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Hypertension has been shown to be both a protective factor and a risk factor for complications in head and neck reconstructive surgery.Retrospective analysis of microvascular free tissue transfer patients using the National Surgical Quality Improvement Program database.Hypertensive patients (n = 1598; 46.9%) had a significantly higher rate of complications, including pneumonia (p 0.001), myocardial infarction (p = 0.003), and intra/post-operative transfusion (p 0.001). In a multivariable model, hypertension was associated with returning to the operating room (OR = 1.45 [95% CI 1.20, 1.76], p 0.001), post-operative medical complications (OR = 1.53 [95% CI 1.24, 1.90], p 0.001), and surgical complications (OR = 1.17 [95% CI 1.00, 1.37], p = 0.047). However, no difference in 30-day readmission was found (p 0.05).Hypertension is a modifiable risk factor for post-operative complications in head and neck free tissue transfer, in which prospective studies are required to establish causation. This study may serve as an impetus for proactive recommendations to manage hypertension before undergoing head and neck microvascular surgery.

Taurine is a non-proteinogenic sulfonic acid found in high concentrations inside vertebrate cardiomyocytes and its movement across the sarcolemmal membrane is critical for cell volume regulation. Taurine deficiency is rare in mammals, where it impairs cardiac contractility and leads to congestive heart failure. In fish, cardiac taurine levels vary substantially between species and can decrease by up to 60% in response to environmental change but its contribution to cardiac function is understudied. We addressed this gap in knowledge by generating a taurine-deficient rainbow trout (Oncorhynchus mykiss) model using a feed enriched with 3% β-alanine to inhibit cellular taurine uptake. Cardiac taurine was reduced by 17% after 4 weeks with no effect on growth or condition factor. Taurine deficiency did not affect routine or maximum rates of O2 consumption, aerobic scope, or critical swimming speed in whole animals but cardiac contractility was significantly impaired. In isometrically contracting ventricular strip preparations, the force–frequency and extracellular Ca2+-sensitivity relationships were both shifted downward and maximum pacing frequency was significantly lower in β-alanine fed trout. Cardiac taurine deficiency reduces sarcoplasmic reticular Ca2+-ATPase activity in mammals and our results are consistent with such an effect in rainbow trout. Our data indicate that intracellular taurine contributes to the regulation of cardiac contractility in rainbow trout. Aerobic performance was unaffected in β-alanine-fed animals, but further study is needed to determine if more significant natural reductions in taurine may constrain performance under certain environmental conditions.

Objective Determine the proportion and characteristics of traumatic injury survivors who perceive a negative impact of the COVID-19 pandemic on their recovery and to define post-injury outcomes for this cohort. Background The COVID-19 pandemic has precipitated physical, psychological, and social stressors that may create a uniquely difficult recovery and reintegration environment for injured patients. Methods Adult (≥18 years) survivors of moderate-to-severe injury completed a survey 6-14 months post-injury during the COVID-19 pandemic. This survey queried individuals about the perceived impact of the COVID-19 pandemic on injury recovery and assessed post-injury functional and mental health outcomes. Regression models were built to identify factors associated with a perceived negative impact of the pandemic on injury recovery, and to define the relationship between these perceptions and long-term outcomes. Results Of 597 eligible trauma survivors who were contacted, 403 (67.5%) completed the survey. Twenty-nine percent reported that the COVID-19 pandemic negatively impacted their recovery and 24% reported difficulty accessing needed healthcare. Younger age, lower perceived-socioeconomic status (SES), extremity injury, and prior psychiatric illness were independently associated with negative perceived impact of the COVID-19 pandemic on injury recovery. In adjusted analyses, patients who reported a negative impact of the pandemic on their recovery were more likely to have new functional limitations, daily pain, lower physical and mental component scores of the SF-12 and to screen positive for PTSD and depression. Conclusions The COVID-19 pandemic is negatively impacting the recovery of trauma survivors. It is essential that we recognize the impact of the pandemic on injured patients while focusing on directed efforts to improve the long-term outcomes of this already at-risk population.

PURPOSE To provide evidence-based recommendations for practicing physicians and other healthcare providers on the management of salivary gland malignancy. METHODS ASCO convened an Expert Panel of medical oncology, surgical oncology, radiation oncology, neuroradiology, pathology, and patient advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2000 through 2020. Outcomes of interest included survival, diagnostic accuracy, disease recurrence, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS The literature search identified 293 relevant studies to inform the evidence base for this guideline. Six main clinical questions were addressed, which included subquestions on preoperative evaluations, surgical diagnostic and therapeutic procedures, appropriate radiotherapy techniques, the role of systemic therapy, and follow-up evaluations. RECOMMENDATIONS When possible, evidence-based recommendations were developed to address the diagnosis and appropriate preoperative evaluations for patients with a salivary gland malignancy, therapeutic procedures, and appropriate treatment options in various salivary gland histologies. Additional information is available at www.asco.org/head-neck-cancer-guidelines .

Adjuvant chemoradiation (CRT), with high-dose cisplatin remains standard treatment for oral cavity squamous cell carcinoma (OCSCC) with high-risk pathologic features. We evaluated outcomes associated with different cisplatin dosing and schedules, concurrent with radiation (RT), and the effect of cumulative dosing of cisplatin. An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I–IVB AJCC 7th edition) treated with primary surgical resection between January 2005 and January 2015, with or without adjuvant therapy, was established from six academic institutions. Patients were categorized by cisplatin dose and schedule, and resultant groups compared for demographic data, pathologic features, and outcomes by statistical analysis to determine disease free survival (DFS) and freedom from metastatic disease (DM). From a total sample size of 1282 pts, 196 pts were identified with high-risk features who were treated with adjuvant CRT. Administration schedule of cisplatin was not significantly associated with DFS. On multivariate (MVA), DFS was significantly better in patients without perineural invasion (PNI) and in those receiving ≥200 mg/m2 cisplatin dose (p &lt, 0.001 and 0.007). Median DFS, by cisplatin dose, was 10.5 (&lt, 200 mg/m2) vs. 20.8 months (≥200 mg/m2). Our analysis demonstrated cumulative cisplatin dose ≥200 mg/m2 was associated with improved DFS in high-risk resected OCSCC pts.

Hypertension, elevated morning blood pressure (BP) surges, and circadian BP variability constitute risk factors for cerebrovascular events. Nevertheless, while evidence indicates that hypertension is associated with cognitive dysfunctions, the link between BP variability and cognitive performance during aging is not clear. The purpose of this study is to determine the interaction between relative morning BP, cerebral blood flow (CBF) levels, and cognitive performance in hypertensive older adults with controlled BP under antihypertensive treatment. Eighty-four participants aged between 60 and 75 years old were separated into normotensive (n=51) and hypertensive (n=33) groups and underwent 24-hour ambulatory BP monitoring. They were also examined for CBF in the gray matter (CBF-GM) by magnetic resonance imaging and 5 cognitive domains: global cognition, working memory, episodic memory, processing speed, and executive functions. There was no difference in cognitive performance and CBF between normotensive and controlled hypertensive participants. Through a sensitivity analysis, we identified that, among relative morning BP variables, the best fit for CBF values in this cohort was the morning-evening difference in BP. The relative morning BP was negatively associated with CBF-GM in these hypertensive older adults only. In turn, CBF-GM levels were negatively associated with working and episodic memory scores in hypertensive older adults. This is the first extended study demonstrating an association between high relative morning BP and lower levels of CBF-GM, including the further impact of CBF-GM levels on the cognitive performance of specific domains in a community-based cohort of older adults with hypertension.

Background After a traumatic brain injury, disturbances in the attentional processes have a direct negative effect on functional recovery and on return to complex activities. To date, there is no good attention remediation treatment available. The primary objective of this review and pilot study is to provide an overview of the research evidence and to evaluate the feasibility of implementing a tDCS protocol to improve attention disorders in patients with mild complicated to severe subacute TBI, hospitalized in an inpatient rehabilitation facility. Our secondary objective is to extract preliminary data and observational information on participants’ response to treatment. Methods Participants were recruited from a consecutive series of patients admitted to the TBI unit of a subspecialized regional rehabilitation center. They received a 20-min tDCS stimulation 3 times a week for 3 weeks. A neuropsychological evaluation was performed before and after the intervention. We collected participants’ sociodemographic and clinical characteristics as well as information about satisfaction, tolerability, and adverse effects. Results One hundred sixty-four patients were admitted between September 2018 and January 2020. One hundred fifty-eight were excluded, and 6 patients with presumed attentional deficits were enrolled. None completed the protocol as intended. No major side effects occurred. Conclusion Non-invasive brain neurostimulation is promising to enhance attention deficits in patients with TBI. Implementation of a tDCS protocol to fulfill this purpose in an intensive inpatient rehabilitation center has its limitations. We made recommendations to facilitate the implementation of similar projects in the future. Trial registration ISRCTN, ISRCTN55243064. Registered 14 October 2020—retrospectively registered.

Objectives: To assess risk factors and non-thyroid specific postoperative complications for thyroid lobectomy compared to total thyroidectomy. Methods: A retrospective, cross-sectional study of adults undergoing a lobectomy or total thyroidectomy using the National Surgical Quality Improvement Program database between 2005 and 2017. Patients not treated by otolaryngologists or general surgeons and with unknown demographic variables were excluded. Results: A total of 106 915 patients were analyzed, 64 763 total thyroidectomies and 42 152 lobectomies. Multivariable analysis demonstrated that total thyroidectomy patients were half as likely to return to the operating room (OR = 0.491 (95%CI 0.445-0.542), P Conclusions: Our multi-institutional study indicates specific risk factors for returning to the operating room that may warrant closer follow up after surgery for total thyroidectomy or thyroid lobectomy. We also identified the most common post-operative complications. During pre-operative planning, these findings should be considered by thyroid surgeons to help mitigate risk to patients.

The heart of tropical fishes is a particularly useful model system in which to investigate mechanisms of hypoxic tolerance. Here we focus on insights gained from two groups of fishes, cichlids and armoured catfishes. Cichlids respond to hypoxia by entering a sustained hypometabolism with decreased heart performance to match whole animal circulatory needs. Heart rate is decreased along with protein turnover to reduce adenosine triphosphate demand. This occurs despite the inherent capacity for high levels of cardiac power development. Although highly hypoxic tolerant at the whole animal level, the heart of cichlids does not have high constitutive activities of glycolytic enzymes compared to other species. Information is conflicting with respect to changes in glycolytic gene expression and enzyme activity following hypoxic exposure with some studies showing increases and others decreases. In contrast to cichlids, species of armoured catfish, that are routinely exposed to water of low oxygen content, do not display hypoxic bradycardia. Under hypoxia there are early changes in glucose trafficking suggestive of activation of glycolysis before lactate accumulation. Thereafter, heart glycogen is mobilized and lactate accumulates in both heart and blood, in some species to very high levels. Heart performance under hypoxia is enhanced by defense of intracellular pH. A functional sarcoplasmic reticulum and binding of hexokinase to the outer mitochondrial membrane may also play a role in cardioprotection. Maintenance of heart performance under hypoxia may relate to a tradeoff between air breathing via a modified stomach and circulatory demands for digestion.

When confined in pairs, juvenile rainbow trout (Oncorhynchus mykiss) form dominance hierarchies in which subordinate fish exhibit characteristic physiological changes including reduced growth rates and chronically elevated plasma cortisol concentrations. We hypothesized that alterations in protein metabolism contribute to the reduced growth rate of socially stressed trout, and predicted that subordinate trout would exhibit reduced rates of protein synthesis coupled with increases in protein degradation. Protein metabolism was assessed in dominant and subordinate fish after 4 days of social interaction, and in fish that were separated after 4 days of interaction for a 4 days recovery period, to determine whether effects on protein metabolism recovered when social stress was alleviated. Protein metabolism was assessed in liver and white muscle by measuring the fractional rate of protein synthesis and markers of protein degradation. In the white muscle of subordinate fish, protein synthesis was inhibited and activities of the ubiquitin-proteasome pathway (UPP) and the autophagy lysosomal system (ALS) were elevated. By contrast, the liver of subordinate fish exhibited increased rates of protein synthesis and activation of the ALS. When allowed to recover from chronic social stress for 4 days, differences in protein metabolism observed in white muscle of subordinate fish during the interaction period disappeared. In liver, protein synthesis returned to baseline levels during recovery from social stress, but markers of protein degradation did not. Collectively, these data support the hypothesis that inhibition of muscle protein synthesis coupled with increases in muscle protein breakdown contribute to the reduced growth rates of subordinate rainbow trout. Supplementary Information The online version contains supplementary material available at 10.1007/s00360-021-01340-6.

Purpose To determine the effectiveness of a single 10-min postural repositioning session on the maximum phonation duration (MPD) of the vowel/a/in individuals with acquired dysarthria. Materials and methods A pre-post interventional design was implemented; five patients with dysarthria (PWDs) underwent a single 2-hour experimental session. MPD capacities were assessed before and immediately after a 10-min postural repositioning intervention by a physical and occupational therapist. Five age- and sex-matched individuals without dysarthria were recruited as controls. The main outcome measure was the MPD of the vowel/a/at conversational and louder voice levels, with a speech-and-language therapist standing 1 and 6 m away, respectively. Secondary outcome measures were thoracic expansion, manometry, electromyographic recordings of axial muscles and perceived effort. Results In PWDs, postural repositioning improved the MPD during the/a/-1-m (80.3% increase) and/a/-6-m tasks (18% increase), increased thoracic expansion and manometric measurements, and reduced the perceived effort necessary to perform the tasks. A triphasic electromyographic pattern was observed during both/a/-1-m and/a/-6-m tasks in controls, but was absent in participants with severe dysarthria, even after postural repositioning. Nonetheless, postural repositioning enabled an earlier onset of EMG activity prior to voice production. Conclusions These data suggest the efficacy of postural repositioning in improving phonatory capacities essential for voice production in PWDs.

Background: Vascular risk factors such as arterial stiffness play an important role in the etiology of Alzheimer’s disease (AD), presumably due to the emergence of white matter lesions. However, the impact of arterial stiffness to white matter structure involved in the etiology of AD, including the corpus callosum remains poorly understood. Objective: The aims of the study are to better understand the relationship between arterial stiffness, white matter microstructure, and perfusion of the corpus callosum in older adults. Methods: Arterial stiffness was estimated using the gold standard measure of carotid-femoral pulse wave velocity (cfPWV). Cognitive performance was evaluated with the Trail Making Test part B-A. Neurite orientation dispersion and density imaging was used to obtain microstructural information such as neurite density and extracellular water diffusion. The cerebral blood flow was estimated using arterial spin labelling. Results: cfPWV better predicts the microstructural integrity of the corpus callosum when compared with other index of vascular aging (the augmentation index, the systolic blood pressure, and the pulse pressure). In particular, significant associations were found between the cfPWV, an alteration of the extracellular water diffusion, and a neuronal density increase in the body of the corpus callosum which was also correlated with the performance in cognitive flexibility. Conclusion: Our results suggest that arterial stiffness is associated with an alteration of brain integrity which impacts cognitive function in older adults.

Despite numerous case reports, the incidence of a secondary diagnosis of head and neck squamous cell carcinoma (HNC) following pegylated liposomal doxorubicin (PLD) treatment is unknown. Computerized pharmacy records were searched at a large, multi-center healthcare system for patients who received PLD. Electronic medical records were searched to identify the patient's age at treatment initiation of PLD, diagnosis for which they were treated with PLD, number of courses and total cumulative dose of PLD (TCDPLD) and secondary malignancies. Published PLD associated HNC was utilized to determine the lowest and median TCDPLD doses associated with HNC. One thousand two hundred ninety eligible patients who had been treated with PLD were identified. The lowest TCDPLD associated HNC in the literature is 405 mg/m2. In our healthcare system, 275 patients received more than 400 mg/m2 yielding a risk of 0.004%. One hundred fifty-one patients received the lowest TCDPLD associated with HNC cancer in our series which was 640 mg/m2 yielding a risk of 0.007%. Four of 30 patients (13.3%) developed HNC who received the median TCDPLD associated with HNC in the literature of 1440 mg/m2. Five of 20 patients (25%) receiving 1650 mg/m2 developed HNC in our healthcare system. Prolonged therapy with PLD is associated with an increased risk of HNC. This risk appears to be related to the cumulative dose varying from 0.004 to 13.3% at the lowest and median TCDPLD of reported cases in the literature, respectively. Oncologists need to be aware of this risk and to screen patients appropriately.

A large proportion of patients affected with hypertension go undetected. A systematic review was conducted to assess the performance of a screening strategy in adults using blood pressure measurement at the time of an emergency department consultation. A systematic literature search on Embase, CINHAL and Medline was carried out. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Diagnostic Test Accuracy. Intervention studies with adults including at least one blood pressure measurement for all participants were included. A repeat blood pressure assessment had to have been carried out to assess the validity of the elevated blood pressure value within the next few days after the emergency department initial visit. Out of 1030 articles identified, published between 1985 and 2018, 10 articles met the inclusion criteria. There were no randomized clinical trials. Mean age of participants was 51.6 years. A single study reports that blood pressure screening was measured according to hypertension guidelines referred to in the study. The average follow-up rate was 61.9% (95% confidence interval 45.5-78.3). For diagnostic confirmation, four studies used a blood pressure measurement method based on the reported guidelines. Half of the patients (50.2%) with elevated blood pressure during the emergency department visit had blood pressure corresponding to uncontrolled elevated blood pressure at follow-up measurement. The contribution of emergency department to the screening for hypertension, by recognizing the presence of elevated blood pressure and then making a referral for diagnostic confirmation, could provide an opportunity to detect a large number of people with hypertension.

Hypertension Canada's 2020 guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children provide comprehensive, evidence-based guidance for health care professionals and patients. Hypertension Canada develops the guidelines using rigourous methodology, carefully mitigating the risk of bias in our process. All draft recommendations undergo critical review by expert methodologists without conflict to ensure quality. Our guideline panel is diverse, including multiple health professional groups (nurses, pharmacy, academics, and physicians), and worked in concert with experts in primary care and implementation to ensure optimal usability. The 2020 guidelines include new guidance on the management of resistant hypertension and the management of hypertension in women planning pregnancy.

Background De-intensified treatment strategies for early human papillomavirus-positive (HPV+) oropharynx cancer (OPC) rely on selecting patients with an excellent prognosis. The criterion for enrollment in current de-intensification trials is ≤10 pack-years. More nuance to the pack-year criteria may expand enrollment, improve patient outcomes, and prevent overtreatment. It was hypothesized that patients with more than 10 pack-years may experience favorable outcomes if smoking cessation has been achieved. Methods From an institutional review board-approved database, patients with HPV+ oropharyngeal squamous carcinoma treated definitively with radiation with or without chemotherapy were retrospectively identified. Patients with a history of smoking who were eligible for national de-intensification trials were included (cT1-2N1-2b or T3N0-2b [American Joint Committee on Cancer, seventh edition]). Cox regression with penalized smoothing splines was used to evaluate nonlinear effects of cessation. Recursive partitioning analysis (RPA) was used to objectively search for relationships between the 2 colinear variables (pack-years and time since cessation). Results Among 330 patients meeting the inclusion criteria, 130 (40%) were never smokers, 139 (42%) were former smokers, and 61 (18%) were current smokers. With standard therapy, all former smokers achieved a progression-free survival (PFS) rate higher than 91%, regardless of pack-year exposure. Nonlinear Cox regression demonstrated that more recent cessation was associated with significantly worse PFS even among those with ≤20 pack-years. RPA demonstrated that only current smokers experienced a 2-year PFS rate lower than 91%; former smokers, regardless of pack-years, experienced a 2-year PFS rate higher than 91%. Conclusions The 10-pack-year rule may not apply to all early HPV+ OPCs, particularly for former smokers. Future randomized de-intensification trials should consider a broader and more nuanced approach until the predictive role of smoking status is established.

Loosening of the trapezial component is a main cause of failure of trapeziometacarpal prostheses. This report presents the preliminary results of scaphometacarpal prostheses used for revision of trapeziometacarpal prostheses and failed trapeziectomies. A retrospective multicentre study was conducted on ten patients. Four had revision surgery after failure of trapeziometacarpal prostheses, five after trapeziectomy and one after a trapezial silicone implant. Pain, mobility, strength, QuickDASH, satisfaction score and radiographs were assessed. Nine patients were assessed (one was lost to follow-up), with a mean follow-up of 34 months. The mean pain score was 1.2/10, Quick-DASH was 39 and opposition according to the Kapandji score was 8.6. Strength was 3 kg for key pinch and 13.6 kg for power grip. One failure was observed, with early loosening of the scaphoid cup. Scaphometacarpal arthroplasty is a reliable medium-term solution for revision of the loosening of a trapeziometacarpal prosthesis with trapezial damage and for failed trapeziectomy. Level of evidence: IV

To investigate the association between tumor volume and locoregional failure (LRF) after concurrent chemoradiation (CCRT) for locally advanced larynx cancer (LC).This is a retrospective cohort study from 2009 to 2014 identified from an institutional review board-approved registry. Fifty-nine of 68 patients with locally advanced larynx cancer treated with definitive CCRT who had available imaging for review were identified. The main endpoint to be assessed was the association between gross tumor volumes (GTV; T = total, P = primary, N = nodal) and LRF. Receiver operative characteristic (ROC) curves were used to investigate diagnostic accuracy.Twenty LRFs were observed, resulting in a 2-year LRF rate of 39% (95% CI, 23-52%). On UVA, the GTV-T (P = .01), GTV-P (P = .05), and GTV-N (P = .04) were statistically significant predictors of LRF. Furthermore, age, smoking status, N-stage, larynx subsite, and tracheostomy/feeding tube dependence were potentially associated with LRF (P .3), whereas T-stage (T3-4 vs. T2) was not (HR 1.05, 95% CI, 0.38-2.91, P = .92). In the multivariable model, GTV-P (HR 1.022, 95% CI, 0.999-1.046, P = .07) and GTV-N (HR 1.053, 95% CI, 1.0004-1.108, P = .05) were the two most impactful covariates on the model's RGTV is associated with LRF after definitive CCRT for LC. Patients with bulky primary and/or nodal tumors may be better served with upfront surgical resection regardless of T-stage. Further investigation into the safety of larynx preservation for low-volume T4 tumors can be considered.4 Laryngoscope, 130:2372-2377, 2020.

INTRODUCTION Hypertension in midlife adults is associated with cognitive decline later in life. In individuals treated for hypertension, blood pressure (BP) loads have been associated with end organ damages. This study examines whether BP load inversely correlates with performance in cognitive tasks in normotensive or controlled hypertensive (CHT) individuals. METHODS Participants between 60 and 75 years old were divided into normotensive participants who did not receive antihypertensive treatment (n = 49) and CHT patients (n = 28). They were evaluated for BP using ambulatory blood pressure monitoring and cognitive functions with tests assessing cognitive flexibility, working and episodic memory, and processing speed. RESULTS Analysis of covariance between normotensive and CHT participants revealed lower cognitive performances on immediate and delayed recall and total number of words of the Rey Auditory Verbal Learning Test (P

ObjectivesComputerised physician order entry (CPOE) systems facilitate the review of medication orders by pharmacists. Reports have emerged that show conception flaws or the misuse of CPOE systems generate prescribing errors. We aimed to characterise pharmacist interventions (PIs) triggered by prescribing errors identified as system-related errors (PISREs) in French hospitals.DesignThis was a cross-sectional observational study based on PIs prospectively documented in the Act-IP observatory database from January 2014 to December 2018.SettingPISREs from 319 French computerised healthcare facilities were analysed.ParticipantsAmong the 319 French hospitals, 232 (72.7%) performed SRE interventions, involving 652 (51%) pharmacists.ResultsAmong the 331 678 PIs recorded, 27 058 were qualified as due to SREs (8.2%). The main drug-related problems associated with PISREs were supratherapeutic (27.5%) and subtherapeutic dosage (17.2%), non-conformity with guidelines/contraindications (22.4%) and improper administration (17.9%). The PI prescriber acceptation rate was 78.9% for SREs vs 67.6% for other types of errors. The PISRE ratio was estimated relative to the total number of PIs. Concerning the certification status of CPOE systems, the PISRE ratio was 9.4% for non-certified systems vs 5.5% for certified systems (pConclusionComputer-related prescribing errors are common. The PI acceptance rate by prescribers was higher than that observed for PIs that were not CPOE related. This suggests that physicians consider the potential clinical consequences of SREs for patients to be more frequently serious than interventions unrelated to CPOE. CPOE medication review requires continual pharmacist diligence to catch these errors. The significantly lower PISRE ratio for certified software should prompt patient safety agencies to undertake studies to identify the safest software and discard software that is potentially dangerous.

Bisphosphonates are used to treat osteoporosis. Despite their benefits on bone mineral density (BMD) and fractures, they have shown adverse effects, sometimes severe, during chronic use. Taken for several years, they achieve long-term bone retention, making deprescribing feasible. This review aimed to synthesize evidence on the success and health outcomes of deprescribing of bisphosphonates in seniors, aged over 60 years. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including articles in English, French, or German published before July 2020. Eligible studies included seniors having discontinued bisphosphonates and reported on health outcomes; some allowed meta-analyses on fracture risk. The review included 9 RCTs and 9 cohort studies of moderate quality. Bisphosphonates were discontinued after 2 to 7 years of use, and BMD or fractures were assessed during follow-up of 0.5 to 5 years. A significant reduction in BMD after discontinuation was observed in 9 of 10 studies. Results on fracture risk after discontinuation are mitigated: 6 RCT extensions showed no increase in the risk of any osteoporotic fractures after discontinuation. Meta-analyses including 4 RCTs showed an increased odds ratio of vertebral fractures of 2.04 (95% CI, 1.39–2.99) among discontinuers. Results from 2 large cohort studies showed no increased risks of any osteoporotic or vertebral fractures, while 2 studies found increased fracture risks. Bisphosphonates have successfully been discontinued low overall fracture risk after at least 3 years of use, but a risk for decreased BMD and increased vertebral fractures remained.

BACKGROUND/AIM Head and neck cancers are often treated with extended courses of radiotherapy (RT), which may prove excessively toxic for frail patients. Split course RT (SCRT) delivers two courses of RT separated by 4-6 weeks, personalizing treatment intensity based on response. In this study, we present our updated experience using this technique. PATIENTS AND METHODS From a single institution database, we identified patients considered for SCRT. For patients undergoing a second course of RT, cumulative incidence of locoregional recurrence (LRR) and overall survival (OS) are reported. RESULTS A total of 98 patients were included, of whom seventy-five percent underwent a second course of RT. The most common fractionation was 30 Gy in 10 fractions for each course, with a median cumulative dose of 60 Gy. In those undergoing a second course of RT, median OS was 9.7 months and cumulative incidence of LRR at 6, 12, and 24 months was 17.0%, 23.1%, and 29.4%, respectively. CONCLUSION SCRT offers an attractive treatment paradigm to personalize radiation intensity based on patient tolerance, while maintaining reasonable safety and efficacy in those unfit for standard full course RT.

BackgroundPancreatic cancer is expected to be the third deadliest cancer in the US in 2021. Evaluation of treatment response in patients with mPDAC necessitates scheduled clinical and radiographic assessments along with monitoring serum CA 19-9 levels. Currently available single-institution data examining the importance of CA 19-9 monitoring cannot be generalized to real-world settings. We investigated the impact of serum CA 19-9 monitoring and its association with clinical outcomes in patients with mPDAC in a population-based setting.MethodsData were extracted from the Flatiron Health electronic health record (EHR)-derived de-identified database for patients diagnosed with mPDAC between January 1, 2015, and June 30, 2020. Serum CA 19-9 levels at baseline – defined as the values obtained ≤ 60 days prior to treatment initiation - and during treatment were extracted. CA 19-9 levels > 40 IU/mL were considered elevated. Survival outcomes were compared based on testing frequency, baseline CA 19-9 levels, and change in CA 19-9.Results6,118 patients with mPDAC who received treatment were included in the analysis. The median age at diagnosis was 68 years (IQR: 61-75). Patients with normal baseline CA 19-9 experienced longer median survival than patients with elevated levels [1L: 8.8 months (95% CI: 7.9 - 10) vs. 7.2 months (6.8 – 7.5), p < 0.001; 2L: 7.2 months (6.1 – 9.2) vs. 5.2 months (4.9 – 5.6), p < 0.001; 3L: 6.1 months (5.4 – 9.1) vs. 3.9 months (3.4 – 4.3), p < 0.001]. Patients with decreasing/stable CA 19-9 during treatment experienced longer survival than patients who experienced an increase in CA 19-9 levels [1L: 10.9 months (10.5 – 11.3) vs. 5.4 months (5.1 – 5.9), p < 0.0001; 2L: 8.2 months (7.7 – 8.5) vs. 4.3 months (4.1 – 4.7), p < 0.001; 3L: 7.5 months (6.6 – 9.2) vs. 3.7 months (3.4 – 4.3), p < 0.001].ConclusionsIn one of the largest, contemporary, real-world studies of patients with mPDAC, elevated CA 19-9 level at treatment initiation demonstrated a prognostic impact. Routine serial monitoring of CA 19-9 levels during treatment may be warranted, in addition to clinical and radiographic assessment, and may translate into better patient outcomes. Further validation studies are needed to understand the generalizability of these results.

Purpose: This study explores the perspectives and opinions towards ED clinicians with lived experience of ED. Methods: Three hundred and eighty-five ED clinicians and 124 non-clinicians from 13 countries, between 18 and 76 years of age completed an online survey about attitudes towards ED clinicians with a personal ED history. Almost half the respondents (n = 242, 47.5%) reported a lifetime ED diagnosis. Survey items included ten multiple-choice and three open questions about clinician disclosure, employer hiring practices, and perceived advantages and disadvantages of clinicians with a personal ED history practicing in the ED field. Multiple-choice responses from clinicians with and without a personal ED history were compared with responses from non-clinicians with and without a personal ED history. Open questions were examined using thematic analysis. Results: Clinicians with no ED history, whose responses often differed from both ED-history groups (clinicians and non-clinicians), were more likely to indicate that clinicians with an ED should not generally treat ED patients, and that clinicians should self-disclose their ED history to employers but not to their patients. Thematic analysis of the open-ended questions revealed that advantages of having clinicians with an ED history include a deep experiential understanding and the ability to be empathic and non-judgmental, whereas disadvantages include the lack of objectivity and the risk of clinicians being triggered. Conclusion: Further research informing guidelines for ED clinicians with a personal ED history, their colleagues and employers are needed to protect and empower the significant minority of ED professionals with “lived experience” of EDs. Level of evidence: Level III, case-control analytic study.

CONTEXT Valid blood pressure (BP) measurements are needed in post-stroke rehabilitation hospital units for the management of hypertension. Automated devices could be used to improve on usual care BP measurement. However, more information is needed about the performance of these devices in such a context. METHODS This prospective nonrandomized study was performed in stroke patients with hypertension hospitalized in a stroke rehabilitation unit. Two in-hospital BP assessment strategies were compared: usual care BP and in-hospital automated office BP (AOBP) standardized measurements. In-office AOBP and ambulatory BP monitoring (ABPM) were also performed on these patients. The main outcome was SBP. Study follow-up was until discharge, up to a maximum of 4 weeks. RESULTS Sixty-two patients with stroke hospitalized in a rehabilitation unit were included. Usual care BP was 130 ± 12/79 ± 9 mmHg and differed from an in-hospital AOBP of 117 ± 14/75 ± 12 mmHg (P

Objective Little is known about self-medication with cannabis post-recreational cannabis legalization in Canada. We aimed to establish a detailed portrait of self-medication with cannabis among adults in Quebec. Methods We conducted an online survey from November 2020 to January 2021 among individuals aged ≥ 21 years, who endorsed using cannabis bought in legal recreational cannabis stores to self-medicate a health condition. Data were analysed using descriptive statistics and stratified according to sex, age and the type of cannabis use (exclusively medical versus medical and recreational use). Results 489 participants were included. Median age was 34 years, and 48% were women. About 25% reported an exclusive medical use of cannabis. Treated conditions included anxiety (70%), insomnia (56%), pain (53%), depression (37%), and many other. Reasons for not consulting in cannabis clinics included lack of information (52%), complexity of the process (39%), accessibility of cannabis clinics (23%) and other.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Merck Sharp & Dohme Corp Program of the Faculty of Medicine of the Université de Montréal The Canadian Institutes of Health Research (CIHR) Background The growing concern on the impact of higher arterial stiffness on cognitive decline in older adults, leads to the question of whether non-pharmacological interventions like physical activity should be introduced to correct or diminish the progression of arterial stiffness. Purpose The goal of this study is to elaborate a model for arterial stiffness as a moderator for the physical activity and global cognition relationship in function of age. Methods One hundred ten healthy older adults aged 60 to 75 years old (46 men and 64 women) were examined for arterial stiffness (carotid-femoral Pulse Wave Velocity (cf-PWV)), global cognition (Montreal Cognitive Assessment and Mini Mental State Examination) and self-reported physical activity (PACED diary). The double moderation analysis used PROCESS macro for SPSS, where physical activity was included as the independent variable (X), global cognition as the dependent variable (Y), arterial stiffness as moderator 1 (W), and age moderator 2 (Z). This study used a cf-PWV cutoff of 8.5 m/s to identify micro-structural damage in the brain related to arterial stiffness. Results Results found that the arterial stiffness x age interaction moderated the effect of physical activity on global cognition (β = -.89, SE = .42, p = .037) (Model: R2 = .15, p = .018). Physical activity had a positive effect on cognition in younger-older adults (aged 60 to 68.5 years) with high arterial stiffness i.e. cf-PWV > 8.5 m/s (β = .57, SE = .222, p = .011, 95% CI .133 to 1.014), and in older-older adults (aged 68.6 to 75 years) with low arterial stiffness i.e. cf-PWV Conclusions These results support targeted physical activity interventions based on age and degree of arterial stiffness, furthering the notion that even daily life physical activity could play an important role in older adults’ cognitive performances. Physical activity on global cognition Conditional effects of physical activity on global cognition Moderators cf-PWV Age Effect SE p CI < 8.5 m/s < 68.5 years .171 .245 .487 -.315 to .657 < 8.5 m/s > = 68.5 years .574 .222 .011* .133 to 1.014 > = 8.5 m/s < 68.5 years .492 .190 .010* .116 to .868 > = 8.5 m/s > = 68.5 years .002 .180 .990 -.355 to .359 Physical activity conditional effects on global cognition at determined values of arterial stiffness and age. SE: Standard Error, CI: Confidence Interval, cf-PWV: carotid-femoral Pulse Wave Velocity, *p-value

Summary Background Middle East respiratory syndrome (MERS) coronavirus causes a highly fatal lower-respiratory tract infection. There are as yet no licensed MERS vaccines or therapeutics. This study (WRAIR-2274) assessed the safety, tolerability, and immunogenicity of the GLS-5300 MERS coronavirus DNA vaccine in healthy adults. Methods This study was a phase 1, open-label, single-arm, dose-escalation study of GLS-5300 done at the Walter Reed Army Institute for Research Clinical Trials Center (Silver Spring, MD, USA). We enrolled healthy adults aged 18–50 years; exclusion criteria included previous infection or treatment of MERS. Eligible participants were enrolled sequentially using a dose-escalation protocol to receive 0·67 mg, 2 mg, or 6 mg GLS-5300 administered by trained clinical site staff via a single intramuscular 1 mL injection at each vaccination at baseline, week 4, and week 12 followed immediately by co-localised intramuscular electroporation. Enrolment into the higher dose groups occurred after a safety monitoring committee reviewed the data following vaccination of the first five participants at the previous lower dose in each group. The primary outcome of the study was safety, assessed in all participants who received at least one study treatment and for whom post-dose study data were available, during the vaccination period with follow-up through to 48 weeks after dose 3. Safety was measured by the incidence of adverse events; administration site reactions and pain; and changes in safety laboratory parameters. The secondary outcome was immunogenicity. This trial is registered at ClinicalTrials.gov (number NCT02670187) and is completed. Findings Between Feb 17 and July 22, 2016, we enrolled 75 individuals and allocated 25 each to 0·67 mg, 2 mg, or 6 mg GLS-5300. No vaccine-associated serious adverse events were reported. The most common adverse events were injection-site reactions, reported in 70 participants (93%) of 75. Overall, 73 participants (97%) of 75 reported at least one solicited adverse event; the most common systemic symptoms were headache (five [20%] with 0·67 mg, 11 [44%] with 2 mg, and seven [28%] with 6 mg), and malaise or fatigue (five [20%] with 0·67 mg, seven [28%] with 2 mg, and two [8%] with 6 mg). The most common local solicited symptoms were administration site pain (23 [92%] with all three doses) and tenderness (21 [84%] with all three doses). Most solicited symptoms were reported as mild (19 [76%] with 0·67 mg, 20 [80%] with 2 mg, and 17 [68%] with 6 mg) and were self-limiting. Unsolicited symptoms were reported for 56 participants (75%) of 75 and were deemed treatment-related for 26 (35%). The most common unsolicited adverse events were infections, occurring in 27 participants (36%); six (8%) were deemed possibly related to study treatment. There were no laboratory abnormalities of grade 3 or higher that were related to study treatment; laboratory abnormalities were uncommon, except for 15 increases in creatine phosphokinase in 14 participants (three participants in the 0·67 mg group, three in the 2 mg group, and seven in the 6 mg group). Of these 15 increases, five (33%) were deemed possibly related to study treatment (one in the 2 mg group and four in the 6 mg group). Seroconversion measured by S1-ELISA occurred in 59 (86%) of 69 participants and 61 (94%) of 65 participants after two and three vaccinations, respectively. Neutralising antibodies were detected in 34 (50%) of 68 participants. T-cell responses were detected in 47 (71%) of 66 participants after two vaccinations and in 44 (76%) of 58 participants after three vaccinations. There were no differences in immune responses between dose groups after 6 weeks. At week 60, vaccine-induced humoral and cellular responses were detected in 51 (77%) of 66 participants and 42 (64%) of 66, respectively. Interpretation The GLS-5300 MERS coronavirus vaccine was well tolerated with no vaccine-associated serious adverse events. Immune responses were dose-independent, detected in more than 85% of participants after two vaccinations, and durable through 1 year of follow-up. The data support further development of the GLS-5300 vaccine, including additional studies to test the efficacy of GLS-5300 in a region endemic for MERS coronavirus. Funding US Department of the Army and GeneOne Life Science.

BACKGROUND Predictive models to forecast the likelihood of specific outcomes after surgical intervention allow informed shared decision-making by surgeons and patients. Previous studies have suggested that existing general surgical risk calculators poorly forecast head and neck surgical outcomes. However, no large study has addressed this question while subdividing subjects by surgery performed. OBJECTIVES To determine the accuracy of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Surgical Risk Calculator in estimating length of hospital stay and risk of postoperative complications after free tissue transfer surgery. STUDY DESIGN A retrospective chart review of patients at one institution was performed using Current Procedural Terminology codes for anterolateral thigh (ALT) flap, fibula free flap (FFF), and radial forearm free flap (RFFF) reconstruction. Output data from the ACS NSQIP surgical risk calculator were compared with the observed rates in our patients. METHODS Incidences of cardiac complications, pneumonia, venous thromboembolism, return to the operating room, and discharge to skilled nursing facility (SNF) were compared to predicted incidences. Length of stay was also compared to the predicted length of stay. RESULTS Three hundred thirty-six free flap reconstructions with 197 ALT flaps, 85 RFFFs, and 54 FFFFs were included. Brier scores were calculated using ACS NSQIP forecast and actual incidences. No Brier score was

Advances in maternal and perinatal care in developed countries have led to improved health outcomes for children. These changes may have impacted the profile of children with a cerebral palsy (CP) and groups at risk for CP over time. Using data from the Canadian CP Registry, the objectives of this retrospective cohort study were to describe the profile of children with CP in Quebec born between 1999 and 2010 and identify possible temporal variation in CP risk factors and phenotypic profile. Our sample consisted of 662 children with CP in Quebec. No change in profile or associated risk factors was observed across the birth cohorts 1999 to 2010. Prematurity remains the largest risk factor for CP in Quebec, and children with CP have multiple comorbidities that contribute to overall CP burden. CP registries offer a unique platform to study spectrum disorders and their longitudinal changes over time.

Abstract. Background: Over-the-counter (OTC) analgesics are frequently used in suicide attempts. Accessibility, toxicity, and unsupervised acquisition of large amounts may be facilitators. Aims: To identify patient characteristics associated with OTC drug use as a suicide attempt method among adults. Method: A cross-sectional study was conducted using chart review of all individuals who presented to the emergency department (ED) of two adult general hospitals following a suicide attempt during 2009–2010 in Montreal, Canada. Results: Among the 369 suicide attempters identified, 181 used overdosing, 47% of whom used OTC drugs. In logistic regression, women and those with medical comorbidity were more likely to use overdosing, while those with substance use disorders were less likely to do so. Among those who overdosed, women were more likely to use OTC drugs, while those who were Caucasian, had children, comorbidities, diagnoses with substance use disorders, and made attempts in the Fall were less likely to do so. Substances most frequently used were: acetaminophen among OTC drugs (30%); antidepressants (37%), anxiolytics (30%), opioids (10%), and anticonvulsants (9%) among prescription drugs; and cocaine (10%) among recreational drugs. Limitations: Reasons for the suicide method choice were not available. Conclusion: OTC drugs, in particular acetaminophen, are frequently used in suicide attempts. Accessibility to these drugs may be an important contributor.

OBJECTIVES Forearm fractures are among the most common pediatric injuries. Procedural sedation is frequently used for analgesia during fracture reduction but requires a prolonged recovery period and can be associated with adverse events. Bier block is a safe alternative for fracture reduction analgesia. This study sought to compare Bier block and procedural sedation for forearm fracture reduction. METHODS We performed a retrospective study of patients aged 6 to 18 years, presenting with forearm fractures requiring closed reduction from June 2012 to March 2014. Outcomes assessed were emergency department length of stay, reduction success rates, adverse events, and unscheduled return visits. RESULTS Overall, 274 patients were included (Bier block, n = 109; procedural sedation, n = 165). Mean length of stay was 82 minutes shorter for Bier block patients (279 vs 361 minutes, P < 0.001). Subanalysis revealed a reduced length of stay among Bier block patients with forearm fractures involving a single bone (286 vs 388 minutes, P < 0.001) and both bones (259 vs 321 minutes, P < 0.05). Reduction success did not differ between Bier block and procedural sedation (98.2% vs 97.6%, P = 0.74). There were no major adverse events in either group, but Bier block patients experienced fewer minor adverse events (2.7% vs 14.5%, P < 0.001). Return visit rates were similar between Bier block and procedural sedation (17.6% vs 16.9%, P = 0.92). CONCLUSIONS Compared with procedural sedation, forearm fracture reduction performed with Bier block was associated with a reduced emergency department length of stay and fewer adverse events, with no differences in reduction success or return visits.

Purpose/Objective(s) The outcomes of second primary head and neck malignancies in survivors of HPV associated OPSCC treated with radiation have not been well documented. The purpose of this study was to review the rate, management, and outcomes of non-metastatic second head and neck malignancies in patients with a history of HPV positive OPSCC treated with definitive or postoperative radiation (RT). Materials/Methods This is a single institution IRB approved retrospective study of patients with HPV positive OPSCC treated from 2001-2017 with definitive radiation and at least 3 years of follow up. Diagnoses were considered to be a second head and neck malignancy if they were distinct from index OPSCC with the exclusion of a primary or regional recurrence, primary site > 2 cm from the index OPSCC, and occurred at least 2 years from prior RT. Patients with second malignancies involving the thyroid were excluded. Actuarial analysis was used to calculate overall survival and disease control rates. Results There were a total of 418 patients who met inclusion criteria with a median follow up of 88.5 months (50.9-150.9 months). A total of 11 patients (2.6%) developed a second primary malignancy in the head and neck (2 larynx, 1 nasal cavity, 6 oral cavity and 2 oropharynx) and all were treated with definitive surgery. Median time between first and second cancers was 73 months (25-123 months). Median follow up for these patients was 25.4 months (7.7-69 months) and the median age at second malignancy was 65 years (range 54-73 years). 64% of patients were former smokers (quit > 3 months) and 36% were never smokers. Pathological tumor stage of the second cancer was T1 in 36%, T2 in 27%, T4a in 36%. The histology was squamous cell carcinoma in 9 patients, spindle cell squamous carcinoma in 1 patient, and adenosquamous carcinoma 1 patient. HPV status was negative in 45.5%, positive in 18.2% and unknown in 36.4%. Post-operative re-irradiation was given in 55%, of which 50% received concurrent chemotherapy. Locoregional control rates at 12 and 24 months were 100% and 62.5% (95% CI: 28.9-96.1%), respectively. Of the 2 patients with local failure, which occurred at 18 and 33 months after diagnosis, salvage therapy with surgery was successful. Regional failure was diagnosed in 2 patients at 13 and 16 months after diagnosis, and both of these patients ultimately died as a result of regional failure. There were no distant failures. One additional patient had died at last follow up which was unrelated to cancer. Estimated 2-year overall survival from the second head and neck malignancy was 78.9% (95% CI: 53.0-100%). Conclusion The risk of a second head and neck malignancy in survivors of HPV associated OPSCC is low, but as the incidence of HPV related OPSCC remains elevated and the likelihood of cure is excellent, secondary malignancy is an important long-term risk. Despite prior RT, consideration of post-operative re-irradiation is important as regional failure may carry a poor prognosis.

Background and aims FIT's value has been ascertained across Canada and worldwide, but still needs to be assessed within the province of Quebec. There also remains a gap between formal indications for FIT, and its actual use in clinical practice. This research aims to evaluate some aspects of FIT's effectiveness in our setting, and its application by prescribers. Methods We retrospectively identified and reviewed all the colonoscopies conducted for a positive FIT in 2014 at 2 hospitals located in Quebec City. Results Five hundred and fifty-nine (559) colonoscopies were reviewed. We obtained PPVs of 6.8% and 46.9% for the detection of CRC and AA, respectively. The PPV for the detection of SCL was higher in men compared to women (OR 1.56, 95%CI 1.11–2.20) and among justified FITs compared to unwarranted ones (OR 1.88, 95%CI 1.34–2.63). The PPV for CRC detection was 25.0% in the presence of unexplained iron deficiency anemia and 6.5% when anemia was absent (p = 0.0058). In 49.9% of cases, the prescription of a FIT was inappropriate. Conclusion The FIT holds a better PPV for detecting SCL among men and when it is indicated. Anemia is associated with a higher CRC detection rate. Half of the FITs were not initially indicated., Highlights • FIT's PPV is slightly higher in our setting than in the rest of Canada. • Male gender, appropriate indication, anemia increase FIT's PPV. • Half of positive tests were not initially warranted. • Physicians should be more aware of FIT's appropriate use.

Objective There is no consensus on the use of cytomegalovirus (CMV)–specific hyperimmunoglobulins (CSHIGs) for suspected congenital CMV infections during pregnancy, but this therapy is currently used in some countries. The objectives of this study were to describe tolerability and pregnancy outcome following treatment with monthly intravenous CSHIG and compare rates of positive PCR and postnatal symptoms according to whether CSHIGs were given or not. Methods This retrospective cohort study included all pregnant women who were diagnosed with primary CMV infection or congenital CMV infection at the Centre Hospitalier Universitaire Sainte-Justine (Montreal, QC) between 2005 and 2016. CSHIG was discussed with pregnant women who received positive CMV PCR results from amniotic fluid or if ultrasound anomalies suggested congenital infection and there was serologic evidence of maternal primary infection (therapeutic group). CSHIG was also offered as prophylaxis in pregnant women without fetal ultrasound anomalies but with evidence of maternal primary infection, when amniocentesis either had negative results or was not performed (prophylactic group). A matched analysis was performed to control for timing of maternal infection, amniocentesis, and type and timing of ultrasound anomaly. Results Sixteen women received CSHIG, and 55 had no CMV-specific treatment. CSHIG treatment was well-tolerated. In bivariate analyses, the risk of congenital CMV infection and postnatal symptoms did not significantly decrease with CSHIG treatment, in both the therapeutic and the prophylactic groups. After matching, there was still no difference in outcomes between CSHIG-treated and untreated women. Conclusion The effectiveness of CSHIG in preventing congenital CMV infection and its clinical manifestations could not be demonstrated.

Outcome objectives 1. Describe the presentation and treatment options of laryngeal NK/T-Cell lymphoma 2. Discuss post-chemoradiotherapy sequelae and airway management Methods Case Report, April 2016. Results A 27-year-old female presented with a three-week history of flu-like symptoms including sore throat, myalgia and insidious nasal congestion. Her hospital course was complicated by pancytopenia, extensive GI bleed of unknown origin and fever. Radiographic studies revealed multifocal centrilobular ground-glass lung nodules, splenomegaly, frontal and paranasal sinus opacification and mucosal thickening and inflammatory process of false and true vocal cords with concentric multi-level narrowing. Extensive rheumatologic, hematologic and infectious workup failed to demonstrate an etiology. Flexible laryngoscopic and bronchoscopic examinations with biopsies exhibited a diffuse supraglottic and glottic exophytic, “heaped-up” infiltration; limited vocal cord motion; and airway narrowing to 3 mm. Pathology yielded NK/T-Cell lymphoma with PET/CT confirming nasopharyngeal and laryngeal involvement sparing the brain and other distant structures. During treatment, the patient's airway became increasingly compromised requiring tracheostomy. Flexible laryngoscopic examination after four rounds of SMILE (dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide) chemotherapy and subsequent radiotherapy with 50 Gy in 25 fractions revealed complete glottic stenosis with alteration of the laryngeal anatomy and a pin-hole aperture seen posteriorly through the tracheostomy. Two dilation procedures performed one month apart, improved her airway considerably which allowed for successful decannulation. She continues to be disease-free post treatment but has persistent supraglottic and glottic scar and has developed tracheal stenosis at her tracheostomal site. Conclusions NK/T-Cell lymphoma of the larynx has been rarely described. Herein, we describe the sequalae of treatment and the requisite airway management.

Forearm fractures are common pediatric injuries. Most displaced or angulated fractures can be managed via closed reduction in the operating room or in the Emergency Department (ED). Previous research has shown that emergency physicians can successfully perform closed reduction within ED; however, the fracture morphology amendable to ED physician reduction is unclear. The aim of this study is to detail the fracture characteristics associated with successful reduction by ED physicians.We conducted a retrospective study of children (aged18 years) presenting to the ED of a tertiary care children's hospital (annual census 90,000) between January 2018 and December 2018 with closed distal and midshaft forearm fractures requiring reduction. Data collected included patient demographics, fracture morphology, management, and complications. Successful ED physician reduction was based on predefined criteria. Orthopedic referrals included those patients sent directly to the operating room, closed reductions performed by orthopedic trainees within the ED, and patients requiring orthopedic consultation after failed ED reduction.A total of 340 patients with forearm fractures were included in the study. ED clinicians attempted to reduce 274 (80.6%) of these fractures and were successful in 256/274 (93.4%) cases. Of the 84 orthopedic referrals, 18 were after failed ED clinician attempt, and 66 were ab initio managed by orthopedics (37 in the operating room and 29 in ED). Compared to the fractures with successful ED reduction (n = 256), factors associated with orthopedic referral (n = 84) included: increasing age, midshaft location, higher degree of angulation, and completely displaced fractures. Angulated distal greenstick fractures were most likely to be successfully reduced by ED clinicians. There were no difference in complication rates between the two groups.In this series, fractures most amenable to reduction by ED clinicians include distal greenstick fractures, whereas midshaft and completely displaced fractures are more likely to need treatment by orthopedics.

Objectives The importance of treating the bilateral neck in lateralized small oral cavity squamous cell carcinoma (OCC) is unclear. We sought to define the incidence and predictors of contralateral neck failure (CLF) in patients who underwent unilateral treatment. Materials and methods We performed a multi-institutional retrospective study of patients with pathologic T1-T2 (AJCC 7th edition) OCC with clinically node negative contralateral neck who underwent unilateral treatment with primary surgical resection ± adjuvant radiotherapy between 2005 and 2015. Incidence of CLF was estimated using the cumulative incidence method. Clinicopathological factors were analyzed by univariate (UVA) and multivariate analysis (MVA) for possible association with CLF. Kaplan-Meier analysis was used to estimate overall survival (OS). Results 176 patients were evaluated with a median of 65.9 months of follow-up. Predominant pathologic T-stage was T1 (68%), 8.5% of patients were N1, 2.8% were N2b. Adjuvant radiotherapy was delivered to 17% of patients. 5-year incidence of CLF was 4.3% (95% CI 1.2–7.4%). Depth of invasion (DOI) > 10 mm and positive ipsilateral neck node were significant predictors for CLF on UVA. DOI > 10 mm remained significant on MVA (HR = 6.7, 95% CI 1.4–32.3, p = 0.02). The 2- and 5-year OS was 90.6% (95% CI 86.2–95.0%) and 80.6% (95% CI 74.5–86.8%), respectively. Conclusion Observation of the clinically node negative contralateral neck in small lateralized OCC can be a suitable management approach in well selected patients, however caution should be applied when DOI upstages small but deeply invasive tumors to T3 on 8th edition AJCC staging.

Objectives: To analyze characteristics, treatment outcomes, and prognostic factors of sarcomatoid squamous cell carcinoma of the head and neck. Study Design: Retrospective chart review. Setting: Tertiary care center. Subjects and Methods: Fifty-five patients were treated for sarcomatoid squamous cell carcinoma of the head and neck between 1996 and 2018. Data collection included clinical history, tumor characteristics, pathology, treatment modality, and outcomes. Mean follow up was 17.1 months. Cox univariate analysis was used to evaluate for associations with locoregional recurrence, distant metastasis, and overall survival. Results: Most patients were white males with a smoking history and median age 66 years (range 41-92) at diagnosis. Twenty-two percent had prior head and neck radiation. Tumor site was most frequently oral cavity (41.8%), followed by larynx (29.1%), and oropharynx (16.4%). Half presented with early T stage disease (15.5% T0, 12.7% T1, 30.9% T2) and the remainder with late stage disease (16.4% T3, 34.5% T4). Locoregional recurrence rate was 60.0%, metastatic recurrence was rate 21.8%, with median time to recurrence of 4 months and mean overall survival of 20 months. Presence of lymphovascular space invasion was statistically associated with locoregional recurrence ( P = .018, HR 3.55 [95% CI 1.24, 10.14]) and poorer overall survival ( P = .015, HR 2.92 [95% CI 1.23, 4.80]). Treatment with multimodality therapy was associated with decreased locoregional recurrence ( P = .039, HR 0.39 [95% CI 0.16, 0.95]) but did not impact overall survival. Conclusion: Sarcomatoid squamous cell carcinoma remains a rare and aggressive disease variant with high recurrence rates and high mortality. High risk features such as lymphovascular space may indicate the need for more aggressive therapy.

Objectives Describe a novel technique for repair of cervical esophageal discontinuity. Study design A 66-year-old female underwent hiatal hernia repair with a Nissen fundoplication. This was complicated by ischemic necrosis of the proximal stomach requiring urgent return to the operative suite for partial gastrectomy, esophageal diversion and subsequent esophagectomy repaired with a colonic interposition graft by Thoracic Surgery. This was further complicated by a cervical esophageal colonic anastomotic leak maturing to a cervical esophageal fistula and necessitating jejunostomy tube placement and consultation to Head and Neck Surgery. Methods Case report. Results In a team approach with Otolaryngology and Thoracic Surgery, she underwent a unique, multilevel repair with a salivary bypass stent bridging the gap between the proximal esophagus and distal colonic conduit. Bilateral local advancement flaps were elevated using the skin lateral to the fistula on each side with a random blood supply pedicled medially. Each flap was rotated medially over the stent and imbricated at midline. Next, a left myogenous pectoralis flap was raised and rotated over the site of imbrication. Lastly, a split thickness skin graft from the thigh was harvested and sutured over the pectoralis flap. Three months postoperatively, the salivary bypass stent was removed and by five months, the fistula was completely closed. With cervical esophageal dilations bimonthly, the patient has graduated to an oral diet without need of her jejunostomy tube for nearly four months. Conclusion This case report describes a novel and efficacious solution to cervical esophageal discontinuity.

To characterize and assess the non-thyroid-specific postoperative complications of completion thyroidectomy as compared with total thyroidectomy.Retrospective analysis: 2005 to 2017.National Surgical Quality Improvement Program database.Patients aged18 years receiving a completion or total thyroidectomy were eligible for inclusion. Patients not treated by otolaryngologists or general surgeons and with unknown demographic variables were excluded.A total of 70,638 patients were analyzed, representing 64,763 total thyroidectomies and 5875 completion thyroidectomies. The 30-day mortality rate was 0.1% for both procedures (National data suggest that total and completion thyroidectomies are relatively safe procedures but that completion thyroidectomies are associated with lower rates of postoperative complications. These findings may play a role in determining treatment plans for patients and optimizing risk reduction.

The objective of this study is to evaluate locoregional and distant failure for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) using American Joint Committee on Cancer eighth edition (AJCC 8) staging.Retrospective cohort study of 457 patients with HPV + OPSCC, treated with platinum-based chemoradiation from 2002 to 2018, followed for a median of 4.3 years. Time to locoregional failure (TTLRF) and distant failure (TTDF) were estimated by Kaplan-Meier method. Log-rank, recursive partitioning analysis (RPA), and multivariable Cox proportional hazards were used to evaluate associated factors and stratify risk.Rates of five-year locoregional control (LRC) and distant control (DC) were 92% (95% CI, 90-95%) and 89% (95% CI, 85-92%), respectively. Smoking, T4, N3, and stage III were associated with significantly worse TTLRF. RPA identified three distinct locoregional failure groups: cT1-3 and 19 pack-years vs. cT1-3 with ≥19 pack-years vs. cT4 (five-year LRC: 97% vs. 90% vs. 82%, P .0001). The only factor associated with significantly worse TTDF was smoking status, while stage was not correlated. RPA identified two prognostic groups: former or never smokers vs. current smokers (five-year DC: 92% vs. 77%, P = .0003).In the largest evaluation of HPV + OPSCC after platinum-based chemoradiation using AJCC 8, risk for locoregional recurrence was stratified by smoking, T category, N category, and overall stage. Risk of distant recurrence was only stratified by smoking status and not related to stage. This has implications for surveillance and clinical trial design.

Objectives Patients with human papillomavirus (HPV) associated squamous cell carcinoma of the oropharynx (SCC-OP) have improved overall survival (OS) after distant metastasis (DM) compared to HPV negative patients. These patients may be appropriate candidates for enrollment on clinical trials evaluating the efficacy of metastasis-directed therapy (MDT). This study seeks to identify prognostic factors associated with OS after DM, which could serve as enrollment criteria for such trials. Materials and methods From an IRB approved multi-institutional database, we retrospectively identified patients with HPV/p16 positive SCC-OP diagnosed between 2001 and 2018. Patterns of distant failure were assessed, including number of lesions at diagnosis and sites of involvement. The primary outcome was OS after DM. Prognostic factors for OS after DM were identified with Cox proportional hazards. Stepwise approach was used for multivariable analysis. Results We identified 621 patients with HPV-associated SCC-OP, of whom 82 (13.2%) were diagnosed with DM. Median OS after DM was 14.6 months. On multivariable analysis, smoking history and number of lesions were significantly associated with prolonged OS. Median OS after DM by smoking (never vs ever) was 37.6 vs 11.2 months (p = 0.006), and by lesion number (1 vs 2–4 vs 5 or more) was 41.2 vs 17.2 vs 10.8 months (p = 0.007). Conclusion Among patients with newly diagnosed metastatic HPV-associated SCC-OP, lesion number and smoking status were associated with significantly prolonged overall survival. These factors should be incorporated into the design of clinical trials investigating the utility of MDT, with or without systemic therapy, in this population.

Sickle cell disease (SCD) is the monogenic hemoglobinopathy where mutated sickle hemoglobin molecules polymerize to form long fibers under deoxygenated state and deform red blood cells (RBCs) into predominantly sickle form. Sickled RBCs stick to the vascular bed and obstruct blood flow in extreme conditions, leading to acute painful vaso-occlusion crises (VOCs) – the leading cause of mortality in SCD. Being a blood disorder of deformed RBCs, SCD manifests a wide-range of organ-specific clinical complications of life (in addition to chronic pain) such as stroke, acute chest syndrome (ACS) and pulmonary hypertension in the lung, nephropathy, auto-splenectomy, and splenomegaly, hand-foot syndrome, leg ulcer, stress erythropoiesis, osteonecrosis and osteoporosis. The physiological inception for VOC was initially thought to be only a fluid flow problem in microvascular space originated from increased viscosity due to aggregates of sickled RBCs; however, over the last three decades, multiple molecular and cellular mechanisms have been identified that aid the VOC in vivo. Activation of adhesion molecules in vascular endothelium and on RBC membranes, activated neutrophils and platelets, increased viscosity of the blood, and fluid physics driving sickled and deformed RBCs to the vascular wall (known as margination of flow) – all of these come together to orchestrate VOC. Microfluidic technology in sickle research was primarily adopted to benefit from mimicking the microvascular network to observe RBC flow under low oxygen conditions as models of VOC. However, over the last decade, microfluidics has evolved as a valuable tool to extract biophysical characteristics of sickle red cells, measure deformability of sickle red cells under simulated oxygen gradient and shear, drug testing, in vitro models of intercellular interaction on endothelialized or adhesion molecule-functionalized channels to understand adhesion in sickle microenvironment, characterizing biomechanics and microrheology, biomarker identification, and last but not least, for developing point-of-care diagnostic technologies for low resource setting. Several of these platforms have already demonstrated true potential to be translated from bench to bedside. Emerging microfluidics-based technologies for studying heterotypic cell–cell interactions, organ-on-chip application and drug dosage screening can be employed to sickle research field due to their wide-ranging advantages.

We report 2 cases of infective endocarditis in injection drug users due to Brucella infection. Although cardiac involvement is a frequent sequela of brucellosis and endocarditis is often seen with injection drug use, Brucella endocarditis in persons who inject drugs without zoonotic exposure has not been reported to date.

Eating disorders (EDs) are increasingly frequent. Their pathophysiology involves disturbance of peptide signaling and the microbiota&ndash, gut&ndash, brain axis. This study analyzed peptides and corresponding immunoglobulin (Ig) concentrations in groups of ED. In 120 patients with restrictive (R), bulimic (B), and compulsive (C) ED, the plasma concentrations of leptin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and insulin were analyzed by Milliplex and those of acyl ghrelin (AG), des-acyl ghrelin (DAG), and &alpha, melanocyte-stimulating hormone (&alpha, MSH) by ELISA kits. Immunoglobulin G (in response to an antigen) concentrations were analyzed by ELISA, and their affinity for the respective peptide was measured by surface plasmon resonance. The concentrations of leptin, insulin, GLP-1, and PYY were higher in C patients than in R patients. On the contrary, &alpha, MSH, DAG, and AG concentrations were higher in R than in C patients. After adjustment for body mass index (BMI), differences among peptide concentrations were no longer different. No difference in the concentrations of the IgG was found, but the IgG concentrations were correlated with each other. Although differences of peptide concentrations exist among ED subtypes, they may be due to differences in BMI. Changes in the concentration and/or affinity of several anti-peptide IgG may contribute to the physiopathology of ED or may be related to fat mass.