Appropriateness of Surgical Aortic Valve Replacement for Severe Aortic Stenosis Is Increasing.

BACKGROUND: The adoption of transcatheter aortic valve replacement led to the development of appropriate use criteria (AUC) for transcatheter and surgical aortic valve replacement (SAVR) for aortic stenosis in 2017. This study hypothesized that appropriateness of SAVR improved after publication of AUC. METHODS: All patients undergoing isolated SAVR for severe aortic stenosis in a regional cardiac surgical quality collaborative were evaluated using data from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (2011-2021). After excluding endocarditis and emergency cases, appropriateness of SAVR (rarely appropriate, may be appropriate, or appropriate) was assigned to patients by using established criteria. The relationship of appropriateness with publication of AUC was assessed, as was variation in appropriateness over time and by center. RESULTS: Of 3035 patients across 17 centers, 106 (3.5%) underwent SAVR for an indication identified as rarely appropriate or may be appropriate. Patients who underwent SAVR for rarely or may be appropriate indications were significantly more likely to experience operative mortality (5.7% vs 1.6%, P = .001) as well as major morbidity (21.7% vs 10.5%, P < .001). Performance of rarely or may be appropriate SAVR significantly decreased over time (slope -0.51%/year, P trend < .001), and it was decreased after the release of the AUC (before release, 3.83% vs after release, 2.06%; P = .036). Substantial interhospital variation in appropriateness was observed (range of may be or rarely appropriate SAVR, 0%-10%). CONCLUSIONS: The majority of isolated SAVR for aortic stenosis was appropriate according to the 2017 AUC. Appropriateness improved after publication of AUC, and this improvement was associated with a significant reduction of major morbidity and mortality.

Immunotyping and Quantification of Melanoma Tumor-Infiltrating Lymphocytes.

The density of tumour-infiltrating lymphocytes (TILs) in melanoma is correlated with improved clinical prognosis; however, standardized TIL immunotyping and quantification protocols are lacking. Herein, we provide a review of the technologies being utilized for the immunotyping and quantification of melanoma TILs.

Association between age and disease specific mortality in medullary thyroid cancer.

BACKGROUND: The aim of this study was to evaluate the association between age and disease specific mortality (DSM) among adults diagnosed with medullary thyroid cancer (MTC). METHOD: Surveillance, Epidemiology, and End Results (SEER-18) was used to analyze adult MTC patients stratified by age (18-64, 65-79, ≥80 years). Associations between patient demographics, tumor size, nodal status, metastatic disease, and extent of surgery on DSM was assessed with multivariable Cox regression. RESULTS: Among 1457 patients with MTC, 1008 (69.2%) were younger adults, 371 (25.5%) older adults, and 78 (5.4%) were super-elderly. A significantly higher proportion of older adults and super-elderly had less than the recommended operation for MTC. On multivariable analysis, older adults and super-elderly were 2.9 and 6.7 times more likely to have an increased DSM (HR:2.91, 95% CI: 1.83-4.63; p < 0.001 and HR: 6.70, 95%CI: 3.69-12.20; p < 0.001). Extent of surgery or lymphadenectomy did not affect DSM. CONCLUSIONS: Increased age is an independent predictor of DSM in patients with MTC.

Rising Cost of Thyroid Surgery in Adult Patients.

BACKGROUND: The aim of this study is to describe the economic trends in adults who underwent elective thyroidectomy. METHODS: We performed a population-based study utilizing the Premier Healthcare Database to examine adult patients who underwent elective thyroidectomy between January 2006 and December 2014. Time was divided into three equal time periods (2006-2008, 2009-2011, and 2012-2014). To examine trend in patient charges, we modeled patient charges using generalized linear regressions adjusting for key covariates with standard errors clustered at the hospital level. RESULTS: Our study cohort consisted of 52,012 adult patients who underwent a thyroid operation. During the study period, the most common procedure changed from a thyroid lobectomy to bilateral thyroidectomy. Over the study period, there was an increase in the proportion of completion thyroidectomies from 1.1% to 1.6% (P < 0.001), malignant diagnoses from 21.7% to 26.8% (P < 0.001), procedures performed at teaching hospitals from 27.7% to 32.9% (P < 0.001), and procedures performed on an outpatient basis from 93.85% to 97.55% (P < 0.001). The annual increase in median patient charge adjusted for inflation was $895 or 4.3% resulting in an increase of 38.8% over 9 y. Higher thyroidectomy charges were associated with male patients, malignant surgical pathology, patients undergoing limited or radical neck dissection, experiencing complications, those with managed health care insurance, and a prolonged length of stay. CONCLUSIONS: Despite recent changes in thyroid surgery practices to decrease the economic burden of hospitals, costs continue to rise 4.3% annually. Additional prospective studies are needed to identify factors associated with this increasing cost.

Transoral thyroid and parathyroid surgery via the vestibular approach-a 2020 update.

Transoral endoscopic thyroidectomy and parathyroidectomy via the vestibular approach (TOET/PVA or TOETVA-TOEPVA) is the latest remote-access technique employed in the central neck. As the only approach that does not leave any cutaneous incision, (TOET/PVA) has become popular in both the Far East and Western series since its original description in 2015. More than just a "scarless" surgery, (TOET/PVA) has been associated with a short learning curve, access to the bilateral central neck compartments, few surgical contraindications, minimal complications, and minimal additional instrumentation. To date, more than 2,000 cases have been completed, including more than 400 in North America, demonstrating brisk utilization of a novel technique relative to earlier remote access central neck approaches. Herein, we describe updates that continue to improve the safety and efficacy of the procedure.

Hepatic Artery Thrombosis and Takotsubo Syndrome After Liver Transplantation - Which Came First?

BACKGROUND Takotsubo syndrome is a transient, reversible, stress-induced cardiomyopathy that affects only 1.4% of liver transplant patients and can cause complications, including cardiogenic shock, arrhythmia, and thromboembolism. Hepatic artery thrombosis is also rare, affecting just 2-4% of these patients, but can have disastrous consequences. Here, we describe a case of concurrent takotsubo syndrome and hepatic artery thrombosis in a postoperative liver transplant recipient. CASE REPORT The patient was a 66-year-old man who underwent living donor liver transplantation for non-alcoholic steatohepatitis. On postoperative day 3, he became lethargic and tachycardic to the 120 s. Work-up, including EKG, troponin I, BNP, and transthoracic echocardiogram, was characteristic for takotsubo syndrome. His LVEF of 15-20% was markedly reduced compared to his baseline of 50-55% from 6 months prior. Hepatic ultrasonography showed no hepatic arterial flow, prompting emergent return to the OR, where intraoperative evaluation revealed hepatic artery thrombosis. The graft was salvaged after hepatic artery thrombectomy and arterial anastomosis revision. We are unable to determine which event caused the other in this case, as both takotsubo syndrome and hepatic artery thrombosis manifested within the same time frame. CONCLUSIONS It is important to recognize takotsubo syndrome as a potential cause of cardiac dysfunction and hepatic artery thrombosis in liver transplant patients, and also be aware that hepatic artery thrombosis can precipitate takotsubo syndrome.

Socioeconomically Distressed Communities Associated With Long-term Mortality After Bariatric Surgery.

BACKGROUND: Surgical outcomes are affected by socioeconomic status, yet these factors are poorly accounted for in clinical databases. We sought to determine if the Distressed Communities Index (DCI), a composite ranking by zip code that quantifies socioeconomic risk, was associated with long-term survival after bariatric surgery. METHODS: All patients undergoing Roux-en-Y gastric bypass (1985-2004) at a single institution were paired with DCI. Scores range from 0 (no distress) to 100 (severe distress) and account for unemployment, education, poverty, median income, housing vacancies, job growth, and business establishment growth. Distressed communities, defined as DCI ≥75, were compared with all other patients. Regression modeling was used to evaluate the effect of DCI on 10-year bariatric outcomes, whereas Cox Proportional Hazards and Kaplan-Meier analysis examined long-term survival. RESULTS: Gastric bypass patients (n = 681) come from more distressed communities compared with the general public (DCI 60.5 ± 23.8 versus 50 ± 10; P < 0.0001). A total of 221 (32.3%) patients came from distressed communities (DCI ≥75). These patients had similar preoperative characteristics, including BMI (51.5 versus 51.7 kg/m2; P = 0.63). Socioeconomic status did not affect 10-year bariatric outcomes, including percent reduction in excess body mass index (57% versus 58%; P = 0.93). However, patients from distressed communities had decreased risk-adjusted long-term survival (hazard ratio, 1.38; P = 0.043). CONCLUSIONS: Patients with low socioeconomic status, as determined by the DCI, have equivalent outcomes after bariatric surgery despite worse long-term survival. Future quality improvement efforts should focus on these persistent disparities in health care.

The association between the ultrasonography TIRADS classification system and surgical pathology among indeterminate thyroid nodules.

BACKGROUND: A high proportion of cytologically indeterminate, Afirma-suspicious thyroid nodules are benign. The Thyroid Imaging Reporting and Data System was proposed by the American College of Radiology in 2015 to determine appropriate management of thyroid nodules in a standardized fashion. Our aim was to determine the diagnostic value of the Thyroid Imaging Reporting and Data System in cytologically indeterminate and Afirma-suspicious nodules. METHODS: We retrospectively queried cytopathology archives for retrospectively for thyroid fine-needle aspiration specimens obtained between February 2012 and September 2016 that were associated with the following: (1) indeterminate diagnosis, (2) ultrasonographic imaging at our institution, (3) an Afirma Gene Expression Classifier-suspicious result, and (4) surgery at our institution. We then calculated the diagnostic value of the Thyroid Imaging Reporting and Data System in predicting surgical pathology. RESULTS: Our cohort consisted of 133 nodules among 131 patients who underwent thyroid surgery for cytologically indeterminate, Afirma-suspicious nodules. A total of 9 nodules (6.8%) were assigned TR2 "not suspicious," 25 (18.8%) TR3 "mildly suspicious," 81 (60.9%) TR4 "moderately suspicious," and 18 (13.5%) TR5 "highly suspicious." Among our cohort, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the Thyroid Imaging Reporting and Data System was 71.4%, 38.1%, 40.2%, 69.6%, and 50.4%, respectively. CONCLUSION: Among cytologically indeterminate and Afirma-suspicious nodules, the Thyroid Imaging and Reporting and Data System was a poor predictor of final surgical pathology. Additional prospective studies are needed to validate these findings.

TIRADS Interobserver Variability Among Indeterminate Thyroid Nodules: A Single-Institution Study.

OBJECTIVES: A high proportion of cytologically indeterminate, Afirma Gene Expression Classifier "suspicious" thyroid nodules are benign. The Thyroid Imaging Reporting and Data System (TIRADS), was proposed by the American College of Radiology in 2017 to help classify thyroid nodules based on ultrasound characteristics in a standardized fashion to guide management. We aim to determine the interobserver variability of TIRADS classification among cytologically indeterminate and Afirma suspicious nodules. METHODS: We retrospectively queried cytopathology archives for thyroid fine-needle aspiration specimens obtained between February 2012 and September 2016 with associated (1) indeterminate diagnosis, (2) ultrasound imaging at our institution, (3) Afirma suspicious result, and (4) surgery at our institution. We compared the TIRADS variability of the 3 blinded radiologists using intraclass correlation coefficients. RESULTS: Our cohort consisted of 127 nodules. Intraclass correlation coefficients can be interpreted as follows: less than 0.4, poor; 0.4 to 0.59, fair; 0.6 to 0.74, good; 0.75 to 1.00, excellent. The intraclass correlation coefficients of the raw TIRADS score and category variability was 0.561 (95% confidence interval [CI]: 0.464-0.651) or fair and 0.547 (95% CI, 0.449-0.640) or fair, respectively. When analyzing composition, echogenicity, shape, margin, and echogenic foci, the ICCs were 0.552 (95% CI, 0.454-0.643), fair; 0.533 (95% CI, 0.432-0.627), fair; 0.359 (95% CI, 0.248-0.469), poor; 0.192 (95% CI, 0.084-0.308), poor; and 0.549 (95% CI, 0.451- 0.641), fair, respectively. CONCLUSIONS: Our results show that among the subset of cytologically indeterminate and Afirma suspicious nodules, TIRADS interobserver variability was fair. Shape and margin criteria were the biggest sources of disagreement. Large prospective studies are needed to evaluate the interobserver variability of TIRADS in this subset of thyroid nodules.

Thyroidectomy in older adults: an American College of Surgeons National Surgical Quality Improvement Program study of outcomes.

BACKGROUND: The growth of the US geriatric population coupled with the rise in thyroid nodular disease and cancer will result in an increased number of thyroidectomies performed in older adults. We aim to evaluate outcomes after thyroidectomy in older adults as compared with younger adults. METHODS: A retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database from 2012-2015 categorized thyroidectomy patients into three age groups: 18-64 y, 65-79 y, and ≥80 y. Thirty-day perioperative outcomes were analyzed using bivariate χ2 test and multivariate logistic regression to estimate risk of outcomes. RESULTS: Our study identified 60,990 patients who underwent thyroidectomy: 47,855 (78.4%) patients between 18 and 64 y old, 11,716 (19.2%) between 65 and 79 y old, and 1419 (2.3%) ≥80 y. Compared with younger adults, patients aged ≥80 y were 2.67 times more likely to develop a complication (95% confidence interval [CI]: 2.02-3.53, P < 0.001), 1.83 times more likely to be readmitted for any reason (95% CI: 1.40-2.38, P < 0.001), 1.54 times more likely to be readmitted for a reason related to the thyroidectomy (95% CI: 1.10-2.16, P < 0.05), and 1.66 times more likely to have an extended hospital stay (95% CI: 1.44-1.91, P < 0.001). Patients aged 65-79 y were 1.40 times more likely to develop a complication (95% CI: 1.19-1.63, P < 0.001). CONCLUSIONS: Patients aged ≥65 y have significantly higher rates of overall complications. In addition, patients aged ≥80 y have higher rates of total and thyroidectomy-related readmissions and extended length of hospital stay.

Preoperative Molecular Markers in Thyroid Nodules.

The need for distinguishing benign from malignant thyroid nodules has led to the pursuit of differentiating molecular markers. The most common molecular tests in clinical use are Afirma® Gene Expression Classifier (GEC) and Thyroseq® V2. Despite the rapidly developing field of molecular markers, several limitations exist. These challenges include the recent introduction of the histopathological diagnosis "Non-Invasive Follicular Thyroid neoplasm with Papillary-like nuclear features", the correlation of genetic mutations within both benign and malignant pathologic diagnoses, the lack of follow-up of molecular marker negative nodules, and the cost-effectiveness of molecular markers. In this manuscript, we review the current published literature surrounding the diagnostic value of Afirma® GEC and Thyroseq® V2. Among Afirma® GEC studies, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) ranged from 75 to 100%, 5 to 53%, 13 to 100%, and 20 to 100%, respectively. Among Thyroseq® V2 studies, Se, Sp, PPV, and NPV ranged from 40 to 100%, 56 to 93%, 13 to 90%, and 48 to 97%, respectively. We also discuss current challenges to Afirma® GEC and Thyroseq® V2 utility and clinical application, and preview the future directions of these rapidly developing technologies.

Octogenarians have worse clinical outcomes after thyroidectomy.

BACKGROUND: The rising proportion of older adults in the US population coupled with an increased prevalence of nodular thyroid disease will result in more thyroidectomies being performed. The aim of this study is to evaluate the clinical outcomes among older adults (age ≥65) undergoing thyroidectomy compared to younger adults (18-64). METHODS: This was a population-based study of adult thyroidectomy patients using the Premier Healthcare Database, 2005-2014. Discharge status, hospital length of stay (LOS), morbidity, and total patient charge were compared between younger adults and older adults in three different age groups: ≥65, ≥70, and ≥80 years old. RESULTS: Among 75,141 thyroidectomy patients, 15,805 (21.0%) patients were ≥65 years, 8834 (11.8%) were ≥70 years, and 1613 (2.2%) were ≥80 years. Patients ≥80 years were 2.6 times (aOR:2.58, 95%CI: 1.72-3.86; p < 0.001) more likely to be discharged to a home health organization than to be discharged to their residence and 1.6 times (aOR:1.61, 95%CI: 1.30-2.00; p < 0.001) more likely to have at least one complication. CONCLUSIONS: Age ≥80 is an independent predictor of worse clinical outcomes after thyroidectomy.

Bilateral chylothorax following reoperative central neck dissection for metastatic papillary thyroid cancer.

Locoregional recurrence of papillary thyroid cancer (PTC) can occur in up to 30% of patients within 10 years after initial treatment. Reoperative surgery can be challenging due to scarring, fibrosis and distorted anatomy and may be associated with increased complications compared with initial operations. Chylothorax is an extremely rare and potentially life-threatening complication that can be associated with neck dissections and thyroid surgery. In this report, we describe an unusual case of bilateral chylothorax following a left central neck dissection for recurrent PTC.

Pimavanserin: novel pharmacotherapy for Parkinson's disease psychosis.

INTRODUCTION: Pimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Areas covered: This review focuses on the preclinical discovery of pimavanserin. It analyzes the pharmacological, behavioral and molecular mechanisms of pimavanserin and their contribution to the therapeutic advantages of the drug as reported in published preclinical and clinical studies, press releases and product labels. Expert opinion: Pimavanserin exhibits a unique pharmacological profile with nanomolar affinity at serotonin 5-HT2A and 5-HT2C receptors. Functionally, it acts as a potent inverse agonist at 5-HT2A receptors, with selectivity over 5-HT2C receptors and no appreciable activity at other neurotransmitter receptors. Behavioral studies found that pimavanserin reversed impaired behaviors in animal models predictive of antipsychotic activity, and with no impairment of motor functions. The drug exhibits long plasma half-life (57 hours), which support its once/day administration. A pivotal phase III clinical trial demonstrated significant improvement in PDP symptoms in patients receiving pimavanserin compared to placebo-treated patients. The drug also displayed relatively benign safety and tolerability profiles. Pimavanserin's mechanism of action might contribute to its unique psychopharmacological properties in the improved treatment of PDP, and perhaps psychosis in other diseases including schizophrenia and dementia-related psychosis.

Thyroid Nodule Diagnostic Markers in the Face of the New NIFTP Category: Time for a Reset?

BACKGROUND: Current thyroid molecular tests are specifically designed for the differential diagnosis of nodules with indeterminate or suspicious fine-needle aspiration (FNA) cytology. SUMMARY: However, their clinical validity faces challenges from both variation among institutions in cancer prevalence and, most recently, the new category of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The latter diagnosis was previously classified as malignant. Relevant to this, all molecular panels on the market today were originally tested and validated within the context of these entities being considered malignant. CONCLUSION: This review examines possible effects of the NIFTP reclassification as a precancerous lesion on the original validation studies and, investigates the effect of the significant reported variability in thyroid cancer prevalence on the performance of these tests.

A garden of parathyroid adenomas.

Despite improvements in parathyroidectomy success rates, patients with persistent primary hyperparathyroidism (PHPT) after initial surgery continue to challenge clinicians. Some of the challenges are due to ectopic parathyroid adenomas, including thymic, intrathyroidal, carotid sheath and mediastinal glands, and others are because of supernumerary glands. While uncommon in PHPT, multigland disease is also an important consideration in patients requiring reoperative surgery for persistent disease. For this reason, localisation studies including sestamibi, ultrasound, CT scan and venous sampling for abnormal glands may be an essential component of the preoperative workup. In this report, we describe an unusual case of a patient who required a total of four operations to cure PHPT arising from seven parathyroid adenomas.

Clinical management of restless legs syndrome in end-stage renal disease patients.

Restless legs syndrome (RLS) is a common neurological movement disorder, characterized by restless and unpleasant sensations in the deep inside of legs. The symptoms of RLS are less noticeable during daytime, but more prevalent at night. Therefore, the disorder can induce low quality of life, insomnia, and impairment of daytime activity. RLS in end-stage renal disease (ESRD) patients is especially problematic due to premature discontinuation of dialysis and increased mortality. The prevalence of RLS among dialysis patients is much higher compared to the prevalence of the same disorder in patients with normal renal functions. Even though there are recommended treatment guidelines for the general population established by Medical Advisory Board of the RLS foundation, which include the use of dopamine agonists, levodopa, gabapentin, benzodiazepines, and opioids, limited information is available on the effects of these therapies in ESRD patients. Since the existing clinical data were extrapolated from small sample sizes in short-term clinical trials, further clinical studies are still needed to better assess the efficacy, safety, and tolerability of these medications in patients with ESRD.

The Preclinical and Clinical Effects of Vilazodone for the Treatment of Major Depressive Disorder.

INTRODUCTION: Major depressive disorder (MDD) is the leading cause of disability worldwide, and according to the STAR*D trial, only 33% of patients with MDD responded to initial drug therapy. Augmentation of the leading class of antidepressant treatment, selective serotonin reuptake inhibitors (SSRIs), with the 5-HT1A receptor agonist buspirone has been shown to be effective in treating patients that do not respond to initial SSRI therapy. This suggests that newer treatments may improve the clinical picture of MDD. The US Food and Drug Administration (FDA) approved the antidepressant drug vilazodone (EMD 68843), a novel SSRI and 5-HT1A receptor partial agonist. Vilazodone has a half-life between 20-24 hours, reaches peak plasma concentrations at 3.7-5.3 hours, and is primarily metabolized by the hepatic CYP450 3A4 enzyme system. AREAS COVERED: The authors review the preclinical and clinical profile of vilazodone. The roles of serotonin, the 5-HT1A receptor, and current pharmacotherapy approaches for MDD are briefly reviewed. Next, the preclinical pharmacological, behavioral, and physiological effects of vilazodone are presented, followed by the pharmacokinetic properties and metabolism of vilazodone in humans. Last, a brief summary of the main efficacy, safety, and tolerability outcomes of clinical trials of vilazodone is provided. EXPERT OPINION: Vilazodone has shown efficacy versus placebo in improving depression symptoms in several double-blind, placebo-controlled trials. The long-term safety and tolerability of vilazodone treatment has also been established. Further studies are needed that directly compare patients treated with an SSRI (both with and without an adjunctive 5-HT1A partial agonist) versus patients treated with vilaozodone.