The impact of variation in access to care on the management of Hirschsprung disease

IntroductionVariation in access to care has a significant impact on the disease management process and outcomes. Variable access to care might have similar effects on the management of Hirschsprung disease (HD). However, such variation has not been highlighted.Materials and MethodsAll patients referred to 3 academic centers (ACs) with HD were reviewed. Patient presentations, referral patterns, timing, and type of surgical intervention were compared between patients born in AC and those born in non-AC. Babies born with major congenital anomalies (MCAs) or total colonic HD were excluded.ResultsBetween 1998 and 2011, 129 patients were identified. After excluding 30 patients, 99 were split into 20 inborn patients (AC) and 79 outborn patients. Outborn patients more often presented with constipation (95% vs 65%, P = .001), whereas inborn patients presented with feeding intolerance or vomiting (75% vs 39%, P = .004). Outborn patients were diagnosed and had their pull-through (PT) at an older median age (in days) of 186 (1-2621) vs 4.5 (1-451) (P = .001) and 345 (11-2757) vs 92 (3-928) (P = .001), respectively. Moreover, inborn patients were more likely to undergo primary PT (75% vs 46%, P = .02) and avoid bowel diversion (95% vs 66%, P = .02).ConclusionVariation in access to care can have a significant impact on the quality of care delivery in HD. Limited access to AC is associated with staged PT in addition to delay in the diagnosis and management.     

Elastic stable intramedullary nailing of tibial shaft fractures in children

Purpose  

Tibial fractures in the skeletally immature patient are usually treated without surgery. Elastic stable intramedullary nailing (ESIN) is commonly used for other diaphyseal fracture locations. Its advantages are minimally invasive surgery with a short hospitalisation duration, primary bone union and early weight bearing. The purpose of this study was to assess the use of ESIN in displaced tibial fractures in children over 6 years old and in cases of polytrauma.     

Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylases in Melanoma

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Synthetic lethal targeting of DNA double-strand break repair deficient cells by human apurinic/apyrimidinic endonuclease inhibitors

An apurinic/apyrimidinic (AP) site is an obligatory cytotoxic intermediate in DNA Base Excision Repair (BER) that is processed by human AP endonuclease 1 (APE1). APE1 is essential for BER and an emerging drug target in cancer. We have isolated novel small molecule inhibitors of APE1. In this study, we have investigated the ability of APE1 inhibitors to induce synthetic lethality (SL) in a panel of DNA double-strand break (DSB) repair deficient and proficient cells; i) Chinese hamster (CH) cells: BRCA2 deficient (V-C8), ATM deficient (V-E5), wild type (V79) and BRCA2 revertant [V-C8(Rev1)]. ii) Human cancer cells: BRCA1 deficient (MDA-MB-436), BRCA1 proficient (MCF-7), BRCA2 deficient (CAPAN-1 and HeLa SilenciX cells), BRCA2 proficient (PANC1 and control SilenciX cells). We also tested SL in CH ovary cells expressing a dominant-negative form of APE1 (E8 cells) using ATM inhibitors and DNA-PKcs inhibitors (DSB inhibitors). APE1 inhibitors are synthetically lethal in BRCA and ATM deficient cells. APE1 inhibition resulted in accumulation of DNA DSBs and G2/M cell cycle arrest. SL was also demonstrated in CH cells expressing a dominant-negative form of APE1 treated with ATM or DNA-PKcs inhibitors. We conclude that APE1 is a promising SL target in cancer.     

Effect of Gum Arabic on plaque-induced gingivitis: A randomised controlled trial

New approaches to treating periodontal diseases aim to balance sustaining the natural oral microbiota and modifying the host immune response. Gum Arabic (GA) is a natural polysaccharide rich in prebiotics.The aim of this study was to assess the effect of GA on clinical (Plaque Index (PI), Gingival Index (GI)) and immunological (Gingival Crevicular Fluid Interleukin 1 Beta (GCF IL-1 β)) parameters in patients with plaque-induced gingivitis.Materials and methodsThis placebo-controlled, double-blinded randomised clinical trial was conducted at the Department of Periodontology at Khartoum Dental Teaching Hospital, Khartoum, Sudan, from July to October 2016. Patients diagnosed with plaque-induced gingivitis meeting the study eligibility criteria were enrolled. At baseline, PI, GI and GCF IL-1β were measured. Patients received full-mouth scaling and were randomly assigned to receive either GA powder (intervention group) or Microcrystalline cellulose powder (placebo group). The patients were instructed to apply the treatment twice a day throughout the study. The PI, GI and GCF IL-1β were reassessed after 30 and 60 days.ResultsA total of 60 patients were enrolled (30 in each group). Compared to the placebo group, the intervention group showed a statistically significant reduction in GI scores after 30 days and improved PI scores at 30 and 60 days. Between baseline and 60 days, patients who received GA exhibited a significant reduction in GCF IL-1β levels compared to the placebo group.ConclusionGA was found to be effective in controlling plaque and gingivitis.Clinical Trial Registration. ISRCTN registry ISRCTN14209449.     

Applicability of the commonly used risk scores for coronary bypass surgery in Algeria

ObjectivesThe applicability of European system for cardiac operative risk evaluation II (EuroSCORE II) and the Society of Thoracic Surgeons Predicted Risk Of Mortality (STS-PROM) as well as the initial logistic Parsonnet risk score, who have been developed from European and American datasets, is questionable outside these regions. We aimed to assess the performance of these three risk scores for patients undergoing isolated coronary artery bypass grafting (CABG) in Algeria.MethodsBetween June 2014 and June 2016, data from 235 consecutive patients, who underwent isolated CABG at a reference center in Algiers, were prospectively collected and scored according to the EuroSCORE II, STS-PROM and the Parsonnet score. Their discriminative power was evaluated by the area under the receiver operating characteristic curve (AUC) while their calibration was tested by the Hosmer–Lemeshow goodness-of-fit test.ResultsThe mean patient age was 59.08 years and 18.3% were female. The mortality at 30 days was 3.40%. The mortality expected by EuroSCORE II, STS-PROM and by Parsonnet risk score was: 1.33%, 0.78% and 3.35%, respectively. Discriminatory ability was fair for the Parsonnet risk score, good for the STS PROM and excellent for EuroSCORE II (AUCs = 0.737, 0.788, and 0.892, respectively). Regarding calibration, EuroSCORE II and STS-PROM under estimated observed mortality (Hosmer–Lemeshow test: P< 0.001 for both scores), while the Parsonnet risk score was well calibrated (Hosmer–Lemeshow test: p = 0.395).ConclusionsEuroSCORE II and STS-PROM had excellent and good discriminating power, respectively, but both underestimated the risk of 30 days mortality following isolated CABG at a reference center in Algiers. The Parsonnet risk score was well calibrated but was moderately discriminating. The development of a local risk score or the recalibration of recent international risk scores is necessary.