Metformin: a modulator of bevacizumab activity in cancer? A case report.

Recurrent type I endometrial cancer ((EC)) has poor prognosis and demands novel therapeutic approaches. Bevacizumab, a VEGF-A neutralizing monoclonal antibody, has shown clinical activity in this setting. To our knowledge, however, although some diabetic cancer patients treated with bevacizumab may also take metformin, whether metformin modulates response to anti-VEGF therapy has not yet been investigated. Here, we report the case of a patient with advanced (EC) treated, among other drugs, with bevacizumab in combination with metformin. The patient affected by relapsed (EC) G3 type 1, presented in march 2010 with liver, lungs and mediastinic metastases. After six cycles of paclitaxel and cisplatin she underwent partial response. Later on, she had disease progression notwithstanding administration of multiple lines of chemotherapy. In march 2013, due to brain metastases with coma, she began steroid therapy with development of secondary diabetes. At this time, administration of Bevacizumab plus Metformin improved her performance status. CT scans performed in this time window showed reduced radiologic density of the lung and mediastinic lesions and of liver disease, suggestive of increased tumor necrosis. Strong F-18-FDG uptake by PET imaging along with high levels of monocarboxylate transporter 4 and lack of liver kinase B1 expression in liver metastasis, highlighted metabolic features previously associated with response to anti-VEGF therapy and phenformin in preclinical models. However, clinical benefit was transitory and was followed by rapid and fatal disease progression. These findingsalbeit limited to a single casesuggest that tumors lacking LKB1 expression and/or endowed with an highly glycolytic phenotype might develop large necrotic areas following combined treatment with metformin plus bevacizumab. As metformin is widely used among diabetes patients as well as in ongoing clinical trials in cancer patients, these results deserve further clinical investigation

Prulifloxacin: a brief review of its potential in the treatment of acute exacerbation of chronic bronchitis

Exacerbations of chronic bronchitis (AECB) are a major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), and their impact on public health is increasing. The new fluoroquinolones have an excellent spectrum providing cover for the most important respiratory pathogens, including atypical and “typical” pathogens. Not surprisingly, different guidelines have inserted these agents among the drugs of choice in the empirical therapy of AECB. The pharmacokinetic and dynamic properties of the new fluoroquinolones have a significant impact on their clinical and bacteriological efficacy. They cause a concentration-dependent killing with a sustained post-antibiotic effect. This review discusses the most recent data on the new fluoroquinolone prulifloxacin and critically analyses its activity and safety in the management of AECB

Microbiological testing of adults hospitalised with community-acquired pneumonia: an international study

This study aimed to describe real-life microbiological testing of adults hospitalised with community-acquired pneumonia (CAP) and to assess concordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) and 2011 European Respiratory Society (ERS) CAP guidelines. This was a cohort study based on the Global Initiative for Methicillin-resistant Staphylococcus aureusPneumonia (GLIMP) database, which contains point-prevalence data on adults hospitalised with CAP across 54 countries during 2015. In total, 3702 patients were included. Testing was performed in 3217 patients, and included blood culture (71.1%), sputum culture (61.8%), Legionella urinary antigen test (30.1%), pneumococcal urinary antigen test (30.0%), viral testing (14.9%), acute-phase serology (8.8%), bronchoalveolar lavage culture (8.4%) and pleural fluid culture (3.2%). A pathogen was detected in 1173 (36.5%) patients. Testing attitudes varied significantly according to geography and disease severity. Testing was concordant with IDSA/ATS and ERS guidelines in 16.7% and 23.9% of patients, respectively. IDSA/ATS concordance was higher in Europe than in North America (21.5% versus 9.8%; p\u3c0.01), while ERS concordance was higher in North America than in Europe (33.5% versus 19.5%; p\u3c0.01). Testing practices of adults hospitalised with CAP varied significantly by geography and disease severity. There was a wide discordance between real-life testing practices and IDSA/ATS/ERS guideline recommendations

What is important for people with nontuberculous mycobacterial disease? An EMBARC-ELF patient survey

Experiencias de los pacientes; Enfermedad pulmonarExperiències dels pacients; Malaltia pulmonarPatient experiences; Lung diseasePatients' experiences of NTM pulmonary disease highlight important and unmet needs for better pharmacological treatment and education of medical staffEuropean Respiratory Society (EMBARC Clinical Research Collaboration

A comprehensive analysis of the impact of <i>Pseudomonas aeruginosa</i> colonization on prognosis in adult bronchiectasis

Rationale: Eradication and suppression of Pseudomonas aeruginosa is a key priority in national guidelines for bronchiectasis and is a major focus of drug development and clinical trials. An accurate estimation of the clinical impact of P. aeruginosa in bronchiectasis is therefore essential. Methods: Data derived from 21 observational cohort studies comparing patients with P. aeruginosa colonization with those without it were pooled by random effects meta-analysis. Data were collected for key longitudinal clinical outcomes of mortality, hospital admissions, exacerbations, and lung function decline, along with cross-sectional outcomes such as quality of life. MeasurementsandMainResults: In the aggregate, the included studies comprised 3,683 patients. P. aeruginosa was associated with a highly significant and consistent increase in all markers of disease severity, including mortality (odds ratio [OR], 2.95; 95% confidence interval [CI], 1.98-4.40; P <0.0001), hospital admissions (OR, 6.57; 95% CI, 3.19-13.51; P <0.0001), and exacerbations (mean difference, 0.97/yr; 95% CI, 0.64-1.30; P <0.0001). The patients with P. aeruginosa also had worse quality of life on the basis of their St. George's Respiratory Questionnaire results (mean difference, 18.2 points; 95% CI, 14.7-21.8; P <0.0001). Large differences in lung function and radiological severity were also observed. The definitions of colonization were inconsistent among the studies, but the findings were robust regardless of the definition used. Conclusion: P. aeruginosa is associated with an approximately threefold increased risk of death and an increase in hospital admissions and exacerbations in adult bronchiectasis

Evaluation of severity score-guided approaches to macrolide use in community-acquired pneumonia

International guidelines including those in the UK, Japan, Australia and South Africa recommend the avoidance of macrolides in patients with low-severity community-acquired pneumonia (CAP). We hypothesised that severity scores are poor predictors of atypical pneumonia and response to macrolide therapy, and thus, inadequate tools for guiding antibiotic prescriptions. Secondary analysis of four independent prospective CAP datasets was conducted. The predictive values of the CURB-65 and pneumonia severity index (PSI) for clinically important groups of causative pathogens were evaluated. The effect of macrolide use according to risk class was assessed by multivariable analysis. Patients (3297) were evaluated, and the predictive values of CURB-65 and PSI for atypical pathogens were poor (AUC values of 0.37 and 0.42, respectively). No significant differences were noted among the effects of macrolide use on mortality in patients with mild, moderate and severe CAP, according to either CURB-65 (interaction testing severe versus mild disease OR=0.74 (0.29–1.89)) or PSI (severe versus mild disease OR=3.4 (0.055–2.10)), indicating that severity scores were not significant modifiers of response to macrolide therapy. Severity scores did not accurately predict response to macrolide therapy in CAP, suggesting that current guidance to use these tools for empirical antibiotic choices might not be justified

Chronic infection with non-tuberculous mycobacteria in patients with non-CF bronchiectasis: Comparison with other pathogens

Abstract Introduction The aim of this study is to compare characteristics of non-cystic fibrosis bronchiectasis (NCFBE) patients with chronic infections with non-tuberculous mycobacteria (NTM) versus those with Pseudomonas aeruginosa or other colonizations. Methods This was an observational, perspective study of consecutive NCFBE adult patients attending the outpatient bronchiectasis clinic at the San Gerardo Hospital in Monza, Italy, during 2012 and 2013. Patients with a chronic infection were included in the study and divided into three groups: those with NTM (Group A); those with P. aeruginosa (Group B); and those with other pathogens (Group C). Patients with both NTM and another pathogen were included in Group A. Comparison among the three study groups was performed using X 2 or Fisher exact test for categorical variables or Kruskal–Wallis or Mann–Whitney test for continuous variables. Results A total of 146 patients (median age 67 years, 40% males) were enrolled: 19 belonged to Group A, 34 to Group B and 93 to Group C. Within group A, 6 patients had only NTM isolation, 7 patients had NTM and P. aeruginosa co-infection and 6 patients had NTM plus another pathogen. The most common isolated pathogens among NTM was Mycobacterium avium complex (15 patients, 79%). A total of 4 patients (21%) with NTM were on active treatment. Patients affected by NTM pulmonary infection had a significantly less severe clinical, functional and radiological involvement compared with patients colonized by P. aeruginosa , see Table. Group A (NTM) n = 19 Group B ( P. aeruginosa ) n = 34 Group C (Others) n = 93 p Value ∗ p Value # p Value + Age (years), median (IQR) 70 (64–75) 74 (67–79) 66 (53–72) 0.001 0.172 0.050 Male, n (%) 8 (42) 15 (44) 36 (33) 0.660 – – BMI, median (IQR) 22 (19–26) 24 (21–25) 24 (21–27) 0.352 – – BSI, median (IQR) 5 (4–9) 12 (8.5–16) 5 (3–7) 0.001 0.001 0.090 Bhalla score, median (IQR) 21 (15–34) 36 (30.5–40.5) 16 (10.5–21.5) 0.001 0.016 0.076 Idiopathic etiology, n (%) 8 (42) 11 (32) 37 (40) 0.721 – – Post-infective etiology, n (%) 8 (42) 16 (47) 29 (31) 0.244 – – Exacerbations/y, median (IQR) 1 (0–2) 2 (1.5–3.5) 2 (1–2) 0.040 0.024 0.132 FEV1%, median (IQR) 85 (59.75–109.5) 58.5 (48.25–74) 84 (62–102) 0.002 0.010 0.857 FVC%, median (IQR) 94.5 (70–109.75) 65 (56–81.5) 88 (69.5–101.5) 0.003 0.003 0.270 ∗ Among the three groups: # Group A vs. Group B; + Group A vs. Group C; BMI: Body mass index; BSI: bronchiectasis severity index; y: year. Conclusions Colonization with P. aeruginosa seems to have the highest impact on the clinical, functional and radiological status of patients with NCFBE. No specific characteristics may help to identify NTM versus other pathogen colonizations. Thus, diagnostics for atypical mycobacteria should be performed on all patients with NCFBE, as suggested by recent international guidelines