The Risk of Cancer from CT Scans and Other Sources of Low-Dose Radiation: A Critical Appraisal of Methodologic Quality

AbstractIntroduction: Concern exists that radiation exposure from computerized tomography (CT) will cause thousands of malignancies. Other experts share the same perspective regarding the risk from additional sources of low-dose ionizing radiation, such as the releases from Three Mile Island (1979; Pennsylvania USA) and Fukushima (2011; Okuma, Fukushima Prefecture, Japan) nuclear power plant disasters. If this premise is false, the fear of cancer leading patients and physicians to avoid CT scans and disaster responders to initiate forcedevacuations is unfounded.Study Objective: This investigation provides a quantitative evaluation of the methodologic quality of studies to determine the evidentiary strength supporting or refuting a causal relationshipbetween low-dose radiation and cancer. It will assess the number of higher qualitystudies that support or question the role of low-dose radiation in oncogenesis.Methods: This investigation is a systematic, methodologic review of articles published from 1975–2017 examining cancer risk from external low-dose x-ray and gamma radiation, defined as less than 200 millisievert (mSv). Following the PRISMA guidelines, the authors performed a search of the PubMed, Cochrane, Scopus, and Web of Science databases. Methodologies of selected articles were scored using the Newcastle Ottawa Scale (NOS) and a tool identifying 11 lower quality indicators. Manuscript methodologies were rankedas higher quality if they scored no lower than seven out of nine on the NOS and contained no more than two lower quality indicators. Investigators then characterized articles as supporting or not supporting a causal relationship between low-dose radiation and cancer.Results: Investigators identified 4,382 articles for initial review. A total of 62 articles met all inclusion/exclusion criteria and were evaluated in this study. Quantitative evaluation of the manuscripts’ methodologic strengths found 25 studies met higher quality criteria while 37 studies met lower quality criteria. Of the 25 studies with higher quality methods, 21 out of 25did not support cancer induction by low-dose radiation (P = .0003).Conclusions: A clear preponderance of articles with higher quality methods found no increased risk of cancer from low-dose radiation. The evidence suggests that exposure to multiple CT scans and other sources of low-dose radiation with a cumulative dose up to 100 mSv (approximately 10 scans), and possibly as high as 200 mSv (approximately 20 scans), does not increase cancer risk

The Role of the Uncinate Margin in Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma: A Survival Analysis

Introduction: Positive margins during pancreaticoduodenectomy for pancreatic cancer portend worse survival, but additional resection of the uncinate margin is typically unfeasible without major vascular reconstruction. The survival benefit of resecting additional neck or bile duct margins in the face of a positive uncinate is also unknown. We examined the impact of re-resection of these margins on survival. Methods: Patients with pancreatic adenocarcinoma who underwent pancreaticoduodenectomy from 2006-2015. Pancreatic neck, bile duct, uncinate, and duodenal frozen section margins were assessed before and after resection of positive margins. Kaplan-Meier survival curves were compared with log-rank tests. Multivariable Cox regression was used to assess the effect of margin status on overall survival. Results: Among 508 patients identified, 388 (76.4%) underwent a pylorus-preserving procedure, 435 (85.6%) had T3 tumors, and 379 (74.6%) had nodal involvement. There were 21 instances where an uncinate margin was concurrently positive with a neck or bile duct margin; this additional neck or bile duct margin was resected in 13 cases (61.9%). Resection of additional margins when the uncinate was concurrently positive was not associated with improved survival (p=0.36). Median survival with and without positive uncinate margins was 13.8 vs. 19.7 months (p=0.04). A positive uncinate margin was associated with decreased survival independent of other margins and cancer stage (HR 1.28 [95% CI 1.00-1.65]). Conclusion: In patients with pancreatic adenocarcinoma, positive uncinate margins are associated with decreased overall survival; resection of additional margins at the neck and bile duct in those with a positive uncinate margin is not warranted

Factors Influencing General Surgeons To Involve Urologists In Bladder Trauma Management

Introduction: Bladder trauma injuries, which are graded by severity, often require immediate care and surgical management by General Surgeons (GS) or Urologists. This study seeks to understand the inconsistencies that exist in collaboration between GS and Urologists in bladder trauma management. We hypothesize that the decision for GS to involve Urologists in bladder trauma management is a multifactorial decision with severity of bladder trauma being the primary determining factor as opposed to other factors like provider experience or hospital setting. Methods: This cross-sectional descriptive study surveyed GS to determine how likely they were to involve Urologists in bladder trauma management and then compared their responses to questionnaires completed by Urologists. The primary outcome for the questionnaire was the likelihood that GS would involve Urologists in bladder trauma management. The questionnaires were developed in collaboration with GS to ensure relevance to both specialties. Results: This study is currently in the data collection phase. There have been 108 GS questionnaire responses (39 respondents are fellowship trained) and 102 Urologist responses (40 respondents are fellowship trained). The response rate provides two similar cohorts for comparison and statistical analysis once the data collection phase is complete and any pending responses are tallied. Discussion: The results thus far demonstrate a meaningful and comparable number of responses from both GS and Urologists despite the difficulty of survey dissemination with limited resources. Once data collection and statical analysis is complete, the results will hopefully improve the understanding of bladder trauma management differences between GS and Urologists

Risk Factors of Not Reaching MCID after Elective Lumbar Spine Surgery: A Case Control Study

Background The therapeutic effect of spine surgery has been traditionally evaluated by physical examination, radiographic findings, and general perception of patient’s health status. However, these assessments are often insufficient to represent surgical outcomes.Patient-reported outcomes (PROs) are tools developed to measures quality outcomes following spinal surgery. Examples include the Patient-Reported Outcomes Measurement Information System Function 4-item Short Form (PROMIS-PF), Visual Analogue Scale (VAS), ODI (Oswestry Disability Index), SF-36 (Short Form Health Survey), and EQ-5D (EuroQuol-5D). The minimum clinically important difference (MCID) is an assessment tool to note the smallest clinical difference in PROs and provides the threshold where patients experience clinical benefit that justifies treatment plans or procedures despite the cost and side effects. MCID results reflect patient-perceived functional improvement, which can be a core metric in lumbar surgery for degenerative disease. Clinical and sociodemographic risk factors may serve to identify high-risk patients via MCID assessment. This study aims to identify risk factors associated with failure of reaching MCID based on PROMIS PF after elective lumbar spine surgery and the data registry from Michigan Spine Surgery Spine Surgery Improvement Collaborative (MSSIC). The results of this study can provide opportunities to optimize medical conditions of patients in prior to any elective lumbar surgery. METHODS MSSIC is a state-wide quality-improvement initiative database including 29 hospitals and 200 orthopedic- and neurosurgeons from various settings. Member hospitals are required to perform an annual minimum of 200 spine surgeries. MSSIC reviews elective spine surgeries for degenerative disease but excludes non-degenerative and/or complex pathology (i.e., spinal cord injury, traumatic fractures, pre-existing infection, grade 3 or 4 spondylolisthesis, scoliosis greater than 25◦, congenital anomalies, or ≥ 4-level fusion). Utilizing MSSIC, 10,922 patients who had undergone elective lumbar spine surgery were selected with 90 day follow up, and 7,200 patients with 1-year follow up. Patients with missing data were excluded from the study. Patient demographics, clinical presentation, medical history, surgical procedure, details of hospital stay, postsurgical adverse events within 90 days of surgery, and patient-reported outcome after surgery were reviewed. A patient was considered to have achieved MCID if there was an increase in ≥4.5 points. RESULTS Of 10,922 patients with 90-day follow-up, 4,453 patients (40.8%) did not reach MCID. Of 7,200 patients with 1-year follow up, 2,361 patients (23.8%) did not achieve MCID. There were significant baseline differences in demographic profiles and operative characteristics for those who had follow-up at 90 days and 1 year after their surgery. At 90 days after surgery, significant factors of not reaching MCID and their relative risk included symptom duration more than 1 year (1.34), previous spine surgery (1.25), African American descent (1.25), chronic opiate use (1.23), less than high school education (1.20), morbid obesity (1.15), ASA class \u3e2 (1.15), current smoking (1.14), chronic obstructive pulmonary disease (COPD) (1.13), depression (1.09), history of DVT (1.08), scoliosis (1.06), anxiety (1.06), baseline PROMIS (1.06), and surgery invasiveness (1.02). At 1 year after surgery, significant factors of not reaching MCID and their relative risk included symptom duration more than 1 year (1.41), less than high school education (1.34), previous spine surgery (1.30), morbid obesity (1.30), chronic opiate use (1.25), age (1.21), current smoking (1.21), African American descent (1.20), ASA class \u3e2 (1.18), history of DVT (1.12), depression (1.10), chronic obstructive pulmonary disease (COPD) (1.09), and baseline PROMIS (1.06). Independent ambulatory status (0.83 and 0.88 for 90-day and 1-year follow-up, respectively) and private insurance (0.83 and 0.85 for 90-day and 1-year follow-up, respectively) were associated with higher likelihood of reaching MCID. CONCLUSION This case control study identifies relevant risk factors of not reaching MCID after elective lumbar spine surgery. The results may assist clinicians in identifying high risk patients and optimizing patients’ medical conditions prior to spinal surgery

Ambulatory teaching: Do approaches to learning predict the site and preceptor characteristics valued by clerks and residents in the ambulatory setting?

BACKGROUND: In a study to determine the site and preceptor characteristics most valued by clerks and residents in the ambulatory setting we wished to confirm whether these would support effective learning. The deep approach to learning is thought to be more effective for learning than surface approaches. In this study we determined how the approaches to learning of clerks and residents predicted the valued site and preceptor characteristics in the ambulatory setting. METHODS: Postal survey of all medical residents and clerks in training in Ontario determining the site and preceptor characteristics most valued in the ambulatory setting. Participants also completed the Workplace Learning questionnaire that includes 3 approaches to learning scales and 3 workplace climate scales. Multiple regression analysis was used to predict the preferred site and preceptor characteristics as the dependent variables by the average scores of the approaches to learning and perception of workplace climate scales as the independent variables. RESULTS: There were 1642 respondents, yielding a 47.3% response rate. Factor analysis revealed 7 preceptor characteristics and 6 site characteristics valued in the ambulatory setting. The Deep approach to learning scale predicted all of the learners' preferred preceptor characteristics (β = 0.076 to β = 0.234, p < .001). Valuing preceptor Direction was more strongly associated with the Surface Rational approach (β = .252, p < .001) and with the Surface Disorganized approach to learning (β = .154, p < 001) than with the Deep approach. The Deep approach to learning scale predicted valued site characteristics of Office Management, Patient Logistics, Objectives and Preceptor Interaction (p < .001). The Surface Rational approach to learning predicted valuing Learning Resources and Clinic Set-up (β = .09, p = .001; β = .197, p < .001). The Surface Disorganized approach to learning weakly negatively predicted Patient Logistics (β = -.082, p = .003) and positively the Learning Resources (β = .088, p = .003). Climate factors were not strongly predictive for any studied characteristics. Role Modeling and Patient Logistics were predicted by Supportive Receptive climate (β = .135, p < .001, β = .118, p < .001). CONCLUSION: Most site and preceptor characteristics valued by clerks and residents were predicted by their Deep approach to learning scores. Some characteristics reflecting the need for good organization and clear direction are predicted by learners' scores on less effective approaches to learning

Dopamine modulates adaptive prediction error coding in the human midbrain and striatum

Learning to optimally predict rewards requires agents to account for fluctuations in reward value. Recent work suggests that individuals can efficiently learn about variable rewards through adaptation of the learning rate, and coding of prediction errors relative to reward variability. Such adaptive coding has been linked to midbrain dopamine neurons in non-human primates, and evidence in support for a similar role of the dopaminergic system in humans is emerging from fMRI data. Here, we sought to investigate the effect of dopaminergic perturbations on adaptive prediction error coding in humans, using a between-subject, placebo-controlled pharmacological fMRI study with a dopaminergic agonist (bromocriptine) and antagonist (sulpiride). Participants performed a previously validated task in which they predicted the magnitude of upcoming rewards drawn from distributions with varying standard deviations. After each prediction, participants received a reward, yielding trial- by-trial prediction errors. Under placebo, we replicated previous observations of adaptive coding in the midbrain and ventral striatum. Treatment with sulpiride attenuated adaptive coding in both midbrain and ventral striatum, and was associated with a decrease in performance, whereas bromocriptine did not have a significant impact. Although we observed no differential effect of SD on performance between the groups, computational modelling suggested decreased behavioral adaptation in the sulpiride group. These results suggest that normal dopaminergic function is critical for adaptive prediction error coding, a key property of the brain thought to facilitate efficient learning in variable environments. Crucially, these results also offer potential insights for understanding the impact of disrupted dopamine function in mental illness.Wellcome Trust, Bernard Wolfe Health Neuroscience Fund, Niels Stensen Foundatio

Disposition of Federally Owned Surpluses

PDZ domains are scaffolding modules in protein-protein interactions that mediate numerous physiological functions by interacting canonically with the C-terminus or non-canonically with an internal motif of protein ligands. A conserved carboxylate-binding site in the PDZ domain facilitates binding via backbone hydrogen bonds; however, little is known about the role of these hydrogen bonds due to experimental challenges with backbone mutations. Here we address this interaction by generating semisynthetic PDZ domains containing backbone amide-to-ester mutations and evaluating the importance of individual hydrogen bonds for ligand binding. We observe substantial and differential effects upon amide-to-ester mutation in PDZ2 of postsynaptic density protein 95 and other PDZ domains, suggesting that hydrogen bonding at the carboxylate-binding site contributes to both affinity and selectivity. In particular, the hydrogen-bonding pattern is surprisingly different between the non-canonical and canonical interaction. Our data provide a detailed understanding of the role of hydrogen bonds in protein-protein interactions