Deep subcutaneous application of poly-L-lactic acid as a filler for facial lipoatrophy in HIV-infected patients

Introduction: Facial lipoatrophy is a crucial problem of HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Poly-L-lactic acid (PLA), provided as New-Fill(R)/Sculptra(TM), is known as one possible treatment option. In 2004 PLA was approved by the FDA as Sculptra(TM) for the treatment of lipoatrophy of the face in HIV-infected patients. While the first trials demonstrated relevant efficacy, this was to some extent linked to unwanted effects. As the depth of injection was considered relevant in this context, the application modalities of the preparation were changed. The preparation was to be injected more deeply into subcutaneous tissue, after increased dilution. Material and Methods: To test this approach we performed a pilot study following the new recommendations in 14 patients. Results: While the efficacy turned out to be about the same, tolerability was markedly improved. The increase in facial dermal thickness was particularly obvious in those patients who had suffered from lipoatrophy for a comparatively small period of time. Conclusion: With the new recommendations to dilute PLA powder and to inject it into the deeper subcutaneous tissue nodule formation is a minor problem. However, good treatment results can only be achieved if lipoatrophy is not too intense; treatment intervals should be about 2 - 3 weeks. Copyright (C) 2005 S. Karger AG, Basel

Association between circulating GDF-15 and cardio-renal outcomes and effect of canagliflozin: results from the CANVAS trial

Background Studies have suggested that sodium glucose co-transporter 2 inhibitors exert anti-inflammatory effects. We examined the association of baseline growth differentiation factor-15 (GDF-15), a marker of inflammation and cellular injury, with cardiovascular events, hospitalization for heart failure (HF), and kidney outcomes in patients with type 2 diabetes in the CANVAS (Canagliflozin Cardiovascular Assessment Study) and determined the effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on circulating GDF-15. Methods and Results The CANVAS trial randomized 4330 people with type 2 diabetes at high cardiovascular risk to canagliflozin or placebo. The association between baseline GDF-15 and cardiovascular (non-fatal myocardial infarction, non-fatal stroke, cardiovascular death), HF, and kidney (40% estimated glomerular filtration rate decline, end-stage kidney disease, renal death) outcomes was assessed using multivariable adjusted Cox regression models. During median follow-up of 6.1 years (N=3549 participants with available samples), 555 cardiovascular, 129 HF, and 137 kidney outcomes occurred. Each doubling in baseline GDF-15 was significantly associated with a higher risk of cardiovascular (hazard ratio [HR], 1.2; 95% CI, 1.0‒1.3), HF (HR, 1.5; 95% CI, 1.2‒2.0) and kidney (HR, 1.5; 95% CI, 1.2‒2.0) outcomes. Baseline GDF-15 did not modify canagliflozin's effect on cardiovascular, HF, and kidney outcomes. Canaglifozin treatment modestly lowered GDF-15 compared with placebo; however, GDF-15 did not mediate the protective effect of canagliflozin on cardiovascular, HF, or kidney outcomes. Conclusions In patients with type 2 diabetes at high cardiovascular risk, higher GDF-15 levels were associated with a higher risk of cardiovascular, HF, and kidney outcomes. Canagliflozin modestly lowered GDF-15, but GDF-15 reduction did not mediate the protective effect of canagliflozin

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Interleukin-6 and Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: New Insights From CANVAS

OBJECTIVE The inflammatory cytokine interleukin-6 (IL-6) is associated with cardiovascular (CV) and kidney outcomes in various populations. However, data in patients with type 2 diabetes are limited. We assessed the association of IL-6 with CV and kidney outcomes in the Canagliflozin Cardiovascular Assessment Study (CANVAS) and determined the effect of canagliflozin on IL-6. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes at high CV risk were randomly assigned to canagliflozin or placebo. Plasma IL-6 was measured at baseline and years 1, 3, and 6. The composite CV outcome was nonfatal myocardial infarction, nonfatal stroke, or CV death; the composite kidney outcome was sustained ≥40% estimated glomerular filtration rate decline, end-stage kidney disease, or kidney-related death. Multi-variable-adjusted Cox proportional hazards regression was used to estimate the associations between IL-6 and the outcomes. The effect of canagliflozin on IL-6 over time was assessed with a repeated-measures mixed-effects model. RESULTS The geometric mean IL-6 at baseline, available in 3,503 (80.2%) participants, was 1.7 pg/mL. Each doubling of baseline IL-6 was associated with 14% (95% CI 4, 24) and 21% (95% CI 1, 45) increased risk of CV and kidney outcomes, respectively. Over 6 years, IL-6 increased by 5.8% (95% CI 3.4, 8.3) in the placebo group. Canagliflozin modestly attenuated the IL-6 increase (absolute percentage difference vs. placebo 4.4% [95% CI 1.3, 9.9; P = 0.01]). At year 1, each 25% lower level of IL-6 compared with baseline was associated with 7% (95% CI 1, 22) and 14% (95% CI 5, 22) lower risks for the CV and kidney outcome, respectively. CONCLUSIONS In patients with type 2 diabetes at high CV risk, baseline IL-6 and its 1-year change were associated with CV and kidney outcomes. The effect of IL-6–lowering therapy on CV, kidney, and safety outcomes remains to be tested

The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study

<p>Introduction: Children presenting for the first time with inflammatory bowel disease (IBD) offer a unique opportunity to study aetiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; Helicobacter and Campylobacter are previously implicated in IBD pathogenesis. We set out to study these and other microaerophilic bacteria in de-novo paediatric IBD.</p> <p>Patients and Methods: 100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella wadsworthensis.</p> <p>Results: 129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was S. wadsworthensis (32 distinct isolates). Unusual Campylobacter were isolated from 8 subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C. showae). No Helicobacter were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S. wadsworthensis 82% vs. 71%, p = 0.312).</p> <p>Conclusions: This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. Campylobacter appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal. Helicobacter species are relatively rare in the paediatric colon.</p&gt

Ten Years of Experience Training Non-Physician Anesthesia Providers in Haiti.

Surgery is increasingly recognized as an effective means of treating a proportion of the global burden of disease, especially in resource-limited countries. Often non-physicians, such as nurses, provide the majority of anesthesia; however, their training and formal supervision is often of low priority or even non-existent. To increase the number of safe anesthesia providers in Haiti, Médecins Sans Frontières has trained nurse anesthetists (NAs) for over 10 years. This article describes the challenges, outcomes, and future directions of this training program. From 1998 to 2008, 24 students graduated. Nineteen (79%) continue to work as NAs in Haiti and 5 (21%) have emigrated. In 2008, NAs were critical in providing anesthesia during a post-hurricane emergency where they performed 330 procedures. Mortality was 0.3% and not associated with lack of anesthesiologist supervision. The completion rate of this training program was high and the majority of graduates continue to work as nurse anesthetists in Haiti. Successful training requires a setting with a sufficient volume and diversity of operations, appropriate anesthesia equipment, a structured and comprehensive training program, and recognition of the training program by the national ministry of health and relevant professional bodies. Preliminary outcomes support findings elsewhere that NAs can be a safe and effective alternative where anesthesiologists are scarce. Training non-physician anesthetists is a feasible and important way to scale up surgical services resource limited settings

Measurement of migration of a humeral head resurfacing prosthesis using radiostereometry without implant marking: An experimental study

Today, the shoulder joint is the third most commonly replaced joint after the hip and knee joints and the incidence is increasing. In Sweden, 1863 primary Shoulder Arthroplasties and 195 revisions were performed in 2017. The most common diagnoses are Osteoarthritis and irreparable tears of the rotator cuff, with or without arthropathy, often referred to as cuff tear arthropathy. Different Shoulder Arthroplasty (SA) concepts include anatomical total shoulder arthroplasty (TSA), hemiarthroplasty (HSA) and reversed shoulder arthroplasty, but also humeral head resurfacing (HHR) and stemless arthroplasties. All concepts offer pain relief, improvement of function and in quality of life for the different diagnoses. Unfortunately, there are sometimes complications after SA. They involve periprosthetic joint infection, humeral and glenoid fractures, stress shielding, loosening of the glenoid and humeral component but also glenoid erosion and cuff rupture. Some of these complications are most common within 1 year after operation, some after several years, both may lead to a revision. This, together with the fact that new designs of implants and methods of fixation of SA continues to develop, stresses the importance of continuous monitoring of implant survival and follow-up. The overall aim of this thesis was to describe clinical examples of different methods to assess the outcome after Shoulder Arthroplasty. The most common methods are clinical examination, radiographic assessment, Patient Reported Outcome Measure (PROM), National Joint registries, where revisions are an important outcome, but also Clinical Trials. All of these methods are used in one or more of the 4 papers in this thesis and shows the complexity of the topic and the practical work. In paper I we used Radio Stereometric Analysis (RSA) in an experimental set-up and concluded that marker-free RSA can be used for a humeral head resurfacing arthroplasty. In paper II we used data from the Swedish Shoulder Arthroplasty Registry (SSAR) with PROM and revisions to conclude that age is the only factor that affects revision when comparing HSA and HHR. Paper III is a long-time follow-up of a Randomized controlled study where we used radiological assessment, PROM and revisions. The conclusion was that both TSA and HSA develop severe radiological changes 10 year after primary operation. Paper IV is a prospective RSA cohort study where we also evaluated PROM and revisions. The conclusion is that HHR seems to obtain a secure fixation in the humerus, after an initial migration. But also that the prostheses shows continuous glenoid wear. The main conclusion of this thesis is that patient’s operated with SA needs continuous monitoring and several methods may be used to evaluate the outcome