Serum phosphate is associated with increased risk of bone fragility fractures in hemodialysis patients.

BACKGROUND: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of CKD-MBD and bone fragility fractures in the COSMOS project. METHODS: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 hemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and PTH (exposure), was assessed using Standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables. RESULTS: During a median follow-up of 24 months 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months respectively. Baseline serum phosphate > 6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models (HR: 1.53[95%CI: 1.10-2.13] and HR: 1.44[95%CI: 1.02-2.05]. The significant association persisted after competitive risk analysis (subHR: 1.42[95%CI: 1.02-1.98]) but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH > 800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis. CONCLUSIONS: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in hemodialysis patients.

[Knowledge, use and opinion about written informed consent in primary healthcare nurses: CONOSER pilot project]. / Conocimiento, implementación y opinión acerca del consentimiento informado por escrito de las enfermeras de atención primaria: proyecto piloto CONOSER.

OBJECTIVE: To know the knowledge, implementation and opinion on informed consent of generalist nurses, specialists and primary care residents. DESIGN: Descriptive cross-sectional study using an online self-administered 'ad hoc' questionnaire. SETTING: Primary care nurses in Madrid, from November 2020 to March 2021. PARTICIPANTS: Sample of 114 nurses: 91 generalist, 20 specialists and 3 residents. MAIN MEASUREMENTS: Sociodemographics, knowledge, implementation and opinion. RESULTS: The response rate was 27.7%. As a general rule, 48.2% indicated that informed consent was collected verbally, as established by law, with differences being found between categories, this percentage being higher in specialists and residents (P=0.004), and within specialists in those who had obtained their speciality by internal resident nurse (IRN) (P<0.0001). In addition, specialists and residents were those who most identified the legal norm regulating informed consent (P<0.0001). In terms of implementation and opinion, all groups obtained similar results. DISCUSSION: There are no previous studies that have analysed these aspects of informed consent comparing the different categories. Studies from other healthcare and geographical areas show that nurses have greater knowledge, although the demand for specific training in bioethics and biolaw is greater in the nurses participating in this study. CONCLUSIONS: Nurses have adequate knowledge about informed consent, use it in clinical practice and have an appropriate conception of it, being higher in some items in specialist nurses IRN and in residents.

Predictors of severe COVID-19 in kidney transplant recipients in the different epidemic waves: Analysis of the Spanish Registry.

SARS-CoV-2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID-19 have been prospectively included in the Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID-19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p < .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti-COVID-19 treatment in the second wave (July-December) than in the first one (March-June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p < .001) but similar in critical patients (66.7% vs. 58.1%, p = .29). The interaction between age and time post-KT should be considered when selecting recipients for transplantation in the COVID-19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.

Three-wavelength broadband soot pyrometry technique for axisymmetric flames.

Soot temperature measurements in laminar flames are often performed through two-color broadband emission pyrometry (BEMI) or modulated absorption/emission (BMAE) techniques, using models to relate the ratio between flame intensities at two different wavelengths with soot temperature. To benefit from wider spectral range and increase the accuracy of experimental estimation of soot temperature, this work proposes a new approach that uses three-color broadband images captured with a basic color camera. The methodology is first validated through simulations using numerically generated flames from the CoFlame code and then used to retrieve soot temperature in an experimental campaign. The experimental results show that using three-color and BEMI provides smoother reconstruction of soot temperature than two-color and BMAE when small disturbances exist in the measured signals due to a reduced experimental noise effect. A sensitivity analysis shows that the retrieved temperature from three-color BEMI is more resilient to variations on the ratio of measured signals than BMAE, which is confirmed by an error propagation analysis based on a Monte Carlo approach.

Harmonizing and improving European education in prescribing: An overview of digital educational resources used in clinical pharmacology and therapeutics.

AIM: Improvement and harmonization of European clinical pharmacology and therapeutics (CPT) education is urgently required. Because digital educational resources can be easily shared, adapted to local situations and re-used widely across a variety of educational systems, they may be ideally suited for this purpose. METHODS: With a cross-sectional survey among principal CPT teachers in 279 out of 304 European medical schools, an overview and classification of digital resources was compiled. RESULTS: Teachers from 95 (34%) medical schools in 26 of 28 EU countries responded, 66 (70%) of whom used digital educational resources in their CPT curriculum. A total of 89 of such resources were described in detail, including e-learning (24%), simulators to teach pharmacokinetics and/or pharmacodynamics (10%), virtual patients (8%), and serious games (5%). Together, these resources covered 235 knowledge-based learning objectives, 88 skills, and 13 attitudes. Only one third (27) of the resources were in-part or totally free and only two were licensed open educational resources (free to use, distribute and adapt). A narrative overview of the largest, free and most novel resources is given. CONCLUSION: Digital educational resources, ranging from e-learning to virtual patients and games, are widely used for CPT education in EU medical schools. Learning objectives are based largely on knowledge rather than skills or attitudes. This may be improved by including more real-life clinical case scenarios. Moreover, the majority of resources are neither free nor open. Therefore, with a view to harmonizing international CPT education, more needs to be learned about why CPT teachers are not currently sharing their educational materials.

Use of tocilizumab in kidney transplant recipients with COVID-19.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.

Geographic and Temporal Variation of Distinct Intracellular Endosymbiont Strains of Wolbachia sp. in the Grasshopper Chorthippus parallelus: a Frequency-Dependent Mechanism?

Wolbachia is an intracellular endosymbiont that can produce a range of effects on host fitness, but the temporal dynamics of Wolbachia strains have rarely been experimentally evaluated. We compare interannual strain frequencies along a geographical region for understanding the forces that shape Wolbachia strain frequency in natural populations of its host, Chorthippus parallelus (Orthoptera, Acrididae). General linear models show that strain frequency changes significantly across geographical and temporal scales. Computer simulation allows to reject the compatibility of the observed patterns with either genetic drift or sampling errors. We use consecutive years to estimate total Wolbachia strain fitness. Our estimation of Wolbachia fitness is significant in most cases, within locality and between consecutive years, following a negatively frequency-dependent trend. Wolbachia spp. B and F strains show a temporal pattern of variation that is compatible with a negative frequency-dependent natural selection mechanism. Our results suggest that such a mechanism should be at least considered in future experimental and theoretical research strategies that attempt to understand Wolbachia biodiversity.

Spanish list of potentially inappropriate drugs in the elderly (ES-PIA project).

PURPOSE: In the last decades, different criteria have been developed for detecting inappropriate prescription in older patients. In Spain, translations and adaptations of international lists are available but it would be necessary a national list which could cope with the peculiarities of our health system, existing pharmaceutical market, and prescription habits. We propose in this project the creation of a Spanish potentially inappropriate drugs list which could be applicable in our clinical scenario. METHODS: We use a Delphi method involving 25 experts from different backgrounds (Clinical Pharmacology, Geriatrics, Rational Use of Drugs and Pharmacy, Primary Care and Pharmacoepidemiology, and Pharmacovigilance) that were asked to participate in two-round questionnaires. For analysis, current recommendations of Worth and Pigni were applied, and every statement was classified into one of three groups: strong, moderate, or low agreement. Statements with strong agreement were accepted to be part of the inadequate prescription list. Moderate agreement statements were selected to enter the second questionnaire, and statements with low agreement were further analyzed to determine if it was due to heterogeneity or due to dispersion in the answers. RESULTS: The first questionnaire consisted of 160 proposed sentences, of which 106 reached a high agreement, 32 a moderate agreement, and 22 a low agreement. All sentences proposed in the second questionnaire reached a strong agreement. The total accepted sentences were 138. CONCLUSIONS: We offer a list of inadequate prescription in older patients adapted to the Spanish pharmacopeia and according to the prescription habits in our environment.

Metabolic and molecular relative percentage coreduction in patients with locally advanced rectal cancer treated with neoadjuvant therapy.

PURPOSE: Vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor-1 (EGFR) and cyclooxygenase-2 (COX-2) stimulate key processes involved in tumour progression and are important targets for cancer therapeutics. (18)F-FDG maximum standardized uptake value (SUVmax) on PET/CT is a marker of tumour metabolic activity. The purpose of this study was to measure percentage reductions in SUVmax (∆SUVmax%), VEGFR-2 (∆VEGFR-2%), EGFR (∆EGFR%) and COX-2 (∆COX-2%) in patients with locally advanced rectal cancer (LARC) after preoperative treatment, and to correlate the changes in these markers of response with pathological response in terms of tumour regression grade (TRG) using Rödel's scale and long-term clinical outcome. METHODS: VEGFR-2, EGFR and COX-2 were measured using a quantitative and qualitative compound immunohistochemistry analysis (immunoreactive score) of the pretreatment endoscopic biopsy and definitive surgical specimens. Composite indexes using ∆SUVmax% and the three molecules were developed to differentiate patients with metabolic and molecular responses from nonresponders. Cox proportional hazards model was used to explore associations between the tumour markers, disease-free survival (DFS) and overall survival (OS). RESULTS: The analysis included 38 patients with a median follow-up of 86 months (range 5 - 113 months). The ∆VEGFR-2%/∆SUVmax% index correctly identified 13 of 19 pathological responders (TRG 3 and 4) and 17 of 19 nonresponders (TRG 0 - 2) (sensitivity 68 %, specificity 89 %, accuracy 79 %, positive predictive value 87 %, negative predictive value 74 %). In multivariate analysis, only the ∆VEGFR-2%/∆SUVmax% index was associated with DFS (HR 0.11, p = 0.001) and OS (HR 0.15, p = 0.02). CONCLUSION: In patients with LARC the ∆VEGFR-2%/∆SUVmax% response index is associated with outcome. Determination of the optimal diagnostic cut-off level for this novel biomarker association should be explored. Evaluation in a clinical trial is required to determine whether selected patients could benefit from treatment with a VEGFR-targeted therapeutic agent.

Thousands of chemical starting points for antimalarial lead identification.

Malaria is a devastating infection caused by protozoa of the genus Plasmodium. Drug resistance is widespread, no new chemical class of antimalarials has been introduced into clinical practice since 1996 and there is a recent rise of parasite strains with reduced sensitivity to the newest drugs. We screened nearly 2 million compounds in GlaxoSmithKline's chemical library for inhibitors of P. falciparum, of which 13,533 were confirmed to inhibit parasite growth by at least 80% at 2 microM concentration. More than 8,000 also showed potent activity against the multidrug resistant strain Dd2. Most (82%) compounds originate from internal company projects and are new to the malaria community. Analyses using historic assay data suggest several novel mechanisms of antimalarial action, such as inhibition of protein kinases and host-pathogen interaction related targets. Chemical structures and associated data are hereby made public to encourage additional drug lead identification efforts and further research into this disease.

A new role for reticulon-4B/NOGO-B in the intestinal epithelial barrier function and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by an impaired intestinal barrier function. We aimed to investigate the role of reticulon-4B (RTN-4B/NOGO-B), a structural protein of the endoplasmic reticulum, in intestinal barrier function and IBD. We used immunohistochemistry, confocal microscopy, real-time PCR, and Western blotting to study tissue distribution and expression levels of RTN-4B/NOGO-B in control and IBD samples from mouse and humans. We also targeted RTN-4B/NOGO-B using siRNAs in cultured human intestinal epithelial cell (IECs). Epithelial barrier permeability was assessed by transepithelial electrical resistance (TEER) measurement. RTN-4B/NOGO-B is expressed in the intestine mainly by IECs. Confocal microscopy revealed a colocalization of RTN-4B, E-cadherin, and polymerized actin fibers in tissue and cultured IECs. RTN-4B mRNA and protein expression were lower in the colon of IL-10(-/-) compared with wild-type mice. Colocalization of RTN-4B/E-cadherin/actin was reduced in the colon of IL-10(-/-) mice. Analysis of endoscopic biopsies from IBD patients showed a significant reduction of RTN-4B/NOGO-B expression in inflamed mucosa compared with control. Treatment of IECs with H2O2 reduced TEER values and triggered phosphorylation of RTN-4B in serine 107 residues as well as downregulation of RTN-4B expression. Acute RTN-4B/NOGO-B knockdown by siRNAs resulted in a decreased TEER values and reduction of E-cadherin and α-catenin expression and in the amount of F-actin-rich filaments in IECs. Epithelial RTN-4B/NOGO-B was downregulated in human and experimental IBD. RTN-4B participates in the intestinal epithelial barrier function, most likely via its involvement in E-cadherin, α-catenin expression, and actin cytoskeleton organization at sites of cell-to-cell contacts.

Human cytomegalovirus and Epstein-Barr virus infection impact on (18)F-FDG PET/CT SUVmax, CT volumetric and KRAS-based parameters of patients with locally advanced rectal cancer treated with neoadjuvant therapy.

PURPOSE: It has long been debated whether human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are associated with rectal cancer. The gene products of HCMV and EBV contribute to cell-cycle progression, mutagenesis, angiogenesis and immune evasion. The aim of this prospective study was to analyse the association between infection of a tumour by HCMV and EBV and clinical, histological, metabolic ((18)F-FDG uptake), volumetric (from CT) and molecular (KRAS status) features and long-term outcomes in a homogeneously treated group of patients with locally advanced rectal cancer. METHODS: HCMV and EBV were detected in pretreatment biopsies using polymerase chain reaction (PCR). The Cox proportional hazards regression model was used to explore associations between viral infection and disease-free survival (DFS) and overall survival (OS). RESULTS: We analysed 37 patients with a median follow-up of 74 months (range 5-173 months). Locoregional control, OS and DFS at 5 years were 93%, 74% and 71%, respectively. Patients with HCMV/EBV coinfection had a significantly higher maximum standardized uptake value than patients without viral coinfection (p = 0.02). Significant differences were also observed in staging and percentage relative reduction in tumour volume between patients with and without HCMV infection (p < 0.01) and EBV infection (p < 0.01). KRAS wildtype status was significantly more frequently observed in patients with EBV infection (p <0.01) and HCMV/EBV co-infection (p = 0.04). No significant differences were observed in OS or DFS between patients with and without EBV infection (p = 0.88 and 0.73), HCMV infection (p = 0.84 and 0.79), and EBV/CMV coinfection (p = 0.24 and 0.39). CONCLUSION: This pilot study showed that viral infections were associated with metabolic staging differences, and differences in the evolution of metabolic and volumetric parameters and KRAS mutations. Further findings of specific features will help determine the best candidates for metabolic and volumetric staging and restaging. Further toxicity profile findings will help to determine the best candidates for specific supportive treatment during pelvic chemoradiotherapy in patients with locally advanced rectal cancer.

Compared decline of residual kidney function in patients treated with automated peritoneal dialysis and continuous ambulatory peritoneal dialysis: a multicenter study.

BACKGROUND: There is controversy concerning the compared rates of decline of residual kidney function (RKF) in patients treated with continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). OBJECTIVES AND METHOD: Following an observational, multicenter design, we studied 493 patients initiating peritoneal dialysis (PD) in four different Spanish units. We explored the effect of the PD modality on the rate of decline of RKF and the probability of anuria during follow-up. We applied logistic regression for intention-to-treat analyses, and linear mixed models to explore time-dependent variables, excluding those affected by indication bias. MAIN RESULTS: Patients started on APD were younger and less comorbid than those initiated on CAPD. Baseline RKF was similar in both groups (p = 0.50). Eighty-seven patients changed their PD modality during follow-up. The following variables predicted a faster decline of RKF: higher (rate of decline) or lower (anuria) baseline RKF, younger age, proteinuria, nonprimary PD, use of PD solutions rich in glucose degradation products, higher blood pressure, and suffering peritonitis or cardiovascular events during follow-up. Overall, APD was not associated with a fast decline of RKF, but stratified analysis disclosed that patients with lower baseline RKF had an increased risk for this outcome when treated with this technique (HR: 2.26, 95% CI: 1.09-4.82, p = 0.023). Moreover, the probability of anuria during follow-up was overtly higher in APD patients (HR: 3.22, 95% CI: 1.25-6.69, p = 0.002). CONCLUSIONS: Starting PD patients directly on APD is associated with a faster decline of RKF and a higher risk of developing anuria than doing so on CAPD. This detrimental effect is more marked in patients initiating PD with lower levels of RKF.

Temporal stability and directional change in a color cline of a marine snail from NW Spain.

The evolution and maintenance of color clines is a classic topic of research in evolutionary ecology. However, studies analyzing the temporal dynamics of such clines are much less frequent, due to the difficulty of obtaining reliable data about past color distributions along environmental gradients. In this article, we describe a case of decades-long temporal stability and directional change in a color cline of the marine snail Littorina saxatilis along the coastal inlet of the Ría de Vigo (NW Spain). L. saxatilis from this area shows a clear color cline with 3 distinct areas from the innermost to the more wave-exposed localities of the Ría: the inner, protected localities show an abundance of fawn-like individuals; the intermediate localities show a high diversity of colors; and the outer, wave-exposed localities show populations with a high frequency of a black and lineated morph. We compare data from the 1970s and 2022 in the same localities, showing that the cline has kept relatively stable for at least over half a century, except for some directional change and local variability in the frequency of certain morphs. Multiple regression analyses and biodiversity measures are presented to provide clues into the selective pressures that might be involved in the maintenance of this color cline. Future research avenues to properly test the explanatory power of these selective agents as well as the possible origins of the cline are discussed.

Precision medicine: "Point of Care Ultrasound" (PoCUS) in the diagnostic approach to the patient with hyponatremia.

Hyponatremia is a multifactorial disorder defined as a decrease in plasma sodium concentration. Its differential diagnosis requires an adequate evaluation of the extracellular volume (ECV). However, ECV determination, simply based on the clinical history, vital signs, physical examination, and laboratory findings can leads to misdiagnosis and inappropriate treatment. The use of Point-of-Care Ultrasound (POCUS), through the combination of Lung Ultrasound (LUS), Venous Excess UltraSound (VExUS) and Focused Cardiac Ultrasound (FoCUS), allows a much more accurate holistic assessment of the patient's ECV status in combination with the other parameters.

¹8F-FDG PET/CT-based treatment response evaluation in locally advanced rectal cancer: a prospective validation of long-term outcomes.

PURPOSE: To prospectively evaluate the usefulness of (18)F-FDG PET/CT) imaging for predicting histopathological response and long-term clinical outcomes in locally advanced rectal cancer (LARC). METHODS: This prospective study included 38 patients with a confirmed diagnosis of LARC (cT3-4 or cN+) who underwent (18)F-FDG PET/CT before and after neoadjuvant therapy (NAT). Total mesorectal excision was scheduled 6 weeks after NAT and was followed by an expert histopathological analysis of the surgical specimen. Baseline variables and previously identified maximum FDG standardized uptake value (SUVmax) cut-off values before NAT (SUVmaxPRE ≥6) and after NAT (SUVmaxPOST ≥2), and the absolute and percentage reductions from baseline SUVmax (∆SUVmax <4 and ∆SUVmax% <65 %, respectively) were applied to differentiate patients showing a metabolic tumour response from nonresponders. These features were correlated with tumour regression grade (TRG), disease-free survival (DFS) and overall survival (OS). RESULTS: Significantly higher 5-year DFS and OS were seen in 19 responders (TRG 3 or 4) than in 19 nonresponders (TRG 0-2; 94.4 vs. 48.8 %, p = 0.001; 94.7 vs. 63.2 %, p = 0.02, respectively). In multivariate analysis the only PET/CT SUVmax-based parameter significantly correlated with the likelihood of recurrence and survival was ∆SUV% <65 % (HR = 5.95, p = 0.02, for DFS; HR = 5.26, p = 0.04, for OS) CONCLUSION: This prospective study proved that (18)F-FDG PET/CT is a valuable imaging tool for assessing rectal cancer TRG and long-term prognosis, and could potentially serve as an intermediate endpoint in treatment optimization research and rectal cancer patient care.

Clinical significance of VEGFR-2 and ¹8F-FDG PET/CT SUVmax pretreatment score in predicting the long-term outcome of patients with locally advanced rectal cancer treated with neoadjuvant therapy.

PURPOSE: Vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor-1 (EGFR), and cyclooxygenase-2 (COX-2) stimulate key processes involved in tumor progression and are important targets for cancer drugs. (18)F-FDG maximum standardized uptake value (SUVmax) is a marker of tumor metabolic activity. The purpose of this study was to measure SUVmax combined with VEGFR-2, EGFR and COX-2 proteins in pretreatment tumor biopsies from patients with locally advanced rectal cancer receiving intensive neoadjuvant treatment and to correlate the findings with clinical outcome. METHODS: VEGFR-2, EGFR and COX-2 were measured using the immunoreactive score (IRS). SUVmax (median 8.4) was quantified in tumors with molecular overexpression (IRS ≥3 + SUVmax ≥ 8.4 indicating active tumors; SUVmax <8.4 indicating inactive tumors). The Cox proportional hazards model was used to explore associations between tumor markers, disease-free survival (DFS) and overall survival (OS). RESULTS: The study group comprised 38 patients with a median follow-up of 69.3 months (range 4.5 - 92 months). Multivariate analysis showed that active tumors (overexpressing VEGFR-2, high SUVmax) were associated with worse DFS (HR 4.73, 95 % CI 1.18 - 22.17; p = 0.04) and OS (HR 4.28, 95 % CI 1.04 - 20.12; p = 0.05). CONCLUSION: Active tumors overexpressing VEGFR-2 are associated with a worse overall outcome in patients with rectal cancer treated with induction chemotherapy followed by pelvic chemoradiation and surgery. The optimal diagnostic cut-off level for this novel biomarker association should be investigated. Evaluation in a clinical trial is required to determine whether selected patients could benefit from a VEGFR-targeting drug.

The 'Phosphorus Week': involvement of Spanish nephrologists in the control of phosphorus blood levels.

BACKGROUND: The adequate control of phosphorus levels is a major concern for professionals involved in the care of patients with chronic kidney disease (CKD), since high phosphorus levels are directly related to an increase in mortality. OBJECTIVES: To know the perception and involvement of Spanish nephrologists on the control of phosphorus levels, the so-called 'Phosphorus Week' was organized (November 13-17, 2017). METHODS: All members of the Spanish Society of Nephrology were invited to participate in an online survey, which included questions on aspects related to phosphorus control in patients with advanced CKD (aCKD) (glomerular filtration rate <30 ml/min/1, 73 m2) and in the different modalities of renal replacement therapies [peritoneal dialysis (PD), hemodialysis (HD) and renal transplantation (KT)]. RESULTS: 72 data entries were obtained in the survey with an inclusion of 7463 patients. Of them, 35.4% were on HD, 34.8% were KT, 24.2% had aCKD and 5.5% were on PD. The serum phosphorus level target for the four groups of patients was 4.5 mg/dl, with minimal variations depending on the area of ​​the national territory. The patients with better control of phosphataemia were patients with KT (93.3% had phosphorus values ​​<4.5 mg/dl), followed by patients with aCKD (65.6% with phosphorus <4.5 mg/dl). Only 53.6% of the patients on HD and 39.4% of those on PD reached the phosphorus goal <4.5 mg/dl. The group of patients on dialysis was the one in whom phosphorus binders prescribed the most (73.5% and 75.6% in HD and PD, respectively), being less frequent in patients with patients with aCKD (39.9%) and only 4.5 % in KT. CONCLUSIONS: The objectives of the Spanish nephrologists are in line with those recommended by the national and international clinical guidelines; however, there is still a wide room for improvement to achieve these goals, especially in HD and PD patients.

Shell color polymorphism in marine gastropods.

Marine gastropods are characterized by an incredible variation in shell color. In this review, we aim to introduce researchers to previous studies of shell color polymorphism in this group of animals, trying to provide an overview of the topic and highlighting some potential avenues for future research. For this, we tackle the different aspects of shell color polymorphism in marine gastropods: its biochemical and genetic basis, its patterns of spatial and temporal distribution, as well as its potential evolutionary causes. In particular, we put special emphasis on the evolutionary studies that have been conducted so far to reveal the evolutionary mechanisms responsible for the maintenance of shell color polymorphism in this group of animals, as it constitutes the least addressed aspect in existing literature reviews. Several general conclusions can be drawn from our review: First, natural selection is commonly involved in the maintenance of gastropod color polymorphism; second, although the contribution of neutral forces (gene flow-genetic drift equilibrium) to shell color polymorphism maintenance do not seem to be particularly important, it has rarely been studied systematically; third, a relationship between shell color polymorphism and mode of larval development (related to dispersal capability) may exist. As for future studies, we suggest that a combination of both classical laboratory crossing experiments and -Omics approaches may yield interesting results on the molecular basis of color polymorphism. We believe that understanding the various causes of shell color polymorphism in marine gastropods is of great importance not only to understand how biodiversity works, but also for protecting such biodiversity, as knowledge of its evolutionary causes may help implement conservation measures in those species or ecosystems that are threatened.

Thermodynamic effects drive countergradient responses in the thermal performance of Littorina saxatilis across latitude.

Thermal performance curves (TPCs) provide a powerful framework to assess the evolution of thermal sensitivity in populations exposed to divergent selection regimes across latitude. However, there is a lack of consensus regarding the extent to which physiological adjustments that compensate for latitudinal temperature variation (metabolic cold adaptation; MCA) may alter the shape of TPCs, including potential repercussion on upper thermal limits. To address this, we compared TPCs for cardiac activity in latitudinally-separated populations of the intertidal periwinkle Littorina saxatilis. We applied a non-linear TPC modelling approach to explore how different metrics governing the shape of TPCs varied systematically in response to local adaptation and thermal acclimation. Both critical upper limits, and the temperatures at which cardiac performance was maximised, were higher in the northernmost (cold-adapted) population and displayed a countergradient latitudinal trend which was most pronounced following acclimation to low temperatures. We interpret this response as a knock-on consequence of increased standard metabolic rate in high latitude populations, indicating that physiological compensation associated with MCA may indirectly influence variation in upper thermal limits across latitude. Our study highlights the danger of assuming that variation in any one aspect of the TPC is adaptive without appropriate mechanistic and ecological context.