Search

Purpose: Adolescent idiopathic scoliosis (AIS) is a common spinal deformity that affects millions of children worldwide. A variety of treatment algorithms exist for patients based on radiographic parameters such as the Cobb angle and the Risser stage. However, there has been a growing focus on nonradiographic outcomes such as back pain, which can cause functional disability and reduced quality of life for patients. In spite of this, back pain in AIS is poorly characterized in the literature. We aimed to summarize various factors that may influence back pain in AIS and the impact of different treatment methods on pain reduction. Methods: A comprehensive systematic review was undertaken using the PubMed and Cochrane database. Keywords that were utilized and combined with “Adolescent Idiopathic Scoliosis” included, “back pain,” “treatment,” “biomechanics,” “biochemistry,” “epidemiology,” and “biopsychosocial.” The literature was subsequently evaluated and deemed relevant or not relevant for inclusion. Results: A total of 93 articles were ultimately included in this review. A variety of contradictory literature was present for all sections related to epidemiology, underlying biomechanics and biochemistry, biopsychosocial factors, and treatment methodologies. Conclusion: Back pain in AIS is common but remains difficult to predict and treat. The literature pertaining to causative factors and treatment options is heterogeneous and inconclusive. Longer-term prospective studies combining biopsychosocial intervention in conjunction with existing curve correction techniques would be meaningful.

The American College of Radiology has published appropriateness criteria to help guide when to use MRI. Many health insurance carriers use proprietary clinical guidelines for prior authorization of imaging studies. The purpose of this study was to compare the specific criteria in those guidelines, for neck pain both with and without radicular symptoms. An online search was conducted to identify the guidelines for authorization of cervical spine MRI used by the largest commercial insurance carriers in the United States by market share. Guidelines were analyzed for neck pain with and without radiculopathy. Cervical trauma, myelopathy, infection, neoplasm, multiple sclerosis, and postprocedural care were excluded. The remaining criteria were broken down into categories including clinical symptoms, conservative therapy, other required radiologic studies, and clinical re-evaluation. Individual criteria within each of the categories were compared. After evaluation of the top 56 insurance companies in the United States, 30 companies using four main utilization management companies remained for analysis. After direct comparison of publicly available guidelines documents, notable discrepancies existed between the four companies in all subcategories analyzed. In addition, varying amounts of evidence-based literature was identified to support criteria requirements for prior authorization. This study demonstrates that the guidelines used by private health insurance companies for cervical MRI authorization in the setting of neck pain with and without cervical radiculopathy are inconsistent and use objective measures that have not been validated in the literature. We think this warrants additional scrutiny and investigation.

Background: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing. Methods: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol. Results: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85–1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63–0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08–1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. Conclusions: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04894877.

In the aftermath of the 11 September 2001 attacks against the United States, people immediately compared the attack with the Japanese assault on Pearl Harbor sixty years prior. In this article, we explore how US and world history textbooks published shortly after Pearl Harbor and 9/11 depicted and contextualized both events. The textbooks demonstrate that the depictions of Pearl Harbor neatly fit within a chapter about the origins, battles and home fronts of the Second World War. However, textbooks struggled to situate 9/11, placing it within histories of terrorism, histories of the modern Middle East, or twenty-first century problems. Moreover, the textbook authors likely relied on the powerful collective memories that each event triggered because the textbook descriptions of both attacks are exceedingly brief.

Defining criteria for mapping material units on airless, rocky bodies is challenging. Where the primary geologic process for most of a body’s history is impact cratering, traditional morphology-based mapping approaches may fail, because differences in morphologic characteristics among the various cratered surfaces can be hard to discern, and surface morphology is muted by the regolith’s physical and mechanical properties. In constructing a global geologic map of Vesta at 1:300,000-scale using the Dawn Framing Camera (FC), DTM-derived slope and contour, and multispectral data, we have countered this problem by utilizing a hybrid method of mapping that first requires creating two maps independently. The first map depends on morphology and topography to define map units, while the second uses spectral data to define units. The unique results of each map are then combined into the hybrid map units. Multispectral data provide unique insight into stratigraphy (material brought up through cratering processes) that is easily lost when using an albedo mosaic as the basemap. However, solely using a “color” ratio mosaic as a basemap easily magnifies potentially misleading data, because spectroscopy in the shorter wavelengths (UV-VIS-near IR) can only sample the upper few µm of the surface, and very little unique material is required to affect the signal of a regolith. Contacts defined by multispectral data may not coincide with clear morphologic boundaries as a result, so caution must be used in how the two maps are merged and clear criteria should be established to define hybrid map units. We found that the crucial exercise in ensuring unique data were retained when combining these two maps was to create a decision tree for determining which data would be primary in choosing where to draw unit boundaries. We divided the decision tree into the following if-then statements:If saturated colors (meaning the color signal in color-ratio spectral data was strong and the color itself was easy to describe) matched unit boundaries derived from morphology, there was no conflict. For example, saturated colors on Vesta tend to be associated with fresher expressions or exposures of regolith, which are more likely found at the youngest, freshest craters/ejecta, easily demarcated morphologically. If muted colors exist, where the morphology is relatively clear, the morphology is the primary guide for unit definition, as it retains the least altered record of geologic processes and the most reliable record of the nature of the rock bodies. Colors provide additional characteristics of such units, allowing for some interpretation of composition. If saturated colors are not associated with morphologic boundaries, the color boundaries are interpreted to record the most recent (even if very thin) impact evidence. In such cases we have mapped the saturated color data as impact material. This preserves the underlying morphology/topography information while supporting stratigraphic interpretations based on excavated subsurface layers revealed by crater ejecta. In the case of muted colors where the morphology is unclear, decisions must be made case-by-case, using all available data to make a reasonable determination of where to mark unit boundaries.

Descending thoracic aortic aneurysms may go undetected until severe and catastrophic complications such as rupture or dissection occur. Few clinical indicators exist to screen for aneurysms or predict risk of dissection or rupture. This study generated a plasma proteomic dataset from 150 patients with descending thoracic aortic disease and 52 controls to identify proteomic signatures capable of differentiating descending thoracic aortic disease from controls, as well as aneurysm from descending aortic dissections. Of the 1,468 peptides and 195 proteins quantified, 853 peptides and 99 proteins were significantly different between disease and controls. Using machine learning to classify disease from control, the highest precision-recall area under the curve (PR AUC) was achieved using significantly different proteins (PR AUC 0.99), followed by significant peptides (PR AUC 0.96). Despite no statistically significant protein signatures between aneurysm and dissection, use of all proteins was able to modestly classify between the disease states (PR AUC 0.77). To address correlation between proteins, a disease versus control classifier was optimized using only seven unique protein clusters, which achieved comparable performance to models trained on all/significant proteins (PR AUC 0.90). Model interpretation with permutation importance revealed that proteins differentiating disease and control function in coagulation, protein-lipid complex remodeling, and acute inflammatory response.

The COVID-19 pandemic has underlined the importance of an efficient and equitable supply of and access to essential health products. These factors are equally pertinent to the antimicrobial resistance pandemic, in which access to a portfolio of existing and pipeline antimicrobials plus complementary diagnostics is crucial. This Viewpoint focuses on market shaping in low-income and middle-income countries (LMICs), where the need for effective antimicrobials and complementary diagnostics is most acute. We propose the creation of a subscription and pooled procurement model that consolidates the growing demand for a portfolio of antimicrobials and diagnostics in LMICs. Anchored by regional market leaders, these pooling mechanisms would guarantee consistent private-sector and public-sector access in participating countries, while creating conditions for long-term best practice in stewardship. Supported by data from South Africa and India, this proposal sets out an innovative approach to tackle the antimicrobial resistance crisis in LMICs.

Aim: Women with evidence of ischemia and no obstructive coronary artery disease (INOCA) have an increased risk of major adverse cardiac events, including heart failure with preserved ejection fraction (HFpEF). To investigate potential links between INOCA and HFpEF, we examined pathophysiological findings present in both INOCA and HFpEF. Methods: We performed adenosine stress cardiac magnetic resonance imaging (CMRI) in 56 participants, including 35 women with suspected INOCA, 13 women with HFpEF, and 8 reference control women. Myocardial perfusion imaging was performed at rest and with vasodilator stress with intravenous adenosine. Myocardial perfusion reserve index was quantified as the ratio of the upslope of increase in myocardial contrast at stress vs. rest. All CMRI measures were quantified using CVI42 software (Circle Cardiovascular Imaging Inc). Statistical analysis was performed using linear regression models, Fisher’s exact tests, ANOVA, or Kruskal-Wallis tests. Results: Age (P = 0.007), Body surface area (0.05) were higher in the HFpEF group. Left ventricular ejection fraction (P = 0.02) was lower among the INOCA and HFpEF groups than reference controls after age adjustment. In addition, there was a graded reduction in myocardial perfusion reserve index in HFpEF vs. INOCA vs. reference controls (1.5 ± 0.3, 1.8 ± 0.3, 1.9 ± 0.3, P = 0.02), which was attenuated with age-adjustment. Conclusion: Reduced myocardial perfusion reserve appears to be a common pathophysiologic feature in INOCA and HFpEF patients.

Preclinical mechanistic studies have pointed towards RNA interference-mediated off-target effects as a major driver of hepatotoxicity for GalNAc–siRNA conjugates. Here, we demonstrate that a single glycol nucleic acid or 2′–5′-RNA modification can substantially reduce small interfering RNA (siRNA) seed-mediated binding to off-target transcripts while maintaining on-target activity. In siRNAs with established hepatotoxicity driven by off-target effects, these novel designs with seed-pairing destabilization, termed enhanced stabilization chemistry plus (ESC+), demonstrated a substantially improved therapeutic window in rats. In contrast, siRNAs thermally destabilized to a similar extent by the incorporation of multiple DNA nucleotides in the seed region showed little to no improvement in rat safety suggesting that factors in addition to global thermodynamics play a role in off-target mitigation. We utilized the ESC+ strategy to improve the safety of ALN-HBV, which exhibited dose-dependent, transient and asymptomatic alanine aminotransferase elevations in healthy volunteers. The redesigned ALN-HBV02 (VIR-2218) showed improved specificity with comparable on-target activity and the program was reintroduced into clinical development.

BACKGROUND: The extent to which health care systems have adapted to the COVID-19 pandemic to provide necessary cardiac diagnostic services is unknown.OBJECTIVES: The aim of this study was to determine the impact of the pandemic on cardiac testing practices, volumes and types of diagnostic services, and perceived psychological stress to health care providers worldwide.METHODS: The International Atomic Energy Agency conducted a worldwide survey assessing alterations from baseline in cardiovascular diagnostic care at the pandemic's onset and 1 year later. Multivariable regression was used to determine factors associated with procedure volume recovery.RESULTS: Surveys were submitted from 669 centers in 107 countries. Worldwide reduction in cardiac procedure volumes of 64% from March 2019 to April 2020 recovered by April 2021 in high- and upper middle-income countries (recovery rates of 108% and 99%) but remained depressed in lower middle- and low-income countries (46% and 30% recovery). Although stress testing was used 12% less frequently in 2021 than in 2019, coronary computed tomographic angiography was used 14% more, a trend also seen for other advanced cardiac imaging modalities (positron emission tomography and magnetic resonance; 22%-25% increases). Pandemic-related psychological stress was estimated to have affected nearly 40% of staff, impacting patient care at 78% of sites. In multivariable regression, only lower-income status and physicians' psychological stress were significant in predicting recovery of cardiac testing.CONCLUSIONS: Cardiac diagnostic testing has yet to recover to prepandemic levels in lower-income countries. Worldwide, the decrease in standard stress testing is offset by greater use of advanced cardiac imaging modalities. Pandemic-related psychological stress among providers is widespread and associated with poor recovery of cardiac testing.

RNA interference is a natural antiviral mechanism that could be harnessed to combat SARS-CoV-2 infection by targeting and destroying the viral genome. We screened lipophilic small-interfering RNA (siRNA) conjugates targeting highly conserved regions of the SARS-CoV-2 genome and identified leads targeting outside of the spike-encoding region capable of achieving ≥3-log viral reduction. Serial passaging studies demonstrated that a two-siRNA combination prevented development of resistance compared to a single-siRNA approach. A two-siRNA combination delivered intranasally protected Syrian hamsters from weight loss and lung pathology by viral infection upon prophylactic administration but not following onset of infection. Together, the data support potential utility of RNAi as a prophylactic approach to limit SARS-CoV-2 infection that may help combat emergent variants, complement existing interventions, or protect populations where vaccines are less effective. Most importantly, this strategy has implications for developing medicines that may be valuable in protecting against future coronavirus pandemics.

Pedicle screw fixation is a technique used to provide rigid fixation in thoracolumbar spine surgery. Safe intraosseous placement of pedicle screws is necessary to provide optimal fixation as well as to avoid damage to adjacent anatomic structures. Despite the wide variety of techniques available, none thus far has been able to fully eliminate the risk of malpositioned screws. Intraoperative 3-dimensional navigation (I3DN) was developed to improve accuracy in the placement of pedicle screws. To our knowledge, no previous studies have investigated whether infection rates are higher with I3DN. A single-institution, retrospective study of patients age > 18 undergoing thoracolumbar fusion and instrumentation was carried out and use of I3DN was recorded. The I3DN group had a significantly greater rate of return to the operating room for culture-positive incision and drainage (17 (4.1%) vs. 1 (0.6%), p = 0.025). In multivariate analysis, the use of I3DM did not reach significance with an OR of 6.49 (0.84–50.02, p = 0.073). Post-operative infections are multifactorial and potential infection risks associated with I3DN need to be weighed against the safety benefits of improved accuracy of pedicle screw positioning.

Background Gadolinium-based contrast agents were not approved in the United States for detecting coronary artery disease (CAD) prior to the current studies. Objectives The purpose of this study was to determine the sensitivity and specificity of gadobutrol for detection of CAD by assessing myocardial perfusion and late gadolinium enhancement (LGE) imaging. Methods Two international, single-vendor, phase 3 clinical trials of near identical design, “GadaCAD1” and “GadaCAD2,” were performed. Cardiovascular magnetic resonance (CMR) included gadobutrol-enhanced first-pass vasodilator stress and rest perfusion followed by LGE imaging. CAD was defined by quantitative coronary angiography (QCA) but computed tomography coronary angiography could exclude significant CAD. Results Because the design and results for GadaCAD1 (n = 376) and GadaCAD2 (n = 388) were very similar, results were summarized as a fixed-effect meta-analysis (n = 764). The prevalence of CAD was 27.8% defined by a ≥70% QCA stenosis. For detection of a ≥70% QCA stenosis, the sensitivity of CMR was 78.9%, specificity was 86.8%, and area under the curve was 0.871. The sensitivity and specificity for multivessel CAD was 87.4% and 73.0%. For detection of a 50% QCA stenosis, sensitivity was 64.6% and specificity was 86.6%. The optimal threshold for detecting CAD was a ≥67% QCA stenosis in GadaCAD1 and ≥63% QCA stenosis in GadaCAD2. Conclusions Vasodilator stress and rest myocardial perfusion CMR and LGE imaging had high diagnostic accuracy for CAD in 2 phase 3 clinical trials. These findings supported the U .S. Food and Drug Administration approval of gadobutrol-enhanced CMR (0.1 mmol/kg) to assess myocardial perfusion and LGE in adult patients with known or suspected CAD.

Background Respiratory motion correction is of importance in studies of coronary plaques employing F-18-NaF; however, the validation of motion correction techniques mainly relies on indirect measures such as test-retest repeatability assessments. In this study, we aim to compare and, thus, validate the respiratory motion vector fields obtained from the positron emission tomography (PET) images directly to the respiratory motion observed during four-dimensional cine-computed tomography (CT) by an expert observer. Purpose To investigate the accuracy of the motion correction employed in a software (FusionQuant) used for evaluation of F-18-NaF PET studies by comparing the respiratory motion of the coronary plaques observed in PET to the respiratory motion observed in 4D cine-CT images. Methods This study included 23 patients who undertook thoracic PET scans for the assessment of coronary plaques using F-18-sodium fluoride (F-18-NaF). All patients underwent a 5-s cine-CT (4D-CT), a coronary CT angiography (CTA), and F-18-NaF PET. The 4D-CT and PET scan were reconstructed into 10 phases. Respiratory motion was estimated for the non-contrast visible coronary plaques using diffeomorphic registrations (PET) and compared to respiratory motion observed on 4D-CT. We report the PET motion vector fields obtained in the three principal axes in addition to the 3D motion. Statistical differences were examined using paired t-tests. Signal-to-noise ratios (SNR) are reported for the single-phase images (end-expiratory phase) and for the motion-corrected image-series (employing the motion vector fields extracted during the diffeomorphic registrations). Results In total, 19 coronary plaques were identified in 16 patients. No statistical differences were observed for the maximum respiratory motion observed in x, y, and the 3D motion fields (magnitude and direction) between the CT and PET (X direction: 4D CT = 2.5 +/- 1.5 mm, PET = 2.4 +/- 3.2 mm; Y direction: 4D CT = 2.3 +/- 1.9 mm, PET = 0.7 +/- 2.9 mm, 3D motion: 4D CT = 6.6 +/- 3.1 mm, PET = 5.7 +/- 2.6 mm, all p >= 0.05). Significant differences in respiratory motion were observed in the systems' Z direction: 4D CT = 4.9 +/- 3.4 mm, PET = 2.3 +/- 3.2 mm, p = 0.04. Significantly improved SNR is reported for the motion corrected images compared to the end-expiratory phase images (end-expiratory phase = 6.8 +/- 4.8, motion corrected = 12.2 +/- 4.5, p = 0.001). Conclusion Similar respiratory motion was observed in two directions and 3D for coronary plaques on 4D CT as detected by automatic respiratory motion correction of coronary PET using FusionQuant. The respiratory motion correction technique significantly improved the SNR in the images.

Introduction: Late sodium channel inhibition with ranolazine may beneficially impact coronary microvascular dysfunction (CMD). We hypothesized that markers of ventricular volume/pressure (N-terminal -pro BNP [NT-proBNP]) and myocardial damage (ultra-high sensitivity cardiac troponin I [u-hs-TnI]) are related to therapeutic response. Methods: We analyzed CMD response in a randomized, double-blind, crossover trial of ranolazine vs. placebo using invasive coronary function testing or non-invasively cardiac magnetic resonance imaging (cMRI) myocardial perfusion reserve index (MPRI). NT pro-BNP and u-hs-TnI values were available in subgroups prior to trial enrollment. Treatment response was change in MPRI (Δ MPRI) or Seattle Angina Questionnaire, angina stability change (ΔSAQ). Spearman correlations and Wilcoxon Rank Sum test were used. Results: Among 128 participants, 12 had NT pro-BNP and 20 had u-hs-TnI available. Median NT pro-BNP and u-hs-TnI were (66 pg/mL) and (0.71 pg/mL), respectively. Higher u-hs-TnI (0.87pg/mL) positively correlated with improved ΔMPRI (Table), but not ΔSAQ (r= 0.03 p=0.80). No significant correlations between NT pro-BNP and ΔMPRI (r= -0.09, p=0.58) or ΔSAQ (r=0.005, P=0.976) were observed. Conclusion: Our study finds that higher u-hs-TnI, a measure of myocardial damage, related to improved cMRI perfusion reserve to the late-sodium channel blocker ranolazine. These results suggest that CMD accompanied by existing myocardial damage, likely secondary to ischemia, may have more favorable response to anti-ischemic therapy. Further studies are needed to validate these results in a larger cohort.

Introduction: Coronary computed tomography angiography (CCTA) in SCOT-HEART led to increased preventive therapy for coronary artery disease (CAD). We hypothesized that atherosclerosis on CCTA would lead to greater preventive therapy changes compared to invasive coronary angiography (ICA). Methods: We studied 429 consecutive patients with available electronic health records and nonobstructive CAD (1-69% epicardial stenosis) by CCTA for assessment of chest pain or exertional dyspnea (n=143), ICA (n=142), or no CAD on CCTA (n=144). Changes in preventive therapies were assessed at 6 weeks and 6 months. Statin intensification was defined as change to greater LDL-lowering capacity. Intensification of antiplatelet agents, ACEI/ARB, or beta-blockers was defined as increased dose. Pairwise comparisons were made with Bonferroni adjustment. Results: There was no difference in age or gender in nonobstructive CAD patients ( Table ). ICA patients had more baseline therapies. Six week statin initiation was more common (p=0.006) in CCTA nonobstructive group, but not statin intensification (p=0.24) ( Table ). Six month LDL lowering was observed in CCTA (114±40 to 94±39 mg/dL, pTable ). Conclusions: Nonobstructive CAD on CCTA is associated with greater statin initiation, but not intensification, at 6 weeks and lowering of LDL compared to ICA. Antiplatelet, beta-blocker, or ACEI/ARB prescriptions were not different in nonobstructive CAD by CCTA vs ICA. More preventive therapy changes occurred in nonobstructive CAD by either modality vs normal coronaries.

Aortic stenosis is a common condition associated with major morbidity, mortality and healthcare costs. Despite this, we currently lack any effective medical therapies that can treat or prevent disease development or progression. Modern advances in echocardiography and computed tomography (CT) have helped improve the assessment of aortic stenosis severity and monitoring of disease progression, whilst cardiac magnetic resonance imaging informs on myocardial health and the development of fibrosis. In a series of recent studies, 18F- sodium fluoride positron emission tomography and computed tomography has been shown to assess valvular disease activity and progression, providing mechanistic insights that can inform potential novel therapeutic approaches. This review will examine the latest advances in the imaging of aortic stenosis and bioprosthetic valve degeneration and explore how these techniques can assist patient management and potentially accelerate novel therapeutic developments.

We recently reported that RNAi-mediated off-target effects are important drivers of the hepatotoxicity observed for a subset of GalNAc–siRNA conjugates in rodents, and that these findings could be mitigated by seed-pairing destabilization using a single GNA nucleotide placed within the seed region of the guide strand. Here, we report further investigation of the unique and poorly understood GNA/RNA cross-pairing behavior to better inform GNA-containing siRNA design. A reexamination of published GNA homoduplex crystal structures, along with a novel structure containing a single (S)-GNA-A residue in duplex RNA, indicated that GNA nucleotides universally adopt a rotated nucleobase orientation within all duplex contexts. Such an orientation strongly affects GNA-C and GNA-G but not GNA-A or GNA-T pairing in GNA/RNA heteroduplexes. Transposition of the hydrogen-bond donor/acceptor pairs using the novel (S)-GNA-isocytidine and -isoguanosine nucleotides could rescue productive base-pairing with the complementary G or C ribonucleotides, respectively. GalNAc-siRNAs containing these GNA isonucleotides showed an improved in vitro activity, a similar improvement in off-target profile, and maintained in vivo activity and guide strand liver levels more consistent with the parent siRNAs than those modified with isomeric GNA-C or -G, thereby expanding our toolbox for the design of siRNAs with minimized off-target activity.

Background Journal clubs exist in a variety of forms in medical schools across the United States. Many incorporate a full spectrum of medical specialties, some are specific to certain interest groups or specialties, and many widely vary in whether or not they are school mandated or student-run. While these clubs are ubiquitously scattered throughout medical education, there has been very little quantitative or qualitative analysis regarding the efficacy of these clubs in enhancing medical students' abilities to evaluate clinical literature. The purpose of this study was to evaluate the effects of attending Surgical Journal Club meetings at Eastern Virginia Medical School from both a qualitative and quantitative perspective. The authors' hypothesis was that regular attendance of these sessions would improve student performance from a multitude of perspectives and demonstrate the value of clinical literature analysis earlier in medical education. Methods A fifteen question Likert survey was administered on an optional basis to thirty-six medical students attending journal club. Responses were analyzed anonymously, and there was no incentive or demerit for completing the survey. Data was compiled and the mean, median, and mode for each question calculated with “5” corresponding to “Strongly Agree” and “1” corresponding to “Strongly Disagree.” RESULTS Twenty-seven of thirty-six attendees to our seventh journal club meeting completed the survey. Student responses were overwhelming positive, with all but one question reaching above “Agree” by analysis of the mean responses. CONCLUSION Journal clubs remain an integral part of medical education but their importance has been diminished in recent years due to the increasing demands of other aspects of the first two years in medical school. We described a medical student run/established journal club that increased students' interest in surgery, their perceived knowledge-base, and comfort in critically analyzing medical journal articles.

The aim of this meta-analysis was to assess the diagnostic performance of various CMR imaging parameters for evaluating acute cardiac transplant rejection.Endomyocardial biopsy is the current gold standard for detection of acute cardiac transplant rejection. Cardiac magnetic resonance (CMR) is uniquely capable of myocardial tissue characterization and may be useful as a noninvasive alternative for the diagnosis of graft rejection.PubMed and Web of Science were searched for relevant publications reporting on the use of CMR myocardial tissue characterization for detection of acute cardiac transplant rejection with endomyocardial biopsy as the reference standard. Pooled sensitivity, specificity, and hierarchical modeling-based summary receiver-operating characteristic curves were calculated.Of 478 papers, 10 studies comprising 564 patients were included. The sensitivity and specificity for the detection of acute cardiac transplant rejection were 84.6 (95% CI: 65.6-94.0) and 70.1 (95% CI: 54.2-82.2) for T1, 86.5 (95% CI: 72.1-94.1) and 85.9 (95% CI: 65.2-94.6) for T2, 91.3 (95% CI: 63.9-98.4) and 67.6 (95% CI: 56.1-77.4) for extracellular volume fraction (ECV), and 50.1 (95% CI: 31.2-68.9) and 60.2 (95% CI: 36.7-79.7) for late gadolinium enhancement (LGE). The areas under the hierarchical modeling-based summary receiver-operating characteristic curve were 0.84 (95% CI: 0.81-0.87) for T1, 0.92 (95% CI: 0.89-94) for T2, 0.78 (95% CI: 0.74-0.81) for ECV, and 0.56 (95% CI: 0.51-0.60) for LGE. T2 values demonstrated the highest diagnostic accuracy, followed by native T1, ECV, and LGE (all P values 0.001 for T1, ECV, and LGE vs T2).T2 mapping demonstrated higher diagnostic accuracy than other CMR techniques. Native T1 and ECV provide high diagnostic use but lower diagnostic accuracy compared with T2, which was related primarily to lower specificity. LGE showed poor diagnostic performance for detection of rejection.

BACKGROUND: To evaluate the impact of respiratory-averaged computed tomography attenuation correction (RACTAC) compared to standard single-phase computed tomography attenuation correction (CTAC) map, on the quantitative measures of coronary atherosclerotic lesions of (18)F-sodium fluoride ((18)F-NaF) uptake in hybrid positron emission tomography and computed tomography (PET/CT). METHODS: This study comprised 23 patients who underwent (18)F-NaF coronary PET in a hybrid PET/CT system. All patients had a standard single-phase CTAC obtained during free-breathing and a 4D cine-CT scan. From the cine-CT acquisition, RACTAC maps were obtained by averaging all images acquired over 5 seconds. PET reconstructions using either CTAC or RACTAC were compared. The quantitative impact of employing RACTAC was assessed using maximum target-to-background (TBR(MAX)) and coronary microcalcification activity (CMA). Statistical differences were analyzed using reproducibility coefficients and Bland-Altman plots. RESULTS: In 23 patients, we evaluated 34 coronary lesions using CTAC and RACTAC reconstructions. There was good agreement between CTAC and RACTAC for TBR(MAX) (median [Interquartile range]): CTAC= 1.65[1.23–2.38], RACTAC= 1.63[1.23–2.33], p=0.55), with coefficient of reproducibility of 0.18, and CMA: CTAC= 0.10 [0–1.0], RACTAC= 0.15[0–1.03], p=0.55 with coefficient of reproducibility of 0.17 CONCLUSION: Respiratory-averaged and standard single-phase attenuation correction maps provide similar and reproducible methods of quantifying coronary (18)F-NaF uptake on PET/CT.

Antimicrobial resistance (AMR) is one of the most serious clinical and public healthcare challenges. In this video Daniel Berman, Nesta Challenges, provides an overview of the Longitude Prize, why the prize was set up and what the prize hopes to achieve. Daniel also provides insight into some of the rapid diagnostic tests currently in the running for the £8 million prize.

How can we prevent the rise of resistance to antibiotics? In this video, Daniel Berman, Nesta Challenges, discusses the global threat of AMR and how prizes like the Longitude Prize can foster the development of rapid diagnostic tests for bacterial infections, helping to contribute towards reducing the global threat of drug resistant bacteria. Daniel outlines how accelerating the development of rapid point-of-care tests will ensure that bacterial infections are treated with the most appropriate antibiotic, at the right time and in the right healthcare setting.

BACKGROUND CONTEXT Lumbar laminotomy (hemilaminectomy), with decompression of nerve root(s), including partial facetectomy, foraminotomy and/or excision of herniated intervertebral disc (CPT code 63030) is a common elective procedure performed by spine surgeons. While clinical indications vary from surgeon to surgeon, The North American Spine Society (NASS) has published surgical indication guidelines for these procedures. However, health insurance carriers and health consulting firms have also developed their own guidelines regarding the same procedure. Each insurance carrier has its own vetting process for developing guidelines and then using these guidelines to approve or reject coverage for patients who undergo procedure code 63030. PURPOSE The purpose of this study was to assess the surgical indication guidelines published by health insurance carriers with the largest market share in the United States for procedure code 63030 and to compare them to the NASS guidelines. STUDY DESIGN/SETTING Not applicable. PATIENT SAMPLE Not applicable. OUTCOME MEASURES Not applicable. METHODS The top ten insurance carriers in the United States were selected based on their national market share value. A web search was utilized to identify the elective surgical coverage policies for each company. Guidelines for emergent procedures indicated for cauda equina or spinal cord compression were excluded from our analysis, as were the guidelines for other means of microdiscectomy including percutaneous and laser techniques. Policy guidelines were reviewed and compared for surgical indication criteria including symptoms, physical exam findings, imaging, nonsurgical management modalities and duration of nonsurgical management. RESULTS The 10 largest insurance carriers in the United States queried were found to hold 51.8% market share. Only 60% of the companies evaluated had clear surgical guidelines accessible on their websites. Of these groups, 67% percent used guidelines purchased from either MCG or eviCore (health consulting firms) and 33% published their own guidelines. All guidelines required a physician to report subjective symptoms of lumbar radiculopathy. However, only 67% of guidelines required objective physical examination findings. Preoperative neuroimaging with MRI/CT was required in all guidelines. Only eviCore specified that the images must be performed within 6 months of surgery. Also, only eviCore required lumbar radiographs to be performed preoperatively. Of carriers, 83% required at least six weeks of failed nonsurgical management with analgesics, physical therapy and/or steroid injections, while one carrier required12 weeks. There was no consistency in the number of attempted nonsurgical modalities. CONCLUSIONS This study demonstrates that 40% of queried insurance carriers do not readily provide their surgical guidelines on the internet. Of the available guidelines, there is an alarming amount of variation among insurance carriers used to determine coverage of procedure code 63030. No carrier had guidelines entirely consistent with NASS guidelines. Patients, and their doctors, have a right to know the details of coverage when making informed decisions about surgical procedures. Our data suggests that further study is warranted to look into these discrepancies in coverage. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

The purpose of this study was to assess potential gender differences in size of the lateral and medial trochlea of the male and female knee as well as the variation within gender of potential osteochondral autograft transfer (OAT) donor site area. Two hundred and twelve skeletally mature patients, 106 males and 106 females, who underwent a 3T magnetic resonance imaging of the knee for a variety of indications were utilized for analysis. Exclusion criteria included degenerative arthritis, trochlear dysplasia, and poor image quality. Medial and lateral femoral trochlear cartilage width was obtained using a linear radiologic measurement tool. Widths were measured from a reproducible anatomic location representing the maximal trochlear dimension in a region where donor plugs are commonly harvested. Trochlear width was also plotted as a function of patient height. Statistical analysis was performed using a two-sample t-test. The mean and standard deviation of the lateral trochlear cartilage width (mm) for males and females were 23.38 +/− 2.14 and 20.44 +/− 2.16, respectively (p

Multiple regions in the human brain are dedicated to accomplish the feat of object recognition; yet our brains must also compute the 2D and 3D locations of the objects we encounter in order to make sense of our visual environments. A number of studies have explored how various object category-selective regions are sensitive to and have preferences for specific 2D spatial locations in addition to processing their preferred-stimulus categories, but there is no survey of how these regions respond to depth information. In a blocked functional MRI experiment, subjects viewed a series of category-specific (i.e., faces, objects, scenes) and unspecific (e.g., random moving dots) stimuli with red/green anaglyph glasses. Critically, these stimuli were presented at different depth planes such that they appeared in front of, behind, or at the same (i.e., middle) depth plane as the fixation point (Experiment 1) or simultaneously in front of and behind fixation (i.e., mixed depth; Experiment 2). Comparisons of mean response magnitudes between back, middle, and front depth planes reveal that face and object regions OFA and LOC exhibit a preference for front depths, and motion area MT+ exhibits a strong linear preference for front, followed by middle, followed by back depth planes. In contrast, scene-selective regions PPA and OPA prefer front and/or back depth planes (relative to middle). Moreover, the occipital place area demonstrates a strong preference for “mixed” depth above and beyond back alone, raising potential implications about its particular role in scene perception. Crucially, the observed depth preferences in nearly all areas were evoked irrespective of the semantic stimulus category being viewed. These results reveal that the object category-selective regions may play a role in processing or incorporating depth information that is orthogonal to their primary processing of object category information.

Bioprosthetic aortic valve degeneration is increasingly common, often unheralded, and can have catastrophic consequences.The authors sought to assess whetherExplanted degenerate bioprosthetic valves were examined ex vivo. Patients with bioprosthetic aortic valves were recruited into 2 cohorts with and without prosthetic valve dysfunction and underwent in vivo contrast-enhanced CT angiography,All ex vivo, degenerate bioprosthetic valves displayed

Surgical repair of articular cartilage defects in the knee currently utilizes surgical algorithms based on absolute defect size. These algorithms, which have not been validated, are currently utilized not only by surgeons but also by insurance carriers for justification of reimbursement policy. However, current algorithms do not account for morphological differences between individual patients and defect size relative to condylar dimension. We hypothesized that a significant difference in relative defect size compared with condylar dimension may exist between individuals. A 3T magnetic resonance imaging from 220 skeletally mature patients, 110 males and 110 females, were analyzed. Exclusion criteria included degenerative arthritis, anatomical defects, poor image quality, and genetic abnormalities such as dwarfism. Utilizing a radiological curved measurement probe, the femoral condylar articular width was obtained for both the medial and lateral condyles. The mean condylar width from a reproducible anatomic location representing the maximal condylar dimension was measured. Statistical analysis was performed using a two-sample t-test. The lateral condyle articular cartilage width (mm) for males and females was 31.62 ± 3.54 and 26.53 ± 3.70, respectively (p

Background Spinal fusion surgery is performed about half a million times per year in the United States and millions more worldwide. It is an effective method for reducing pain, increasing stability, and correcting deformity in patients with various spinal conditions. In addition to being a well-established risk factor for a variety of medical conditions, smoking has deleterious effects on the bone healing of spinal fusions. This review aims to specifically analyze the ways in which smoking affects the outcomes of spinal fusion and to explore ways in which these negative consequences can be avoided. Purpose This article provides a complete understanding of the ways smoking affects spinal fusion from a biochemical and clinical perspective. Recommendations are also provided for ways in which surgeons can limit patient exposure to the most serious negative outcomes associated with cigarette smoking. Study Design/Setting This study was a retrospective literature review done using the NCBI database. The research was compiled at NYU Hospital for Joint Diseases and the NYU Center for Musculoskeletal Care. Methods A comprehensive literature review was done spanning research on a variety of subjects related to smoking and spinal fusion surgery. The biochemistry of smoking and fusion healing were examined in great detail. In addition, both in vivo animal studies and human clinical studies were evaluated to explore fusion success related to the effects of smoking and its biochemical factors on spinal fusion surgery. Results Smoking significantly increases the risk of pseudoarthrosis for patients undergoing both lumbar and cervical fusions. In addition to nonunion, smoking also increases the risk of other perioperative complications such as infection, adjacent-segment pathology, and dysphagia. Treatment options are available that can be explored to reduce the risk of smoking-related morbidity, such as nicotine replacement therapy and use of bone morphogenetic proteins (BMPs). Conclusions It has been clearly demonstrated from both a biochemical and clinical perspective that smoking increases the rate of perioperative complications for patients undergoing spinal fusion surgery, particularly pseudoarthosis. It has also been shown that there are certain approaches that can reduce the risk of morbidity. The most important recommendation is smoking cessation for four weeks after surgery. In addition, patients may be treated with certain surgical techniques, including the use of BMPs, to reduce the risk of pseudoarthrosis. Lastly, nicotine replacement therapy is an area of continued interest in relation to spinal fusion outcomes and more research needs to be done to determine its efficacy moving forward.