Eddy-driven diazotroph distribution in the subtropical North Atlantic: horizontal variability prevails over particle sinking speed.

Mesoscale eddies influence the distribution of diazotrophic (nitrogen-fixing) cyanobacteria, impacting marine productivity and carbon export. Non-cyanobacterial diazotrophs (NCDs) are emerging as potential contributors to marine nitrogen fixation, relying on organic matter particles for resources, impacting nitrogen and carbon cycling. However, their diversity and biogeochemical importance remain poorly understood. In the subtropical North Atlantic along a single transect, this study explored the horizontal and vertical spatial variability of NCDs associated with suspended, slow-sinking, and fast-sinking particles collected with a marine snow catcher. The investigation combined amplicon sequencing with hydrographic and biogeochemical data. Cyanobacterial diazotrophs and NCDs were equally abundant, and their diversity was explained by the structure of the eddy. The unicellular symbiotic cyanobacterium UCYN-A was widespread across the eddy, whereas Trichodesmium and Crocosphaera accumulated at outer fronts. The diversity of particle-associated NCDs varied more horizontally than vertically. NCDs constituted most reads in the fast-sinking fractions, mainly comprising Alphaproteobacteria, whose abundance significantly differed from the suspended and slow-sinking fractions. Horizontally, Gammaproteobacteria and Betaproteobacteria exhibited inverse distributions, influenced by physicochemical characteristics of water intrusions at the eddy periphery. Niche differentiations across the anticyclonic eddy underscored NCD-particle associations and mesoscale dynamics, deepening our understanding of their ecological role and impact on ocean biogeochemistry.

Correlation and validity of imputed PaO2/FiO2 and SpO2/FiO2 in patients with invasive mechanical ventilation at 2600m above sea level.

OBJECTIVE: To establish the correlation and validity between PaO2/FiO2 obtained on arterial gases versus noninvasive methods (linear, nonlinear, logarithmic imputation of PaO2/FiO2 and SpO2/FiO2) in patients under mechanical ventilation living at high altitude. DESIGN: Ambispective descriptive multicenter cohort study. SETTING: Two intensive care units (ICU) from Colombia at 2600m a.s.l. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients older than 18 years with at least 24h of mechanical ventilation were included from June 2016 to June 2019. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, physiological messures, laboratory findings, oxygenation index and clinical condition. Nonlinear, linear and logarithmic imputation formulas were used to calculate PaO2 from SpO2, and at the same time the SpO2/FiO2 by severe hypoxemia diagnosis. The intraclass correlation coefficient, area under the ROC curve, sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratio were calculated. RESULTS: The correlation between PaO2/FiO2 obtained from arterial gases, PaO2/FiO2 derived from one of the proposed methods (linear, non-linear, and logarithmic formula), and SpO2/FiO2 measured by the intraclass correlation coefficient was high (greater than 0.77, p<0.001). The different imputation methods and SpO2/FiO2 have a similar diagnostic performance in patients with severe hypoxemia (PaO2/FiO2 <150). PaO2/FiO2 linear imputation AUC ROC 0,84 (IC 0.81-0.87, p<0.001), PaO2/FiO2 logarithmic imputation AUC ROC 0.84 (IC 0.80-0.87, p<0.001), PaO2/FiO2 non-linear imputation AUC ROC 0.82 (IC 0.79-0.85, p<0.001), SpO2/FiO2 oximetry AUC ROC 0.84 (IC 0.81-0.87, p<0.001). CONCLUSIONS: At high altitude, the SaO2/FiO2 ratio and the imputed PaO2/FiO2 ratio have similar diagnostic performance in patients with severe hypoxemia ventilated by various pathological conditions.

Correlation and validity of imputed PaO2/FiO2 and SpO2/FiO2 in patients with invasive mechanical ventilation at 2600m above sea level / Correlación y validez de la PaO2/FiO2 y SpO2/FiO2 imputadas en pacientes con ventilación mecánica invasiva a 2.600 metros sobre el nivel del mar

Objective To establish the correlation and validity between PaO2/FiO2 obtained on arterial gases versus noninvasive methods (linear, nonlinear, logarithmic imputation of PaO2/FiO2 and SpO2/FiO2) in patients under mechanical ventilation living at high altitude. Design Ambispective descriptive multicenter cohort study. Setting Two intensive care units (ICU) from Colombia at 2600m a.s.l. Patients or participants Consecutive critically ill patients older than 18 years with at least 24h of mechanical ventilation were included from June 2016 to June 2019. Interventions None. Variables Variables analyzed were demographic, physiological messures, laboratory findings, oxygenation index and clinical condition. Nonlinear, linear and logarithmic imputation formulas were used to calculate PaO2 from SpO2, and at the same time the SpO2/FiO2 by severe hypoxemia diagnosis. The intraclass correlation coefficient, area under the ROC curve, sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratio were calculated. Results The correlation between PaO2/FiO2 obtained from arterial gases, PaO2/FiO2 derived from one of the proposed methods (linear, non-linear, and logarithmic formula), and SpO2/FiO2 measured by the intraclass correlation coefficient was high (greater than 0.77, p<0.001). The different imputation methods and SpO2/FiO2 have a similar diagnostic performance in patients with severe hypoxemia (PaO2/FiO2 <150). PaO2/FiO2 linear imputation AUC ROC 0,84 (IC 0.81–0.87, p<0.001), PaO2/FiO2 logarithmic imputation AUC ROC 0.84 (IC 0.80–0.87, p<0.001), PaO2/FiO2 non-linear imputation AUC ROC 0.82 (IC 0.79–0.85, p<0.001), SpO2/FiO2 oximetry AUC ROC 0.84 (IC 0.81–0.87, p<0.001). Conclusions At high altitude, the SaO2/FiO2 ratio and the imputed PaO2/FiO2 ratio have similar diagnostic performance in patients with severe hypoxemia ventilated by various pathological conditions (AU)

Objetivo Establecer la correlación y validez entre PaO2/FiO2 obtenida en gases arteriales versus métodos no invasivos (imputación lineal, no lineal, logarítmica de PaO2/FiO2 y SpO2/FiO2) en pacientes bajo ventilación mecánica que viven en altitudes elevadas. Diseño Estudio de cohorte multicéntrico descriptivo ambispectivo Ámbito Dos unidades de cuidados intensivos de Colombia a 2.600 m s.n.m. Pacientes o participantes Se incluyeron pacientes consecutivos en estado crítico mayores de 18 años con al menos 24h de ventilación mecánica desde junio de 2016 a junio de 2019. Intervenciones Ninguna. Variables Las variables analizadas fueron demográficas, fisiológicas, hallazgos de laboratorio, índice de oxigenación y estado clínico. Se utilizaron fórmulas de imputación no lineales, lineales y logarítmicas para calcular la PaO2 a partir de la SpO2, y al mismo tiempo la SpO2/FiO2 mediante el diagnóstico de hipoxemia severa. Se calculó el coeficiente de correlación intraclase, el área bajo la curva ROC, la sensibilidad, la especificidad, el valor predictivo positivo, el valor predictivo negativo, la razón de verosimilitud positiva y negativa. Resultados La correlación entre PaO2/FiO2 obtenida a partir de gases arteriales, PaO2/FiO2 derivada de uno de los métodos propuestos (fórmula lineal, no lineal y logarítmica) y SpO2/FiO2 medida por el coeficiente de correlación intraclase fue alta (mayor a 0,77, p<0,001). Los diferentes métodos de imputación y SpO2/FiO2 tienen un rendimiento diagnóstico similar en pacientes con hipoxemia severa (PaO2/FiO2<150). PaO2/FiO2 imputación lineal AUC ROC 0,84 (IC 0,81-0,87; p<0,001), PaO2/FiO2 imputación logarítmica AUC ROC 0,84 (IC 0,80-0,87; p<0,001), PaO2/Imputación no lineal de FiO2 AUC ROC 0,82 (IC 0,79-0,85; p<0,001), oximetría de SpO2/FiO2 AUC ROC 0,84 (IC 0,81-0,87; p<0,001). Conclusiones A gran altitud, el cociente SaO2/FiO2 y el cociente PaO2/FiO2 (AU)

Clinical utility of comprehensive circulating tumor DNA genotyping compared with standard of care tissue testing in patients with newly diagnosed metastatic colorectal cancer.

BACKGROUND: Comprehensive biomarker testing is essential in selecting optimal treatment for patients with metastatic colorectal cancer (mCRC); however, incomplete genotyping is widespread, with most patients not receiving testing for all guideline-recommended biomarkers, in part due to reliance on burdensome sequential tissue-based single-biomarker tests with long waiting times or availability of only archival tissue samples. We aimed to demonstrate that liquid biopsy, associated with rapid turnaround time (TAT) and lower patient burden, effectively identifies guideline-recommended biomarkers in mCRC relative to standard of care (SOC) tissue testing. PATIENTS AND METHODS: Prospectively enrolled patients with previously untreated mCRC undergoing physician discretion SOC tissue genotyping submitted pretreatment blood samples for comprehensive circulating tumor DNA (ctDNA) analysis with Guardant360 and targeted RAS and BRAF analysis with OncoBEAM. RESULTS: Among 155 patients, physician discretion SOC tissue genotyping identified a guideline-recommended biomarker in 82 patients, versus 88 identified with comprehensive ctDNA (52.9% versus 56.8%, noninferiority demonstrated down to α = 0.005) and 69 identified with targeted PCR ctDNA analysis (52.9% versus 44.5%, noninferiority rejected at α = 0.05). Utilizing ctDNA in addition to tissue increased patient identification for a guideline-recommended biomarker by 19.5% by rescuing those without tissue results either due to tissue insufficiency, test failure, or false negatives. ctDNA median TAT was significantly faster than tissue testing when the complete process from sample acquisition to results was considered (median 10 versus 27 days, P < 0.0001), resulting in accelerated biomarker discovery, with 52.0% biomarker-positive patients identified by ctDNA versus 10.2% by SOC tissue 10 days after sample collection (P < 0.0001). CONCLUSIONS: Comprehensive ctDNA genotyping accurately identifies guideline-recommended biomarkers in patients with mCRC at a rate at least as high as SOC tissue genotyping, in a much shorter time. Based on these findings, the addition of ctDNA genotyping to clinical practice has significant potential to improve the care of patients with mCRC.

Correlation between proximal serrated polyp detection and clinically significant serrated polyps: inter-endoscopist variability.

INTRODUCTION AND AIMS: The adenoma detection rate (ADR) is the most important quality indicator for the prevention of colorectal cancer but serrated polyps are also precursor lesions of the disease. The aim of our study was to compare the detection rate of proximal serrated polyps (PSPs) and that of clinically significant serrated polyps (CSSPs) between endoscopists and analyze the relation of those parameters to the ADR. METHODS: An observational, prospective, cross-sectional study was conducted on all patients that underwent colonoscopy at the Policlínico Peruano Japonés within the time frame of July 2015 and August 2016. The ADR and PSP and CSSP detection rates between endoscopists were compared through multivariate logistic regression and the association between those parameters was calculated through the Pearson correlation coefficient. RESULTS: The study included 15 endoscopists and 1,378 colonoscopies. The PSP detection rate ranged from 1.8-17% between endoscopists and had an almost perfect correlation with the CSSP detection rate (p = 0.922), as well as strongly correlating with the ADR (p = 0.769). CONCLUSIONS: There was great variability in the PSP detection rate between endoscopists. It also had an almost perfect correlation with the CSSP detection rate and strongly correlated with the ADR. Those results suggest a high CSSP miss rate at endoscopy and a low PSP detection rate.

Correlation and validity of imputed PaO2/FiO2 and SpO2/FiO2 in patients with invasive mechanical ventilation at 2600m above sea level.

OBJECTIVE: To establish the correlation and validity between PaO2/FiO2 obtained on arterial gases versus noninvasive methods (linear, nonlinear, logarithmic imputation of PaO2/FiO2 and SpO2/FiO2) in patients under mechanical ventilation living at high altitude. DESIGN: Ambispective descriptive multicenter cohort study. SETTING: Two intensive care units (ICU) from Colombia at 2600m a.s.l. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients older than 18 years with at least 24h of mechanical ventilation were included from June 2016 to June 2019. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, physiological messures, laboratory findings, oxygenation index and clinical condition. Nonlinear, linear and logarithmic imputation formulas were used to calculate PaO2 from SpO2, and at the same time the SpO2/FiO2 by severe hypoxemia diagnosis. The intraclass correlation coefficient, area under the ROC curve, sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratio were calculated. RESULTS: The correlation between PaO2/FiO2 obtained from arterial gases, PaO2/FiO2 derived from one of the proposed methods (linear, non-linear, and logarithmic formula), and SpO2/FiO2 measured by the intraclass correlation coefficient was high (greater than 0.77, p<0.001). The different imputation methods and SpO2/FiO2 have a similar diagnostic performance in patients with severe hypoxemia (PaO2/FiO2 <150). PaO2/FiO2 linear imputation AUC ROC 0,84 (IC 0.81-0.87, p<0.001), PaO2/FiO2 logarithmic imputation AUC ROC 0.84 (IC 0.80-0.87, p<0.001), PaO2/FiO2 non-linear imputation AUC ROC 0.82 (IC 0.79-0.85, p<0.001), SpO2/FiO2 oximetry AUC ROC 0.84 (IC 0.81-0.87, p<0.001). CONCLUSIONS: At high altitude, the SaO2/FiO2 ratio and the imputed PaO2/FiO2 ratio have similar diagnostic performance in patients with severe hypoxemia ventilated by various pathological conditions.

SEOM clinical guideline for management of adult medulloblastoma (2020)

Recent advances in molecular profiling, have reclassified medulloblastoma, an undifferentiated tumor of the posterior fossa, in at least four diseases, each one with differences in prognosis, epidemiology and sensibility to different treatments. The recommended management of a lesion with radiological characteristics suggestive of MB includes maximum safe resection followed by a post-surgical MR < 48 h, LCR cytology and MR of the neuroaxis. Prognostic factors, such as presence of a residual tumor volume > 1.5 cm2, presence of micro- or macroscopic dissemination, and age > 3 years as well as pathological (presence of anaplastic or large cell features) and molecular findings (group, 4, 3 or p53 SHH mutated subgroup) determine the risk of relapse and should guide adjuvant management. Although there is evidence that both high-risk patients and to a lesser degree, standard-risk patients benefit from adjuvant craneoespinal radiation followed by consolidation chemotherapy, tolerability is a concern in adult patients, leading invariably to dose reductions. Treatment after relapse is to be considered palliative and inclusion on clinical trials, focusing on the molecular alterations that define each subgroup, should be encouraged. Selected patients can benefit from surgical rescue or targeted radiation or high-dose chemotherapy followed by autologous self-transplant. Even in patients that are cured by chemorradiation presence of significant sequelae is common and patients must undergo lifelong follow-up (AU)

SEOM clinical guideline for management of adult medulloblastoma (2020).

Recent advances in molecular profiling, have reclassified medulloblastoma, an undifferentiated tumor of the posterior fossa, in at least four diseases, each one with differences in prognosis, epidemiology and sensibility to different treatments. The recommended management of a lesion with radiological characteristics suggestive of MB includes maximum safe resection followed by a post-surgical MR < 48 h, LCR cytology and MR of the neuroaxis. Prognostic factors, such as presence of a residual tumor volume > 1.5 cm2, presence of micro- or macroscopic dissemination, and age > 3 years as well as pathological (presence of anaplastic or large cell features) and molecular findings (group, 4, 3 or p53 SHH mutated subgroup) determine the risk of relapse and should guide adjuvant management. Although there is evidence that both high-risk patients and to a lesser degree, standard-risk patients benefit from adjuvant craneoespinal radiation followed by consolidation chemotherapy, tolerability is a concern in adult patients, leading invariably to dose reductions. Treatment after relapse is to be considered palliative and inclusion on clinical trials, focusing on the molecular alterations that define each subgroup, should be encouraged. Selected patients can benefit from surgical rescue or targeted radiation or high-dose chemotherapy followed by autologous self-transplant. Even in patients that are cured by chemorradiation presence of significant sequelae is common and patients must undergo lifelong follow-up.

Efficacy of Bifidobacterium breve CECT7263 for infantile colic treatment: an open-label, parallel, randomised, controlled trial.

Infantile colic is a prevalent condition characterised by excessive crying with no effective treatment available. We aimed to evaluate the efficacy of Bifidobacterium breve CECT7263 and a combination of this and Lactobacillus fermentum CECT5716 versus simethicone in reducing the daily time spent crying in colicky infants. A multicentre randomised, open-label, parallel, controlled trial of 28 days was performed in 150 infants who were diagnosed with colic according to the Rome III criteria and who randomly received simethicone (80 mg/day; Simethicone group), B. breve CECT7263 (2×108 cfu/day, Bb group), or a combination of L. fermentum CECT5716 and B. breve CECT7263 (1×108 cfu/day per strain, Bb+Lf group). The main outcomes were minutes of crying per day and the percentage of reduction in daily crying from baseline. Data were analysed per intention to treat. All treatments significantly decreased the daily crying time at the end of the intervention (P-time <0.001). However, the infants in the Bb group had significantly decreased crying time from the first week of the study (P<0.05), whereas the Bb+Lf group and the simethicone group had significantly decreased crying time from the second week (P<0.05). The percentage of reduction in the minutes of crying from baseline in the Bb group was significantly higher than that in the Simethicone group every week of the intervention (-40.3 vs -27.6% at 1-week; -59.2 vs -43.2% at 2-weeks; -64.5 vs -53.5% at 3-week and -68.5 vs -59.5% at 4-weeks, P<0.05). Additionally, in the Bb group, infants had better night sleep, and parents reported a more positive mood at the end of the intervention. All the products used in the study were safe and well tolerated. In conclusion, the breastmilk-isolated probiotic strain B. breve CECT7263 is a safe and effective treatment for infantile colic, presenting an earlier and more robust effect than the reference prescribed drug, simethicone.

Correlation between proximal serrated polyp detection and clinically significant serrated polyps: inter-endoscopist variability. / Correlación entre la detección de pólipos serratos proximales y pólipos serratos clínicamente significativos: variabilidad interendoscopista.

INTRODUCTION AND AIMS: The adenoma detection rate (ADR) is the most important quality indicator for the prevention of colorectal cancer but serrated polyps are also precursor lesions of the disease. The aim of our study was to compare the detection rate of proximal serrated polyps (PSPs) and that of clinically significant serrated polyps (CSSPs) between endoscopists and analyze the relation of those parameters to the ADR. METHODS: An observational, prospective, cross-sectional study was conducted on all patients that underwent colonoscopy at the Policlínico Peruano Japonés within the time frame of July 2015 and August 2016. The ADR and PSP and CSSP detection rates between endoscopists were compared through multivariate logistic regression and the association between those parameters was calculated through the Pearson correlation coefficient. RESULTS: The study included 15 endoscopists and 1,378 colonoscopies. The PSP detection rate ranged from 1.8-17% between endoscopists and had an almost perfect correlation with the CSSP detection rate (p = 0.922), as well as strongly correlating with the ADR (p = 0.769). CONCLUSIONS: There was great variability in the PSP detection rate between endoscopists. It also had an almost perfect correlation with the CSSP detection rate and strongly correlated with the ADR. Those results suggest a high CSSP miss rate at endoscopy and a low PSP detection rate.

La adherencia a los medicamentos en pacientes hipertensos y en muestra de la población general / Characterization of medication adherence in a sample of the general population and another of hypertensive patients in Panama

OBJETIVO: Caracterizar la adherencia al tratamiento farmacológico en la población adulta, y en pacientes hipertensos atendidos en dos centros de atención primaria de la Caja de Seguro Social en Panamá. MÉTODOS: Aplicación de encuesta poblacional sobre la adherencia medicamentosa a 1.200 personas en las 4 ciudades de mayor población y crecimiento económico en Panamá y otra encuesta a pacientes hipertensos atendidos en centros de atención primaria de la Seguridad Social, durante los meses de septiembre a octubre del 2016. RESULTADOS: De 1.200 personas que participaron en la encuesta, 671 tomaban medicamentos, 54% eran mujeres y 54% con estudios universitarios. El 91% manifestaron padecer algún tipo de enfermedad y uso de diversos medicamentos. El 55% contestó que alguna vez había olvidado tomar el medicamento. Fueron 176 pacientes encuestados en los centros de atención primaria, 67% mujeres, 42% con grado universitario. El 97% eran hipertensos, 48% diabéticos. El 80% de los hipertensos tomaban diversos medicamentos. Al aplicarse el test de Morisky-Green a los pacientes, el 40% indicó haber dejado de tomar los medicamentos por lo tanto no cumplían con la farmacoterapia ordenada. De acuerdo al test de Batalla, los pacientes mostraron tener un gran conocimiento sobre su enfermedad. CONCLUSIONES: La mayoría de la población encuestada sufría HTA y habían olvidado tomar los medicamentos. Los pacientes reconocieron padecer y conocer la hipertensión, sin embargo, no fueron adherentes al tratamiento medicamentoso. Se hace necesario una toma de conciencia y participación en el control de su enfermedad e impulsar campañas nacionales sobre la adherencia medicamentosa

OBJECTIVE: To characterize adherence to pharmacological treatment in the adult population, and in hypertensive patients treated in two primary care centers of the Social Security in Panama. METHODS: A survey on drug adherence was applied to 1,200 study participants in 4 major cities in Panama. The survey for hypertensive patients was applied in primary health care centers. RESULTS: Of 1,200 study participants, 671 were taking medications, 54% were women and 54% university degrees. 91% reported suffering from some type of illness and use of various medications. 55% replied that they had once forgotten to take the medication whereas 80% of the participants said they forget medication intake frequently. There were 176 hypertensive patients survey in primary care centers, 67% women, and 42% with university degree. 97% were hypertensive and 48% diabetic. 80% of patients with hypertension took various medications. When the Morisky-Green test was applied to patients, 40% indicated that they stopped taking the medications; therefore, they did not comply with the ordered pharmacotherapy. According to the Batalla test, patients showed great knowledge about their disease. CONCLUSIONS: The majority of the population surveyed suffered from hypertension and had forgotten to take the medications. The patients recognized suffering and knowing the hypertension, however, they were not adherent to the drug treatment. Awareness and participation in the control of your disease is necessary and to promote national campaigns on drug adherence

Evaluation of the safety, tolerance and efficacy of 1-year consumption of infant formula supplemented with Lactobacillus fermentum CECT5716 Lc40 or Bifidobacterium breve CECT7263: a randomized controlled trial.

BACKGROUND: The microorganism present in breast milk, added to other factors, determine the colonization of infants. The objective of the present study is to evaluate the safety, tolerance and effects of the consumption of a milk formula during the first year of life that is supplemented with L. fermentum CECT5716 or Bifidobacterium breve CECT7263, two strains originally isolated from breast milk. METHODS: A randomized, double blind, controlled, parallel group study including healthy, formula-fed infants was conducted. Two hundred and thirty-six 1-month-old infants were selected and randomly divided into three study groups according to a randomization list. Infants in the control group received a standard powdered infant formula until 12 months of age. Infants in the probiotic groups received the same infant formula but supplemented with L. fermentum CECT5716 Lc40 or B. breve CECT7263. Main outcome was weigh-gain of infants as safety marker. RESULTS: One hundred and eighty-nine infants completed the eleven months of intervention (61 in control group, 65 in Lf group and 63 in Bb group). The growth of infants in the three groups was consistent with standards. No significant differences were observed in the main outcome, weight-gain (Control group: 5.77 Kg ± 0.95, Lf group: 5.77 Kg ± 1.31, Bb group: 5.58 Kg ± 1.10; p = 0.527). The three milk formulae were well tolerated, and no adverse effects were related to the consumption of any of the formula. Infants receiving B. breve CECT7263 had a 1.7 times lower risk of crying than the control group (OR = 0.569, CI 95% 0.568-0.571; p = 0.001). On the other hand, the incidence of diarrhoea in infants receiving the formula supplemented with L. fermentum CECT5716 was a 44% lower than in infants receiving the control formula (p = 0.014). The consumption of this Lactobacillus strain also reduced the duration of diarrhoea by 2.5 days versus control group (p = 0.044). CONCLUSIONS: The addition of L. fermentum CECT5716 Lc40 or B. breve CECT7263, two probiotic strains naturally found in breast milk, to infant formulae is safe and induces beneficial effects on the health of infants. TRIAL REGISTRATION: The trial was retrospectively registered in the US Library of Medicine ( www.clinicaltrial.gov ) with the number NCT03204630 . Registered 11 August 2016.

First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD).

BACKGROUND: Treatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC. METHODS: Frail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features. MAIN OBJECTIVE: to assess progression-free survival (PFS) rate at 6 months. Treatment consisted of 28-day cycles of orally administered regorafenib 160 mg/day (3 weeks followed by 1 week rest). RESULTS: Forty-seven patients were included in the study. Median age was 81 years (range 63-89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6 months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6 months (95%CI 2.7-8.4). Median overall survival (OS) was 16 months (95%CI 7.8-24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3-4 adverse events (AEs). The most common grade 3-4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%). CONCLUSIONS: The study did not meet the pre-specified boundary of 55% PFS rate at 6 months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach. TRIAL REGISTRATION: This trial was prospectively registered at EudraCT ( 2013-000236-94 ). Date of trial registration: April 9th, 2013.

Fauna parasitária e relação parasito-hospedeiro de tambaquis criados na região do Baixo São Francisco, nordeste do Brasil / Parasitic fauna and parasite-host relationship of tambaqui reared in São Francisco river basin, Brazilian northeast

Este trabalho teve como objetivo avaliar a fauna parasitária de tambaquis na região do Baixo São Francisco-AL/SE-Brasil e correlacionar os índices de prevalência e intensidade média com fatores bióticos e abióticos. Foram coletados 252 espécimes para análise parasitológica de 10 pisciculturas. Os parasitos foram contabilizados, identificados, e determinaram-se os índices de prevalência e intensidade média, que foram correlacionados com fatores bióticos e abióticos. Dos peixes coletados, 65,5% estavam parasitados por pelo menos um táxon. Foram encontrados 10 táxons: Monogeneas, Ichthyophthirius multifiliis, tricodinídeos, Piscinoodinium pillulare, Ichthyobodo sp., Dolops carvalhoi, Lernaea cyprinacea, Procamallanus (Spirocamallanus) inopinatus, Henneguya sp. e Myxobolus sp. As maiores prevalências foram encontradas para Monogeneas (49,2%) e Myxobolus sp. (31,5%). Correlações negativas entre prevalência e fatores bióticos (peso e comprimento) foram observadas para Monogeneas (r2= -0,49; r2= -0,43), Myxobolus sp. (r²= -0,46; r²= -0,39) e Henneguya sp. (r²= -0,41; r²= -0,39). O fator abiótico temperatura apresentou correlação negativa com as prevalências de Lernaea cyprinacea (r= -0,39) e tricodinídeos (r= -0,33), enquanto a condutividade elétrica apresentou correlação positiva (r= 0,40) com a prevalência de tricodinídeos. Conclui-se que a fauna parasitária dos tambaquis cultivados na região do Baixo São Francisco é diversificada e com a carga parasitária dependente da qualidade de água e do estágio de desenvolvimento dos peixes.(AU)

This study investigated the parasitic fauna of tambaquis reared in lower Sao Francisco region-Al/SE-Brazil correlating parasitic indices to abiotic and biotic factors. A total of 252 specimens of tambaqui were collected in ten fish farms for parasitological analysis. The parasites were counted, identified and the parasitological indices were determined and correlated to biotic and abiotic factors. Of all collected fish, 65,5 % were parasitized by at least one taxon. Ten taxa were found: Monogeneans, Ichthyophthirius multifiliis, trichodinids Piscinoodinium pillulare, Ichthyobodo sp, Dolops carvalhoi, Lernaea cyprinacea, Procamallanus (Spirocamallanus) inopinatus, Henneguya sp. and Myxobolus sp. The higher prevalences were found to monogeneans (49.2%) and Myxobolus sp. (31.5%). Negative correlation of prevalence and biotic factor (weight and length) were observed to monogeneans (r 2 = -0.49, r 2 = -0.43), Myxobolus sp (r²= -0.46; r²= -0.39) and Henneguya sp (r²= -0.41; r²= -0.39). Abiotic factor of temperature presented a negative correlation to prevalence of Lernaea cyprinacea and trichodinids (r= -0.39 e r= -0.33, respectively) and the electric conductivity presented positive correlation to trichodinids (r= 0.40). It was concluded that parasitic fauna of tambaquis cultured in Lower São Francisco region is diversified and the parasitic load dependent on water parameters and fish growth.(AU)

In vivo selection for Haemonchus contortus resistance to monepantel.

Gastrointestinal nematodes significantly affect the ovine industry, and Haemonchus contortus is considered the most pathogenic parasite in tropical regions. This situation is aggravated when the main strategy to control worms fails because of the genetic resistance that parasites acquire against anthelmintics. Aiming to anticipate the events involved in anthelmintic resistance, we induced monepantel resistance in H. contortus by in vivo subdosing of sheep hosts. Four successive passages of a monepantel-susceptible H. contortus isolate in Santa Ines or Ile de France sheep hosts resulted in three monepantel-resistant (efficacy varying from 0 to 58.5%) H. contortus isolates. Sheep hosts were treated from 0.075 mg/kg to the therapeutic dose of 2.5 mg/kg of monepantel in 19-26 rounds of selection for 112-133 weeks. Success in inducing H. contortus resistance to monepantel may have been affected by worm burden and by host-parasite interactions, including a possible effect of the breed of sheep hosts. We conclude that subdosing of sheep, although time-consuming, is an efficient in vivo strategy for the induction of monepantel resistance in H. contortus. The resistant parasites can be used in further studies to elucidate the genetic and biochemical events involved in the acquisition of anthelmintic resistance.

SEOM clinical guidelines for diagnosis and treatment of metastatic colorectal cancer (2018)

Colorectal cancer (CRC) is the second cause of cancer death in Spain, the objective of this guide published by the Spanish Society of Medical Oncology is to develop a consensus for the diagnosis and management of metastatic disease. The optimal treatment strategy for patients with metastatic CRC should be discussed in a multidisciplinary expert team to select the most appropriate treatment, and integrate systemic treatment and other options such as surgery and ablative techniques depending on the characteristics of the tumour, the patient and the location of the disease and metastases

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SEOM clinical guidelines for diagnosis and treatment of metastatic colorectal cancer (2018).

Colorectal cancer (CRC) is the second cause of cancer death in Spain, the objective of this guide published by the Spanish Society of Medical Oncology is to develop a consensus for the diagnosis and management of metastatic disease. The optimal treatment strategy for patients with metastatic CRC should be discussed in a multidisciplinary expert team to select the most appropriate treatment, and integrate systemic treatment and other options such as surgery and ablative techniques depending on the characteristics of the tumour, the patient and the location of the disease and metastases.

Molecular mechanisms involved in the protective actions of Selective Estrogen Receptor Modulators in brain cells.

Synthetic selective modulators of the estrogen receptors (SERMs) have shown to protect neurons and glial cells against toxic insults. Among the most relevant beneficial effects attributed to these compounds are the regulation of inflammation, attenuation of astrogliosis and microglial activation, prevention of excitotoxicity and as a consequence the reduction of neuronal cell death. Under pathological conditions, the mechanism of action of the SERMs involves the activation of estrogen receptors (ERs) and G protein-coupled receptor for estrogens (GRP30). These receptors trigger neuroprotective responses such as increasing the expression of antioxidants and the activation of kinase-mediated survival signaling pathways. Despite the advances in the knowledge of the pathways activated by the SERMs, their mechanism of action is still not entirely clear, and there are several controversies. In this review, we focused on the molecular pathways activated by SERMs in brain cells, mainly astrocytes, as a response to treatment with raloxifene and tamoxifen.

First-line mFOLFOX plus cetuximab followed by mFOLFOX plus cetuximab or single-agent cetuximab as maintenance therapy in patients with metastatic colorectal cancer: Phase II randomised MACRO2 TTD study.

BACKGROUND: This multicentre, randomised, and phase II study evaluated mFOLFOX+cetuximab followed by maintenance mFOLFOX+cetuximab or single-agent cetuximab in metastatic colorectal cancer (mCRC) patients (NCT01161316). PATIENTS AND METHODS: Previously, untreated mCRC patients (wild-type KRAS) were randomised to receive cetuximab+mFOLFOX-6 (8 cycles for 2 weeks) followed by maintenance therapy: single-agent cetuximab (Arm-A) or mFOLFOX-6 + cetuximab (Arm-B) until progression. Primary endpoint was progression-free survival (PFS) at 9 months. RESULTS: One hundred ninety-three patients (median [range] age 60 [33-74] years) were randomised (2:1): 129 Arm-A versus 64 Arm-B. PFS at 9 months (95% confidence interval) showed non-inferiority between arms (Arm-A/Arm-B: 60 [52, 69]%/72 [61, 83]%, p [non-inferiority]<0.1). There were no statistically significant differences in the PFS (Arm-A/Arm-B: 9 [95% CI 7, 10] months/10 [7,13] months, hazard ratio [HR] = 1.19 [0.80, 1.79]) or overall survival (23 [19, 28] months/27 [18, 36] months, HR = 1.24 [0.85, 1.79]) between arms. The objective response rate was also similar (48 [39, 57]%/39 [27, 52]%). The safety profile was similar between arms, and all patients experienced at least one adverse event (AE) (Arm-A/Arm-B grade ≥III AEs: 70%/68%). The most common grade ≥III AEs were as follows: neutropenia (Arm-A/Arm-B: 28%/26%), rash acneiform (15%/24%) and sensory neuropathy (2%/15%) in any group. Arm-A was associated with less grade ≥III rash and sensory neuropathy and a lower rate of serious AEs (20%/27%). CONCLUSION(S): This phase II exploratory trial with a non-inferiority design suggests that maintenance therapy with single-agent cetuximab following mFOLFOX+cetuximab induction could be a valuable option compared with mFOLFOX+cetuximab treatment continuation. We await phase III trials to confirm single-agent cetuximab as maintenance therapy in mCRC patients.

Long-term outcomes of transmesenteric portal vein recanalization for the treatment of chronic portal vein thrombosis after pediatric liver transplantation.

Portal vein thrombosis (PVT) may occur at any time following liver transplantation. We describe our experience with portal vein recanalization in cases of thrombosis after liver transplantation. Twenty-eight children (5%) out of 566 liver transplant recipients underwent portal vein recanalization using a transmesenteric approach. All children received left hepatic segments, developed PVT, and had symptoms or signs of portal hypertension. Portal vein recanalization was performed via the transmesenteric route in all cases. Twenty-two (78.6%) patients underwent successful recanalization and stent placement. They received oral anticoagulants after the procedure, and clinical symptoms subsided. Symptoms recurred due to portal vein restenosis/thrombosis in seven patients. On an intention-to-treat basis, the success rate of the proposed treatment was 60.7%. Only 17 out of 28 children with posttransplant chronic PVT retained stent patency (primary + assisted) at the end of the study period. In cases of portal vein obstruction, the transmesenteric approach via minilaparotomy is technically feasible with good clinical and hemodynamic results. It is an alternative procedure to reestablish the portal flow to the liver graft that can be performed in selected cases and a therapeutic addition to other treatment strategies currently used to treat chronic PVT.