Adenovirus-induced hemorrhagic cystitis after CD19-targeted chimeric antigen receptor T-cell therapy in a patient with large B-cell lymphoma.

Chimeric antigen receptor (CAR) T cells targeting CD19 have changed the treatment landscape of patients with relapsed/refractory diffuse large B-cell lymphoma. Infections are one of the most frequent complications after CAR T-cell therapy. Most of these infections are bacterial, although viral infections can also occur in this setting. Adenovirus-induced hemorrhagic cystitis is a rare infectious complication and is usually observed after bone marrow or solid organ transplantation. Herein we report a case of adenovirus-induced hemorrhagic cystitis in a patient experiencing urinary symptoms within the first month after CAR T-cell infusion. Based on our experience and a literature review, we discuss the diagnostic approach and potential treatment options for this infrequent infection after CAR T-cell therapy.

Lymphoma is an aggressive blood cell cancer. A treatment called chimeric antigen receptor (CAR) T-cell therapy has recently been developed for patients with lymphoma and other blood cancers. CAR T-cell therapy is based on the genetic change of the patient's T cells. T cells are a type of white blood cell, which help to attack cancer. CAR T-cell treatment is very effective, but it also carries a risk of adverse events, including infections. These infections can be caused by bacteria or viruses and can affect several organs, including the bladder. Patients with blood cancers who develop bladder infections can have severe pain and bleeding. These bleeding bladder infections are mostly caused by adenovirus or BK virus and are usually seen in patients who have received a bone marrow transplant. However, these infections are rarely observed in patients receiving CAR T cells. We report here a case of bleeding bladder infection caused by adenovirus in a patient receiving CAR T-cell therapy. We discuss the diagnostic approach and possible treatment options for this rare infection in CAR T-cell patients.

Laparoscopic Sleeve Gastrectomy for High-Risk Patients in a Monocentric Series: Long-Term Outcomes and Predictors of Success.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has gained popularity as a stand-alone bariatric procedure, but only a few reports provide data of long-term outcomes on high-risk patients. OBJECTIVE: To evaluate long-term efficacy of LSG as a definitive management on high-risk obese patients and to study factors that predict its success. SETTING: University hospital in Spain. METHODS: A retrospective analysis of prospectively collected data from 134 high-risk patients undergoing LSG from January 2007 through December 2016. Long-term weight loss, resolution of comorbidities, morbidity, and mortality were analyzed. RESULTS: One hundred thirty-four high-risk patients underwent LSG. The mean overall follow-up time was 70.9 ± 4.5 months. The mean age was 47 ± 11.0 years. The mean preoperative body mass index (BMI) was 55.9 ± 6.7 kg/m2 (83.5% were super-obese and 24.6% had BMI ≥ 60). The incidence of postoperative complications was 15%. Mean percentage of total weight loss (%TWL) at 5, 6, 7, and 8 years was 30.7 ± 12.8%, 28.7 ± 14.0%, 29.7 ± 12.3%, and 27.9 ± 11.1%, respectively. Differences were found in age, preoperative BMI, time to reach nadir weight and percentage of excess weight loss (%EWL) at 1 year between patients considered a failure compared to those considered a success. Using multivariate regression analysis, only age (p = 0.009) and time to reach nadir weight after surgery (p = 0.008) correlated with %EWL at 4 years. Resolution of type 2 diabetes (T2DM) was achieved in 62.2% of patients. CONCLUSION: This study supports effectiveness and durability of LSG as a definitive bariatric procedure in high-risk patients.

Utilización de adhesivos biológicos a base de fibrina en la prevención de fugas anastomóticas en anastomosis del tubo digestivo de alto riesgo: resultados preliminares del ensayo clínico fase iv multicéntrico, prospectivo, aleatorizado y controlado simple ciego: Protissucol001 / Use of fibrin based biological adhesives in the prevention of anastomotic leaks in the high risk digestive tract: preliminary results of the multicentre, prospective, randomised, controlled, and simple blind phase IV clinical trial: Protissucol001

Introducción: Con el objetivo de demostrar la eficacia de los adhesivos biológicos a base de fibrina en la prevención de fugas anastomóticas, en enero de 2007 iniciamos un estudio multicéntrico, prospectivo, aleatorizado, controlado, simple ciego, sobre la prevención de fugas anastomóticas en anastomosis del tubo digestivo de alto riesgo mediante la utilización de adhesivos biológicos a base de fibrina. Material y métodos En enero de 2007 iniciamos un ensayo clínico multicéntrico en el que participan los hospitales Gregorio Marañón, Universitario de San Carlos y Hospital del Sureste, de Madrid sobre la prevención de defectos de cicatrización anastomótica mediante la aplicación de adhesivos biológicos a base de fibrina en la linea de sutura. Los pacientes reclutados se aleatorizan asignando al paciente en función de esta aleatorización a uno de los 2 grupos: grupo de estudio en el que se aplica adhesivo en la línea de sutura y grupo control en el que no se aplica. La variable principal del estudio es la presencia o ausencia de fugas. El ensayo ha sido aprobado por los correspondientes Comités de Ética e Investigación Clínica, por la Agencia Española del Medicamento y registrado en www.clinicaltrials.gov (NCT01306851). Ninguno de los autores manifiesta tener conflicto de interés con la empresa Baxter, que comercializa el producto en España. Resultados Desde enero de 2007 hasta noviembre de 2010, se ha reclutado a 104 pacientes que han sido asignados tras aleatorización, 52 al grupo de estudio y 52 al grupo control. Se han registrado 22 fugas anastomóticas de las cuales 7 en el grupo de estudio (13, 4%) y 15 en el grupo control (28, 8%) con un valor de la P de 0,046. El índice de riesgo de fugas fue de 0,384, es decir, se produce una reducción del 61% en las fugas de los pacientes a los que se aplica adhesivo biológico a (..) (AU)

Introduction: A multicentre, prospective, randomised, controlled, and simple blind clinicaltrial was started in January 2007, with the aim of demonstrating the eficacy of fibrin-based biological adhesives in the prevention of anastomotic leaks in the high risk digestive tract. Material and methods: A study on the prevention of anastomotic healing defects by applying biological adhesives along the suture line began in January 2007, and included the hospitals, Gregorio Marañón, Universitario de San Carlos, and Hospital del Sureste, in Madrid. The enrolled patients were randomised to one of 2 groups: the study group in which the adhesive was applied to the suture line, and a control group in which it was not applied. The primary outcome of the study was the presence or absence of leaks. The trial was approved by the corresponding Clinical Research Ethics Committees and the Spanish Medicines Agency(AEMPS) and registered www.clinicaltrials.gov (NCT01306851). The authors declared not to have any (..) (AU)

[Use of fibrin based biological adhesives in the prevention of anastomotic leaks in the high risk digestive tract: preliminary results of the multicentre, prospective, randomised, controlled, and simple blind phase IV clinical trial: Protissucol001]. / Utilización de adhesivos biológicos a base de fibrina en la prevención de fugas anastomóticas en anastomosis del tubo digestivo de alto riesgo: resultados preliminares del ensayo clínico fase iv multicéntrico, prospectivo, aleatorizado y controlado simple ciego: Protissucol001.

INTRODUCTION: A multicentre, prospective, randomised, controlled, and simple blind clinical trial was started in January 2007, with the aim of demonstrating the efficacy of fibrin-based biological adhesives in the prevention of anastomotic leaks in the high risk digestive tract. MATERIAL AND METHODS: A study on the prevention of anastomotic healing defects by applying biological adhesives along the suture line began in January 2007, and included the hospitals, Gregorio Marañón, Universitario de San Carlos, and Hospital del Sureste, in Madrid. The enrolled patients were randomised to one of 2 groups: the study group in which the adhesive was applied to the suture line, and a control group in which it was not applied. The primary outcome of the study was the presence or absence of leaks. The trial was approved by the corresponding Clinical Research Ethics Committees and the Spanish Medicines Agency (AEMPS) and registered www.clinicaltrials.gov (NCT01306851). The authors declared not to have any conflict of interests with the company, Baxter, which markets the product in Spain. RESULTS: A total of 104 patients were recruited between January 2007 and November 2010, of whom 52 were randomised to the study group, and 52 to the control group. A total of 22 anastomotic leaks were recorded, of which 7 (13.4%) were in the study group, and 15 (28.8%) in the control group (P=.046). The leak risk index was 0.384, which means that there was a 61% reduction in leaks in the patients who had the fibrin-based biological adhesive applied. There were 3 (5.7%) further surgeries in the study group, compared to 12 (23%) in the control group (P=.12). On analysing the mortality, it was observed that 3 patients in the study group and 4 patients in the control group died (5.7% vs. 7.7%, P=.5). No other significant differences were found as regards the type of suture, surgical time, or pre-surgical history, except that the use of drainages appeared to be a protective factor of anastomotic leak (P=.041), although the use or not of a drainage was not a controlled factor, but at the discretion of each surgeon. CONCLUSIONS: Our study demonstrates, significantly, that in the 104 patients in the study that fibrin based biological adhesives are capable of preventing anastomotic leaks in the high risk digestive tract, reducing the risk of leaks by 61% and a further surgeries. This is the first clinical trial that shows these significant results. If our results are maintained at the end of the study, it will show that anastomotic leaks can be prevented with the application of these adhesives, thus their application may be recommended in all the anastomosis of the high risk digestive tract.

Colecistectomía laparoscópica de puerto único en un programa de CMA / Single port laparoscopic cholecystectomy in major ambulatory surgery (MAS)

Introducción: La cirugía endoscópica por orificios naturales es una nueva modalidad quirúrgica en fase de desarrollo. La vía más natural para los cirujanos es usar una cicatriz ya existente como es el ombligo. La reciente introducción de trocares diseñados para este fin ha hecho posible su puesta en práctica. Material y métodos: En este estudio presentamos nuestra experiencia preliminar en la colecistectomía laparoscópica con puerto de acceso único umbilical, mediante un estudio prospectivo que incluye a 26 pacientes intervenidos entre enero 2009 y enero 2010. También pretendemos conocer su posible realización en régimen de CMA. Resultados: Todos los pacientes presentaban colelitiasis no complicadas, aunque en 5 se identifico una colecistitis en la cirugía. El tiempo quirúrgico promedio fue de 51,2min. La estancia hospitalaria media fue 25,7h. En el 76,92% de los pacientes el ingreso fue menor de 24h. No hubo ningún reingreso ni complicación intraoperatoria o postoperatoria importante. Conclusiones: A la vista de nuestros resultados la colecistectomía laparoscópica por puerto único favorece su inclusión en un programa de cirugía mayor ambulatoria (AU)

Introduction: Natural orifice endoscopic surgery is a new surgical procedure still in the development phase. The most natural entry for surgeons is to use an already existing scar, such as the navel. The recent introduction of trocars designed for this purpose has made it possible to put this into practice. Material and methods: We present our preliminary experience in single trans‐umbilical incision laparoscopic cholecystectomy, by means of a prospective study which included 26 patients operated on between January 2009 and January 2010. We also attempt to find out whether it can be performed in a MAS programme. Results: All patients had uncomplicated cholelithiasis, although in 5 of them cholecystitis was identified during the surgery. The mean surgical time was 51.2min. The mean hospital stay was 25.7h, and 76.92% of patients were admitted for less than 24h. There were no re-admissions or significant intra-operative or post-operative complications. Conclusions: On looking at our results, single port laparoscopic cholecystectomy could be included in a major ambulatory surgery programme (AU)

[Single port laparoscopic cholecystectomy in major ambulatory surgery (MAS)]. / Colecistectomía laparoscópica de puerto único en un programa de CMA.

INTRODUCTION: Natural orifice endoscopic surgery is a new surgical procedure still in the development phase. The most natural entry for surgeons is to use an already existing scar, such as the navel. The recent introduction of trocars designed for this purpose has made it possible to put this into practice. MATERIAL AND METHODS: We present our preliminary experience in single trans-umbilical incision laparoscopic cholecystectomy, by means of a prospective study which included 26 patients operated on between January 2009 and January 2010. We also attempt to find out whether it can be performed in a MAS programme. RESULTS: All patients had uncomplicated cholelithiasis, although in 5 of them cholecystitis was identified during the surgery. The mean surgical time was 51.2 min. The mean hospital stay was 25.7h, and 76.92% of patients were admitted for less than 24h. There were no re-admissions or significant intra-operative or post-operative complications. CONCLUSIONS: On looking at our results, single port laparoscopic cholecystectomy could be included in a major ambulatory surgery programme.

Factores predictores de mortalidad en la colitis isquémica grave: análisis de 101 pacientes intervenidos / Predictive factors of mortality in severe ischaemic colitis: post-operative analysis of 101 patients

Introducción La colitis isquémica (CI) es la forma más frecuente de enfermedad isquémica digestiva y está infradiagnosticada. Objetivos Describir los resultados obtenidos en pacientes con CI que necesitaron de intervención quirúrgica en nuestro centro, y evaluar los factores predictores de mortalidad. Métodos Los datos fueron obtenidos de la base de CI del Hospital Gregorio Marañón. Las características demográficas, clínicas, los métodos diagnósticos, las técnicas quirúrgicas empleadas y la mortalidad fueron analizados estadísticamente empleando la prueba de la χ2 y la t de Student. Resultados Entre 1991 y 2006, se operó a 101 pacientes con CI. La mayoría de éstos tenían antecedentes cardiovasculares y 35 casos fueron diagnosticados durante su ingreso hospitalario por otra causa. Tanto los signos como los síntomas fueron inespecíficos en el 40% de los casos. La morbilidad y la mortalidad total fue del 39,6 y el 41,6%, respectivamente. En los casos de CI postoperatoria, la mortalidad se elevó hasta el 68% (p<0,01); el 93% de los paciente que fallecieron tenían necrosis transmural durante la cirugía (p<0,05) y el 69% tenía acidosis metabólica. Conclusiones La mortalidad en pacientes afectos de CI que necesitan intervención quirúrgica es alta, especialmente si el diagnóstico se hace en el postoperatorio de otra cirugía o si se evidencia necrosis transmural durante la intervención. Para mejorar estos resultados el diagnóstico precoz es la mejor arma, y debe basarse en un alto índice de sospecha(AU)

IntroductionIschaemic colitis (IC) is the most common form of bowel ischaemia and is often under-diagnosed. Objectives To report the results obtained in patients with IC who required surgical intervention in our Hospital, and to evaluate the predictive factors of mortality. Methods The data were obtained from the Gregorio Marañon Hospital CI database. The demographic and clinical characteristics, diagnostic methods, surgical techniques employed and mortality were analysed statistically, using the χ2 and Student t test. Results One-hundred and one patients with CI were operated on between 1991 and 2006. The majority of them had cardiovascular histories and 35 cases were diagnosed during their hospital stay due to another cause. The signs and the symptoms were non-specific in 40% of the cases. Total morbidity and mortality was 39.6% and 41.6% respectively. In the post-operative IC cases, the death rate increased to 68% (p<0.01); 93% of the patients who died had transmural necrosis during the surgery (p<0.05) and 69% had a metabolic acidosis. Conclusions The death rate in patients with IC that requires surgery is high, particularly if the diagnosis is made in the post-operative period after surgery for another cause, or if there is evidence of transmural necrosis during the intervention. Early diagnosis is the best tool to improve these results (AU)

[Predictive factors of mortality in severe ischaemic colitis: post-operative analysis of 101 patients]. / Factores predictores de mortalidad en la colitis isquémica grave: análisis de 101 pacientes intervenidos.

INTRODUCTION: Ischaemic colitis (IC) is the most common form of bowel ischaemia and is often under-diagnosed. OBJECTIVES: To report the results obtained in patients with IC who required surgical intervention in our Hospital, and to evaluate the predictive factors of mortality. METHODS: The data were obtained from the Gregorio Marañon Hospital CI database. The demographic and clinical characteristics, diagnostic methods, surgical techniques employed and mortality were analysed statistically, using the chi(2) and Student t test. RESULTS: One-hundred and one patients with CI were operated on between 1991 and 2006. The majority of them had cardiovascular histories and 35 cases were diagnosed during their hospital stay due to another cause. The signs and the symptoms were non-specific in 40% of the cases. Total morbidity and mortality was 39.6% and 41.6% respectively. In the post-operative IC cases, the death rate increased to 68% (p<0.01); 93% of the patients who died had transmural necrosis during the surgery (p<0.05) and 69% had a metabolic acidosis. CONCLUSIONS: The death rate in patients with IC that requires surgery is high, particularly if the diagnosis is made in the post-operative period after surgery for another cause, or if there is evidence of transmural necrosis during the intervention. Early diagnosis is the best tool to improve these results.

Synthesis of Sansalvamide A derivatives and their cytotoxicity in the MSS colon cancer cell line HT-29.

We report the synthesis of thirty-six Sansalvamide A derivatives, and their biological activity against colon cancer HT-29 cell line, a microsatellite stable (MSS) colon cancer cell-line. The thirty-six compounds can be divided into three subsets, where the first subset of compounds contains L-amino acids, the second subset contains D-amino acids, and the third subset contains both D- and L-amino acids. Five compounds exhibited excellent inhibitory activity (>75% inhibition). The structure-activity relationship (SAR) of the compounds established that a single D-amino acid in position 2 or 3 gave up to a 10-fold improved cytotoxicity over Sansalvamide A peptide. This work highlights the importance of residues 2 and 3 and the role of D-amino acids in the extraordinary SAR for this compound class.

Novel antibiotics: C-2 symmetrical macrocycles inhibiting Holliday junction DNA binding by E. coli RuvC.

Holliday junctions (HJs) are formed as transient DNA intermediates during site-specific and homologous recombination. Both of these genetic exchange pathways are critical for normal DNA metabolism and repair. Trapping HJs leads to bacterial cell death by preventing proper segregation of the resulting interlinked chromosomes. Macrocyclic peptides designed to target this intermediate were synthesized with the goal of identifying compounds with specificity for this unique molecular target. We discovered ten macrocycles, both hexameric and octameric peptides, capable of trapping HJs in vitro. Those macrocycles containing tyrosine residues proved most effective. These data demonstrate that C-2 symmetrical macrocycles offer excellent synthetic targets for the development of novel antibiotic agents. Furthermore, the active compounds identified provide valuable tools for probing different pathways of recombinational exchange.

Synthesis and cytotoxicity of novel sansalvamide A derivatives.

Described are the syntheses of 14 derivatives of the natural product Sansalvamide A, where two are more active against HCT 116 colon cancer cell lines than the natural product. These derivatives were synthesized using a combinatorial-type strategy that permits elucidation of the amino acid role in the cytotoxicity, and they lay the groundwork for development of new anticancer agents. [structure: see text]