Magnesium Supplementation Is Associated with a Lower Cardio-Metabolic Risk in Patients Submitted to Bariatric Surgery.

PURPOSE: Literature has demonstrated an inverse relation between magnesium (Mg) consumption and development of type 2 diabetes mellitus (T2DM), hypertension (HT), and dyslipidemia. After bariatric surgery (BS), micronutrients deficiencies are common, it being important to ensure appropriate supplementation. There is no recommendation about Mg supplementation and to our knowledge, its effect has not been studied to date. Our aim was to evaluate the effect of Mg supplementation in cardio-metabolic risk factors on post-bariatric patients. MATERIALS AND METHODS: A retrospective observational study of patients with obesity who underwent BS was performed. Data was assessed preoperatively and yearly (4-year follow-up). RESULTS: A total of 3363 patients were included. In the first year of follow-up, 79.8% (n = 2123) of the patients were supplemented with Mg, with evidence of slightly decreased percentages in the following years. Mg deficiency (serum Mg < 1.52 mEq/L) was more common among patients who were not supplemented during each year of follow-up (p < 0.05). Among those who underwent Mg supplementation, the percentage of T2DM, HT, or low-density lipoprotein cholesterol (LDL-C) > 130 mg/dL was significantly lower. In the first year post-surgery, the supplementation group had a lower risk of T2DM (OR = 0.545, p < 0.0001), LDL-C > 130 mg/dL (OR = 0.612, p < 0.0001), and HT (OR = 0.584, p < 0.0001). The OR for having these metabolic comorbidities persisted lower during the 4 years' follow-up. Patients who had Mg deficiency had higher prevalence of T2DM and HT. CONCLUSION: Mg supplementation seems to have a protective effect on the development of T2DM, HT, and LDL-C > 130 mg/dL in post-bariatric patients.

Brain Doppler abnormalities in fetuses with open spina bifida.

BACKGROUND: To describe the brain Doppler changes in fetuses with isolated open spina bifida (OSB). STUDY DESIGN: Doppler ultrasound measurements including the umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, and their combination into the cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR) were performed in a cohort of fetuses with OSB. Included patients were individually matched to a control group without structural anomalies and similar gestational ages. MCA-PI and/or CPR values below the 5th centile were considered abnormal and indicative of cerebral blood redistribution, while UCR and UA-PI above the 95th centile were considered abnormal. RESULTS: During the study period, 266 fetuses were recruited, 133 normally grown fetuses with OSB and 133 matched controls. Doppler recordings were successfully obtained in all fetuses at a median gestational age of 30.9 weeks. All cases showed UA-PI within normal ranges, but fetuses with OSB showed significantly higher frequency of cerebral blood redistribution (15.0 vs. 3.0%, p < .01), MCA-PI <5th centile (10.5% vs. 3.0%, p = .01), decreased CPR (9.8% vs. 2.3%, p = .01) and increased UCR (17.2 % vs 7.5 %, p =.02). The rate of cerebral blood redistribution was significantly higher in the OSB group with ventriculomegaly in comparison to those with OSB and normal lateral ventricle diameter (18.6% vs. 3.2%, respectively; p <.05). CONCLUSION: A proportion of fetuses with isolated open spina bifida showed cerebral blood redistribution.

Doppler changes in umbilical artery, middle cerebral artery, cerebroplacental ratio and ductus venosus during open fetal microneurosurgery for intrauterine open spina bifida repair.

OBJECTIVE: To describe changes in fetal Doppler parameters during a novel technique for open fetal microneurosurgery for open spina bifida (OSB) repair. METHODS: This was a prospective study of 44 fetuses undergoing open fetal surgery for OSB repair using a novel microneurosurgery approach that is characterized by a mini-hysterotomy (diameter of 15 mm), minimal fetal manipulation and maintenance of a constant normal amniotic fluid volume throughout the procedure. Doppler velocimetry of the umbilical artery (UA), fetal middle cerebral artery (MCA) and ductus venosus (DV) was performed before the start of surgery and at prespecified timepoints during fetal surgery. UA pulsatility index (PI) > 95th percentile, DV-PI > 95th percentile, MCA-PI < 5th percentile and cerebroplacental ratio (CPR) < 5th percentile were considered abnormal. RESULTS: Median gestational age at fetal surgery was 25.2 weeks (range, 22.9-27.9 weeks). Doppler recordings were successfully obtained in all cases during all timepoints throughout the surgery. As compared with Doppler values before surgery, there was a significant increase in the proportion of fetuses with MCA-PI < 5th percentile (63.6% vs 13.6%; P < 0.001), CPR < 5th percentile (65.9% vs 15.9%; P < 0.001) and DV-PI > 95th percentile (22.7% vs 0%; P = 0.01) and a non-significant increase in the proportion of fetuses with UA-PI > 95th percentile (11.4% vs 0%; P = 0.12) during fetal surgery. None of the fetuses showed absent or reversed end-diastolic velocity in the UA or absent or reversed DV a-wave at any stage during OSB repair. All abnormal Doppler parameters returned to normal after surgery. CONCLUSIONS: During open fetal surgery for OSB repair, a small hysterotomy, reduced fetal manipulation and maintenance of a normal amniotic fluid volume seem to prevent severe fetal Doppler abnormalities. The mild Doppler changes observed during fetal surgery could be a manifestation of fetal adaptation to the stress of fetal surgery. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

High-dose neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery in potentially-resectable stage IIIA-N2 NSCLC. A multi-institutional retrospective study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

BACKGROUND: The optimal induction treatment in potentially-resectable stage IIIA-N2 NSCLC remains undefined. AIM: To compare neoadjuvant high-dose chemoradiotherapy (CRT) to neoadjuvant chemotherapy (CHT) in patients with resectable, stage IIIA-N2 non-small-cell lung cancer (NSCLC). METHODS: Retrospective, multicentre study of 99 patients diagnosed with stage cT1-T3N2M0 NSCLC who underwent neoadjuvant treatment (high-dose CRT or CHT) followed by surgery between January 2005 and December 2014. RESULTS: 47 patients (47.5%) underwent CRT and 52 (52.5%) CHT, with a median follow-up of 41 months. Surgery consisted of lobectomy (87.2% and 82.7%, in the CRT and CHT groups, respectively) or pneumonectomy (12.8% vs. 17.3%). Nodal downstaging (to N1/N0) and Pathologic complete response (pCR; pT0pN0) rates were significantly higher in the CRT group (89.4% vs. 57.7% and 46.8% vs. 7.7%, respectively; p < 0.001)). Locoregional recurrence was significantly lower in the CRT group (8.5% vs. 13.5%; p = 0.047) but distant recurrence rates were similar in the two groups. Median PFS was 45 months (CHT) vs. "not reached" (CRT). Median OS was similar: 61 vs. 56 months (p = 0.803). No differences in grade ≥3 toxicity were observed. On the Cox regression analysis, advanced pT stage was associated with worse OS and PFS (p < 0.001) and persistent N2 disease (p = 0.002) was associated with worse PFS. CONCLUSIONS: Compared to neoadjuvant chemotherapy alone, a higher proportion of patients treated with preoperative CRT achieved nodal downstaging and pCR with better locoregional control. However, there were no differences in survival. More studies are needed to know the optimal treatment of these patients.

Coexistence of DIPNECH and carotid body paraganglioma: is it just a coincidence?

SUMMARY: We describe the case of a 56 year-old woman with the almost simultaneous appearance of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and a carotid body paraganglioma. Of interest, 6 years earlier, the patient underwent total thyroidectomy due to papillary thyroid carcinoma and, in the meantime, she was submitted to mastectomy to treat an invasive ductal carcinoma of the breast. In order to explain these lesions, an extensive genetic study was performed. Results showed positivity for the presence of the tumor suppressor gene PALB2, whose presence had already been detected in a niece with breast cancer. The patient underwent different procedures to treat the lesions and currently she is symptom-free over 2 years of follow-up. LEARNING POINTS: The presence of two rare neoplasms in a single person should raise the suspicion of a common etiology. To the best of our knowledge, this is the first case that shows the coexistence of DIPNECH and paraganglioma. The contribution of the PALB2 gene in the etiology of these rare neoplasms is a possibility.

Survival outcome in severe left-sided congenital diaphragmatic hernia with and without fetal endoscopic tracheal occlusion in a country with suboptimal neonatal management.

OBJECTIVE: To evaluate the impact of fetal endoscopic tracheal occlusion (FETO) on improving survival of fetuses with severe left-sided congenital diaphragmatic hernia (CDH), as compared with contemporaneous cases managed expectantly during pregnancy, in a country with suboptimal neonatal management. METHODS: In this prospective cohort study, consecutive fetuses with isolated left-sided CDH, normal karyotype and severe pulmonary hypoplasia (defined as liver herniation and observed/expected lung-to-head circumference ratio below 26%) were selected for FETO at less than 32 weeks of gestation in a single tertiary referral center in Queretaro, Mexico. Postnatal outcome (survival up to 28 days after birth) was compared between fetuses treated with FETO and contemporaneous cases with similar lung size managed expectantly during pregnancy. RESULTS: Twenty-five fetuses with isolated severe left-sided CDH treated with FETO were matched individually with 25 cases managed expectantly during pregnancy. Endotracheal placement of the balloon was performed successfully on the first attempt in all cases. The median gestational age (GA) at balloon placement was 29.1 (range, 25.6-31.8) weeks and 34.1 (range, 30.0-36.1) weeks at balloon removal. There were no technical problems with the introduction or removal of the balloon in any cases. The median GA at delivery was significantly lower in the group treated with FETO than in those managed expectantly (35.3 vs 37.7 weeks; P = 0.04). The survival rate was significantly higher in the group treated with FETO than in those without fetal intervention (32% vs 0%; P < 0.001). CONCLUSION: In settings with suboptimal neonatal management, FETO was associated with improved neonatal survival in fetuses with isolated left-sided CDH and severe pulmonary hypoplasia. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Resultado de supervivencia en una hernia diafragmática congénita grave del lado izquierdo, con y sin oclusión traqueal endoscópica fetal en un país con un tratamiento neonatal subóptimo OBJETIVO: Evaluar el impacto de la oclusión traqueal endoscópica fetal (OTEF) en la mejora de la supervivencia de los fetos con hernia diafragmática congénita (HDC) grave del lado izquierdo, en comparación con los casos actuales tratados como embarazo gestante, en un país con un tratamiento neonatal subóptimo. MÉTODOS: En este estudio prospectivo de cohortes, se seleccionaron fetos consecutivos con HDC aislada del lado izquierdo, cariotipo normal e hipoplasia pulmonar grave (definida como hernia hepática y una proporción observada/esperada de la circunferencia pulmonar-cabeza inferior al 26%) para una OTEF antes de las 32 semanas de gestación, en un único centro de medicina especializada terciaria en Querétaro (México). El resultado postnatal (supervivencia hasta los 28 días después del nacimiento) se comparó entre fetos tratados con OTEF y los casos contemporáneos con tamaño pulmonar similar, tratados como embarazo gestante. RESULTADOS: Veinticinco fetos con HDC grave aislada del lado izquierdo que habían sido tratados con OTEF fueron emparejados individualmente con 25 casos tratados como embarazo gestante. La colocación endotraqueal del globo se realizó con éxito en el primer intento en todos los casos. La mediana de la edad gestacional (EG) en el momento de la colocación del globo fue de 29,1 (rango, 25,6-31,8) semanas y 34,1 (rango, 30,0-36,1) semanas cuando se retiró el globo. En ningún caso hubo problemas técnicos con la introducción o la retirada del globo. La mediana de la EG en el momento del parto fue significativamente menor en el grupo tratado con OTEF que en el grupo tratado como gestante (35,3 vs 37,7 semanas; P=0,04). La tasa de supervivencia fue significativamente más alta en el grupo tratado con OTEF que en los casos sin intervención fetal (32% vs 0%; P<0,001). CONCLUSIÓN: En los entornos con un tratamiento neonatal subóptimo, la OTEF se asoció con una mejora de la supervivencia neonatal en los fetos con HDC aislada del lado izquierdo y con hipoplasia pulmonar grave. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Impact of Bariatric Surgery on Long-term Cardiovascular Risk: Comparative Effectiveness of Different Surgical Procedures.

INTRODUCTION: Several reports highlight bariatric surgery as an efficient and long-lasting strategy for weight loss. Herein, we aimed to evaluate the impact of bariatric surgery on 10-year cardiovascular disease (CVD) risk and to compare the effectiveness of different surgical procedures, employing the Framingham Risk Score (FRS). METHODS: Retrospective longitudinal observational study of patients undergoing bariatric surgery. Data was assessed preoperatively and during a 4-year follow-up period. RESULTS: We evaluated 1449 individuals, 85.2% female, age of 42.4 ± 10.6 years, and preoperative BMI of 44.3 ± 5.8 kg/m2; 58.0% underwent Roux-en-Y gastric bypass (RYGB), 23.4% sleeve gastrectomy (SG), and 18.6% adjustable gastric band (AGB). The 10-year CVD risk decreased 43.6% in the first postoperative year. The decrease in FRS was more pronounced in the RYGB group (50.5% in the first postoperative year) (p < 0.001). Although there was a subsequent slight increase in FRS during the follow-up period, the cardiovascular benefits were maintained when compared with baseline. For all surgical procedures, CVD risk showed a quadratic trend with a J-shaped curve. A negative interaction between the RYGB group CVD risk and time was observed (ß = - 0.072 (95% CI, - 0.109; - 0.035)). In the RYGB group, FRS decreased more when compared with the SG and AGB groups and, from the second postoperative year onwards, increased more slowly, regardless of gender. The SG group showed similar trend as that of the AGB (ß = - 0.002 (95% CI, - 0.049; 0.053)). CONCLUSION: Our study showed a significant reduction of 10-year CVD risk after bariatric surgery. This decrease was more pronounced in the first postoperative year, and RYGB was the procedure with the greatest decrease of the 10-year CVD risk.

Prognostic factors in neoadjuvant treatment followed by surgery in stage IIIA-N2 non-small cell lung cancer: a multi-institutional study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

PURPOSE: To evaluate the prognostic factors associated with survival in patients treated with neoadjuvant treatment [chemoradiotherapy (CRT) or chemotherapy] followed by surgery (CRTS) in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC). METHODS: A retrospective study was conducted of 118 patients diagnosed with stage T1-T3N2M0 NSCLC and treated with CRTS at 14 hospitals in Spain between January 2005 and December 2014. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis was performed. RESULTS: Surgery consisted of lobectomy (74.5% of cases), pneumectomy (17.8%), or bilobectomy (7.6%). Neoadjuvant treatment was CRT in 62 patients (52.5%) and chemotherapy alone in 56 patients (47.5%). Median follow-up was 42.5 months (5-128 months). 5-year OS and PFS were 51.1% and 49.4%, respectively. The following variables were independently associated with worse OS and PFS: pneumonectomy (vs. lobectomy); advanced pathologic T stage (pT3 vs. pT0-pT2); and presence of persistent N2 disease (vs. ypN0-1) in the surgical specimen. CONCLUSIONS: In this sample of patients with stage IIIA-N2 NSCLC treated with CRTS, 5-year survival (both OS and PFS) was approximately 50%. After CRTS, the patients with the best prognosis were those whose primary tumour and/or mediastinal nodal metastases were downstaged after induction therapy and those who underwent lobectomy. These findings provide further support for neoadjuvant therapy followed by surgery in selected patients.

Neoadjuvant treatment followed by surgery versus definitive chemoradiation in stage IIIA-N2 non-small-cell lung cancer: A multi-institutional study by the oncologic group for the study of lung cancer (Spanish Radiation Oncology Society).

OBJECTIVES: The role of surgery in stage IIIA-N2 non-small cell lung cancer (NSCLC) is an actively debated in oncology. To evaluate the value of surgery in this patient population, we conducted a multi-institutional retrospective study comparing neoadjuvant chemoradiotherapy or chemotherapy plus surgery (CRTS) to definitive chemoradiotherapy (dCRT). MATERIAL AND METHODS: A total of 247 patients with potentially resectable stage T1-T3N2M0 NSCLC treated with either CRTS or dCRT between January 2005 and December 2014 at 15 hospitals in Spain were identified. A centralized review was performed to ensure resectability. A propensity score matched analysis was carried out to balance patient and tumor characteristics (n = 78 per group). RESULTS: Of the 247 patients, 118 were treated with CRTS and 129 with dCRT. In the CRTS group, 62 patients (52.5%) received neoadjuvant CRT and 56 (47.4%) neoadjuvant chemotherapy. Surgery consisted of either lobectomy (97 patients; 82.2%) or pneumonectomy (21 patients; 17.8%). In the matched samples, median overall survival (OS; 56 vs 29 months, log-rank p = .002) and progression-free survival (PFS; 46 vs 15 months, log-rank p < 0.001) were significantly higher in the CRTS group. This survival advantage for CRTS was maintained in the subset comparison between the lobectomy subgroup versus dCRT (OS: 57 vs 29 months, p < 0.001; PFS: 46 vs 15 months, p < 0.001), but not in the comparison between the pneumonectomy subgroup and dCRT. CONCLUSION: The findings reported here indicate that neoadjuvant chemotherapy or chemoradiotherapy followed by surgery (preferably lobectomy) yields better OS and PFS than definitive chemoradiotherapy in patients with resectable stage IIIA-N2 NSCLC.

Abaloparatide, a novel PTH receptor agonist, increased bone mass and strength in ovariectomized cynomolgus monkeys by increasing bone formation without increasing bone resorption.

Abaloparatide, a novel PTH1 receptor agonist, increased bone formation in osteopenic ovariectomized cynomolgus monkeys while increasing cortical and trabecular bone mass. Abaloparatide increased bone strength and maintained or enhanced bone mass-strength relationships, indicating preserved or improved bone quality. INTRODUCTION: Abaloparatide is a selective PTH1R activator that is approved for the treatment of postmenopausal osteoporosis. The effects of 16 months of abaloparatide administration on bone formation, resorption, density, and strength were assessed in adult ovariectomized (OVX) cynomolgus monkeys (cynos). METHODS: Sixty-five 9-18-year-old female cynos underwent OVX surgery, and 15 similar cynos underwent sham surgery. After a 9-month period without treatments, OVX cynos were allocated to four groups that received 16 months of daily s.c. injections with either vehicle (n = 17) or abaloparatide (0.2, 1, or 5 µg/kg/day; n = 16/dose level), while Sham controls received s.c. vehicle (n = 15). Bone densitometry (DXA, pQCT, micro-CT), qualitative bone histology, serum calcium, bone turnover markers, bone histomorphometry, and bone strength were among the key measures assessed. RESULTS: At the end of the 9-month post-surgical bone depletion period, just prior to the treatment phase, the OVX groups exhibited increased bone turnover markers and decreased bone mass compared with sham controls. Abaloparatide administration to OVX cynos led to increased bone formation parameters, including serum P1NP and endocortical bone formation rate. Abaloparatide administration did not influence serum calcium levels, bone resorption markers, cortical porosity, or eroded surfaces. Abaloparatide increased bone mass at the whole body, lumbar spine, tibial diaphysis, femoral neck, and femoral trochanter. Abaloparatide administration was associated with greater lumbar vertebral strength, and had no adverse effects on bone mass-strength relationships for the vertebrae, femoral neck, femoral diaphysis, or humeral cortical beams. CONCLUSIONS: Abaloparatide administration was associated with increases in bone formation, bone mass and bone strength, and with maintenance of bone quality in OVX cynos, without increases in serum calcium or bone resorption parameters.

Reduced Glutathione and ATP in the Seminal Cryopreservation of Tambaqui.

BACKGROUND: The aim of this study was to analyze the effect of reduced glutathione (GR) and adenosine triphosphate (ATP) in cryopreserved sperm tambaqui, Colossoma macropomum.. OBJECTIVE: Semen samples were frozen at different concentrations of GR (2, 4, and 6 mM) and ATP (7.5, 15, 30 mM) evaluated separately. MATERIALS AND METHODS: Different concentrations of GR and ATP were added to the diluent Beltsville Thawing Solution 10 % of DMSO (extender control). The thawed sperm was evaluated as the kinetic parameters for Computer Assisted Semen Analysis (CASA) and cell feature parameters by flow cytometry. RESULTS: All concentrations of GR and ATP had gradual reduction in the production of reactive oxygen species, mainly ATP 15; 22.5 mM and 30 mM, which decreased by 50% or more when compared to the control. All concentrations of GR and ATP did not change (P> 0.05) DNA fragmentation and lipid peroxidation. The membrane fluidity GR in concentrations 4 and 6 mM were better than control; and the concentrations of 2 and 4 mM maintained more efficiently to motility period, total and progressive motility. CONCLUSION: Thus, it is indicated the use of BTS extender with 10% DMSO added 4 mM GR thawed sperm Tambaqui C. macropomum.

Ovarian fragment sizes affect viability and morphology of preantral follicles during storage at 4°C.

The method of transportation and the conditions imposed on the ovarian tissue are pivotal aspects for the success of ovarian tissue cryopreservation (OTC). The aim of this study was to evaluate the effect of the size of the ovarian tissue (e.g. whole ovary, biopsy size and transplant size) during different times of storage (0, 6, 12 and 24 h) on the structural integrity of equine ovarian tissue transported at 4°C. Eighteen pairs of ovaries from young mares (<10 years old) were harvested in a slaughterhouse and processed to simulate the fragment sizes (biopsy and transplant size groups) or kept intact (whole ovary group) and stored at 4°C for up to 24 h in α-MEM-enriched solution. The effect of the size of the ovarian tissue was observed on the morphology of preantral follicles, stromal cell density, DNA fragmentation and mitochondrial membrane potential. The results showed that (i) biopsy size fragments had more morphologically normal preantral follicles after 24 h of storage at 4°C; (ii) mitochondrial membrane potential was the lowest during each storage time when the whole ovary was used; (iii) DNA fragmentation rate in the ovarian cells of all sizes of fragments increased as storage was prolonged and (iv) transplant size fragments had increased stromal cell density during storage at cool temperature. In conclusion, the biopsy size fragment was the best to preserve follicle morphology for long storage (24 h); however, transportation/storage should be prior determined according to the distance (time of transportation) between patient and reproduction centers/clinics.

Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis.

OBJECTIVES: To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. DESIGN: A cross-sectional study with a two-step cluster analysis. SETTINGS: A tertiary referral multicenter study. PARTICIPANTS: Nine hundred and eighty-eight adult patients with unilateral MD. MAIN OUTCOME MEASURES: best predictors to define clinical subgroups with potential different aetiologies. RESULTS: We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. CONCLUSIONS: Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials.

Collagen-rich stroma in aggressive colon tumors induces mesenchymal gene expression and tumor cell invasion.

Gene expression-based classification systems have identified an aggressive colon cancer subtype with mesenchymal features, possibly reflecting epithelial-to-mesenchymal transition (EMT) of tumor cells. However, stromal fibroblasts contribute extensively to the mesenchymal phenotype of aggressive colon tumors, challenging the notion of tumor EMT. To separately study the neoplastic and stromal compartments of colon tumors, we have generated a stroma gene filter (SGF). Comparative analysis of stromahigh and stromalow tumors shows that the neoplastic cells in stromahigh tumors express specific EMT drivers (ZEB2, TWIST1, TWIST2) and that 98% of differentially expressed genes are strongly correlated with them. Analysis of differential gene expression between mesenchymal and epithelial cancer cell lines revealed that hepatocyte nuclear factor 4α (HNF4α), a transcriptional activator of intestinal (epithelial) differentiation, and its target genes are highly expressed in epithelial cancer cell lines. However, mesenchymal-type cancer cell lines expressed only part of the mesenchymal genes expressed by tumor-derived neoplastic cells, suggesting that external cues were lacking. We found that collagen-I dominates the extracellular matrix in aggressive colon cancer. Mimicking the tumor microenvironment by replacing laminin-rich Matrigel with collagen-I was sufficient to induce tumor-specific mesenchymal gene expression, suppression of HNF4α and its target genes, and collective tumor cell invasion of patient-derived colon tumor organoids. The data connect collagen-rich stroma to mesenchymal gene expression in neoplastic cells and to collective tumor cell invasion. Targeting the tumor-collagen interface may therefore be explored as a novel strategy in the treatment of aggressive colon cancer.

Prevalencia y factores asociados a la adherencia al tratamiento no farmacológico en pacientes con hipertensión y diabetes en servicios de baja complejidad / Prevalence and factors associated with adherence to non-pharmacological treatment of hypertensive and diabetic patients at low complexity services / Prevalência e fatores associados à aderência ao tratamento não-farmacológico em pacientes com hipertensão e diabete em serviços de baixa complexidade

OBJETIVO: determinar la prevalencia y los factores relacionados con la adherencia no farmacológica en pacientes con hipertensión arterial (HTA) y diabetes mellitus (DM). METODOLOGIA: estudio observacional transversal en pacientes adultos mayores de 35 años con diagnóstico de HTA o DM, atendidos en un programa de Renoprotección en cuidado primario en Cali, Colombia. Se excluyeron aquellos pacientes con enfermedad renal crónica en estadío KDOQI 4-5, los que presentaran comorbilidades adicionales que deterioraran la función renal o con trastornos neuropsiquiátricos diagnosticados previamente. La adherencia no farmacológica se determinó mediante un cuestionario de autoreporte y los factores asociados a la misma se determinaron mediante regresión de Poisson con varianza robusta. RESULTADOS : la prevalencia de la adherencia no farmacológica fue de 9,4%. La inactividad física estuvo presente en 75% de los pacientes, y más del 19% de la población consumía sal frecuentemente. Entre los diabéticos, 18% consumía carbohidratos con frecuencia. Los hombres mostraron ser menos adherentes que las mujeres (RP: 0,21; p = 0,002). Los factores asociados positivamente con la adherencia no farmacológica fueron: estar estudiando, desempleado o pensionado (RP: 4,42; p = 0,019), recibir apoyo del equipo de salud (RP: 3,17; p = 0,032), tener diagnóstico de diabetes (RP: 7,79; p = 0,000) y la función renal en KDOQI-3 (RP: 5,14; p = 0,008). CONCLUSION: la adherencia no farmacológica fue muy baja en la población de estudio, en particular en relación con la inactividad física. Los factores asociados positivamente a la adherencia fueron el sexo femenino, tener una ocupación diferente al hogar, diagnostico de diabetes, enfermedad renal en KDOQI-3 y contar con apoyo del equipo de salud.

OBJECTIVE: To determine the prevalence and factors associated with adherence to non-pharmacological treatment in patients with high blood pressure (HBP) and diabetes mellitus (DM). METHODOLOGY: A cross-sectional and observational study conducted with adult patients older than 35, diagnosed with HBP or DM and receiving health care in a primary care renal protection program in Cali, Colombia. Patients with chronic kidney disease at the KDOQI 4-5 stage, additional comorbidities which impair the renal function or with previously diagnosed neuropsychiatric disorders were excluded. Adherence to non-pharmacological treatment was determined using a self-report questionnaire. Factors associated with adherence were obtained through a Poisson regression with robust variance. RESULTS : The prevalence of patient adherence was 9.4%.Physical inactivity was present in 75% of the patients and 19% of the population often consumed salt. Among the diabetics, 18% often consumed carbohydrates. Men showed less adherence than women (RP: 0.21; p = 0.002). Factors positively associated with adherence to non-pharmacological treatment were: being a student, unemployed or retired(RP: 4.42; p = 0.019), getting help from the health care team (RP: 3.17; p = 0.032), being diagnosed with diabetes (RP: 7.79; p = 0.000) and having the renal function in the KDOQI-3 stage (RP: 5.14; p = 0.008). CONCLUSION: Adherence to non-pharmacological treatment was very low in the studied population, particularly in relation to physical inactivity. The factors positively associated with treatment adherence were being female, not being a housewife, having diabetes, having a renal disease at the KDOQI-3 stage and having the support of a health care team.

OBJETIVO: Determinar a prevalência e os fatores ligados à aderência não-farmacológica em pacientes com hipertensão arterial (HTA) e diabetes mellitus (DM). METODOLOGIA: Estudo observacional transversal em pacientes adultos maiores de 35 anos com diagnóstico de HTA ou DM, atendidos em um programa de Renoproteção em cuidado primário em Cali, Colômbia.Foram excluídos aqueles pacientes com doença renal crônica em etapa KSOQI 4-5, aqueles com comorbilidades adicionais que deterioram a função renal ou com transtornos neuropsiquiátricos diagnosticados previamente.A aderência não farmacológica foi determinada por meio de um questionário de auto-relato e os fatores associados a ela foram determinados por meio de regressão de poisson com variância robusta. RESULTADOS: A prevalência da aderência não farmacológica foi de 9.4%.A inatividade física esteve presente em 75% dos pacientes e mais de 19% da população consumia sal frequentemente.Entre os diabéticos 18% consumia frequentemente carboidratos. Os homens mostraram ser menos aderentes do que as mulheres (RP: 0,21; p = 0,002). Os fatores associados positivamente à aderência não farmacológica foram os fatos de estarem estudando, desempregados ou aposentados(RP: 4,42; p = 0,019), receber apoio da equipe de saúde (RP: 3,17; p = 0,032), ter diagnóstico de diabetes (RP: 7,79; p = 0,000) e a função renal em KDOQI-3 (RP: 5,14; p = 0,008). CONCLUSÃO: Aderência não farmacológica foi muito baixa na população analisada, em particular em relação com a atividade física.Os fatores associados positivamente à aderência foram o gênero feminino, ter uma ocupação diferente do lar, diagnóstico de diabetes, doença renal em KDOQI-3 e contar com apoio da equipe de saúde.

What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?

MSCs derived from the umbilical cord tissue, termed UCX, were investigated for their immunomodulatory properties and compared to bone marrow-derived MSCs (BM-MSCs), the gold-standard in immunotherapy. Immunogenicity and immunosuppression were assessed by mixed lymphocyte reactions, suppression of lymphocyte proliferation and induction of regulatory T cells. Results showed that UCX were less immunogenic and showed higher immunosuppression activity than BM-MSCs. Further, UCX did not need prior activation or priming to exert their immunomodulatory effects. This was further corroborated in vivo in a model of acute inflammation. To elucidate the potency differences observed between UCX and BM-MSCs, gene expression related to immune modulation was analysed in both cell types. Several gene expression profile differences were found between UCX and BM-MSCs, namely decreased expression of HLA-DRA, HO-1, IGFBP1, 4 and 6, ILR1, IL6R and PTGES and increased expression of CD200, CD273, CD274, IL1B, IL-8, LIF and TGFB2. The latter were confirmed at the protein expression level. Overall, these results show that UCX seem to be naturally more potent immunosuppressors and less immunogenic than BM-MSCs. We propose that these differences may be due to increased levels of immunomodulatory surface proteins such as CD200, CD273, CD274 and cytokines such as IL1ß, IL-8, LIF and TGFß2.