Multiple neoplasms in patients with uveal melanoma: a systematic review.

PURPOSE: Uveal melanoma is the most prevalent intraocular malignancy in adults, derived from uveal tract melanocytes. This study focuses on the frequency and risk of second primary malignancies in UM patients. METHODS: A PubMed search (1980-2023) identified studies on SPM incidence in UM patients. From 191 references, 14 studies were chosen, focusing on UM, SPMs, and analysing data on demographics and types of neoplasms. RESULTS: Among 31,235 UM patients in 14 studies, 4695 had 4730 SPMs (15.03% prevalence). Prostate (15%), breast (12%), and colorectal (9%) cancers were most common. Digestive system malignancies were highest (19%), with colorectal cancer leading (51%). Breast and prostate cancers were prevalent in respective systems. Lung, bladder, and non-Hodgkin's lymphoma were also notable. The study observed an increasing trend in the frequency of SPMs over time, reflecting broader trends in cancer survivorship and the growing prevalence of multiple malignancies. CONCLUSION: The study highlights a significant presence of SPMs in UM patients, with an increasing trend in frequency over time, emphasizing prostate and breast cancers. This underscores the need for focused surveillance and tailored follow-up for UM survivors, considering their higher risk of additional malignancies. Future research should further investigate SPM aetiology in UM patients.

Characteristics of patients who died in the hospital emergency service during the SARS-CoV-2 pandemic: a retrospective cohort study in a tertiary hospital in Spain.

The objective of this study is to analyze the characteristics of patients who died in the Hospital Emergency Department (HED) of a Spanish third-level hospital, with a special focus on those who died due to SARS-CoV-2. A retrospective cohort study was conducted, including all patients over 18 years old who died in the Hospital Emergency Department (HED) of a Spanish third-level hospital located in Badalona, Spain, from Jun 2019 to Dec 2020. Various sociodemographic, clinical, and diagnostic variables of the patients were analyzed to identify potential risk factors associated with mortality. During the first wave of the COVID-19 pandemic, a total of 72 patients died in the HED, representing a 42% increase compared to the pre-pandemic period. Of the deceased patients, 11% were attributed to SARS-CoV-2. Furthermore, it was found that patients who died from SARS-CoV-2 during the first wave were significantly younger than those in the second wave, with an average age of 78.6 ± 3.1 years in the first wave and 91.8 ± 4.8 years in the second wave. No significant differences were found regarding gender or associated comorbidities. Overall, the mortality rate at the HED in relation to COVID-19 was low, and infected patients died at younger ages during the first wave compared to the second wave.

Preliminary results of the effect of music therapy treatment on anxiety, sadness, physical discomfort, mood, and quality of life in hospitalized onco-haematological patients.

BACKGROUND: Physical and psychological distress may occur in patients facing an onco-haematological diagnosis and undergoing complex therapies such as intensive chemotherapy, stem cell transplantation, and immunotherapy. Studies have shown the need for incorporating different therapeutic modalities to respond to patients' physical and psychosocial needs. AIMS: The purpose of this study was to evaluate the effectiveness of music therapy treatment on mood, anxiety, depression, and physical discomfort in hospitalized onco-haematological patients. METHODS: Forty patients were included in this music therapy study from November 2021 to May 2023. Treatment consisted of individual weekly music therapy sessions. Participants completed the following evaluation instruments before and after the intervention: the Hospital Anxiety and Depression Scale (HADS), Profile of Mood States-Short Form A-Version (POMS-A), and European Organization for Research and Treatment of Cancer-Quality of Life Core Questionnaire-30 (EORTC QLQ-C30). A three-item numerical rating scale (NRS) for anxiety, sadness, and physical discomfort was administered at the beginning and end of each session (pre-/postsession). RESULTS: Differences (p < 0.05) were shown in NRS scores for anxiety, sadness, and physical discomfort before and after the music therapy sessions. Quality of life (QoL) was affected in almost all items, and patients could be anxious at a nonclinical level, but they were clinically depressed. EORTC QLQ-C30 scores for insomnia and pain related to the hospitalization process got worse after discharge. CONCLUSIONS: The interim results of our study showed that music therapy sessions can positively change emotional distress and improve the mood of haematological patients after every session. Despite the difficulties and limitations of this study, this preliminary report contributes to a greater understanding of the potential benefits of music therapy in hospitalized onco-haematological patients.

Impact of the COVID-19 pandemic on visits to the hospital emergency service in two hospitals in Spain, from March 14, 2020 to June 21, 2020.

This study will describe trends in the use of emergency departments before and after the Spanish State of Alarm, especially in pathologies not directly related to this infection. A cross-sectional study was conducted of all visits to the emergency departments in two third-level hospitals in two Spanish communities during the Spanish State of Alarm, compared with the same period of the previous year. The variables collected included the day of the week, the time of the visit, the duration of the visit, the final destination of the patients (home, admission to a conventional hospitalization ward, admission to the intensive care unit, and death), and the diagnosis at discharge according to the International Classification of Diseases 10th Revision. During the Spanish State of Alarm period, an overall decrease in care demand of 48% was observed, which reached 69.5% in pediatric emergency departments. We also saw a drop of between 20 and 30% in time-dependent pathologies (heart attack, stroke, sepsis, poisoning). The decrease in overall attendance in the emergency departments and absence of serious pathologies, such as time-dependent diseases, observed during the Spanish State of Alarm compared to the previous year highlights the need to strengthen the messages addressed to the population to encourage them to seek care without delay in case of alarming symptoms and reduce the high morbidity and mortality rate if the diagnosis is delayed.

mRNA-1273 SARS-CoV-2 vaccine in recently transplanted allogeneic hematopoietic cell transplant recipients: Dynamics of cellular and humoral immune responses and booster effect.

Allogeneic hematopoietic stem cell transplant (HCT) recipients are at high risk of severe COVID-19 despite vaccination. Little is known about cellular response to SARS-CoV-2 vaccine in this population, especially in recently transplanted patients (RTP). In this single-center study we examined cellular and humoral response to the mRNA-1273 (Spikevax®) vaccine in recently transplanted patients (RTP, n = 49), and compared them to long-term transplanted patients (LTTP, n = 19) and healthy controls (n = 20) at three different timepoints: one and three months after the second dose (T1 and T2, respectively, 28 days apart), and one month after the third dose (T3). Controls did not receive a third dose. RTPs showed lower IgG anti-S1 titers than healthy controls at both T1 (mean 0.50 vs 0.94 arbitrary units -AU-, p < 0.0001) and T2 (0.37 vs 0.79 AU, p < 0.0001). They also presented lower titers than LTTPs at T1 (0.50 vs 0.66, p = 0.01), but no differences at T2 (0.37 vs 0.40 AU, p = 0.55). The rate of positive T-cell responses was lower in RTPs than in controls at both T1 and T2 (61.2 % vs 95 %, p = 0.007; 59.2 % vs 100 %, p = 0.001, respectively), but without statistically significant differences between transplanted groups. At T3 no differences were seen between RTPs and LTTPs as well, neither in IgG antibodies (p = 0.82) nor in cellular responses (p = 0.15), although a third dose increased the rate of positive cellular and humoral responses in approximately 50 % of recently transplanted patients. However, active immunosuppressive treatment severely diminished their chances to produce an adequate response.

Early and late onset cardiotoxicity following anthracycline-based chemotherapy in breast cancer patients: Incidence and predictors.

INTRODUCTION: Cardiotoxicity represents a major limitation for the use of anthracyclines or trastuzumab in breast cancer patients. Data on longitudinal studies about early and late onset cardiotoxicity in this group of patients is scarce. The objective of the present study was to assess predictors of early and late onset cardiotoxicity in patients with breast cancer treated with A. METHODS: 100 consecutive patients receiving anthracycline-based chemotherapy (CHT) to treat breast cancer were included in this prospective study. All patients underwent evaluation at baseline, at the end of CHT, 3 months after the end of CHT and 1 and 4 years after the beginning of CHT. Clinical data, systolic and diastolic echo parameters and cardiac biomarkers including high sensitivity Troponin T (TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP) and Heart-type fatty acid binding protein (H-FABP) were assessed. RESULTS: Mean doxorubicin dose was 243 mg/m2. Mean follow-up was 51.8 ± 8.2 months. At one-year incidence of anthracycline related-cardiotoxicity (AR-CT) was 4% and at the end of follow-up was 18% (15 patients asymptomatic left ventricular systolic dysfunction, 1 patients heart failure and 2 patients a sudden cardiac death). Forty-nine patients developed diastolic dysfunction (DD) during first year. In the univariate analysis DD during first year was the only parameter associated with AR-CT (Table 1). In the logistic regression model DD was independently related with the development of AR-CT, with an odds ratio value of 7.5 (95% CI 1.59-35.3). CONCLUSIONS: Incidence of late-onset cardiotoxicity is high but mostly subclinical. Diastolic dysfunction early after chemotherapy is a strong predictor of anthracycline cardiotoxicity.

Feasibility of a New Model of Care for Allogeneic Stem Cell Transplantation Recipients Facilitated by eHealth: The MY-Medula Pilot Study.

The use of allogeneic stem cell transplantation (allo-SCT) for the treatment of hematologic diseases is steadily increasing; however, allo-SCT has the downside of causing considerable treatment-related morbidity and mortality. Mobile technology applied to healthcare (mHealth) has proven to be a cost-effective strategy to improve care and offer new services to people with multimorbidity, but there are little data on its usefulness in allo-SCT recipients. Here we describe a new integrated healthcare model facilitated by an mHealth platform, EMMASalud-MY-Medula, and to report the results of a feasibility and usability pilot study. The MY-Medula platform was developed in 4 phases. First, patient and healthcare professional needs were identified, and technological development and pretesting tests were conducted (phases 1 to 3, January 2016 to March 2021). Then a nonrandomized, prospective, observational, single-center pilot study was conducted (October 2021 to January 2022) at the adult SCT unit of a tertiary university hospital. Twenty-eight volunteer allo-SCT recipients were included in the pilot study, of whom one-half were outpatients in the first-year post-SCT and one-half were affected by steroid-dependent graft-versus-host disease (SR-GVHD). All patients used the MY-Medula app during the 2-month follow-up period, with a median number of visits to the app of 143 (range, 6 to 477). A total of 2067 self-monitoring records were created, and 205 text messages were received, most of them related to symptoms description (47%) and doubts about medication (21%). In 3.4% of the cases, drug dosage was adjusted by the pharmacist because of dosing errors or interactions. At the end of the study, a 6-question Likert-type questionnaire for patients and a 22-question test for healthcare professionals showed a high degree of satisfaction (95% and 100%, respectively) with the new healthcare pathway. Reengineering the follow-up of allo-SCT recipients into an integrated, multidisciplinary model of care facilitated by mHealth tools is feasible and has been associated with high usability and a high degree of satisfaction by patients and healthcare professionals. A randomized trial aiming to determine the cost-effectiveness of MY-Medula-based follow-up post-SCT is currently enrolling participants.

mRNA-1273 SARS-CoV-2 vaccine safety and COVID-19 risk perception in recently transplanted allogeneic hematopoietic stem cell transplant recipients.

PURPOSE: This study aims to describe the incidence and severity of adverse events (AEs) following the mRNA-1273 SARS-CoV-2 vaccine and explore the risk perception of COVID-19 in allogeneic hematopoietic stem cell transplant (HCT) recipients. METHODS: We performed a single-center prospective study including recently transplanted (< 2 years post-infusion) allogeneic HCT recipients. AEs were assessed through phone calls and graded from 0 to 4, while COVID-19 risk perception was measured using the Brief Illness Perception Questionnaire (BIP-Q5). RESULTS: Fifty-four HCT recipients were evaluated. Incidence and grades of AE (94.4% and 85.2% after the first and second dose, respectively) were similar to those described in the general population. The most common AE was pain at the site of injection. Three patients (5.6%) developed a grade ≥ 3 AE. Vaccine-related cytopenias and graft-versus-host disease flares were not observed. Female sex (OR 3.94, 95% CI 1.14-13.58, p = 0.03) and time since HCT (per month since HCT: OR 1.09, 95% CI 1.01-1.18, p = 0.04) were associated with the occurrence of any AE. The patients' risk perception level of COVID-19 decreased over time (p < 0.05). CONCLUSION: Our study confirms that the mRNA-1273 SARS-CoV-2 vaccine is safe in recent HCT recipients and suggests that the perceived risk of COVID-19 decreases over time.

Evidências da utilização do treino metacognitivo na pessoa com psicose: revisão integrativa da literatura / Evidence of the use of metacognitive training in persons with psychosis: integrative literature review / Evidencia del uso del entrenamiento metacognitivo en personas com psicosis: revisión integrativa de la literatura

Resumo Contexto: Numa sociedade com grande carga global de doença associada às perturbações mentais, é primordial o desenvolvimento de intervenções psicoterapêuticas como o treino metacognitivo para pessoas com psicose, coadjuvante do tratamento psicofarmacológico. Objetivo: Analisar as evidências da utilização do treino metacognitivo na pessoa com psicose. Metodologia: Formulada a questão PICO, pesquisaram-se artigos publicados entre dezembro de 2017 e dezembro de 2020, nas bases de dados: Complementary index; MEDLINE complete, Academic Search Complete, CINAHL Complete, ScienceDirect e eBook Index. O processo de avaliação metodológica foi realizado por dois revisores independentes, com recurso aos instrumentos de avaliação do Joanna Briggs Institute. Foram definidos critérios de inclusão e exclusão, obtendo no total 8 artigos para a revisão. Resultados: Como principais resultados, após análise dos artigos incluídos, concluímos que, o treino metacognitivo aplicado em grupo, em pessoas com psicose, em contexto comunitário, demonstra eficácia quanto à redução da sintomatologia positiva (delírios e alucinações) e aumento dos níveis de insight clínico e cognitivo. Conclusão: O treino metacognitivo demonstra ser uma intervenção eficaz em pessoas com psicose, devendo por essa razão, ser desenvolvido em contexto da prática clínica de enfermagem de saúde mental e psiquiátrica. Sendo uma intervenção com recente implementação, emerge a necessidade contínua de investigação dos seus efeitos na população com sintomatologia psicótica, maiormente, nas variáveis da afetividade, funcionamento social, risco suicidário e recaídas.

Abstract Context: In a society with a great global burden of disease associated with mental disorders, the development of psychotherapeutic interventions such as metacognitive training for people with psychosis, adjunct to psychopharmacological treatment, is paramount. Objective: Analyze the evidence of the use of metacognitive training in the person with psychosis. Review Method: Formulated the PICO question, articles published between December 2017 and December 2020 were researched in the databases: Complementary index; MEDLINE complete, Academic Search Complete, CINAHL Complete, ScienceDirect and eBook Index. The methodological evaluation process was carried out by two independent reviewers, using the evaluation instruments of the Joanna Briggs Institute. Inclusion and exclusion criteria are defined, bringing together a total of 8 articles for review. Results: As main results, after analysis of the included articles, we conclude that the metacognitive training applied in a group, in people with psychosis, in a community context, demonstrates efficacy in reducing positive symptomatology (delusions and hallucinations), and increasing levels of clinical and cognitive insight. Conclusion: Metacognitive training proves to be an effective intervention in people with psychosis and should therefore be developed in the context of clinical practice of mental and psychiatric health nursing. Being an intervention with recent implementation, emerges the continuous need to investigate its effects on the population with psychotic symptomatology, mainly, in the variables of affectivity, social functioning, suicide risk and relapses.

Resumen Contexto: En una sociedad con una gran carga global de enfermedad asociada a los trastornos mentales, el desarrollo de intervenciones psicoterapéuticas como el entrenamiento metacognitivo para personas con psicosis es fundamental, como complemento del tratamiento psicofarmacológico. Objetivo: Analizar la evidencia del uso del entrenamiento metacognitivo en personas con psicosis. Metodología: Una vez formulada la pregunta PICO, se buscaron los artículos publicados entre diciembre de 2017 y diciembre de 2020, en las siguientes bases de datos: Índice complementario; MEDLINE completo, búsqueda académica completa, CINAHL completo, ScienceDirect y eBook Index. El proceso de evaluación metodológica fue realizado por dos revisores independientes, utilizando los instrumentos de evaluación del Instituto Joanna Briggs. Se definieron criterios de inclusión y exclusión, obteniendo un total de 8 artículos para revisión. Resultados: Como principales resultados, luego de analizar los artículos incluidos, se concluye que el entrenamiento metacognitivo aplicado en grupos, en personas con psicosis, en un contexto comunitario, demuestra efectividad para reducir los síntomas positivos (delirios y alucinaciones) y aumentar los niveles de insight clínico y cognitivo. Conclusión: El entrenamiento metacognitivo demuestra ser una intervención eficaz en personas con psicosis, por lo que debe desarrollarse en el contexto de la práctica clínica en salud mental y enfermería psiquiátrica. Como intervención de reciente implementación, existe una necesidad continua de investigar sus efectos en la población con síntomas psicóticos, principalmente en las variables de afectividad, funcionamiento social, riesgo de suicidio y recaídas.

Moral experiences in caring for voluntary pregnancy losses: A meta-ethnography.

Voluntary abortions are relatively frequent and their care is complex due to the social stigma that surrounds these losses. This interpretive meta-ethnography of 11 original qualitative articles aims to synthesize the moral experiences of nurses and midwives who cared for women and couples that decided to abort or terminate the pregnancy due to foetal abnormalities. Lines of argument synthesis emerged after reciprocal and refutational translations, together with the metaphor, 'Going with the flow or swimming against the tide'. Caring in these situations was an ethical dilemma when a conflict existed between their professional duty and their moral principles. In these instances, care was associated with a significant emotional cost. They did not feel sufficiently prepared or with adequate resources, which favoured avoidance behaviours. However, the feeling of professional duty was stronger than their prejudices, and they became engaged in caring. These results could improve knowledge, clinical practice and education, being a (highly) reasonable representation of the phenomenon of interest.

Risk of infectious complications in adult patients after allogeneic hematopoietic stem cell transplantation depending on the site of central venous catheter insertion-multicenter prospective observational study, from the IDWP EBMT and Nurses Group of EBMT.

The current guidelines for prevention of infections in hematopoietic stem cell transplantation (HSCT) do not specify which central venous catheter (CVC) insertion site should be preferred in allogeneic HSCT recipients-internal jugular vein (IJV) or subclavian vein (SCV). We designed a multicenter prospective observational study comparing the risk of infectious and non-infectious complications between the two most common sites of CVC insertion (IJV and SCV) in allogeneic HSCT. There were in total 232 consecutive patients (86 IJV and 146 SCV) who underwent adult allogeneic HSCT reported from 11 centers in 8 countries. The center independent analysis of central line associated/related blood stream infections with ECDC criteria has shown statistically significant difference favoring SCV (23% IJV vs 13% SCV (OR 2.03 (1.01-4.06), p = 0.047)). The differences in CLABSI per 1000 days of CVC use favored SCV over IJV (7.93/1000 days IJV vs 2.79/1000 days SCV, p = 0.002). The frequency of all non-infectious complications was similar in both arms-13% IJV and 12% SCV (OR 1.1 (0.5-2.5), p = 0.8). This multicenter prospective study showed statistically significant lower confirmed number of CLABSI per 1000 days of CVC use without higher risk of noninfectious complications related to the subclavian insertion site in allogeneic HSCT recipients.

Results of the FLAC European Database of Metastatic Castration-Resistant Prostate Cancer Patients Treated With Docetaxel, Cabazitaxel, and Androgen Receptor-Targeted Agents.

BACKGROUND: Several agents have demonstrated an overall survival (OS) benefit in patients with metastatic castration-resistant prostate cancer (mCRPC); however, the optimal sequencing of these therapies is unknown as a result of a lack of prospective randomized controlled trials. This retrospective study aimed to identify clinical factors influencing outcomes and to determine optimal treatment sequencing in patients with mCRPC treated with cabazitaxel (CABA) and/or androgen receptor-targeted agents (ART) after androgen-deprivation therapy (ADT) and docetaxel (DOC). PATIENTS AND METHODS: Records of 574 consecutive patients treated (2012-2016) at 44 centers in 6 countries were retrospectively examined. RESULTS: A total of 267 patients received ADT → DOC → CABA (group 1), 183 patients ADT → DOC → ART → CABA (group 2), and 124 patients ADT → DOC → CABA → ART (group 3), with respective median OS from diagnosis of mCRPC of 38.3, 44.45, and 53.9 months (P = .012 for group 3 vs. group 1). Multivariate analysis showed response to first ADT ≤ 12 months, Gleason score of 8 to 10, clinical progression, and high prostate-specific antigen levels at mCRPC diagnosis were associated with worse OS. Prior receipt of ART did not influence activity of CABA. CONCLUSION: OS appeared to increase with the number of life-extending therapies, with a sequence including DOC, CABA, and an ART providing the greatest OS benefit.

Phase Ib study evaluating safety and clinical activity of the anti-HER3 antibody lumretuzumab combined with the anti-HER2 antibody pertuzumab and paclitaxel in HER3-positive, HER2-low metastatic breast cancer.

Purpose To investigate the safety and clinical activity of comprehensive human epidermal growth factor receptor (HER) family receptor inhibition using lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2-low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors. Patients received lumretuzumab (1000 mg in Cohort 1; 500 mg in Cohorts 2 and 3) plus pertuzumab (840 mg loading dose [LD] followed by 420 mg in Cohorts 1 and 2; 420 mg without LD in Cohort 3) every 3 weeks, plus paclitaxel (80 mg/m2 weekly in all cohorts). Patients in Cohort 3 received prophylactic loperamide treatment. Results Diarrhea grade 3 was a dose-limiting toxicity of Cohort 1 defining the maximum tolerated dose of lumretuzumab when given in combination with pertuzumab and paclitaxel at 500 mg every three weeks. Grade 3 diarrhea decreased from 50% (Cohort 2) to 30.8% (Cohort 3) with prophylactic loperamide administration and omission of the pertuzumab LD, nonetheless, all patients still experienced diarrhea. In first-line MBC patients, the objective response rate in Cohorts 2 and 3 was 55% and 38.5%, respectively. No relationship between HER2 and HER3 expression or somatic mutations and clinical response was observed. Conclusions Combination treatment with lumretuzumab, pertuzumab and paclitaxel was associated with a high incidence of diarrhea. Despite the efforts to alter dosing, the therapeutic window remained too narrow to warrant further clinical development. TRIAL REGISTRATION: on ClinicalTrials.gov with the identifier NCT01918254 first registered on 3rd July 2013.

[Drug abuse in nursing students]. / Consumo de drogas en estudiantes de enfermería.

OBJECTIVE: To determine the patterns of substance abuse of students attending the Lugo School of Nursing. METHOD: Observational, descriptive and cross-sectional study in the classroom carried out by survey research in April 2015. RESULTS: 61.5% of students participated (185), 83.2% of whom were females. The first addictive substance consumed by participants was tobacco (at 15 years old). In the last month cigarettes were consumed by 36.2% of students, while alcohol was consumed by 89.9% (58.4% of the total got drunk). 2.2% were consuming tranquilizers/hypnotics in the same time period. The most widely used illegal drug was cannabis (17.8%) and then cocaine (2.2%). There is a significant correlation between illegal drug consumption and being male, smoking cigarettes or drinking alcohol, living alone or with friends (not family), have poor academic performance and public drinking (botellón). There were no association between illegal drugs and sports or reading. Polydrug use was also studied: a 16.2% declared to have consumed alcohol and cannabis simultaneously, and a 4.9% alcohol and cocaine. CONCLUSIONS: Consumption patterns are similar compared to the general population in that age group, with some of them being higher. Therefore, it is necessary to take measures in order to prevent substance abuse at the university level.

AI-related BMD variation in actual practice conditions: A prospective cohort study.

The aim of the study was to evaluate the progression of bone mineral density (BMD) during 3 years of aromatase inhibitors (AI) therapy in actual practice conditions. This prospective, clinical cohort study of Barcelona-Aromatase induced Bone Loss in Early breast cancer (B-ABLE) assessed BMD changes during 3 years of AI treatment in women with breast cancer. Patients with osteoporosis (T score < -2.5 or T score ≤ -2.0) and a major risk factor and/or prevalent fragility fractures were treated with oral bisphosphonates (BPs). Of 685 women recruited, 179 (26.1%) received BP treatment. By the third year of AI therapy, this group exhibited increased BMD in the lumbar spine (LS; 2.59%) and femoral neck (FN; 2.50%), although the increase was significant only within the first year (LS: 1.99% and FN: 2.04%). Despite BP therapy, however, approximately 15% of these patients lost more than 3% of their baseline bone mass. At 3 years, patients without BP experienced BMD decreases in the LS (-3.10%) and FN (-2.79%). In this group, BMD changes occurred during the first (LS: -1.33% and FN: -1.25%), second (LS: -1.19% and FN: -0.82%), and third (LS: -0.57% and FN: -0.65%) years of AI treatment. Increased BMD (>3%) was observed in just 7.6% and 10.8% of these patients at the LS and FN, respectively. Our data confirm a clinically relevant bone loss associated with AI therapy amongst nonusers of preventative BPs. We further report on the importance of BMD monitoring as well as calcium and 25-hydroxy vitamin D supplementation in these patients.

Diastolic Dysfunction Following Anthracycline-Based Chemotherapy in Breast Cancer Patients: Incidence and Predictors.

INTRODUCTION: Cardiotoxicity represents a major limitation for the use of anthracyclines or trastuzumab in breast cancer patients. Data from longitudinal studies of diastolic dysfunction (DD) in this group of patients are scarce. The objective of the present study was to assess the incidence, evolution, and predictors of DD in patients with breast cancer treated with anthracyclines. METHODS: This analytical, observational cohort study comprised 100 consecutive patients receiving anthracycline-based chemotherapy (CHT) for breast cancer. All patients underwent clinical evaluation, echocardiogram, and measurement of cardiac biomarkers at baseline, end of anthracycline-based CHT, and at 3 months and 9 months after anthracycline-based CHT was completed. Fifteen patients receiving trastuzumab were followed with two additional visits at 6 and 12 months after the last dose of anthracycline-based CHT. A multivariate analysis was performed to find variables related to the development of DD. Fifteen of the 100 patients had baseline DD and were excluded from this analysis. RESULTS: At the end of follow-up (median: 12 months, interquartile range: 11.1-12.8), 49 patients (57.6%) developed DD. DD was persistent in 36 (73%) but reversible in the remaining 13 patients (27%). Four patients developed cardiotoxicity (three patients had left ventricular systolic dysfunction and one suffered a sudden cardiac death). None of the patients with normal diastolic function developed systolic dysfunction during follow-up. In the logistic regression model, body mass index (BMI) and age were independently related to the development of DD, with the following odds ratio values: BMI: 1.19 (95% confidence interval [CI]: 1.04-1.36), and age: 1.12 (95% CI: 1.03-1.19). Neither cardiac biomarkers nor remaining clinical variables were predictors of DD. CONCLUSION: Development of diastolic dysfunction after treatment with anthracycline or anthracycline- plus trastuzumab chemotherapy is common. BMI and age were independently associated with DD following anthracycline chemotherapy.

Emergence of Multiple EGFR Extracellular Mutations during Cetuximab Treatment in Colorectal Cancer.

PURPOSE: Patients with colorectal cancer who respond to the anti-EGFR antibody cetuximab often develop resistance within several months of initiating therapy. To design new lines of treatment, the molecular landscape of resistant tumors must be ascertained. We investigated the role of mutations in the EGFR signaling axis on the acquisition of resistance to cetuximab in patients and cellular models. EXPERIMENTAL DESIGN: Tissue samples were obtained from 37 patients with colorectal cancer who became refractory to cetuximab. Colorectal cancer cells sensitive to cetuximab were treated until resistant derivatives emerged. Mutational profiling of biopsies and cell lines was performed. Structural modeling and functional analyses were performed to causally associate the alleles to resistance. RESULTS: The genetic profile of tumor specimens obtained after cetuximab treatment revealed the emergence of a complex pattern of mutations in EGFR, KRAS, NRAS, BRAF, and PIK3CA genes, including two novel EGFR ectodomain mutations (R451C and K467T). Mutational profiling of cetuximab-resistant cells recapitulated the molecular landscape observed in clinical samples and revealed three additional EGFR alleles: S464L, G465R, and I491M. Structurally, these mutations are located in the cetuximab-binding region, except for the R451C mutant. Functionally, EGFR ectodomain mutations prevent binding to cetuximab but a subset is permissive for interaction with panitumumab. CONCLUSIONS: Colorectal tumors evade EGFR blockade by constitutive activation of downstream signaling effectors and through mutations affecting receptor-antibody binding. Both mechanisms of resistance may occur concomitantly. Our data have implications for designing additional lines of therapy for patients with colorectal cancer who relapse upon treatment with anti-EGFR antibodies.