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Purpose: To evaluate the clinical–pathological and prognostic significance of the circulating PD-L1 level in patients with surgically treated NSCLC, by combining data for PD-L1 expression with other immune-related markers and tumor metabolism. Methods: Overall, 40 patients with resected NSCLC (stage Ia–IIIa) who had preoperative blood storage and underwent staging PET/CT were enrolled for the study. In all cases, we determined plasma levels of PD-L1 (pg/ml), immune-reactive areas (IRA %) covered by CD3, CD68, CD20, CD8, PD-1, and PD-L1 in the tumor specimen, and metabolic parameters on PET, i.e., SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Variables were statistically analyzed to establish their association with disease-free survival (DFS). Results: The circulating levels of PD-L1 in the bloodstream could be determined in 38/40 (95%) samples. The mean and median expression levels were 34.86 pg/ml and 24.83 pg/ml, respectively. We did not find any statistically significant correlation between circulating PD-L1 and tissue expression of PD-L1/PD-1. Some mild degree of positive correlation was determined between tissue PD-L1 and SUVmax (ρ = 0.390; p = 0.0148). Hierarchical clustering combining circulating, tissue, and metabolic parameters identified clusters with high metabolic tumor burden or high expression of plasma PD-L1 levels (Z score ≥ 2) as having a poor DFS (p = 0.033). The multivariate analysis detected stage and metabolism (i.e., SUVmax and SUVpeak) as independent prognostic factors for DFS. Conclusion: Plasma levels of PD-L1 are independent of the expression of PD-1/PD-L1 in NSCLC tumor tissue and, when combined with other clinical–pathological parameters, allow for the identification of clusters with different outcomes. [ABSTRACT FROM AUTHOR]

Mutations in the TREM2 gene confer risk for Alzheimer's disease and susceptibility for Parkinson's disease (PD). We evaluated the effect of TREM2 deletion in a 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)–induced PD mouse model, measuring neurodegeneration and microglia activation using a combined in vivo imaging and postmortem molecular approach. In wild-type mice, MPTP administration induced a progressive decrease of [ 11 C]FECIT uptake, culminating at day 7. Neuronal loss was accompanied by an increase of TREM2, IL-1β, and translocator protein (TSPO) transcript levels, [ 11 C]PK11195 binding and GFAP staining (from day 2), and an early and transient increase of TNF-α, Galectin-3, and Iba-1 (from day 1). In TREM2 null (TREM2 −/− ) mice, MPTP similarly affected neuron viability and microglial cells, as shown by the lower level of Iba-1 staining in basal condition, and reduced increment of Iba-1, TNF-α, and IL-1β in response to MPTP. Likely to compensate for TREM2 absence, TREM2 −/− mice showed an earlier increment of [ 11 C]PK11195 binding and a significant increase of IL-4. Taken together, our data demonstrate a central role of TREM2 in the regulation of microglia response to acute neurotoxic insults and suggest a potential modulatory role of TSPO in response to immune system deficit. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The prognosis of malignant gliomas remains largely unsatisfactory for the intrinsic characteristics of the pathology and for the delayed diagnosis. Multimodal imaging based on PET and MRI may assess the dynamics of disease onset and progression allowing the validation of preclinical models of glioblastoma multiforme (GBM). The aim of this study was the characterization of a syngeneic rat model of GBM using combined in vivo imaging and immunohistochemistry. Methods: Four groups of Fischer rats were implanted in a subcortical region with increasing concentration of rat glioma F98 cells and weekly monitored with Gd-MR, [18F]FDG- and [18F]FAZA-PET starting one week after surgery. Different targets were evaluated on post mortem brain specimens using immunohistochemistry: VEGF, GFAP, HIF-1α, Ki-67 and nestin. Results: Imaging results indicated that tumor onset but not progression was related to the number of F98 cells. Hypoxic regions identified with [18F]FAZA and high-glucose metabolism regions recognized with [18F]FDG were located respectively in the core and in external areas of the tumor, with partial overlap and remodeling during disease progression. Histological and immunohistochemical analysis confirmed PET/MRI results and revealed that our model resumes biological characteristics of human GBM. IHC and PET studies showed that necrotic regions, defined on the basis of [18F]FDG uptake reduction, may include hypoxic clusters of vital tumor tissue identified with [18F]FAZA. This last information is particularly relevant for the identification of the target volume during image-guided radiotherapy. Conclusions: In conclusion, the combined use of PET and MRI allows in vivo monitoring of the biological modification of F98 lesions during tumor progression. [Copyright &y& Elsevier]

Abstract: The quinoline nucleus of the previously described 4-phenylquinoline-3-carboxamides NK1 receptor ligands 7 has been transformed into either substituted or azole—(i.e., triazole or tetrazole) fused pyridine moieties of compounds 9 and 10, respectively, in order to obtain NK1 receptor ligands showing lower molecular weight or higher hydrophilicity. The program of molecular manipulations produced NK1 receptor ligands showing affinity in the nanomolar range. In particular, 4-methyl-1-piperazinyl derivative 9j showed an IC50 value of 4.8nM and was proved to behave as a NK1 antagonist blocking Sar9-SP-sulfone induced proliferation and migration of microvascular endothelial cells. Therefore, compound 9j has been labeled with [11C]CH3I (t 1/2 =20.4min, β + =99.8%) starting from the corresponding des-methyl precursor 9i using with a radiochemical yield of about 10% (not decay corrected) and a specific radioactivity>1Ci/μmol in order to be used as a radiotracer in next PET studies. [Copyright &y& Elsevier]

Introduction: Streptococcus pneumoniae (Spn) is occasionally implicated as a cause of intra-abdominal infection (IIASpn) that can be 1) spontaneous bacterial peritonitis (SBP) in elderly patients with previous peritoneal disease, associated with cirrhosis, in most of the cases 2) associated or adjacent to an intra-abdominal organ or postsurgical. (IIAbq) 3) peritonitis in previously healthy young women (PHYW). Our objective is report 18 cases of IIASpn describing: clinical presentation, comorbidities, need for surgery, microbiological findings, sensitivity of Spn to antimicrobials, therapeutic behavior, and evolution., Methods: study of 18 adult patients with IIASpn. Clinical and microbiological characteristics and evolution of infections were analyzed., Results: IIASpn occurred in 9 PHYW, 6 men and 1 woman with SBP, and 2 men with appendicitis. The PHYW were operated on (4 pelviperitonitis, 3 salpingitis, 2 and tubo ovarian abscess) and had a favorable evolution. In the intraoperative samples, pure culture of Spn sensitive to penicillin was isolated. Three of four patients had positive blood culture. Five of seven patients with SBP died and in the peritoneal fluid developed Spn in pure culture. A large percentage of strains presented decreased sensitivity to penicillin. Four of five had a positive blood culture. Patients with appendicitis had favorable evolution., Conclusions: IIASpn in PHYW was the most frequent presentation, surgery played a significant role in treatment and the clinical response was excellent. The second presentation occurred in elderly patients with cirrhosis, most of whom died. Appendicitis was the third presentation in patients who evolved favorably., (Universidad Nacional de Córdoba)

Introduction: Aeromonas is a common cause of gastroenteritis but occasionally it can cause extraintestinal infections. The incidence of bacteremia by this genus is very low and in general the patients have associated base diseases., Materials and Methods: Retrospective analysis of episodes of bacteremia by Aeromonas spp. during a period of eight years in the National Hospital of Clinics of the city of Córdoba, emphasizing age, sex, associated comorbidities, clinical presentation, focus, origin of the infection, clinical evolution, species prevalence and antimicrobial sensitivity of the same ., Results: 10 episodes of bacteremia were recorded by Aeromonas spp. 60% corresponded to women and 40% to men. The average age was 65 years. In seven patients the origin of the infection was community and in three nosocomial. 70% of the patients presented predisposing base pathologies. The focus of bacteremia was abdominal in two cases. A. hydrophila complex was responsible for 50% of the cases. 80% of bacteremia were monomicrobial. The isolates generally showed high percentages of sensitivity., Conclusion: Bacteremia occurred in elderly patients of both sexes, most of whom had associated comorbidities. The majority of the infections originated in the community. While bacteremia by Aeromonas spp. it is rare, the mortality found in our study was relatively high despite the high percentage of sensitivity to antimicrobials., (Universidad Nacional de Córdoba)

Introduction: Streptococcus agalactiae (GBS) is a recognized pathogen associated with infections in newborns and small infants, pregnant women, and puerperal women. In recent years there has been an increase in infections by this agent in non-pregnant adult patients, being more frequent in people over 65 years of age and with some comorbidity., Methods: retrospective and observational study of samples from non-pregnant adult patients analyzed in the Bacteriology Laboratory of the Hospital Nacional de Clínicas of the city of Córdoba, from January 2008 to December 2017. Age and sex of the patients, comorbidities, and type of sample were analyzed shows., Results: The total of positive samples was 187, 91 (49%) corresponded to women and 96 (51%) to men. The average age was 67 years. Of the samples, urine was the prevalent one with 90 isolates (48.1%), followed by blood with 39 (20.8%) and skin and soft tissues with 38 (20.3%). Of the 187 adults, 177 (95%) had at least one comorbidity, the most frequent being diabetes, followed by neoplasms. Only 10 (5%) did not present comorbidities., Conclusions: The findings in our work, as well as those published by various authors, show the need to consider Streptococcus agalactiae not only a pathogen of neonates and pregnant women, but also of elderly patients with different comorbidities, especially those who suffer from DBT or neoplasia., (Revista de la Facultad de Ciencias Médicas de Córdoba)

Background Community acquired urinary tract infections (caUTI) in adults are common ailments. Older adults are prone to infectious diseases, diagnosis can be difficult, their etiologic and antimicrobial resistance are poorly known. Objectives To evaluate the incidence discriminated by sex, symptoms, and to determine pathogens and their antimicrobial resistance rate. Methods A retrospective, descriptive and comparative study. We analyze uricultures among 2013 in the Hospital Nacional de Clinicas (Córdoba-Argentina). Patients over 65 years old, admitted with a caUTI diagnose were included; we exclude those with urinary catheter. Variables used: Sex, symptoms, pathogen isolation, antimicrobial resistance. For symptom variable was performed a comparative test. Descriptive statistics were used to analyze remaining variables. Results Were analyzed 349 patients: 1) Positive uricultures 191 (case), negative 158 (control). 2) Average age 77 (76% women, 24% men). 3) Symptoms: fever (45%), sepsis criteria (17%), altered mental status (14%), heart failure (11%). 4) Uriculture: monomicrobial 95.29%. 5) Isolation and resistance rate: Escherichia coli (67,7%): ampicillin/sulbactam 52.7%, ciprofloxacin 51.9%, trimethoprim/sulfamethoxazole 45.7%, cefotaxime: 12,9 %, amikacin: 3,9 %, Klebsiella pneumoniae (11,97%): ciprofloxacin 60.8%, trimethoprim/ sulfamethoxazole 50%, cefotaxime 47.8%, amikacin 4.7%. Enterococcus spp. (9,89%): ampicillin 0%, vancomycin 0%. Also isolated: Cándida spp. (3.66%), Proteus mirabilis (2,6%), Staphylococcus aureus (2,6%), Enterobacter cloacae (1,56%), Pseudomonas aeruginosa (1,56%). There were no imipenem resistances among gram negatives. Conclusions Isolations were mostly monomicrobial and at female gender. E. coli was the main uropathogen. The elevated resistance rate to ciprofloxacin, ampicillin/sulbactam and trimethoprim/sulfamethoxazole is remarkable. We suggest to avoid their empiric use in this population.

Microorganisms of the genera Corynebacterium, specie pseudodiphtheriticum are a part of the indigenous microbiota of human skin and oropharinx. Nevertheless in recent decades these bacilli are emerging as opportunistic pathogens causing clinically significant infections in patients with previous compromise. We report the case of a 76 years old female patient, with a history of hypertension, hypothyroidism, type 2 diabetes and chronic renal failure, who presented pneumonia during their stay at the intensive care unit. The induced sputum revealed a representative sample with monomicrobial gram positive pleomorphic coryneform rods (Gram stain) and cultures demonstrated the presence of C. pseudodiphtheriticum as the only bacteria recovered. The pacient received an empirical third generation cephalosporin medication with a succesfull recovery., (Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Enterococcal bacteremia has acquired considerable importance in recent years, mainly due to an increased number of cases that occur during hospital admission. We describe the episodes of enterococcal bacteremia in adult patients recorded at our hospital. Between January 2000 and December 2013, 117 episodes were analyzed. Sixty one percent (61%) of the patients were male and 39% female. The mean age was 68. Predisposing factors were present in 91% of patients. The primary source of infection was intraabdominal. Enterococcus faecalis was responsible for 65% of the cases; E. faecium for 28%; and other species for 7%. Thirty four percent (34%) of cases were polymicrobial bacteremia. All E. faecalis isolates were susceptible to ampicillin and vancomycin. Eighty eight percent (88%) of E. faecium were resistant to ampicillin and 54% to vancomycin and teicoplanin. In our hospital, Enterococcus is the sixth pathogen causing nosocomial bacteremia, with high incidence of ampicillin and vancomycin-resistant E. faecium., (Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Bacteremia is an important cause of morbimortality. This study describes the episodes of communityacquired bacteremia in adult patients registered at our hospital. Between January 2005 and December 2013, 645 episodes were studied. A total of 51% of patients were male and 49% female. The mean age was 67. The most frequent comorbidities were: diabetes (18%), neoplasia (15%), heart disease (10%) and HIV infection (6%). The focus was: urinary (22%), respiratory (18%), cutaneous (15%), abdominal (13%), and others (4%). Gram-negative bacteria prevailed (51.88%). The most frequent microorganisms were Escherichia coli (30.29%), Streptococcus pneumoniae (15.51%), y Staphylococcus aureus (14.06%). Bacteremia was polymicrobial in 7.14% of the cases. Forty percent of E. coli isolates were resistant to ciprofloxacin and 6% to ceftazidime. Fifteen percent of S. aureus strains were resistant to methicillin whereas only 7% of S. pneumoniae expressed high resistance to penicillin with MICs = 2 µg/ mL, according to meningitis breakpoints.

Bacteremia is an important cause of morbimortality. This study describes the episodes of community-acquired bacteremia in adult patients registered at our hospital. Between January 2005, and December 2009, 271 episodes were studied. The diagnostic yield of blood cultures was 13.5 %. A total of 52 % of patients were male and 48 % female. The mean age was 60. The most frequent comorbidities were: diabetes (21 %), neoplasia (18 %), cardiopathy (11 %), and HIV infection (8 %). The focus was- respiratory (21 %), urinary (15 %), cutaneous (9 %), and others (13 %). Gram-positive bacteria prevailed (51.4%). The most frequent microorganisms were Escherichia coli (25 %), Streptococcus pneumoniae (22.9 %), and Staphylococcus aureus (12.3 %). Bacteremia was polymicrobial in 7 % of the cases. Thirty three percent of E. coli isolates were resistant to ciprofloxacin and 6 % to ceftazidime. Fourteen percent of S. aureus strains were resistant to oxacillin whereas only 7 % of S. pneumoniae expressed high resistance to penicillin with MICs = 2 ug/ml, according to meningitis breakpoints.

Bacteremia continues to be one of the main causes of morbidity and mortality in adult patients despite the existence of numerous antimicrobial agents and an increase in support measures. The aim of this study was to analyze the cases of community and hospital-acquired bacteremia, by evaluating the prevalence of species, risk factors, source of infection and antimicrobial susceptibility of the microorganisms involved. From January 2000 to December 2004, 129 cases of bacteremia due to enterobacteria were detected in 45 outpatients (35%) and 84 inpatients (65%). The most common risk factors were neoplasia (33.3%) and diabetes (12.4%); being urinary (29.5%) and abdominal (13.9%) the most frequently found sources of infection. E. coli was the most common enterobacteria isolated in both populations, followed by Klebsiella spp. (21.7%), and Enterobacter spp. (12.4%). Klebsiella spp. bacteremia was most common in ICU patients and, together with Enterobacter spp., constituted the most antibiotic-resistant microorganisms.

Between April 1, 1999 and June 30, 2000, 144 isolates of enterococci (one per patient) from cultures of several anatomic sites were collected. One hundred and nineteen (82.6%) E. faecalis, 11 (7.6%) E. faecium and 14 (9.7%) of other species (5 E. raffinosus, 4 E. avium, 3 E. casseliflavus, 1 E. pseudoavium, and 1 E. dispar) were associated with clinical infections. The most common sites of isolation were: the urinary tract 54.9%, abdominal cavity 12.5%, surgical wounds 12.5%, abscesses 6.9% and diabetic foot 6.2%. High-level resistance to gentamicin or streptomycin or both was detected in 48.6% of the isolates. E. faecium and E. raffinosus were significantly more resistant than E. faecalis to ampicilin and imipenem. None of the strains exhibited beta-lactamase activity. One strain of E. faecium (0.7%) was resistant to vancomicin and teicoplanin (Van A phenotype) and two strains of E. casseliflavus (1.4%) showed low level of resistance to vancomicin (Van C phenotype). Because of these diverse antimicrobial resistance mechanisms, successful treatment and control of enterococcal infections with current antimicrobial agents are becoming increasingly difficult.

The purpose of this work was to evaluate the efficacy and safety of a single dose of 400 mg of fleroxacin for the empiric antibiotic treatment of acute diarrhea in adult patients. A prospective, double-blind, placebo-controlled, randomized trial was designed. All the adult patients who consulted in our hospital for acute diarrhea from December 1994 to April 1995 were included. 72 patients were randomized to receive a single dose of fleroxacin 400 mg and 73 were placebo. Thirty-eight patients in each group were evaluable for efficacy. Between both groups there were not statistically significant differences in age, sex, number of loose stools per day at inclusion, days since the onset of symptoms up to inclusion, other symptoms than diarrhea at inclusion, percentages of bacterial pathogens and parasites isolated and symptomatic treatment indicated. At the third day since inclusion, clinical cure occurred in 72.2% of the patients receiving fleroxacin, compared with 36.4% of those receiving placebo; p = 0.002. The mean +/- SD time to cure was 2.2 +/- 1.2 days in the fleroxacin group and 3.2 +/- 2.0 days in the placebo group; p = 0.01. Twenty-eight and 16.7% of patients reported adverse effects in the fleroxacin and placebo groups respectively; p = 0.3. It is concluded that a single dose of fleroxacin 400 mg is an effective and safe alternative for the empiric antibiotic treatment of acute diarrhea in adults.

Lactobacillus endocarditis is a rare infection. In fact, only 42 cases have been described in the literature from 1938 up to date. In only 17 previously reported cases have patients been cured with medical therapy alone. Although infections produced by Lactobacillus spp, have been described in our country, none of them included endocarditis. We report herein a case of endocarditis due to a vancomycin-resistant strain of Lactobacillus casei sub. rhamnosus in a 29-year-old man with prolapse of the mitral valve. He required surgical replacement of his valve because of the poor response to antimicrobial therapy with penicillin and gentamicin. The patient displayed a successful clinical outcome, with no evidence of recurrence along the subsequent 2 years. We point out the need to accurately identify Lactobacillus spp. in isolates from blood cultures of patients with endocarditis, since these bacteria may often be mistaken for other species more frequently associated to this infection, which usually respond to conventional antimicrobial therapy. Furthermore, we suggest that early surgical replacement should be considered when lactobacillus endocarditis is diagnosed.

Results of an investigation of 134 subjects with atopic dermatitis and 29 controls are described. The investigation involved: 1) an allergological enquiry into each patient's medical history, with particular reference to consumption of eggs, milk and fish; 2) a total IgE assay; 3) RAST with egg, milk, cod; 4) a challenge test. Recording of medical histories revealed the existence of clinical sensitivity to egg, milk and cod in respectively 21, 17 and 7 of the 134 subjects with atopic dermatitis, but in none of the controls. In the atopic subjects, RAST demonstrated egg, milk and cod antibodies in 37, 28 and 14 cases respectively, while of the controls only 2 had antibodies--and then in minimal amounts. The maximum incidence of egg and milk antibodies was demonstrated in the initial 3 years of life. Clinical sensitization to cod manifests itself in the form of attacks (urticaria, angi-oedema, vomiting) showing significant correlation between clinical history, results of RAST and the response to challenge, while in the case of sensitivity to eggs and, even less evidently, to milk, the symptoms are more often referred to as "exacerbation of the dermatosis" and the results of RAST, of challenging and the clinical history tend to be contradictory.