Baseline BMI and BMI variation during first line pembrolizumab in NSCLC patients with a PD-L1 expression >= 50%: a multicenter study with external validation

Background The association between obesity and outcomes in patients receiving programmed death-1/ programmed death ligand-1 (PD-L1) checkpoint inhibitors has already been confirmed in pre-treated non-small cell lung cancer (NSCLC) patients, regardless of PD-L1 tumor expression. Methods We present the outcomes analysis according to baseline body mass index (BMI) and BMI variation in a large cohort of metastatic NSCLC patients with a PD-L1 expression ≥50%, receiving first line pembrolizumab. We also evaluated a control cohort of metastatic NSCLC patients treated with first line platinum-based chemotherapy. Normal weight was set as control group. Results 962 patients and 426 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Obese patients had a significantly higher objective response rate (ORR) (OR=1.61 (95% CI: 1.04– 2.50)) in the pembrolizumab cohort, while overweight patients had a significantly lower ORR (OR=0.59 (95% CI: 0.37–0.92)) within the chemotherapy cohort. Obese patients had a significantly longer progression-free survival (PFS) (HR=0.61 (95% CI: 0.45–0.82)) in the pembrolizumab cohort. Conversely, they had a significantly shorter PFS in the chemotherapy cohort (HR=1.27 (95% CI: 1.01–1.60)). Obese patients had a significantly longer overall survival (OS) within the pembrolizumab cohort (HR=0.70 (95% CI: 0.49–0.99)), while no significant differences according to baseline BMI were found in the chemotherapy cohort. BMI variation significantly affected ORR, PFS and OS in both the pembrolizumab and the chemotherapy cohorts. Conclusions Baseline obesity is associated to significantly improved ORR, PFS and OS in metastatic NSCLC patients with a PD-L1 expression of ≥50%, receiving first line pembrolizumab, but not among patients treated with chemotherapy. BMI variation is also significantly related to clinical outcomes

Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients: A case–control matched analysis from a large multicenter study

Background: Improved outcome in tobacco smoking patients with non-small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first-line immunotherapy in patients with high PD-L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts. Methods: We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first-line pembrolizumab and platinum-based chemotherapy. Results: A total of 962 NSCLC patients with PD-L1 expression ≥50% who received first-line pembrolizumab and 462 NSCLC patients who received first-line platinum-based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio [HR] = 1.49 [95% CI: 1.15–1.92], p = 0.0022) and death (HR = 1.38 [95% CI: 1.02–1.87], p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 [95% CI: 0.52–1.05], p = 0.1003) and death (HR = 0.67 [95% CI: 0.45–1.01], p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case–control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression-free survival (PFS) (HR = 1.68 [95% CI: 1.17–2.40], p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 [95% CI: 0.84–2.07], p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 [95% CI: 0.49–0.95], p = 0.0255) and OS (HR = 0.66 [95% CI: 0.45–0.97], p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking status and treatment modality was concordantly statistically significant with respect to ORR (p = 0.0074), PFS (p = 0.0001) and OS (p = 0.0020), confirming the significantly different impact of smoking status across the two cohorts. Conclusions: Among metastatic NSCLC patients with PD-L1 expression ≥50% receiving first-line pembrolizumab, current/former smokers experienced improved PFS and OS. On the contrary, worse outcomes were reported among current/former smokers receiving first-line chemotherapy

Thoracentesis in cancer patients with severe thrombocytopenia: ultrasound guide improves safety

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Isolation and antibiotic resistance of Ureaplasma spp. isolated from urogenital specimen between 2002 to 2007

Ureaplasma spp. and Mycoplasma hominis are frequently isolated from urogenital samples. Ureaplasma spp is responsible for cervicovaginitis, salpingitis, urethritis, epididymitis, male and female infertility, spontaneous abortion, and during pregnancy, for the premature rupture of the membranes, because of chorionamnionitis. Our study aimed to establish the pattern of antimicrobial resistance among Ureaplasma spp isolated in the area of Andria,Apulia Region, from January 2002 to December 2007. 240/781 (30.7%) of the urogenital samples examined were found Ureaplasma spp.-positive. 152/240 (63.3 %) were >104 UFC/ml and 88/240 (36.7 %) were <104 UFC/ml. With regard to the resistance rate, we observed significant increase in resistance to ciprofloxacin, ofloxacin, erythromycin, clarithromycin, and azithromycin. While we did not observe resistance to doxycycline, strains resistant to tetracycline, josamycin, and pristinamycins, were isolated during last years of investigation. Our data may help improve the management of these infections above all in consideration of the differences among isolates in different geographic regions

Chronic cocaine administration modulates the expression of transcription factors involved in midbrain dopaminergic neuron function

Chronic cocaine use leads to pronounced alterations in neuronal functions in brain circuits associated with reward. In the present study, we examined in the rat midbrain the effects of acute, subchronic (5 days) and chronic cocaine treatments (14 days) on the gene expression of transcription factors involved in the development and maintenance of dopaminergic neurons. We show that chronic, but not acute or subchronic, cocaine administration downregulates Nurr1 and Pitx3 transcripts whereas En1 transcripts are upregulated. Conversely, Lmx1b and En2 transcripts are not affected by the drug treatment, indicating that the modulation of the midbrain transcription factors analyzed is highly selective. Interestingly, modification of the gene expression for these transcription factors persists in midbrain as long as two weeks after the last drug administration, suggesting that it may account for some of the enduring alterations in midbrain dopaminergic circuits associated with chronic cocaine us

Effects of Tolouidine blue-mediated photodinamic therapy on periopathogens and periodontal biofilm:in vitro evaluation

Photodynamic therapy (PDT) is a selective modality of killing targeted cells, mostly known for its application in neoplasms. PDT can be considered to be an alternative method for the elimination of periodontal bacteria from the pocket without harms for the resident tissues. Therefore, PDT may replace systemic antibiotics and enhance the effect of mechanical treatments of periodontal defects. This effort focused on the in vitro sensitization of periopathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia ) Toluidine Blue mediated and on the use of a Diode laser emitting source. The objective of this research was to evaluate the bactericidal in vitro effect of laser diodes 830 nm (as the light source) after photosensitization with Toluidine Blue (TBO) on the following periopathogenic bacteria: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia. After evaluating the effect on the single bacterial strain, the ability of Diode Laser to disrupt the structure of biofilms produced by A. actinomycetemcomitans after photosensitization with TBO was also analyzed. The study suggests that the association of TBO and diode laser light 830 nm is effective for the killing of bacteria strains and determines the photoinactivation of Aggregatibacter biofilms. In summary, photodynamic therapy has effectively shown its capabilities and, therefore, it can be considered a valid alternative approach to antimicrobial therapy of periodontitis

Photoexcitations in oriented tetrahexyl-sexithiophene thin films

We report the photoexcitation properties of alkyl substituted sexithiophene thin films grown on a single crystal of potassium acid phtalate by organic molecular-beam deposition. These films possess a layered supramolecular structure with anisotropic optical properties due to the preferential molecular orientation. The poorly structured photoluminescence spectra retain the polarization properties of the absorption, which are consistent with the emission originating from the weakly interacting bulk molecules as well as from molecules at the grain boundaries rather than from immobile x traps. The layered card pack structure combined with the presence of lateral alkyl chains results in a very weak electronic coupling between oligothiophene molecules in all but one direction, namely the card pack axis. This is clearly confirmed by the photoluminescence time decay, which is very well accounted for by a one-dimensional diffusion process towards nonradiative quenching centers within the oriented crystalline domains.