Baseline extracellular vesicle TGF-ß is a predictive biomarker for response to immune checkpoint inhibitors and survival in non-small cell lung cancer.

BACKGROUND: Immune-checkpoint inhibitors (ICIs) are an effective therapeutic strategy, improving the survival of patients with lung cancer compared with conventional treatments. However, novel predictive biomarkers are needed to stratify which patients derive clinical benefit because the currently used and highly heterogenic histological PD-L1 has shown low accuracy. Liquid biopsy is the analysis of biomarkers in body fluids and represents a minimally invasive tool that can be used to monitor tumor evolution and treatment effects, potentially reducing biases associated with tumor heterogeneity associated with tissue biopsies. In this context, cytokines, such as transforming growth factor-ß (TGF-ß), can be found free in circulation in the blood and packaged into extracellular vesicles (EVs), which have a specific delivery tropism and can affect in tumor/immune system interaction. TGF-ß is an immunosuppressive cytokine that plays a crucial role in tumor immune escape, treatment resistance, and metastasis. Thus, we aimed to evaluate the predictive value of circulating and EV TGF-ß in patients with non-small-cell lung cancer receiving ICIs. METHODS: Plasma samples were collected in 33 patients with advanced non-small-cell lung cancer before and during treatment with ICIs. EV were isolated from plasma by serial ultracentrifugation methods and circulating and EV TGF-ß expression levels were evaluated by enzyme-linked immunosorbent assay. RESULTS: Baseline high expression of TGF-ß in EVs was associated with nonresponse to ICIs as well as shorter progression-free survival and overall survival, outperforming circulating TGF-ß levels and tissue PD-L1 as a predictive biomarker. CONCLUSION: If validated, EV TGF-ß could be used to improve patient stratification, increasing the effectiveness of treatment with ICIs and potentially informing combinatory treatments with TGF-ß blockade. PLAIN LANGUAGE SUMMARY: Treatment with immune-checkpoint inhibitors (ICIs) has improved the survival of some patients with lung cancer. However, the majority of patients do not benefit from this treatment, making it essential to develop more reliable biomarkers to identify patients most likely to benefit. In this pilot study, the expression of transforming growth factor-ß (TGF-ß) in blood circulation and in extracellular vesicles was analyzed. The levels of extracellular vesicle TGF-ß before treatment were able to determine which patients would benefit from treatment with ICIs and have a longer survival with higher accuracy than circulating TGF-ß and tissue PD-L1, which is the currently used biomarker in clinical practice.

A Case-Control Study of Cognitive Function in Patients with End-Stage Renal Disease Before and After Hemodialysis in Southern Spain.

BACKGROUND Cognitive problems are frequent in patients with end-stage renal disease (ESRD) treated with hemodialysis. However, previous studies used only a single cognitive screening test or a small number of cognitive indices, which is inadequate for an exhaustive evaluation of cognitive deficits. This case-control study aimed to evaluate cognitive function in patients with ESRD before and after hemodialysis at centers in southern Spain, and included analysis of associations between cognitive function and duration of hemodialysis, biochemistry, body composition, and treatment variables. MATERIAL AND METHODS Cognitive performance was evaluated in 42 healthy participants (HPs) and in 43 ESRD patients, before and after hemodialysis. The tests measured verbal and visual memory, sustained/selective attention, and processing speed. The diagnostic criterion for ESRD was a glomerular filtration rate.

Quantification and Characterization of CTCs and Clusters in Pancreatic Cancer by Means of the Hough Transform Algorithm.

Circulating Tumor Cells (CTCs) are considered a prognostic marker in pancreatic cancer. In this study we present a new approach for counting CTCs and CTC clusters in patients with pancreatic cancer using the IsofluxTM System with the Hough transform algorithm (Hough-IsofluxTM). The Hough-IsofluxTM approach is based on the counting of an array of pixels with a nucleus and cytokeratin expression excluding the CD45 signal. Total CTCs including free and CTC clusters were evaluated in healthy donor samples mixed with pancreatic cancer cells (PCCs) and in samples from patients with pancreatic ductal adenocarcinoma (PDAC). The IsofluxTM System with manual counting was used in a blinded manner by three technicians who used Manual-IsofluxTM as a reference. The accuracy of the Hough-IsofluxTM approach for detecting PCC based on counted events was 91.00% [84.50, 93.50] with a PCC recovery rate of 80.75 ± 16.41%. A high correlation between the Hough-IsofluxTM and Manual-IsofluxTM was observed for both free CTCs and for clusters in experimental PCC (R2 = 0.993 and R2 = 0.902 respectively). However, the correlation rate was better for free CTCs than for clusters in PDAC patient samples (R2 = 0.974 and R2 = 0.790 respectively). In conclusion, the Hough-IsofluxTM approach showed high accuracy for the detection of circulating pancreatic cancer cells. A better correlation rate was observed between Hough-IsofluxTM approach and with the Manual-IsofluxTM for isolated CTCs than for clusters in PDAC patient samples.

[The Public Health Services at the Metropolitan Region (MR) of Chile have nine acute psychiatric beds per 100,000 over 18 years old inhabitants, insufficient for current need]. / Los Servicios de Salud Públicos de la Región Metropolitana (RM) cuentan con 9 camas psiquiátricas de corta estadía por 100.000 habitantes mayores de 18 años, insuficiente para la necesidad actual.

BACKGROUND: The Public Health Services at the Metropolitan Region (MR) of Chile have nine acute psychiatric beds per 100,000 inhabitants, under international recommendations. AIM: The present study will evaluate the resolution capacity of the main MR Psychiatric Emergency Room (PER), which may help assess the impact of the availability of acute beds in the MR. MATERIAL AND METHODS: A retrospective observational study of electronic patient records for all adult patients attending PER of the Psychiatric Institute "Dr. José Horwitz B." between 2017 and 2020 was analyzed. Crude and adjusted Incidence Rate Ratios were obtained for the indication of hospitalization, admissions, and those rejected due to lack of acute psychiatric beds. RESULTS: 90,464 attendances were evaluated on 41,541 patients, and hospitalization was indicated for 12.5% of them. Admissions were carried out in 59.5%, and 35.9% did not occur due to a lack of acute psychiatric beds. When comparing the adjusted Incidence Rates, only a higher hospitalization rate was observed for users from regions (IRR = 1,267; 95% CI: 1,11-1,44; p-value < 0.001) and during the first half of 2020 (IRR = 1.49; CI95%: 1.35-1.65; p-value < 0.001). CONCLUSIONS: The demand for psychiatric hospitalizations and the low availability of acute psychiatric beds in the MR probably have unsuspected consequences. The solution requires multilevel planning among all the actors involved.

Impact of SARS-CoV-2 Pandemic on Vascular Liver Diseases.

BACKGROUND & AIMS: Vascular liver diseases (VLDs) are represented mainly by portosinusoidal vascular disease (PSVD), noncirrhotic splanchnic vein thrombosis (SVT), and Budd Chiari syndrome (BCS). It is unknown whether patients with VLDs constitute a high-risk population for complications and greater coronavirus disease 2019 (COVID-19)-related mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to assess the prevalence and severity of SARS-CoV-2 infection among patients with VLDs, as well as to assess its impact on hepatic decompensation and survival. METHODS: This is an observational international study analyzing the prevalence and severity of SARS-CoV-2 infection in VLDs between March 2020 and March 2021, compared with the general population (GP). Patients from Spain (5 centers; n = 493) and France (1 center; n = 475) were included. RESULTS: Nine hundred sixty-eight patients were included: 274 with PSVD, 539 with SVT, and 155 with BCS. Among them, 138 (14%) were infected with SARS-CoV-2: 53 with PSVD, 77 with SVT, and 8 with BCS. The prevalence of SARS-CoV-2 infection in patients with PSVD (19%) and SVT (14%) was significantly higher than in the GP (6.5%; P < .05), whereas it was very similar in patients with BCS (5%). In terms of infection severity, patients with VLDs also presented a higher need of hospital admission (14% vs 7.3%; P < .01), intensive care unit admission (2% vs 0.7%; P < .01), and mortality (4% vs 1.5%; P < .05) than the GP. Previous history of ascites (50% vs 8%; P < .05) and post-COVID-19 hepatic decompensation (50% vs 4%; P < .05) were associated with COVID-19 mortality. CONCLUSIONS: Patients with PSVD and SVT could be at higher risk of infection by SARS-CoV-2 and at higher risk of severe COVID-19 disease.

Predictive value of the modified Bhalla score for assessment of pulmonary exacerbations in adults with cystic fibrosis.

OBJECTIVES: The objective of this study was to analyze the predictive value of the modified Bhalla score in high-resolution computed tomography (HRCT) for assessment of pulmonary exacerbations (PEx) in cystic fibrosis (CF) patients. We also describe the relationship between this score and pulmonary function test results. METHODS: We performed a multicenter and prospective study where adult patients with CF were included consecutively over 18 months. All patients underwent HRCT with acquisition in inspiration and expiration. The results were analyzed by an expert radiologist who assigned a modified Bhalla score value. Lung function was also assessed, and clinical variables were collected. Follow-up lasted approximately 1 year, and PEx were registered. RESULTS: The study population comprised 160 subjects selected from 360 CF patients monitored in the participating CF units. The mean age was 28 years, 47.5% were women, and mean forced expiratory volume in 1 s (FEV1) was 67.5%. The mean global modified Bhalla score was 14.5 ± 0.31 points. Pulmonary function test (PFT) results and the modified Bhalla score correlated well, mainly forced vital capacity (FVC) and FEV1. We constructed a statistical model based on the overall Bhalla score to predict the number of PEx. CONCLUSIONS: The overall modified Bhalla score can predict future PEx in CF patients. This useful tool can help to prevent PEx in higher risk patients. KEY POINTS: • Pulmonary function test results and the modified Bhalla score correlated well with FVC and FEV1. • The total modified Bhalla score can predict the number of exacerbations in adult CF patients. • Our findings highlight the need to establish a unified protocol for chest HRCT during the follow-up of adult patients with CF in order to anticipate possible complications and determine their impact on pulmonary function.

Facial Emotion Recognition and Executive Functions in Fibromyalgia.

OBJECTIVE: The ability to accurately identify facial expressions of emotions is crucial in human interaction. Although a previous study suggested deficient emotional face recognition in patients with fibromyalgia, not much is known about the origin of this impairment. Against this background, the present study investigated the role of executive functions. Executive functions refer to cognitive control mechanisms enabling implementation and coordination of basic mental operations. Deficits in this domain are prevalent in fibromyalgia. METHODS: Fifty-two fibromyalgia patients and thirty-two healthy individuals completed the Ekman-60 Faces Test, which requires classification of facial displays of happiness, sadness, anger, fear, surprise, and disgust. They also completed eight tasks assessing the executive function components of shifting, updating, and inhibition. Effects of comorbid depression and anxiety disorders, as well as medication use, were tested in stratified analyses of patient subgroups. RESULTS: Patients made more errors overall than controls in classifying the emotional expressions. Moreover, their recognition accuracy correlated positively with performance on most of the executive function tasks. Emotion recognition did not vary as a function of comorbid psychiatric disorders or medication use. CONCLUSIONS: The study supports impaired facial emotion recognition in fibromyalgia, which may contribute to the interaction problems and poor social functioning characterizing this condition. Facial emotion recognition is regarded as a complex process, which may be particularly reliant on efficient coordination of various basic operations by executive functions. As such, the correlations between cognitive task performance and recognition accuracy suggest that deficits in higher cognitive functions underlie impaired emotional communication in fibromyalgia.

Factors associated with the absence of cocaine craving in treatment-seeking individuals during inpatient cocaine detoxification.

BACKGROUND: Anecdotal evidence suggests a substantial proportion of individuals with cocaine use disorder do not report craving during inpatient detoxification. OBJECTIVE: To examine prevalence and clinical correlates of consistent absence of cocaine craving among inpatients during detoxification. We hypothesized that craving absence would be associated with less severity of cocaine use, depression, and anxiety. Alternative explanations were also explored. METHODS: Craving absence (i.e., non-cravers) was defined as a daily score of zero across two separate craving visual analogue scales in each of the inpatient days. Participants scoring ≥1 on ≥1 day were considered cravers. Severity of cocaine use disorder as well as in-treatment depression and anxiety were assessed. Alternative contributors included presence of cocaine and other substances in urine at admission, in-treatment prescription of psychotropic medications, treatment motivation, executive function, interoception, and social desirability. RESULTS: Eighty-seven participants (78.2% males) met criteria as either non-cravers (n = 29; 33.3%) or cravers (n = 58; 66.7%). Mean length of admission in non-cravers and cravers was, respectively, 10.83 and 13.16 days. Binary logistic regression model showed that non-cravers scored significantly lower than cravers on cocaine use during last month before treatment (OR, 95% CI; 0.902, 0.839-0.970), in-treatment depression (OR, 95% CI; 0.794, 0.659-0.956), and in-treatment prescribing of antipsychotics (OR, 95% CI; 0.109, 0.014-0.823). Model prediction accuracy was 88.9%. CONCLUSIONS: One in three patients undergoing inpatient detoxification experienced absence of craving, linked to less pretreatment cocaine use, better mood, and decreased administration of antipsychotics. Findings may inform pretreatment strategies and improve treatment cost-effectiveness.

Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy.

BACKGROUND: Breast cancer patients under neoadjuvant chemotherapy includes a heterogeneous group of patients who eventually develop distal disease, not detectable by current methods. We propose the use of exosomal miRNAs and circulating tumor cells as diagnostic and predictive biomarkers in these patients. METHODS: Fifty-three breast cancer women initially diagnosed with localized breast cancer under neoadjuvant chemotherapy were prospectively enrolled in this study. However, six of them were later re-evaluated and diagnosed as metastatic breast cancer patients by PET-CT scan. Additionally, eight healthy donors were included. Circulating tumor cells and serum exosomal miRNAs were isolated from blood samples before and at the middle of neoadjuvant therapy and exosomal miRNA levels analyzed by qPCR. RESULTS: Before neoadjuvant therapy, exosomal miRNA-21 and 105 expression levels were higher in metastatic versus non-metastatic patients and healthy donors. Likewise, higher levels of miRNA-222 were observed in basal-like (p = 0.037) and in luminal B versus luminal A (p = 0.0145) tumor subtypes. Exosomal miRNA-222 levels correlated with clinical and pathological variables such as progesterone receptor status (p = 0.017) and Ki67 (p = 0.05). During neoadjuvant treatment, exosomal miRNA-21 expression levels directly correlated with tumor size (p = 0.039) and inversely with Ki67 expression (p = 0.031). Finally, higher levels of exosomal miRNA-21, miRNA-222, and miRNA-155 were significantly associated with the presence of circulating tumor cells. CONCLUSION: Liquid biopsies based on exosomal miRNAs and circulating tumor cells can be a complementary clinical tool for improving breast cancer diagnosis and prognosis.

Bowel Preparation Improves the Accuracy of Transvaginal Ultrasound in the Diagnosis of Rectosigmoid Deep Infiltrating Endometriosis: A Prospective Study.

STUDY OBJECTIVE: To compare the accuracy of transvaginal ultrasound (TVUS) with and without bowel preparation (BP) to detect and describe intestinal nodules of deep infiltrating endometriosis (DIE) with laparoscopic findings. DESIGN: A prospective study of paired data (Canadian Task Force classification II.1). SETTING: A tertiary university hospital from November 2014 to November 2015. PATIENTS: A cohort of women awaiting surgery for endometriosis. INTERVENTIONS: The wall of the rectum and the lower sigmoid colon of the patients were evaluated by 2 TVUSs: the first ultrasound was performed without previous BP, and the second was done after a 3-day low-residue diet and two 250-mL enemas 12 hours and 3 hours before TVUS. MEASUREMENTS AND MAIN RESULTS: The presence or absence of rectosigmoid nodules visualized by TVUS with and without BP was compared with laparoscopic results. Forty patients with a mean age of 36.8 ± 5.0 years were included in the study. By comparing the surgical findings histologically confirmed (the presence or absence of bowel nodules and localization) with those of the 2 TVUSs with and without BP, the sensitivity, specificity, and Cohen kappa were 100%, 96%, and 0.95 and 73%, 88%, and 0.61, respectively. Laparoscopy showed that up to 37.5% of patients (15/40) presented bowel involvement. Variables were clearly more evaluable with than without BP. CONCLUSION: TVUS with BP has a higher accuracy than TVUS without BP. BP allows and facilitates the detection of more rectal nodules of DIE in patients with suspected endometriosis and surgical criteria.

Significance of EGFR Expression in Circulating Tumor Cells.

This chapter focuses on a deep description of the epidermal growth factor receptor (EGFR) expression in circulating tumor cells (CTCs) and its main role in cancer progression, genetic changes related to metastasis , and resistance to treatment. The aberrant behavior of cancer cells is caused by genetic mutations and altered patterns of gene expression. These changes can be responsible for an increase in cell motility but also an ability of CTCs to survival in different microenvironments, as well as developing therapy-resistant clones. Finally, CTCs can acquire the ability to invade distant organs, where metastatic foci can develop.

Unusual presence of the immune evasion gene cluster in livestock-associated MRSA of lineage CC398 causing peridural and psoas abscesses in a poultry farmer.

OBJECTIVE: To characterize a methicillin-resistant Staphylococcus aureus (MRSA) isolate responsible for an aggressive infection (peridural and psoas abscess secondary to haematogenous septic arthritis) in a poultry farmer. METHODS: Molecular characterization was performed, including spa- and multilocus sequence typing of the isolate, assessment of its resistance phenotype and detection of tetracycline resistance and of virulence and immune evasion cluster (IEC) genes were performed. RESULTS: The MRSA isolate was tetracycline- and fluorquinolone-resistant, and was ascribed to CC398, spa-t1451. The isolate harboured tet(M) (distinctive of livestock-associated (LA) MRSA-CC398 clade) and IEC-type B system (characteristic of the methicillin-susceptible human lineage, but typically absent in LA-MRSA-CC398 strains), and lacked toxin-coding genes lukF/lukS-PV, tsst-1, eta and etb. CONCLUSION: IEC re-acquisition by LA-MRSA-CC398-LA strains is an unusual finding, but could constitute an emerging public health problem. It would represent an evolutionary step towards LA-MRSA-CC398's adaptation to human hosts, and might enhance its invasiveness and ability to be transmitted to humans.

Preoperative Assessment of Myometrial Invasion in Endometrial Cancer by 3D Ultrasound and Diffusion-Weighted Magnetic Resonance Imaging: A Comparative Study.

OBJECTIVE: The prognosis of endometrial cancer depends on the correct surgical staging. In early stages, 18% to 30% rate of positive lymph nodes is reported with a myometrial invasion of 50% or more. According to this, patients with International Federation of Gynecology and Obstetrics stage Ib would benefit from staging lymphadenectomy. Therefore, it is important to classify these patients preoperatively to plan the surgery. In the recent years, 3-dimensional (3D) ultrasound and diffusion-weighted magnetic resonance imaging (DW-MRI) have been incorporated in the preoperative management of these patients. The aim of this study was to assess the usefulness of 3D ultrasound and DW-MRI as predictor of myometrial invasion in endometrial cancer. MATERIAL AND METHODS: We retrospectively compared the assessment of myometrial invasion by 3D ultrasound and DW-MRI with final pathologic evaluation on hysterectomy specimens, in 98 patients diagnosed of early-stage endometrial cancer, who underwent surgery at the Hospital Clinic of Barcelona between 2012 and 2015. RESULTS: Evaluation of the depth of myometrial invasion with 3D ultrasound had a sensitivity, specificity, and accuracy of 77%, 83% and 81%, respectively. Evaluation of the depth of myometrial invasion with DW-MRI had a sensitivity, specificity, and accuracy of 69%, 86%, and 81%, respectively. Association of both techniques improved all the values, showing a sensitivity, specificity, and accuracy of 87%, 93%, and 91%, respectively. In both 3D ultrasound and DW-MRI, the presence of leiomyomas was the first detectable cause of false negative (3% and 4%, respectively) and false-positive (3% and 1%, respectively). CONCLUSIONS: We conclude that the implementation of the 2 studies in early-stage endometrial cancer provides low false-negatives and false-positives rates. In cases of patients with leiomyomas, adenomiosis, or intrauterine fluid collection, definitive evaluation of myometrial invasion could be better deferred to intraoperative biopsy in an attempt to reduce false-negatives and false-positives rates.

Ultrasound-Assisted Extraction of Stilbenes from Grape Canes.

An analytical ultrasound-assisted extraction (UAE) method has been optimized and validated for the rapid extraction of stilbenes from grape canes. The influence of sample pre-treatment (oven or freeze-drying) and several extraction variables (solvent, sample-solvent ratio and extraction time between others) on the extraction process were analyzed. The new method allowed the main stilbenes in grape canes to be extracted in just 10 min, with an extraction temperature of 75 °C and 60% ethanol in water as the extraction solvent. Validation of the extraction method was based on analytical properties. The resulting RSDs (n = 5) for interday/intraday precision were less than 10%. Furthermore, the method was successfully applied in the analysis of 20 different grape cane samples. The result showed that grape cane byproducts are potentially sources of bioactive compounds of interest for pharmaceutical and food industries.

Impulsivity in men with prescription of benzodiazepines and methadone in prison. / Impulsividad en varones con prescripción de benzodiacepinas y metadona en prisión.

Benzodiazepines and methadone use has been associated with various neuropsychological impairments. However, to the best of our knowledge, no studies have been carried out on the effect of these substances (either separately or combined) on impulsive personality, including studies in prisoners. The aim of this study is to examine the impulsive personality of a sample of 134 male prisoners using the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (Torrubia, Avila, Molto, & Caseras, 2001) and the UPPS-P Scale (Cyders et al., 2007). Some of these were methadone users, methadone and benzodiazepines users, polydrug users in abstinence and non-dependent drug users. The results showed that drug users have greater sensitivity to reward, positive urgency, negative urgency and sensation seeking than non-dependent users. Methadone users showed more sensitivity to punishment and lack of perseverance with respect to other users. No differences were found between methadone+benzodiazepines users and other groups. The secondary aim is to examine which impulsive personality dimensions are related to the two motivational systems proposed by Gray (BIS-BAS) using exploratory factor analysis. Results showed two different components. One component was defined by the subscales sensitivity to reinforcement, positive urgency, negative urgency and sensation seeking. The second component was defined by the subscales sensitivity to punishment, lack of perseverance and lack of premeditation.

El consumo de benzodiacepinas y metadona se ha asociado a diversas alteraciones neuropsicológicas. Sin embargo, no conocemos estudios sobre el efecto de estas sustancias tanto de forma separada como de forma combinada en rasgos de personalidad impulsiva, y en menor medida  en población penitenciaria.  El objetivo principal de este estudio es examinar la impulsividad rasgo, medida con  el Cuestionario de Sensibilidad al Castigo Sensibilidad a la Recompensa (Torrubia, Avila, Moltó y Caseras, 2001), y la escala de Evaluación del Comportamiento Impulsivo UPPS-P (Cyders et al., 2007), en una muestra de 134 varones de un centro penitenciario con consumo de metadona, metadona y benzodiacepinas, abstinentes de consumo, y no dependientes del consumo de sustancias (criterios DSM-IV). Los resultados mostraron que los grupos de consumidores presentan mayor sensibilidad a la recompensa, urgencia positiva, urgencia negativa y búsqueda de sensaciones que los no consumidores; los grupos de consumo de metadona presentan mayor sensibilidad al castigo y falta de perseverancia. El grupo de  no consumidores presenta menor falta de perseverancia que el grupo de metadona y el grupo de metadona+benzodiacepinas. No se han encontrado diferencias específicamente del grupo de metadona+benzodiacepinas con el resto de los grupos. Como objetivo secundario, examinar, mediante análisis factorial exploratorio, qué dimensiones de personalidad impulsiva se relacionan con los dos sistemas motivacionales propuestos por Gray (SIC-SAC). Los resultados mostraron un componente definido por las subescalas sensibilidad al refuerzo, urgencia positiva, urgencia negativa y búsqueda de sensaciones, y un segundo definido por las subescalas sensibilidad al castigo, falta de perseverancia y falta de premeditación.

Is sphere assay useful for the identification of cancer initiating cells of the ovary?

OBJECTIVE: Current evidence suggests that the presence of tumor-initiating cells (TICs) in epithelial ovarian cancer (EOC) has a role in chemoresistance and relapse. Surface markers such as CD44(+)/CD24(-), CD117(+), and CD133(+) expression have been reported as potential markers for TICs related to ovarian cancer and tumorigenic cell lines. In this study, we have investigated if spheroid forms are TIC specific or whether they can also be produced by somatic stem cells from healthy tissue in vitro. In addition, we also investigated the specificity of surface markers to identify TICs from papillary serous EOC patients. METHODS: Cells were obtained from fresh tumors from 10 chemotherapy-naive patients with EOC, and cells from ovarian and tubal epithelium were obtained from 5 healthy menopausal women undergoing surgery for benign pathology and cultured in standard and in selective medium. Cells forming nonadherent spheroids were considered TICs, and the adherent cells were considered as non-TIC-like. Percentages of CD24(+), CD44(+), CD117(+), CD133(+), and vascular endothelial growth factor receptor (VEGF-R)(+) cell surface markers were analyzed by flow cytometry. RESULTS: Four of 10 EOC cell tissues were excluded from the study. Tumor cells cultured in selective medium developed spheroid forms after 1 to 7 weeks in 5 of 6 EOC patients. No spheroid forms were observed in cultures of cells from healthy women. Unlike previously published data, low levels of CD24(+), CD44(+), CD117(+), and VEGF-R(+) expression were observed in spheroid cells, whereas expression of CD133(+) was moderate but higher in adherent cells from papillary serous EOC cells in comparison with adherent cells from controls. CONCLUSIONS: Papillary serous EOC contains TICs that form spheroids with low expression of CD44(+), CD24(+), CD117(+) and VEGF-R(+). Further research is required to find specific surface markers to identify papillary serous TICs.

Intestinal surgery performed by gynecologists.

INTRODUCTION: Our objective was to compare the feasibility and safety of surgical procedures to treat gynecological pathologies with intestinal involvement performed by skilled gynecological surgeons and by a multidisciplinary team of gynecologists plus colorectal surgeons. MATERIAL AND METHODS: We performed a comparative, observational, prospective study at a tertiary referral center. The population included all women undergoing bowel surgery for gynecological pathologies over a 3-year period. Cases were analyzed by the specialty of the main surgeon performing the intestinal procedure. The main outcome measures were surgical procedure characteristics and postoperative outcomes and complications. RESULTS: A total of 65 women were included. Surgery was exclusively performed by a subspecialized gynecologist in 30.8% of the women, and undertaken by a multidisciplinary team (colorectal surgeons and gynecologists) in 69.2%. The main demographic and clinical characteristics were comparable in both groups. Main indications for bowel resection in gynecological surgery were advanced ovarian cancer and deep infiltrating endometriosis. In addition to the standard gynecological surgical procedures, a total of 135 intestinal segments were resected, with sigmoid colon the most frequent intestinal segment resected in both groups (53% in the gynecologist group and in 60% in the multidisciplinary group). No significant differences were observed between the two groups in the distribution and frequency of surgical techniques used, rate of complications, mean hospitalization time or frequency of re-intervention. CONCLUSION: Skilled gynecological surgeons appear to be equally good at handling common intestinal problems as a team of gynecologist and colorectal surgeons.

[Neuropsychological impairments in patients undergoing peritoneal dialysis treatment]. / Alteraciones neuropsicológicas en pacientes en tratamiento con diálisis peritoneal.

BACKGROUND: Patients with chronic kidney disease on hemodialysis (HD) often have cognitive deficits. However, there are few studies that have examined the neuropsychological impairments of patients receiving peritoneal dialysis (PD). METHODS: Executive functions, processing speed and verbal memory were assessed in 27 PD patients, 42 HD patients, and 42 healthy participants (HP). Systolic blood pressure and total time on renal replacement therapy (RRT) were controlled statistically. Associations between performance and clinical factors were analyzed using correlations and multiple regression. RESULTS: The DP group showed better performance compared to the HD group in verbal fluency, working memory, cognitive flexibility, planning and decision making. The DP group showed worse execution than the HP group in verbal inhibition and memory. Executive function scores were positively associated with total months on PD, total months on RRT, total months on HD, albumin, total cholesterol, and phosphorus, and negatively with ferritin. CONCLUSION: Global executive functioning was more optimal in PD patients than in HD patients. The results show the positive effect of PD on executive functions, which must be taken into account when choosing the TRS. The associations observed between biochemical factors and performance show the importance of maintaining an adequate nutritional status in these patients.

Resectable Non-Small Cell Lung Cancer Heterogeneity and Recurrence Assessed by Tissue Next-Generation Sequencing Genotyping and Circulating Tumor Cell EZH2 Characterization.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is the most common type of lung neoplasm. Despite surgical resection, it has a high relapse rate, accounting for 30-55% of all cases. Next-generation sequencing (NGS) based on a customized gene panel and the analysis of circulating tumor cells (CTCs) can help identify heterogeneity, stratify high-risk patients, and guide treatment decisions. In this descriptive study involving a small prospective cohort, we focus on the phenotypic characterization of CTCs, particularly concerning EZH2 expression (a member of the Polycomb Repression Complex 2), as well as on the mutation profiles of the tissue using a customized gene panel and their association with poor outcomes in NSCLC. METHODS: Isolation and characterization of EZH2 on CTCs were evaluated before surgical resection (CTC1) and one month after surgery (CTC2) in resectable NSCLC patients. Targeted NGS was performed using a customized 50-gene panel on tissue samples from a subset of patients. RESULTS: 76 patients with resectable NSCLC were recruited. The top mutated genes in the cohort included TP53, FLT1, MUC5AC, EGFR, and NLRP3. Pair of genes that had mutually exclusive mutations was TP53-RIN3, and pairs of genes with co-occurring mutations were CD163-TLR4, FGF10-FOXP2, ADAMTSL3-FLT1, ADAMTSL3-MUC5AC and MUC5AC-NLRP3. CTCs decreased significantly between the two time points CTC1 and CTC2 (p<0.0001), and CTCs+ patients with high EZH2 expression had an 87% increased risk of death (p=0.018). CONCLUSIONS: Integrating molecular profiling of tumors and CTC characterization can provide valuable insights into tumor heterogeneity and improve patient stratification for resectable NSCLC.

Unveiling the impact of circulating tumor cells: Two decades of discovery and clinical advancements in solid tumors.

Circulating tumor cells (CTCs) enumeration and molecular profiling hold promise in revolutionizing the management of solid tumors. Their understanding has evolved significantly over the past two decades, encompassing pivotal biological discoveries and clinical studies across various malignancies. While for some tumor types, such as breast, prostate, and colorectal cancer, CTCs are ready to enter clinical practice, for others, additional research is required. CTCs serve as versatile biomarkers, offering insights into tumor biology, metastatic progression, and treatment response. This review summarizes the latest advancements in CTC research and highlights future directions of investigation. Special attention is given to concurrent evaluations of CTCs and other circulating biomarkers, particularly circulating tumor DNA. Multi-analyte assessment holds the potential to unlock the full clinical capabilities of liquid biopsy. In conclusion, CTCs represent a transformative biomarker in precision oncology, offering extraordinary opportunities to translate scientific discoveries into tangible improvements in patient care.