Sedation-risk-free colonoscopy for minimizing the burden of colorectal cancer screening

Unsedated colonoscopy is available worldwide, but is not a routine option in the United States (US). We conducted a literature review supplemented by our experience and expert commentaries to provide data to support the use of unsedated colonoscopy for colorectal cancer screening. Medline data from 1966 to 2009 were searched to identify relevant articles on the subject. Data were summarized and co-authors provided critiques as well as accounts of unsedated colonoscopy for screening and surveillance. Diagnostic colonoscopy was initially developed as an unsedated procedure. Procedure-related discomfort led to wide adoption of sedation in the US, although unsedated colonoscopy remains the usual practice elsewhere. The increased use of colonoscopy for colorectal cancer screening in healthy, asymptomatic individuals suggests a reassessment of the burden of sedation in colonoscopy for screening is appropriate in the US for lowering costs and minimizing complications for patients. A water method developed to minimize discomfort has shown promise to enhance outcomes of unsedated colonoscopy. The use of scheduled, unsedated colonoscopy in the US appears to be feasible for colorectal cancer screening. Studies to assess its applicability in diverse practice settings deserve to be conducted and supported.     

Saudi Meds: a competence specification for Saudi medical graduates

A national competence framework has been developed by medical schools in the Kingdom of Saudi Arabia. The framework has seven domains - approach to daily Practice, Dr and patient, Dr and community, communication skills, professionalism, Dr and information technology, Dr and research. The framework will guide curriculum development and assessment in the Kingdom and ensure that medical education adapts to changing needs. The creation of a national framework promises the delivery of equivalent standards between medical schools while at the same time guaranteeing the schools' autonomy.     

Child healthcare in the United Kingdom and Nigeria

Child healthcare differs widely from one country to another. The differences vary even more widely between developed and developing countries. The Nigerian and British child healthcare system share some similarities, but are significantly different in many areas. The structure of the healthcare system is quite similar and in the area of immunisation, the government of the two countries give childhood immunisation programme a priority. However, differences exist in areas of accessibility to child healthcare, parental attitude towards immunisation and efficiency of the child healthcare system. The aim of this paper is, to share with the medical community, the similarities and differences in child healthcare between the two countries. This would be of interest to colleagues who have not worked in both systems.     

Novel use of poly(3,4-ethylenedioxythiophene) nanoparticles for fluorescent nucleic acid detection

In this paper, we demonstrate the novel use of poly(3,4-ethylene dioxythiophene) (PEDOT) nanoparticle as a very effective fluorescent sensing platform for the detection of nucleic acid sequences. The principle of the assay lies in the fact that the adsorption of the fluorescently labeled single-stranded DNA (ssDNA) probe by PEDOT nanoparticle leads to substantial fluorescence quenching, followed by specific hybridization with the complementary region of the target DNA sequence. This results in desorption of the hybridized complex from PEDOT nanoparticle surface and subsequent recovery of fluorescence. A detection limit as low as 30 pM could be achieved in this sensing system. We also demonstrate its application for multiplexed detection of nucleic acid sequences. Furthermore, this sensing system can realize the detection of single-base mismatch even in multiplexed format. It is of importance to note that the successful use of this sensing platform in human blood serum system is also demonstrated.     

Burkholderia cenocepacia O polysaccharide chain contributes to caspase-1-dependent IL-1beta production in macrophages

Burkholderia cenocepacia infections in CF patients involve heightened inflammation, fatal sepsis, and high antibiotic resistance. Proinflammatory IL-1β secretion is important in airway inflammation and tissue damage. However, little is known about this pathway in macrophages upon B. cenocepacia infection. We report here that murine macrophages infected with B. cenocepacia K56-2 produce proinflammatory cytokine IL-1β in a TLR4 and caspase-1-mediated manner. We also determined that the OPS (O antigen) of B. cenocepacia LPS contributes to IL-1β production and pyroptotic cell death. Furthermore, we showed that the malfunction of the CFTR channel augmented IL-1β production upon B. cenocepacia infection of murine macrophages. Taken together, we identified eukaryotic and bacterial factors that contribute to inflammation during B. cenocepacia infection, which may aid in the design of novel approaches to control pulmonary inflammation.     

Axial spondylometaphyseal dysplasia: additional reports

Axial spondylometaphyseal dysplasia (SMD) (OMIM 602271) is an uncommon skeletal dysplasia characterized by metaphyseal changes of truncal-juxtatruncal bones, including the proximal femora, and retinal abnormalities. The disorder has not attracted much attention since initially reported; however, it has been included in the nosology of genetic skeletal disorders [Warman et al. (2011); Am J Med Genet Part A 155A:943-968] in part because of a recent publication of two additional cases [Isidor et al. (2010); Am J Med Genet Part A 152A:1550-1554]. We report here on the clinical and radiological manifestations in seven affected individuals from five families (three sporadic cases and two familial cases). Based on our observations and Isidor's report, the clinical and radiological hallmarks of axial SMD can be defined: The main clinical findings are postnatal growth failure, rhizomelic short stature in early childhood evolving into short trunk in late childhood, and thoracic hypoplasia that may cause mild to moderate respiratory problems in the neonatal period and later susceptibility to airway infection. Impaired visual acuity comes to medical attention in early life and function rapidly deteriorates. Retinal changes are diagnosed as retinitis pigmentosa or pigmentary retinal degeneration on fundoscopic examination and cone-rod dystrophy on electroretinogram. The radiological hallmarks include short ribs with flared, cupped anterior ends, mild spondylar dysplasia, lacy iliac crests, and metaphyseal irregularities essentially confined to the proximal femora. Equally affected sibling pairs of opposite gender and parental consanguinity are strongly suggestive of autosomal recessive inheritance.     

A novel missense and a recurrent mutation in SLC2A10 gene of patients affected with arterial tortuosity syndrome

Arterial tortuosity syndrome is an autosomal recessive disorder characterized by severe tortuosity of greater and systemic arteries in affected individuals. In addition, patients display connective tissue features which include hyperextensible skin, hypermobility of joints and characteristic facial features. This syndrome is caused by mutation in SLC2A10 gene which encodes for the facilitative glucose transporter, GLUT10. We describe seven patients of two unrelated Saudi Arabian families who display tortuosity, dilatation and stenosis of arteries, pulmonary hypertension and other cardiovascular manifestations. These patients exhibit characteristic connective tissue phenotypes and distinctive facial features. In the single patient of Family 1, sequencing of the candidate gene, SLC2A10, identified a novel missense c.313C>T mutation encoding a p.Arg105Cys substitution in the second extracellular domain of GLUT10. The Arg105 in GLUT10 is highly conserved across species and its replacement with cysteine is predicted to be pathogenic. In the second family, all of the six affected individuals carry recurrent c.243C>G missense mutation encoding a p.Ser81Arg change in the third transmembrane domain of GLUT10. The present study suggests that there exists an intra- and inter-familial phenotypic variability in arterial tortuosity patients carrying identical or different mutations in SLC2A10 gene. While skin hyperextensibility, small joint hypermobility, and facial features are similarly expressed in these patients, there is a range of other phenotypes which include arterial tortuosity and associated complications, and abnormalities of other organs.     

Incidence,Predictors, and Outcomes of Acute Ischemic Stroke Following Percutaneous Coronary Intervention

ObjectivesThe aim of this study was to assess temporal trends in the incidence of ischemic stroke among patients undergoing percutaneous coronary intervention (PCI), predictors of post-PCI ischemic stroke, and the impact of post-PCI ischemic stroke on in-hospital morbidity, mortality, length of stay, and cost.BackgroundData on the incidence and outcomes of ischemic stroke in patients undergoing PCI in the contemporary era are limited.MethodsThe National Inpatient Sample was used to identify patients who underwent PCI between January 1, 2003, and December 31, 2016. The incidence of post-PCI ischemic stroke was calculated, and its predictors were assessed. In-hospital outcomes of patients with and those without post-PCI stroke were also compared.ResultsThe adjusted incidence of post-PCI ischemic stroke increased during the study period from 0.6% to 0.96% following PCI for ST-segment elevation myocardial infarction, from 0.5% to 0.6% following PCI for non–ST-segment elevation myocardial infarction, and from 0.3% to 0.72% following PCI for unstable angina or stable ischemic disease (p_trend <0.001). Carotid disease, cardiogenic shock, atrial fibrillation, and older age were the strongest predictors of post-PCI ischemic stroke. Post-PCI stroke rates were lower at high-volume versus low- to intermediate-volume centers. Thrombolytics, cerebral angiography, and mechanical thrombectomy use increased over time but remained infrequent. After propensity score matching, in-hospital mortality was higher among patients with post-PCI stroke (23.5% vs. 11.0%, 9.5% vs. 2.8%, and 11.5% vs. 2.4% in the ST-segment elevation myocardial infarction, non–ST-segment elevation myocardial infarction, and unstable angina or stable ischemic heart disease cohorts, respectively; p < 0.001). Post-PCI stroke was associated with a >2-fold increase in length of stay, a >3-fold increase in nonhome discharges, and a >60% increase in cost.ConclusionsThe incidence of post-PCI ischemic stroke increased significantly over the past decade, partially because of the increasing complexity of patients undergoing PCI over time. Further studies are needed to systematically assess contributors to this worrisome trend and to identify effective strategies for its mitigation.     

Phase I Dose-Escalation Study of Stereotactic Body Radiotherapy in Patients With Hepatic Metastases

Purpose

To identify a tolerable and effective dose for 5-fraction stereotactic body radiotherapy for hepatic metastases.

Methods

Patients were enrolled onto three dose-escalation cohorts: 30 Gy in 3 fractions, 50 Gy in 5 fractions, and 60 Gy in 5 fractions. Eligible patients had one to five hepatic metastases, ability to spare a critical hepatic volume (volume receiving <21 Gy) of 700 ml, adequate baseline hepatic function, no concurrent antineoplastic therapy, and a Karnofsky performance score of ≥60. Dose-limiting toxicity included treatment-related grade 3 toxicity in the gastrointestinal, hepatobiliary/pancreas, and metabolic/laboratory categories. Any grade 4 or 5 event attributable to therapy was defined as a dose-limiting toxicity. Local control (LC) and complete plus partial response rates were assessed.

Results

Twenty-seven patients, 9 in each cohort, with 37 lesions were enrolled and treated: 17 men and 11 women; median age 62 (range 48–86) years; most common site of primary disease, colorectal (44.4%). Median follow-up was 20 (range 4–53) months. There was no grade 4 or 5 toxicity or treatment-related grade 3 toxicity. Actuarial 24-month LC rates for the 30-, 50-, and 60-Gy cohorts were 56%, 89%, and 100%, respectively. There was a statistically significant difference for LC between the 60- and 30-Gy cohorts (P = 0.009) but not between the 60- and 50-Gy cohorts (P = 0.56) or the 50- and 30-Gy cohorts (P = 0.091). The maximum tolerated dose was not reached.

Conclusions

A dose of 60 Gy in 5 fractions can be safely delivered to selected patients with hepatic metastases as long as the critical liver volume is respected. A dose of 60 Gy in 5 fractions yields an excellent level of LC.