Neuroprotective role of statins in treating Alzheimer's disease: a comparative study of biomedical and clinical trials

Thesis (M.A.)--Boston UniversityAlzheimer’s disease is a neurodegenerative disorder that occurs most commonly in the elderly. The formation of amyloid plaques and neurofibrillary tangles affects the brain tissue, causing mental deficits ranging in severity from memory loss to incontinence and feeding problems. Currently, the only approved treatments are designed to treat the symptoms of the disease, rather than prevention or slowing the progression. Yet, over the course of the last few decades, researchers have sought new ways of treating the condition. One such drug with promising effects is the cholesterol lowering statin medication. Yet the efficacy shown in the laboratory has not translated to clinical trials to treat AD patients. Therefore, this study analyzed various important biomedical and clinical studies in the literature to elucidate why this disparity exists. On examination of biomedical studies, there was a wide range of support for statins due to its many pleiotropic effects. This drug was shown to be permeable through the blood brain barrier, helping to reverse the damage caused by amyloid plaque formation in brain vessel walls. Other studies showed the link between high cholesterol and AD by analyzing the effects of memory deficits in mice while they attempted various tasks. They used analogs to simulate the disease and found that statins helped delay or reverse some of these changes. On examination of clinical studies, the majority of studies could not find a statistically significant correlation between statin use and neuroprotection against AD. Those that did find a positive correlation needed further study to account for any confounding variables. After examination of these papers it became clear that the disparity between the two realms of study was due to the design of the experiments themselves. The biomedical studies focused on various effects of statins rather than on how the mechanisms of action directly affected AD progression. As of yet not all of the pleiotropic effects have been examined and definitely not within the context of how they effect and complement one another. Thus clinical trials trying to integrate this information have been very discouraging and the designs of these studies, both prospective trials and epidemiological studies further complicate the answers sought. They all varied in the age groups they examined, how early treatment was initiated, which statin was used, and how other confounding variables (such as sociodemographics and smoking) were accounted for. After analyzing the literature, it is in our opinion that statins play a protective role if initiated much earlier than the first clinical signs. However the only way to know how it biochemically may help AD patients is through further study. So, it is our recommendation for more in depth study on the pleiotropic effects of statins on AD, before further clinical intervention occurs

Temperature mapping of stacked silicon dies from x-ray diffraction intensities

Increasing power densities in integrated circuits has led to an increased prevalence of thermal hotspots in integrated circuits. Tracking these thermal hotspots is imperative to prevent circuit failures. In 3D integrated circuits, conventional surface techniques like infrared thermometry are unable to measure 3D temperature distribution and optical and magnetic resonance techniques are difficult to apply due to the presence of metals and large current densities. X-rays offer high penetration depth and can be used to probe 3D structures. We report a method utilizing the temperature dependence of x-rays diffraction intensity via the Debye-Waller factor to simultaneously map the temperature of an individual silicon die that is a part of a stack of dies. Utilizing beamline 1-ID-E at the Advanced Photon Source (Argonne), we demonstrate for each individual silicon die, a temperature resolution of 3 K, a spatial resolution of 100 um x 400 um and a temporal resolution of 20 s. Utilizing a sufficiently high intensity laboratory source, e.g., from a liquid anode source, this method can be scaled down to laboratories for non-invasive temperature mapping of 3D integrated circuits

Internal Maxillary Artery Preoperative Embolization Using n-Butyl Cyanoacrylate and Pushable Coils for Temporomandibular Joint Ankylosis Surgery

BACKGROUND: Temporomandibular joint (TMJ) ankylosis causes disability through impaired digestion, mastication, speech, and appearance. Surgical treatment increases range of motion with resultant functional improvement. However, substantial perioperative blood loss can occur (up to 3 L) if the internal maxillary artery (IMAX) is injured as it traverses the ankylotic mass. Achieving hemostasis is difficult because of limited proximal IMAX access and poor visualization. Our aim is to investigate the technical feasibility and preliminary safety of preoperative IMAX embolization in patients undergoing TMJ ankylosis surgery. METHODS: Case series using chart reviews of 2 patients who underwent preoperative embolization before TMJ ankylosis surgery. RESULTS: Both patients were women (28 and 51 years old) who had severely restricted mouth opening. Embolization was performed using general anesthesia with nasal intubation on the same day of TMJ surgery. Both patients underwent bilateral IMAX embolization using pushable coils (Vortex, Boston Scientific) of distal IMAX followed by n-butyl-cyanoacrylate (Trufill, Cordis) embolization from coil mass up to proximal IMAX. There were no complications from the embolization procedures. Both patients had normal neurologic examination results. TMJ surgery occurred with minimal operative blood loss (≤300 mL for each surgery). Maximum postoperative mouth opening was 35 mm and 34 mm, respectively. One patient had a postoperative TMJ wound infection that was managed with antibiotics. CONCLUSIONS: Preoperative IMAX embolization before TMJ ankylosis surgery is technically feasible with encouraging preliminary safety. There were no complications from the embolization procedures and surgeries occurred with low volumes of blood loss

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine