Microbiome diversity in African American, European American, and Egyptian colorectal cancer patients

Purpose: Although there is an established role for microbiome dysbiosis in the pathobiology of colorectal cancer (CRC), CRC patients of various race/ethnicities demonstrate distinct clinical behaviors. Thus, we investigated microbiome dysbiosis in Egyptian, African American (AA), and European American (EA) CRC patients. Patients and methods: CRCs and their corresponding normal tissues from Egyptian (n = 17) patients of the Alexandria University Hospital, Egypt, and tissues from AA (n = 18) and EA (n = 19) patients at the University of Alabama at Birmingham were collected. DNA was isolated from frozen tissues, and the microbiome composition was analyzed by 16S rRNA sequencing. Differential microbial abundance, diversity, and metabolic pathways were identified using linear discriminant analysis (LDA) effect size analyses. Additionally, we compared these profiles with our previously published microbiome data derived from Kenyan CRC patients. Results:Differential microbiome analysis of CRCs across all racial/ethnic groups showed dysbiosis. There were high abundances of Herbaspirillum and Staphylococcus in CRCs of Egyptians, Leptotrichia in CRCs of AAs, Flexspiria and Streptococcus in CRCs of EAs, and Akkermansia muciniphila and Prevotella nigrescens in CRCs of Kenyans (LDA score \u3e4, adj. p-value Conclusions: Our findings showed altered mucosa-associated microbiome profiles of CRCs and their metabolic pathways across racial/ethnic groups. These findings provide a basis for future studies to link racial/ethnic microbiome differences with distinct clinical behaviors in CRC

Genital-Sparing Cystectomy versus Standard Urethral-Sparing Cystectomy Followed with Orthotopic Neobladder in Women with Bladder Cancer: Incidence and Causes of Hypercontinence with an Ultrastructure Study of Urethral Smooth Muscles

BACKGROUND: Bladder cancer in women is an indication for radical cystectomy (RC) when the tumour is confined muscle-invasive bladder cancer (MIBC) of T2 N0M0, or high risk progressive non-muscle invasive bladder cancer (NMIBC). Radical cystectomy is either genital-sparing cystectomy (GSC) or standard urethra-sparing cystectomy (USC) that is followed with orthotopic ileal neobladder (ONB). Post-operative chronic retention “Hypercontinence†had been reported in different series following URS or GSC and ONB. In long-term follow-up, we evaluated the functional outcome of women who developed hypercontinence after USC or GSC and ONB. AIM: An ultrastructure study of female urethral smooth muscle was done to elucidate the underlying causes of hypercontinence. MATERIAL AND METHODS: Retrospective study was conducted on 71 women who underwent RC and ONB, 45women had undergone USC, and 26 women had GSC, follow-up ranged from 5 to 15 years. Ultrastructure studies were done on 5 urethral biopsy specimens from 5 women who had hypercontinence, and 4 biopsies were from a normal control. RESULTS: Follow-up showed that women who had undergone USC and ONB, 28.88% developed hypercontinence, where in the series of GSC and ONB three women out of 26 developed hypercontinence (7.80%). Three women who had hypercontinence following USC and ONB, they developed stones in the ileal pouch. Ultrastructure study of urethral smooth muscles in women who had hypercontinence showed organized collagen fibrils, absent myelin sheath, and non-detected lymphatic vessels. Normal urethra showed collagen fibrils within the interstitial matrix, preserved myelin sheath of nerve fibres, the presence of lymphatic vessels in the matrix. CONCLUSION: The present study shoes that GSC with ONB leads to the minimal incidence of hypercontinence (7.80%), while standard USC lead to higher incidence (28.88%). Ultrastructure changes of the female urethra who had hypercontinence were fibrotic changes, loss of myelin sheath and minimal vascularity, their findings explains the underlying cause of hypercontinence and support the technique of GSC rather than the standard USC

Upregulation of Twist2 in Non-Muscle Invasive Urothelial Carcinoma of the Bladder Correlate with Response to Treatment and Progression

BACKGROUND: Twist2 is a transcription factor and an epithelial-to-mesenchymal transition that plays an important role in cell polarity, cell adhesion, and has a role in tumour invasion and metastases.AIM: In this study, we examined the expression of Twist2 in non-muscle invasive bladder carcinoma (NMIBC) and correlated the expression with response to treatment and tumour progression.METHODS: Data of 305 patients with NMIBC of Ta, T1 were retrieved from hospitals archives. Twist2 expression was examined in tissue samples by immunohistochemistry at initial diagnosis and final follow-up, normal control was 10 normal urothelium, 10 patients with muscle-invasive bladder cancer (MIBC) were a positive control. Treatment of NMIBC was implemented according to the European Association of Urology guidelines on NMIBC. The descriptive statistical analysis included means, standard deviation, p-value; Univariate and multivariate Cox regression analyses.RESULTS: Twist2 expression score was identified as negative, low (1-15%); medium (15-40%); and high (40-100%). Patients who had low or low medium scores at the initial diagnosis had a good response and a favourable prognosis. Expression of a high score of Twist2 in patients having high-grade T1 tumours showed non-responsiveness to repeated courses of intravesical bacillus Calmette Guerin (BCG) therapy and was upstaged to MIBC.CONCLUSION: Twist2 expression in tissue samples of NMIBC would indicate the tumour response to therapy, upgrading and upstaging in the follow up after intravesical BCG therapy

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Diffusion tensor imaging in trigeminal neuralgia: beyond the normal morphology

Abstract Background Trigeminal neuralgia (TN) is an electric-like recurrent pain of a sudden onset and is localized to the area supplied by the trigeminal nerve, and the patients are usually free in between the attacks. It’s one of the most common causes of facial pain and is commonly induced by mechanical irritation, and there’s strong evidence suggesting an insult at the trigeminal nerve root which is usually caused by a neurovascular compression. The aim of the study was to evaluate the role of diffusion tensor imaging (DTI) in the detection of microstructural changes of normal appearing trigeminal nerve in patients with trigeminal neuralgia and the correlation between DTI parameters and pain severity. Results Thirty one cases were included in the study (16 patients with TN and 15 healthy controls) underwent MRI with diffusion tensor imaging. The fractional anisotropy (FA) values of the trigeminal nerves were recorded and then comparison between the affected and unaffected sides in TN patients and healthy controls was done, also the degree of FA reduction was correlated with the pain severity in TN groups. The mean FA value of the affected trigeminal nerves was 0.43 ± 0.083, while that of the unaffected sides was 0.56 ± 0.058. The mean FA value of the trigeminal nerves in the healthy controls was 0.54 ± 0.057. A significant statistical differences was found between affected and unaffected sides (P < 0.00001) and between the affected sides and healthy controls (P < 0.0003), while no statistically significant difference was detected between the unaffected side and the healthy controls. A strong negative correlation was found between the pain score and the degree of FA reduction (P < 0.001). Conclusions Diffusion tensor imaging is a functional MRI technique which can detect the microstructural changes in the normal appearing trigeminal nerves in patients with trigeminal neuralgia with a strong negative correlation between the severity of pain and the degree of FA reduction of the affected trigeminal nerve

Molecular Subtyping and Survival Analysis of Osteosarcoma Reveals Prognostic Biomarkers and Key Canonical Pathways

Osteosarcoma (OS) is a common bone malignancy in children and adolescents. Although histological subtyping followed by improved OS treatment regimens have helped achieve favorable outcomes, a lack of understanding of the molecular subtypes remains a challenge to characterize its genetic heterogeneity and subsequently to identify diagnostic and prognostic biomarkers for developing effective treatments. In the present study, global analysis of DNA methylation, and mRNA and miRNA gene expression in OS patient samples were correlated with their clinical characteristics. The mucin family of genes, MUC6, MUC12, and MUC4, were found to be highly mutated in the OS patients. Results revealed the enrichment of molecular pathways including Wnt signaling, Calcium signaling, and PI3K-Akt signaling in the OS tumors. Survival analyses showed that the expression levels of several genes such as RAMP1, CRIP1, CORT, CHST13, and DDX60L, miRNAs and lncRNAs were associated with survival of OS patients. Molecular subtyping using Cluster-Of-Clusters Analysis (COCA) for mRNA, lncRNA, and miRNA expression; DNA methylation; and mutation data from the TARGET dataset revealed two distinct molecular subtypes, each with a distinctive gene expression profile. Between the two subtypes, three upregulated genes, POP4, HEY1, CERKL, and seven downregulated genes, CEACAM1, ABLIM1, LTBP2, ISLR, LRRC32, PTPRF, and GPX3, associated with OS metastasis were found to be differentially regulated. Thus, the molecular subtyping results provide a strong basis for classification of OS patients that could be used to develop better prognostic treatment strategies