The global epidemic of prediabetes and diabetes has led to a corresponding epidemic of complications of these disorders. The most prevalent complication is neuropathy, of which distal symmetric ...polyneuropathy (for the purpose of this Primer, referred to as diabetic neuropathy) is very common. Diabetic neuropathy is a loss of sensory function beginning distally in the lower extremities that is also characterized by pain and substantial morbidity. Over time, at least 50% of individuals with diabetes develop diabetic neuropathy. Glucose control effectively halts the progression of diabetic neuropathy in patients with type 1 diabetes mellitus, but the effects are more modest in those with type 2 diabetes mellitus. These findings have led to new efforts to understand the aetiology of diabetic neuropathy, along with new 2017 recommendations on approaches to prevent and treat this disorder that are specific for each type of diabetes. In parallel, new guidelines for the treatment of painful diabetic neuropathy using distinct classes of drugs, with an emphasis on avoiding opioid use, have been issued. Although our understanding of the complexities of diabetic neuropathy has substantially evolved over the past decade, the distinct mechanisms underlying neuropathy in type 1 and type 2 diabetes remains unknown. Future discoveries on disease pathogenesis will be crucial to successfully address all aspects of diabetic neuropathy, from prevention to treatment.
Diabetic peripheral neuropathy (DPN), a complication of metabolic syndrome, type I and type II diabetes, leads to sensory changes that include slow nerve conduction, nerve degeneration, loss of ...sensation, pain, and gate disturbances. These complications remain largely untreatable, although tight glycemic control can prevent neuropathy progression. Nonpharmacologic approaches remain the most impactful to date, but additional advances in treatment approaches are needed.
This review highlights several emerging interventions, including a focus on dietary interventions and physical activity, that continue to show promise for treating DPN. We provide an overview of our current understanding of how exercise can improve aspects of DPN. We also highlight new studies in which a ketogenic diet has been used as an intervention to prevent and reverse DPN.
Both exercise and consuming a ketogenic diet induce systemic and cellular changes that collectively improve complications associated with DPN. Both interventions may involve similar signaling pathways and benefits but also impact DPN through unique mechanisms.
These lifestyle interventions are critically important as personalized medicine approaches will likely be needed to identify specific subsets of neuropathy symptoms and deficits in patients, and determine the most impactful treatment. Overall, these two interventions have the potential to provide meaningful relief for patients with DPN and provide new avenues to identify new therapeutic targets.
We sought is to determine the mechanism of failure among primary total knee arthroplasties (TKAs) performed at a single high-volume institution by asking the following research questions: (1) What ...are the most common failure modes for modern TKA designs? and (2) What are the preoperative risk factors for failure following primary TKA?
From May 2007 to December 2012, 18,065 primary TKAs performed on 16,083 patients at a single institution were recorded in a prospective total joint arthroplasty registry with a minimum of 5-year follow-up. We retrospectively reviewed patient charts to determine a cause of failure for primary TKAs. A cox proportional hazard model was used to determine the risk of revision surgery following primary TKA.
The most common reasons for failure within 2 years after TKA were infection and stiffness. The multivariable regression identified the following preoperative risk factors for TKA failure: history of drug abuse (hazard ratio HR 4.68; P = 0.03), deformity/mechanical preoperative diagnosis (HR 3.52; P < .01), having a constrained condylar knee implant over posterior-stabilized implant (HR 1.99; P < .01), post-traumatic/trauma preoperative diagnosis (HR 1.78; P = .03), and younger age (HR 0.61; P < .01)
These findings add to the growing data that primary TKAs are no longer failing from polyethylene wear-related issues. This study identified preoperative risk factors for failure of primary TKAs, which may be useful information for developing strategies to improve outcomes following TKA.
We employ robust weak gravitational lensing measurements to improve cosmological constraints from measurements of the galaxy cluster mass function and its evolution, using X-ray selected clusters ...detected in the ROSAT All-Sky Survey. Our lensing analysis constrains the absolute mass scale of such clusters at the 8 per cent level, including both statistical and systematic uncertainties. Combining it with the survey data and X-ray follow-up observations, we find a tight constraint on a combination of the mean matter density and late-time normalization of the matter power spectrum, ..., with marginalized, one-dimensional constraints of ... and ... For these two parameters, this represents a factor of 2 improvement in precision with respect to previous work, primarily due to the reduced systematic uncertainty in the absolute mass calibration provided by the lensing analysis. Our new results are in good agreement with constraints from cosmic microwave background (CMB) data, both Wilkinson Microwave Anisotropy Probe (WMAP) and Planck (plus WMAP polarization), under the assumption of a flat ...CDM cosmology with minimal neutrino mass. Consequently, we find no evidence for non-minimal neutrino mass from the combination of cluster data with CMB, supernova and baryon acoustic oscillation measurements, regardless of which all-sky CMB data set is used (and independent of the recent claimed detection of B modes on degree scales). We also present improved constraints on models of dark energy (both constant and evolving), modifications of gravity, and primordial non-Gaussianity. Assuming flatness, the constraints for a constant dark energy equation of state from the cluster data alone are at the 15 per cent level, improving to ~6 per cent when the cluster data are combined with other leading probes. (ProQuest: ... denotes formulae/symbols omitted.)
Dietary interventions are promising approaches to treat pain associated with metabolic changes because they impact both metabolic and neural components contributing to painful neuropathy. Here, we ...tested whether consumption of a ketogenic diet could affect sensation, pain, and epidermal innervation loss in type 1 diabetic mice. C57Bl/6 mice were rendered diabetic using streptozotocin and administered a ketogenic diet at either 3 weeks (prevention) or 9 weeks (reversal) of uncontrolled diabetes. We quantified changes in metabolic biomarkers, sensory thresholds, and epidermal innervation to assess impact on neuropathy parameters. Diabetic mice consuming a ketogenic diet had normalized weight gain, reduced blood glucose, elevated blood ketones, and reduced hemoglobin-A1C levels. These metabolic biomarkers were also improved after 9 weeks of diabetes followed by 4 weeks of a ketogenic diet. Diabetic mice fed a control chow diet developed rapid mechanical allodynia of the hind paw that was reversed within a week of consumption of a ketogenic diet in both prevention and reversal studies. Loss of thermal sensation was also improved by consumption of a ketogenic diet through normalized thermal thresholds. Finally, diabetic mice consuming a ketogenic diet had normalized epidermal innervation, including after 9 weeks of uncontrolled diabetes and 4 weeks of consumption of the ketogenic diet. These results suggest that, in mice, a ketogenic diet can prevent and reverse changes in key metabolic biomarkers, altered sensation, pain, and axon innervation of the skin. These results identify a ketogenic diet as a potential therapeutic intervention for patients with painful diabetic neuropathy and/or epidermal axon loss.
Abstract We used a large prospective institutional registry to determine if there is a ‘safe zone’ that exists for acetabular component position within which the risk of hip dislocation is low and if ...other patient and implant factors affect the risk of hip dislocation. Patients who reported a dislocation event within six months after hip arthroplasty surgery were identified, and acetabular component position was measured with anteroposterior radiographs. The frequency of dislocation was 2.1% (147 of 7040 patients). No significant difference was found in the number of dislocated hips among the radiographic zones (± 5°, ± 10°, ± 15° boundaries). Dislocators < 50 years old were less active preoperatively than nondislocators ( P = 0.006). Acetabular component position alone is not protective against instability.
Abstract Background Modularity at the head-neck junction in total hip arthroplasty (THA) allows for intraoperative adjustments, but may be a source of metallic debris. We determined how flexural ...rigidity, taper angle, contact length, and lever arm affect fretting and corrosion at this junction. Methods 77 metal-on-polyethylene THAs retrieved over a 10-year period at a single institution were obtained. Head tapers and stem trunnions were graded for fretting and corrosion. Results Stem fretting was inversely related to rigidity and taper angle, while positively correlated to contact length. Head fretting and head and stem corrosion were not associated with any of these parameters. Conclusion Design and assembly factors at the modular head-neck connection affected stem fretting among the retrieved components, suggesting that these parameters are important to consider when choosing a modular system.
Early flowering plants are thought to have been woody species restricted to warm habitats. This lineage has since radiated into almost every climate, with manifold growth forms. As angiosperms spread ...and climate changed, they evolved mechanisms to cope with episodic freezing. To explore the evolution of traits underpinning the ability to persist in freezing conditions, we assembled a large species-level database of growth habit (woody or herbaceous; 49,064 species), as well as leaf phenology (evergreen or deciduous), diameter of hydraulic conduits (that is, xylem vessels and tracheids) and climate occupancies (exposure to freezing). To model the evolution of species' traits and climate occupancies, we combined these data with an unparalleled dated molecular phylogeny (32,223 species) for land plants. Here we show that woody clades successfully moved into freezing-prone environments by either possessing transport networks of small safe conduits and/or shutting down hydraulic function by dropping leaves during freezing. Herbaceous species largely avoided freezing periods by senescing cheaply constructed aboveground tissue. Growth habit has long been considered labile, but we find that growth habit was less labile than climate occupancy. Additionally, freezing environments were largely filled by lineages that had already become herbs or, when remaining woody, already had small conduits (that is, the trait evolved before the climate occupancy). By contrast, most deciduous woody lineages had an evolutionary shift to seasonally shedding their leaves only after exposure to freezing (that is, the climate occupancy evolved before the trait). For angiosperms to inhabit novel cold environments they had to gain new structural and functional trait solutions; our results suggest that many of these solutions were probably acquired before their foray into the cold.
Background
Sitting pelvic tilt dictates the proximity of the rim of the acetabulum to the proximal femur and, therefore, the risk of impingement in patients undergoing total hip arthroplasty (THA). ...Sitting position is achieved through a combination of lumbar spine segmental motions and/or femoroacetabular articular motion in the lumbar-pelvic-femoral complex. Multilevel degenerative disc disease (DDD) may limit spine flexion and therefore increase femoroacetabular flexion in patients having THAs, but this has not been well characterized. Therefore, we measured standing and sitting lumbar-pelvic-femoral alignment in patients with radiographic signs of DDD and in patients with no radiographic signs of spine arthrosis.
Questions/purposes
We asked: (1) Is there a difference in standing and sitting lumbar-pelvic-femoral alignment before surgery among patients undergoing THA who have no radiographic signs of spine arthrosis compared with those with preexisting lumbar DDD? (2) Do patients with lumbar DDD experience less spine flexion moving from a standing to a sitting position and therefore compensate with more femoroacetabular flexion compared with patients who have no radiographic signs of arthrosis?
Methods
Three hundred twenty-five patients undergoing primary THA had preoperative low-dose EOS spine-to-ankle lateral radiographs in standing and sitting positions. Eighty-three patients were excluded from this study for scoliosis (39 patients), spondylolysis (15 patients), not having five lumbar vertebrae (7 patients), surgical or disease fusion (11 patients), or poor image quality attributable to high BMI (11 patients). In the remaining 242 of 325 patients (75%), two observers categorized the lumbar spine as either without radiographic arthrosis or having DDD based on defined radiographic criteria. Sacral slope, lumbar lordosis, and proximal femur angles were measured, and these angles were used to calculate lumbar spine flexion and femoroacetabular flexion in standing and sitting positions. Patients were aligned in a standardized sitting position so that their femurs were parallel to the floor to achieve approximately 90° of apparent hip flexion.
Results
After controlling for age, sex, and BMI, we found patients with DDD spines had a mean of 5° more posterior pelvic tilt (95% CI, −2° to −8° lower sacral slope angles; p < 0.01) and 7° less lumbar lordosis (95% CI, −10° to −3°; p < 0.01) in the standing position compared with patients without radiographic arthrosis. However, in the sitting position, patients with DDD spines had 4° less posterior pelvic tilt (95% CI, 1°–7° higher sacral slope angles; p = 0.02). From standing to sitting position, patients with DDD spines experienced 10° less spine flexion (95% CI, −14° to −7°; p < 0.01) and 10° more femoroacetabular flexion (95% CI, 6° to 14°; p < 0.01).
Conclusions
Most patients undergoing THA sit in a similar range of pelvic tilt, with a small mean difference in pelvic tilt between patients with DDD spines and those without radiographic arthrosis. However, in general, the mechanism by which patients with DDD of the lumbar spine achieve sitting differs from those without spine arthrosis with less spine flexion and more femoroacetabular flexion.
Clinical Relevance
When planning THA, it may be important to consider which patients sit with less posterior pelvic tilt and those who rotate their pelvises forward to achieve a sitting position, as both mechanisms will limit or reduce the functional anteversion of the acetabular component in a patient with a THA. Our study provides some additional perspective on normal relationships between pelvic tilt and femoroacetabular flexion, but further research might better characterize this relationship in outliers and the possible implications for posterior instability after THA.
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