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Introduction This multi-center, observational cohort study aimed to evaluate the real-world effectiveness and safety of two first-line chemoimmunotherapy combinations—pembrolizumab plus chemotherapy and nivolumab/ipilimumab plus chemotherapy—in patients with metastatic non-small cell lung cancer (NSCLC) and programmed death ligand-1 (PD-L1) expression < 50%. Patients and Methods The primary objectives were progression-free survival (PFS) and overall survival (OS) in the overall population. Secondary objectives included the incidence of chemotherapy-related and immune-related adverse events (irAEs). Results A total of 495 patients were enrolled, with 348 (70.3%) receiving pembrolizumab plus chemotherapy and 147 (29.7%) treated with nivolumab/ipilimumab plus chemotherapy. Overall, median follow-up was 11 (95% CI: 10.2 12.2) months. The median PFS was 10.9 months (95% CI: 9.6–13), and the median OS was 21.1 months (95% CI: 16.8–NR) in the overall population. In multivariable analysis, ECOG PS ≥ 2, PD-L1 expression < 1%, squamous histology, baseline steroid use, and the presence of CNS, bone, or liver metastases were significantly associated with shorter survival. No significant differences were observed between the pembrolizumab and nivolumab/ipilimumab cohorts in terms of PFS (11.83 vs. 9.83 months; HR 0.86, 95% CI: 0.67–1.11, p  = 0.3) or OS (21.3 vs. 20.6 months; HR 1.03, 95% CI: 0.76–1.39, p  = 0.9). Chemotherapy-related adverse events were more frequent in the pembrolizumab cohort, whereas irAEs were more common in the nivolumab/ipilimumab cohort. Conclusion In this real-world study, chemoimmunotherapy combinations demonstrated manageable toxicity profiles, with effectiveness comparable to that reported in pivotal phase 3 randomized trials. Pembrolizumab and nivolumab/ipilimumab showed similar real-world effectiveness but significantly different toxicity profiles.

LDH may represent an indirect marker of neo-angiogenesis and worse prognosis in many tumour types. We assessed the correlation between LDH and clinical outcome for biliary tract cancer (BTC) patients treated with first-line chemotherapy. Overall, 114 advanced BTC patients treated with first-line gemcitabine and cisplatin were included. Patients were divided into two groups (low vs. high LDH), according to pre-treatment LDH values. Patients were also classified according to pre- and post-treatment variation in LDH serum levels (increased vs. decreased). Median progression free survival (PFS) was 5.0 and 2.6 months respectively in patients with low and high pre-treatment LDH levels (p = 0.0042, HR = 0.56, 95% CI: 0.37–0.87). Median overall survival (OS) was 7.7 and 5.6 months (low vs. high LDH) (p = 0.324, HR = 0.81, 95% CI: 0.54–1.24). DCR was 71% vs. 43% (low vs. high LDH) (p = 0.002). In 38 patients with decreased LDH values after treatment, PFS and OS were respectively 6.2 and 12.1 months, whereas in 76 patients with post-treatment increased LDH levels, PFS and OS were respectively 3.0 and 5.1 months (PFS: p = 0.0009; HR = 0.49; 95% IC: 0.33–0.74; OS: p < 0.0001; HR = 0.42; 95% IC: 0.27–0.63). Our data seem to suggest that LDH serum level may predict clinical outcome in BTC patients receiving first-line chemotherapy.

Background: Chemoimmunotherapy combinations represent the standard first-line treatment for non-oncogene addicted metastatic NSCLC (mNSCLC). However, evidence in elderly patients remains limited and conflicting. We conducted an analysis of the efficacy and safety of chemoimmunotherapy in patients aged ≥75 years enrolled in the Real-Combo Lung study, an observational study including patients with non-oncogene-addicted mNSCLC and PD-L1 expression < 50%. Patients and Methods: The primary objective of the study was to compare progression-free survival (PFS) and overall survival (OS) between patients aged ≥75 (elderly cohort) and those aged <75 years (non-elderly cohort). Safety outcomes were evaluated as a secondary objective. Results: A total of 495 patients were enrolled, with 89 (18%) aged ≥75 and 406 (82%) aged <75 years. No significant differences in PFS and OS were observed between the two cohorts. The median PFS was 13.3 months (95% CI: 9.3–NR) in the elderly cohort and 10.5 months (95% CI: 9.5–12.9) in the non-elderly cohort (unadjusted HR 0.84, 95% CI: 0.61–1.16, p = 0.29). The median OS was 17.5 months (95% CI: 14.7–NR) versus 21.4 months (95% CI: 17–NR), respectively (unadjusted HR 1.09, 95% CI: 0.76–1.56, p = 0.63). In multivariable analysis, ECOG PS ≥ 2 and baseline use of steroids were significantly associated with a worse outcome in the elderly cohort for both PFS and OS. Safety data did not differ significantly between cohorts. Conclusions: In this real-world study, elderly patients with mNSCLC derived outcomes comparable to those of younger patients, with similar efficacy and a manageable safety profile when treated with chemoimmunotherapy combinations.

Precision medicine stems from a new approach to the prevention, diagnosis and treatment of patients, due to the shift in focus away from pathology and towards the uniqueness of the individual, personalising the diagnostic–therapeutic pathway. This paradigm shift has been made possible by the emergence of new high-throughput technologies capable of generating large amounts of data on multiple levels of a biological system, identifying pathology-related genes, transcripts, proteins and metabolites. Metabolomics plays a primary role in this context, providing, through non-invasive sampling, a very close image of the phenotype of the organism being studied by detecting metabolites, end products downstream of gene transcription, present in cells, tissues, organs and biological fluids. The enormous amount of data that these modern technologies make available, together with the need to elucidate the complex interplay of the various biological levels by combining data from distinct omics, has led to the need to employ advanced informatics techniques, among which artificial intelligence has recently emerged. These innovations are of great interest in the field of perinatology, representing an attempt to optimise the diagnostic timeline for the most critical newborns. In addition, they may contribute to the improvement of prevention strategies available to date. All these contributions prove to be crucial at very vulnerable life stages, allowing crucial intervention opportunities. In this review, we have analysed studies that have integrated metabolomics with at least one other omics in the perinatal field, attempting to highlight the usefulness of multiomics integration and the different methods employed.

Objectives. To define the prevalence and determinants of peripheral microvascular endothelial dysfunction (ED) in a large series of rheumatoid arthritis (RA) patients free of previous cardiovascular events. Materials and Methods. Data from 874 RA patients enrolled in the EDRA study (Endothelial Dysfunction Evaluation for Coronary Heart Disease Risk Estimation in Rheumatoid Arthritis—ClinicalTrials.gov: NCT02341066) were analyzed. Log-transformed reactive hyperemia index (Ln-RHI) was evaluated by peripheral arterial tonometry (PAT) using the EndoPAT2000 device: values of Ln-RHI < 0.51 were considered indicative of peripheral ED. Results. Peripheral microvascular ED was documented in one-third of RA patients (33.5%); in multiple logistic regression analysis, ACPA negativity and higher triglycerides concentrations were independently associated with the presence of peripheral ED [OR (95% CI) = 1.708 (1.218–2.396), p<0.01 and OR (95% CI) = 1.005 (1.002–1.009), p<0.01, respectively]. Multiple regression analysis showed a positive correlation between Ln-RHI values and systolic blood pressure and HDL cholesterol levels; furthermore, higher values of Ln-RHI were associated with ACPA positivity, while smoking habit was associated with lower Ln-RHI values. Conclusions. This study demonstrates for the first time a high prevalence of peripheral microvascular ED in patients with RA free of previous cardiovascular events that appear to be only partially driven by traditional cardiovascular risk factors. The association between ACPA negativity and ED warrants further exploration.

Trichomonas vaginalis is an anaerobic protist, responsible for the most prevalent non-viral sexually transmitted infection in humans. One of the most intriguing aspects of T. vaginalis pathobiology is the complex relationship with intracellular microbial symbionts: a group of dsRNA viruses belonging to family of Totiviridae (T. vaginalis virus), and eubacteria belonging to the Mycoplasma genus, in particular Mycoplasma hominis. Both microorganisms seem to strongly influence the lifestyle of T. vaginalis, suggesting a role of the symbiosis in the high variability of clinical presentation and sequelae during trichomoniasis. In the last few years many aspects of this unique symbiotic relationship have been investigated: M. hominis resides and replicates in the protozoan cell, and T. vaginalis is able to pass the bacterial infection to both mycoplasma-free protozoan isolates and human epithelial cells; M. hominis synergistically upregulates the proinflammatory response of human monocytes to T. vaginalis. Furthermore, the influence of M. hominis over T. vaginalis metabolism and physiology has been characterized. The identification of a novel species belonging to the class of Mollicutes (Candidatus Mycoplasma girerdii) exclusively associated to T. vaginalis opens new perspectives in the research of the complex series of events taking place in the multifaceted world of the vaginal microbiota, both under normal and pathological conditions.

Purpose To reveal the morphological and functional substrates of memory impairment and conversion to Alzheimer disease (AD) from the stage of amnestic mild cognitive impairment (aMCI). Methods Brain MRI and FDG-PET were performed in 20 patients with aMCI and 12 controls at baseline. During a mean follow-up of about 2 years, 9 patients developed AD (converters), and 11 did not (nonconverters). All images were processed with SPM2. FDG-PET and segmented grey matter (GM) images were compared in: (1) converters versus controls, (2) nonconverters versus controls, and (3) converters versus nonconverters. Results As compared to controls, converters showed lower GM density in the left parahippocampal gyrus and both thalami, and hypometabolism in the precuneus, posterior cingulate and superior parietal lobule in the left hemisphere. Hypometabolism was found in nonconverters as compared to controls in the left precuneus and posterior cingulated gyrus. As compared to nonconverters, converters showed significant hypometabolism in the left middle and superior temporal gyri. Conclusion The discordant topography between atrophy and hypometabolism reported in AD is already present at the aMCI stage. Posterior cingulate–precuneus hypometabolism seemed to be an early sign of memory deficit, whereas hypometabolism in the left temporal cortex marked the conversion to AD.

Oxidative stress and RAAS play an important role in the occurrence of anthracyclines-induced cardiotoxicity. Telmisartan, an angiotensin II type 1 receptor blocker, inhibits activation of superoxide sources and induces anti-inflammatory effects. The possible role of telmisartan in preventing myocardial damage induced by epirubicin (EPI) was investigated. Forty-nine patients free from cardiovascular diseases affected by a variety of solid cancers were examined. Eligible patients were randomized to receive telmisartan (40 mg/d; TEL, n = 25) or placebo (PLA, n = 24) starting 1 week before chemotherapy. Patients were studied by means of echocardiography, tissue Doppler, and strain and strain rate (SR) imaging. We also measured plasma levels of inflammatory and oxidative stress markers. All parameters were assessed at baseline and 7 days after every new EPI dose of 100 mg/m 2. An impairment of the SR peak was observed at the EPI dose of 200 mg/m 2, with no significant differences between TEL and PLA (1.41 ± 0.31 vs 1.59 ± 0.36/s). At growing cumulative doses of EPI, SR normalized only in TEL, showing a significant difference in comparison to PLA at EPI doses of 300 mg/m 2 (1.69 ± 0.42 vs 1.34 ± 0.18/s, P < .001) and 400 mg/m 2 (1.74 ± 0.27 vs 1.38 ± 0.24/s, P < .001). Moreover, a significant increase in reactive oxygen species and interleukin-6 was found in PLA; but these remained unchanged in TEL. We confirmed that EPI-induced cardiotoxicity is primarily related to the inactivation of the cardiac antioxidant defenses. In addition, we showed that telmisartan can reduce EPI-induced radical species, antagonize the inflammation, and reverse the early myocardial impairment.

This study aims to provide a picture of University of Cagliari students’ alcohol-related behaviour and to explore factors associated with it. Data were collected by administering a questionnaire to 992 freshmen university students from different programs consisting of twelve closed questions, including three questions from the Alcohol Use Disorders Identification Test for Consumption (AUDIT-C short form). Three subgroups of alcohol-related behaviour were distinguished (risky drinkers, social drinkers and abstainers). In order to explore factors associated with patterns of alcohol consumption, a multivariate logistic regression was performed. The prevalence of risky drinkers was 35%. A binge-drinking behaviour at least once in the last twelve months was declared by 65% (more widespread in men and in students living away from their parents). Risky consumption is significantly associated with age of onset of alcohol use, living away from parents’ home, drinking outside meals and attending health courses. Regarding the levels of daily alcohol consumption perceived as a health risk, 66% of men and 88% of women indicate values higher than those recommended. The results underline the need for tailored prevention measures. University could be a promising setting to implement actions according to a health promotion perspective, to empower students to control their alcohol consumption.

Exclusive breastfeeding is currently recommended until at least 6 months of postnatal age, due to maternal breast milk (BM) unique composition and beneficial properties. In fact, BM modifies itself according to gestational age (GA) at birth, adapting its composition to neonatal requests during lactation. Multiple births represent about 3% of the whole pregnancies; such neonates result more vulnerable than full-term newborns, due to lower GA and birth weight (BW) and the higher incidence of perinatal complications. Although an adequate nutrition is fundamental for twins and other multiples, studies on this topic are lacking. We collected and analyzed BM from mothers of 19 twins and 5 triplets showing GA < 33 weeks and BW < 1500 g, comparing it to a control group of 28 preterm singletons. As a result, at GA ≤ 28 weeks, we observed that protein content is higher in BM for multiples (1.53 vs. 1.29 g per 100 ml), lactose concentration is greater in BM for singletons (6.72 vs. 6.34 g per 100 ml) and GA results the most relevant factor influencing BM protein composition. BM for multiples results higher in proteins and lower in lactose, if compared with singleton’s samples; this could promote and sustain growth and organ development in this vulnerable category. BM from multiples shows a trophic and immunologic role, since these neonates often show lower GA and BW instead of singletons. These findings could help in optimizing nutritional strategies and improving BM individualized fortification.