Serpine1 mRNA confers mesenchymal characteristics to the cell and promotes CD8+ T cells exclusion from colon adenocarcinomas.

Serine protease inhibitor clade E member 1 (SERPINE1) inhibits extracellular matrix proteolysis and cell detachment. However, SERPINE1 expression also promotes tumor progression and plays a crucial role in metastasis. Here, we solve this apparent paradox and report that Serpine1 mRNA per se, independent of its protein-coding function, confers mesenchymal properties to the cell, promoting migration, invasiveness, and resistance to anoikis and increasing glycolytic activity by sequestering miRNAs. Expression of Serpine1 mRNA upregulates the expression of the TRA2B splicing factor without affecting its mRNA levels. Through transcriptional profiling, we found that Serpine1 mRNA expression downregulates through TRA2B the expression of genes involved in the immune response. Analysis of human colon tumor samples showed an inverse correlation between SERPINE1 mRNA expression and CD8+ T cell infiltration, unveiling the potential value of SERPINE1 mRNA as a promising therapeutic target for colon tumors.

Safety, Efficacy, and Cost-effectiveness of Outpatient Surgery for Uncomplicated Acute Appendicitis: The PENDI-CSI Randomized Clinical Trial.

OBJECTIVE: To evaluate the safety, efficacy, and cost-effectiveness of outpatient appendectomy in patients with uncomplicated acute appendicitis. BACKGROUND: Given that acute appendicitis is the most common cause of acute abdomen, the introduction of outpatient appendectomy protocols could significantly improve the effectiveness and sustainability of health care systems. METHODS: A total of 300 patients were enrolled from October 2018 to June 2021 in the PENDI-CSI randomized clinical trial: 149 were assigned to the outpatient surgery (OPS) group and 151 to the inpatient surgery (IPS) group, followed by 1 month postoperatively. All patients were aged older than 14 years and had uncomplicated acute appendicitis. Exclusion criteria were pregnancy, neoplasms, inflammatory bowel disease, and high anesthetic risk (ASA IV). The OPS group was discharged from the postanesthesia care unit while the IPS group was admitted. RESULTS: In total, 128 patients in the OPS group (85.9%) were discharged without admission. Predictors whether patients in the OPS group had to be admitted were aged over 31 years [relative risk (RR): 2.42 (1.04-5.65)], hypertension [RR: 6.21 (3.22-11.97)], anesthetic risk II-III [RR: 2.63 (1.17-5.94)], previous abdominal surgery [RR: 3.34 (1.55-7.20)], postoperative pain with visual analog scale >6 [RR: 4.28 (2.67-6.86)], and postoperative fear [RR: 2.2 (1.04-4.67)]. There were no differences in terms of complications, readmissions, and reinterventions, and the perceived quality was similar in both groups. The outpatient modality produced savings of €1 034.97 per patient ( P < 0.001). CONCLUSIONS: Outpatient appendectomy is safe and effective for uncomplicated acute appendicitis. Patient-perceived quality is similar to that of IPS, although it successfully reduces hospital costs compared with inpatient appendectomy.

Personalized additive manufacturing of devices for the management of enteroatmospheric fistulas.

Additive manufacturing techniques allow the customized design of medical devices according to the patient's requirements. Enteroatmospheric fistula is a pathology that benefits from this personalization due to its extensive clinical variability since the size and morphology of the wound differ extensively among patients. Standard prosthetics do not achieve proper isolation of the wound, leading to a higher risk of infections. Currently, no effective personalized technique to isolate it has been described. In this work, we present the workflow for the design and manufacture of customized devices adapted to the fistula characteristics as it evolves and changes during the treatment with Negative Pressure Wound Therapy (NPWT). For each case, a device was designed with dimensions and morphology depending on each patient's requirements using white light scanning, CAD design, and additive manufacturing. The design and manufacture of the devices were performed in 230.50 min (184.00-304.75). After the placement of the device, the wound was successfully isolated from the intestinal content for 48-72 h. The therapy was applied for 27.71 ± 13.74 days, and the device was redesigned to adapt to the wound when geometrical evolutionary changes occur during the therapy. It was observed a decrease in weekly cures from 23.63 ± 10.54 to 2.69 ± 0.65 (p = 0.001). The fistulose size was reduced longitudinal and transversally by 3.25 ± 2.56 cm and 6.06 ± 3.14 cm, respectively. The wound depth also decreased by 1.94 ± 1.08 cm. In conclusion, customization through additive manufacturing is feasible and offers promising results in the generation of personalized devices for the treatment of enteroatmospheric fistula.

Development of a liver graft assessment expert machine-learning system: when the artificial intelligence helps liver transplant surgeons.

Background: The complex process of liver graft assessment is one point for improvement in liver transplantation. The main objective of this study is to develop a tool that supports the surgeon who is responsible for liver donation in the decision-making process whether to accept a graft or not using the initial variables available to it. Material and method: Liver graft samples candidate for liver transplantation after donor brain death were studied. All of them were evaluated "in situ" for transplantation, and those discarded after the "in situ" evaluation were considered as no transplantable liver grafts, while those grafts transplanted after "in situ" evaluation were considered as transplantable liver grafts. First, a single-center, retrospective and cohort study identifying the risk factors associated with the no transplantable group was performed. Then, a prediction model decision support system based on machine learning, and using a tree ensemble boosting classifier that is capable of helping to decide whether to accept or decline a donor liver graft, was developed. Results: A total of 350 liver grafts that were evaluated for liver transplantation were studied. Steatosis was the most frequent reason for classifying grafts as no transplantable, and the main risk factors identified in the univariant study were age, dyslipidemia, personal medical history, personal surgical history, bilirubinemia, and the result of previous liver ultrasound (p < 0.05). When studying the developed model, we observe that the best performance reordering in terms of accuracy corresponds to 76.29% with an area under the curve of 0.79. Furthermore, the model provides a classification together with a confidence index of reliability, for most cases in our data, with the probability of success in the prediction being above 0.85. Conclusion: The tool presented in this study obtains a high accuracy in predicting whether a liver graft will be transplanted or deemed non-transplantable based on the initial variables assigned to it. The inherent capacity for improvement in the system causes the rate of correct predictions to increase as new data are entered. Therefore, we believe it is a tool that can help optimize the graft pool for liver transplantation.

Polarimetric imaging for the detection of synthetic models of SARS-CoV-2: A proof of concept.

Objective: To conduct a proof-of-concept study of the detection of two synthetic models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using polarimetric imaging. Approach: Two SARS-CoV-2 models were prepared as engineered lentiviruses pseudotyped with the G protein of the vesicular stomatitis virus, and with the characteristic Spike protein of SARS-CoV-2. Samples were prepared in two biofluids (saline solution and artificial saliva), in four concentrations, and deposited as 5-µL droplets on a supporting plate. The angles of maximal degree of linear polarization (DLP) of light diffusely scattered from dry residues were determined using Mueller polarimetry from87 samples at 405 nm and 514 nm. A polarimetric camera was used for imaging several samples under 380-420 nm illumination at angles similar to those of maximal DLP. Per-pixel image analysis included quantification and combination of polarization feature descriptors in 475 samples. Main results: The angles (from sample surface) of maximal DLP were 3° for 405 nm and 6° for 514 nm. Similar viral particles that differed only in the characteristic spike protein of the SARS-CoV-2, their corresponding negative controls, fluids, and the sample holder were discerned at 10-degree and 15-degree configurations. Significance: Polarimetric imaging in the visible spectrum may help improve fast, non-contact detection and identification of viral particles, and/or other microbes such as tuberculosis, in multiple dry fluid samples simultaneously, particularly when combined with other imaging modalities. Further analysis including realistic concentrations of real SARS-CoV-2 viral particles in relevant human fluids is required. Polarimetric imaging under visible light may contribute to a fast, cost-effective screening of SARS-CoV-2 and other pathogens when combined with other imaging modalities.

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.

TARTESSUS: A Customized Electrospun Drug Delivery System Loaded with Irinotecan for Local and Sustained Chemotherapy Release in Pancreatic Cancer.

Post-surgical chemotherapy in pancreatic cancer has notorious side effects due to the high dose required. Multiple devices have been designed to tackle this aspect and achieve a delayed drug release. This study aimed to explore the controlled and sustained local delivery of a reduced drug dose from an irinotecan-loaded electrospun nanofiber membrane (named TARTESSUS) that can be placed on the patients' tissue after tumor resection surgery. The drug delivery system formulation was made of polycaprolactone (PCL). The mechanical properties and the release kinetics of the drug were adjusted by the electrospinning parameters and by the polymer ratio between 10 w.t.% and 14 w.t.% of PCL in formic acid:acetic acid:chloroform (47.5:47.5:5). The irinotecan release analysis was performed and three different release periods were obtained, depending on the concentration of the polymer in the dissolution. The TARTESSUS device was tested in 2D and 3D cell cultures and it demonstrated a decrease in cell viability in 2D culture between 72 h and day 7 from the start of treatment. In 3D culture, a decrease in viability was seen between 72 h, day 7 (p < 0.001), day 10 (p < 0.001), 14 (p < 0.001), and day 17 (p = 0.003) as well as a decrease in proliferation between 72 h and day 10 (p = 0.030) and a reduction in spheroid size during days 10 (p = 0.001), 14 (p < 0.001), and 17 (p < 0.001). In conclusion, TARTESSUS showed a successful encapsulation of a chemotherapeutic drug and a sustained and delayed release with an adjustable releasing period to optimize the therapeutic effect in pancreatic cancer treatment.

Laparoscopic vs. Open Approach in Emergent Inguinal Hernia: Our Experience and Review of Literature.

There is currently no consensus or homogeneous recommendation about the role of the laparoscopic approach in emergent inguinal hernia surgery. The aim of this manuscript is showing our experience and results of laparoscopic approach for emergent groin hernia repair comparing with open approach. A retrospective review of a prospectively maintained database between January 2011 and December 2021 of acute incarcerated groin hernia that were operated at Virgen del Rocio University Hospital. In this period, they were identified 463 patients with groin hernia that required an emergency repair. 454 patients underwent open surgery (group 1) and 36 patients underwent laparoscopic approach (TAPP procedure) (group 2). Median length stay was 1 day in lap group and 2 days in open approach. Reintervention was necessary in 20 cases (4.40%) from group 1 and one (2.27%) from group 2. In laparoscopic approach, no mortality was described but in open approach, 10 patients (2.20%) died. Globally, 58 cases (12.77%) from group 1 and six patients (16.66%) from group 2 presented any complication. Wound infection was higher in group of open repairs (5.94% vs. 2.77%). Non-surgical complications were higher in open approach (19 vs. 0). There is no statistical significance in any of these items. Laparoscopic approach is a safe, feasible and effective therapeutic option for the treatment of incarcerated groin hernia that require emergency surgery, but prospective and randomized comparative studies are needed to establish the best approach.

COVID-19 contagion forecasting framework based on curve decomposition and evolutionary artificial neural networks: A case study in Andalusia, Spain.

Many types of research have been carried out with the aim of combating the COVID-19 pandemic since the first outbreak was detected in Wuhan, China. Anticipating the evolution of an outbreak helps to devise suitable economic, social and health care strategies to mitigate the effects of the virus. For this reason, predicting the SARS-CoV-2 transmission rate has become one of the most important and challenging problems of the past months. In this paper, we apply a two-stage mid and long-term forecasting framework to the epidemic situation in eight districts of Andalusia, Spain. First, an analytical procedure is performed iteratively to fit polynomial curves to the cumulative curve of contagions. Then, the extracted information is used for estimating the parameters and structure of an evolutionary artificial neural network with hybrid architectures (i.e., with different basis functions for the hidden nodes) while considering single and simultaneous time horizon estimations. The results obtained demonstrate that including polynomial information extracted during the training stage significantly improves the mid- and long-term estimations in seven of the eight considered districts. The increase in average accuracy (for the joint mid- and long-term horizon forecasts) is 37.61% and 35.53% when considering the single and simultaneous forecast approaches, respectively.

Prevertebral cervical approach to posterior mediastinum parathyroid adenomas.

BACKGROUND: About 4 years ago, we described the pure endoscopic cervical approach to posterior mediastinum parathyroid adenomas, which we called the "prevertebral cervical approach". At that time, we had operated on three patients and did not have enough quality videos to demonstrate this approach. After broadening our experience, we present our results and show this technique through a video. METHODS: From June 2015 to January 2021, information on patients undergoing the prevertebral cervical approach was obtained from a specific prospective database, including clinical presentation, biochemistry, preoperative imaging, surgical approach and patient outcomes. The step by step technique is described for both right- and left-sided adenomas, by means of a short video clip. RESULTS: Ten patients were operated on using this technique. Seven adenomas were right-sided and three were left-sided. The mean surgical time was 33 ± 7 min. There were neither intraoperative nor major postoperative complications. Seven patients presented with a slight subcutaneous emphysema, which did not cause complaints. All patients were discharged the day after surgery, except for one patient with a previous open neck removal of four glands due to secondary hyperparathyroidism, which required calcium replacement. Calcium and parathyroid hormone levels were normalised in the other nine patients after surgery. One patient experienced a transient recurrent laryngeal nerve injury which was spontaneously resolved within 1 month. No permanent recurrent laryngeal nerve injury was found. The postoperative cosmetic outcomes were excellent. CONCLUSION: In our experience, the pure cervical endoscopic approach has shown a high feasibility and short operation time, with excellent postoperative results regarding patient comfort, length of stay and disease cure. This approach also offers a very reasonable procedure cost, and may result in a less aggressive surgical option when compared with thoracic approaches.

Optical imaging spectroscopy for rapid, primary screening of SARS-CoV-2: a proof of concept.

Effective testing is essential to control the coronavirus disease 2019 (COVID-19) transmission. Here we report a-proof-of-concept study on hyperspectral image analysis in the visible and near-infrared range for primary screening at the point-of-care of SARS-CoV-2. We apply spectral feature descriptors, partial least square-discriminant analysis, and artificial intelligence to extract information from optical diffuse reflectance measurements from 5 µL fluid samples at pixel, droplet, and patient levels. We discern preparations of engineered lentiviral particles pseudotyped with the spike protein of the SARS-CoV-2 from those with the G protein of the vesicular stomatitis virus in saline solution and artificial saliva. We report a quantitative analysis of 72 samples of nasopharyngeal exudate in a range of SARS-CoV-2 viral loads, and a descriptive study of another 32 fresh human saliva samples. Sensitivity for classification of exudates was 100% with peak specificity of 87.5% for discernment from PCR-negative but symptomatic cases. Proposed technology is reagent-free, fast, and scalable, and could substantially reduce the number of molecular tests currently required for COVID-19 mass screening strategies even in resource-limited settings.

Long-term influence of frailty in elderly patients after surgical emergencies.

PURPOSE: Frailty is known to increase vulnerability to stressful factors, and motivate a higher morbidity and mortality in several health conditions. However, long-term impact of frailty after surgical procedures remains unclear. The purpose of this study was to evaluate the relationship between frailty and long-term clinical outcomes after emergency surgery. METHODS: Prospective cohort study in patients older than 70 years undergoing emergency procedures. A total of 82 patients (mean age 78.5 years, 53.3% women) were consecutively enrolled. Data on demographics, surgical procedures, complications after 30 postoperative days, and frailty according to the clinical frailty scale, Triage Risk Screening Tool (TRST), and FRAIL scale were recorded. Readmission, mortality, and transition to frailty rates were analyzed at 6 and 18 months postoperatively. RESULTS: The prevalence of frailty ranged between 14.6 and 29.6% depending on the scale used. The overall mortality rate at 18 months was 19.5% (16 patients), and the survival curves demonstrated a significant difference in mortality between frail and non-frail patients assessed using the FRAIL scale and TRST (p = 0.049 and p = 0.033, respectively), with a hazard ratio of 2.28 (95% confidence interval 1.24-6.44). Logistic regression analysis showed that diabetes (p = 0.013) was an independent risk factor for transition to frailty, and antidepressant drug use was close to statistical significance (p = 0.08). CONCLUSION: Frailty is a predictive marker of long-term mortality in patients undergoing emergency procedures. Diabetes and depression may represent independent risk factors for transition to frailty over time.

Fluid administration in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: neither too much nor too little.

INTRODUCTION: Intraoperative fluid therapy in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy plays an important role in postoperative morbidity. Studies have found an association between overload fluid therapy and increased postoperative complications, advising restrictive intraoperative fluid therapy. Our objective in this study was to compare the morbidity associated with restrictive versus non-restrictive intraoperative fluid therapy. METHODS: Retrospective analysis of a database collected prospectively in the Anesthesiology Service of Virgen del Roc.ío Hospital, from December 2016 to April 2019. One hundred and six patients who underwent complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were divided into two cohorts according to Fluid Therapy received 1. Restrictive.ß..±.ß9.ßmL.kg-1.h-1 (34 patients), 2. Non-restrictive .ß.ß....ß9.ßmL.kg-1.h-1 (72 patients). Percentage of major complications (Clavien-Dindo grade III...IV) and length hospital stay were the main outcomes variables. RESULTS: Of the 106 enrolled patients, 68.9% were women; 46.2% had ovarian cancer, 35.84% colorectal cancer, and 7.5% peritoneal cancer. The average fluid administration rate was 11.ß...ß3.58.ßmL.kg-1.h-1. The restrictive group suffered a significantly higher percentage of Clavien-Dindo grade III...IV complications (35.29%) compared with the non-restrictive group (15.27%) (p.ß=.ß0.02). The relative risk associated with restrictive therapy was 1.968 (95% confidence interval: 1.158...3.346). We also found a significant difference for hospital length of stay, 20.91 days in the restrictive group vs 16.19 days in the non-restrictive group (p.ß=.ß0.038). CONCLUSIONS: Intraoperative fluid therapy restriction below 9.ßmL.kg-1.h-1 in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy was associated with a higher percentage of major postoperative complications.

Circulating Tumor Cells Enumeration from the Portal Vein for Risk Stratification in Early Pancreatic Cancer Patients.

BACKGROUND: Effective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of single circulating tumor cell (CTC) and CTC clusters from the central venous catheter (CVC) and portal blood (PV). METHODS: In total, 7 mL of PV and CVC blood from 35 patients with early pancreatic cancer were analyzed. CTC were isolated using a positive immunomagnetic selection. The detection and identification of CTC were performed by immunocytochemistry (ICC) and were analyzed by Epi-fluorescence and confocal microscopy. RESULTS: CTC and the clusters were detected both in PV and CVC. In both samples, the CTC number per cluster was higher in patients with grade three or poorly differentiated tumors (G3) than in patients with well (G1) or moderately (G2) differentiated. Patients with fewer than 185 CTC in PV exhibited a longer OS than patients with more than 185 CTC (24.5 vs. 10.0 months; p = 0.018). Similarly, patients with fewer than 15 clusters in PV showed a longer OS than patients with more than 15 clusters (19 vs. 10 months; p = 0.004). These significant correlations were not observed in CVC analyses. CONCLUSIONS: CTC presence in PV could be an important prognostic factor to predict poor prognosis in early pancreatic cancer. In addition, the number of clustered-CTC correlate to a tumor negative differentiation degree and, therefore, could be used as a diagnostic biomarker for pancreatic cancer.

Hyperspectral image processing for the identification and quantification of lentiviral particles in fluid samples.

Optical spectroscopic techniques have been commonly used to detect the presence of biofilm-forming pathogens (bacteria and fungi) in the agro-food industry. Recently, near-infrared (NIR) spectroscopy revealed that it is also possible to detect the presence of viruses in animal and vegetal tissues. Here we report a platform based on visible and NIR (VNIR) hyperspectral imaging for non-contact, reagent free detection and quantification of laboratory-engineered viral particles in fluid samples (liquid droplets and dry residue) using both partial least square-discriminant analysis and artificial feed-forward neural networks. The detection was successfully achieved in preparations of phosphate buffered solution and artificial saliva, with an equivalent pixel volume of 4 nL and lowest concentration of 800 TU·[Formula: see text]L-1. This method constitutes an innovative approach that could be potentially used at point of care for rapid mass screening of viral infectious diseases and monitoring of the SARS-CoV-2 pandemic.

Is the use of endoloops safe and efficient for the closure of the appendicular stump in complicated and uncomplicated acute appendicitis?

INTRODUCTION: There is still controversy regarding the ideal technique to close the appendicular stump in laparoscopic appendectomy (LA). The objective of this study was to determine the safety and efficiency of the use of an endoloop (EL) and endostapler (ES) in complicated and uncomplicated acute appendicitis. METHODS: Retrospective cohort study of patients undergoing LA from February 2013 to December 2019. Acute uncomplicated and complicated appendicitis were analysed separately, establishing two groups according to the stump closure technique: EL or ES. Seven hundred-nine patients were included (535 uncomplicated and 174 complicated). In uncomplicated appendicitis, an EL was used in 447 of the patients (83.55%) and an ES was used in 88 patients (16.45%). In complicated appendicitis, an EL was used in 85 patients (48.85%) and an ES was used in 89 patients (51.15%). An analysis of effectiveness and a cost analysis of each technique were performed. RESULTS: In uncomplicated appendicitis, we found no differences with respect to global complications, although there were significant differences in the total mean hospital stay (EL group 1.55 (SD 1.48) days; ES group 2.21 (SD 1.69) days; p = 0.046). This meant a savings of 514.12€ per patient using the EL p < 0.001). In complicated appendicitis, the reoperations classified as Clavien-Dindo IIIB in the EL group (6.4%) were greater than in the ES group (0%) (p = 0.012), although the rate of postoperative abscesses (p = 0.788) and the mean volume of abscesses (p = 0.891) were similar. CONCLUSION: The systematic use of an EL could reduce costs in uncomplicated appendicitis, while in complicated cases, both options are valid. Prospective studies with a greater number of patients are needed to observe differences in postoperative complications.

Análisis de los resultados en seguridad de pacientes y profesionales durante la pandemia COVID-19 en el contexto de la cirugía urgente / Analysis of the safety of patients and professionals during the COVID-19 pandemic in the context of emergency surgery

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