Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure.

BACKGROUND AND AIMS: Oxaliplatin (OX) has been described as a potential etiologic agent for porto-sinusoidal vascular disorder (PSVD). Our aim was to describe the natural history of PSVD due to OX in colon cancer (CRC) and identify risk factors for its development. METHODS: We made a multicenter retrospective case-control (ratio 1:3) study with patients diagnosed of PSVD-OX. Baseline data, end of treatment, years of follow-up and diagnosis of PSVD were collected and compared to controls (without PSVD). Besides, 16 different SNPs were selected from bibliography and analyzed by genotyping in the case group to identify potential genetic risk factors. RESULTS: 41 cases were identified, with a median time to PSVD diagnosis after the end of OX of 34 months. Spleen diameter was the strongest predictor of PSVD during treatment (OR 43.94 (14.48-133.336); p < 0.0001). Additionally, thrombocytopenia (<150 × 10^9) at one year was a significant disease risk marker (OR 9.35; 95% CI: 3.71-23.58; p = 0.001). We could not establish any significant association between the selected SNPs and PSVD diagnosis. CONCLUSION: The increase of spleen diameter is the strongest predictor of PSVD in patients treated with OX for CRC. These patients could be candidates for a specific follow-up of portal hypertension-related complications.

Hipotensión intracraneal espontánea. Una puesta al día

Introducción: La hipotensión intracraneal espontánea es un síndrome causado por la disminución del volumen de líquido cefalorraquídeo consecuencia de su fuga al espacio extradural. Aunque la ICHD-3 proporciona un alto nivel de especificidad diagnóstica, esta enfermedad puede manifestarse de forma atípica. Hasta en un 30% no es posible establecer el punto de escape, pero con el refinamiento de los exámenes de imágenes este porcentaje se ha reducido a un 15%-20%. Actualmente, su manejo no se encuentra estandarizado y las recomendaciones se basan en evidencia de limitada calidad metodológica, además de la variabilidad de protocolos entre distintos centros. Desarrollo En esta revisión actualizamos los procedimientos diagnósticos y terapéuticos. Por un lado, analizamos el rol de la resonancia nuclear magnética de encéfalo y médula espinal completa como primer paso diagnóstico y, por otro lado, señalamos los exámenes destinados a determinar la fuga de líquido cefalorraquídeo. Tal es el caso de la mielo-resonancia, la mielo-tomografía computarizada, tanto estándar, dinámica y por sustracción digital, además de la cisternografía con 111-Indium-DPTA. Sin embargo, determinar cuál de estos exámenes es el óptimo es objeto de debate. Lo mismo ocurre con el tratamiento: reposo; parche sanguíneo epidural a ciegas, parche guiado por fluoroscopia o tomografía computarizada, parche de fibrina; o cirugía. Conclusiones Se requiere de una mayor investigación, especialmente con trabajos multicéntricos controlados, para una mejor comprensión de la fisiopatología, el diagnóstico por imágenes, los enfoques terapéuticos y evaluación objetiva de los resultados clínicos. Solo así se establecerán pautas diagnósticas y de tratamiento validadas.

Introducction: Spontaneous intracranial hypotension is a syndrome caused by decreased CSF volume secondary to its leakage into the extradural space Although ICHD-3 provides a high level of diagnostic specificity, manifestations may be atypical, making diagnosis challenging. The site of leakage may be undetermined in point Up to 30% of cases, although with recent refinement of imaging, this percentage has been reduced to 15-20%. Currently, management is not standardized and recommendations are based on inconclusive evidence, with variability of protocols between centres. Development. In this review, we update diagnostic and therapeutic procedures. We analyse the role of whole brain and spinal cord MRI as a first investigation and review tests aimed at determining cerebrospinal fluid leakage, such as MRI myelography, conventional CT myelography, dynamic CT myelography, and digital subtraction CT myelography, as well as 111-Indium-DPTA cisternography. Determining optimal use of these investigations remains a matter of debate. The same is true for treatment: rest, blind epidural blood patch, fluoroscopy or CT-guided epidural blood patch, fibrin patch and surgery are discussed. Conclusión: Further research, especially multicentre controlled studies, is required to improve understanding of pathophysiology, diagnostic imaging, therapeutic approaches and to objectively assess clinical outcomes. Only then will diagnostic and treatment guidelines be evidence-based.

Pharmaceutical active compounds in sewage sludge: Degradation improvement and conversion into an organic amendment by bioaugmentation-composting processes.

Around 143,000 chemicals find their fate in wastewater treatment plants in the European Union. Low efficiency on their removal at lab-based studies and even poorer performance at large scale experiments have been reported. Here, a coupled biological technology (bioaugmentation and composting) is proposed and proved for pharmaceutical active compounds degradation and toxicity reduction. The optimization was conducted through in situ inoculation of Penicillium oxalicum XD 3.1 and an enriched consortium (obtained from non-digested sewage sludge), into pilot scale piles of sewage sludge under real conditions. This bioaugmentation-composting system allowed a better performance of micropollutants degradation (21 % from the total pharmaceuticals detected at the beginning of the experiment) than a traditional composting process. Particularly, inoculation with P. oxalicum allowed the degradation of some recalcitrant compounds like carbamazepine, cotinine and methadone, and also produced better stabilization features in the mature compost (significant passivation of copper and zinc, higher macronutrients value, adequate physicochemical conditions for soil direct application and less toxic effect on germination) compared to the control and the enriched culture. These findings provide a feasible, alternative strategy to obtain a safer mature compost and a better removal of micropollutants performance at large scale.

Microbial indicators of efficient performance in an anaerobic/anoxic/aerobic integrated fixed-film activated sludge (A2O-IFAS) and a two-stage mesophilic anaerobic digestion process.

An analysis of the community structure, diversity and population dynamics of Bacteria and Archaea in the suspended and attached biomass fractions of a pilot-scale anaerobic/anoxic/aerobic integrated fixed-film activated sludge (A2O-IFAS) was executed. Along with this, the effluents of the acidogenic (AcD) and methanogenic (MD) digesters of a two-stage mesophilic anaerobic (MAD) system treating the primary sludge (PS) and waste activated sludge (WAS) generated by the A2O-IFAS were also analyzed. Non-metric multidimensional scaling (MDS) and Biota-environment (BIO-ENV) multivariate analyses were performed to link population dynamics of Bacteria and Archaea to operating parameters and removal efficiencies of organic matter and nutrients, in search of microbial indicators associated with optimal performance. In all samples analyzed, Proteobacteria, Bacteroidetes and Chloroflexi were the most abundant phyla, while the hydrogenotrophic methanogens Methanolinea, Methanocorpusculum and Methanobacterium were the predominant archaeal genera. BIO-ENV analysis disclosed strong correlations between the population shifts observed in the suspended and attached bacterial communities of the A2O-IFAS and the removal rates of organic matter, N and P. It is noteworthy that the incorporation of carriers combined with a short sludge retention time (SRT = 4.0 ± 1.0 days) enhanced N removal performance of the A2O by favoring the enrichment of bacterial genera able to denitrify (Bosea, Dechloromonas, Devosia, Hyphomicrobium, Rhodobacter, Rhodoplanes, Rubrivivax, and Sulfuritalea) in the attached biomass fraction. In addition, operation at short SRT enabled the generation of a highly biodegradable WAS, which enhanced the biogas and methane yields in the two-stage MAD. An increase in the relative abundance of Acetobacteroides (uncultured Blvii28 wastewater-sludge group of Rikenellaceae family) correlated positively with the volatile solids removal rate (%VSR), CH4 recovery rate and %CH4 in the biogas (r > 0.8), supporting their relevance for an efficient methanogenesis in two-stage systems.

Shift change handovers between nurses in Critical Care Units.

AIM: To know the characteristics of the handover performed by nurses working in Critical Care Units in Spain. METHODS: Descriptive and cross-sectional study, whose population was nurses working in Critical Care Units in Spain. An ad hoc questionnaire was used to explore the characteristics of the process, the training received, the information forgotten and the influence of this activity on patient care. The questionnaire was online and dissemination was done through social networks. The sample was selected by convenience. A descriptive analysis was performed according to the nature of the variables and comparison of groups through ANOVA with R software version 4.0.3 (R Project for Statistical Computing). RESULTS: The sample was 420 nurses. Most of them answered that (79,5%) perform this activity in an individual way, from outgoing nurse to incoming nurse. Location varied according to the size of the unit (p<0,05). Interdisciplinary handover was rare (p<0.05). In the last month, with regard to the time of data collection, 29,5% had to contact the unit due to forgetting relevant information, using WhatsApp as the first channel to transmit this information. CONCLUSIONS: There is a lack of standardization in the handoff between shifts, in terms of the physical space where it is done, tools to structure the information, participation of other professionals and the use of unofficial communication channels to contact for omitted information during the handover. Shift change was identified as a vital process to ensure continuity of care and patient safety, so further researchs are important for patients handoffs.

Indications and results of sentinel lymph node biopsy in breast cancer: Changes observed in 2018 compared to 2012.

BACKGROUND AND OBJECTIVE: Over the last 15 years, breast cancer (BC) treatment has undergone numerous changes, which have also affected the indications for Sentinel Lymph Node Biopsy (SLNB) as well as the procedures depending on its outcome. The aim of this study is to compare the results of the SLNB carried out at our Center during 2012, when we stopped performing an axillary lymph node dissection (ALND) after the finding of a micrometastasis, with those conducted in 2018, when we started applying Z011 criteria. MATERIALS AND METHODS: We have performed a comparative retrospective observational study, including cN0 BC patients that underwent a SLNB in 2012 versus those that underwent this procedure in 2018. RESULTS: 174 patients from 2012 and 165 from 2018 were studied. We found significant differences between the two groups: in 2018 there were fewer lobular invasive cancers (14 vs 28) (P < .05), a smaller mean pathological size (P < .001), a higher proportion of HER2 and triple negative tumors (28 vs 49) (P < .01) and, finally, an increase in use of neoadjuvant treatments (42.0% vs 6.7%). Regarding axillary involvement, we observed a decrease in both the presence of a positive sentinel node (24.1% in 2018 vs 42.4% in 2012) (P < .0001) as well as in the proportion of ALND performed (12.6% in 2018 vs 21.2% in 2012) and the presence of positive non sentinel nodes after a ALND (59.1% vs74.3%) (ns) CONCLUSION: Although the 2018 cohort that underwent SLNB had more aggressive tumors, there were fewer positive SN and ALND performed. This is probably due to a more accurate radiological diagnosis with ultrasound, that enables to detect cN1 cases before surgery, and to the increasing use of neoadjuvant treatments that may downstage the axilla.

Insights into the removal of pharmaceutically active compounds from sewage sludge by two-stage mesophilic anaerobic digestion.

The removal efficiencies (REs) of twenty-seven pharmaceutically active compounds (PhACs) (eight analgesic/anti-inflammatories, six antibiotics, four ß-blockers, two antihypertensives/diuretics, three lipid regulators and four psychiatric drugs) were evaluated in a pilot-scale two-stage mesophilic anaerobic digestion (MAD) system treating thickened sewage sludge from a pilot-scale A2O™ wastewater treatment plant (WWTP) which was fed with wastewater from the pre-treatment of the full-scale WWTP Murcia Este (Murcia, Spain). The MAD system was long-term operated using two different sets of sludge retention times (SRTs) for the acidogenic (AcD) and methanogenic (MD) digesters (phase I, 2 and 12 days; and phase II, 5 and 24 days, in AcD and MD, respectively). Quantitative PCR (qPCR) and Illumina MiSeq sequencing were used to estimate the absolute abundance of Bacteria, Archaea, and Fungi and investigate the structure, diversity and population dynamics of their communities in the AcD and MD effluents. The extension of the SRT from 12 (phase I) to 24 days (phase II) in the MD was significantly linked with an improved removal of carbamazepine, clarithromycin, codeine, gemfibrozil, ibuprofen, lorazepam, and propranolol. The absolute abundances of total Bacteria and Archaea were higher in the MD regardless of the phase, while the diversity of bacterial and archaeal communities was lower in phase II, in both digesters. Non-metric multidimensional scaling (MDS) plots showed strong negative correlations among phyla Proteobacteria and Firmicutes and between genera Methanosaeta and Methanosarcina throughout the full experimental period. Strong positive correlations were revealed between the relative abundances of Methanospirillum and Methanoculleus and the methanogenesis performance parameters (volatile solids removal, CH4 recovery rate and %CH4 in the biogas), which were also related to longer SRT. The REs of several PhACs (naproxen, ketoprofen, ofloxacin, fenofibrate, trimethoprim, and atenolol) correlated positively (r > 0.75) with the relative abundances of specific bacterial and archaeal groups, suggesting their participation in biodegradation/biotransformation pathways.

Numerical simulation of the aqueous humor flow in the eye drainage system; a healthy and pathological condition comparison.

The present work describes the motion of aqueous humor through the anterior chamber and the trabecular drainage system, considering several distributions of the collector channels. The 3D computational model, implemented into the open-source software, was reconstructed from an optical coherence tomography. The model has been employed to simulate the aqueous humor dynamics considering buoyancy effects. The presence of the anterior chamber, the trabecular meshwork, and the Schlemm's canal were taken into consideration with 14 different distributions of collector channels. The influence of collector channels position on the intraocular pressure and shear stress has been analyzed, for a healthy and a glaucomatous condition. Aqueous humor velocity, pressure, temperature, wall shear stress, skin friction coefficient and Nusselt number, are presented for the different cases. The results indicate that the position of the collector channels has a strong influence on the wall shear stress on the Schlemm's canal and collector channels.

Impact of immune-mediated diseases in inflammatory bowel disease and implications in therapeutic approach.

Inflammatory bowel diseases (IBD) belong to the group of immune-mediated diseases (IMIDs). The effect of associated IMIDs in the prognosis in IBD is nowadays unknown. To describe IMIDs associated to IBD patients and evaluate differences linked to the presence or absence of IMIDs. A unicentric retrospective descriptive study was designed. A cohort of 1,448 patients were categorized according to the presence of IMIDs. Clinical characteristics were obtained from IBD database. Univariate and multivariate analysis were performed. 385 patients were diagnosed with associated IMIDs while 1,063 had no associated IMIDs. A prevalence of 26.6% IMIDs associated to IBD was observed. Asthma, skin psoriasis and rheumatoid diseases were most commonly found. Factors associated to the presence of IMIDs were women (OR 1.48; 95 CI 1.17-1.87) and Crohn's disease (OR 1.35; 95 CI 1.07-1.70). Patients with associated IMIDs required more immunomodulator (OR 1.61; 95 CI 1.27-2.43) and biological treatment (OR 1.81; 95 CI 1.47-2.43). More surgical risk was observed in multivariate analysis in those patients diagnosed with IMIDs prior to the onset of IBD (OR 3.71; 95% CI 2.1-6.56). We considered the presence of IMIDs a poor prognostic factor and suggest a closer monitoring of these patients.

Linking microbial diversity and population dynamics to the removal efficiency of pharmaceutically active compounds (PhACs) in an anaerobic/anoxic/aerobic (A2O) system.

The removal efficiencies (REs) of nineteen pharmaceutically active compounds (PhACs) (six antibiotics-clarithromycin, ofloxacin, sulfadiazine, sulfamethazine, sulfamethoxazole and trimethoprim -, four ß-blockers -atenolol, metoprolol, propranolol and sotalol-, two antihypertensives/diuretics -furosemide and hydrochlorothiazide-, three lipid regulators -bezafibrate, fenofibrate and gemfibrozil-, and four psychiatric medications -carbamazepine, diazepam, lorazepam and paroxetine) were ascertained in a pilot-scale anaerobic/anoxic/aerobic (A2O) system treating urban wastewater, long term operated during two experimental phases using different sets of environmental conditions and operating parameters. Illumina MiSeq sequencing was used to investigate the structure, diversity and population dynamics of bacteria, archaea and fungi communities in the activated sludge. The results showed that mixed liquor suspended solids (MLSS) and food-to-microorganisms ratio (F/M) were operational parameters significantly influencing the REs of five of the analyzed PhACs in the A2O system. Biota-environment (BIO-ENV) analysis revealed strong correlations between population shifts of the activated sludge community and the REs of PhACs of the different pharmaceutical families. Increased REs of clarithromycin, furosemide, bezafibrate and gemfibrozil were concomitant to higher relative abundances of bacterial phylotypes classified within the Rhodobacteraceae and Sphingomonadaceae (Alphaproteobacteria), while those of Betaproteobacteria, Chloroflexi and Methanomethylovorans (Euryarchaea) correlated positively with the REs of up to seven PhACs belonging to different therapeutic groups.

Numerical model of aqueous humor drainage: effects of collector channel position.

Glaucoma is a progressive and a degenerative eye disease that gradually deteriorates the vision. The origin of glaucoma is still under debate. Recent studies report that 50% of the aqueous humor outflow resistance resides on collector channels and Schlemm's canal (SC). This paper provides a descriptive analysis of the aqueous humor outflow through the anterior chamber, the trabecular meshwork (TM) and the SC. The aim of this work is to determine the influence of the collector channels position on the intraocular pressure (IOP) and its contribution to the development of glaucoma. Pressure and wall shear stress distributions are presented for four cases. The first case has an arrangement of collector channels according to micro CT (Gong and Francis, 2014). The remaining cases have an symmetrical distribution; case 2 has all open quadrants (AOQ), cases 3 have three quadrants completely open and just one quadrant semi closed (SCQ), and finally cases 4 consider that a quadrant is completely closed (CQ). Symmetrical and micro CT cases have 29 collector channels. The results show that the position and the opening of the collector channels have a strong influence on the IOP.

Assessment of ocular redness measurements obtained with keratograph 5M and correlation with subjective grading scales.

OBJECTIVE: To examine correlations between ocular redness scores provided by the Keratograph 5M and those determined using two image-based grading scales. METHODS: Observational prospective cross-sectional study. Two hundred and twenty six eyes of two hundred and twenty six participants (175 patients using anti-glaucoma eye drops and 51 subjects untreated). All subjects were scored automatically using the keratograph 5M. These redness scores (RS) were then correlated with the gradings provided by the Efron and McMonnies/Chapman-Davies scale (MC-D) scales (two observers). RESULTS: Excellent reproducibility was observed for both the Efron (weighted K=0.897, 95% CI 0.823-0.904) and MC-D (weighted K=0.783, 95% CI 0.752-0.795) scales. Keratograph RS and the scores obtained with both Efron (Spearman's Rho=0.43, P<0.001) and MC-D (Spearman's Rho=0.48, P<0.001) scales were significantly correlated. RS for the bulbar and limbal - nasal and temporal quadrants also correlated moderately with the two subjective scales. Through Bland Altman analysis, poor agreement was detected between the objective and subjective methods: agreement values for the Efron scale or MC-D scale (matching scorers between observers) versus overall RS showed high biases (-15.58 and -22.05 respectively) and wide limits of agreement (LOA) (-46.169 to 15.005 and -52.534 to 8.19 respectively). Lowest bias was observed between temporal limbal RS and Observer 2 Efron score (-0.04). CONCLUSIONS: Although it emerged as a reliable objective method, the keratograph 5M overestimated the scores compared with the subjective grading scales when used to grade the degree of ocular redness. Therefore, they should not be interchangeable methods.

Removal of anti-inflammatory/analgesic pharmaceuticals from urban wastewater in a pilot-scale A2O system: Linking performance and microbial population dynamics to operating variables.

In this study, the removal rates of eight anti-inflammatory and/or analgesic pharmaceuticals, AIAPs (acetaminophen, ibuprofen, naproxen, ketoprofen, diclofenac, codeine, indomethacin and propyphenazone) were assessed in a pilot-scale A2O system (including anaerobic/anoxic/aerobic zones), long term operated during two experimental phases using different sets of environmental conditions and operating parameters. qPCR was used to quantify the absolute abundances of total Bacteria, total Archaea, mycolic-acid containing filamentous Actinobacteria (Mycolata) and Fungi within the activated sludge microbial community developed in the system. Multivariate analyses and Spearman correlation coefficients were used in search of significant links among the removal rates of the AIAPs, the abundances of the targeted microbial groups in the activated sludge, and the changes of environmental/operating variables in the A2O system. Improved removal efficiencies of several of the AIAPs analyzed (acetaminophen, ibuprofen, naproxen, ketoprofen) were correlated to higher organic load in the influent water, higher concentration of mixed liquor suspended solids (MLSS), lower temperature and lower food-to-microorganisms ratio (F/M). Removal efficiencies of several pharmaceuticals correlated with increased abundances of Mycolata in the A2O system, pointing at this group of bacteria as candidate key players for AIAPs removal in activated sludge.

Análisis, por Simulación, de los Esfuerzos Cortantes en la Superficie del Iris, en Presencia de Lentes Fáquicos Intraoculares / Analysis, by Simulation, of shear stresses on the Surface of Iris, in Presence of Intraocular Factor Lenses

Resumen: En este estudio, se presenta una metodología para evaluar lentes fáquicos intraoculares, cuando el flujo del humor acuoso es asimétrico, debido a modificaciones en el área de salida del fluido. El objetivo es determinar el efecto que tienen las asimetrías del flujo del humor acuoso en el esfuerzo cortante sobre el iris y la córnea en presencia de un lente fáquico intraocular. Se considera la geometría del ojo propuesta por Repetto et al.,7 y se resuelve el flujo del humor acuso con y sin lente empleando simulaciones mediante el método de elemento finito. Para validar el método, se compara la solución numérica obtenida con los resultados de Tychsen et al.8 obteniendo valores del mismo orden. Los resultados obtenidos son perfiles de velocidad, líneas de corriente y esfuerzos cortantes en las superficies del iris y la córnea. El modelo no toma en cuenta las variaciones de la temperatura, por lo que no se consideran los efectos de flotación. Los resultados muestran que las asimetrías tienen un gran impacto en la dinámica del humor acuoso e incrementan los esfuerzos cortantes; sin embargo no son suficientes como para causar desprendimiento de las céluas del iris o de la córnea.

Abstract: The study presents a methodology to evaluate intraocular phakic lenses, considering asymmetric aqueous humor flow due to modified conditions of the fluid outlet area. The main objective is to determine the effect of asymmetries on shear stresses with and without phakik lenses. A finite element numerical simulation was developed using the eye geometry proposed by Repetto et al.6 The numerical method was tested with the results obtained by Tychsen et al.8, giving results of the same order of magnitude. Velocity profiles, pressure distribution and shear stress at the solid boundaries are shown. The model does not take into account temperature variations. Therefore no buoyancy effects were considered. The results show that the induced asymmetries have a significant impact on aqueous humor velocity and on shear forces; however the shear stresses are not sufficient to cause cell detachment so the lens can be considered as harmless.

Influencia de la Posición de los Canales Colectores en la Presión Intraocular / Influence of the Collector Channels on the Intraocular Pressure

RESUMEN: El objetivo del presente trabajo es determinar la influencia que tiene la posición de los canales colectores en la presión intraocular y su contribución en el desarrollo del glaucoma. Para realizar el análisis se llevaron acabo simulaciones numéricas utilizando el método de elemento finito para dos casos de estudio. El primer caso es un modelo simplificado de sección rectangular que simula el flujo entre dos canales colectores; el segundo modelo describe el flujo en todo el canal de Schlemm (CS), considerando que es un aro rígido de espesor constante, con cuatro distribuciones de los canales colectores. Se obtuvieron los perfiles de presión y velocidad en los dos casos. En el caso simplificado se tienen diferencias de 10 P a entre las presiones medias. El segundo modelo muestra que el arreglo simétrico tiene una distribución de presiones constante mientras que los casos asimétricos presentan variaciones de 2 P a. Los resultados confirman que la posición de los canales colectores tiene influencia en la presión intraocular. Este estudio da lugar a realizar un análisis en estado transitorio, considerando las propiedades elásticas del CS así como las variaciones de diámetro de los canales colectores.

ABSTRACT: The aim of the present study is to determine the influence of the position of the collecting channels on intraocular pressure and its contribution to the development of glaucoma. Numerical simulations were performed using the finite element method for two case studies. The first case is a simplified model of rectangular section that simulates the flow between two collecting channels. The second model describes flow throughout the Schlemm channel (CS), considering that it is a rigid ring of constant thickness, with four distributions of the collector channels. The pressure and velocity profiles are shown for both cases. In the simplified case, there are differences of 10 P a between the average pressures. The second model shows that the symmetric arrangement has a constant pressure distribution while the asymmetric cases have variations of 2 P a. The results confirm that the position of the collecting channels influences the intraocular pressure. This study shows that a transient analysis is needed to understand the whole process, considering the elastic properties of the CS as well as the variations of diameter of the collecting channels.