Preoperative and postoperative optimisation of patients undergoing thyroid surgery: a multicentre quality improvement project at Barts Health NHS Trust.

Hypocalcaemia following thyroid surgery can occur in up to 38% of patients. With over 7100 thyroid surgeries performed in 2018 in the UK, this is a common postoperative complication. Undertreated hypocalcaemia can result in cardiac arrhythmias and death. Preventing adverse events from hypocalcaemia requires preoperative identification and treatment of at-risk patients with vitamin D deficiency, timely recognition of postoperative hypocalcaemia and prompt appropriate treatment with calcium supplementation. This project aimed to design and implement a perioperative protocol for prevention, detection and management of post-thyroidectomy hypocalcaemia. A retrospective audit of thyroid surgeries (n=67; October 2017 to June 2018) was undertaken to establish baseline practice of (1) preoperative vitamin D levels assessment, (2) postoperative calcium checks and incidence of postoperative hypocalcaemia and (3) management of postoperative hypocalcaemia. A multidisciplinary team approach following quality improvement principles was then used to design a perioperative management protocol with all relevant stakeholders involved. After dissemination and implementation, the above measures were reassessed prospectively (n=23; April-July 2019). The percentage of patients having their preoperative vitamin D measured increased from 40.3% to 65.2%. Postoperative day-of-surgery calcium checks increased from 76.1% to 87.0%. Hypocalcaemia was detected in 26.8% of patients before and 30.43% of patients after protocol implementation. The postoperative component of the protocol was followed in 78.3% of patients. Limitations include low number of patients which precluded from analysis of the impact of the protocol on length of stay. Our protocol provides a foundation for preoperative risk stratification and prevention, early detection and subsequent management of hypocalcaemia in thyroidectomy patients. This aligns with enhanced recovery protocols. Moreover, we offer suggestions for others to build on this quality improvement project with the aim to further advance the perioperative care of thyroidectomy patients.

Glucocorticoids-Induced Neuropsychiatric Disorders in Patients With Inflammatory Bowel Disease: A Systematic Review.

Inflammatory bowel disease (IBD) is a globally rising chronic intestinal disease that affects individuals in many parts of the world. Immunosuppressive medications such as corticosteroids are used to manage flare-ups and to induce remission in IBD. Corticosteroids are said to cause several systemic symptoms, but they are also associated with drug-induced neuropsychiatric disorders. This article examines the existing data on psychiatric and cognitive effects associated with corticosteroid therapy in relation to IBD. Many studies have found that corticosteroids appear to cause mood disturbances such as mania, hypomania, depression, and cognitive problems in the first few weeks of therapy, but these effects are dose-dependent and often mild. The purpose of this literature review is to shed light on the impact corticosteroids can have on individuals' mental health, which will aid physicians in the future when treating patients with IBD. Healthcare professionals should advise patients of this risk and assess the need for intervention. While there is evidence that corticosteroids can elicit neuropsychiatric symptoms, more data on people with IBD who are on corticosteroid therapy is needed to determine the prevalence of glucocorticoid-induced mood changes in this population.

Adverse Effects of Cannabinoids and Tobacco Consumption on the Cardiovascular System: A Systematic Review.

With the recent legalization of marijuana in several countries for recreational use, a controversial belief is spreading about it being "safe". In this systematic review, we decided to investigate this belief and present the adverse effects of marijuana and tobacco smoking on the cardiovascular system. We carried out an electronic search on databases including PubMed, PubMed Central, and Medline. Medical Subject Headings (MeSH) terms and different keywords were used for data collection. We included studies published in the last 10 years that were in English. All types of study subjects were accepted. Grey literature, books, case reports and case series, overlapping and duplicate studies, and studies older than 10 years were excluded. In this review, we included 18 studies, which we then separated into the "tobacco and cardiovascular disease" arm and the "cannabinoids and cardiovascular disease" arm. We had 11 and seven studies for each of the arms, respectively. The types of articles included in this review were traditional and systematic reviews and meta-analyses. After reviewing all the data included in this article, we found out that cannabinoid consumption has a more devastating effect on the cardiovascular system when compared to tobacco. The shocking fact was that in several cases, deadly adverse effects were observed in patients within a few hours after consumption or even during their first time using cannabinoids.

Systematic Review of Pediatric Brain Tumors in Neurofibromatosis Type 1: Status of Gene Therapy.

As oncology practice is rapidly shifting away from toxic chemotherapy, gene therapy provides a highly specific therapeutic approach for brain tumors. In this systematic review, we investigate gene therapy's status in pediatric brain tumors and future recommendations. The search was conducted systematically using PubMed, Cochrane, Google Scholar, and ClinicalTrials.gov databases. The field search used in the process was selected based on the keywords and Medical Subject Headings (MeSH), depending on the database used. We included cases of neurofibromatosis type 1 (NF1) brain tumors in all age groups with the additional inclusion of English language, free full text, articles published within the last 20 years, randomized controlled trials (RCTs), observational studies, systematic reviews, and meta-analyses. We excluded case reports, case studies, and editorials. The search identified a total of 1,213 articles from the databases. We included 19 studies with 16 narrative reviews, one systematic review, and two randomized clinical trials with 43 patients. After reviewing all data in the articles, we found that gene therapy can improve standard treatment efficacy when used as adjuvant therapy. It can be used to overcome barriers such as chemotherapy resistance by downregulating resistance genes. It is associated with mild toxicity when compared with other available treatment options, but given the overall poor prognosis in pediatric brain tumors, further studies are warranted.

Is Leukotriene Receptor Antagonist the Direct Cause of Churg-Strauss Syndrome in Asthmatic Patients?

One of the main reasons for continuous, persistent asthma is when there is a change in the structure of the airways and the Lung parenchyma. These persistent changes bring a much worse prognosis to asthmatic conditions and predispose the situation to severe asthmatic syndromes such as Churg-Strauss syndrome (CSS). CSS is an inflammation of systemic blood vessels and is a rare disorder that can be suspected in long-standing asthmatic patients. Leukotriene antagonists receptor antagonists (LTRA) have been used to treat asthma along with tapering steroids. But after the introduction of LTRA therapy in these patients suggests a causal relation between LTRA initiation and the development of CSS, or it is an unmasking of CSS as the dose of steroid tapers down with LTRA therapy. This review highlights the relationship between leukotriene antagonists and the pathogenesis of CSS. It summarizes the current literature regarding the development of CSS with the initiation of LTRA therapy on asthmatic patients. The literature on this topic was reviewed using different research/article searches, manual library searches, conference abstracts, and internet searches.

Nonalcoholic Fatty Liver Disease and Hypothyroidism: What You Need to Know.

Non-alcoholic fatty liver disease (NAFLD) represents one of the leading causes of chronic liver disease globally, perhaps because of the drastic increase in prevalence around the world during the last 20 years and continues growing. The disease starts from simple steatosis (NAFL) that can progress to non-alcoholic steatohepatitis (NASH) and, in some patients, progress to cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis and pathophysiology of NAFLD are complex and involve different factors (genetic, metabolic, endocrinopathies, and others). One of the concerns that appeared in recent years is hypothyroidism-induced NAFLD. The pathogenesis is compound and not well understood, and an association between hypothyroidism and NAFLD remains controversial because of insufficient studies that can confirm it. More research is needed to determine the association between hypothyroidism and NAFLD and the underlying mechanisms. In this review, we will discuss a more in-depth analysis of the physiology of thyroid hormones (TH) as well as the pathophysiology of hypothyroidism-induced NAFLD and, based on the recent meta-analyses, the association of thyroid hormones and NAFLD.

A Systematic Review on the Safety and Efficacy of PCSK9 Inhibitors in Lowering Cardiovascular Risks in Patients With Chronic Kidney Disease.

Cardiovascular events caused by dyslipidemia are one of the leading causes of death in patients with Chronic Kidney Disease (CKD). Statins are the first line of treatment for patients with hyperlipidemia and in the treatment regimen for patients with CKD. Therefore, the introduction of Proprotein Convertase Subtilisin-Kexin type 9 inhibitors (PCSK9 inhibitors) is a viable and possibly effective treatment option for patients who, despite high doses of statins, struggle to lower their low-density lipoprotein cholesterol (LDL-C) levels. Our paper's objective is to explore the safety of these biological agents, particularly in patients with varying stages of impaired kidney function, and the correlating effectiveness in lowering their LDL-C levels, thereby reducing cardiovascular risks in these patients. We methodically retrieved relevant articles from PubMed, PubMed Central, Medline, and Google scholar in April 2022. We used the Medical Subject Heading (MeSH) Strategy and used the relevant keyword, then applied our inclusion and exclusion criteria; the initial search gave 10,542 results; with the removal of duplicates, irrelevant articles, and application of quality assessments done, we finally included 15 papers for our review with 37,188 patients. PCSK9 inhibitors are reliable, safe, and efficient therapy in lowering LDL-C levels in patients with CKD. However, its safety and efficacy in severe and end-stage kidney disease are grey, as other factors such as infections lead to morbidity and mortality. Future trials on chronic kidney disease and PCSK9 inhibitors should investigate the inhibitors' ability to improve kidney functions at all stages of kidney disease while lowering lipid levels and finally analyze the safety in patients with end-stage kidney disease.

Establishing the Association Between Osteoporosis and Peptic Ulcer Disease: A Systematic Review.

Osteoporosis is one of the most common metabolic bone diseases. Many studies were conducted to find the association between peptic ulcer disease (PUD), Helicobacter pylori infection, proton-pump inhibitor (PPI) use, and increased risk for fracture, but results remain ambiguous. We performed this systematic review to understand the association between PUD and osteoporosis. We comprehensively searched relevant articles on April 19, 2022, by exploring different databases including PubMed, PubMed Central (PMC), and Medline using relevant keywords. After applying inclusion and exclusion criteria and undergoing quality assessment, we retained 25 studies published in and after 2015. For our systematic review, we included a total of 5,600,636 participants. The studies included in our review demonstrated a significant association between PUD, H. pylori infection, and the risk of osteoporosis. Long-term PPI use was also found to be a risk factor for osteoporosis. Malabsorption of nutrients, increase in inflammatory cytokines, and alterations in hormone status were found to be the notable factors behind the association. Early management of H. pylori infection and cautious use of long-term PPIs may protect against osteoporosis. Further randomized controlled trials (RCTs) are necessary to establish a causal relationship.

Comparison of Non-Oncological Postoperative Outcomes Following Robotic and Laparoscopic Colorectal Resection for Colorectal Malignancy: A Systematic Review and Meta-Analysis.

The objective of this systematic review and meta-analysis is to compare the postoperative outcomes of robotic and laparoscopic colorectal resection for colorectal malignancy. We performed a systematic review using a comprehensive search strategy on several electronic databases (PubMed, PubMed Central, Medline, and Google Scholar) in April 2022. Postoperative outcomes of robotic versus laparoscopic surgery for colorectal cancer were compared using 12 end points. Observational studies, randomized controlled trials, and nonrandomized clinical trials comparing robotic and laparoscopic resection for colorectal cancer were included. The statistical analysis was performed using the risk ratio (RR) for categorical variables and the standardized mean differences (SMD) for continuous variables. Sixteen studies involving 2,318 patients were included. The difference in length of hospital stay was significantly shorter with robotic access (SMD = -0.10, 95% CI = -0.19, -0.01, P = 0.04, I2 = 0%). Regarding intra-abdominal abscesses, the analysis showed an advantage in favor of the robotic group, but the result was not statically significant (RR = 0.54, 95% CI = 0.28, 1.05, P = 0.07, I2 = 0%). Mechanical obstruction was found to be higher in robotic group, favoring laparoscopic access, but was not significant (RR = 1.91, 95% CI = 0.95, 3.83, P = 0.07, I2 = 0%). There was no difference in time to pass flatus and consume a soft diet. The rates of anastomotic leakage, ileus, wound infection, readmission, mortality, and incisional hernias were similar with both approaches. Robotic surgery for colorectal cancer is associated with a shorter hospital stay, with no differences in mortality and postoperative morbidity.

A Systematic Review of SARS-CoV-2-Associated Hepatic Dysfunction and the Impact on the Clinical Outcome of COVID-19.

Coronavirus disease 2019 (COVID-19) has rapidly spread across the globe since December 2019. The spectrum of clinical manifestations of COVID-19 ranges from mild to life-threatening forms. Alteration of hepatic function in COVID-19 is multifactorial. The objective of this systematic review is to assess the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced hepatic dysfunction and the clinical outcome in patients infected with COVID-19. We methodically explored several electronic databases (PubMed, PubMed Central, MEDLINE, and Google Scholar) in April 2022 using focused words and terms of medical subject headings for appropriate studies. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for conducting our systematic review. Hepatic dysfunction was identified as elevation of liver function tests (LFTs) above the upper limit of normal. The clinical outcome was described as a combination of mortality, intensive care unit (ICU) transfer, and the need for mechanical ventilation (MV). The initial search yielded a total of 7187 studies. After elimination of duplicates, exclusion of studies based on irrelevant titles and abstracts, comprehensive analysis of full-text formats, and evaluation of quality, a total of 16 studies were eligible to be included in our systematic review. In the 16 selected studies, there were 23,962 patients. The SARS-CoV-2 virus can negatively affect several organ systems by interacting with specific receptors widely expressed in the human body. A multifactorial etiology of hepatic dysfunction is observed in COVID-19. SARS-CoV-2 infection is associated with abnormal LFTs. Significantly higher mortality, ICU admissions, and requirement for MV are associated with LFT alterations. For this reason, patients infected with COVID-19 must have their hepatic function closely monitored.

Why Is There an Increased Risk for Sudden Cardiac Death in Patients With Early Repolarization Syndrome?

The last two decades have changed the viewpoint on early repolarization syndrome (ERS). The prevalence of the early repolarization pattern is variable and ranges between 3-24% depending upon age, gender, and criteria used for J-point upliftment from baseline (0.05mV vs. 1 mV). While this pattern was previously linked with a benign result, multiple recent investigations have found a link between early repolarization and Sudden Cardiac Death (SCD) by causing life-threatening arrhythmias like Ventricular tachycardia/Ventricular fibrillation, a condition known as early repolarization syndrome. The syndrome falls under a broader bracket of J wave syndromes, which can be caused by early repolarization or depolarization abnormalities. The characteristics of early repolarization that are considered high risk for Sudden Cardiac Death include the amplitude of J-point upliftment from baseline ( > 0.2 mV), Inferior-lateral location of Early Repolarization pattern, and horizontal and downsloping ST-segment. Patients with symptomatic early repolarisation patterns on ECG are more likely to have repeated cardiac episodes. Implantable Cardioverter-Defibrillator (ICD) implantation and isoproterenol are the recommended treatments in symptomatic patients. On the other hand, asymptomatic patients with early repolarization patterns are prevalent and have a better outcome. Risk categorization is still obscure in asymptomatic early repolarization patterns. This traditional review outlines the known knowledge of pathophysiology behind the increased risk of sudden cardiac death, risk stratification of patients with ERS, and the treatment guidelines for patients with ERS. Further prospective studies are recommended to elucidate the exact mechanism for ventricular arrhythmogenesis in ERS patients and to risk stratifying asymptomatic patients with ERS.

Absolute Versus Relative Changes in Cardiac Troponins in the Diagnosis of Myocardial Infarction: A Systematic Review and Meta-Analysis.

Ischemic heart disease (IHD) is one of the leading causes of death globally. Rapid diagnosis of myocardial infarction (MI) will enable earlier initiation of the treatment and improve patient outcomes. Practice guidelines for non-ST-elevation acute coronary syndromes by the American College of Cardiology (ACC)/American Heart Association (AHA) had listed the diagnostic performance of absolute versus relative changes in evidence gaps. We aimed to address this evidence gap by examining the diagnostic accuracy of absolute versus relative changes in cardiac troponins at various time intervals in diagnosing MI. Grey literature, conference abstracts, animal studies, and reports published before 2009 and in languages other than English were excluded. We included reports that investigated absolute or relative changes in highly sensitive cardiac troponin T (hs-cTnT) or sensitive/highly sensitive cardiac troponin I (s/hs-cTnI) assays after specific time intervals (1, 2, or 3 h) in patients presenting with symptoms suggestive of the acute coronary syndrome. After screening, we arranged the reports in 12 separate groups based on the variables for which the data was reported. Quality assessment of the diagnostic accuracy studies-2 (QUADAS-2) was used to assess the risk of bias in the included studies. The weighted summary area under the curve (AUC) was calculated for each pool. We then performed two-sided (or two-tailed) tests to compare independent receiver operating characteristic (ROC) curves. MedCalc version 20.106 (MedCalc Software Ltd., Ostend, Belgium) was used for all statistical analysis. We included eight reports with 23,450 patients in the meta-analysis. Weighted summary estimates and their respective 95% confidence intervals (CI) under random-effects model for ROC-AUC are as follows: absolute hs-cTnI at 1 h - 0.94 (95% CI: 0.922 to 0.959, p < 0.001); absolute hs-cTnT at 1 h - 0.921 (95% CI: 0.902 to 0.941, p < 0.001); absolute s/hs-cTnI at 2 h - 0.953 (95% CI: 0.926 to 0.980, p < 0.001); absolute hs-cTnT at 2 h 0.951 (95% CI: 0.940 to 0.962, p < 0.001); relative hs-cTnT at 2 h - 0.818 (95% CI: 0.733 to 0.903, p < 0.001); relative s/hs-cTnI at 2 h - 0.762 (95% CI: 0.726 to 0.798, p < 0.001); absolute hs-cTnI at 3 h - 0.967 (95% CI: 0.95 to 0.984, p < 0.001); absolute hs-cTnT at 3 h - 0.959 (95% CI: 0.950 to 0.968, p < 0.001); and relative hs-cTnT at 3 h - 0.926 (95% CI: 0.907 to 0.945, p < 0.001). P-values of comparison of absolute and relative changes are as follows: hs-cTnT at 1 h: <0.0001; hs-cTnI at 1 h: <0.0001; hs-cTnT at 2 h: 0.0024; s/hs-cTnI at 2 h: <0.0001; hs-cTnT at 3 h: 0.0022; and hs-cTnI at 3 h: 0.0005. Our analysis found absolute changes to be superior to relative changes in both hs-cTnT and s/hs-cTnI at 1, 2, and 3 h in the diagnosis of MI. There was no statistically significant difference in comparing s/hs-cTnI vs. hs-cTnT using absolute or relative changes at any time interval. Our findings suggest that future research investigating a potential 0 h/30 min algorithm should use absolute Δ over relative Δ. A suboptimal number of reports in the groups limited our ability to establish the robustness of the results. We did not receive any funding for this review.

Enhanced recovery after laryngectomy: A feasibility study in 25 patients.

PURPOSE: To describe the development and implementation of an enhanced recovery programme for patients undergoing total laryngectomy. METHODS: A feasibility study set in a tertiary head and neck unit in London, United Kingdom. The programme was developed based on Enhanced Recovery After Surgery (ERAS) Society guidelines for head and neck cancer surgery and local expert group consensus. An ERAS 'booklet' was devised which accompanied all laryngectomy patients during their inpatient stay. Contributors included otolaryngologists, anaesthetists, dieticians, physiotherapists, speech and language therapists and nurses. A 12-month pilot study was undertaken. The main outcome measures were feasibility and adherence. RESULTS: An enhanced recovery programme for 25 people undergoing total laryngectomy was successfully piloted in a tertiary referral head and neck unit. Median length of stay was reduced in the post-ERAS group by 1.5 days. No statistically significant difference in length of stay, time to first gastrografin swallow, rate of fistula nor postoperative normalcy of eating between the pre and post-ERAS patients who underwent laryngectomy was observed. Clavien-Dindo-grouped complication rates were significantly higher in the post-ERAS group. CONCLUSION: This enhanced recovery programme for patients undergoing laryngectomy is the first of its kind in the literature. Implementation has been demonstrated feasible. Further longitudinal studies are required to reliably inform us on ERAS programmes' effects on laryngectomy outcomes.

ThyroidEx: Development and Preliminary Validation of a Thyroid Surgery Expectations Measure.

OBJECTIVE: To address the lack of validated patient-reported outcome (PRO) instruments that define and quantify patient expectations in thyroid cancer surgery, we developed and initially validated ThyroidEx, a novel disease-specific PRO instrument. STUDY DESIGN: Survey study. SETTING: Single-institution tertiary care cancer center. METHODS: An expert panel drafted an initial set of thyroid cancer-specific concepts, which was used in semistructured concept elicitation interviews with patients with thyroid cancer 4 weeks before and 8 weeks after surgery. Candidate items were generated per patient responses and refined via cognitive interviewing and additional review by the expert panel. The draft ThyroidEx was then preoperatively administered to a separate cohort undergoing thyroid cancer surgery to establish a final item set and initial psychometric evidence. RESULTS: Prospective concept elicitation interviews generated 358 patient-elicited concepts (n = 15 patients). These were then placed into 70 unique subcategories from which 41 items were generated for cognitive interviews with 20 patients preoperatively and 28 postoperatively. After expert panel review, ThyroidEx included 18 items across 2 scales (Expectations and Concerns), with an additional item about beliefs. In the preoperative cohort in phase 2 (n = 67), internal consistency Cronbach's α values ranged from 0.81 to 0.89. Descriptive analysis showed significant differences between patients' concerns and expectations and clinicians' perceptions. CONCLUSION: Defining expectations represents an important modifier in the measurement of PROs. Preliminary validation of ThyroidEx revealed incongruent expectations between expert opinion and patients. Future development and implementation of ThyroidEx may affect preoperative consultation and the consent process.

Inactivation of the Glucose-Dependent Insulinotropic Polypeptide Receptor Improves Outcomes following Experimental Myocardial Infarction.

Incretin hormones exert pleiotropic metabolic actions beyond the pancreas. Although the heart expresses both incretin receptors, the cardiac biology of GIP receptor (GIPR) action remains incompletely understood. Here we show that GIPR agonism did not impair the response to cardiac ischemia. In contrast, genetic elimination of the Gipr reduced myocardial infarction (MI)-induced ventricular injury and enhanced survival associated with reduced hormone sensitive lipase (HSL) phosphorylation; it also increased myocardial triacylglycerol (TAG) stores. Conversely, direct GIPR agonism in the isolated heart reduced myocardial TAG stores and increased fatty acid oxidation. The cardioprotective phenotype in Gipr-/- mice was partially reversed by pharmacological activation or genetic overexpression of HSL. Selective Gipr inactivation in cardiomyocytes phenocopied Gipr-/- mice, resulting in improved survival and reduced adverse remodeling following experimental MI. Hence, the cardiomyocyte GIPR regulates fatty acid metabolism and the adaptive response to ischemic cardiac injury. These findings have translational relevance for developing GIPR-based therapeutics.

Neurturin and a GLP-1 Analogue Act Synergistically to Alleviate Diabetes in Zucker Diabetic Fatty Rats.

Neurturin (NRTN), a member of the glial-derived neurotrophic factor family, was identified from an embryonic chicken pancreatic cDNA library in a screen for secreted factors. In this study, we assessed the potential antidiabetic activities of NRTN relative to liraglutide, a glucagon-like peptide 1 receptor agonist, in Zucker diabetic fatty (ZDF) rats. Subcutaneous administration of NRTN to 8-week-old male ZDF rats prevented the development of hyperglycemia and improved metabolic parameters similar to liraglutide. NRTN treatment increased pancreatic insulin content and ß-cell mass and prevented deterioration of islet organization. However, unlike liraglutide-treated rats, NRTN-mediated improvements were not associated with reduced body weight or food intake. Acute NRTN treatment did not activate c-Fos expression in key feeding behavior and metabolic centers in ZDF rat brain or directly enhance glucose-stimulated insulin secretion from pancreatic ß-cells. Treating 10-week-old ZDF rats with sustained hyperglycemia with liraglutide resulted in some alleviation of hyperglycemia, whereas NRTN was not as effective despite improving plasma lipids and fasting glucose levels. Interestingly, coadministration of NRTN and liraglutide normalized hyperglycemia and other metabolic parameters, demonstrating that combining therapies with distinct mechanism(s) can alleviate advanced diabetes. This emphasizes that therapeutic combinations can be more effective to manage diabetes in individuals with uncontrolled hyperglycemia.

Long-term local control rates of patients with adenoid cystic carcinoma of the head and neck managed by surgery and postoperative radiation.

OBJECTIVES: To report long-term local control in patients with adenoid cystic cancer (ACC) of the head and neck managed by surgery and identify factors predictive for local failure. STUDY DESIGN: Single-institution retrospective cohort study. METHODS: Eighty-seven patients who had surgery for ACC between 1985 and 2009 were identified. Patient, tumor, and treatment characteristics were recorded. Local recurrence-free survival (LRFS) was recorded by the Kaplan-Meier method. Predictors of local control were identified. RESULTS: The median age was 54 years. Seventy-two (83%) patients had perineural invasion, 61 (70%) had close/positive margins, and 58 (67%) had pT 1T2. Fifty-nine (68%) patients had postoperative radiation therapy (PORT). With a median follow-up of 85 months, the 10-year LRFS was 78.7%. There were 14 local recurrences. On multivariable analysis, pathological tumor (T)3T4 stage and no PORT were independent predictors for local failure. Patients with no PORT had a 13-fold increased risk of local failure compared to patients treated with PORT (P = 0.003) after adjusting for stage. CONCLUSION: After adjusting for T stage, patients who do not get PORT are more likely to have local recurrence. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2265-2269, 2017.

Nomograms for predicting survival and recurrence in patients with adenoid cystic carcinoma. An international collaborative study.

BACKGROUND: Due to the rarity of adenoid cystic carcinoma (ACC), information on outcome is based upon small retrospective case series. The aim of our study was to create a large multiinstitutional international dataset of patients with ACC in order to design predictive nomograms for outcome. METHODS: ACC patients managed at 10 international centers were identified. Patient, tumor, and treatment characteristics were recorded and an international collaborative dataset created. Multivariable competing risk models were then built to predict the 10 year recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and cancer specific mortality (CSM). All predictors of interest were added in the starting full models before selection, including age, gender, tumor site, clinical T stage, perineural invasion, margin status, pathologic N-status, and M-status. Stepdown method was used in model selection to choose predictive variables. An external dataset of 99 patients from 2 other institutions was used to validate the nomograms. FINDINGS: Of 438 ACC patients, 27.2% (119/438) died from ACC and 38.8% (170/438) died of other causes. Median follow-up was 56 months (range 1-306). The nomogram for OS had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N-status and M-status) with a concordance index (CI) of 0.71. The nomogram for CSM had the same variables, except margin status, with a concordance index (CI) of 0.70. The nomogram for RFP had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N status and perineural invasion) (CI 0.66). The nomogram for DRFP had 6 variables (gender, clinical T stage, tumor site, pathologic N-status, perineural invasion and margin status) (CI 0.64). Concordance index for the external validation set were 0.76, 0.72, 0.67 and 0.70 respectively. INTERPRETATION: Using an international collaborative database we have created the first nomograms which estimate outcome in individual patients with ACC. These predictive nomograms will facilitate patient counseling in terms of prognosis and subsequent clinical follow-up. They will also identify high risk patients who may benefit from clinical trials on new targeted therapies for patients with ACC. FUNDING: None.

Distant Metastases in Patients with Carcinoma of the Major Salivary Glands.

BACKGROUND: This study aimed to show the incidence of distant metastases (DM) in salivary gland cancer as well as the types of histology most commonly associated with it and to identify factors predictive of DM. METHODS: The study identified 301 patients who underwent surgery for cancer of the major salivary glands at Memorial Sloan-Kettering Cancer center between 1985 and 2009. Clinical, tumor, and treatment characteristics were recorded. Tumors were categorized as low-, intermediate-, and high-risk pathology based on histologic subtype and grade. Factors predictive of distant recurrence-free probability (DRFP) were determined by uni- and multivariable analyses. RESULTS: The primary tumor was parotid in 266 patients (88 %), and 96 tumors (32 %) were clinical T3/T4. For 57 patients (18.9 %), DM developed with a 5-year DRFP of 72.7 %. The most common site of metastasis was the lung (50 %). The clinical predictors were male gender, cT4 stage, cN+ stage, and clinical overall stage. The multivariable analysis of clinical variables showed male gender (p = 0.018), cT4 stage (p < 0.001), and cN+ stage (p = 0.004) to be significant. The pathologic predictors were high-risk and high-grade pathology, vascular invasion, perineural invasion, positive margins, pT4 stage, pN+ stage, and overall stage. The multivariable analysis of pathologic variables showed high-grade pathology (p < 0.001), perineural invasion (p = 0.005), and pN+ stage (p = 0.002) to be significant. CONCLUSIONS: Distant metastases developed in approximately 20 % of the patients with salivary gland cancer. The most common site of metastases was the lung. The significant predictors of DM were cT4, cN+, male gender, high-grade pathology, perineural invasion, and positive nodal disease.

Cardiomyocyte glucagon receptor signaling modulates outcomes in mice with experimental myocardial infarction.

OBJECTIVE: Glucagon is a hormone with metabolic actions that maintains normoglycemia during the fasting state. Strategies enabling either inhibition or activation of glucagon receptor (Gcgr) signaling are being explored for the treatment of diabetes or obesity. However, the cardiovascular consequences of manipulating glucagon action are poorly understood. METHODS: We assessed infarct size and the following outcomes following left anterior descending (LAD) coronary artery ligation; cardiac gene and protein expression, acylcarnitine profiles, and cardiomyocyte survival in normoglycemic non-obese wildtype mice, and in newly generated mice with selective inactivation of the cardiomyocyte Gcgr. Complementary experiments analyzed Gcgr signaling and cell survival in cardiomyocyte cultures and cell lines, in the presence or absence of exogenous glucagon. RESULTS: Exogenous glucagon administration directly impaired recovery of ventricular pressure in ischemic mouse hearts ex vivo, and increased mortality from myocardial infarction after LAD coronary artery ligation in mice in a p38 MAPK-dependent manner. In contrast, cardiomyocyte-specific reduction of glucagon action in adult Gcgr (CM-/-) mice significantly improved survival, and reduced hypertrophy and infarct size following myocardial infarction. Metabolic profiling of hearts from Gcgr (CM-/-) mice revealed a marked reduction in long chain acylcarnitines in both aerobic and ischemic hearts, and following high fat feeding, consistent with an essential role for Gcgr signaling in the control of cardiac fatty acid utilization. CONCLUSIONS: Activation or reduction of cardiac Gcgr signaling in the ischemic heart produces substantial cardiac phenotypes, findings with implications for therapeutic strategies designed to augment or inhibit Gcgr signaling for the treatment of metabolic disorders.