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The increasing use of electronic health records (EHRs) and biobanks offers unique opportunities to study Mendelian diseases. We described a novel approach to summarize clinical manifestations from patient EHRs into phenotypic evidence for cystic fibrosis (CF) with potential to alert unrecognized patients of the disease. We estimated genetically predicted expression (GReX) of cystic fibrosis transmembrane conductance regulator (CFTR) and tested for association with clinical diagnoses in the Vanderbilt University biobank (N = 9142 persons of European descent with 71 cases of CF). The top associated EHR phenotypes were assessed in combination as a phenotype risk score (PheRS) for discriminating CF case status in an additional 2.8 million patients from Vanderbilt University Medical Center (VUMC) and 125,305 adult patients including 25,314 CF cases from MarketScan, an independent external cohort. GReX of CFTR was associated with EHR phenotypes consistent with CF. PheRS constructed using the EHR phenotypes and weights discovered by the genetic associations improved discriminative power for CF over the initially proposed PheRS in both VUMC and MarketScan. Our study demonstrates the power of EHRs for clinical description of CF and the benefits of using a genetics-informed weighing scheme in construction of a phenotype risk score. This research may find broad applications for phenomic studies of Mendelian disease genes.

OBJECTIVE To assess the safety, feasibility and treatment outcomes of holmium laser enucleation of the prostate (HoLEP) as a same day surgery (SDS). METHODS HoLEPs performed from November 2013 to December 2018 at our institution were reviewed retrospectively. Inclusion criteria for same day surgery (SDS) included living in the local metropolitan area with access to local hospital and Eastern Cooperative Oncology Group (ECOG) 0-2, regardless of prostate size and anticoagulation status. Those patients who were discharged directly from the postoperative care unit were identified as SDS cases. Patients admitted overnight after HoLEP during the same period were used as a matched cohort. Patient demographics, disease characteristics and treatment outcomes were compared. RESULTS A total of 377 patients were identified, including 199 SDS and 178 non-SDS patients. No statistical difference was present between the 2 groups regarding the post-op complication and readmission rates. The non-SDS group had a significantly higher percentage of patients with history of urinary retention, lower pre-op Qmax, and larger prostate volume. The SDS group had shorter operative time, length of stay (LOS), and catherization time (all P CONCLUSION Same day outpatient surgery for HoLEP is safe in patients who live in close proximity and have ECOG status 0-2. Our readmission rate and complication rate are comparable to those reported in the literature with markedly decreased LOS. Long-term functional outcome is not compromised by SDS.

Human evolution is characterized by a dramatic increase in brain size and complexity. To probe its genetic basis, we examined the evolution of genes involved in diverse aspects of nervous system biology. We found that these genes display significantly higher rates of protein evolution in primates than in rodents. Importantly, this trend is most pronounced for the subset of genes implicated in nervous system development. Moreover, within primates, the acceleration of protein evolution is most prominent in the lineage leading from ancestral primates to humans. Thus, the remarkable phenotypic evolution of the human nervous system has a salient molecular correlate, i.e., accelerated evolution of the underlying genes, particularly those linked to nervous system development. In addition to uncovering broad evolutionary trends, our study also identified many candidate genes—most of which are implicated in regulating brain size and behavior—that might have played important roles in the evolution of the human brain.