Fecal Microbiota and Associated Volatile Organic Compounds Distinguishing No-Adenoma from High-Risk Colon Adenoma Adults.

Microbiota and the metabolites they produce within the large intestine interact with the host epithelia under the influence of a range of host-derived metabolic, immune, and homeostatic factors. This complex host-microbe interaction affects intestinal tumorigenesis, but established microbial or metabolite profiles predicting colorectal cancer (CRC) risk are missing. Here, we aimed to identify fecal bacteria, volatile organic compounds (VOC), and their associations that distinguish healthy (non-adenoma, NA) from CRC prone (high-risk adenoma, HRA) individuals. Analyzing fecal samples obtained from 117 participants ≥15 days past routine colonoscopy, we highlight the higher abundance of Proteobacteria and Parabacteroides distasonis, and the lower abundance of Lachnospiraceae species, Roseburia faecis, Blautia luti, Fusicatenibacter saccharivorans, Eubacterium rectale, and Phascolarctobacterium faecium in the samples of HRA individuals. Volatolomic analysis of samples from 28 participants revealed a higher concentration of five compounds in the feces of HRA individuals, isobutyric acid, methyl butyrate, methyl propionate, 2-hexanone, and 2-pentanone. We used binomial logistic regression modeling, revealing 68 and 96 fecal bacteria-VOC associations at the family and genus level, respectively, that distinguish NA from HRA endpoints. For example, isobutyric acid associations with Lachnospiraceae incertae sedis and Bacteroides genera exhibit positive and negative regression lines for NA and HRA endpoints, respectively. However, the same chemical associates with Coprococcus and Colinsella genera exhibit the reverse regression line trends. Thus, fecal microbiota and VOC profiles and their associations in NA versus HRA individuals indicate the significance of multiple levels of analysis towards the identification of testable CRC risk biomarkers.

Dynamic monitoring of PD-L1 and Ki67 in circulating tumor cells of metastatic non-small cell lung cancer patients treated with pembrolizumab.

Programmed cell death protein ligand-1 (PD-L1) expression in non-small cell lung cancer (NSCLC) tumors guides treatment selection. PD-L1 expression in circulating tumor cells (CTCs) may provide further information. We have explored PD-L1 and marker of proliferation Ki-67 (Ki67; also known as MKI67) in CTCs in longitudinal samples of 47 advanced NSCLC patients receiving pembrolizumab. A triple immunofluorescence, against cytokeratin, PD-L1, and Ki67, was performed on peripheral blood mononuclear cells, at baseline, post-first cycle, post-third, and primary resistance (PMR). Patients displaying PMR (progression at first evaluation) were classified as progressive disease (PD) and those with clinical benefit as disease control (DC). CTCs were categorized as PD-L1high/low/medium/negative and Ki67+ or Ki67- . CTC evaluation revealed a significant increase in the PD-L1low CTC rate at PMR compared to baseline (2.5% at baseline vs. 36.5% at PMR), whereas a reduction in the PD-L1high CTC rate was observed (31.5% vs. 0%, respectively). Investigation of CTC status between PD and DC patients showed that PD patients more frequently increased total and PD-L1low CTCs after first cycle compared to DC (83% of PD vs. 37% of DC and 67% of PD vs. 8% of DC, respectively). Progression-free survival (PFS) was longer in patients with decreased total and PD-L1low CTCs after first cycle compared to those with increased CTCs (median PFS: not reached vs. 2 months). PD-L1+ patients presenting a high Ki67 index (% Ki67+ CTCs > 30%) before treatment had a shorter PFS compared to those with a low Ki67 (≤ 30%), and overall survival (OS) was shorter in PD-L1+ patients harboring Ki67+ CTCs compared to those not presenting (median OS: 11.8 months vs. 33.1 months, respectively). In sequential samples of patients with a durable benefit, a low Ki67 index was observed. Our results suggest that monitoring PD-L1 and Ki67 expression in CTCs of NSCLC patients treated with pembrolizumab may be predictive for pembrolizumab efficacy.

A systematic review of miRNAs as biomarkers for chemotherapy-induced cardiotoxicity in breast cancer patients reveals potentially clinically informative panels as well as key challenges in miRNA research.

Breast cancer patients are at a particularly high risk of cardiotoxicity from chemotherapy having a detrimental effect on quality-of-life parameters and increasing the risk of mortality. Prognostic biomarkers would allow the management of therapies to mitigate the risks of cardiotoxicity in vulnerable patients and a key potential candidate for such biomarkers are microRNAs (miRNA). miRNAs are post-transcriptional regulators of gene expression which can also be released into the circulatory system and have been associated with the progression of many chronic diseases including many types of cancer. In this review, the evidence for the potential application of miRNAs as biomarkers for chemotherapy-induced cardiotoxicity (CIC) in breast cancer patientsis evaluated and a simple meta-analysis is performed to confirm the replication status of each reported miRNA. Further selection of miRNAs is performed by reviewing the reported associations of each miRNA with other cardiovascular conditions. Based on this research, the most representative panels targeting specific chemotherapy agents and treatment regimens are suggested, that contain several informative miRNAs, including both general markers of cardiac damage as well as those for the specific cancer treatments.

Colon Cancer: From Epidemiology to Prevention.

Colorectal cancer (CRC) is one of the most prevalent cancers affecting humans, with a complex genetic and environmental aetiology. Unlike cancers with known environmental, heritable, or sex-linked causes, sporadic CRC is hard to foresee and has no molecular biomarkers of risk in clinical use. One in twenty CRC cases presents with an established heritable component. The remaining cases are sporadic and associated with partially obscure genetic, epigenetic, regenerative, microbiological, dietary, and lifestyle factors. To tackle this complexity, we should improve the practice of colonoscopy, which is recommended uniformly beyond a certain age, to include an assessment of biomarkers indicative of individual CRC risk. Ideally, such biomarkers will be causal to the disease and potentially modifiable upon dietary or therapeutic interventions. Multi-omics analysis, including transcriptional, epigenetic as well as metagenomic, and metabolomic profiles, are urgently required to provide data for risk analyses. The aim of this article is to provide a perspective on the multifactorial derailment of homeostasis leading to the initiation of CRC, which may be explored via multi-omics and Gut-on-Chip analysis to identify much-needed predictive biomarkers.

Exercise and Occupational Stress among Firefighters.

The aim of our study was to evaluate the potential association between physical activity and occupational stress among firefighters. Data were collected from Cypriot firefighters through a web-based battery of internationally validated questionnaires completed anonymously (COPSOQ, DASS). A total of 430 firefighters (response rate 68%) completed the survey (age range: 21-60 years). More than half of the firefighters (54%) reported either no or minimal physical activity. A total of 11% of firefighters reported moderate to extremely severe stress based on the DASS-S scale. Using multivariable-adjusted logistic regression models, we showed that firefighters who exercised had 50% lower risk of occupational stress, and using a categorical model, we found that every hour per week of increased physical activity among firefighters was associated with 16% lower risk of occupational stress after adjusting for age, education, smoking, and body mass index (OR = 1.16; p = 0.05). In addition, our findings suggest an inverse dose-response relationship between physical activity and occupational stress among firefighters. Physical activity appears to be inversely associated with occupational stress and serves as an important mitigating factor of occupational stress in firefighters. Further research is warranted to evaluate the potential effect of exercise interventions on occupational stress, and the overall mental health of firefighters and other occupational groups.

Bifidobacterium Is Enriched in Gut Microbiome of Kashmiri Women with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a very common endocrine condition in women in India. Gut microbiome alterations were shown to be involved in PCOS, yet it is remarkably understudied in Indian women who have a higher incidence of PCOS as compared to other ethnic populations. During the regional PCOS screening program among young women, we recruited 19 drug naive women with PCOS and 20 control women at the Sher-i-Kashmir Institute of Medical Sciences, Kashmir, North India. We profiled the gut microbiome in faecal samples by 16S rRNA sequencing and included 40/58 operational taxonomic units (OTUs) detected in at least 1/3 of the subjects with relative abundance (RA) ≥ 0.1%. We compared the RAs at a family/genus level in PCOS/non-PCOS groups and their correlation with 33 metabolic and hormonal factors, and corrected for multiple testing, while taking the variation in day of menstrual cycle at sample collection, age and BMI into account. Five genera were significantly enriched in PCOS cases: Sarcina, Megasphaera, and previously reported for PCOS Bifidobacterium, Collinsella and Paraprevotella confirmed by different statistical models. At the family level, the relative abundance of Bifidobacteriaceae was enriched, whereas Peptococcaceae was decreased among cases. We observed increased relative abundance of Collinsella and Paraprevotella with higher fasting blood glucose levels, and Paraprevotella and Alkalibacterium with larger hip, waist circumference, weight, and Peptococcaceae with lower prolactin levels. We also detected a novel association between Eubacterium and follicle-stimulating hormone levels and between Bifidobacterium and alkaline phosphatase, independently of the BMI of the participants. Our report supports that there is a relationship between gut microbiome composition and PCOS with links to specific reproductive health metabolic and hormonal predictors in Indian women.

Outcomes of 556 consecutive patients with stage I-III colon cancer managed in a single center over 10 years.

BACKGROUND: The Bank of Cyprus Oncology Center is the largest cancer center in Cyprus, providing standalone oncology services to a population of just under a million. METHODS: The aim of the study was to calculate disease-free survival (DFS) and overall survival (OS) for consecutive patients with stage I-III colon cancer over a 10-year period, by collecting retrospective data from patients' medical charts. RESULTS: We identified 556 patients with a median age at diagnosis of 67 (range 18-88). The majority of them were male (60%). Just over half of stage II patients received chemotherapy: capecitabine (44%) and FOLFOX/CapeOx (7%). Treatment administered in stage III was as follows: CapeOx (48%); FOLFOX (28%); capecitabine (12%); 5-fluorouracil (4%); and 8% received no treatment. DFS at 5 years was: stage I 90%; stage II 85%; and stage III 69%. Cancer-specific OS at 5 years was: stage I 94%; stage II 93%; and stage III 81%. Favorable outcomes were also maintained at 10 years (stage I 94%; stage II 84%; and stage III 70%). On multivariate analysis, only stage was statistically significant as a prognostic factor, whereas high-risk features (pT4±pN2), disease location (right vs. left), and age >70 years old did not reach statistical significance. CONCLUSIONS: Despite our country's fragmented healthcare system, with multiple referring surgeons from the private and public sectors, the outcomes achieved were highly consistent with those published in the international literature. This can be attributed to optimal multidisciplinary management and follow-up care.

A quantitative method for the assessment of dysarthrophonia in myasthenia gravis.

Speech and voice symptomatology (dysarthrophonia) are often reported by patients with myasthenia gravis (MG). However, they have been poorly investigated despite their significant impact on quality of life. Quantitative methods for the assessment of dysarthrοphonia could facilitate the evaluation of these common MG symptoms. The goal of this study was to investigate the phonatory (sustained phonation and reading) and speech (diadochokinesis) function in MG patients using quantitative measures. The voice/speech of 12 MG patients (7 with anti-AchR and 5 with anti-MuSK antibodies) and 24 age-matched healthy controls was recorded and analyzed using electroglottography (EGG) and speech acoustics. For the analysis of voice, the variables that were found to distinguish MG patients compared to healthy controls were a higher average fundamental frequency (P<0.05), a higher standard deviation of the average fundamental frequency (P<0.001), a higher mean fundamental frequency of the vibrating vocal folds (P<0.005) and a higher fundamental frequency range (P<0.005). The analysis of diadochokinesis showed that MG patients had a higher mean duration of the silent interval between a series of repetitive /pa/ syllables (P<0.05), of the sound /t/ (P=0.05) and of the silent interval between a series of repetitive /ka/syllables (P<0.05). No statistical differences were found in any of these variables between the MG subgroups with anti-AchR or anti-MuSK antibodies. This study demonstrates that non-invasive physiological methods (EGG and speech acoustics) offer essential tools for the assessment of dysarthrophonia in MG patients.

Rapid on-site evaluation with the Hemacolor rapid staining method of medical thoracoscopy biopsy specimens for the management of pleural disease.

BACKGROUND AND OBJECTIVE: Medical thoracoscopy (MT) is useful for the management of pleural disease. Rapid on-site evaluation (ROSE) of transbronchial needle aspirates proved to be useful during bronchoscopy. We aimed to evaluate the diagnostic performance of ROSE of MT biopsy specimens and thoracoscopists' impression of the macroscopic appearance and assess the intermodality agreement between ROSE and final histopathologic diagnosis. METHODS: Sixty two patients with exudative pleural effusions further investigated with MT were enrolled. MT was performed under local anaesthesia and conscious sedation, using the rigid pleuroscope. ROSE with the Hemacolor rapid staining method of the biopsy specimens was performed. Thoracoscopists' impression of the macroscopic appearance was recorded. The final diagnosis was established following histopathological examination. RESULTS: Thoracoscopic pleural biopsies were diagnosed in 61 patients (98.4%). Group A (n = 25) consisted of patients with malignancy and group B (n = 37) with benign disorders. Area under the curve of ROSE for the diagnosis of malignancy was 0.86 (95% CI: 0.76-0.96, P < 0.001), with a sensitivity of 79.17%, specificity of 94.59%, diagnostic accuracy of 88.5%, positive predictive value of 90.5% and negative predictive value of 87.5%. Intermodality agreement between ROSE and histopathology was good (κ ± SE = 0.615 ± 0.084, P < 0.001). Area under the curve of the thoracoscopists' impression of macroscopic appearance was 0.72 (95% CI: 0.58-0.85, P = 0.001), with a sensitivity of 100%, specificity of 44.7%, positive predictive value of 53.33% and negative predictive value of 100%. CONCLUSION: Rapid on-site evaluation during MT was found to have high accuracy for predicting malignancy. ROSE can provide the thoracoscopist with an on-site preliminary diagnosis, especially in cases with inconclusive macroscopic appearance.