New approach to testing treatments for osteoarthritis: FastOA.

Animal models of post traumatic osteoarthritis have shown many promising treatments for disease, but human trials have mostly failed to identify effective treatments. This viewpoint suggests that the frequent failure of drug and treatment development in osteoarthritis is due, in part, to the advanced stage of disease of patients in trials and suggests that mirroring the animal model approach might be more successful. It suggests a path forward by enriching trial enrollees with those likely to develop post traumatic OA quickly.

Quantitative, Point-of-Care Immunoassay Platform to Guide and Monitor Sickle Cell Disease Therapy.

Sickle cell patients often require monthly transfusions with normal blood to treat the many complications of the disease. In this therapy, the clinician lowers the amount of hemoglobin S (HbS) containing red blood cells (RBCs) by transfusing normal blood units containing hemoglobin A (HbA). We have developed a point-of-care (POC) quantitative immunoassay for HbS to serve as a diagnostic aid for clinicians providing this life-saving treatment. The test consists of a small-footprint reader and cartridges that quantify the percentage of HbS in a small volume of patient blood. The test reports % HbS values in the range from 5 to 86% that highly correlate (slope 1.03, R(2) = 0.97) with currently used central laboratory HPLC systems. The test also shows a 1% limit of blank, 2% limit of detection, and 5% limit of quantitation. The test was also shown to encounter minimal effects from potential interferences. This cost-effective, POC HbS quantitative approach will allow for real-time transfusion monitoring in sickle cell treatment settings and therefore improve workflow and allow clinicians to quickly make informed therapeutic decisions.

Validation of a novel point of care testing device for sickle cell disease.

BACKGROUND: Sickle cell disease is one of the most common inherited blood disorders. Universal screening and early intervention have significantly helped to reduce childhood mortality in high-resource countries. However, persons living in low-resource settings are often not diagnosed until late childhood when they present with clinical symptoms. In addition, confirmation of disease in affected individuals in the urgent care setting is limited in both high- and low-resource areas, often leading to delay in treatment. All of the current diagnostic methods rely on advanced laboratory systems and are often prohibitively expensive and time-consuming in low-resource settings. To address this need, the Sickle SCAN™ test has been developed to diagnose sickle cell disease and sickle cell trait at the point of care without electricity or advanced equipment. METHODS: This study was conducted to evaluate and validate the diagnostic accuracy of the Sickle SCAN™ test, a novel point of care test for sickle cell disease. Thus, we describe the laboratory testing and clinical validation of the Sickle SCAN™ test in individuals >1 year of age using capillary blood. The Sickle SCAN™ test was created using advanced, qualitative lateral flow technology using capillary blood to identify the presence of hemoglobin A, S, and C allowing for detection of results with the naked eye. RESULTS: Laboratory testing using venous blood demonstrated 99 % sensitivity and 99 % specificity for the diagnosis of HbSS, HbAS, HbSC, HbAC, and HbAA. Seventy-one subjects underwent capillary blood sampling at the point of care for further validation. This test detected the correct A, S, and C presence with an overall diagnostic accuracy of 99 % at the bedside. CONCLUSION: The Sickle SCAN™ test has the potential to significantly impact the diagnosis and treatment for sickle cell disease worldwide as well as enhance genetic counseling at the point of care. Further validation testing will be conducted in newborns in resource-poor settings in upcoming studies.

Topical Cyclosporine A 1% for the Treatment of Chronic Follicular Conjunctivitis.

OBJECTIVE: To evaluate the use of topical cyclosporine A (CSA) 1% in the treatment of chronic follicular conjunctivitis (CFC). METHODS: Retrospective chart review from 2001 to 2012 identified 12 patients (22 eyes) with CFC (mean ± standard deviation [SD] age, 50.2 ± 15.4 years; 75% female; 92% white) treated with CSA. Main outcome measures included inflammation grade, visual acuity, concurrent corticosteroid (CS) therapy, effect on CS taper, and adverse effects. RESULTS: Mean ± SD follow-up time was 11.7 ± 9.7 months. Mean ± SD time from diagnosis to CSA treatment initiation was 2.4 ± 3.2 months. Mean ± SD duration of CSA treatment was 5.8 ± 2.8 months. Four patients (33%) complained of irritation (n = 2), redness (n = 1), itching (n = 1), and burning (n = 1) but none discontinued treatment. Concurrent CSs were tapered off in all patients after a mean ± SD of 5.0 ± 2.5 weeks. Mean ± SD initial vision was 0.078 ± 0.093 logMAR, whereas vision at final examination was 0.056 ± 0.081 logMAR (P = 0.02). Mean ± SD initial inflammation grade of 1.9 ± 1.0 was significantly reduced to final grade of 0.7 ± 0.9 (P = 0.0002). Mean ± SD time to initial inflammation control in 9 patients (75%) was 33.2 ± 24.5 days. Two patients (17%) switched to oral CSA because of lack of inflammation control. CONCLUSIONS: Topical CSA 1% is an effective and well-tolerated therapy that decreased chronic inflammation and tapered topical CS in patients with CFC. The use of CSA in such patients warrants further investigation.

Topical cyclosporine a 1% for the treatment of chronic ocular surface inflammation.

OBJECTIVE: To evaluate the use of topical cyclosporine A (CsA) 1% emulsion in the treatment of chronic ocular surface inflammation (OSI). METHODS: We conducted a retrospective chart review of patients with various forms of OSI treated with topical CsA 1% from 2001 to 2012. RESULTS: Twenty-nine patients (52 eyes) with various forms of OSI, including epidemic keratoconjunctivitis (n=14), chronic follicular conjunctivitis (n=12), Thygeson superficial punctate keratopathy (n=2), and vernal keratoconjunctivitis (n=1), were included. Twenty-seven patients had inflammation refractory to prior therapies. Twenty-four patients received concurrent medications with CsA 1%. Twenty-three of 24 patients on concurrent corticosteroids (CS) were able to taper their use while receiving CsA 1%. Thirteen patients experienced ocular discomfort with CsA 1%; one patient discontinued therapy all together as a result of these side effects; another switched to CsA 0.5% with improvement of adverse symptoms. Inflammation was controlled in 22 (92%) of the 24 patients who received CsA 1% for at least 2 months in duration. CONCLUSION: Topical CsA 1% helps to control inflammation and spares CS use in patients with chronic OSI.

Visual narratives in medicine - Bridging the gap in graphic medicine with an illustrated narrative of osteoarthritis.

Objective: Visual narratives have been used in medicine to share information in the form of stories with the potential to improve understanding of conditions and change behaviours. One genre of visual narratives is "graphic medicine", which integrates comics into medical education and the delivery of healthcare. Graphic medicine can maximise the impact of research findings by presenting them in a more accessible format, which may be particularly useful in certain populations, such as those with low levels of health literacy. Those with lower health literacy levels and osteoarthritis (OA) are less likely to manage their condition with guideline recommended management strategies, experience a higher burden of disease, and have lower access to care. Our objectives were to review the current visual narratives in the field of and create a graphic medicine visual narrative based on existing research. Design: This paper summarises the current visual narratives in OA and presents a graphic medicine visual narrative to illustrate the experience of living with OA. Considerations for the dissemination of visual narratives to target audiences are also discussed. Results: The most common visual narratives in are infographics, videos, and graphic medicine. A graphic medicine visual narrative, based on previous qualitative work and informed by a framework, was created to illustrate two distinct narratives - impairment and participatory. Conclusion: Visual narratives remain an emerging field in OA but may serve as a useful resource for patients or clinicians to discuss various aspects of OA management. Future research should evaluate and validate the use of visual narratives in OA.

Arthritis Foundation/HSS Workshop on Hip Osteoarthritis, Part 4: Nonoperative Options, Machine Learning in Predicting Total Hip Arthroplasty, Robotics, and Phenotyping to Guide Precision Rehabilitation.

Far more publications are available for osteoarthritis of the knee than of the hip. Recognizing this research gap, the Arthritis Foundation (AF), in partnership with the Hospital for Special Surgery (HSS), convened an in-person meeting of thought leaders to review the state of the science of and clinical approaches to hip osteoarthritis. This article summarizes the recommendations gleaned from presentations given in the "late-stage osteoarthritis" session of the 2023 Hip Osteoarthritis Clinical Studies Conference, which took place on February 17 and 18, 2023, in New York City. It covers conservative treatment, decision-making in end-stage hip osteoarthritis, advancements in robotics, and the role of phenotyping in precision rehabilitation post-total hip arthroplasty (THA).

Arthritis Foundation/HSS Workshop on Hip Osteoarthritis, Part 3: Rehabilitation and Exercise.

Far more publications are available for osteoarthritis of the knee than of the hip. Recognizing this research gap, the Arthritis Foundation (AF), in partnership with the Hospital for Special Surgery (HSS), convened an in-person meeting of thought leaders to review the state of the science of and clinical approaches to hip osteoarthritis. This article summarizes the recommendations gleaned from 5 presentations given on hip-related rehabilitation at the 2023 Hip Osteoarthritis Clinical Studies Conference, which took place on February 17 and 18, 2023, in New York City.

Arthritis Foundation/HSS Workshop on Hip Osteoarthritis, Part 1: Epidemiology, Early Development, and Cohorts From Around the World.

Far more publications are available for osteoarthritis of the knee than of the hip. Recognizing this research gap, the Arthritis Foundation, in partnership with the Hospital for Special Surgery, convened an in-person meeting of thought leaders to review the state of the science of and clinical approaches to hip osteoarthritis. This article summarizes the recommendations and clinical research gaps gleaned from 5 presentations given in the "how hip osteoarthritis begins" session of the 2023 Hip Osteoarthritis Clinical Studies Conference, which took place on February 17 and 18, 2023, in New York City.

Arthritis Foundation/HSS Workshop on Hip Osteoarthritis, Part 2: Detecting Hips at Risk: Early Biomechanical and Structural Mechanisms.

Far more publications are available for osteoarthritis of the knee than of the hip. Recognizing this research gap, the Arthritis Foundation (AF), in partnership with the Hospital for Special Surgery (HSS), convened an in-person meeting of thought leaders to review the state of the science of and clinical approaches to hip osteoarthritis. This article summarizes the recommendations gleaned from 5 presentations given in the "early hip osteoarthritis" session of the 2023 Hip Osteoarthritis Clinical Studies Conference, which took place on February 17 and 18, 2023, in New York City. It also summarizes the workgroup recommendations from a small-group discussion on clinical research gaps.

The OARSI Joint Effort Initiative: Priorities for osteoarthritis management program implementation and research 2024-2028.

Objective: The Joint Effort Initiative (JEI) is an international collaboration of clinicians, researchers, and consumer organisations with a shared vision of improving the implementation of osteoarthritis management programs (OAMPs). This study aimed to identify JEI's future priorities and guide direction. Design: A two-part international survey to prioritise topics of importance to our membership and research stakeholders. Survey one presented a list of 40 topics under 5 themes. Consenting participants were asked to choose their top three topics in each theme. A short list of 25 topics was presented in survey two. Participants were asked to rank the importance (100-point NRS scale, 100 â€‹= â€‹highest priority). Response frequency (median, IQR) was used to rank the top priorities by theme. Results: Ninety-five participants completed survey one (61% female, 48% clinicians) and 57 completed survey two. The top ranked topic/s were:i. Promotion and advocacy: support training for health professionals (median 85, IQR 24).ii. Education and training: incorporating behaviour change into OAMPs (80, 16), advanced OA skills (80, 30), and integration of OA education into clinical training (80, 36).iii. Improving OAMPs delivery: regular updates on changes to best-evidence OA care (84, 24).iv. Future research: improve uptake of exercise, physical activity, and weight-loss (89, 16).v. Enhancing relationships, alliances, and shared knowledge: promote research collaborations (81, 30), share challenges and opportunities for OAMP implementation (80, 23). Conclusions: These topics will set the JEI's research and collaboration agenda for the next 5 years and stimulate ideas for others working in the field.

Anaplastic Lymphoma Kinase Positive Mesenteric Inflammatory Myofibroblastic Tumor in Adult Woman.

Inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms containing spindle cells and inflammatory components that can be locally aggressive. They have unclear biological behavior and may recur after resection. A 31-year-old woman presented with three months of cough, fatigue, weight loss, abdominal pain, anemia, and elevated inflammatory markers. CT showed a large well-circumscribed enhancing mass in the right colic mesentery. The patient underwent a laparoscopic right colectomy. Pathologic review showed fascicular spindle cells with admixed chronic inflammatory cells. Cells stained diffusely positive for SMA and anaplastic lymphoma kinase (ALK), diagnostic of an IMT. Post-operatively, the patient reported symptom resolution and had normalization of lab values. She remains disease-free at 20 months. IMT is rare in adults, accounting for 0.7%-1.0% of lung tumors. Up to 30% of patients present with elevated inflammatory markers. On imaging, IMTs are soft tissue masses with variable enhancement and fibrosis, often suspected to be malignant neoplasms. Up to 80% of IMTs are driven by altered tyrosine kinase signaling and half of IMTs express ALK, which may be treated in unresectable/recurrent cases using ALK-inhibitors. IMT may recur in 10%-15% of patients. The roles of adjuvant treatments are unclear given the rarity and unpredictable biological behavior. Long-term follow-up with regular radiologic and laboratory surveillance is recommended given possible local recurrence. IMTs are best managed in a multidisciplinary setting given their unpredictable nature. Surgery is the mainstay of IMT treatment with long-term control expected in >80% of adult patients.

Summary Report of the Arthritis Foundation and the American Orthopaedic Foot & Ankle Society's Symposium on Targets for Osteoarthritis Research: Part 1: Epidemiology, Pathophysiology, and Current Imaging Approaches.

This first of a 2-part series of articles recounts the key points presented in a collaborative symposium sponsored jointly by the Arthritis Foundation and the American Orthopaedic Foot & Ankle Society with the intent to survey the state of scientific knowledge related to incidence, diagnosis, pathologic mechanisms, and injection treatment options for osteoarthritis (OA) of the foot and ankle. A meeting was held virtually on December 3, 2021. A group of experts were invited to present brief synopses of the current state of knowledge and research in this area. Part 1 overviews areas of epidemiology and pathophysiology, current approaches in imaging, diagnostic and therapeutic injections, and genetics. Opportunities for future research are discussed. The OA scientific community, including funding agencies, academia, industry, and regulatory agencies, must recognize the needs of patients that suffer from arthritis of foot and ankle. The foot and ankle contain a myriad of interrelated joints and tissues that together provide a critical functionality. When this functionality is compromised by OA, significant disability results, yet the foot and ankle are generally understudied by the research community. Level of Evidence: Level V - Review Article/Expert Opinion.

Summary Report of the Arthritis Foundation and the American Orthopaedic Foot & Ankle Society's Symposium on Targets for Osteoarthritis Research: Part 2: Treatment Options.

This second of a 2-part series of articles recounts the key points presented in a collaborative symposium sponsored jointly by the Arthritis Foundation and the American Orthopaedic Foot & Ankle Society with the intent to survey current treatment options for osteoarthritis (OA) of the foot and ankle. A meeting was held virtually on December 10, 2021. A group of experts were invited to present brief synopses of the current state of knowledge and research in this area. Topics were chosen by meeting organizers, who then identified and invited the expert speakers. Part 2 overviews the current treatment options, including orthotics, non-joint destructive procedures, as well as arthroscopies and arthroplasties in ankles and feet. Opportunities for future research are also discussed, such as developments in surgical options for ankle and the first metatarsophalangeal joint. The OA scientific community, including funding agencies, academia, industry, and regulatory agencies, must recognize the importance to patients of addressing the foot and ankle with improved basic, translational, and clinical research. Level of Evidence: Level V, review article/expert opinion.

FDA/Arthritis Foundation osteoarthritis drug development workshop recap: Assessment of long-term benefit.

OBJECTIVE: To summarize proceedings of a workshop convened to discuss the current state of science in the disease of osteoarthritis (OA), identify the knowledge gaps, and examine the developmental and regulatory challenges in bringing these products to market. DESIGN: Summary of the one-day workshop held virtually on June 22nd, 2021. RESULTS: Speakers selected by the Planning Committee presented data on the current approach to assessment of OA therapies, biomarkers in OA drug development, and the assessment of disease progression and long-term benefit. CONCLUSIONS: Demonstrated by numerous failed clinical trials, OA is a challenging disease for which to develop therapeutics. The challenge is magnified by the slow time of onset of disease and the need for clinical trials of long duration and/or large sample size to demonstrate the effect of an intervention. The OA science community, including academia, pharmaceutical companies, regulatory agencies, and patient communities, must continue to develop and test better clinical endpoints that meaningfully reflect disease modification related to long-term patient benefit.

Utilization of microparticles in next-generation assays for microflow cytometers.

Micron-sized particles have primarily been used in microfabricated flow cytometers for calibration purposes and proof-of-concept experiments. With increasing frequency, microparticles are serving as a platform for assays measured in these small analytical devices. Light scattering has been used to measure the agglomeration of antibody-coated particles in the presence of an antigen. Impedance detection is another technology being integrated into microflow cytometers for microparticle-based assays. Fluorescence is the most popular detection method in flow cytometry, enabling highly sensitive multiplexed assays. Finally, magnetic particles have also been used to measure antigen levels using a magnetophoretic micro-device. We review the progress of microparticle-based assays in microflow cytometry in terms of the advantages and limitations of each approach.

A hard microflow cytometer using groove-generated sheath flow for multiplexed bead and cell assays.

With a view toward developing a rugged microflow cytometer, a sheath flow system was micromachined in hard plastic (polymethylmethacrylate) for analysis of particles and cells using optical detection. Six optical fibers were incorporated into the interrogation region of the chip, in which hydrodynamic focusing narrowed the core stream to ~35 µm × 40 µm. The use of a relatively large channel at the inlet as well as in the interrogation region (375 µm × 125 µm) successfully minimized the risk of clogging. The device could withstand pressures greater than 100 psi without leaking. Assays using both coded microparticles and cells were demonstrated using the microflow cytometer. Multiplexed immunoassays detected nine different bacteria and toxins using a single mixture of coded microspheres. A549 cancer cells processed with locked nucleic acid probes were evaluated using fluorescence in situ hybridization.

Multi-wavelength microflow cytometer using groove-generated sheath flow.

A microflow cytometer was developed that ensheathed the sample (core) fluid on all sides and interrogated each particle in the sample stream at four different wavelengths. Sheathing was achieved by first sandwiching the core fluid with the sheath fluid laterally via fluid focusing. Chevron-shaped groove features fabricated in the top and bottom of the channel directed sheath fluid from the sides to the top and bottom of the channel, completely surrounding the sample stream. Optical fibers inserted into guide channels provided excitation light from diode lasers at 532 and 635 nm and collected the emission wavelengths. Two emission collection fibers were connected to PMTs through a multimode fiber splitter and optical filters for detection at 635 nm (scatter), 665 nm and 700 nm (microsphere identification) and 565 nm (phycoerythrin tracer). The cytometer was capable of discriminating microspheres with different amounts of the fluorophores used for coding and detecting the presence of a phycoerythrin antibody complex on the surface of the microspheres. Assays for Escherichia coli were compared with a commercial Luminex flow cytometer.