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.

Classification, detection, and segmentation performance of image-based AI in intracranial aneurysm: a systematic review.

BACKGROUND: The detection and management of intracranial aneurysms (IAs) are vital to prevent life-threatening complications like subarachnoid hemorrhage (SAH). Artificial Intelligence (AI) can analyze medical images, like CTA or MRA, spotting nuances possibly overlooked by humans. Early detection facilitates timely interventions and improved outcomes. Moreover, AI algorithms offer quantitative data on aneurysm attributes, aiding in long-term monitoring and assessing rupture risks. METHODS: We screened four databases (PubMed, Web of Science, IEEE and Scopus) for studies using artificial intelligence algorithms to identify IA. Based on algorithmic methodologies, we categorized them into classification, segmentation, detection and combined, and then their merits and shortcomings are compared. Subsequently, we elucidate potential challenges that contemporary algorithms might encounter within real-world clinical diagnostic contexts. Then we outline prospective research trajectories and underscore key concerns in this evolving field. RESULTS: Forty-seven studies of IA recognition based on AI were included based on search and screening criteria. The retrospective results represent that current studies can identify IA in different modal images and predict their risk of rupture and blockage. In clinical diagnosis, AI can effectively improve the diagnostic accuracy of IA and reduce missed detection and false positives. CONCLUSIONS: The AI algorithm can detect unobtrusive IA more accurately in communicating arteries and cavernous sinus arteries to avoid further expansion. In addition, analyzing aneurysm rupture and blockage before and after surgery can help doctors plan treatment and reduce the uncertainties in the treatment process.

High Area Deprivation Index is Associated With Not Achieving the Patient-acceptable Symptom State After TKA.

BACKGROUND: The Area Deprivation Index (ADI) approximates a patient's relative socioeconomic deprivation. The ADI has been associated with increased healthcare use after TKA, but it is unknown whether there is an association with patient-reported outcome measures (PROMs). Given that a high proportion of patients are dissatisfied with their results after TKA, and the large number of these procedures performed, knowledge of factors associated with PROMs may indicate opportunities to provide support to patients who might benefit from it. QUESTIONS/PURPOSES: (1) Is the ADI associated with achieving the minimum clinically important difference (MCID) for the Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain, Joint Replacement (JR), and Physical Function (PS) short forms after TKA? (2) Is the ADI associated with achieving the patient-acceptable symptom state (PASS) thresholds for the KOOS pain, JR, and PS short forms? METHODS: This was a retrospective study of data drawn from a longitudinally maintained database. Between January 2016 and July 2021, a total of 12,239 patients underwent unilateral TKA at a tertiary healthcare center. Of these, 92% (11,213) had available baseline PROM data and were potentially eligible. An additional 21% (2400) of patients were lost before the minimum study follow-up of 1 year or had incomplete data, leaving 79% (8813) for analysis here. The MCID is the smallest change in an outcome score that a patient is likely to perceive as a clinically important improvement, and the PASS refers to the threshold beyond which patients consider their symptoms acceptable and consistent with adequate functioning and well-being. MCIDs were calculated using a distribution-based method. Multivariable logistic regression models were created to investigate the association of ADI with 1-year PROMs while controlling for patient demographic variables. ADI was stratified into quintiles based on their distribution in our sample. Achievement of MCID and PASS thresholds was determined by the improvement between preoperative and 1-year PROMs. RESULTS: After controlling for patient demographic factors, ADI was not associated with an inability to achieve the MCID for the KOOS pain, KOOS PS, or KOOS JR. A higher ADI was independently associated with an increased risk of inability to achieve the PASS for KOOS pain (for example, the odds ratio of those in the ADI category of 83 to 100 compared with those in the 1 to 32 category was 1.34 [95% confidence interval 1.13 to 1.58]) and KOOS JR (for example, the OR of those in the ADI category of 83 to 100 compared with those in the 1 the 32 category was 1.29 [95% CI 1.10 to 1.53]), but not KOOS PS (for example, the OR of those in the ADI category of 83 to 100 compared with those in the 1 the 32 category was 1.09 [95% CI 0.92 to 1.29]). CONCLUSION: Our findings suggest that social and economic factors are associated with patients' perceptions of their overall pain and function after TKA, but such factors are not associated with patients' perceptions of their improvement in symptoms. Patients from areas with higher deprivation may be an at-risk population and could benefit from targeted interventions to improve their perception of their healthcare experience, such as through referrals to nonemergent medical transportation and supporting applications to local care coordination services before proceeding with TKA. Future research should investigate the mechanisms underlying why socioeconomic disadvantage is associated with inability to achieve the PASS, but not the MCID, after TKA. LEVEL OF EVIDENCE: Level III, therapeutic study.

Disease diagnosis and arthroplasty type are strongly associated with short-term postoperative patient-reported outcomes in patients undergoing primary total shoulder arthroplasty.

BACKGROUND: Prognostic factors for total shoulder arthroplasty (TSA) clinical outcomes are incompletely understood. This study investigates the associations of preoperative patient, disease-specific, and surgical factors with 1-year postoperative PENN Shoulder Score (PSS) in patients undergoing primary TSA. METHODS: Cleveland Clinic patients undergoing primary anatomic TSA (aTSA) or reverse TSA (rTSA) for glenohumeral osteoarthritis (GHOA) or rotator cuff tear arthropathy (CTA) between February 2015 and August 2019, and having complete preoperative and 1-year postoperative patient-reported outcome measures (PROMs), were included. Twenty preselected preoperative patient, disease-specific, and surgical factors were used to fit multivariable models for 1-year PSS and its subscores. RESULTS: Of 1427 eligible primary TSAs, 1174 had 1-year follow-up by PROMs (82%), with 1042 analyzed after additional exclusions, including 30% rTSAs for CTA (n = 308), 26% rTSAs for GHOA (n = 275), and 44% aTSAs for GHOA (n = 459). All PROMs showed statistically significant improvements postoperatively, with 89% of patients reaching an acceptable symptom state. Lower 1-year PSS was associated with younger age, female sex, current smoking, chronic pain diagnosis, history of prior surgery, worker's compensation claim, lower preoperative mental health, lower baseline PSS, absence of glenoid bone loss, and diagnosis-arthroplasty type (CTA-rTSA < GHOA-rTSA < GHOA-aTSA). The most important prognostic factors associated with 1-year PSS were diagnosis-arthroplasty type, baseline mental health status, and insurance status. CONCLUSIONS: Disease diagnosis, arthroplasty type, and several other baseline factors are strongly and individually associated with PROMs following primary TSA, with patients undergoing aTSA for GHOA demonstrating the highest PROM scores at 1-year follow-up. Patient, disease-specific, and surgical factors can be used to guide postoperative prognosis following primary TSA for improved preoperative patient counseling regarding expected outcomes of these procedures.

What Are the Diagnosis-Specific Thresholds of Minimal Clinically Important Difference and Patient Acceptable Symptom State in Hip Disability and Osteoarthritis Outcome Score After Primary Total Hip Arthroplasty?

BACKGROUND: This study aimed to determine the minimal clinically important difference (MCID) and Patient Acceptable Symptom State (PASS) thresholds for Hip Disability and Osteoarthritis Outcome Score (HOOS) pain, physical short form (PS), and joint replacement (JR) 1 year after primary total hip arthroplasty stratified by preoperative diagnosis of osteoarthritis (OA) versus non-OA. METHODS: A prospective institutional cohort of 5,887 patients who underwent primary total hip arthroplasty (January 2016 to December 2018) was included. There were 4,184 patients (77.0%) who completed a one-year follow-up. Demographics, comorbidities, and baseline and one-year HOOS pain, PS, and JR scores were recorded. Patients were stratified by preoperative diagnosis: OA or non-OA. Minimal detectable change (MDC) and MCIDs were estimated using a distribution-based approach. The PASS values were estimated using an anchor-based approach, which corresponded to a response to a satisfaction question at one year post surgery. RESULTS: The MCID thresholds were slightly higher in the non-OA cohort versus OA patients. (HOOS-Pain: OA: 8.35 versus non-OA: 8.85 points; HOOS-PS: OA: 9.47 versus non-OA: 9.90 points; and HOOS-JR: OA: 7.76 versus non-OA: 8.46 points). Similarly, all MDC thresholds were consistently higher in the non-OA cohort compared to OA patients. The OA cohort exhibited similar or higher PASS thresholds compared to the non-OA cohort for HOOS-Pain (OA: ≥80.6 versus non-OA: ≥77.5 points), HOOS-PS (OA: ≥83.6 versus non-OA: ≥83.6 points), and HOOS-JR (OA: ≥76.8 versus non-OA: ≥73.5 points). A similar percentage of patients achieved MCID and PASS thresholds regardless of preoperative diagnosis. CONCLUSIONS: While MCID and MDC thresholds for all HOOS subdomains were slightly higher among non-OA than OA patients, PASS thresholds for HOOS pain and JR were slightly higher in the OA group. The absolute magnitude of the difference in these thresholds may not be sufficient to cause major clinical differences. However, these subtle differences may have a significant impact when used as indicators of operative success in a population setting.

Predictive Modeling of Medical- and Orthopaedic-Related 90-Day Readmissions Following Primary Total Hip Arthroplasty.

BACKGROUND: The rate of unplanned hospital readmissions following total hip arthroplasty (THA) varies from 3 to 10%, representing a major economic burden. However, it is unknown if specific factors are associated with different types of complications (ie, medical or orthopaedic-related) that lead to readmissions. Therefore, this study aimed to: (1) determine the overall, medical-related, and orthopaedic-related 90-day readmission rate; and (2) develop a predictive model for risk factors affecting overall, medical-related, and orthopaedic-related 90-day readmissions following THA. METHODS: A prospective cohort of primary unilateral THAs performed at a large tertiary academic center in the United States from 2016 to 2020 was included (n = 8,893 patients) using a validated institutional data collection system. Orthopaedic-related readmissions were specific complications affecting the prosthesis, joint, and surgical wound. Medical readmissions were due to any other cause requiring medical management. Multivariable logistic regression models were used to investigate associations between prespecified risk factors and 90-day readmissions, as well as medical and orthopaedic-related readmissions independently. RESULTS: Overall, the rate of 90-day readmissions was 5.6%. Medical readmissions (4.2%) were found to be more prevalent than orthopaedic-related readmissions (1.4%). The area under the curve for the 90-day readmission model was 0.71 (95% confidence interval: 0.69 to 0.74). Factors significantly associated with medical-related readmissions were advanced age, Black race, education, Charlson Comorbidity Index, surgical approach, opioid overdose risk score, and nonhome discharge. In contrast, risk factors linked to orthopaedic-related readmissions encompassed body mass index, patient-reported outcome measure phenotype, nonosteoarthritis indication, opioid overdose risk, and nonhome discharge. CONCLUSIONS: Of the overall 90-day readmissions following primary THA, 75% were due to medical-related complications. Our successful predictive model for complication-specific 90-day readmissions highlights how different risk factors may disproportionately influence medical versus orthopaedic-related readmissions, suggesting that patient-specific, tailored preventive measures could reduce postoperative readmissions in the current value-based health care setting.

Aromatic Terpenes and Their Biosynthesis in Dendrobium, and Conjecture on the Botanical Perfumer Mechanism.

This review presents a systematic analysis of the studies on volatiles in Dendrobium. Among the various components, aromatic terpenes are a crucial component in the development of the aromatic characteristics of Dendrobium and other plants. Recent advancements in detection and sequencing technology have resulted in a considerable rise in research on the biosynthetic processes of aromatic terpenes in Dendrobium and other flowering plants. Nevertheless, the inquiry into the precise means by which plants regulate the proportion of diverse aromatic terpenes in their floral scent, thereby preserving their olfactory traits, requires further investigation. A conjecture on the botanical perfumer mechanism, which condensed the findings of earlier studies, was put forward to address this area of interest. Specific transcription factors likely govern the coordinated expression of multiple key terpene synthase (TPS) genes during the flowering stage of plants, thereby regulating the proportional biosynthesis of diverse aromatic terpenes and sustaining the distinctive aromatic properties of individual plants. This review serves as a significant theoretical reference for further investigations into aromatic volatile compounds in Dendrobium.

Transcutaneous Oximetry Does Not Reliably Predict Wound-healing Complications in Preoperatively Radiated Soft Tissue Sarcoma.

BACKGROUND: Surgical wound-healing complications after tumor resections in tissue that has been preoperatively radiated are a major clinical problem. Most studies have reported that complications occur in more than 30% of patients undergoing such resections in the lower extremity. There is currently no available method to predict which patients are likely to have a complication. Transcutaneous oximetry has been identified in preliminary studies as potentially useful, but the available evidence on its efficacy for this application thus far is inconclusive. QUESTIONS/PURPOSES: (1) Does transcutaneous oximetry measurement below 25 mmHg at any location in the surgical wound bed predict a wound-healing complication? (2) Does recovery (increase) in transcutaneous oxygen measurement during the rest period between the end of radiation and the time of surgery protect against wound-healing complications? METHODS: A prospective, multi-institution study was coordinated to measure skin oxygenation at three timepoints in patients undergoing surgery for a lower extremity soft tissue sarcoma after preoperative radiation. Between 2016 and 2020, the five participating centers treated 476 patients for lower extremity soft tissue sarcoma. Of those, we considered those with a first-time sarcoma treated with radiation before limb salvage surgery as potentially eligible. Based on that, 21% (98 of 476) were eligible; a further 12% (56 of 476) were excluded because they refused to participate or ultimately, they were treated with a flap, amputation, or skin graft. Another 1% (3 of 476) of patients were lost because of incomplete datasets or follow-up less than 6 months, leaving 8% (39 of 476) for analysis here. The mean patient age was 62 ± 14 years, 62% (24 of 39) of the group were men, and 18% (7 of 39) of patients smoked cigarettes; 87% (34 of 39) of tumors were intermediate/high grade, and the most common histologic subtype was undifferentiated pleomorphic sarcoma. In investigating complications, a cutoff of 25 mmHg was chosen based on a pilot investigation that identified this value. All patients were assessed for surgical wound-healing complications, which were defined as: those resulting in a return to the operating room, initiation of oral or IV antibiotics, intervention for seroma, or prolonged wound packing or dressing changes. To answer the first research question, we compared the proportion of patients who developed a wound-healing complication between those patients who had any reading below 25 mmHg (7 of 39) and those who did not (32 of 39). To answer the second question, we compared the group with stable or decreased skin oxygenation (22 of 37 patient measurements [two patients missed the immediate postoperative measurement]) to the group that had increased skin oxygen measurement (15 of 37 measurements) during the period between the end of radiation and the surgical procedure; again, the endpoint was the development of a wound-healing complication. This study was powered a priori to detect an unadjusted odds ratio for wound-healing complications as small as 0.71 for a five-unit (5 mmHg) increase in TcO 2 between the groups, with α set to 0.05, ß set to 0.2, and a sample size of 40 patients. RESULTS: We found no difference in the odds of a wound-healing complication between patients whose transcutaneous oxygen measurements were greater than or equal to 25 mmHg at all timepoints compared with those who had one or more readings below that threshold (odds ratio 0.27 [95% confidence interval (CI) 0.05 to 1.63]; p = 0.15). There was no difference in the odds of a wound-healing complication between patients who had recovery of skin oxygenation between radiation and surgery and those who did not (OR 0.63 [95% CI 0.37 to 5.12]; p = 0.64). CONCLUSION: Transcutaneous oximetry cannot be considered a reliable test in isolation to predict wound-healing complications. This may be a function of the fact that transcutaneous oximetry samples a relatively small portion of the landscape in which a wound-healing complication could potentially arise. In the absence of a reliable diagnostic test, clinicians must still use their best judgment regarding surgical timing and work to address modifiable risk factors to avoid complications. The unanswered question that remains is whether there is a skin perfusion or oxygenation issue at the root of these complications, which seems likely. Alternative approaches that can assess the wound more broadly and in real time, such as fluorescent probes, may be deserving of further investigation. LEVEL OF EVIDENCE: Level II, diagnostic study.

Preoperative Colonization With Staphylococcus Aureus in THA Is Associated With Increased Length of Stay.

BACKGROUND: Staphylococcus aureus is a common organism implicated in prosthetic joint infection after THA and TKA, prompting preoperative culturing and decolonization to reduce infection rates. It is unknown whether colonization is associated with other noninfectious outcomes of THA or TKA. QUESTIONS/PURPOSES: (1) What is the association between preoperative S. aureus colonization (methicillin-sensitive S. aureus [MSSA] and methicillin-resistant S. aureus [MRSA]) and the noninfectious outcomes (discharge destination, length of stay, Hip/Knee Disability and Osteoarthritis Outcome Score [HOOS/KOOS] pain score, HOOS/KOOS physical function score, 90-day readmission, and 1-year reoperation) of THA and TKA? (2) What factors are associated with colonization with S. aureus ? METHODS: Between July 2015 and March 2019, 8078 patients underwent primary THA in a single healthcare system, and 17% (1382) were excluded because they were not tested preoperatively for S. aureus nasal colonization, leaving 6696 patients in the THA cohort. Between June 2015 and March 2019, 9434 patients underwent primary TKA, and 12% (1123) were excluded because they were not tested for S. aureus colonization preoperatively, leaving 8311 patients in the TKA cohort. The goal of the institution's standardized care pathways is to test all THA and TKA patients preoperatively for S. aureus nasal colonization; the reason the excluded patients were not tested could not be determined. Per institutional protocols, all patients were given chlorhexidine gluconate skin wipes to use on the day before and the day of surgery, and patients with positive S. aureus cultures were instructed to use mupirocin nasal ointment twice daily for 3 to 5 days preoperatively. Adherence to these interventions was not tracked, and patients were not rescreened to test for S. aureus control. The minimum follow-up time for each outcome and the percentage of the cohort lost for each was: for discharge destination, until discharge (0 patients lost); for length of stay, until discharge (0.06% [4 of 6696] lost in the THA group and 0.01% [1 of 8311] lost in the TKA group); for HOOS/KOOS pain score, 1 year (26% [1734 of 6696] lost in the THA group and 24% [2000 of 8311] lost in the TKA group); for HOOS/KOOS physical function, 1 year (33% [2193 of 6696] lost in the THA group and 28% [2334 of 8311] lost in the TKA group); for 90-day readmission, 90 days (0.06% [4 of 6696] lost in the THA group and 0.01% [1 of 8311] lost in the TKA group); and for 1-year reoperation, 1 year (30% [1984 of 6696] lost in the THA group and 30% [2475 of 8311] lost in the TKA group). Logistic regression models were constructed to test for associations between MSSA or MRSA and nonhome discharge, length of stay greater than 1 day, improvement in the HOOS/KOOS pain subscale (≥ the minimum clinically important difference), HOOS/KOOS physical function short form (≥ minimum clinically important difference), 90-day readmission, and 1-year reoperation. We adjusted for patient-related and hospital-related factors, such as patient age and hospital site. Variable significance was assessed using the likelihood ratio test with a significance level of p < 0.05. To assess factors associated with S. aureus colonization, we constructed a logistic regression model with the same risk factors. RESULTS: Among the THA cohort, after controlling for potentially confounding variables such as patient age, smoking status, and BMI, S. aureus colonization was associated with length of stay greater than 1 day (MSSA: odds ratio 1.32 [95% CI 1.08 to 1.60]; MRSA: OR 1.88 [95% CI 1.24 to 2.85]; variable p < 0.001 by likelihood ratio test) but not the other outcomes of THA. Male sex (OR 1.26 [95% CI 1.09 to 1.45]; p = 0.001) and BMI (OR 1.02 for a one-unit increase over median BMI [95% CI 1.01 to 1.03]; p = 0.003) were patient-related factors associated with S. aureus colonization, whereas factors associated with a lower odds were older age (OR 0.99 [95% CI 0.98 to 0.99]; p < 0.001) and Black race compared with White race (OR 0.64 [95% CI 0.50 to 0.82]; p < 0.001). Among the TKA cohort, S. aureus colonization was associated with 90-day readmission (MSSA: OR 1.00 [95% CI 0.99 to 1.01]; MRSA: OR 1.01 [95% CI 1.00 to 1.01]; variable p = 0.007 by likelihood ratio test). Male sex (OR 1.19 [95% CI 1.05 to 1.34]; p = 0.006) was associated with S. aureus colonization, whereas factors associated with a lower odds of colonization were older age (OR 0.99 [95% CI 0.98 to 0.99]; p < 0.001), Veterans RAND-12 mental component score (OR 0.99 [95% CI 0.99 to 1.00]; p = 0.027), Black race compared with White race (OR 0.70 [95% CI 0.57 to 0.85]; p < 0.001), and being a former smoker (OR 0.86 [95% CI 0.75 to 0.97]; p = 0.016) or current smoker (OR 0.70 [95% CI 0.55 to 0.90]; p = 0.005) compared with those who never smoked. CONCLUSION: After controlling for the variables we explored, S. aureus colonization was associated with increased length of stay after THA and 90-day readmission after TKA, despite preoperative decolonization. Given that there is little causal biological link between colonization and these outcomes, the association is likely confounded but may be a proxy for undetermined social or biological factors, which may alert the surgeon to pay increased attention to outcomes in patients who test positive. Further study of the association of S. aureus colonization and increased length of stay after THA and readmission after TKA may be warranted to determine what the confounding variables are, which may be best accomplished using large cohorts or registry data. LEVEL OF EVIDENCE: Level III, therapeutic study.

The Impact of Surgeon Variability on Patient-Reported Outcomes in Total Hip Arthroplasty.

BACKGROUND: Patient-related and surgery-related factors have been shown to be drivers of outcomes after total hip arthroplasty (THA); however, the impact of intersurgeon variability is poorly understood. The purpose of this study is to assess the following: (1) overall effect of surgeon on 1-year patient-reported outcome measures (PROMs), length of stay (LOS), discharge disposition, and 90-day readmission following THA; and (2) variability in 1-year PROMs among surgeons. METHODS: A prospective cohort of 3,695 patients who underwent THA between 2016 and 2018 was included. Seventy-eight percent of patients completed 1-year follow-up. Thirty-one surgeons from a large healthcare system were included. Likelihood ratio tests analyzed the relationship among surgeon and 1-year Hip Disability and Osteoarthritis Outcome Score (HOOS)-Pain, HOOS-Physical Function Short-Form, HOOS-Joint Replacement, University of California, Los Angeles activity score, Patient Acceptable Symptom State, LOS, discharge disposition, and 90-day readmission. Mixed-effect proportional odds and logistic regression models were used to determine variable importance for each outcome. RESULTS: In total, 90.5% of patients responded positively to 1-year Patient Acceptable Symptom State. There was a significant association among surgeon and 1-year PROMs, LOS, discharge disposition (P < .001), and readmission (P = .002). For HOOS-Pain, Physical Function Short-Form, and Joint Replacement, surgeon (Akaike information criterion increase: 34.6, 18.7, 17.1, respectively) was a greater contributor to outcome than patient-level factors, including age, gender, and comorbidity. Differences in the highest and lowest median probability of achieving any given score on 1-year PROMs ranged from 11% to 18.5%. Variability was not explained by approach (P = .431) or case volume (correlation coefficient, ρ = 0.19). CONCLUSION: Surgeon-level variability appears to be a greater driver of 1-year PROMs than some patient-level characteristics. Incorporating surgeon as a variable is beneficial for model-fitting and important for increasing value in THA.

Staged Versus Simultaneous Bilateral Knee Arthroplasty: Does Minimal Cost Difference Justify Risks?

BACKGROUND: Simultaneous bilateral total knee arthroplasty (BTKA) is associated with a higher risk but can be perceived to afford faster improvement and mitigated costs versus staged BTKA. We aimed to explore (1) health care utilization, (2) surgical supply costs of simultaneous BTKA; and (3) 1-year improvement in patient-reported pain, function, and quality of life (QOL) versus staged BTKA. METHODS: A prospective cohort of 198 simultaneous and 625 staged BTKAs was obtained (2016-2020). Simultaneous BTKA cohort was propensity score-matched (1:2) to a similar group of staged patients (simultaneous = 198 versus staged = 396). Outcomes included length of stay, discharge disposition, 90-day readmission, 1-year reoperation, surgical episode supply cost, Knee Injury and Osteoarthritis Outcome Score (KOOS)-pain, KOOS-Physical Function Short Form, and KOOS-QOL. Rates of attaining minimal clinically important difference and Patient Acceptable Symptomatic State were calculated. RESULTS: Compared to both staged BTKA surgeries combined, simultaneous BTKA demonstrated shorter median net length of stay (2.00 [2.00, 3.00] days versus 2.00 [2.00, 4.00] days; P < .001) but higher rates of nonhome discharge (n = 56 [28.3%] versus n = 32 [4.04%]; P < .001), 90-day readmission (n = 20 [10.1%] versus n = 48 [6.06%]; P = .047) and similar reoperation rates (P = .44). Simultaneous BTKA afforded slight reduction in net surgical cost compared to that of both staged BTKAs combined ($643; P = .028). There was no significant difference in 1-year improvement and minimal clinically important difference attainment rates with simultaneous versus staged BTKA for KOOS-pain (P = .137 and P = .99), KOOS-QOL (P = .095 and P = .81), or KOOS-Physical Function Short Form (P = .75 and P = .49, respectively) or Patient Acceptable Symptomatic State (P = .12). CONCLUSION: Staged BTKA is associated with similar 1-year pain, function, and QOL at a better safety profile and minimal surgical supply cost increase compared to simultaneous BTKA.

Expression and cellular localization of insulin-like growth factor 3 in gonads of the seasonal breeding teleost silver pomfret (Pampus argenteus).

Insulin-like growth factor 3 plays an important role in gonad development in teleost fish. Previous studies found that igf3 was specifically expressed in gonads of silver pomfret (Pampus argenteus). Unlike in other fish, IGF3 is a membrane protein in silver pomfret, and its specific role in gonads is unclear. Herein, we explored the importance of IGF3 in oogenesis and spermatogenesis in silver pomfret by analyzing gene expression and cellular localization. During follicular development, igf3 was detected in ovaries at both mRNA and protein levels during the critical stages of vitellogenesis (IV-VI). Localization analysis detected igf3 mRNA and protein in somatic cells, including theca and granulosa cells around oocytes. Similar to cathepsin L and cathepsin K, igf3 was consistently expressed in ovaries during vitellogenesis, suggesting that it might play a key role in vitellogenesis of oocytes. During spermatogenesis, igf3 mRNA and protein levels were high in stages II, IV, and V, similar to sycp3 and dmc1, and the highest igf3 mRNA and protein levels were reached in stage VI. Furthermore, igf3 mRNA and protein were detected in spermatogonia, spermatocytes, spermatids, and surrounding Sertoli cells, but not in spermatozoon, indicating that IGF3 might be involved in differentiation and meiosis of spermatogonia.

Mechanistic Insight into Copper-Mediated Trifluoromethylation of Aryl Halides: The Role of CuI.

The synthesis, characterization, and reactivity of key intermediates [Cu(CF3)(X)]-Q+ (X = CF3 or I, Q = PPh4) in copper-mediated trifluoromethylation of aryl halides were studied. Qualitative and quantitative studies showed [Cu(CF3)2]-Q+ and [Cu(CF3)(I)]-Q+ were not highly reactive. Instead, a much more reactive species, ligandless [CuCF3] or DMF-ligated species [(DMF)CuCF3], was generated in the presence of excess CuI. On the basis of these results, a general mechanistic map for CuI-promoted trifluoromethylation of aryl halides was proposed. Furthermore, on the basis of this mechanistic understanding, a HOAc-promoted protocol for trifluoromethylation of aryl halides with [Ph4P]+[Cu(CF3)2]- was developed.

Dopamine D1 receptor alleviates doxorubicin-induced cardiac injury by inhibiting NLRP3 inflammasome.

Doxorubicin (DOX) is a broad-spectrum antineoplastic drug; however, its serious cardiotoxic side effects in inflammatory responses limit its use in clinical applications. Dopamine D1 receptor (DRD1), a G protein-coupled receptor, is crucial for the development and function of the nervous system; additionally, it also play a role in immune regulation. However, the specific role of DRD1 in DOX-induced cardiac inflammation has not yet been clarified. Here, we discovered that DRD1 expression was induced by DOX treatment in H9C2 cardiomyocytes. DRD1 activation by A-68930, a DRD1-specific agonist, decreased DOX-induced nucleotide-binding domain-like receptor protein 3 (NLRP3) expression, caspase-1 activation, and IL-1ß maturation in H9C2 cells. Expression of the cytokines IL-1ß and IL-18 in the supernatants was also inhibited by A-68930 treatment. DRD1 knockdown, using siRNA, abolished the effects of A-68930 on the DOX-induced NLRP3 inflammasome. Furthermore, we found that DRD1 signaling downregulated the NLRP3 inflammasome in H9C2 cells through cyclic adenosine monophosphate (cAMP). Moreover, application of A-68930 to activate DRD1 reduced cardiac injury and fibrosis in a DOX-treated mouse model by suppressing the NLRP3 inflammasome in the heart. These findings indicate that DRD1 signaling may protect against DOX-induced cardiac injury by inhibiting the NLRP3 inflammasome-mediated inflammation.

Safety of recombinant zoster vaccine: a retrospective study of 622 rheumatology patients.

OBJECTIVES: To provide insight into the safety of recombinant zoster vaccine (RZV) in patients with immune-mediated inflammatory diseases (IMID). METHODS: Patients who received RZV in a single-centre rheumatology department were retrospectively included. An IMID flare was defined as (i) a documentation of flare in the office notes or patient portal communication or (ii) new prednisone prescription, in the 12 weeks after each dose. RESULTS: Six-hundred and twenty-two patients were included (67% female, median age 67 years), 8.5% of them experienced adverse events (AEs) and herpes zoster (HZ) incidence was 0.6% after median follow-up of 36 weeks. Of 359 IMID patients: 88 had RA (25%), 50 vasculitis (14%) and 29 PMR (8%). At vaccination, 35% were on glucocorticoids (GC). Fifty-nine patients (16%) experienced a flare, 18 flares occurred in temporal relation to a treatment change (31%). RA patients had the highest flare rate (n = 21, 24%), 25% of patients who flared required adjustment of immunosuppression. In a multivariate analysis, use of GC at time of vaccination was associated with flare after vaccination [odds ratio (OR) 2.31 (1.3-4.1), P =0.004]. A time-to-flare survival analysis (Cox-model) showed that GC was a significant predictor of IMID flare after first RZV dose [hazard ratio (HR) 2.4 (1.3-4.5), P =0.0039] and that a flare after the first dose was associated with flaring after the second RZV dose [HR 3.9 (1.7-9), P =0.0015]. CONCLUSION: RZV administration in patients with IMIDs was generally well-tolerated, though mild flares were not uncommon in the first 12 weeks after vaccination. These data may provide useful information for patient education when considering RZV administration.

Three-dimensional computed tomography analysis of pathologic correction in total shoulder arthroplasty based on severity of preoperative pathology.

BACKGROUND: The purpose of this study was to quantify correction of glenoid deformity and humeral head alignment in anatomic total shoulder arthroplasty as a function of preoperative pathology (modified Walch classification) and glenoid implant type in a clinical cohort using 3-dimensional computed tomography (CT) analysis. METHODS: Patients undergoing anatomic total shoulder arthroplasty with a standard glenoid (SG) (n = 110) or posteriorly stepped augmented glenoid (AG) (n = 62) component were evaluated with a preoperative CT scan and a postoperative CT scan within 3 months of surgery. Glenoid version, inclination, and medial-lateral (ML) joint line position, as well as humeral head alignment, were assessed on both CT scans, with preoperative-to-postoperative changes analyzed relative to pathology and premorbid anatomy based on the modified Walch classification and glenoid implant type. RESULTS: On average, correction to the premorbid ML joint line position was significantly less in type A2 glenoids than in type A1 glenoids (-2.3 ± 2.1 mm vs. 1.1 ± 0.9 mm, P < .001). Correction to premorbid version was not different between type B2 glenoids with AG components and type A1 glenoids with SG components (-1.7° ± 6.6° vs. -1.0° ± 4.0°, P = .57), and the premorbid ML joint line position was restored on average in both groups (0.3 ± 1.6 mm vs. 1.1 ± 0.9 mm, P = .006). Correction to premorbid version was not different between type B3 glenoids with AG components and type A1 glenoids with SG components (-0.6° ± 5.1° vs. -1.0° ± 4.0°, P = .72), but correction relative to the premorbid ML joint line position was significantly less in type B3 glenoids with AG components than in type A1 glenoids with SG components (-2.2 ± 2.1 mm vs. 1.1 ± 0.9 mm, P < .001). Postoperative humeral glenoid alignment was not different in any group comparisons. DISCUSSION: In cases with posterior glenoid bone loss and retroversion (type B2 or B3 glenoids), an AG component can better correct retroversion and the glenoid ML joint line position compared with an SG component, with correction to premorbid version comparable to a type A1 glenoid with an SG component. However, restoration of the premorbid ML joint line position may not always be possible with SG or AG components in cases with more advanced central glenoid bone loss (type A2 or B3 glenoids). Further follow-up is needed to determine the clinical consequences of these findings.

Inter-rater agreement of rotator cuff tendon and muscle magnetic resonance imaging parameters evaluated preoperatively and during the first postoperative year following rotator cuff repair.

BACKGROUND: Magnetic resonance imaging (MRI) is standard of care for rotator cuff evaluation, with clinical interpretation usually limited to qualitative judgments. The reliability of MRI-based measurements and scoring systems has been evaluated only preoperatively or ≥6 months following rotator cuff repair, when repairs are in the later stages of healing. This study describes the MRI assessments and inter-rater agreement of various rotator cuff tendon and muscle parameters evaluated preoperatively and 4 times during the first postoperative year. METHODS: Two musculoskeletal radiologists independently assessed MRI scans of 42 patients preoperatively and 3, 12, 26, and 52 weeks after rotator cuff repair. Using standardized reading rules, readers assessed tendon integrity (5-point Sugaya classification), tear dimensions, muscle fat (5-point Goutallier classification) and atrophy (4-point Warner classification), muscle cross-sectional areas, and myotendinous junction distance. Raw exact agreement proportions, κ statistics, and correlation coefficients were used to quantify inter-rater agreement. RESULTS: Readers showed moderate to substantial above-chance agreement in scoring rotator cuff tendon integrity and supraspinatus muscle atrophy and good to excellent agreement on tear dimensions and muscle cross-sectional areas but only fair to moderate agreement for fatty infiltration and myotendinous junction distance. Only fatty infiltration grades evidenced observer bias. Inter-rater agreement did not appear time dependent. CONCLUSION: By use of defined reading rules in a research setting, MRI evaluations of rotator cuff tendon integrity, tear dimensions, muscle atrophy, and cross-sectional areas have reasonable reliability at all time points in the first postoperative year. However, the presence of clinically significant disagreements, even in such favorable circumstances, indicates the need for improved imaging tools for precise rotator cuff evaluation.

Reliability of the modified Walch classification for advanced glenohumeral osteoarthritis using 3-dimensional computed tomography analysis: a study of the ASES B2 Glenoid Multicenter Research Group.

BACKGROUND: Variations in glenoid morphology affect surgical treatment and outcome of advanced glenohumeral osteoarthritis (OA). The purpose of this study was to assess the inter- and intraobserver reliability of the modified Walch classification using 3-dimensional (3D) computed tomography (CT) imaging in a multicenter research group. METHODS: Deidentified preoperative CTs of patients with primary glenohumeral OA undergoing anatomic or reverse total shoulder arthroplasty (TSA) were reviewed with 3D imaging software by 23 experienced shoulder surgeons across 19 institutions. CTs were separated into 2 groups for review: group 1 (96 cases involving all modified Walch classification categories evaluated by 12 readers) and group 2 (98 cases involving posterior glenoid deformity categories [B2, B3, C1, C2] evaluated by 11 readers other than the first 12). Each case group was reviewed by the same set of readers 4 different times (with and without the glenoid vault model present), blindly and in random order. Inter- and intraobserver reliabilities were calculated to assess agreement (slight, fair, moderate, substantial, almost perfect) within groups and by modified Walch classification categories. RESULTS: Interobserver reliability showed fair to moderate agreement for both groups. Group 1 had a kappa of 0.43 (95% confidence interval [CI]: 0.38, 0.48) with the glenoid vault model absent and 0.41 (95% CI: 0.37, 0.46) with it present. Group 2 had a kappa of 0.38 (95% CI: 0.33, 0.43) with the glenoid vault model absent and 0.37 (95% CI: 0.32, 0.43) with it present. Intraobserver reliability showed substantial agreement for group 1 with (0.63, range 0.47-0.71) and without (0.61, range 0.52-0.69) the glenoid vault model present. For group 2, intraobserver reliability showed moderate agreement with the glenoid vault model absent (0.51, range 0.30-0.72), which improved to substantial agreement with the glenoid vault model present (0.61, range 0.34-0.87). DISCUSSION: Inter- and intraobserver reliability of the modified Walch classification were fair to moderate and moderate to substantial, respectively, using standardized 3D CT imaging analysis in a large multicenter study. The findings potentially suggest that cases with a spectrum of posterior glenoid bone loss and/or dysplasia can be harder to distinguish by modified Walch type because of a lack of defined thresholds, and the glenoid vault model may be beneficial in determining Walch type in certain scenarios. The ability to reproducibly separate patients into groups based on preoperative pathology, including Walch type, is important for future studies to accurately evaluate postoperative outcomes in TSA patient cohorts.

Physical Exercise and Longitudinal Trajectories in Alzheimer Disease Biomarkers and Cognitive Functioning.

INTRODUCTION: Associations of physical exercise with Alzheimer disease (AD) biomarkers and cognitive functioning have been observed cross-sectionally. However, the effects of exercise on longitudinal change in AD biomarkers have not been thoroughly investigated. The current study examined whether individuals with higher baseline exercise exhibited less longitudinal change in AD biomarkers and cognitive functioning, and whether APOE and/or brain-derived neurotrophic factor (BDNF) genotypes moderated the effects of exercise on longitudinal changes. METHODS: Clinically normal individuals completed a questionnaire on physical exercise over the prior 10-year period at baseline. Ninety-five individuals had serial cerebrospinal fluid samples collected to examine Aß42, ptau181 and total tau; 181 individuals underwent multiple assessments of amyloid positron emission tomography imaging with Pittsburgh Compound-B; 327 individuals underwent multiple cognitive assessments, including measures of episodic memory, executive functions, verbal fluency, and processing speed. RESULTS: Greater exercise was associated with less steep decline in processing speed. Baseline exercise did not robustly impact longitudinal change for any other outcomes. Neither APOE nor BDNF genotype robustly moderated the effect of exercise on trajectories of AD biomarkers or cognitive decline. INTERPRETATION: Results suggest that self-reported physical exercise may be limited as a moderator of changes in AD biomarkers.

CSCD: a database for cancer-specific circular RNAs.

Circular RNA (circRNA) is a large group of RNA family extensively existed in cells and tissues. High-throughput sequencing provides a way to view circRNAs across different samples, especially in various diseases. However, there is still no comprehensive database for exploring the cancer-specific circRNAs. We collected 228 total RNA or polyA(-) RNA-seq samples from both cancer and normal cell lines, and identified 272 152 cancer-specific circRNAs. A total of 950 962 circRNAs were identified in normal samples only, and 170 909 circRNAs were identified in both tumor and normal samples, which could be further used as non-tumor background. We constructed a cancer-specific circRNA database (CSCD, http://gb.whu.edu.cn/CSCD). To understand the functional effects of circRNAs, we predicted the microRNA response element sites and RNA binding protein sites for each circRNA. We further predicted potential open reading frames to highlight translatable circRNAs. To understand the association between the linear splicing and the back-splicing, we also predicted the splicing events in linear transcripts of each circRNA. As the first comprehensive cancer-specific circRNA database, we believe CSCD could significantly contribute to the research for the function and regulation of cancer-associated circRNAs.