Infectious complications among patients receiving ibrutinib for the treatment of hematological malignancies.

PURPOSE: Ibrutinib is a Bruton's tyrosine kinase inhibitor used to treat multiple hematologic malignancies and graft-versus-host disease. Though less myelosuppressive than cytotoxic chemotherapy, increased infections, including invasive fungal infections (IFIs), have been reported with ibrutinib use. This study aimed to determine the characteristics and risk factors for infection associated with ibrutinib at our institution. METHODS: Patients who received ibrutinib between June 2014 and August 2019 were included. Primary endpoints were the incidence of any infection and the incidence of serious infection (defined as hospitalization, parenteral antimicrobial therapy, or pneumonia regardless of hospitalization). Infection risk factors were assessed using logistic regression. RESULTS: One hundred thirty-two patients were identified (78% male; median age, 71 years). The most common indications for ibrutinib were chronic lymphocytic leukemia (67%) and mantle cell lymphoma (12%). Infection and serious infection occurred in 94 (71%) and 47 (36%) patients, respectively; when pneumonia was excluded as a criterion for serious infection, the serious infection rate was 27%. The median time from ibrutinib initiation to first infection was 125 days. Prior allogeneic hematopoietic stem cell transplantation (allo-HSCT) (odds ratio [OR], 4.60; 95% CI, 1.22-17.4) and corticosteroid use (OR, 5.55; 95% CI, 1.52-20.3) were significant risk factors for serious infection. IFIs were diagnosed in 7 patients (5%): 5 had Pneumocystis jirovecii pneumonia and 2 were infected with invasive molds. CONCLUSION: Serious infection and IFI rates are high but similar to those previously described. Risk factors for serious infection included allo-HSCT and corticosteroid use. Targeted antimicrobial prophylaxis should be evaluated in prospective studies in patients on ibrutinib to reduce serious infections and IFI.

How I approach diarrhea in hematological transplant patients: A practical tool.

Diarrhea in hematopoietic stem-cell transplantation (HSCT) remains a multifactorial challenge that demands a nuanced diagnostic approach. The causes of infectious diarrhea in HSCT recipients are diverse and influenced by patient-specific risk factors, the post-transplant timeline, and local epidemiology. During the past decade, our understanding of diarrhea in HSCT has witnessed a transformative shift through the incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels. However, the judicious application of these panels is imperative to avoid overtesting and prevent adverse outcomes. The challenge lies in distinguishing between the diverse causes of diarrhea, ascertaining the clinical significance of detected pathogens, and navigating the diagnostic uncertainty presented by several non-infectious conditions such as mucositis, intestinal dysbiosis, and acute graft-versus-host disease (aGvHD), all of which mimic infection. This review examines the landscape of infectious diarrhea in the HSCT population, encompassing both established (e.g., Cytomegalovirus, Clostridioides difficile, and norovirus) and emerging pathogens (e.g., sapoviruses, astroviruses). We propose a multifaceted diagnostic algorithm that combines clinical assessment, risk stratification, and tailored utilization of molecular platforms. While multiplex GI panels present invaluable opportunities for rapid and comprehensive pathogen detection, their judicious use is pivotal in preserving diagnostic stewardship. Customization of diagnostic algorithms tailored to local epidemiology ensures optimal patient care and resource utilization.

Infectious complications following CAR-t cell therapy for B cell non-Hodgkin lymphoma: a single-center experience and review of the literature.

Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed (R/R) B-cell non-Hodgkin lymphoma (NHL). Several risk factors including CAR-T cell-related toxicities and their treatments often lead to infectious complications (ICs); however, the pattern and timeline is not well established. We evaluated ICs in 48 patients with R/R B-cell NHL following CAR-T cell therapy at our institution. Overall, 15 patients experienced 22 infection events. Eight infections (4 bacterial, 3 viral and 1 fungal) occurred within the first 30 days and 14 infections (7 bacterial, 6 viral, 1 fungal) between days 31 to 180 following CAR-T infusion. Most infections were mild-to-moderate and fifteen infections involved the respiratory tract. Two patients developed mild-to-moderate COVID-19 infection and one patient a cytomegalovirus reactivation after CAR-T infusion. Two patients developed IFIs: one case each of fatal disseminated candidiasis and invasive pulmonary aspergillosis at day 16 and 77, respectively. Patients with more than 4 prior antitumor regimens and patient's ≥ 65 years had a higher infection rate. Infections in patients with relapsed/refractory B-cell NHL are common after CAR-T despite the use of infection prophylaxis. Age ≥ 65 years and having > 4 prior antitumor treatments were identified as risk factors for infection. Fungal infections carried significant impact in morbidity and mortality, suggesting a role for increase fungal surveillance and/or anti-mold prophylaxis following high-dose steroids and tocilizumab. Four of ten patients developed an antibody response following two doses of SARS-CoV-2 mRNA vaccine.

Hemofilia A adquirida: un diagnóstico de infarto / Acquired Hemophilia A: a heart attacking diagnosis

Resumen La hemofilia A adquirida es una entidad poco reportada y potencialmente fatal, que se asocia con la aparición de autoanticuerpos contra el factor VIII de la coagulación. Si bien puede estar subestimada, se calcula una incidencia aproximada de 1 a 1.5 casos por millón de habitantes con una mortalidad reportada entre el 9 y el 33%. Se manifiesta con equimosis extensas espontáneas y sangrado en mucosas, tracto gastrointestinal o en el periodo postparto. Se debe sospechar en adultos a partir de la cuarta década de la vida con sangrados espontáneos y un tiempo parcial de tromboplastina prolongado en ausencia de anticoagulante lúpico. Se reporta el caso de un adulto mayor con cardiopatía isquémica, en quien, en el contexto de un evento coronario agudo, se diagnosticó hemofilia A adquirida ante la presencia de sangrado subcutáneo extenso en cuello, con compresión de faringe y laringe que amenazó su vida representando un verdadero reto terapéutico.

Abstract Acquired hemophilia A is an underreported and potentially fatal entity that is associated with the formation of autoantibodies against coagulation factor VIII. Although it may be underestimated, the estimated incidence is between 1-1.5 cases per million people with a reported mortality between 9 and 33%2. It presents with extensive spontaneous ecchymosis, mucosal, gastrointestinal, or postpartum bleeding. It should be suspected in adults from the fourth decade of life with spontaneous bleeding and prolonged TPT in the absence of lupus anticoagulant. We report the case of an older adult with ischemic heart disease in the context of an acute coronary syndrome, who was diagnosed with acquired hemophilia A and presented with significant cervical subcutaneous bleeding with pharyngeal and laryngeal compression that threatened his life, constituting a real therapeutic challenge.

Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective?

Background: Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant. Methods: In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation. Results: Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall. Conclusions: In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.

Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. METHODS: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 µg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475. FINDINGS: Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. INTERPRETATION: Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. FUNDING: The National Institute of Allergy and Infectious Diseases (USA).

Comportamiento clínico-epidemiológico de pacientes con dengue. Estudio comparativo de dos series de casos / Patients with dengue clinical-epidemiological behavior. Comparative study of two case series

RESUMEN Fundamento La enfermedad causada por el virus del dengue constituye un serio problema de salud para los países tropicales. En la última década se ha asistido a la reemergencia de esta entidad en Cuba, con evidentes cambios en su comportamiento clínico. Objetivo comparar el comportamiento clínico-epidemiológico entre dos series de casos de pacientes con diagnóstico confirmado de dengue, en períodos de tiempo diferentes. Métodos: estudio descriptivo, comparativo, que incluyó a dos series de casos de pacientes hospitalizados con diagnóstico confirmado de dengue: la serie A, con una muestra de 83 pacientes atendidos en 2017; y la serie B, con muestra de 327 atendidos en 2018. Se analizaron variables como: edad, signos y síntomas, hallazgos clínicos, signos de alarma, formas graves e indicadores de calidad de atención en pacientes con dengue. Resultados en general, predominó el síndrome febril agudo, aunque otros signos y síntomas como la astenia, anorexia, rash y dolor retro-ocular, manifestaron mayor incidencia en la serie B. En ambos grupos el hallazgo paraclínico más frecuente fue la linfocitosis. En la serie B los estándares de calidad para la atención a pacientes con dengue se vieron más afectados; así como también presentó mayor tasa de signos de alarma, formas graves y complicaciones. Conclusión Aunque el estudio analizó series de pacientes en dos períodos consecutivos, fue evidente el comportamiento más complejo en la segunda, dado por la mayor incidencia de síntomas, y por cifras menos favorables de los estándares de calidad establecidos para la enfermedad.

ABSTRACT Background The disease caused by the dengue virus constitutes a serious health problem for tropical countries. The last decade has seen the re-emergence of this entity in Cuba, with evident changes in its clinical behavior. Objective to compare the clinical-epidemiological behavior between two series of cases of patients with dengue confirmed diagnosis, in different periods of time. Methods a descriptive, comparative study that included two series of cases of hospitalized patients with dengue confirmed diagnosis: series A, sample of 83 patients seen in 2017; and series B, sample of 327 seen in 2018. Variables such as: age, signs and symptoms, clinical findings, alarm signs, severe forms, and indicators of quality of care in dengue patients were analyzed. Results in general, the acute febrile syndrome predominated, although other signs and symptoms such as asthenia, anorexia, rash and retro-ocular pain, manifested a higher incidence in series B. In both groups the most frequent paraclinical finding was lymphocytosis. In series B, the quality standards for the care of patients with dengue were more affected; as well as it also presented a higher rate of alarm signs, serious forms and complications. Conclusions Although the study analyzed series of patients in two consecutive periods, the more complex behavior was evident in the second, due to the higher incidence of symptoms and less favorable figures for the quality standards established for the disease.

Real-Time Handheld Probe Tracking and Image Formation Using Digital Frequency-Domain Diffuse Optical Spectroscopy.

OBJECTIVE: Frequency-domain diffuse optical spectroscopic imaging (FD-DOS) is a non-invasive method for measuring absolute concentrations of tissue chromophores such as oxy- and deoxy-hemoglobin in vivo. The utility of FD-DOS for clinical applications such as monitoring chemotherapy response in breast cancer has previously been demonstrated, but challenges for further clinical translation, such as slow acquisition speed and lack of user feedback, remain. Here, we propose a new high speed FD-DOS instrument that allows users to freely acquire measurements over the tissue surface, and is capable of rapidly imaging large volumes of tissue. METHODS: We utilize 3D monocular probe tracking combined with custom digital FD-DOS hardware and a high-speed data processing pipeline for the instrument. Results are displayed during scanning over the surface of the sample using a probabilistic Monte Carlo light propagation model. RESULTS: We show this instrument can measure absorption and scattering coefficients with an error of 7% and 1% respectively, with 0.7 mm positional accuracy. We demonstrate the equivalence of our visualization methodology with a standard interpolation approach, and demonstrate two proof-of-concept in vivo results showing superficial vasculature in the human forearm and surface contrast in a healthy human breast. CONCLUSION: Our new FD-DOS system is able to compute chromophore concentrations in real-time (1.5 Hz) in vivo. SIGNIFICANCE: This method has the potential to improve the quality of FD-DOS image scans while reducing measurement times for a variety of clinical applications.

Conceptualización para la formulación del diagnóstico fisioterapéutico en comunidad / Conceptual bases for the formulation of the Physiotherapeutic diagnosis in the community

RESUMEN Objetivo Proponer una base conceptual que soporte la estructura de diagnóstico en comunidad a partir de la fisioterapia, específicamente, desde una revisión de documentos sobre abordajes comunitarios en la profesión. Método Se realizó una investigación descriptiva documental. Por la especificidad de los conceptos, se realizó una búsqueda abierta en Google Académico mediante una lectura cuidadosa de los documentos con adecuada calidad metodológica y conceptual de información proveniente de investigaciones previas y documentos disciplinares disponibles en la web y en registros impresos. Resultados La realización de un diagnóstico fisioterapéutico en comunidad involucra aspectos multidimensionales y necesariamente multiprofesionales. Es imprescindible un análisis conjunto de problemas y necesidades tal como los manifiestan los involucrados, la identificación de los recursos disponibles más allá de lo económico (diferenciando aquellos que pueden ser extraídos de la comunidad, como aquellos que deben ser gestionados para su acceso) y los ejes de articulación con las demás profesiones, de modo que sean claros aquellos objetivos que se logran por más de un profesional. Asimismo, es importante vincular los objetos de estudio. No se busca limitar las profesiones; por el contrario, se quiere encontrar cómo se conjugan los saberes para la resolución de la problemática. Conclusiones Este documento identificó elementos conceptuales estructurales para realizar diagnóstico fisioterapéutico en comunidad. Reconoció, además, la necesidad de abordajes interdisciplinarios diferenciados por los objetos de estudio de cada profesión, que pueden ser realizados conjuntamente desde diferentes áreas de conocimiento.

ABSTRACT Objective To propose the conceptual basis that supports a structure of a community diagnosis in physiotherapy from a review of documents about community approaches in the profession. Method A descriptive literature review was made of professional documents available on the web and in printed records. Due to the specificity of the concepts to be searched, an open search was made in Google academic, making a careful reading of the documents with methodological quality and adequate conceptual information. Results The development of a physiotherapeutic diagnosis in community involves multidimensional and necessarily multiprofessional aspects. It is imperative a combined analysis of problems and needs as expressed by those involved, as well as the identification of resources available beyond the economic; differentiating both resources those that can be extracted from the community, and those to be managed; and the articulation with other professions. Conclusion This document identified the conceptual elements that can be considered structural to perform a physiotherapist diagnosis in community. He also recognized the need for interdisciplinary approaches differentiated by the objects of study of each profession, and those actions that can be carried by different areas of knowledge.

Cut it out! Thoracic surgeon's approach to pulmonary mucormycosis and the role of surgical resection in survival.

BACKGROUND: Mucormycosis portends a poor prognosis with mortality rates ranging from 50% to 70% in pulmonary mucormycosis (PM) and up to 95% in disseminated disease. However, detailed outcomes data have been lacking. It remains unknown how to identify patients who would benefit from surgical resection. OBJECTIVES: We present our experience with patients undergoing surgical resection for PM, including an analysis of factors affecting postoperative survival. We also describe a thoracic surgeon's approach through illustrative cases. PATIENTS/METHODS: We conducted a single-centre retrospective study of all adult patients with PM who received antifungal therapy and underwent surgical resection or who received antifungal therapy alone at Stanford between January 2004 and June 2018. RESULTS: Twelve patients received antifungal therapy and underwent surgical resection and 13 patients received antifungal therapy alone. From infection onset to death (or right-censoring if still alive), patients who underwent surgical resection had a median survival of 406 days (mean, 561.3; range, 22-2510), and patients who received antifungal therapy alone had a median survival of 28 days (mean, 66.7; range, 8-447). In patients who underwent surgical resection, median postoperative survival time was 154 days (range, 11-2495), in-hospital mortality was 16.7%, and 1-year mortality was 50.0%. Age, primary disease, ASA status, extrapulmonary dissemination, laterality, multilobar involvement, number of lesions, largest lesion size, platelet count, surgical approach, type of resection or extent of resection were not significantly associated with postoperative survival. CONCLUSIONS: Surgical resection significantly increases survival and should be strongly considered for selected patients with PM.

Eremothecium coryli bloodstream infection in a patient with acute myeloid leukemia: first case report of human infection.

Eremothecium coryli is a dimorphic fungus of the Saccharomycetes class. While species within this class are known to cause human infection, Eremothecium species have previously only been known as phytopathogens and never been isolated from a human sample. Here, we report the first known case of human E. coryli infection.

Prevention of infectious diseases in patients with Good syndrome.

PURPOSE OF REVIEW: Good syndrome is a profoundly immunocompromising condition with heterogeneous immune deficits characterized by the presence of thymoma, low-to-absent B-lymphocyte counts, hypogammaglobulinemia, and impaired cell-mediated immunity. Opportunistic infectious diseases associated with Good syndrome represent a diagnostic and therapeutic challenge, given their protean clinical manifestations. Although these infectious complications have been reviewed in prior publications, recommendations regarding their prevention have been lacking. RECENT FINDINGS: Good syndrome usually occurs in adult patients between the ages of 40 and 70 years. Immunologically, it is characterized by low or absent peripheral blood B lymphocytes, hypogammaglobulinemia, and variable defects in cell-mediated immunity including low CD4 T counts, inverted CD4:CD8 T-lymphocyte ratio, and reduced T-lymphocyte mitogen proliferative responses. Patients with Good syndrome are susceptible to a variety of infectious diseases, of which the most common are recurrent bacterial sinopulmonary infections, mucocutaneous candidiasis, and CMV tissue-invasive disease. Preventive guidelines including targeted antimicrobial prophylaxis and vaccination strategies can mitigate infectious complications in patients with Good syndrome. SUMMARY: Immunological deficits and infectious complications in Good syndrome have been described for over 60 years. Further research is needed to elucidate its exact pathogenesis and define the mechanistic relationship between thymoma and hypogammaglobulinemia. However, tailored prophylactic strategies can be recommended for patients with Good syndrome.

Phenolic content analysis of coffee leaves subjected to htst and convective drying / Análisis del contenido fenólico de hojas de café sujetas a secado htst y convectivo

SUMMARY As a potential beverage, coffee leaf tea may possess both qualities of brewed coffee and regular tea. Thus, making it an attractive beverage in years to come. One of the main qualities is the leaf's phenolic content, which is chiefly attributed with health benefits. However, the leaf's total phenolic content may be adversely affected by heat during the drying process. Coffee leaves were dried using a combined drying process, high-temperature short-time (HTST) and convective drying, to assess the optimal drying parameters for both total phenolic content preservation and drying time reduction. To reach conclusions, a central composite rotational design (CCRD) was employed. With both temperature and thickness as independent variables, a response surface using time as dependent variable was generated. The temperature ranged from 80°C to 110°C and the thickness from 1cm to 3cm. Results indicate that the HTST pretreatment significantly reduced the drying time without affecting the total phenolic content; that is, the CCRD analysis on the effect of the HTST pretreatment on the total phenolic content did not yield statistically significant results.

RESUMEN Como bebida potencial, el té de hojas de café posee cualidades, tanto de café preparado como de té regular, por lo tanto, será una bebida interesante en los próximos años. Una de las principales cualidades es el contenido fenólico de las hojas, a lo cual, se atribuyen beneficios sobre la salud; sin embargo, el contenido fenólico total (TPC), se puede ver afectado negativamente por el calor, durante el proceso de secado. Hojas de café fueron secadas usando un proceso de secado combinado, tiempo corto y alta temperatura (HTST) y secado convectivo, para establecer los parámetros óptimos de secado, tanto para la preservación del TPC como para la reducción del tiempo de secado. Para obtener conclusiones, un diseño de experimentos rotacional central compuesto (CCRD) fue aplicado. Usando como variables independientes la temperatura y el espesor, se generó una superficie de respuesta, empleando el tiempo, como variable dependiente. El rango de temperatura usado fue entre 80 y 110 y de espesor, entre 1 y 3cm. Los resultados indican que el pretratamiento de HTST redujo significativamente el tiempo de secado, sin afectar el TPC, es decir, el análisis del CCRD sobre el efecto del pretratamiento del HTST en el TPC no obtuvo resultados estadísticamente significativos.

Performance of Targeted Fungal Sequencing for Culture-Independent Diagnosis of Invasive Fungal Disease.

BACKGROUND: Identification of fungi causing invasive fungal disease (IFD) is critical for guiding antifungal therapy. We describe the performance and clinical impact of a targeted panfungal polymerase chain reaction (PCR) amplicon sequencing assay for culture-independent diagnosis of IFD. METHODS: Between January 2009 and September 2016, 233 specimens, consisting of fresh and formalin-fixed, paraffin-embedded (FFPE) tissues and sterile body fluids with known diagnosis of IFD based on reference method results (n = 117), and specimens with negative fungal culture, but with microscopic and ancillary findings indicative of IFD (n = 116), were included. PCR amplicons from the internal transcribed spacer 2 and the D2 region of 28S ribosomal RNA gene were sequenced and fungi identified. RESULTS: Sensitivity and specificity of fungal sequencing in specimens with known diagnosis were 96.6% (95% confidence interval [CI], 87.4%-99.4%; 58/60) and 98.2% (95% CI, 89.4%-99.9%; 56/57). In patients with suspected IFD, the diagnostic yield of fungal sequencing was 62.9% (73/116) overall and 71.3% (57/80) in patients classified with proven IFD based on the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and Mycoses Study Group (EORTC/MSG) criteria. Samples obtained by open biopsy had a significantly higher diagnostic yield (71.5% [40/56]) compared with core-needle biopsy (50% [17/34] P = .04) and fine needle aspiration (0% [0/2]; P = .009). Additionally, D2 sequencing diagnosed 5 cases of invasive protozoal infections due to Toxoplasma gondii (n = 3), Trypanosoma cruzi, and Leishmania species. Sequencing results altered patient management in the majority of suspected cases. CONCLUSIONS: The targeted fungal sequencing assay allowed accurate identification of fungi causing IFD and additionally provided partial-protozoal coverage. The diagnostic yield was dependent on the amount of tissue available for testing.

Factores asociados a nefrotoxicidad por polimixina B en un hospital universitario de Neiva, Colombia. 2011-2015 / Risk factors for acute kidney injury in patients treated with polymyxin B experience from 139 cases at a tertiary university hospital in Colombia

Background: The rise of infections caused by multidrug-resistant Gram negative bacilli (MDR-GNB), added to paucity of newer therapy, have led to increase polymyxin B use, despite adverse renal toxicity profile. Aim: To determine the incidence and risk factors associated to acute kidney injury (AKI) and polymyxin B use, in patients with infections caused by MDR-GNB. Methods: A retrospective cohort, with a nested case-control study of adults who received polymyxin B for more than 48 hours at a tertiary university hospital in Colombia (2011-2015) was performed. AKI was defined by AKIN criteria. Results: Of 139 patients included in our study, 102 were male with median age of 49 years (IQR:28-64). Sixty-one patients (44%) developed AKI. Independent risk factors for development of AKI included: total polymyxin B daily dose (OR = 2.19, 95% CI, 1.04-4.64); length of stay at ICU (OR = 1.03, 95% CI, 1.00-1.06); nosocomial infection (OR = 6.43, 95% CI, 2.12, -19.47); and vasopressor use (OR = 5.38, 95% CI, 2.40-12.07). Mortality was higher among AKI-patients (58.6%) compared with non-AKI patients (25.6%) (p = 0.001). Conclusion: In this study, the rate of AKI associated to polymyxin B use was greater than reported in studies from last decade, and associated with increased mortality. AKI associated to polymyxin B use is likely multifactorial and aggravated by the critically ill state of patients suffering nosocomial infections caused by mdr-gnb.

Introducción: El surgimiento de infecciones graves causadas por bacilos gramnegativos multi-resistentes (BGN-MR), sumado a la carencia de nuevas opciones terapéuticas efectivas, ha llevado a retomar el uso de polimixina B, a pesar de su perfil de nefrotoxicidad. Objetivo: Determinar la incidencia y factores relacionados con el desarrollo de nefrotoxicidad asociada al uso de polimixina B, en pacientes adultos con infecciones causadas por BGN-MR. Materiales y Métodos: Estudio observacional, analítico, tipo cohorte histórica, con un análisis de casos y controles anidado, realizado en un hospital universitario de tercer nivel de Colombia entre 2011 y 2015, en pacientes que recibieron polimixina B intravenosa por más de 48 h. Resultados: De 139 pacientes incluidos en el estudio, 61 (44%) desarrollaron falla renal aguda por criterios AKIN. Los factores de riesgo independientes para nefrotoxicidad fueron: dosis diaria de polimixina B (OR 2,19; IC 95% 1,04-4,64), días de estancia en UCI (OR 1,03; IC 95% 1,00-1,06), presencia de infección nosocomial (OR 6,43; IC 95% 2,12-19,47) y requerimiento de fármacos vasopresores (OR 5,38; IC 95%: 2,40-12,07). Conclusión: La tasa de nefrotoxicidad observada en pacientes que recibieron polimixina B es considerable; su origen probablemente multifactorial y agravada por estado crítico de pacientes con infecciones nosocomiales por BGN-MR.

Actualización del reporte de biopsiapor aspiración con aguja fina de mama / Report of breast fine needle aspiration biopsy: an update

Las recomendaciones para la biopsia por aspiración con aguja fina de mama se desarrollaron y aprobaron en 1997 por el Instituto Nacional de Cáncer en Bethesda, Estados Unidos y fueron adaptadas a nuestro país en 2007, sin embargo, en los últimos años no se han realizado cambios formales en estas indicaciones. El objetivo de este módulo es presentar la actualización del reporte de biopsia por aspiración con aguja fina de mama, usando el sistema de reporte Bethesda, realizado por consenso con un grupo de patólogos, clínicos, radiólogos, cirujanos de mama y otros profesionales de la salud de Colombia y otros países, y con base en la experiencia realizando biopsia por aspiración con aguja fina de mama del Hospital Pablo Tobón Uribe y de Dinámica IPS.

Recommendations for breast fine needle aspiration biopsy were developed and approved in 1997 by The National Cancer Institute of Bethesda, United States, , and were adapted to our country on 2007, however, in last years these indications have not changed in a formal manner. The purpose of this review was to provide an update of the report for breast fine needle aspiration biopsy using the Bethesda system. This guide was made by consensus with pathologists, clinicians, radiologists, breast surgeons and other health professionals of Colombia and other countries. The update was basis on the experience of Hospital Pablo Tobon Uribe and Dinamica IPS in performing breast fine needle aspiration biopsy.

Implementación de un manojo de medidas (bundle) de inserción para prevenir la infección del torrente sanguíneo asociada a dispositivo intravascular central en Cuidado Intensivo en Colombia / Implementation of an insertion bundle for preventing central line-associated bloodstream infections in an Intensive Care Unit in Colombia

Central line-associated bloodstream infections (CLABSI) related to insertion and device care in intensive care units are frequent and preventable events. Aim: To evaluate the reduction in the rate of CLABSI through implementation of an insertion bundle. Methods: A study was conducted in the Adult-ICU at the University Hospital of Neiva comparing a pre-interventional period with an interventional one, each lasting 6 months; the intervention consisting of implementing a bundle of measures for the insertion of central venous catheters (CVC). In the pre-intervention period (2010) the rate of CLABSI and the population's characteristics were evaluated. The bundle for the insertion of the CVC consisted in: hands hygiene, use of 2% clorhexidine, maximum sterile barriers and avoiding femoral access. Results: The rate of CLABSI decreased from 5.56 to 3.26 per 1000 catheter days. The length of ICU stay and catheter duration were associated with a higher risk of infection associated to these devices (p < 0.05). Compliance with the bundle is a protective factor against the development of CLABSI (OR 0.45, p = 0.615). The staff adherence to the bundle was over 80%. Conclusion: Implementing a Central Line Insertion Bundle proved to be a useful measure in prevention of CLABSI in our hospital. This strategy could be implemented in other hospitals of similar complexity.

Las infecciones asociadas a la instalación y manejo de catéteres venosos centrales (CVC) son eventos frecuentes en unidades de cuidados intensivos pero evitables. Objetivo: Evaluar la eficacia en disminuir la tasa de infección asociada a catéter (IACVC) obtenida con la implementación de un manojo de medidas (bundle) durante la inserción del dispositivo. Material y Métodos: Se condujo un estudio que compara un período pre-intervención con uno de intervención, de 6 meses cada uno, consistente en la implementación de un manojo de medidas para la inserción de catéter venoso central (CVC), en la Unidad de Cuidado Intensivo (UCI) del Hospital Universitario de Neiva, Colombia. En el período pre-intervención (2010) se evaluó la tasa de IACVC y las características de la población. Durante la intervención (2011) se implementó un manojo de medidas para la inserción de CVC que consistió en: higiene de manos, uso de clorhexidina 2%, empleo de máximas barreras estériles y evitar el acceso femoral. Resultados: Se obtuvo reducción de la tasa de IACVC de 5,56 a 3,26 X 1.000 días CVC. Los días de estancia en UCI y de exposición al CVC se asociaron a mayor riesgo de desarrollar IACVC (p < 0,05); el cumplimiento del manojo de medidas fue un factor protector contra IACVC (OR 0,45; p = 0,615). La adherencia del personal al manojo de medidas fue mayor de 80%. Conclusión: La implementación de un manojo de medidas para la inserción de CVC resultó ser una medida útil para la prevención de IACVC en nuestro hospital, lo que podría implementarse en otras instituciones hospitalarias de complejidad similar.

Febrile neutropenia in the tropics: a description of clinical and microbiological findings and their impact on inappropriate therapy currently used at an oncological reference center in Colombia.

INTRODUCTION: Febrile neutropenia is a common complication of chemotherapy treatment of malignant hematological diseases. However, there is insufficient information regarding the infectious complications of febrile neutropenia in our country. Objective. We will evaluate the microbial characteristics of bacterial and fungal isolates and the clinical outcome of patients with febrile neutropenia who received medical attention at an oncological reference center in Colombia. MATERIALS AND METHODS: A prospective case series included patients with histologically confirmed oncological disease, who were admitted because of febrile neutropenia or presented with febrile neutropenia during hospitalization. Patients with benign hematological diseases were excluded. Demographic, microbiological, and clinical features as well as treatment and outcome information from patients with febrile neutropenia were obtained. We performed univariate and multivariate analyses, with mortality defined as the outcome. RESULTS: One hundred and thirty episodes of febrile neutropenia were identified in 104 patients. The mean patient age was 19, and 53% of the patients were male. Approximately 86% of the episodes occurred in patients with hematological disorders. An infectious site was identified in 65% of patients; 41% and 24% of the febrile neutropenia pateints´ episodes exhibited a localized infectious focus and developed bloodstream infections, respectively. The majority of infections were found in blood, urine, gastrointestinal tract, and soft tissue. Distribution analysis of microbiological isolates revealed 46.4% Gram-negative bacilli, 38.4% Gram-positive cocci, 8% fungi, and 7.1% parasites; there was a 7.7% mortality rate. Appropriate empirical antimicrobial therapy was a protection-related factor in multivariate analyses (OR= 0.17; 0.034 - 0.9 95% CI; p= 0.037). CONCLUSIONS: The mortality rate was relatively low and comparable to the rate reported by developed countries. Inappropriate empirical antimicrobial therapy was the main factor associated with mortality.