Comparing R-Bendamustine vs. R-CHOP Plus Maintenance Therapy as First-Line Systemic Treatment in Follicular Lymphoma: A Multicenter Retrospective GELTAMO Study.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and R-bendamustine (R-B) are the most common frontline treatment strategies for advanced-stage follicular lymphoma (FL). After R-CHOP induction therapy, using rituximab for maintenance therapy notably improves outcomes; however, whether this can be achieved by using the same approach after R-B therapy is still being determined. This retrospective analysis compared 476 FL patients from 17 GELTAMO centers who received R-based regimens followed by rituximab maintenance therapy for untreated advanced-stage FL. The complete response rate at the end of induction was higher with R-B and relapses were more frequent with R-CHOP. During induction, cytopenias were significantly more frequent with R-CHOP and so was the use of colony-stimulating factors. During maintenance therapy, R-B showed more neutropenia and infectious toxicity. After a median follow-up of 81 months (95% CI: 77-86), the 6-year rates of progression-free survival (PFS) were 79% (95% CI: 72-86) for R-bendamustine vs. 67% (95% CI: 61-73) for R-CHOP (p = 0.046), and 6-year overall survival (OS) values were 91% (95% CI: 86-96) for R-B vs. 91% (95% CI: 87-94) for R-CHOP (p = 0.49). In conclusion, R-B followed by rituximab maintenance therapy in patients with previously untreated FL resulted in significantly longer PFS than R-CHOP, with older patients also benefiting from this treatment without further toxicity. Adverse events during maintenance were more frequent with R-B without impacting mortality.

Comparative Study of the Effectiveness of Vedolizumab Versus Ustekinumab After Anti-TNF Failure in Crohn's Disease (Versus-CD): Data from the ENEIDA Registry.

BACKGROUND: Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited. AIMS: To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. METHODS: CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. RESULTS: A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02-3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00-1.62], moderate-severe activity in HBI [HR 1.79; 95% CI: 1.20-2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02-1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them. CONCLUSION: In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.

Low-risk HPLLs/ABC score patients with splenic marginal zone lymphoma can be safely managed without treatment: Results from a prospective Spanish study.

The aims of our study were to analyse compliance with the 2014 GELTAMO SMZL Guidelines, in patients with splenic marginal zone lymphoma (SMZL), and to evaluate the outcome according to the HPLLs/ABC-adapted therapeutic strategy. Observational prospective multicenter study of 181 SMZL patients diagnosed between 2014 and 2020. Lymphoma-specific survival (LSS), composite event-free survival (CEFS) and response rates were assessed. 57% of the 168 patients included in the analysis followed the Guidelines. The overall response rate was higher in the rituximab chemotherapy and in the rituximab arms compared with the splenectomy arm (p < 0.001). The 5-year overall survival was 77% and the 5-year LSS of 93%. There were no differences in the 5-year LSS according to the treatment received (p = 0.68). The 5-year CEFS in the overall series was 45%, and there were significant differences between scores A and B (p = 0.036). There were no significant differences when comparing LSS and progression-free survival in patients treated with rituximab or rituximab chemotherapy at diagnosis or after observation. Our data support HPLLs/ABC score as a practical tool for the management of SMZL, observation as the best approach for patients in group A and rituximab as the best treatment for group B.

Evolución de los pacientes con infección crónica por hepatitis C con fibrosis avanzada o cirrosis curados con antivirales de acción directa. Seguimiento a largo plazo / Evolution of patients with chronic hepatitis C infection with advanced fibrosis or cirrhosis cured with direct-acting antivirals. Long-term follow-up

Objetivos: Analizar la evolución analítica, clínica y de la fibrosis en pacientes F3-F4 curados con antivirales de acción directa (AAD). Pacientes y métodos: Estudio unicéntrico, observacional y prospectivo. Se incluyeron todos los pacientes con hepatitisC F3-F4 curados con AAD del 1 de noviembre de 2014 al 31 de agosto de 2019. Se realizó una visita basal (VB) y a las 12semanas (12s), 1, 2, 3 y 4años tras finalizar el tratamiento. Se recogieron variables demográficas, analíticas, medición no invasiva de la fibrosis, marcadores indirectos de hipertensión portal, presencia de varices esofágicas, descompensaciones de la cirrosis y hepatocarcinoma. Resultados: Se trataron 169 pacientes: 123 (72,8%) hombres, edad 57,5±12 años; 117 (69,2%) presentaban cirrosis, 99 (84,6%) ChildA. El 96,4% consiguieron respuesta virológica sostenida (RVS). La mediana de seguimiento fue de 46,14 (2,89-62,55) meses. Durante el seguimiento se observó precozmente un aumento significativo de plaquetas (155×103/μl [VB]; 163×103/μl [12s]), colesterol (158mg/dl [VB]; 179mg/dl [12s]) y albúmina (4,16g/dl [VB]; 4,34g/dl [12s]), y un descenso significativo de GPT (82UI/l [VB]; 23UI/l [12s]), GOT (69UI/l [VB]; 26UI/l [12s]), GGT (118UI/l [VB]; 48UI/l [12s]), y bilirrubina (0,9mg/dl [VB]; 0,7mg/dl [12s]). La fibrosis disminuyó, también inicialmente, tanto con métodos serológicos como Fibroscan (19,9KPa [VB]; 14,8KPa [12s]); p<0,05). El 8,1% de los pacientes con cirrosis compensada presentaron alguna descompensación. El 4,5% desarrollaron varices esofágicas. Nueve (5,52%) pacientes presentaron hepatocarcinoma de novo; seis (3,68%) lo presentaban basalmente, y el 40% sufrieron recidiva. Durante el seguimiento la mortalidad fue del 9,2%. Conclusiones: Existe mejoría de los parámetros analíticos y de la fibrosis hepática medida por métodos no invasivos en los pacientes F3-F4 curados con AAD.(AU)

Aims: To analyze laboratory parameters, clinical and fibrosis evolution in F3-F4 patients cured with direct-acting antivirals (DAA). Patients and methods: Unicenteric, observational and prospective study. All F3–F4 hepatitis C patients cured with DAA from 01/11/2014 to 31/08/2019 were included. A basal visit (BV) was performed and at 12 weeks (12w), 1, 2, 3 and 4 years after treatment. Demographic and laboratory variables, fibrosis measured by non-invasive tests, indirect markers of portal hypertension, the presence of esophageal varices, cirrhosis decompensation and hepatoceullar carcinoma were collected. Results: 169 patients were treated: 123 (72.8%) men, age 57.5±12 years; 117 (69.2%) with cirrhosis, 99 (84.6%) ChildA. 96,4% achieved SVR. The study was conducted for a median follow-up of 46.14 (2.89-62.55) months. It was observed a significant increase in platelets [155×103/μL (BV); 163×103/μL (12w)], cholesterol [158mg/dL (BV); 179mg/dL (12w)] and albumin [4.16g/dL (BV); 4.34g/dL (12w)] and a significant decrease in ALT [82UI/L (BV); 23UI/L (12w], AST [69UI/L (BV); 26UI/L (12w)], GGT [118UI/L (BV); 48UI/L (12w)] and bilirrubin [0.9mg/dL (BV); 0.7mg/dL (12w)]. Fibrosis also improved early in follow-up, both by serological methods and Fibroscan [19.9kPa (BV); 14.8kPa (12w; P<.05]. 8.1% of compensated cirrhosis patients had some decompensation. 4.5% developed esophageal varices. Nine patients (5.52%) had de novo hepatocellular carcinoma; 6 (3.68%) had hepatoceullar carcinoma in BV and 40% had a recurrence. During follow-up mortality was 9.2%. Conclusions: There is an improvement in laboratory parameters and fibrosis measured by non-invasive methods in F3-F4 patients cured with DAA. However, the risk of decompensation and the incidence/recurrence of hepatocellular carcinoma still remain, so there is a need to follow these patients.(AU)

Cribado de infección por virus de la hepatitis B y C en pacientes hospitalizados con infección por SARS-CoV-2 / Hepatitis B and C screening in hospitalized patients with SARS-CoV-2 infection

Objetivo: Evaluar el resultado del cribado de hepatitis B y C en pacientes ingresados con COVID-19.Pacientes y métodos: Estudio transversal, prospectivo, realizado en dos hospitales españoles de tercer nivel. Se estudiaron marcadores de hepatitis B (HBsAg, anti-HBc) y C (anti-VHC, ARN VHC) a todos los pacientes hospitalizados con COVID-19 del 1 de marzo al 31 de diciembre de 2020.Resultados: En este periodo ingresaron 4662 pacientes con COVID-19: 56,3% fueron varones, la edad mediana fue 76 (0-104) años. Se realizó serología de hepatitis B a 2915 (62,5%) pacientes; 253 (8,75%) presentaban anti-HBc+y 11 (0,38%) HBsAg+. De los 11 pacientes, 4 desconocían el diagnóstico, 7 recibieron esteroides y uno recibió profilaxis. Hubo un caso de reactivación del VHB. Se determinaron anticuerpos anti-VHC a 2895 (62%) pacientes; 24 (0,83%) fueron positivos. De ellos, 13 pacientes estaban diagnosticados: 10 habían recibido tratamiento, uno se había curado espontáneamente y dos no habían sido tratados. De los 11 restantes, 10 tenían ARN VHC indetectable. En total, solo 3 (0,10%) pacientes tenían carga viral detectable. Sin embargo, ninguno recibió tratamiento (2> 90 años con comorbilidades, uno falleció por COVID-19).Conclusiones: El cribado de hepatitis C en pacientes ingresados por COVID-19 en nuestro medio ha mostrado menor utilidad de la esperada. La baja prevalencia de infección activa tras los tratamientos antivirales y la alta edad mediana de nuestra población limitan la detección de potenciales candidatos a tratamiento. El cribado de hepatitis B debería dirigirse a prevenir la reactivación en pacientes que precisen tratamientos inmunosupresores.(AU)

Aims: To evaluate the results of a hepatitis B and C screening program in hospitalized COVID-19 patients.Method: Transversal prospective study conducted in two Spanish hospitals. Patients admitted from March 1st to December 31st 2020 with a diagnosis of COVID-19 were tested for markers of hepatitis B (HBsAg, anti-HBc) and C (anti-HCV, HCV RNA) infection.Results: In this period, 4662 patients with COVID-19 were admitted to our centers: 56.3% were male, median age was 76 (0–104) years. Data regarding HBV infection was available in 2915 (62.5%) patients; 253 (8.75%) were anti-HBc+ and 11 (0.38%) HBsAg+. From these, 4 patients did not have a previous diagnosis of hepatitis B, 7 received corticosteroids and one received prophylaxis. There was one HBV reactivation. Anti-HCV was available in 2895 (62%) patients; 24 (0.83%) were positive. From these, 13 patients had a previous hepatitis C diagnosis: 10 patients had been treated with SVR, one achieved spontaneous cure and 2 did not receive treatment. From the 11 previously unknown anti-VHC+patients, 10 had a negative HCV RNA. Overall, only 3 (0.10%) patients tested RNA HCV+. However, none received HCV treatment (2 older than 90 years with comorbidities, 1 died from COVID-19).Conclusion: Screening of hepatitis C infection in hospitalized COVID-19 patients seems less useful than expected. The low prevalence of active infection after antiviral treatments and the high age of our population limit the detection of potential candidates for treatment. HBV screening should be aimed to prevent reactivation under immunosuppressive treatments.(AU)

[Imaging findings in renal angiosarcoma.] / Hallazgos de imagen del angiosarcoma renal.

Los angiosarcomas son tumores malignos de alto grado poco frecuentes y de mal pronóstico. Constituyen el 2% de todos los sarcomas de tejidos blandos. Se originan en el endotelio de los vasos linfáticos y vasculares...

Los angiosarcomas son tumores malignos de altogrado poco frecuentes y de mal pronóstico. Constituyenel 2% de todos los sarcomas de tejidos blandos.Se originan en el endotelio de los vasos linfáticos yvasculares...

Evolution of patients with chronic hepatitis C infection with advanced fibrosis or cirrhosis cured with direct-acting antivirals. Long-term follow-up. / Evolución de los pacientes con infección crónica por hepatitis C con fibrosis avanzada o cirrosis curados con antivirales de acción directa. Seguimiento a largo plazo.

AIMS: To analyze laboratory parameters, clinical and fibrosis evolution in F3-F4 patients cured with direct-acting antivirals (DAA). PATIENTS AND METHODS: Unicenteric, observational and prospective study. All F3-F4 hepatitis C patients cured with DAA from 01/11/2014 to 31/08/2019 were included. A basal visit (BV) was performed and at 12 weeks (12w), 1, 2, 3 and 4 years after treatment. Demographic and laboratory variables, fibrosis measured by non-invasive tests, indirect markers of portal hypertension, the presence of esophageal varices, cirrhosis decompensation and hepatoceullar carcinoma were collected. RESULTS: 169 patients were treated: 123 (72.8%) men, age 57.5±12 years; 117 (69.2%) with cirrhosis, 99 (84.6%) ChildA. 96,4% achieved SVR. The study was conducted for a median follow-up of 46.14 (2.89-62.55) months. It was observed a significant increase in platelets [155×103/µL (BV); 163×103/µL (12w)], cholesterol [158mg/dL (BV); 179mg/dL (12w)] and albumin [4.16g/dL (BV); 4.34g/dL (12w)] and a significant decrease in ALT [82UI/L (BV); 23UI/L (12w], AST [69UI/L (BV); 26UI/L (12w)], GGT [118UI/L (BV); 48UI/L (12w)] and bilirrubin [0.9mg/dL (BV); 0.7mg/dL (12w)]. Fibrosis also improved early in follow-up, both by serological methods and Fibroscan [19.9kPa (BV); 14.8kPa (12w; P<.05]. 8.1% of compensated cirrhosis patients had some decompensation. 4.5% developed esophageal varices. Nine patients (5.52%) had de novo hepatocellular carcinoma; 6 (3.68%) had hepatoceullar carcinoma in BV and 40% had a recurrence. During follow-up mortality was 9.2%. CONCLUSIONS: There is an improvement in laboratory parameters and fibrosis measured by non-invasive methods in F3-F4 patients cured with DAA. However, the risk of decompensation and the incidence/recurrence of hepatocellular carcinoma still remain, so there is a need to follow these patients.

Screening for Prognostic microRNAs Associated with Treatment Failure in Diffuse Large B Cell Lymphoma.

Diffuse large B cell lymphoma (DLBCL) treatment with R-CHOP regimen produces 5-year progression-free survival and overall survival of around 60-70%. Our objective was to discover prognostic biomarkers allowing early detection of the remaining 30-40% with poor long-term outcome. For this purpose, we applied a novel strategy: from a cohort of DLBCL patients, treated with standard therapy, a discovery group of 12 patients with poor prognosis (advanced stage III-IV, R-IPI > 2) was formed, consisting of six chemoresistant (refractory/early relapse < 12 months) and six chemosensitive (complete remission > 3 years) subjects. By using microarray assays, the most differentially expressed miRNAs were defined as an initial set of prognostic miRNA candidates. Their expression was then analyzed in a validation cohort of 68 patients and the three miRNAs with the most significant impact on event-free and overall survival were selected. In the DLBCL cell line U-2932 the transfection with miR-1244 and miR-193b-5p, but not miR-1231, blocked the effect of CHOP on cell viability. A subsequent gene set enrichment analysis in patients revealed the implication of the first two miRNAs in cell cycle control and chemoresistance-related pathways, whereas the last one was involved in immunological processes. In conclusion, this novel strategy identified three promising prognostic markers for DLBCL patients at high risk of failure with standard therapy.

Hepatitis B and C screening in hospitalized patients with SARS-CoV-2 infection. / Cribado de infección por virus de la hepatitis B y C en pacientes hospitalizados con infección por SARS-CoV-2.

AIMS: To evaluate the results of a hepatitis B and C screening program in hospitalized COVID-19 patients. METHOD: Transversal prospective study conducted in two Spanish hospitals. Patients admitted from March 1st to December 31st 2020 with a diagnosis of COVID-19 were tested for markers of hepatitis B (HBsAg, anti-HBc) and C (anti-HCV, HCV RNA) infection. RESULTS: In this period, 4662 patients with COVID-19 were admitted to our centers: 56.3% were male, median age was 76 (0-104) years. Data regarding HBV infection was available in 2915 (62.5%) patients; 253 (8.75%) were anti-HBc+ and 11 (0.38%) HBsAg+. From these, 4 patients did not have a previous diagnosis of hepatitis B, 7 received corticosteroids and one received prophylaxis. There was one HBV reactivation. Anti-HCV was available in 2895 (62%) patients; 24 (0.83%) were positive. From these, 13 patients had a previous hepatitis C diagnosis: 10 patients had been treated with SVR, one achieved spontaneous cure and 2 did not receive treatment. From the 11 previously unknown anti-VHC+patients, 10 had a negative HCV RNA. Overall, only 3 (0.10%) patients tested RNA HCV+. However, none received HCV treatment (2 older than 90 years with comorbidities, 1 died from COVID-19). CONCLUSION: Screening of hepatitis C infection in hospitalized COVID-19 patients seems less useful than expected. The low prevalence of active infection after antiviral treatments and the high age of our population limit the detection of potential candidates for treatment. HBV screening should be aimed to prevent reactivation under immunosuppressive treatments.

[Ectopic pregnancy on uterine scar from cesarean section] / Embarazo ectópico sobre cicatriz uterina por cesárea.

Ectopic pregnancy is defined as the implantation of the fertilized egg outside the uterine cavity. About 95% of ectopic pregnancies are located in the tube. Non-tubal forms, in particular on the scar of a cesarean section, are a very rare entity whose early diagnosis and treatment are essential to avoid serious complications and preserve fertility.

El embarazo ectópico se define como la implantación del óvulo fecundado fuera de la cavidad uterina. Alrededor del 95% de los embarazos ectópicos se localizan en la trompa. Las formas no tubáricas, en concreto sobre la cicatriz de una cesárea, son una entidad muy poco frecuente cuyo diagnóstico y tratamiento precoz son imprescindibles para evitar complicaciones graves y preservar la fertilidad.

Total Lesion Glycolysis Improves Tumor Burden Evaluation and Risk Assessment at Diagnosis in Hodgkin Lymphoma.

Hodgkin lymphoma (HL) is a hematological malignancy with an excellent prognosis. However, we still need to identify those patients that could experience failed standard frontline chemotherapy. Tumor burden evaluation and standard decisions are based on Ann Arbor (AA) staging, but this approach may be insufficient in predicting outcomes. We aim to study new ways to assess tumor burden through volume-based PET parameters to improve the risk assessment of HL patients. We retrospectively analyzed 101 patients with HL from two hospitals in the Balearic Islands between 2011 and 2018. Higher metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were significantly associated with a higher incidence of III-IV AA stages, B-symptoms, hypoalbuminemia, lymphopenia, and higher IPS. Standardized uptake value (SUVmax) was significantly related to AA stage and hypoalbuminemia. We found that TLG or the combination of SUVmax, TLG, and MTV significantly improved the risk assessment when compared to AA staging. We conclude that TLG is the best single PET/CT-related tumor-load parameter that significantly improves HL risk assessment when compared to AA staging. If confirmed in a larger and validated sample, this information could be used to modify standard frontline therapy and justifies the inclusion of TLG inside an HL prognostic score.

Severe infections in patients with lymphoproliferative diseases treated with new targeted drugs: A multicentric real-world study.

BACKGROUND: Lymphoid neoplasms treatment has recently been renewed to increase antitumor efficacy and conventional chemotherapies toxicities. Limited data have been published about the infection risk associated with these new drugs, therefore this study analyzes the infectious complications in patients with lymphoproliferative diseases (LPD) treated with monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, nivolumab, or pembrolizumab), BTK inhibitors (ibrutinib and acalabrutinib), PI3K inhibitors (idelalisib) and BCL2 inhibitors (venetoclax). METHODS: Multicenter retrospective study of 458 LPD patients treated with targeted therapies in real-life setting, in 18 Spanish institutions, from the time of their commercial availability to August 2020. RESULTS: Severe infections incidence was 23% during 17-month median follow-up; cumulative incidence was higher in the first 3-6 months of targeted drug treatment and then decreased. The most frequent etiology was bacterial (54%). Nine (6%) Invasive fungal infections (IFI) were observed, in its majority in chronic lymphocytic leukemia (CLL) patients treated predominantly with ibrutinib. Significant risk factors for severe infection were: severe lymphopenia (p = 0.009, OR 4.7, range 1.3-1.7), combined targeted treatment vs single agent treatment (p = 0.014 OR 2.2 range 1.1-4.2) and previous rituximab (p = 0.03 OR 1.8, range 1.05-3.3). Infection-related mortality was 6%. In 22% of patients with severe infections, definitive discontinuation of the targeted drug was observed. CONCLUSION: A high proportion of patients presented severe infections during follow-up, with non-negligible attributable mortality, but infection incidence is not superior to the one observed during the chemotherapy era. In selected cases with specific risk factors for infection, antimicrobial prophylaxis should be considered.

SEGHI Study: Defining the Best Surveillance Strategy in Hodgkin Lymphoma after First-Line Treatment.

The optimal strategy for early surveillance after first complete response is unclear in Hodgkin lymphoma. Thus, we compared the various follow-up strategies in a multicenter study. All the included patients had a negative positron emission tomography/computed tomography at the end of induction therapy. From January 2007 to January 2018, we recruited 640 patients from 15 centers in Spain. Comparing the groups in which serial imaging were performed, the clinical/analytical follow-up group was exposed to significantly fewer imaging tests and less radiation. With a median follow-up of 127 months, progression-free survival at 60 months of the entire series was 88% and the overall survival was 97%. No significant differences in survival or progression-free survival were found among the various surveillance strategies. This study suggests that follow-up approaches with imaging in Hodgkin lymphoma provide no benefits for patient survival, and we believe that clinical/analytical surveillance for this group of patients could be the best course of action.

CIBERESUCICOVID: un proyecto estratégico para una mejor comprensión y manejo clínico de la COVID-19 en pacientes críticos / CIBERESUCICOVID: A strategic project for a better understanding and clinical management of COVID-19 in critical patients

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