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Mechanisms Underlying Reshuffling of Visual Responses by Optogenetic Stimulation in Mice and Monkeys
No full textProximal junctional failure in primary thoracolumbar fusion/fixation to the sacrum/pelvis for adult symptomatic lumbar scoliosis: long-term follow-up of a prospective multicenter cohort of 160 patients.
No full textObjectiveProximal junctional failure (PJF) is a severe form of proximal junctional kyphosis. Previous reports on PJF have been limited by heterogeneous cohorts and relatively short follow-ups. The authors' objectives herein were to identify risk factors for PJF and to assess its long-term incidence and revision rates in a homogeneous cohort.MethodsThe authors reviewed data from the Adult Symptomatic Lumbar Scoliosis 1 trial (ASLS-1), a National Institutes of Health-sponsored prospective multicenter study. Inclusion criteria were an age ≥ 40 years, ASLS (Cobb angle ≥ 30° and Oswestry Disability Index [ODI] ≥ 20 or Scoliosis Research Society revised 22-item questionnaire [SRS-22r] score ≤ 4.0 in pain, function, or self-image domains), and primary thoracolumbar fusion/fixation to the sacrum/pelvis of ≥ 7 levels. PJF was defined as a postoperative proximal junctional angle (PJA) change > 20°, fracture of the uppermost instrumented vertebra (UIV) or UIV+1 with > 20% vertebral height loss, spondylolisthesis of UIV/UIV+1 > 3 mm, or UIV screw dislodgment.ResultsOne hundred sixty patients (141 women) were included in this analysis and had a median age of 62 years and a mean follow-up of 4.3 years (range 0.1-6.1 years). Forty-six patients (28.8%) had PJF at a median of 0.92 years (IQR 0.14, 1.23 years) following surgery. Based on Kaplan-Meier analyses, PJF rates at 1, 2, 3, and 4 years were 14.4%, 21.9%, 25.9%, and 27.4%, respectively. On univariate analysis, PJF was associated with greater age (p = 0.0316), greater body mass index (BMI; p = 0.0319), worse baseline patient-reported outcome measures (PROMs; ODI, SRS-22r, and SF-12 Physical Component Summary [PCS]; all p ConclusionsAmong 160 primary ASLS patients with a median age of 62 years and predominant coronal deformity, the PJF rate was 28.8% at a mean 4.3-year follow-up, with a revision rate of 34.8%. On univariate analysis, PJF was associated with a greater age and BMI, worse baseline PROMs, the use of PCOs, and greater postoperative TK and PJA. The use of UIV hooks was protective against PJF. On multivariate analysis (without postoperative measures), a higher risk of PJF was associated with greater BMI and preoperative TK and lower preoperative PJA
Comparisons of Infant and Adult Mice Reveal Age Effects for Liver Depot Gene Therapy in Pompe Disease.
No full textPompe disease is caused by the deficiency of lysosomal acid α-glucosidase (GAA). It is expected that gene therapy to replace GAA with adeno-associated virus (AAV) vectors will be less effective early in life because of the rapid loss of vector genomes. AAV2/8-LSPhGAA (3 × 1010 vector genomes [vg]/mouse) was administered to infant (2-week-old) or adult (2-month-old) GAA knockout mice. AAV vector transduction in adult mice significantly corrected GAA deficiency in the heart (p 50 weeks. However, in infant mice, the same treatment only partially corrected GAA deficiency in the heart (p < 0.05), diaphragm (p < 0.05), and quadriceps (p < 0.05). The clearance of glycogen was much more efficient in adult mice compared with infant mice. Improved wire hang test latency was observed for treated adults (p < 0.05), but not for infant mice. Abnormal ventilation was corrected in both infant and adult mice. Vector-treated female mice demonstrated functional improvement, despite a lower degree of biochemical correction compared with male mice. The relative vector dose for infants was approximately 3-fold higher than adults, when normalized to body weight at the time of vector administration. Given these data, the dose requirement to achieve similar efficacy will be higher for the treatment of young patients
Patients with spinal deformity over the age of 75: a retrospective analysis of operative versus non-operative management.
No full textPurposeThe goal of the present study was to compare the outcomes of operative and non-operative patients with adult spinal deformity (ASD) over 75 years of age.MethodsA retrospective review of a multicenter prospective adult spinal deformity database was conducted examining patients with ASD over the age of 75 years. Demographics, comorbidities, operation-related variables, complications, radiographs, and Health-related quality of life (HRQOL) measures collected included Oswestry Disability Index, Short Form-36, and Scoliosis Research Society-22 preoperatively, and at 1 and 2 years later. Minimum clinically important difference (MCID) was calculated and also compared.Results27 patients (12 operative, 15 non-operative) were studied. There were no significant differences (p > 0.05) between operative and non-operative patients for age, body mass-index, and comorbidities, but operative patients had worse baseline HRQOL than non-operative patients. Operative patients had a significant improvement in radiographic parameters in 2-year HRQOL, whereas non-operative patients did not (p > 0.05). Operative patients were significantly more likely to reach MCID (range 41.7-81.8 vs. 0-33.3 %, p ConclusionsIn the largest series to date comparing operative and non-operative management of adult spinal deformity in elderly patients greater than 75 years of age, reconstructive surgery provides significant improvements in pain and disability over a 2-year period. Furthermore, operative patients were more likely to reach MCID than non-operative patients. When counseling elderly patients with ASD, such data may be helpful in the decision-making process regarding treatment
Improving the rates of Aspergillus detection: an update on current diagnostic strategies.
No full textIntroductionThe spectrum of disease caused by Aspergillus spp. is dependent on the immune system of the host, and ranges from invasive aspergillosis (IA) to chronic pulmonary aspergillosis (CPA). Early and reliable diagnosis of Aspergillus disease is important to decrease associated morbidity and mortality. Areas covered: The following review will give an update on current diagnostic strategies for the diagnosis of IA and CPA. Expert commentary: Several new diagnostics for IA (including point-of-care tests) are now available to complement galactomannan testing. In particular, immunoPET/MRI imaging may be a promising approach for diagnosing IA in the near future. Notably, nearly all new biomarkers and tests for IA have been evaluated in the hematology setting only. Validation of biomarkers and tests is therefore needed for the increasing proportion of patients who develop IA outside the hematology setting. As an important first step, reliable definitions of IA are needed for non-hematology settings as clinical presentation and radiologic findings differ in these settings. CPA diagnosis is based on a combination of radiological findings in chest CT, mycological evidence (e.g. by the Aspergillus-specific IgG assay), exclusion of alternative diagnosis and chronicity. ([18F]FDG) PET/CT and immuno PET/MRI imaging are promising new imaging approaches
Transcriptomic and Proteomic Analysis of Clear Cell Foci (CCF) in the Human Non-Cirrhotic Liver Identifies Several Differentially Expressed Genes and Proteins with Functions in Cancer Cell Biology and Glycogen Metabolism.
No full textClear cell foci (CCF) of the liver are considered to be pre-neoplastic lesions of hepatocellular adenomas and carcinomas. They are hallmarked by glycogen overload and activation of AKT (v-akt murine thymoma viral oncogene homolog)/mTOR (mammalian target of rapamycin)-signaling. Here, we report the transcriptome and proteome of CCF extracted from human liver biopsies by laser capture microdissection. We found 14 genes and 22 proteins differentially expressed in CCF and the majority of these were expressed at lower levels in CCF. Using immunohistochemistry, the reduced expressions of STBD1 (starch-binding domain-containing protein 1), USP28 (ubiquitin-specific peptidase 28), monad/WDR92 (WD repeat domain 92), CYB5B (Cytochrome b5 type B), and HSPE1 (10 kDa heat shock protein, mitochondrial) were validated in CCF in independent specimens. Knockout of Stbd1, the gene coding for Starch-binding domain-containing protein 1, in mice did not have a significant effect on liver glycogen levels, indicating that additional factors are required for glycogen overload in CCF. Usp28 knockout mice did not show changes in glycogen storage in diethylnitrosamine-induced liver carcinoma, demonstrating that CCF are distinct from this type of cancer model, despite the decreased USP28 expression. Moreover, our data indicates that decreased USP28 expression is a novel factor contributing to the pre-neoplastic character of CCF. In summary, our work identifies several novel and unexpected candidates that are differentially expressed in CCF and that have functions in glycogen metabolism and tumorigenesis
Social networks, health-promoting behaviors, and health-related quality of life in older adults with and without arthritis.
No full textThe purpose of this secondary analysis study was to compare social networks, health-promoting behaviors, and health-related quality of life of South Korean adults, aged 65 years or older, with and without arthritis, and to identify factors that are related to health-related quality of life. The sample consisted of 103 adults with arthritis and 123 adults without arthritis. Data were analyzed using a two-way analysis of variance, χ2-test, Pearson's correlation, and multiple regression analysis. All variables except age and religion showed statistically significant differences between older adults with and without arthritis. The group with arthritis reported lower scores on social networks, health-promoting behaviors, and health-related quality of life compared to the healthy group without arthritis. Analyzed using multiple regression, 43.8% of the older adults with arthritis had the factors related to health-related quality of life (F = 40.71, p < .001) including exercise (β = .43, p < .001) and living with someone (β = .32, p = .001). In the group of older adults without arthritis, 26.2% had the factors related to health-related quality of life (F = 15.44, p < .001) including exercise (β = .31, p = .001), social gatherings, and employment status. Exercise was one of the factors that showed the strongest relationship to health-related quality of life. The provision of resources that can enable an individual to engage in physical activities is warranted
Calibration of a comprehensive predictive model for the development of proximal junctional kyphosis and failure in adult spinal deformity patients with consideration of contemporary goals and techniques.
No full textObjectiveThe objective of this study was to calibrate an updated predictive model incorporating novel clinical, radiographic, and prophylactic measures to assess the risk of proximal junctional kyphosis (PJK) and failure (PJF).MethodsOperative patients with adult spinal deformity (ASD) and baseline and 2-year postoperative data were included. PJK was defined as ≥ 10° in sagittal Cobb angle between the inferior uppermost instrumented vertebra (UIV) endplate and superior endplate of the UIV + 2 vertebrae. PJF was radiographically defined as a proximal junctional sagittal Cobb angle ≥ 15° with the presence of structural failure and/or mechanical instability, or PJK with reoperation. Backstep conditional binary supervised learning models assessed baseline demographic, clinical, and surgical information to predict the occurrence of PJK and PJF. Internal cross validation of the model was performed via a 70%/30% cohort split. Conditional inference tree analysis determined thresholds at an alpha level of 0.05.ResultsSeven hundred seventy-nine patients with ASD (mean 59.87 ± 14.24 years, 78% female, mean BMI 27.78 ± 6.02 kg/m2, mean Charlson Comorbidity Index 1.74 ± 1.71) were included. PJK developed in 50.2% of patients, and 10.5% developed PJF by their last recorded visit. The six most significant demographic, radiographic, surgical, and postoperative predictors of PJK/PJF were baseline age ≥ 74 years, baseline sagittal age-adjusted score (SAAS) T1 pelvic angle modifier > 1, baseline SAAS pelvic tilt modifier > 0, levels fused > 10, nonuse of prophylaxis measures, and 6-week SAAS pelvic incidence minus lumbar lordosis modifier > 1 (all p ConclusionsPJK and PJF remain critical concerns in ASD surgery, and efforts to reduce the occurrence of PJK and PJF have resulted in the development of novel prophylactic techniques and enhanced clinical and radiographic selection criteria. This study demonstrates a validated model incorporating such techniques that may allow for the prediction of clinically significant PJK and PJF, and thus assist in optimizing patient selection, enhancing intraoperative decision making, and reducing postoperative complications in ASD surgery
An analysis from the Quality Outcomes Database, Part 1. Disability, quality of life, and pain outcomes following lumbar spine surgery: predicting likely individual patient outcomes for shared decision-making.
No full textOBJECTIVE Quality and outcomes registry platforms lie at the center of many emerging evidence-driven reform models. Specifically, clinical registry data are progressively informing health care decision-making. In this analysis, the authors used data from a national prospective outcomes registry (the Quality Outcomes Database) to develop a predictive model for 12-month postoperative pain, disability, and quality of life (QOL) in patients undergoing elective lumbar spine surgery. METHODS Included in this analysis were 7618 patients who had completed 12 months of follow-up. The authors prospectively assessed baseline and 12-month patient-reported outcomes (PROs) via telephone interviews. The PROs assessed were those ascertained using the Oswestry Disability Index (ODI), EQ-5D, and numeric rating scale (NRS) for back pain (BP) and leg pain (LP). Variables analyzed for the predictive model included age, gender, body mass index, race, education level, history of prior surgery, smoking status, comorbid conditions, American Society of Anesthesiologists (ASA) score, symptom duration, indication for surgery, number of levels surgically treated, history of fusion surgery, surgical approach, receipt of workers' compensation, liability insurance, insurance status, and ambulatory ability. To create a predictive model, each 12-month PRO was treated as an ordinal dependent variable and a separate proportional-odds ordinal logistic regression model was fitted for each PRO. RESULTS There was a significant improvement in all PROs (p < 0.0001) at 12 months following lumbar spine surgery. The most important predictors of overall disability, QOL, and pain outcomes following lumbar spine surgery were employment status, baseline NRS-BP scores, psychological distress, baseline ODI scores, level of education, workers' compensation status, symptom duration, race, baseline NRS-LP scores, ASA score, age, predominant symptom, smoking status, and insurance status. The prediction discrimination of the 4 separate novel predictive models was good, with a c-index of 0.69 for ODI, 0.69 for EQ-5D, 0.67 for NRS-BP, and 0.64 for NRS-LP (i.e., good concordance between predicted outcomes and observed outcomes). CONCLUSIONS This study found that preoperative patient-specific factors derived from a prospective national outcomes registry significantly influence PRO measures of treatment effectiveness at 12 months after lumbar surgery. Novel predictive models constructed with these data hold the potential to improve surgical effectiveness and the overall value of spine surgery by optimizing patient selection and identifying important modifiable factors before a surgery even takes place. Furthermore, these models can advance patient-focused care when used as shared decision-making tools during preoperative patient counseling
High-Resolution Multi-Shot Diffusion Imaging of Structural Networks in Healthy Neurocognitive Aging.
No full textHealthy neurocognitive aging has been associated with the microstructural degradation of white matter pathways that connect distributed gray matter regions, assessed by diffusion-weighted imaging (DWI). However, the relatively low spatial resolution of standard DWI has limited the examination of age-related differences in the properties of smaller, tightly curved white matter fibers, as well as the relatively more complex microstructure of gray matter. Here, we capitalize on high-resolution multi-shot DWI, which allows spatial resolutions 3 to be achieved on clinical 3T MRI scanners. We assessed whether traditional diffusion tensor-based measures of gray matter microstructure and graph theoretical measures of white matter structural connectivity assessed by standard (1.5 mm3 voxels, 3.375 μl volume) and high-resolution (1 mm3 voxels, 1μl volume) DWI were differentially related to age and cognitive performance in 61 healthy adults 18-78 years of age. Cognitive performance was assessed using an extensive battery comprising 12 separate tests of fluid (speed-dependent) cognition. Results indicated that the high-resolution data had larger correlations between age and gray matter mean diffusivity, but smaller correlations between age and structural connectivity. Moreover, parallel mediation models including both standard and high-resolution measures revealed that only the high-resolution measures mediated age-related differences in fluid cognition. These results lay the groundwork for future studies planning to apply high-resolution DWI methodology to further assess the mechanisms of both healthy aging and cognitive impairment