Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach.

BACKGROUND: TNM8 staging for oropharyngeal squamous cell carcinomas (OPSCC) surrogates p16 immunohistochemistry for HPV testing. Patients with p16+ OPSCC may lack HPV aetiology. Here, we evaluate the suitability of TNM8 staging for guiding prognosis in such patients. METHODS: HPV status was ascertained using p16 immunohistochemistry and high-risk HPV RNA and DNA in situ hybridisation. Survival by stage in a cohort of OPSCC patients was evaluated using TNM7/TNM8 staging. Survival of p16+/HPV- patients was compared to p16 status. RESULTS: TNM8 staging was found to improve on TNM7 (log rank p = 0·0190 for TNM8 compared with p = 0·0530 for TNM7) in p16+ patients. Patients who tested p16+ but were HPV- (n = 20) had significantly reduced five-year survival (33%) compared to p16+ patients (77%) but not p16- patients (35%). Cancer stage was reduced in 95% of p16+/HPV- patients despite having a mortality rate twice (HR 2.66 [95% CI: 1.37-5.15]) that of p16+/HPV+ patients under new TNM8 staging criteria. CONCLUSION: Given the significantly poorer survival of p16+/HPV- OPSCCs, these data provide compelling evidence for use of an HPV-specific test for staging classification. This has particular relevance in light of potential treatment de-escalation that could expose these patients to inappropriately reduced treatment intensity as treatment algorithms evolve.

Anti-α-Gal antibodies detected by novel neoglycoproteins as a diagnostic tool for Old World cutaneous leishmaniasis caused by Leishmania major.

Outbreaks of Old World cutaneous leishmaniasis (CL) have significantly increased due to the conflicts in the Middle East, with most of the cases occurring in resource-limited areas such as refugee settlements. The standard methods of diagnosis include microscopy and parasite culture, which have several limitations. To address the growing need for a CL diagnostic that can be field applicable, we have identified five candidate neoglycoproteins (NGPs): Galα (NGP3B), Galα(1,3)Galα (NGP17B), Galα(1,3)Galß (NGP9B), Galα(1,6)[Galα(1,2)]Galß (NGP11B), and Galα(1,3)Galß(1,4)Glcß (NGP1B) that are differentially recognized in sera from individuals with Leishmania major infection as compared with sera from heterologous controls. These candidates contain terminal, non-reducing α-galactopyranosyl (α-Gal) residues, which are known potent immunogens to humans. Logistic regression models found that NGP3B retained the best diagnostic potential (area under the curve from receiver-operating characteristic curve = 0.8). Our data add to the growing body of work demonstrating the exploitability of the human anti-α-Gal response in CL diagnosis.

Correction: Protocol: The role of defunctioning stoma prior to neoadjuvant therapy for locally advanced colonic and rectal cancer-A systematic review.

[This corrects the article DOI: 10.1371/journal.pone.0275025.].

The impact of the European Association of Endoscopic Surgery research grant scheme-a mixed qualitative quantitative methodology study protocol.

Background: The European Association of Endoscopic Surgery (EAES) is a surgical society who promotes the development and expansion of minimally invasive surgery to surgeons and surgical trainees. It does so through its activities in education, training, and research. The EAES research committee aims to promote the highest quality clinical research in endoscopic and minimally invasive surgery. They have provided grant funding since 2009 in education, surgery, and basic science. Despite the success and longevity of the scheme, the academic and non-academic impact of the research funding scheme has not been evaluated. Aims: The primary aim of this project is to assess the short, long term academic and real world impact of the EAES funding scheme. The secondary aims are to identify barriers and facilitators for achieving good impact. Methods: This will be a mixed qualitative and quantitative study. Semi-structured interviews will be performed with previous grant recipients. The questions for the interviews will be selected after a consensus is achieved amongst the members of the steering committee of this project. The responses will be transcribed and thematic analysis will be applied. The results of the thematic analysis will be used to populate a questionnaire which will be disseminated to grant recipients. This study is kindly funded by the EAES. Discussion: The first question this project is expected to answer is whether the EAES research funding scheme had a significant positive impact on research output, career progression but also non-academic output such as change in clinical guidelines, healthcare quality and cost-effectiveness improvement. This project however is also expected to identify facilitators and barriers to successful completion of projects and to achieving high impact. This will inform EAES and the rest of the surgical and academic communities as to how clinicians would like to be supported when conducting research. There should also be a positive and decisive change towards removing factors that hinder the timely and successful completion of projects.

A nationwide analysis of gallbladder surgery in England between 2000 and 2019.

BACKGROUND: There are no reports on nationwide trends in subtotal cholecystectomy (STC) and cholecystostomy in England. We hypothesized that, as in the United States, a substantial increase in the utilization of these surgical procedures, over time, may be observed. We aimed to generate a reliable report on 4 of the most common gallbladder surgical procedures in England to allow cross-procedure comparisons and highlight significant changes in the management of benign gallbladder disease over time. METHODS: We obtained data from NHS Digital and extracted population estimates from the Office of National Statistics. We examined the trends in the use of STC, cholecystostomy, cholecystolithotomy and total cholecystectomy (TC) between 2000 and 2019. RESULTS: Of the 1,234,319 gallbladder surgeries performed, TC accounted for 96.8% (n = 1,194,786) and the other 3 surgeries for 3.2% (n = 39,533). The total number of gallbladder surgeries performed annually increased by 80.4% from 2000 to 2019. We detected increases in the counts of cholecystostomies by 723.1% (n = 290 in 2000 vs n = 2,387 in 2019) and STCs by 716.6% (n = 217 in 2000 vs n = 1,772 in 2019). Consequently, there was a decrease in the ratio of TC to STC (180:1 in 2000 vs 38:1 in 2019). A similar decrease was observed in the ratio of cholecystectomy to cholecystostomy (135:1 in 2000 vs 29:1 in 2019). CONCLUSION: Increased utilization of STC and cholecystostomy was detected in England. These findings highlight the importance of regular monitoring of nationwide trends in gallbladder surgery and the associated clinical outcomes.

Protocol: The role of defunctioning stoma prior to neoadjuvant therapy for locally advanced colonic and rectal cancer-A systematic review.

Defunctioning stomas (ileostomy and colostomy) may be used prior to commencement of neoadjuvant therapy in patients with locally advanced colon or rectal cancer, in order to prevent clinical large bowel obstruction caused by radiotherapy associated oedema or progression of disease in patients who are not obstructed. However, the exact rate of clinical obstruction in patients undergoing neoadjuvant therapy who do not receive a defunctioning stoma is not known. Furthermore, it is not clear which factors predispose patients to developing clinical large bowel obstruction. Given that defunctioning stomas are associated with post operative and intra-operative risks, it is not currently possible to tailor defunctioning stomas to patients who have the greatest risk of developing obstruction. This systematic review which is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA), aims to define the role of defunctioning stomas in prevention of obstruction patients with locally advanced colon or rectal cancer while undergoing neoadjuvant therapy. Two researchers will perform the literature search which will include all published and "in process" articles published in the English language between 2002-2022 in the following databases: EMBASE (OVID), MEDLINE (EBSCO), CINHAL complete, Web of Science, Cochrane Central Registry of Controlled Trials, Clinical Trials Registry. The full text of the selected articles will be independently screened by two researchers against the inclusion criteria. Data will be extracted from each article regarding: study design, participants, type of intervention and outcomes. The effect size will be expressed in incidence rates and when appropriate in relative risk with 95% confidence intervals. If possible, we will perform a meta-analysis. Heterogeneity will be assessed using I2 statistics. We will pool the data extracted from the randomised controlled trials to perform a meta-analysis using the Review Manager 5 software (RevMan 5). The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system will be used to assess the certainty of the evidence.

A profile of a major trauma centre of North West England between 2011 and 2018.

This study examined the trends and patterns of major trauma (MT) activities, causes, mortality and survival at the Aintree Major Trauma Centre (MTC), Liverpool, between 2011 and 2018. The number of trauma team activations (TTAs) rose sharply over time (n = 699 in 2013; n = 1522 in 2018). The proportion of TTAs that involved MT patients decreased from 75.1% in 2013 to 67.4% in 2018. The leading cause of MT was a fall from less than 2 m (36%). There has been a fivefold increase in the overall number of trauma procedures between 2011 and 2018. Orthopaedic surgeons have performed 80% of operations (n = 7732), followed by neurosurgeons, oral and maxillofacial surgeons, and general trauma surgeons. Both types of fall (> 2 m and < 2 m) and road traffic accidents were the three leading causes of death during the study period. The observed mortality rates exceeded that of expected rates in years 2012, 2014, 2016 and 2017. The all-cause observed to expected mortality ratio was 1.08 between 2012 and 2018. A change in care for MT patients was not directly associated with improved survival, although the marginally ascending trend line in survival rates between 2012 and 2018 reflects a gradual positive change.

Risks associated with subtotal cholecystectomy and the factors influencing them: A systematic review and meta-analysis of 85 studies published between 1985 and 2020.

BACKGROUND: Subtotal cholecystectomy is recognized as a rescue procedure performed in grossly suboptimal circumstances that would deem a total cholecystectomy too risky to execute. An earlier systematic review based on 30 studies published between 1985 and 2013 concluded that subtotal cholecystectomy had a morbidity rate comparable to that of total cholecystectomy. This systematic review appraises 17 clinical outcomes in patients undergoing subtotal cholecystectomy. METHODS: The study protocol was registered with the International Prospective Register for Systematic Reviews (CRD42020172808). MEDLINE, Embase, Cochrane bibliographic databases, and Google Scholar were used to identify papers published between 1985 and June 2020. Data related to the surgical setting, approach, intervention on the hepatic wall of the gallbladder, type of completion of subtotal cholecystectomy, year of study, and study design were collected. Seventeen clinical outcomes were considered. Meta-analyses were performed using a random-effects model, and the effect size was presented as risk ratios with 95% confidence intervals. RESULTS: From 1,017 records, 85 eligible studies were identified and included. These included 3,645 patients who underwent subtotal cholecystectomy. Laparoscopic (80.1%, n = 2,918) and reconstituting (74.6%, n = 2,719) approaches represented the majority of all subtotal cholecystectomy cases. Seven (0.2%) cases of injury to the bile duct were reported. Bile leak was reported in 506 (13.9%) patients. Reconstituting subtotal cholecystectomy was associated with a lower risk for 11 clinical outcomes. Open subtotal cholecystectomy was associated with an increased rate of 30-day mortality and wound infections. CONCLUSION: Subtotal cholecystectomy is associated with significant morbidity. Laparoscopic and reconstituting surgery may reduce the risks of some perioperative complications and long-term sequelae after subtotal cholecystectomy.

Evaluating the Patient and Setting-Specific Factors That Influenced the Quality of Informed Consent in a Retrospective Cohort of Subtotal Cholecystectomy Patients.

Introduction: Cholecystectomy is the most frequently performed procedure in general surgery. The consent procedure for cholecystectomy needs to inform patients about the possibility of subtotal cholecystectomy (STC) as an alternative procedure used for "difficult gallbladders" as it is associated with increased postoperative morbidity. We sought to determine the quality of informed consent for patients who were scheduled for cholecystectomy but underwent STC, and evaluate whether patient or procedural factors influenced the information discussed in consenting. Materials and Methods: We classified 57 components of information necessary for a patient to give informed consent for cholecystectomy. We retrospectively reviewed the consent forms of patients scheduled for conventional cholecystecomy but instead undergoing STC between 2011 and 2017. Consent quality was measured as the percentage of components completed. Subgroup analyses were conducted to determine whether age, gender, American Society of Anesthesiologists grade, setting (elective/nonelective), operation mode (open/laparoscopic), or the responsible surgeon affected consent quality. Results: Across 174 patients, just 9 (5.2%) had been informed about the possibility of undergoing STC, whereas the overall quality of consent was 37.5%. Patient and setting-specific factors affected the completion of specific consent components. Patients were more likely to receive a patient information leaflet if they were female (relative risk [RR] 2.76; 95% confidence interval [CI] 1.09-7.00), <60 years (RR 3.32; 95% CI 1.39-7.90) or undergoing laparoscopic surgery (RR 8.04; 95% CI 2.50-25.88). Conclusion: The suboptimal quality of consent and multiple inconsistencies in the information disclosed to different patient cohorts emphasize the need for a more transparent and consistent consenting process.

The Role of the Computed Tomography (CT) Thorax in the Diagnosis of COVID-19 for Patients Presenting with Acute Surgical Emergencies. A Single Institute Experience.

The current Coronavirus disease 2019 (COVID-19) pandemic has had a huge impact on emergency surgical services in the UK. The Royal College of Surgeons (RCS) published guidelines about COVID-19 pandemic in March, 2020 to aid decision making for the surgeons. These guidelines recommended that all patients requiring urgent surgery should have reverse transcriptase polymerase chain reaction (RT-PCR) and/or computed tomography (CT) thorax pre-operatively. However, it is currently unclear whether the use of CT thorax is a sensitive and specific diagnostic test. The objective of this study was to find out whether CT thorax is a reliable and accurate test in the diagnosis of COVID-19 compared to RT-PCR. This is particularly important in surgical patients where there is no time to wait for RT-PCR results. A prospective cohort study of patients presented with acute surgical emergencies at a University Teaching Hospital was conducted. Data was collected from March 23, to May 15, 2020, during the peak of the crisis in the UK. All adult patients presented with operable general surgical emergencies were considered eligible. Another group of patients, admitted with acute medical emergencies but with suspected COVID-19 infection, was used for comparison. Data was manually collected, and sensitivity, specificity and predictive value were calculated using the MedCalc statistical software version 19.2.6. Standard reporting for COVID-19 infection for CT chest based on guidelines from British Society of Thoracic Imaging (BSTI) and Radiological Society of North America (RSNA) was used. Patients who had their CT thorax reported as typical or classic of COVID 19 (high probability) were treated as infected cases with extra precautions in the wards and surgical theatres as suggested by health and safety executive (HSE). These patients had serial RT-PCR during their admissions or in the post-operative phase, if the first swab was negative. For the study, 259 patients were considered eligible for inclusion from both groups. Patients admitted for acute surgical emergencies were treated according to RCS guidelines and subjected to RT-PCR test and/or CT scan of the thorax. There were 207 patients with high clinical suspicion of COVID-19. Of those 207 patients, 77 patients had CT thorax with radiographic features consistent with COVID-19 pneumonia. However, only 40 patients had a positive RT-PCR result. CT thorax was normal in 130 patients, out of which 29 patients were found to have COVID-19 diagnosis after swab test. Sensitivity of CT scan to diagnose COVID-19 infection was found to be 58% (95% CI; 45.48% to 69.76%) whilst specificity was 73% (95% CI; 64.99% to 80.37%) with a negative predictive value of 77.69% (95% CI; 72.17% to 82.39%). CT scan was found to be a reliable tool in the diagnosis of COVID-19. With a negative predictive value of up to 82.4%, CT thorax can play an important role to help surgeons in their decision making for asymptomatic suspected cases of COVID-19. However, over-reliance on CT scan which also has a high false positive rate for diagnosis of COVID-19 infections can lead to overtreatment, overuse of resources and delays in decision-making process. Hence, results should be interpreted with caution and correlated with clinical presentation and swab test results.

Chinese Herbal Medicine Glycyrrhiza inflataReduces Aß Aggregation and Exerts Neuroprotection through Anti-Oxidation and Anti-Inflammation.

Amyloid [Formula: see text] (A[Formula: see text]) plays a major role in the pathogenesis of Alzheimer's disease (AD). The accumulation of misfolded A[Formula: see text] causes oxidative and inflammatory damage leading to apoptotic cell death. Chinese herbal medicine (CHM) has been widely used in clinical practice to treat neurodegenerative diseases associated with oxidative stress and neuroinflammation. This study examined the neuroprotection effects of CHM extract Glycyrrhiza inflata (G. inflata) and its active constituents, licochalcone A and liquiritigenin in AD. We examined A[Formula: see text] aggregation inhibition, anti-oxidation and neuroprotection in Tet-On A[Formula: see text]-GFP 293/SH-SY5Y cells and anti-inflammatory potential in lipopolysaccharide (LPS)-stimulated RAW 264.7 and LPS and interferon (IFN)-[Formula: see text] (LPS/IFN-[Formula: see text])-activated BV-2 cells. In addition, we applied conditioned media (CM) of BV-2 cells primed with LPS/IFN-[Formula: see text] to A[Formula: see text]-GFP SH-SY5Y cells to uncover the neuroprotective mechanisms. Our results showed that G. inflata extract and its two constituents displayed potentials of A[Formula: see text] aggregation inhibition and radical-scavenging in biochemical assays, A[Formula: see text] misfolding inhibition and reactive oxygen species (ROS) reduction in A[Formula: see text]-GFP 293 cells, as well as neurite outgrowth promotion, acetylcholinesterase inhibition and SOD2 up-regulation in A[Formula: see text]-GFP SH-SY5Y cells. Meanwhile, both G. inflata extract and its constituents suppressed NO, TNF-[Formula: see text], IL-1[Formula: see text], PGE2 and/or Iba1 productions in inflammation-stimulated RAW 264.7 or BV-2 cells. G. inflata extract and its constituents further protected A[Formula: see text]-GFP SH-SY5Y cells from BV-2 CM-induced cell death by ameliorating reduced BCL2 and attenuating increased IGFBP2, cleaved CASP3, BAD and BAX. Collectively, G. inflata extract, licochalcone A and liquiritigenin display neuroprotection through exerting anti-oxidative and anti-inflammatory activities to suppress neuronal apoptosis.

Associations of Matrix Metalloproteinase-9 and Tissue Inhibitory Factor-1 Polymorphisms With Parkinson Disease in Taiwan.

Matrix metalloproteinases (MMPs) function in the degradation of extracellular matrix and are considered to play a role in the pathogenesis of neurodegenerative diseases including Parkinson disease (PD). MMPs activities are modulated by tissue inhibitors of metalloproteinases (TIMPs). This study examined whether the genetic polymorphisms of MMP-3, gelatinase (MMP-2 and MMP-9), TIMP-2, and TIMP-1 were associated with PD in Taiwan.A total of 359 PD patients and 332 controls were enrolled. The candidate genetic variants included MMP-2 rs2285053 (-735 C > T), MMP-3 rs3025058 (-1171 5A > 6A), MMP-9 rs3918241 (-1831 T > A), rs17576 (G > A, R279Q), and rs3787268 (G > A, intron), TIMP-1 rs4898 (T > C, F124F), and TIMP-2 rs7503607 (-269 G > T). Associations were tested by logistic regression, adjusted with gender and age at onset.Minor allele frequency of TIMP-1 rs4898 (36.0%) was significantly lower in the male PD patients than in the male controls (51.2%) (χ test, P = 0.004). When adjusted with gender and age at onset, MMP-9 rs17576 AA genotype was associated with PD susceptibility in a recessive fashion (odds ratios [OR] = 2.28, 95% confidence intervals [95% CI] = 1.12-4.62, P = 0.02). In males, TIMP-1 rs4898 C allele was associated with a protective effect on PD (OR = 0.75, 95% CI = 0.60-0.94, P = 0.014). We did not find association between the examined genetic variants of MMP-2, MMP-3, and TIMP-2 and PD susceptibility.This is the first study that demonstrated a protective effect of TIMP-1 rs4898 C allele on male PD and a modest association of MMP-9 rs17576 AA genotype with PD susceptibility in the Taiwan population. Further replication is needed for confirmation.