Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with limited options of targeted therapy. Recent findings suggest that the clinical course of TNBC may be modified by the presence of tumor-infiltrating lymphocytes (TILs) and chemokine’s expression, such as CCL5. Diverse studies have shown that CCL5 suppresses anti-tumor immunity and it has been related to poor outcome in different types of cancer while in other studies, this gene has been related with a better outcome. We sought to determine the association of CCL5 with the recruitment of TILs and other immune cells. With this aim we evaluated a retrospective cohort of 72 TNBC patients as well as publicly available datasets. TILs were correlated with residual tumor size after neoadjuvant chemotherapy (NAC) and CCL5 expression. In univariate analysis, TILs and CCL5 were both associated to the distant recurrence free survival; however, in a multivariate analysis, TILs was the only significant marker (HR = 0.336; 95%IC: 0.150–0.753; P = 0.008). CIBERSORT analysis suggested that a high CCL5 expression was associated with recruitment of CD8 T cells, CD4 activated T cells, NK activated cells and macrophages M1. The CD8A gene (encoding for CD8) was associated with an improved outcome in several public breast cancer datasets.
Introduction: This study aimed to describe the clinical characteristics of patients with COVID-19 co-infected with multiple multidrug-resistant bacteria.Methods: Patients hospitalized in the AUNA network between January and May 2021, diagnosed with COVID-19 and at least two other infecting microorganisms, were retrospectively included in the analysis. Clinical and epidemiological data were extracted from clinical records. The susceptibility levels of the microorganisms were determined using automated methods. Antibiotic resistance was established among infecting bacteria accounting for ≥5 isolates.Results: A total of 27 patients (21 male and 6 female patients) met the inclusion criteria, with a maximum of eight co-infecting bacteria or fungi during admission time. Seven patients (25.9%) died, with a higher but not significant lethality among women (50% vs. 19.0%). A total of 15 patients presented at least one established comorbidity, with hypertension being the most frequent. The time elapsed between COVID-19 diagnosis and hospital attendance was 7.0 days, with that of patients with a fatal outcome being longer than that of living patients (10.6 vs. 5.4). Up to 20 different microorganisms were isolated, with Pseudomonas aeruginosa being the most common (34 isolates). In general, antibiotic resistance levels were high, especially in Acinetobacter baumannii isolates, with resistance levels of 88.9% to all antimicrobial agents tested, except colistin (0%).Conclusion: In conclusion, the present results show the presence of multiple microorganisms that co-infect COVID-19 patients. When fatal outcome rates are in the range of other reports, the presence of a series of multidrug-resistant microorganisms is of concern, showing the need to reinforce control measures to limit the expansion of almost untreatable microorganisms.
ROS proto-oncogene 1 (ROSI) encodes a type I integral membrane protein with tyrosine kinase activity and whose activating alterations are involved in the aggressiveness of several tumor types. Fusions involving ROSI gene are present in 1–2% of lung adenocarcinomas and other solid tumors. Entrectinib, also known as RXDX-101, is a potent second-generation, multitarget oral inhibitor against NTRK1, NTRK2, NTRK3, ALK, and ROS1 with the ability to cross the blood–brain barrier. Results of Phase I and II trials have led the Food and Drug Administration to grant approval to entrectinib for the treatment of patients with metastatic, ROSI-positive non-small cell lung cancer (NSCLC). In this review, we will describe the biology of ROSI, as well as results of the efficacy and safety of different clinical trials evaluating entrectinib in ROSI-positive NSCLC.
Stenotrophomonas maltophilia
is an opportunistic pathogen, often associated with nosocomial infections. Ten
S. maltophilia
were isolated from clinical samples during the period January 2021 and June 2022. Eight (80%) patients had cancer as a background disease and 2 patients had coronavirus disease 2019. A fatal outcome was recorded in 4 cases (40% of patients). All the isolates were susceptible to minocycline and levofloxacin. Trimethoprim/sulfamethoxazole and ceftazidime resistance rates were 20% and 40% respectively. Eight different patterns were observed by Pulsed-Field Gel Electrophoresis, only two isolates being clonally identical. The isolation of
S. maltophilia
in clinical settings requires the implementation of infection prevention measures.
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