Síndrome de Hedinger secundario a Tumor neuroendocrino bronquial. Presentación de un caso

El síndrome carcinoide es un síndrome paraneoplásico que se presenta en tumores neuroendocrinos. Aunque es una entidad infrecuente suele ser la primera manifestación de la enfermedad. La baja incidencia junto a la presentación inespecífica genera retrasos diagnósticos importantes. Se presenta el caso de una paciente con síntomas digestivos y tuforadas que posteriormente agrega insuficiencia cardíaca, logrando mediante un ecocardiograma típico y marcadores analíticos el diagnóstico de síndrome carcinoide. Posteriormente se evidencia que su origen en un tumor neuroendocrino bronquial. Conocer las características de este síndrome es fundamental para mantener una alta sospecha clínica en pacientes con síntomas sugestivos logrando un diagnóstico precoz y adecuado.

Carcinoid syndrome is a paraneoplastic syndrome that occurs in neuroendocrine tumors. Although It is an uncommon entity, it is usually the first manifestation of the disease. The low incidence besides the non-specific presentation generates important diagnostic delays. We present the case of a patient presenting digestive symptoms and flushing that subsequently adds heart failure, achieving though a typical echocardiogram and analytical markers the diagnosis of carcinoid syndrome. Later it is discovered its origin in a bronchial neuroendocrine tumor. Knowing the characteristics of this syndrome is essential to maintain a high clinical suspicion in patients with suggestive symptoms, in order to achieve an early and adequate diagnosis.

El síndrome carcinoide é um síndrome paraneoplásico que ocorre em tumores neuroendócrinos. Embora seja uma entidade rara, geralmente é a primeira manifestação da doença. A baixa incidência, juntamente com a apresentação inespecífica, resulta em atrasos importantes no diagnóstico. Apresentamos o caso de uma paciente com sintomas digestivos e ruborização cutânea, que posteriormente desenvolve insuficiência cardíaca. O diagnóstico de síndrome carcinoide foi estabelecido por meio de um ecocardiograma característico e marcadores analíticos. Posteriormente, foi evidenciada a origem em um tumor neuroendócrino brônquico. Conhecer as características deste síndrome é fundamental para manter uma alta suspeita clínica em pacientes com sintomas sugestivos, permitindo um diagnóstico precoce e adequado.

Cronología de la investigación sobre la dinámica cerebral de Justo Gonzalo / Chronology of Justo Gonzalo’s research on brain dynamics

Introducción: El neurocientífico español Justo Gonzalo y Rodríguez-Leal (1910-1986) investiga la organización funcional de la corteza cerebral durante más de cuatro décadas. Sus hallazgos le llevan a formular una teoría neurofisiológica basada en las leyes de la excitabilidad nerviosa, que denomina dinámica cerebral. En el presente trabajo se expone de forma cronológica cómo surgen las principales ideas sobre las que se articula.Desarrollo: En 1939 Gonzalo observa los denominados fenómenos de acción dinámica: desfasamiento, facilitación y repercusión cerebral. Le siguen dos principios: efecto cerebral de la lesión según la magnitud y posición (1941), y organización sensorial, según un desarrollo espiral (1947). Paralelamente, caracteriza lo que llama el síndrome central de la corteza cerebral. En la década de los cincuenta desarrolla los conceptos de gradiente cortical, similitud y alometría. En contraposición a las concepciones modulares de la corteza cerebral, en las que una región es responsable de una función, Gonzalo expresa que ‘los gradientes corticales dan la localización de los sistemas mientras la similitud y alometría revelan su trama funcional’.Conclusiones: La teoría de dinámica cerebral se articula en dos etapas. La primera (de 1938 a 1950) se caracteriza por una importante base clínica con observación de nuevos fenómenos y formulación de nuevos conceptos. La segunda (de 1950 a 1960) incluye la introducción de conceptos de mayor alcance, como el gradiente funcional cortical, y leyes de alometría que se basan en un cambio de escala. Actualmente, varios autores consideran que el concepto de gradiente es clave para entender la organización cerebral.(AU)

Introduction: The Spanish neuroscientist Justo Gonzalo y Rodríguez-Leal (1910-1986) investigated the functional organisation of the cerebral cortex over more than four decades. His findings led him to formulate a neurophysiological theory based on the laws of nervous excitability, which he called brain dynamics. This paper presents in chronological order how the main ideas on which it is based arose.Development: In 1939, Gonzalo observed the phenomena of dynamic action: asynchrony or disaggregation, facilitation and cerebral repercussion. This was followed by two principles: the cerebral effect of lesions according to their magnitude and position (1941), and spiral development of the sensory field (1947). At the same time, he characterised what he called the central syndrome of the cerebral cortex. In the 1950s he developed the concepts of the cortical gradient, similarity and allometry. In contrast to modular conceptions of the cerebral cortex, in which one region is responsible for one function, Gonzalo argued that ‘cortical gradients provide the location of systems, while similarity and allometry reveal their functional mechanism.’Conclusions: The theory of brain dynamics was established in two stages. The first (between 1938 and 1950) had an important clinical foundation, involving the observation of new phenomena and the formulation of new concepts. The second (between 1950 and 1960) included the introduction of more far-reaching concepts, such as the functional cortical gradient, and allometry laws based on a change of scale. Today, various authors believe that the concept of the gradient is crucial for understanding how the brain is organised.(AU)

Emergencia hipertensiva como debut de síndrome de Cushing paraneoplásico / Hypertensive Emergency as the Debut of Paraneoplastic Cushing Syndrome

Presentamos el caso de un paciente con antecedentes de hipertensión arterial vasculorrenal tratada un año antes, que acude a urgencias por emergencia hipertensiva (HTA) y disnea. Descartada primera sospecha de reestenosis de arteria renal con angiografía por tomografía computarizada (angioTC), se completa el estudio confirmándose diagnóstico de cáncer de pulmón mediante prueba de imagen y anatomía patológica. En el estudio de hipertensión se detecta elevación de hormona adrenocorticótropa (ACTH), hipercortisolismo y datos analíticos de hiperaldosteronismo. Con el diagnóstico final de síndrome de Cushing secundario a producción ectópica de ACTH se inicia tratamiento médico, sin llegar a recibir nada más por fallecimiento del paciente a los pocos días.(AU)

We present the case of a patient with a history of renal-vascular hypertension treated with stent one year previously, who attended the emergency room due to hypertensive emergency and dyspnea. Once the first suspicion of renal artery restenosis was ruled out with CT angiography, the study was completed, confirming the diagnosis of lung cancer through imaging and pathological anatomy. In the hormonal study, elevation of ACTH, hypercortisolism and analytical data of hyperaldosteronism were detected. With the final diagnosis of Cushing's syndrome secondary to ectopic production of ACTH, medical treatment was started, without being able to receive anything else due to the death of the patient after a few days.(AU)

Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice / Tratamiento concomitante de safinamida y antidepresivos: Datos de seguridad sobre la práctica en la vida real

Background and purpose: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. Methods: We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. Results: Clinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years ± 8.43 and H&Y stage was 3 [2–4]. Mean dose of levodopa used was 703.75 mg ± 233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. Conclusions: Our real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.(AU)

Objetivos: El objetivo de este estudio ha sido evaluar las posibles interacciones farmacológicas entre safinamida y antidepresivos; en particular la aparición del síndrome serotoninérgico mediante datos obtenidos en la vida real. Material y métodos: Realizamos un estudio observacional retrospectivo de pacientes con enfermedad de Parkinson (EP) de nuestra unidad de trastornos del movimiento, que estaban en tratamiento con algún fármaco antidepresivo y safinamida. Específicamente, se examinaron los síntomas sugestivos de síndrome serotoninérgico. Además, se recogieron tiempos de uso simultáneo, dosis de levodopa y otros fármacos antiparkinsonianos concomitantes. Resultados: Se revisaron las historias clínicas correspondientes al período de estudio de septiembre de 2018 a septiembre de 2019. Setenta y ocho pacientes con EP se encontraban en tratamiento con safinamida, de los cuales 25 (32,05%) se encontraban recibiendo además un fármaco antidepresivo, siendo sertralina y escitalopram los más frecuentes. La edad media fue de 80 años ± 8,43 y el estadio H&Y fue de 3 [2-4]. La dosis media de levodopa utilizada fue de 703,75 mg ± 233,15. La mediana de duración del tratamiento concomitante con safinamida y un fármaco antidepresivo fue de 6 meses (IQR: 20,5), y más de 18 meses en 5 casos. No se registró ningún caso de síndrome serotoninérgico, ni tampoco ninguno de sus síntomas de forma aislada. Conclusión: Nuestro estudio de práctica clínica real sugiere que el uso concomitante de safinamida con fármacos antidepresivos en pacientes con EP parece ser seguro y bien tolerado, incluso a largo plazo. Sin embargo, es necesaria precaución, individualizando los regímenes de tratamiento, y controlando la posible aparición de efectos adversos.(AU)

Sepsis death risk factor score based on systemic inflammatory response syndrome, quick sequential organ failure assessment, and comorbidities.

OBJECTIVE: In this study, we aimed to evaluate the death risk factors of patients included in the sepsis protocol bundle, using clinical data from qSOFA, SIRS, and comorbidities, as well as development of a mortality risk score. DESIGN: This retrospective cohort study was conducted between 2016 and 2021. SETTING: Two university hospitals in Brazil. PARTICIPANTS: Patients with sepsis. INTERVENTIONS: Several clinical and laboratory data were collected focused on SIRS, qSOFA, and comorbidities. MAIN VARIABLE OF INTEREST: In-hospital mortality was the primary outcome variable. A mortality risk score was developed after logistic regression analysis. RESULTS: A total of 1,808 patients were included with a death rate of 36%. Ten variables remained independent factors related to death in multivariate analysis: temperature ≥38 °C (odds ratio [OR] = 0.65), previous sepsis (OR = 1.42), qSOFA ≥ 2 (OR = 1.43), leukocytes >12,000 or <4,000 cells/mm3 (OR = 1.61), encephalic vascular accident (OR = 1.88), age >60 years (OR = 1.93), cancer (OR = 2.2), length of hospital stay before sepsis >7 days (OR = 2.22,), dialysis (OR = 2.51), and cirrhosis (OR = 3.97). Considering the equation of the binary regression logistic analysis, the score presented an area under curve of 0.668, is not a potential model for death prediction. CONCLUSIONS: Several risk factors are independently associated with mortality, allowing the development of a prediction score based on qSOFA, SIRS, and comorbidities data, however, the performance of this score is low.

Clinical features and predictors of delayed neurological syndrome in carbon monoxide poisoning: the AMICO study. / Caracterización clínica y factores predictivos de desarrollo de síndrome neurológico tardío en la intoxicación por monóxido de carbono: estudio AMICO.

OBJECTIVES: To identify predictors for developing delayed neurological syndrome (DNS) after an initial episode of carbon monoxide (CO) poisoning in the interest of detecting patients most likely to develop DNS so that they can be followed. MATERIAL AND METHODS: Retrospective review of cases of CO poisoning treated in the past 10 years in the emergency departments of 4 hospitals in the AMICO study (Spanish acronym for the multicenter analysis of CO poisoning). We analyzed demographic characteristics of the patients and the clinical characteristics of the initial episode. The records of the cohort of patients with available follow-up information were reviewed to find cases of DNS. Data were analyzed by multivariant analysis to determine the relationship to characteristics of the initial exposure to CO. RESULTS: A total of 240 cases were identified. The median (interquartile range) age of the patients was 36.2 years (17.6-49.6 years); 108 patients (45.0%) were men, and the poisoning was accidental in 223 cases (92.9%). The median carboxyhemoglobin concentration on presentation was 12.7% (6.2%-18.7%). Follow-up details were available for 44 patients (18.3%). Eleven of those patients (25%) developed DNS. A low initial Glasgow Coma Scale score predicted the development of DNS with an odds ratio (OR) of 0.61 (95% CI, 0.41-0.92) and an area under the receiver operating characteristic curve of 0.876 (95% CI, 0.761-0.990) (P .001). CONCLUSION: The initial Glasgow Coma Scale score seems to be a clinical predictor of DNS after CO poisoning. We consider it important to establish follow-up protocols for patients with CO poisoning treated in hospital EDs.

OBJETIVO: Identificar factores pronósticos de desarrollo de síndrome neurológico tardío (SNT) después de un episodio inicial de intoxicación por monóxido de carbono (ICO), con el fin detectar precozmente a la población más susceptible y facilitar su acceso a un seguimiento específico. METODO: Revisión retrospectiva de todos los casos de ICO que acudieron a los servicios de urgencias (SU) de 4 hospitales durante los últimos 10 años. Se analizaron datos demográficos y características clínicas en el momento del episodio. En la cohorte de pacientes con datos de seguimiento disponibles, se evaluó la aparición de SNT y su relación con diferentes variables en la exposición inicial al CO a través de técnicas de análisis multivariante. RESULTADOS: Se identificaron 240 pacientes. La mediana de edad fue de 36,2 años (17,6-49,6). De ellos 108 (45,0%) eran hombres y 223 casos (92,9%) fueron accidentales. El nivel medio de COHb fue del 12,7% (6,2-18,7). En 44 (18,3%) episodios se disponía de datos de un seguimiento específico. En esta cohorte, 11 (25%) pacientes desarrollaron SNT. Una puntuación inicial más baja en la Escala Coma de Glasgow (GCS) (OR: 0,61, IC 95%: 0,41-0,92) fue predictor independiente del desarrollo del SNT, con un ABC en la curva COR de 0,876 (IC 95%: 0,761-0,990, p 0,001). CONCLUSIONES: Una puntuación inicial baja en la GCS parece ser un predictor clínico de desarrollo de SNT en la ICO. Dada la incidencia de SNT, consideramos fundamental establecer protocolos de seguimiento específico de estos pacientes tras su asistencia inicial en los SU.

Influence of sex on the timing of coronary angiography and the prescription of antiplatelet therapy in patients with nonST-segment elevation myocardial infarction. / Impacto del sexo en los tiempos de cateterismo y en el uso de pretratamiento antiagregante plaquetario en pacientes con síndrome coronario agudo sin elevación del segmento ST (SCASEST).

OBJECTIVES: To assess differences in the clinical management of nonST-segment elevation myocardial infarction (NSTEMI), including in-hospital events, according to biological sex. MATERIAL AND METHODS: Prospective observational multicenter study of patients diagnosed with NSTEMI and atherosclerosis who underwent coronary angiography. RESULTS: We enrolled 1020 patients in April and May 2022; 240 (23.5%) were women. Women were older than men on average (72.6 vs 66.5 years, P .001), and more women were frail (17.1% vs 5.6%, P .001). No difference was observed in pretreatment with any P2Y12 inhibitor (prescribed in 68.8% of women vs 70.2% of men, P = .67); however, more women than men were prescribed clopidogrel (56% vs 44%, P = .009). Women prescribed clopidogrel were more often under the age of 75 years and not frail. Coronary angiography was performed within 24 hours less corooften in women (29.8% vs 36.9%, P = .03) even when high risk was recognized. Frailty was independently associated with deferring coronary angiography in the adjusted analysis; biological sex by itself was not related. The frequency and type of revascularization were the same in both sexes, and there were no differences in in-hospital cardiovascular events. CONCLUSION: Women were more often prescribed less potent antithrombotic therapy than men. Frailty, but not sex, correlated independently with deferral of coronary angiography. However, we detected no differences in the frequency of coronary revascularization or in-hospital events according to sex.

OBJETIVO: Evaluar las diferencias en el manejo clínico y eventos intrahospitalarios en una cohorte de pacientes con síndrome coronario agudo sin elevación del segmento ST (SCASEST) en función del sexo. METODO: Estudio observacional, prospectivo y multicéntrico que incluyó pacientes consecutivos con diagnóstico de SCASEST sometidos a coronariografía con enfermedad ateroesclerótica responsable. RESULTADOS: Entre abril y mayo de 2022 se incluyeron 1.020 pacientes; de ellos, 240 eran mujeres (23,5%). En comparación con los hombres, las mujeres fueron mayores (72,6 años vs 66,5 años; p 0,001) y más frágiles (17,1% vs 5,6%; p 0,001). No hubo diferencias en el pretratamiento con un inhibidor del receptor P2Y12 (68,8% vs 70,2%, p = 0,67), aunque las mujeres recibieron más pretratamiento con clopidogrel (56% vs 44%, p = 0,009), principalmente aquellas de edad 75 años y sin fragilidad. En las mujeres se realizaron menos coronariografías precoces (# 24 h) (29,8% vs 36,9%; p = 0,03) a pesar de presentar la misma indicación (criterios de alto riesgo). En el análisis ajustado, la fragilidad, pero no el sexo, se asoció de forma independiente con la realización de una coronariografía diferida. La tasa y el tipo de revascularización fue igual en ambos sexos, y no hubo diferencias en los eventos cardiovasculares intrahospitalarios. CONCLUSIONES: Las mujeres recibieron con mayor frecuencia un tratamiento antitrombótico menos potente. La fragilidad y no el sexo se asoció con la realización de coronariografía diferida. Sin embargo, no hubo diferencias en la tasa de revascularización coronaria ni en los eventos intrahospitalarios en función del sexo.

Prevalence of irritable bowel syndrome and other functional gastrointestinal disorders in Uruguay.

INTRODUCTION AND AIMS: Irritable bowel syndrome (IBS) is one of the most frequent functional gastrointestinal disorders. Prevalence worldwide is estimated at 11%. There is little information on the prevalence of the other functional bowel disorders (FBDs). Our aim was to establish the prevalence of IBS and other FBDs according to the Rome IV criteria, in Uruguay. MATERIALS AND METHODS: An observational, population-based prevalence study was conducted. Data were collected through an online questionnaire, utilizing the Rome IV criteria. RESULTS: Of the 1,052 participants (79% women, mean patient age 44 years), 47.2% met the Rome IV diagnostic criteria for at least one of the FBDs analyzed. Functional constipation (FC) was the most frequent, at 18.7% (16.4-21.1), followed by IBS at 17.1% (14.9-19.4) and functional diarrhea (FD) at 15.4% (13.3-17.6). IBS with constipation (IBS-C) was the most frequent IBS subtype (35%) and the IBS with diarrhea (IBS-D) subtype predominated in men. All FBDs were more prevalent in women and youths. Of the survey participants with a FBD, 59% stated that they perceived no worsening of their symptoms related to the COVID-19 pandemic. CONCLUSIONS: Ours is the first prevalence study on FBDs conducted on the Uruguayan general population. Half of the participants surveyed presented with a FBD analyzed in the study. FC was the most frequent, followed by IBS and FD. The prevalence rate of IBS was the highest, based on the Rome IV diagnostic criteria, and constipation was the most frequent subtype.

Post-pandemic acute respiratory distress syndrome: A New Global Definition with extension to lower-resource regions.

Acute respiratory distress syndrome (ARDS), first described in 1967, is characterized by acute respiratory failure causing profound hypoxemia, decreased pulmonary compliance, and bilateral CXR infiltrates. After several descriptions, the Berlin definition was adopted in 2012, which established three categories of severity according to hypoxemia (mild, moderate and severe), specified temporal aspects for diagnosis, and incorporated the use of non-invasive ventilation. The COVID-19 pandemic led to changes in ARDS management, focusing on continuous monitoring of oxygenation and on utilization of high-flow oxygen therapy and lung ultrasound. In 2021, a New Global Definition based on the Berlin definition of ARDS was proposed, which included a category for non-intubated patients, considered the use of SpO2, and established no particular requirement for oxygenation support in regions with limited resources. Although debates persist, the continuous evolution seeks to adapt to clinical and epidemiological needs, and to the search of personalized treatments.

Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice.

BACKGROUND AND PURPOSE: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. METHODS: We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. RESULTS: Clinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years±8.43 and H&Y stage was 3 [2-4]. Mean dose of levodopa used was 703.75mg±233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. CONCLUSIONS: Our real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.

Physicochemical and microbiological stability study of two new preservative-free methylprednisolone eye drops. / Estudio de estabilidad fisicoquímica y microbiológica de 2 nuevos colirios de metilprednisolona sin conservantes.

OBJECTIVE: To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 mg/ml and 10 mg/ml eye drops for use in ocular pathologies such as Sjögren's syndrome and dry eye syndrome. METHOD: The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5 ±3 °C), at room temperature (25 ± 2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones. RESULTS: The eye drops stored at 5 °C were the most stable; in the 1 mg/ml eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/ml eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/ml, presented a white precipitate from day 14 and 28 respectively. Non-refrigerated 1 mg/ml eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers. CONCLUSIONS: 1 mg/ml MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/ml eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening.

Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas. / [[Artículo traducido]]Experiencia con bexaroteno en linfoma cutáneo de células T: un estudio del Grupo Español de Linfomas Cutáneos (GELC).

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combinationwith other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.

Multiple and hereditary renal tumors: a review for radiologists.

80% of renal carcinomas (RC) are diagnosed incidentally by imaging. 2-4% of "sporadic" multifocality and 5-8% of hereditary syndromes are accepted, probably with underestimation. Multifocality, young age, familiar history, syndromic data, and certain histologies lead to suspicion of hereditary syndrome. Each tumor must be studied individually, with a multidisciplinary evaluation of the patient. Nephron-sparing therapeutic strategies and a radioprotective diagnostic approach are recommended. Relevant data for the radiologist in major RC hereditary syndromes are presented: von-Hippel-Lindau, Chromosome-3 translocation, BRCA-associated protein-1 mutation, RC associated with succinate dehydrogenase deficiency, PTEN, hereditary papillary RC, Papillary thyroid cancer- Papillary RC, Hereditary leiomyomatosis and RC, Birt-Hogg-Dubé, Tuberous sclerosis complex, Lynch, Xp11.2 translocation/TFE3 fusion, Sickle cell trait, DICER1 mutation, Hereditary hyperparathyroidism and jaw tumor, as well as the main syndromes of Wilms tumor predisposition. The concept of "non-hereditary" familial RC and other malignant and benign entities that can present as multiple renal lesions are discussed.

A Palearctic view of a bat fungal disease.

The fungal infection causing white-nose disease in hibernating bats in North America has resulted in dramatic population declines of affected species, since the introduction of the causative agent Pseudogymnoascus destructans. The fungus is native to the Palearctic, where it also infects several bat species, yet rarely causes severe pathology or the death of the host. Pseudogymnoascus destructans infects bats during hibernation by invading and digesting the skin tissue, resulting in the disruption of torpor patterns and consequent emaciation. Relations among pathogen, host, and environment are complex, and individuals, populations, and species respond to the fungal pathogen in different ways. For example, the Nearctic Myotis lucifugus responds to infection by mounting a robust immune response, leading to immunopathology often contributing to mortality. In contrast, the Palearctic M. myotis shows no significant immunological response to infection. This lack of a strong response, resulting from the long coevolution between the hosts and the pathogen in the pathogen's native range, likely contributes to survival in tolerant species. After more than 15 years since the initial introduction of the fungus to North America, some of the affected populations are showing signs of recovery, suggesting that the fungus, hosts, or both are undergoing processes that may eventually lead to coexistence. The suggested or implemented management methods of the disease in North America have encompassed, for example, the use of probiotics and fungicides, vaccinations, and modifying the environmental conditions of the hibernation sites to limit the growth of the pathogen, intensity of infection, or the hosts' responses to it. Based on current knowledge from Eurasia, policy makers and conservation managers should refrain from disrupting the ongoing evolutionary processes and adopt a holistic approach to managing the epizootic.

Vista paleártica de una enfermedad fúngica de murciélagos Resumen La enfermedad fúngica que produce el síndrome de nariz blanca en murciélagos en hibernación en Norte América ha resultado en declinaciones poblacionales dramáticas en las especies afectadas desde la introducción del agente causante, Pseudogymnoascus destructans. El hongo es nativo del Paleártico, donde también infecta a varias especies de murciélagos; sin embargo, raramente causa patología severa o la muerte del hospedero. Pseudogymnoascus destructans infecta a los murciélagos durante la hibernación invadiendo y digiriendo el tejido de la piel, lo que resulta en la disrupción de los patrones de torpor y la consecuente emaciación. Las relaciones entre el patógeno, el huésped y el ambiente son complejas, y los individuos, las especies y poblaciones responden al patógeno fúngico de distintas maneras. Por ejemplo, Myotis lucifugus, especie del Neártico, responde a la infección montando una respuesta inmune robusta, produciendo una inmunopatología que a menudo contribuye a la mortalidad. En contraste, M. myotis del Paleártico no presenta respuesta inmunológica significativa a la infección. La falta de una fuerte respuesta, resultado de la larga coevolución entre hospederos y el patógeno en el rango nativo de distribución del patógeno, probablemente contribuye a la supervivencia en especies tolerantes. Después de más de 15 años desde la introducción del hongo en Norte América, algunas de las poblaciones afectadas están mostrando señales recuperación, lo que sugiere que el hongo, hospederos, o ambos, están pasando por procesos que eventualmente pueden conducir a la coexistencia. Los métodos de manejo de la enfermedad sugeridos o implementados en Norte América han abarcado, por ejemplo, el uso de probióticos y fungicidas, vacunaciones y modificación de las condiciones ambientales de los sitios de hibernación para limitar el crecimiento del patógeno, la intensidad de la infección o las respuestas de los hospederos. Con base en conocimiento actual de Eurasia, los formuladores de políticas y los manejadores de la conservación deberían abstenerse de alterar los procesos evolutivos en curso y adoptar un enfoque holístico para gestionar la epizootia.

Atrial fibrillation de novo in acute coronary syndrome.

One of the complications during an acute coronary syndrome event is the presence of arrhythmias. Among them, those of the supraventricular type, especially atrial fibrillation, carry a poor prognosis both in the short and long term, being the cause of situations such as cerebrovascular event, ventricular arrhythmias, and increased mortality. The arrhythmia tends to appear in a certain population group with particular risk factors during the index event in approximately 10% of cases. Appropriate treatment at the time of its onset, thanks to the use of drugs that modulate heart rate, rhythm, and anticoagulant management in the most vulnerable groups, will lead to a less bleak outcome for these patients.

Una de las complicaciones durante un evento de síndrome coronario agudo es la presencia de arritmias. Dentro de ellas, las de tipo supraventricular, en especial fibrilación auricular, acarrea un mal pronóstico tanto a corto como a largo plazo y es la causa de situaciones como evento vascular cerebral, arritmias ventriculares y aumento de la mortalidad. Dicha arritmia tiende a aparecer en cierto grupo de población con particulares factores de riesgo durante el evento índice en aproximadamente 10% de los casos. Un tratamiento apropiado en el momento de su aparición, gracias al uso de fármacos que modulan la frecuencia cardiaca, el ritmo y el manejo anticoagulante en los grupos más vulnerables conllevará un desenlace menos sombrío para estos pacientes.

SER recommendations on treatment of refractory Behçet's syndrome.

OBJECTIVE: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (BS) (difficult to treat, severe resistant, severe relapse) to conventional treatment. METHODS: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format (patient, intervention, comparison and outcome). Systematic reviews of the evidence were conducted, the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations Assessment, Development, and Evaluation (GRADE). After that, the multidisciplinary panel formulated the specific recommendations. RESULTS: 4 PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with BS with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. CONCLUSIONS: The treatment of most severe clinical manifestations of BS lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official Recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.

Cytokine storm in Chikungunya: Can we call it multisystem inflammatory syndrome associated with Chikungunya?

Paraguay is currently facing a new outbreak of Chikungunya virus. This report summarizes two severe cases of Chikungunya (CHIKV) infection, confirmed by real-time reverse transcription polymerase chain reaction. We present the cases of patients with acute CHIKV infection and multisystem involvement, with fever, rash, abdominal pain, vomiting, myocarditis, and coronary artery anomalies, very similar to the cases described in MIS-C related to SARS-CoV-2 during the COVID-19 Pandemic. Both patients received IVIG and methylprednisolone, with good clinical response. In this setting of cytokine storm in Chikungunya, can we call it "Multisystem inflammatory syndrome associated with Chikungunya"?.

Switches in non-invasive respiratory support strategies during acute hypoxemic respiratory failure: Need to monitoring from a retrospective observational study

Objective To explore combined non-invasive-respiratory-support (NIRS) patterns, reasons for NIRS switching, and their potential impact on clinical outcomes in acute-hypoxemic-respiratory-failure (AHRF) patients. Design Retrospective, single-center observational study. Setting Intensive Care Medicine. Patients AHRF patients (cardiac origin and respiratory acidosis excluded) underwent combined NIRS therapies such as non-invasive-ventilation (NIV) and High-Flow-Nasal-Cannula (HFNC). Interventions Patients were classified based on the first NIRS switch performed (HFNC-to-NIV or NIV-to-HFNC), and further specific NIRS switching strategies (NIV trial-like vs. Non-NIV trial-like and single vs. multiples switches) were independently evaluated. Main variables of interest Reasons for switching, NIRS failure and mortality rates. Results A total of 63 patients with AHRF were included, receiving combined NIRS, 58.7% classified in the HFNC-to-NIV group and 41.3% in the NIV-to-HFNC group. Reason for switching from HFNC to NIV was AHRF worsening (100%), while from NIV to HFNC was respiratory improvement (76.9%). NIRS failure rates were higher in the HFNC-to-NIV than in NIV-to-HFNC group (81% vs. 35%, p < 0.001). Among HFNC-to-NIV patients, there was no difference in the failure rate between the NIV trial-like and non-NIV trial-like groups (86% vs. 78%, p = 0.575) but the mortality rate was significantly lower in NIV trial-like group (14% vs. 52%, p = 0.02). Among NIV to HFNC patients, NIV failure was lower in the single switch group compared to the multiple switches group (15% vs. 53%, p = 0.039), with a shorter length of stay (5 [2–8] vs. 12 [8–30] days, p = 0.001). Conclusions NIRS combination is used in real life and both switches’ strategies, HFNC to NIV and NIV to HFNC, are common in AHRF management. Transitioning from HFNC to NIV is suggested as a therapeutic escalation and in this context performance of a NIV-trial could be beneficial. ... (AU)

Objetivo Explorar los patrones combinados de soporte-respiratorio-no-invasivo (SRNI), las razones para cambiar de SRNI y su potencial impacto en los resultados clínicos en pacientes con insuficiencia-respiratoria-aguda-hipoxémica (IRAH). Diseño Estudio observacional retrospectivo unicéntrico. Ámbito Cuidados Intensivos. Pacientes Pacientes con IRAH (excluyendo causa cardíaca y acidosis respiratoria) que recibieron tanto ventilación-no-invasiva (VNI) como cánula-nasal-de-alto-flujo (CNAF). Intervenciones Se categorizó a los pacientes según el primer cambio de SRNI realizado (CNAF-to-VNI o VNI-to-CNAF) y se evaluaron estrategias específicas de SRNI (VNI trial-like vs. Non-VNI trial-like y cambio único vs. múltiples cambios de NIRS) de manera independiente. Variables de interés principales Razones para el cambio, así como las tasas de fracaso de SRNI y la mortalidad. Resultados Un total de 63 pacientes recibieron SRNI combinado, 58,7% clasificados en el grupo CNAF-to-VNI y 41,3% en el grupo VNI-to-CNAF. Los cambios de CNAF a VNI ocurrieron por empeoramiento de la IRHA (100%) y de VNI a CNAF por mejora respiratoria (76.9%). Las tasas de fracaso de SRNI fueron mayores de CNAF a VNI que de VNI a CNAF (81% vs. 35%, p < 0.001). Dentro de los pacientes de CNAF a VNI, no hubo diferencia en las tasas de fracaso entre los grupos VNI trial-like y no-VNI trial-like (86% vs. 78%, p = 0.575), pero la mortalidad fue menor en el grupo VNI trial-like (14% vs. 52%, p = 0.02). Dentro de los pacientes de VNI a CNAF, el fracaso de VNI fue menor en grupo de cambio único vs. múltiple (15% vs. 53%, p = 0.039). Conclusiones Los cambios de estrategia de SRNI son comunes en el manejo clínico diario de la IRHA. El cambio de CNAF a VNI impresiona de ser una escalada terapéutica y en este contexto la realización de un VNI-trial puede ser beneficioso. Al contrario, cambiar de VNI a CNAF impresiona de ser una desescalada terapéutica y parece segura si no hay fracaso ... (AU)

Análisis retrospectivo de las hipoglucemias inducidas por venlafaxina en pacientes con sobredosis / Retrospective analysis of venlafaxine-induced hypoglycemia in patients with overdose

Introducción: Estudios recientes en intoxicaciones por venlafaxina (VLF) relacionan la presencia de hipoglucemia con la dosis. Nuestro objetivo fue analizar las características clínicas de los pacientes que presentaron hipoglucemia inducida por sobredosis de VLF.Pacientes y métodosEstudio retrospectivo realizado en las Islas Baleares (2020-2023). Como criterios de inclusión se tomaron en cuenta las concentraciones séricas de VLF + ortodesmetilvenlafaxina (O-VLF) > 800 ng/mL. Se compararon las características de los pacientes con y sin hipoglucemia.ResultadosSe incluyeron 21 pacientes, ocho (38,1%) con hipoglucemia. No se hallaron diferencias en las dosis referidas en ambos grupos. Las concentraciones máximas de VLF + O-VLF (ng/mL) fueron 9.783 (4.459-17.976) en sujetos con hipoglucemia y 1.413 (930-1.769) en aquellos sin esta enfermedad (p<0,0001). La presencia de hipoglucemia se asoció con: menor edad y nivel de conciencia; y mayor frecuencia de tentativas suicidas, convulsiones, midriasis, taquicardia y síndrome serotoninérgico, soporte respiratorio invasivo, sueroterapia e ingreso en la Unidad de Cuidados Intensivos (UCI) (p < 0,05).ConclusionesLa detección de hipoglucemia en individuos intoxicados por VLF es un marcador fácilmente disponible para sospechar la gravedad del paciente. En cualquier caso, las concentraciones séricas, cuando se disponen, permiten confirmar la intoxicación. (AU)

Introduction: Recent publications relate the presence of hypoglycemia in venlafaxine (VLX) poisoning depending on the dose. Our aim was to analyze the clinical characteristics of patients who presented hypoglycemia induced by VLF overdose.Patients and methodsRetrospective study carried out in the Balearic Islands (2020–2023). Inclusion criteria: serum concentrations of VLX + O-desmethyl-venlafaxine (O-VLX)>800 ng/mL. The characteristics of patients with and without hypoglycemia were compared.ResultsTwenty-one patients were included, 8 (38.1%) with hypoglycemia. No differences were found in the doses referred to in both groups. Peak concentrations of VLX + O-VLX (ng/mL) were 9,783 [4,459–17,976] in patients with hypoglycemia and 1,413 [930–1,719] in patients without hypoglycemia (p<0.0001). The presence of hypoglycemia was associated with: lower age and level of consciousness; and higher frequency of suicide attempts, seizures, mydriasis, tachycardia and serotonin syndrome, invasive respiratory support, fluid therapy and ICU admission (p<0.05).ConclusionsThe detection of hypoglycemia in a VLX overdose case is a readily available marker to suspect the severity of the patient. In any case, serum concentrations when available allow us to confirm intoxication. (AU)

Síndrome del pulmón encogido asociado a lupus eritematoso sistémico: estudio de 9 pacientes / Shrinking lung syndrome in systemic lupus erythematosus: A study of 9 patients

Introducción: El síndrome de pulmón encogido (SPE) es una manifestación rara del lupus eritematoso sistémico. Nuestro objetivo fue describir las características clínicas, radiológicas y funcionales de una cohorte con SPE y su evolución en el tiempo.MétodosEstudio retrospectivo entre 2009 y 2018. Se recogieron datos demográficos, clínicos, funcionales, radiológicos y de tratamiento.ResultadosDe un total de 225 pacientes, 11 presentaron SPE (prevalencia del 4,8%). Dos fueron excluidos. La edad media fue 39,33±16 años, 6 eran mujeres. Los síntomas principales fueron la disnea y el dolor pleurítico. La capacidad vital forzada media fue del 49%, la capacidad pulmonar total del 60%, la capacidad de difusión de monóxido de carbono del 66%, el factor de transferencia para el monóxido de carbono del 128%, la presión inspiratoria máxima del 66% y la presión espiratoria máxima del 82%. Todos los pacientes recibieron corticosteroides. Después de una mediana de seguimiento de 19 meses, 4 casos presentaron mejoría y 4 estabilización.ConclusionesEl SPE debe tenerse presente en todo paciente lúpico con disnea de causa no evidente. Si bien suele evolucionar con mejoría, la mayoría queda con deterioro persistente a pesar del tratamiento. (AU)

Introduction: Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus. Our aim was to describe the clinical, radiological, and functional characteristics of a cohort with SLS and its evolution over time.MethodsA retrospective study was conducted between 2009 and 2018. Demographic, clinical, functional, radiological, and treatment data were collected.ResultsOut of a total of 225 patients, 11 presented with SLS (prevalence of 4.8%). Two patients were excluded. The mean age was 39.33±16 years, and 6 were female. The main symptoms were dyspnea and pleuritic pain. The mean forced vital capacity was 49%, total lung capacity was 60%, carbon monoxide diffusing capacity was 66%, carbon monoxide transference factor was 128%, maximal inspiratory pressure was 66%, and maximal expiratory pressure was 82%. All patients received corticosteroids. After a median follow-up of 19 months, 4 cases showed improvement, and 4 cases remained stable.ConclusionsSLS should be considered in every lupus patient with unexplained dyspnea. Although it often shows improvement, many cases experience persistent deterioration despite treatment. (AU)