Case Report: Glossopharyngeal Allodynia-Related Odynophagia and Dysphagia Post Anterior Cervical Discectomy and Fusion Managed with Glossopharyngeal Nerve Block.

Dysphagia after anterior cervical spine surgery has a 5% to 15% incidence beyond 1-year postsurgery, often attributed to mechanical factors such as pharyngeal thickening and epiglottis inversion. Despite normal neurological examination and electromyography, nerve distortion related to stretching also remains a possibility in these patients and may cause allodynia resulting in odynophagia and dysphagia. Current treatment options for dysphagia after anterior cervical discectomy and fusion are limited to local intraoperative steroid injections and tracheal traction exercises. In our patient, a glossopharyngeal nerve block was effectively used to manage the glossopharyngeal allodynia, thereby reducing the odynophagia and dysphagia, ultimately enhancing oral tolerance.

Assessing the Influence of Intraoperative Core Body Temperature on Postoperative Venous Thromboembolism after Abdominal Wall Reconstruction.

Background: Venous thromboembolism (VTE) is a dangerous postoperative complication after abdominal wall reconstruction (AWR). Intraoperative core body temperature has been associated with thrombotic events in other surgical contexts. This study examines the effects of intraoperative temperature on VTE rate after AWR. Methods: A retrospective study was performed on AWR patients. Cohorts were defined by postoperative 30-day VTE. Intraoperative core body temperature was recorded as the minimum, maximum, and mean intraoperative temperatures. Study variables were analyzed with logistic regression and cutoff analysis to assess for association with VTE. Results: In total, 344 patients met inclusion criteria. Fourteen patients were diagnosed with 30-day VTE for an incidence of 4.1%. The VTE cohort had a longer median inpatient stay (8 days versus 5 days, P < 0.001) and greater intraoperative change in peak inspiratory pressure (3 mm H2O versus 1 mm H2O, P = 0.01) than the non-VTE cohort. Operative duration [odds ratio (OR) = 1.32, P = 0.01], length of stay (OR = 1.07, P = 0.001), and intraoperative PIP difference (OR = 1.18, P = 0.045) were significantly associated with 30-day VTE on univariable regression. Immunocompromised status (OR = 4.1, P = 0.023; OR = 4.0, P = 0.025) and length of stay (OR = 1.1, P < 0.001; OR = 1.1, P < 0.001) were significant predictors of 30-day VTE on two multivariable regression models. No significant associations were found between temperature metrics and 30-day VTE on cutoff point or regression analysis. Conclusions: Intraoperative core body temperature did not associate with 30-day VTE after AWR, though operative duration, length of stay, immunocompromised status, and intraoperative PIP difference did. Surgeons should remain mindful of VTE risk after AWR, and future research is warranted to elucidate all contributing factors.

Tobacco cessation after head and neck cancer diagnosis is an independent predictor of treatment response and long-term survival.

Head and neck squamous cell carcinoma (HNSCC) patients who are current smokers when diagnosed have inferior clinical outcomes compared to never-smokers or previous smokers. However, the impact of quitting after HNSCC diagnosis has not been quantified. In this retrospective, case-control study (n = 134), the odds of complete response to first-line therapy were 3.7 times higher among smokers at diagnosis who quit before treatment initiation (quitters; n = 55) than among those continuing to smoke (p = 0.03). Disease-free survival was also higher among quitters (aHR, 0.33; 95 % CI, 0.12-0.90; p = 0.029). Quitters were 67 % less likely to die of all causes than active smokers (aHR, 0.33; 95 % CI, 0.15-0.71; p = 0.004). These data show for the first time that, smoking cessation after HNSCC diagnosis is predictive of higher therapy efficacy and long-term survival.

Cholecalciferol and metformin protect against lipopolysaccharide-induced endothelial dysfunction and senescence by modulating sirtuin-1 and protein arginine methyltransferase-1.

Endothelial cell activation through nuclear factor-kappa-B (NFkB) and mitogen-activated protein kinases leads to increased biosynthesis of pro-inflammatory mediators, cellular injury and vascular inflammation under lipopolysaccharide (LPS) exposure. Recent studies report that LPS up-regulated global methyltransferase activity. In this study, we observed that a combination treatment with metformin (MET) and cholecalciferol (VD) blocked the LPS-induced S-adenosylmethionine (SAM)-dependent methyltransferase (SDM) activity in Eahy926 cells. We found that LPS challenge (i) increased arginine methylation through up-regulated protein arginine methyltransferase-1 (PRMT1) mRNA, intracellular concentrations of asymmetric dimethylarginine (ADMA) and homocysteine (HCY); (ii) up-regulated cell senescence through mitigated sirtuin-1 (SIRT1) mRNA, nicotinamide adenine dinucleotide (NAD+) concentration, telomerase activity and total antioxidant capacity; and (iii) lead to endothelial dysfunction through compromised nitric oxide (NOx) production. However, these LPS-mediated cellular events in Eahy926 cells were restored by the synergistic effect of MET and VD. Taken together, this study identified that the dual compound effect inhibits LPS-induced protein arginine methylation, endothelial senescence and dysfunction through the components of epigenetic machinery, SIRT1 and PRMT1, which is a previously unidentified function of the test compounds. In silico results identified the presence of vitamin D response element (VDRE) sequence on PRMT1 suggesting that VDR could regulate PRMT1 gene expression. Further characterization of the cellular events associated with the dual compound challenge, using gene silencing approach or adenoviral constructs for SIRT1 and/or PRMT1 under inflammatory stress, could identify therapeutic strategies to address the endothelial consequences in vascular inflammation-mediated atherosclerosis.

Avaliação da Senescência de Células Sanguíneas Mononucleares Periféricas e na Disfunção Endotelial entre Adultos com Alto Risco Cardiovascular / Assessment of Peripheral Blood Mononuclear Cells Senescence and Endothelial Dysfunction among Adults with High Cardiovascular Risk

Resumo Fundamento Doenças cardiovasculares (DCV) são uma das principais causas de mortalidade e morbidade em todo o mundo. O envelhecimento biológico tem sido associado à ocorrência de resultados cardiovasculares. Entretanto, o mecanismo subjacente desse processo ainda é desconhecido. Objetivos Buscamos avaliar se a senescência das células sanguíneas mononucleares periféricas (CSMP) e biomarcadores endoteliais poderiam influenciar o risco cardiovascular (CV) e ser marcadores adequados para a detecção precoce de doenças cardiovasculares em adultos. Métodos Neste estudo transversal, pacientes livres de DCV foram classificados como baixo (n=32) e alto (n=28) escore de risco intracardaco (IHR) A senescência das CSMP foi avaliada estimando-se a atividade de telomerase (AT) e detectando-se a presença de células senescentes e disfunção endotelial, estimando-se a concentração de nitrito e nitrato e a capacidade antioxidante total (CAT). A análise estatística foi realizada com o software SPSS, versão 16.0 (SPSS Inc., Chicago, IL). Todos os p-valores <0,05 foram considerados estatisticamente significativos. Resultados A senescência de CSMP de 0,95 [p-valor = 0,0001; 95% IC (0,874-1,026)] foi um indicador significativo de pacientes com escore de IHR mais alto, com um valor de corte de 21,65, com sensibilidade e especificidade de 92% e 88% respectivamente. Identificou-se que a senescência de CSMP, nitrito e nitrato, e AT eram independentemente associadas a um escore de IHR alto. Conclusão Os status de nitrito e nitrato e AT, e a senescência de CSMP são medidas adequadas para prever o alto risco cardiovascular em adultos com risco CV. Entretanto devem ser realizados estudos de acompanhamento de longo prazo para confirmar esses achados. (Arq Bras Cardiol. 2021; 116(1):37-47)

Abstract Background Cardiovascular diseases (CVD) are one of the leading causes of mortality and morbidity worldwide. Biological aging has been associated with the occurrence of adverse cardiovascular outcomes; however, the underlying mechanism of this process remains unknown. Objectives This study sought to evaluate if peripheral blood mononuclear cell (PBMC) senescence and endothelial biomarkers could influence cardiovascular (CV) risk and be suitable markers for the early detection of cardiovascular diseases in adults. Methods In this cross-sectional study patients free of CVD were classified as lower (n=32) and higher Interheart Risk (IHR) scores (n=28). PBMC senescence was assessed by estimating the telomerase activity (TA) and detecting the presence of senescent cells and endothelial dysfunction by estimating the concentration of nitrite and nitrate and of total antioxidant capacity (TAC). Statistical analysis was performed with SPSS version 16.0 (SPSS Inc., Chicago, IL). All p-values <0.05 were considered statistically significant. Results PBMC senescence 0.95 [p-value = 0.0001; 95% CI (0.874-1.026)] was a significant predictor of patients with higher IHR scores with a cut-off value of 21.65 with a sensitivity and specificity of 92% and 88% respectively. PBMC senescence, nitrite and nitrate and TA were found to be independently associated with high IHR scores. Conclusion PBMC senescence, TA and nitrite, and nitrate status are suitable measures to predict high cardiovascular risk in adults with CV risk. Nevertheless, long-term follow-up studies are needed to confirm these findings. (Arq Bras Cardiol. 2021; 116(1):37-47)

Radiation Oncologist Perceptions and Utilization of Digital Patient Assessment Platforms.

BACKGROUND: Patient engagement is increasing in the presence of digital patient assessment platforms, or physician rating websites. Despite this rapid growth, data remains insufficient regarding how these evaluations impact radiation oncologists. OBJECTIVES: The purpose of this study was to assess radiation oncologists worldwide on their awareness and noted effects of digital patient assessment platforms. METHODS: An electronic survey was delivered to 6,199 members of the American Society of Radiation Oncology. Subjects were radiation oncologists practicing throughout the world. The survey consisted of 14 questions focused on demographics, practice details, patient volume, institutional utilization of patient reviews, and perceptions of radiation oncologists on health care reviews provided by patients. RESULTS: There were 447 responses from practicing radiation oncologists in total, 321 (72%) of which are in the US. Most respondents (228; 51%) either agreed or strongly agreed that patients consider online reviews when deciding which physician to visit. Of all respondents, 188 (42%) reported that their institution checks their online feedback, whereas 157 (36%) and 99 (22%) respectively reported not knowing, or to their knowledge their institution does not check their online feedback. Respondents who saw more than the average number of consults per week were significantly more likely to receive negative feedback (P = 0.005). Forty-five percent of respondents agreed or strongly agreed that online virtual assessment tools contribute to physician burnout. Respondents (100; 22%) who received inappropriate or misdirected feedback were significantly more likely to report that virtual reviews contribute to burnout (P = 0.001). CONCLUSIONS: Radiation oncologists need to be aware that self-reported patient assessments are a data point in the quality of a physician and health care establishment. To best ensure appropriate feedback of a physician's capabilities as a doctor, leadership and employee alignment for patient experience are now more important than ever.

Atypical Cardiac Tamponade Manifesting as Left Ventricular Diastolic Collapse: A Case Report.

Cardiac tamponade is a medical emergency, the diagnosis of which is predominantly clinical with supportive echocardiographic findings. Echocardiographic findings highly suggestive of cardiac tamponade include chamber collapse, inferior vena cava (IVC) plethora, and respiratory volume/flow variations. The right-sided cardiac chambers are a low-pressure system and are the first to show signs of collapse with high specificity for tamponade. We report the case of a 35-year-old woman who demonstrated left ventricular (LV) diastolic collapse on echocardiogram following a tricuspid valve replacement. Although left-sided chamber collapse with tamponade has been reported with localized pericardial effusions postoperatively, our patient had a large circumferential pericardial effusion. Selective chamber compression can be a presenting sign of postoperative tamponade after cardiac surgery. Our case highlights the importance of recognizing atypical forms of cardiac tamponade to help in early identification and emergent management in such patients.

Forskolin attenuates doxorubicin-induced accumulation of asymmetric dimethylarginine and s-adenosylhomocysteine via methyltransferase activity in leukemic monocytes.

Doxorubicin (DOX) is an antitumor drug, associated with cardiomyopathy. Strategies to address DOX-cardiomyopathy are scarce. Here, we identify the effect of forskolin (FSK) on DOX-induced-asymmetric-dimethylarginine (ADMA) accumulation in monocytoid cells. DOX-challenge led to i) augmented cytotoxicity, reactive-oxygen-species (ROS) production and methyltransferase-enzyme-activity identified as ADMA and s-adenosylhomocysteine (SAH) accumulation (SAH-A). However, except cytotoxicity, other DOX effects were decreased by metformin and FSK. FSK, did not alter the DOX-induced cytotoxic effect, but, decreased SAH-A by >50% and a combination of three drugs restored physiological methyltransferase-enzyme-activity. Together, protective effect of FSK against DOX-induced SAH-A is associated with mitigated methyltransferase-activity, a one-of-a-kind report.

Caveolin1/protein arginine methyltransferase1/sirtuin1 axis as a potential target against endothelial dysfunction.

Endothelial dysfunction (ED), an established response to cardiovascular risk factors, is characterized by increased levels of soluble molecules secreted by endothelial cells (EC). Evidence suggest that ED is an independent predictor of cardiac events and that it is associated with a deficiency in production or bioavailability of nitric oxide (NO) and/or an imbalance in the relative contribution of endothelium-derived relaxing and contracting factors. ED can be reversed by treating cardiovascular risk factors, hence, beyond ambiguity, ED contributes to initiation and progression of atherosclerotic disease. Majority of cardiovascular risk factors act by a common pathway, oxidative stress (OS), characterized by an imbalance in bioavailability of NO and reactive oxygen species (ROS). Enhanced ROS, through several mechanisms, alters competence of EC that leads to ED, reducing its potential to maintain homeostasis and resulting in development of cardiovascular disease (CVD). Influential mechanisms that have been implicated in the development of ED include (i) presence of elevated levels of NOS inhibitor, asymmetric dimethylarginine (ADMA) due to augmented enzyme activity of protein arginine methyl transferase-1 (PRMT1); (ii) decrease in NO generation by endothelial nitric oxide synthase (eNOS) uncoupling, or by reaction of NO with free radicals and (iii) impaired post translational modification of protein (PTM) such as eNOS, caveolin-1 (cav1) and sirtuin-1 (SIRT1). However, the inter-related mechanisms that concur to developing ED is yet to be understood. The events that possibly overlay include OS-induced sequestration of SIRT1 to caveolae facilitating cav1-SIRT1 association; potential increase in lysine acetylation of enzymes such as eNOS and PRMT1 leading to enhanced ADMA formation; imbalance in acetylation-methylation ratio (AMR); diminished NO generation and ED. Here we review current literature from research showing interdependent association between cav1-PRMT1-SIRT1 to the outcomes of experimental and clinical research aiming to preserve endothelial function with gene- or pharmaco-therapy.