Patients with aggressive B-cell lymphoma receiving CAR T-cell therapy have a low rate of severe infections despite lack of universal antibacterial and antifungal prophylaxis.

OBJECTIVES: Our aim was to describe the frequency and severity of infectious complications after chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma (LBCL). METHODS: We retrospectively reviewed clinical records of LBCL patients treated with CD19-targeted CAR T-cell therapy from July/2018 to December/2021 at our institution, and identified all infectious episodes from CAR T-cell infusion until disease progression, death or last follow-up. RESULTS: Overall, 137 patients were included. Thirty six percent had received ≥3 previous lines of therapy and 26% an autologous hematopoietic cell transplantation (auto-HCT). Cytokine release syndrome occurred in 87 (64%) patients. Antibacterial prophylaxis was not used in any patient; only 38% received antifungal prophylaxis. Sixty three infectious events were observed in 41 (30%) patients. Fifty two (83%) of the infectious events had at least one pathogen identified (bacteria [n = 38], virus [n = 11], and fungi [n = 3]). Most of the infectious events occurred during hospitalization for CAR-T treatment. Infection-related mortality was observed in two patients. Independent risk factors for infection included male gender, previous auto-HCT, ≥3 lines of treatment and pre-lymphodepletion neutropenia. CONCLUSIONS: Infections after CAR T-cell therapy in patients with lymphoma are frequent but generally not severe. A conservative and tailored antimicrobial prophylaxis seems to be a safe approach.

Low frequency of cytomegalovirus (CMV) disease despite high prevalence of CMV viraemia in patients with advanced HIV infection: a clinical and immunological 48-week follow-up study.

OBJECTIVES: The aim of the study was to investigate the dynamics of cytomegalovirus (CMV) replication and CMV-specific immune response recovery after antiretroviral treatment (ART) initiation in patients with advanced HIV infection. METHODS: A prospective observational study of patients with HIV infection and CD4 counts of < 100 cells/µL was carried out (September 2015 to July 2018). HIV viral load (VL), CD4 count and CMV VL were determined by quantitative polymerase chain reaction (PCR) at baseline and at 4, 12, 24 and 48 weeks, and CMV-specific immune response was determined by QuantiFERON-CMV assay at baseline and 48 weeks. All patients were started on ART but only those with CMV end-organ disease (EOD) received anti-CMV treatment. RESULTS: Fifty-three patients with a median age of 43.6 [interquartile range (IQR) 36.7-52.4] years were included in the study. At baseline, the median CD4 count was 30 cells/µL (IQR 20-60 cells/µL) and the median HIV VL was 462 000 HIV-1 RNA copies/mL (IQR 186 000-1 300 000 copies/mL). At baseline, 32% patients had detectable CMV viraemia but none had detectable CMV viraemia at 48 weeks. Only one of 53 (1.9%) patients developed EOD during follow-up. Seven (13.2%) patients were lost to follow-up and six (11.3%) died; none of the deaths was related to CMV. Similar percentages of patients had a CMV-specific immune response at baseline (71.7%) and at 48 weeks (70.0%). The magnitude of this response tended to increase over time [median 1.63 (IQR 0.15-5.77) IU/mL at baseline vs. median 2.5 (IQR 0.1-8.325) IU/mL at 48 weeks; P = 0.11]. We did not find any risk factors associated with 48-week mortality. CONCLUSIONS: Although the prevalence of CMV viraemia in patients with advanced HIV infection remains high, achieving a good immunological recovery through ART is enough to suppress CMV viraemia, without an increased risk of CMV EOD. The prevalence of a CMV-specific immune response was high and endured over time.

The Jarisch-Herxheimer reaction in syphilis: could molecular typing help to understand it better?

OBJECTIVES: The Jarisch-Herxheimer reaction (JHR) is a febrile inflammatory reaction that may occur in patients after treatment of syphilis. The overall rate is estimated to be 10-25% with broad variations over time. It appears to be related to factors like stage of the disease or reagin titres. In this study, we aimed to describe the incidence of and risk factors including strain typing for JHR among patients with syphilis. METHODS: From January through October 2015, 224 consecutive patients (82 of them with HIV) who were diagnosed with early syphilis were enrolled in this prospective observational study in a referral STI clinic in Barcelona. An appointment was offered to them after 10-14 days of treatment to inquire about the reaction with the use of a standardized form. Treponema pallidum molecular typing was made to detect a possible strain related to reaction. RESULTS: Overall, 28% of patients developed JHR. This varied from 56% in secondary, 37% in primary to 7% in early latent syphilis. The most frequent types of reaction were fever (57.5%) and worsening of the lesions (31%). The median time to development of JHR was 6 h [IQR 4-10 h] and lasted a median of 9 h [IQR 4-24 h]. The JHR was less probable in early latent compared to primary/secondary syphilis (P = 0.04) and in patients treated with doxycycline compared to those treated with penicillin (P = 0.01). No differences were seen regarding reagin titres or HIV status, and no association with a specific strain was found. CONCLUSIONS: In this study, JHR occurred in a similar frequency as in other contemporary studies. Symptomatic syphilis and treatment with penicillin were associated with an increased risk of JHR, whereas the previous episode of syphilis was associated with a low risk of it. We could not find associations with specific strains of T. pallidum.

Infectious encephalitis: utility of a rational approach to aetiological diagnosis in daily clinical practice.

In this study we attempt to assess the utility of a simplified step-wise diagnostic algorithm to determinate the aetiology of encephalitis in daily clinical practice and to describe the main causes in our setting. This was a prospective cohort study of all consecutive cases of encephalitis in adult patients diagnosed between January 2010 and March 2015 at the University Hospital Vall d'Hebron in Barcelona, Spain. The aetiological study was carried out following the proposed step-wise algorithm. The proportion of aetiological diagnoses achieved in each step was analysed. Data from 97 patients with encephalitis were assessed. Following a simplified step-wise algorithm, a definite diagnosis was made in the first step in 53 patients (55 %) and in 12 additional cases (12 %) in the second step. Overall, a definite or probable aetiological diagnosis was achieved in 78 % of the cases. Herpes virus, L. monocytogenes and M. tuberculosis were the leading causative agents demonstrated, whereas less frequent aetiologies were observed, mainly in immunosuppressed patients. The overall related mortality was 13.4 %. According to our experience, the leading and treatable causes of encephalitis can be identified in a first diagnostic step with limited microbiological studies. L. monocytogenes treatment should be considered on arrival in some patients. Additional diagnostic effort should be made in immunosuppressed patients.

Circulation of a novel human respiratory syncytial virus Group B genotype during the 2014-2015 season in Catalonia (Spain).

Human respiratory syncytial virus (HRSV) is one of the most common viral aetiological agents in the youngest population. In the present study a novel HRSV-B BA genotype is first described based on the phylogenetic analysis of the coding hypervariable region 2 sequences of G protein from strains detected during the 2014-2015 season. Among all strains detected in the last season, 44% belonged to this new genotype. Therefore, it highlights the importance of a continuous HRSV surveillance to monitor the emergence and spread of new genotypes or variants with genetic changes that may affect antigenic and tropism features.

Multicenter study of epidemiological cutoff values and detection of resistance in Candida spp. to anidulafungin, caspofungin, and micafungin using the Sensititre YeastOne colorimetric method.

Neither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established for Candida spp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable. Candida species wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007 Candida albicans, 186 C. dubliniensis, 3,188 C. glabrata complex, 119 C. guilliermondii, 493 C. krusei, 205 C. lusitaniae, 3,136 C. parapsilosis complex, and 1,016 C. tropicalis isolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing ≥97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 µg/ml for C. albicans, 0.12, 0.25, and 0.03 µg/ml for C. glabrata complex, 4, 2, and 4 µg/ml for C. parapsilosis complex, 0.5, 0.25, and 0.06 µg/ml for C. tropicalis, 0.25, 1, and 0.25 µg/ml for C. krusei, 0.25, 1, and 0.12 µg/ml for C. lusitaniae, 4, 2, and 2 µg/ml for C. guilliermondii, and 0.25, 0.25, and 0.12 µg/ml for C. dubliniensis. Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81 Candida isolates with identified fks mutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities of Candida spp. to caspofungin by reference methodologies is not recommended.

Plan de formación y docencia en un centro integral de cáncer: estrategia e implementación / Continuing education and teaching plans in a comprehensive cancer centre: strategy and implementation

Introducción. El Institut Català d’Oncologia (ICO) puso en marcha la Unidad de Formación y Docencia (UFiD), en el año2006, con el objetivo de potenciar el desarrollo profesional, la difusión del conocimiento y la calidad de la atención oncológica. En el presente artículo se describe el proceso de puesta en marcha de la UFiD, los resultados del estudio de las necesidades formativas realizada por los profesionales y colectivos de la institución, las acciones formativas organizadas, y en el área de docencia, los resultados de la reorganización de las trayectorias docentes de los diferentes servicios, así como el apoyo de nuevas iniciativas. Materiales y métodos. Durante el periodo 2008-2009, se implantaron acciones formativas y docentes en concordancia con los resultados del estudio de necesidades y con las líneas estratégicas de la institución. Se realizaron un total de 71actividades formativas, con 898 participantes de todas las categorías profesionales, con una tasa de satisfacción de los participantes de 7,8 sobre 10. En el apartado de docencia, durante el mismo periodo se realizaron 3 másteres, 3 posgrados,59 cursos de actualización con metodología semipresencial y 19 cursos con metodología online, todos ellos con acreditación académica. La satisfacción media fue de 8 sobre 10.Resultados y conclusiones. La actividad llevada a cabo por la UFiD ha permitido, por una parte, articular la formación continuada en base al estudio de las necesidades de los profesionales, lo que ha contribuido a promover el desarrollo profesional y la calidad asistencial de éstos, y por otra parte, dar soporte a las actividades docentes ya existentes y promover nuevas iniciativas para favorecer la difusión de conocimientos en el área oncológica, lo que ha posicionado al ICO como un centro absolutamente comprometido con la formación oncológica (AU)

Introduction. The Oncology Catalonian Institute (ICO) launched the training and education unit (UFiD) in 2006, in order to enhance professional development, dissemination of knowledge and quality of the oncology care. Here are described the tune-up of this process and the results of the training needs survey carried out among the professionals and collectives of the centre. Materials and methods. Training and educational actions deployed during 2008 and 2009 and its evaluation results are presented. A total of 60 training activities were carried out in which 719 students of all professional categories participated, and with a score of participant’s satisfaction of 7.8 out of 10. In the area of education, the paths of the different services were reorganized and new initiatives were supported. A total of 3 masters, 3 post-graduate degrees, 59 update courses with semi-presential (blended learning) methodology and 19 on-line methodology courses, all of them with academicaccreditation were imparted with a satisfaction average score of 8 out of 10.Results and conclusions. The activity carried out by the UFiD during this period, has made possible to articulate the continuing training based on the study of the professionals needs. This has allowed promoting the professional development and the quality of the care. Supporting existing training activities and promoting new initiatives encourage the dissemination of knowledge in the area of oncology and has positioned us as a centre committed to oncology training (AU)

Nationwide sentinel surveillance of bloodstream Candida infections in 40 tertiary care hospitals in Spain.

Candidemia studies have documented geographic differences in rates and epidemiology, underscoring the need for surveillance to monitor trends. We conducted prospective candidemia surveillance in Spain to assess the incidence, species distribution, frequency of antifungal resistance, and risk factors for acquiring a Candida infection. Prospective laboratory-based surveillance was conducted from June 2008 to June 2009 in 40 medical centers located around the country. A case of candidemia was defined as the isolation of a Candida species from a blood culture. Incidence rates were calculated per 1,000 admissions. Antifungal susceptibility tests were performed by using broth microdilution assay according to the guidelines of the Clinical and Laboratory Standards Institute. We detected 984 cases, for an overall incidence of 1.09 cases per 1,000 admissions. The crude mortality was 20.20%. Candida albicans was the most common species (49.08%), followed by C. parapsilosis (20.73%), C. glabrata (13.61%), and C. tropicalis (10.77%). Overall, decreased susceptibility to fluconazole occurred in 69 (7.01%) incident isolates. Antifungal resistance was rare, and a moderate linear correlation between fluconazole and voriconazole MICs was observed. This is the largest multicenter candidemia study conducted to date and shows the substantial morbidity and mortality of candidemia in Spain.

Alineación del rediseño de procesos con las estrategias de Sistemas de Información / Alignment of process re-design with Information System strategies

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La reorganización de recursos para atender la sobredemanda de ingresos hospitalarios en invierno / The reorganization of resources to fulfill the over-demand of hospital admissions in the winter

Objetivos del estudio: absorber un mínimo de 700 ingresos de sobredemanda invernal, mantener un número de ingresos ubicados fuera de su servicio de referencia inferior o igual al 2 por ciento del número total de ingresos diarios, contribuir a disminuir la saturación de urgencias manteniendo unos tiempos de preingreso < 6 horas. Material y método: la intervención realizada ha sido la redistribución de recursos dedicando 30 camas de medicina interna a dar apoyo a urgencias, junto con tres médicos internistas centrados en la gestión de dicha sala; simultáneamente se controló los circuitos de dichas camas mediante criterios explícitos. El estudio se realizó de manera prospectiva con una duración total de 120 días. Se recogieron las características de los pacientes y la práctica médica. Resultados: se realizaron 701 ingresos, con una edad media de 72 ñ 16 años; su media de estancia fue 4,22 ñ 2,9 días vs 9,8 ñ 4,2 días en las camas normales, con un índice de rotación de 5,8 enf./cama vs 3,8 enf./cama de las citadas camas normales; durante el 72 por ciento del período de estudio sólo se produjo un 2 por ciento de ingresos fuera de los servicios adecuados a la patología del paciente; los tiempos de espera preingresos fueron de 11,5 h, y sólo un 34,3 por ciento de los ingresos esperaron < 6 h. Comentario: las camas de apoyo a urgencias permitieron absorber la sobredemanda invernal, mejorando la presión sobre los servicios, pero sin mejorar los tiempos de espera preingreso hospitalario (AU)