The outcome of early-stage glottic carcinoma patients treated with radiotherapy: Egyptian National Cancer Institute (NCI-Egypt) experience.

Background: Radiotherapy (RT) is an appropriate treatment option for early-stage glottic cancer (ESGC) that achieves high local control and preserves voice quality. However, the optimal radiation treatment schedule remains unknown. We present our institution's 14-year experience in treating ESGC with definitive radiotherapy between 2005 and 2019 inclusively. Materials and methods: We reviewed the medical records of 104 patients; 63 (60.5%) were treated with conventional fractionation (CF), and 41 (39.5%) were treated with hypofractionated radiotherapy (HF). The clinical T-stage was T1a in 50 patients (48%), T1b in 27 (26%), and T2 in 27 (26%). Age, gender, anterior commissure involvement, stage, radiotherapy technique, radiation fraction size, and overall treatment time (OTT) were analyzed as prognostic factors. The survival outcomes, local regional control (LRC), and laryngeal preservation rate were evaluated. Results: The 5-year overall survival (OS) and LCR were 83.3% and 78%, respectively. On univariate analysis, treatment with CF (p = 0.02), prolonged OTT > 49 days in CF and > 40 days in HF (p = 0.04), and RT total dose < 66 Gy (p = 0.03) were associated with poor LRC. Multivariate analysis showed a non-significant association with LRC (all p > 0.05). The 5-year OS rate in the CF and HF-treated patients was 84.9% and 72.1%, respectively (p = 0.99), and in patients who had T1a, T1b, and T2 disease, were 78.2%, 96.0%, and 82.1%, respectively (p = 0.43). All patients and tumor variables showed no statistically significant association with OS. Only low-grade acute toxicity was observed. Conclusion: Non-inferiority results supported the HF schedule to ESGC, including high local disease control and decreased overall treatment time. Our study supports its efficacy in the primary care of ESGC with manageable side effects.

Extracardiac Fontan completion after the Kawashima procedure with a custom-made bifurcated graft.

The patient is a 5-year-old girl who underwent a previous Kawashima procedure with a left-sided bidirectional cavopulmonary anastomosis as a stage I palliation for her functional single ventricle. Her cardiac defect consisted of an unbalanced, right-dominant complete atrioventricular septal defect and a double outlet right ventricle. She also had heterotaxy syndrome with left isomerism, polysplenia, and an interrupted inferior vena cava with azygous continuation to a right-sided superior vena cava. Her native main pulmonary artery was left in continuity with her branch pulmonary arteries. She developed sinus node dysfunction, dilated ascending aorta, and progressive cyanosis. We proceeded with the completion Fontan using a bifurcated graft from both hepatic veins to the pulmonary arterial confluence, replacement of her dilated ascending aorta, disconnection of her native main pulmonary artery with excision of the pulmonary valve cusps, and placement of a dual-chamber epicardial pacemaker.

Draft Genome Sequences of Cefepime-Resistant and -Susceptible Escherichia coli Strains and Imipenem-Resistant and -Susceptible Pseudomonas aeruginosa Strains.

Draft genome sequences of Escherichia coli and Pseudomonas aeruginosa strains collected from clinical infections were used to determine the prevalence of newly emerging antibiotic resistance genes in Maine. Comparisons between cefepime-resistant and -susceptible E. coli strains and imipenem-resistant and -susceptible P. aeruginosa strains are being conducted.

Health System Redesign to Shift to Hospital Delivery for Maternal and Newborn Survival: Feasibility Assessment in Kakamega County, Kenya.

Maternal and newborn health (MNH) service delivery redesign aims to improve maternal and newborn survival by shifting deliveries from poorly equipped primary care facilities to adequately prepared designated delivery hospitals. We assess the feasibility of such a model in Kakamega County, Kenya, by determining the capacity of hospitals to provide services under the redesigned model and the acceptability of the concept to providers and users. We find many existing system assets to implement redesign, including political will to improve MNH outcomes, a strong base of support among providers and users, and a good geographic spread of facilities to support implementation. There are nonetheless health workforce gaps, infrastructure deficits, and transportation challenges that would need to be addressed ahead of policy rollout. Implementing MNH redesign would require careful planning to limit unintended consequences and rigorous evaluation to assess impact and inform scale-up.

Core outcomes in gestational diabetes for treatment trials: The Gestational Metabolic Group treatment set.

AIMS: With the rising number of outcomes being reported following gestational diabetes (GDM), the outcomes in existing studies vary widely making it challenging to compare and contrast the effectiveness of different interventions for GDM. The purpose of this study was to develop a core outcome and measurement set (COS) for GDM treatment trials. MATERIALS & METHODS: A Delphi study with structured consultation with stakeholders and discussion within a specialist Gestational Metabolic Group (GEM) were combined with a comprehensive systematic search across different databases (PubMed, Cochrane Library, and Embase). Several Delphi rounds over 2 years were conducted culminating in this report. RESULTS: The process resulted in a targeted set of outcomes constituting a "GEM treatment set" aligned with expert opinion. The final COS also included a measurement set for the 11 important clinical outcomes from three major domains: maternal metabolic, fetal, and pregnancy related. CONCLUSIONS: Based on the results of this study, it is recommended that future clinical trials on GDM report outcomes uniformly keeping to the recommended COS outcomes.

Metformin is comparable to insulin for pharmacotherapy in gestational diabetes mellitus: A network meta-analysis evaluating 6046 women.

CONTEXT: The comparative efficacy of gestational diabetes (GDM) treatments lack conclusive evidence for choice of first-line treatment. OBJECTIVES: The aim of this study was to compare the efficacy of metformin and glibenclamide to insulin using a core outcome set (COS) to unify outcomes across trials investigating the treatment of gestational diabetes mellitus. STUDY DESIGN: A network meta-analysis (NMA) was conducted. DATA-SOURCE: PubMed, Embase, and Cochrane Controlled Register of Trials were searched from inception to January 2020. STUDY SELECTION: RCTs that enrolled pregnant women who were diagnosed with GDM and that compared the efficacy of different pharmacological interventions for the treatment of GDM were included. META-ANALYSIS: A generalized pairwise modelling framework was employed. RESULTS: A total of 38 RCTs with 6046 participants were included in the network meta-analysis. Compared to insulin, the estimated effect of metformin indicated improvements for weight gain (WMD -2·39 kg; 95% CI -3·31 to -1·46), maternal hypoglycemia (OR 0.34; 95% CI 0.12 to 0·97) and LGA (OR 0.61; 95% CI 0.38 to 0·98). There were also improvements in estimated effects for neonatal hypoglycemia (OR 0.48; 95% CI 0.19 to 1·25), pregnancy induced hypertension (OR 0.63; 95% CI 0.37 to 1·06), and preeclampsia (OR 0.74; 95% CI 0.538 to 1·04), though with limited evidence against our model hypothesis of equivalence with insulin for these outcomes. CONCLUSION: Metformin is, at least, comparable to insulin for the treatment of GDM. Glibenclamide appears less favorable, in comparison to insulin, than metformin.

Physical activity in pregnancy prevents gestational diabetes: A meta-analysis.

AIMS: The effectiveness of physical activity (PA) programs for prevention of gestational diabetes (GDM) lacks conclusive evidence. The aim of this study was to generate clear evidence regarding the effectiveness of physical activity programs in GDM prevention to guide clinical practice. METHODS: PubMed/Medline, ISI Web of Science, Scopus, and EMBASE were searched to identify the randomized trials (RCTs) published until June 2019. Randomised controlled trials enrolling women at high risk before the 20th week of gestation comparing the effect of PA interventions with usual care for prevention of GDM were retrieved. Data obtained were synthesised using a bias-adjusted model of meta-analysis. RESULTS: A total of 1467 adult women in 11 eligible trials were included. The risk of GDM was significantly lower with PA, but only when it was delivered in the healthcare facility (RR 0.53; 95% CI 0.38-0.74). The number needed to treat with PA in pregnancy (compared to usual care) to prevent one GDM event was 18 (95% CI 14 - 29). The overall effect of PA interventions regardless of location of the intervention was RR 0.69 (95% CI 0.51 - 0.94). CONCLUSIONS: This study provides evidence that in-facility physical activity programs started before the 20th week of gestation can significantly decrease the incidence of GDM among women at high risk.

Umbilical Cord Tissue as a Source of Young Cells for the Derivation of Induced Pluripotent Stem Cells Using Non-Integrating Episomal Vectors and Feeder-Free Conditions.

The clinical application of induced pluripotent stem cells (iPSC) needs to balance the use of an autologous source that would be a perfect match for the patient against any safety or efficacy issues that might arise with using cells from an older patient or donor. Drs. Takahashi and Yamanaka and the Office of Cellular and Tissue-based Products (PMDA), Japan, have had concerns over the existence of accumulated DNA mutations in the cells of older donors and the possibility of long-term negative effects. To mitigate the risk, they have chosen to partner with the Umbilical Cord (UC) banks in Japan to source allogeneic-matched donor cells. Production of iPSCs from UC blood cells (UCB) has been successful; however, reprogramming blood cells requires cell enrichment with columns or flow cytometry and specialized growth media. These requirements add to the cost of production and increase the manipulation of the cells, which complicates the regulatory approval process. Alternatively, umbilical cord tissue mesenchymal stromal cells (CT-MSCs) have the same advantage as UCB cells of being a source of young donor cells. Crucially, CT-MSCs are easier and less expensive to harvest and grow compared to UCB cells. Here, we demonstrate that CT-MSCs can be easily isolated without expensive enzymatic treatment or columns and reprogramed well using episomal vectors, which allow for the removal of the reprogramming factors after a few passages. Together the data indicates that CT-MSCs are a viable source of donor cells for the production of clinical-grade, patient matched iPSCs.

Spatial distribution of breast cancer in Sudan 2010-2016.

BACKGROUND: Breast cancer is the most prevalent cancer among females worldwide including Sudan. The aim of this study was to determine the spatial distribution of breast cancer in Sudan. MATERIALS AND METHODS: A facility based cross-sectional study was implemented in eighteen histopathology laboratories distributed in the three localities of Khartoum State on a sample of 4630 Breast Cancer cases diagnosed during the period 2010-2016. A master database was developed through Epi InfoTM 7.1.5.2 for computerizing the data collected: the facility name, type (public or private), and its geo-location (latitude and longitude). Personal data on patients were extracted from their respective medical records (name, age, marital status, ethnic group, state, locality, administrative unit, permanent address and phone number, histopathology diagnosis). The data was summarized through SPSS to generate frequency tables for estimating prevalence and the geographical information system (ArcGIS 10.3) was used to generate the epidemiological distribution maps. ArcGIS 10.3 spatial analysis features were used to develop risk maps based on the kriging method. RESULTS: Breast cancer prevalence was 3.9 cases per 100,000 female populations. Of the 4423 cases of breast cancer, invasive breast carcinoma of no special type (NST) was the most frequent (79.5%, 3517/4423) histopathological diagnosis. The spatial analysis indicated as high risk areas for breast cancer in Sudan the States of Nile River, Northern, Red Sea, White Nile, Northern and Southern Kordofan. CONCLUSIONS: The attempt to develop a predictive map of breast cancer in Sudan revealed three levels of risk areas (risk, intermediate and high risk areas); regardless the risk level, appropriate preventive and curative health interventions with full support from decision makers are urgently needed.

Banking Mesenchymal Stromal Cells from Umbilical Cord Tissue: Large Sample Size Analysis Reveals Consistency Between Donors.

Mesenchymal stromal cells (MSCs) have emerged as candidate cells with therapeutic potential to treat different pathologies. The underlying mechanism is paracrine signaling. The cells secrete proteins that can impact inflammation, apoptosis, angiogenesis, and cell proliferation. All are important in wound healing and tissue regeneration. Although the bone marrow has been the most widely used source of MSCs, umbilical cord tissue (CT) presents a source that is just starting to be used in the clinic, yet can be obtained with more ease and easily stored. Here, we characterize CT-MSCs obtained from multiple donors by analyzing cell surface proteins, differentiation capacity, and proteome profile. Analysis of low, medium, and high passage cells indicates that the morphology and proliferation rate stay constant and with the exception of cluster of differentiation (CD) 105 at late passage, there are no changes in the cell surface protein characteristics, indicating the population does not change with passage. TNF-stimulated gene 6 protein was measured in a subset of samples and variable expression was observed, but this did not impact the ability of the cells to enhance skin regeneration. In conclusion, CT-MSC represents a consistent, easily accessible source of cells for cell therapy. Stem Cells Translational Medicine 2019;8:1041-1054.

Emotional real-world scenes impact visual search.

Research shows that emotional stimuli can capture attention, and this can benefit or impair performance, depending on the characteristics of a task. Additionally, whilst some findings show that attention expands under positive conditions, others show that emotion has no influence on the broadening of attention. The current study investigated whether emotional real-world scenes influence attention in a visual search task. Participants were asked to identify a target letter embedded in the centre or periphery of emotional images. Identification accuracy was lower in positive images compared to neutral images, and response times were slower in negative images. This suggests that real-world emotional stimuli have a distracting effect on visual attention and search. There was no evidence that emotional images influenced the spatial spread of attention. Instead, it is suggested that findings may provide support for the argument that positive emotion encourages a global processing style and negative emotion promotes local processing.

Reactivation of a Vaccine Escape Hepatitis B Virus Mutant in a Cambodian Patient During Anti-Hepatitis C Virus Therapy.

A 76-year-old Cambodian man co-infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) 6c-1 presented for care. HBV DNA was intermittently detectable despite anti-HBs levels being above the protective threshold. During treatment for HCV, HBV DNA levels increased. Sequencing revealed multiple mutations including vaccine escape mutation and mutations predicted to enhance fitness. This case represents exacerbation of an HBV vaccine escape mutant during a direct-acting antiviral therapy.

Hepatitis B virus outreach to immigrant population in Greater Boston Area: Key to improving hepatitis B knowledge.

AIM: To characterize the understanding of hepatitis B virus (HBV) and determine if outreach improves HBV understanding among Greater Boston Area immigrants. METHODS: Six outreach sessions were held in various community venues in the Greater Boston Area. Verbal consent was obtained from participants prior to starting each session. Each session included a pre-session questionnaire, followed by a teaching session, and then a post-session questionnaire. In person interpreters were present for translation during the teaching session and assistance for questionnaire completion when needed. The questions were developed based on the HBV clinical experience of physicians who serve largely immigrant populations. Questionnaires included Likert-type scale, open-ended, and true-false questions. All results were anonymous. RESULTS: One hundred and one people participated in this study. Participants were 30% male with ages ranging from 19 to 87 years. The study population included immigrants from 21 countries, as well as seven United States-born participants. The greatest numbers of participants were from Somalia (44%), Morocco (10%), and Cameroon (8%). Pre session questionnaires revealed that 42% of participants were unaware that HBV can cause cancer, and 50% were unaware that therapies for HBV exist. Our brief teaching intervention led to improved scores on post session questionnaires. For example, at baseline, 58% of participants responded correctly to the question "HBV infection can cause scarring of the liver and liver cancer", whereas 79% of participants responded correctly after the teaching session (P = 0.01). Furthermore, the mean of total correct answers in the true or false portion of the questionnaire increased from 5.5 to 7.6 (P < 0.001). CONCLUSION: A teaching session targeting Boston Immigrants at-risk for HBV helped improve scores on HBV knowledge questionnaires. Outreach may empower at-risk patients to pro-actively seek HBV care.