A Specialized Mechanism of Translation Mediated by FXR1a-Associated MicroRNP in Cellular Quiescence.

MicroRNAs predominantly decrease gene expression; however, specific mRNAs are translationally upregulated in quiescent (G0) mammalian cells and immature Xenopus laevis oocytes by an FXR1a-associated microRNA-protein complex (microRNP) that lacks the microRNP repressor, GW182. Their mechanism in these conditions of decreased mTOR signaling, and therefore reduced canonical (cap-and-poly(A)-tail-mediated) translation, remains undiscovered. Our data reveal that mTOR inhibition in human THP1 cells enables microRNA-mediated activation. Activation requires shortened/no poly(A)-tail targets; polyadenylated mRNAs are partially activated upon PAIP2 overexpression, which interferes with poly(A)-bound PABP, precluding PABP-enhanced microRNA-mediated inhibition and canonical translation. Consistently, inhibition of PARN deadenylase prevents activation. P97/DAP5, a homolog of canonical translation factor, eIF4G, which lacks PABP- and cap binding complex-interacting domains, is required for activation, and thereby for the oocyte immature state. P97 interacts with 3' UTR-binding FXR1a-associated microRNPs and with PARN, which binds mRNA 5' caps, forming a specialized complex to translate recruited mRNAs in these altered canonical translation conditions.

Investigating the relationship between heat load and shade seeking behaviour in dairy buffaloes.

The study presented in this Research Communication aimed to investigate the relationship between physiological responses, body surface temperature and shade-seeking behaviour in Nili Ravi dairy buffaloes during summer months. We enrolled 60 buffaloes, and each animal was observed for three consecutive days starting before sunrise until they moved towards the shade structures. A repeated measures ANOVA was employed to assess the changes in physiological parameters and body surface temperature between the early morning and the occurrence of shade-seeking behaviour. The average temperature humidity index and heat load index during the behavioural monitoring period (0400 to 1200 h) were 81.3 ± 6.5 and 92.9 ± 17, respectively (mean ± sd). There was no significant difference in core body temperature between sunrise and the time of shade-seeking event. However, the buffaloes had a slightly higher respiration rate at the time of shade-seeking (19.2 vs. 22.4 breaths/min). In addition, body surface temperature, measured at the flank region, shoulder, base of the ear and forehead was significantly higher at the occurrence of shade-seeking behaviour compared to the early morning. On average, the buffaloes sought shade when the surface temperature was 2°C higher than the temperature recorded before sunrise. Overall, the current findings suggest that body surface temperature, rather than core body temperature was strongly associated with shade-seeking behaviour in dairy buffaloes. These findings could be useful in developing strategies to mitigate the effects of heat stress in dairy buffalo herds and thereby improve animal welfare.

Effect of Averaging Measurements From Multiple MRI Pulse Sequences on Kidney Volume Reproducibility in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Total kidney volume (TKV) is an important biomarker for assessing kidney function, especially for autosomal dominant polycystic kidney disease (ADPKD). However, TKV measurements from a single MRI pulse sequence have limited reproducibility, ± ~5%, similar to ADPKD annual kidney growth rates. PURPOSE: To improve TKV measurement reproducibility on MRI by extending artificial intelligence algorithms to automatically segment kidneys on T1-weighted, T2-weighted, and steady state free precession (SSFP) sequences in axial and coronal planes and averaging measurements. STUDY TYPE: Retrospective training, prospective testing. SUBJECTS: Three hundred ninety-seven patients (356 with ADPKD, 41 without), 75% for training and 25% for validation, 40 ADPKD patients for testing and 17 ADPKD patients for assessing reproducibility. FIELD STRENGTH/SEQUENCE: T2-weighted single-shot fast spin echo (T2), SSFP, and T1-weighted 3D spoiled gradient echo (T1) at 1.5 and 3T. ASSESSMENT: 2D U-net segmentation algorithm was trained on images from all sequences. Five observers independently measured each kidney volume manually on axial T2 and using model-assisted segmentations on all sequences and image plane orientations for two MRI exams in two sessions separated by 1-3 weeks to assess reproducibility. Manual and model-assisted segmentation times were recorded. STATISTICAL TESTS: Bland-Altman, Schapiro-Wilk (normality assessment), Pearson's chi-squared (categorical variables); Dice similarity coefficient, interclass correlation coefficient, and concordance correlation coefficient for analyzing TKV reproducibility. P-value < 0.05 was considered statistically significant. RESULTS: In 17 ADPKD subjects, model-assisted segmentations of axial T2 images were significantly faster than manual segmentations (2:49 minute vs. 11:34 minute), with no significant absolute percent difference in TKV (5.9% vs. 5.3%, P = 0.88) between scans 1 and 2. Absolute percent differences between the two scans for model-assisted segmentations on other sequences were 5.5% (axial T1), 4.5% (axial SSFP), 4.1% (coronal SSFP), and 3.2% (coronal T2). Averaging measurements from all five model-assisted segmentations significantly reduced absolute percent difference to 2.5%, further improving to 2.1% after excluding an outlier. DATA CONCLUSION: Measuring TKV on multiple MRI pulse sequences in coronal and axial planes is practical with deep learning model-assisted segmentations and can improve TKV measurement reproducibility more than 2-fold in ADPKD. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

The impact of voluntary folate fortification of corn masa flour on US pregnancies complicated by neural tube defects.

INTRODUCTION: In 1996, the US Food and Drug Administration (FDA) mandated folic acid fortification for all enriched cereal grains. This resulted in a reduction of neural tube defect (NTD)-affected pregnancies. However, Hispanic women continued to be twice as likely to give birth to a child affected by NTD compared to non-Hispanic White women. Some hypotheses explaining this difference focus on cultural variation in dietary intake of cereal grains. In 2016, the FDA approved voluntary folic acid fortification for corn masa flour products to focus on the Hispanic diet staple. This study investigates rates of NTDs in predominantly Hispanic-populated zip codes before and after the voluntary fortification of corn masa flour with folic acid. METHODS: Normal pregnancies and those complicated by NTDs between 1/1/2016 and 9/30/2020 were identified using ICD-9 and ICD-10 codes in an all-payor claims database. The post-fortification period began 12 months after the fortification recommendation. The US Census data was used to stratify pregnancies in predominantly Hispanic zip codes (≥ 75% of households) vs. non-Hispanic zip codes. The causal impact of the FDA's recommendation was assessed by means of a Bayesian structural time series model. RESULTS: A total of 2,584,366 pregnancies were identified among females aged 15-50 years. Of these, 365,983 took place in predominantly Hispanic zip codes. Mean quarterly NTDs per 100,000 pregnancies did not significantly differ between predominantly Hispanic zip codes and predominantly non-Hispanic zip codes pre-FDA recommendation (184.5 vs. 175.6; p = 0.427), nor post-recommendation (188.2 vs. 185.9; p = 0.713). Rates of NTDs predicted to occur if no FDA recommendation had been made were compared to the actual rate post-recommendation: no significant difference was observed in predominantly Hispanic zip codes (p = 0.245) or overall (p = 0.116). CONCLUSIONS: Rates of neural tube defects were not significantly reduced in predominantly Hispanic zip codes following the 2016 FDA approval of voluntary folic acid fortification of corn masa flour. Further research and implementation of comprehensive approaches to advocacy, policy, and public health are necessary to decrease preventable congenital disease rates. Mandatory rather than voluntary fortification of corn masa flour products may achieve more substantial prevention of neural tube defects in at-risk US populations.

Outcomes of patients undergoing single-level arthroplasty versus anterior lumbar interbody fusion.

BACKGROUND: Compared to vertebral body fusion, artificial discs are thought to lessen the risks of adjacent segment disease and the need for additional surgery by maintaining spinal mobility as they mimic the intervertebral disc structure. No studies have compared the rates of postoperative complications and the requirement for secondary surgery at adjacent segments among patients who have undergone anterior lumbar interbody fusions (ALIF) versus those undergoing lumbar arthroplasty. METHODS: An all-payer claims database identified 11,367 individuals who underwent single-level ALIF and lumbar arthroplasty for degenerative disc disease (DDD) between January 2010 and October 2020. Rates of complications following surgery, the need for additional lumbar surgeries, length of stay (LOS), and postoperative opioid utilization were assessed in matched cohorts based on logistic regression models. Kaplan-Meyer plots were created to model the probability of additional surgery. RESULTS: Following 1:1 exact matching, 846 records of patients who had undergone ALIF or lumbar arthroplasty were analyzed. All-cause readmission within 30-30 days following surgery was significantly higher in patients undergoing ALIF versus arthroplasty (2.6% vs. 0.71%, p = 0.02). LOS was significantly lower among the patients who had undergone ALIF (1.043 ± 0.21 vs. 2.17 ± 1.7, p < .001). CONCLUSIONS: ALIF and lumbar arthroplasty procedures are equally safe and effective in treating DDD. Our findings do not support that single-level fusions may biomechanically necessitate revisional surgeries.

Evaluating the impact of sprinkler cycle and flow rate on dairy buffalo performance during heat stress.

The aim of this study was to evaluate the effect of the sprinkler cycle and flow rate on physiological, behavioural, and productive responses in dairy buffaloes. Nine Nili Ravi lactating buffaloes were subjected to three sprinkler cycles and two flow rates using a double replicated 3 × 3 Latin square design. The flow rates were 1.25 and 2 l/min, and the sprinkler cycles (minutes water on/off, number of cycles/h) were: 3/3, 10 cycles; 3/6, 7 cycles and 3/9, 5 cycles. The showering was applied from 0800 till 1630 h daily. In the first square of 21 d, each of the three sprinkler cycles was applied using a 1.25 l/min flow rate for 7 d per cycle. In the later square, the same treatments (sprinkler cycles) were applied using the 2 l/min flow rate. The average temperature humidity index during the study period was 85.7 ± 3.8 (Mean ± sd). The result showed that the 3/3 treatment group had lower body temperature and respiration rate than the other groups. The buffaloes in the 3/3 group produced 0.5 and 0.7 kg more milk with 1.4 and 2.4% more fat than the 3/6 and the 3/9 treatment groups, respectively. Similarly, the 2 l/min flow rate had a lower core body temperate and respiration rate and higher milk yield than the 1.25 l/min group. The 3/3 showering cycle with a 2 l/min flow rate appeared effective in improving physiological responses and milk yield in dairy buffaloes.

Association of Bariatric Surgery and Risk of Cancer in Patients With Morbid Obesity.

OBJECTIVE: This study investigates the rates of obesity-related cancers in patients undergoing vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), or no surgical intervention. SUMMARY BACKGROUND DATA: Obesity has been previously associated with increased rates of cancers; however, weight loss surgeries have not been explored to demonstrate their potential risk reduction impact. METHODS: Patients meeting bariatric eligibility criteria between January 2010 and December 2018 were identified. Exact 1:1:1 matching based on baseline patient demographics and comorbidities was used to create 3 groups with identical covariates: patients undergoing VSG, RYGB, and no surgery. RESULTS: A total of 28, bariatric-eligible patients equally split into patients undergoing VSG (n = 9636, 33.3%), RYGB (n = 9636, 33.3%), and those with no surgical intervention (n = 9636, 33.3%). Bariatric-eligible patients that did not undergo surgical intervention had significantly higher rates and odds of developing numerous cancer types included in our study when compared to either surgical cohorts, with any cancer type (4.61%), uterine (0.86%), colorectal (0.57%), and lung cancers (0.50%) being most common. Individuals undergoing RYGB were significantly less likely to develop colorectal cancer compared to patients without any surgical intervention [odds ratio (OR) 0.47, 95% confidence interval (CI) 0.30-0.75]. Additionally, those undergoing VSG were significantly less likely to develop lung cancer than the bariatric eligible no surgery cohort (OR 0.42, 95% CI 0.25-0.70). CONCLUSION: Postoperative rates of any cancer type, lung, ovarian, and uterine cancer were significantly lower in obese patients undergoing either vertical sleeve gastrectomy (VSG) or RYGB compared to bariatric-eligible patients without any surgical intervention.

The role of bone mineral density in adult spinal deformity patients undergoing corrective surgery: a matched analysis.

STUDY DESIGN: Retrospective cohort. BACKGROUND: Over 44 million adults are estimated to have either osteoporosis or osteopenia. Adult spinal deformity (ASD) is estimated to affect between 32 and 68% of the elderly population. OBJECTIVE: Retrospective investigation comparing rates of postoperative complications following thoracolumbar scoliosis surgery in patients with normal bone mineral density (BMD) to those with osteopenia or osteoporosis in addition to analyzing the effects of pretreatment with anti-osteoporotic medications in patients with low BMD. METHODS: Using administrative database of Humana beneficiaries, ICD-9 and ICD-10 diagnosis codes were used to identify ASD patients undergoing multilevel thoracolumbar fusions between 2007 and 2017. RESULTS: The propensity matched population analyzed in this study contained 1044 patients equally represented by those with a history of osteopenia, osteoporosis, or normal BMD. Osteopenia and osteoporosis were associated with increased odds of revision surgery (OR 2.01 95% CI 1.36-2.96 and OR 1.57, 95% CI 1.05-2.35), respectively. Similarly, there was an almost twofold increased odds of proximal and distal junctional kyphosis in patients with osteopenia and osteoporosis (OR 1.95, 95% CI 1.40-2.74 and OR 1.88, 95% CI 1.34-2.64), respectively. A total of 258 (37.1%) patients with osteoporosis were pretreated with anti-osteoporotic medications and there was no statistically significant decrease in odds of proximal or distal junctional kyphosis or revision surgery in these patients. CONCLUSION: Patients with ASD undergoing multilevel thoracolumbar fusion surgery have significantly higher rates of postoperative pseudarthrosis, proximal and distal junctional kyphosis, and revision surgery rates compared to patients with normal BMD.

Isolation, Structure Elucidation and Antimicrobial Evaluation of Natural Pentacyclic Triterpenoids and Phytochemical Investigation of Different Fractions of Ziziphus spina-christi (L.) Stem Bark Using LCHRMS Analysis.

Ziziphus spina-christi L. (ZSC-L) is a tree with thorny branches, belongs to the family Rhamnaceae and grows in the sub-tropics. The purpose of this research is to isolate and partially purify bioactive components from the crude ethanol extract of the stem bark of ZSC-L. Besides, bioassay-guided fractionation of ZSC-L stem bark was conducted using different solvents. The solvents were reutilized to minimize the production cost and environmental harm. In addition, the antimicrobial activities of the fractions were analyzed, followed by metabolic profiling using LC-HRMS. The n-butanol fraction showed the highest antimicrobial efficacy, so it was subjected to further purification. For the first time, two major compounds were isolated from the stem bark of ZSC-L and identified as lupane-type pentacyclic triterpenoids betulinic acid and betulin. Both compounds were used as antibacterial and anticancer agents and considered as a green product as the extraction procedure reduced the use of hazardous chemicals. Metabolic characterization of ZSC-L and its bioactive fractions were performed using LC-HR-ESI-MS and the results revealed the dereplication of 36 compounds belonging to different chemical classes. Flavonoids and triterpenes were the most prominent metabolite classes in the different fractions. The molecular docking results were obtained by studying the interaction of betulin and betulinic acid with antimicrobial receptors (4UYM, 1IYL, 1AJ2, 6J7L, 1AD4, 2VEG) to support the in vitro results. Our study highlights that Ziziphus spina-christi and its phytoconstituents, especially triterpenoids, act as a promising antimicrobial candidate in pharmaceutical and clinical applications.

Pulmonary Embolism in Hospitalized Patients with COVID-19: A Multicenter Study.

Background Pulmonary embolism (PE) commonly complicates SARS-CoV-2 infection, but incidence and mortality reported in single-center studies, along with risk factors, vary. Purpose To determine the incidence of PE in patients with COVID-19 and its associations with clinical and laboratory parameters. Materials and Methods In this HIPAA-compliant study, electronic medical records were searched retrospectively for demographic, clinical, and laboratory data and outcomes among patients with COVID-19 admitted at four hospitals from March through June 2020. PE found at CT pulmonary angiography and perfusion scintigraphy was correlated with clinical and laboratory parameters. The d-dimer level was used to predict PE, and the obtained threshold was externally validated among 85 hospitalized patients with COVID-19 at a fifth hospital. The association between right-sided heart strain and embolic burden was evaluated in patients with PE undergoing echocardiography. Results A total of 413 patients with COVID-19 (mean age, 60 years ± 16 [standard deviation]; age range, 20-98 years; 230 men) were evaluated. PE was diagnosed in 102 (25%; 95% CI: 21, 29) of 413 hospitalized patients with COVID-19 who underwent CT pulmonary angiography or perfusion scintigraphy. PE was observed in 21 (29%; 95% CI: 19, 41) of 73 patients in the intensive care unit (ICU) versus 81 (24%; 95% CI: 20, 29) of 340 patients who were not in the ICU (P = .37). PE was associated with male sex (odds ratio [OR], 1.74; 95% CI: 1.1, 2.8; P = .02); smoking (OR, 1.86; 95% CI: 1.0, 3.4; P = .04); and increased d-dimer (P < .001), lactate dehydrogenase (P < .001), ferritin (P = .001), and interleukin-6 (P = .02) levels. Mortality in hospitalized patients was similar between patients with PE and those without PE (14% [13 of 102]; 95% CI: 8, 22] vs 13% [40 of 311]; 95% CI: 9, 17; P = .98), suggesting that diagnosis and treatment of PE were not associated with excess mortality. The d-dimer levels greater than 1600 ng/mL [8.761 nmol/L] helped predict PE with 100% sensitivity and 62% specificity in an external validation cohort. Embolic burden was higher in patients with right-sided heart strain among the patients with PE undergoing echocardiography (P = .03). Conclusion Pulmonary embolism (PE) incidence was 25% in patients hospitalized with COVID-19 suspected of having PE. A d-dimer level greater than 1600 ng/mL [8.761 nmol/L] was sensitive for identification of patients who needed CT pulmonary angiography. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Ketai in this issue.

Radiographic clues to the unstable knee: are findings of trochlear dysplasia on lateral knee radiographs reliable and predictive of patellar dislocation?

BACKGROUND: Trochlear dysplasia (TD) is a key predisposing risk factor for patellar instability (PI) and lateral patellar dislocation (LPD) injuries. It is useful to understand the reliability of radiographic findings of TD and the accuracy of knee radiographs in diagnosing patients with recent LPD. PURPOSE: The purposes of our study are to evaluate the inter-rater reliability of specific radiographic signs of PI and staging of TD between radiologists and orthopedic surgeons, and to identify which findings are associated with recent LPD. METHODS: This retrospective study comprised 336 patients aged 8 to 18 who obtained knee radiographs over a 3-year period. Two radiologists and two orthopedic surgeons, blinded to patient history, examined radiographs for indicators of PI. Using data from 19 confirmed LPD cases and 317 controls, inter-observer agreement (kappa, Pearson's correlation coefficient) was assessed, as was the odds ratio for likelihood of LPD. RESULTS: There was nearly perfect agreement between radiologists for patella-tendon ratios (Pearson's correlation coefficient 0.8377, P < 0.0001) and discrimination between normal knees and high-grade TD (kappa 0.9213, P < 0.0001). There is fair agreement between radiologists and surgeons distinguishing between normal knees and high-grade TD (kappa 0.5843, P < 0.0001). Lateral knee radiographs interpreted as high-grade TD were highly predictive of LPD (odds ratio 7.58-54.8) among all readers. CONCLUSIONS: There is high agreement between radiologists when evaluating lateral knee radiographs for signs of TD, validating the results of prior literature. Radiographic findings TD, patella alta, and effusion are variable predictors of recent LPD, greatest among patients with TD.

Surface plasmon resonance sensing of Ebola virus: a biological threat.

Here, different monoclonal antibodies (mAb1, mAb2 and mAb3) of Ebola virus were screened in a real-time and label-free manner using surface plasmon resonance (SPR) to select an appropriate antibody for biosensor applications against a biological warfare agent. For this purpose, a gold SPR chip was modified with 4-mercaptobenzoic acid (4-MBA), and modification was confirmed by FTIR-ATR and EIS. The 4-MBA-modified gold SPR chip was used for immobilization of the recombinant nucleoprotein of Ebola (EBOV-rNP), and the interactions of mAb1, mAb2 and mAb3 were then investigated to determine the best mAb based on the affinity constant (KD), expressed as equilibrium dissociation constant. KD values of 809 nM, 350 pM and 52 pM were found for the interaction of mAb1, mAb2 and mAb3 of Ebola with the immobilized EBOV-rNP, respectively, thus reflecting the high affinity of mAb3. This was confirmed by ELISA results. The thermodynamic parameters (ΔG, ΔH and ΔS) for the interaction between mAb3 and EBOV-rNP were also determined, which revealed that the interaction was spontaneous, endothermic and driven by entropy. The SPR limit of detection of EBOV-rNP with mAb3 was 0.5 pg ml-1, showing mAb3 to be the best high-affinity antibody in our study. This study has opened up new possibilities for SPR screening of different monoclonal antibodies of BWA through the convergence of materials science and optical techniques.

Global trends in the evaluation and management of cerebrospinal fluid shunt infection: a cooperative ISPN survey.

INTRODUCTION: Ventriculoperitoneal shunts (VPS) is commonly performed by pediatric neurosurgeons and there is no consensus in management of VPS infection as it relates to diagnosis and treatment. OBJECTIVE: We utilized an international practitioner-based survey to study the variability in VPS infection diagnostic and therapeutic measures. METHODS: A survey gauging practice patterns of pediatric neurosurgeons regarding VPS and its complication management was distributed. Survey endpoints were analyzed by VPS case volume and pediatric-focused case volume regarding diagnostic measures, use of cerebrospinal fluid (CSF) profile, microbiology, and treatment. RESULTS: A total of 439 surveys were distributed, with a response rate of 31%. Responders ranged from Americas (44.9%), European (31.4%), Asian (18.6%), African (2.5%), to Australian continents (2.5%). Practitioners were stratified based on number and percentage pediatric VPS performed. Institutions performing highest VPS and percentage pediatric case volumes had lower rate of VPS infection. Shunt tap was the most widely used diagnostic study. Overall CSF profile did not affect decision making towards VPS internalization, except for leukocyte count ≤ 20 × 109/L. Practitioners utilized 3 negative cultures prior to VPS internalization. Discrepancies in surgical management were noted amongst centers with high versus low VPS volume and proportion of pediatric-focused case volume. Practice patterns were not noted to be organism dependent. Antibiotic-impregnated shunts were utilized in the Americas and Europe over other regions but only in one third of all initial VPS or as a preventive strategy after a VPS infection has been resolved respectively. DISCUSSION: Survey results from 6 continents in VPS management revealed patterns of lower infection in high-volume centers, 3 negative cultures prior to internalization and aggressive surgical VPS infection management in high-volume institutions.

An Exportin-1-dependent microRNA biogenesis pathway during human cell quiescence.

The reversible state of proliferative arrest known as "cellular quiescence" plays an important role in tissue homeostasis and stem cell biology. By analyzing the expression of miRNAs and miRNA-processing factors during quiescence in primary human fibroblasts, we identified a group of miRNAs that are induced during quiescence despite markedly reduced expression of Exportin-5, a protein required for canonical miRNA biogenesis. The biogenesis of these quiescence-induced miRNAs is independent of Exportin-5 and depends instead on Exportin-1. Moreover, these quiescence-induced primary miRNAs (pri-miRNAs) are modified with a 2,2,7-trimethylguanosine (TMG)-cap, which is known to bind Exportin-1, and knockdown of Exportin-1 or trimethylguanosine synthase 1, responsible for (TMG)-capping, inhibits their biogenesis. Surprisingly, in quiescent cells Exportin-1-dependent pri-miR-34a is present in the cytoplasm together with a small isoform of Drosha, implying the existence of a different miRNA processing pathway in these cells. Our findings suggest that during quiescence the canonical miRNA biogenesis pathway is down-regulated and specific miRNAs are generated by an alternative pathway to regulate genes involved in cellular growth arrest.

Association of osteopenia and osteoporosis with higher rates of pseudarthrosis and revision surgery in adult patients undergoing single-level lumbar fusion.

OBJECTIVE: Patients with osteopenia or osteoporosis who require surgery for symptomatic degenerative spondylolisthesis may have higher rates of postoperative pseudarthrosis and need for revision surgery than patients with normal bone mineral densities (BMDs). To this end, the authors compared rates of postoperative pseudarthrosis and need for revision surgery following single-level lumbar fusion in patients with normal BMD with those in patients with osteopenia or osteoporosis. The secondary outcome was to investigate the effects of pretreatment with medications that prevent bone loss (e.g., teriparatide, bisphosphonates, and denosumab) on these adverse outcomes in this patient cohort. METHODS: Patients undergoing single-level lumbar fusion between 2007 and 2017 were identified. Based on 1:1 propensity matching for baseline demographic characteristics and comorbidities, 3 patient groups were created: osteopenia (n = 1723, 33.3%), osteoporosis (n = 1723, 33.3%), and normal BMD (n = 1723, 33.3%). The rates of postoperative pseudarthrosis and revision surgery were compared between groups. RESULTS: The matched populations analyzed in this study included a total of 5169 patients in 3 groups balanced at baseline, with equal numbers (n = 1723, 33.3%) in each group: patients with a history of osteopenia, those with a history of osteoporosis, and a control group of patients with no history of osteopenia or osteoporosis and with normal BMD. A total of 597 complications were recorded within a 2-year follow-up period, with pseudarthrosis (n = 321, 6.2%) being slightly more common than revision surgery (n = 276, 5.3%). The odds of pseudarthrosis and revision surgery in patients with osteopenia were almost 2-fold (OR 1.7, 95% CI 1.26-2.30) and 3-fold (OR 2.73, 95% CI 1.89-3.94) higher, respectively, than those in patients in the control group. Similarly, the odds of pseudarthrosis and revision surgery in patients with osteoporosis were almost 2-fold (OR 1.92, 95% CI 1.43-2.59) and > 3-fold (OR 3.25, 95% CI 2.27-4.65) higher, respectively, than those in patients in the control group. Pretreatment with medications to prevent bone loss prior to surgery was associated with lower pseudarthrosis and revision surgery rates, although the differences did not reach statistical significance. CONCLUSIONS: Postoperative pseudarthrosis and revision surgery rates following single-level lumbar spinal fusion are significantly higher in patients with osteopenia and osteoporosis than in patients with normal BMD. Pretreatment with medications to prevent bone loss prior to surgery decreased these complication rates, although the observed differences did not reach statistical significance.

Increased Hip Intracapsular Pressure Decreases Perfusion of the Capital Femoral Epiphysis in a Skeletally Immature Porcine Model.

BACKGROUND: Increased intracapsular hip pressure is thought to be one of the possible etiologies of femoral head avascular necrosis after intra-articular proximal femoral fractures or acute slipped capital femoral epiphysis. The purpose of this study was to evaluate the relationship between intra-articular hip pressure (IAP) and epiphyseal perfusion pressure (EPP), and its dependency on skeletal maturity using a porcine model. METHODS: Seven female Yorkshire-hybrid pigs were used to study the direct relationship between IAP and EPP. A needle inserted into the capsule provided both IAP monitoring and saline infiltration until IAP was above mean arterial pressure (MAP). Video simultaneously documented IAP, EPP, MAP. Parameters for all trials in each hip were averaged and compared between the 2 age groups. Significance was P<0.05. RESULTS: Four young hips (in pigs 10.3±1.0 wk, 27.4±2.0 kg) and 5 older hips (21.1±0.1 wk, 89.4±7.1 kg) were studied. There was no significant difference in the MAP (50.0±11.8 and 55.5±7.0 mm Hg respectively, P=0.411) between the 2 age groups. In the older hips, biphasic EPP persisted despite increasing IAP to an average of 177 mm Hg over MAP. In the young pigs, the biphasic EPP waveform ceased with increased IAP to an average of 28 mm Hg over MAP. Biphasic waveforms returned once IAP fell to an average of 5 mm Hg over MAP. CONCLUSIONS: Increased IAP resulted in tamponade of epiphyseal perfusion in the young, but not in the older hips. An intact physis may preclude intraosseous metaphyseal vessels from penetrating the epiphysis, leaving it vulnerable to retinacular artery tamponade. CLINICAL RELEVANCE: The IAP and EPP relationship has direct clinical practice implications. Hip capsulotomy and decompression in young patients with intra-articular proximal femoral fractures and increased intracapsular pressure may decrease avascular necrosis risk.

Pediatric Brainstem Gliomas: A Retrospective Study of 180 Patients from the SEER Database.

BACKGROUND/AIMS: Large population-based studies are needed to assess the epidemiology and survival risk factors associated with pediatric brainstem gliomas. This retrospective study explores factors that may influence survival in this population. METHODS: Utilizing the SEER database, the authors retrospectively assessed survival in histologically confirmed brainstem gliomas in patients aged 17 and younger. Survival was described with Kaplan-Meyer curves and multivariate regression analysis. RESULTS: This analysis of 180 cases showed that age (hazard ratio [HR] 1.04, 95% CI 0.96-1.14, p = 0.34), non-white race (HR 1.00, 95% CI 0.35-2.85 p > 0.99), distant or invasive extension of the tumor (HR 0.4, 95% CI 0.08-2.53, p = 0.37), and radiation therapy (HR 1.27, 95% CI 0.52-3.11, p = 0.61) were not associated with decreased survival. High-grade tumor status (HR 8.64, 95% CI 3.49-21.41, p < 0.001) was associated with decreased survival. Partial resection (HR 0.11, 95% CI 0.04-0.30, p < 0.001) and gross-total resection (HR 0.03, 95% CI 0.01-0.14, p < 0.001) were associated with improved survival. CONCLUSIONS: High-grade brainstem gliomas have a worse prognosis. Early diagnosis and surgery appear to be associated with improved survival, while the role of radiation is unclear.

Impact of multidisciplinary foot care team on outcome of diabetic foot ulcer in term of lower extremity amputation at a tertiary care unit in Karachi, Pakistan.

To compare the outcomes of diabetic foot ulcers (DFU) in terms of healing and lower extremity amputation (LEA) rate before and after training of multidisciplinary foot care team (MDFCT). Subjects were categorised into two groups; Group-A cases seen between 1997 and 2006 (before upgrading of training and services of MDFCT) and Group-B cases seen between 2007 and 2016 (after upgrading of training and services of MDFCT). Baseline demographic characteristics, biochemical results, and outcomes of DFU in terms of healing or amputation were analysed by using statistical package social science (SPSS) version 20. Total 7994 DFU cases seen, 888 in group A and 7106 in group B. Mean age of patients was 53.80 ± 10.40 years and mean haemoglobin (HbA1c) was 10.12 ± 2.44. Overall, decreasing trends of amputations were observed from baseline 27.5% to 3.92% during the period of 20 years. In group A, 479 (78.8%) subjects healed completely compared with 3806 (89.1%) in group B. Significant reduction in toe amputations ([13.81%] vs [8.11%]) and below knee amputations [(5.26%) vs (1.82%)] were seen. Similarly, rates of above knee amputation ([1.80%] vs [0.35%] P-value 0.008) in two groups was also significant. Significant improvement was observed in outcomes of DFU in terms of amputation through multidisciplinary team approach.

Factors predicting ablation site recurrence following percutaneous microwave ablation of colorectal hepatic metastases.

BACKGROUND: Microwave ablation (MWA) is a recognised treatment option for liver metastases. The size of the tumour is a well-established factor that influences the success of MWA. However, the effect of "heat sink" on the success of MWA for hepatic metastases is unclear. The aim of this study was to determine whether heat sink effect is a factor that contributes to ablation site recurrence (ASR). METHODS: A prospectively maintained database of patients who underwent percutaneous MWA for treatment of colorectal liver metastases was analysed. Imaging and demographic characteristics were compared between metastases that recurred following ablation and those that did not. Proximity to a large hepatic vein was defined as <10 mm. RESULTS: 126 ablations in 87 patients met the inclusion criteria and were studied over a median follow-up period of 28 (12-75) months. ASR was detected in 43 ablations (34%) and was associated with clinical risk score (CRS) ≥2 (OR 2.2 95% CI 1.3-3.3, p = 0.029), metastasis size (OR 0.953 95% CI (0.929-0.978), p < 0.001) and proximity to a large hepatic vein (OR 7.5 95%CI 2.4-22.8, p < 0.001). Proximity to a large hepatic vein was not associated with reduced overall survival (OS) but was associated with liver-specific recurrence (HR 4.7 95%CI 1.7-12.5, p = 0.004). CONCLUSIONS: In addition to tumour size proximity to large hepatic venous structures is an independent predictor of ASR and liver-specific recurrence following MWA. However, this was not associated with overall survival.

Identification of reversible causes of minority inequity in stroke: severity related to race and socio-economic status.

OBJECTIVES: Previous reports of a higher incidence and risk of stroke in minorities were associated primarily with race and ethnicity, yet the relationship between socio-economic status (SES) and racial disparities in stroke is less well known. We have investigated the effects of SES on the incidence of stroke type and its severity in minorities. METHODS: The clinical and demographic data on 140 patients diagnosed with a stroke in the North Lawndale neighbourhood of Chicago, one of the city's poorest communities, were collected prospectively over a 13-month period and then were retrospectively analysed. RESULTS: Overall, haemorrhagic stroke occurred in 31% of cases, differing from the previously reported haemorrhagic stroke incidence of 15%. When accounting for SES, the incidence of haemorrhagic stroke in the uninsured versus the privately or Medicaid-insured increased to 50%. Uninsured African-American patients experienced even higher rates of haemorrhagic stroke at 55%. CONCLUSIONS: Patients who are uninsured minorities may be at an increased risk for severe strokes. This increase in risk appears to be related to the increased incidence of risk factors and lack of treatment. The lack of funds, care access, and limited education in these patients may be related to their increase in risk factors. This paper identifies potentially reversible environmental and societal factors that can lead to improved outcomes in indigent minority patients.