Patellar resurfacing versus retention in cruciate-retaining and posterior-stabilized total knee arthroplasty.

Aims: This systematic review and meta-analysis aimed to compare the influence of patellar resurfacing following cruciate-retaining (CR) and posterior-stabilized (PS) total knee arthroplasty (TKA) on the incidence of anterior knee pain, knee-specific patient-reported outcome measures, complication rates, and reoperation rates. Methods: A systematic review of MEDLINE, PubMed, and Google Scholar was performed to identify randomized controlled trials (RCTs) according to search criteria. Search terms used included: arthroplasty, replacement, knee (Mesh), TKA, prosthesis, patella, patellar resurfacing, and patellar retaining. RCTs that compared patellar resurfacing versus unresurfaced in primary TKA were included for further analysis. Studies were evaluated using the Scottish Intercollegiate Guidelines Network assessment tool for quality and minimization of bias. Data were synthesized and meta-analysis performed. Results: There were 4,135 TKAs (2,068 resurfaced and 2,027 unresurfaced) identified in 35 separate cohorts from 33 peer-reviewed studies. Anterior knee pain rates were significantly higher in unresurfaced knees overall (odds ratio (OR) 1.84; 95% confidence interval (CI) 1.20 to 2.83; p = 0.006) but more specifically associated with CR implants (OR 1.95; 95% CI 1.0 to 3.52; p = 0.030). There was a significantly better Knee Society function score (mean difference (MD) -1.98; 95% CI -1.1 to -2.84; p < 0.001) and Oxford Knee Score (MD -2.24; 95% CI -0.07 to -4.41; p = 0.040) for PS implants when patellar resurfacing was performed, but these differences did not exceed the minimal clinically important difference for these scores. There were no significant differences in complication rates or infection rates according to implant design. There was an overall significantly higher reoperation rate for unresurfaced TKA (OR 1.46 (95% CI 1.04 to 2.06); p = 0.030) but there was no difference between PS or CR TKA. Conclusion: Patellar resurfacing, when performed with CR implants, resulted in lower rates of anterior knee pain and, when used with a PS implant, yielded better knee-specific functional outcomes. Patellar resurfacing was associated with a lower risk of reoperation overall, but implant type did not influence this.

Patellar resurfacing was not associated with a clinically significant advantage when a modern patellar friendly total knee arthroplasty is employed: A systematic review and meta-analysis.

BACKGROUND: Modern total knee arthroplasty (TKA) femoral components are designed to provide a more optimal articular surface for the patella whether or not it has been resurfaced. Previous systematic reviews comparing outcomes of patellar resurfacing and no resurfacing combine both historic and modern designs. AIMS: The aim of this study was to investigate the effect of patellar resurfacing in modern "patellar friendly" implants on (1) incidence of anterior knee pain, (2) patient reported outcomes (3) complication rates, and (4) reoperation rates compared with unresurfaced patellae in primary TKA. METHODS: MEDline, PubMed and google scholar studies were evaluated using SIGN assessment tool and data analysis was conducted using Review Manager 5.2 on only randomised controlled trials. The search terms were: arthroplasty, replacement, knee (Mesh), TKA, prosthesis, patella, patellar resurfacing, patellar retaining. RESULTS: Thirty-two randomised controlled studies were identified that reported the type of TKA implant used: 11 used modern "patellar friendly" implants; and 21 older "patellar non-friendly" implants. Among "patellar friendly" TKAs there were no significant differences in anterior knee pain rates between resurfaced and unresurfaced groups. Patellar resurfacing with "patellar friendly" implants had significantly higher clinical (mean difference (MD) -0.77, p = 0.007) and functional (MD -1.87, p < 0.0001) knee society scores (KSS) than unresurfaced counterparts but these did not exceed the minimal clinically important difference (MCID). Resurfacing with "patellar friendly" implants was not associated with a significant (p = 0.59) difference in the Oxford knee score (OKS), in contrast when a "patellar non-friendly" implant was used there was a significant difference (MD 3.3, p = 0.005) in favour of resurfacing. There was an increased risk of reoperation for unresurfaced TKAs with "non-patellar friendly" implants (Odds ratio (OR) 1.68, 95% CI 1.03-2.74, p = 0.04), but not for unresurfaced patellae with "patellar friendly" implants (OR 1.17, CI 0.59-2.30). CONCLUSIONS: Patellar resurfacing in combination with a modern patellar friendly implant was not associated with a lower rate of anterior knee pain, complications, or reoperations compared to not resurfacing, nor did it give a clinically significant improvement in knee specific function. In contrast patellar resurfacing in combination with a "non-friendly" TKA implant was associated with a significantly better OKS and lower reoperation rate. Implant design should be acknowledged when patellar resurfacing is being considered.

Relationships among norepinephrine levels, exercise capacity, and chronotropic responses in heart failure patients.

In heart failure (HF) patients, the pathophysiological mechanisms of severe exercise intolerance and impaired exercise capacity are related to both central and peripheral abnormalities. The central abnormalities in HF patients include impaired cardiac function and chronotropic incompetence (CI). Indeed, CI, the inability to adequately increase heart rate (HR) from rest to exercise often exhibited by HF patients, is related to activation of the sympathetic nervous system (SNS) yielding a rise in circulating norepinephrine (NE). CI may result from downregulation of ß-adrenergic receptors, ß-blocker usage, high baseline HR, or due to a combination of factors. This paper discusses the role of elevated NE in altering chronotropic responses in HF patients and consequently resulting in impaired exercise capacity. We suggest that future research should focus on the potential treatment of CI with rate-adaptive pacing, using a sensor to measure physical activity, without inducing deleterious hormonal activation of the sympathetic system.

Evaluation of Host Cell Impurity Effects on the Performance of Sterile Filtration Processes for Therapeutic Viruses.

Efficient downstream processing represents a significant challenge in the rapidly developing field of therapeutic viruses. While it is known that the terminal sterile filtration step can be a major cause of product loss, there is little known about the effect of host cell impurities (DNA and protein) on filtration performance. In this study, fractions of relatively pure Vero host cell protein and DNA were spiked into a highly pure preparation of vesicular stomatitis virus (VSV). Then, the resulting solutions were sterile filtered using two commercially available 0.22 µm rated microfiltration membranes. A combination of transmembrane pressure measurements, virus recovery measurements, and post-filtration microscopy images of the microfiltration membranes was used to evaluate the sterile filtration performance. It was found that increasing the amount of host cell protein from approximately 1 µg/mL (in the un-spiked VSV preparation) to 25 µg/mL resulted in a greater extent of membrane fouling, causing the VSV recovery to decrease from 89% to 65% in experiments conducted with the highly asymmetric Express PLUS PES membrane and to go as low as 48% in experiments conducted with the symmetric Durapore PVDF membrane. Similar effects were not seen when bovine serum albumin, a common model protein used in filtration studies, was spiked into the VSV preparation, which indicates that the sterile filtration performance is critically dependent on the complex composition of the mixture of host cell proteins rather than the presence of any protein. The results presented in this work provide important insights into the role of host cell impurities on the performance of sterile filtration processes for therapeutic viruses.

Usability of novel major TraumaApp for digital data collection.

BACKGROUND: Delivery of major trauma care is complex and often fast paced. Clear and comprehensive documentation is paramount to support effective communication during complex clinical care episodes, and to allow collection of data for audit, research and continuous improvement. Clinical events are typically recorded on paper-based records that are developed for individual centres or systems. As one of the priorities laid out by the Scottish Trauma Network project was to develop an electronic data collection system, the TraumaApp was created as a data collection tool for major trauma that could be adopted worldwide. METHODS: The study was performed as a service evaluation based at the Queen Elizabeth University Hospital Emergency Department. Fifty staff members were recruited in pairs and listened to five paired major trauma standby and handover recordings. Participants were randomised to input data to the TraumaApp and one into the existing paper proforma. The time taken to input data add into was measured, along with time for clarifications and any errors made. Those using the app completed a System Usability Score. RESULTS: No statistically significant difference was demonstrated between times taken for data entry for the digital and paper documentation, apart from the Case 5 Handover (p < 0.05). Case 1 showed a significantly higher time for clarifications and number of errors with digital data collection (p = 0.01 and p = 1.79E-05 respectively). There were no other differences between data for the app and the proforma. The mean System Usability score for this cohort was 75 out of 100, with a standard deviation of 17 (rounded to nearest integer). CONCLUSION: Digital real-time recording of clinical events using a tool such as the TraumaApp is comparable to completion of paper proforma. The System Usability Score for the TraumaApp was above the internationally validated standard of acceptable usability. There was no evidence of improvement in use over time or familiarity, most likely due to the brevity of the assessments and the refined user interface. This would benefit from further research, exploring data completeness and a potential mixed methods approach to explore training requirements for use of the TraumaApp.

One Versus Two Veins in Free Anterolateral Thigh Flap Reconstruction: A Systematic Review and Meta-Analysis.

There is considerable debate in the literature as to whether one or two venous anastomoses are optimal in the anterolateral thigh (ALT) free-flap reconstruction. The literature is currently devoid of a systematic review and meta-analysis of studies evaluating these procedures. This review will therefore be the first to address this clinical question. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, two authors (EW and SR) independently searched the following electronic databases: MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL). Case-control, randomised control and observational studies were included. The authors did not include case reports, case series, letters or abstracts. All patients were included regardless of age, co-morbidity status, and the anatomical site of reconstruction. Venous congestion/thrombosis, flap take-back rate due to venous insufficiency, flap loss and operative time were the primary outcome measures. Secondary outcome measures included partial flap loss and haematoma formation. The Newcastle Ottawa Scale was used to assess the risk of bias in the included studies. Review Manager 5.4 data synthesis software was used for the analysis. The authors identified eight observational studies, with a total of 1741 patients reviewed, demonstrating a significantly lower flap take-back rate for a double venous anastomosis and a shorter operative time in the single venous anastomosis group. However, other reported measures, including venous congestion and flap loss, showed a non-significant difference (P>0.05). The limitations of the evidence included in this review were that all studies were observational in design. The flap take-back rate is significantly less when anastomosing two veins, and the authors recommend that utilising a second vein can circumvent the caveat of venous compromise.

A Positive Cocaine Urine Toxicology Test and the Effect on Intraoperative Hemodynamics Under General Anesthesia.

BACKGROUND: Cocaine has a short biological half-life, but inactive urine metabolites may be detectable for a week following use. It is unclear if patients who test positive for cocaine but have a normal electrocardiogram and vital signs have a greater percentage of hemodynamic events intraoperatively. METHODS: A total of 328 patients with a history of cocaine use who were scheduled for elective noncardiac surgery under general anesthesia were enrolled. Patients were categorized into cocaine-positive versus cocaine-negative groups based on the results of their urine cocaine toxicology test. The primary aim of this study was to evaluate whether asymptomatic cocaine-positive patients had similar percentages of intraoperative hemodynamic events, defined as (1) a mean arterial blood pressure (MAP) of <65 or >105 mm Hg and (2) a heart rate (HR) of <50 or >100 beats per minute (bpm) compared to cocaine-negative patients. The study was powered to assess if the 2 groups had an equivalent mean percent of intraoperative hemodynamic events within specific limits using an equivalence test of means consisting of 2 one-sided tests. RESULTS: The cocaine-positive group had a blood pressure (BP) that was outside the set limits 19.4% (standard deviation [SD] 17.7%) of the time versus 23.1% (SD 17.7%) in the cocaine-negative group (95% confidence interval [CI], 0.5-7.0). The cocaine-positive group had a HR outside the set limits 9.6% (SD 16.2%) of the time versus 8.2% (SD 14.9%) in the cocaine-negative group (95% CI, 4.3-1.5). Adjusted for age, sex, body mass index (BMI), smoking status, and the presence of comorbid hypertension, renal disease, and psychiatric illness, the cocaine-positive and cocaine-negative patients were similar within a 7.5% margin of equivalence for MAP data (ß coefficient = 2%, P = .003, CI, 2-6) and within a 5% margin of equivalence for HR data (ß coefficient = 0.2%, P < .001, CI, 4-3). CONCLUSIONS: Asymptomatic cocaine-positive patients undergoing elective noncardiac surgery under general anesthesia have similar percentages of intraoperative hemodynamic events compared to cocaine-negative patients.

Feasibility, Safety, and Effectiveness of a Mobile Application in Cardiac Rehabilitation.

BACKGROUND: Cardiac rehabilitation (CR) is underutilized globally despite evidence of clinical benefit. Major obstacles for wider adoption include distance from the rehabilitation center, travel time, and interference with daily routine. Tele-cardiac rehabilitation (tele-CR) can potentially address some of these limitations, enabling patients to exercise in their home environment or community. OBJECTIVES: To evaluate the clinical and physiological outcomes as well as adherence to tele-CR in patients with low cardiovascular risk and to assess exercise capacity, determined by an exercise stress test, using a treadmill before and following the 6-month intervention. METHODS: A total of 22 patients with established coronary artery disease participated in a 6-month tele-CR program. Datos Health (Ramat Gan, Israel), a digital health application and care-team dashboard, was used for remote monitoring, communication, and management of the patients. RESULTS: Following the 6-month tele-CR intervention, there was significant improvement in exercise capacity, assessed by estimated metabolic equivalents with an increase from 10.6 ± 0.5 to 12.3 ± 0.5 (P = 0.002). High-density lipoproteins levels significantly improved, whereas low-density lipoproteins, triglyceride, glycosylated hemoglobin, and systolic and diastolic blood pressure levels were not significantly changed. Exercise adherence was consistent among patients, with more than 63% of patients participating in a moderate intensity exercise program for 150 minutes per week. CONCLUSIONS: Patients who participated in tele-CR adhered to the exercise program and attained clinically significant functional improvement. Tele-CR is a viable option for populations that cannot, or elect not to, participate in center-based CR programs.

Improving characterization and diagnosis quality of myofascial pain syndrome: a systematic review of the clinical and biomarker overlap with delayed onset muscle soreness.

INTRODUCTION: Myofascial pain syndrome (MPS) is one of the most common conditions of chronic musculoskeletal pain, yet its mechanisms are still poorly understood. Delayed Onset Muscle Soreness (DOMS) is also a regional pain syndrome that has clinical similarities to MPS, but has been better investigated. Emerging research suggests that DOMS may be a valid experimental model for studying MPS; however, a comparison of the similarities and differences of these two conditions has previously not been performed. Herein, we aimed to identify the similarities and differences in the clinical features and biomarkers between DOMS and MPS in order to better define MPS and identify future areas of (DOMS-informed) MPS research. EVIDENCE ACQUISITION: In order to identify similarities and differences in the clinical manifestation and biomarkers of DOMS and MPS, scoping literature searches were performed using Medline (1965-2019), Embase (1966-2019) and Central (1966-2019) databases. Fifty-three full-text articles were reviewed out of the 2836 articles retrieved in the search. EVIDENCE SYNTHESIS: A scoping review of the literature demonstrated that DOMS and MPS similarly present as conditions of musculoskeletal pain that are associated with decreased strength and limited range of motion. However, while taut bands and discrete tender spots were described in DOMS, none of the studies reviewed have characterized whether these tender points represent the classic myofascial trigger point phenomenon observed in MPS. Certain systemic circulation biomarkers, including inflammatory cytokines and growth factors, were commonly elevated in MPS and DOMS; further research is needed to determine if other biomarkers that are currently characterized in DOMS are useful to enhance the clinical evaluation of MPS. CONCLUSIONS: DOMS and MPS share clinical and biomarker similarities suggesting that DOMS may be a useful model for studying MPS.

Neurohormones, inflammatory mediators, and cardiovascular injury in the setting of heart failure.

Neurohormones and inflammatory mediators have effects in both the heart and the peripheral vasculature. In patients with heart failure (HF), neurohormonal activation and increased levels of inflammatory mediators promote ventricular remodeling and development of HF, as well as vascular dysfunction and arterial stiffness. These processes may lead to a vicious cycle, whereby arterial stiffness perpetuates further ventricular remodeling leading to exacerbation of symptoms. Although significant advances have been made in the treatment of HF, currently available treatment strategies slow, but do not halt, this cycle. The current treatment for HF patients involves the inhibition of neurohormonal activation, which can reduce morbidity and mortality related to this condition. Beyond benefits associated with neurohormonal blockade, other strategies have focused on inhibition of inflammatory pathways implicated in the pathogenesis of HF. Unfortunately, attempts to target inflammation have not yet been successful to improve prognosis of HF. Further work is required to interrupt key maladaptive mechanisms involved in disease progression.

Development of isoporous microslit silicon nitride membranes for sterile filtration applications.

The widely used 0.2/0.22 µm polymer sterile filters were developed for small molecule and protein sterile filtration but are not well-suited for the production of large nonprotein biological therapeutics, resulting in significant yield loss and production cost increases. Here, we report on the development of membranes with isoporous sub-0.2 µm rectangular prism pores using silicon micromachining to produce microslit silicon nitride (MSN) membranes. The very high porosity (~33%) and ultrathin (200 nm) nature of the 0.2 µm MSN membranes results in a dramatically different structure than the traditional 0.2/0.22 µm polymer sterile filter, which yielded comparable performance properties (including gas and hydraulic permeance, maximum differential pressure tolerance, nanoparticle sieving/fouling behavior). The results from bacteria retention tests, conducted according to the guidance of regulatory agencies, demonstrated that the 0.2 µm MSN membranes can be effectively used as sterile filters. It is anticipated that the results and technologies presented in this study will find future utility in the production of non-protein biological therapeutics and in other biological and biomedical applications.

Can improvement in hormonal and energy balance reverse cardiovascular risk factors in athletes with amenorrhea?

Female athletes display a high prevalence of hypothalamic amenorrhea as a result of energy imbalance. In these athletes with amenorrhea, decreased luteinizing hormone/follicule-stimulating hormone secretion leads to deficiency in endogenous estrogen. The severe estrogen deficiency in these athletes may increase cardiovascular risk similar to that in postmenopausal women. This review discusses the potential cardiovascular risk factors in athletes with amenorrhea as a result of hypoestrogenism, which include endothelial dysfunction and unfavorable lipid profiles. We also consider the potential to reverse the cardiovascular risk by restoring energy or hormonal imbalance along the reproductive axis in athletes with amenorrhea.

Microfluidic wound model for studying the behaviors of Pseudomonas aeruginosa in polymicrobial biofilms.

Pseudomonas aeruginosa is a particularly problematic opportunistic pathogen due to its capacity to form recalcitrant biofilm structures, while cohabiting with other harmful/pathogenic species and harboring the capability to release toxins that cause tissue necrosis. Although it is now recognized that the majority of biofilm infections are polymicrobial, little is known about the complex interactions that occur within polymicrobial communities and few tools exist for studying these interactions. In this study, we have designed a microfluidic model that mimics the relevant physiological properties of wound microenvironment, while incorporating materials present in the human extracellular matrix/wound environment. Using microfluidics combined with imaging techniques, we have validated the robustness of our model comparing traditional GFP-tagging to new fluorescent staining techniques to visualize/resolve individual species within a polymicrobial habitat. We have also demonstrated that chemotactic stimuli may be incorporated into our model through specialized ports in our chamber. Our system is specifically designed for use with high resolution imaging techniques, allowing for data collection throughout the life of the biofilm and in real-time. Ultimately, this model can be used to investigate the spatio-temporal mechanobiological structures of the wound environment, and the response of the bacteria to the drug transport which will significantly contribute to our understanding of the development and progression of polymicrobial biofilm infections.

Single cell swimming dynamics of Listeria monocytogenes using a nanoporous microfluidic platform.

Listeria monocytogenes remains a significant foodborne pathogen due to its virulence and ability to become established in food processing facilities. The pathogen is characterized by its ability to grow over a wide temperature range and withstand a broad range of stresses. The following reports on the chemotaxis and motility of the L. monocytogenes when exposed to relatively small concentrations of acetic acid. Using the developed nanoporous microfluidic device to precisely modulate the cellular environment, we exposed the individual Listeria cells to acetic acid and, in real time and with high resolution, observed how the cells reacted to the change in their surroundings. Our results showed that concentrations of acetic acid below 10 mM had very little, if any, effect on the motility. However, when exposed to 100 mM acetic acid, the cells exhibited a sharp drop in velocity and displayed a more random pattern of motion. These results indicate that at appropriate concentrations, acetic acid has the ability to disable the flagellum of the cells, thus impairing their motility. This drop in motility has numerous effects on the cell; its main effects being the obstruction of the cell's ability to properly form biofilms and a reduction in the overall infectivity of the cells. Since these characteristics are especially useful in controlling the proliferation of L. monocytogenes, acetic acid shows potential for application in the food industry as an active compound in designing a food packaging environment and as an antimicrobial agent.

Rhg1 alleles from soybean PI 437654 and PI 88788 respond differentially to isolates of Heterodera glycines in the greenhouse.

The production of resistant soybean [Glycine max (L.) Merr.] cultivars is the most effective means for controlling losses from soybean cyst nematode (SCN) (Heterodera glycines Ichinohe). The major resistance gene in most SCN resistance sources is rhg1, which has been mapped as a quantitative trait locus onto linkage group G. Our objective was to determine whether the SCN resistance sources PI 437654 and PI 88788 have different functional alleles at rhg1 based on resistance phenotypes. Populations segregating for resistance alleles at rhg1 from both PI 88788 and PI 437654 and at Rhg4, a second SCN resistance gene from PI 437654, were developed. These populations were screened for resistance to the H. glycines inbred isolates PA3 (HG type 7) and TN14 (HG type 1.2.5.7) in the greenhouse and evaluated with molecular markers linked to both rhg1 and Rhg4. Each isolate test was repeated, and the evaluations were done on a single-plant and a line-mean basis in Test 1, and solely on a single-plant basis in Test 2. Across two tests with the TN14 isolate, plants with the PI 437654 allele for a marker linked to rhg1 had significantly (P<0.0001) less SCN reproduction than plants carrying the PI 88788 allele. A marker linked to Rhg4, however, was not significantly associated with resistance to TN14. Across two tests with the PA3 isolate, alleles of rhg1 from both sources gave a resistant reaction, although plants homozygous for the PI 88788 allele had significantly (P<0.05) greater resistance than plants with the PI 437654 allele. The marker allele from PI 437654 linked to Rhg4 was significantly (P<0.0005) associated with greater resistance than the PI 88788 allele in both PA3 tests, and resistance was dominant. There was a significant interaction between alleles at rhg1 and Rhg4 in both PA3 tests. These results suggest that PI 437654 and PI 88788 each have a different functional SCN resistance allele at or close to rhg1. These allelic differences have implications that breeders should consider before incorporation into cultivars.