Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)

Background. Few data are reported in the literature about the outcome of patients with severe extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy.Methods. A multicenter retrospective study was performed in Italy (June 2016-June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy.Results. C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; P < .001) were associated with clinical success.Conclusions. Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT

ALK rearrangement in specific subtypes of lung adenocarcinoma: immunophenotypic and morphological features

Lung adenocarcinomas are characterized by a variety of genetic and epigenetic changes that lead to activation of specific signaling pathways. This allowed the classification of lung adenocarcinomas according to genetic alterations and the clinical development of novel anticancer agents that affect the activity of specific oncoproteins. In such a context, chromosomal rearrangements that cause constitutive activation of ALK gene define a category of lung adenocarcinomas that is amenable to targeted therapy with ALK inhibitors. Thus, a major issue of current research is to define the morphological and immunophenotypic features of lung ALK-rearranged adenocarcinomas to improve the selection of tumors suitable for molecular genotyping. ALK status was determined, by immunohistochemistry and fluorescence in situ hybridization, in 94 surgically resected lung adenocarcinomas and correlated with histomorphological parameters. Indeed, ALK rearrangement was observed in 10/94 (11%) lung adenocarcinomas and enriched in tumors with a predominant mucinous (46%; p < 0.05) and solid (29%; p < 0.05) pattern. By contrast, it was lacking or sporadically observed in lung adenocarcinomas with predominant acinar, papillary or lepidic pattern. Moreover, the presence of signet-ring cells was predominantly observed in ALK-rearranged tumors (47%; p < 0.05). These data suggest that ALK rearrangement is associated with specific and distinct clinical–pathological characters compared to other genotypes. Thus, the knowledge of these characteristics can improve the diagnostic accuracy and lead to a better understanding of the behavior of ALK-rearranged NSCLC

An Urologic Face of Chronic Lymphocytic Leukemia:Sequential Prostatic and Penis Localization

We report a patient with chronic lymphocytic leukemia (CLL) in whom a leukemic involvement of prostate and penis occurred in the advanced phase of his disease. Obstructive urinary symptoms were indicative of prostatic CLL infiltration, followed by the occurrence of an ulcerative lesion on the glans. Histologic examination confirmed  the  neoplastic B-cell infiltration. Both localizations responded to conventional treatments. A review of the literature confirms that leukemic involvement of the genito-urinary system is   uncommon in CLL patients. However, such an involvement should be considered in CLL patients with urologic symptoms and a long history of the disease

Undefined/non-malignant hepatic nodules are associated with early occurrence of HCC in DAA-treated patients with HCV-related cirrhosis

An unexpected early increased incidence, recurrence and clinical aggressiveness of hepatocellular carcinoma (HCC) has been reported in HCV cirrhotic patients after treatment with direct-acting antivirals (DAA), but denied in other studies. To clarify this controversy, we performed a prospective multicenter study on consecutively enrolled cirrhotic patients with or without history of HCC undergoing DAA therapy

Long term effectiveness of DAA therapy in patients with chronic HCV and Mixed Cryoglobulinemic Syndrome

Background: Mixed cryoglobulinemia is the most frequent extrahepatic HCV-induced disorder. Promising data exists on the effectiveness and safety of direct-acting antiviral (DAA) therapy, but prospective, long-term posttreatment follow-up studies are lacking. Using data from the prospective multicentric PITER cohort we aimed to evaluate the clinical effect of DAA therapy following viral eradication. Methods: Patients with cryoglobulins and symptoms before antiviral treatment were prospectively followed-up during and after treatment collecting clinical data in a dedicated eCRF. Results: Of the 458 patients who had a Cryoglobulinemic Syndrome (mean age:63; SD 11 years; 64% female; 33% with liver cirrhosis) and were treated with DAAs from 2014-2017, the SVR was 96%. At the end of treatment, the clinical responses were: Full Complete (disappearance of all symptoms) in 12%; Complete (improvement of all symptoms) in 20%; Partial (improvement in ≥50% of symptoms) in 23%; Non Response (improvement in less than 50% or persistence of all symptoms) in 45%. In 402 patients a follow-up (mean:561 days SD 308) was available after the SVR. At the end of the follow-up the clinical responses were: Full Complete in 27%, Complete in 29%, Partial in 22% and Non Response in 18%. A new appearance of symptoms (Clinical Relapse) was observed in 15 (3.7%) patients. After SVR a complete disappearance of cryoglobulins was achieved in 73%, in 19% a significant reduction of cryocrit was observed, in the remaining 8% of patients cryocrit values did not change significantly. Nephropathy was the only independent factor associated to Non Response by Cox Regression analysis (HR:2.8; CI:95%:1.4-5.4). Presence of cryoglobulins following the SVR was the only independent predictor of Clinical Relapse (HR:28; 95% CI 3-249). Among the 150 patients in whom four points (every 6 months) of clinical evaluation were available, fluctuations in the clinical response (from Non Response to Full Complete Response and vice versa in the different time points) were observed in 72% of patients. Conclusion: DAA therapy induces a high virologic and clinical response. However a follow-up evaluation of Symptomatic HCV-Cryoglobulinemic patients is necessary because a fluctuating pattern is observed in clinical response during follow-up in a consistent proportion of cases