Randomized Controlled Trial of a Brief Mindfulness-Based Intervention for Suicidal Ideation Among Veterans.

INTRODUCTION: This study was a preliminary evaluation of a manualized, brief mindfulness-based intervention (MB-SI) for veterans with suicidal ideation (SI), admitted into an inpatient psychiatric unit (IPU). MATERIALS AND METHODS: A randomized, controlled pilot study of 20 veterans aged 18-70 years with SI, admitted into a psychiatric unit, assigned to treatment as usual (TAU) or MB-SI groups. Outcome data were collected at three time points: preintervention (beginning of first session), postintervention (end of last session), and 1-month postintervention. Primary outcomes were safety and feasibility. Secondary outcome measures were SI and behavior, mindfulness state and trait, cognitive reappraisal, and emotion regulation. Additionally, psychiatric and emergency department admissions were examined. Data analysis included Generalized Linear Models, Wilcoxon Signed-Rank, Mann-Whitney U, and Fisher's exact tests for secondary outcomes. RESULTS: Mindfulness-based intervention for suicidal ideation was feasible to implement on an IPU, and there were no associated adverse effects. Mindfulness-based intervention for suicidal ideation participants experienced statistically significant increase in Toronto Mindfulness Scale curiosity scores 1-month postintervention compared to preintervention and greater Toronto Mindfulness Scale decentering scores 1-month postintervention compared to TAU. Emotion Regulation Questionnaire Reappraisal scores significantly increased for the MB-SI group and significantly decreased for TAU over time. IPU and emergency department admissions were not statistically different between groups or over time. Both TAU and MB-SI participants experienced a significant reduction in Columbia-Suicide Severity Rating Scale-SI scores after the intervention. MB-SI participants experienced a higher increase in Five-Facet Mindfulness Questionnaire scores postintervention compared to TAU. CONCLUSIONS: Mindfulness-based intervention for suicidal ideation is feasible and safe to implement among veterans during an inpatient psychiatric admission with SI, as it is not associated with increased SI or adverse effects. Preliminary evidence suggests that MB-SI increases veterans' propensity to view experiences with curiosity while disengaging from experience without emotional overreaction. Further, more rigorous research is warranted to determine efficacy of MB-SI. TRIAL REGISTRATION: The clinicaltrials.gov registration number is NCT04099173 and dates are July 16, 2019 (initial release) and February 24, 2022 (most recent update).

Mindfulness-based Therapeutic Sailing for Veterans With Psychiatric and Substance Use Disorders.

INTRODUCTION: Complementary interventions have the potential to enhance treatment engagement and/or response among veterans with psychiatric disorders and/or substance use disorders (SUDs). Mindfulness-based therapeutic sailing (MBTS) is a novel three-session, complementary intervention, which combines nature exposure via recreational sailing and mindfulness training. It was developed specifically to augment both treatment response and engagement among veterans with psychiatric disorders or SUDs. The study reports a follow-up investigation of a version of MBTS modified based upon a previous initial pilot study. MATERIALS AND METHODS: This is an institutional review board-approved study of 25 veterans, 23 males and 2 females, who participated in MBTS along with a diagnosis-, gender-, and age-matched control group. All participants had at least one psychiatric disorder or SUD and most (92%) had two or more conditions, with the most common being any SUD (76%) and PTSD (72%). Instruments used to evaluate within-subjects pre- to post-intervention psychological changes were the Acceptance and Action Questionnaire II (AAQII), the Toronto Mindfulness Scale (TMS), and the Five Facet Mindfulness Questionnaire (FFMQ). The Physical Activity Enjoyment Scale (PACES) was administered to evaluate how much the participants enjoyed the intervention. Outcome measures were collected for 1-year pre-intervention and 1-year post-intervention for between-subject analyses. These were numbers of medical and psychiatric hospitalizations, emergency department visits, mental health (MH) and substance abuse treatment visits, and MH and substance abuse treatment failed appointments. Data analysis consisted of using paired, two-tailed t-tests on psychological instrument results, Poisson regression on discrete outcome measures, and chi-square test of independence on demographic factors. RESULTS: Within-subjects comparisons revealed significant mean pre- to post-intervention increases in AAQII (P = .04) and TMS scores (P = .009). The FFMQ scores increased but the change was nonsignificant (P = .12). The PACES scores were high for all sessions, indicating enjoyment of the intervention by participants. Although the coefficient was nonsignificant, Poisson regression uncovered reduction in substance abuse treatment visits post-intervention. There were no significant differences for the other variables. For demographic factors, the differences between intervention and control groups were not statistically significant. CONCLUSIONS: The MBTS is associated with increases in psychological flexibility (AAQII) and state mindfulness (TMS). The intervention was perceived as pleasurable by participants (PACES) and is potentially associated with decreased utilization of substance use treatment services. These results must be considered as preliminary; however, these finding corroborate results from a previous pilot study and indicate that MBTS holds promise as a complementary intervention that could result in enhanced treatment engagement and/or outcomes for the population studied. A randomized controlled trial of MBTS is warranted. Further, the model of a three-session intervention combining mindfulness training with nature exposure could be adapted for other types of nature exposure, such as hiking or snowshoeing or other complementary interventions including equine-assisted activities and therapies.

Mindfulness Training plus Nature Exposure for Veterans with Psychiatric and Substance Use Disorders: A Model Intervention.

There is a need to develop novel complementary interventions aimed at enhancing treatment engagement and/or response for veterans with psychiatric and substance use disorders. There is evidence that both mindfulness training and nature exposure (MT/NE) may be beneficial for this population and that combining the two approaches into one intervention might result in synergistic benefit. However, to date, the MT/NE concept has not been tested. This article reports a pilot feasibility and acceptability study of MT/NE which was, in this case, provided via recreational sailing. The primary aim of this project was to develop a model intervention and evaluation process that could be used for future studies of MT/NE interventions using a variety of methods of nature exposure (e.g., hiking, skiing, mountain biking). Results indicate preliminary evidence that it is feasible to utilize MT/NE interventions for the population studied and that the MT/NE model described can serve as a template for future investigations. Further, there were significant pre- to post-intervention decreases in state anxiety, as well as increases in trait mindfulness. Three psychological instruments were identified that might be used in future studies to evaluate MT/NE outcomes. Results from this project provide a model MT/NE intervention template along with evaluation metrics for use in future studies.

A postoperative parathyroid hormone-based algorithm to reduce symptomatic hypocalcemia following completion/total thyroidectomy: A retrospective analysis of 591 patients.

BACKGROUND: An institutional protocol for selective calcium/calcitriol supplementation after completion/total thyroidectomy was established based on the 4-hour postoperative parathyroid hormone level. The aim of this study was to evaluate the outcomes of this protocol 5 years after implementation. METHODS: All patients who underwent completion/total thyroidectomy from January 2012 to December 2016 were reviewed. Predictors of a 4-hour parathyroid hormone level <10 pg/mL and symptomatic hypocalcemia were assessed. RESULTS: Of 591 patients, 448 (76%) had a 4-hour parathyroid hormone ≥10, 72 (12%) had a 4-hour parathyroid hormone of 5-10, and 71 (12%) had a 4-hour parathyroid hormone <5. Hypocalcemic symptoms were infrequent (30/448, 7%) if the 4-hour parathyroid hormone was ≥10; 56% (40/71) of those with a 4-hour parathyroid hormone <5 reported symptoms. With 4-hour parathyroid hormone of 5-10, symptoms were reported in 32 of 72 (44%) patients; supplementation at discharge included calcium (n = 55, 76%), calcium and calcitriol (n = 12, 17%), or none (n = 5, 7%). Ten patients subsequently received calcitriol for persistent symptoms. On multivariate analysis, predictors of 4-hour parathyroid hormone <10 included incidental parathyroidectomy, malignancy, and thyroiditis; predictors of hypocalcemic symptoms included age <55 and 4-hour parathyroid hormone <10. CONCLUSION: After completion/total thyroidectomy, patients with a 4-hour parathyroid hormone ≥10 can be safely discharged without routine supplementation. The addition of calcitriol to calcium supplementation should be strongly considered for patients with a 4-hour parathyroid hormone of 5-10.

Evaluation of GalNAc-siRNA Conjugate Activity in Pre-clinical Animal Models with Reduced Asialoglycoprotein Receptor Expression.

The hepatocyte-specific asialoglycoprotein receptor (ASGPR) is an ideal candidate for targeted drug delivery to the liver due to its high capacity for substrate clearance from circulation together with its well-conserved expression and function across species. The development of GalNAc-siRNA conjugates, in which a synthetic triantennary N-acetylgalactosamine-based ligand is conjugated to chemically modified siRNA, has enabled efficient, ASGPR-mediated delivery to hepatocytes. To investigate the potential impact of variations in receptor expression on the efficiency of GalNAc-siRNA conjugate delivery, we evaluated the pharmacokinetics and pharmacodynamics of GalNAc-siRNA conjugates in multiple pre-clinical models with reduced receptor expression. Despite greater than 50% reduction in ASGPR levels, GalNAc conjugate activity was retained, suggesting that the remaining receptor capacity was sufficient to mediate efficient uptake of potent GalNAc-siRNAs at pharmacologically relevant dose levels. Collectively, our data support a broad application of the GalNAc-siRNA technology for hepatic targeting, including disease states where ASGPR expression may be reduced.

Multimodal fluorescence molecular imaging for in vivo characterization of skin cancer using endogenous and exogenous fluorophores.

Similarity of skin cancer with many benign skin pathologies requires reliable methods to detect and differentiate the different types of these lesions. Previous studies have explored the use of disparate optical techniques to identify and estimate the invasive nature of melanoma and basal cell carcinoma with varying outcomes. Here, we used a concerted approach that provides complementary information for rapid screening and characterization of tumors, focusing on squamous cell carcinoma (SCC) of the skin. Assessment of in vivo autofluorescence lifetime (FLT) imaging of endogenous fluorophores that are excitable at longer wavelengths (480 nm) than conventional NADH and FAD revealed a decrease in the short FLT component for SCC compared to normal skin, with mean values of 0.57 ± 0.026 ?? ns and 0.61 ± 0.021 ?? ns , respectively ( p = 0.004 ). Subsequent systemic administration of a near-infrared fluorescent molecular probe in SCC bearing mice, followed by the implementation of image processing methods on data acquired from two-dimensional and three-dimensional fluorescence molecular imaging, allowed us to estimate the tumor volume and depth, as well as quantify the fluorescent probe in the tumor. The result suggests the involvement of lipofuscin-like lipopigments and riboflavin in SCC metabolism and serves as a model for staging SCC.

Effect of vitamin D supplementation on oral glucose tolerance in individuals with low vitamin D status and increased risk for developing type 2 diabetes (EVIDENCE): A double-blind, randomized, placebo-controlled clinical trial.

AIMS: Low serum 25-hydroxyvitamin-D (25(OH)D) concentrations are associated with insulin resistance, ß-cell dysfunction and type 2 diabetes. We conducted a 24-week double-blind, randomized, placebo-controlled trial to examine the effect of 28 000 IU of vitamin D3 once weekly on plasma glucose after a 2 hour-75 g oral glucose tolerance test (2hrPC glucose), insulin sensitivity and ß-cell function. STUDY DESIGN AND METHODS: A total of 71 participants with serum 25(OH)D ≤65 nmol/L, impaired fasting glucose and elevated glycated hemoglobin were randomly assigned to receive 28 000 IU of vitamin D3 (VitD; n = 35) or placebo (n = 36) in cheese once weekly for 24 weeks. The primary outcome was the change in 2hPC glucose. Secondary outcomes were fasting glucose, fasting and postprandial insulin, indices of insulin sensitivity and ß-cell function, glycated hemoglobin and lipid profile. Participants underwent an oral glucose tolerance test to determine 2hPC glucose. RESULTS: Mean baseline serum 25(OH)D was 48.1 and 47.6 nmol/L in the VitD and placebo groups, respectively. Serum 25(OH)D significantly increased to 98.7 nmol/L (51 nmol/L increase; P < .0001) in the VitD group. No significant differences in fasting ( P = .42) or 2hPC glucose ( P = .55) or other indices of glucose metabolism, including ß-cell function and insulin sensitivity, were observed between groups. A subgroup analysis of individuals with 25(OH)D < 50 nmol/L and prediabetes did not change these results. The VitD group exhibited a significant reduction in LDL cholesterol (-0.27 vs 0.01 mmol/L, P = .03). CONCLUSION: Weekly doses of vitamin D3 in individuals with suboptimal vitamin D levels who were at risk for type 2 diabetes did not improve oral glucose tolerance or markers of glycaemic status.

The role and timing of parathyroid hormone determination after total thyroidectomy.

Postoperative hypocalcemia is a common complication of total thyroidectomy resulting from manipulation, resection, or devascularization of the parathyroid glands. Parathyroid hormone (PTH) levels assessed in the perioperative period have been used to predict development of hypocalcemia. Articles examining the role of PTH measurement in the perioperative period following total or completion thyroidectomy are reviewed. Focus is placed on the timing of PTH measurement and the ability to predict which patients will develop hypocalcemia requiring supplementation. Postoperative PTH determination is highly accurate in predicting the development of hypocalcemia. Studies have examined PTH levels drawn at differing time points, ranging from intraoperatively until postoperative day 1 (POD1) with similar accuracy. This data is used to guide postoperative selective calcium and calcitriol supplementation in patients at highest risk for hypocalcemia. When evaluated within the first 4 hours postoperatively, predictive accuracy is maintained but can allow for earlier discharge for those patients at lower risk. Alternatively, some authors argue for routine supplementation, which can reduce the rate of postoperative hypocalcemia but increases the rate of unnecessary supplementation and potential risks associated with hypercalcemia. PTH determination at four hours after total thyroidectomy is an accurate predictor of hypocalcemia and can guide selective calcium supplementation for those at high risk, as well as facilitate a safe earlier hospital discharge for those at low risk of developing postoperative hypocalcemia.

The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism.

Importance: Primary hyperparathyroidism (pHPT) is a common clinical problem for which the only definitive management is surgery. Surgical management has evolved considerably during the last several decades. Objective: To develop evidence-based guidelines to enhance the appropriate, safe, and effective practice of parathyroidectomy. Evidence Review: A multidisciplinary panel used PubMed to review the medical literature from January 1, 1985, to July 1, 2015. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Findings: Initial evaluation should include 25-hydroxyvitamin D measurement, 24-hour urine calcium measurement, dual-energy x-ray absorptiometry, and supplementation for vitamin D deficiency. Parathyroidectomy is indicated for all symptomatic patients, should be considered for most asymptomatic patients, and is more cost-effective than observation or pharmacologic therapy. Cervical ultrasonography or other high-resolution imaging is recommended for operative planning. Patients with nonlocalizing imaging remain surgical candidates. Preoperative parathyroid biopsy should be avoided. Surgeons who perform a high volume of operations have better outcomes. The possibility of multigland disease should be routinely considered. Both focused, image-guided surgery (minimally invasive parathyroidectomy) and bilateral exploration are appropriate operations that achieve high cure rates. For minimally invasive parathyroidectomy, intraoperative parathyroid hormone monitoring via a reliable protocol is recommended. Minimally invasive parathyroidectomy is not routinely recommended for known or suspected multigland disease. Ex vivo aspiration of resected parathyroid tissue may be used to confirm parathyroid tissue intraoperatively. Clinically relevant thyroid disease should be assessed preoperatively and managed during parathyroidectomy. Devascularized normal parathyroid tissue should be autotransplanted. Patients should be observed postoperatively for hematoma, evaluated for hypocalcemia and symptoms of hypocalcemia, and followed up to assess for cure defined as eucalcemia at more than 6 months. Calcium supplementation may be indicated postoperatively. Familial pHPT, reoperative parathyroidectomy, and parathyroid carcinoma are challenging entities that require special consideration and expertise. Conclusions and Relevance: Evidence-based recommendations were created to assist clinicians in the optimal treatment of patients with pHPT.

Investigating the role of MRGPRC11 and capsaicin-sensitive afferent nerves in the anti-influenza effects exerted by SLIGRL-amide in murine airways.

BACKGROUND: The hexapeptide SLIGRL-amide activates protease-activated receptor-2 (PAR-2) and mas-related G protein-coupled receptor C11 (MRGPRC11), both of which are known to be expressed on populations of sensory nerves. SLIGRL-amide has recently been reported to inhibit influenza A (IAV) infection in mice independently of PAR-2 activation, however the explicit roles of MRGPRC11 and sensory nerves in this process are unknown. Thus, the principal aim of this study was to determine whether SLIGRL-amide-induced inhibition of influenza infection is mediated by MRGPRC11 and/or by capsaicin-sensitive sensory nerves. METHODS: The inhibitory effect of SLIGRL-amide on IAV infection observed in control mice in vivo was compared to effects produced in mice that did not express MRGPRC11 (mrgpr-cluster∆ (-/-) mice) or had impaired sensory nerve function (induced by chronic pre-treatment with capsaicin). Complementary mechanistic studies using both in vivo and ex vivo approaches investigated whether the anti-IAV activity of SLIGRL-amide was (1) mimicked by either activators of MRGPRC11 (BAM8-22) or by activators (acute capsaicin) or selected mediators (substance P, CGRP) of sensory nerve function, or (2) suppressed by inhibitors of sensory nerve function (e.g. NK1 receptor antagonists). RESULTS: SLIGRL-amide and BAM8-22 dose-dependently inhibited IAV infection in mrgpr-cluster∆ (-/-) mice that do not express MRGPRC11. In addition, SLIGRL-amide and BAM8-22 each inhibited IAV infection in capsaicin-pre-treated mice that lack functional sensory nerves. Furthermore, the anti-IAV activity of SLIGRL-amide was not mimicked by the sensory neuropeptides substance P or CGRP, nor blocked by either NK1 (L-703,606, RP67580) and CGRP receptor (CGRP8-37) antagonists. Direct stimulation of airway sensory nerves through acute exposure to the TRPV1 activator capsaicin also failed to mimic SLIGRL-amide-induced inhibition of IAV infectivity. The anti-IAV activity of SLIGRL-amide was mimicked by the purinoceptor agonist ATP, a direct activator of mucus secretion from airway epithelial cells. Additionally, both SLIGRL-amide and ATP stimulated mucus secretion and inhibited IAV infectivity in mouse isolated tracheal segments. CONCLUSIONS: SLIGRL-amide inhibits IAV infection independently of MRGPRC11 and independently of capsaicin-sensitive, neuropeptide-releasing sensory nerves, and its secretory action on epithelial cells warrants further investigation.

Preclinical evaluation of RNAi as a treatment for transthyretin-mediated amyloidosis.

ATTR amyloidosis is a systemic, debilitating and fatal disease caused by transthyretin (TTR) amyloid accumulation. RNA interference (RNAi) is a clinically validated technology that may be a promising approach to the treatment of ATTR amyloidosis. The vast majority of TTR, the soluble precursor of TTR amyloid, is expressed and synthesized in the liver. RNAi technology enables robust hepatic gene silencing, the goal of which would be to reduce systemic levels of TTR and mitigate many of the clinical manifestations of ATTR that arise from hepatic TTR expression. To test this hypothesis, TTR-targeting siRNAs were evaluated in a murine model of hereditary ATTR amyloidosis. RNAi-mediated silencing of hepatic TTR expression inhibited TTR deposition and facilitated regression of existing TTR deposits in pathologically relevant tissues. Further, the extent of deposit regression correlated with the level of RNAi-mediated knockdown. In comparison to the TTR stabilizer, tafamidis, RNAi-mediated TTR knockdown led to greater regression of TTR deposits across a broader range of affected tissues. Together, the data presented herein support the therapeutic hypothesis behind TTR lowering and highlight the potential of RNAi in the treatment of patients afflicted with ATTR amyloidosis.

Why such differing stances? A review of position statements on home birth from professional colleges.

UNLABELLED: Despite low rates of home birth throughout most Western countries, the topic generates considerable debate. This is reflected by the differing positions on home birth adopted by professional colleges representing obstetricians and midwives. We reviewed position statements of midwifery and obstetric colleges in the UK, USA, Australia, New Zealand, and Canada to explore how the same body of research evidence leads to different positions. Aside from a joint statement from the UK we found widely differing stances, reflecting traditional midwifery perspectives of birth as a physiological process versus obstetric perspectives of potential pathology. We feel the differences in position statements are largely the end product of significant confirmatory bias. TWEETABLE ABSTRACT: Review of organisational position on home birth suggests bias in literature interpretation.

A single parathyroid hormone level obtained 4 hours after total thyroidectomy predicts the need for postoperative calcium supplementation.

BACKGROUND: Parathyroid hormone (PTH) levels after total thyroidectomy have been shown to predict the development of symptomatic hypocalcemia and the need for calcium supplementation. This study aimed to determine whether a PTH level drawn 4 hours postoperatively is as effective as a level drawn on postoperative day 1 (POD1) in predicting this need. STUDY DESIGN: This is a single-institution retrospective review of 4-hour and POD1 PTH levels in patients who underwent total thyroidectomy from January 2012 to September 2012. If POD1 PTH was ≥10 pg/mL, patients did not routinely receive supplementation; if PTH was <10 pg/mL, patients received oral calcium with or without calcitriol. RESULTS: Of 77 patients, 20 (26%) had a 4-hour PTH <10 pg/mL; 18 (90%) of these patients had a POD1 PTH <10 pg/mL. No patient with a 4-hour PTH ≥10 pg/mL had a POD1 PTH <10 pg/mL. All 18 patients with POD1 PTH <10 pg/mL received calcium supplementation. Three additional patients received supplementation due to reported symptoms or surgeon preference. A 4-hour PTH ≥10 pg/mL compared with a POD1 PTH had a similar ability to predict which patients would not need calcium supplementation; sensitivity was 98% vs 98%, specificity was 90% vs 86%, and and negative predictive value was 95% vs 95%. Of 21 patients who received supplementation, 13 (62%) also received calcitriol, including 9 patients (69%) with a 4-hour PTH <6 pg/mL. CONCLUSIONS: A single PTH level obtained 4 hours after total thyroidectomy that is ≥10 pg/mL accurately identifies patients who do not need calcium supplementation or additional monitoring of serum calcium levels. Same-day discharge, if deemed safe, can be accomplished with or without calcium supplementation based on the 4-hour PTH level. Greater consideration should be given to calcitriol supplementation in patients with a 4-hour PTH <6 pg/mL.

Papillary thyroid microcarcinoma: an over-treated malignancy?

BACKGROUND: The clinical importance of papillary thyroid microcarcinoma (PTMC) remains controversial, with current guidelines suggesting that thyroid lobectomy alone is sufficient. The purpose of this study was to identify population-level treatment patterns in the USA for PTMC. METHODS: Patients with PTMC in SEER (1998-2010) were included; demographic, clinical (extent of surgery, administration of post-operative radioactive iodine [RAI]), and pathologic characteristics were examined. Outcomes of interest were 5- and 10-year overall survival (OS) and disease-specific survival (DSS). RESULTS: The cohort consisted of 29,512 patients. Mean age at diagnosis was 48.5 years; mean tumor size was 0.53 cm. Overall, 73.4 % of patients underwent total thyroidectomy, and RAI was administered to 31.3 %. In multivariate analysis, total thyroidectomy was more frequently performed in patients with multifocal (odds ratio [OR] 2.55), 'regional', or 'distant' PTMC (OR 2.90 and 2.59). Non-operative management was associated with male patients (OR 4.24) and those aged ≥65 years (OR 6.31). Post-operative RAI was associated with multifocal PTMC (OR 2.57). Overall, 5- and 10-year DSS was 99.6 and 99.3 %, respectively, with no difference in DSS between patients who underwent partial versus total thyroidectomy. OS of patients with PTMC who underwent any thyroid operation was similar to that of the general population of the USA. CONCLUSIONS: An increasing number of patients are undergoing total thyroidectomy and RAI for PTMC. While there may be a subset of patients for whom more aggressive therapy is indicated, many patients with PTMC may be over-treated, with no demonstrable benefit to survival.

Persistent elevation in serum parathyroid hormone levels in normocalcemic patients after parathyroidectomy: does it matter?

BACKGROUND: The clinical importance of elevated serum parathyroid hormone (PTH) levels in patients with normocalcemia after curative parathyroidectomy (PTX) for primary hyperparathyroidism (pHPT) is unclear. This study sought to determine whether these patients, when compared with those with normal PTH levels, differ in preoperative and pathologic factors and are at increased risk of recurrent pHPT. METHODS: A chart review was performed of sporadic pHPT patients who underwent PTX between December 1999 and July 2011. RESULTS: Of 1,037 patients who underwent PTX, 310 had 6-month serum calcium, vitamin D, and PTH levels evaluated. PTX was curative (normocalcemia at ≥6 months) in 97%. At 6 months, 62 (21%) had elevated serum PTH levels. Compared with patients with normal postoperative PTH levels, patients with elevated PTH levels had greater BMI (P < .0001), greater PTH levels (P < .0001), and lesser vitamin D levels (P = .014) preoperatively and lesser vitamin D levels at 6 months (P = .05). At ≥1 year follow-up, 38 (61%) patients had calcium levels checked; all remained normocalcemic. PTH levels were available for 32 patients; 17 had persistently increased PTH levels. CONCLUSION: Patients with elevated PTH levels after curative PTX do not have greater rates of recurrence than patients with normal PTH levels. The greater PTH levels and lesser vitamin D levels support postoperative vitamin D supplementation in these patients.

Predicting the need for calcium and calcitriol supplementation after total thyroidectomy: results of a prospective, randomized study.

BACKGROUND: The optimal protocol for the detection and treatment of postthyroidectomy hypoparathyroidism is unknown. We sought to identify and treat patients at risk for symptomatic hypocalcemia on the basis of a single parathyroid hormone (PTH) obtained the morning after surgery (POD1). METHODS: We performed a prospective, randomized study of total thyroidectomy patients who had POD1 calcium and PTH (pg/mL) levels. Randomization was determined by POD1 PTH: if ≥ 10, patients received no supplementation unless symptomatic; if <10, patients were randomized to calcium, calcium and calcitriol, or no supplementation. RESULTS: Of 143 patients, 112 (78%) had a POD1 PTH ≥ 10. Hypocalcemic symptoms were transiently reported in 11 (10%) and managed with outpatient calcium. Of 31 patients with PTH <10, 15 (48%) developed symptoms, including 5 who required intravenous calcium. On multivariate logistic regression analysis, when we adjusted for postoperative calcium level and performance of central neck dissection, we found that predictors of hypocalcemic symptoms were younger age (odds ratio 1.59, 95% confidence interval 1.07-2.32) and a PTH <10 (odds ratio 1.08, 95% confidence interval 1.04-1.12). There were no patient or treatment-related factors that predicted a POD1 PTH <10. CONCLUSION: A single POD1 PTH level <10 can accurately identify those patients at risk for clinically significant hypocalcemia. All total thyroidectomy patients with a postoperative PTH ≥ 10 can be safely discharged without supplementation. Given the small number of patients with PTH <10, it is unclear whether both calcium and calcitriol are needed for these higher-risk patients.

Effect of prophylactic central compartment neck dissection on serum thyroglobulin and recommendations for adjuvant radioactive iodine in patients with differentiated thyroid cancer.

BACKGROUND: Controversy exists in the management of patients with differentiated thyroid cancer (DTC). The purpose of this study was to examine the effect of prophylactic central compartment neck dissection (CCND) on serum thyroglobulin (Tg) levels and recommendations for adjuvant radioactive iodine (RAI). METHODS: The records of 103 patients who underwent completion/total thyroidectomy for DTC between January 2009 and November 2010 were reviewed. Prophylactic CCND was defined as removal of central compartment lymph nodes with no preoperative or intraoperative evidence of lymphadenopathy. Institutional protocol included a diagnostic whole-body scan before RAI; patients with a negative scan and Tg < 2.0 did not receive adjuvant RAI. RESULTS: Among the 103 patients, therapeutic CCND was performed in 17 (17 %) and prophylactic CCND in 49 (48 %). Of the 49 patients, 20 (41 %) had positive cervical lymph nodes. Positive lymph nodes changed American Joint Committee on Cancer tumor, node, metastasis staging in 17 patients and recommendations for RAI in 14. At a median follow-up of 21 months, there was no difference in Tg level based on the application of CCND; however, 92 % of patients with M0 disease had an undetectable Tg. One patient had recurrent DTC based on serum Tg only. CONCLUSIONS: Prophylactic CCND resulted in detection of unsuspected metastatic lymphadenopathy in 20 (41 %) of 49 patients and changed RAI recommendations in 14 (33 %). To date, most patients have an undetectable Tg. Longer follow-up is needed to detect potential differences in recurrent disease based on the use of CCND or long-term effects of RAI.

Epilepsy control following intracranial monitoring without resection in young children.

PURPOSE: Intracranial monitoring (IM) is a key diagnostic procedure for select patients with treatment-resistant epilepsy (TRE). Seizure focus resection may improve seizure control in both lesional and nonlesional TRE. IM itself is not considered to have therapeutic potential. We describe a cohort of patients with improved seizure control following IM without resective surgery. METHODS: Over 12.5 years, 161 children underwent 496 surgeries including intracranial monitoring. We retrospectively reviewed the patients' charts, operative reports, and radiologic scans, under an institutional review board-approved protocol. KEY FINDINGS: Seventeen patients underwent only IM, without additional resective surgery, and seven had a dramatic improvement in their epilepsy; six of the seven patients are seizure-free (Engel class I), and one rarely has seizures (Engel class II). All seven patients had frequent seizures that led to IM: either daily (five patients) or 1-2 per week (two patients). The mean age (± standard deviation, SD) at seizure onset was 1.6 ± 1.3 years (range 0.5-4 years). Etiologies were tuberous sclerosis (3 patients), trauma (1 patient), and unknown (3 patients). Mean age at surgery (± SD) was 4.1 ± 2 years (range 1-7 years), and duration of epilepsy 2.5 ± 1.1 years (range 0.5-4 years). Duration of IM was 11.7 ± 5.6 days (5-19 days). Six patients had bilateral and one unilateral invasive electrodes. At last follow-up, four patients required fewer antiepileptic drugs (AEDs), one had the same medication but a higher dose, and two patients were taking additional AEDs. Follow-up was 30.6 ± 9.5 months (range 19-41 months). SIGNIFICANCE: Although uncommon, patients with TRE may improve after IM alone. The explanation for this observation remains unclear; however, perioperative medications including steroids, direct cortical manipulation, or other factors may influence the epileptogenic network.

Postoperative calcium supplementation in patients undergoing thyroidectomy.

PURPOSE OF REVIEW: Postoperative hypocalcemia is one of the most common complications following thyroidectomy. This review examines recent literature on predictive factors for hypocalcemia, measurement of serum calcium and parathyroid hormone (PTH) levels, and algorithms for supplementation with calcium and/or vitamin D. RECENT FINDINGS: Risk factors for developing postthyroidectomy hypocalcemia include hyperthyroidism, vitamin D deficiency, female sex, substernal thyroid disease, and thyroid cancer, necessitating central neck lymphadenectomy. Several studies have shown that routine postoperative oral calcium and calcitriol supplementation results in lower rates of tetany. Recent studies have focused on the predictive value of intraoperative and postoperative serum PTH levels for the development of symptomatic hypocalcemia. Although the exact timing and serum levels of PTH have been variable, studies have confirmed that patients with very low postoperative PTH levels require oral calcitriol and calcium supplementation. A societal-level cost-utility analysis examining the use of routine vs. selective oral calcium and calcitriol supplementation found that routine supplementation is more cost-effective, and is associated with improved quality of life, irrespective of the surgeons' specific rates of hypocalcemia. SUMMARY: Although some clinicians favor routine supplementation postoperatively, others advocate selective supplementation, guided by postoperative PTH levels. The optimal algorithm is unknown, although a recent cost-analysis study suggests that routine supplementation may be favored at the societal level.

NrCAM deletion causes topographic mistargeting of thalamocortical axons to the visual cortex and disrupts visual acuity.

NrCAM is a neural cell adhesion molecule of the L1 family that has been linked to autism spectrum disorders, a disease spectrum in which abnormal thalamocortical connectivity may contribute to visual processing defects. Here we show that NrCAM interaction with neuropilin-2 (Npn-2) is critical for semaphorin 3F (Sema3F)-induced guidance of thalamocortical axon subpopulations at the ventral telencephalon (VTe), an intermediate target for thalamic axon sorting. Genetic deletion of NrCAM or Npn-2 caused contingents of embryonic thalamic axons to misproject caudally in the VTe. The resultant thalamocortical map of NrCAM-null mutants showed striking mistargeting of motor and somatosensory thalamic axon contingents to the primary visual cortex, but retinogeniculate targeting and segregation were normal. NrCAM formed a molecular complex with Npn-2 in brain and neural cells, and was required for Sema3F-induced growth cone collapse in thalamic neuron cultures, consistent with a vital function for NrCAM in Sema3F-induced axon repulsion. NrCAM-null mice displayed reduced responses to visual evoked potentials recorded from layer IV in the binocular zone of primary visual cortex (V1), particularly when evoked from the ipsilateral eye, indicating abnormal visual acuity and ocularity. These results demonstrate that NrCAM is required for normal maturation of cortical visual acuity, and suggest that the aberrant projection of thalamic motor and somatosensory axons to the visual cortex in NrCAM-null mutant mice impairs cortical functions.