Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance

The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment options for BSI caused by GNB with DTR, namely extended-spectrum Beta-lactamase-producing Enterobacteriales; carbapenem-resistant Enterobacteriales; DTR Pseudomonas aeruginosa; and DTR Acinetobacter baumannii

Gas Chromatography Combustion Isotope Ratio Mass Spectrometry to detect differences in four compartments of Simmental cows fed on C3 and C4 diets

Fatty acids (FAs) metabolism in animals represents an important field of study since they influence the quality and the properties of the meat. The aim of this study is to assess the possibility to discriminate the diets of cows in different animal compartments and to study the fate of dietary FAs in the bovine organism, using carbon isotopic ratios. Five FAs, both essential (linoleic and linolenic) and non-essential (palmitic, stearic, and oleic) in four compartments (feed, rumen, liver, meat) of animals fed two different diets (based on either C3 or C4 plants) were considered. For all compartments, the carbon isotopic ratio (δ13C) of all FAs (with few exceptions) resulted significantly lower in cows fed on C3 than C4 plants, figuring as a powerful tool to discriminate between different diets. Moreover, chemical reactions taking place in each animal compartment result in fraction processes affecting the δ13C values. The δ13CFAs tendentially increase from feed to meat in group C3. On the other hand, the δ13CFAs generally increase from rumen to liver in group C4, while δ13CFAs of rumen and meat are mostly not statistically different. Different trends in the δ13CFAs of the two groups suggested different FAs fates depending on the die

A Real-World, Multicenter, Observational Retrospective Study of Durvalumab After Concomitant or Sequential Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer

Introduction: For unresectable stage III non-small cell lung cancer (NSCLC), the standard therapy consists of chemoradiotherapy (CRT) followed by durvalumab maintenance for responding patients. The present study reports on the safety and outcome of durvalumab use after CRT in a real-world, multicenter, retrospective cohort. Methods: Two hundred thirty-eight patients have been included. We collected data on systemic therapy, radiation therapy, the timing between CRT and durvalumab, number of durvalumab cycles, reasons for non-starting or discontinuation, incidence and grade of adverse events (AEs), and progression-free survival (PFS) and overall survival (OS). Results: One hundred fifty-five patients out of 238 (65.1%) received at least one durvalumab dose: 91 (58.7%) after concomitant CRT (cCRT) and 64 (41.3%) after sequential CRT (sCRT). Programmed-death ligand 1 (PD-L1) status was unknown in 7/155 (4.5%), negative in 14 (9.1%), and positive ≥1% in 134/155 (86.4%). The main reasons for non-starting durvalumab were progression (10.1%), PD-L1 negativity (7.5%), and lung toxicity (4.6%). Median follow-up time was 14 months (range 2–29); 1-year PFS and OS were 83.5% (95%CI: 77.6–89.7) and 97.2% (95%CI: 94.6–99.9), respectively. No significant differences in PFS or OS were detected for cCRT vs. sCRT, but the median PFS was 13.5 months for sCRT vs. 23 months for cCRT. Potentially immune-related AEs were recorded in 76/155 patients (49.0%). Pneumonitis was the most frequent, leading to discontinuation in 11/155 patients (7.1%). Conclusions: Durvalumab maintenenace after concurrent or sequential chemoradiation for unresectable, stage III NSCLC showed very promising short-term survival results in a large, multicenter, restrospective, real-world study. Durvalumab was the first drug obtaining a survival benefit over CRT within the past two decades, and the present study contributes to validating its use in clinical practice

PET/CT And The Response To Immunotherapy In Lung Cancer

In the recent years, the introduction of immune checkpoint inhibitors has significantly changed the outcome of patients affected by lung cancer and cutaneous melanoma. Although the clinical advantages, the selection of patients and the evaluation of response to immunotherapy remain unclear. The immune-related Response Evaluation Criteria in Solid Tumor (irRECIST) was proposed as an update of the RECIST criteria for the assessment of response to immunotherapy. However, morphological images cannot predict the early response to therapy that represents a challenge in clinical practice. 18F-FDG PET/CT before and after immunotherapy has an indeterminate role, demonstrating ambiguous results due to inflammatory effects secondary to the activation of immune system. The aim of the present review was to analyze the role of PET/CT as a guide for immunotherapy, by analyzing the current status and future perspectives

Electrochemotherapy for Superficially Metastatic Melanoma

Cutaneous metastases are not unusual in the clinical course of malignant melanoma, occurring in 2\u201320 % of patients, depending on primary tumor features and disease stage. Patients with superficially metastatic melanoma comprise a heterogeneous group as to prognosis, including those with local recurrences, satellite nodules, and in-transit metastases (stages IIIB and IIIC), as well as those with distant skin, subcutaneous, and soft tissue metastases (stage IV-M1a disease). Patients with superficially metastatic melanoma have peculiar supportive care needs due to increased psychosocial distress and wound care. Local treatment with electrochemotherapy (ECT) has been introduced in the management of melanoma since the 1990s. In these early clinical experiences, ECT showed sustained antitumor activity and favorable toxicity profile. In 2006, the procedure was standardized, and the European Standard Operating Procedure of electrochemotherapy (ESOPE) entered the routine practice of dermato-oncology. More recent experiences confirm ECT as a valuable tool that ensures prolonged local control (2-year local progression-free survival estimated 74\u201387 %), particularly in patients with locoregional disease and few, small tumor nodules. Unfortunately, the majority of patients require further ECT cycles due to disease progression outside treatment field. As a consequence, treatment intent can range from curative to merely palliative. To overcome this hurdle, researchers are actively investigating the way to implement electroporation technology as well as to rationally combine local ECT treatment with newly available immune (anti-CTLA4 [cytotoxic T-lymphocyte-associated antigen 4], anti-PD1 [programmed death-1]), or targeted (BRAF and MEK inhibitors) therapies, which have greatly improved patient survival during the past few years. In the meantime, it is advisable that clinicians recognize that the occurrence of skin metastases represents a troubling circumstance that requires immediate and focused attention. Before undergoing ECT, each patient should be managed by a multidisciplinary team, and its members should take into consideration the disparity in clinical course between patients with locoregional (in whom ECT intent can be curative) and distant metastases (in whom treatment intent is mainly palliative). Quality trial evidence is needed to clarify the impact of this innovative treatment for melanoma patients

Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance

The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment options for BSI caused by GNB with DTR, namely extended-spectrum Beta-lactamase-producing Enterobacteriales; carbapenem-resistant Enterobacteriales; DTR Pseudomonas aeruginosa; and DTR Acinetobacter baumannii

Carbon isotopic ratio of lipid fraction to trace fractionation processes in cull cows organism and to discriminate between different feeding regimes

In the present work, the quantification of the lipids and the carbon isotopic ratio (δ13C) of diet, rumen, liver and meat lipids of cows fed on different diets (based on either C3 or C4 plants) are provided. The δ13C of the four compartments had different trends in the two diets, which could give information about the fractionation processes and the factors influencing the lipids metabolic path in cows fed on different regimes. The δ13C of liver and meat lipids resulted to be statistically different for cows of groups C3 and C4, and can therefore be a suitable tool to discriminate between the two groups