Research on the association between
in the disc space and type 1 Modic changes in adjacent vertebrae is limited and has produced mixed results. The prevalence of bacteria in intervertebral discs ...contradicts the prior understanding that skeletal areas in the human anatomy are sterile; yet it opens new treatment possibilities. We investigated the relationship of
and type 1 Modic changes in the cervical spine.
Over a 36-month period, we collected intraoperative biopsies of patients undergoing a routine cervical spine operation for degenerative disc diseases. The disc material was cultured aerobically and anaerobically for 7 days. All preoperative MR images were evaluated for Modic changes by a board-certified neuroradiologist. Medical records were reviewed for other spine interventions before the operation.
The study population consisted of 48 patients. Of these, 14 patients tested positive for
(29%) at ≥1 level. Additionally, 13 patients had type 1 Modic changes (27%) at ≥1 level; 54% (95% CI, 27%-84%) of patients who had type 1 Modic changes were also positive for
compared with 20% (95% CI, 7%-33%) of patients without type 1 Modic changes. The difference between these proportions was 34% (95% CI, 4%-64%). The Fisher exact test produced a
value of .03 for the association between
and MC1, and .53 for the association between
and prior procedures.
We conclude that
was prevalent in the degenerated cervical spine and that type 1 Modic changes were predictive of a culture positive for
. We also found that the prevalence of
was not associated with previous interventions. If these results are validated by future studies, they could have a major impact on the standard of care for back and neck pain.
Summary
Hyperkyhosis is thought to be a fall risk factor in older adults. This large study of older men found that fall risk increased with greater kyphosis measured with the blocks method, but did ...not find an association between kyphosis and falls when measured by the commonly used the Cobb angle method.
Introduction
Research suggests an association between hyperkyphosis and falls in community-dwelling older adults, though this has not been investigated within large, population-based studies. This study sought to determine whether two measures of kyphosis prospectively predict fall risk over 3 years among older men.
Methods
Within the Osteoporotic Fractures in Men Study (MrOS), we conducted two 3-year prospective studies of 2346 and 2928 men. The first group had kyphosis measured by the Cobb angle at visit 1, while the second group had kyphosis assessed with the blocks method at visit 3; both groups then self-reported falls tri-annually for 3 years. Poisson regression with GEE was used to obtain relative risks (RR) of falls.
Results
The fall rates over 3 years were 651/1000 person-years among the visit 1 sample (mean age 74 ± 6 years) and 839/1000 person-years among the visit 3 sample (mean age 79 ± 5 years). In adjusted models of the visit 3 sample, the risk of falls was increased by 12% for each standard deviation increase (1.4 blocks) in the number of blocks required to achieve a neutral head and neck position (RR = 1.12, 95% CI = 1.06, 1.18). The Cobb angle was not associated with falls in the visit 1 sample.
Conclusions
Although the Cobb angle did not predict falls in community-dwelling older men over 3 years, the blocks method of measuring kyphosis was predictive of falls in this population. This difference could be due to the Cobb angle’s focus on thoracic kyphosis, whereas the blocks method may additionally capture abnormal cervical spine curvature.
To rigorously evaluate the time course of cognitive change in a cohort of individuals with HIV-associated neurocognitive disorders (HAND) initiating combination antiretroviral therapy (CART), and to ...investigate which demographic, laboratory, and treatment factors are associated with neuropsychological (NP) outcome (or "any NP improvement").
Study participants included 37 HIV+ individuals with mild to moderate NP impairment who initiated CART and underwent NP testing at 12, 24, 36, and 48 weeks thereafter. NP change was assessed using a regression-based change score that was normed on a separate NP-stable group thereby controlling for regression toward the mean and practice effect. Mixed-effect regression models adjusting for loss to follow-up were used to evaluate the time course of cognitive change and its association with baseline and time-varying predictors.
In persons with HAND initiating CART, cognitive improvement happens soon after initiation (13% at week 12), but more often 24, 36, and up to 48 weeks after initiation (up to 41%), with fewer than 5% demonstrating significant worsening. In multivariate analyses, unique predictors of NP improvement included more severe baseline NP impairment and higher CART CNS penetration index. Greater viral load decrease was associated with NP improvement only in univariate analyses.
Clinically meaningful neuropsychological improvement seemed to peak around 24-36 weeks after combination antiretroviral therapy initiation and was prolonged over the 1-year study period. This study also provides new evidence that benefit may be maximized by choosing antiretroviral medications that reach therapeutic concentrations in the CNS.
Aim
Patients with synchronous colon cancer metastases have highly variable overall survival (OS), making accurate predictive models challenging to build. We aim to use machine learning to more ...accurately predict OS in these patients and to present this predictive model in the form of nomograms for patients and clinicians.
Methods
Using the National Cancer Database (2010–2014), we identified right colon (RC) and left colon (LC) cancer patients with synchronous metastases. Each primary site was split into training and testing datasets. Nomograms predicting 3‐ year OS were created for each site using Cox proportional hazard regression with lasso regression. Each model was evaluated by both calibration (comparison of predicted vs observed OS) and validation (degree of concordance as measured by the c‐index) methodologies.
Results
A total of 11 018 RC and 8346 LC patients were used to construct and validate the nomograms. After stratifying each model into five risk groups, the predicted OS was within the 95% CI of the observed OS in four out of five risk groups for both the RC and LC models. Externally validated c‐indexes at 3 years for the RC and LC models were 0.794 and 0.761, respectively.
Conclusions
Utilization of machine learning can result in more accurate predictive models for patients with metastatic colon cancer. Nomograms built from these models can assist clinicians and patients in the shared decision‐making process of their cancer care.
We study model selection for clustered data, when the focus is on cluster specific inference. Such data are often modelled using random effects, and conditional Akaike information was proposed in ...Vaida & Blanchard (2005) and used to derive an information criterion under linear mixed models. Here we extend the approach to generalized linear and proportional hazards mixed models. Outside the normal linear mixed models, exact calculations are not available and we resort to asymptotic approximations. In the presence of nuisance parameters, a profile conditional Akaike information is proposed. Bootstrap methods are considered for their potential advantage in finite samples. Simulations show that the performance of the bootstrap and the analytic criteria are comparable, with bootstrap demonstrating some advantages for larger cluster sizes. The proposed criteria are applied to two cancer datasets to select models when the cluster-specific inference is of interest.
The objective of this study was to examine the spectrum of human immunodeficiency virus (HIV) brain pathology and its clinical correlates in the antiretroviral era. We carried out a cross-sectional ...survey, analyzing prospective clinical and neuropathological data collected by the National NeuroAIDS Tissue Consortium (NNTC), comprising 589 brain samples from individuals with advanced HIV disease collected from 1999 onwards. We assessed gender, ethnicity/race, mode of transmission, age, year of death, nadir CD4, plasma viral load, last antiretroviral regimen, presence of parenchymal HIV brain pathology, HIV-associated neurocognitive disorder, and major depressive disorder. We compared cohort demographic variables with Centers for Disease Control and Prevention US HIV/AIDS statistics and examined associations of parenchymal HIV brain pathology with demographic, clinical, and HIV disease factors. With regard to Centers for Disease Control and Prevention US data, the NNTC was similar in age distribution, but had fewer females and African Americans and more Hispanics and men who have sex with men. Only 22% of the brains examined were neuropathologically normal. Opportunistic infections occurred in 1% to 5% of the cohort. Parenchymal HIV brain pathology was observed in 17.5% of the cohort and was associated with nadir CD4 and plasma viral load. Brains without parenchymal HIV brain pathology often had other noninfectious findings or minimal nondiagnostic abnormalities that were associated with HIV-associated neurocognitive disorder. Clinically, 60% of the cohort reported a lifetime episode of major depressive disorder and 88% had a HIV-associated neurocognitive disorder. No pathological finding correlated with major depressive disorder. Both antiretroviral treatment regimen and elevated plasma HIV viral load were associated with presence of parenchymal HIV brain pathology; however, multivariate analyses suggest a stronger association with plasma viral load. The frequency of HIV brain pathology was lower than previous pre-antiretroviral reports, and was predicted by lower nadir CD4 and higher plasma viral load. Noninfectious pathologies and minimal changes correlated with HIV-associated neurocognitive disorder, suggesting a shift in pathogenesis from florid HIV replication to other, diverse mechanisms.
HIV enters the brain soon after infection causing neuronal damage and microglial/astrocyte dysfunction leading to neuropsychological impairment. We examined the impact of HIV on resting cerebral ...blood flow (rCBF) within the lenticular nuclei (LN) and visual cortex (VC).
This cross-sectional study used arterial spin labeling MRI (ASL-MRI) to measure rCBF within 33 HIV+ and 26 HIV- subjects. Nonparametric Wilcoxon rank sum test assessed rCBF differences due to HIV serostatus. Classification and regression tree (CART) analysis determined optimal rCBF cutoffs for differentiating HIV serostatus. The effects of neuropsychological impairment and infection duration on rCBF were evaluated.
rCBF within the LN and VC were significantly reduced for HIV+ compared to HIV- subjects. A 2-tiered CART approach using either LN rCBF < or =50.09 mL/100 mL/min or LN rCBF >50.09 mL/100 mL/min but VC rCBF < or =37.05 mL/100 mL/min yielded an 88% (29/33) sensitivity and an 88% (23/26) specificity for differentiating by HIV serostatus. HIV+ subjects, including neuropsychologically unimpaired, had reduced rCBF within the LN (p = 0.02) and VC (p = 0.001) compared to HIV- controls. A temporal progression of brain involvement occurred with LN rCBF significantly reduced for both acute/early (<1 year of seroconversion) and chronic HIV-infected subjects, whereas rCBF in the VC was diminished for only chronic HIV-infected subjects.
Resting cerebral blood flow (rCBF) using arterial spin labeling MRI has the potential to be a noninvasive neuroimaging biomarker for assessing HIV in the brain. rCBF reductions that occur soon after seroconversion possibly reflect neuronal or vascular injury among HIV+ individuals not yet expressing neuropsychological impairment.
Sensory neuropathy (HIV-SN) is a common cause of pain in HIV-infected people. Establishing a diagnosis of HIV-SN is important, especially when contemplating opioid use in high-risk populations. ...However physical findings of HIV-SN may be subtle, and sensitive diagnostic tools require specialized expertise. We investigated the association between self-report of distal neuropathic pain and/or paresthesias (DNPP) and objective signs of HIV-SN. Data were obtained from the Central Nervous System HIV Antiretroviral Therapy Effects Research (CHARTER) study. Out of 237 participants, 101 (43%) reported DNPP. Signs of HIV-SN were measured by a modified Total Neuropathy Score (TNS), composed of six objective sensory subscores (pin sensibility, vibration sensibility, deep tendon reflexes, quantitative sensory testing for cooling and vibration, and sural sensory amplitude). Self-report of DNPP was associated with all six TNS items in univariate analysis and with four TNS items in multivariate analysis. The sensitivity and specificity of self-report of DNPP in detecting the presence of a sensory abnormality were 52% and 92%, respectively with a PPV of 96% and a NPV of 34%. Increasing intensity of pain measured on a visual analog scale was associated with increasing severity of sensory abnormality. In summary, our results suggest that HIV-infected patients reporting symptoms consistent with HIV-SN, such as tingling, pins and needles, or aching or stabbing pain in the distal lower extremities, usually have objective evidence of HIV-SN on neurologic examination or with neurophysiologic testing. This finding holds true regardless of demographic factors, depression or substance use history.
Resting-state functional connectivity MRI (rs-fcMRI) may provide insight into the neurophysiology of HIV and aging.
In this cross-sectional study, we used rs-fcMRI to investigate intra- and ...internetwork connectivity among 5 functional brain networks in 58 HIV-infected (HIV+) participants (44% receiving highly active antiretroviral therapy) and 53 HIV-uninfected (HIV-) controls. An analysis of covariance assessed the relationship among age, HIV laboratory markers, or degree of cognitive impairment and brain networks.
Individuals who were HIV+ had decreased rs-fcMRI intranetwork correlations in the default mode (DMN, p = 0.01), control (CON, p = 0.02), and salience (SAL, p = 0.02) networks, but showed no changes in the sensorimotor (SMN) or dorsal attention (DAN) network. Compared with HIV- controls, participants who were HIV+ had a significant loss of internetwork correlations between the DMN-DAN (p = 0.02), trending loss in DMN-SAL (p = 0.1) and CON-SMN (p = 0.1), and trending increase in CON-SAL (p = 0.1). Neither HIV markers (plasma HIV viral load or CD4(+) cell count) nor degree of cognitive impairment correlated with rs-fcMRI measures. Aging correlated with a decrease in the magnitude of intranetwork functional connectivity within the DMN (p = 0.04) and SAL (p = 0.006) and with decreased magnitude of internetwork functional connectivity between DMN and SAL (p = 0.009) for both HIV+ and HIV- participants. No interaction was observed between HIV and aging.
HIV and aging may cause independent decreases in rs-fcMRI. HIV may lead to a baseline decrease in brain function similar to deterioration that occurs with aging.
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