How inflammation influences psychiatric disease.

Recent studies highlight the strong correlation between infectious diseases and the development of neuropsychiatric disorders. In this editorial, we comment on the article "Anti-infective therapy durations predict psychological stress and laparoscopic surgery quality in pelvic abscess patients" by Zhang et al, published in the recent issue of the World Journal of Psychiatry 2023; 13 (11): 903-911. Our discussion highlighted the potential consequences of anxiety, depression, and psychosis, which are all linked to bacterial, fungal, and viral infections, which are relevant to the impact of inflammation on the sequelae in mental health as those we are observing after the coronavirus disease 2019 pandemic. We focus specifically on the immune mechanisms triggered by inflammation, the primary contributor to psychiatric complications. Importantly, pathophysiological mechanisms such as organ damage, post-injury inflammation, and infection-induced endocrine alterations, including hypocortisolism or autoantibody formation, significantly contribute to the development of chronic low-grade inflammation, promoting the emergence or development of psychiatric alterations in susceptible individuals. As inflammation can have long-term effects on patients, a multidisciplinary treatment plan can avoid complications and debilitating health issues, and it is crucial to recognize and address the mental health implications.

Role of Angiotensin II in Non-Alcoholic Steatosis Development.

Fatty liver is a multifactorial disease characterized by excessive accumulation of lipids in hepatocytes (steatosis), insulin resistance, oxidative stress, and inflammation. This disease has a major public health impact because it is the first stage of a chronic and degenerative process in the liver that can lead to steatohepatitis, cirrhosis, and liver cancer. Although this disease is mainly diagnosed in patients with obesity, type 2 diabetes mellitus, and dyslipidemia, recent evidence indicates that vasoactive hormones such as angiotensin II (ANGII) not only promote endothelial dysfunction (ED) and hypertension, but also cause fatty liver, increase adipose tissue, and develop a pro-steatotic environment characterized by a low-grade systemic pro-inflammatory and pro-oxidant state, with elevated blood lipid levels. The role of ANGII in lipid accumulation has been little studied, so this review aims to summarize existing reports on the possible mechanism of action of ANGII in inducing lipid accumulation in hepatocytes.

Metabolic Recovery with the Persistence of Proinflammatory Leucocyte Dysfunction After Bariatric Intervention for Obesity.

PURPOSE: A suitable option for severe obesity treatment is a surgical approach. After surgery, metabolic markers and weight frequently return to adequate values; however, concerning systemic inflammatory mediators, the results are inconsistent. Furthermore, it has been suggested that leucocyte function may be affected even after weight normalization. This study aimed to determine if the surgical treatment of obesity influences the production of cytokines by LPS-stimulated as a function of leucocytes. MATERIALS AND METHODS: We performed a cross-sectional study that investigated the production of cytokines in response to lipopolysaccharide (LPS) along a kinetic of simulation by leucocytes recovered from individuals with normal weight (NW, n = 8), persons living with obesity (Ob, n = 7), persons living with obesity and diabetes mellitus (Ob-DM, n = 17), and persons that used to live with obesity who underwent bypass surgery (fOb + bypass, n = 8) and recover normal weigh. RESULTS: IL-6 levels were significantly higher in the Ob and fOb + bypass groups than in NW (p = 0.043). IL-10 secretion without LPS was significantly higher in the NW group than in the other groups explored (p < 0.05). When exposed to LPS, the IL-10 levels increased in all groups except the NW group. As also observed for IL-18 and IL-33, the secretion curve of the fOb + bypass group was more similar to the Ob group, even when they had reached normal weight, as opposed to the NW group. CONCLUSION: Our results show that in patients with fOb + bypass, inflammatory and anti-inflammatory cytokine production dynamics remain disrupted even with improved metabolic control and normal weight recovery.

Potential biomarkers for fatal outcome prognosis in a cohort of hospitalized COVID-19 patients with pre-existing comorbidities.

The difficulty in predicting fatal outcomes in patients with coronavirus disease 2019 (COVID-19) impacts the general morbidity and mortality due to severe acute respiratory syndrome-coronavirus 2 infection, as it wears out the hospital services that care for these patients. Unfortunately, in several of the candidates for prognostic biomarkers proposed, the predictive power is compromised when patients have pre-existing comorbidities. A cohort of 147 patients hospitalized for severe COVID-19 was included in a descriptive, observational, single-center, and prospective study. Patients were recruited during the first COVID-19 pandemic wave (April-November 2020). Data were collected from the clinical history whereas immunophenotyping by multiparameter flow cytometry analysis allowed us to assess the expression of surface markers on peripheral leucocyte. Patients were grouped according to the outcome in survivors or non-survivors. The prognostic value of leucocyte, cytokines or HLA-DR, CD39, and CD73 was calculated. Hypertension and chronic renal failure but not obesity and diabetes were conditions more frequent among the deceased patient group. Mixed hypercytokinemia, including inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines, was more evident in deceased patients. In the deceased patient group, lymphopenia with a higher neutrophil-lymphocyte ratio (NLR) value was present. HLA-DR expression and the percentage of CD39+ cells were higher than non-COVID-19 patients but remained similar despite the outcome. Receiver operating characteristic analysis and cutoff value of NLR (69.6%, 9.4), percentage NLR (pNLR; 71.1%, 13.6), and IL-6 (79.7%, 135.2 pg/mL). The expression of HLA-DR, CD39, and CD73, as many serum cytokines (other than IL-6) and chemokines levels do not show prognostic potential, were compared to NLR and pNLR values.

Chronic Comorbidities in Middle Aged Patients Contribute to Ineffective Emergency Hematopoiesis in Covid-19 Fatal Outcomes.

BACKGROUND AND AIMS: Mexico is among the countries with the highest estimated excess mortality rates due to the COVID-19 pandemic, with more than half of reported deaths occurring in adults younger than 65 years old. Although this behavior is presumably influenced by the young demographics and the high prevalence of metabolic diseases, the underlying mechanisms have not been determined. METHODS: The age-stratified case fatality rate (CFR) was estimated in a prospective cohort with 245 hospitalized COVID-19 cases, followed through time, for the period October 2020-September 2021. Cellular and inflammatory parameters were exhaustively investigated in blood samples by laboratory test, multiparametric flow cytometry and multiplex immunoassays. RESULTS: The CFR was 35.51%, with 55.2% of deaths recorded in middle-aged adults. On admission, hematological cell differentiation, physiological stress and inflammation parameters, showed distinctive profiles of potential prognostic value in patients under 65 at 7 days follow-up. Pre-existing metabolic conditions were identified as risk factors of poor outcomes. Chronic kidney disease (CKD), as single comorbidity or in combination with diabetes, had the highest risk for COVID-19 fatality. Of note, fatal outcomes in middle-aged patients were marked from admission by an inflammatory landscape and emergency myeloid hematopoiesis at the expense of functional lymphoid innate cells for antiviral immunosurveillance, including NK and dendritic cell subsets. CONCLUSIONS: Comorbidities increased the development of imbalanced myeloid phenotype, rendering middle-aged individuals unable to effectively control SARS-CoV-2. A predictive signature of high-risk outcomes at day 7 of disease evolution as a tool for their early stratification in vulnerable populations is proposed.

Starting from scratch: Step-by-step development of diagnostic tests for SARS-CoV-2 detection by RT-LAMP.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide. Public health strategies to reduce viral transmission are based on widespread diagnostic testing to detect and isolate contagious patients. Several reverse transcription (RT)-PCR tests, along with other SARS-CoV-2 diagnostic assays, are available to attempt to cover the global demand. Loop-mediated isothermal amplification (LAMP) based methods have been established as rapid, accurate, point of care diagnostic tests for viral infections; hence, they represent an excellent alternative for SARS-CoV-2 detection. The aim of this study was to develop and describe molecular detection systems for SARS-CoV-2 based on RT-LAMP. Recombinant DNA polymerase from Bacillus stearothermophilus and thermostable engineered reverse transcriptase from Moloney Murine Leukemia Virus were expressed using a prokaryotic system and purified by fast protein liquid chromatography. These enzymes were used to set up fluorometric real time and colorimetric end-point RT-LAMP assays. Several reaction conditions were optimized such as reaction temperature, Tris-HCl concentration, and pH of the diagnostic tests. The key enzymes for RT-LAMP were purified and their enzymatic activity was determined. Standardized reaction conditions for both RT-LAMP assays were 65°C and a Tris-HCl-free buffer at pH 8.8. Colorimetric end-point RT-LAMP assay was successfully used for viral detection from clinical saliva samples with 100% sensitivity and 100% specificity compared to the results obtained by RT-qPCR based diagnostic protocols with Ct values until 30. The developed RT-LAMP diagnostic tests based on purified recombinant enzymes allowed a sensitive and specific detection of the nucleocapsid gene of SARS-CoV-2.

Potential of ATR-FTIR-Chemometrics in Covid-19: Disease Recognition.

The COVID-19 pandemic has caused major disturbances to human health and economy on a global scale. Although vaccination campaigns and important advances in treatments have been developed, an early diagnosis is still crucial. While PCR is the golden standard for diagnosing SARS-CoV-2 infection, rapid and low-cost techniques such as ATR-FTIR followed by multivariate analyses, where dimensions are reduced for obtaining valuable information from highly complex data sets, have been investigated. Most dimensionality reduction techniques attempt to discriminate and create new combinations of attributes prior to the classification stage; thus, the user needs to optimize a wealth of parameters before reaching reliable and valid outcomes. In this work, we developed a method for evaluating SARS-CoV-2 infection and COVID-19 disease severity on infrared spectra of sera, based on a rather simple feature selection technique (correlation-based feature subset selection). Dengue infection was also evaluated for assessing whether selectivity toward a different virus was possible with the same algorithm, although independent models were built for both viruses. High sensitivity (94.55%) and high specificity (98.44%) were obtained for assessing SARS-CoV-2 infection with our model; for severe COVID-19 disease classification, sensitivity is 70.97% and specificity is 94.95%; for mild disease classification, sensitivity is 33.33% and specificity is 94.64%; and for dengue infection assessment, sensitivity is 84.27% and specificity is 94.64%.

Increased TNF-α production in response to IL-6 in patients with systemic inflammation without infection.

Acute systemic inflammation can lead to life-threatening organ dysfunction. In patients with sepsis, systemic inflammation is triggered in response to infection, but in other patients, a systemic inflammatory response syndrome (SIRS) is triggered by non-infectious events. IL-6 is a major mediator of inflammation, including systemic inflammatory responses. In homeostatic conditions, when IL-6 engages its membrane-bound receptor on myeloid cells, it promotes pro-inflammatory cytokine production, phagocytosis, and cell migration. However, under non-physiologic conditions, such as SIRS and sepsis, leucocyte dysfunction could modify the response of these cells to IL-6. So, our aim was to evaluate the response to IL-6 of monocytes from patients diagnosed with SIRS or sepsis. We observed that monocytes from patients with SIRS, but not from patients with sepsis, produced significantly more TNF-α than monocytes from healthy volunteers, after stimulation with IL-6. Monocytes from SIRS patients had a significantly increased baseline phosphorylation of the p65 subunit of NF-κB, with no differences in STAT3 phosphorylation or SOCS3 levels, compared with monocytes from septic patients, and this increased phosphorylation was maintained during the IL-6 activation. We found no significant differences in the expression levels of the membrane-bound IL-6 receptor, or the serum levels of IL-6, soluble IL-6 receptor, or soluble gp130, between patients with SIRS and patients with sepsis. Our results suggest that, during systemic inflammation in the absence of infection, IL-6 promotes TNF-α production by activating NF-κB, and not the canonical STAT3 pathway.

Molecular changes in adipocyte-derived stem cells during their interplay with cervical cancer cells.

PURPOSE: Obesity is as an important risk factor and has been associated with a worse prognosis in at least 13 distinct tumor types. This is partially due to intercellular communication between tumor cells and adipose tissue-derived stem cells (ADSCs), which are increased in obese individuals. As yet, however, little is known about the molecular changes occurring in ADSCs in these conditions. Cervical cancer has a high incidence and mortality rate in women from developing countries, particularly in those with a high body mass index (BMI). METHODS: We analyzed the expression profile of ADSCs co-cultured with cervical cancer cells through massive RNA sequencing followed by evaluation of various functional alterations resulting from the modified transcriptome. RESULTS: A total of 761 coding and non-coding dysregulated RNAs were identified in ADSCs after co-culture with HeLa cells (validation in CaSki and SiHA cells). Subsequent network analysis showed that these changes were correlated with migration, stemness, DNA repair and cytokine production. Functional experiments revealed a larger ALDHhigh subpopulation and a higher migrative capacity of ADSCs after co-culture with HeLa cells. Interestingly, CXCL3 and its intragenic long-noncoding RNA, lnc-CXCL3, were found to be co-regulated during co-culture. A loss-of-function assay revealed that lnc-CXCL3 acts as a key regulator of CXCL3 expression. CONCLUSIONS: Our results suggest that intercellular communication between ADSCs and cervical cancer cells modifies the RNA expression profile in the former, including that of lncRNAs, which in turn can regulate the expression of diverse chemokines that favor malignancy-associated capacities such as migration.

Cellular Markers of Immunosuppression in Sepsis.

Sepsis is a pathological condition frequently caused by invasion of a pathogen and the subsequent unregulated response that threatens the patient's life through diverse organ failure. The incidence of sepsis is increasing, and there is no specific therapy. Despite technological contributions to treat sepsis or increased knowledge of its molecular pathophysiology, mortality remains high, and sepsis is a global health problem. Knowledge of the role of the cells involved in the host response through the synthesis of inflammatory mediators and their different effects on cells, tissues or systems is key to the development of medical treatments that regulate systems involved in such responses to pathogens. This review addresses new insights into the role of cells, their mediators, and the interaction between them that lead to the development of a state of immunosuppression.

Accurate diagnosis of sepsis using a neural network: Pilot study using routine clinical variables.

BACKGROUND AND OBJECTIVES: Sepsis is a severe infection that increases mortality risk and is one if the main causes of death in intensive care units. Accurate detection is key to successful interventions, but diagnosis of sepsis is complicated because the initial signs and symptoms are not specific. Biomarkers that have been proposed have low specificity and sensitivity, are expensive, and not available in every hospital. In this study, we propose the use of artificial intelligence in the form of a neural network to diagnose sepsis using only common laboratory tests and vital signs that are routine and widely available. METHODS: A retrospective, cross sectional cohort of 113 patients from an intensive care unit, each with 48 routinely evaluated vital signs and biochemical parameters was used to train, validate and test a neural network with 48 inputs, 10 neurons in a single hidden layer and one output. The sensitivity and specificity of the neural network as a point sampled diagnostic test was calculated. RESULTS: All but one case were correctly diagnosed by the neural network, with 91% sensitivity and 100% specificity in the validation data set, and 100% sensitivity and specificity in the test data set. CONCLUSIONS: The designed neural network system can identify patients with sepsis, with minimal resources using standard laboratory tests widely available in most health care facilities. This should reduce the burden on the medical staff of a difficult diagnosis and should improve outcomes for patients with sepsis.

Surgical initial experience in patients with COVID-19.

ANTECEDENTES: La pandemia de COVID-19 ha ocasionado que los servicios de cirugía y de salud en todo el mundo tengan que reorganizarse y planear para poder brindar la mejor atención a los pacientes, con la protección necesaria para el personal de salud. Algunos de estos pacientes requerirán tratamiento quirúrgico, ya sea electivo o de urgencia. OBJETIVO: Reportar la experiencia inicial en el manejo de pacientes con COVID-19 que ameritaron tratamiento quirúrgico por los servicios de cirugía de un hospital de referencia. MÉTODO: Revisión de los protocolos quirúrgicos, equipo de protección personal usado por los equipos quirúrgicos y resultados del tratamiento de 42 pacientes sometidos a cirugía en un periodo de 4 meses. RESULTADOS: Fueron intervenidos 42 pacientes con COVID-19. Treinta pacientes tenían diagnóstico de infección por SARS-CoV-2 y en 12 casos el diagnóstico fue clínico y por imagen. Las cirugías más frecuentes fueron traqueostomía en 16 pacientes (38%) y laparotomías exploradoras en 8 pacientes (19%). La mediana de estancia posoperatoria fue de 17 días y la mortalidad durante los primeros 30 días fue del 26%. CONCLUSIONES: Es necesaria la reorganización de los departamentos quirúrgicos y del hospital para poder atender adecuadamente a los pacientes con COVID-19 y proteger al personal de salud. Los pacientes pueden presentan patologías que requieran tratamiento quirúrgico. Relacionado con la infección y la mayor frecuencia de comorbilidad, la mortalidad de estos pacientes es elevada. INTRODUCTION: the COVID-19 pandemic has caused a reorganization of hospital and general surgery departments worldwide to assure the best medical and surgical treatment of patients with this disease and protection of the health-related personnel. Some of them will require surgical treatment either elective or urgent. OBJECTIVE: report the initial experience in the management of patients with COVID-19 in a third level hospital. MATERIAL AND METHODS: a review of the surgical protocols, personal protection equipment used by the surgical teams, and results of the treatment of forty-two patients submitted to surgery. RESULTS: During four months (April-July 2020) forty-two patients with suspicion or confirmed infection of SARS-CoV2 underwent surgical treatment. The most common surgery was tracheostomy in 16 patients (38%) followed by exploratory laparotomy in 8 patients (19%). The median postoperative stay was 17 days and the thirty-day postoperative mortality rate was 26%. CONCLUSIONS: reorganization of the general surgery department and the hospital, favors adequate management and treatment of patients with COVID-19 and protection to the health-related personnel. Due to the usual co-existence of comorbidities and pulmonary complications the postoperative mortality of these patients is high.

Diagnostic accuracy of symptoms as a diagnostic tool for SARS-CoV 2 infection: a cross-sectional study in a cohort of 2,173 patients.

BACKGROUND: The SARS-CoV-2 pandemic continues to be a priority health problem; According to the World Health Organization data from October 13, 2020, 37,704,153 confirmed COVID-19 cases have been reported, including 1,079,029 deaths, since the outbreak. The identification of potential symptoms has been reported to be a useful tool for clinical decision-making in emergency departments to avoid overload and improve the quality of care. The aim of this study was to evaluate the performances of symptoms as a diagnostic tool for SARS -CoV-2 infection. METHODS: An observational, cross-sectional, prospective and analytical study was carried out, during the period of time from April 14 to July 21, 2020. Data (demographic variables, medical history, respiratory and non-respiratory symptoms) were collected by emergency physicians. The diagnosis of COVID-19 was made using SARS-CoV-2 RT-PCR. The diagnostic accuracy of these characteristics for COVID-19 was evaluated by calculating the positive and negative likelihood ratios. A Mantel-Haenszel and multivariate logistic regression analysis was performed to assess the association of symptoms with COVID-19. RESULTS: A prevalence of 53.72% of SARS-CoV-2 infection was observed. The symptom with the highest sensitivity was cough 71%, and a specificity of 52.68%. The symptomatological scale, constructed from 6 symptoms, obtained a sensitivity of 83.45% and a specificity of 32.86%, taking ≥2 symptoms as a cut-off point. The symptoms with the greatest association with SARS-CoV-2 were: anosmia odds ratio (OR) 3.2 (95% CI; 2.52-4.17), fever OR 2.98 (95% CI; 2.47-3.58), dyspnea OR 2.9 (95% CI; 2.39-3.51]) and cough OR 2.73 (95% CI: 2.27-3.28). CONCLUSION: The combination of ≥2 symptoms / signs (fever, cough, anosmia, dyspnea and oxygen saturation < 93%, and headache) results in a highly sensitivity model for a quick and accurate diagnosis of COVID-19, and should be used in the absence of ancillary diagnostic studies. Symptomatology, alone and in combination, may be an appropriate strategy to use in the emergency department to guide the behaviors to respond to the disease. TRIAL REGISTRATION: Institutional registration R-2020-3601-145, Federal Commission for the Protection against Sanitary Risks 17 CI-09-015-034, National Bioethics Commission: 09 CEI-023-2017082 .

A Shift Towards an Immature Myeloid Profile in Peripheral Blood of Critically Ill COVID-19 Patients.

BACKGROUND: SARS-CoV-2, the etiological agent causing COVID-19, has infected more than 27 million people with over 894000 deaths worldwide since its emergence in December 2019. Factors for severe diseases, such as diabetes, hypertension, and obesity have been identified however, the precise pathogenesis is poorly understood. To understand its pathophysiology and to develop effective therapeutic strategies, it is essential to define the prevailing immune cellular subsets. METHODS: We performed whole circulating immune cells scRNAseq from five critically ill COVID-19 patients, trajectory and gene ontology analysis. RESULTS: Immature myeloid populations, such as promyelocytes-myelocytes, metamyelocytes, band neutrophils, monocytoid precursors, and activated monocytes predominated. The trajectory with pseudotime analysis supported the finding of immature cell states. While the gene ontology showed myeloid cell activation in immune response, DNA and RNA processing, defense response to the virus, and response to type 1 interferon. Lymphoid lineage was scarce. Expression of genes such as C/EBPß, IRF1and FOSL2 potentially suggests the induction of trained immunity. CONCLUSIONS: Our results uncover transcriptomic profiles related to immature myeloid lineages and suggest the potential induction of trained immunity.

Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients.

BACKGROUND: COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood. METHODS: We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells. RESULTS: Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2). CONCLUSIONS: The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy. Key messages Critically ill COVID-19 patients show emergency myelopoiesis. HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets. HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events.

Evaluation of predictive value of olfactory dysfunction, as a screening tool for COVID-19.

OBJECTIVES: At the end of 2019, SARS-CoV-2 was identified, the one responsible for the COVID-19 disease. Between a 5.1% and a 98% of COVID-19 patients present some form of alteration in their sense of smell. The objective of this study is to determine the diagnostic yield of the smell dysfunction as screening tool for COVID-19. METHODS: Cross-sectional, observational, and pro-elective study was performed in a tertiary care hospital from May 25th to June 30th, 2020. One hundred and thirty-nine patients were included in the study. Demographic characteristics were collected from anamnesis. A Self-Perception Questionnaire and psychophysical olfactory test (POT) were applied to all participants. The presence of SARS-CoV2, was detected by RT-PCR methods. RESULTS: 51.7% of patients were SARS-CoV-2 positive. A sensitivity of 50% was obtained for the self-perception questionnaire as a screening tool for SARS-CoV2, with a specificity of 80.59%. The positive predictive value (PPV) was of 73.46%, the negative predictive value (NPV) was of 60%. The POT as a screening tool had a PPV of 82.35%, a NPV of 52.45%, a LR+ of 4.34, a LR- 0.84. The combination of anosmia (according to the POT) plus cough and asthenia got an OR of 8.25 for the SARS CoV-2 infection. CONCLUSION: There is a strong association between olfactory dysfunction and COVID-19. However, it is not really efficient in the screening of SARS-CoV-2 infection and thus, they should not be considered as a single diagnostic instrument. LEVEL OF EVIDENCE: 4.

Adipose-derived mesenchymal stem cells promote the malignant phenotype of cervical cancer.

Epidemiological studies indicate that obesity negatively affects the progression and treatment of cervical-uterine cancer. Recent evidence shows that a subpopulation of adipose-derived stem cells can alter cancer properties. In the present project, we described for the first time the impact of adipose-derived stem cells over the malignant behavior of cervical cancer cells. The transcriptome of cancer cells cultured in the presence of stem cells was analyzed using RNA-seq. Changes in gene expression were validated using digital-PCR. Bioinformatics tools were used to identify the main transduction pathways disrupted in cancer cells due to the presence of stem cells. In vitro and in vivo assays were conducted to validate cellular and molecular processes altered in cervical cancer cells owing to stem cells. Our results show that the expression of 95 RNAs was altered in cancer cells as a result of adipose-derived stem cells. Experimental assays indicate that stem cells provoke an increment in migration, invasion, angiogenesis, and tumorigenesis of cancer cells; however, no alterations were found in proliferation. Bioinformatics and experimental analyses demonstrated that the NF-kappa B signaling pathway is enriched in cancer cells due to the influence of adipose-derived stem cells. Interestingly, the tumor cells shift their epithelial to a mesenchymal morphology, which was reflected by the increased expression of specific mesenchymal markers. In addition, stem cells also promote a stemness phenotype in the cervical cancer cells. In conclusion, our results suggest that adipose-derived stem cells induce cervical cancer cells to acquire malignant features where NF-kappa B plays a key role.

The Importance of Abdominal Wall Closure After Definitive Surgery for Enterocutaneous Fistula.

INTRODUCTION: The coexistence of an enterocutaneous fistula (ECF) with large abdominal wall defects represent one of the most demanding situations seen by a surgeon. Simultaneous treatment of ECF closure with abdominal wall defect closure has been widely debated. Our objective was to determine if the type of abdominal wall closure was associated with fistula recurrence after definitive surgery for ECF. MATERIALS AND METHODS: Consecutive patients submitted to fistula resection with primary anastomosis for ECF closure. Among several variables, total abdominal wall closure (primary independent variable) was assessed as a factor related to the recurrence of the ECF (dependent variable). Univariate and multivariate analyses were performed. RESULTS: One-hundred and fourteen patients were included. Fistula recurred in 39 patients (34%). Total abdominal wall closure was done in 37 patients (32%). ECF recurred in 16% (6 of 37 patients) when abdominal wall closure was performed, compared to 43% (33 of 77 patients) when this was not (p < 0.02). After multivariate analyses, abdominal wall closure was found as a protective factor against recurrence (p < 0.02). Patients with total abdominal wall closure had one-fourth of risk for recurrence compared to patients without it. Other factors associated to recurrence of ECF were multiple fistulas (p < 0.05), intraoperative blood loss >325 mL (p < 0.05) and preoperative C-reactive protein >0.5 mg/dL (p < 0.01). CONCLUSION: Our results suggest that total abdominal wall closure is a protective factor against fistula recurrence after definitive surgery for ECF.

Anti-interleukin 6 receptor antibody treatment in patients with COVID-19, is it key to reduce mortality? / Tratamiento con el anticuerpo contra el receptor de la interleucina 6 en pacientes con COVID-19, ¿clave para reducir la mortalidad?

Interleukin 6 receptor antagonists are used for the treatment of severe chronic inflammatory diseases. Recently they have been proposed as a treatment for severe COVID-19 patients. However, there is scarce scientific evidence to support this, which is why it is necessary to generate scientific evidence and perform clinical trials to evaluate the appropriateness of this therapeutic strategy.

Los antagonistas del receptor de la interleucina 6 se usan para el tratamiento de diversas enfermedades inflamatorias crónicas. Recientemente se han propuesto para el tratamiento de los pacientes con COVID-19 grave. Sin embargo, hasta ahora la evidencia científica para respaldar esta intervención es escasa, por lo que es necesario generar mayor evidencia científica y hacer ensayos clínicos que permitan evaluar la pertinencia de esta estrategia terapéutica.

Effect of Preoperative Administration of Oral Arginine and Glutamine in Patients with Enterocutaneous Fistula Submitted to Definitive Surgery: a Prospective Randomized Trial.

BACKGROUND: The use of glutamine and arginine has shown several advantages in postoperative outcomes in patients after gastrointestinal surgery. We determined the effects of its use in patients with enterocutaneous fistula after operative treatment. PATIENTS AND METHODS: Forty patients with enterocutaneous fistula were randomly assigned to one of two groups. The control group received the standard medical care while the patients of the experimental group were supplemented with enteral administration of 4.5 g of arginine and 10 g of glutamine per day for 7 days prior to the surgery. The primary outcome variable was the recurrence of the fistula and the secondary outcomes were preoperative and postoperative serum concentrations of interleukin 6 and C-reactive protein and postoperative infectious complications. RESULTS: Twenty patients were assigned to each group. The fistula recurred in two patients (10%) of the experimental group and in nine patients (45%) of the control group (P < 0.001). We found a total of 13 infectious complications in six patients of the control group (all with fistula recurrence) and none in the experimental group. Mean preoperative serum concentrations of interleukin 6 and C-reactive protein were lower in patients from the experimental group. In addition, these levels were lower in patients who had recurrence if compared to patients that did not recur. CONCLUSION: Preoperative administration of oral arginine and glutamine could be valuable in the postoperative recovery of patients with enterocutaneous fistulas submitted to definitive surgery.