Advancements in Subchondral Bone Biomechanics: Insights from Computed Tomography and Micro-Computed Tomography Imaging in Equine Models.

PURPOSE OF REVIEW: This review synthesizes recent advancements in understanding subchondral bone (SCB) biomechanics using computed tomography (CT) and micro-computed tomography (micro-CT) imaging in large animal models, particularly horses. RECENT FINDINGS: Recent studies highlight the complexity of SCB biomechanics, revealing variability in density, microstructure, and biomechanical properties across the depth of SCB from the joint surface, as well as at different joint locations. Early SCB abnormalities have been identified as predictive markers for both osteoarthritis (OA) and stress fractures. The development of standing CT systems has improved the practicality and accuracy of live animal imaging, aiding early diagnosis of SCB pathologies. While imaging advancements have enhanced our understanding of SCB, further research is required to elucidate the underlying mechanisms of joint disease and articular surface failure. Combining imaging with mechanical testing, computational modelling, and artificial intelligence (AI) promises earlier detection and better management of joint disease. Future research should refine these modalities and integrate them into clinical practice to enhance joint health outcomes in veterinary and human medicine.

The variability of MCID, SCB, PASS, and MOI thresholds for PROMs in the reverse total shoulder arthroplasty literature: a systematic review.

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) is a common procedure utilized to address degenerative pathologies of the glenohumeral joint and rotator cuff. Increased reliance on patient-reported outcome measures (PROMs) have placed emphasis on the utilization of the minimum clinically important difference (MCID), substantial clinical benefit (SCB), patient acceptable symptom state (PASS), and maximal outcome improvement (MOI) thresholds to assess the clinical efficacy of RTSA. In this study, we systematically reviewed the MCID, SCB, PASS, and MOI thresholds reported for PROMs following RTSA. METHODS: PubMed, Embase, MEDLINE, Cochrane Library, and Google Scholar were queried for articles from January 1, 2000 to August 31, 2023 reporting MCID, SCB, PASS, or MOI values for PROMs following RTSA. Patient demographic data, study characteristics, MCID/SCB/PASS/MOI thresholds, and threshold calculation methods were extracted. RESULTS: One hundred and forty-one articles were screened with 39 ultimately included, comprising 11,984 total patients that underwent RTSA. 34 (87%) studies reported MCID thresholds, 20 (51%) reported SCB, 5 (13%) reported PASS, and 2 (5%) reported MOI. 25/39 (64%) studies referenced a previous study when reporting MCID, SCB, PASS, or MOI values, 11 (28%) used an anchor-based method to calculate threshold values, 1 (3%) used a distribution-based method, and 2 (5%) used both anchor and distribution methods. There were 19 newly calculated MCID (11), SCB (5), PASS (1), and MOI (2) thresholds. For 5 of the 6 most utilized PROMs (ASES, SST, Constant, UCLA, and SPADI), the range of reported MCID values exceeded 50% of the most common threshold. For 3 of 6, the range of SCB values exceeded 25% of the most common threshold. CONCLUSION: There is substantial variability in the MCID and SCB threshold values reported in the RTSA literature. Standardizing the methodologic calculation and utilization of MCID, SCB, PASS, and MOI thresholds for RTSA may allow for improved assessment of PROMs.

Stratification of the minimal clinically important difference, substantial clinical benefit, and patient acceptable symptomatic state after total shoulder arthroplasty by implant type, preoperative diagnosis, and sex.

BACKGROUND: Clinical significance, as opposed to statistical significance, has increasingly been utilized to evaluate outcomes after total shoulder arthroplasty (TSA). The purpose of this study was to identify thresholds of the minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptomatic state (PASS) for TSA outcome metrics and determine if these thresholds are influenced by prosthesis type (anatomic or reverse TSA), sex, or preoperative diagnosis. METHODS: A prospectively collected international multicenter database inclusive of 38 surgeons was queried for patients receiving a primary aTSA or rTSA between 2003 and 2021. Prospectively, outcome metrics including ASES, shoulder function score (SFS), SST, UCLA, Constant, VAS Pain, shoulder arthroplasty smart (SAS) score, forward flexion, abduction, external rotation, and internal rotation was recorded preoperatively and at each follow-up. A patient satisfaction question was administered at each follow-up. Anchor-based MCID, SCB, and PASS were calculated as defined previously overall and according to implant type, preoperative diagnosis, and sex. The percentage of patients achieving thresholds was also quantified. RESULTS: A total of 5851 total shoulder arthroplasties (TSAs) including aTSA (n = 2236) and rTSA (n = 3615) were included in the study cohort. The following were identified as MCID thresholds for the overall (aTSA + rTSA irrespective of diagnosis or sex) cohort: VAS Pain (-1.5), SFS (1.2), SST (2.1), Constant (7.2), ASES (13.9), UCLA (8.2), SPADI (-21.5), and SAS (7.3), Abduction (13°), Forward elevation (16°), External rotation (4°), Internal rotation score (0.2). SCB thresholds for the overall cohort were: VAS Pain (-3.3), SFS (2.9), SST 3.8), Constant (18.9), ASES (33.1), UCLA (12.3), SPADI (-44.7), and SAS (18.2), Abduction (30°), Forward elevation (31°), External rotation (12°), Internal rotation score (0.9). PASS thresholds for the overall cohort were: VAS Pain (0.8), SFS (7.3), SST (9.2), Constant (64.2), ASES (79.5), UCLA (29.5), SPADI (24.7), and SAS (72.5), Abduction (104°), Forward elevation (130°), External rotation (30°), Internal rotation score (3.2). MCID, SCB, and PASS thresholds varied depending on preoperative diagnosis and sex. CONCLUSION: MCID, SCB, and PASS thresholds vary depending on implant type, preoperative diagnosis, and sex. A comprehensive understanding of these differences as well as identification of clinically relevant thresholds for legacy and novel metrics is essential to assist surgeons in evaluating their patient's outcomes, interpreting the literature, and counseling their patients preoperatively regarding expectations for improvement. Given that PASS thresholds are fragile and vary greatly depending on cohort variability, caution should be exercised in conflating them across different studies.

Clinically significant outcome thresholds and rates of achievement by shoulder arthroplasty type and preoperative diagnosis.

BACKGROUND: Clinically significant outcome (CSO) benchmarks have been previously established for shoulder arthroplasty by assimilating preoperative diagnoses and arthroplasty types. The purpose of this study was to establish unique CSO thresholds and compare the time-to-achievement of these for reverse shoulder arthroplasty (RSA) for osteoarthritis (GHOA), RSA for rotator cuff arthropathy (RCA), and total shoulder arthroplasty (TSA) for GHOA. MATERIALS AND METHODS: Consecutive patients who underwent elective RSA for GHOA, TSA for GHOA, or RSA for RCA between February 2015 and May 2020, with 2-year minimum follow-up, were retrospectively identified from a prospectively maintained single surgeon registry. The American Shoulder and Elbow Surgeons (ASES) score was administered preoperatively and postoperatively at 2-week, 6-week, 3-month, 6-month, 1-year, and 2-year timepoints. Satisfaction and subjective overall improvement anchor questionnaires were administered at the time of final follow-up. Distribution-based methods were used to calculate the Minimal Clinically Important Difference (MCID), and anchor-based methods were used to calculate the Substantial Clinical Benefit (SCB) and the Patient Acceptable Symptom State (PASS) for each patient group. Median time to achievement, individual incidence of achievement at each time point, and cumulative incidence of achievement calculated using Kaplan-Meier survival curve analysis with interval censoring were compared between groups for each CSO. Cox-regression analyses were also performed to determine which patient factors were significantly associated with early or delayed achievement of CSOs. RESULTS: There were 471 patients eligible for study analysis: 276 RSA for GHOA, 107 TSA for GHOA, and 88 RSA for RCA. The calculated MCID, SCB, and PASS scores differed for each group. There were no significant differences in median time to achievement of any CSO between groups. Log-rank testing revealed that cumulative achievements significantly differed between groups for MCID (P = .014) but not for SCB (P = .053) or PASS (P = .620). On cox regression analysis, TSA patients had earlier achievement of SCB, whereas TSA and RSA for GHOA patients had earlier achievement of MCID. At 2-years, a significantly higher percentage of RSA for GHOA patients achieved MCID and SCB compared to RSA for RCA (MCID:100%, 95.5%, P = .003, SCB:94.6%, 86.4%, P = .036). CONCLUSION: Calculated CSO thresholds differ according to preoperative diagnosis and shoulder arthroplasty type. Patients undergoing TSA and RSA for GHOA achieve CSOs earlier than RSA for RCA patients, and a significantly higher percentage of RSA for GHOA patients achieve CSOs by 2 years compared to RSA for RCA patients.

Superior Boosting of Neutralizing Titers Against Omicron SARS-CoV-2 Variants by Heterologous SCB-2019 Vaccine vs a Homologous Booster in CoronaVac-Primed Adults.

BACKGROUND: We compared homologous and heterologous boosting in adults in the Philippines primed with 2 or 3 doses of CoronaVac, with recombinant protein vaccine, SCB-2019. METHODS: CoronaVac-immunized adults (18-72 years) received a homologous or heterologous full or half dose SCB-2019 booster. We assessed all neutralizing antibody (NAb) responses against prototype SARS-CoV-2 after 15 days and NAb against SARS-CoV-2 Delta and Omicron variants in subsets (30‒50 per arm). Participants recorded adverse events. RESULTS: In 2-dose CoronaVac-primed adults prototype NAb geometric mean titers (GMT) were 203 IU/mL (95% confidence interval [CI], 182-227) and 939 IU/mL (95% CI, 841-1049) after CoronaVac and SCB-2019 boosters; the GMT ratio (4.63; 95% CI, 3.95-5.41) met predefined noninferiority and post-hoc superiority criteria. After 3-dose CoronaVac-priming prototype NAb GMTs were 279 IU/mL (95% CI, 240-325), 1044 IU/mL (95% CI, 898-1213), and 668 IU/mL (95% CI, 520-829) following CoronaVac, full and half-dose SCB-2019 boosters, respectively. NAb GMT ratios against Delta and Omicron comparing SCB-2019 with CoronaVac were all greater than 2. Mild to moderate reactogenicity was evenly balanced between groups. No vaccine-related serious adverse events were reported. CONCLUSIONS: Full or half dose SCB-2019 boosters were well tolerated with superior immunogenicity than homologous CoronaVac, particularly against newly emerged variants. Clinical Trials Registration. NCT05188677.

Impact of Vaccination With the SCB-2019 Coronavirus Disease 2019 Vaccine on Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Household Contact Study in the Philippines.

BACKGROUND: An exploratory household transmission study was nested in SPECTRA, the phase 2/3 efficacy study of the adjuvanted recombinant protein-based COVID-19 vaccine SCB-2019. We compared the occurrence of confirmed COVID-19 infections between households and household contacts of infected SPECTRA placebo or SCB-2019 recipients. METHODS: SPECTRA participants at 8 study sites in the Philippines who developed real-time reverse transcriptase-polymerase chain reaction (rRT-PCR)-confirmed COVID-19 were contacted by a study team blinded to assignment of index cases to vaccine or placebo groups to enroll in this household transmission study. Enrolled households and household contacts were monitored for 3 weeks using rRT-PCR and anti-SARS-CoV-2 N-antigen IgG/IgM testing to detect new COVID-19 infections. RESULTS: One hundred fifty-four eligible COVID-19 index cases (51 vaccinees, 103 placebo) were included. The secondary attack rate per household for symptomatic COVID-19 infection was 0.76% (90% CI: .15-3.90%) if the index case was an SCB-2019 vaccinee compared with 5.88% (90% CI: 3.20-10.8%) for placebo index cases, a relative risk reduction (RRR) of 79% (90% CI: -28% to 97%). The RRR of symptomatic COVID-19 per household member was similar: 84% (90% CI: 28-97%). The impact on attack rates in household members if index cases were symptomatic (n = 130; RRR = 80%; 90% CI: 7-96%) or asymptomatic (n = 24; RRR = 100%; 90% CI: -76% to 100%) was measurable but the low numbers undermine the clinical significance. CONCLUSIONS: In this prospective household contact study vaccination with SCB-2019 reduced SARS-CoV-2 transmission compared with placebo in households and in household members independently of whether or not index cases were symptomatic.

Revealing Inter-regional Environmental Inequities Hidden in China's Energy Transition.

Energy transition is an important way to control air pollution, but it may conflict with the economic goal of alleviating regional inequality due to its inherently different cost burdens. As one of the effective measures of energy transition, this paper takes small coal-fired boiler (SCB) upgrading as an example to explore the regional mismatch between upgrading costs and health benefits. Here, we construct a boiler-level inventory of SCB upgrades for the North China Plain (NCP) during 2013-2017 and propose an integrated modeling framework to quantify the spatial contribution of economic costs and health benefits associated with SCB upgrading. We find that although the total health benefits could offset the total costs for the entire region, the developed municipalities (Beijing and Tianjin) are likely to gain more health benefits from less-developed neighboring provinces at lower costs. These developed municipalities contribute only 14% to the total health benefits but gain 21% of the benefits within their territories, 56% of which come from neighboring provinces. Their benefits are approximately 5.6 times their costs, which is much higher than the 1.5 benefit-cost ratio in neighboring provinces. Our findings may be useful in shaping more equitable and sound environmental policies in China or other regions of the world with serious coal-related air pollution.

Minimal clinically important difference (MCID) and substantial clinical benefit (SCB) of upper extremity PROMIS scores following arthroscopic rotator cuff repairs.

PURPOSE: To calculate and determine what factors are associated with achieving the Minimal Clinically Important Difference (MCID) and the Substantial Clinical Benefit (SCB) of Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity Computer Adaptive Testing v2.0 (UE), Pain Interference (P-Interference), and Pain Intensity (P-Intensity) in patients undergoing arthroscopic rotator cuff repair (aRCR). METHODS: The change in PROMIS scores representing the optimal cutoff for a ROC curve with an area under the curve analysis was used to calculate the anchor-based MCID and SCB. To assess the responsiveness of each PROM, effect sizes and standardized response means (SRM) were calculated. To identify factors associated with attaining the MCID and SCB, univariate and multivariate logistic regression analyses were performed. RESULTS: A total of 323 patients with an average age of 59.9 ± 9.5 were enrolled in this study, of which, 187/323 [57.9%] were male and 136/323 [42.1%] were female. The anchor-based MCID for PROMIS UE, P-Interference, and P-Intensity was: 9.0, 7.5, and 11.2, respectively. The respective SCB was 10.9, 9.3, and 12.7. Effect size and SRM were: PROMIS UE (1.4, 1.3), P-Interference (1.8, 1.5), and P-Intensity (2.3, 2.0). Lower preoperative P-Intensity scores (p = 0.02), dominant arm involvement (p = 0.03), and concomitant biceps tenodesis (p = 0.03) were associated with patients achieving the SCB for PROMIS UE. CONCLUSION: A large responsiveness for each of the PROMIS instruments due to the majority of patients reporting great improvement after aRCR and a small standard deviation across all outcome measures was shown in our study. Lower preoperative P-Intensity scores and concomitant biceps tenodesis were associated with higher odds of achieving the SCB for PROMIS UE. The knowledge of MCID and SCB values for PROMIS instruments will allow the surgeon to determine whether the improvements in the PROMIS scores after aRCR are clinically meaningful. LEVEL OF EVIDENCE: Level III.

Quantifying success after first revision reverse total shoulder arthroplasty: the minimal clinically important difference, substantial clinical benefit, and patient acceptable symptomatic state.

BACKGROUND: When patients require revision of primary shoulder arthroplasty, revision reverse total shoulder arthroplasty (rTSA) is most commonly performed. However, defining clinically important improvement in these patients is challenging because benchmarks have not been previously defined. Our purpose was to define the minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptomatic state (PASS) for outcome scores and range of motion (ROM) after revision rTSA and to quantify the proportion of patients achieving clinically relevant success. METHODS: This retrospective cohort study used a prospectively collected single-institution database of patients undergoing first revision rTSA between August 2015 and December 2019. Patients with a diagnosis of periprosthetic fracture or infection were excluded. Outcomes scores included the ASES, raw and normalized Constant, SPADI, SST, and University of California, Los Angeles (UCLA) scores. ROM measures included abduction, forward elevation (FE), external rotation (ER), and internal rotation (IR) score. Anchor-based and distribution-based methods were used to calculate the MCID, SCB, and PASS. The proportions of patients achieving each threshold were assessed. RESULTS: Ninety-three revision rTSAs with minimum 2-year follow-up were evaluated. Mean age was 67 years, 56% were female, and average follow-up was 54 months. Revision rTSA was performed most commonly for failed anatomic TSA (n = 47), followed by hemiarthroplasty (n = 21), rTSA (n = 15), and resurfacing (n = 10). The indication for revision rTSA was most commonly glenoid loosening (n = 24), followed by rotator cuff failure (n = 23), subluxation and unexplained pain (n = 11 for both). The anchor-based MCID thresholds (% of patients achieving) were as follows: ASES, 20.1 (42%); normalized Constant, 12.6 (80%); UCLA, 10.2 (54%); SST, 0.9 (78%); SPADI, -18.4 (58%); abduction, 13° (83%); FE, 18° (82%); ER, 4° (49%); and IR, 0.8 (34%). The SCB thresholds (% of patients achieving) were as follows: ASES, 34.1 (25%); normalized Constant, 26.6 (43%); UCLA, 14.1 (28%); SST, 3.9 (48%); SPADI, -36.4 (33%); abduction, 20° (77%); FE, 28° (71%); ER, 15° (15%); and IR, 1.0 (29%). The PASS thresholds (% of patients achieving) were as follows: ASES, 63.5 (53%); normalized Constant, 59.1 (61%); UCLA, 25.4 (48%); SST, 7.0 (55%); SPADI, 42.4 (59%); abduction, 98° (61%); FE, 110° (56%); ER, 19° (73%); and IR, 3.3 (59%). CONCLUSIONS: This study establishes thresholds for the MCID, SCB, and PASS at minimum 2-years after revision rTSA, providing physicians an evidence-based method to counsel patients and assess patient outcomes postoperatively.

Electronic Structure and Chemical Bonding of the First-, Second-, and Third-Row-Transition-Metal Monoborides: The Formation of Quadruple Bonds in RhB, RuB, and TcB.

Boron presents an important role in chemistry, biology, and materials science. Diatomic transition-metal borides (MBs) are the building blocks of many complexes and materials, and they present unique electronic structures with interesting and peculiar properties and a variety of bonding schemes which are analyzed here. In the first part of this paper, we present a review on the available experimental and theoretical studies on the first-row-transition-metal borides, i.e., ScB, TiB, VB, CrB, MnB, FeB, CoB, NiB, CuB, and ZnB; the second-row-transition-metal borides, i.e., YB, ZrB, NbB, MoB, TcB, RuB, RhB, PdB, AgB, and CdB; and the third-row-transition-metal borides, i.e., LaB, HfB, TaB, WB, ReB, OsB, IrB, PtB, AuB, and HgB. Consequently, in the second part, the second- and third-row MBs are studied via DFT calculations using the B3LYP, TPSSh, and MN15 functionals and, in some cases, via multi-reference methods, MRCISD+Q, in conjunction with the aug-cc-pVQZ-PPM/aug-cc-pVQZB basis sets. Specifically, bond distances, dissociation energies, frequencies, dipole moments, and natural NPA charges are reported. Comparisons between MB molecules along the three rows are presented, and their differences and similarities are analyzed. The bonding of the diatomic borides is also described; it is found that, apart from RhB(X1Σ+), which was just recently found to form quadruple bonds, RuB(X2Δ) and TcB(X3Σ-) also form quadruple σ2σ2π2π2 bonds in their X states. Moreover, to fill the gap existing in the current literature, here, we calculate the TcB molecule.

Significant improvement after hip arthroscopy for femoroacetabular impingement in women.

PURPOSE: This study was designed to evaluate outcomes in women after hip arthroscopy (HA) for femoroacetabular impingement syndrome (FAIS) and compare these results with men. METHODS: Retrospective study of a prospective database of patients undergoing hip arthroscopy between 2015 and 2018. Inclusion criteria were patients between 18 and 50 years of age, diagnosis of FAIS, complete clinical patient-reported outcomes (PROs), radiographic measurements, and underwent at least a 2-year HA follow-up. For each woman, two men underwent HA were matched in a 1:2 ratio based on age within 5 years, and date of surgery within 6 months. Diagnostic arthroscopy was performed to evaluate labral and chondral status. Radiographic evaluation, a self-administered Hip Outcome Score (HOS) questionnaire, with activity of daily living (ADL) and sports subscale (SSS), and a self-administered short version of the International Hip Outcome Tool (iHOT-12) were assessed at 6 months, 12 months, and then yearly. Clinical relevance was measured with the minimal clinical important difference (MCID), patient acceptable symptom state (PASS), and substantial clinical benefit (SCB) for HOS-ADL, HOS-SSS, and iHOT-12. RESULTS: One hundred and eighty-five patients met the inclusion criteria. Fifty-two women were matched with 104 men. Significant differences in terms of demographics, radiographic results, intraoperative findings and arthroscopic procedures were found between women and men. Mean follow-up was 48.4 months in women and 50.2 months in men. Both groups showed significant improvement from preoperative PROs to the latest follow-up. There were no significant differences between groups in preoperative PROs, latest follow-up PROs and PROs improvements. The difference in frequency of patients achieving MCID, PASS, and SCB was only significant greater for iHOT-12 PASS in women compared with men. CONCLUSION: Significant improvements in PROs in women after HA for FAIS at 4-year follow-up were found. Differences between women and men in PROs and rates of achieving MCID, SCB and PASS were only significant for iHOT-12 PASS. LEVEL OF EVIDENCE: IV.

Establishing the Minimal Clinically Important Difference and Substantial Clinical Benefit for the Pain Visual Analog Scale in a Postoperative Hand Surgery Population.

PURPOSE: Although the pain visual analog scale (VAS-pain) is a ubiquitous patient-reported outcome instrument, it remains unclear how to interpret changes or differences in scores. Therefore, our purpose was to calculate the minimal clinically important difference (MCID) and substantial clinical benefit (SCB) for the VAS-pain instrument in a nonshoulder hand and upper extremity postoperative population. METHODS: Adult postoperative patients treated by 1 of 5 fellowship-trained orthopedic hand surgeons at a single tertiary academic medical center were identified. Inclusion required VAS-pain scores at baseline (up to 3 months before surgery) and follow-up (up to 4 months after surgery), in addition to a response to a pain-specific anchor question at follow-up. The MCID estimates were calculated with (1) the 1/2 standard deviation method; and (2) an anchor-based approach. The SCB estimates were calculated with (1) an anchor-based approach; and (2) a receiver operator curve method that maximized the sensitivity and specificity for detecting a "much improved" pain status. RESULTS: There were 667 and 148 total patients included in the MCID and SCB analyses, respectively. The 1/2 standard deviation MCID estimate was 1.6, and the anchor-based estimate was 1.9. The anchor-based SCB estimate was 2.2. The receiver operator curve analysis yielded an SCB estimate of 2.6, with an area under the curve of 0.72, consistent with acceptable discrimination. CONCLUSIONS: We propose MCID values in the range of 1.6 to 1.9 and SCB values in the range of 2.2 to 2.6 for the VAS-pain instrument in a nonshoulder hand and upper extremity postoperative population. CLINICAL RELEVANCE: These MCID and SCB estimates may be useful for powering clinical studies and when interpreting VAS-pain score changes or differences reported in the hand surgery literature. These values are to be applied at a population level, and should not be applied to assess the improvement, or lack thereof, for individual patients.

Characterization of ASES score pain and functional improvement after anatomic total shoulder arthroplasty: a patient-centered perspective.

BACKGROUND: Interpretation of anchor-based clinical differences in the context of pain and functional change remains undefined. The purpose of this study was to characterize American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores for patients after anatomic total shoulder arthroplasty with minimum 1 year of follow-up in terms of pain and change in each functional element on the ASES. METHODS: We performed a retrospective study of a prospective institutional patient database of primary anatomic total shoulder arthroplasties from 2017-2020 with baseline and 1-year postoperative ASES scores. Three clinical outcome groups were established using an anchor-based global rating of change assessment: minimal clinically important difference (MCID), moderate clinical benefit (MCB), and substantial clinical benefit (SCB). Pain and functional outcomes in each group where then characterized and compared. RESULTS: A total of 67 patients were analyzed in terms of demographics and clinical outcomes. Two-thirds (65%) of patients achieved the SCB, 24% achieved the MCB, and 10% achieved the MCID. Washing, reaching for a shelf, and throwing were the most common functional deficits experienced preoperatively and accounted for the largest improvement in function postoperatively. Patients in the MCID group had higher preoperative visual analog scale (VAS) pain scores (7.1 ± 3.0) than the MCB (5.8 ± 2.5) or SCB (5.8 ± 2.2) groups (P = .0612). The MCID group had the least amount of preoperative functional deficits when compared to the MCB and SCB groups (P = .041). Postoperative VAS pain scores improved by 5.1 in the SCB, 3.6 in the MCB, and 3.7 in the MCID groups. Functional change in each element of the ASES improved by 1.4/4 in the SCB, followed by 0.9/4 in the MCB group and 0.05/4 in the MCID group (P < .001). CONCLUSION: The MCID group had higher preoperative pain scores and the least amount of preoperative functional deficits when compared to the MCB and SCB groups. The MCID was realized through pain improvement only, whereas the MCB and SCB consisted of meaningful improvements in pain and function.

Outcomes of reverse shoulder arthroplasty following failed superior capsular reconstruction.

BACKGROUND: Superior capsular reconstruction (SCR) can be used for massive irreparable rotator cuff tears in the absence of significant degenerative changes; however, those who fail an SCR may require reverse shoulder arthroplasty (RSA). The effect of a previously performed SCR on outcomes following RSA remains unknown. METHODS: Subjects who underwent RSA from May 2015 to January 2021 at 2 separate institutions were retrospectively identified through prospectively collected databases. Patients who underwent RSA after failed SCR were matched to those who underwent RSA after failed rotator cuff repair (RCR) based on the number of previous ipsilateral shoulder procedures (n = 1, 2, ≥3) and secondarily by age within 5 years. American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score, Single Assessment Numeric Evaluation (SANE), visual analog scale (VAS) for pain, and Western Ontario Osteoarthritis of the Shoulder index (WOOS) scores were compared between groups. The minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptomatic state (PASS) thresholds were calculated to determine clinically relevant differences between groups. RESULTS: Forty-five patients were included (32 RSA following RCR, 13 following SCR). There were more smokers (P = .001) and worker's compensation cases (P = .034) in the SCR group. The RCR cohort was older (P = .007) and had a greater incidence of mental health (P > .999) and somatic disorders (P = .698), although these did not reach statistical significance. The mean follow-up for the RCR and SCR groups were 24.2 ± 23.3 and 20.4 ± 14.9 months following RSA, respectively (P = .913). The time from index RCR or SCR to RSA were 94.4 ± 22.2 and 89.2 ± 5.3 months, respectively (P = .003). Pre- and postoperative range of motion were similar between groups, as was the overall change in forward flexion (P = .879), abduction (P = .971), and external rotation (P = .968) following RSA. The RCR group had lower postoperative VAS pain (P = .009), higher SANE (P = .015), higher ASES (P = .008), and higher WOOS (P = .018) scores. The percentage achieving the MCID (P = .676) and SCB (P > .999) were similar; however, 56.7% of the RCR group met the SANE PASS threshold compared with 0.0% in the SCR group (P = .005). There were no differences in postoperative complications (P = .698) or revision rates (P = .308) following RSA between cohorts. CONCLUSION: When matched for number of previous procedures to the ipsilateral extremity and age, patients who underwent RSA following failed SCR had worse clinical outcome scores than their RSA following failed RCR counterparts. No patient in the SCR group met the SANE PASS threshold, whereas more than half of the RCR group did.

Phase I Dose-Escalation Study of SCB01A, a Microtubule Inhibitor with Vascular Disrupting Activity, in Patients with Advanced Solid Tumors.

LESSONS LEARNED: SCB01A is a novel microtubule inhibitor with vascular disrupting activity. This first-in-human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity. SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity. BACKGROUND: SCB01A, a novel microtubule inhibitor, has vascular disrupting activity. METHODS: In this phase I dose-escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m2 to the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT). SCB01A-induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints. RESULTS: Treatment-related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m2 cohort; grade 3 gastric hemorrhage in the 6.5 mg/m2 cohort; grade 2 thromboembolic event in the 24 mg/m2 cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m2 cohort. The MTD was 24 mg/m2 , and average half-life was ~2.5 hours. The area under the curve-dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A-induced neurotoxicity was reversible in vitro. CONCLUSION: The MTD of SCB01A was 24 mg/m2 every 21 days; it is safe and tolerable in patients with solid tumors.

How can we define clinically important improvement in pain scores after biceps tenodesis?

BACKGROUND: Patient postoperative pain is an important consideration following biceps tenodesis. The visual analog scale (VAS) for pain is one of the most commonly used measures for perioperative pain assessment. Currently, there is limited understanding of clinically significant improvement in VAS pain. PURPOSE: To define the substantial clinical benefit (SCB), patient acceptable symptomatic state (PASS), and minimal clinically important difference (MCID) for the VAS pain score in patients undergoing open subpectoral (OSPBT) or arthroscopic suprapectoral biceps tenodesis (ASPBT) at 1 year from surgery; and to identify preoperative predictors of achieving each outcome end point. METHODS: Data from consecutive patients who underwent isolated biceps tenodesis between January 2014 and March 2017 were collected and analyzed. Baseline data and postoperative patient-reported outcome (PRO) scores were recorded at 1 year postoperatively. In order to quantify the clinical significance of outcome achievement for the VAS pain score, the MCID, PASS, and SCB were calculated. RESULTS: A total of 165 patients were included in the final analysis. The VAS pain score threshold for achieving MCID was defined as a decrease of 12.9 (0-100). PASS was defined as achieving a 2-year postoperative score of 27.4 points (0-100), and SCB was defined as a decrease of 25.1 (0-100) at 1-year follow-up. The rates of achieving MCID, PASS, and SCB were 73.3%, 52.8%, and 45.9%, respectively. Multivariate regression analysis demonstrated that ASPBT (P = .01) and a lower preoperative Constant-Murley score were predictive of achieving the MCID (P = .01). In contrast, a lower preoperative score on the SF-12 Physical Component Summary (P = .01) and a higher score on the preoperative American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (P < .001) were predictive of achieving the SCB and PASS, respectively. Preoperative duration of symptoms >6 months was predictive of a reduced likelihood to achieve PASS. CONCLUSION: This study identified scores for VAS pain that can be used to define clinically significant outcome after biceps tenodesis. Specifically, a decrease in pain score of 12.9 was a clinically important improvement in VAS pain, whereas a decrease of 25.1 represented the upper threshold of VAS pain improvement. Additionally, there were both modifiable and nonmodifiable factors that predicted achieving clinically significant levels of postoperative pain improvement.

Establishing clinically significant outcomes of the Patient-Reported Outcomes Measurement Information System Upper Extremity questionnaire after primary reverse total shoulder arthroplasty.

BACKGROUND AND HYPOTHESIS: Since its introduction, the Patient-Reported Outcomes Measurement Information System Upper Extremity (PROMIS UE) assessment has been increasingly used in shoulder arthroplasty outcome measurement. However, determination of clinically significant outcomes using the PROMIS UE has yet to be investigated following reverse total shoulder arthroplasty (RTSA). We hypothesized that we could establish clinically significant outcomes of the PROMIS UE outcome assessment in patients undergoing primary RTSA and identify significant baseline patient factors associated with achievement of these measures. METHODS: Consecutive patients undergoing primary RTSA between 2018 and 2019 who received preoperative baseline and follow-up PROMIS UE assessments at 12 months after surgery were retrospectively reviewed. Domain-specific anchor questions pertaining to pain and function assessed at 12 months after surgery were used to determine minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptomatic state (PASS) values for the PROMIS UE using receiver operating characteristic curve and area-under-the-curve (AUC) analysis. Univariate logistic regression analysis was then performed to identify significant patient factors associated with achieving the MCID, SCB, or PASS. RESULTS: A total of 95 patients met all inclusion criteria and were included in the analysis. By use of an anchor-based method, the PASS value was 36.68 (sensitivity, 0.795; specificity, 0.765; AUC, 0.793) and the SCB value was 11.62 (sensitivity, 0.597; specificity, 1.00; AUC, 0.806). By use of a distribution-based method, the MCID value was calculated to be 4.27. Higher preoperative PROMIS UE scores were a positive predictor in achievement of the PASS (odds ratio [OR], 1.107; P = .05), whereas lower preoperative PROMIS UE scores were associated with obtaining SCB (OR, 0.787; P < .001). Greater baseline forward flexion was negatively associated with achievement of the PASS (OR, 0.986; P = .033) and MCID (OR, 0.976, P = .013). Of the patients, 83.2%, 69.5%, and 47.4% achieved the MCID, PASS, and SCB, respectively. CONCLUSION: This study defines the MCID, SCB, and PASS for the PROMIS UE outcome assessment in patients undergoing primary RTSA, of whom the majority achieved meaningful outcome improvement at 12 months after surgery. These values may be used in assessing the outcomes and extent of functional improvement following RTSA.

Establishing clinically significant outcome thresholds for the Single Assessment Numeric Evaluation 2 years following total shoulder arthroplasty.

BACKGROUND: Single Assessment Numerical Evaluation (SANE) is a simple, time-efficient patient-reported outcome measure (PROM) used to assess postoperative shoulder function. Clinically significant outcome values and ability to correlate with longer legacy PROM scores at 2 years following shoulder arthroplasty are unknown. METHODS: A retrospective analysis was performed using SANE, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), and Constant scores that were collected at a minimum 2-year follow-up. A total of 153 patients who underwent anatomic total shoulder arthroplasty (TSA) or reverse total shoulder arthroplasty (RTSA) were included. A distribution-based method was used to determine the minimal clinically important difference (MCID). An anchor-based method was used to determine substantial clinical benefit (SCB). The following anchor question was collected alongside the PROMs and graded on a 15-point Likert-type scale to establish the SCB: "Since your surgery, has there been any change in the pain in your shoulder?" Linear regression was used to assess correlations between PROMs. RESULTS: SANE showed moderate correlation with ASES (R2 = 0.493) and Constant (R2 = 0.586) scores (P < .001). The MCID value was 14.9, and the SCB absolute value was 80.4 (area under the curve = 0.663) for SANE. Multivariate logistic regression demonstrated that patients undergoing RTSA were less likely to achieve SCB on all 3 outcome measures (P < .02). CONCLUSIONS: This study establishes concurrent construct validity for SANE and suggests that it is a valid metric to assess the MCID and SCB at 2 years following anatomic TSA and RTSA. SANE demonstrated moderate correlations with ASES and Constant scores. Patients undergoing RTSA demonstrated a lower propensity to achieve SCB at 2 years postoperatively compared with anatomic TSA.

Molecular Characterization of Xyloglucanase cel74a from Trichoderma reesei.

BACKGROUND: The filamentous fungus Trichoderma reesei is used on an industrial scale to produce enzymes of biotechnological interest. This fungus has a complex cellulolytic system involved in the degradation of lignocellulosic biomass. However, several aspects related to the regulation of the expression of holocellulolytic genes and the production of cellulases by this fungus are still understood. METHODS: Here, we constructed a null mutant strain for the xyloglucanase cel74a gene and performed the characterization of the Δcel74a strain to evaluate the genetic regulation of the holocellulases during sugarcane bagasse (SCB) cultivation. RESULTS: Our results demonstrate that the deletion of xyloglucanase cel74a may impact the regulation of holocellulase expression during SCB cultivation. The expression of cellulases cel7a, cel7b, and cel6a was reduced in Δcel74a strain, while the hemicellulases xyn1 and xyn2 were increased in the presence of SCB. The cel74a mutation also affected the xyloglucan hydrolysis patterns. In addition, CEL74A activity was modulated in the presence of calcium, suggesting that this ion may be required for efficient degradation of xyloglucan. CONCLUSIONS: CEL74A affects the regulation of holocellulolytic genes and the efficient degradation of SCB in T. reesei. This data makes a significant contribution to our understanding of the carbon utilization of fungal strains as a whole.

Detection of Induced GNSS Spoofing Using S-Curve-Bias.

In Global Navigation Satellite System (GNSS), a spoofing attack consists of forged signals which possibly cause the attacked receivers to deduce a false position, a false clock, or both. In contrast to simplistic spoofing, the induced spoofing captures the victim tracking loops by gradually adjusting it's parameters, e.g., code phase and power. Then the victims smoothly deviates from the correct position or timing. Therefore, it is more difficult to detect the induced spoofing than the simplistic one. In this paper, by utilizing the dynamic nature of such gradual adjustment process, an induced spoofing detection method is proposed based on the S-curve-bias (SCB). Firstly, SCB in the inducing process is theoretically derived. Then, in order to detect the induced spoofing, a detection metric is defined. After that, a series of experiments using the Texas spoofing test battery (TEXBAT) are performed to demonstrate the effectiveness of the proposed algorithm.