Cross-Sectional Analysis of Exome Sequencing Diagnosis in Patients With Neurologic Phenotypes Facing Barriers to Clinical Testing.

Background and Objectives: Exome sequencing (ES) demonstrates a 20-50 percent diagnostic yield for patients with a suspected monogenic neurologic disease. Despite the proven efficacy in achieving a diagnosis for such patients, multiple barriers for obtaining exome sequencing remain. This study set out to assess the efficacy of ES in patients with primary neurologic phenotypes who were appropriate candidates for testing but had been unable to pursue clinical testing. Methods: A total of 297 patients were identified from the UCLA Clinical Neurogenomics Research Center Biobank, and ES was performed, including bioinformatic assessment of copy number variation and repeat expansions. Information regarding demographics, clinical indication for ES, and reason for not pursuing ES clinically were recorded. To assess diagnostic efficacy, variants were interpreted by a multidisciplinary team of clinicians, bioinformaticians, and genetic counselors in accordance with the American College of Medical Genetics and Genomics variant classification guidelines. We next examined the specific barriers to testing for these patients, including how frequently insurance-related barriers such as coverage denials and inadequate coverage of cost were obstacles to pursuing exome sequencing. Results: The cohort primarily consisted of patients with sporadic conditions (n = 126, 42.4%) of adult-onset (n = 239, 80.5%). Cerebellar ataxia (n = 225, 75.8%) was the most common presenting neurologic phenotype. Our study found that in this population of mostly adult patients with primary neurologic phenotypes that were unable to pursue exome sequencing clinically, 47 (15.8%) had diagnostic results while an additional 24 patients (8.1%) had uncertain results. Of the 297 patients, 206 were initially recommended for clinical exome but 88 (42.7%) could not pursue ES because of insurance barriers, of whom 14 (15.9%) had diagnostic findings, representing 29.8% of all patients with diagnostic findings. In addition, the incorporation of bioinformatic repeat expansion testing was valuable, identifying a total of 8 pathogenic repeat expansions (17.0% of all diagnostic findings) including 3 of the common spinocerebellar ataxias and 2 patients with Huntington disease. Discussion: These findings underscore the importance and value of clinical ES as a diagnostic tool for neurogenetic disease and highlight key barriers that prevent patients from receiving important clinical information with potential treatment and psychosocial implications for patients and family members.

Open or robotic? Radical cystectomies for patients with non-metastatic bladder cancer: A systematic review and meta-analysis.

Background: This systematic review and meta-analysis will review randomized control trials for localized bladder cancer, evaluating surgical and pathologic outcomes of ORC versus RARC. Methods: Randomized studies evaluating adults with non-metastatic bladder cancer who underwent a radical cystectomy. Randomized trials were selected for final review. Data was extracted and analyzed with Revman 5 software. The primary outcome was complication rates within 90 days. Secondary outcomes included postoperative quality of life, estimated intraoperative blood loss, and other perioperative outcomes. Continuous variables were reported using mean difference with 95% confidence intervals, and dichotomous variables were reported using risk difference with 95% confidence intervals with RARC as the experimental group and ORC as the reference group. Results: Of 134 articles screened, six unique randomized studies were selected. For Grade I-II complications, the risk ratio (RR) was 0.92 (95% CI [0.79,1.08], p = 0.33), and for Grade III-V complications, RR 0.93 (95% CI [0.73,1.18], p = 0.59). RARC resulted in decreased blood loss (95% CI [-438.08, -158.44], p < 0.00001) and longer operative time (95% CI [55.23, 133.13], p < 0.00001). Quality of life using the EORTC-QLQ-30 global health score at 3 months post-op appeared to favor RARC with a mean difference of 4.46 points (95% CI [1.78, 7.15], p = 0.001). Pathologic outcomes neither statistically nor clinically favored one modality, as there was no significant difference between mean lymph node yield (p = 0.49), positive lymph nodes (p = 1.00), and positive surgical margins (p = 0.85) between the surgical modalities. Conclusions: Although one surgical modality is not overtly superior, the choice may be decided by mitigating individual operative risk factors like intraoperative blood loss, operative time, post-operative quality of life, as well as institutional costs and learning curve among surgeons.

Whole exome sequencing in Serbian patients with hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases with a high genetic and clinical heterogeneity. Numerous HSP patients remain genetically undiagnosed despite screening for known genetic causes of HSP. Therefore, identification of novel variants and genes is needed. Our previous study analyzed 74 adult Serbian HSP patients from 65 families using panel of the 13 most common HSP genes in combination with a copy number variation analysis. Conclusive genetic findings were established in 23 patients from 19 families (29%). In the present study, nine patients from nine families previously negative on the HSP gene panel were selected for the whole exome sequencing (WES). Further, 44 newly diagnosed adult HSP patients from 44 families were sent to WES directly, since many studies showed WES may be used as the first step in HSP diagnosis. WES analysis of cohort 1 revealed a likely genetic cause in five (56%) of nine HSP families, including variants in the ETHE1, ZFYVE26, RNF170, CAPN1, and WASHC5 genes. In cohort 2, possible causative variants were found in seven (16%) of 44 patients (later updated to 27% when other diagnosis were excluded), comprising six different genes: SPAST, SPG11, WASCH5, KIF1A, KIF5A, and ABCD1. These results expand the genetic spectrum of HSP patients in Serbia and the region with implications for molecular genetic diagnosis and future causative therapies. Wide HSP panel can be the first step in diagnosis, alongside with the copy number variation (CNV) analysis, while WES should be performed after.

Automated Detection and Segmentation of Bone Metastases on Spine MRI Using U-Net: A Multicenter Study.

OBJECTIVE: To develop and evaluate a deep learning model for automated segmentation and detection of bone metastasis on spinal MRI. MATERIALS AND METHODS: We included whole spine MRI scans of adult patients with bone metastasis: 662 MRI series from 302 patients (63.5 ± 11.5 years; male:female, 151:151) from three study centers obtained between January 2015 and August 2021 for training and internal testing (random split into 536 and 126 series, respectively) and 49 MRI series from 20 patients (65.9 ± 11.5 years; male:female, 11:9) from another center obtained between January 2018 and August 2020 for external testing. Three sagittal MRI sequences, including non-contrast T1-weighted image (T1), contrast-enhanced T1-weighted Dixon fat-only image (FO), and contrast-enhanced fat-suppressed T1-weighted image (CE), were used. Seven models trained using the 2D and 3D U-Nets were developed with different combinations (T1, FO, CE, T1 + FO, T1 + CE, FO + CE, and T1 + FO + CE). The segmentation performance was evaluated using Dice coefficient, pixel-wise recall, and pixel-wise precision. The detection performance was analyzed using per-lesion sensitivity and a free-response receiver operating characteristic curve. The performance of the model was compared with that of five radiologists using the external test set. RESULTS: The 2D U-Net T1 + CE model exhibited superior segmentation performance in the external test compared to the other models, with a Dice coefficient of 0.699 and pixel-wise recall of 0.653. The T1 + CE model achieved per-lesion sensitivities of 0.828 (497/600) and 0.857 (150/175) for metastases in the internal and external tests, respectively. The radiologists demonstrated a mean per-lesion sensitivity of 0.746 and a mean per-lesion positive predictive value of 0.701 in the external test. CONCLUSION: The deep learning models proposed for automated segmentation and detection of bone metastases on spinal MRI demonstrated high diagnostic performance.

The Impact of COVID-19 and Exposure to Violent Media Content on Cyber Violence Victimization Among Adolescents in South Korea: National Population-Based Study.

BACKGROUND: Because of the COVID-19 pandemic and consequent stay-at-home mandates, adolescents faced isolation and a decline in mental health. With increased online activity during this period, concerns arose regarding exposure to violent media content and cyber victimization among adolescents. Yet, the precise influence of pandemic-related measures on experiences of cyber violence remains unclear. Hence, it is pertinent to investigate whether the pandemic altered the dynamics of cyber violence victimization for individuals. OBJECTIVE: This study aims to investigate the effects of COVID-19 and exposure to violent media content on cyber violence victimization among adolescents in South Korea. METHODS: We used national survey data from 2019 (n=4779) and 2020 (n=4958) to investigate the potential impact of COVID-19 on the prevalence of cyber violence among young adolescents. The data encompassed responses from elementary fourth-grade students to senior high school students, probing their exposure to violent media content, average internet use, as well as experiences of victimization and perpetration. RESULTS: The analysis revealed a noteworthy decline in cyber victimization during 2020 compared with 2019 (B=-0.12, t=-3.45, P<.001). Furthermore, being a perpetrator significantly contributed to cyber victimization (B=0.57, t=48.36, P<.001). Additionally, younger adolescents (ß=-.06, t=-6.09, P<.001), those spending more time online (ß=.18, t=13.83, P<.001), and those exposed to violent media (ß=.14, t=13.89, P<.001) were found to be more susceptible to victimization. CONCLUSIONS: Despite the widespread belief that cyber violence among adolescents surged during COVID-19 due to increased online activity, the study findings counter this assumption. Surprisingly, COVID-19 did not exacerbate cyber victimization; rather, it decreased it. Given the strong correlation between cyber victimization and offline victimization, our attention should be directed toward implementing real-life interventions aimed at curbing violence originating from in-person violence at school.

Assessing visibility and bone changes of spinal metastases in CT scans: a comprehensive analysis across diverse cancer types.

OBJECTIVES: To analyze the characteristics of spinal metastasis in CT scans across diverse cancers for effective diagnosis and treatment, using MRI as the gold standard. METHODS: A retrospective study of 309 patients from four centers, who underwent concurrent CT and spinal MRI, revealing spinal metastasis, was conducted. Data on metastasis including total number, volume, visibility on CT (visible, indeterminate, or invisible), and type of bone change were collected. Through chi-square and Mann-Whitney U tests, we characterized the metastasis across diverse cancers and investigated the variation in the intra-individual ratio representing the percentage of lesions within each category for each patient. RESULTS: Out of 3333 spinal metastases from 309 patients, 55% were visible, 21% indeterminate, and 24% invisible. Sclerotic and lytic lesions made up 47% and 43% of the visible and indeterminate categories, respectively. Renal cell carcinoma (RCC), prostate cancer, and hepatocellular carcinoma (HCC) had the highest visibility at 86%, 73%, and 67% (p < 0.0001, p < 0.0001, and p = 0.003), while pancreatic cancer was lowest at 29% (p < 0.0001). RCC and HCC had significantly high lytic metastasis ratios (interquartile range (IQR) 0.96-1.0 and 0.31-1.0, p < 0.001 and p = 0.005). Prostate cancer exhibited a high sclerotic lesion ratio (IQR 0.52-0.97, p < 0.001). About 39% of individuals had invisible or indeterminate lesions, even with a single visible lesion on CT. The intra-individual ratio for indeterminate and invisible metastases surpassed 18%, regardless of the maximal size of the visible metastasis. CONCLUSIONS: This study highlights the variability in characteristics of spinal metastasis based on the primary cancer type through unique lesion-centric analysis.

Neurosarcoidosis involving cervical nerve root with unusual MRI findings: a case report and systematic literature review.

BACKGROUND: Neurosarcoidosis is rare, and among its manifestations, nerve root involvement has been reported in only a few cases. Therefore, magnetic resonance imaging (MRI) findings of neurosarcoidosis, particularly those involving nerve roots, are scarce in the literature. METHODS: We presented the case of neurosarcoidosis involving cervical nerve roots and cranial nerves, alongside a systematic literature review. RESULTS: A 28-year-old female suddenly developed right facial numbness as well as left upper extremity and left hand pain. Initial brain and spine MRI showed a bulging mass of T2 iso-to-high signal intensity in the left Meckel's cave/trigeminal nerve, as well as diffuse enlargement of the right C6 and C7 nerve roots. Follow-up MRI at 2 months revealed a reduction in the size of the initial lesion and the appearance of new similar lesions on the contralateral side (right Meckel's cave, left C3-C8 nerve roots). In particular, the lesions involving the nerve roots demonstrated central enlargement along the nerve roots, without involvement of the adjacent spinal cord. All these lesions exhibited enhancement, leading to the differentiation between sarcoidosis and lymphoma. Sarcoidosis was subsequently confirmed through biopsy of a hilar lymph node. CONCLUSIONS: This report presents a distinctive MRI feature of neurosarcoidosis involving spinal nerve roots, representing the first of its kind, and describes the evolution of MRI findings throughout the clinical course.

[Lumbar Facet Joint Injection: A Review of Efficacy and Safety]. / 요추 í›„ê´€ì ˆ 주사: ìž„ìƒì  ìœ ìš©ì„±ê³¼ ì•ˆì „ì„±ì— 대한 ê³ ì°°.

Facet joint arthrosis is a progressive degenerative disease that is frequently associated with other spinal degenerative disorders such as degenerative disc disease or spinal stenosis. Lumbar facet joint arthrosis can induce pain in the proximal lower extremities. However, symptoms and imaging findings of "facet joint syndrome" are not specific as they mimic the pain from herniated discs or nerve root compression. Currently, evidence for therapeutic intra-articular lumbar facet joint injections is still considered low, with a weak recommendation strength. Nevertheless, some studies have reported therapeutic effectiveness of facet joint injections. Moreover, the use of therapeutic facet joint injections in clinical practice has increased. This review article includes opinions based on the authors' experience with facet joint injections. This review primarily aimed to investigate the efficacy of lumbar facet joint injections and consider their associated safety aspects.

[Imaging of Sequestered Lumbar Discs]. / 요추 분리추간판의 영상 소견.

Intervertebral disc herniation is frequently encountered in radiological practice. Sequestered disc herniation occurs when the disc material undergoes degeneration and completely loses continuity with the parent nucleus pulposus. Sequestered discs can reside within and outside the spinal canal, exerting a mass effect on adjacent structures, compressing nerve pathways, and eliciting a range of clinical symptoms. In particular, sequestered discs within the dura cannot be identified without durotomy. Therefore, precise preoperative localization is crucial for surgical planning. On MRI, the signal intensity of the sequestered disc may vary due to independent degeneration processes. Additionally, most sequestered disc fragments show varying degrees of peripheral enhancement depending on the degree of angiogenesis and granulation around the isolated tissue. In this article, we review various imaging findings and the location of the sequestered disc to provide patients with an accurate diagnosis and appropriate treatment direction.

Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes compulsive-like behaviors in mice.

Compulsive behaviors are observed in a range of psychiatric disorders, however the neural substrates underlying the behaviors are not clearly defined. Here we show that the basolateral amygdala-dorsomedial striatum (BLA-DMS) circuit activation leads to the manifestation of compulsive-like behaviors. We revealed that the BLA neurons projecting to the DMS, mainly onto dopamine D1 receptor-expressing neurons, largely overlap with the neuronal population that responds to aversive predator stress, a widely used anxiogenic stressor. Specific optogenetic activation of the BLA-DMS circuit induced a strong anxiety response followed by compulsive grooming. Furthermore, we developed a mouse model for compulsivity displaying a wide spectrum of compulsive-like behaviors by chronically activating the BLA-DMS circuit. In these mice, persistent molecular changes at the BLA-DMS synapses observed were causally related to the compulsive-like phenotypes. Together, our study demonstrates the involvement of the BLA-DMS circuit in the emergence of enduring compulsive-like behaviors via its persistent synaptic changes.

Unveiling genetics of non-syndromic albinism using whole exome sequencing: A comprehensive study of TYR, TYRP1, OCA2 and MC1R genes in 17 families.

BACKGROUND: Oculocutaneous albinism (OCA) is a group of skin depigmentation disorders. Clinical presentation of OCA includes defects in melanocyte differentiation, melanin biosynthesis, and melanosome maturation and transport. OBJECTIVES: A molecular diagnostics study of families presenting oculocutaneous albinism. METHODS: In this study, 17 consanguineous OCA families consisting of 93 patients were investigated. Whole Exome Sequencing (WES) of the index patient in each family were performed. Short listed variants of WES were Sanger validated for Mendelian segregation in obligate carriers and other available family members. Variant prioritization and pathogenicity were classified as per the criteria of American College Medical Genetics and Genomics (ACMG). Comparative computational modelling was performed to predict the potential damaging effect of the altered proteins. RESULTS: 15 pathogenic variations: c.132 T > A, c.346C > T, c.488C > G, c.1037G > A in TYR, c.1211C > T, c.1441G > A, c.1706_1707insT, c.2020C > G, c.2402G > C, c.2430del, in OCA2, c.1067G > A in TYRP1 and c.451C > T, c.515G > T, c.766C > T, c.917G > A in MC1R genes were identified. Three variants in OCA2 gene were characterized: c.1706_1707insT, c.2430del, and c.2402G > C, all of which were not reported before in OCA families. CONCLUSION: A few studies focusing on mutation screening of OCA patients have been reported before; however, this study has uniquely presents the Pakhtun ethnic population residing on the North-Western boarder. It explains that TYR, OCA2, TYRP1, and MC1R variations lead to non-syndromic OCA phenotype The overlapping phenotypes of OCA can precisely be diagnosed for its molecular pathogenicity using WES. This study recommends WES as a first-line molecular diagnostic tool, and provides a basis for developing customized genetic tests i.e. pre-marital screening to reduce the disease burden in the future generations.

Coronal plane in opportunistic screening of osteoporosis using computed tomography: comparison with axial and sagittal planes.

OBJECTIVE: To compare the coronal plane with axial and sagittal planes in opportunistic screening of osteoporosis using computed tomography (CT). MATERIALS AND METHODS: A total of 100 patients aged ≥ 50 years who underwent both lumbar spine CT and dual-energy X-ray absorptiometry within 3 months were included. Osteoporosis was diagnosed based on dual-energy X-ray absorptiometry results. The CT number was measured at the center of the vertebral body in coronal, axial, and sagittal planes. To compare the coronal plane with axial and sagittal planes in diagnosing osteoporosis, the areas under the receiver operating characteristic curve (AUC) were compared and intraclass correlation coefficient (ICC) was calculated. The optimal cutoff values were calculated using Youden's index. RESULTS: The AUC of the coronal plane (0.80; 95% confidence interval [CI], 0.71-0.89) was not significantly different from that of the axial plane (0.78; 95% CI, 0.68-0.87; P = 0.39) and that of the sagittal plane (0.78; 95% CI, 0.69-0.87; P = 0.68). Excellent concordance rates were observed between coronal and axial planes with ICC of 0.95 (95% CI, 0.92-0.96) and between coronal and sagittal planes with ICC of 0.93 (95% CI, 0.85-0.96). The optimal cutoff values for the coronal, axial, and sagittal planes were 110, 112, and 112 HU, respectively. CONCLUSION: The coronal plane does not significantly differ from axial and sagittal planes in opportunistic screening of osteoporosis. Thus, the coronal plane as well as axial and sagittal planes can be used interchangeably in measuring bone mineral density using CT.

Enhancing the selective electrical activation of human vagal nerve fibers: a comparative computational modeling study with validation in a rat sciatic model.

Objective.Vagus nerve stimulation (VNS) is an emerging treatment option for a myriad of medical disorders, where the method of delivering electrical pulses can vary depending on the clinical indication. In this study, we investigated the relative effectiveness of electrically activating the cervical vagus nerve among three different approaches: nerve cuff electrode stimulation (NCES), transcutaneous electrical nerve stimulation (TENS), and enhanced TENS (eTENS). The objectives were to characterize factors that influenced nerve activation and to compare the nerve recruitment properties as a function of nerve fiber diameter.Methods.The Finite Element Model, based on data from the Visible Human Project, was implemented in COMSOL. The three simulation types were compared under a range of vertical and horizontal displacements relative to the location of the vagus nerve. Monopolar anodic stimulation was examined, along with latency and activation of different fiber sizes. Nerve activation was determined via the activating function and McIntyre-Richardson-Grill models, and activation thresholds were validated in anin-vivorodent model.Results.While NCES produced the lowest activation thresholds, eTENS generally performed superior to TENS under the range of conditions and fiber diameters, producing activation thresholds up to three times lower than TENS. eTENS also preserved its enhancement when surface electrodes were displaced away from the nerve. Anodic stimulation revealed an inhibitory region that removed eTENS benefits. eTENS also outperformed TENS by up to four times when targeting smaller diameter nerve fibers, scaling similar to a cuff electrode. In latency and activation of smaller diameter nerve fibers, eTENS results resembled those of NCES more than a TENS electrode. Activation threshold ratios were consistent inin-vivovalidation.Significance.Our findings expand upon previously identified mechanisms for eTENS and further demonstrate how eTENS emulates a nerve cuff electrode to achieve lower activation thresholds. This work further characterizes considerations required for VNS under the three stimulation methods.

The retrograde IFT dynein is required for normal function of diverse mechanosensory cilia in Drosophila.

Introduction: Cilia biogenesis relies on intraflagellar transport (IFT), a conserved transport mechanism which functions bi-directionally to bring protein complexes to the growing ciliary tip and recycle signaling and transport proteins between the cilium and cell body. In Drosophila, anterograde IFT is critical for assembly of sensory cilia in the neurons of both chordotonal (ch) organs, which have relatively long ciliary axonemes, and external sensory (es) organs, which have short axonemal segments with microtubules in distal sensory segments forming non-axonemal bundles. We previously isolated the beethoven (btv) mutant in a mutagenesis screen for auditory mutants. Although many btv mutant flies are deaf, some retain a small residual auditory function as determined both by behavior and by auditory electrophysiology. Results: Here we molecularly characterize the btv gene and demonstrate that it encodes the IFT-associated dynein-2 heavy chain Dync2h1. We also describe morphological changes in Johnston's organ as flies age to 30 days, and we find that morphological and electrophysiological phenotypes in this ch organ of btv mutants become more severe with age. We show that NompB protein, encoding the conserved IFT88 protein, an IFT complex B component, fails to be cleared from chordotonal cilia in btv mutants, instead accumulating in the distorted cilia. In macrochaete bristles, a class of es organ, btv mutants show a 50% reduction in mechanoreceptor potentials. Discussion: Thus, the btv-encoded Dync2h1 functions as the retrograde IFT motor in the assembly of long ciliary axonemes in ch organs and is also important for normal function of the short ciliary axonemes in es organs.

GSTT1 as a Predictive Marker and Enhancer for Osteogenic Potential of Human Adipose-Derived Stromal/Stem Cells.

Adipose-derived stromal/stem cells (ASCs) have been extensively studied as cell sources for regenerative medicine for bone because of their excellent proliferative capacity and the ability to obtain a large number of cells with minimal donor morbidity. On the other hand, the differentiation potential of ASCs is generally lower than that of bone marrow-derived stromal/stem cells and varies greatly depending on donors. In this study, we mined a marker that can predict the osteogenic potential of ASC clones and also investigated the usefulness of the molecule as the enhancer of osteogenic differentiation of ASCs as well as its mechanism of action. Through RNA-seq gene analysis, we discovered that GSTT1 (Glutathione S-transferase theta-1) was the most distinguished gene marker between highly osteogenic and poorly osteogenic ASC clones. Knockdown of GSTT1 in high osteogenic ASCs by siGSTT1 treatment reduced mineralized matrix formation. On the other hand, GSTT1 overexpression by GSTT1 transfection or GSTT1 recombinant protein treatment enhanced osteogenic differentiation of low osteogenic ASCs. Metabolomic analysis confirmed significant changes of metabolites related to bone differentiation in ASCs transfected with GSTT1. A high total antioxidant capacity, low levels of cellular reactive oxygen species, and increased GSH/GSSG ratios were also detected in GSTT1-transfected ASCs. When the in vivo effect of GSTT1-transfected ASCs on bone regeneration was investigated with segmental long-bone defect model in rats, bone regeneration was significantly better after implantation of GSTT1-transfected ASCs compared with that of control vector-transfected ASCs. In conclusion, GSTT1 can be a useful marker to screen the highly osteogenic ASC clones and also a therapeutic factor to enhance the osteogenic differentiation of poorly osteogenic ASC clones. © 2023 American Society for Bone and Mineral Research (ASBMR).

Evaluation of sarcopenia in patients receiving intravesical Bacillus Calmette-Guérin for non-muscle invasive bladder cancer.

BACKGROUND: Sarcopenia is associated with adverse outcomes for patients with muscle invasive bladder cancer (MIBC), but less is known about its impact in the setting of non-muscle invasive bladder cancer (NMIBC). Sarcopenia, skeletal muscle density, and adipose tissue area have been studied as markers of malnutrition and can be determined radiographically. The purpose of this study is to characterize the prevalence of sarcopenia in patients with NMIBC receiving intravesical Bacillus Calmette-Guérin (BCG). METHODS: Following institutional review board approval, patients with NMIBC having received intravesical BCG were identified using institutional pharmacy records. Patients having undergone computed tomography (CT) of the abdomen and pelvis within 90 days of treatment were included in the analysis. Using sliceOmatic 5.0 software, skeletal muscle area (cm2) was measured at the L3 level to calculate skeletal muscle index (SMI), a marker of sarcopenia. Subcutaneous, visceral, and intramuscular adipose tissue areas in addition to skeletal muscle density were also measured. Frailty was evaluated as a secondary aim using the 5-Item Modified Frailty Index (mFI-5). Using predefined cutoffs, the prevalence of sarcopenia was determined. Descriptive statistics were used to characterize frailty and secondary body composition characteristics. Statistical analysis was performed to evaluate the impact of sarcopenia on recurrence rate and progression. RESULTS: A total of 308 patients having received BCG between 2015 and 2020 were identified, of which 90 met criteria for analysis. Nearly all (94%) patients completed at least 5 out of 6 BCG induction instillations. Median body mass index (kg/m2) was 27.64 (IQR 24.9, 30.5) for females and 27.7 (IQR 24.9, 30.66) for males. Median SMI (cm2/m2) was 49.44 (IQR 39.39, 55.17) for females and 49.58 (IQR 40.25, 55.58) for males. A majority (61%) of patients were found to be sarcopenic. High-risk frailty was identified 36% of patients. There was no association between sarcopenia and recurrence rate or progression. CONCLUSIONS: Sarcopenia and frailty are highly prevalent amongst patients with NMIBC. A diagnosis of NMIBC represents a window of opportunity to identify and intervene on modifiable risk factors such as sarcopenia and frailty, which are associated with adverse outcomes in more advanced disease states.

MR evaluation of the posteromedial corner of the knee: association of posterior horn medial meniscus tear with posterior oblique ligament and distal semi-membranosus tendon tear.

OBJECTIVE: To assess if posterior oblique ligament and distal semi-membranosus tendon tears are associated with posterior horn medial meniscus tears on MRI. METHODS: From January 1, 2018 to December 31, 2019, 56 patients who met the inclusion criteria were enrolled in this study. Of the 56 patients, 43 patients who had a posterior horn of medial meniscus tear were included in the study group. A control group of 13 individuals was formed for comparison. Two radiologists reviewed the MR images and recorded the presence and grades of posterior oblique ligament and distal semi-membranosus tendon tears. We used the independent t-test and one-way ANOVA to compare the tear grades. Interobserver agreement was analyzed using a Cohen's κ coefficient (κ value) for categorical variables. RESULTS: The mean grades for the posterior oblique ligament and distal semi-membranosus tendon tears were significantly higher in the study group (all, p < 0.001). Interobserver agreement between the two readers was substantial in assessing the grade of posterior oblique ligament tear (κ = 0.653±0.087) and almost perfect in assessing the grade of distal semi-membranosus tendon tear (κ = 0.876±0.060). CONCLUSION: Posterior oblique ligament and distal semi-membranosus tendon tears are significantly associated with posterior horn of medial meniscus tear and medial meniscus posterior root tears, and the peel-back mechanism could be related to this association. ADVANCES IN KNOWLEDGE: Presenting this paper could adjust radiologist search patterns and potentially help orthopedists with management and pre-surgical planning for the posteromedial corner injury of the knee.

Androgen aggravates aortic aneurysms via suppressing PD-1 in mice.

Androgen has long been recognized for its pivotal role in the sexual dimorphism of cardiovascular diseases, including aortic aneurysms, a devastating vascular disease with a higher prevalence and mortality rate in men than women. However, the molecular mechanism by which androgen mediates aortic aneurysms is largely unknown. Here, we report that male but not female mice develop aortic aneurysms in response to aldosterone and high salt (Aldo-salt). We demonstrate that both androgen and androgen receptors (AR) are crucial for the sexually dimorphic response to Aldo-salt. We identify T cells expressing programmed cell death protein 1 (PD-1), an immune checkpoint molecule important in immunity and cancer immunotherapy, as a key link between androgen and aortic aneurysms. We show that intraperitoneal injection of anti-PD-1 antibody reinstates Aldo-salt-induced aortic aneurysms in orchiectomized mice. Mechanistically, we demonstrate that AR binds to the PD-1 promoter to suppress its expression in the spleen. Hence, our study reveals an important but unexplored mechanism by which androgen contributes to aortic aneurysms by suppressing PD-1 expression in T cells. Our study also suggests that cancer patients predisposed to the risk factors of aortic aneurysms may be advised to screen for aortic aneurysms during immune checkpoint therapy.

Intra-individual comparison of lumbar spine CT, abdomen-pelvis contrast enhanced CT, and low-dose chest CT for bone density measurement.

BACKGROUND: Dual-energy X-ray absorptiometry (DXA) is the reference standard for the measurement of bone mineral density (BMD) and subsequent diagnosis of osteoporosis. Since various computed tomography (CT) protocols are scanned for various indications, we can incidentally measure BMD using CT. Previous studies have revealed a correlation between BMD and Hounsfield unit (HU) values obtained with different CT protocols. PURPOSE: To compare the diagnostic value of CT protocols (lumbar spine CT [LSCT], abdomen-pelvis contrast-enhanced CT [APCT], and low-dose chest CT [LDCT]) for osteoporosis. MATERIAL AND METHODS: We retrospectively included 17 patients (6 men, 11 women; mean age=68 years) who had undergone all four imaging studies within six months, during 2011-2021. HU values were manually measured at the center of the L1 vertebra by a radiology resident. Pearson correlation test was performed between HU values and BMD of L1 vertebra. The diagnostic performance of each CT protocol was assessed with receiver operating characteristic (ROC) analysis. Intra-individual concordance of the four tests to diagnose osteoporosis was analyzed by tabulating. RESULTS: The mean HU values were 104.4 ± 47.2 HU with LSCT, 149.0 ± 56.9 HU with APCT, and 114.3 ± 60.0 HU with LDCT. HU values from each protocol were positively correlated (r = 0.676-0.735; P < 0.005) with BMD. LDCT had the highest diagnostic performance (area under the ROC curve [AUC] = 0.701) and APCT the lowest (AUC = 0.569). APCT was discordant with the other protocols for diagnosing osteoporosis. CONCLUSION: LDCT had the highest diagnostic performance for osteoporosis with predetermined cutoff value. APCT requires the increase of cutoff value for osteoporosis diagnosis.

Dual-layer spectral detector CT arthrography of the shoulder: assessment of image quality and value in differentiating calcium from iodine.

BACKGROUND: Dual-layer spectral detector computed tomography (DLCT) may potentially improve CT arthrography through enhanced image quality and analysis of the chemical composition of tissue. PURPOSE: To evaluate the image quality of monoenergetic reconstructions from DLCT arthrography of the shoulder and assess the additional diagnostic value in differentiating calcium from iodine. MATERIAL AND METHODS: Images from consecutive shoulder DLCT arthrography examinations performed between December 2016 and February 2018 were retrospectively reviewed for hyperattenuating lesions within the labrum and tendons. The mean attenuation of the target lesion, noise, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of the virtual monoenergetic images obtained at 40-200 keV were compared with conventional 140-kVp images. Two evaluators independently classified each target lesion as contrast media or calcification, without and with DLCT spectral data. Receiver operating curve (ROC) analysis was performed to assess the diagnostic performance of shoulder DLCT arthrography, without and with the aid of spectral data. RESULTS: The study included 20 target lesions (18 DLCT arthrography examinations of 17 patients). The SNRs of the monoenergetic images at 40-60 keV were significantly higher than those of conventional images (P < 0.05). The CNRs of the monoenergetic images at 40-70 keV were significantly higher than those of conventional images (P < 0.001). The ability to differentiate calcium from iodine, without and with DLCT spectral data, did not significantly differ (P = 0.441 and P = 0.257 for reviewers 1 and 2, respectively). CONCLUSION: DLCT had no additive value in differentiating calcium from iodine in small, hyperattenuating lesions in the labrum and tendons.