Distinctive CD56dim NK subset profiles and increased NKG2D expression in blood NK cells of Parkinson's disease patients.

Mounting data suggest an important role for the immune system in Parkinson's disease (PD). Previous evidence of increased natural killer (NK) cell populations in PD suggests a potential role of NK cells in the pathogenesis of the disease. Previous studies have analyzed NK cell populations using aggregation by variable expression of CD56 and CD16. It remains unknown what differences may exist between NK cell subpopulations when stratified using more nuanced classification. Here, we profile NK cell subpopulations and elucidate the expressions of activating, NKG2D, inhibitory, NKG2A, and homing, CX3CR1, receptors on NK cell subpopulations in PD and healthy controls (HC). We analyzed cryopreserved PMBC samples using a 10-color flow cytometry panel to evaluate NK cell subpopulations in 31 individuals with sporadic PD and 27 HC participants. Here we identified significant differences in the CD56dim NK subset that changes with disease severity in PD. Furthermore, the expressions of NKG2D in all three NK cell subsets were significantly elevated in PD patients compared to HC. Notably, NKG2A expression in the CD56bright NK subset increased in PD patients with longer disease duration but there were no changes in CX3CR1. In summary, our data suggests that changes in NK cells may be influenced by the clinical severity and duration of PD.

Iatrogenic Excessive Clavicle Resection as a Complication of Arthroscopic Distal Clavicle Excision.

Arthroscopic distal clavicle excision (DCE) is a reliable procedure to treat acromioclavicular joint arthritis. Typically, only 1 to 2 cm of distal clavicle should be removed. Resection of too much bone can lead to instability of the joint or lack of support to the shoulder. We describe 2 patients who had excessive clavicular bone removed arthroscopically, leading to irreparable clavicular pain and dysfunction. The 2 female patients, ages 56 and 60 years, presented to our clinic with continued pain after DCE. Both had pain intractable with nonoperative treatment and loss of range of motion of the shoulder. Radiographs revealed a distal clavicle defect of 7.5 cm in 1 patient. The second patient had a 2-cm distal clavicular defect with an adjacent 2-cm clavicle bone fragment between the defect and residual clavicle shaft. Both underwent surgery with subtotal claviculectomy for pain control. During surgery, 1 patient had a subclavian vein requiring vascular repair. After 1 year of follow-up, both patients had reduced but residual pain and restricted range of motion. Only 1 patient could rejoin her preinjury occupation. Neither patient could continue with preinjury recreational sports. Excessive removal of the distal clavicle during DCE can result in continued pain and disability of the shoulder. Methods to visualize the anatomy of the distal clavicle and its articulation to the acromion should be considered when performing this operation arthroscopically. Reoperation to remove subtotal clavicle has good clinical outcomes but may lead to serious complications due to the proximity to major neurovascular structures. [Orthopedics. 2024;47(1):e57-e60.].

Editorial Commentary: Extreme Medial Repair of Massive Rotator Cuff Tears With Atrophy Warrants Caution: Robbing Peter to Pay Paul.

Medialization of the rotator cuff insertion as a technique to manage massive rotator cuff tears has been described for decades. However, "extreme medialization" as a means to manage massive rotator cuff tears with significant atrophy warrants caution. Nonanatomic reconstruction almost always carries a price. Biomechanical studies show extreme medialization results in significant and obligate restriction of motion, and it is difficult to imagine how extreme medialization would allow normal clinical motion without substantial scapulothoracic compensation. Similarly, obligatory loss of strength could be expected. Based on the current evidence, I will not indicate this technique for my own patients at the present time.

Electroosmotic Perfusion, External Microdialysis: Simulation and Experiment.

Information about the rates of hydrolysis of neuropeptides by extracellular peptidases can lead to a quantitative understanding of how the steady-state and transient concentrations of neuropeptides are controlled. We have created a small microfluidic device that electroosmotically infuses peptides into, through, and out of the tissue to a microdialysis probe outside the head. The device is created by two-photon polymerization (Nanoscribe). Inferring quantitative estimates of a rate process from the change in concentration of a substrate that has passed through tissue is challenging for two reasons. One is that diffusion is significant, so there is a distribution of peptide substrate residence times in the tissue. This affects the product yield. The other is that there are multiple paths taken by the substrate as it passes through tissue, so there is a distribution of residence times and thus reaction times. Simulation of the process is essential. The simulations presented here imply that a range of first order rate constants of more than 3 orders of magnitude is measurable and that 5-10 min is required to reach a steady state value of product concentration following initiation of substrate infusion. Experiments using a peptidase-resistant d-amino acid pentapeptide, yaGfl, agree with simulations.

Anatomic glenohumeral arthroplasty: State of the art.

Anatomical total shoulder arthroplasty in its modern form where it reproduces the normal shoulder has been utilized clinically for more than half a century. As the technology and the designs have changed to recreate the humeral and glenoid sides of the joint, the sophistication of design has resulted in the growing number of cases annually worldwide. This increase is due in part to the increasing number of indications that the prosthesis can treat with successful results. On the humeral side, there have been design changes to better reflect the proximal humeral anatomy, and humeral stems are increasingly placed safely without cement. Platform systems which allow conversion of a failed arthroplasty to a reverse configuration without stem extraction is another design change. Similarly, there has been increasing utilization of short stem and stemless humeral components. Extensive experience with shorter stem and stemless devices, however, has yet to demonstrate the purported advantages of these devices, as recent studies have demonstrated equivalent blood loss, fracture rates, operative times, and outcome scores. Easier revision with these shorter stems remains to be definitively established, with only one study comparing the ease of revision between stem types. On the glenoid side, hybrid cementless glenoids, inlay glenoids, cementless all-polyethylene glenoids, and augmented glenoids have all been investigated; however, the indications for these devices remain unclear. Lastly, innovative surgical approaches to implanting shoulder arthroplasty and the use of patient specific guides and computerized planning, while interesting concepts, still await validation before they are utilized on a widespread basis. While reverse shoulder arthroplasty has been increasingly used to reconstruct the arthritic shoulder, anatomic glenohumeral replacement maintains a significant role in the armamentarium of the shoulder surgeon.

Editorial Commentary: Return to Play in Overhead Athletes After Biceps Tenodesis for SLAP Lesions Is Inconsistent.

The optimal surgical management for the superior labrum anterior to posterior (SLAP) lesion in the overhead athlete remains elusive. Return to play (RTP) or return to sport (RTS) with both SLAP repair and biceps tenodesis in this subgroup has been inconsistent, complicated by incomplete description of what RTP actually involves. While the recent literature regarding biceps tenodesis for SLAP lesions is encouraging, longer-term follow-up and a clear definition of criteria that define what "RTP" looks like will be critical prior to universally embracing biceps tenodesis as a definitive SLAP management option for overhead athletes.

Soluble Angiotensin-Converting Enzyme 2 as a Prognostic Biomarker for Disease Progression in Patients Infected with SARS-CoV-2.

Predicting disease severity in patients infected with SARS-CoV-2 is difficult. Soluble angiotensin-converting enzyme 2 (sACE2) arises from the shedding of membrane ACE2 (mACE2), which is a receptor for SARS-CoV-2 spike protein. We evaluated the predictive value of sACE2 compared with known biomarkers of inflammation and tissue damage (CRP, GDF-15, IL-6, and sFlt-1) in 850 patients with and without SARS-CoV-2 with different clinical outcomes. For univariate analyses, median differences between biomarker levels were calculated for the following patient groups (classified by clinical outcome): RT-PCR-confirmed SARS-CoV-2 positive (Groups 1−4); RT-PCR-confirmed SARS-CoV-2 negative following previous SARS-CoV-2 infection (Groups 5 and 6); and 'SARS-CoV-2 unexposed' patients (Group 7). Median levels of CRP, GDF-15, IL-6, and sFlt-1 were significantly higher in hospitalized patients with SARS-CoV-2 compared with discharged patients (all p < 0.001), whereas levels of sACE2 were significantly lower (p < 0.001). ROC curve analysis of sACE2 provided cut-offs for predicting hospital admission (≤0.05 ng/mL (positive predictive value: 89.1%) and ≥0.42 ng/mL (negative predictive value: 84.0%)). These findings support further investigation of sACE2, as a single biomarker or as part of a panel, to predict hospitalization risk and disease severity in patients with SARS-CoV-2 infection.

Editorial Commentary: To Properly Apply Delphi Consensus Conclusions, Strengths and Weaknesses of the Process Require Consideration: Unified Expert Opinion or Toxic Fumes Resulting in a Strange Trance?

The Delphi Consensus Process is a tool to allow diverse expert opinion to be consolidated to better understand complex problems. The process has recently been applied to orthopaedic treatment options. While a piece of the puzzle, the strengths and weaknesses of this process must be understood to allow the orthopaedist to apply the conclusions of the Delphi Consensus process effectively. It is important to recognize that expert opinion has been upended time and time again by carefully collected clinical-outcome data. It is unclear whether the visions of the Oracle are due to wisdom or toxic fumes resulting in a strange trance.

Integrating Physicians Into Lean Quality Improvement Through a Structured Educational Program: The ECLIPSE Program.

In the increasingly complex health care system, physicians require skills and knowledge to participate with multidisciplinary team members in quality improvement (QI) that adds value to health care organizations. The Educational and Clinical Leaders Improving Performance with Structured E3L training (ECLIPSE) program was developed to address this challenge. Clinically relevant components of lean management were leveraged to create an online, flipped-classroom curriculum, and this was paired with Kaizen adapted specifically for physicians and multidisciplinary clinicians to promote experiential skills utilization. The focus of each adapted Kaizen was a topic of institutional QI priority, such as improving patient throughput or reducing readmission rates. Participants were awarded certification in the E3 Leadership management system-a patient-centered, equity-focused system based on lean principles. After 4 years, 50 E3 Leadership certificates were awarded to multidisciplinary clinicians, including 30 to physicians; participants scored an average 85% on module quizzes. The ECLIPSE program has improved physician participation in multidisciplinary QI projects with institutional alignment.

Validation of Dexamethasone-Enhanced Continuous-Online Microdialysis for Monitoring Glucose for 10 Days after Brain Injury.

Traumatic brain injury (TBI) induces a pathophysiologic state that can be worsened by secondary injury. Monitoring brain metabolism with intracranial microdialysis can provide clinical insights to limit secondary injury in the days following TBI. Recent enhancements to microdialysis include the implementation of continuously operating electrochemical biosensors for monitoring the dialysate sample stream in real time and dexamethasone retrodialysis to mitigate the tissue response to probe insertion. Dexamethasone-enhanced continuous-online microdialysis (Dex-enhanced coMD) records long-lasting declines of glucose after controlled cortical impact in rats and TBI in patients. The present study employed retrodialysis and fluorescence microscopy to investigate the mechanism responsible for the decline of dialysate glucose after injury of the rat cortex. Findings confirm the long-term functionality of Dex-enhanced coMD for monitoring brain glucose after injury, demonstrate that intracranial glucose microdialysis is coupled to glucose utilization in the tissues surrounding the probes, and validate the conclusion that aberrant glucose utilization drives the postinjury glucose decline.

Closed form approximations to predict retention times and peak widths in gradient elution under conditions of sample volume overload and sample solvent mismatch.

Closed form expressions for the prediction of retention times and peak widths for gradient liquid chromatography are particularly useful in understanding, rationalizing and optimizing separations. These expressions are obtained by integrating differential equations, in conjunction with a model of the variation of the retention factor as a function of mobile phase composition. Two of these models, the linear solvent strength (LSS) model and the Neue-Kuss (NK) model are explored in the present work. Here, we expand on these closed form expressions to account for effects of sample volume overload and a mismatch between the sample solvent and the initial mobile phase composition for the gradient. We show that there have been errors in expressions reported in the literature, and we have evaluated the accuracy of the predictions from the closed form expressions reported here using a recently developed liquid chromatography simulator. The expressions assume a constant plate height and consider elution across four zones of the gradient profile - elution in the sample solvent, elution in the initial (isocratic) mobile phase caused by the gradient delay volume, elution during a linear gradient, and elution post-gradient at the final (isocratic) mobile phase composition. The expressions generally give reasonably accurate predictions for retention times and peak widths, except for cases where the solute elutes during transitions between the different zones. The average magnitude of the prediction errors for retention time and peak width relative to simulation were 0.093% and 0.40% for the LSS expressions for ten amphetamine solutes at 36 different separation conditions, and 0.22% and 1.8% for the NK expressions for eight alkylbenzene solutes at 36 different separation conditions, respectively.

Editorial Commentary: Mechanics Versus Biology: Both Are Relevant Principles in Understanding Superior Capsular Reconstruction.

The topic of superior capsular reconstruction remains controversial. Whereas identifying the best time-zero graft configuration for this procedure remains important, the success or failure of the procedure will be dependent on the biology, not just the bench performance. Any conforming object placed in the subacromial space at time zero could center the humeral head and decrease superior translation compared with a massive rotator cuff tear but may not restore translation to normal. It does appear that a thicker graft is better in this regard, but how much thicker is better is unclear. Most of all, whether the mechanical benefits of a thicker graft will be offset by a thicker and potentially less biologically compatible construct is also unclear. In most orthopaedic settings, autografts remain consistently superior to allografts. The contrast in results may be better explained by biology, and the excellent superior capsular reconstruction results reported with autograft have not been replicated universally with dermal allograft.

Editorial Commentary: The Top Cited Rotator Cuff Repair Articles: It's All About Popular.

The Thomson Institute for Scientific Information Web of Science database was used to rank the top 50 articles regarding rotator cuff repair by number of citations received. Although the number of citations is a useful benchmark, it must be taken as only one of many indices of the value of an article to the study of orthopaedics. The most cited articles are out of date, reflecting that a longer time in publication allows more time for citation, and most have low levels of evidence (Level IV, retrospective case series absent a control group).

Column-in-valve designs to minimize extra-column volumes.

We report on the design and performance of in-house built column cartridges that can be directly screwed into the ports of a commercial rotor-stator valve to minimize extra-column band broadening and pressure-drop losses when pursuing ultra-fast separations such as those needed in 2D and 3D-LC separations. Two basic designs were evaluated and were compared with the results obtained with a commercial screw-in column cartridge. The system produces an extra-column band broadening as low as 0.05 to 0.1 µL2 for the employed UV-detector set-up. Despite these very low values, the obtained separation efficiency of the in-house fabricated cartridge columns was very low, corresponding to a reduced minimal plate height around h=7 at the very best, which, for the 1.7 µm particle and 26.4 mm long columns corresponds to a number of theoretical plates of N=2200 under isocratic conditions. A similar poor performance was obtained with a commercial column cartridge with similar dimensions using the same set-up. One possible explanation of the observed performance could be found in the inner diameter of the column cartridges (i.d. =0.75 mm and 1 mm) which, for the employed sub 2-µm particles, falls into a region of column diameters that, according to literature models, is most likely to suffer from inherent packing problems.

FDA public workshop: Orthopaedic sensing, measuring, and advanced reporting technology (SMART) devices.

Traditional orthopaedic devices do not communicate with physicians or patients post-operatively. After implantation, follow-up of traditional orthopaedic devices is generally limited to episodic monitoring. However, the orthopaedic community may be shifting towards incorporation of smart technology. Smart technology in orthopaedics is a term that encompasses a wide range of potential applications. Smart orthopaedic implants offer the possibility of gathering data and exchanging it with an external reader. They incorporate technology that enables automated sensing, measuring, processing, and reporting of patient or device parameters at or near the implant. While including advanced technology in orthopaedic devices has the potential to benefit patients, physicians, and the scientific community, it may also increase the patient risks associated with the implants. Understanding the benefit-risk profile of new smart orthopaedic devices is critical to ensuring their safety and effectiveness. The 2018 FDA public workshop on orthopaedic sensing, measuring, and advanced reporting technology (SMART) devices was held on April 30, 2018, at the FDA White Oak Campus in Silver Spring, MD with the goal of fostering a collaborative dialogue amongst the orthopaedic community. Workshop attendees discussed four key areas related to smart orthopaedic devices: engineering and technology considerations, clinical and patient perspectives, cybersecurity, and regulatory considerations. The workshop presentations and associated discussions highlighted the need for the orthopaedic community to collectively craft a responsible path for incorporating smart technology in musculoskeletal disease care.

Case Studies AAOS Clinical Practice Guideline: Management of Rotator Cuff Injuries.

Shoulder disease is a major cause of musculoskeletal disability in the United States. Chronic shoulder pain has been estimated to affect approximately 8% of all American adults, second only to chronic knee pain in our society's burden of musculoskeletal disease. Rotator cuff pathology is the leading cause of shoulder-related disability seen by orthopaedic surgeons, and surgical volume is on the rise. One study, for example, notes a 141% increase in rotator cuff repairs from 1996 to 2006 in the United States. Because rotator cuff disease is such a common condition with evidence of various strength supporting different common treatments, the American Academy of Orthopaedic Surgeons published a clinical practice guideline to help elucidate best practices for its treatment. A summary of these guidelines with the strength of the recommendations is available at OrthoGuidelines (http://www.orthoguidelines.org/topic?id=1027) with links to rationale behind each of the conclusions. This study will illustrate the use of these guidelines through presentation and discussion of hypothetical clinical cases.

Challenges to the Application of Spatially Explicit Stochastic Simulation Models for Foot-and-Mouth Disease Control in Endemic Settings: A Systematic Review.

Simulation modeling has become common for estimating the spread of highly contagious animal diseases. Several models have been developed to mimic the spread of foot-and-mouth disease (FMD) in specific regions or countries, conduct risk assessment, analyze outbreaks using historical data or hypothetical scenarios, assist in policy decisions during epidemics, formulate preparedness plans, and evaluate economic impacts. Majority of the available FMD simulation models were designed for and applied in disease-free countries, while there has been limited use of such models in FMD endemic countries. This paper's objective was to report the findings from a study conducted to review the existing published original research literature on spatially explicit stochastic simulation (SESS) models of FMD spread, focusing on assessing these models for their potential use in endemic settings. The goal was to identify the specific components of endemic FMD needed to adapt these SESS models for their potential application in FMD endemic settings. This systematic review followed the PRISMA guidelines, and three databases were searched, which resulted in 1176 citations. Eighty citations finally met the inclusion criteria and were included in the qualitative synthesis, identifying nine unique SESS models. These SESS models were assessed for their potential application in endemic settings. The assessed SESS models can be adapted for use in FMD endemic countries by modifying the underlying code to include multiple cocirculating serotypes, routine prophylactic vaccination (RPV), and livestock population dynamics to more realistically mimic the endemic characteristics of FMD. The application of SESS models in endemic settings will help evaluate strategies for FMD control, which will improve livestock health, provide economic gains for producers, help alleviate poverty and hunger, and will complement efforts to achieve the Sustainable Development Goals.