Results from the INMUNOSUN-SOGUG trial: a prospective phase II study of sunitinib as a second-line therapy in patients with metastatic renal cell carcinoma after immune checkpoint-based combination therapy.

BACKGROUND: The INMUNOSUN trial had the objective of prospectively evaluating the efficacy and safety of sunitinib as a pure second-line treatment in patients with metastatic renal cell carcinoma (mRCC) who have progressed to first-line immune checkpoint inhibitor (ICI)-based therapies. PATIENTS AND METHODS: A multicenter, phase II, single-arm, open-label study was carried out in patients with a histologically confirmed diagnosis of mRCC with a clear-cell component who had progressed to a first-line regimen of ICI-based therapies. All patients received sunitinib 50 mg once daily orally for 4 weeks, followed by a 2-week rest period following package insert instructions. The primary outcome was the objective response rate. RESULTS: Twenty-one assessable patients were included in the efficacy and safety analyses. Four patients [19.0%, 95% confidence interval (CI) 2.3% to 35.8%] showed an objective response (OR), and all of them had partial responses. Additionally, 14 (67%) patients showed a stable response, leading to clinical benefit in 18 patients (85.7%, 95% CI 70.7% to 100%). Among the four assessable patients who showed an OR, the median duration of the response was 7.1 months (interquartile range 4.2-12.0 months). The median progression-free survival (PFS) was 5.6 months (95% CI 3.1-8.0 months). The median overall survival (OS) was 23.5 months (95% CI 6.3-40.7 months). Patients who had better antitumor response to first-line ICI-based treatment showed a longer PFS and OS with sunitinib. The most frequent treatment-emergent adverse events were diarrhea (n = 11, 52%), dysgeusia (n = 8, 38%), palmar-plantar erythrodysesthesia (n = 8, 38%), and hypertension (n = 8, 38%). There was 1 patient who exhibited grade 5 pancytopenia, and 11 patients experienced grade 3 adverse events. Eight (38%) patients had serious adverse events, four of which were considered to be related to sunitinib. CONCLUSION: Although the INMUNOSUN trial did not reach the pre-specified endpoint, it demonstrated that sunitinib is active and can be safely used as a second-line option in patients with mRCC who progress to new standard ICI-based regimens.

Infección por SARS-CoV-2 y seroprevalencia en pacientes con esclerosis múltiple / SARS-CoV-2 infection and seroprevalence in patients with multiple sclerosis

Introducción: El efecto de la infección por SARS-CoV-2 en los pacientes con esclerosis múltiple (EM) y la influencia de los tratamientos modificadores de la enfermedad (TME) es desconocida. Hasta el momento no se ha observado que los pacientes con EM tengan mayor riesgo de infección por COVID-19, ni peor curso evolutivo de la misma.MétodosEstudio descriptivo de pacientes con EM e infección por SARS-CoV-2 diagnosticada mediante PCR. Hemos analizado variables demográficas, clínicas, de laboratorio y de tratamiento en nuestra muestra. Se ha determinado la presencia de anticuerpos frente a SARS-CoV-2 en estos pacientes.ResultadosLa forma de esclerosis múltiple remitente recurrente (EMRR) fue la más frecuente en lo pacientes con EM e infección por COVID-19. El 10,2% presentó una evolución desfavorable, relacionada con una mayor edad y una Expanded Disability Status Scale (EDSS) más elevada. La seroprevalencia de anticuerpos frente a SARS-CoV-2 en nuestro estudio ha sido del 83,3%. El desarrollo de anticuerpos no está relacionado con el TME, la presencia de linfopenia u otros factores analizados.ConclusionesLa incidencia de COVID-19 ha sido ligeramente inferior a la de la población general de nuestra provincia. La evolución desfavorable se ha relacionado con una mayor edad y una puntuación elevada en la EDSS. El TME y la linfopenia no se han relacionado con el curso de la infección por COVID-19. La seroprevalencia es similar a la encontrada en población general con PCR positiva, sin poder determinar la influencia de los distintos TME. (AU)

Introduction: The effect of SARS-CoV-2 infection in patients with multiple sclerosis (MS) and the influence of disease-modifying therapies (DMT) for MS on COVID-19 are unknown. To date, patients with MS have not been shown to present greater risk of COVID-19 or more severe progression of the disease.MethodsWe performed a descriptive study of patients with MS presenting SARS-CoV-2 infection diagnosed with PCR. We analysed demographic, clinical, laboratory, and treatment variables in our sample. Presence of antibodies against the virus was also determined.ResultsRelapsing-remitting MS (RRMS) was the most frequent form of MS in our sample. Prognosis was unfavourable in 10.2% of patients, and was associated with older age and higher scores on the Expanded Disability Status Scale (EDSS). Seroprevalence of antibodies against SARS-CoV-2 was 83.3% in our sample. Development of antibodies was not associated with DMT, lymphocytopaenia, or any of the other variables analysed.ConclusionsThe incidence of COVID-19 was slightly lower in our sample than in the general population in our province. Unfavourable prognosis was associated with older age and higher EDSS scores. DMT and lymphocytopaenia did not influence the clinical course of COVID-19. Seroprevalence of antibodies against the virus in our sample was similar to that reported for the general population with positive PCR results for the virus; the influence of specific DMTs could not be determined. (AU)

SARS-CoV-2 infection and seroprevalence in patients with multiple sclerosis.

INTRODUCTION: The effect of SARS-CoV-2 infection in patients with multiple sclerosis (MS) and the influence of disease-modifying therapies (DMT) for MS on COVID-19 are unknown. To date, patients with MS have not been shown to present greater risk of COVID-19 or more severe progression of the disease. METHODS: We performed a descriptive study of patients with MS presenting SARS-CoV-2 infection diagnosed with PCR. We analysed demographic, clinical, laboratory, and treatment variables in our sample. Presence of antibodies against the virus was also determined. RESULTS: Relapsing-remitting MS (RRMS) was the most frequent form of MS in our sample. Prognosis was unfavourable in 10.2% of patients, and was associated with older age and higher scores on the Expanded Disability Status Scale (EDSS). Seroprevalence of antibodies against SARS-CoV-2 was 83.3% in our sample. Development of antibodies was not associated with DMT, lymphocytopaenia, or any of the other variables analysed. CONCLUSIONS: The incidence of COVID-19 was slightly higher in our sample than in the general population in our province. Unfavourable prognosis was associated with older age and higher EDSS scores. DMT and lymphocytopaenia did not influence the clinical course of COVID-19. Seroprevalence of antibodies against the virus in our sample was similar to that reported for the general population with positive PCR results for the virus; the influence of specific DMTs could not be determined.

SARS-CoV-2 infection and seroprevalence in patients with multiple sclerosis. / Infección por SARS-CoV-2 y seroprevalencia en pacientes con esclerosis múltiple.

INTRODUCTION: The effect of SARS-CoV-2 infection in patients with multiple sclerosis (MS) and the influence of disease-modifying therapies (DMT) for MS on COVID-19 are unknown. To date, patients with MS have not been shown to present greater risk of COVID-19 or more severe progression of the disease. METHODS: We performed a descriptive study of patients with MS presenting SARS-CoV-2 infection diagnosed with PCR. We analysed demographic, clinical, laboratory, and treatment variables in our sample. Presence of antibodies against the virus was also determined. RESULTS: Relapsing-remitting MS (RRMS) was the most frequent form of MS in our sample. Prognosis was unfavourable in 10.2% of patients, and was associated with older age and higher scores on the Expanded Disability Status Scale (EDSS). Seroprevalence of antibodies against SARS-CoV-2 was 83.3% in our sample. Development of antibodies was not associated with DMT, lymphocytopaenia, or any of the other variables analysed. CONCLUSIONS: The incidence of COVID-19 was slightly lower in our sample than in the general population in our province. Unfavourable prognosis was associated with older age and higher EDSS scores. DMT and lymphocytopaenia did not influence the clinical course of COVID-19. Seroprevalence of antibodies against the virus in our sample was similar to that reported for the general population with positive PCR results for the virus; the influence of specific DMTs could not be determined.

MiR-16 mediates trastuzumab and lapatinib response in ErbB-2-positive breast and gastric cancer via its novel targets CCNJ and FUBP1.

ErbB-2 amplification/overexpression accounts for an aggressive breast cancer (BC) subtype (ErbB-2-positive). Enhanced ErbB-2 expression was also found in gastric cancer (GC) and has been correlated with poor clinical outcome. The ErbB-2-targeted therapies trastuzumab (TZ), a monoclonal antibody, and lapatinib, a tyrosine kinase inhibitor, have proved highly beneficial. However, resistance to such therapies remains a major clinical challenge. We here revealed a novel mechanism underlying the antiproliferative effects of both agents in ErbB-2-positive BC and GC. TZ and lapatinib ability to block extracellular signal-regulated kinases 1/2 and phosphatidylinositol-3 kinase (PI3K)/AKT in sensitive cells inhibits c-Myc activation, which results in upregulation of miR-16. Forced expression of miR-16 inhibited in vitro proliferation in BC and GC cells, both sensitive and resistant to TZ and lapatinib, as well as in a preclinical BC model resistant to these agents. This reveals miR-16 role as tumor suppressor in ErbB-2-positive BC and GC. Using genome-wide expression studies and miRNA target prediction algorithms, we identified cyclin J and far upstream element-binding protein 1 (FUBP1) as novel miR-16 targets, which mediate miR-16 antiproliferative effects. Supporting the clinical relevance of our results, we found that high levels of miR-16 and low or null FUBP1 expression correlate with TZ response in ErbB-2-positive primary BCs. These findings highlight a potential role of miR-16 and FUBP1 as biomarkers of sensitivity to TZ therapy. Furthermore, we revealed miR-16 as an innovative therapeutic agent for TZ- and lapatinib-resistant ErbB-2-positive BC and GC.

Passenger Lymphocyte Syndrome After Simultaneous Pancreas-Kidney Transplantation: A Case Report of an Unusual Cause of Alloimmune Hemolytic Anemia.

BACKGROUND: Passenger lymphocyte syndrome (PLS) is a disease in which the donor's lymphocytes produce antibodies to the red blood cell antigens of the recipient, causing alloimmune hemolysis. CASE REPORT: We report the case of a 39-year-old woman with stage V chronic kidney disease on hemodialysis secondary to poorly controlled diabetes mellitus type 1. She received a simultaneous pancreas-kidney transplant from a cadaver donor. The donor was A- and the recipient was A+ without initial complications with normal renal and pancreatic function, and her hemoglobin (Hb) level was 10.2 g/dL at discharge. Four weeks later she was admitted with acute pyelonephritis of the renal graft, with a Hb level of 7.5 g/dL, creatinine level of 0.7 mg/dL, and glucose level of 80 mg/dL. The study of anemia showed direct polyspecific direct Coombs weakly positive (w/+), presenting 2 alloantibodies against the Rh system: anti-D, anti-E. We increased Prednisone dose to 1 mg/kg/d and then decreased it in a pattern. Eight days after discharge, without transfusion, her Hb level was 9.9 g/dL and then it normalized. CONCLUSIONS: PLS is a very rare condition and should be suspected in the first few weeks after transplantation. In our case anemia was probably due to a residual population of Rh-negative donor cells in the transplanted pancreas-kidney received. It is usually a sudden onset of hemolytic anemia in patients with a solid organ transplant and different Rh or ABO lower incompatibility.

Capsaicin induction of esophageal symptoms in different phenotypes of gastroesophageal reflux disease.

BACKGROUND: Type 1 vanilloid receptors (TRPV1) have been described on esophageal afferent sensitive neurons. Stimulation of TRPV1 receptors with capsaicin may induce heartburn. Capsaicin is the pungent component of chili and the most extensively studied TRPV1 agonist. OBJECTIVES: To investigate the effect of esophageal stimulation with intraesophageal capsaicin administration on induction of esophageal symptoms and on esophageal chemo-sensitization to acid in different gastroesophageal reflux disease (GERD) phenotypes. METHODS: Healthy volunteers and patients with GERD (non-erosive [NERD], erosive GERD [EE] and Barrett's esophagus [BE]) were prospectively studied. All subjects were randomized to receive either intraesophageal perfusion capsaicin or saline 0.9%. Thirty minutes after saline or capsaicin infusion an acid perfusion test of HCl was performed. A week later, a crossover phase with capsaicin versus saline was performed. Five symptoms were evaluated every 5 min during the first 30 minutes after capsaicin, saline, and acid perfusion: chest burning, chest pain, heartburn, epigastric burning, and epigastric pain. RESULTS: 17 healthy subjects and 31 GERD patients (10 NERD, 11 EE, and 10 BE) were included. Twenty- eight (90%) of GERD and 6 (35%) of healthy subjects had esophageal symptoms after capsaicin perfusion. Mean for the 5 evaluated symptoms induced by capsaicin was significantly higher in the GERD group compared to the control group. The highest symptom severity was in the erosive subgroup. Capsaicin decreased the 5 symptoms induced by acid perfusion in both healthy volunteers and GERD patients. Total score of esophageal symptom severity (produced by acid perfusion) was significantly reduced by capsaicin infusion in the BE group. CONCLUSIONS: Capsaicin induces esophageal and gastric symptoms in healthy volunteers and GERD patients. Capsaicin reduces esophageal chemosensitivity to acid, especially in patients with BE.

Tratamiento con 131I de restos tiroideos en paciente con carcinoma papilar de tiroides e insuficiencia renal crónica terminal / Treatment with 131I of thyroid remnants in a patient with papillary thyroid carcinoma and end-stage chronic renal failure

El seguimiento y tratamiento del cáncer de tiroides presenta diversos aspectos para debatir, como el manejo en pacientes con insuficiencia renal crónica terminal (IRCT). Presentamos el caso de una paciente con IRCT y carcinoma papilar de tiroides, que requirió un proceso de coordinación entre diferentes servicios (Endocrinología, Medicina Nuclear, Nefrología, y Física y Protección Radiológica). Tanto la gammagrafía diagnóstica con 123I como el tratamiento ablativo con 131I posterior se realizaron con administración de hormonoterapia sustitutiva recombinante humana (TSH rh). Se acondicionó la habitación de terapia metabólica para realizar hemodiálisis periódica a la paciente. La dosis de radioyodo fue un 80% de la habitual, lo que permitió garantizar el efecto terapéutico y que el ingreso hospitalario durara únicamente 5 días. Durante todo el proceso diagnóstico y terapéutico no se observaron efectos adversos atribuibles a la TSH rh ni al radioyodo. La coordinación entre los servicios implicados permitió un proceso efectivo y seguro para la paciente(AU)

The follow-up and treatment of thyroid cancer presents several aspects subject to discussion, such as its management in patients with End-Stage Renal Failure (ESRF). We present a patient with ESRF and papillary thyroid carcinoma, which had to be coordinated among different departments (Endocrinology, Nuclear Medicine, Nephrology and Physics and Radiation Protection). Both the diagnostic scintigraphy with 123I and the ablative treatment with 131I performed later were performed with the administration of rh TSH. The room in which the metabolic therapy was to be performed was prepared for the patient's periodic hemodialysis. The 131I dose used was 80% of the usual dose. This made it possible to assure the therapeutic effect and that the patient's stay in hospital would only be for 5 days. Throughout the whole diagnostic and therapeutic process, no adverse effects attributable to rh TSH or radioiodine were observed. The coordination among the departments involved enabled an effective and safe process for the patient

[Treatment with (131)I of thyroid remnants in a patient with papillary thyroid carcinoma and end-stage chronic renal failure]. / Tratamiento con (131)I de restos tiroideos en paciente con carcinoma papilar de tiroides e insuficiencia renal crónica terminal.

The follow-up and treatment of thyroid cancer presents several aspects subject to discussion, such as its management in patients with End-Stage Renal Failure (ESRF). We present a patient with ESRF and papillary thyroid carcinoma, which had to be coordinated among different departments (Endocrinology, Nuclear Medicine, Nephrology and Physics and Radiation Protection). Both the diagnostic scintigraphy with (123)I and the ablative treatment with (131)I performed later were performed with the administration of rh TSH. The room in which the metabolic therapy was to be performed was prepared for the patient's periodic hemodialysis. The (131)I dose used was 80% of the usual dose. This made it possible to assure the therapeutic effect and that the patient's stay in hospital would only be for 5 days. Throughout the whole diagnostic and therapeutic process, no adverse effects attributable to rh TSH or radioiodine were observed. The coordination among the departments involved enabled an effective and safe process for the patient.

Short communication: oral lesions in HIV/AIDS patients undergoing HAART including efavirenz.

Oral lesions (OL) have an important prognostic value for HIV/AIDS patients. However, the behavior of OL in HIV/AIDS patients undergoing highly active antiretroviral therapy including efavirenz (HAART/EFV) has not been documented. Our objective was to establish the prevalence of OL in HIV/AIDS patients undergoing HAART/EFV and to compare it with the prevalence of OL in patients undergoing antiretroviral therapy including a protease inhibitor (HAART/PI). Seventy-three HIV/AIDS patients undergoing antiretroviral treatment for at least for 6 months at "La Raza" Medical Center's Internal Medicine Unit (IMSS, Mexico City) were included. To detect OL, a detailed examination of oral soft tissues was performed in each patient. Patient records recorded gender, seropositivity time, route of contagion, antiretroviral therapy type and duration, CD4 lymphocyte count/ml, and viral load. Two groups were formed: 38 patients receiving HAART/EFV [two nucleoside analogue reverse transcriptase inhibitors (NARTI) plus efavirenz] and 35 patients receiving HAART/PI (two NARTIs plus one PI). OL prevalence was established in each study group. The Chi-square test was applied (p < 0.05(IC95%)). OL prevalence in the HAART/EFV group (32%) was lower (p < 0.007) than in the HAART/PI group (63%). Candidosis was the most prevalent OL in both groups. Herpes labialis, HIV-associated necrotizing periodontitis, xerostomia, hairy leukoplakia, and nonspecific oral sores were identified. The highest prevalence for all OL was found in the HAART/PI group. These findings suggest that HIV/AIDS patients undergoing HAART/EFV show a lower prevalence of oral lesions than patients undergoing HAART/PI.

Cefalosporinas: de la primera a la cuarta generación / Cephalosporin: the fourth and the first generation

Las cefalosporinas son antibióticos similares a las penicilinas pero resultan más efectivas porque han mostrado tener una mejor resistencia contra las B-lactamasas. Dichos antibióticos se obtienen del ácido 7-ACA el cual al ser modificado ha dado origen a cuatro generaciones bien diferenciadas y actualmente se esta ensayando producir cefalosporinas de acción dual enlazando quinolonas a la posición 3' de la cefalosporina, lo cual resulta en un aumento de su actividad contra bacterias gram negativas y positivas las cuales tienen como mecanismo de resistencia al antibiótico la hidrólisis del anillo betalactámico por inducción cromosomal de B-lactamasas tipo I. En la actualidad se esta estudiando un nuevo grupo de estos antibióticos entre las que se encuentran el cefozopran, cefpiramide, E 1100, FK 037 y DQ-2556 y han mostrado buenos resultados en el manejo de infecciones por gérmenes gram positivos y negativos especialmente en los casos de procesos nosocomiales en los que otros antibióticos han visto su uso limitado

[Clinical characteristics of 104 patients with obsessive compulsive disorder]. / Características clínicas de 104 pacientes con diagnóstico de trastorno obsesivo compulsivo.

INTRODUCTION: Obsessive compulsive disorder is a common disorder, but research on its clinical features is scarce. The goal of this study is to describe the clinical characteristics and demographic features of a large sample of patients with Obsessive compulsive disorder. METHOD: The characteristics of 104 patients who sought psychiatric treatment and who were diagnosed as having Obsessive compulsive disorder were assessed by means of a structured questionnaire. RESULTS: The mean age of onset was 20 years and the mean time before soliciting treatment was 4 years. Most of the patients reported an insidious onset and related the onset to an stressful event. The most frequent obsessions were doubt, aggressiveness and contamination. Checking, need to ask and mental rituals were the most frequent compulsions. Cleaning and repetition compulsions were most frequent in women. DISCUSSION: Our results regarding age at onset of illness, way of onset or prevalence of certain obsessions and compulsions are similar to previous research. No agreement was obtained with previous research regarding the link between stress and illness onset, the course of the disorder or the time before treatment was sought. The differences with respect to previous studies could be accounted for the use of different instruments or criteria. The need for the development of instruments allowing to shed light on these discrepancies is stressed.

Características clínicas de 104 pacientes con diagnóstico de trastorno obsesivo compulsivo / Clinical characteristics of 104 patients with obsessive compulsive disorder

Introducción: El trastorno obsesivo compulsivo es un trastorno frecuente, pero los estudios sobre características clínicas son escasos. El objetivo del presente estudio es describir las características demográficas y clínicas de un grupo amplio de pacientes con trastorno obsesivo compulsivo. Material y métodos: Se evaluaron mediante un cuestionario estructurado las características de 104 pacientes que solicitaron tratamiento psiquiátrico y que recibieron el diagnóstico de trastorno obsesivo compulsivo. Resultados: La edad media de inicio del trastorno era de 20 años y el tiempo medio hasta solicitar tratamiento cuatro años. La mayoría de pacientes referían un inicio insidioso del trastorno y asociaban su comienzo con una experiencia estresante. Las obsesiones más frecuentes eran las de duda, agresividad y contaminación. Las compulsiones más habituales eran de comprobación, necesidad de preguntar y rituales mentales. Las compulsiones de limpieza y repetición eran más frecuentes en mujeres. Discusión: Los resultados obtenidos en la edad o forma de inicio del trastorno y la prevalencia de determinadas obsesiones y compulsiones son similares a investigaciones previas. No existe acuerdo con trabajos anteriores en otras variables como la asociación del inicio de la enfermedad con el estrés, el curso del trastorno o el tiempo transcurrido hasta solicitar tratamiento. Estas diferencias respecto a trabajos anteriores podrían deberse a la utilización de criterios o instrumentos de evaluación diferentes. Parece necesaria la elaboración de instrumentos que permitan aclarar estas discrepancias (AU)