Sequential Activation of Two Pathogen-Sensing Pathways Required for Type I Interferon Expression and Resistance to an Acute DNA Virus Infection.

Toll-like receptor 9 (TLR9), its adaptor MyD88, the downstream transcription factor interferon regulatory factor 7 (IRF7), and type I interferons (IFN-I) are all required for resistance to infection with ectromelia virus (ECTV). However, it is not known how or in which cells these effectors function to promote survival. Here, we showed that after infection with ECTV, the TLR9-MyD88-IRF7 pathway was necessary in CD11c(+) cells for the expression of proinflammatory cytokines and the recruitment of inflammatory monocytes (iMos) to the draining lymph node (dLN). In the dLN, the major producers of IFN-I were infected iMos, which used the DNA sensor-adaptor STING to activate IRF7 and nuclear factor κB (NF-κB) signaling to induce the expression of IFN-α and IFN-ß, respectively. Thus, in vivo, two pathways of DNA pathogen sensing act sequentially in two distinct cell types to orchestrate resistance to a viral disease.

Concurrent Validity and Reliability of Manual Versus Specific Device Transcostal Measurements for Breathing Diaphragm Thickness by Ultrasonography in Lumbopelvic Pain Athletes.

The use of rehabilitative ultrasound imaging (RUSI) to evaluate diaphragm thickness during breathing in athletes who suffer from non-specific lumbopelvic pain presents some measurement errors. The purpose of this study was to evaluate intra- and inter-sessions, intra- and inter-rater reliabilities, and concurrent validity of diaphragm thickness measurements during breathing using transcostal RUSI with a novel thoracic orthotic device that was used to fix the US probe versus those measurements obtained using manual fixation. A total of 37 athletes with non-specific lumbopelvic pain were recruited. Intra- (same examiner) and inter-rater (two examiners) and intra- (same day) and inter-session (alternate days) reliabilities were analyzed. All measurements were obtained after manual probe fixation and after positioning the thoracic orthotic device to fix the US probe in order to correctly correlate both measurement methods. Both left and right hemi-diaphragm thickness measurements were performed by transcostal RUSI at maximum inspiration, expiration, and the difference between the two parameters during relaxed breathing. Intra-class correlation coefficients (ICC), standard errors of measurement (SEM), minimum detectable changes (MCD), systematic errors, and correlations (r) were assessed. Orthotic device probe fixation showed excellent reliability (ICC = 0.852-0.996, SEM = 0.0002-0.054, and MDC = 0.002-0.072), and most measurements did not show significant systematic errors (p > 0.05). Despite manual probe fixation with a reliability ranging from good to excellent (ICC = 0.714-0.997, SEM = 0.003-0.023, and MDC = 0.008-0.064 cm), several significant systematic measurement errors (p < 0.05) were found. Most significant correlations between both orthotic device and manual probe fixation methods were moderate (r = 0.486-0.718; p < 0.05). Bland-Altman plots indicated adequate agreement between both measurement methods according to the agreement limits. The proposed novel thoracic orthotic device may allow ultrasound probe fixation to provide valid and reliable transcostal RUSI measurements of diaphragmatic thickness during relaxed breathing thus reducing some measurement errors and avoiding systematic measurement errors. It may be advisable to measure diaphragm thickness and facilitate visual biofeedback with respect to diaphragm re-education during normal breathing in athletes with non-specific lumbopelvic pain.

Cutting Edge: Protection by Antiviral Memory CD8 T Cells Requires Rapidly Produced Antigen in Large Amounts.

Numerous attempts to produce antiviral vaccines by harnessing memory CD8 T cells have failed. A barrier to progress is that we do not know what makes an Ag a viable target of protective CD8 T cell memory. We found that in mice susceptible to lethal mousepox (the mouse homolog of human smallpox), a dendritic cell vaccine that induced memory CD8 T cells fully protected mice when the infecting virus produced Ag in large quantities and with rapid kinetics. Protection did not occur when the Ag was produced in low amounts, even with rapid kinetics, and protection was only partial when the Ag was produced in large quantities but with slow kinetics. Hence, the amount and timing of Ag expression appear to be key determinants of memory CD8 T cell antiviral protective immunity. These findings may have important implications for vaccine design.

Boosting Multi-Vehicle Tracking with a Joint Object Detection and Viewpoint Estimation Sensor.

In this work, we address the problem of multi-vehicle detection and tracking for traffic monitoring applications. We preset a novel intelligent visual sensor for tracking-by-detection with simultaneous pose estimation. Essentially, we adapt an Extended Kalman Filter (EKF) to work not only with the detections of the vehicles but also with their estimated coarse viewpoints, directly obtained with the vision sensor. We show that enhancing the tracking with observations of the vehicle pose, results in a better estimation of the vehicles trajectories. For the simultaneous object detection and viewpoint estimation task, we present and evaluate two independent solutions. One is based on a fast GPU implementation of a Histogram of Oriented Gradients (HOG) detector with Support Vector Machines (SVMs). For the second, we adequately modify and train the Faster R-CNN deep learning model, in order to recover from it not only the object localization but also an estimation of its pose. Finally, we publicly release a challenging dataset, the GRAM Road Traffic Monitoring (GRAM-RTM), which has been especially designed for evaluating multi-vehicle tracking approaches within the context of traffic monitoring applications. It comprises more than 700 unique vehicles annotated across more than 40.300 frames of three videos. We expect the GRAM-RTM becomes a benchmark in vehicle detection and tracking, providing the computer vision and intelligent transportation systems communities with a standard set of images, annotations and evaluation procedures for multi-vehicle tracking. We present a thorough experimental evaluation of our approaches with the GRAM-RTM, which will be useful for establishing further comparisons. The results obtained confirm that the simultaneous integration of vehicle localizations and pose estimations as observations in an EKF, improves the tracking results.

Case of a Missed Giant Cell Tumor of Bone: An Opportunity to Observe its Natural History Disease.

Giant cell tumor of bone (GCT) is a benign neoplasm that most commonly presents with pain and is rarely diagnosed as an incidental finding. We present the report of a young woman whose pre-operative MRI was only noted to have a tear of the anterior cruciate ligament (ACL). Subsequently, the patient underwent anACL reconstruction. A second MRI, performed four years later, demonstrated an enlarged mass in the same location. A retrospective evaluation of the initial MRI revealed an eccentric metaphyseal lesion. Histology obtained from the lesion demonstrated a giant cell tumor of bone. We present the case of an asymptomatic GCT discovered retrospectively as an incidental finding and reevaluated four years later. 'Ihis case serves as a reminder of the importance for the critical review of routine preoperative imaging and also offers a unique perspective on the natural history of giant cell tumor of bone.

Antibody inhibition of a viral type 1 interferon decoy receptor cures a viral disease by restoring interferon signaling in the liver.

Type 1 interferons (T1-IFNs) play a major role in antiviral defense, but when or how they protect during infections that spread through the lympho-hematogenous route is not known. Orthopoxviruses, including those that produce smallpox and mousepox, spread lympho-hematogenously. They also encode a decoy receptor for T1-IFN, the T1-IFN binding protein (T1-IFNbp), which is essential for virulence. We demonstrate that during mousepox, T1-IFNs protect the liver locally rather than systemically, and that the T1-IFNbp attaches to uninfected cells surrounding infected foci in the liver and the spleen to impair their ability to receive T1-IFN signaling, thus facilitating virus spread. Remarkably, this process can be reversed and mousepox cured late in infection by treating with antibodies that block the biological function of the T1-IFNbp. Thus, our findings provide insights on how T1-IFNs function and are evaded during a viral infection in vivo, and unveil a novel mechanism for antibody-mediated antiviral therapy.

Low Back Pain: Utilization of Urgent Cares Relative to Emergency Departments.

STUDY DESIGN/SETTING: Retrospective study. OBJECTIVE: To understand why patients utilize emergency departments (EDs) versus urgent care centers for low back pain (LBP). SUMMARY OF BACKGROUND DATA: LBP is a common reason for ED visits. In the setting of trauma or recent surgery, the resources of EDs may be needed. However, urgent care centers may be appropriate for other cases. MATERIALS AND METHODS: Adult patients below 65 years of age presenting to the ED or urgent care on the day of diagnosis of LBP were identified from the 2019 PearlDiver M151 administrative database. Exclusion criteria included history of radiculopathy or sciatica, spinal surgery, spinal cord injury, other traumatic, neoplastic, or infectious diagnoses in the 90 days prior, or Medicare insurance. Patient age, sex, Elixhauser comorbidity index, geographic region, insurance, and management strategies were extracted. Factors associated with urgent care relative to ED utilization were assessed using multivariable analysis. RESULTS: Of 356,284 LBP patients, ED visits were identified for 345,390 (96.9%) and urgent care visits for 10,894 (3.1%). Factors associated with urgent care use relative to the ED were: geographic region [relative to Midwest; Northeast odds ratio (OR): 5.49, South OR: 1.54, West OR: 1.32], insurance (relative to Medicaid; commercial OR: 4.06), lower Elixhauser comorbidity index (OR: 1.28 per two-point decrease), and higher age (OR: 1.10 per decade), female sex (OR: 1.09), and use of advanced imaging (OR: 0.08) within 1 week ( P <0.001 for all). CONCLUSIONS: Most patients presenting for a first diagnosis of isolated LBP went to the ED relative to urgent care. The greatest drivers of urgent care versus ED utilization for LBP were insurance type and geographic region. Utilization of advanced imaging was higher among ED patients, but rates of surgical intervention were similar between those seen in the ED and urgent care.

Total spine MRI for the preoperative evaluation of adolescent idiopathic scoliosis: part 1.

Adolescent idiopathic scoliosis is a commonly encountered condition often diagnosed on screening examination. Underlying, asymptomatic neural axis abnormalities may be present at the time of diagnosis. At certain institutions, total spine MRI is obtained preoperatively to identify these abnormalities. We provide a framework for the radiologist to follow while interpreting these studies. In part 1, we discuss Arnold Chiari malformations, syringomyelia, and the tethered cord. In part 2, we focus on spinal cord tumors, dysraphisms, to include diastematomyelia, and vertebral anomalies.

Total spine MRI for the preoperative evaluation of adolescent idiopathic scoliosis: Part 2 - spinal cord tumors, dysraphisms, diastematomyelia, and vertebral anomalies.

Adolescent idiopathic scoliosis is a commonly encountered condition often diagnosed on screening examination. Underlying, asymptomatic neural axis abnormalities may be present at the time of diagnosis. At certain institutions, total spine MRI is obtained preoperatively to identify these abnormalities. We provide a framework for the radiologist to follow while interpreting these studies. In part 1, we discuss Arnold Chiari malformations, syringomyelia, and the tethered cord. In part 2, we focus on spinal cord tumors, dysraphisms, to include diastematomyelia, and vertebral anomalies.

Robotic Versus Navigation Assisted Posterior Lumbar Fusion: A National Database Study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Compare perioperative adverse events and reoperations between navigation-assisted and robotic-assisted posterior lumbar fusion. SUMMARY OF BACKGROUND DATA: Navigation has become increasingly utilized for posterior lumbar fusion (PLF). More recently, robotic assistance systems have been gaining traction. However, the incremental advantage of these systems has been unclear in the literature. METHODS: Patients undergoing one to three level PLF (with or without anterior or posterior interbody fusion) were identified from the 2015-2022 M161Ortho PearlDiver Database using CPT codes. Navigation assistance was identified based on CPT coding and robotic assistance was based on ICD-10 procedural coding. Navigation-assisted cases were matched 4:1 to robotic assisted patients based on age, sex, Elixhauser Comorbidity Index, number of levels fuse, and concomitant anterior fusion. Incidence of 90-day adverse outcomes were assessed and compared with multivariable logistical regression. Bonferroni correction was applied for multiple testing. Rate of reoperation was assessed using a Kaplan-Meier survival analysis. RESULTS: From 2015 to 2022, there has been a significant increase in both navigation and robotic assisted lumbar fusions, with navigation-assisted surgery being significantly more common. After matching, there were 2,401 navigation-assisted cases and 651 robotic-assisted cases. On multivariate analysis, there no significant differences in 90-day any, severe, or minor adverse events. There was a significant increase odd of readmissions in the robotic cohort (OR: 1.77, P<0.001). There were no differences in three-year reoperation rates between the navigation-assisted and robotic-assisted cohorts (95.8% versus 94.0%, P=0.30). CONCLUSIONS: As spinal navigation has been gaining popularity and robotic assistance is starting to be further utilized, the incremental advantage of different techniques may be questioned. While further study and technique evolution are ongoing, the current study was not able to demonstrate 90-day or 3-year incremental advantages for robotics relative to navigation based on the metrics evaluated.

Effectiveness of simultaneous bilateral visual diaphragm biofeedback under low back pain: influence of age and sex.

Introduction: The aim of the present study was to determine the effectiveness of simultaneous bilateral visual diaphragm biofeedback (BFB) from ultrasonography in conjunction with inspiratory muscle training (IMT) on diaphragmatic thickness during normal breathing and respiratory and clinical outcomes in patients with non-specific low back pain (NSLBP) and determine the influence of age and sex. Methods: A single-blind randomized clinical trial was carried out (NCT04582812). A total sample of 96 patients with NSLBP was recruited and randomized by sex-based stratification into IMT (n = 48) and BFB + IMT (n = 48) interventions over 8 weeks. Bilateral diaphragmatic thickness at maximum inspiration (Tins) and expiration (Texp), respiratory pressures, lung function, pain intensity, bilateral pressure pain threshold (PPT), disability, and quality of life were measured at baseline and after 8 weeks. Results: The BFB + IMT group showed significant differences (p < 0.05) with increased left hemidiaphragm thickness at Tins and Tins-exp (d = 0.38-053), and right and left PPT (d = 0.71-0.74) versus the IMT group. The interaction with sex was statistically significant (p = 0.007; F(1,81) = 7.756; ηp 2 = 0.087) and higher left hemidiaphragm thickness at Tins was predicted by the BFB + IMT group (R 2 = 0.099; ß = 0.050; F(1,82) = 8.997; p = 0.004) and male sex (R 2 = 0.079; ß = 0.045; F(1,81) = 7.756;p = 0.007). Furthermore, greater left hemidiaphragm thickness at Tins-exp was predicted by younger age (R 2 = 0.052; ß = -0.001; F(1,82) = 4.540; p = 0.036). Discussion: The simultaneous bilateral visual diaphragm biofeedback by ultrasonography in conjunction with IMT was effective in both increasing the left diaphragmatic thickness during inspiration, which was positively influenced and predicted by male sex and younger age, and increasing the bilateral PPT of the paraspinal muscles in patients with NSLBP.

A Secondary Analysis of Gender Respiratory Features for Ultrasonography Bilateral Diaphragm Thickness, Respiratory Pressures, and Pulmonary Function in Low Back Pain.

The aim of the present study was to determine the gender respiratory differences of bilateral diaphragm thickness, respiratory pressures, and pulmonary function in patients with low back pain (LBP). A sample of 90 participants with nonspecific LBP was recruited and matched paired by sex (45 women and 45 men). Respiratory outcomes included bilateral diaphragm thickness by ultrasonography, respiratory muscle strength by maximum inspiratory (MIP) and expiratory (MEP) pressures, and pulmonary function by forced expiratory volume during 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC spirometry parameters. The comparison of respiratory outcomes presented significant differences (p < 0.001), with a large effect size (d = 1.26-1.58) showing means differences (95% CI) for MIP of -32.26 (-42.99, -21.53) cm H2O, MEP of -50.66 (-64.08, -37.25) cm H2O, FEV1 of -0.92 (-1.18, -0.65) L, and FVC of -1.00 (-1.32, -0.69) L, with lower values for females versus males. Gender-based respiratory differences were presented for maximum respiratory pressures and pulmonary function in patients with nonspecific LBP. Women presented greater inspiratory and expiratory muscle weakness as well as worse lung function, although these differences were not linked to diaphragm thickness during normal breathing.

Memory CD8+ T cells specific for a single immunodominant or subdominant determinant induced by peptide-dendritic cell immunization protect from an acute lethal viral disease.

The antigens recognized by individual CD8(+) T cells are small peptides bound to major histocompatibility complex (MHC) class I molecules. The CD8(+) T cell response to a virus is restricted to several peptides, and the magnitudes of the effector as well as memory phases of the response to the individual peptides are generally hierarchical. The peptide eliciting a stronger response is called immunodominant (ID), and those with smaller-magnitude responses are termed subdominant (SD). The relative importance of ID and SD determinants in protective immunity remains to be fully elucidated. We previously showed that multispecific memory CD8(+) T cells can protect susceptible mice from mousepox, an acute lethal viral disease. It remained unknown, however, whether CD8(+) T cells specific for single ID or SD peptides could be protective. Here, we demonstrate that immunization with dendritic cells pulsed with ID and some but not all SD peptides induces memory CD8(+) T cells that are fully capable of protecting susceptible mice from mousepox. Additionally, while natural killer (NK) cells are essential for the natural resistance of nonimmune C57BL/6 (B6) to mousepox, we show that memory CD8(+) T cells of single specificity also protect B6 mice depleted of NK cells. This suggests it is feasible to produce effective antiviral CD8(+) T cell vaccines using single CD8(+) T cell determinants and that NK cells are no longer essential when memory CD8(+) T cells are present.

Imaging in spinal infections: Current status and future directions.

Imaging plays an important role in the diagnosis of spinal infections. Early diagnosis is paramount in the treatment of spinal infections and leads to improved outcomes. This article reviews the imaging and relevant clinical details of infections of the spine: pyogenic spondylodiscitis, tuberculous spondylodiscitis, septic facet arthritis, epidural abscess, and subdural abscess. Though radiographs can reveal subtle changes with infections, advanced imaging modalities have increased sensitivity to aid in early diagnosis. Magnetic resonance imaging (MRI) is emphasized given it is generally the most sensitive and specific advanced imaging modality. However, nuclear medicine imaging and computer tomography (CT) play a role diagnosis in cases where MRI is not available or contra-indicated. Additionally, CT is also important for image-guided biopsy to guide antimicrobial treatment.

Incidental Durotomy After Posterior Lumbar Decompression Surgery Associated With Increased Risk for Venous Thromboembolism.

INTRODUCTION: Incidental durotomies can occur during posterior lumbar decompression surgery. Not only can this slow patient recovery but many surgeons recommend a period of bed rest in these situations, which can further slow mobilization. This immobility might be associated with increased risk of venous thromboembolism (VTE) after spinal surgery. This study aims to determine whether incidental durotomies are associated with increased risk of VTE in patients undergoing lumbar decompression surgery. METHODS: Adult patients undergoing laminectomy or laminotomy (excluding any with concomitant fusion procedures) for degenerative etiologies and with a minimum of 90-day follow-up were identified from the MSpine Pearldiver dataset. Incidental durotomies were identified based on hospital administrative coding, and patient demographics, comorbidities, and the occurrence and timing of VTE (deep vein thrombosis [DVT] and/or pulmonary embolism) were defined. Univariate and multivariate analyses were performed. RESULTS: Of 156,488 lumbar decompression patients included in the study, incidental durotomies was noted for 2,036 (1.3%). Markedly more VTEs were observed in the first five days in the incidental durotomies group ( P < 0.001) but not incrementally any day after ( P > 0.05). On univariate analyses, a significant increased risk of VTE, DVT, and PE was observed ( P < 0.001 for each). On multivariate analyses controlling for age, sex, and comorbidities, odds were significantly increased for VTE (Odds ratios = 1.75, P < 0.001) and DVT (OR = 1.70, P < 0.001) but not independently significant for pulmonary embolism. DISCUSSION: Patients who have incidental durotomies during lumbar laminectomy or laminotomy surgery were found to have increased odds of VTE, primarily in the first five days. Although not all factors associated with this could be directly determined, slower mobilization would seem to be a likely contributing factor. Increasing mobilization and/or adjusting chemoprophylaxis in this group would seem appropriately considered.

Postoperative spine surgical site infections: high rate of failure of one-stage irrigation and debridement.

BACKGROUND CONTEXT: Following spine surgery, postoperative surgical site infection (SSI) is a rare but potentially devastating complication. Previous studies have assessed risk factors for spine SSI and one aimed to develop risk stratification tool to assess management options, but this tool has not been externally validated or regularly used. PURPOSE: The current study aimed to investigate the rate of SSI following elective spine surgery, surgical management pursued, and success of traditionally utilized one-stage of irrigation and debridement (I&D) with closure over drains. STUDY DESIGN: Retrospective case-control study. PATIENT SAMPLE: Adult, elective spine surgeries performed at a single academic institution between 2013 and 2021 were evaluated. Patients who developed SSI requiring surgical intervention were identified. OUTCOME MEASURES: Those who underwent initial management with I&D and closure over drains were assessed for need of subsequent I&D (considered failure of initial infection management). METHODS: Of spine surgeries meeting inclusion criteria, those with SSI were identified and management was characterized. For those who did and did not fail attempted one stage I&D with closure over drains, pre-operative and surgical variables from the index procedure as well as infection characteristics were assessed and compared with univariable and multivariable analyses. RESULTS: Of 11,023 elective spine surgeries, SSI was identified for 76 (0.7%). For initial management, I&D with closure over drains was used for 66 (86.8%) while I&D and wound vacuum management was used 10 (13.2%). Failure of attempted one stage I&D (requiring subsequent I&D procedure) was identified for 18 (27% of those undergoing I&D and closure over drains). Of multiple patient, surgical, and infection characteristics, the only factor identified as independently predictive of one stage I&D failure was presence of bacteremia (odds ratio [OR] 38.3, p=0.0007). Within the sub-cohort of patients with bacteremia, failure of attempted one stage I&D was noted for 80%. CONCLUSION: Less than one percent of a large cohort of patients undergoing spine surgery were found to develop SSIs. Of those undergoing attempted one stage I&D, most patient, surgical, and infection variables did not influence outcome of the intervention. However, those with bacteremia were at 38.3 times greater odds of failing attempted one-stage I&D. These results suggest considering delayed closure approaches in these cases.

Weight loss makes the difference: perioperative outcomes following posterior lumbar fusion in patients with and without weight loss following bariatric surgery.

BACKGROUND CONTEXT: Morbid obesity (MO) has been associated with increased risk of adverse events following procedures such as posterior lumbar fusion (PLF). While preemptive bariatric surgery (BS) has been considered for those with MO (body mass index [BMI] ≥35 kg/m2), not all undergoing such intervention have significant weight loss, and the impact of BS has been shown to correlate with weight loss after different related procedures. PURPOSE: To examine outcomes following isolated single level PLF among patients with history of BS who subsequently did and did not transition out of the morbidly obese category. STUDY DESIGN/SETTING: Retrospective case-control study. PATIENT SAMPLE: The PearlDiver 2010-Q1 2020 MSpine database was used to identify adult patients undergoing elective isolated PLF. Patients were excluded if they had a history of infection, neoplasm, or trauma in the 90-days prior to their PLF and if they were not active in the database for at least 90 days following their surgery. Three sub-cohorts were defined: 1) MO controls without a history of BS (-BS+MO), 2) patients with prior BS procedure who remained MO (+BS+MO), and 3) patients with prior BS who were no longer MO at the time of PLF (+BS-MO). Matched 1:1:1 populations were created for these three sub-cohorts based on age, sex and Elixhauser Comorbidity Index (ECI). OUTCOME MEASURES: Ninety-day adverse events and readmission rates were assessed and compared between the three sub-cohorts (-BS+MO, +BS+MO, +BS-MO). METHODS: Univariable analyses and multivariable logistic regression were performed on the matched population to compare 90-day adverse events and readmission rates controlling for age, sex, and ECI. RESULTS: The current study identified PLF patients who were MO at the time of surgery but did not have a history of BS (-BS+MO, n=34,236), those who had BS and remained MO (+BS+MO, n=564), and those who had MS and were no longer MO (+BS-MO, n=209 which was only 27% of those who had BS). On multivariable analysis of the matched populations, those that had BS but remained MO (+BS+MO) were not at reduced odds of 90-day adverse events. However, those that had BS and were no longer MO (+BS-MO) were at reduced odds of 90-day any, severe, and minor adverse events (OR 0.41, 0.51, and 0.37, respectively with p<0.05 for all). CONCLUSIONS: Only 27% of those with a history of BS prior to PLF transitioned out of the MO category. Compared to those who were morbidly obese without BS, those who had BS were only at reduced risk of 90-day adverse events if they actually lost weight sufficient to drop out of morbidly obesity. These findings should be taken into account when counseling patients and interpreting prior studies.

Current approaches to evaluate the function of cytotoxic T-cells in non-human primates.

Cytotoxic T-lymphocytes (CTL) are a subset of T-cells that play a critical role in protecting against intracellular infections and cancer, and have the ability to identify and kill infected or transformed cells expressing non-self peptides associated with major histocompatibility (MHC) Class I molecules. Conversely, aberrant CTL activity can contribute to immune-related pathology under conditions of overwhelming infection or autoimmunity. Disease-modifying therapeutics can have unintended effects on CTL, and a growing number of therapeutics are intended to either suppress or enhance CTL or their functions. The susceptibility of CTL to unintended effects from common therapeutic modalities underscores the need for a better understanding of the impact that such therapies have on CTL function and the associated safety implications. While there are reliable ways of quantifying CTL, notably via flow cytometric analysis of specific CTL markers, it has been a greater challenge to implement fit-for-purpose methods measuring CTL function in the context of safety studies of therapeutics. This review focuses on methods for measuring CTL responses in the context of drug safety and pharmacology testing, with the goals of informing the reader about current approaches, evaluating their pros and cons, and providing perspectives on the utility of these approaches for safety evaluation.

Ultrasonographic reliability and repeatability of simultaneous bilateral assessment of diaphragm muscle thickness during normal breathing.

Background: The diaphragm is considered the main muscle involved in breathing and also linked to trunk stabilization functions. Up to date, rehabilitative ultrasound imaging (RUSI) has been the most used technique to evaluate unilaterally the transcostal diaphragm thickness. Nevertheless, the inspiratory activity of both hemi-diaphragms is bilaterally performed at the same time, and its simultaneous evaluation with a thoracic orthosis could improve its assessment as well as its re-education with visual biofeedback of both hemi-diaphragms at the same time. The purpose was to evaluate the reliability and repeatability of simultaneous thickness measurements of both hemi-diaphragms bilaterally during normal breathing using a thoracic orthosis that allowed bilateral fixation of both right and left ultrasound probes. Methods: The study was conducted in 46 healthy subjects, whose diaphragm thickness was measured bilaterally and simultaneously in the anterior axillary line during relaxed breathing with a designed thoracic orthosis and 2 ultrasound tools. Intra-examiner (same examiner), inter-examiner (2 examiners), intra-session (1 hour) and inter-session (1 week) reliability and repeatability between each pair of measurements of diaphragm muscle thickness were analyzed during normal breathing. Results: Reliability and repeatability for intra-session evaluations using the thoracic orthosis were excellent to evaluate simultaneous thickness of both hemi-diaphragms by bilateral probes fixation (intraclass correlation coefficient =0.919-0.997; standard error of measurement =0.002-0.007 cm; minimum detectable change =0.006-0.020 cm), without systematic errors (P>0.05) between each pair of measurements. Nevertheless, inter-session evaluations varied from good to excellent using the bilateral probes fixation (intraclass correlation coefficient =0.614-0.984; standard error of measurement =0.006-0.028 cm; minimum detectable change =0.017-0.079 cm), although some systematic errors were presented (P<0.05). Conclusions: Good to excellent reliability and repeatability was shown for simultaneous thickness measurements of both hemi-diaphragms bilaterally during normal breathing. Despite systematic errors were presented for some inter-examiner assessments, the use of the thoracic orthosis that allowed bilateral fixation of ultrasound probes could be recommended for simultaneous hemi-diaphragms breathing re-education by visual biofeedback.

Severe contracture in the lower extremity resulting from an osteoid osteoma of the lumbar spine in close proximity to neural elements in an adolescent: a case report.

CASE: We report a rare case of a right-sided L4-5 facet osteoid osteoma in a 11-year-old female who presented with lower extremity pain, contractures, and gait disturbance in the setting of failed radiofrequency ablation. After open excision and single-level posterolateral fusion with instrumentation, her symptoms resolved and her spinopelvic parameters normalized. CONCLUSIONS: This case highlights the contracture that may occur as a result of neurogenic pain from an osteoid osteoma in close proximity to neural structures.