Characteristics of tumor-infiltrating lymphocytes prior to and during immune checkpoint inhibitor therapy

The tumor immune contexture plays a major role for the clinical outcome of patients. High densities of CD45RO + T helper 1 cells and CD8 + T cells are associated with improved survival of patients with various cancer entities. In contrast, a higher frequency of tumor-infiltrating M2 macrophages is correlated with poor prognosis. Recent studies provide evidence that the tumor immune architecture also essentially contributes to the clinical efficacy of immune checkpoint inhibitor (CPI) therapy in patients. Pretreatment melanoma samples from patients who experienced a clinical response to anti-programmed cell death protein 1 (PD-1) treatment show higher densities of infiltrating CD8 + T cells compared to samples from patients that progressed during therapy. Anti-PD-1 therapy results in an increased density of tumor-infiltrating T lymphocytes in treatment responders. In addition, elevated frequencies of melanoma-infiltrating TCF7 + CD8 + T cells are correlated with beneficial clinical outcome of anti-PD-1-treated patients. In contrast, a high density of tumor-infiltrating, dysfunctional PD-1 + CD38 hi CD8 + cells in melanoma patients is associated with anti-PD-1 resistance. Such findings indicate that comprehensive tumor immune contexture profiling prior to and during CPI therapy may lead to the identification of underlying mechanisms for treatment response or resistance, and the design of improved immunotherapeutic strategies. Here, we focus on studies exploring the impact of intratumoral T and B cells at baseline on the clinical outcome of CPI-treated cancer patients. In addition, recent findings demonstrating the influence of CPIs on tumor-infiltrating lymphocytes are summarized

Different Patterns of Inappropriate Antimicrobial Use in Surgical and Medical Units at a Tertiary Care Hospital in Switzerland: A Prevalence Survey

Audits of individual patient care provide important data to identify local problems in antimicrobial prescription practice. In our study, antimicrobial prescriptions without indication, and divergence from institutional guidelines were frequent errors. Based on these results, we will tailor education, amend institutional guidelines and further develop the infectious diseases consultation service

JOURNAL OF CHEMOTHERAPY

Stenotrophomonas maltophilia is an important nosocomial pathogen with increasing frequency in recent years, especially in immunocompromised and clinically debilitated patients. The aim of this study is to describe the characteristics of 35 episodes of S. maltophilia bacteremia at Celal Bayar University hospital in Turkey over a 3-year period from January 2003 to December 2005. Cases were identified with microbiology laboratory records and clinical data were collected from the medical record of each patient. The source of bacteremia was central venous catheter (CVC) in 65.7% (23) and respiratory tract infection in 2.9% (1) of episodes while the source of bacteremia was unknown in 11 (31.4%) episodes of bacteremia. Factors significantly associated with mortality were age of >= 65 years, APACHE score of >= 16, the presence of the total parenterall nutrition, anemia, low creatinine clearance level and shock. The most sensitive antibiotic was found as trimethoprim-sulfamethoxazole (91.4%) in antibiotic susceptibility testing of the isolates. Susceptibilities of piperacillin-tazobactam and netilmicin which frequently used antibiotics as an empirical therapy were 62.8% and 68.6%, respectively

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS

The emergence of antibiotic resistant bacteria is a major problem throughout the world and a rational use of antibiotics is therefore very important. This study was performed to estimate the appropriateness of antimicrobial drug use in Celal Bayar University Hospital in Manisa. The data of all inpatients (n = 937) between October and December 1998 were collected according to the Kunin and Jones criteria. Of the patients, 16.6% (n = 156) were receiving antibiotics, and in 63.5, 23.0 and 13.5% of these, a single, two and three agents were used, respectively. The purpose of antibiotic use was for prophylaxis in 23.9%, as an empiric decision in 71.4% and for therapeutic culture-based reasons in 4.7%. The rate of rational antibiotic use was 45.7% and it was statistically higher in those patients from whom specimens had been taken for culture than in patients receiving prophylactic or empiric antibiotics. On medical wards, rational antibiotic usage was 55.1%, while it was 26.3% in surgical wards (P < 0.0001). The low rate of appropriate antibiotic use in our university hospital reflects the urgent need of rationalization. (C) 2000 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved

JNMS-JOURNAL OF THE NEUROMUSCULOSKELETAL SYSTEM

Psoas abscesses are rarely seen and usually misdiagnosed infections of the musculoskeletal system. A case of secondary psoas abscess due to Brucella spp. that was successfully treated with percutaneous computed tomography-guided aspiration and antimicrobial therapy is presented. The reported cases, diagnostic and therapeutic recommendations are also reviewed

SAUDI MEDICAL JOURNAL

Objective: To investigate if combination therapy with liposomal amphotericin B (LAmB), and caspofungin (CAS) is superior to monotherapies in an experimental model with azole-resistant Candida albicans Methods: This study was carried out between October 2006 and August 2007 in Celal Bayar University, Manisa, Turkey. A total of 144 mice were included in the study, and divided into 4 groups as: control (n=36), CAS treatment group (n=36), LAmB treatment group (n=36), and combination therapy group (n=36). Treatment efficacy was assessed by determining survival, as well as the decrease in tissue fungal densities. Results: The fungal densities in tissues were significantly reduced, and the survival rates were prolonged with either CAS only, or LAmB only, or with combination therapy compared to those of controls (p<0.05). There was no significant difference between monotherapy groups. Decrease in tissue fungal densities were significant in CAS and LAmB (1mg/kg) combination group, compared to CAS (1mg/kg) and LAmB (1mg/kg) groups (p=0.004 for CAS, p=0.009 for LAmB). Survival rates were similar in both treatment groups. Conclusion: The combination treatment was superior with 1mg/kg of doses of LAmB and CAS in terms of reducing the tissue fungal burden. Although with combination therapy the survival rates prolonged in all subgroups, no significant difference between the combination and monotherapies could be shown. Additional studies with a large number of cases are warranted to investigate the superiority of combination therapy

JOURNAL OF INFECTION IN DEVELOPING COUNTRIES

Background: Development of resistance to antimicrobial agents and increase of cost as the result of unnecessary and inappropriate use of antibiotics has become a global health problem. Therefore many strategies, which are aimed at optimizing antibiotic therapy, have been developed until now. In Turkey, an antibiotic restriction policy as a governmental solution was applied to decrease the antibiotic use and especially costs by Ministry of Health in 2003. The aim of this study is to evaluate the rational antibiotic use and the impact of the implementation of new restriction policy, with their reinforcement by infectious disease specialist, on the hospital wide use of antibiotics. Methodology: The data of the inpatients received antibiotics (n=495) during January-June 2006 were compared with our previous study performed by the same methodology before the restriction policy in 1998. In both studies, prospective active daily surveillance of patients was performed by three infectious disease specialists. The appropriateness of antibiotic therapy was determined using the criteria described by Kunin and Jones. The data were analyzed by using SPSS for Windows. Results: While the rate of antibiotic use decreased from 16.6% to 11.3%, rational use increased after the restriction policy (p<0.001). Besides the specific antibiotic use increasing, prophylactic antibiotic use was found decreased (p<0.001). Mostly determined irrationality was the prophylactic uses in both studies. As expected, infectious disease specialist examinations resulted in an increase in the appropriate antibiotic use. Conclusions: The restriction policy was effective in decreasing the antibiotic consumption and increasing the rational antibiotic prescription in our hospital

In vitro effectiveness of quinupristin/dalfopristin against Staphylococcus aureas strains

WOS: 000183033400018PubMed ID: 1272708