Abstract A systematic meta-analysis was performed to evaluate if cutaneous melanoma (CM) risk factors differ depending on body site and histological type. Adjusted estimates were extracted from 24 ...observational studies, for a total of 16,180 cases. Multivariate random-effects models were used to obtain summary relative risk (RR) estimates for all risk factors by body site and histological type. Summary RRs suggest that high naevus counts are strongly associated with CM on usually not sun exposed sites ( p < 0.001) while different patterns of sun exposure show a tendency for higher RRs for CM on usually sun exposed sites than on other body sites ( p = 0.087). Continuous pattern was found to be significantly inversely associated with CM for unexposed sites ( p = 0.01). RRs also differed by body site for skin ( p = 0.01) and hair colour ( p = 0.01), and these differences could be attributed to gene variability. This finding seems to suggest different aetiologic pathways of melanoma development by anatomical site.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Ventricular fibrillation amplitude spectral area (AMSA) and end-tidal carbon dioxide (ETCO2) are predictors of shock success, understood as restoration of an organized rhythm, and return of ...spontaneous circulation (ROSC). However, little is known about their combined use. We aimed to assess the prediction accuracy when combined, and to clarify if they are correlated in out of hospital cardiac arrest' victims.
Records acquired by external defibrillators in out-of-hospital cardiac arrest patients of the Lombardia Cardiac Arrest registry were processed. The 1-min pre-shock ETCO2 median value (METCO2) was computed from the capnogram and AMSA (2–48 mV.Hz range) computed applying the Fast Fourier Transform to a 2-second pre-shock filtered ECG interval (0.5−30 Hz). Support Vector Machine (SVM) predictive models based on METCO2, AMSA and their combination were fit; results were given as the area under the curve (AUC) of the receiver operating characteristic (ROC) curves.
We considered 112 patients with 391 shocks delivered. METCO2 and AMSA were predictors of shock success AUC (IQR) of the ROC curve: 0.59 (0.56−0.62); 0.68 (0.65−0.72), respectively and of ROSC 0.56 (0.53−0.59); 0.74 (0.71−0.78),. Their combination in a SVM model increased the accuracy for predicting shock success AUC (IQR) of the ROC curve: 0.71 (0.68−0.75) and ROSC 0.77 (0.73−0.8). AMSA and METCO2 were significantly correlated only in patients who achieved ROSC (rho = 0.33 p = 0.03).
AMSA and ETCO2 predict shock success and ROSC after every shock, and their predictive power increases if combined. Notably, they were correlated only in patients who achieved ROSC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Cell motility and invasion play an essential role in the development of metastasis. Evidence suggests that the enzyme phospholipase Cγ1 (PLCγ1) may be involved in tumor progression and ...possibly development of metastasis. In this study, we show that down-regulation of PLCγ1 expression severely impairs activation of the small GTP-binding protein Rac and cell invasion in breast cancer cell lines and U87 in vitro. Experimental metastasis assays in nude mice show that inducible knockdown of PLCγ1 strongly inhibits development of MDA-MB-231–derived lung metastasis and reverts metastasis formation. In addition, analysis of 60 breast cancer patients' tissues revealed an increase of PLCγ1 expression in metastasis compared with the primary tumor in 50% of tissues analyzed. These data show a critical role of PLCγ1 in the metastatic potential of cancer cells, and they further indicate that PLCγ1 inhibition has a therapeutic potential in the treatment of metastasis dissemination. Cancer Res 2008;68(24):10187–96
Objective: To validate previously identified associations between radiological features and clinical features with Epidermal Growth Factor Receptor (EGFR)/ Kirsten RAt Sarcoma (KRAS) alterations in ...an independent group of patients with Non-Small Cell Lung Cancer (NSCLC).
Material and methods: A total of 122 patients with NSCLC tested for EGFR/KRAS alterations were included. Clinical and radiological features were recorded.
Univariate analysis were performed to look at the associations of the studied features with EGFR/KRAS alterations. Previously calculated composite model parameters for each gene alteration prediction were applied to this validation cohort. ROC (Receiver Operating Characteristic) curves were drawn using the previously validated composite models, and also for each significant individual characteristic of the previous training cohort model. The Area Under the ROC Curve (AUC) with 95% Confidence Intervals (CI) was calculated and compared between the full models.
Results: At univariate analysis, EGFR+ confirmed an association with an internal air bronchogram, pleural retraction, emphysema and lack of smoking; KRAS+ with round shape, emphysema and smoking. The AUC (95%CI) in the new cohort was confirmed to be high for EGFR+ prediction, with a value of: 0.82 (0.69-0.95) vs. 0.82 in the previous cohort, whereas it was smaller for KRAS+ prediction, with a value of 0.60 (0.48-0.72) vs. 0.67 in the previous cohort. Looking at single features in the new cohort, we found that the AUC for the models including only smoking was similar to that of the full model (including radiological and clinical features) for both gene alterations.
Conclusions: Although this study validated the significant association of clinical and radiological features with EGFR/KRAS alterations, models based on these composite features are not superior to smoking history alone to predict the mutations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aim:Clostridia are relevant commensals of the human gut due to their major presence and correlations to the host. In this study, we investigated intestinal Clostridia of 51 healthy subjects and ...reconstructed their taxonomy and phylogeny. The relatively small number of intestinal Clostridia allowed a systematic whole genome approach based on average amino acid identity (AAI) and core genome with the aim of revising the current classification into genera and determining evolutionary relationships. Methods: 51 healthy subjects’ metagenomes were retrieved from public databases. After the dataset’s validation through comparison with Human Microbiome Project (HMP) samples, the metagenomes were profiled using MetaPhlAn3 to identify the population ascribed to the class Clostridia. Intestinal Clostridia genomes were retrieved and subjected to AAI analysis and core genome identification. Phylogeny investigation was conducted with RAxML and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) algorithms, and SplitsTree for split decomposition. Results: 225 out of 406 bacterial taxonomic units were ascribed to Bacillota Firmicutes, among which 124 were assigned to the class Clostridia. 77 out of the 124 taxonomic units were referred to a species, altogether covering 87.7% of Clostridia abundance. According to the lowest AAI genus boundary set at 55%, 15 putative genera encompassing more than one species (G1 to G15) were identified, while 19 species did not cluster with any other one and each appeared to belong to a diverse genus. Phylogenetic investigations highlighted that most of the species clustered into three main evolutive clades. Conclusion: This study shed light on the species of Clostridia colonizing the gut of healthy adults and pinpointed several gaps in knowledge regarding the taxonomy and the phylogeny of Clostridia.
This study sought to validate the ability of amplitude spectrum area (AMSA) to predict defibrillation success and long-term survival in a large population of out-of-hospital cardiac arrests.
ECGs ...recorded by automated external defibrillators from different manufacturers were obtained from patients with cardiac arrests occurring in 8 city areas. A database, including 2447 defibrillations from 1050 patients, was used as the derivation group, and an additional database, including 1381 defibrillations from 567 patients, served as validation. A 2-second ECG window before defibrillation was analyzed, and AMSA was calculated. Univariable and multivariable regression analyses and area under the receiver operating characteristic curve were used for associations between AMSA and study end points: defibrillation success, sustained return of spontaneous circulation, and long-term survival. Among the 2447 defibrillations of the derivation database, 26.2% were successful. AMSA was significantly higher before a successful defibrillation than a failing one (13 ± 5 versus 6.8 ± 3.5 mV-Hz) and was an independent predictor of defibrillation success (odds ratio, 1.33; 95% confidence interval, 1.20-1.37) and sustained return of spontaneous circulation (odds ratio, 1.22; 95% confidence interval, 1.17-1.26). Area under the receiver operating characteristic curve for defibrillation success prediction was 0.86 (95% confidence interval, 0.85-0.88). AMSA was also significantly associated with long-term survival. The following AMSA thresholds were identified: 15.5 mV-Hz for defibrillation success and 6.5 mV-Hz for defibrillation failure. In the validation database, AMSA ≥ 15.5 mV-Hz had a positive predictive value of 84%, whereas AMSA ≤ 6.5 mV-Hz had a negative predictive value of 98%.
In this large derivation-validation study, AMSA was validated as an accurate predictor of defibrillation success. AMSA also appeared as a predictor of long-term survival.
Abstract Background Obesity is associated with an increased risk of high-grade prostate cancer (PCa). The effect of body mass index (BMI) as a predictor of progression in men with low-risk PCa has ...been only poorly assessed. In this study, we evaluated the association of BMI with progression in patients with low-risk PCa who met the inclusion criteria for the active surveillance (AS) protocol. Methods We assessed 311 patients who underwent radical prostatectomy and were eligible for AS according to the following criteria: clinical stage T2a or less, prostate-specific antigen level<10 ng/ml, 2 or fewer cores involved with cancer, Gleason score ≤6 grade, and prostate-specific antigen density<0.2 ng/ml/cc. Reclassification was defined as upstaged (pathological stage>pT2) and upgraded (Gleason score ≥7; primary Gleason pattern 4) disease. Seminal vesicle invasion, positive lymph nodes, and tumor volume≥0.5 ml were also recorded. Results We found that high BMI was significantly associated with upgrading, upstaging, and seminal vesicle invasion, whereas it was not associated with positive lymph nodes or large tumor volume. At multivariate analysis, 1 unit increase of BMI significantly increased the risk of upgrading, upstaging, seminal vesicle invasion, and any outcome by 21%, 23%, 27%, and 20%, respectively. The differences between areas under the receiver operating characteristics curves comparing models with and without BMI were statistically significant for upgrading ( P = 0.0002), upstaging ( P = 0.0007), and any outcome ( P = 0.0001). Conclusions BMI should be a selection criterion for inclusion of patients with low-risk PCa in AS programs. Our results support the idea that obesity is associated with worse prognosis and suggest that a close AS program is an appropriate treatment option for obese subjects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To verify whether both doublet chemotherapy with a modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) and monochemotherapy with fluorouracil plus leucovorin (5-FU + LV) achieve ...satisfactory efficacy when both regimens are combined with panitumumab (PAN) as initial treatment of elderly patients with
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wild-type metastatic colorectal cancer (mCRC).
PANDA (ClinicalTrials.gov identifier: NCT02904031) was an open-label, randomized phase II noncomparative trial in previously untreated patients age 70 years and older with unresectable
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wild-type mCRC. Patients were randomly assigned 1:1 to mFOLFOX + PAN (arm A) or 5-FU + LV + PAN (arm B) for up to 12 cycles, followed by PAN maintenance. The primary end point was progression-free survival (PFS). In each arm, assuming a null hypothesis of median PFS time
6 months and target PFS ≥9.65, 90 patients per arm were needed to achieve 90% power and 5% type I error (one-sided Brookmeyer-Crowley test).
Between July 2016 and April 2019, 91 patients were randomly assigned to arm A and 92 to arm B. At a median follow-up of 50.0 months (IQR, 45.6-56.4), median PFS was 9.6 and 9.0 months for arm A and B, respectively (
< .001 in each arm). Overall response rate was 69% and 52%, whereas median overall survival was 23.5 and 22.0 months in arm A and B, respectively. The overall rate of grade >2 chemotherapy-related adverse events was 60% and 37%, respectively. Baseline G8 and Chemotherapy Risk Assessment Scale for High-Age Patients scores were prognostic, but they were not associated with efficacy and safety of the two arms.
Both mFOLFOX and 5-FU + LV + PAN are reasonable options as initial therapy of elderly patients with
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wild-type mCRC. 5-FU + LV + PAN is associated with a better safety profile.
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