A Pilot Clinical Study on the Prognostic Relevance of Plasmatic Exosomes Levels in Oral Squamous Cell Carcinoma Patients

Background: To evaluate the relationship between the plasmatic CD63 and CAV1 positive exosome levels, in patients with OSCC before and after surgical treatment and to correlate it with their overall survival. Methods: A double-blind pilot study over 10 patients OSCC and T4 stage without distant metastases or local bone invasion has been performed. The average follow-up period was 37.64 months (34.3–40.84). We obtained 2 plasma tubes of 1 mL each before surgery and 7 days after surgery. Before performing the immunocapture-based analysis, EVs (Extracellular Vesicles) were isolated from the plasma and characterized with western blot analysis. Results: Mean values of CD63 positive plasmatic exosomes (EXO-CD63) after surgery decreased from 750.88 ± 286.67 to 541.71 ± 244.93 (p = 0.091). On the other hand, CAV-1 positive plasmatic exosomes (EXO-CAV-1) increased after surgery from 507 ± 483.39 to 1120.25 ± 1151.17 (p = 0.237). Patients with EXO-CD63 levels lower than the mean global value before the surgery had a survival of 36.04 months compared with the group with EXO-CD63 higher than the average who only survived 12.49 ± 1.67 months from the diagnosis, p = 0.225. When EXO-CAV-1 levels before surgery was lower than the average (813.94 ± 801.21) overall survival was 24.69 ± 22.23 months in contrast when it was higher that was only 11.64 months, p = 0.157. Patients with lower EXO-CD63 levels after surgery lived an average of 23.84 ± 23.9 months, while those with higher plasmatic levels of EXO-CD63 live 13.35 months, p = 0.808. When EXO-CAV-1 levels after surgery were lower, the average overall survival was 20.344 ± 15.40 months, in contrast when the EXO-CAV-1 levels were higher showing rather an estimate survival expectation of 1.64 months. Conclusions: Surgical treatment induced a dramatic reduction of the plasmatic levels of exosomes expressing CD63 as early as 1 week after resection. This first result suggests that the tumour mass is responsible of the high levels of circulating exosomes detected in cancer patients. At the same time point exosome expressing CAV-1 increased, possibly due to the inflammatory reaction immediately after surgery. Lastly, statistical analysis showed that lower levels of plasmatic exosomes both before and after surgery correlated with a better life expectancy of OSCC patients. Hopefully, this approach will prove useful in the clinical follow-up of cancer patientsS

Dissecting the proton transport pathway in oral squamous cell carcinoma: state of the art and theranostics implications

Cancer cells overexpress proton exchangers at the plasma membrane in order acidify the extracellular matrix and maintain the optimal pH for sustaining cancer growth. Among the families of proton exchangers implicated in carcinogenesis, carbonic anhydrases (CAs), monocarboxylate transporters (MCTs), Na+/H+ exchangers (NHEs), sodium bicarbonate cotransporters (NBCs), and vacuolar ATPases (V-ATPases) are highlighted. Considerable research has been carried out into the utility of the understanding of these machineries in the diagnosis and prognosis of several solid tumors. In addition, as therapeutic targets, the interference of their functions has contributed to the discovery or optimization of cancer therapies. According to recent reports, the study of these mechanisms seems promising in the particular case of oral squamous cell carcinoma (OSCC). In the present review, the latest advances in these fields are summarized, in particular, the usefulness of proton exchangers as potential prognostic biomarkers and therapeutic targets in OSCCS

Mortality of emergency abdominal surgery in high-, middle- and low-income countries

Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low- or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI). Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression. Results: Data were obtained for 10 745 patients from 357 centres in 58 countries; 6538 were from high-, 2889 from middle- and 1318 from low-HDI settings. The overall mortality rate was 1⋅6 per cent at 24 h (high 1⋅1 per cent, middle 1⋅9 per cent, low 3⋅4 per cent; P < 0⋅001), increasing to 5⋅4 per cent by 30 days (high 4⋅5 per cent, middle 6⋅0 per cent, low 8⋅6 per cent; P < 0⋅001). Of the 578 patients who died, 404 (69⋅9 per cent) did so between 24 h and 30 days following surgery (high 74⋅2 per cent, middle 68⋅8 per cent, low 60⋅5 per cent). After adjustment, 30-day mortality remained higher in middle-income (odds ratio (OR) 2⋅78, 95 per cent c.i. 1⋅84 to 4⋅20) and low-income (OR 2⋅97, 1⋅84 to 4⋅81) countries. Surgical safety checklist use was less frequent in low- and middle-income countries, but when used was associated with reduced mortality at 30 days. Conclusion: Mortality is three times higher in low- compared with high-HDI countries even when adjusted for prognostic factors. Patient safety factors may have an important role. Registration number: NCT02179112 (http://www.clinicaltrials.gov)

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Increased Plasmatic Levels of Exosomes Are Significantly Related to Relapse Rate in Patients with Oral Squamous Cell Carcinoma: A Cohort Study

Background: Oral squamous cell carcinoma (OSCC) is characterized by an immunosuppressive tumor microenvironment. Their plasma-derived exosomes deliver immunomodulatory molecules and cargo that correlate significantly with clinical parameters. This study aims to assess the exosomal profile as a potential tool for early detection of relapse and long-term outcomes in OSCC patients undergoing conventional therapy. Methods: 27 OSCC patients with a median 38-month follow-up were included in this study. The relationship between NTA-derived parameters and clinical pathological parameters was examined, and receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic efficacy of these values in detecting cancer relapse. Results: Plasmatic levels of exosomes prior to surgery showed a drastic reduction after surgical intervention (8.08E vs. 1.41 × 109 particles/mL, p = 0.006). Postsurgical concentrations of exosomes were higher in patients who experienced relapse compared to those who remained disease-free (2.97 × 109 vs. 1.11 × 109 particles/mL, p = 0.046). Additionally, patients who relapsed exhibited larger exosome sizes after surgery (141.47 vs. 132.31 nm, p = 0.03). Patients with lower concentrations of exosomes prior to surgery demonstrated better disease-free survival compared to those with higher levels (p = 0.012). ROC analysis revealed an area under the curve of 0.82 for presurgical exosome concentration in identifying relapse. Conclusions: Presurgical exosomal plasmatic levels serve as independent predictors of early recurrence and survival in OSCC. All in all, our findings indicate that the detection of peripheral exosomes represents a novel tool for the clinical management of OSCC, with potential implications for prognosis assessment

Prejuicio y distancia social hacia las personas gays y lesbianas en una muestra de empleados en Puerto Rico: estudio exploratorio

Through a quantitative, exploratory-descriptive and non-experimental study, the prejudiced attitude (PA) and social distancing (SD) towards lesbian and gay people were examined in a sample of workers in Puerto Rico. The sample consisted of 779 participants, in which, 61 %were women between the age range of 21 to 40 years. The results indicated that workers exhibited low levels of PA (M=85.47) and low levels of SD (M=18.14) towards (LG) people. Moreover, we found a direct, moderately high and significant relationship between these variables, r (777) = .63, p<.01. When considering sexual orientation, heterosexuals expressed higher PA and SD towards LG people than non-heterosexuals. In respect to political perspective, conservatives showed more PA and SD than liberals. Finally, when considering religious practices, those who reported attending to some religious services weekly indicated higher PA and SD than those who reported never attending. In conclusion, although the PA and SD in workers towards LG people are expressed in low levels, they continue to be present. A relatively high proportion of non-heterosexuals participating in the study (29 %) may have had an impact on the low levels of PA and SD found. This study provides relevant information about the attitudes of workers in relation to sexual minorities, which allows organizations to develop diversity programs that are more inclusive and LGBT-friendlyMediante un estudio cuantitativo, exploratorio-descriptivo y no experimental, se examinó la actitud prejuiciada (AP) y el distanciamiento social (DS) hacia las personas lesbianas y gays (LG) en una muestra de trabajadores en Puerto Rico. La muestra estuvo compuesta por 779 participantes, de los cuales 61 % fueron mujeres entre el rango de edad de 21 a 40 años. Los resultados reflejaron que los trabajadores muestran niveles bajos de AP (M=85.47) y niveles bajos de DS (M=18.14) hacia las personas LG. Igualmente, encontramos una relación directa, moderadamente alta y significativa entre dichas variables, r (777) = .63, p<.01. Al considerar la orientación sexual, los heterosexuales manifestar on mayor AP y DS hacia las personas LG que los no-heterosexuales. Respecto a la perspectiva política, los conservadores manifestaron más AP y DS que los liberales. Por último, al considerar las prácticas religiosas, los que asisten semanalmente a algún servicio religioso mostraron mayor AP y DS que los que nunca van. En conclusión, aunque las AP y la DS de los trabajadores hacia las personas LG se manifiestan en niveles bajos, aún siguen presentes. Una participación relativamente alta de personas no-heterosexuales (29 %) pudo haber incidido en los niveles bajos de AP y DS hallados. Este estudio provee información relevante sobre las actitudes de los trabajadores en relación a las minorías sexuales, lo que permite a las organizaciones desarrollar programas dediversidad más inclusivos y LGBT-amigable

Prejuicio y distancia social hacia las personas gays y lesbianas en una muestra de empleados en Puerto Rico: estudio exploratorio

Through a quantitative, exploratory-descriptive and non-experimental study, the prejudiced attitude (PA) and social distancing (SD) towards lesbian and gay people were examined in a sample of workers in Puerto Rico. The sample consisted of 779 participants, in which, 61 % were women between the age range of 21 to 40 years. The results indicated that workers exhibited low levels of PA (M=85.47) and low levels of SD (M=18.14) towards (LG) people. Moreover, we found a direct, moderately high and significant relationship between these variables, r (777) = .63, p&lt;.01. When considering sexual orientation, heterosexuals expressed higher PA and SD towards LG people than non-heterosexuals. In respect to political perspective, conservatives showed more PA and SD than liberals. Finally, when considering religious practices, those who reported attending to some religious services weekly indicated higher PA and SD than those who reported never attending. In conclusion, although the PA and SD in workers towards LG people are expressed in low levels, they continue to be present. A relatively high proportion of non-heterosexuals participating in the study (29 %) may have had an impact on the low levels of PA and SD found. This study provides relevant information about the attitudes of workers in relation to sexual minorities, which allows organizations to develop diversity programs that are more inclusive and LGBT-friendly.Mediante un estudio cuantitativo, exploratorio-descriptivo y no experimental, se examinóla actitud prejuiciada (AP) y el distanciamiento social (DS) hacia las personas lesbianas y gays (LG) en una muestra de trabajadores en Puerto Rico.&nbsp;La muestra estuvo compuesta por779 participantes, de los cuales 61&nbsp;%fueron mujeres entre el rango de edad de 21 a 40 años.&nbsp;Los resultados reflejaron&nbsp;que los trabajadores muestranniveles bajos de AP (M=85.47) y niveles&nbsp;bajos de&nbsp;DS (M=18.14) hacia las personas LG. Igualmente, encontramos una relación directa, moderadamente alta y significativa&nbsp;entre dichas variables,&nbsp;r&nbsp;(777) = .63,&nbsp;p&lt;.01.Al considerar la orientación sexual, los heterosexuales manifestaron mayor APy DS hacia las personas LG que los no-heterosexuales.&nbsp;Respecto a la perspectiva política, los conservadores manifestaron más AP y DS que los liberales.&nbsp;Por último, alconsiderar las prácticas religiosas, los que asisten semanalmente a algún servicio religioso mostraron mayor AP y DS que los que nunca van.&nbsp;En conclusión, aunque las AP y la DS de los trabajadores hacia las personas LG se manifiestan en niveles bajos, aún siguen presentes y son consistentes con otros estudios. Lo anterior representa serias implicaciones para el sector gay y lésbico en el contexto laboral. Al comparar este&nbsp;estudio con otros, éste provee información relevante del pensar de los trabajadores en relación a las minorías sexuales, aspecto no auscultado anteriormente y que permite a las organizaciones desarrollar programas de diversidad más inclusivos y LGBT-amigables.&nbsp