A study of the interaction between TMAO and urea in water using NMR spectroscopy.

Trimethylamine N-oxide (TMAO) and urea are small organic biological molecules. While TMAO is known as a protective osmolyte that promotes the native form of biomolecules, urea is a denaturant. An understanding of the impact of TMAO and urea on water structure may aid in uncovering the molecular mechanisms that underlie this activity. Here we investigate binary solutions of TMAO-water, urea-water and ternary solutions of TMAO-urea-water using NMR spectroscopy at 300 K. An enhancement of the total hydrogen bonding in water was found upon the addition of TMAO and this effect was neutralised by a mole ratio of 1-part TMAO to 4-parts urea. Urea was found to have little effect on the strength of water's hydrogen bonding network and the dynamics of water molecules. Evidence was found for a weak interaction between TMAO and urea. Taken together, these results suggest that TMAO's function as a protective osmolyte, and its counteraction of urea, may be driven by the strength of its hydrogen bond interactions with water, and by a secondary reinforcement of water's own hydrogen bond network. They also suggest that the TMAO-urea complex forms through the donation of a hydrogen bond by urea.

Time-Temperature Superposition of the Dissolution of Silk Fibers in the Ionic Liquid 1-Ethyl-3-methylimidazolium Acetate.

This study investigated the dissolution of silk multifilament fibers in the ionic liquid 1-ethyl-3-methylimidazolium acetate. The dissolution process was found to create a silk composite fiber, comprising undissolved silk multifilaments surrounded by a coagulated silk matrix. The dissolution procedure was carried out for a range of temperatures and times. The resulting composite fibers were studied using a combination of optical microscopy, wide-angle X-ray diffraction (XRD), and tensile testing. An azimuthal (α) XRD scan enabled the orientation of the composite silk filaments to be quantified through a second Legendre polynomial function (P2). The P2 results could be shifted to construct a single master curve using time-temperature superposition (TTS). The shifting factors were found to have an Arrhenius behavior with an activation energy of 138 ± 13 kJ/mol. Using a simple rule of mixtures, the P2 measurements were used to calculate the dissolved silk matrix volume fraction (Vm), which also displayed TTS forming a single master curve with an activation energy of 139 ± 15 kJ/mol. The tensile Young's modulus of each silk composite filament was measured, and these results similarly formed a master curve with an activation energy of 116 ± 12 kJ/mol.

Oxidized Zirconium Components Maintain a Smooth Articular Surface Except Following Hip Dislocation.

BACKGROUND: Oxidized zirconium (OxZr) offers theoretical advantages in total hip and knee arthroplasty (THA and TKA, respectively) relative to other biomaterials by combining the tribological benefits of ceramics with the fracture toughness of metals. Yet, some studies have found that OxZr does not improve outcomes or wear rates relative to traditional bearing materials such as cobalt-chromium (CoCr). Separately, effacement of the thin ceramic surface layer has been reported for OxZr components, though the prevalence and sequelae are unclear. METHODS: To elucidate the in vivo behavior of OxZr implants, the articular surfaces of 94 retrieved THA and TKA femoral components (43 OxZr TKA, 21 OxZr THA, 30 CoCr THA) were analyzed using optical microscopy, non-contact profilometry, and scanning electron microscopy. RESULTS: We found that OxZr components maintain a smooth articular surface except following hip dislocation. Three of four OxZr femoral heads revised following dislocation exhibited severe damage to the articular surface, including macroscopic regions of ceramic-layer effacement and exposure of the underlying metal substrate; these components were 23-32 times rougher than pristine OxZr controls. When revised for dislocation, OxZr femoral heads were substantially rougher than CoCr femoral heads (median Sa = 0.431 v. 0.020 µm, P = .03). In contrast, CoCr femoral heads exhibited low overall roughness values regardless of whether they dislocated (median Sa = 0.020 v. 0.008 µm, P = .09, CoCr dislocators v. non-dislocators). CONCLUSIONS: Effacement of the ceramic surface layer and substantial articular surface roughening is not atypical following dislocation of OxZr femoral heads, making OxZr much less tolerant than CoCr to hip dislocation.

Impact of Telemonitoring of Critically Ill Emergency Department Patients Awaiting ICU Transfer.

OBJECTIVES: Because of overcrowding and limited critical care resources, critically ill patients in the emergency department may spend hours to days awaiting transfer to the ICU. In these patients, often termed "ICU boarders," delayed ICU transfer is associated with poor outcomes. We implemented an emergency department-based, electronic ICU monitoring system for ICU boarders. Our aim was to investigate the effect of this initiative on morbidity, mortality, and ICU usage. DESIGN: Single-center, retrospective cohort study. SETTING: Nonprofit, tertiary care, teaching hospital with greater than 100,000 emergency department visits per year. PATIENTS: Emergency department patients with admission orders for the medical ICU, who spent more than 2 hours boarding in the emergency department after being accepted for admission to the medical ICU, were included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the study period, a total of 314 patients were admitted to the medical ICU from the emergency department, 214 of whom were considered ICU boarders with a delay in medical ICU transfer over 2 hours. Of ICU boarders, 115 (53.7%) were enrolled in electronic ICU telemonitoring (electronic ICU care), and the rest received usual emergency department care (emergency department care). Age, mean illness severity (Acute Physiology and Chronic Health Evaluation IVa scores), and admitting diagnoses did not differ significantly between ICU boarders receiving electronic ICU care and emergency department care. Forty-one electronic ICU care patients (36%) were ultimately transitioned to a less intensive level of care in lieu of ICU admission while still in the emergency department, compared with zero patients in the emergency department care group. Among all ICU boarders transferred to the ICU, in-hospital mortality was lower in the electronic ICU care cohort when compared with the emergency department care cohort (5.4% vs 20.0%; adjusted odds ratio, 0.08). CONCLUSIONS: In critically ill patients awaiting transfer from the emergency department to the medical ICU, electronic ICU care was associated with decreased mortality and lower ICU resource utilization.

Early stages of fat crystallisation evaluated by low-field NMR and small-angle X-ray scattering.

Low-field time-domain nuclear magnetic resonance (NMR; 20 MHz) is commonly used in the studies of fats in the form of solid fat content (SFC) measurements. However, it has the disadvantage of low sensitivity to small amounts of crystalline material (0.5%), thus often incorrectly determining crystallisation induction times. From spin-lattice relaxation rate measurements (R1 ) during the isothermal crystallisation measurements of cocoa butter between 0.01 and 10 MHz using fast field cycling NMR, we learnt previously that the most sensitive frequency region is below 1 MHz. Thus, we focused on analysing our 10-kHz data in detail, by observing the time dependence of R1 and comparing it with standard SFCNMR and SFC determinations from small-angle X-ray scattering (SFCSAXS ). Although not reflecting directly the SFC, the R1 at this low frequency is very sensitive to changes in molecular aggregation and hence potentially serving as an alternative for determination of crystallisation induction times. Alongside R1 , we also show that SFCSAXS is more sensitive to early stages of crystallisation, that is, standard SFCNMR determinations become more relevant when crystal growth starts to dominate the crystallisation process but fail to pick up earlier crystallisation steps. This paper thus demonstrates the potential of studying triacylglycerols at frequencies below 1 MHz for obtaining further understanding of the early crystallisation stages of fats and presents an alternative and complementary method to estimate SFC by SAXS.

Novel Acetabular Cup for Revision THA Improves Hip Center of Rotation: A Radiographic Evaluation.

BACKGROUND: Bone loss in patients undergoing revision THA poses a considerable challenge for orthopaedic surgeons. Often, to achieve better fixation in remaining bone, larger diameter acetabular components and reaming superiorly may be necessary. However, this is likely to raise the hip center of rotation, which may lead to altered biomechanics, specifically, insufficiency of the abductor muscles, altered gait, and increased risk of dislocation from impingement. More recently, a newer acetabular shell has been designed to more closely replicate the native hip center of rotation in these circumstances while maintaining adequate fixation. QUESTIONS/PURPOSES: The purpose of this study was to compare the radiographic parameters of this newer design with conventional hemispheric cups in revision THA. Specifically, we assessed the differences in (1) vertical center of rotation (COR) displacement and (2) horizontal COR displacement. METHODS: Between January 2016 and April 2016, five reconstructive surgeons at five institutions utilized a newer highly porous acetabular shell designed with peripheral screw holes and vertically eccentric COR to allow for restoration of center of hip rotation in revision THA. We included all patients who received this device. During this time, the general indications at these sites for using the new device included Paprosky Stage IIA, IIB, IIC, or IIIA acetabular defects. This yielded 29 patients who were subsequently matched (one to two) by cup size and sex to a cohort who underwent revision THA with conventional hemispheric cups between January 2015 and May 2016. To determine hip COR, radiographic measurements were performed. A circle contiguous to the acetabulum was drawn and the center was determined as the hip COR. All measurements were made from the interteardrop line for both the revised and native hips. A line through the teardrops was used for all horizontal measurements. Center position adjustments were made based on the manufacturer-specified values. Comparisons were performed using chi-square tests for categorical and t-tests for continuous variables. There was no difference in the severity of bone loss before the revision in the groups, as evidenced by Paprosky staging of preoperative radiographs. RESULTS: The mean vertical COR displacement was smaller in patients who had the novel cup (3.5 mm; range, -12 to 15 mm; mean difference, -7.3 mm; 95% confidence interval [CI], -13.2 to -1.5) as compared with those who had the conventional cup (10.5 mm; range, -4 to 50 mm; mean difference, 7.3 mm; 95% CI, -12.5 to -2.2; p = 0.003). There was no difference in mean horizontal displacement between the two groups (-0.06 ± 6.1 versus 1.7 ± 7.1; mean difference, -1.8; p = 0.903). CONCLUSIONS: Although hip COR was improved based on radiographic measurements with the use of this novel acetabular design, and although this may improve hip biomechanics, more studies are required before its widespread adoption for revision cases of this nature can be recommended. Both implant costs and the risks associated with using a new design in practice will have to be justified by studies that evaluate fixation, clinical function and implant survival, and patient-reported outcome scores, all of which were beyond the scope of this preliminary report. LEVEL OF EVIDENCE: Level III, therapeutic study.

Perioperative Gabapentin Does Not Reduce Postoperative Delirium in Older Surgical Patients: A Randomized Clinical Trial.

BACKGROUND: Postoperative pain and opioid use are associated with postoperative delirium. We designed a single-center, randomized, placebo-controlled, parallel-arm, double-blinded trial to determine whether perioperative administration of gabapentin reduced postoperative delirium after noncardiac surgery. METHODS: Patients were randomly assigned to receive placebo (N = 347) or gabapentin 900 mg (N = 350) administered preoperatively and for the first 3 postoperative days. The primary outcome was postoperative delirium as measured by the Confusion Assessment Method. Secondary outcomes were postoperative pain, opioid use, and length of hospital stay. RESULTS: Data for 697 patients were included, with a mean ± SD age of 72 ± 6 yr. The overall incidence of postoperative delirium in any of the first 3 days was 22.4% (24.0% in the gabapentin and 20.8% in the placebo groups; the difference was 3.20%; 95% CI, 3.22% to 9.72%; P = 0.30). The incidence of delirium did not differ between the two groups when stratified by surgery type, anesthesia type, or preoperative risk status. Gabapentin was shown to be opioid sparing, with lower doses for the intervention group versus the control group. For example, the morphine equivalents for the gabapentin-treated group, median 6.7 mg (25th, 75th quartiles: 1.3, 20.0 mg), versus control group, median 6.7 mg (25th, 75th quartiles: 2.7, 24.8 mg), differed on the first postoperative day (P = 0.04). CONCLUSIONS: Although postoperative opioid use was reduced, perioperative administration of gabapentin did not result in a reduction of postoperative delirium or hospital length of stay.

The Importance of Ground Critical Care Transport.

Critical care transport (CCT) teams are specialized transport services, comprised of highly trained paramedics, nurses, and occasionally respiratory therapists, offering an expanded scope of practice beyond advanced life support (ALS) emergency medical service teams. We report 4 cases of patients with severe acute respiratory distress syndrome from influenza in need of extracorporeal membrane oxygenation evaluation at a tertiary care center, transported by ground. Our medical center did not previously have a ground CCT service, and therefore, in these cases, a physician and/or a respiratory therapist was sent with the paramedic team. In all 4 cases, the ground transport team enhanced the intensive care provided to these patients prior to arrival at the tertiary care center. In 2 of the cases, although limited by the profound hypoxemia, the team decreased the pressures and tidal volumes in an effort to approach evidence-based ventilator goals. In 3 cases, they stopped bicarbonate drips being used to treat mixed metabolic and respiratory acidosis, and in 1 case, they administered furosemide. In 1 case, they started cisatracurium, and in 3 others, they initiated inhaled epoprostenol. Existing literature supports the use of CCT teams over ALS teams for transport of the most critically ill patients, and helicopter CCT is not always available or practical. Therefore, offering comparable air and ground options, with similar staffing and resources, is a hallmark of a mature medical system with an integrated approach to CCT.

Length of Endoprosthetic Reconstruction in Revision Knee Arthroplasty Is Associated With Complications and Reoperations.

BACKGROUND: Complex revision total knee arthroplasty (TKA) often calls for endoprosthetic reconstruction to address bone loss, poor bone quality, and soft tissue insufficiency. Larger amounts of segmental bone loss in the setting of joint replacement may be associated with greater areas of devascularized tissue, which could increase the risk of complications and worsen functional results. QUESTIONS/PURPOSES: Are longer endoprosthetic reconstructions associated with (1) higher risk of deep infection; (2) increased risk of reoperation and decreased implant survivorship; or (3) poorer ambulatory status? METHODS: This is a single-institution retrospective case series of nononcologic femoral endoprosthetic reconstructions for revision TKA from 1995 to 2013 (n = 32). Cases were categorized as distal (n = 17) or diaphyseal (n = 15) femoral reconstructions based on extension to or above the supracondylar metaphyseal-diaphyseal junction, respectively. Five patients from each group were lost to followup before 2 years (distal mean 4 years [range, 2-8 years]; diaphyseal mean = 6 years [range, 2-16 years]), and one of the 12 distal reconstructions and two of the 10 diaphyseal reconstructions had not been evaluated within the past 5 years. Clinical outcomes and ambulatory status (able to walk or not) were assessed through chart review by authors not involved in any cases. Prior incidence of periprosthetic joint infection was high in both groups (distal = seven of 12 versus diaphyseal = four of 10; p = 0.670). RESULTS: Patients with diaphyseal femoral replacements were more likely to develop postoperative deep infections than patients with distal femoral replacements (distal = three of 12 versus diaphyseal = nine of 10; p = 0.004). Implant survivorship (revision-free) for diaphyseal reconstructions was worse at 2 years (distal = 100%, 95% confidence interval [CI], 100%-100% versus diaphyseal = 40%, 95% CI, 19%-86%; p = 0.001) and 5 years (distal = 90%, 95% CI, 75%-100% versus diaphyseal = 30%, 95% CI, 12%-73%; p = 0.001). Infection-free, revision-free survival (retention AND no infection) was worse for diaphyseal femoral replacing reconstructions than for distal femoral replacements at 2 years (distal = 70%, 95% CI, 48%-100% versus diaphyseal = 20%, 95% CI, 6%-69%; p = 0.037) and 5 years (distal = 70%, 95% CI, 48%-100% versus diaphyseal = 10%, 95% CI, 2%-64%; p = 0.012). There was no difference with the small numbers available in proportion of patients able to walk (distal reconstruction = eight of 11 versus diaphyseal = seven of 10; p = 1.000), although all but one patient in each group required walking aids. CONCLUSIONS: Endoprosthetic femoral reconstruction is a viable salvage alternative to amputation for treatment of failed TKA with segmental distal femoral bone loss. In our small series even with substantial loss to followup and likely best-case estimates of success, extension proximal to the supracondylar metaphyseal-diaphyseal junction results in higher infection and revision risk. In infection, limb salvage remains possible with chronic antibiotic suppression, which we now use routinely for all femoral replacement extending into the diaphysis. LEVEL OF EVIDENCE: Level III, therapeutic study.

Comparison of Head Center Position and Screw Fixation Options Between a Jumbo Cup and an Offset Center of Rotation Cup in Revision Total Hip Arthroplasty: A Computer Simulation Study.

Jumbo acetabular cups are commonly used in revision total hip arthroplasty (THA). A straightforward reaming technique is used which is similar to primary THA. However, jumbo cups may also be associated with hip center elevation, limited screw fixation options, and anterior soft tissue impingement. A partially truncated hemispherical shell was designed with an offset center of rotation, thick superior rim, and beveled anterior and superior rims as an alternative to a conventional jumbo cup. A three dimensional computer simulation was used to assess head center position and safe screw trajectories. Results of this in vitro study indicate that a modified hemispherical implant geometry can reduce head center elevation while permitting favorable screw fixation trajectories into the pelvis in comparison to a conventional jumbo cup.

Correlating high-resolution magic angle spinning NMR spectroscopy and gene analysis in osteoarthritic cartilage.

Osteoarthritis (OA) is a common multifactorial and heterogeneous degenerative joint disease, and biochemical changes in cartilage matrix occur during the early stages of OA before morphological changes occur. Thus, it is desired to measure regional biochemical changes in the joint. High-resolution magic angle spinning (HRMAS) NMR spectroscopy is a powerful method of observing cartilaginous biochemical changes ex vivo, including the concentrations of alanine and N-acetyl, which are markers of collagen and total proteoglycan content, respectively. Previous studies have observed significant changes in chondrocyte metabolism of OA cartilage via the altered gene expression profiles of ACAN, COL2A1 and MMP13, which encode aggrecan, type II collagen and matrix metalloproteinase 13 (a protein crucial in the degradation of type II collagen), respectively. Employing HRMAS, this study aimed to elucidate potential relationships between N-acetyl and/or alanine and ACAN, COL2A1 and/or MMP13 expression profiles in OA cartilage. Thirty samples from the condyles of five subjects undergoing total knee arthroplasty to treat OA were collected. HRMAS spectra were obtained at 11.7 T for each sample. RNA was subsequently extracted to determine gene expression profiles. A significant negative correlation between N-acetyl metabolite and ACAN gene expression levels was observed; this provides further evidence of N-acetyl as a biomarker of cartilage degeneration. The alanine doublet was distinguished in the spectra of 15 of the 30 specimens of this study. Alanine can only be detected with HRMAS NMR spectroscopy when the collagen framework has been degraded such that alanine is sufficiently mobile to form a distinguished peak in the spectrum. Thus, HRMAS NMR spectroscopy may provide unique localized measurements of collagenous degeneration in OA cartilage. The identification of imaging markers that could provide a link between OA pathology and chondrocyte metabolism will facilitate the development of more sensitive diagnostic techniques and will improve methods of monitoring treatment for patients suffering from OA.

Critical care telemedicine: evolution and state of the art.

OBJECTIVES: To review the growth and current penetration of ICU telemedicine programs, association with outcomes, studies of their impact on medical education, associations with medicolegal risks, identify program revenue sources and costs, regulatory aspects, and the ICU telemedicine research agenda. DATA SOURCES: Review of the published medical literature, governmental documents, and opinions of experts from the Society of Critical Care Medicine ICU Telemedicine Committee. DATA SYNTHESIS: Formal ICU telemedicine programs now support 11% of nonfederal hospital critically ill adult patients. There is increasingly robust evidence of association with lower ICU (0.79; 95% CI, 0.65-0.96) and hospital mortality (0.83; 95% CI, 0.73-0.94) and shorter ICU (-0.62 d; 95% CI, -1.21 to -0.04 d) and hospital (-1.26 d; 95% CI, -2.49 to -0.03 d) length of stay. Physicians in training report experiences with telemedicine intensivists that are positive and increased patient safety. Early studies suggest that implementation of ICU telemedicine programs has been associated with lower numbers of malpractice claims and costs. The requirements for Medicare reimbursement and states with legislation addressing providing professional services by telemedicine are detailed. CONCLUSIONS: The inclusion of an ICU telemedicine program as a major part of their critical care delivery paradigm has been implemented for 11% of critically ill U.S. adults as a solution for the problem of access to adult critical care services. Implementation of an ICU telemedicine program is one practical way to increase access and reduce mortality as well as length of stay. ICU telemedicine research including comparative effectiveness studies is urgently needed.