Exploring value creation in a virtual community of practice: a framework analysis for knowledge and skills development among primary care professionals.

BACKGROUND: Healthcare professionals traditional education reflects constraints to face the complex needs of people with chronic diseases in primary care settings. Since more innovative and practical solutions are required, Virtual Community of Practices (vCoP) seem to better respond to learning updates, improving professional and organizational knowledge. However, little is known about the value created in vCoPs as social learning environments. The objective of this project was to explore the value creation process of a gamified vCoP ("e-mpodera vCoP") aimed at improving the knowledge and attitudes of primary healthcare professionals (PCPs) (nurses and general practitioners) to the empowerment of people with chronic conditions. METHODS: A framework analysis assessed the value creation process using a mixed methods approach. The framework provided awareness about knowledge and usefulness in a learning community through five cycles: (1) immediate value, (2) potential value, (3) applied value, (4) realized value, and (5) reframing value. Quantitative data included vCoP analytics such as logins, contributions, points, badges, and performance metrics. Qualitative data consisted of PCPs' forum contributions from Madrid, Catalonia, and Canary Islands over 14 months. RESULTS: A total of 185 PCPs had access to the e-mpodera vCoPs. The vCoP showed the dynamic participation of 146 PCPs, along 63 content activities posted, including a total of 3,571 contributions (including text, images, links to webpages, and other files). Regarding the value creation process, the e-mpodera vCoP seems to encompass a broad spectrum of value cycles, with indicators mostly related to cycle 1 (immediate value - activities and interactions) and cycle 2 (potential value - knowledge capital); and to a lesser extent for cycle 3 (applied value - changes in practice) and for cycle 4 (realized value - performance improvement). The presence of indicators related to cycle 5 (reframing value), was minimal, due to few individual redefinitions of success. CONCLUSION: To reach a wider range of value possibilities, a combination of learning objectives, competence framework, challenged-based gamified platform, and pathway model of skill development seems crucial. However, additional research is required to gain clearer insights into organizational values, professionals' lifelong educational needs in healthcare, and the long-term sustainability of performance improvement. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02757781. Registered on 02/05/2016.

Three-Day Icatibant on Top of Standard Care in Patients With Coronavirus Disease 2019 Pneumonia: A Randomized, Open-Label, Phase 2, Proof-of-Concept Trial.

BACKGROUND: We aimed to evaluate icatibant, a competitive antagonist of the bradykinin B2 receptors, for the treatment of inpatients with coronavirus disease 2019 (COVID-19) pneumonia admitted in the early hypoxemic stage. METHODS: The randomized, open-label clinical trial of icatibant for COVID-19 pneumonia (ICAT·COVID, registered as NCT04978051 at ClinicalTrials.gov) was conducted in Barcelona. Inpatients requiring supplemental but not high-flow oxygen or mechanical ventilation were allocated (1:1) to treatment with either three 30-mg icatibant doses/d for 3 consecutive days plus standard care or standard care alone, and followed for up to 28 days after initial discharge. The primary and key secondary outcomes were clinical response on study day 10/discharge and clinical efficacy at 28 days from initial discharge, respectively. RESULTS: Clinical response occurred in 27 of 37 patients (73.0%) in the icatibant group and 20 of 36 patients (55.6%) in the control group (rate difference, 17.42; 95% confidence interval [CI], -4.22 to 39.06; P = .115). Clinical efficacy ensued in 37 patients (100.0%) in the icatibant group and 30 patients (83.3%) in the control group (rate difference, 16.67; 95% CI, 4.49-28.84; P = .011). No patient died in the icatibant group, compared with 6 patients (16.7%) in the control group (P = .011). All patients but 1 had adverse events, which were evenly distributed between study arms. No patient withdrew because of adverse events. CONCLUSIONS: Adding icatibant to standard care was safe and improved both COVID-19 pneumonia and mortality in this proof-of-concept study. A larger, phase 3 trial is warranted to establish the clinical value of this treatment. CLINICAL TRIALS REGISTRATION: NCT04978051.

Ethical, legal, organizational and social issues related to the use of scalp cooling for the prevention of chemotherapy-induced alopecia: A systematic review.

INTRODUCTION: Scalp cooling (SC) aims to prevent chemotherapy-induced alopecia. The goal of this systematic review is to tackle ethical, legal, organizational and social issues related to SC. METHODS: A critical appraisal of the literature was carried out using a systematic review design. MEDLINE, Embase and Web of Science databases were searched up until 2 June 2021. Studies addressing these aspects in English or Spanish were considered. Representatives of both patient associations and professional scientific societies related to the topic participated in the design of the protocol and the review of the findings. RESULTS: A total of 17 studies were included. Articles were critically appraised using the MMAT and SANRA. Findings were organized into four categories: (1) ethical aspects focused on equal access, gender equity and doctor-patient communication supported by Patient Decision Aids (PtDAs); (2) patient perspective and acceptability; (3) professional perspective and acceptability; (4) organizational aspects focused on accessibility and feasibility. CONCLUSION: Cancer patients' expectations when using SC need to be adjusted to reduce the potential distress associated with hair loss. PtDAs could help patients clarify their values and preferences regarding SC. Equal access to technology should be guaranteed. PATIENT OR PUBLIC CONTRIBUTION: In this systematic review, the representatives of the patient associations (Ms. María Luz Amador Muñoz of the Spanish Association Against Cancer [AECC] and Ms. Catiana Martinez Cánovas of the Spanish Breast Cancer Federation [FECMA]) participated in the review of the study protocol, as well as in the results, discussion and conclusions, making their contributions. In the type of design of these studies (systematic reviews), it is not usual to have the direct participation of patients, but in this one, we have done so, as it is a systematic review that is part of a report of the Spanish Network of Health Technology Assessment Agencies (ETS).

A Virtual Community of Practice to Improve Primary Health Care Professionals' Attitudes Toward Patient Empowerment (e-MPODERA): A Cluster Randomized Trial.

PURPOSE: We aimed to evaluate the effectiveness of a virtual community of practice (vCoP) in improving primary health care professionals' (HCPs') attitudes toward empowering patients with chronic disease. METHODS: We conducted a cluster randomized controlled trial. Practices were units of randomization, and primary HCPs and patients were units of analysis. Sixty-three practices in Madrid, Catalonia, and the Canary Islands were randomly allocated to the intervention or control groups. Randominzation of practices was performed after HCP and patient recruitment. The patients and statistician were anonymized to group allocation; it was not possible to anonymize HCPs. The intervention was a 12-month multicomponent tailored vCoP built on the Web 2.0 concept and focused on skills toward patient empowerment. The primary outcome was Patient-Provider Orientation Scale (PPOS) score at baseline and at 12 months. The secondary outcome was the Patient Activation Measure (PAM) score. RESULTS: A total of 321 HCPs and 1,921 patients were assessed. The intervention had a positive effect on PPOS total score (0.14 points higher in the vCoP arm; 95% CI, 0.03-0.25; P = .011) and the PPOS Sharing subscale (0.3 points higher in the vCoP arm; 95% CI, 0.15-0.44; P < .001). No effect was found for the PPOS Caring subscale, and no significant differences were found for PAM scores. CONCLUSIONS: A vCoP led to a minor increase in the PPOS Sharing component and the total score but not in the Caring component. However, considerable uncertainty remains, given the observed attrition and other limitations of the study. Further research is needed on the effectiveness of the vCoP model and on how to improve HCP engagement.VISUAL ABSTRACT.

Information needs and research priorities in long-term survivorship of breast cancer: Patients and health professionals' perspectives.

OBJECTIVE: The objective of this work is to identify unmet information needs of long-term-survivors of breast cancer (BC) and future research needs from the perspectives of patients and health care professionals. METHODS: Two online Delphi surveys were conducted. Participants in Survey 1 were patients. Participants in Survey 2 were health care professionals from both primary and secondary care involved in BC care. Both surveys included three successive rounds. The first round aimed to identify research and information needs; the second round aimed to rank the relative importance of those needs; the third round aimed to find consensus. RESULTS: The most important information needs were self-management recommendations of common health problems after treatment and complications of breast reconstruction after 5 years. The most important research priorities were related to interventions and tools to increase information provision by professionals about certain tests, diet, and coordinated action between primary and specialised care during follow-up, and indications and safety issues of pregnancy in survivors. CONCLUSIONS: Two fundamental ideas were identified: (1) Patients request information about self-management common health problems after treatment and breast reconstruction complications. (2) Health care professionals emphasise the need for a standardised approach based on protocols, recommendations, and coordinated actions in the provision of information. IMPLICATIONS FOR CANCER SURVIVORS: Given the increasing number of BC survivors, it is essential to identify information and research needs to improve their care and health outcomes.

Decision aids linked to the recommendations in clinical practice guidelines: results of the acceptability of a decision aid for patients with generalized anxiety disorder.

BACKGROUND: Generalized anxiety disorder (GAD) is one of the most prevalent mental health problems. Patients with GAD have unmet needs related to the information received about their disorder, its treatments and their participation in the decision-making process. The aim of this study is to develop and assess the acceptability of a patient decision aid (PtDA) for patients with GAD. METHOD: The PtDA was developed following the International Patient Decision Aid Standards. The recommendations of the Spanish clinical practice guideline (CPG) for patients with GAD were used as the basis. The first prototype was developed by an expert committee, further improvements were made with patients (n = 2), clinical experts (n = 13) and the project management group (n = 7). The acceptability of this second draft was assessed by patients non-involved in the previous phases (n = 11). RESULTS: The final PtDA version included a brief description of GAD and its treatments. Most participants agreed that the PtDA was easy to use, visually appealing and useful. At least half of the participants learned new things about treatments and adverse effects. CONCLUSIONS: A PtDA was developed for patients with GAD based on recommendations from the Spanish CPG. It was improved and accepted by patients and clinical experts involved. An evaluation of its effectiveness on the shared decision-making process during the clinical encounter is planned.

Health Related Quality of Life in Major Depressive Disorder: evolution in time and factors associated.

Major Depressive Disorder (MDD) is the most prevalent mental disorder. We aimed to analyze which factors were associated to their Health-Related Quality of Life (HRQoL) perception in patients diagnosed of MDD and how they evolved over six months.

Cross-cultural validation of the patient-practitioner orientation scale among primary care professionals in Spain.

BACKGROUND: In recent decades, many self-report instruments have been developed to assess the extent to which patients want to be informed and involved in decisions about their health as part of the concept of person-centred care (PCC). The main objective of this research was to translate, adapt and validate the Patient-Practitioner Orientation Scale (PPOS) using a sample of primary care health-care professionals in Spain. METHODS: Baseline analysis of PPOS scores for 321 primary care professionals (general practitioners and nurses) from 63 centres and 3 Spanish regions participating in a randomized controlled trial. We analysed missing values, distributions and descriptive statistics, item-to-scale correlations and internal consistency. Performed were confirmatory factor analysis (CFA) of the 2-factor model (sharing and caring dimensions), scale depuration and principal component analysis (PCA). RESULTS: Low inter-item correlations were observed, and the CFA 2-factor model only obtained a good fit to the data after excluding 8 items. Internal consistency of the 10-item PPOS was acceptable (0.77), but low for individual subscales (0.70 and 0.55). PCA results suggest a possible 3-factor structure. Participants showed a patient-oriented style (mean = 4.46, SD = 0.73), with higher scores for caring than sharing. CONCLUSION: Although the 2-factor model obtained empirical support, measurement indicators of the PPOS (caring dimension) could be improved. Spanish primary care health-care professionals overall show a patient-oriented attitude, although less marked in issues such as patients' need for and management of medical information.

Information needs and research priorities for fertility preservation in women with breast cancer: patients and experts' perspectives.

OBJECTIVE: To identify the information needs and research priorities that women with breast cancer (BC), their families and BC experts perceive on the fertility preservation. METHODS: We conducted two Delphi-based studies through three online rounds. The first was aimed to identify information and research needs; the second one to assess the importance of those needs and the third one to obtain consensus, defined as an interquartile range ≤2. RESULTS: The participation rate was 76.2% in study 1 and 53.7% in study 2. The most important information needs were the referral protocol, pregnancy options for women with BC, side effects of tamoxifen and menopause as a consequence of treatment. The most important research priorities were the participation of different health professionals to provide oncofertility information, referral protocols and efficacy and safety of FP options. CONCLUSION: Information about fertility preservation in the context of BC and different ways to get pregnant, considering risks and benefits, has emerged as an unmet need for patients and careers. The need for a participatory and coordinated approach to the provision of information on oncofertility has been agreed. Other research needs are described in an attempt to focus future research in the most necessary areas.

F4- and F18-Positive Enterotoxigenic Escherichia coli Isolates from Diarrhea of Postweaning Pigs: Genomic Characterization.

This study aimed to characterize in silico enterotoxigenic Escherichia coli F4- and F18-positive isolates (n = 90) causing swine postweaning diarrhea, including pathogenic potential, phylogenetic relationship, antimicrobial and biocide resistance, prophage content, and metal tolerance rates. F4 strains belonged mostly to the O149 and O6 serogroups and ST100 and ST48 sequence types (STs). F18 strains were mainly assigned to the O8 and O147 serogroups and ST10, ST23, and ST42. The highest rates of antimicrobial resistance were found against streptomycin, sulfamethoxazole, tetracycline, trimethoprim, and ampicillin. No resistance was found toward ciprofloxacin, cefotaxime, ceftiofur, and colistin. Genes conferring tolerance to copper (showing the highest diversity), cadmium, silver, and zinc were predicted in all genomes. Enterotoxin genes (ltcA, 100% F4, 62% F18; astA, 100% F4, 38.1% F18; sta, 18.8% F4, 38.1% F18; stb, 100% F4, 76.2% F18) and fimbria-encoding genes typed as F4ac and F18ac were detected in all strains, in addition to up to 16 other virulence genes in individual strains. Phage analysis predicted between 7 and 20 different prophage regions in each strain. A highly diverse variety of plasmids was found; IncFII, IncFIB, and IncFIC were prevalent among F4 isolates, while IncI1 and IncX1 were dominant among F18 strains. Interestingly, F4 isolates from the early 1990s belonged to the same clonal group detected for most of the F4 strains from 2018 to 2019 (ONT:H10-A-ST100-CH27-0). The small number of single-nucleotide polymorphism differences between the oldest and recent F4 ST100 isolates suggests a relatively stable genome. Overall, the isolates analyzed in this study showed remarkably different genetic traits depending on the fimbria type.IMPORTANCE Diarrhea in the postweaning period due to enterotoxigenic E. coli (ETEC) is an economically relevant disease in pig production worldwide. In Denmark, prevention is mainly achieved by zinc oxide administration (to be discontinued by 2022). In addition, a breeding program has been implemented that aims to reduce the prevalence of this illness. Treatment with antimicrobials contributes to the problem of antimicrobial resistance (AMR) development. As a novelty, this study aims to deeply understand the genetic population structure and variation among diarrhea-associated isolates by whole-genome sequencing characterization. ST100-F4ac is the dominant clonal group circulating in Danish herds and showed high similarity to ETEC ST100 isolates from China, the United States, and Spain. High rates of AMR and high diversity of virulence genes were detected. The characterization of diarrhea-related ETEC is important for understanding the disease epidemiology and pathogenesis and for implementation of new strategies aiming to reduce the impact of the disease in pig production.

Framing the process in the implementation of care for people with generalized anxiety disorder in primary care: a qualitative evidence synthesis.

BACKGROUND: Generalized anxiety disorder (GAD) is one of the most common mental disorders in primary care (PC). GAD has low remission and high relapse rates over long follow-up periods. Qualitative evidence was synthesized to understand the implementation of care and treatment options for people with GAD in PC. METHODS: Research published from 2008 to September 2020 was searched in five databases (MEDLINE, EMBASE, CINAHL, WOS and PsycArticles). Studies that used qualitative methods for data collection and analysis to investigate the implementation of care and treatment options for people with GAD in PC and outpatient settings were included. Non-qualitative studies, mixed methods studies that did not separately report qualitative findings and studies in languages other than English or Spanish were excluded. We used the Confidence in the Evidence from Reviews of Qualitative Research (CERQual) framework to assess the overall confidence in the findings. RESULTS: The results with a moderate level of confidence showed that the trajectory of care for people with GAD in PC and outpatient settings is long and fluctuates over time, involving multiple difficulties in accessing and maintaining initial treatment or successive treatment options. In addition, there are wide variations in the preferences for and acceptability of different treatment options. The results with a high level of confidence indicated that more information on GAD and its treatment options is needed for PC practitioners, GAD patients and their carers. The results with a low level of confidence suggested that patients use antidepressants for longer than recommended and that the interruption of treatment is not usually planned. CONCLUSIONS: Initial resistance to new treatments among people with GAD can make access and adherence to treatment difficult. Improving care may require patients to be informed of possible trajectories in stepped care pathways before the initiation of treatment so they are aware that they may need to try a number of options until the most effective treatment for them is found. Increased awareness of and information materials on GAD may facilitate both appropriate diagnosis and long-term care.

Characterizing the Fused TvG6PD::6PGL Protein from the Protozoan Trichomonas vaginalis, and Effects of the NADP+ Molecule on Enzyme Stability.

This report describes a functional and structural analysis of fused glucose-6-phosphate dehydrogenase dehydrogenase-phosphogluconolactonase protein from the protozoan Trichomonas vaginalis (T. vaginalis). The glucose-6-phosphate dehydrogenase (g6pd) gene from T. vaginalis was isolated by PCR and the sequence of the product showed that is fused with 6pgl gene. The fused Tvg6pd::6pgl gene was cloned and overexpressed in a heterologous system. The recombinant protein was purified by affinity chromatography, and the oligomeric state of the TvG6PD::6PGL protein was found as tetramer, with an optimal pH of 8.0. The kinetic parameters for the G6PD domain were determined using glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide phosphate (NADP+) as substrates. Biochemical assays as the effects of temperature, susceptibility to trypsin digestion, and analysis of hydrochloride of guanidine on protein stability in the presence or absence of NADP+ were performed. These results revealed that the protein becomes more stable in the presence of the NADP+. In addition, we determined the dissociation constant for the binding (Kd) of NADP+ in the protein and suggests the possible structural site in the fused TvG6PD::6PGL protein. Finally, computational modeling studies were performed to obtain an approximation of the structure of TvG6PD::6PGL. The generated model showed differences with the GlG6PD::6PGL protein (even more so with human G6PD) despite both being fused.

EQ-5D-5L utilities per health states in Spanish population with knee or hip osteoarthritis.

BACKGROUND: The objective of this study was to obtain utilities by means of EQ-5D-5L for different health states in patients with knee osteoarthritis (KOA) or hip osteoarthritis (HOA) in Spain, and to compare these values with those used in foreign studies with the aim of discussing their transferability for their use in economic evaluations conducted in Spain. METHODS: Primary study: Observational prospective study of KOA or HOA patients in Spain. Sociodemographic and clinical characteristics were collected to characterize the sample. Utilities were elicited using the EQ-5D-5L questionnaire. ANOVA and bivariable analyses were conducted to identify differences between health states. LITERATURE REVIEW: Using the bibliographic databases NSH EED and CEA Registry, we conducted searches of model-based cost utilities analyses of technologies in KOA or HOA patients. Health states and utilities were extracted and compared with values obtained from the Spanish sample. RESULTS: Three hundred ninety-seven subjects with KOA and 361 subjects with HOA were included, with average utilities of 0.544 and 0.520, respectively. In both samples, differences were found in utilities according to level of pain, stiffness and physical function (WOMAC) and severity of symptoms (Oxford scales), so that the worst the symptoms, the lower the utilities. The utilities after surgery were higher than before surgery. Due to limitations from our study related to sample size and observational design, it was not possible to estimate utilities for approximately half the health states included in the published models because they were directly related to specific technologies. For almost 100% of health states of the selected studies we obtained very different utilities from those reported in the literature. CONCLUSIONS: To our knowledge this is the first article with detailed utilities estimated using the EQ-5D-5L in Spain for KOA and HOA patients. In both populations, utilities are lower for worse health states in terms of level of pain, stiffness and physical function according to WOMAC, and according to the Oxford scales. Most utilities obtained from the Spanish sample are lower than those reported in the international literature. Further studies estimating utilities from local populations are required to avoid the use of foreign sources in economic evaluations.

Effectiveness of a decision aid for promoting colorectal cancer screening in Spain: a randomized trial.

BACKGROUND: Colorectal cancer (CRC) screening has shown to reduce incidence and mortality rates, and therefore is widely recommended for people above 50 years-old. However, despite the implementation of population-based screening programs in several countries, uptake rates are still low. Decision aids (DAs) may help patients to make informed decisions about CRC screening. METHODS: We performed a randomized controlled trial to assess the effectiveness of a DA developed to promote CRC screening, with patients from two primary care centers in Spain who never had underwent CRC screening. Contrary to center B (n = 24), Center A (n = 83) attended patients from an area where the population-based screening program was not implemented at that moment. Outcome measures were decisional conflict, knowledge of the disease and available screening options, intention to uptake the test, and concordance between patients' goals/concerns and intention. RESULTS: In center A, there were significant differences favoring the DA in decisional conflict (p < 0.001) and knowledge (p < 0.001). The absolute differences favoring DA group in intention to undergo fecal occult blood test (10.5%) and colonoscopy (13.7%) were significant only before correction for attenuation. In center B the differences were significant only for knowledge (p < 0.001). Patients' goals and concerns regarding the screening did not significantly predict their intention, and therefore we could not calculate a measure of concordance between the two constructs. CONCLUSIONS: A DA improved the decisional process of participants who had never been invited to participate in the Spanish public CRC screening program, replicating previous results in this field. Future research is needed to identify subgroups that could benefit more from these interventions. TRIAL REGISTRATION: International Standard Registered Clinical/social Study Number: ISRCTN98108615 (Retrospectively registered on 27 December 2018).

Cross-cultural adaptation and validation of the Spanish version of the Oxford Hip Score in patients with hip osteoarthritis.

BACKGROUND: Osteoarthritis (OA) of the hip is a disease that entails a major burden for patients and the society as a whole. One way of measuring this burden for the patient is through impact on Health-related Quality of Life (HRQL). The Oxford Hip Score (OHS) is a well-known tool to measure HRQL in patients with OA of the hip. This study aims to assess the psychometric properties of the Spanish-adapted version of the OHS, including its reliability, validity, and sensitivity to change. METHODS: Prospective observational study that included 361 patients diagnosed with hip OA (according to the criterion of the American College of Rheumatology) from 3 different Spanish regions. Their HRQL was assessed using a generic questionnaire, the EQ-5D-5 L, and two specific ones (the Western Ontario and McMaster Universities Osteoarthritis Index, WOMAC, and the OHS) adapted to Spanish. There was a follow-up period of 6 months, and the acceptability, psychometric properties, presence of ceiling and floor effects, validity, reliability, and sensitivity to changes of the OHS were measured. RESULTS: The OHS was fully answered in 99.4% of cases with no indication of ceiling or floor effects. Its factor structure can be explained in a single dimension. Its discriminative capacity was very good compared to the groups generated by the WOMAC and the EQ-5D-5 L. The correlation between the OHS and dimensions of the WOMAC or EQ-5D-5 L utilities was ≥0.7. Excellent test-retest reliability (ICC = 0.992; CI95%: 0.994-0.998) and internal consistency (Cronbach's α = 0.928) were observed. The minimal clinically important difference (MCID) was 7.0 points, and the minimum detectable change (MDC) was 5.5 points. The effect size for moderate improvement in perceived HRQL was 0.73, similar to that of WOMAC dimensions and higher than the EQ-5D-5 L. CONCLUSIONS: The Spanish-adapted version of the OHS is a useful, acceptable tool for the assessment of perceived HRQL in patients with hip OA, and has psychometric properties similar to those of the WOMAC that allow for discriminating both a patient's condition at a given moment and changes that can occur over time.

Tumor-derived exosomes are enriched in ΔNp73, which promotes oncogenic potential in acceptor cells and correlates with patient survival.

Tumor-derived exosomes are emerging as local and systemic cell-to-cell mediators of oncogenic information through the horizontal transfer of mRNAs, microRNAs and proteins during tumorigenesis. The exosomal content has been described as biologically active when taken up by the recipient cell. Identifying the specific molecular cargo of exosomes will help to determine their function in specific steps of the tumorigenic process. Here we evaluate whether ΔNp73 is selectively packaged in tumor-derived exosomes, its function in the acceptor cells in vitro and in vivo and its prognosis potential in cancer. ΔNp73 messenger is enriched in tumor-derived exosomes, suggesting its active sorting in these microvesicles. We observed the transmission of this exosome cargo to different cell types and how it confers proliferation potential and chemoresistance to the acceptor cells in vitro and in animal models. Finally, our data support the potential prognostic value of exosomal ΔNp73 in colon cancer patients.

Use of denosumab in a dialysis patient with bone metastases from breast cancer and hepatorenal polycystic disease: a case report.

Cancer patients with severe renal dysfunction represent a challenge for the physician. This is the first case report on the use of denosumab in a dialysis patient with bone metastases. We present the clinical case of a 45-year-old woman who had hepatorenal polycystic disease, diagnosed during childhood, and stage IV chronic kidney failure at the time of breast cancer diagnosis. Three years after surgery plus adjuvant hormonal therapy she suffered a further worsening of renal function, requiring dialysis, and very advanced bone metastasis in the hip with severe pain. As pamidronate was the only bone agent available in the center, she received it for 4 months (before a dialysis session), during which time the bone metastases stabilized. In March 2014, the patient switched to denosumab (which had become available in the center), and continued with hormone therapy. Seven months after denosumab initiation, the patient had almost complete pain relief, and the bone metastases exhibited radiological improvement. The tolerability was excellent, without any related adverse event. There were no changes in albumin-adjusted serum calcium, serum phosphorus, and intact parathyroid hormone, except for a transient and mild hypocalcemia at 3 months and an increase in intact parathyroid hormone levels, which required adjustment of vitamin D analog dose. Denosumab can be administered to prevent skeletal-related events in patients with bone metastasis from solid tumors and severely impaired renal function, even in those requiring dialysis. In this particular patient, the safety was good.

Different exosome cargo from plasma/bronchoalveolar lavage in non-small-cell lung cancer.

Tumor-derived exosomes mediate tumorigenesis by facilitating tumor growth, metastasis, development of drug resistance, and immunosuppression. However, little is known about the exosomes isolated from bronchoalveolar lavage (BAL) in patients with lung neoplasm. Exosomes isolated in plasma and BAL from 30 and 75 patients with tumor and nontumor pathology were quantified by acetylcholinesterase activity and characterized by Western Blot, Electron Microscopy, and Nanoparticle Tracking Analysis. Differences in exosome cargo were analyzed by miRNA quantitative PCR in pooled samples and validated in a second series of patients. More exosomes were detected in plasma than in BAL in both groups (P < 0.001). The most miRNAs evaluated by PCR array were detected in tumor plasma, tumor BAL, and nontumor BAL pools, but only 56% were detected in the nontumor plasma pool. Comparing the top miRNAs with the highest levels detected in each pool, we found close homology only between the BAL samples of the two pathologies. In tumor plasma, we found a higher percentage of miRNAs with increased levels than in tumor BAL or in nontumor plasma. The data reveal differences between BAL and plasma exosome amount and miRNA content.

Protumorigenic effects of Snail-expression fibroblasts on colon cancer cells.

Snail1 is a transcriptional factor that plays an important role in epithelial-mesenchymal transition and in the acquisition of invasive properties by epithelial cells. In colon tumors, Snail1 expression in the stroma correlates with lower specific survival of cancer patients. However, the role(s) of Snail1 expression in stroma and its association with patients' survival have not been determined. We used human primary carcinoma-associated fibroblasts (CAFs) or normal fibroblasts (NFs) and fibroblast cell lines to analyze the effects of Snail1 expression on the protumorigenic capabilities in colon cancer cells. Snail1 expression was higher in CAFs than in NFs and, as well as α-SMA, a classic marker of activated CAFs. Moreover, in tumor samples from 50 colon cancer patients, SNAI1 expression was associated with expression of other CAF markers, such as α-SMA and fibroblast activation protein. Interestingly, coculture of CAFs with colon cells induced a significant increase in epithelial cell migration and proliferation, which was associated with endogenous SNAI1 expression levels. Ectopic manipulation of Snail1 in fibroblasts demonstrated that Snail1 expression controlled migration as well as proliferation of cocultured colon cancer cells in a paracrine manner. Furthermore, expression of Snail1 in fibroblasts was required for the coadjuvant effect of these cells on colon cancer cell growth and invasion when coxenografted in nude mice. Finally, cytokine profile changes, particularly MCP-3 expression, in fibroblasts are put forward as mediators of Snail1-derived effects on colon tumor cell migration. In summary, these studies demonstrate that Snail1 is necessary for the protumorigenic effects of fibroblasts on colon cancer cells.