Sex-Related Differences in Life Expectancy Compared to General Population after Surgery for Ascending Aortic Aneurysm.

Background/Objectives: Understanding sex-based differences in cardiovascular outcomes is paramount to improving clinical outcomes. Surgery is an aggressive but effective therapy for ascending aortic aneurysm. We sought to determine if being a woman is a risk factor for long-term mortality after this surgery. We compared their life expectancy with a general population of the same age, sex, year, and region. Methods: We compared men and women undergoing AAA surgery at our institution from 2000 to 2019. After balancing the population with propensity score (PS) matching, we compared long-term mortality control with a Cox regression. We determined the RS using the Ederer II method and compared it to a healthy reference population of the same age, sex, and region. Results: From 2000 to 2019, 232 women and 506 men underwent ascending aortic aneurysm surgery. After a mean follow-up of 51.5 ± 34.5 months, sex was not an independent risk factor for long-term mortality in the multivariable analysis [HR: 0.68 (95% CI 0.43-1.07, p = 0.23)]. Matching by baseline characteristics, 196 pairs were analyzed with no differences regarding mortality in the Cox regression [HR: 1.11 (95% CI 0.65-1.9, p = 0.23)]. Men and women who survived the postoperative period presented a relative survival of 100.3% (95% CI 97.4-101%) and 100.3% (95% CI 98.9-101.1%), respectively, similar to the reference population without the disease. Conclusions: For patients undergoing AAA surgery, sex was not an independent predictor of mortality. Men and women who survived the postoperative period presented a similar life expectancy to that of the reference population (people free from the disease of the same age, sex, year, and region).

Combined PIK3CA and SOX2 Gene Amplification Predicts Laryngeal Cancer Risk beyond Histopathological Grading.

The PIK3CA and SOX2 genes map at 3q26, a chromosomal region frequently amplified in head and neck cancers, which is associated with poor prognosis. This study explores the clinical significance of PIK3CA and SOX2 gene amplification in early tumorigenesis. Gene copy number was analyzed by real-time PCR in 62 laryngeal precancerous lesions and correlated with histopathological grading and laryngeal cancer risk. Amplification of the SOX2 and PIK3CA genes was frequently detected in 19 (31%) and 32 (52%) laryngeal dysplasias, respectively, and co-amplification in 18 (29%) cases. The PIK3CA and SOX2 amplifications were predominant in high-grade dysplasias and significantly associated with laryngeal cancer risk beyond histological criteria. Multivariable Cox analysis further revealed PIK3CA gene amplification as an independent predictor of laryngeal cancer development. Interestingly, combined PIK3CA and SOX2 amplification allowed us to distinguish three cancer risk subgroups, and PIK3CA and SOX2 co-amplification was found the strongest predictor by ROC analysis. Our data demonstrate the clinical relevance of PIK3CA and SOX2 amplification in early laryngeal tumorigenesis. Remarkably, PIK3CA amplification was found to be an independent cancer predictor. Furthermore, combined PIK3CA and SOX2 amplification is emerging as a valuable and easy-to-implement tool for cancer risk assessment in patients with laryngeal precancerous lesions beyond current WHO histological grading.

Manejo de Alteraciones Neurosensoriales Asociadas a Procedimientos Quirúrgicos Mandibulares, Scoping Review

Las alteraciones neurosensoriales son complicaciones que se pueden presentar posterior a la realización de ciertos procedimientos quirúrgicos orales. Múltiples reportes indican específicamente el territorio inervado por el nervio alveolar inferior y nervio lingual como las regiones mayormente afectadas. Dar a conocer las diferentes alternativas terapéuticas para estas complicaciones, sería de suma relevancia para el clínico, con el propósito de mejorar el pronóstico en cuanto a la recuperación neurosensorial de estos nervios. El objetivo de este trabajo fue describir el manejo terapéutico de las alteraciones neurosensoriales asociadas al daño del nervio alveolar inferior y nervio lingual, en procedimientos quirúrgicos mandibulares. La búsqueda de la literatura científica fue realizada en las bases de datos PubMed, Scopus y Web of Science. Se utilizaron los términos de búsqueda "Trigeminal nerve injuries", "lingual nerve", "mandibular nerve", "oral surgical procedures", "treatment" en conjunto al conector booleano "AND" y "OR". Fueron considerados artículos publicados entre los años 2012 y 2022. En la selección de los artículos primarios se eliminaron los duplicados y se aplicaron los criterios de inclusión y exclusión. Finalmente se realizó el análisis a texto completo con un total de 14 artículos seleccionados. Un total de 14 artículos fueron revisados. Del total de artículos, 6 corresponden a terapia láser de bajo nivel, 2 a medicación y bloqueo del ganglio estrellado, 1 a bloqueo de ganglio estrellado e irradiación con luz xenón y 5 artículos corresponden a tratamiento mediante reparación microquirúrgica. La terapia láser de bajo nivel, el bloqueo del ganglio estrellado, la administración de vitamina B12/ATP y la reparación microquirúrgica son tratamientos efectivos para las alteraciones neurosensoriales ocasionadas por lesiones del nervio alveolar inferior y nervio lingual.

SUMMARY: Neurosensory abnormalities are complications can occur after performing certain oral surgical procedures. Multiple reports specifically indicate the area innervated by the inferior alveolar nerve and the lingual nerve as the most affected regions. Presenting the different therapeutic alternatives for these complications would be extremely relevant for the clinician, in order to improve the prognosis in terms of neurosensory recovery of these nerves. The objective of this study was to describe the therapeutic management of neurosensory abnormalities associated with damage to the inferior alveolar nerve and lingual nerve, in mandibular surgical procedures. The search for scientific literature was carried out in the PubMed, Scopus and Web of Science databases. The search terms "Trigeminal nerve injuries", "lingual nerve", "mandibular nerve", "oral surgical procedures", "treatment" together with the boolean connector "AND" and "OR" were used. Articles published between the years 2012 and 2022 were considered. In the selection of primary articles, duplicates were eliminated and the inclusion and exclusion criteria were applied. Finally, the full text analysis was carried out with a total of 14 selected articles. A total of 14 articles were reviewed. About the articles, 6 correspond to low-level laser therapy, 2 to medication and stellate ganglion block, 1 to stellate ganglion block and xenon light irradiation, and 5 articles correspond to treatment by microsurgical repair. Low-level laser therapy, stellate ganglion block, vitamin B12/ATP administration, and microsurgical repair are effective treatments for neurosensory abnormalities caused by inferior alveolar nerve and lingual nerve injuries.

Beyond the anti-PD-1/PD-L1 era: promising role of the BTLA/HVEM axis as a future target for cancer immunotherapy.

Recent introduction of monoclonal antibodies targeting immune checkpoints to harness antitumor immunity has revolutionized the cancer treatment landscape. The therapeutic success of immune checkpoint blockade (ICB)-based therapies mainly relies on PD-1/PD-L1 and CTLA-4 blockade. However, the limited overall responses and lack of reliable predictive biomarkers of patient´s response are major pitfalls limiting immunotherapy success. Hence, this reflects the compelling need of unveiling novel targets for immunotherapy that allow to expand the spectrum of ICB-based strategies to achieve optimal therapeutic efficacy and benefit for cancer patients. This review thoroughly dissects current molecular and functional knowledge of BTLA/HVEM axis and the future perspectives to become a target for cancer immunotherapy. BTLA/HVEM dysregulation is commonly found and linked to poor prognosis in solid and hematological malignancies. Moreover, circulating BTLA has been revealed as a blood-based predictive biomarker of immunotherapy response in various cancers. On this basis, BTLA/HVEM axis emerges as a novel promising target for cancer immunotherapy. This prompted rapid development and clinical testing of the anti-BTLA blocking antibody Tifcemalimab/icatolimab as the first BTLA-targeted therapy in various ongoing phase I clinical trials with encouraging results on preliminary efficacy and safety profile as monotherapy and combined with other anti-PD-1/PD-L1 therapies. Nevertheless, it is anticipated that the intricate signaling network constituted by BTLA/HVEM/CD160/LIGHT involved in immune response regulation, tumor development and tumor microenvironment could limit therapeutic success. Therefore, in-depth functional characterization in different cancer settings is highly recommended for adequate design and implementation of BTLA-targeted therapies to guarantee the best clinical outcomes to benefit cancer patients.

The TINCR ubiquitin-like microprotein is a tumor suppressor in squamous cell carcinoma.

The TINCR (Terminal differentiation-Induced Non-Coding RNA) gene is selectively expressed in epithelium tissues and is involved in the control of human epidermal differentiation and wound healing. Despite its initial report as a long non-coding RNA, the TINCR locus codes for a highly conserved ubiquitin-like microprotein associated with keratinocyte differentiation. Here we report the identification of TINCR as a tumor suppressor in squamous cell carcinoma (SCC). TINCR is upregulated by UV-induced DNA damage in a TP53-dependent manner in human keratinocytes. Decreased TINCR protein expression is prevalently found in skin and head and neck squamous cell tumors and TINCR expression suppresses the growth of SCC cells in vitro and in vivo. Consistently, Tincr knockout mice show accelerated tumor development following UVB skin carcinogenesis and increased penetrance of invasive SCCs. Finally, genetic analyses identify loss-of-function mutations and deletions encompassing the TINCR gene in SCC clinical samples supporting a tumor suppressor role in human cancer. Altogether, these results demonstrate a role for TINCR as protein coding tumor suppressor gene recurrently lost in squamous cell carcinomas.

Targeting oncogenic functions of miR-301a in head and neck squamous cell carcinoma by PI3K/PTEN and MEK/ERK pathways.

Treatment of head and neck squamous cell carcinomas (HNSCC), the sixth most frequent cancer worldwide, remains challenging. miRNA dysregulation is closely linked to tumorigenesis and tumor progression, thus emerging as suitable targets for cancer treatment. Transcriptomic analysis of TCGA HNSCC dataset revealed that miR-301a expression levels significantly increased in primary tumors, as compared to patient-matched normal tissue. This prompted us to investigate its pathobiological role and potential as new therapeutic target using different preclinical HNSCC models. miR-301a overexpression in HNSCC-derived cell lines led to enhanced proliferation and invasion, whereas miR-301 inhibition reduced these effects. In vivo validation was performed using an orthotopic mouse model. Results concordantly showed that the mitotic counts, the percentage of infiltration depth and Ki67 proliferative index were significantly augmented in the subgroup of mice harboring miR-301a-overexpressing tumors. Further mechanistic characterization revealed PI3K/PTEN/AKT and MEK/ERK pathways as central signaling nodes responsible for mediating the oncogenic activity of miR-301a observed in HNSCC cells. Notably, pharmacological disruption of PI3K and ERK signals with BYL-719 and PD98059, respectively, was effective to completely revert/abolish miR-301a-promoted tumor cell growth and invasion. Altogether, these findings demonstrate that miR-301a dysregulation plays an oncogenic role in HNSCC, thus emerging as a candidate therapeutic target for this disease. Importantly, available PI3K and ERK inhibitors emerge as promising anti-tumor agents to effectively target miR-301a-mediated signal circuit hampering growth-promoting and pro-invasive functions.

Association of the Surgical Technique With the Structural Valve Deterioration of a Bioprosthesis: A Prospective Cohort Study.

The Trifecta aortic valve is a prosthesis with externally mounted leaflets and a stent which may be deformed during implant. Our aim was to know if the use of the holder as a protection device during the knotting has an impact on the incidence of structural valve deterioration (SVD) or endocarditis. Prospective cohort study where all patients who underwent aortic valve replacement with a Trifecta aortic valve between 2013 and 2018 were included. The use of the holder as a protection device was collected in a database. Propensity-score matched methods were used and analyses were based on competing events. Death without SVD or prosthesis replacement not due to SVD was considered competing events. 782 patients were included, 352 pairs after the matching. Rates of SVD at 5 and 8 years were 5.8% (95% CI 3.5-8.7) and 13.6% (95% CI 9.2-18.9) in the group without holder and 2.3% (95% CI 1-4.5) and 7% (95% CI 4.2-10.8) in the group with holder; sHR = 0.49 (95% CI 0.27-0.86; P = 0.015). The risk of endocarditis at 8 years was 4.8% (95% CI 2.8-7.4) in the group without holder and 2.3% (95% CI 1.1-4.3) in the group with holder, sHR = 0.49 (95% CI 0.21-1.15, P = 0.1). The use of holder as a protection device during the knotting of the Trifecta aortic valve is associated with less risk of SVD.

Remote ophthalmology with a smartphone adapter handled by nurses for the diagnosis of eye posterior pole pathologies during the COVID-19 pandemic.

INTRODUCTION: The use of smartphones to provide specialist ophthalmology services is becoming a more commonly used method to support patients with eye pathologies. During the COVID-19 pandemic, demand for telehealth services such as tele-ophthalmology, is increasing rapidly. METHODS: In 2019, the agreement between diagnostic tests was investigated by comparing the diagnostic performance for eye posterior pole pathologies of the images obtained by a smartphone coupled to a medical device known as open retinoscope (OR), handled by a nurse and subsequently assessed by an ophthalmologist versus the images obtained by an ophthalmologist using a slit lamp associated to a 76 diopter indirect ophthalmic lens (Volk Super FieldVR ) (SL-IOL) at the outpatient department of a hospital. The OR used in this study worked with a 28 diopter indirect lens. RESULTS: An examination of 151 dilated eyes (79 adult patients, mean age of 66.7 years, 59.5% women) was conducted. Sensitivity was 98.9%, specificity was 89.8%, the positive predictive value was 93.8% and the negative predictive value was 98.2%. The kappa index between both tests was 0.90 (95% CI: 0.83-0.97) in basic diagnosis, 0.81 (95% CI: 0.74-0.89) in syndromic diagnosis (13 categories) and 0.70 (95% CI: 0.62-0.77) in advanced diagnosis (23 categories). DISCUSSION: Images obtained by a nurse using a smartphone coupled to the OR and subsequently assessed by an ophthalmologist showed a high diagnostic performance for eye posterior pole pathologies, which could pave the way for remote ophthalmology systems for this patient group.

Análisis de riesgo de un microorganismo objetable en un suplemento dietario para la liberación de lotes

RESUMEN La contaminación con microorganismos objetables en los productos farmacéuticos no estériles puede tener el potencial de disminuir o inactivar la actividad farmacológica y terapéutica del principio activo y por ende representar un peligro de gran riesgo para la salud de la persona que está en tratamiento con fármacos; adicionalmente la presencia de estos microorganismos dependiendo de su capacidad para producir enfermedad en huéspedes susceptibles pueden ocasionar infecciones no esperadas o enfermedades que afecten al paciente o consumidor de estos medicamentos no estériles. El objetivo del trabajo fue desarrollar un análisis de riesgo microbiológico de microorganismos objetables en un suplemento dietario de una industria farmacéutica como herramienta en la gestión de seguridad. La metodología fue observacional-descriptivo de corte transverso. En la industria farmacéutica (en el suplemento dietario) se desarrolló un análisis de riesgo estudiando todos los parámetros, teniendo como resultado, que las cápsulas blandas con aceite de Krill, no presentan microorganismo objetable del tipo patógeno, como producto de bajo riesgo, por lo que es aprobado para la liberación del lote siguiendo estos parámetros. En Paraguay no existen normativas acerca del análisis de microorganismos objetables, en comparación con otros países como Argentina, y desde hace tiempo en EE. UU y países europeos (por reportes de la FDA) por lo cual, este trabajo es relevante y de vital importancia para establecer legislaciones nacionales con miras a la fabricación de medicamentos seguros, confiables y eficaces.

ABSTRACT Contamination with objectionable microorganisms in non sterile pharmaceutical products may have the potential to decrease or inactivate the pharmacological and therapeutic activity of the active principle and therefore represent a danger of great risk to the health of the person who is being treated with drugs, additionally, the presence of these microorganisms, depending on their ability to produce disease in susceptible hosts, can cause unexpected infections or diseases that affect the patient or consumer of these non sterile drugs. The objective of the work was to develop a microbiological risk analysis of objectionable microorganisms in a dietary supplement of a pharmaceutical industry as a tool in safety management. This was an observational-descriptive cross-sectional study. In the pharmaceutical industry (in the dietary supplement) a risk analysis was developed studying all the parameters, having as a result that the soft capsules with Krill oil do not present objectionable microorganisms of the pathogenic type, as a low risk product, therefore it is approved for batch release following these parameters. In Paraguay there are no regulations about the analysis of objectionable microorganisms, in comparison with other countries such as Argentina, and for a long time in the US and European countries (due to FDA reports). Therefore, this work is relevant and very vital important to establish national legislation with a view of the manufacture of safe, reliable and effective drugs.

Premature STEMI in Men and Women: Current Clinical Features and Improvements in Management and Prognosis.

Background: Coronary artery disease (CAD) is the most frequent cause of ST-segment elevation myocardial infarction (STEMI). Etiopathogenic and prognostic characteristics in young patients may differ from older patients and young women may present worse outcomes than men. We aimed to evaluate the clinical characteristics and prognosis of men and women with premature STEMI. METHODS: A total 1404 consecutive patients were referred to our institution for emergency cardiac catheterization due to STEMI suspicion (1 January 2014-31 December 2018). Patients with confirmed premature (<55 years old in men and <60 in women) STEMI (366 patients, 83% men and 17% women) were included (359 atherothrombotic and 7 spontaneous coronary artery dissection (SCAD)). RESULTS: Premature STEMI patients had a high prevalence of classical cardiovascular risk factors. Mean follow-up was 4.1 years (±1.75 SD). Mortality rates, re-hospitalization, and hospital stay showed no significant differences between sexes. More than 10% of women with premature STEMI suffered SCAD. There were no significant differences between sexes, neither among cholesterol levels nor in hypolipemiant therapy. The global survival rates were similar to that expected in the general population of the same sex and age in our region with a significantly higher excess of mortality at 6 years among men compared with the general population. CONCLUSION: Our results showed a high incidence of cardiovascular risk factors, a high prevalence of SCAD among young women, and a generally good prognosis after standardized treatment. During follow-up, 23% suffered a major cardiovascular event (MACE), without significant differences between sexes and observed survival at 1, 3, and 6 years of follow-up was 96.57% (95% CI 94.04-98.04), 95.64% (95% CI 92.87-97.35), and 94.5% (95% CI 91.12-97.66). An extra effort to prevent/delay STEMI should be invested focusing on smoking avoidance and optimal hypolipemiant treatment both in primary and secondary prevention.

Ion Channel Dysregulation in Head and Neck Cancers: Perspectives for Clinical Application.

Head and neck cancers are a highly complex and heterogeneous group of malignancies that involve very diverse anatomical structures and distinct aetiological factors, treatments and clinical outcomes. Among them, head and neck squamous cell carcinomas (HNSCC) are predominant and the sixth most common cancer worldwide with still low survival rates. Omic technologies have unravelled the intricacies of tumour biology, harbouring a large diversity of genetic and molecular changes to drive the carcinogenesis process. Nonetheless, this remarkable heterogeneity of molecular alterations opens up an immense opportunity to discover novel biomarkers and develop molecular-targeted therapies. Increasing evidence demonstrates that dysregulation of ion channel expression and/or function is frequently and commonly observed in a variety of cancers from different origin. As a consequence, the concept of ion channels as potential membrane therapeutic targets and/or biomarkers for cancer diagnosis and prognosis has attracted growing attention. This chapter intends to comprehensively and critically review the current state-of-art ion channel dysregulation specifically focusing on head and neck cancers and to formulate the major challenges and research needs to translate this knowledge into clinical application. Based on current reported data, various voltage-gated potassium (Kv) channels (i.e. Kv3.4, Kv10.1 and Kv11.1) have been found frequently aberrantly expressed in HNSCC as well as precancerous lesions and are highlighted as clinically and biologically relevant features in both early stages of tumourigenesis and late stages of disease progression. More importantly, they also emerge as promising candidates as cancer risk markers, tumour markers and potential anti-proliferative and anti-metastatic targets for therapeutic interventions; however, the oncogenic properties seem to be independent of their ion-conducting function.

Survival After Thoracoscopic Surgery or Open Lobectomy: Systematic Review and Meta-Analysis.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has been shown to reduce hospital stays and pain compared with open lobectomy to treat non-small cell lung cancer. Because of the low rate of deaths, it is difficult to show differences in survival in individual studies. The objective of this study was to compare short- and long-term mortality by means of a systematic review and meta-analysis. METHODS: The reviewers systematically searched studies that compared VATS vs open lobectomy and provided data on 30-day mortality or long-term survival (>5 years). For long-term outcomes, studies included patients with the same cancer stage or, if several stages were included, the studies had to control for cancer stage in their propensity score model. A pooled odds ratio and hazard ratio (HR) was respectively calculated for short- and long-term outcomes. RESULTS: A total of 33 works were identified, comprising 61,633 patients. VATS led to lower postoperative mortality (odds ratio, 0.64; 95% confidence interval [CI], 0.56 to 0.73) and higher long-term survival (HR, .88; 95% CI, 0.81 to 0.96). Disease-free survival was similar in both groups (HR, 0.94; 95% CI, 0.80 to 1.10). CONCLUSIONS: For non-small cell lung cancer treated with lobectomy, VATS was associated with lower postoperative mortality and greater long-term survival compared with open lobectomy. Disease-free survival was similar between both groups.

Long term follow up of percutaneous treatment for degenerated Mitroflow prosthesis with self-expanding transcatheter aortic valve implantation.

BACKGROUND: The durability of aortic valve bioprosthesis and the structural valve deterioration (SVD) are could be treated with valve-in-valve (VIV) transcatheter aortic valve implantation (TAVI). This technique has been proven to be a feasible procedure with good results in selected patients. The aim of this work was to assess the long-term results of this TAVI with an autoexpandable valve in patients with failed Mitroflow (MF) bioprosthetic aortic valves. METHODS: Single center, observational and prospective study that included 65 consecutive patients with symptomatic failed MF bioprosthetic aortic valve, treated with VIV-TAVI. The primary endpoints were clinical long-term events including all-cause mortality, cardiovascular mortality, re-hospitalization due to heart failure, stroke/transient ischemic attack (TIA) and endocarditis. Secondary endpoints were the absence of SVD or patient-prosthesis mismatch (PPM) and valve hemodynamics analysis at follow-up. RESULTS: Between March 2012 to July 2019, 65 symptomatic patients (age 80.4±5.9 years) with degenerated MF valves (numbers 19: 27.7%; 21: 38.5%; 23: 21.5%; 25: 12.3%) underwent CoreValve (n=11) or Evolut R (n=54) implantation (23, 26 and 29 mm sizes). The STS predicted risk of mortality was 6.39%±5.62%. The primary combined endpoint occurred in 32.3% of the cases. A total of 13 patients (20%) died during follow-up, but 4 (7.3%) from cardiovascular causes. Two patients were reported of having a stroke/TIA and 5 readmissions for cardiovascular causes were reported (2 of them within the first 30 days). Twenty-five patients (38.5%) presented PPM during follow-up, being PPM severe in 15 (23.1%). CONCLUSIONS: Self-expanding TAVI for degenerated MF bioprosthesis has favourable long-term outcomes. It is a good option in order to avoid the risks of redo surgery in selected patients.

Prognostic Significance of the Pluripotency Factors NANOG, SOX2, and OCT4 in Head and Neck Squamous Cell Carcinomas.

Cancer stem cells (CSCs) play major roles in tumor initiation, progression, and resistance to cancer therapy. Several CSC markers have been studied in head and neck squamous cell carcinomas (HNSCC), including the pluripotency factors NANOG, SOX2, and OCT4; however, their clinical significance is still unclear. NANOG, SOX2, and OCT4 expression was evaluated by immunochemistry in 348 surgically-treated HNSCC, and correlated with clinicopathological parameters and patient outcomes. mRNA expression was further analyzed in 530 The Cancer Genome Atlas (TCGA) HNSCC. NANOG protein expression was detected in 250 (72%) cases, more frequently in patients with lymph node metastasis (p = 0.003), and was an independent predictor of better survival in multivariate analysis. While OCT4 expression was undetectable, SOX2 expression was observed in 105 (30%) cases, and strongly correlated with NANOG expression. Combined expression of both proteins showed the highest survival rates, and double-negative cases the worst survival. Strikingly, the impact of NANOG and SOX2 on outcome varied depending on tumor site and lymph node infiltration, specifically showing prognostic significance in pharyngeal tumors. Correlation between NANOG and SOX2 at mRNA and protein was specifically observed in node positive (N+) patients, and consistently correlated with better survival rates. According to our findings, NANOG protein expression is frequent in HNSCC, thereby emerging as an independent predictor of better prognosis in pharyngeal tumors. Moreover, this study uncovers a differential impact of NANOG and SOX2 expression on HNSCC prognosis, depending on tumor site and lymph node infiltration, which could facilitate high-risk patient stratification.

Expression of E-cadherin and ß-catenin in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas. / Expresión de E-cadherina y ß-catenina en carcinomas de células escamosas de laringe e hipofaringe.

INTRODUCTION AND OBJECTIVES: Dysfunction of the E-cadherin/catenin complex is directly related to carcinogenesis and metastases development. The aim of this paper is to investigate the prognostic significance of E-cadherin and ß-catenin expression in surgically treated laryngeal and hypopharyngeal squamous cell carcinomas. MATERIAL AND METHODS: Tumour tissue samples were obtained from 133 consecutive patients with squamous cell carcinomas of the head and neck: 68 of the larynx and 65 hypopharyngeal carcinomas, who underwent surgical treatment in our hospital between 2000 and 2005. E-cadherin and ß-catenin expression was analysed by immunohistochemistry, quantifying the percentage of stained cells and the intensity of staining. RESULTS: E-cadherin and ß-catenin expression was evaluable in 59 laryngeal carcinomas and in 58 cases of hypopharyngeal carcinomas. In the laryngeal tumours, a significant association was found between the low expression of membrane ß-catenin with T4 tumours and tumour recurrence. In the hypopharynx there was a significant association between positive expression of nuclear ß-catenin and poor histological differentiation (P=.02). In the multivariate analysis, only the presence of lymph node metastases was an independent predictive factor of decreased disease-specific survival in laryngeal squamous cell carcinomas. CONCLUSIONS: The expression of E-cadherin and ß-catenin does not show prognostic significance in laryngeal and hypopharyngeal squamous cell carcinomas over the TNM classification.

PD-L1 expression correlates with tumor-infiltrating lymphocytes and better prognosis in patients with HPV-negative head and neck squamous cell carcinomas.

INTRODUCTION: The importance of immune tumor microenvironment in the prognosis of patients with head and neck squamous carcinomas (HNSCC) is increasingly recognized. We analyzed the prognostic relevance of PD-L1 and PD-1 expressions in relation to the infiltration by CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs). METHODS: Samples from 372 surgically treated HPV-negative HNSCC patients were evaluated by immunohistochemistry for PD-L1 expression [both tumor proportion score (TPS) and combined proportion score (CPS)], PD-1 expression in immune cells, and density of infiltrating CD8+ and FOXP3+ TILs. PD-L1 expression and CD8+ TIL density were combined to establish the type of tumor microenvironment. RESULTS: 29.5% cases exhibited PD-L1 TPS positivity (≥ 1%), whereas PD-L1 CPS positivity (≥ 1%) was observed in 40% cases. 47.5% cases showed positive PD-1 expression (≥ 1%). PD-L1 and PD-1 positivity correlated with a high density of both CD8+ and FOXP3+ TILs. In univariate analysis, PD-L1 TPS positivity (P = 0.026), PD-L1 CPS positivity (P = 0.004), high density of CD8+ TIL (P = 0.001), and high density of FOXP3+ TIL (P = 0.004) were associated with a better disease-specific survival (DSS). However, in multivariate analysis, only high density of CD8+ TIL was associated with a better DSS (P = 0.002). The type of tumor microenvironment correlated with DSS (P = .008), with the better DSS observed in cases with type I (PD-L1 CPS positivity and high density of CD8+ TIL). CONCLUSIONS: High infiltration by CD8+ TIL is associated with better survival outcomes. Positive PD-L1 expression correlates with a high infiltration by TILs, explaining its association with better prognosis.

Life Expectancy after Surgery for Ascending Aortic Aneurysm.

Introduction: The life expectancy of patients who undergo ascending aortic replacement is unknown. The life expectancy of a population depends on a collection of environmental and socio-economic factors of the territory where they reside. Our aim was to compare the life expectancy of patients undergoing surgery for ascending aortic aneurysm with that of the general population matching by age, sex, and territory. In addition, we aimed to know the late complications, causes of death and risk factors. Methods: All patients who underwent elective replacement of an ascending aortic aneurysm at our institution between 2000 and 2019 were included. The long-term survival of the sample was compared with that of the general population using data of the National Institute of Statistics. Results: For patients who survived the postoperative period, observed cumulative survival at three, five and eight years was 94.07% (95% CI 91.87%-95.70%), 89.96% (95% CI 86.92%-92.33%) and 82.72% (95% CI 77.68%-86.71%). Cumulative survival of the general population at three, five and eight years was 93.22%, 88.30%, and 80.27%. Cancer and cardiac failure were the main causes of death. Conclusions: Long-term survival of patients undergoing elective surgery for ascending aortic aneurysm who survive the postoperative period completely recover their life expectancy.

Life expectancy of patients undergoing surgical aortic valve replacement compared with that of the general population.

OBJECTIVES: Surgical aortic valve replacement (SAVR) changes the natural history of severe aortic stenosis. However, whether the life expectancy of patients with severe aortic stenosis undergoing this surgical procedure is fully restored is unknown. The objective of this study was to assess if the life expectancy of patients aged >75 years is fully restored after undergoing surgery for severe aortic stenosis. METHODS: We compared long-term survival of a group of patients aged >75 years, who underwent SAVR at our institution with the long-term survival of the general population. We matched each patient with 100 simulated individuals (control group) of the same age, sex and geographical region who died as indicated by the National Institute of Statistics. We compared survival curves and calculated hazard ratio (HR) or incidence rate ratio. Statistical significance existed if confidence intervals (CIs) did not overlap or did not include the value 1, as appropriate. RESULTS: Average life expectancy of surgical patients who survived the postoperative period was 90.91 months (95% CI 82.99-97.22), compared to 92.94 months (95% CI 92.39-93.55) in the control group. One-, 5- and 8-year survival rates for SAVR patients who were discharged from the hospital were 94.9% (95% CI 92.74-96.43%), 71.66% (95% CI 67.37-75.5%) and 44.48% (95% CI 38.14-50.61%), respectively, compared to that of the general population: 95.8% (95% CI 95.64-95.95%), 70.64% (95% CI 70.28%-71%) and 47.91% (95% CI 47.52-48.31%), respectively (HR 1.07, 95% CI 0.94-1.22). CONCLUSION: For patients over the age of 75 years who underwent SAVR and survived the postoperative period, life expectancy and survival rates were similar to that of the general population.

Cerebral protection devices for transcatheter aortic valve replacement.

Aortic stenosis is the most prevalent primary valve disease in developed countries. Its prevalence is increasing due to population aging. Transcatheter aortic valve replacement (TAVR) is a sterling therapy for symptomatic patients with severe aortic stenosis and high or intermediate surgery risk. The number of procedures has increased exponentially expanding to younger and lower risk patients. Despite new-generation TAVR devices and enhanced operator skills, cerebrovascular events (CVEs) carry on being one of the most severe complications, increasing morbi-mortality. CVE might be under reported because there are few studies with rigorous neurological clinical assessment. Several imaging studies show most of CVE after TAVR has a probable embolic etiology. The risk of CVE ranges from 2.7% to 5.5% at 30 days. As TAVR expands to younger and lower risk patients, the prevention of stroke plays an increasingly important role. Cerebral protection devices (CPD) were designed to reduce the risk of CVE during TAVR. This review describes the scientific evidence on CVE after TAVR and summarizes the performance and results of the main CPDs.