Cognitive deficits are a common feature of psychiatric disorders. The authors investigated the nature of disruptions in neural circuitry underlying cognitive control capacities across psychiatric ...disorders through a transdiagnostic neuroimaging meta-analysis.
A PubMed search was conducted for whole-brain functional neuroimaging articles published through June 2015 that compared activation in patients with axis I disorders and matched healthy control participants during cognitive control tasks. Tasks that probed performance or conflict monitoring, response inhibition or selection, set shifting, verbal fluency, and recognition or working memory were included. Activation likelihood estimation meta-analyses were conducted on peak voxel coordinates.
The 283 experiments submitted to meta-analysis included 5,728 control participants and 5,493 patients with various disorders (schizophrenia, bipolar or unipolar depression, anxiety disorders, and substance use disorders). Transdiagnostically abnormal activation was evident in the left prefrontal cortex as well as the anterior insula, the right ventrolateral prefrontal cortex, the right intraparietal sulcus, and the midcingulate/presupplementary motor area. Disruption was also observed in a more anterior cluster in the dorsal cingulate cortex, which overlapped with a network of structural perturbation that the authors previously reported in a transdiagnostic meta-analysis of gray matter volume.
These findings demonstrate a common pattern of disruption across major psychiatric disorders that parallels the "multiple-demand network" observed in intact cognition. This network interfaces with the anterior-cingulo-insular or "salience network" demonstrated to be transdiagnostically vulnerable to gray matter reduction. Thus, networks intrinsic to adaptive, flexible cognition are vulnerable to broad-spectrum psychopathology. Dysfunction in these networks may reflect an intermediate transdiagnostic phenotype, which could be leveraged to advance therapeutics.
Disrupted emotional processing is a common feature of many psychiatric disorders. The authors investigated functional disruptions in neural circuitry underlying emotional processing across a range of ...tasks and across psychiatric disorders through a transdiagnostic quantitative meta-analysis of published neuroimaging data.
A PubMed search was conducted for whole-brain functional neuroimaging findings published through May 2018 that compared activation during emotional processing tasks in patients with psychiatric disorders (including schizophrenia, bipolar or unipolar depression, anxiety, and substance use) to matched healthy control participants. Activation likelihood estimation (ALE) meta-analyses were conducted on peak voxel coordinates to identify spatial convergence.
The 298 experiments submitted to meta-analysis included 5,427 patients and 5,491 control participants. ALE across diagnoses and patterns of patient hyper- and hyporeactivity demonstrated abnormal activation in the amygdala, the hippocampal/parahippocampal gyri, the dorsomedial/pulvinar nuclei of the thalamus, and the fusiform gyri, as well as the medial and lateral dorsal and ventral prefrontal regions. ALE across disorders but considering directionality demonstrated patient hyperactivation in the amygdala and the hippocampal/parahippocampal gyri. Hypoactivation was found in the medial and lateral prefrontal regions, most pronounced during processing of unpleasant stimuli. More refined disorder-specific analyses suggested that these overall patterns were shared to varying degrees, with notable differences in patterns of hyper- and hypoactivation.
These findings demonstrate a pattern of neurocircuit disruption across major psychiatric disorders in regions and networks key to adaptive emotional reactivity and regulation. More specifically, disruption corresponded prominently to the "salience" network, the ventral striatal/ventromedial prefrontal "reward" network, and the lateral orbitofrontal "nonreward" network. Consistent with the Research Domain Criteria initiative, these findings suggest that psychiatric illness may be productively formulated as dysfunction in transdiagnostic neurobehavioral phenotypes such as neurocircuit activation.
Objectives: There are some common occupational agents and exposure circumstances for which evidence of carcinogenicity is substantial but not yet conclusive for humans. Our objectives were to ...identify research gaps and needs for 20 agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans. Data sources: For each chemical agent (or category of agents), a systematic review was conducted of new data published since the most recent pertinent International Agency for Research on Cancer (IARC) Monograph meeting on that agent. Data extraction: Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches. Data synthesis: Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress, and immuno- and hormonal modulation. Conclusions: Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes.
Abstract Microtubules (MTs) are linked to cell mechanobiology. “Stable” and “dynamically unstable” microtubule (MT) subtypes are differentially sensitive to growth and distribution in serum starved ...(SS) versus full serum (FS) conditions. Atomic Force and Immunofluorescence microscopies were used to study the nanomechanical properties of the cell membrane in response to serum conditions and nocodazole.Nanomechanical properties of the cell membrane remain unchanged under SS/FS conditions even though there are drastic MT changes. The cell membrane is shown to depend on unstable MTs and the intermediate filament (IF) networks to maintain local stiffness. Measurements of local membrane nanomechanics in response to nocodazole display characteristic serum dependent decays. The responses suggest that the cell exists in a mechanical transition state. Stiffness is shown to depend on the interplay between dynamically unstable MTs, stable MTs and IFs which all act to impart a distinct cellular type of transient “metastability”.
Abstract Background context Over the past decade, the number of Adult Spinal Deformity (ASD) surgeries has more than doubled in the United States. The complex surgeries needed to manage ASD are ...associated with significant resource utilization and high cost making them a primary target for increased scrutiny . Accordingly, it is important to not only demonstrate value in ASD surgery as clinical effectiveness but also to translate outcome assessment to cost-effectiveness. Purpose To compare the difference between Medicare allowable rates and the actual, direct hospital costs for ASD surgeries. Study design Longitudinal cohort Patient sample Consecutive patients enrolled in an ASD database from a single institution Outcome measures Short Form -6D Methods Consecutive patients enrolled in an ASD database from a single institution from 2008–2013 were identified. Direct hospital costs were collected from hospital administrative records for the entire inpatient episode of surgical care. Medicare allowable rates were calculated for the same inpatient stays using the year-appropriate Center for Medicare-Medicaid Services Inpatient Pricer Payment System Tool. The SF-6D, a utility index derived from the SF-36v1, was used to determine quality-adjusted life-years (QALY).Costs and QALYs were discounted at 3.5% annually. Results Of 580 surgical ASD patients eligible for two-year follow up, 346 (60%) had complete baseline and 2-year data, and 60 were Medicare beneficiaries comprising the cohort for this study. Mean SF-6D gained was 0.10 during year one after surgery and 0.02 at year two; resulting in a cumulative SF-6D gain of 0.12 over two years. Mean Medicare allowable rates over the two years was $82,050 (range, $42,383 to $220,749) and mean direct costs were $99,114 (range, $28,447 to $217,717). Mean cost/QALY over two years was $683,750 using Medicare allowable rates $825,950 using direct costs. This difference of $17,181 between the two cost calculation represents a 17% difference, which was statistically significant (p <0.001). Conclusion There is a significant difference in direct hospital costs versus Medicare allowable rates in ASD surgery and in turn, there is a similar difference in the cost/QALY calculation. Utilizing Medicare allowable rates not only underestimates (17%) the cost- of ASD surgery, but it creates inaccurate and unrealistic expectations for researchers and policymakers.
Propensity-matched case control.
To compare the perioperative complication rate between single- and two-stage posterior-only VCRs (2-pVCR).
A vertebral column resection (VCR) for severe spinal ...deformity is a technically challenging and lengthy procedure with a potentially high complication rate. Planned staging has an advantage of distributing operative time into 2 smaller, more manageable, intervals.
Adult and pediatric spinal deformity patients undergoing a VCR were retrospectively identified from a single institution's surgical database from 1985 to 2013. Propensity scoring was used to match 2-pVCR and single-staged patients. Each group was matched for 15 preoperative risk factors including demographic, operative, and radiographic characteristics. Perioperative complications were defined as occurring within 2 months of initial surgery. Additionally, a binary logistic regression analysis was performed with complications as the outcome.
A total of 183 consecutive patients were identified as undergoing a VCR, with 172 meeting the inclusion criteria (posterior-only). Forty-four patients underwent planned 2-pVCR whereas 124 had a single-staged VCR. Consistent with propensity-matching, no statistically significant difference between the single- and 2-pVCR cohorts existed for all matching parameters, except pulmonary function tests. There was no significant difference (p = .290) between complication rates for single-stage (12/35; 34%) and 2-pVCR (8/35; 23%) patients. Stepwise binary logistic regression analysis showed that age (p = .014; OR = 0.94, CI = 0.89-0.99) and body mass index (p = .030; OR = 1.13 CI = 1.01-1.26) influenced the occurrence of a complication.
Planned staging of posterior-only VCRs does not increase the occurrence of perioperative complications in adult and pediatric spinal deformity patients.
III (Propensity-matched case control).
Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. ...Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of ∼90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression.
Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 4 weeks after treatment.
At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group.
SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.
Retrospective cohort.
To determine if the use of cell saver reduces overall blood costs in adult spinal deformity (ASD) surgery.
Recent studies have questioned the clinical value of cell saver during ...spine procedures.
ASD patients enrolled in a prospective, multicenter surgical database who had complete preoperative and surgical data were identified. Patients were stratified into (1) cell saver available during surgery, but no intraoperative autologous infusion (No Infusion group), or (2) cell saver available and received autologous infusion (Infusion group).
There were 427 patients in the Infusion group and 153 in the No infusion group. Patients in both groups had similar demographics. Mean autologous infusion volume was 698 mL. The Infusion group had a higher percentage of EBL relative to the estimated blood volume (42.2%) than the No Infusion group (19.6%, p < .000). Allogeneic transfusion was more common in the Infusion group (255/427, 60%) than the No Infusion group (67/153, 44%, p = .001). The number of allogeneic blood units transfused was also higher in the Infusion group (2.4) than the No Infusion group (1.7, p = .009). Total blood costs ranged from $396 to $2,146 in the No Infusion group and from $1,262 to $5,088 in the Infusion group. If the cost of cell saver blood was transformed into costs of allogeneic blood, total blood costs for the Infusion group would range from $840 to $5,418. Thus, cell saver use yielded a mean cost savings ranging from $330 to $422 (allogeneic blood averted). Linear regression showed that after an EBL of 614 mL, cell saver becomes cost-efficient.
Compared to transfusing allogeneic blood, cell saver autologous infusion did not reduce the proportion or the volume of allogeneic transfusion for patients undergoing surgery for adult spinal deformity. The use of cell saver becomes cost-efficient above an EBL of 614 mL, producing a cost savings of $330 to $422.
Level III.
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