Reliability of the Sigmoid Notch Classification of the Distal Radioulnar Joint.

Background The Tolat sigmoid notch classification is a commonly used classification to characterize the distal radioulnar joint (DRUJ). This classification was based on a limited assessment of the entire joint, which may lead to inaccuracies in sigmoid notch evaluation. Questions/Purposes The purpose of this study is to assess the reliability of the Tolat classification for sigmoid notch characterization. Methods The sigmoid notch of 52 models of cadaveric forearms was assessed by applying the Tolat classification to the three-dimensional (3D) modeled notch and then slices at the start of the notch (0 mm) and 4 mm more proximal. The inter- and intrarater agreement was assessed using Cohen's and Fleiss' kappa statistic. Results Agreement between iterations regardless of slices or surgeons/radiologists was moderate. Intrarater agreement between pairs of slices (0 vs 4 mm, 0 mm vs 3D, 4 mm vs 3D) was moderate, whereas agreement between all slices was slight. Agreement between surgeons and between radiologists was moderate, while agreement across all raters and slices was fair. Models described as "other" were more consistent in 3D classifications and were commonly classified as a reverse ski slope. Conclusions Classification using the Tolat scheme is fair to moderate at best. Classification of the sigmoid notch using an axial view of the distal radius may not accurately reflect the anatomy throughout the notch. Clinical Relevance The Tolat classification supplies a limited analysis of the sigmoid notch, and does not represent a comprehensive evaluation of the entire joint. Future classification systems should characterize the entire sigmoid notch.

Education in Mathematics and the Spread of COVID-19.

We investigate the effect of standardized mathematics scores for young adults on the number of COVID-19 cases in the USA. We find that a one-grade-level increase in test scores led to a decrease in COVID-19 cases 30, 60, and 90 days after the first case in each county. Our findings suggest that if states and localities implement policies that increase the level of education and comprehension of mathematics at the K-12 level, that people may be better prepared to find and interpret information in a future public health crisis.

Stay-at-Home Orders, Mobility Patterns, and Spread of COVID-19.

Objectives. To understand how stay-at-home orders changed mobility patterns and influenced the spread of COVID-19.Methods. I merged 2020 data from the Virginia Department of Health, Google Mobility Reports, and the US Census to estimate a series of 2-way fixed-effect event-study regression models.Results. A stay-at-home order caused people to increase the amount of time spent at home by 12 percentage points and decrease the time the spent at work by 30 percentage points, retail and recreation venues by 40 percentage points, and grocery stores and pharmacies by 10 percentage points. People did not sustain changes in mobility and gradually returned to prepandemic levels before the stay-at-home order was lifted. In areas where people spent the most time at indoor locations, there was a large increase in COVID-19.Conclusions. A more robust and stricter policy response coordinated at the national level combined with a strong economic response from policymakers could have increased the effectiveness of the stay-at-home order.

Sarcoid-Like Lesions Mimicking Pulmonary Metastasis: A Case Series and Review of the Literature.

BACKGROUND: The association of sarcoid-like lesions and malignancy is well described. Nonetheless, pulmonary lesions in malignant disease are typically presumed metastatic, and do not routinely receive histological validation. Here, we report on pulmonary sarcoid-like lesions identified in patients with a primary malignancy where pulmonary metastatic disease was suspected. METHODS: Patients who underwent thoracic surgical procedures for confirmation or treatment of suspected pulmonary metastasis were retrospectively analysed. RESULTS: In 8/186 patients (4.3%), histology revealed sarcoid-like lesions. In these cases, there were no clinical symptoms suggestive of sarcoidosis. All underlying primary malignancies in the sarcoid-like patients were treated with curative intent. The median age of patients with sarcoid-like lesions was 46.3 years (range 26-61). The median interval between primary diagnosis of malignancy and diagnosis of pulmonary lesions was 188 days (range 0-794), with thoracic surgical intervention performed at a median of 250 days (range 183-675). FDG-avidity was demonstrated in the sarcoid-like lesions in 2 out of 3 patients who underwent PET-CT. CONCLUSION: Sarcoid-like lesions may be challenging to identify and can mimic pulmonary metastases. Therefore, considering sarcoidosis as a differential diagnosis whenever first pulmonary metastasis is suspected is warranted. Carefully considered, histological validation of initial suspected pulmonary metastasis may avoid subsequent over- or undertreatment.

Evaluation of a novel 2D perfusion angiography technique independent of pump injections for assessment of interventional treatment of peripheral vascular disease.

To evaluate a novel 2D-perfusion angiography (2D-PA) technique allowing pro- and retrospective flow analysis based on a proximal reference region of interest (ROI) and distal target ROI in patients treated for peripheral arterial disease. 2D-PA allows quantifying blood flow by post-processing of digital subtraction angiography (DSA). 2D-PA was performed pre and post interventional treatment of peripheral arterial disease (PAD; n = 24; 13 angioplasties, 11 stents) in 21 patients (17 men, 72 ± 9y) with Fontaine stage IIB / III. Time-to-peak (TTP), peak density (PD) and area-under-the-curve (AUC) were calculated. Ratios reference/target ROI (TTPOUTFLOW/TTPINFLOW; PDOUTFLOW/PDINFLOW; AUCOUTFLOW/AUCINFLOW) were calculated and correlated to changes in the ankle-brachial-index (ABI). 2D-PA was technically feasible in all cases. A significant increase in ABI was seen after interventional treatment (+39%; p < 0.0001). ABI increase was accompanied by an increase of 36% of PDOUTFLOW/PDINFLOW (p < 0.0001), a 52% decrease of TTPOUTFLOW/TTPINFLOW (p = 0.0007) and a 69% increase of AUCOUTFLOW/AUCINFLOW (p < 0.0001). The difference of TTP pre- and post-intervention showed a correlation with the difference in ABI (r = -0.53, p = 0.0081). The other measured parameters failed to demonstrate significant correlation with improved ABI. The presented 2D-PA technique allows quantitative assessment of arterial flow before, during and after interventional treatment in PAD.

Parametric response mapping of contrast-enhanced biphasic CT for evaluating tumour viability of hepatocellular carcinoma after TACE.

OBJECTIVES: To determine the feasibility and role of parametric response mapping (PRM) for quantitative assessment of regional contrast-enhancement patterns in hepatocellular carcinoma (HCC). METHODS: Biphasic CT of 19 patients receiving repetitive conventional transarterial chemoembolisation (cTACE) for intermediate stage HCC were retrospectively analysed at baseline and follow-up at 3, 6, and 9 months. Voxel-based registration of arterial and porto-venous phases, with segmentation of the largest target lesion was performed. Frequency distribution plots of density-pairs of segmented voxels were generated. To differentiate necrotic, hypervascular and non-hypervascular tumour, and lipiodol/calcification, thresholds of 30, 100, and 300 HU were applied. Changes in density frequency plots over time were analysed and compared to response and assessment criteria (WHO, RECIST, EASL, mRECIST) and survival. RESULTS: PRM was feasible in all cases. Tumour volumes and hypervascular/non-hypervascular volume ratio showed significant longitudinal decrease (p < 0.05). Hypervascular volume at baseline was inversely correlated to survival (R = -0.57, p = 0.005). The only predictive parameter following cTACE to show significant survival difference was the change of the viable/non-viable ratio (p = 0.044), whereas common response assessment criteria showed no significant difference in survival. CONCLUSIONS: PRM allows a quantitative and more precise assessment of regional tumour vascularisation patterns and may be helpful for TACE treatment planning and response assessment. KEY POINTS: • PRM allows more precise assessment of tumour vascularisation compared to conventional evaluation • PRM is beneficial for cTACE treatment planning and response assessment • PRM allows a quantitative assessment of regional contrast enhancement patterns.

RB116: an RB1+ retinoblastoma cell line expressing primitive markers.

PURPOSE: Retinoblastoma (RB), an intraocular tumor of childhood, is commonly associated with mutations in the RB1 gene. RB116 is a novel, early passage RB cell line that has not been previously characterized. In this study, we examined RB116 for the expression of RB1 and tested the hypothesis that RB116 cells would express stem cell markers as well as retinal progenitor cell markers. We compared RB116 cells with other well known RB cell lines, including Y79 and WERI-RB27. METHODS: We evaluated expression of RB1 in RB116 cells by sequencing, multiplex ligation-dependent probe amplification, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), western immunoblot, and immunocytochemistry. Next, RB116 cells, along with Y79 and WERI-RB27 cells, were examined for expression of stem cell markers (ABCG2, Nanog, Oct3/4, ALDH1A1) and retinal progenitor markers (PAX6, CHX10) by quantitative immunocytochemistry. Immunocytochemical findings were accompanied by PCR analysis. RESULTS: RB116 cells expressed RB1 at the mRNA and protein levels, with no mutations detected by either sequencing analysis, or gene dosage abnormalities detected by multiplex ligation-dependent probe amplification. The RB1 protein was immunoreactive in RB116 cells with an atypical perinuclear localization. RB116 cells also expressed stem cell markers, with 3%-5% of cells immunopositive for ABCG2, Oct3/4 and ALDH1A1, with at least 18% of cells immunoreactive to Nanog. These findings were confirmed by RT-PCR. Small percentages of RB116 cells also exhibited immunoreactivity to retinal progenitor markers PAX6 (9.8%) and CHX10 (1.2%). Expression of mRNAs for these markers was confirmed by qRT-PCR. CONCLUSIONS: RB116 cells demonstrate RB1 expression accompanied by atypical perinuclear localization. RB116 cells also express primitive stem cell and retinal progenitor cell markers. Further studies on the phenotypes of both RB1-positive and RB1-negative human RB cells may be important in assessing differentiation potential of these cells, as well as designing targeted differentiation therapies.

The 'Ethereal' nature of TLR4 agonism and antagonism in the AGP class of lipid A mimetics.

To overcome the chemical and metabolic instability of the secondary fatty acyl residues in the AGP class of lipid A mimetics, the secondary ether lipid analogs of the potent TLR4 agonist CRX-527 (2) and TLR4 antagonist CRX-526 (3) were synthesized and evaluated along with their ester counterparts for agonist/antagonist activity in both in vitro and in vivo models. Like CRX-527, the secondary ether lipid 4 showed potent agonist activity in both murine and human models. Ether lipid 5, on the other hand, showed potent TLR4 antagonist activity similar to CRX-526 in human cell assays, but did not display any antagonist activity in murine models and, in fact, was weakly agonistic. Glycolipids 2, 4, and 5 were synthesized via a new highly convergent method utilizing a common advanced intermediate strategy. A new method for preparing (R)-3-alkyloxytetradecanoic acids, a key component of ether lipids 4 and 5, is also described.

Are oral bisphosphonates effective in improving lumbar bone mineral density in breast cancer survivors with osteopenia or osteoporosis?

OBJECTIVE: Breast cancer survivors with osteoporosis or osteopenia are commonly encountered in primary care and gynaecology practices. Our objective was to determine whether treatment with oral bisphosphonates (alendronate or cyclic etidronate) was more effective than calcium with vitamin D in improving lumbar spine bone mineral density (BMD) within one year in breast cancer survivors. METHODS: Breast cancer survivors with at least one year of clinical follow-up were identified from the prospective observational Canadian Database of Osteoporosis and Osteopenia (CANDOO). Analysis of covariance was used to examine the effects of bisphosphonate therapy on change in lumbar spine BMD at one year compared with the effects of calcium with vitamin D (analysis adjusted for baseline L2-L4 BMD, current tamoxifen use, number of prevalent vertebral fractures [VFs], and time since diagnosis of breast cancer, and age). RESULTS: Eighteen patients took calcium and vitamin D, 25 took cyclic etidronate, and 27 took oral alendronate. Adjusted one-year BMD increases for alendronate and cyclic etidronate compared to calcium and vitamin D were as follows: alendronate 4.53% (95% confidence interval [CI] 1.26%, 7.81%, P = 0.008), and cyclic etidronate 1.85% (-1.55%, 5.25%, P = 0.280). BMD increases were significantly greater in patients with prevalent VF compared to those without VF (P = 0.025). In contrast, time since diagnosis of breast cancer was significantly associated with a decrease in BMD (P = 0.002). We were unable to detect any effect of current tamoxifen use, baseline lumbar spine BMD, or age on changes in BMD at one year. CONCLUSION: Treatment with alendronate was associated with significantly greater improvements in lumbar spine BMD within one year in breast cancer survivors when compared with treatment with cyclic etidronate or calcium and vitamin D.

Are there differences between men and women prescribed bisphosphonate therapy in canadian subspecialty osteoporosis practices?

OBJECTIVE: To determine if there are differences between men and women referred for treatment of osteoporosis in Canada. METHODS: We performed an observational study of 1588 patients (163 men, 1425 women), 50 years of age and older, who were prescribed cyclic etidronate or alendronate for treatment of osteoporosis or osteopenia and had at least 2 years of followup registered in the Canadian Database for Osteoporosis and Osteopenia Patients (CANDOO). Comparisons of characteristics between men and women were performed using Pearson chi-square test, Student's t test, or a Kruskal-Wallis test, whichever was most appropriate. RESULTS: Mean baseline femoral neck and lumbar spine bone mineral densities were significantly higher in men than women at both the femoral neck and lumbar spine (p < 0.05, respectively). Men had double the rate of prevalent vertebral fractures (44%, 72/163) compared to women (22%, 315/1425; p < 0.001) and triple the rate of multiple prevalent vertebral fractures (10%, 17/163) compared to women (3%, 37/1425, p < 0.001). Furthermore, men were twice as likely as women to sustain a fracture within 2 years of starting treatment during observation in the CANDOO study (men: 4%, 7/163, women: 2%, 24/1425, p = 0.033). CONCLUSION: Osteoporosis may be under-recognized in men until the condition is at an advanced stage. A form of gender bias may exist in recognition and treatment (or referral for treatment) of osteoporosis in men.

What predicts early fracture or bone loss on bisphosphonate therapy?

Factors predicting early fracture or bone loss on bisphosphonate therapy are not well defined. We studied 1588 patients over the age of 50 yr who were started on cyclic etidronate (1119) or alendronate (469) in the CANDOO (Canadian Database for Osteoporosis and Osteopenia Patients) Study. Incident fracture within 2 yr of starting therapy occurred in 31 patients and was independently predicted by a previous history of nonvertebral fracture (odds ratio [OR], 2.98, 95% confidence interval [CI], 1.30, 6.83, p = 0.010). Two hundred and fifty-seven patients lost >/=3% bone mass at the hip or spine (early bone loss) while on bisphosphonate therapy. Protection from early bone loss was most strongly independently predicted by treatment with alendronate with no previous history of etidronate use (OR, 0.29, CI, 0.13, 0.62, p = 0.002). In conclusion, early fracture on bisphosphonate therapy is most strongly predicted by a previous history of fracture and early bone loss is most strongly predicted by the potency of the prescribed bisphosphonate.