Classical Prognostic Factors Predict Prognosis Better than Inflammatory Indices in Locally Advanced Cervical Cancer: Results of a Comprehensive Observational Study including Tumor-, Patient-, and Treatment-Related Data (ESTHER Study)

Systemic inflammation indices were found to be correlated with therapeutic outcome in several cancers. This study retrospectively analyzes the predictive role of a broad range of systemic inflammatory markers in patients with locally advanced cervical cancer (LACC) including patient-, tumor-, and treatment-related potential prognostic factors. All patients underwent definitive chemoradiation and pretreatment values of several inflammatory indices (neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio, monocyte/lymphocyte ratio, systemic immune inflammation index (SII), leukocyte/lymphocyte ratio, combination of platelet count and NLR, aspartate aminotransferase/platelet ratio index, aspartate aminotransferase/lymphocyte ratio index, systemic inflammatory response index, and aspartate transaminase/neutrophil ratio index) were calculated. Their correlation with local control (LC), distant metastasis-free (DMFS), disease-free (DFS), and overall survival (OS) was analyzed. One hundred and seventy-three patients were included. At multivariable analysis significant correlations were recorded among clinical outcomes and older age, advanced FIGO stage, lower hemoglobin levels, larger tumor size, and higher body mass index values. The multivariate analysis showed only the significant correlation between higher SII values and lower DMFS rates (p < 0.01). Our analysis showed no significant correlation between indices and DSF or OS. Further studies are needed to clarify the role of inflammation indices as candidates for inclusion in predictive models in this clinical setting

Decoding the Complexity of Systemic Inflammation Predictors in Locally Advanced Cervical Cancer, with Hemoglobin as the Hidden Key (the ESTHER Study)

Simple Summary We explored whether specific factors, like inflammation indicators in the blood, could help predict treatment outcomes for locally advanced cervical cancer (LACC). LACC is generally treated with a combination of chemotherapy and radiation. We wanted to see if these factors could help physicians personalize treatments for better results. Our study involved looking at various aspects, including inflammation indices in the blood and various clinical treatment details, in LACC patients. While some factors, such as age and hemoglobin levels, seemed to predict outcomes, there was no clear connection between inflammation indicators in the blood and results. These findings challenge previous ideas and highlight the importance of considering multiple factors to predict the prognoses of LACC patients.Abstract Locally advanced cervical cancer (LACC) is treated with concurrent chemoradiation (CRT). Predictive models could improve the outcome through treatment personalization. Several factors influence prognosis in LACC, but the role of systemic inflammation indices (IIs) is unclear. This study aims to assess the correlation between IIs and prognosis in a large patient cohort considering several clinical data. We retrospectively analyzed pretreatment IIs (NLR, PLR, MLR, SII, LLR, COP-NLR, APRI, ALRI, SIRI, and ANRI) in 173 LACC patients. Patient, tumor, and treatment characteristics were also considered. Univariate and multivariate Cox's regressions were conducted to assess associations between IIs and clinical factors with local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). Univariate analysis showed significant correlations between age, HB levels, tumor stage, FIGO stage, and CRT dose with survival outcomes. Specific pretreatment IIs (NLR, PLR, APRI, ANRI, and COP-NLR) demonstrated associations only with LC. The multivariate analysis confirmed Hb levels, CRT dose, and age as significant predictors of OS, while no II was correlated with any clinical outcome. The study findings contradict some prior research on IIs in LACC, emphasizing the need for comprehensive assessments of potential confounding variables

Managing Polyploidy in Ex Situ Conservation Genetics: The Case of the Critically Endangered Adriatic Sturgeon (Acipenser naccarii)

While the current expansion of conservation genetics enables to address more efficiently the management of threatened species, alternative methods for genetic relatedness data analysis in polyploid species are necessary. Within this framework, we present a standardized and simple protocol specifically designed for polyploid species that can facilitate management of genetic diversity, as exemplified by the ex situ conservation program for the tetraploid Adriatic sturgeon Acipenser naccarii. A critically endangered endemic species of the Adriatic Sea tributaries, its persistence is strictly linked to the ex situ conservation of a single captive broodstock currently decimated to about 25 individuals, which represents the last remaining population of Adriatic sturgeon of certain wild origin. The genetic variability of three F1 broodstocks available as future breeders was estimated based on mitochondrial and microsatellite information and compared with the variability of the parental generation. Genetic data showed that the F1 stocks have only retained part of the genetic variation present in the original stock due to the few parent pairs used as founders. This prompts for the urgent improvement of the current F1 stocks by incorporating new founders that better represent the genetic diversity available. Following parental allocation based on band sharing values, we set up a user-friendly tool for selection of candidate breeders according to relatedness between all possible parent-pairs that secures the use of non-related individuals. The approach developed here could also be applied to other endangered tetraploid sturgeon species overexploited for caviar production, particularly in regions lacking proper infrastructure and/or expertise

Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6

Background: The most common spinocerebellar ataxias (SCA)—SCA1, SCA2, SCA3, and SCA6—are caused by (CAG)n repeat expansion. While the number of repeats of the coding (CAG)n expansions is correlated with the age at onset, there are no appropriate models that include both affected and preclinical carriers allowing for the prediction of age at onset. Methods: We combined data from two major European cohorts of SCA1, SCA2, SCA3, and SCA6 mutation carriers: 1187 affected individuals from the EUROSCA registry and 123 preclinical individuals from the RISCA cohort. For each SCA genotype, a regression model was fitted using a log-normal distribution for age at onset with the repeat length of the alleles as covariates. From these models, we calculated expected age at onset from birth and conditionally that this age is greater than the current age. Results: For SCA2 and SCA3 genotypes, the expanded allele was a significant predictor of age at onset (−0.105±0.005 and −0.056±0.003) while for SCA1 and SCA6 genotypes both the size of the expanded and normal alleles were significant (expanded: −0.049±0.002 and −0.090±0.009, respectively; normal: +0.013±0.005 and −0.029±0.010, respectively). According to the model, we indicated the median values (90% critical region) and the expectancy (SD) of the predicted age at onset for each SCA genotype according to the CAG repeat size and current age. Conclusions: These estimations can be valuable in clinical and research. However, results need to be confirmed in other independent cohorts and in future longitudinal studies.This study was supported by grants EUROSCA/LSHM-CT-2004-503304 from the European Union, grant from the European Community's Seventh Framework Programme (FP7/2007-2013 n° 2012-305121 NEUROMICS), GeneMove/01 GM 0503 from the German Ministry of Education and Research, within the framework of the ERA-Net for Research Programmes on Rare Diseases, grant 3 PO5B 019 24 from the Polish Ministry of Scientific Research and Information Technology, and grant No 674N—RISCA/2010—2014 from Polish Ministry of Science and Higher Education. The research leading to these results has received funding from the programme ‘Investissements d'avenir’ ANR-10-IAIHU-06. BPvdW is supported by research grants from the Netherlands Brain Foundation, the Royal Dutch Society for Physical Therapy, BBMRI-NL, and the Radboud University Medical Centre. MB is supported by the grant OTKA K 103983. AF was supported by a grant from POR CREME 2007-20013. AB was supported by the grant EUROSCA/LSHM-CT-2004-503304 and by the grant NEUROMICS (7th framework programme) from the European Union. AB, AD and GS received funding from the VERUM Foundation. AD received support from ANR (French Research Agency) and Eranet for the Risca project, PG and AC work at University College London Hospitals/University College London which receives a proportion of its funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme. Paola Giunti receives funding from the EC (HEALTH-F2-2010-242193; FP7 Grant). DeNDRoN, Ataxia UK and NIHR, Department of Health

Novel vaccination strategies based on optimal stimulation of CD4+ T helper cells for the treatment of oral squamous cell carcinoma

Oral Squamous Cell Carcinoma (OSCC) is the most common malignant tumor of the oral cavity. Despite recent advances in the field of oral cancer therapy, including the introduction of immunotherapeutic approaches, the 5-year survival rate remains steadily assessed around 50%. Thus, there is an urgent need for new therapeutic strategies. After the characterization of the immune phenotype of three human OSCC cell lines (CAL-27, SCC-25, and SCC-4) and one mouse OSCC cell line (MOC2) showing their similarities to resected patient tumors, we explored for the first time an experimental preclinical model of therapeutic vaccination with mouse OSCC MOC2 cell line stably expressing MHC class II antigens after CIITA gene transfection (MOC2-CIITA). Mice injected with MOC2-CIITA reject or strongly retard tumor growth; more importantly, vaccinated animals that fully reject MOC2-CIITA tumors display anti-tumor immunological memory protective against challenge with parental MOC2 tumor cells. Further experiments of adoptive cell transfer or in vivo cell depletion show that both CD4+ and CD8+ T lymphocytes prove fundamental in tumor rejection. This unprecedented approach for oral cancer opens the way for possible future translation of novel immunotherapeutic strategies to the human setting for the treatment of this tumor

Genome-wide expression profiling and functional characterization of SCA28 lymphoblastoid cell lines reveal impairment in cell growth and activation of apoptotic pathways

BACKGROUND: SCA28 is an autosomal dominant ataxia associated with AFG3L2 gene mutations. We performed a whole genome expression profiling using lymphoblastoid cell lines (LCLs) from four SCA28 patients and six unrelated healthy controls matched for sex and age. METHODS: Gene expression was evaluated with the Affymetrix GeneChip Human Genome U133A 2.0 Arrays and data were validated by real-time PCR. RESULTS: We found 66 genes whose expression was statistically different in SCA28 LCLs, 35 of which were up-regulated and 31 down-regulated. The differentially expressed genes were clustered in five functional categories: (1) regulation of cell proliferation; (2) regulation of programmed cell death; (3) response to oxidative stress; (4) cell adhesion, and (5) chemical homeostasis. To validate these data, we performed functional experiments that proved an impaired SCA28 LCLs growth compared to controls (p\u2009<\u20090.005), an increased number of cells in the G0/G1 phase (p\u2009<\u20090.001), and an increased mortality because of apoptosis (p\u2009<\u20090.05). We also showed that respiratory chain activity and reactive oxygen species levels was not altered, although lipid peroxidation in SCA28 LCLs was increased in basal conditions (p\u2009<\u20090.05). We did not detect mitochondrial DNA large deletions. An increase of TFAM, a crucial protein for mtDNA maintenance, and of DRP1, a key regulator of mitochondrial dynamic mechanism, suggested an alteration of fission/fusion pathways. CONCLUSIONS: Whole genome expression profiling, performed on SCA28 LCLs, allowed us to identify five altered functional categories that characterize the SCA28 LCLs phenotype, the first reported in human cells to our knowledge. \ua9 2013 Mancini et al.; licensee BioMed Central Ltd

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Timing of Complete Multivessel Revascularization in Acute Coronary Syndrome: 2-Year Results of the BIOVASC Study

Background: In patients with acute coronary syndromes (ACS) and multivessel coronary disease, immediate complete revascularization was noninferior to staged complete revascularization for the primary composite outcome at 1 year. The authors report clinical outcomes at 2 years of follow-up. Methods: Patients with ACS and multivessel coronary disease were randomly assigned to immediate complete revascularization or to staged complete revascularization at 29 sites in Europe. The primary outcome was the composite of all-cause mortality, myocardial infarction, any unplanned ischemia-driven revascularization, and cerebrovascular event. Results: In total, 764 patients were enrolled and randomly allocated to the immediate complete revascularization arm and 761 to the staged complete revascularization arm. Two-year follow-up was complete for 97.6% of patients. At 2 years, the primary outcome had occurred in 12.5% of patients in the immediate complete revascularization group and 12.4% of patients in the staged complete revascularization group (HR: 0.98; 95% CI: 0.73-1.30; P = 0.88). Myocardial infarction occurred more frequently in the staged complete revascularization group (6.2% vs 3.8%; HR: 0.60; 95% CI: 0.37-0.96; P = 0.032). In the immediate complete revascularization and staged complete revascularization groups, the rates of all-cause mortality (3.3% vs 2.0%; HR: 1.67; 95% CI: 0.88-3.16; P = 0.12), any unplanned ischemia-driven revascularization (7.0% vs 7.9%; HR: 0.87; 95% CI: 0.60-1.26; P = 0.57), and cerebrovascular event (2.5% vs 1.7%; HR: 1.39; 95% CI: 0.68-2.83; P = 0.37) were not significantly different. Conclusions: In patients with ACS and multivessel disease, there was no significant difference between immediate complete revascularization and staged complete revascularization with respect to the composite outcome of all-cause mortality, myocardial infarction, any unplanned ischemia-driven revascularization, and cerebrovascular event at 2 years. Immediate complete revascularization was associated with a significant reduction in myocardial infarction, mainly due to fewer early events