Relationship Between Quantitative MRI Biomarkers and Patient-Reported Outcome Measures After Cartilage Repair Surgery: A Systematic Review.

Background:Treatment of articular cartilage injuries remains a clinical challenge, and the optimal tools to monitor and predict clinical outcomes are unclear. Quantitative magnetic resonance imaging (qMRI) allows for a noninvasive biochemical evaluation of cartilage and may offer advantages in monitoring outcomes after cartilage repair surgery. Hypothesis:qMRI sequences will correlate with early pain and functional measures. Study Design:Systematic review; Level of evidence, 3. Methods:A PubMed search was performed with the following search terms: knee AND (cartilage repair OR cartilage restoration OR cartilage surgery) AND (delayed gadolinium-enhanced MRI OR t1-rho OR T2 mapping OR dgemric OR sodium imaging OR quantitative imaging). Studies were included if correlation data were included on quantitative imaging results and patient outcome scores. Results:Fourteen articles were included in the analysis. Eight studies showed a significant relationship between quantitative cartilage imaging and patient outcome scores, while 6 showed no relationship. T2 mapping was examined in 11 studies, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) in 4 studies, sodium imaging in 2 studies, glycosaminoglycan chemical exchange saturation transfer (gagCEST) in 1 study, and diffusion-weighted imaging in 1 study. Five studies on T2 mapping showed a correlation between T2 relaxation times and clinical outcome scores. Two dGEMRIC studies found a correlation between T1 relaxation times and clinical outcome scores. Conclusion:Multiple studies on T2 mapping, dGEMRIC, and diffusion-weighted imaging showed significant correlations with patient-reported outcome measures after cartilage repair surgery, although other studies showed no significant relationship. qMRI sequences may offer a noninvasive method to monitor cartilage repair tissue in a clinically meaningful way, but further refinements in imaging protocols and clinical interpretation are necessary to improve utility

Arthroscopic Anterior Shoulder Stabilization With Incorporation of a Comminuted Bony Bankart Lesion.

Bony Bankart lesions are a common finding in patients with anterior glenohumeral dislocation. Although there are no defined guidelines, small bony Bankart fractures are typically treated arthroscopically with suture anchors. The 2 main techniques used are double- and single-row suture anchor stabilization, with debate over superiority. Biomechanical studies have shown improved reduction and stabilization with the double-row over the single-row suture anchor technique; however, this has not been reported for small or comminuted bony fragments. Both techniques have shown promising preliminary clinical outcomes. In this Technical Note, we describe our preferred technique for arthroscopic instability repair using a single-row all-suture anchor method with the incorporation of a comminuted bony Bankart fragment in the lateral decubitus position

Medical Comorbidities and Functional Dependent Living Are Independent Risk Factors for Short-Term Complications Following Osteotomy Procedures about the Knee

© The Author(s) 2018. Objective: To characterize rates and risk factors for adverse events following distal femoral osteotomy (DFO), high tibial osteotomy (HTO), and tibial tubercle osteotomy (TTO) procedures. Design: Patients undergoing DFO, HTO, or TTO procedures during 2005 to 2016 were identified in the American College of Surgeons National Surgical Quality Improvement Program. Rates of adverse events were characterized for each procedure. Demographic, comorbidity, and procedural factors were tested for association with occurrence of any adverse events. Results: A total of 1,083 patients were identified. Of these, 305 (28%) underwent DFO, 273 (25%) underwent HTO, and 505 (47%) underwent TTO. Mean ages for patients undergoing each procedure were the following: DFO, 51 ± 23 years; HTO, 40 ± 13 years; and TTO, 31 ± 11 years. The most common comorbidities for DFO were hypertension (34%) and smoking (17%); for HTO, hypertension (22%) and smoking (21%); and for TTO, smoking (20%) and hypertension (11%). Independent risk factors for occurrence of any adverse event were age ⩾45 years for DFO (odds ratio [OR] = 3.1, P \u3c 0.001) and HTO (OR = 2.3, P = 0.029), and body mass index \u3e30 for HTO (OR = 2.5, 95% confidence interval = 1.1-5.7, P = 0.031). When all osteotomy procedures were analyzed collectively, additional variables including diabetes mellitus (OR = 2.2, P = 0.017), chronic obstructive pulmonary disease (OR = 5.5, P = 0.003), and dependent functional status (OR = 3.0, P = 0.004) were associated with adverse events. Conclusions: The total rate of adverse events was not independently associated with the type of osteotomy procedure. In addition, patients with age \u3e45, diabetes mellitus, chronic obstructive pulmonary disease, and dependent functional status have greater odds for adverse events and should be counseled and monitored accordingly

Ventricular structure, function, and mechanics at high altitude: chronic remodeling in Sherpa vs. short-term lowlander adaptation

Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function. exposure to high altitude (HA) challenges the cardiovascular system to meet the metabolic demand for oxygen (O2) in an environment where arterial O2 content is markedly reduced. The drop in arterial O2 has both direct and indirect consequences for the heart, including depressed inotropy of cardiac muscle (40, 44), changes in blood volume and viscosity, and vasoconstriction of the pulmonary arteries (33). Despite these broad physiological changes, which have been reviewed previously (28, 49), there is evidence that the heart copes relatively well at HA (29, 34). Short-term HA exposure in lowland natives is characterized by a decreased plasma volume (PV), an increased sympathetic nerve activity, and pulmonary vasoconstriction (17, 30, 37), all of which have considerable impact on cardiac function and in time, could stimulate cardiac remodeling. Himalayan native Sherpa, who are of Tibetan lineage and have resided at HA for ∼25,000 yr (2), are well adapted to life at HA, demonstrating greater lung-diffusing capacity (11) and an absence of polycythemia compared with acclimatized lowlanders (4). Previous studies have also reported Sherpa to have higher maximal heart rates (HRs) and only moderate pulmonary hypertension compared with lowlanders at HA (11, 25). Due to their longevity at HA, Sherpa provide an excellent model to investigate the effects of chronic hypoxic exposure. Despite this, neither the acute nor lifelong effects of HA on right- and left-ventricular (RV and LV, respectively) structure and function have been fully assessed in lowlanders or the unique Sherpa population. Due to the unique arrangement of myofibers, cardiac form and function are intrinsically linked, as reflected in the cardiac mechanics (LV twist and rotation and ventricular strain) that underpin ventricular function. In response to altered physiological demand, ventricular mechanics acutely change (16, 41) and chronically remodel (31, 42) to reduce myofiber stress and achieve efficient ejection (5, 47). Therefore, concomitant examination of myocardial mechanics and ventricular structure in both the acute and chronic HA setting will provide novel insight into human adaptation to hypoxia. To investigate the effects of chronic hypoxic exposure, we compared ventricular volumes and mechanics in Sherpa at 5,050 m with lowlanders at sea level (SL). In addition, to reveal potential stimuli for remodeling and to examine the time course of adaptation, we compared Sherpa with lowlanders after short-term HA exposure. We hypothesized that: 1) Sherpa would exhibit smaller LV volumes and a higher RV/LV ratio than lowlanders at SL, 2) LV mechanics in Sherpa will closely resemble those of lowlanders at SL, and 3) following partial acclimatization to HA, LV volumes would be reduced in lowlanders and LV mechanics acutely increased

Patients With Generalized Joint Hypermobility Have Thinner Superior Hip Capsules and Greater Hip Internal Rotation on Physical Examination

PURPOSE: To compare preoperative hip range of motion (ROM), hip capsular thickness on magnetic resonance imaging (MRI), and bony morphology on radiographs and computed tomography (CT) between patients with and without joint hypermobility as measured by the Beighton Test score (BTS), with subanalysis based on sex and age. METHODS: Consecutive patients who underwent hip arthroscopy for a diagnosis of femoroacetabular impingement syndrome with or without dysplasia were retrospectively reviewed. Patient BTS, hip ROM, demographics, surgical data, morphologic measures on radiographs and CT, and MRI findings including hip capsule thickness at various locations were compiled. Multiple statistical tests were performed, including multivariable linear or logistic regression models, while controlling for BTS, age, and sex. RESULTS: In total, 99 patients were included with a mean age of 29 ± 9.9 years; 62 (62.6%), were female. Forty patients (40.4%) had a BTS ≥4. Female patients (P \u3c .001) and younger patients (26.7 vs 30.9 years, P = .030) were more likely to have a BTS ≥4. Male patients had significantly thicker superior capsules (3.4 mm vs. 2.8 mm, P = .034). BTS was not associated with capsular thickness when controlling for sex. On CT, femoral version (18.9° vs 11.4°, P \u3c .001), and McKibben index (37.8° vs. 28.2°, P \u3c .001) were significantly greater in those with a BTS ≥4. Patients with a BTS ≥4 had more hip internal rotation at 90° of flexion (15.0° vs 10.0°, P \u3c .001), when prone (30.0° vs 20.0°, P = .004), and in extension (10.0° vs. 5.0°, P \u3c .001). CONCLUSIONS: All female patients, regardless of Beighton score, and all patients with a BTS ≥4 indicated for primary hip arthroscopy for femoroacetabular impingement syndrome with or without dysplasia were more likely to have thinner superior hip capsules on MRI and greater hip internal rotation on exam. Bony morphologic differences exist between sexes and between patients with and without hypermobility, likely contributing to differences in ROM. LEVEL OF EVIDENCE: III, retrospective cohort study

Isotropic-nematic phase transition in suspensions of filamentous virus and the neutral polymer Dextran

We present an experimental study of the isotropic-nematic phase transition in an aqueous mixture of charged semi-flexible rods (fd virus) and neutral polymer (Dextran). A complete phase diagram is measured as a function of ionic strength and polymer molecular weight. At high ionic strength we find that adding polymer widens the isotropic-nematic coexistence region with polymers preferentially partitioning into the isotropic phase, while at low ionic strength the added polymer has no effect on the phase transition. The nematic order parameter is determined from birefringence measurements and is found to be independent of polymer concentration (or equivalently the strength of attraction). The experimental results are compared with the existing theoretical predictions for the isotropic-nematic transition in rods with attractive interactions.Comment: 8 Figures. To be published in Phys. Rev. E. For more information see http://www.elsie.brandeis.ed

Impaired myocardial function does not explain reduced left ventricular filling and stroke volume at rest or during exercise at high altitude

Impaired myocardial systolic contraction and diastolic relaxation have been suggested as possible mechanisms contributing to the decreased stroke volume (SV) observed at high altitude (HA). To determine whether intrinsic myocardial performance is a limiting factor in the generation of SV at HA, we assessed left ventricular (LV) systolic and diastolic mechanics and volumes in 10 healthy participants (aged 32 ± 7; mean ± SD) at rest and during exercise at sea level (SL; 344 m) and after 10 days at 5,050 m. In contrast to SL, LV end-diastolic volume was ∼19% lower at rest (P = 0.004) and did not increase during exercise despite a greater untwisting velocity. Furthermore, resting SV was lower at HA (∼17%; 60 ± 10 vs. 70 ± 8 ml) despite higher LV twist (43%), apical rotation (115%), and circumferential strain (17%). With exercise at HA, the increase in SV was limited (12 vs. 22 ml at SL), and LV apical rotation failed to augment. For the first time, we have demonstrated that EDV does not increase upon exercise at high altitude despite enhanced in vivo diastolic relaxation. The increase in LV mechanics at rest may represent a mechanism by which SV is defended in the presence of a reduced EDV. However, likely because of the higher LV mechanics at rest, no further increase was observed up to 50% peak power. Consequently, although hypoxia does not suppress systolic function per se, the capacity to increase SV through greater deformation during submaximal exercise at HA is restricted. during initial exposure to hypobaric hypoxia at high altitude (HA), cardiac output for a given absolute workload is increased to compensate for a lower arterial oxygen content before returning to baseline levels with acclimatization (8). However, after 2-5 days of acclimatization, the required cardiac output is generated through a lower stroke volume (SV) and higher heart rate (38). The reduced SV is suggestive of either lower ventricular filling, potentially caused in part by an impaired myocardial relaxation, or impaired ejection secondary to systolic contractile dysfunction. There is, however, a paucity of data in humans supporting a direct effect of hypoxia on myocardial function at HA (25, 41). The suggestion that hypoxia may impair myocardial systolic function during exercise was proposed nearly 50 years ago (3) and has been revisited more recently (27–29). Negative inotropic effects of hypoxia (arterial oxygen tension of 44 mmHg) have been shown in intact animal models (39) and isolated myocardial fibers under severe hypoxia (1% O2) (33). Exercise training under hypobaric hypoxia is also associated with altered mechanical properties at a cellular level in rodents (9), although chronic hypoxia alone did not decrease myofilament sensitivity to calcium. However, in contrast to animal studies, data in humans indicate that systolic function is maintained or enhanced at HA. For example, Suarez et al. (37) reported the maintenance of systolic function after gradual decompression to a barometric pressure of 282 mmHg, a finding that was subsequently confirmed by numerous investigations during acute and prolonged hypoxic exposure (6, 10, 12, 23, 31). However, of these studies, only Suarez et al. (37) investigated systolic function during light exercise (60 W), where function appeared to be maintained. It is not known whether systolic function is maintained at higher exercise intensities. It has also been speculated that reduced oxygen availability may impair diastolic relaxation at HA (15, 18) and thus explain the decreased left ventricular (LV) end-diastolic volume (EDV) commonly observed (2, 6, 18). However, despite numerous studies reporting a decrease in plasma volume and altered transmitral filling patterns (2, 6, 20), myocardial relaxation was only previously investigated during hypoxia in dogs (15), and no data exist examining LV relaxation during exercise at high altitude. By using sensitive, noninvasive imaging techniques (two-dimensional speckle tracking), it is now possible to examine the LV deformation mechanics (strain, twist, and untwist velocity) that underpin LV systolic and diastolic function. LV strain and twist have been shown to be sensitive measures of global and regional myocardial function, and reveal subclinical dysfunction in patients where ejection fraction is unchanged (16, 22). In addition, diastolic LV untwist velocity correlates well with invasive measures of LV stiffness and provides a temporal link between relaxation and the development of intraventricular pressure gradients (30, 43). Therefore, examination of LV mechanics at HA may determine whether the decreased SV observed at HA is dependent on impaired myocardial relaxation and/or myocardial contractile dysfunction or confirm previous findings of preserved ventricular function during exercise (37). We therefore assessed systolic and diastolic ventricular mechanics during incremental exercise at sea level and HA to examine whether impaired myocardial relaxation or systolic dysfunction explains the previously reported reduction in SV at HA. We hypothesized that at HA, 1) ventricular filling would be lower at rest and during exercise and would be accompanied by a reduction in untwist velocity and 2) systolic mechanics would be impaired during exercise at HA

Evaluation of Pulse Counting for the Mars Organic Mass Analyzer (MOMA) Ion Trap Detection Scheme

The Mars Organic Mass Analyzer is being developed at Goddard Space Flight Center to identify organics and possible biological compounds on Mars. In the process of characterizing mass spectrometer size, weight, and power consumption, the use of pulse counting was considered for ion detection. Pulse counting has advantages over analog-mode amplification of the electron multiplier signal. Some advantages are reduced size of electronic components, low power consumption, ability to remotely characterize detector performance, and avoidance of analog circuit noise. The use of pulse counting as a detection method with ion trap instruments is relatively rare. However, with the recent development of high performance electrical components, this detection method is quite suitable and can demonstrate significant advantages over analog methods. Methods A prototype quadrupole ion trap mass spectrometer with an internal electron ionization source was used as a test setup to develop and evaluate the pulse-counting method. The anode signal from the electron multiplier was preamplified. The an1plified signal was fed into a fast comparator for pulse-level discrimination. The output of the comparator was fed directly into a Xilinx FPGA development board. Verilog HDL software was written to bin the counts at user-selectable intervals. This system was able to count pulses at rates in the GHz range. The stored ion count nun1ber per bin was transferred to custom ion trap control software. Pulse-counting mass spectra were compared with mass spectra obtained using the standard analog-mode ion detection. Prelin1inary Data Preliminary mass spectra have been obtained for both analog mode and pulse-counting mode under several sets of instrument operating conditions. Comparison of the spectra revealed better peak shapes for pulse-counting mode. Noise levels are as good as, or better than, analog-mode detection noise levels. To artificially force ion pile-up conditions, the ion trap was overfilled and ions were ejected at very high scan rates. Pile-up of ions was not significant for the ion trap under investigation even though the ions are ejected in so-called 'ion-micro packets'. It was found that pulse counting mode had higher dynamic range than analog mode, and that the first amplification stage in analog mode can distort mass peaks. The inherent speed of the pulse counting method also proved to be beneficial to ion trap operation and ion ejection characterization. Very high scan rates were possible with pulse counting since the digital circuitry response time is so much smaller than with the analog method. Careful investigation of the pulse-counting data also allowed observation of the applied resonant ejection frequency during mass analysis. Ejection of ion micro packets could be clearly observed in the binned data. A second oscillation frequency, much lower than the secular frequency, was also observed. Such an effect was earlier attributed to the oscillation of the total plasma cloud in the ion trap. While the components used to implement pulse counting are quite advanced, due to their prevalence in consumer electronics, the cost of this detection system is no more than that of an analog mode system. Total pulse-counting detection system electronics cost is under $25

Effects of Noise on Ecological Invasion Processes: Bacteriophage-mediated Competition in Bacteria

Pathogen-mediated competition, through which an invasive species carrying and transmitting a pathogen can be a superior competitor to a more vulnerable resident species, is one of the principle driving forces influencing biodiversity in nature. Using an experimental system of bacteriophage-mediated competition in bacterial populations and a deterministic model, we have shown in [Joo et al 2005] that the competitive advantage conferred by the phage depends only on the relative phage pathology and is independent of the initial phage concentration and other phage and host parameters such as the infection-causing contact rate, the spontaneous and infection-induced lysis rates, and the phage burst size. Here we investigate the effects of stochastic fluctuations on bacterial invasion facilitated by bacteriophage, and examine the validity of the deterministic approach. We use both numerical and analytical methods of stochastic processes to identify the source of noise and assess its magnitude. We show that the conclusions obtained from the deterministic model are robust against stochastic fluctuations, yet deviations become prominently large when the phage are more pathological to the invading bacterial strain.Comment: 39 pages, 7 figure

Discovery of diverse and functional antibodies from large human repertoire antibody libraries

AbstractPhage display antibody libraries have a proven track record for the discovery of therapeutic human antibodies, increasing the demand for large and diverse phage antibody libraries for the discovery of new therapeutics. We have constructed naïve antibody phage display libraries in both Fab and scFv formats, with each library having more than 250billion clones that encompass the human antibody repertoire. These libraries show high fidelity in open reading frame and expression percentages, and their V-gene family distribution, VH-CDR3 length and amino acid usage mirror the natural diversity of human antibodies. Both the Fab and scFv libraries show robust sequence diversity in target-specific binders and differential V-gene usage for each target tested, supporting the use of libraries that utilize multiple display formats and V-gene utilization to maximize antibody-binding diversity. For each of the targets, clones with picomolar affinities were identified from at least one of the libraries and for the two targets assessed for activity, functional antibodies were identified from both libraries