Post-CART-T Cell Infection: Etiology, pathogenesis, and therapeutic approaches.

Chimeric antigen receptor (CAR) T cell therapy targeting CD-19 has revolutionized the treatment of refractory B-cell malignancies. However, patients undergoing this therapy face an increased risk of infections due to compromised immune function, lymphodepleting chemotherapy, hospitalization, and therapy-related complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome. Patients with systemic corticosteroid use, low immunoglobulin levels, and severe CRS, are at higher risk of infection. This review article highlights the spectrum of infections encountered in CAR T cell therapy, including bacterial, viral, and fungal infections. Following consensus guidelines for vaccination and immunoglobulin replacement is recommended. Clear criteria for antibiotic usage and vaccinating household members against respiratory viruses are crucial. Understanding the risk factors, spectrum of infections, and implementing appropriate prophylactic measures are essential to optimize outcomes in patients undergoing CAR T cell therapy. By prioritizing infection prevention strategies, healthcare professionals can effectively improve patient care.

Identifying the most important data for research in the field of infectious diseases: thinking on the basis of artificial intelligence.

OBJECTIVE: Clinical data on which artificial intelligence (AI) algorithms are trained and tested provide the basis to improve diagnosis or treatment of infectious diseases (ID). We aimed to identify important data for ID research to prioritise efforts being undertaken in AI programmes. METHODS: We searched for 1,000 articlesfrom high-impact ID journals on PubMed, selecting 288 of the latest articles from 10 top journals. We classified them into structured or unstructured data. Variables were homogenised and grouped into the following categories: epidemiology, admission, demographics, comorbidities, clinical manifestations, laboratory, microbiology, other diagnoses, treatment, outcomes and other non-categorizable variables. RESULTS: 4,488 individual variables were collected, from the 288 articles. 3,670 (81.8%) variables were classified as structured data whilst 818 (18.2%) as unstructured data. From the structured data, 2,319 (63.2%) variables were classified as direct-retrievable from electronic health records-whilst 1,351 (36.8%) were indirect. The most frequent unstructured data were related to clinical manifestations and were repeated across articles. Data on demographics, comorbidities and microbiology constituted the most frequent group of variables. CONCLUSIONS: This article identified that structured variables have comprised the most important data in research to generate knowledge in the field of ID. Extracting these data should be a priority when a medical centre intends to start an AI programme for ID. We also documented that the most important unstructured data in this field are those related to clinical manifestations. Such data could easily undergo some structuring with the use of semi-structured medical records focusing on a few symptoms.

COVID-19 and fungal infections: Etiopathogenesis and therapeutic implications.

Invasive fungal infection often complicates patients with severe viral infection, especially those admitted to critical care units. Severe SARS-CoV-2 infection has been no exception and a significant association with Aspergillus spp. has been documented, resulting in high patient mortality. In this summary we describe the clinical presentation, the underlying diseases most commonly linked with this association, radiological manifestations and therapeutic management of CAPA.

Experience with the use of siltuximab in patients with SARS-CoV-2 infection.

OBJECTIVE: The study aims to describe characteristics and clinical outcome of patients with SARS-CoV-2 infection that received siltuximab according to a protocol that aimed to early block the activity of IL-6 to avoid the progression of the inflammatory flare. METHODS: Retrospective review of the first 31 patients with SARS-CoV-2 treated with siltuximab, in Hospital Clinic of Barcelona or Hospital Universitario Salamanca, from March to April 2020 with positive polymerase-chain reaction (PCR) from a nasopharyngeal swab. RESULTS: The cohort included 31 cases that received siltuximab with a median (IQR) age of 62 (56-71) and 71% were males. The most frequent comorbidity was hypertension (48%). The median dose of siltuximab was 800 mg ranging between 785 and 900 mg. 7 patients received siltuximab as a salvage therapy after one dose of tocilizumab. At the end of the study, a total of 26 (83.9) patients had been discharged alive and the mortality rate was 16.1% but only 1 out of 24 that received siltuximab as a first line option (4%). CONCLUSIONS: Siltuximab is a well-tolerated alternative to tocilizumab when administered as a first line option in patients with COVID-19 pneumonia within the first 10 days from symptoms onset and high C-reactive protein.

Tocilizumab reduces the risk of ICU admission and mortality in patients with SARS-CoV-2 infection.

OBJECTIVE: In some patients the immune response triggered by SARS-CoV-2 is unbalanced, presenting an acute respiratory distress syndrome which in many cases requires intensive care unit (ICU) admission. The limitation of ICU beds has been one of the major burdens in the management around the world; therefore, clinical strategies to avoid ICU admission are needed. We aimed to describe the influence of tocilizumab on the need of transfer to ICU or death in non-critically ill patients. METHODS: A retrospective study of 171 patients with SARS-CoV-2 infection that did not qualify as requiring transfer to ICU during the first 24h after admission to a conventional ward, were included. The criteria to receive tocilizumab was radiological impairment, oxygen demand or an increasing of inflammatory parameters, however, the ultimate decision was left to the attending physician judgement. The primary outcome was the need of ICU admission or death whichever came first. RESULTS: A total of 77 patients received tocilizumab and 94 did not. The tocilizumab group had less ICU admissions (10.3% vs. 27.6%, P=0.005) and need of invasive ventilation (0 vs 13.8%, P=0.001). In the multivariable analysis, tocilizumab remained as a protective variable (OR: 0.03, CI 95%: 0.007-0.1, P=0.0001) of ICU admission or death. CONCLUSIONS: Tocilizumab in early stages of the inflammatory flare could reduce an important number of ICU admissions and mechanical ventilation. The mortality rate of 10.3% among patients receiving tocilizumab appears to be lower than other reports. This is a non-randomized study and the results should be interpreted with caution.

Real-life use of remdesivir in hospitalized patients with COVID-19.

OBJECTIVE: Controversial results on remdesivir efficacy have been reported. We aimed to report our real-life experience with the use of remdesivir from its availability in Spain. METHODS: We performed a descriptive study of all patients admitted for ≥48 hours with confirmed COVID-19 who received remdesivir between the 1st of July and the 30th of September 2020. RESULTS: A total of 123 patients out of 242 admitted with COVID-19 at our hospital (50.8%) received remdesivir. Median age was 58 years, 61% were males and 56.9 % received at least one anti-inflammatory treatment. No adverse events requiring remdesivir discontinuation were reported. The need of intensive care unit admission, mechanical ventilation and 30-days mortality were 19.5%, 7.3% and 4.1%, respectively. CONCLUSIONS: In our real-life experience, the use of remdesivir in hospitalized patients with COVID-19 was associated with a low mortality rate and good safety profile.

Cuantificación de la concentración del iodo con TC de doble energía en pacientes con pancreatitis aguda / Quantification of iodine concentration by dual-energy CT in patients with acute pancreatitis

OBJETIVO: Determinar si existen diferencias en la concentración de iodo cuantificada con TC de doble energía en el páncreas de pacientes con pancreatitis aguda y pacientes sin signos analíticos ni en imagen de patología pancreática. MATERIAL Y MÉTODOS: Se estudian 27 casos de pancreatitis aguda a los que se realizó una TC con energía dual a las 48-72 horas del inicio de los síntomas, realizada con contraste intravenoso y una sola fase con un retraso de 55 segundos. Se compara con un grupo control de 11 pacientes con una TC realizada con el mismo protocolo, pero sin datos radiológicos de pancreatitis y amilasa y lipasa normales. Mediante posprocesado se obtienen reconstrucciones con mapa de iodo y se realizan tres regiones de interés en cabeza, cuerpo y cola pancreática para obtener los valores de concentración de iodo (mg/ml) y se comparan entre ambos grupos. Se hace un segundo cálculo normalizando la densidad de iodo con la aorta. RESULTADOS:En las pancreatitis, el valor medio de densidad de iodo es 2,5mg/ml. En el grupo de los controles es de 3,65mg/ml (p = 0,02). Hay tres casos con necrosis glandular en los que la densidad de iodo es 1,53mg/ml. CONCLUSIONES: Existen diferencias significativas en la concentración de iodo del páncreas medida en TC con energía dual entre pacientes con pancreatitis aguda en fases iniciales y pacientes sin signos analíticos ni en imagen de patología pancreática

OBJECTIVE: To determine whether pancreatic iodine concentrations quantified by dual-energy CT differ between patients with acute pancreatitis and those without imaging or laboratory findings indicative of pancreatic disease. MATERIAL AND METHODS: We compared findings on single-phase dual-energy CT images acquired 55seconds after the intravenous administration of contrast material in 27 patients with acute pancreatitis who underwent the examination 48 to 72hours after the onset of symptoms versus in 11 patients (controls) with no imaging findings suggestive of pancreatic disease and normal amylase and lipase who underwent the examination with the same protocol for other purposes. Imaging postprocessing included the generation of iodine maps. Three regions of interest were selected (pancreatic head, body, and tail) to obtain iodine concentrations (mg/ml) to compare between groups. Iodine concentrations were also calculated a second time by normalizing the density of iodine with the aorta. RESULTS: The mean density of iodine was 2.5mg/ml in patients with pancreatitis vs. 3.65mg/ml in controls (p = 0.02). In three patients with glandular necrosis, the density of iodine was 1.53mg/ml. CONCLUSIONS: The concentration of iodine in the pancreas measured with dual-energy CT differs significantly between patients with initial-stage acute pancreatitis and those without imaging or laboratory findings indicative of pancreatic disease

Quantification of iodine concentration by dual-energy CT in patients with acute pancreatitis. / Cuantificación de la concentración del iodo con TC de doble energía en pacientes con pancreatitis aguda.

OBJECTIVE: To determine whether pancreatic iodine concentrations quantified by dual-energy CT differ between patients with acute pancreatitis and those without imaging or laboratory findings indicative of pancreatic disease. MATERIAL AND METHODS: We compared findings on single-phase dual-energy CT images acquired 55seconds after the intravenous administration of contrast material in 27 patients with acute pancreatitis who underwent the examination 48 to 72hours after the onset of symptoms versus in 11 patients (controls) with no imaging findings suggestive of pancreatic disease and normal amylase and lipase who underwent the examination with the same protocol for other purposes. Imaging postprocessing included the generation of iodine maps. Three regions of interest were selected (pancreatic head, body, and tail) to obtain iodine concentrations (mg/ml) to compare between groups. Iodine concentrations were also calculated a second time by normalizing the density of iodine with the aorta. RESULTS: The mean density of iodine was 2.5mg/ml in patients with pancreatitis vs. 3.65mg/ml in controls (p = 0.02). In three patients with glandular necrosis, the density of iodine was 1.53mg/ml. CONCLUSIONS: The concentration of iodine in the pancreas measured with dual-energy CT differs significantly between patients with initial-stage acute pancreatitis and those without imaging or laboratory findings indicative of pancreatic disease.