Citations

Hypertension is a major cause of cardiovascular disease and deaths worldwide especially in low- and middle-income countries. Despite the availability of safe, well-tolerated, and cost-effective blood pressure (BP)-lowering therapies, <14% of adults with hypertension have BP controlled to a systolic/diastolic BP <140/90 mm Hg. We report new hypertension treatment guidelines, developed in accordance with the World Health Organization Handbook for Guideline Development. Overviews of reviews of the evidence were conducted and summary tables were developed according to the Grading of Recommendations, Assessment, Development, and Evaluations approach. In these guidelines, the World Health Organization provides the most current and relevant evidence-based guidance for the pharmacological treatment of nonpregnant adults with hypertension. The recommendations pertain to adults with an accurate diagnosis of hypertension who have already received lifestyle modification counseling. The guidelines recommend BP threshold to initiate pharmacological therapy, BP treatment targets, intervals for follow-up visits, and best use of health care workers in the management of hypertension. The guidelines provide guidance for choice of monotherapy or dual therapy, treatment with single pill combination medications, and use of treatment algorithms for hypertension management. Strength of the recommendations was guided by the quality of the underlying evidence; the tradeoffs between desirable and undesirable effects; patient’s values, resource considerations and cost-effectiveness; health equity; acceptability, and feasibility consideration of different treatment options. The goal of the guideline is to facilitate standard approaches to pharmacological treatment and management of hypertension which, if widely implemented, will increase the hypertension control rate world-wide.

Summary Introduction Esophageal adenocarcinoma (EAC) is an aggressive cancer, associated with reflux esophagitis and intestinal metaplasia (IM). One underlying biological mechanism, which possibly drives the development of EAC, is the dysregulated expression of Bone Morphogenetic Proteins (BMPs). Aim To investigate if local delivery of Noggin, a BMP antagonist, reduced EAC. Methods After obtaining proof of principal on local delivery of a Noggin/Sucralfate substance, a randomized controlled trial to test the effects of Noggin on EAC development was performed in a surgical rat model. In the model, an esophago-jejunostomy leads to development of reflux-esophagitis, IM and eventually EAC. Rats were treated by Noggin/Sucralfate or Sucralfate alone. Treatment was administered from 26 to 29 weeks after the operation. Results Of the 112 operated rats, 52 survived beyond 26 weeks. Finally, 25 rats treated with Noggin/Sucralfate and 21 with Sucralfate, were evaluated. At the end, 39 (85%) of the animals had IM while 28 (61%) developed cancer. There were significantly more cancers in the Noggin/Sucralfate arm (50%) versus the Sucralfate group (73%) (Chi square, P &lt; 0.05). Most cancers were mucous producing T3 adenocarcinomas. There were no significant differences in the amount of IM, size or grade of the cancers, or expression of columnar and squamous markers between the two groups. Conclusion In this study, we demonstrated that inhibition of BMPs by Noggin reduced development of EAC in a surgical esophagitis-IM-EAC rat model. In future, effective targeting of the BMP pathway with selective BMP-inhibitors could become an important asset to improve EAC patient outcome.

Abstract Objective To study the prevalence, risk and clinical associations of hypothyroidism among several forms of vasculitis. Methods Patients with GCA, Takayasu’s arteritis (TAK), PAN and the three forms of ANCA-associated vasculitis [AAV; granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (EGPA)] enrolled in a prospective, multicentre, longitudinal study were included. Results The study included data on 2085 patients [63% female, 90% White] with a mean age of 54.6 years (s.d. 17.2). Diagnoses were GCA (20%), TAK (11%), PAN (5%), GPA (42%), microscopic polyangiitis (8%) and EGPA (14%). Hypothyroidism was present in 217 patients (10%) (83% female), with a mean age 59.8 years (s.d. 14.5). Age- and sex-adjusted risk of hypothyroidism was GCA, odds ratio (OR) 0.61 (95% CI 0.41, 0.90); TAK, OR 0.57 (95% CI 0.31, 1.03); PAN, OR 0.59 (95% CI 0.25, 1.38); GPA, OR 1.51 (95% CI 1.12, 2.05); microscopic polyangiitis, OR 1.81 (95% CI 1.18, 2.80) and EGPA, OR 0.82 (95% CI 0.52, 1.30). Among patients with AAV, age- and sex-adjusted risk of hypothyroidism was higher with positive MPO-ANCA [OR 1.89 (95% CI 1.39, 2.76)]. The clinical manifestations of vasculitis were similar in patients with and without hypothyroidism, except transient ischaemic attacks, which were more frequently observed in patients with GCA and hypothyroidism (12% vs 2%; P = 0.001). Conclusions Differences in the risk of hypothyroidism among vasculitides may be due to genetic susceptibilities or immune responses. This study confirms an association of hypothyroidism with MPO-ANCA.

Abstract IntroductionRadiotherapy is considered standard of care for adjuvant peri-operative treatment of many spinal tumors, including those with instrumented fusion. Unfortunately, radiation treatment has been linked to increased risk of pseudoarthrosis. Newerfocused radiotherapy strategies with enhanced conformalitycould offer improved fusion rates for these patients, but this has not been confirmed.MethodsWe performed a retrospective analysis of patients at three tertiary care academic institutions withprimary and secondary spinal malignancies that underwent resection, instrumented fusion, and peri-operative radiotherapy. Two board certified neuro-radiologists used theLenke fusion score to grade fusion status at6 and 12-months after surgery. Secondary outcomes includedclinical pseudoarthrosis, wound complications, and the effect of radiation timing, radiobiological dose delivered, the use of photons versus protons, tumor type, tumor location,and use of autograft on fusion outcomes.ResultsAfter reviewof 1252 spinal tumor patients, there were 60 patients with at least 6 months follow-up that were included in our analyses. Twenty-five of these patients received focused radiotherapy,20 patients received conventional radiotherapy, and 15 patients were treated with protons. There was no significant difference between the groups for covariates such assmoking status,obesity, diabetes, intraoperative use of autograft, and use of peri-operative chemotherapy. There was a significantly higher rate of fusion for patients treated with focused radiotherapy compared to those treated with conventional radiotherapy at 6-months (64.0% versus 30.0%, Odds ratio: 4.15, p=0.036) and 12-months (80.0% versus 42.1%, OR: 5.50, p=0.022). There was a significantly higher rate of clinical pseudoarthrosis in the conventional radiotherapy cohortcompared to patients in the focused radiotherapy cohort (19.1% versus 0%,p=0.037). There was no difference in fusion outcomes for any of the secondary outcomes except for use of autograft. The use ofintra-operative autograft was associated with an improved fusion at 12-months (66.7% versus 37.5%, OR: 3.33, p=0.043). ConclusionFocused radiotherapy may be associated withan improved rate of fusion and clinical pseudoarthrosis when compared to conventional radiation delivery strategiesin patients with spinal tumors.Use of autograft at the time of surgery may be associated with improved 12-month fusion rates.Further large-scale prospective and randomized controlled studies are needed to better stratify the effects of radiation delivery modality in these patients.

Introduction: Retinal imaging is a non-invasive tool to study both retinal vasculature and neurodegeneration. In this exploratory retinal curcumin-fluorescence imaging (RFI) study, we sought to determine whether retinal vascular features combined with retinal amyloid burden correlate with the neurocognitive status. Methods: We used quantitative RFI in a cohort of patients with cognitive impairment to automatically compute retinal amyloid burden. Retinal blood vessels were segmented, and the vessel tortuosity index (VTI), inflection index, and branching angle were quantified. We assessed the correlations between retinal vascular and amyloid parameters, and cognitive domain Z-scores using linear regression models. Results: Thirty-four subjects were enrolled and twenty-nine (55% female, mean age 64 ± 6 years) were included in the combined retinal amyloid and vascular analysis. Eleven subjects had normal cognition and 18 had impaired cognition. Retinal VTI was discriminated among cognitive scores. The combined proximal mid-periphery amyloid count and venous VTI index exhibited significant differences between cognitively impaired and cognitively normal subjects (0.49 ± 1.1 vs. 0.91 ± 1.4, p = 0.006), and correlated with both the Wechsler Memory Scale-IV and SF-36 mental component score Z-scores (p < 0.05). Conclusion: This pilot study showed that retinal venular VTI combined with the proximal mid-periphery amyloid count could predict verbal memory loss. Future research is needed to finesse the clinical application of this retinal imaging-based technology.

Abstract: Many sports medicine physicians are currently considering introducing regenerative medicine into their practice. Regenerative medicine and the subclassification of orthobiologics are a complicated topic and have produced widely varying opinions. Although there is concern by government regulators, clinicians, scientists, patient advocacy organizations, and the media regarding the use of regenerative medicine products, there is also excitement about the potential benefits with growing evidence that certain regenerative medicine products are safe and potentially efficacious in treating musculoskeletal conditions. Sports medicine physicians would benefit from decision-making guidance about whether to introduce orthobiologics into their practice and how to do it responsibly. The purpose of this position statement is to provide sports medicine physicians with information regarding regenerative medicine terminology, a brief review of basic science and clinical studies within the subclassification of orthobiologics, regulatory considerations, and best practices for introducing regenerative medicine into clinical practice. This information will help sports medicine physicians make informed and responsible decisions about the role of regenerative medicine and orthobiologics in their practice.