Temporal relationship between sarcoidosis and malignancies in a nationwide cohort of 1942 patients.

PURPOSE: To investigate the phenotype of sarcoidosis according to the time when a malignancy is diagnosed (preexisting to the diagnosis of sarcoidosis, concomitant, or sequential) and to identify prognostic factors associated with malignancies in a large cohort of patients with sarcoidosis. METHODS: We searched for malignancies in the SARCOGEAS cohort, a multicenter nationwide database of consecutive patients diagnosed with sarcoidosis according to the ATS/ESC/WASOG criteria. Solid malignancies were classified using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) nomenclature, and hematological malignancies using the 2016 WHO classification. We excluded patients with a biopsy-proven diagnosis of sarcoidosis based exclusively on demonstrating granulomas in tissues also involved by malignant cells. RESULTS: Out of 1942 patients with sarcoidosis, 233 (12%) developed 250 malignancies, including solid (n = 173), hematological (n = 57), and both types of malignancies (n = 3). Concerning the time interval between the diagnoses of both conditions, 83 (36%) patients were diagnosed with malignancy at least 1 year before sarcoidosis diagnosis, 22 (9%) had s synchronous diagnosis of both diseases, and 118 (51%) developed malignancies at least 1 year after the diagnosis of sarcoidosis (the remaining cases developed malignancies in different time intervals). The multivariate-adjusted model showed that individuals with sarcoidosis who developed a malignancy had an hazard ratio (HR) of 2.27 [95% confidence interval (CI), 1.62-3.17] for having an asymptomatic clinical phenotype at diagnosis of sarcoidosis and that spleen (presence vs. absence: HR = 2.06; 95% CI, 1.21-3.51) and bone marrow (presence vs. absence: HR = 3.04; 95% CI, 1.77-5.24) involvements were independent predictors for the development of all-type malignancies. No predictive factors were identified when the analysis was restricted to the development of solid malignancies. The analysis limited to the development of hematological malignancies confirmed the presence of involvement in the spleen (HR = 3.73; 95% CI, 1.38-10.06) and bone marrow (presence vs. absence: HR = 8.00; 95% CI, 3.15-20.35) at the time of sarcoidosis diagnosis as predictive factors. CONCLUSION: It is essential to consider the synchronous or metachronous timing of the diagnosis of malignancies in people with sarcoidosis. We found that half of the malignancies were diagnosed after a diagnosis of sarcoidosis, with spleen and bone marrow involvement associated with a four to eight times higher risk of developing hematological malignancies. Key messages What is already known on this topic Malignancies are one of the comorbidities more frequently encountered in people with sarcoidosis What this study adds Malignancies occur in 12% of patients with sarcoidosis Malignancy may precede, coincide with, or follow the diagnosis of sarcoidosis One-third were identified before sarcoidosis, and half were diagnosed after Spleen and bone marrow involvement are risk factors for developing hematological malignancies How this study might affect research, practice or policy Patients with sarcoidosis should be regularly monitored for neoplasms, informed of the increased risk, and educated on early detection. Those with spleen or bone marrow involvement must be closely followed.

Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma.

BACKGROUND: Recent studies indicate an association between immunosuppression for immune-related adverse events (irAEs) and impaired survival in patients who received immune checkpoint inhibitors. Whether this is related to corticosteroids or second-line immunosuppressants is unknown. In the largest cohort thus far, we assessed the association of immunosuppressant type and dose with survival in melanoma patients with irAEs. METHODS: Patients with advanced melanoma who received immunosuppressants for irAEs induced by first-line anti-PD-1 ± anti-CTLA-4 were included from 18 hospitals worldwide. Associations of cumulative and peak dose corticosteroids and use of second-line immunosuppression with survival from start of immunosuppression were assessed using multivariable Cox proportional hazard regression. RESULTS: Among 606 patients, 404 had anti-PD-1 + anti-CTLA-4-related irAEs and 202 had anti-PD-1-related irAEs. 425 patients (70 %) received corticosteroids only; 181 patients (30 %) additionally received second-line immunosuppressants. Median PFS and OS from starting immunosuppression were 4.5 (95 %CI 3.4-8.1) and 31 (95 %CI 15-not reached) months in patients who received second-line immunosuppressants, and 11 (95 %CI 9.4-14) and 55 (95 %CI 41-not reached) months in patients who did not. High corticosteroid peak dose was associated with worse PFS and OS (HRadj 1.14; 95 %CI 1.01-1.29; HRadj 1.29; 95 %CI 1.12-1.49 for 80vs40mg), while cumulative dose was not. Second-line immunosuppression was associated with worse PFS (HRadj 1.32; 95 %CI 1.02-1.72) and OS (HRadj 1.34; 95 %CI 0.99-1.82) compared with corticosteroids alone. CONCLUSIONS: High corticosteroid peak dose and second-line immunosuppressants to treat irAEs are both associated with impaired survival. While immunosuppression is indispensable for treatment of severe irAEs, clinicians should weigh possible detrimental effects on survival against potential disadvantages of undertreatment.

Enfermedad de Castleman, fisiopatología, avances en el diagnóstico y tratamiento / Castleman's disease, pathophysiology, advances in diagnosis and treatment

La enfermedad de Castleman (EC) engloba a un conjunto heterogéneo de procesos linfoproliferativos que comparten rasgos histológicos bien definidos. Se considera una enfermedad rara o minoritaria u su incidencia no es del todo conocida, aunque se estima en menos de uno por cada 100.000 habitantes. Tiene una distribución bimodal (30-40 años y luego los 60-80 años). Su incidencia es similar en ambos sexos, aunque la variante unicéntrica parece tener ligero predominio en mujeres con proporción 2:1. La EC se clasifica en una forma hialinovascular (siendo esta la más frecuente) y otra plasmocelular, relacionadas con el virus de la inmunodeficiencia humana (VIH) y el virus herpes humano tipo 8 (VHH-8), que junto a otros mecanismos autoinmunitarios desarrollan la hiperproducción de interleucina-6 (IL-6) por parte de los linfocitos B. Existen diferentes líneas de tratamiento, donde destaca el uso de anti IL-6, siendo el siltuximab el más utilizado y catalogado como el fármaco huérfano de esta patología.(AU)

Castleman's disease (CD) encompasses a heterogeneous set of reactive lymphoproliferative processes that share well-defined histologic features. CD is considered a rare or minority disease. The incidence of CD is not fully known, although it is estimated at less than 1 per 100,000 inhabitants. It has a bimodal distribution (30–40 years and then 60–80 years). The incidence is similar in both sexes, although the unicentric variant seems to have a slight predominance in women with a 2:1 ratio. CD is classified into a hyalinovascular form (this being the most frequent) and a plasmocellular form, related to the HIV and VHH-8 viruses, which together with other autoimmune mechanisms develop hyperproduction of interleukin-6 (IL-6) by B lymphocytes. There are different lines of treatment, where the use of anti IL-6 stands out, being siltuximab the most used as orphan drug in this pathology.(AU)

Disfunción tiroidea y lipídica asociada a bexaroteno en el linfoma cutáneo de células T / Thyroid and lipidic dysfunction associated with bexarotene in cutaneous T-cell lymphoma

Fundamento y objetivo: El bexaroteno es un rexinoide sintético selectivo del receptor X aprobado para el tratamiento sistémico del linfoma cutáneo de células T. Durante el tratamiento es muy frecuente la aparición de hipotiroidismo e hiperlipidemia mixta grave, siendo ambos efectos adversos reversibles y dependientes de la dosis. La elevación del colesterol LDL y los triglicéridos (hasta unos niveles aumentados que incluso se han asociado a pancreatitis en algunos casos) está ampliamente descrita (al igual que sucede con otros retinoides), siendo el descenso del colesterol HDL menos conocido. Revisamos nuestra experiencia con el uso de bexaroteno. Material y métodos: Se presenta una serie de 3 casos de pacientes tratados con bexaroteno en los que, además de sufrir los efectos adversos bien conocidos, se observó un grave descenso del colesterol HDL. Resultados: Los 3 pacientes estudiados presentaron complicaciones metabólicas en forma de hipotiroidismo central e hiperlipidemia mixta grave, con especial énfasis en el marcado descenso que experimentaron nuestros pacientes (descenso medio > 83%) en las cifras de colesterol HDL. El tratamiento hipolipidemiante y hormonal sustitutivo con levotiroxina dio lugar a una mejoría de los parámetros, sin llegar a alcanzarse los objetivos. Conclusiones: El bexaroteno produce, como efectos secundarios predecibles, una hiperlipidemia mixta grave con descenso marcado de los niveles de colesterol HDL e hipotiroidismo central, los cuales son reversibles y dependientes de la dosis. Se incluye una reflexión sobre los posibles mecanismos etológicos e implicaciones de este fenómeno (AU)

Background and objective: Bexarotene is a synthetic selective X receptor rexinoide approved for the systemic treatment of cutaneous T-cell lymphoma. During treatment is very frequent the occurrence of hypothyroidism and severe mixed hyperlipidemia, both are reversibles and dose-dependent adverse events. Increase of triglycerides and LDL-cholesterol level (up to even higher levels have been associated with pancreatitis in some cases) is widely described (as is the case with other retinoids) but decrease in HDL-cholesterol is poored know. We review our experience with the use of bexarotene. Material and methods: We present a serie of 3 clinical report of patients treated with bexarotene in whose, in addition to these well-known adverse event, a serious lowering of HDL-cholesterol was observed. Results: The 3 patients studied had metabolic complications like central hypothyroidism and severe mixed hyperlipidemia; with special emphasis on the sharp fall (mean decrease > 83%) in the HDL-cholesterol level. Cholesterol lowering medication and substitutive hormonal replacement with levotiroxine resulted in an improvement of the biochimical parameters without reaching the correct goals. Conclusions: Bexarotene produce as predictable side effects severe mixed hyperlipidemia with marked decrease in HDL-cholesterol levels and central hypothyroidism, being the both reversible and dose-dependent. A reflection on the possible aetiological mechanisms and implications of this phenomenon are included (AU)

Proceso de transición de la asistencia pediátrica a la adulta en pacientes con errores congénitos del metabolismo. Documento de consenso / Transition process from paediatric to adult care in patients with inborn errors of metabolism. Consensus statement

Antecedentes y objetivo: El proceso de transición de la asistencia pediátrica a la adulta es un tema de gran interés en los últimos años, especialmente en enfermedades crónicas de inicio en la infancia, como los errores congénitos del metabolismo (ECM). Los avances en el diagnóstico y el tratamiento de estas enfermedades han mejorado su pronóstico, encontrando en la actualidad un elevado número de pacientes con ECM que alcanzan la edad adulta y necesitan ser atendidos por profesionales no pediátricos. El objetivo de este trabajo es establecer unas pautas de actuación para que los especialistas involucrados garanticen una transición exitosa de la atención sanitaria de estos pacientes. Metodología: Tras realizar una revisión bibliográfica del tema, los autores, partiendo de su propia experiencia, elaboraron un documento inicial que fue sometido a sucesivos debates hasta obtener el documento definitivo. En caso de discrepancia de criterio, la recomendación de consenso se decidió por mayoría. Resultados: Se presentan una serie de recomendaciones para el mejor abordaje clínico de la transición asistencial de los pacientes con ECM desde el entorno pediátrico a la asistencia de adultos, con el objetivo de conseguir los mejores resultados en este proceso, dadas las características especiales de este subgrupo de pacientes, así como las principales dificultades que conlleva el proceso de transición Conclusiones: Se resalta el papel del médico internista en este proceso de transición y su correcta articulación con el entorno pediátrico y social. Asimismo, se recomiendan acciones y actitudes para mejorar la calidad de dicha transición (AU)

Background and objective: The transition process from paediatric to adult care is a subject of great interest in recent years, especially in chronic diseases with childhood onset, such as inborn errors of metabolism (IEM). Advances in diagnosis and treatment of these diseases have improved their prognosis, with a high number of patients with IEM who currently reach adult age and need to be attended to by non-paediatric professionals. The objective of this work is to establish action guidelines so that the specialists involved can guarantee a successful transition of these patients’ healthcare. Methodology: After carrying out a bibliographic review of the subject, the authors, beginning with their own experience, produced an initial document which was subjected to successive debates until the final document was obtained. The consensus recommendation was decided by the majority in case of criterion discrepancy. Results: A series of recommendations are presented for the best clinical management of the transitions of care of patients with IEM from the paediatric to adult care setting in order to achieve the best results in this process given the special characteristics of this patient subgroup and the main difficulties entailed in the transition process. Conclusions: The role of the internal medicine doctor in this transition process and correct interrelation with the paediatric and social setting is stressed. Furthermore, actions and attitudes are suggested to improve the quality of said transition (AU)

Características clínicas, bases celulares y moleculares de la hipertensión arterial del anciano / Clinical characteristics, cellular and molecular basis of hypertension in elderly

Con la edad aumenta la prevalencia de hipertensión arterial (HTA),que, por otra parte, adquiere una serie de características clínicas quela diferencian de la HTA en el joven o en las edades medias de la vida.En la presente revisión estudiamos los mecanismos moleculares y celularesque relacionan HTA y envejecimiento, y discutimos ciertas peculiaridadesclínicas de la HTA del anciano, como son la relación conla rigidez arterial y la HTA sistólica aislada. Finalizamos planteandoobjetivos de control de la presión arterial en el anciano y medidaspara retrasar o prevenir el desarrollo de esta forma, no siempre bienconocida, de HTA

The prevalence of arterial hypertensión (AH) increases with ageing,and, on the other hand, it acquires a series of clinical characteristicsthat differentiates it from AH in young persons or in subjects in averageages of the life. In the present article we will study several cellularor molecular mechanisms, which relate AH and aging. Moreover, wewill discuss certain clinical peculiarities of AH in the elderly such asthe relation with arterial stiffness and with isolated systolic hypertension.We will finalize proposing objectives of control of blood pressurein the elderly as well as marking strategies to delay, or prevent, the development of this, not always well-known, form of AH (AU)

Réplica. Manejo del paciente pluripatológico en una unidad de hospitalización domiciliaria / Reply. Managing the patient with multimorbidity in a hospital at home unit

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Absceso hepático por Klebsiella pneumoniae en inmigrante oriental / Hepatic abscess due to Klebsiella pneumoniae in an oriental immigrant

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Incidencia y características clínicas de los pacientes con pluripatología ingresados en una unidad de medicina interna / Incidence and clinical features of patients with comorbidity attended in internal medicine areas

Fundamento y objetivo: Analizar la incidencia y características clínicas y evolutivas de pacientes con pluripatología (PP), según la definición propuesta por una comisión de expertos (2 o más enfermedades crónicas distribuidas en 7 categorías). Pacientes y método: Estudio prospectivo observacional en áreas de medicina interna de un hospital de tercer nivel durante junio de 2003. Se estratificó a los pacientes en PP, paliativo (PL) y general (GE) según los criterios de una comisión de expertos. Se analizó la incidencia de PP, procedencia, limitación funcional basal, al ingreso y al alta, evolución y consumo de recursos (atenciones urgentes, programadas, y hospitalizaciones) en los 12 meses previos. Se realizó un análisis multivariante de los factores asociados a la supervivencia y al deterioro funcional significativo (descenso en la escala de Barthel de 10 o más puntos entre basal-alta) en la cohorte de PP. Resultados: Se incluyó a 339 pacientes (cohorte PP: 132; PL: 52; GE: 155). La incidencia global de PP fue 38,9/100 ingresos/mes. En comparación con la cohorte GE, los PP tuvieron mayor edad (media [desviación estándar] 75 [11] frente a 67 [16] años); mayor mortalidad (un 19,3 frente al 6,1%; riesgo relativo [RR] = 3,66; [intervalo de confianza [IC] del 95%, 1,65-8,13]); mayor limitación funcional basal (45 frente a 95), al ingreso (20 frente as 75) y al alta (20 frente a 95); mayor porcentaje de deterioro funcional significativo (un 16 frente al 7%; RR = 2,47 [IC del 95%, 1,15-5,35]); y mayor consumo de recursos en términos de asistencia urgente (3,6 [3,4] episodios frente a 2,4 [1,9]) y hospitalizaciones (1,9 [1,3] frente a 1,5 [1]). La supervivencia se asoció con padecer enfermedad del aparato digestivo (odds ratio [OR] = 48,3 [IC del 95%, 2,4-980,9]) o arteriopatía periférica/diabetes con repercusión visceral (OR = 5,6 [IC del 95%, 1,1-28,6]) y una mayor puntuación Barthel al ingreso. Se asociaron a un deterioro funcional significativo el sexo femenino (OR = 46,6 [IC del 95%, 4,5-486,9]) y padecer enfermedad pulmonar crónica (OR = 8,9 [IC del 95%, 1,2-64]) o enfermedad neurológica con discapacidad (OR = 8 [IC del 95%, 1,1-58,9]). Conclusiones: En áreas de medicina interna la incidencia de PP es elevada. La definición propuesta identifica a una población con especial fragilidad clínica, con una mayor necesidad de recursos hospitalarios y un deterioro funcional importante. La escala de Barthel constituyó un buen identificador común de grupo y un marcador pronóstico independiente

Background and objective: Our objective was to assess the incidence and clinical features of patients with numerous disorders--comorbidity patients (CP)--and to clinically validate the CP criteria defined by a panel of experts (patients with 2 or more chronic diseases, distributed into seven cathegories). Patients and method: Prospective observational study of all patients, attended in internal medicine areas of a tertiary teaching hospital, during June 2003. Patients were stratified in 3 cohorts: CP, palliative, and general (GE). Incidence of CP, functional evaluation (at baseline, at admission, and at discharge), and burden of hospital care (by means of urgent and programmed visits, as well as episodes of hospitalization) in the last 12 months were analyzed. A multivariate analysis of predictors of survival and functional deterioration (fall in Barthel's scale >= 10 points between baseline-discharge values) was performed in the CP cohort. Results: 339 patients (CP cohort: 132; palliative: 52; GE: 155) were included. The overall incidence was 38.9/100 admissions/month. CP were older (75 [11] vs 67 [16]); had higher mortality (19.3% vs 6.1%; relative risk [RR]: 3.66 [95% confidence interval [CI], 1.65-8.13]; lower functional ability at baseline (45 vs 95), at admission (20 vs 75), and at discharge (20 vs 95); higher rates of significant functional deterioration (16% vs 7%; RR = 2.47 [95% CI, 1.15-5.35]); and required more burden of hospital care by means of urgent care (3.6 [3.4] episodes vs 2.4 [1.9]), and hospitalizations (1.9 [1.3] vs 1.5 [1]) than GE patients. Chronic digestive/hepatic diseases (odds ratio [OR] = 48.3 [2.4-980.9], peripheric vascular disease/diabetes with visceral involvement (OR = 5.6 [CI 95%, 1.1-28.6]), and better functional ability at admission were associated with survival. Female gender (OR ) 46.6 [CI 95%, 4.5-486.9]), chronic lung disease (OR = 8.9 [CI 95%, 1.2-64]), and neurologic disease with disability (OR = 8 [CI 95%, 1.1-58.9]), were associated with significant functional deterioration during hospital stay. Conclusions: The defined CP criteria were highly accurate in detecting a population of patients with high attention in Internal Medicine areas, high mortality rates, clinical frailty (more need of hospital care), and significant functional deterioration. Barthel's scale identified correctly this group of patients, and was independently associated with survival

Disminución de la actividad de la 11- ß-hidroxiesteroide deshidrogenasa en pacientes con síndrome de Cushing / Decreased activity of 11-ß-hydroxysteroid dehydrogenase in patients with Cushing's syndrome

Fundamento: Análisis de la actividad de la 11-ß-hidroxiesteroide deshidrogenasa en el síndrome de Cushing. Pacientes y método: Determinación de la eliminación en orina de 24 h de cortisol, cortisona y sus tetrahidroderivados en 15 pacientes con síndrome de Cushing y 24 controles sanos. Resultados: Existía una relación lineal significativa entre cortisol y cortisona (r = 0,70; p < 0,0001) y entre sus tetrahidroderivados (r = 0,75; p < 0,0001) en los controles, pero no en los pacientes. Conclusiones: Los pacientes con síndrome de Cushing presentan un déficit de la actividad de la 11-ß-hidroxiesteroide deshidrogenasa (AU)

Diagnóstico tardío en la roturatraumática del páncreas y el conductopancreático / Delayed diagnosis in the traumatic disruption of pancreatic duct

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Crisis hipertensiva y bloqueo transitorio de rama izquierda con prolongación del intervalo QT asociados a moxifloxacino / Hypertensive crisis and transitory left bruch block with QT interval prolongation associated to monxifloxacin

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Piomiositis primaria por Rhodococcus spp. en un paciente inmunocompetente / Primary pyomiositis by Rhodococcus spp. in immunocompetent patient

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