Do chronic myeloid leukemia patients with late "warning" responses benefit from "watch and wait" or switching therapy to a second generation tyrosine kinase inhibitor?

In the latest recommendations for the management of chronic-phase chronic myeloid leukemia suboptimal responses have been reclassified as "warning responses." In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first-line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]). One hundred and forty-six patients remained on imatinib, while 52 patients changed treatment to a second generation tyrosine kinase inhibitor (2GTKI). Changing therapy did not correlate with an increase in overall survival or progression-free survival. Nevertheless, a significant improvement was observed in the probability of a MMR: 24% vs. 42% by 12 months and 43% vs. 64% by 24 months (P = 0.002); as well as the probability of achieving a deep molecular responses (MR(4.5) ): 1% vs. 17% and 7% vs. 23% by 12 and 24 months, respectively (P = <0.001) .The treatment change to 2GTKI remained safe; however, we have observed a 19% of treatment discontinuation due to side effects. We have observed an improvement of molecular responses after changing treatment to 2GTKI in patients with late suboptimal response treated with imatinib first line. However, these benefits were not correlated with an improvement of progression free survival or overall survival.

A Digital Tool for Measuring Healing of Chronic Wounds Treated with an Antioxidant Dressing: A Case Series.

(1) Abstract: Wound monitoring is an essential aspect in the evaluation of wound healing. This can be carried out with the multidimensional tool HELCOS, which develops a quantitative analysis and graphic representation of wound healing evolution via imaging. It compares the area and tissues present in the wound bed. This instrument is used for chronic wounds in which the healing process is altered. This article describes the potential use of this tool to improve the monitoring and follow-up of wounds and presents a case series of various chronic wounds with diverse etiology treated with an antioxidant dressing. (2) Methods: A secondary analysis of data from a case series of wounds treated with an antioxidant dressing and monitored with the HELCOS tool. (3) Results: The HELCOS tool is useful for measuring changes in the wound area and identifying wound bed tissues. In the six cases described in this article, the tool was able to monitor the healing of the wounds treated with the antioxidant dressing. (4) Conclusions: the monitoring of wound healing with this multidimensional HELCOS tool offers new possibilities to facilitate treatment decisions by healthcare professionals.

Role of Multiparametric Prostate Magnetic Resonance Imaging before Confirmatory Biopsy in Assessing the Risk of Prostate Cancer Progression during Active Surveillance.

OBJECTIVE: To evaluate the impact of multiparametric magnetic resonance imaging (mpMRI) before confirmatory prostate biopsy in patients under active surveillance (AS). MATERIALS AND METHODS: This retrospective study included 170 patients with Gleason grade 6 prostate cancer initially enrolled in an AS program between 2011 and 2019. Prostate mpMRI was performed using a 1.5 tesla (T) magnetic resonance imaging system with a 16-channel phased-array body coil. The protocol included T1-weighted, T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging sequences. Uroradiology reports generated by a specialist were based on prostate imaging-reporting and data system (PI-RADS) version 2. Univariate and multivariate analyses were performed based on regression models. RESULTS: The reclassification rate at confirmatory biopsy was higher in patients with suspicious lesions on mpMRI (PI-RADS score ≥ 3) (n = 47) than in patients with non-suspicious mpMRIs (n = 61) and who did not undergo mpMRIs (n = 62) (66%, 26.2%, and 24.2%, respectively; p < 0.001). On multivariate analysis, presence of a suspicious mpMRI finding (PI-RADS score ≥ 3) was associated (adjusted odds ratio: 4.72) with the risk of reclassification at confirmatory biopsy after adjusting for the main variables (age, prostate-specific antigen density, number of positive cores, number of previous biopsies, and clinical stage). Presence of a suspicious mpMRI finding (adjusted hazard ratio: 2.62) was also associated with the risk of progression to active treatment during the follow-up. CONCLUSION: Inclusion of mpMRI before the confirmatory biopsy is useful to stratify the risk of reclassification during the biopsy as well as to evaluate the risk of progression to active treatment during follow-up.

R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study.

BACKGROUND: The role of re-treatment with rituximab in aggressive B-cell lymphomas still needs to be defined. This study evaluated the influence of prior exposure to rituximab on response rates and survival in patients with diffuse large B-cell lymphoma treated with rituximab plus etoposide, cytarabine, cisplatinum and methylprednisolone (R-ESHAP). DESIGN AND METHODS: We retrospectively analyzed 163 patients with relapsed or refractory diffuse large B-cell lymphoma who received R-ESHAP as salvage therapy with a curative purpose. Patients were divided into two groups according to whether rituximab had been administered (n=94, "R+" group) or not (n=69, "R-" group) prior to R-ESHAP. RESULTS: Response rates were significantly higher in the R- group in the univariate but not in the multivariate analysis. In the analysis restricted to the R+ group, we observed very low complete remission and overall response rates in patients with primary refractory disease (8% and 33%, respectively), as compared to those in patients who were in first partial remission (41% and 86%) or who had relapsed disease (50% and 75%) (p<0.01 in both cases). Overall, 60% and 65% of patients in the R+ and R- groups, respectively, underwent stem-cell transplantation after the salvage therapy. With a median follow-up of 29 months (range, 6-84), patients in the R+ group had significantly worse progression-free survival (17% vs. 57% at 3 years, p<0.0001) and overall survival (38% v 67% at 3 years, p=0.0005) than patients in the R- group. Prior exposure to rituximab was also an independent adverse prognostic factor for both progression-free survival (RR: 2.0; 95% CI: 1.2-3.3, p=0.008) and overall survival (RR: 2.2; 95% CI: 1.3-3.9, p=0.004). CONCLUSIONS: R-ESHAP was associated with a high response rate in patients who were not refractory to upfront rituximab-based chemotherapy. However, the survival outcome was poor for patients previously exposed to rituximab, as compared to in those who had not previously been treated with rituximab.

[Impact of the use of simulators on the mental workload and confidence in a digital rectal examination and bladder catheterization workshop.] / Impacto del uso de simuladores sobre la carga mental y la confianza en un taller de tacto rectal y cateterización vesical en estudiantes.

OBJECTIVES: Primary: to assess the use of simulators in prostate digital rectal examination and bladder catheterization on mental workload and the level of confidence in medical students. Secondary: to analyze student satisfaction and skills acquired by students with simulators. METHODS: We conducted a prospective, randomized study on medical students. Participants were divided into two groups: Group 1 (G1) (only the explanation) and group 2 (G2) (explanation + simulator workshop). For workload assessment, the validated NASA-TLX questionnaire was completed. The acceptability of the activity, the degree of confidence and the skills acquired were also evaluated. RESULTS: A total of 28 students participated in the practice of prostate examination. All participants reported a higher level of confidence after the theoretical explanation. 34 students participated in the bladder catheterization workshop and all of them increased their confidence after the activity. The G2 showed better scores on the acquired skills exam than the G1. Most students considered positive the incorporation of these models in their learning. According to the NASA-TLX results, less frustration is experienced with the use of simulators in both activities. CONCLUSIONS: The implementation of simulators in the training of students may improve their level of confidence, reducing frustration when performing these explorations in the future and improving care quality.

Simultaneous pancreas-kidney transplant: a single-center long-term outcome.

BACKGROUND: In patients with type 1 diabetes mellitus and end-stage renal disease, simultaneous pancreas-kidney transplantation is associated with increased survival when compared with solitary deceased kidney transplant or dialysis. We consider that the analysis of our long-term program (based in a single center) of simultaneous pancreas-kidney transplantation would provide valuable information for this therapeutic approach regarding patient and organ survival. METHODS: The outcome of 57 consecutive pancreas-kidney transplants patients was analyzed. The analysis included characteristics of the donor and recipient and survival rates of patients and both grafts. We also analyzed age and modality of renal replacement treatment as possible mortality risk factors. RESULTS: Ten-year patient, kidney and pancreas graft survival rates were 75.8%, 57.2% and 42.7%, respectively. Censoring for patient death, the results for 10-year kidney and pancreas survival were 78.5% and 58%, respectively. CONCLUSION: Our results add evidence to support the notion that the double and simultaneous pancreas-kidney transplantation is in fact the treatment of choice in selected patients with end-stage renal failure due to type 1 diabetes mellitus.

Evaluation of clinical and biological prognostic factors in relapsed or refractory diffuse large B-cell lymphoma patients after previous treatment with rituximab and chemotherapy: results of the PRO-R-IPI study.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity, showing a highly variable outcome. In patients with DLBCL relapsed/refractory to first-line treatment with rituximab the usefulness of the revised International Prognostic Index (R-IPI) as a prognostic tool remains unexplored. Some biological parameters (B-cell lymphoma 6 [Bcl-6], Bcl-2, p53, and multiple myeloma 1 [MUM1]) and blood populations (lymphocyte and monocyte counts) have been described as International Prognostic Index-independent prognostic factors. The objective was to evaluate the R-IPI to predict the outcome of DLBCL patients at the time of relapse after a front-line treatment with chemotherapy and rituximab and to establish in this population the relationship between biological parameters and outcome. PATIENTS AND METHODS: We included patients with refractory/relapsed DLBCL after first-line treatment with rituximab-containing regimens; patients must have already finished a rescue treatment also including rituximab. Immunohistochemical assessment of Bcl-2, Bcl-6, p53, and MUM1 expression were undertaken in available biopsies. R-IPI factors were identified from the clinical data at diagnosis and at relapse. Response was assessed using National Cancer Institute-sponsored Working Group guidelines. RESULTS: R-IPI prognosis at relapse was not significantly associated with overall response rate (ORR) after Rituximab-chemotherapy rescue therapy. None of the immunohistochemical parameters analyzed correlated with rescue therapy results. In contrast, patients with absolute lymphocyte count (ALC) ≥ 1 × 10(9)/L at relapse were more likely to respond than patients with ALC < 1 × 10(9)/L (P = .05). CONCLUSION: The R-IPI score calculated at relapse could not predict the ORR to second-line treatment. Lymphopenia is a simple and useful predictor for outcome in relapsed/refractory DLBCL and the only prognostic factor that in our hands could predict the overall response to a second-line treatment with rituximab and chemotherapy.

Switching to second-generation tyrosine kinase inhibitor improves the response and outcome of frontline imatinib-treated patients with chronic myeloid leukemia with more than 10% of BCR-ABL/ABL ratio at 3 months.

Chronic myeloid leukemia patients display heterogeneous responses to imatinib. Survival depends on baseline clinical characteristics (including prognostic scoring systems) and on early response (such as >10% BCR-ABL/ABL ratio at 3 months of therapy). The results of switching to second-generation tyrosine kinase inhibitors (2GTKIs) may contain a bias since, in the majority of these studies, patients who switch treatment due to intolerance or failure are censored or excluded. We analyzed the Spanish Registry data on switching in an intention-to-treat analysis of patients in standard clinical practice. Switching to 2GTKIs improves responses from 45% to 75% of complete cytogenetic response (CCyR) and from 15% to 45% of major molecular response (MMR) in the group without molecular response 1 (MR1) at 3 months and from 70% to 87% in CCyR and from 52% to 87% in MMR in the group with MR1. The final response rate is poorer in the group with no MR1 at 3 months. Nevertheless, the differences in the rates of response were not translated into differences in major events (transformations or deaths), and the final progression-free survival and overall survival were similar.

Acquired hemophilia A: three different presentations of the same disease.

Acquired hemophilia A is a rare disorder characterized by the presence of an autoantibody (mainly immunoglobulin G) to the clotting factor VIII with a clinical resemblance to hemophilia A. This autoantibody may arise because of dysregulation of the immune system. It is associated with various autoimmune or dermatologic diseases, pregnancy, or drug ingestion, but in almost 50% patients, the cause is unknown. In the present study, we have reported three different clinical presentations of acquired hemophilia. In two cases, the underlying disorder was the probable respiratory chronic disease (asthma), and in the other, it was idiopathic. We reviewed the response to a given treatment. The severity of the clinical presentation was different in all the cases, and was taken into account when we decided on the best course of treatment. The present report presents two patients successfully treated with a tapering course of steroids, and one with the anti-CD20 monoclonal antibody not given as first line treatment.

Impacto del uso de simuladores sobre la carga mental y la confianza en un taller de tacto rectal y cateterización vesical en estudiantes / Impact of the use of simulators on the mental workload and confidence in a digital rectal examination and bladder catheterization workshop

OBJETIVOS: Primario: Evaluar el efecto del uso de simuladores en exploración prostática y sondaje vesical sobre la carga mental de trabajo soportada y la confianza adquirida en estudiantes de medicina. Secundario: Analizar el grado de satisfacción y habilidades adquiridas por parte de los estudiantes al usar simuladores como método docente. MÉTODOS: Estudio prospectivo y aleatorizado sobre estudiantes de medicina. Hubo dos grupos de estudio: El grupo 1 (G1) recibió sólo explicación teórica y el grupo 2 (G2) explicación teórica + taller con simuladores. La valoración de la carga mental de trabajo se hizo a través del cuestionario validado NASA-TLX. El grado de confianza, de satisfacción y las habilidades adquiridas fueron también evaluadas. RESULTADOS: Veintiocho estudiantes participaron en el taller de exploración prostática. Todos obtuvieron un mayor nivel de confianza tras la explicación teórica, siendo superior en el grupo que recibió también el taller con simuladores. En el taller de cateterismo vesical donde participaron 34 estudiantes todos aumentaron su confianza tras la actividad. El G2 mostró mejores puntuaciones en el examen de habilidades adquiridas que el G1. La mayoría consideró muy positiva la incorporación de simuladores en su aprendizaje. El uso de simuladores en ambos talleres produjo menos frustración según los resultados del NASA-TLX. CONCLUSIONES: La formación de los alumnos mediante la implementación con simuladores podría lograr una mejora en el nivel de confianza, con un menor nivel de frustración al realizar estas exploraciones en el futuro y así una mejor calidad asistencial

OBJECTIVES: Primary: to assess the use of simulators in prostate digital rectal examination and bladder catheterization on mental workload and the level of confidence in medical students. Secondary: to analyze student satisfaction and skills acquired by students with simulators. METHODS: We conducted a prospective, randomized study on medical students. Participants were divided into two groups: Group 1 (G1) (only the explanation) and group 2 (G2) (explanation + simulator workshop). For workload assessment, the validated NASA-TLX questionnaire was completed. The acceptability of the activity the degree of confidence and the skills acquired were also evaluated. RESULTS: A total of 28 students participated in the practice of prostate examination. All participants reported a higher level of confidence after the theoretical explanation. 34 students participated in the bladder catheterization workshop and all of them increased their confidence after the activity. The G2 showed better scores on the acquired skills exam than the G1. Most students considered positive the incorporation of these models in their learning. According to the NASA-TLX results, less frustration is experienced with the use of simulators in both activities. CONCLUSION: The implementation of simulators in the training of students may improve their level of confidence, reducing frustration when performing these explorations in the future and improving care quality

Aneyaculación como síntoma inicial atípico en un paciente con fibrosis retroperitoneal idiopática / Anejaculation as an atypical initial symptom in a patient with retroperitoneal idiopathic fibrosis

La fibrosis retroperitoneal es una enfermedad rara de causa desconocida. Fue descrita por primera vez en la literatura inglesa en 1948 por Ormond. Se caracteriza por una inflamación crónica e inespecífica del retroperitoneo, la cual puede atrapar y obstruir las estructuras que allí se encuentran, particularmente a los uréteres. En algunas ocasiones se han documentado trastornos de la eyaculación, siendo este un síntoma poco frecuente. La histología parece necesaria para un diagnóstico de certeza, no siendo imprescindible por el alto rendimiento de las pruebas diagnósticas. Su importancia radica en su diagnóstico precoz e inicio de tratamiento para impedir una evolución tórpida y sus complicaciones asociadas. Presentamos el caso de un paciente varón de 46 años con el diagnóstico de fibrosis retroperitoneal idiopática, que comienza con aneyaculación e hidronefrosis bilateral como síntomas principales (AU)

Retroperitoneal fibrosis is an uncommon disease of unclear cause. It was described for the first time in English literature by Ormond in 1948. It is characterised by chronic non-specific inflammation of the retroperitoneum that can entrap and obstruct retroperitoneal structures, notably the ureters. In some rare instances, it has been coupled with ejaculatory disorders. Histology would appear to be required for accurate diagnosis, but it does not affect the efficiency of diagnostic tests and procedures. Its importance lies in early diagnosis and early treatment to prevent a negative prognosis and further complications. We present the case of a 46-year-old male patient with a diagnosis of idiopathic retroperitoneal fibrosis, whose first symptoms were anejaculation and bilateral hydronephrosis (AU)

Adenocarcinoma y linfoma gástricos sincrónicos en el contexto de una gastropatía hipertrófica / Gastric synchronous adenocarcinoma and lymphoma in a case of hypertrophic gastrophaty. Case history

Introducción: La coexistencia de un adenocarcinomagástrico y un linfoma gástrico primario fue descrito por primeravez en 1931. Material y Metodos: Presentamos uncaso en una paciente de 40 años con epigastralgia y perdidade peso. La gastroscopia muestra un engrosamiento de plieguesgástricos. Se realiza gastrectomía total. Resultados: Elexamen histológico muestra un adenocarcinoma de patróndifuso con presencia de células en anillo de sello en el senode un infiltrado linfoide denso y difuso con presencia detípicas lesiones linfoepiteliales. Conclusiones: La presentaciónsimultanea de un adenocarcinoma gástrico y un linfomatipo M.A.L.T en un mismo paciente es muy infrecuente,siendo la infección por Helicobacter pylori un factor etiopatogénicoen el desarrollo de ambas neoplasias

Background: A case of simultaneous gastric adenocarcinomaand primary gastric lymphoma was first describedin 1931. Methods: The case we describe corresponds to a40 year-old patient suffering from epigastralgia and loss ofweight. The gastroscopy shows thickened gastric folds. Acomplete gastrectomy is performed. Results: The histologicalexamination shows an adenocarcinoma with a diffusepattern presenting signet ring cells in the core of a dense anddiffuse lymphoid infiltrate, which also presents typicallymphoepithelial lesions. Conclusions: The case of simultaneousgastric adenocarcinoma and mucous associatedlymphoid tissue lymphoma in a patient is very infrequent.The infection by Helicobacter Pylori is an etopathogenicfactor in the development of both neoplasms

Tumor mülleriano mixto maligno (carcinosarcoma heterólogo) de trompa uterina / Malignant mixed mullerian tumor of the fallopian tube (heterologous carcinosarcoma)

Introducción: El Tumor mülleriano mixto maligno esun tumor de localización ginecológica poco común. Latrompa de Falopio es la localización menos frecuente.Material y Métodos: El caso que nosotros describimoscorresponde a una paciente de 66 años con dolor abdominaly presencia de una masa pélvica en el anejo izquierdo. Serealiza histerectomía y doble anexectomía. Resultados: Laneoplasia distendía y distorsionaba la trompa de Falopioizquierda. Al corte, la trompa estaba ocupada por un tumorblando con áreas hemorrágicas. Microscópicamente eltumor estaba compuesto por elementos malignos epitelialesy estromales con focos diferenciación rabdomiosarcomatosay cartilaginosa. Conclusiones: Cuatro teorías han sidoformuladas para explicar la histogénesis tumoral de los carcinosarcomasde trompa de Falopio. La sobreexpresión dec-erbB-2 en ambos componentes, epitelial y mesenquimal,sugiere un mecanismo carcinogénico común y apoya lahipótesis de histogénesis por conversión implicando unpapel dominante del componente epitelial

Background: Malignant mixed mullerian tumor is anuncommon neoplasm of the female genital tract. The Fallopiantube is most uncommon site. Patients and Methods:The reported case corresponds to a 66 year old woman withabdominal pain. A total hysterectomy with bilateral salpingo-oophorectomy was performed. Results: The neoplasmdistended and distorted the left Fallopian tube. On cut sectionthe tube was filled and expanded by a soft tumor withhemorrhagic areas. Microscopically it was composed ofmalignant epithelial and stromal elements with foci of cartilaginousand rhabdomyosarcomatous differentiation. Conclusions:Four theories have been put forward to explain theorigins of the Fallopian tube carcinosarcomas. C-erbB-2over-expression in both epithelial and mesenchymal componentssuggests a common carcinogenic mechanism for bothcomponents and supports the conversion-histogenesis hypothesisimplicating a dominant role for epithelial component

Hemangioendotelioma epitelioide de pulmón. Presentación de un caso con hemoptisis masiva / Epíthelíoíd haemangíoendothelíoma of the lung. Report of a case wíth massíve haemoptysís

Introducción: El hemangioendotelioma epitelioide se describió inicialmente en 1982 como un tumor multicéntrico con afectación de pulmón, hígado y de partes blandas. Su histogénesis y su carácter multifocal/metastásico han sido muy debatidos.Material y métodos: Presentamos un caso en una paciente de 62 años con hemoptisis y un patrón radiológico intersticial bilateral. Se realizó lobectomía superior izquierda.Resultados: La pieza de lóbectomía mostraba un aspecto hemorrágico y condensado, hete-rogéneo, sin masas- definidas. Microscópicamente correspondía a un tumor multicéntrico cre-ciendo con un patrón pseudopolipoide, obliterando los espacios aéreos. En otras áreas crecía con -un `patrón angiosarcomatoso. Las células mostraban citoplasmas amplios; sincitiales y núcleos hendidos; inmunohistoqu micamente expresaba factor Vlll y CD31.Conclusiones: Se trata de un tumor vascular de diagnóstico difícil debido a su aspecto epi-telioide y a que muy raramente se presenta con hemoptisis. Es un tumor de malignidad inter-media cuyas características morfológicas no permiten predecir su pronóstico. (AU)