Matthew V. Abola

Association between treatment toxicity and outcomes in oncology clinical trials

BACKGROUND Whether or not toxicity predicts clinical outcomes has long been a question regarding cancer treatments. While prior studies have focused on specific cancers, therapies, and toxicities, no comprehensive evidence exists on whether treatment toxicity predicts favorable outcomes. METHODS We abstracted treatment toxicity and clinical outcome data from a sample of phase III oncology randomized clinical trials (n = 99 trials). We investigated whether treatments with relatively greater toxicity compared with their controls had relatively higher, lower, or equivocal rates of clinical efficacy, measured by progression-free survival (PFS) and overall survival (OS). Several toxicities were assessed (all grades, grades III/IV, cutaneous rash, gastrointestinal toxicity, and myelosuppression). RESULTS Toxicity and efficacy were greater among treatments than controls (e.g. 3.5 instances of all-grade toxicity per patient in treatment arms versus 2.8 instances in controls, P < 0.001; mean PFS of 9.1 months across treatment arms versus 7.1 months across controls, P < 0.001; mean OS of 18.6 months across treatment arms versus 16.9 months across controls, P < 0.001). Across trials, greater relative treatment toxicity was strongly associated with greater PFS in treatments versus controls (P < 0.001), but not OS (P = 0.44). Although higher relative rates of myelosuppression and cutaneous rash among treatments were not associated with greater treatment efficacy, greater relative gastrointestinal toxicity among treatments was associated with greater relative PFS compared with controls (P = 0.007). CONCLUSION Across trials, treatments with relatively greater all-grade toxicity compared with controls are associated with relatively greater PFS but not OS.

Is retinol binding protein 4 a link between adiposity and cancer

Abstract Retinol binding protein 4 (RBP4) is synthesized in the liver where it binds vitamin A, retinol, and transports it to tissues throughout the body. It has been shown in some studies that the level of circulating RBP4 increases with body mass, and the protein has been implicated as a mediator in the development of insulin resistance and the metabolic disease. Adipose tissue serves as another site of RBP4 synthesis, accounting for its designation as an adipokine. In addition to its function as a transport protein, RBP4 serves as a signaling molecule which, by binding to the membrane receptor STRA6, triggers downstream activation of pro-oncogenic pathways including JAK2/STAT3/5. Taken together, available information suggests the possibility that RBP4 may be a link between obesity and cancer.

Industry Funding of Cancer Patient Advocacy Organizations

results indicate that reducing work hours is an effective individual strategy to reduce burnout for many physicians. In summary, the increase in burnout observed in US physicians between 2011 and 2014 likely translated into approximately a 1% reduction in the professional effort of the US physician workforce. This loss is roughly equivalent to eliminating the graduating class of 7 US medical schools. This estimate does not include other potential impacts of burnout on the physician workforce such as early retirement or physicians leaving the profession to pursue nonmedical careers. Reducing professional work effort does appear to be an effective strategy for individual physicians to reduce burnout. Although this approach may help individual physicians, at the societal level it has the potential to exacerbate the pending physician workforce shortage. To preserve adequate access to care, there is a societal imperative to provide physicians a better option than burning out, working parttime, or leaving the profession.

Trends in Authorship Patterns in High-Impact Radiology Publications, 1980–2013

RATIONALE AND OBJECTIVES Concerns have been raised about authorship inflation in medical literature. The purpose of this study was to determine how the number of authors per radiology article has changed over time with regard to study type and geographic factors. MATERIALS AND METHODS We collected data on study type, authorship count, and the country of the corresponding author for a sample of articles published in Radiology, American Journal of Roentgenology, and European Radiology in 1980, 1990, 2000, and 2013. Only original research and review articles were considered. We computed trends in the mean number of authors per article for each journal and compared authorship trends between study types and geographic region. The study did not involve human subjects and was therefore exempt from institutional board review at our institution. RESULTS A total of 682 articles were reviewed, of which 572 were original research articles (83.9%) and 110 review articles (16.1%). The overall number of authors per article doubled from 3.6 in 1980 to 7.3 in 2013 (P < .001). From 1990 to 2013, the largest absolute increase in authorship count was in Radiology (4.4-8.1, 84.1%, P < .001). The largest increase in authorship occurred in original research articles (3.7-7.8, 111%, P < .001). Although authorship counts were greatest in Asia over most study period, growth in authorship count was highest in Europe. CONCLUSIONS Authorship count has dramatically increased in radiology journals in the last 3 decades, particularly in original research articles and in Europe.

Do heads of government age more quickly? Observational study comparing mortality between elected leaders and runners-up in national elections of 17 countries

Objectives To determine whether being elected to head of government is associated with accelerated mortality by studying survival differences between people elected to office and unelected runner-up candidates who never served. Design Observational study. Setting Historical survival data on elected and runner-up candidates in parliamentary or presidential elections in Australia, Austria, Canada, Denmark, Finland, France, Germany, Greece, Ireland, Italy, New Zealand, Norway, Poland, Spain, Sweden, United Kingdom, and United States, from 1722 to 2015. Participants Elected and runner-up political candidates. Main outcome measure Observed number of years alive after each candidate’s last election, relative to what would be expected for an average person of the same age and sex as the candidate during the year of the election, based on historical French and British life tables. Observed post-election life years were compared between elected candidates and runners-up, adjusting for life expectancy at time of election. A Cox proportional hazards model (adjusted for candidate’s life expectancy at the time of election) considered years until death (or years until end of study period for those not yet deceased by 9 September 2015) for elected candidates versus runners-up. Results The sample included 540 candidates: 279 winners and 261 runners-up who never served. A total of 380 candidates were deceased by 9 September 2015. Candidates who served as a head of government lived 4.4 (95% confidence interval 2.1 to 6.6) fewer years after their last election than did candidates who never served (17.8 v 13.4 years after last election; adjusted difference 2.7 (0.6 to 4.8) years). In Cox proportional hazards analysis, which considered all candidates (alive or deceased), the mortality hazard for elected candidates relative to runners-up was 1.23 (1.00 to 1.52). Conclusions Election to head of government is associated with a substantial increase in mortality risk compared with candidates in national elections who never served.

Stool DNA-based versus colonoscopy-based colorectal cancer screening: patient perceptions and preferences

Objective Stool DNA (sDNA) tests offer a noninvasive form of colon cancer screening for patients, and although the test is expected to increase uptake of colon cancer screening, it is unknown if patients’ perceptions of the sDNA test differ according to race and other patient characteristics. Methods We conducted a self-administered survey of patients undergoing both a colonoscopy and an sDNA test to evaluate perceptions of sDNA testing. Results Of the 613 participants who were sent surveys, 423 responded (69% response rate). Respondents self-identified as African American (n=127, 30%), Caucasian (n=284, 67%), and other ethnicity (n=12, 3%). In general, participants found the sDNA test more suitable than a colonoscopy (n=309, 75%). In univariate analyses, a higher percentage of Caucasians as compared with African Americans found the sDNA test more suitable than a colonoscopy (89% vs. 76%, p<0.01), and more Caucasians than African Americans preferred the sDNA test (43% vs. 32%, p<0.05). Adjustment for covariates reduced these racial differences to no significance. A family history of colorectal cancer remains a significant factor for patient’s preferences for screening regardless of race. Conclusions Our study shows no racial differences in the perception of and preference for sDNA testing for colon screening. Intervention to increase the uptake of sDNA testing may help reduce racial disparities in colorectal cancer.

Relationship Between Foraminal Area and Degenerative Changes in the Lower Cervical Spine With Implications for C5 Nerve Root Palsy

Preoperative foraminal stenosis at C4/5 is a predisposing risk factor for C5 nerve root palsy in elderly patients. However, the area of the C4/5 intervertebral foramen and its relationship to the extent of arthrosis and lower foraminal areas (C5/6 and C6/7) are unknown. The authors sought to compare the areas of the cervical intervertebral foramen at the C4/5, C5/6, and C6/7 levels, noting any differences across race or sex and the relationship between foraminal area and arthrosis grade. A total of 600 cervical foramina from an osseous collection were examined. One hundred specimens between the ages of 60 and 80 years were selected, 50 from each sex and race (white and African American). Foramina were photographed bilaterally at C4/5, C5/6, and C6/7. Vertical height and mid-sagittal width were digitally measured. The degree of arthrosis within each intervertebral foramen was graded by 2 of the authors independently using the Kellgren-Lawrence grading system. Average age of death for specimens was 69.3±5.9 years. The mean foraminal areas at C4/5 (P=.001) and C5/6 (P<.001) were significantly smaller than at C6/7. Whites had larger foraminal areas than African Americans at C4/5 (P=.05) and C6/7 (P=.01). Arthrosis grade was found to make a significant contribution to foraminal area at C4/5 (standardized beta=-0.267; P<.001), but not at C5/6 or C6/7. A higher grade of arthrosis was associated with a narrower intervertebral foramen at the C4/5 level in osseous specimens from elderly individuals. [Orthopedics. 2018; 41(4):e506-e510.].

Preoperative Hyponatremia Is Associated with Reoperation and Prolonged Length of Hospital Stay following Total Knee Arthroplasty

&NA; Hyponatremia is a risk factor for adverse surgical outcomes, but limited information is available on the prognosis of hyponatremic patients who undergo total knee arthroplasty (TKA). The purpose of this investigation was to compare the incidence of major morbidity (MM), 30‐day readmission, 30‐day reoperation, and length of hospital stay (LOS) between normonatremic and hypontremic TKA patients.The American College of Surgeons National Surgical Quality Improvement Program database was used to identify all primary TKA procedures. Hyponatremia was defined as <135 mEq/L and normonatremia as 135 to 145 mEq/L; hypernatremic patients (>145 mEq/L) were excluded. Multivariable logistic regression was used to determine the association between hyponatremia and outcomes after adjusting for demographics and comorbidities. An &agr; level of 0.002 was used and calculated using the Bonferroni correction. Our final analysis included 88,103 patients of which 3,763 were hyponatremic and 84,340 were normonatremic preoperatively. In our multivariable models, hyponatremic patients did not have significantly higher odds of experiencing an MM (odds ratio [OR]: 1.05; 99% confidence interval [CI] 0.93‐1.19) or readmission (OR: 1.12; 99% CI: 1‐1.24). However, patients with hyponatremia did experience significantly greater odds for reoperation (OR: 1.24; 99% CI: 1.05‐1.46) and longer hospital stay (OR: 1.15; 99% CI: 1.09‐1.21). We found that hyponatremic patients undergoing TKA had increased odds of reoperation and prolonged hospital stay. Preoperative hyponatremia may be a modifiable risk factor for adverse outcomes in patients undergoing TKA, and additional prospective studies are warranted to determine whether preoperative correction of hyponatremia can prevent complications.

Differences in Cross-Sectional Intervertebral Foraminal Area From C3 to C7

Study Design: Anatomical comparative study. Objectives: Few studies have evaluated foraminal areas in the cervical spine without degenerative changes. The purpose of this study was to determine and compare the mean cross-sectional foraminal areas between the C3/4, C4/5, C5/6, and C6/7 levels while also analyzing specimens for differences between sexes and races. Methods: We performed an anatomic study of the intervertebral foramen at 4 levels (C3/4, C4/5, C5/6, C6/7) in 100 skeletally mature osseous specimens. Specimens were selected to obtain equal number of African American and Caucasian males and females (n = 25/group) aged 20 to 40 years at time of death. Foramina were photographed bilaterally with and without a silicone rubber disc. The maximal vertical height and mid-sagittal width of each foramen were digitally measured and the areas were calculated using an ellipse as a model. Results: The average age at death for all specimens was 30 ± 6 years. The mean cross-sectional area of the C4/5 foramen was significantly smaller compared with the C5/6 (P < .001). C5/6 was significantly narrower than C6/7 (P < .001) foramen with and without disc augmentation. C3/4 was not significantly different from more caudal levels. There was no difference between male and female specimens, while African Americans had smaller foraminal sizes than Caucasians. Conclusions: This study provides the largest anatomical reference of the cervical intervertebral foramen. In a mature spine without facet joint hypertrophy or osteophytic changes, the C4/5 foramen was narrower than C5/6, which was narrower than C6/7. Understanding the relative foraminal areas in the nonpathological cervical spine is crucial to understanding degenerative changes as well as the anatomical changes in pathologies that affect the intervertebral foramen.

Historical Perspective: Henry H. Bohlman (1937-2010): The Father of Contemporary Spine Surgery.

The incredible career of Henry H. Bohlman, MD, spanned over four decades at University Hospitals Case Medical Center. He was an innovator and pioneer, designing several techniques for the management of several spinal pathologies while advocating the anterior approach to the spine. Dr. Bohlmans legacy is preserved in his fellows who have become leaders in spine surgery throughout the world.