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.

Recommendations on the use of azole antifungals in hematology-oncology patients.

The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.

Carriage of multidrug-resistant Gram-negative bacilli: duration and risk factors.

Identification of risk factors influencing the duration of carriage of multidrug-resistant Gram-negative bacilli (MDR-GNB) may be useful for infection control. The aim of this study is to estimate the impact of several factors collected for routine hospital surveillance on the duration of carriage of selected MDR-GNB. From January 2015 to July 2021, patients with at least two clinical/surveillance samples positive for MDR-GNB different from ESBL-producing E. coli or AmpC - exclusively producing Enterobacterales were assessed. Microorganisms, age, number of admissions, clinical or rectal sample, sex, and admission service were evaluated as risk factors. Multivariate analysis was performed by a Cox proportional hazard model. A total of 1981 episodes of colonization were included. Involved microorganisms were ESBL-Klebsiella pneumoniae (KP) in 1057 cases (53.4%), other ESBL-non-E. coli Enterobacterales in 91 (4.6%), OXA-48-KP in 263 (13.3%), KPC-KP in 90 (4.5%), VIM-KP in 29 (1.5%), carbapenemase-producing non-KP Enterobacterales (CP-non-KP) in 124 (6.3%), and MDR Pseudomonas aeruginosa (MDR-PAER) in 327 (16.5%). No differences in duration of colonization were observed among ESBL-KP (median colonization time 320 days), ESBL-non-E. coli Enterobacterales (226 days), OXA48-KP (305 days), and MDR-PAER (321 days). For each group, duration of colonization was significantly longer than that of KPC-KP (median colonization time 60 days), VIM-KP (138 days), and CP-non-KP (71 days). Male sex (HR = 0.88; 95% CI 0.78-0.99), detection in Hepatology-Gastroenterology (HR = 0.71; 95% CI 0.54-0.93), clinical sample (HR = 0.61; 95% CI 0.53-0.69), and > 2 admissions after first detection (HR = 0.47; 95% CI 0.42-0.52) were independent predictors of longer carriage, whereas VIM-KP (HR = 1.61; 95% CI 1.04-2.48), KPC-KP (HR = 1.85; 95% CI 1.49-2.3), and CP-non-KP (HR = 1.92; 95% CI 1.49-2.47) were associated with shorter colonization time. Duration of colonization was significantly longer for ESBL-KP, other ESBL-non-E. coli Enterobacterales, OXA-48-KP, and MDR-PAER. For these microorganisms, prolonging surveillance up to 2.5-3 years should be considered. Male sex, clinical sample, multiple readmissions, admission service, and type of microorganism are independent predictors of the duration of carriage.

Oncological monitoring after transanal total mesorectal excision (TaTME) for rectal neoplasia.

BACKGROUND: The surgical treatment of choice for rectal neoplasia is total mesorectal excision (TME). The transanal approach enables a better approach in male and obese patients and/or those with a narrow pelvis and in patients with small tumors. Short-term results are comparable with those for laparoscopy or the open approach, but the medium- and long-term oncological data are sparse. The aim of the present study was to evaluate our early experience with transanal TME (TaTME). METHODS: This was a retrospective study conducted on patients who underwent TaTME at our center between August 2013 and April 2017 with a follow-up ≥ 3 years. Histopathology, complications, mortality, neoplastic recurrence and disease-free survival were analyzed. RESULTS: One hundred patients (68 men and 32 women,, median age 66.8 years [range 29.6-91.2 years]) were included. There were 67 T3 cases (67%) with 74 N0 cases (74%), the mesorectal quality was graded optimal for 87.6% and only 2 cases of radial margin involvement were detected (2%). The median follow-up period was 47.6 months (range 11.8-78.9 months). Eighteen cases of recurrence were diagnosed, of which 3 (3%) recurred locally with an average disease-free period of 43.1 months. Overall survival was 80% and mortality due to progression of disease was 13%. CONCLUSIONS: TaTME is a safe surgical procedure with surgical, anatomopathological and oncological results at 3 years (medium-term) comparable with those for the laparoscopic and open approaches. Better monitoring is required with studies of the long-term functional and quality of life outcomes, i.e., at 5 or 10 years.

Antimicrobial resistance in Gram-negative bacilli in Spain: an experts' view.

BACKGROUND: Antibiotic resistance in Gram-negative bacilli poses a serious problem for public health. In hospitals, in addition to high mortality rates, the emergence and spread of resistance to practically all antibiotics restricts therapeutic options against serious and frequent infections. OBJECTIVE: The aim of this work is to present the views of a group of experts on the following aspects regarding resistance to antimicrobial agents in Gram-negative bacilli: 1) the current epidemiology in Spain, 2) how it is related to local clinical practice and 3) new therapies in this area, based on currently available evidence. METHODS: After reviewing the most noteworthy evidence, the most relevant data on these three aspects were presented at a national meeting to 99 experts in infectious diseases, clinical microbiology, internal medicine, intensive care medicine, anaesthesiology and hospital pharmacy. RESULTS AND CONCLUSIONS: Subsequent local debates among these experts led to conclusions in this matter, including the opinion that the approval of new antibiotics makes it necessary to train the specialists involved in order to optimise how they use them and improve health outcomes; microbiology laboratories in hospitals must be available throughout a continuous timetable; all antibiotics must be available when needed and it is necessary to learn to use them correctly; and the Antimicrobial Stewardship Programs (ASP) play a key role in quickly allocating the new antibiotics within the guidelines and ensure appropriate use of them.

Antiviral drugs against SARS-CoV-2.

The use of antiviral drugs represents an important progress in the therapeutic management of COVID-19, leading to a substantial reduction of SARS-CoV-2-related complications and mortality. In immunocompetent host, peak viral replication occurs around the symptom's onset, and it prolongs for 5 to 7 days that is the window of opportunity for giving an antiviral. Accordingly, early and rapid diagnostic of the infection in the outpatient clinic is essential as well as the availability of oral agents that can be easily prescribe. Remdesivir has demonstrated its efficacy in hospitalized patients requiring oxygen support and in mild/moderate cases to avoid the hospitalization, however, the intravenous administration limits its use among outpatients. Molnupiravir and nirmatrelvir/ritonavir are potent oral antiviral agents. In the present review we discuss the potential targets against SARS-CoV-2, and an overview of the main characteristics and clinical results with the available antiviral agents for the treatment of SARS-CoV-2.

New treatments for multidrug-resistant non-fermenting Gram-negative bacilli Infections.

Ceftolozane/tazobactam, ceftazidime/avibactam and cefiderocol belong to a novel generation of antibiotics that correspond with the ß-lactam family. It is necessary to having new options in treating infections caused by Gram-negative, non-fermenting multidrug-resistant bacilli due to the significant increase in multidrug resistance in the last decades. Knowing the main characteristics of each drug is key for correct use.

Der p 23 sensitisation in patients with house dust mite respiratory allergy.

Summary: Background. The sensitization profile of patients allergic to house dust mites (HDM) and its molecular diagnosis may determine treatment and evolution of the disease. The present study investigates the prevalence of Der p 23 sensitization and its relation to asthma in a population of HDM-allergic patients. Methods. We conducted a cross-sectional study of 891 patients with HDM allergy with symptoms of rhinitis and 52.1% of them with asthma. Total and specific IgE (sIgE) was measured against Dermatophagoides pteronyssinus and its molecular components (Der p 1, Der p 2 and Der p 23) and the storage mite Lepidoglyphus destructor using ImmunoCAP. Prevalence of sensitization and levels of sIgE were analysed according to asthma diagnosis and asthma severity. Results. Der p 23 was the predominant allergen in this population (83.7%) but IgE levels were lower than those of sIgE to Der p 1 and Der p 2. A good correlation was found between sIgE to Der p 23 and the other allergens. A total of 8.2% patients were monosensitized to Der p 23. Asthma was more frequent in patients with positive sIgE against Der p 23 than in patients without this sensitization (52.8% vs 42.8%, p = 0.027). A tendency to increase both total IgE and sIgE was observed in relation to the severity of asthma from intermittent mild asthma to persistent moderate asthma but a substantial decrease in total IgE and sIgE was detected in more severe asthmatics. Conclusions. Der p 23 might be a prevalent allergen in regions with high rates of HDM exposure. Even though sIgE levels against this allergen are usually low, its presence could increase the risk of asthma.

A systematic literature review and expert consensus on risk factors associated to infection progression in adult patients with respiratory tract or rectal colonisation by carbapenem-resistant Gram-negative bacteria.

OBJECTIVE: Risk factors (RFs) associated with infection progression in patients already colonised by carbapenem-resistant Gram-negative bacteria (CRGNB) have been addressed in few and disperse works. The aim of this study is to identify the relevant RFs associated to infection progression in patients with respiratory tract or rectal colonisation. METHODS: A systematic literature review was developed to identify RFs associated with infection progression in patients with CRGNB respiratory tract or rectal colonisation. Identified RFs were then evaluated and discussed by the expert panel to identify those that are relevant according to the evidence and expert's experience. RESULTS: A total of 8 articles were included for the CRGNB respiratory tract colonisation and 21 for CRGNB rectal colonisation, identifying 19 RFs associated with pneumonia development and 44 RFs associated with infection progression, respectively. After discussion, the experts agreed on 13 RFs to be associated with pneumonia development after respiratory tract CRGNB colonisation and 33 RFs to be associated with infection progression after rectal CRGNB colonisation. Respiratory tract and rectal colonisation, previous stay in the ICU and longer stay in the ICU were classified as relevant RF independently of the pathogen and site of colonisation. Previous exposure to antibiotic therapy or previous carbapenem use were also common relevant RF for patients with CRGNB respiratory tract and rectal colonisation. CONCLUSIONS: The results of this study may contribute to the early identification of CRGNB colonized patients at higher risk of infection development, favouring time-to-effective therapy and improving health outcomes.

Major Allergen Content in Allergen Immunotherapy Products: The Limited Value of Numbers.

The prevalence of allergic disorders has increased drastically over the last 50 years to the extent that they can be considered epidemic. At present, allergen-specific immunotherapy (AIT) is the only therapy that targets the underlying cause of allergic disorders, and evidence of its superiority is based on data accumulated from clinical trials and observational studies demonstrating efficacy and safety. However, several aspects remain unresolved, such as harmonization and standardization of manufacturing and quantification procedures across manufacturers, homogeneous reporting of strength, and the establishment of international reference standards for many allergens. This article discusses issues related to the measurement of major allergen content in AIT extracts, raising the question of whether comparison of products from different manufacturers is an appropriate basis for selecting a specific AIT product. Allergen standardization in immunotherapy products is critical for ensuring quality and, thereby, safety and efficacy. However, lack of harmonization in manufacturing processes, allergen quantification (methodologies and references), national regulatory differences, clinical practice, and labeling shows that the comparison of AIT products based solely on major allergen amounts is not rational and, in fact, impossible. Moreover, when rating the information given for a specific product, it is necessary to take into account further inherent characteristics of products and their application in clinical practice, such as the state of extract modification, addition of adjuvant or adjuvant system, route of administration (sublingual/ subcutaneous), and cumulative dose as per posology (including the volume per administration). Finally, only convincing clinical data can serve as the basis for product-specific evaluation and cross-product comparability of individual products.