Exploring miR-155-5p and miR-1246 as Diagnostic and Prognostic Markers in Oral Squamous cell carcinoma.

INTRODUCTION: Oral Squamous Cell Carcinoma (OSCC) is one of the leading cancers worldwide, significantly impacting developing nations. This study aimed to explore the diagnostic and prognostic potential of miR-155-5p and miR-1246 in OSCC in the Indian population, as their comparative roles in this context remain unexplored. MATERIAL AND METHODS: The present cross-sectional study comprised 50 histopathologically confirmed OSCC cases, with adjacent normal mucosa as controls. MiRNA expression was assessed via qRT-PCR and correlated with clinicopathological factors. MiRwalk and miRTargetlink were used for miRNA:mRNA interaction prediction, and gprofiler was employed to analyze validated targets for functional insights. RESULTS: The expression analysis showed a significant upregulation of miR-155-5p and miR-1246 in OSCC tissues compared to adjacent controls. Receiver operating curve analysis revealed that miR-1246 exhibited excellent diagnostic accuracy (AUC = 0.94) compared to miR-155-5p (AUC = 0.69). Higher miRNA levels were associated with age and extracapsular extension while overexpression of miR-1246 was correlated significantly with increased tumor size, tumor grade, TNM staging, and depth of invasion. The analysis for target prediction unveiled a set of validated targets, among which were WNT5A, TP53INP1, STAT3, CTNNB1, PRKAR1A, and NFIB. CONCLUSION: miR-155-5p and miR-1246 may be used as potential prognostic biomarkers in OSCC, with miR-1246 demonstrating superior diagnostic accuracy.

2023 Update on Vascular Anesthesia.

The authors thank the editors for this opportunity to review the recent literature on vascular surgery and anesthesia and provide this clinical update. The last in a series of updates on this topic was published in 2019.1 This review explores evolving discussions and current trends related to vascular surgery and anesthesia that have been published since then. The focus is on the major points discussed in the recent literature in the following areas: carotid artery surgery, infrarenal aortic surgery, peripheral vascular surgery, and the preoperative evaluation of vascular surgical patients.

Comparison of Landmark-Guided Versus Fluoroscopy-Guided Cerebrospinal Fluid Drain-Related Complications After Aortic Repairs.

OBJECTIVE: Cerebrospinal fluid drains (CSFDs) are efficacious in preventing spinal cord injury after thoracic or thoracoabdominal aortic repair with extensive coverage. Increasingly, fluoroscopy is used to guide placement instead of the traditional landmark-based approach, but it is unknown which approach is associated with fewer complications. DESIGN: A retrospective cohort study. SETTING: In the operating room. PARTICIPANTS: Patients having undergone thoracic or thoracoabdominal aortic repair with a CSFD over a 7-year period at a single center. INTERVENTIONS: No intervention. MEASUREMENTS AND MAIN RESULTS: Groups were reviewed and statistically compared with respect to baseline characteristics, ease of CSFD placement, and major and minor complications directly related to placement. A total of 150 CSFDs were placed with landmark guidance as opposed to 95 with fluoroscopy guidance. Compared to the landmark group, patients with fluoroscopy-guided CSFDs were older (p < 0.008), had lower American Society of Anesthesiologists physical status scores (p = 0.008), required fewer CSFD placement attempts (p = 0.011), had the CSFD in place for longer duration (p < 0.001), and had a similar incidence of CSFD-related complications (p > 0.999). Composites of both major (4.5% of cases) and minor CSFD-related complications (6.1% of cases), the primary outcomes of the study, occurred with similar incidences between the 2 groups (p > 0.999 for both comparisons) after adjusting potential confounders. CONCLUSIONS: In patients undergoing thoracic or thoracoabdominal aortic repairs, there were no significant differences in the risk of major and minor CSFD-related complications between fluoroscopic guidance and the landmark approach. Although the authors' institution is a high-volume center for this type of procedure, the study was limited by a small sample size. Hence, regardless of the technique used for the placement of CSFD, the risks related to the placement should be balanced carefully against the potential benefits resulting from spinal cord injury prevention. Fluoroscopy-aided insertion of CSFD requires fewer attempts and, hence, may be better tolerated by patients.

Right Heart Failure Management: Focus on Mechanical Support Options.

Millions of American adults suffer from right heart failure (RHF), a condition associated with high rates of hospitalization, organ failure, and death. There is a multitude of etiologies and mechanisms that lead to RHF, often in a feedforward spiral of decline. The management of advanced cases of RHF can be particularly difficult. For patients who are refractory to the medical optimization of volume status, hemodynamic and pharmacologic support, and rhythm control, mechanical therapies may be warranted. Currently available mechanical assist devices for RHF include venoarterial extracorporeal oxygenation and right ventricular assist devices, both surgical and percutaneous. Each advanced therapy has its own potential advantages and limitations, and often is appropriate in different clinical contexts. In this review, the authors describe the pathophysiology and medical therapies for RHF and then focus on the different types of advanced therapies that currently exist to help inform medical decision-making for this complicated patient cohort.

Hypothermia and Prolonged Time From Procedure End to Extubation After Endovascular Thoracic Aortic Surgery.

OBJECTIVE: Perioperative hypothermia (core temperature <36°C) occurs in 50%-to-80% of patients recovering from thoracic aortic surgery, though its effects have not been described fully in this context. The authors, therefore, sought to characterize the incidence of perioperative hypothermia and its association with time from procedure end to extubation in endovascular aortic surgical patients. DESIGN: A retrospective cohort study. SETTING: At a single academic tertiary center. PARTICIPANTS: Patients recovering from thoracic aortic surgery with lumbar drains. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: A total of 196 patients were included in this study, 55 of whom were hypothermic with temperatures <35.0°C at the end of surgery. Though the unadjusted time to extubation was not statistically different in the hypothermic group (median 8 minutes, IQR 5-13.5 minutes) compared to the normothermic group (median 7 minutes, IQR 4-12 minutes; p = 0.062), multivariate predictors of increased time from procedure end to extubation included hypothermia (p = 0.011), age (p = 0.009), diabetes (p = 0.015), history of carotid disease (p = 0.040), and crystalloid volume (p = 0.019). CONCLUSIONS: Hypothermia in patients recovering from endovascular aortic surgery was associated with prolonged time from procedure end to extubation. Because of the retrospective observational nature of the authors' analysis, it was not possible to determine the extent to which prolonged mechanical ventilation was influenced by low temperature.

Propofol Versus Remifentanil Sedation for Transcatheter Aortic Valve Replacement: A Single Academic Center Experience.

OBJECTIVE: Comparison of remifentanil versus propofol for sedation during transcatheter aortic valve replacement (TAVR) procedures to analyze the risk of sedation-related hypoxemia and hypotension. Secondary outcomes included the rate of conversion to general anesthesia, procedure length, rate of intensive care unit (ICU) admission, ICU and hospital lengths of stay, and 30-day mortality. DESIGN: Retrospective cohort study. SETTING: A single tertiary teaching hospital. PARTICIPANTS: Two hundred fifty-nine patients who had propofol or remifentanil sedation for TAVR between March 2017 and March 2020. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: There were 130 patients (50.2%) in the propofol cohort and 129 patients (49.8%) in the remifentanil cohort. The primary outcomes were oxygen saturation nadir values and vasopressor infusion use. Remifentanil was associated with a lower oxygen saturation nadir, as compared to propofol (91.3% v . 95.4%, p < 0.001). Risk factors associated with hypoxemia (defined as <92%) were body mass index (p = 0.0004), obstructive sleep apnea (p = 0.004), and remifentanil maintenance (p < 0.001). Vasopressor infusion use was significantly higher with propofol (64.9% v . 8.5%, p < 0.001). Propofol maintenance and angiotensin-converting enzyme inhibitor/angiotensin II receptor-blocker use were the only variables identified as risk factors for vasopressor use (p < 0.001 and p = 0.009). CONCLUSIONS: For patients undergoing TAVR with conscious sedation, remifentanil was associated with more hypoxemia while propofol was associated with a higher rate of vasopressor use.

Measuring Health-Related Quality of Life With Multimodal Data: Viewpoint.

The ability to objectively measure aspects of performance and behavior is a fundamental pillar of digital health, enabling digital wellness products, decentralized trial concepts, evidence generation, digital therapeutics, and more. Emerging multimodal technologies capable of measuring several modalities simultaneously and efforts to integrate inputs across several sources are further expanding the limits of what digital measures can assess. Experts from the field of digital health were convened as part of a multi-stakeholder workshop to examine the progress of multimodal digital measures in two key areas: detection of disease and the measurement of meaningful aspects of health relevant to the quality of life. Here we present a meeting report, summarizing key discussion points, relevant literature, and finally a vision for the immediate future, including how multimodal measures can provide value to stakeholders across drug development and care delivery, as well as three key areas where headway will need to be made if we are to continue to build on the encouraging progress so far: collaboration and data sharing, removal of barriers to data integration, and alignment around robust modular evaluation of new measurement capabilities.

Factors predicting mortality among patients with COVID-19 associated hospital acquired pneumonia: insights from a tertiary care center.

Hospital acquired pneumonia (HAP) is a severe and dangerous complication in patients admitted with COVID-19, causing significant morbidity and mortality globally. However, the early detection and subsequent management of high-risk cases may prevent disease progression and improve clinical outcomes. This study was undertaken in order to identify predictors of mortality in COVID-19 associated HAP. A retrospective study was performed on all patients who were admitted to a tertiary care center with COVID-19 associated HAP from July 2020 till November 2020. Data was collected on relevant demographic, clinical and laboratory parameters to determine their association with in-hospital mortality; 1574 files were reviewed, out of which 162 were included in the final study. The mean age of subjects was 59.4±13.8 and a majority were male (78.4%). There were 71 (48.3%) mortalities in the study sample. Klebsiella pneumoniae (31.5%) and Pseudomonas aeruginosa (30.2%) were the most common organisms overall. Clinically significant growth of Aspergillus sp. was observed in 41 (29.0%) of patients. On univariate analysis, several factors were found to be associated with mortality, including male gender (p=0.04), D-dimers >1.3 mg/L (p<0.001), ferritin >1000 µg/mL (p<0.001), LDH >500I.U/mL (p<0.001) and procalcitonin >2.0 µg/mL (p<0.001). On multivariate analysis, ferritin >1000ng/mL, initial site of care in Special Care Units or Intensive Care Units, developing respiratory failure and developing acute kidney injury were factors independently associated with mortality in our patient sample. These results indicate that serum ferritin levels may be a potentially useful biomarker in the management of COVID-19 associated HAP.

Anesthesia for Combined Heart and Liver Transplantation.

A heart or liver transplantation procedure performed in isolation itself presents multiple challenges for the perioperative team. Accordingly, combining both transplants yields a vastly more complicated surgery, with many unique multisystem and multidisciplinary considerations. Although combined heart and liver transplantations are being performed with increasing frequency, nationwide experience is relatively limited at most institutions. The aim of this review is to discuss the perioperative challenges presented to the anesthesiology teams and provide evidence-based guidance for the management of these daunting procedures.

Mapping out Violence Against Women of Influence on Twitter Using the Cyber-Lifestyle Routine Activity Theory.

The study applies and expands the routine activity theory to examine the dynamics of online harassment and violence against women on Twitter in India. We collected 931,363 public tweets (original posts and replies) over a period of 1 month that mentioned at least one of 101 influential women in India. By undertaking both manual and automated text analysis of "hateful" tweets, we identified three broad types of violence experienced by women of influence on Twitter: dismissive insults, ethnoreligious slurs, and gendered sexual harassment. The analysis also revealed different types of individually motivated offenders: "news junkies," "Bollywood fanatics," and "lone-wolves", who do not characteristically engage in direct targeted attacks against a single person. Finally, we question the effectiveness of Twitter's form of "guardianship" against online violence against women, as we found that a year after our initial data collection in 2017, only 22% of hostile posts with explicit forms of harassment have been deleted. We conclude that in the social media age, online and offline public spheres overlap and intertwine, requiring improved regulatory approaches, policies, and moderation tools of "capable" guardianship that empower women to actively participate in public life.

One-year Results of a Factorial Randomized Trial of Aspirin versus Placebo and Clonidine versus Placebo in Patients Having Noncardiac Surgery.

BACKGROUND: The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown. METHODS: The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h. RESULTS: Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1). CONCLUSIONS: Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect.

Anesthesia for Resection and Reconstruction of the Trachea and Carina.

Airway surgery poses a host of unique challenges to both the surgical and anesthesiology teams. Accordingly, there are a variety of surgical, anesthetic, and airway management options to be strategically considered. Management can be challenging during multidisciplinary preoperative planning, during the surgical procedure itself, and during recovery. In this review, emphasis is placed on anesthesia challenges for patients undergoing major tracheal or carinal surgery with specific considerations related to perioperative management.

Endotracheal tube mucus as a source of airway mucus for rheological study.

Muco-obstructive lung diseases (MOLDs), like cystic fibrosis and chronic obstructive pulmonary disease, affect a spectrum of subjects globally. In MOLDs, the airway mucus becomes hyperconcentrated, increasing osmotic and viscoelastic moduli and impairing mucus clearance. MOLD research requires relevant sources of healthy airway mucus for experimental manipulation and analysis. Mucus collected from endotracheal tubes (ETT) may represent such a source with benefits, e.g., in vivo production, over canonical sample types such as sputum or human bronchial epithelial (HBE) mucus. Ionic and biochemical compositions of ETT mucus from healthy human subjects were characterized and a stock of pooled ETT samples generated. Pooled ETT mucus exhibited concentration-dependent rheologic properties that agreed across spatial scales with reported individual ETT samples and HBE mucus. We suggest that the practical benefits compared with other sample types make ETT mucus potentially useful for MOLD research.

Assessment of Interleukin-18 gene polymorphism and serum levels in oral lichen planus in an Indian population.

BACKGROUND: Oral lichen planus (OLP) is a chronic, inflammatory disease with uncertain etiology. The aim of this study was to assess Interleukin-18 (IL-18) gene polymorphism and serum levels in OLP cases of Indian origin and to compare them with a control population of similar background. METHODS: The assessment of single-nucleotide polymorphisms (SNPs) of IL-18 gene at promoter regions -137(G/C) and -607(C/A) was done in 70 OLP cases and 70 healthy controls using sequence-specific primer-polymerase chain reaction (SSP-PCR). In a subset of this cohort, comprising of 41 OLP cases and 41 controls, serum IL-18 levels were assessed using enzyme-linked immunosorbent assay (ELISA). RESULTS: Mean serum levels of IL-18 among OLP cases were significantly higher when compared to controls. Genotypic and allelic frequencies of IL-18 at position -137(G/C) showed that GG genotype and allele G was significantly higher in OLP cases, whereas, GC genotype and C allele was high in the control group. Polymorphism of IL-18 at position -607(C/A) showed no significant differences. CONCLUSIONS: Gene polymorphism at -137GG genotype and allele G seems to be associated with genetic susceptibility to OLP whereas -137GC and allele C may have a protective role against its development. However, our study lacks clear statistical correlation, the differences observed could be caused by sampling problems and the results could not be fully representative of Indian patients with OLP. Further studies are warranted to explore the role of IL-18 genetic polymorphisms in OLP development.

Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery.

Background: Uncertainty remains about the effects of aspirin in patients with prior percutaneous coronary intervention (PCI) having noncardiac surgery. Objective: To evaluate benefits and harms of perioperative aspirin in patients with prior PCI. Design: Nonprespecified subgroup analysis of a multicenter factorial trial. Computerized Internet randomization was done between 2010 and 2013. Patients, clinicians, data collectors, and outcome adjudicators were blinded to treatment assignment. (ClinicalTrials.gov: NCT01082874). Setting: 135 centers in 23 countries. Patients: Adults aged 45 years or older who had or were at risk for atherosclerotic disease and were having noncardiac surgery. Exclusions were placement of a bare-metal stent within 6 weeks, placement of a drug-eluting stent within 1 year, or receipt of nonstudy aspirin within 72 hours before surgery. Intervention: Aspirin therapy (overall trial, n = 4998; subgroup, n = 234) or placebo (overall trial, n = 5012; subgroup, n = 236) initiated within 4 hours before surgery and continued throughout the perioperative period. Of the 470 subgroup patients, 99.9% completed follow-up. Measurements: The 30-day primary outcome was death or nonfatal myocardial infarction; bleeding was a secondary outcome. Results: In patients with prior PCI, aspirin reduced the risk for the primary outcome (absolute risk reduction, 5.5% [95% CI, 0.4% to 10.5%]; hazard ratio [HR], 0.50 [CI, 0.26 to 0.95]; P for interaction = 0.036) and for myocardial infarction (absolute risk reduction, 5.9% [CI, 1.0% to 10.8%]; HR, 0.44 [CI, 0.22 to 0.87]; P for interaction = 0.021). The effect on the composite of major and life-threatening bleeding in patients with prior PCI was uncertain (absolute risk increase, 1.3% [CI, -2.6% to 5.2%]). In the overall population, aspirin increased the risk for major bleeding (absolute risk increase, 0.8% [CI, 0.1% to 1.6%]; HR, 1.22 [CI, 1.01 to 1.48]; P for interaction = 0.50). Limitation: Nonprespecified subgroup analysis with small sample. Conclusion: Perioperative aspirin may be more likely to benefit rather than harm patients with prior PCI. Primary Funding Source: Canadian Institutes of Health Research.

ZMapp Reinforces the Airway Mucosal Barrier Against Ebola Virus.

Filoviruses, including Ebola, have the potential to be transmitted via virus-laden droplets deposited onto mucus membranes. Protecting against such emerging pathogens will require understanding how they may transmit at mucosal surfaces and developing strategies to reinforce the airway mucus barrier. Here, we prepared Ebola pseudovirus (with Zaire strain glycoproteins) and used high-resolution multiple-particle tracking to track the motions of hundreds of individual pseudoviruses in fresh and undiluted human airway mucus isolated from extubated endotracheal tubes. We found that Ebola pseudovirus readily penetrates human airway mucus. Addition of ZMapp, a cocktail of Ebola-binding immunoglobulin G antibodies, effectively reduced mobility of Ebola pseudovirus in the same mucus secretions. Topical delivery of ZMapp to the mouse airways also facilitated rapid elimination of Ebola pseudovirus. Our work demonstrates that antibodies can immobilize virions in airway mucus and reduce access to the airway epithelium, highlighting topical delivery of pathogen-specific antibodies to the lungs as a potential prophylactic or therapeutic approach against emerging viruses or biowarfare agents.