Citations 2
The genetic determinants of recurrent somatic mutations in 43,693 blood genomes
Weinstock, Joshua S. , Laurie, Cecelia , Broome, Jai , Taylor, Kent D. , Guo, Xiuqing , Shuldiner, Alan R. , O’Connell, Jeffrey R. , Lewis, Joshua P. , Boerwinkle, Eric , Barnes, Kathleen C. , Chami, Nathalie , Loos, Ruth J. F. , Fornage, Myriam , Redline, Susan , Cade, Brian E. , Chen, Zhanghua , Gauderman, W. James , Schleimer, Robert P. , Bis, Joshua C. , Brody, Jennifer A. , Silverman, Edwin K. , Qiao, Dandi , Lasky‐Su, Jessica , DeMeo, Dawn L. , Palmer, Nicholette D. , Bowden, Donald W. , Johnson, Andrew D. , Yanek, Lisa R. , Becker, Lewis C. , Kardia, Sharon L.R., Kaplan, Robert C. , Heckbert, Susan R. , Smith, Nicholas L. , Arnett, Donna K. , Irvin, Marguerite R. , Tiwari, Hemant K., Raffield, Laura M. , Gao, Yan , Rotter, Jerome I. , Wheeler, Marsha M. , Duggirala, Ravindranath , Xiao, Shujie, Williams, L. Keoki , Meyers, Deborah A. , Ortega, Victor E. , McGarvey, Stephen T. , Chen, Yii‐Der Ida , Lee, Wen‐Jane , Shoemaker, M. Benjamin , Roden, Dan M. , Blackwell, Thomas W. , Smith, Albert V. , Kang, Hyun Min , Mathias, Rasika A. , Natarajan, Pradeep , Jaiswal, Siddhartha , Reiner, Alex P. , Bick, Alexander G. , Kaplan, Robert C. , Broome, Jai , Kenny, Eimear E , Loos, Ruth J F , Fornage, Myriam , Redline, Susan , Cade, Brian E , Gauderman, W James , Grammer, Leslie , Schleimer, Robert P , Bis, Joshua C , Brody, Jennifer A , Silverman, Edwin K , Yun, Jeong H , Qiao, Dandi , Weiss, Scott T , Palmer, Nicholette D , Freedman, Barry I , Cho, Michael H , Vasan, Ramachandran S , Johnson, Andrew D , Yanek, Lisa R , Becker, Lewis C , He, Jiang , Heckbert, Susan R , Wiggins, Kerri L , Arnett, Donna K , Correa, Adolfo , Raffield, Laura M , Gao, Yan , Rotter, Jerome I , Rich, Stephen S , Manichaikul, Ani W , Konkle, Barbara A , Johnsen, Jill M , Custer, Brian S , Duggirala, Ravindranath , Curran, Joanne E , Li, Xingnan , McGarvey, Stephen T , Gu, C Charles , Lee, Wen-Jane , Darbar, Dawood , Roden, Dan M. , Kooperberg, Charles , Desai, Pinkal M , Smith, Albert V , Kang, Hyun M , Mathias, Rasika A , Natarajan, Pradeep , Jaiswal, Siddhartha , Bick, Alexander G , Weinstock, Joshua S , Shuldiner, Alan R , Taylor, Kent D , Guo, Xiuqing , Lasky-Su, Jessica , Gilliland, Frank D. , Kumar, Rajesh , Psaty, Bruce M. , Yun, Jeong H. , Weiss, Scott T. , Freedman, Barry I. , Cho, Michael H. , Vasan, Ramachandran S. , He, Jiang , Wiggins, Kerri L. , Andrade, Mariza de , Rich, Stephen S. , Manichaikul, Ani , Konkle, Barbara A. , Custer, Brian , Curran, Joanne E. , Blangero, John , Gui, Hongsheng , Li, Xingnan , Darbar, Dawood , Albert, Christine M. , Kooperberg, Charles , Desai, Pinkal , Abecasis, Gonçalo R.
Science Advances | April 26, 2023 | Volume: 9 | Issue: 17 | Pages: No page available
Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences.
Predictors of patient dissatisfaction at 1 and 2 years after lumbar surgery
Macki, Mohamed, Alvi, Mohammed Ali , Kerezoudis, Panagiotis , Xiao, Shujie, Schultz, Lonni, Bazydlo, Michael , Bydon, Mohamad , Park, Paul , Chang, Victor , _, _, Alvi, Mohammed Ali , _, _
Journal of Neurosurgery: Spine | November 22, 2019 | Volume: 32 | Issue: 3 | Pages: 373-382
OBJECTIVE As compensation transitions from a fee-for-service to pay-for-performance healthcare model, providers must prioritize patient-centered experiences. Here, the authors’ primary aim was to identify predictors of patient dissatisfaction at 1 and 2 years after lumbar surgery. METHODS The Michigan Spine Surgery Improvement Collaborative (MSSIC) was queried for all lumbar operations at the 1- and 2-year follow-ups. Predictors of patients’ postoperative contentment were identified per the North American Spine Surgery (NASS) Patient Satisfaction Index, wherein satisfied patients were assigned a score of 1 (“the treatment met my expectations”) or 2 (“I did not improve as much as I had hoped, but I would undergo the same treatment for the same outcome”) and unsatisfied patients were assigned a score of 3 (“I did not improve as much as I had hoped, and I would not undergo the same treatment for the same outcome”) or 4 (“I am the same or worse than before treatment”). Multivariable Poisson generalized estimating equation models were used to report adjusted risk ratios (RR adj ). RESULTS Among 5390 patients with a 1-year follow-up, 22% reported dissatisfaction postoperatively. Dissatisfaction was predicted by higher body mass index (RR adj =1.07, p < 0.001), African American race compared to white (RR adj = 1.51, p < 0.001), education level less than high school graduation compared to a high school diploma or equivalent (RR adj = 1.25, p = 0.008), smoking (RR adj = 1.34, p < 0.001), daily preoperative opioid use > 6 months (RR adj = 1.22, p < 0.001), depression (RR adj = 1.31, p < 0.001), symptom duration > 1 year (RR adj = 1.32, p < 0.001), previous spine surgery (RR adj = 1.32, p < 0.001), and higher baseline numeric rating scale (NRS)–back pain score (RR adj = 1.04, p = 0.002). Conversely, an education level higher than high school graduation, independent ambulation (RR adj = 0.90, p = 0.039), higher baseline NRS–leg pain score (RR adj = 0.97, p = 0.013), and fusion surgery (RR adj = 0.88, p = 0.014) decreased dissatisfaction. Among 2776 patients with a 2-year follow-up, 22% reported dissatisfaction postoperatively. Dissatisfaction was predicted by a non-white race, current smoking (RR adj = 1.26, p = 0.004), depression (RR adj = 1.34, p < 0.001), symptom duration > 1 year (RR adj = 1.47, p < 0.001), previous spine surgery (RR adj = 1.28, p < 0.001), and higher baseline NRS–back pain score (RR adj = 1.06, p = 0.003). Conversely, at least some college education (RR adj = 0.87, p = 0.035) decreased the risk of dissatisfaction. CONCLUSIONS Both comorbid conditions and socioeconomic circumstances must be considered in counseling patients on postoperative expectations. After race, symptom duration was the strongest predictor of dissatisfaction; thus, patient-centered measures must be prioritized. These findings should serve as a tool for surgeons to identify at-risk populations that may need more attention regarding effective communication and additional preoperative counseling to address potential barriers unique to their situation.