Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study.

BACKGROUND: CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study. MATERIALS AND METHODS: Select TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose-escalation and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and the outcome of treatment with immune-modulating medication (IMM) was evaluated. RESULTS: The analysis included 262 patients. The most common sTRAE was skin (35.5%), followed by gastrointestinal (14.5%) and hepatic (14.1%) events; the majority were grade 1/2, with 10.7% of patients experiencing grade 3/4 events. One patient had grade 5 pneumonitis. Median (range) TTO ranged from 3.6 (0.1-59.9) weeks for skin sTRAEs to 47.6 (47.1-48.0) weeks for renal sTRAEs. Overall, 68% of sTRAEs resolved, with median (range) TTR ranging from 3.7 (0.1-123.3+) weeks for gastrointestinal sTRAEs to 28.4 (0.1-79.1) weeks for endocrine sTRAEs. Most gastrointestinal and all hepatic events resolved with treatment in accordance with established toxicity management algorithms. In 57 patients (40%), sTRAEs were managed with IMM. Reoccurrence of sTRAEs was uncommon following rechallenge with nivolumab. CONCLUSION: Nivolumab demonstrated a manageable safety profile in this analysis of patients with advanced HCC. A majority of sTRAEs resolved with treatment. IMPLICATIONS FOR PRACTICE: Nivolumab is a viable treatment option for patients with previously treated advanced hepatocellular carcinoma as it has demonstrated durable tumor responses and promising survival. Nivolumab has a manageable safety profile. The most common select treatment-related adverse events (sTRAEs) in this analysis were skin related (35%). Gastrointestinal and hepatic sTRAEs were observed in approximately 14% of patients. The majority of sTRAEs resolved (68%). Safety events are easier to manage if addressed early. Patient education on signs and symptoms to watch out for and the importance of early reporting and consultation should be emphasized.

Phase 1-2 pilot clinical trial in patients with decompensated liver cirrhosis treated with bone marrow-derived endothelial progenitor cells.

The aim of this nonrandomized, open label, phase 1 clinical trial was to evaluate the safety and the feasibility of the treatment with autologous bone marrow-derived endothelial progenitor cells (EPC) in decompensated liver cirrhosis. In addition, the changes in liver function and hepatic venous pressure gradient (HVPG) and their relation with the characteristics of the cellular product were analyzed. Twelve patients with Child-Pugh ≥8 liver cirrhosis underwent bone marrow harvest for ex vivo differentiation of EPC. The final product was administered through the hepatic artery in a single administration. Patients underwent clinical and radiologic follow-up for 12 months. The phenotype and the ability to produce cytokines and growth factors of the final cellular suspension were analyzed. Eleven patients were treated (feasibility 91%). No treatment-related severe adverse events were observed as consequence of any study procedure or treatment. Model for end-stage liver disease score improved significantly (P 0.042) in the first 90 days after cells administration and 5 of the 9 patients alive at 90 days showed a decreased of HVPG. There was a direct correlation between the expression of acetylated-low density lipoprotein and von Willebrand factor in the cellular product and the improvement in liver function and HVPG. The treatment with EPCs in patients with decompensated liver cirrhosis is safe and feasible and might have therapeutic potential. Patients receiving a higher amount of functionally active EPC showed an improvement of liver function and portal hypertension suggesting that the potential usefulness of these cells for the treatment of liver cirrhosis deserves further evaluation.

Evaluación de un programa comunitario para reducir el aislamiento de personas mayores debido a barreras arquitectónicas / Evaluation of a community program to reduce isolation in older people due to architectural barriers

Objetivo. Se llevó a cabo una intervención comunitaria para reducir el aislamiento de las personas mayores debido a barreras arquitectónicas. Este estudio evalúa sus efectos. Métodos. Estudio cuasiexperimental antes-después. Se localizaron en la comunidad personas mayores aisladas en tres zonas desfavorecidas en 2009-11. Salieron quincenalmente con voluntariado y una silla-oruga motorizada. Se estudió la satisfacción y se comparó, con pruebas de McNemar, su estado de salud percibido, su calidad de vida y su salud mental antes y después de cuatro salidas. Resultados. Participaron 74 personas (edad mediana: 83 años; rango intercuartílico: 78-89). La salud percibida mejoró un 21%, la mental un 24% y el malestar psicológico se redujo un 16%. El 98% estaban satisfechas. Conclusiones. La intervención mejoró la salud percibida y la salud mental de las personas participantes. Debería evitarse que estas personas residan en edificios con barreras arquitectónicas, y si no es posible, implementar programas similares a éste (AU)

Objective. Social isolation impairs health. An intervention to reduce isolation due to architectural barriers in elderly persons was carried out in Barcelona (Spain). This study aimed to evaluate its effects on health. Methods. We conducted a quasi-experimental before-after study. Isolated older people were identified in three deprived urban areas from 2009 to 2011. Participants had twice-weekly outings with volunteers in a stair-climbing power wheelchair. User satisfaction was evaluated and perceived health status, quality of life, and mental health before and after four outings were compared with McNemar tests. Results. There were 74 participants (median age: 83 years; IQR: 78-89). Perceived health improved by 21%, mental health by 24%, and psychological distress was reduced by 16%. Most participants (98%) were satisfied. Conclusion. The intervention improved perceived health and mental health. Elderly people with impaired mobility should not live in buildings with architectural barriers and, if this cannot be avoided, similar programs should be implemented (AU)

[Evaluation of a community program to reduce isolation in older people due to architectural barriers]. / Evaluación de un programa comunitario para reducir el aislamiento de personas mayores debido a barreras arquitectónicas.

OBJECTIVE: Social isolation impairs health. An intervention to reduce isolation due to architectural barriers in elderly persons was carried out in Barcelona (Spain). This study aimed to evaluate its effects on health. METHODS: We conducted a quasi-experimental before-after study. Isolated older people were identified in three deprived urban areas from 2009 to 2011. Participants had twice-weekly outings with volunteers in a stair-climbing power wheelchair. User satisfaction was evaluated and perceived health status, quality of life, and mental health before and after four outings were compared with McNemar tests. RESULTS: There were 74 participants (median age: 83 years; IQR: 78-89). Perceived health improved by 21%, mental health by 24%, and psychological distress was reduced by 16%. Most participants (98%) were satisfied. CONCLUSION: The intervention improved perceived health and mental health. Elderly people with impaired mobility should not live in buildings with architectural barriers and, if this cannot be avoided, similar programs should be implemented.

Feasibility of a community action model oriented to reduce inequalities in health.

OBJECTIVE: To assess the feasibility and achievements of a systematic community action model, Health in the Neighbourhoods, in two deprived areas of Barcelona. METHODS: The feasibility of the model implementation in two neighbourhoods was assessed. The model developed three stages aiming: (1) to make alliances with partners and stakeholders, (2) to develop a participatory needs and assets assessment, and (3) to plan, implement and evaluate interventions on the community prioritised needs. The feasibility of the model at each stage was assessed through the percentage of achievement of 18 indicators. It was evaluated between 2007 and 2011. RESULTS: The achievement of the indicators exceeded an average of 75% in both neighbourhoods. In stage 1 community working groups were set up. In stage 2 a comprehensive assets and health needs assessment was done through quantitative and qualitative methods, as well as participative prioritizations of community health problems. In stage 3, the community working groups defined an action plan and a number of interventions against the prioritised problems, based on evidence and local assets reviews. Interventions were developed, implemented and evaluated. CONCLUSION: This structured model, including a small set of indicators, enabled the implementation of a community action model with neighbourhoods' stakeholders. The model showed flexibility to adapt to neighbourhoods' characteristics and the objectives were successfully met. The alliances and partnerships with community and municipal sectors promoted the sustainability of most interventions.

Liquen estriado del adulto: experiencia en un servicio de Dermatología / Adult lichen striatus: experience in dermatology service

Introducción. El liquen estriado es una dermatosis que sigue el trayecto de las líneas de Blaschko, se presenta característicamente en población pediátrica y es rara en pacientes adultos. Objetivo. Describir las características epidemiológicas y clínicas de los pacientes adultos con diagnóstico de liquen estriado diagnosticados en el período 1998-2010 en el Hospital Nacional Daniel Alcides Carrión (HNDAC). Material y Métodos. Estudio descriptivo de tipo serie de casos. Se revisó las historias clínicas de los casos de liquen estriado y se obtuvo datos epidemiológicos (edad, sexo), antecedentes de importancia (comorbilidad) y aspectos clínicos de los pacientes (tiempo de enfermedad, características de las lesiones, síntomas asociados). Los datos obtenidos fueron registrados en un instrumento de recolección de datos. Resultados. Ingresaron al estudio un total de 10 casos, el promedio de edad fue de 27 años (rango 16-48 años), 80% de los casos fueron de sexo femenino. Las lesiones clínicas eran placas formadas por pápulas milimétricas levemente descamativas de color piel, eritematosas o ligeramente hipopigmentada de distribución lineal y que seguían las líneas de Blaschko. Las lesiones se presentaron con mayor frecuencia en miembros inferiores (60%) y tronco (40%). El síntoma más frecuentemente referido porlos pacientes fue prurito (70%). La comorbilidad más frecuente fue atopía que se presentó en 40% de los pacientes. Conclusión. Los pacientes adultos con diagnóstico de liquen estriado del HNDAC presentan características clínicas similares a las descritas en pacientes pediátricos. La atopía constituye la comorbilidad más frecuente.

Back ground. Lichen adult is a dermatosis that follows the Blaschko lines, tipically it present in pediatrics population and is rare in adult patients. Objective. Describe the epidemiological and clinical characteristics with diagnosis of lichen striatus that were diagnosed between1998-2010 at National Hospital Daniel Alcides Carrion (HNDAC). Material and methods. Descriptive study of a case series. Clinical records were reviewed, obtaining epidemiological data (age, genre), background of importance (comorbidity) and clinical aspects of the patients ( time of illness , characteristics of the injuries, associated symptoms) that were recorded in a data collection instrument. Results. Ten cases were enrolled, the age average was 27 years old (range 16-48 years), 80% of cases corresponded to females. Clinical injuries were plates formed by millimeter papules slightly descamatives of skin color, eritematoses or slightly hypopigmentated od linear distribution and that followed the blaschko lines. Injuries were presented with more frequency at the lower limbs (60%) andin trunk (40%). The most frequent symptom was the pruritus (70%).The most frequent comorbidity was the atopy, presents in 40% of the patients. Conclusion. Adult patients with diagnosis of lichen striatus atthe HNDAC present clinical characteristics similar to pediatrics patients. The comorbility more frequent is the atopy.

Placa hiperpigmentada en la palma de mano de un anciano / Hyperpygmented patch in a old man´s palm

Se presenta el caso de un paciente anciano que acude por una placa marrón en la palma de una mano asintomática. Se comprometen posteriormente la otra palma y las plantas de ambos pies. Presenta serología treponémica positiva, dermatitis en banda con infiltrado inflamatoria a predominio de células plasmáticas, tinción argéntica sugerente y respuesta terapéutica por lo que se concluye que se trataba de un cuadro de sífilis secundaria simulando una tina negra.

We present the case of an old man who seeks medical care because a brown patch in a hand palm without symptoms. A couple of weeks after that both soles and the other hand has been compromised too. We get a positive luetic serology, band dermatitis with great amount of plasma cells, suggestive silver dye, and therapeutic response. We conclude that the case was a luetic secondarily mimic black tinea.

[Making peripheral blood vessels adequate for access in emergency ward services]. / Adecuación de las vías venosas periféricas en urgencias.

Accessing peripheral blood vessels is one of the most frequently practiced invasive techniques carried out in emergency wards for diagnostic and/or therapeutic purposes. The authors of this article study the peripheral blood vessels and evaluate making their access adequate for treatment by means of a transversal descriptive study. The results of the authors' study show that 33% of the blood vessels catheterized do not comply with the criteria for their adequacy described in the methodology to consider them adequate for catheterization. This relatively high percentage, besides increasing the economic costs in terms of human and material resources, has a negative effect on the functioning of an emergency ward, leading to increased waiting times for other patients pending evaluation-treatment, with the risk that this implies. The elaboration and implementation of a guide to prescribe peripheral blood vessels catheterization may prove useful in order to reduce the number of inadequate blood vessels catheterized and to improve the quality of the care provide by emergency ward personnel.

Adecuación de las vías venosas periféricas en urgencias / Making peripheral blood vessels adequate for access in emergency ward services

El acceso venoso periférico supone una de las técnicas invasivas más frecuentemente practicadas en los Servicios de Urgencias, con fines diagnósticos y/o terapéuticos. Se estudian las vías venosas periféricas y se valora su adecuación mediante un estudio descriptivo transversal. Los resultados obtenidos demuestran que un 33% de las vías canalizadas no cumple los criterios de adecuación descritos en la metodología para considerarlas adecuadas. Este porcentaje bastante elevado, además de aumentar el coste económico de los recursos humanos y materiales, repercute de forma negativa en el funcionamiento del Servicio, alargando el tiempo de espera de otros pacientes pendientes de valorar, con el riesgo que esto implica. La elaboración e implantación de una guía para prescribir la cateterización venosa periférica puede resultar útil para disminuir el número de vías inadecuadas y mejorar la calidad de la asistencia(AU)

Accessing peripheral blood vessels is one of the most frequently practiced invasive techniques carried out in emergency wards for diagnostic and/or therapeutic purposes. The authors of this article study the peripheral blood vessels and evaluate making their access adequate for treatment by means of a transversal descriptive study. The results of the authors’ study show that 33% of the blood vessels catheterized do not comply with the criteria for their adequacy described in the methodology to consider them adequate for catheterization. This relatively high percentage, besides increasing the economic costs in terms of human and material resources, has a negative effect on the functioning of an emergency ward, leading to increased waiting times for other patients pending evaluation-treatment, with the risk that this implies. The elaboration and implementation of a guide to prescribe peripheral blood vessels catheterization may prove useful in order to reduce the number of inadequate blood vessels catheterized and to improve the quality of the care provide by emergency ward personnel(AU)

Sistematización del estudio de las formas clínicas de Liquen escleroso y atrófico en adultos / Adult lichen sclerosus et atrophicus clinical forms study systematization

El liquen escleroso puede ser encontrado en cualquier grupo etáreo, sexo o raza. En la literatura se ha descrito varias formas deliquen escleroso. Objetivo: Facilitar el estudio de liquen escleroso, sistematizando sus caracteres clínicos. Materiales y métodos: Ensayar una clasificación sobre formas clínicas de liquen escleroso, de acuerdo a su frecuencia y la consistencia de cómo son definidos en la literatura médica. Resultados: Entre enero a noviembre de 2006, en 1417 pacientes encontramos 8 diferentes formasclínicas. Formas clásicas: en reloj de arena o forma de 8 (1 forma), balanitis xerótica obliterante (1), pequeñas placas en el pene (3) -relacionado a circuncisión previa por fimosis (2) -. Formas no clásicas: generalizada (1 forma), asociado a carcinoma escamoso de vulva (1), concomitante a hemorragia uterina disfuncional (1), superpuesta a morfea y dermatitis infectiva en una paciente infectada con el HTLV-I (1). Conclusiones: Las 8 diferentes formas de liquen escleroso encontradas en este trabajo sugieren la necesidad de continuar buscando una clasificación que permita un adecuado reconocimiento de estas diferentes formas.

Lichen sclerosus can be found at any age, sex or race. Several clinical forms of lichen sclerosus have been described in the literature. Objective: To facilitate lichen sclerosus study organizing its clinical features. Materials and methods: A classification of the clinical forms of lichen sclerosus was assayed. Clinical features were organized according to frequency and consistency as defined in medical references. Results: Between January and November 2006, we found 11 cases of lichen sclerosus in 1417 dermatology patients. Eight different clinic forms were found. Classical forms: æfigure of eightÆ shape (1 form),balanitis xerotica obliterans (1), small plaques in penis (3) related to previous circumcision for phimosis (2). Non-classical forms: generalized (1 form), associated to vulvar squamous carcinoma (1), concomitant to morphoea and dysfunctional uterine bleeding (1) and superimposed to morphoea and infective dermatitis in an HTLV-I infected patient (1). Conclusions: The finding of eight different forms of lichen sclerosus suggests the need to continue looking for an ideal classification to adequately recognize these different clinical forms.