7%) patients had stones or sludge cleared by ERCP, whereas 3 (14.3%) had normal common bile ducts without evidence of stones. Five of 24 (20.8%) had significant post-ERCP complications. Seven of 24 (29.2%) had more than one admission. Sixty of 81 patients underwent LC with IOC ± CBDE. Twenty one of 60 (36.2%) were found to have abnormal IOC. Eight of 15 (53.3%) attempted laparoscopic CBDE were successful. Eleven of 21 (52.4%) patients with abnormal IOC had post-LC ERCP (10) and EUS (1). Patients admitted to the Pediatric Surgery service were more likely to undergo LC first than ERCP/EUS (OR 3.46, 95% CI 1.26 to 9.45, P = 0.016). Patients undergoing LC first had a shorter length of stay (mean LOS 5.13 d versus 4.07, median 5.0 versus 3.0 d, P-value < 0.05). CONCLUSIONS: Successful and safe laparoscopic treatment of choledocholithiasis is possible in the pediatric patient. A laparoscopic-first approach to suspected choledocholithiasis may reduce the number of procedures needed in this patient population.

Steroid use for refractory hypotension in congenital diaphragmatic hernia.

PURPOSE: Guidelines for diagnosis and treatment of adrenal insufficiency (AI) in newborns with congenital diaphragmatic hernia (CDH) are poorly defined. METHODS: From 2002 to 2016, 155 infants were treated for CDH at our institution. Patients with shock refractory to vasopressors (clinically diagnosed AI) were treated with hydrocortisone (HC). When available, random cortisol levels <10 µg/dL were considered low. Outcomes were compared between groups. RESULTS: Hydrocortisone was used to treat AI in 34% (53/155) of patients. That subset of patients was demonstrably sicker, and mortality was expectedly higher for those treated with HC (37.7 vs. 17.6%, p = 0.0098). Of the subset of patients with random cortisol levels measured before initiation of HC, 67.7% (21/31) had low cortisol levels. No significant differences were seen in survival between the high and low groups, but mortality trended higher in patients with high cortisol levels that received HC. After multivariate analysis, duration of HC stress dose administration was associated with increased risk of mortality (OR 1.11, 95% CI 1.02-1.2, p = 0.021), and total duration of HC treatment was associated with increased risk of sepsis (OR 1.04, 95% CI 1.005-1.075, p = 0.026). CONCLUSION: AI is prevalent amongst patients with CDH, but prolonged treatment with HC may increase risk of mortality and sepsis.

4-Hour postoperative PTH level predicts hypocalcemia after thyroidectomy in children.

BACKGROUND: Hypocalcemia occurs frequently after a total thyroidectomy in pediatric patients. Four hour postoperative PTH monitoring predicts the need for calcium supplementation in the adult thyroidectomy population. We evaluated the role of the 4 h postoperative PTH level in determining the need for calcium supplementation after thyroidectomy in the pediatric population. METHODS: This is a retrospective review of children undergoing total thyroidectomy by a single pediatric surgeon from July 2011 through July 2018. Intact PTH obtained four hours postoperatively determined the need for calcium supplementation for patients beginning in November 2014 onward. Serum total calcium levels were monitored concurrently with serum intact PTH levels. Serum calcium levels were followed in our Multispecialty Pediatric Endocrine Surgery clinic within the month following thyroidectomy. RESULTS: From July 2011 through July 2018, there were a total of 56 total thyroidectomies at our institution. Prior to November 2014, all pediatric total thyroidectomies received calcium supplementation per our institutional protocol. Based on ionized calcium levels, 26.3% (5/19) of children developed hypocalcemia. From November 2014 to July 2018, 37 pediatric patients required total thyroidectomies. 29.7% (11/37) had low 4-h postoperative PTH levels. 72.7% (8/11) patients with low 4-h postoperative PTH levels had corresponding postoperative day 1 total calcium levels less than 8.5 or ionized calcium levels less than 1.12, and five children (45.5%) developed symptomatic hypocalcemia. 70% (26/37) of children had normal 4-h postop PTH levels, with only 5 (19%) ever developing hypocalcemia. No patients with a normal postop PTH level developed symptomatic hypocalcemia or required IV calcium repletion. A single 4-h postoperative PTH <10 pg/dl for identifying hypocalcemia has a sensitivity of 81% and specificity of 91%, with AUC 0.81. CONCLUSION: The 4-h postoperative serum PTH level can help determine the need for calcium supplementation in pediatric patients undergoing total thyroidectomy, thereby reducing unnecessary calcium supplementation and serial lab draws to monitor for postoperative hypocalcemia. LEVEL OF EVIDENCE: Level II.

When to Intervene for Subclinical Cushing's Syndrome.

Without the overt clinical signs and symptoms associated with Cushing's syndrome, the diagnosis of subclinical Cushing's syndrome (SCS) is primarily based on biochemical evaluation. Despite being labeled as "subclinical," SCS is associated with significant morbidity that can be improved with adrenalectomy. Minimally invasive adrenalectomy is associated with low morbidity in the hands of experienced adrenal surgeons and is recommended as the treatment of choice for SCS patients with SCS-associated comorbidities.

Comparison of early versus delayed strategies for repair of congenital diaphragmatic hernia on extracorporeal membrane oxygenation.

PURPOSE: For the last seven years, our institution has repaired infants with CDH that require ECMO early after cannulation. Prior to that, we attempted to decannulate before repair, but repaired on ECMO if we were unable to wean after two weeks. This study compares those strategies. METHODS: From 2002 to 2016, 65 infants with CDH required ECMO. 67.7% were repaired on ECMO, and 27.7% were repaired after decannulation. Data were compared between patients repaired ≤5days after cannulation ("early protocol", n=30) and >5days after cannulation or after de-cannulation ("late protocol", n=35). We used Cox regression to assess differences in outcomes between groups. RESULTS: Survival for the early and late protocol groups was 43.3% and 68.8%, respectively (p=0.0485). For patients that were successfully decannulated before repair, survival was 94.4%. Moreover, the early repair protocol was associated with prolongation of ECMO (16.8±7.4 vs. 12.6±6.8days, p=0.0216). After multivariate regression, the early repair protocol was an independent predictor of both mortality (HR=3.48, 95% CI=1.28-9.45, p=0.015) and days on ECMO (IRR=1.39, 95% CI=1.07-1.79, p=0.012). All bleeding occurred in patients repaired on ECMO (29.5%, 13/44). CONCLUSIONS: Our data suggest that protocolized CDH repair early after ECMO cannulation may be associated with increased mortality and prolongation of ECMO. However, early repair is not necessarily harmful for those patients who would otherwise be unable to wean from ECMO before repair. Further work is needed to better move towards individualized patient care. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: Level III.

Oxidative stress and neuronal death/survival signaling in cerebral ischemia.

It has been demonstrated by numerous studies that apoptotic cell death pathways are implicated in ischemic cerebral injury in ischemia models in vivo. Experimental ischemia and reperfusion models, such as transient focal/global ischemia in rodents, have been thoroughly studied and the numerous reports suggest the involvement of cell survival/death signaling pathways in the pathogenesis of apoptotic cell death in ischemic lesions. In these models, reoxygenation during reperfusion provides oxygen as a substrate for numerous enzymatic oxidation reactions and for mitochondrial oxidative phosphorylation to produce adenosine triphosphate. Oxygen radicals, the products of these biochemical and physiological reactions, are known to damage cellular lipids, proteins, and nucleic acids and to initiate cell signaling pathways after cerebral ischemia. Genetic manipulation of intrinsic antioxidants and factors in the signaling pathways has provided substantial understanding of the mechanisms involved in cell death/survival signaling pathways and the role of oxygen radicals in ischemic cerebral injury. Future studies of these pathways could provide novel therapeutic strategies in clinical stroke.

Flumazenil administration attenuates cognitive impairment in immature rats after controlled cortical impact.

Evidence suggests that the gamma-aminobutyric acid (GABA)ergic system may be involved in cognitive dysfunction following traumatic brain injury (TBI). We investigated the effect of flumazenil treatment, a benzodiazepine antagonist approved by the U.S. Food and Drug Administration, on learning and memory in the immature rat following experimental brain injury. Post-natal day 17 rats were injured using controlled cortical impact. Systemic treatment with flumazenil at 1, 5, and 10 mg/kg was initiated on post-injury day 1 and administered for 13 days via daily intraperitoneal injections. Morris water maze (MWM) testing was used to measure latency to find a submerged platform and the results from experimental and control animals were compared. We demonstrated a significant dose-dependent improvement in MWM performance in drug-treated animals. This is the first study demonstrating the efficacy of flumazenil in reducing post-TBI cognitive deficits and we propose that these effects may be related to modulation of the GABA(A) receptor.

Akt/Bad signaling and motor neuron survival after spinal cord injury.

The serine-threonine kinase Akt is a cell survival signaling pathway that inactivates the proapoptotic BCL-2 family protein Bad and promotes cell survival in cerebral ischemia. Involvement of the Akt/Bad signaling pathway after spinal cord injury (SCI) is, however, uncertain. Our results showed that phospho-Akt (serine-473) and phospho-Bad (serine-136) were significantly upregulated at 1 day after SCI. In addition, phospho-Akt and phospho-Bad were colocalized in motor neurons that survived SCI and inhibition of PI3-K reduced expression of phospho-Akt and phospho-Bad. Dimerization of Bad with 14-3-3 in the cytosol was increased whereas Bad/Bcl-XL binding in the mitochondria was decreased after SCI. We further found that reduced oxidative stress by SOD1 overexpression in rats enhanced the expression of phospho-Akt, phospho-Bad, Bad/14-3-3 binding and reduced Bad/Bcl-XL binding after SCI, as compared to wild-type rats. We conclude that oxidative stress may play a role in modulating Akt/Bad signaling and subsequent motor neuron survival after SCI.