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Histological Findings of Resected Tracheal Ring in SARS-CoV-2-Positive and -Negative Tracheostomized Patients.
No full text20.500.12530/87912The aim of this study was to compare the histopathological findings in the resected tracheal ring of tracheotomized critically ill patients with or without severe SARS-CoV-2 infection. This is a prospective case-control study. The data collection period was between May 2020 and 2022. Eighty tracheostomies were performed on patients with long intubation, and the resected tracheal ring was examined by standard microscopy. Forty consecutive tracheotomies were carried out in COVID-19-positive and -negative patients. The mean age was 67.1 (6.9 SD) years in the COVID-19 group and 67.8 (9.6 SD) in the control group (p = 0.3). The number of men in each group was 30 (75.0%) versus 27 (67.5%), respectively (p = 0.5). No relevant histological alterations were found in 82.5% of samples. Chronic subepithelial inflammation was found in 13.8% of cases. Two cases presented with vasculitis (2.5%), and one case presented with thrombotic microangiopathy (1.2%), all of them in the COVID-19 group. We found no statistically significant dependence between relevant histologic findings versus no alterations (X2 = 0.779, p= 0.377) and no significant risk indices (RR = 1.8, OR = 2.032, PAR = 44%). There is no evidence of increased risk of histopathological findings in the resected tracheal ring of patients with long intubation and COVID-19 disease
Rate of recurrence after discontinuing anticoagulation in patients with venous thromboembolism within 30 days after COVID-19 vaccine.
No full text20.500.12530/87854This study generated evidence to guide anticoagulation in patients with VTE after vaccination for COVID-19. We provided data on the low recurrence rate after cessation of anticoagulant therapy and the findings for this study offer timely insights into the management of a potentially vaccine-related adverse event
BARICITINIB IN RHEUMATOID ARTHRITIS INTERSTITIAL LUNG DISEASE. NATIONAL MULTICENTER STUDY OF 60 PATIENTS
No full text20.500.12530/8787
A plasmid-chromosome crosstalk in multidrug resistant enterobacteria.
No full text20.500.12530/87854Conjugative plasmids promote the dissemination and evolution of antimicrobial resistance in bacterial pathogens. However, plasmid acquisition can produce physiological alterations in the bacterial host, leading to potential fitness costs that determine the clinical success of bacteria-plasmid associations. In this study, we use a transcriptomic approach to characterize the interactions between a globally disseminated carbapenem resistance plasmid, pOXA-48, and a diverse collection of multidrug resistant (MDR) enterobacteria. Although pOXA-48 produces mostly strain-specific transcriptional alterations, it also leads to the common overexpression of a small chromosomal operon present in Klebsiella spp. and Citrobacter freundii strains. This operon includes two genes coding for a pirin and an isochorismatase family proteins (pfp and ifp), and shows evidence of horizontal mobilization across Proteobacteria species. Combining genetic engineering, transcriptomics, and CRISPRi gene silencing, we show that a pOXA-48-encoded LysR regulator is responsible for the plasmid-chromosome crosstalk. Crucially, the operon overexpression produces a fitness benefit in a pOXA-48-carrying MDR K. pneumoniae strain, suggesting that this crosstalk promotes the dissemination of carbapenem resistance in clinical settings
Physicochemical stability of bortezomib solutions for subcutaneous administration
No full text20.500.12530/87893For the majority of cytotoxic drug preparations, such as bortezomib, the unit dose information is not available. In addition, there is a lack of information on the physicochemical stability of the pharmaceutical preparation after opening; this information is crucial for its administration to patients in successive visits, and the per-patient cost can be affected. The purpose of our proposed physicochemical stability study is to determine the shelf life of the reconstituted liquid product under refrigeration and clinical practice conditions. This evaluation was extended to both vials and ready-to-use syringes prefilled with the contents of the open vial. The stability test design includes the specified storage conditions and the critical physicochemical parameters of reconstituted injectable bortezomib. Furthermore, this approach includes the determination of impurities, the monitoring of the purity of the mean peak using a photodiode array, the control of the mass balance, the monitoring of subvisible particles using a laser diffraction analyser, and the setting of stability specifications. For the chemical stability study, the amount of bortezomib and its degradation products were determined using a stability-indicating HPLC method. The physical inspection of the samples was performed throughout the stability study, and their pH values were also monitored. Bortezomib (2.5 mg/mL) in 0.9% sodium chloride remained stable for 7 days when stored in both polypropylene syringes and vials at 5 +/- 3 degrees C (refrigeration) and shielded from light. Additionally, it exhibits stability for 24 h under storage conditions simulating clinical use (20-30 degrees C and protected from light). The proposed protocol provides the stability in the vials once reconstituted and in prefilled refrigerated syringes; this protocol can be used to reduce waste and increase cost savings
Recurrent Clostridioides difficile infections in solid organ transplant recipients: The international CALIPSO study.
No full text20.500.12530/87912To evaluate the risk of recurrent Clostridioides difficile infection (CDI) in solid-organ transplant (SOT) recipients. Retrospective multicenter study including SOT recipients with a first CDI episode in the year after transplantation (Jan 2017-June 2020). The primary outcome measure was recurrence, defined as a new CDI ≤56 days from the first episode. A competing risk analysis was performed using the sub-distribution hazard model multivariable analysis. 191 SOT recipients were included: 101 (52.9%) were kidney, 66 (34.6%) liver, 11 (5.8%) lung, 8 (4.2%) simultaneous pancreas-kidney, 4 (2.1%) heart and 1 (0.5%) pancreas alone recipients. Treatment for the first CDI were: vancomycin (n = 114,59.7%), vancomycin+metronidazole (n = 39,20.4%), metronidazole (n = 26,13.6%), fidaxomicin (n = 9,4.7%), 3 patients did not receive any therapy. After the first CDI, 17/191 (8.9%) patients died within 56-day mortality without having a recurrence, while 23/191 (12%) patients had a recurrence. Among patients with recurrent CDI, 56-day mortality rate was 30.4% (7/23 patients). On multivariable analysis, severe CDI (sHR4.01, 95% CI 1.77-9.08, p Metronidazole monotherapy is associated with increased risk of recurrent CDI in SOT recipients. Therapeutic strategies aimed to reduce the risk of recurrence should be implemented in this setting
Efficacy of Risankizumab in Patients with Suboptimal Response or Failure to Ustekinumab: A Multicenter Retrospective Study in Spain
No full text20.500.12530/87885Background. Current psoriasis treatment goals emphasize achieving complete or near-complete skin clearance while preserving the quality of life, necessitating treatment modification for a suboptimal or inadequate response. Despite risankizumab's demonstrated efficacy, evidence remains limited for patients switching from ustekinumab, particularly those with suboptimal or inadequate response. Objective. This study assesses risankizumab's real-world effectiveness in patients with suboptimal response (PASI 2-3), inadequate response (PASI 3-5), or failure (PASI >5) to ustekinumab, based on a multicenter retrospective cohort in Spain. Method. A multicenter retrospective study across 24 Spanish hospitals included 102 patients previously treated with ustekinumab and switched to risankizumab. Results. Out of 102 patients, 78 experienced ustekinumab treatment failure (PASI >5), while 24 had an inadequate response (PASI 3-5), including 6 with a suboptimal response (PASI 2-3). Remarkably, after one year of treatment with risankizumab, all patients demonstrated improvement, achieving near-complete or complete skin clearance (PASI 0-1). Conclusion. Risankizumab displayed effectiveness in patients with suboptimal/inadequate response or treatment failure to ustekinumab, aligning with the current treatment goals of complete or near-complete skin clearance. These real-world results corroborate clinical trial data, emphasizing risankizumab's potential as a powerful therapeutic alternative for this patient population. Further prospective studies are essential to validate these findings
Mycobacterium interjectum Infection in an Immunocompetent Host Following Contact With Aquarium Fish.
No full textProstate-specific Antigen at 3 Months as a Predictor of Radiologic Progression-free Survival in Metastatic Hormone-sensitive Prostate Cancer Treated with Apalutamide: Analysis of 633 Patients in a Real-world Database.
No full text20.500.12530/87907The depth of the prostate-specific antigen (PSA) decline after androgen receptor pathway inhibitor (ARPI) treatment combined with androgen deprivation therapy for patients with metastatic hormone-sensitive prostate cancer (mHSPC) may affect prognosis. The primary objective in our study was the correlation between the PSA response at 3 mo and radiologic progression-free survival (rPFS) at 24 mo. Three groups were defined according to the PSA decline: complete response (PSA ≤0.02 ng/ml), partial response (PSA >0.02 and ≤0.2 ng/ml), and incomplete response (PSA >0.2 ng/ml). Secondary objectives were correlation between the PSA response at 3 mo and overall survival, and the development of a model predicting complete PSA response. We conducted a retrospective multicenter study of patients with mHSPC treated with apalutamide from May 2018 to September 2023 registered in the Real-World Evidence APA registry across 20 centers. We included 633 patients with mHSPC. The median age at diagnosis was 68 yr (interquartile range [IQR] 63-75) and median PSA was 16 ng/ml (IQR 7.5-64). Some 63% of the short had low-volume disease, 51% had de novo disease, 48% had recurrent disease. At 3 mo, 27% had a complete response, 42% a partial response, and 31% an incomplete response, with corresponding rRFS rates at 24 mo of 92%, 86%, and 63%. According to the predictive model, a complete PSA response at 3 mo was associated with the use of next-generation imaging and PSA Patients with a complete PSA response after 3 mo of apalutamide treatment face a very low risk of progression within 2 yr. Conversely, nearly 50% of patients with an incomplete PSA response will experience disease progression. For patients with metastatic prostate cancer that is still responsive to hormone therapy, a complete response after treatment with a drug called apalutamide is associated with a very low risk of progression within 2 years. However, nearly half of patients with an incomplete response to apalutamide will experience progression of their cancer
Overview of the Role of Liquid Biopsy in Non-small Cell Lung Cancer (NSCLC).
No full textSolid tumour tissue has traditionally been used for cancer molecular diagnostics. Recently, biomarker assessment in blood or liquid biopsies has become relevant because it allows genotyping in a less invasive and costly manner. In addition, it is a very useful technique in cases with insufficient tumour samples. Recent data have shown that this method can provide the baseline molecular characteristics of the tumour and resistance changes that emerge during cancer treatment. In terms of diagnostic application, the platforms available for clinical use in lung cancer focus on the isolation and detection of circulating DNA (ctDNA) and generally cover a limited number of mutations in genes such as epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS) and BRAF, as well as anaplastic lymphoma kinase (ALK) rearrangements. In parallel, there are plasma genotyping platforms based on next-generation sequencing (NGS) techniques, which are much broader in scope, allowing multiple genes to be studied simultaneously in a more efficient manner. More recently, promising research scenarios for liquid biopsy have emerged, such as its utility for early diagnosis and evaluation of minimal residual disease after oncological treatment. In light of these advances, knowledge of the benefits and limitations of liquid biopsy, as well as awareness of emerging information on new indications for this technique in non-small cell lung cancer (NSCLC), are of paramount importance in developing more effective management strategies for patients with this neoplasm