Universal control of a six-qubit quantum processor in silicon.

Future quantum computers capable of solving relevant problems will require a large number of qubits that can be operated reliably1. However, the requirements of having a large qubit count and operating with high fidelity are typically conflicting. Spins in semiconductor quantum dots show long-term promise2,3 but demonstrations so far use between one and four qubits and typically optimize the fidelity of either single- or two-qubit operations, or initialization and readout4-11. Here, we increase the number of qubits and simultaneously achieve respectable fidelities for universal operation, state preparation and measurement. We design, fabricate and operate a six-qubit processor with a focus on careful Hamiltonian engineering, on a high level of abstraction to program the quantum circuits, and on efficient background calibration, all of which are essential to achieve high fidelities on this extended system. State preparation combines initialization by measurement and real-time feedback with quantum-non-demolition measurements. These advances will enable testing of increasingly meaningful quantum protocols and constitute a major stepping stone towards large-scale quantum computers.

The Association of Preoperative Opioid Use with Post-Discharge Outcomes: A Cohort Study of the Michigan Surgical Quality Collaborative.

OBJECTIVE: To examine the association of prescription opioid fills over the year prior to surgery with postoperative outcomes. BACKGROUND: Nearly one third of patients report opioid use in the year preceding surgery, yet an understanding of how opioid exposure influences patient-reported outcomes after surgery remains incomplete. Therefore, this study was designed to test the hypothesis that preoperative opioid exposure may impede recovery in the postoperative period. METHODS: This retrospective cohort study used a statewide clinical registry from 70 hospitals linked to opioid fulfillment data from the state's prescription drug monitoring program to categorize patients' preoperative opioid exposure as none (naïve), minimal, intermittent, or chronic. Outcomes were patient-reported pain intensity (primary), as well as 30-day clinical and patient-reported outcomes (secondary). RESULTS: Compared to opioid-naïve patients, opioid exposure was associated with higher reported pain scores at 30 days after surgery. Predicted probabilities was higher among the opioid exposed versus naive group for reporting moderate pain (43.5% [95% CI 42.6 - 44.4%] vs 39.3% [95% CI 38.5 - 40.1%]) and severe pain (13.% [95% CI 12.5 - 14.0%] vs 10.0% [95% CI 9.5 - 10.5%]), and increasing probability was associated increased opioid exposure for both outcomes. Clinical outcomes (incidence of ED visits, readmissions, and reoperation within 30-days) and patient-reported outcomes (reported satisfaction, regret, and quality of life) were also worse with increasing preoperative opioid exposure for most outcomes. CONCLUSIONS: This study is the first to examine the effect of presurgical opioid exposure on both clinical and non-clinical outcomes in a broad cohort of patients, and shows that exposure is associated with worse postsurgical outcomes. A key question to be addressed is whether and to what extent opioid tapering before surgery mitigates these risks after surgery.

The Effect of Artificial Intelligence on Patient-Physician Trust: Cross-Sectional Vignette Study.

BACKGROUND: Clinical decision support systems (CDSSs) based on routine care data, using artificial intelligence (AI), are increasingly being developed. Previous studies focused largely on the technical aspects of using AI, but the acceptability of these technologies by patients remains unclear. OBJECTIVE: We aimed to investigate whether patient-physician trust is affected when medical decision-making is supported by a CDSS. METHODS: We conducted a vignette study among the patient panel (N=860) of the University Medical Center Utrecht, the Netherlands. Patients were randomly assigned into 4 groups-either the intervention or control groups of the high-risk or low-risk cases. In both the high-risk and low-risk case groups, a physician made a treatment decision with (intervention groups) or without (control groups) the support of a CDSS. Using a questionnaire with a 7-point Likert scale, with 1 indicating "strongly disagree" and 7 indicating "strongly agree," we collected data on patient-physician trust in 3 dimensions: competence, integrity, and benevolence. We assessed differences in patient-physician trust between the control and intervention groups per case using Mann-Whitney U tests and potential effect modification by the participant's sex, age, education level, general trust in health care, and general trust in technology using multivariate analyses of (co)variance. RESULTS: In total, 398 patients participated. In the high-risk case, median perceived competence and integrity were lower in the intervention group compared to the control group but not statistically significant (5.8 vs 5.6; P=.16 and 6.3 vs 6.0; P=.06, respectively). However, the effect of a CDSS application on the perceived competence of the physician depended on the participant's sex (P=.03). Although no between-group differences were found in men, in women, the perception of the physician's competence and integrity was significantly lower in the intervention compared to the control group (P=.009 and P=.01, respectively). In the low-risk case, no differences in trust between the groups were found. However, increased trust in technology positively influenced the perceived benevolence and integrity in the low-risk case (P=.009 and P=.04, respectively). CONCLUSIONS: We found that, in general, patient-physician trust was high. However, our findings indicate a potentially negative effect of AI applications on the patient-physician relationship, especially among women and in high-risk situations. Trust in technology, in general, might increase the likelihood of embracing the use of CDSSs by treating professionals.

Neighborhood socioeconomic disadvantages influence outcomes following rotator cuff repair in the non-Medicaid population.

BACKGROUND: Prior investigations have utilized various surrogate markers of socioeconomic status to assess how health care disparities impact outcomes after rotator cuff repair (RCR). When taken as individual markers, these factors have inconsistent associations. Medicaid insurance status is an accessible marker that has recently been correlated with less optimal outcomes after RCR. Socioeconomic disparities exist within the non-Medicaid population as well and are arguably more difficult to characterize. The Area Deprivation Index (ADI) uses seventeen socioeconomic variables to establish a spectrum of neighborhood health care disparity. The purpose of this study was to determine the influence of neighborhood socioeconomic disadvantages, quantified by ADI, on 2-year patient reported outcome scores following RCR in the non-Medicaid population. METHODS: A retrospective review of patients who underwent RCR from 2015 to 2020 was performed. All procedures were performed by a group of 7 surgeons at a large academic center. Patient demographics and comorbidities were collected from charts. Rotator cuff tear size was assessed from arthroscopic pictures. ADI scores were calculated based on patients' home addresses using the Neighborhood Atlas tool. The primary outcome measure was American Shoulder and Elbow Surgeons (ASES) score with a minimum follow-up of 2 years. A linear regression analysis with covariate control for age and patient comorbidities was performed. RESULTS: There were 287 patients with a mean age of 60.11 years. The linear regression model between ADI and 2-year ASES score was significant (P = .02). When controlling for both age and patient comorbidities, every 0.9-point reduction in ADI resulted in a 1-point increase in the ASES score (P = .03). Patients with an ADI of 8, 9, or 10 had lower mean 2-year ASES scores than those with an ADI of 1 (87.08 vs. 93.19, P = .04), but both groups had similar change from preoperative ASES score (40.17 vs. 32.88, P = .12). The change in ASES score at 2-years in our study surpassed all established minimal clinically important difference values irrespective of ADI. CONCLUSION: Patients with greater levels of disparity in their home neighborhoods have worse final ASES scores at 2 years, but patients significantly improve from their preoperative state regardless of social disadvantages. This is the first study to the authors' knowledge that examines ADI and outcomes following RCR. Providers should be aware that patients with higher ADI scores may have inferior preoperative shoulder function. The results of this study support the utilization of primary RCR in applicable tears regardless of socioeconomic status.

Measure what matters: Single Assessment Numeric Evaluation (SANE) score as the critical measure for shoulder outcomes.

BACKGROUND: Implementation of a system anchored in patient outcomes is challenged to gain widespread adoption required to demonstrate the value of care provided for shoulder conditions. This is in large part because of the administrative burden created by current tools and clinical implementation barriers that limit practical use and therefore leave most clinicians, administrators, payers, and patients without a measure of what matters most: Are patients improving? Thus, we must ask ourselves, How do we accurately and efficiently measure and report quality of care in a simple, reliable, and easily communicated manner? We propose that the Single Assessment Numeric Evaluation (SANE) score is the best solution to measure patient improvement and can be used universally for all shoulder conditions. The measure is simple, valid, reliable, and sensitive to change and has the lowest implementation barrier compared with all other outcome measures. METHODS: We synthesized the available literature (11 studies) that demonstrates strong psychometrics comparable to legacy measures across >4000 patients with a wide range of shoulder conditions. RESULTS: SANE scores range from 40% to 60% at baseline for most patients before treatment and range from 75% to 85% at 1 year after therapy depending on the condition, similar to legacy scores such as the American Shoulder and Elbow Surgeons score. Additionally, the SANE score shows similar baseline and post-care measures across conditions that can be used to guide clinical care. This finding shows that the observed baseline and improvement scores can provide valuable patient assessment and can be used in aggregate for quality improvement and other value-based purposes. CONCLUSION: We strongly recommend the SANE score as the primary patient outcome measure for patients with all shoulder conditions, given the value of measuring every patient's progress and growing pressure to quantify patient outcomes.

ICD-10 diagnosis codes in electronic health records do not adequately capture fracture complexity for proximal humerus fractures.

BACKGROUND: The ability to do comparative effectiveness research (CER) for proximal humerus fractures (PHF) using data in electronic health record (EHR) systems and administrative claims databases was enhanced by the 10th revision of the International Classification of Diseases (ICD-10), which expanded the diagnosis codes for PHF to describe fracture complexity including displacement and the number of fracture parts. However, these expanded codes only enhance secondary use of data for research if the codes selected and recorded correctly reflect the fracture complexity. The objective of this project was to assess the accuracy of ICD-10 diagnosis codes documented during routine clinical practice for secondary use of EHR data. METHODS: A sample of patients with PHFs treated by orthopedic providers across a large, regional health care system between January 1, 2016, and December 31, 2018, were retrospectively identified from the EHR. Four fellowship-trained orthopedic surgeons reviewed patient radiographs and recorded the Neer Classification characteristics of displacement, number of parts, and fracture location(s). The fracture characteristics were then reviewed by a trained coder, and the most clinically appropriate ICD-10 diagnosis code based on the number of fracture parts was assigned. We assessed congruence between ICD-10 codes documented in the EHR and radiograph-validated codes, and assessed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for EHR-documented ICD-10 codes. RESULTS: There were 761 patients with unilateral, closed PHF who met study inclusion criteria. On average, patients were 67 years of age and 77% were female. Based on radiograph review, 37% were 1-part fractures, 42% were 2-part, 11% were 3-part, and 10% were 4-part fractures. Of the EHR diagnosis codes recorded during clinical practice, 59% were "unspecified" fracture diagnosis codes that did not identify the number of fracture parts. Examination of fracture codes revealed PPV was highest for 1-part (PPV = 0.66, 95% confidence interval [CI] 0.60-0.72) and 4-part fractures (PPV = 0.67, 95% CI 0.13-1.00). CONCLUSIONS: Current diagnosis coding practices do not adequately capture the fracture complexity needed to conduct subgroup analysis for PHF. Conclusions drawn from population studies or large databases using ICD-10 codes for PHF classification should be interpreted within this limitation. Future studies are warranted to improve diagnostic coding to support large observational studies using EHR and administrative claims data.

Judicious use of corticosteroid injections prior to shoulder arthroplasty does not compromise outcomes at a minimum of 2 years following surgery.

BACKGROUND: The use of total shoulder arthroplasty is continuing to rise with its expanding indications. For patients with chronic conditions, such as glenohumeral arthritis and rotator cuff arthropathy, nonoperative treatment is typically done prior to arthroplasty and often includes corticosteroid injections (CSIs). Recent studies in the shoulder arthroplasty literature as well as applied from the hip and knee literature have focused on the risk of periprosthetic infection. Literature is lacking as to whether the judicious use of corticosteroids in the year prior to arthroplasty influences patient-reported outcomes (PROs). The purpose of this study was to determine if preoperative CSIs prior to shoulder arthroplasty affected 2-year PROs. METHODS: Retrospective review of anatomic and reverse total shoulder arthroplasty (RSA) patients (n = 230) was performed at a single institution including multiple surgeons. Patients were included if they had preoperative and a minimum of 2-year postoperative PROs, including: American Shoulder and Elbow Surgeons (ASES), visual analog scale, Single Assessment Numeric Evaluation, Veteran's RAND 12 Physical Component Score, and Veteran's RAND 12 Mental Component Score. Patients were included in the injection group if they had received an injection, either glenohumeral or subacromial, within 12 months prior to arthroplasty (inject = 134). Subgroup analysis included anatomic (total shoulder arthroplasty [TSA] = 92) and RSA (RSA = 138) as well as those with no injection within 12 months prior to surgery. An analysis of variance was used to compare outcomes between patients who received an injection and those who did not prior to TSA and RSA. RESULTS: There were 230 patients included with 134 patients in the injection group and 96 in the no injection group. Patients who received an injection in the year prior to arthroplasty displayed a significantly higher ASES (82 [16.23 standard deviation] vs. 76 [19.43 standard deviation], P < .01) and Single Assessment Numeric Evaluation (70 [24.49 standard deviation] vs. 63 [29.22 standard deviation], P < .01) scores vs. those who had not received injection. There was no difference when comparing preoperative injection vs. no injection in patients undergoing TSA. Those patients undergoing RSA displayed significantly higher ASES scores (P < .01). There were no significant differences in visual analog scale, Veteran's RAND 12 Physical Component Score, and Veteran's RAND 12 Mental Component Score among any analysis (P > .05), and the minimal clinically important difference in ASES was not different between groups (P.09). CONCLUSION: CSIs within 12 months prior to anatomic and RSA do not compromise PROs during a minimum of 2-year follow-up. Although more complications occurred in the injection group, it did not reach statistical significance and warrants further study in a larger population.

No clinical difference in outcomes between inlay and onlay arthroscopic biceps tenodesis techniques during rotator cuff repair.

BACKGROUND: Both inlay and onlay arthroscopic biceps tenodesis (ABT) are common procedures performed during rotator cuff repair. The inlay method involves creating a bone socket in the bicipital groove to secure the long head of the biceps tendon using an interference screw. The onlay method utilizes a suture anchor to secure the long head of the biceps tendon on the surface of the bicipital groove. Little is known on the long-term differences in patient-reported outcomes between these 2 techniques. The primary purpose of this study was to compare patient-reported outcomes of inlay vs. onlay ABT with a minimum follow-up of 2 years. Secondary aims were to evaluate the impact of rotator cuff tear size on outcomes and compare rates of complications between the 2 techniques. METHODS: A retrospective chart review was performed to identify patients who had an ABT during a full-thickness rotator cuff repair. Any symptom specific to the biceps were noted, including pain and cramping, Popeye deformity, or revision surgery. Complication rates were compared between groups. The visual analog scale pain score, American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation, and Veteran's RAND-12 score (VR-12) scores were compared at 2 years. The impact of rotator cuff tear size was analyzed by categorizing into small/medium or large/massive based on operative reports and arthroscopic images. RESULTS: There were 165 patients identified (106 in the inlay group and 59 in the onlay group). No revision surgeries were performed secondary to the biceps tendon in either group. Eleven patients (10%) in the inlay group complained of biceps pain or cramping compared to 2 patients (3%) in the onlay group (P = .11). One Popeye deformity was noted in each group (P = .67). No significant differences were found between groups for visual analog scale (P = .41), ASES functional (P = .61), ASES index (P = .91), Single Assessment Numeric Evaluation (P = .09), VR-12 Physical Component Score (P = .77), or VR-12 Mental Component Score (P = .09). Rotator cuff tear size within the groups also did not demonstrate statistical significance. CONCLUSION: No clinical differences or complications were found at minimum 2-year follow-up between inlay and onlay ABT in patients undergoing rotator cuff repair when controlling for tear size. The clinical relevance suggests either technique is effective and can be based on surgeon preference.

Addressing Atropisomerism in the Development of Sotorasib, a Covalent Inhibitor of KRAS G12C: Structural, Analytical, and Synthetic Considerations.

Nearly a century after its first description, configurationally stable axial chirality remains a rare feature in marketed drugs. In the development of the KRASG12C inhibitor sotorasib (LUMAKRAS/LUMYKRAS), an axially chiral biaryl moiety proved a critical structural element in engaging a "cryptic" protein binding pocket and enhancing inhibitor potency. Restricted rotation about this axis of chirality gave rise to configurationally stable atropisomers that demonstrated a 10-fold difference in potency. The decision to develop sotorasib as a single-atropisomer drug gave rise to a range of analytical and synthetic challenges, whose resolution we review here.Assessing the configurational stability of differentially substituted biaryl units in early inhibitor candidates represented the first challenge to be overcome, as differing atropisomer stability profiles called for differing development strategies (e.g., as rapidly equilibrating rotamers vs as single atropisomers). We relied on a range of NMR, HPLC, and computational methods to assess atropisomer stability. Here, we describe the various variable-temperature NMR, time-course NMR, and chiral HPLC approaches used to assess the configurational stability of axially chiral bonds displaying a range of rotational barriers.As optimal engagement of the "cryptic" pocket of KRASG12C was ultimately achieved with a configurationally stable atropisomeric linkage, the second challenge to be overcome entailed preparing the preferred (M)-atropisomer of sotorasib on industrial scale. This synthetic challenge centered on the large-scale synthesis of an atropisomerically pure building block comprising the central azaquinazolinone and pyridine rings of sotorasib. We examined a range of strategies to prepare this compound as a single atropisomer: asymmetric catalysis, chiral chromatographic purification, and classical resolution. Although chiral liquid and simulated moving bed chromatography provided expedient access to initial multikilo supplies of this key intermediate, a classical resolution process was ultimately developed that proved significantly more efficient on metric-ton scale. To avoid discarding half of the material from this resolution, this process was subsequently refined to enable thermal recycling of the undesired atropisomer, providing an even more efficient commercial process that proved both robust and green.While the preparation of sotorasib as a single atropisomer significantly increased both the analytical and synthetic complexity of its development, the axially chiral biaryl linkage that gave rise to the atropisomerism of sotorasib proved a key design element in optimizing sotorasib's binding to KRASG12C. It is hoped that this review will help in outlining the range of analytical techniques and synthetic strategies that can be brought to bear in addressing the challenges posed by such axially chiral compounds and that this account may provide helpful guidelines for future efforts aimed at the development of such single atropisomer, axially chiral pharmaceutical agents.

Development of PSMA-PET-guided CT-based radiomic signature to predict biochemical recurrence after salvage radiotherapy.

PURPOSE: To develop a CT-based radiomic signature to predict biochemical recurrence (BCR) in prostate cancer patients after sRT guided by positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET). MATERIAL AND METHODS: Consecutive patients, who underwent 68Ga-PSMA11-PET/CT-guided sRT from three high-volume centers in Germany, were included in this retrospective multicenter study. Patients had PET-positive local recurrences and were treated with intensity-modulated sRT. Radiomic features were extracted from volumes of interests on CT guided by focal PSMA-PET uptakes. After preprocessing, clinical, radiomics, and combined clinical-radiomic models were developed combining different feature reduction techniques and Cox proportional hazard models within a nested cross validation approach. RESULTS: Among 99 patients, median interval until BCR was the radiomic models outperformed clinical models and combined clinical-radiomic models for prediction of BCR with a C-index of 0.71 compared to 0.53 and 0.63 in the test sets, respectively. In contrast to the other models, the radiomic model achieved significantly improved patient stratification in Kaplan-Meier analysis. The radiomic and clinical-radiomic model achieved a significantly better time-dependent net reclassification improvement index (0.392 and 0.762, respectively) compared to the clinical model. Decision curve analysis demonstrated a clinical net benefit for both models. Mean intensity was the most predictive radiomic feature. CONCLUSION: This is the first study to develop a PSMA-PET-guided CT-based radiomic model to predict BCR after sRT. The radiomic models outperformed clinical models and might contribute to guide personalized treatment decisions.

Association of Genetic Variants with Postsurgical Pain: A Systematic Review and Meta-analyses.

BACKGROUND: Postsurgical pain is a key component of surgical recovery. However, the genetic drivers of postsurgical pain remain unclear. A broad review and meta-analyses of variants of interest will help investigators understand the potential effects of genetic variation. METHODS: This article is a systematic review of genetic variants associated with postsurgical pain in humans, assessing association with postsurgical pain scores and opioid use in both acute (0 to 48 h postoperatively) and chronic (at least 3 months postoperatively) settings. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from 2000 to 2022 for studies using search terms related to genetic variants and postsurgical pain in humans. English-language studies in adult patients examining associations of one or more genetic variants with postsurgical pain were included. The primary outcome was association of genetic variants with either acute or chronic postsurgical pain. Pain was measured by patient-reported pain score or analgesic or opioid consumption. RESULTS: A total of 163 studies were included, evaluating 129 unique genes and 594 unique genetic variants. Many of the reported significant associations fail to be replicated in other studies. Meta-analyses were performed for seven variants for which there was sufficient data (OPRM1 rs1799971; COMT rs4680, rs4818, rs4633, and rs6269; and ABCB1 rs1045642 and rs2032582). Only two variants were associated with small differences in postsurgical pain: OPRM1 rs1799971 (for acute postsurgical opioid use standard mean difference = 0.25; 95% CI, 0.16 to 0.35; cohort size, 8,227; acute postsurgical pain score standard mean difference = 0.20; 95% CI, 0.09 to 0.31; cohort size, 4,619) and COMT rs4680 (chronic postsurgical pain score standard mean difference = 0.26; 95% CI, 0.08 to 0.44; cohort size, 1,726). CONCLUSIONS: Despite much published data, only two alleles have a small association with postsurgical pain. Small sample sizes, potential confounding variables, and inconsistent findings underscore the need to examine larger cohorts with consistent outcome measures.

Greater male variability in daily energy expenditure develops through puberty.

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.

Discovery of mobocertinib, a potent, oral inhibitor of EGFR exon 20 insertion mutations in non-small cell lung cancer.

In the treatment of non-small cell lung cancer (NSCLC), patients harboring exon 20 insertion mutations in the epidermal growth factor receptor (EGFR) gene (EGFR) have few effective therapies because this subset of mutants is generally resistant to most currently approved EGFR inhibitors. This report describes the structure-guided design of a novel series of potent, irreversible inhibitors of EGFR exon 20 insertion mutations, including the V769_D770insASV and D770_N771insSVD mutants. Extensive structure-activity relationship (SAR) studies led to the discovery of mobocertinib (compound 21c), which inhibited growth of Ba/F3 cells expressing the ASV insertion with a half-maximal inhibitory concentration of 11 nM and with selectivity over wild-type EGFR. Daily oral administration of mobocertinib induced tumor regression in a Ba/F3 ASV xenograft mouse model at well-tolerated doses. Mobocertinib was approved in September 2021 for the treatment of adult patients with advanced NSCLC with EGFR exon 20 insertion mutations with progression on or after platinum-based chemotherapy.

Value of PET ECG gating in a cross-validation study of cardiac function assessment by PET/MR imaging.

BACKGROUND: This work investigated the impact of different cardiac gating methods on the assessment of cardiac function by FDG-PET in a cross-validation PET/MR study. METHODS AND RESULTS: MR- and PET-based left ventricular end-diastolic, end-systolic volumes, and ejection fraction (EDV, ESV, and EF) were delineated in 30 patients with a PET/MR examination. Cardiac PET imaging was performed using three ECG gating methods: fixed number of gates per beat (STD), STD with a beat acceptance window (STD-BR), and fixed gate duration (FW). High MR-PET correlations were found in all the values. ESVs correlated better than EDVs and EFs: Pearson's r coefficient [0.92, 0.92, 0.92] in ESV vs [0.75, 0.81, 0.80] in EDV and [0.79, 0.91, 0.87] in EF, for each method [STD, STD-BR, FW]. Biases with respect to MRI for all the evaluated PET methods were less than 13% in EDV, 5% in ESV, and 14% in EF, but with wide limits of agreements, in the range (59-68)% in EDV, (65-70)% in ESV, and (49-71)% in EF. STD showed the strongest disagreement, while there were no marked differences between STD-BR and FW. CONCLUSION: Based on these findings, PET- and MR-based cardiac function parameters were highly correlated but in substantial disagreement with variabilities introduced by the selected PET ECG gating method. The most significant differences were associated with the ECG gating method susceptible to highly irregular beats, while similar performance was observed in the methods using uniform adjustment of gates width per beat with the beat acceptance window, and fixed gate width along all the beats. Thus, strict quality controls of R peak detection are needed to minimize its impact on the function assessment.

Multi-center study of inter-rater reproducibility, image quality, and diagnostic accuracy of CZT versus conventional SPECT myocardial perfusion imaging.

BACKGROUND: Cadmium-zinc-telluride (CZT)-based detectors exhibit higher diagnostic sensitivity in myocardial perfusion imaging (MPI) than conventional Anger-MPI for detection of coronary artery disease (CAD); however, reduced specificity and diagnostic accuracy of CZT-MPI were observed. This study aims to compare these different camera systems and to examine the degree of inter-rater reproducibility among readers with varying experience in MPI. METHODS: 83 patients who underwent double stress/rest examinations using both a CZT and conventional SPECT cameras within one visit were included. Anonymized and randomized MPI-images were distributed to 15 international readers using a standardized questionnaire. Subsequent coronary angiography findings of ten patients served as a reference for analysis of sensitivity and specificity. RESULTS: Image quality was significantly better in CZT-MPI with significantly lower breast attenuation (P < 0.05). CZT-MPI exhibited higher sensitivity than Anger-MPI (87.5% vs. 62.5%) and significantly reduced specificity (40% vs. 100%). Readers experienced with both camera systems had the highest inter-rater agreement indicating higher reproducibility (CZT 0.54 vs. conv. 0.49, P < 0.05). CONCLUSIONS: Higher diagnostic sensitivity of CZT-MPI offers advantages in detection of CAD yet potentially of at the cost of reduced specificity, therefore it requires special training and a differentiated evaluation approach, especially for non-experienced readers with such camera systems.

Visualization of fibroblast activation using 68Ga-FAPI PET/CT after pulmonary vein isolation with pulsed field compared with cryoballoon ablation.

BACKGROUND: Pulsed-field ablation (PFA) is a novel ablation modality for atrial fibrillation (AF) ablating myocardium by electroporation without tissue-heating. With its different mechanism of tissue ablation, it is assumed that lesion creation is divergent to thermal energy sources. 68Ga-fibroblast-activation protein inhibitor (FAPI) PET/CT targets FAP-alpha expressed by activated fibroblasts. We aimed to assess 68Ga-FAPI uptake in pulmonary veins as surrogate for ablation damage after PFA and cryoballoon ablation (CBA). METHODS: 26 patients (15 PFA, 11 CBA) underwent 68Ga-FAPI-PET/CT after ablation. Standardized uptake values (SUV) and fibroblast-activation volumes of localized tracer uptake were assessed. RESULTS: Patient characteristics were comparable between groups. In PFA, focal FAPI uptake was only observed in 3/15 (20%) patients, whereas in the CBA cohort, 10/11 (90.9%) patients showed atrial visual uptake. We observed lower values of SUVmax (2.85 ± 0.56 vs 4.71 ± 2.06, P = 0.025) and FAV (1.13 ± 0.84 cm3 vs 3.91 ± 2.74 cm3, P = 0.014) along with a trend towards lower SUVpeak and SUVmean in PFA vs CBA patients, respectively. CONCLUSION: Tissue response with respect to fibroblast activation seems to be less pronounced in PFA compared to established thermal ablation systems. This functional assessment might contribute to a better understanding of lesion formation in thermal and PFA ablation potentially contributing to better safety outcomes.

Pentoxifylline reduces inflammation and prevents myocardial perfusion derangements in experimental chronic Chagas' cardiomyopathy.

BACKGROUND: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters. METHODS AND RESULTS: We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 ± 1.6 to 9.4 ± 9.7%), but not in CH + PTX (1.9 ± 3.0% to 2.7 ± 2.7%) that exhibited MPD area similar to CO (0.0 ± 0.0% to 0.0 ± 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 ± 88.3 cell/mm2), as compared to CH + SLN (515.1 ± 133.0 cell/mm2), but larger than CO (193.0 ± 25.7 cell/mm2). The fibrosis and TNF-α expression was higher in both infected groups. CONCLUSIONS: The prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC.

Modern pied pipers: Child social media influencers and junk food on YouTube: A study from Germany.

Kid influencers (under the age of 13) have profiles on social media platforms and create content to generate views and engagements. To reach young consumers, food companies are increasingly using kid influencers, perceived as highly trustworthy among children of the same age, to promote their (high-calorie) food products. Exposure to such content can lead to an increase in calorie intake. Therefore, this study aimed to identify which foods and beverages are featured in the videos of the four kid influencer channels most popular in Germany and, if possible, which Nutri-Score category these products receive. Of each channel, 50 of the most popular and 50 of the newest videos were analyzed regarding the food and beverage products and brands appearing in the video and the thumbnail. To analyze the number of appearances, each product was categorized as to whether it was branded or unbranded. Where possible, the Nutri-Score was then calculated for each product that appeared. Within the total video sample (N = 373), food and/or beverages appeared in almost 70% of the videos, of which 220 were branded and 178 were unbranded products. Due to incomplete nutrition labels of branded products, only 146 branded products could be analyzed, from which 66% received the worst Nutri-Score categories D and E. The unbranded foods were evaluated using products as similar as possible, of which the majority received Nutri-Score A. The most common brands included McDonald's, Kinder, and Coca-Cola, and the most frequent product categories were chocolate, candy, soft drinks, and fruit. The high number of high-calorie products in the videos shows that kid influencers might be regarded as a risk factor when it comes to childhood obesity.

Unanticipated costs associated with interscalene nerve catheters for shoulder surgery.

BACKGROUND: Regional anesthesia has become a mainstay of analgesia following shoulder arthroscopic and reconstructive procedures. Local anesthetic can be injected in the perineural space of the brachial plexus by a single shot or continuously by an indwelling catheter. Although previous studies have compared efficacy and direct cost of single shot to catheters, few have evaluated unanticipated costs of ongoing care or complications. Pulmonary complications can lead to unexpected admissions and emergency department visits. The purpose of the study was to identify unplanned hospital admissions or emergency department visits related to regional anesthesia after shoulder surgery and determine the additional associated costs. METHODS: A series of 1888 shoulder surgeries were identified in 1856 unique patients at a single, large academic center. As part of an interscalene nerve catheter program, a continuous interscalene block (CIB) was given to 1728 patients, whereas 160 patients had a single-shot interscalene block (SSIB). A hospital-employed quality control nurse contacted all patients receiving a CIB at 1, 2, 7, and 14 days following surgery. All emergency department visits and readmissions were recorded, and the associated billing charges were reviewed for the inpatient and any outpatient visits immediately preceding or immediately following the readmission. The regional average Medicare fee schedule was used to determine a cost for these episodes of care. RESULTS: Of the 1728 patients who had CIB, 10 patients were readmitted following open or arthroscopic surgery or presented to the emergency department in the immediate postoperative period for pulmonary compromise. No patient in the SSIB group had an emergency department visit or readmission. The average age of the 10 patients with readmission was 60 years (7 females, 3 males). The majority were diagnosed with hypoxemia on admission (R09.02). Length of stay during readmission ranged from 0 to 4 days, with 1 patient requiring admission to the intensive care unit. The average cost of admission to the hospital or visit to the emergency department was $6849 (range, $1988-$19,483). These costs were primarily related to chest radiographs and electrocardiogram (9/10), chest computed tomography (CT) with contrast (3/10), and head CT (2/10). CONCLUSION: Although uncommon, unanticipated pulmonary complications after CIB can result in significant cost compared to SSIB. The indirect costs of pulmonary workup after readmission or emergency department workup may be overlooked if only considering direct costs, such as medication charges, medical supplies, and physician fees.

The Canonical Wnt Signaling Pathway Inhibits the Glucocorticoid Receptor Signaling Pathway in the Trabecular Meshwork.

Glucocorticoid-induced glaucoma is a secondary open-angle glaucoma. About 40% of the general population may develop elevated intraocular pressure on prolonged glucocorticoid treatment secondary to damages in the trabecular meshwork (TM), a tissue that regulates intraocular pressure. Therefore, identifying the key molecules responsible for glucocorticoid-induced ocular hypertension is crucial. In this study, Dickkopf-related protein 1 (Dkk1), a canonical Wnt signaling inhibitor, was found to be elevated in the aqueous humor and TM of glaucoma patients. At the signaling level, Dkk1 enhanced glucocorticoid receptor (GR) signaling, whereas Dkk1 knockdown or Wnt signaling activators decreased GR signaling in human TM cells as indicated by luciferase assays. Similarly, activation of the GR signaling inhibited Wnt signaling. At the protein level, glucocorticoid-induced extracellular matrix was inhibited by Wnt activation using Wnt activators or Dkk1 knockdown in primary human TM cells. In contrast, inhibition of canonical Wnt signaling by ß-catenin knockdown increased glucocorticoid-induced extracellular matrix proteins. At the physiological level, adenovirus-mediated Wnt3a expression decreased glucocorticoid-induced ocular hypertension in mouse eyes. In summary, Wnt and GR signaling inhibit each other in the TM, and canonical Wnt signaling activators may prevent the adverse effect of glucocorticoids in the eye.