BackgroundAntimicrobial resistance is one of the most challenging issues in modern medicine.MethodsWe evaluated the secular trends of the relative frequency of blood isolates and of the pattern of their in vitro antimicrobial susceptibility in our hospital during the last four and a half years.ResultsOverall, the data regarding the relative frequency of blood isolates in our newly founded hospital do not differ significantly from those of hospitals that are functioning for a much longer period of time. A noteworthy emerging problem is the increasing antimicrobial resistance of Gram-negative bacteria, mainly Acinetobacter baumannii and Klebsiella pneumoniae to various classes of antibiotics. Acinetobacter baumannii isolates showed an increase of resistance to amikacin (p = 0.019), ciprofloxacin (p = 0.001), imipenem (p < 0.001), and piperacillin/tazobactam (p = 0.01) between the first and second period of the study.ConclusionAn alarming increase of the antimicrobial resistance of Acinetobacter baumannii isolates has been noted during our study.
A rare case of a thyroid abscess due to mixed anaerobic flora containing Fusobacterium mortiferum in an immunocompetent patient is described. The patient was successfully treated with immediate surgical intervention and appropriate antimicrobial agents. CASE REPORTA 27-year-old white male patient was admitted with an enlarging, painful neck mass accompanied by high fever. He reported a viral upper respiratory tract illness 3 weeks prior to admission, which 10 days later was complicated by pain in the area of the thyroid. After extensive investigation that included ultrasound, a computed tomography scan, and nuclear scanning, he was diagnosed with subacute thyroiditis. He was initially treated with prednisone, and his symptoms improved. However, 5 days into treatment, he developed high fever and a painful neck mass, resulting in odynophagia and dysphagia. This did not respond to a course of antibiotics and the patient was admitted. He was acutely ill with a temperature of 38.4°C and tachycardia. Examination of the neck revealed a large tender, warm, and fluctuant mass occupying the region of the left lobe of the thyroid gland and no further extension. The trachea was shifted to the right. Laboratory investigations revealed a leukocyte count of 17,600 with 84% polymorphonuclear cells and a hemoglobin value of 9.5 g/dl. Plain radiographs of the neck and chest in frontal and lateral views showed a homogenous soft-tissue density anterior to the trachea, displacing it to the right. The retropharyngeal space had normal dimensions on radiographs. Computed tomography revealed cystic areas in both lobes of the thyroid gland. The larger was nonhomogeneous and extended into the superior mediastinum without any distortion of the mediastinal structures (Fig. 1). Needle aspiration of this lesion disclosed thick yellow pus. Free triiodothyronine and free thyroxine levels were mildly elevated, and thyroid-stimulating hormone levels were within normal range. The ear, nose, and throat (ENT) service intervened with incision and drainage of the affected area. The patient was treated with intravenous meropenem at a dose of 2 g three times a day and clindamycin at a dose of 900 mg three times a day. In the first few days of his admission, he developed pneumonia of the left lung and pericardial effusion.
Skin melanoma cells are tightly interconnected with their tumor microenvironment (TME), which influences their initiation, progression, and sensitivity/resistance to therapeutic interventions. An immune-active TME favors patient response to immune checkpoint inhibition (ICI), but not all patients respond to therapy. Here, we assessed differential gene expression in primary and metastatic tumors from the TCGA-SKCM dataset, compared to normal skin samples from the GTEx project and validated key findings across 4 independent GEO datasets, as well as using immunohistochemistry in independent patient cohorts. We focused our attention on examining the expression of various immune receptors, immune-cell fractions, immune-related signatures and mutational signatures across cutaneous melanomas with diverse tumor mutation burdens (TMB). Globally, the expression of most immunoreceptors correlated with patient survival, but did not differ between TMBhigh and TMBlow tumors. Melanomas were enriched in “naive T-cell”, “effector memory T-cell”, “exhausted T-cell”, “resting Treg T-cell” and “Th1-like” signatures, irrespective of their BRAF, NF1 or RAS mutational status. Somatic mutations in IDO1 and HLA-DRA were frequent and could be involved in hindering patient response to ICI therapies. We finally analyzed transcriptome profiles of ICI-treated patients and associated their response with high levels of IFNγ, Merck18, CD274, CD8, and low levels of myeloid-derived suppressor cells (MDSCs), cancer-associated fibroblasts (CAFs) and M2 macrophages, irrespective of their TMB status. Overall, our findings highlight the importance of pre-existing T-cell immunity in ICI therapeutic outcomes in skin melanoma and suggest that TMBlow patients could also benefit from such therapies.
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