An acceleromyographic train-of-four ratio of 1.0 reliably excludes respiratory muscle weakness after major abdominal surgery: a randomized double-blind study

Purpose

This randomized double-blind study was designed to determine if respiratory muscle weakness – measured by maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), forced vital capacity (FVC), and forced expiratory volume in one second (FEV₁) – persists even if an acceleromyographic train-of-four ratio (TOFR) of 1.0 is reached after major abdominal surgery.

Methods

Twenty patients underwent respiratory function tests before induction of anesthesia. Rocuronium was given, and the tests were repeated after extubation when the TOFR reached 1.0. The patients were then randomized to receive sugammadex 1 mg·kg^-1 or placebo, and the same tests were repeated five and 20 min later. Between-group comparisons were carried out with a mixed-model analysis of variance analysis.

Results

After anesthesia and adequate epidural analgesia, MIP and MEP decreased by 60% in both groups. In the placebo group, MIP decreased from a pre-induction value (median [range]) of 61.8 [31.3-96.1] to 19.6 [8.3-58.3] cm H₂O after extubation without significant variation five and 20 min after placebo. In the sugammadex group, MIP decreased from a pre-induction value of 57.8 [13.0-96.4] to 20.5 [6.4-67.3] cm H₂O after extubation. No differences were recorded after sugammadex administration (P = 0.246 between groups). In the placebo group, MEP decreased from 88.8 [65.1-120.3] before induction to 37.6 [13.4-70.6] cm H₂O after extubation. In the sugammadex group, MEP decreased from 85.5 [58.6-132.7] to 30.8 [10.5-60.5] cm H₂O, with no improvement five and 20 min after either placebo or sugammadex administration (P = 0.648). Similarly, the FCV and FEV₁ decreased 30-40% after extubation in both study groups.

Conclusion

Acceleromyographic TOFR of 1.0 excludes residual neuromuscular paralysis. However, major respiratory dysfunction is observed after abdominal surgery. This trial was registered at ClinicalTrials.gov: NCT01503840.     

Massive isotopic effect in vacuum UV photodissociation of N2 and implications for meteorite data

Nitrogen isotopic distributions in the solar system extend across an enormous range, from −400‰, in the solar wind and Jovian atmosphere, to about 5,000‰ in organic matter in carbonaceous chondrites. Distributions such as these require complex processing of nitrogen reservoirs and extraordinary isotope effects. While theoretical models invoke ion-neutral exchange reactions outside the protoplanetary disk and photochemical self-shielding on the disk surface to explain the variations, there are no experiments to substantiate these models. Experimental results of N₂ photolysis at vacuum UV wavelengths in the presence of hydrogen are presented here, which show a wide range of enriched δ¹⁵N values from 648‰ to 13,412‰ in product NH₃, depending upon photodissociation wavelength. The measured enrichment range in photodissociation of N₂, plausibly explains the range of δ¹⁵N in extraterrestrial materials. This study suggests the importance of photochemical processing of the nitrogen reservoirs within the solar nebula.Nitrogen isotopic analyses of meteorites, terrestrial planets, atmospheres of giant planets and their moons, solar wind, comets, and interplanetary dust particles (1) may advance understanding of volatile chemistry and prebiotic processes in the early solar system.     

GAP,an aequorin-based fluorescent indicator for imaging Ca2+ in organelles

Genetically encoded calcium indicators allow monitoring subcellular Ca²⁺ signals inside organelles. Most genetically encoded calcium indicators are fusions of endogenous calcium-binding proteins whose functionality in vivo may be perturbed by competition with cellular partners. We describe here a novel family of fluorescent Ca²⁺ sensors based on the fusion of two Aequorea victoria proteins, GFP and apo-aequorin (GAP). GAP exhibited a unique combination of features: dual-excitation ratiometric imaging, high dynamic range, good signal-to-noise ratio, insensitivity to pH and Mg²⁺, tunable Ca²⁺ affinity, uncomplicated calibration, and targetability to five distinct organelles. Moreover, transgenic mice for endoplasmic reticulum-targeted GAP exhibited a robust long-term expression that correlated well with its reproducible performance in various neural tissues. This biosensor fills a gap in the actual repertoire of Ca²⁺ indicators for organelles and becomes a valuable tool for in vivo Ca²⁺ imaging applications.Ca²⁺ is involved in the regulation of many intracellular processes that take place both in the cytosol and inside organelles (1–3). Therefore, accurate measurement of the calcium concentration ([Ca²⁺]) inside organelles is essential to discriminate discrete Ca²⁺ signals between the different compartments. Although synthetic Ca²⁺ indicators can be loaded into organelles, the signal has poor selectivity, as the dye is also present in the cytosol and must be carefully removed before measurements (4). The main advantage of Genetically Encoded Ca²⁺ Indicators (GECIs) is their ability to be targeted to specific intracellular locations. Both bioluminescent and fluorescent proteins have been successfully used to measure subcellular [Ca²⁺]. The photoprotein aequorin (5), purified from the jellyfish Aequorea victoria, was the first protein-based Ca²⁺ indicator, injected into cells in the early 1970s (6). After cloning of its cDNA (7), recombinant aequorin became the most frequently used probe to measure Ca²⁺ in organelles, including mitochondria (8), the endoplasmic reticulum (ER) (9), the nucleus (10), the Golgi apparatus (11), or secretory vesicles (12).Fluorescent GECIs achieve a better spatial resolution than bioluminescent sensors. They are generally composed of one or two fluorescent proteins, most of them variants of GFP, fused to a Ca²⁺-binding protein (13). Recently, a single EF-hand motif has been inserted in the GFP moiety to generate a Ca²⁺ fluorescent probe (14). Since the first cameleon based on FRET (15), the number of GECIs has exponentially increased, attempting optimization of critical features such as adequate expression, signal strength, or dynamic range. However, the in vivo use in mammals, one of the main applications of GECIs, has grown more slowly and has disclosed severe limitations (16, 17). Transgenic sensors usually showed a low expression, often resulting in its inactivation or reduced dynamic range. With the exception of troponin derivatives, most of the available GECIs, namely cameleons, camgaroos, pericams, or GCaMPs (circularly permutated EGFP-based Ca²⁺ sensors), are based on calmodulin, a highly regulated ubiquitous protein that binds a large number of targets (13). Although the interference with endogenous calmodulin has been reduced in the improved cameleons (18), the interaction with other cellular proteins cannot be ruled out. Thus, the loss of Ca²⁺ sensitivity observed in vivo may reflect the interaction of the probe with endogenous partners, which may disturb cellular functions.The jellyfish aequorin exhibits a number of advantages over mammalian EF-hand proteins. It is not toxic and appears not to interfere with other intracellular Ca²⁺-binding molecules, even when microinjected at high concentrations in mammalian cells. Moreover, the use of aequorin as a bioluminescence sensor has been extensively reported, ranging from subcellular Ca²⁺ measurements in many different cell types up to whole organisms, including transgenic animals (19–21).Here we describe a family of fluorescent Ca²⁺ sensors based on the fusion of two jellyfish proteins, GFP and apoaequorin. This Ca²⁺ probe shows a larger dynamic range compared with other GECIs and a robust photonic and thermal stability. It can be targeted to distinct compartments such as the nucleus, cytosol, or mitochondria, where it selectively and accurately monitors dynamic Ca²⁺ changes. In addition, we have generated a variant with a lower Ca²⁺ affinity suited for imaging Ca²⁺ changes in organelles with high resting [Ca²⁺] such as the ER or the Golgi apparatus. Finally, we demonstrate its in vivo applicability by generating transgenic mice where the Ca²⁺ biosensor maintained its in vitro features.     

Insulin Resistance and Bone Strength: Findings From the Study of Midlife in the United States

Although several studies have noted increased fracture risk in individuals with type 2 diabetes mellitus (T2DM), the pathophysiologic mechanisms underlying this association are not known. We hypothesize that insulin resistance (the key pathology in T2DM) negatively influences bone remodeling and leads to reduced bone strength. Data for this study came from 717 participants in the Biomarker Project of the Midlife in the United States Study (MIDUS II). The homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated from fasting morning blood glucose and insulin levels. Projected 2D (areal) bone mineral density (BMD) was measured in the lumbar spine and left hip using dual‐energy X‐ray absorptiometry (DXA). Femoral neck axis length and width were measured from the hip DXA scans, and combined with BMD and body weight and height to create composite indices of femoral neck strength relative to load in three different failure modes: compression, bending, and impact. We used multiple linear regressions to examine the relationship between HOMA‐IR and bone strength, adjusted for age, gender, race/ethnicity, menopausal transition stage (in women), and study site. Greater HOMA‐IR was associated with lower values of all three composite indices of femoral neck strength relative to load, but was not associated with BMD in the femoral neck. Every doubling of HOMA‐IR was associated with a 0.34 to 0.40 SD decrement in the strength indices (p < 0.001). On their own, higher levels of fasting insulin (but not of glucose) were independently associated with lower bone strength. Our study confirms that greater insulin resistance is related to lower femoral neck strength relative to load. Further, we note that hyperinsulinemia, rather than hyperglycemia, underlies this relationship. Although cross‐sectional associations do not prove causality, our findings do suggest that insulin resistance and in particular, hyperinsulinemia, may negatively affect bone strength relative to load. © 2014 American Society for Bone and Mineral Research.     

TiLoop® Bra mesh used for immediate breast reconstruction: comparison of retropectoral and subcutaneous implant placement in a prospective single-institution series

Background

Immediate implant reconstruction after a conservative mastectomy is an attractive option made easier by prosthetic devices. Titanized polypropylene meshes are used as a hammock to cover the lower lateral implant pole. We conducted a prospective nonrandomized single-institution study of reconstructions using titanium-coated meshes either in a standard muscular mesh pocket or in a complete subcutaneous approach. The complete subcutaneous approach means to wrap an implant with titanized mesh in order to position the implant subcutaneously and spare muscles.

Methods

Between November 2011 and January 2014, we performed immediate implant breast reconstructions after conservative mastectomies using TiLoop® Bra, either with the standard retropectoral or with a prepectoral approach. Selection criteria included only women with normal Body Mass Index (BMI), no large and very ptotic breasts, no history of smoking, no diabetes, and no previous radiotherapy. We analyzed short-term outcomes of such procedures and compared the outcomes to evaluate implant losses and surgical complications.

Results

A total of 73 mastectomies were performed. Group 1 comprised 29 women, 5 bilateral procedures, 34 reconstructions, using the standard muscular mesh pocket. Group 2 comprised 34 women, 5 bilateral procedures, 39 reconstructions with the prepectoral subcutaneous technique. Baseline and oncologic characteristics were homogeneous between the two groups. After a median follow-up period of 13 and 12 months, respectively, no implant losses were recorded in group 1, and one implant loss was recorded in group 2. We registered three surgical complications in group 1 and two surgical complications in group 2.

Conclusions

Titanium-coated polypropylene meshes, as a tool for immediate definitive implant breast reconstruction, resulted as safe and effective in a short-term analysis, both for a retropectoral and a totally subcutaneous implant placement. Long-term results are forthcoming. A strict selection is mandatory to achieve optimal results. Level of Evidence: Level II, therapeutic study.     

Podiatrist care and outcomes for patients with diabetes and foot ulcer

We examined whether outcomes of care (amputation and hospitalisation) among patients with diabetes and foot ulcer differ between those who received pre‐ulcer care from podiatrists and those who did not. Adult patients with diabetes and a diagnosis of a diabetic foot ulcer were found in the MarketScan Databases, 2005–2008. Multivariate Cox proportional hazard models estimated the hazard of amputation and hospitalisation. Logistic regression estimated the likelihood of these events. Propensity score weighting and regression adjustment were used to adjust for potentially different characteristics of patients who did and did not receive podiatric care. The sample included 27 545 patients aged greater than 65+ years (Medicare‐eligible patients with employer‐sponsored supplemental insurance) and 20 208 patients aged lesser than 65 years (non Medicare‐eligible commercially insured patients). Care by podiatrists in the year prior to a diabetic foot ulcer was associated with a lower hazard of lower extremity amputation, major amputation and hospitalisations in both non Medicare‐eligible commercially insured and Medicare‐eligible patient populations. Systematic differences between patients with diabetes and foot ulcer, receiving and not receiving care from podiatrists were also observed; specifically, patients with diabetes receiving care from podiatrists tend to be older and sicker.