Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are associated with poor outcomes depending on patient’s conditions, clinical severity and type of infection, and treatment is challenging given the limited therapeutic options available. The aim of this study was to describe the clinical and microbiological characteristics of two outbreaks caused by CRAB in an intensive care unit (ICU). In addition, the mechanisms of resistance detected in these strains and the treatment chosen according to the available therapeutic options were analyzed. Overall, 28 patients were included. Ten patients (35.71%) had ventilator-associated pneumonia (VAP), ten (35.71%) had a bloodstream infection (BSI), and eight (28.57%) were only colonized. Recurrent infection occurred in 25% (5/20) of infected patients. Two different strains of A. baumannii were isolated from the index patient of the first outbreak. The first strain belonged to the ST85 and carried the bla_NDM-1 carbapenemase gene, while the second belonged to the ST2 and carried bla_OXA-23, and bla_OXA-66 carbapenemase genes. The phylogenetic analysis revealed that the ST2 strain was the cause of the major outbreak, and mutations in the AmpC gene were related to progressive increasing minimum inhibitory concentration (MIC) and finally, cefiderocol-resistance in one strain. The CRAB isolates from the second outbreak were also identified as ST2. Cefiderocol-resistant strains tests identified by the disc diffusion method were involved in 24% (6/25) of nosocomial infections. Using broth microdilution (BMD) ComASP^® only, 33.3% (2/6) of these strains were cefiderocol-resistant. All-cause ICU mortality was 21.4%. Conclusions: Cefiderocol is the first approved siderophore cephalosporin for the treatment of CRAB infections. Cefiderocol-resistant strains were related with bla_NDM-1 carbapenemase and mutations in the AmpC gene. Cefiderocol-resistant strains or that cannot be properly interpreted by disk diffusion, should be retested using BMD for definitive categorization.

Muscle-invasive bladder tumors are associated with a high risk of relapse and metastasis even after neoadjuvant chemotherapy and radical cystectomy. Therefore, further therapeutic options are needed and molecular characterization of the disease may help to identify new targets. The aim of this study was to characterize muscle-invasive bladder tumors at the molecular level using computational analyses. The TCGA cohort of muscle-invasive bladder cancer patients was used to describe these tumors. Probabilistic graphical models, layer analyses based on sparse k-means coupled with Consensus Cluster, and Flux Balance Analysis were applied to characterize muscle-invasive bladder tumors at a functional level. Luminal and Basal groups were identified, and an immune molecular layer with independent value was also described. Luminal tumors showed decreased activity in the nodes of epidermis development and extracellular matrix, and increased activity in the node of steroid metabolism leading to a higher expression of the androgen receptor. This fact points to the androgen receptor as a therapeutic target in this group. Basal tumors were highly proliferative according to Flux Balance Analysis, which makes these tumors good candidates for neoadjuvant chemotherapy. The Immune-high group showed a higher degree of expression of immune biomarkers, suggesting that this group may benefit from immune therapy. Our approach, based on layer analyses, established a Luminal group candidate for therapy with androgen receptor inhibitors, a proliferative Basal group which seems to be a good candidate for chemotherapy, and an immune-high group candidate for immunotherapy.

Background: Estimation of life expectancy in older patients is relevant to select the best treatment strategy. We aimed to develop and validate a score to predict early mortality in older patients with cancer. Patients and Methods: A total of 749 patients over 70 years starting new chemotherapy regimens were prospectively included. A prechemotherapy assessment that included sociodemographic variables, tumor/treatment variables, and geriatric assessment variables was performed. Association between these factors and early death was examined using multivariable logistic regression. Score points were assigned to each risk factor. External validation was performed on an independent cohort. Results: In the training cohort, the independent predictors of 6-month mortality were metastatic stage (OR 4.8, 95% CI [2.4–9.6]), ECOG-PS 2 (OR 2.3, 95% CI [1.1–5.2]), ADL ≤ 5 (OR 1.7, 95% CI [1.1–3.5]), serum albumin levels ≤ 3.5 g/dL (OR 3.4, 95% CI [1.7–6.6]), BMI < 23 kg/m² (OR 2.5, 95% CI [1.3–4.9]), and hemoglobin levels < 11 g/dL (OR 2.4, 95% CI (1.2–4.7)). With these results, we built a prognostic score. The area under the ROC curve was 0.78 (95% CI, 0.73 to 0.84), and in the validation set, it was 0.73 (95% CI: 0.67–0.79). Conclusions: This simple and highly accurate tool can help physicians making decisions in elderly patients with cancer who are planned to initiate chemotherapy treatment.

Background: Tracheostomy is one of the most frequent techniques in intensive care units (ICU). Fiberoptic bronchoscopy (FB) is a safety measure when performing a percutaneous dilatational tracheostomy (PDT), but the controversy surrounding the routine use of FB as part of the procedure remains open. National surveys in some European countries showed that the use of FB is non-standardized. Retrospective studies have not shown a significant difference in complications between procedures performed with or without a bronchoscope. International guidelines have not been able to establish recommendations regarding the use of FB in PDT due to lack of evidence.Design: This is a multicenter (three centers at the time of publishing this paper) randomized controlled clinical trial to examine the safety of percutaneous tracheostomy using FB. We will include all consecutive adult patients admitted to the ICU in whom percutaneous tracheostomy for prolonged mechanical ventilation is indicated and with no exclusion criteria for using FB. Eligible patients will be randomly assigned to receive blind PDT or PDT under endoscopic guidance. All procedures will be performed by experienced intensivists in PDT and FB. A Data Safety and Monitoring Board (DSMB) will monitor the trial. The primary outcome is the incidence of perioperative complications.Discussion: FB is a safe technique when performing PDT although its use is not universally accepted in all ICUs as a routine practice. Should PDT be monitored routinely with endoscopic guidance? This study will assess the role of FB monitoring during PDT.Trial registration: ClinicalTrials.gov NCT04265625. Registered on February 11, 2020

Purpose: To explore the tumor proteome of patients diagnosed with localized clear cell renal cancer (ccRCC) and treated with surgery. Material and methods: A total of 165 FFPE tumor samples from patients diagnosed with ccRCC were analyzed using DIA-proteomics. Proteomics ccRCC subtypes were defined using a consensus cluster algorithm (CCA) and characterized by a functional approach using probabilistic graphical models and survival analyses. Results: We identified and quantified 3091 proteins, including 2026 high-confidence proteins. Two proteomics subtypes of ccRCC (CC1 and CC2) were identified by CC using the high-confidence proteins only. Characterization of molecular differences between CC1 and CC2 was performed in two steps. First, we defined 514 proteins showing differential expression between the two subtypes using a significance analysis of microarrays analysis. Proteins overexpressed in CC1 were mainly related to translation and ribosome, while proteins overexpressed in CC2 were mainly related to focal adhesion and membrane. Second, a functional analysis using probabilistic graphical models was performed. CC1 subtype is characterized by an increased expression of proteins related to glycolysis, mitochondria, translation, adhesion proteins related to cytoskeleton and actin, nucleosome, and spliceosome, while CC2 subtype showed higher expression of proteins involved in focal adhesion, extracellular matrix, and collagen organization. Conclusions: ccRCC tumors can be classified in two different proteomics subtypes. CC1 and CC2 present specific proteomics profiles, reflecting alterations of different molecular pathways in each subtype. The knowledge generated in this type of studies could help in the development of new drugs targeting subtype-specific deregulated pathways.

We investigated B-cell-activating factor (BAFF) in relation to response to treatment with TNF inhibitors (TNFis) in rheumatoid arthritis (RA). This was a longitudinal study including 158 patients with RA treated with TNFis and followed up for 6 months. Clinical response at 6 months of treatment was defined according to the EULAR criteria for good responders (GRs). BAFF concentration was measured in serum samples, collected at baseline and at 6 months. Associations with EULAR response were evaluated using univariable and multivariable logistic regression models. ROC analysis was performed to determine the optimal threshold of serum BAFF concentration associated with good EULAR response to treatment. After 6 months of TNFi treatment, 24% of patients were GRs. They had a lower BMI, lower baseline DAS28 and lower baseline serum BAFF concentration than non-responders. After 6 months of TNFi treatment, autoantibody-positive patients who attained GR had significantly lower serum BAFF concentrations compared with patients who did not. Serum BAFF < 968 pg/mL at 6 months represented the concentration likely to best discriminate between GR and non-GR at 6 months of TNFi treatment. Autoantibody-seropositive patients who had serum BAFF < 968 pg/mL at 6 months demonstrated a more than four-fold increased probability to be GRs compared with patients with higher BAFF concentrations. In conclusion, serum BAFF concentrations were associated with response to TNFis in seropositive RA patients, corroborating the importance of the B-cell compartment in RA.