A comparison of the National Surgical Quality Improvement Program and the Society of Thoracic Surgery Cardiac Surgery preoperative risk models: a cohort study.

BACKGROUND: Cardiac surgery prediction models and outcomes from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) have not been reported. The authors sought to develop preoperative prediction models and estimates of postoperative outcomes for cardiac surgery using the ACS-NSQIP and compare these to the Society of Thoracic Surgeons Adult Cardiac Surgery Database (STS-ACSD). METHODS: In a retrospective analysis of the ACS-NSQIP data (2007-2018), cardiac operations were identified using cardiac surgeon primary specialty and sorted into cohorts of coronary artery bypass grafting (CABG) only, valve surgery only, and valve+CABG operations using CPT codes. Prediction models were created using backward selection of the 28 non-laboratory preoperative variables in ACS-NSQIP. Rates of nine postoperative outcomes and performance statistics of these models were compared to published STS 2018 data. RESULTS: Of 28 912 cardiac surgery patients, 18 139 (62.8%) were CABG only, 7872 (27.2%) were valve only, and 2901 (10.0%) were valve+CABG. Most outcome rates were similar between the ACS-NSQIP and STS-ACSD, except for lower rates of prolonged ventilation and composite morbidity and higher reoperation rates in ACS-NSQIP (all P <0.0001). For all 27 comparisons (9 outcomes × 3 operation groups), the c-indices for the ACS-NSQIP models were lower by an average of ~0.05 than the reported STS models. CONCLUSIONS: The ACS-NSQIP preoperative risk models for cardiac surgery were almost as accurate as the STS-ACSD models. Slight differences in c-indexes could be due to more predictor variables in STS-ACSD models or the use of more disease- and operation-specific risk variables in the STS-ACSD models.

Attitudes about use of preoperative risk assessment tools: a survey of surgeons and surgical residents in an academic health system.

BACKGROUND: Formal surgical risk assessment tools have been developed to predict risk of adverse postoperative patient outcomes. Such tools accurately predict common postoperative complications, inform patients and providers of likely perioperative outcomes, guide decision making, and improve patient care. However, these are underutilized. We studied the attitudes towards and techniques of how surgeons preoperatively assess risk. METHODS: Surgeons at a large academic tertiary referral hospital and affiliate community hospitals were emailed a 16-question survey via REDCap (Research Electronic Data Capture) between 8/2019-6/2020. Reminder emails were sent once weekly for three weeks. All completed surveys by surgical residents and attendings were included; incomplete surveys were excluded. Surveys were analyzed using descriptive statistics (frequency distributions and percentages for categorical variables, means, and standard deviations for continuous variables), and Fisher's exact test and unpaired t-tests comparing responses by surgical attendings vs. residents. RESULTS: A total of 108 surgical faculty, 95 surgical residents, and 58 affiliate surgeons were emailed the survey. Overall response rates were 50.0% for faculty surgeons, 47.4% for residents, and 36.2% for affiliate surgeons. Only 20.8% of surgeons used risk calculators most or all of the time. Attending surgeons were more likely to use prior experience and current literature while residents used risk calculators more frequently. Risk assessment tools were more likely to be used when predicting major complications and death in older patients with significant risk factors. Greatest barriers for use of risk assessment tools included time, inaccessibility, and trust in accuracy. CONCLUSIONS: A small percentage of surgeons use surgical risk calculators as part of their routine practice. Time, inaccessibility, and trust in accuracy were the most significant barriers to use.

Comparison of Preoperative Surgical Risk Estimated by Thoracic Surgeons vs a Standardized Surgical Risk Prediction Tool.

Considerable variability exists between surgeons' assessments of a patient's individual preoperative surgical risk. Surgical risk calculators are not routinely used despite their validation. We sought to compare thoracic surgeons' prediction of patients' risk of postoperative adverse outcomes vs a surgical risk calculator, the Surgical Risk Preoperative Assessment System (SURPAS). We developed vignettes from 30 randomly selected patients who underwent thoracic surgery in the American College of Surgeons' National Surgical Quality Improvement Program database. Twelve thoracic surgeons estimated patients' preoperative risks of postoperative morbidity and mortality. These were compared to SURPAS estimates of the same vignettes. C-indices and Brier scores were calculated for the surgeons' and SURPAS estimates. Agreement between surgeon estimates was examined using intraclass correlation coefficients (ICCs). Surgeons estimated higher morbidity risk compared to SURPAS for low-risk patients (ASA classes 1-2, 11.5% vs 5.1%, P ≤ 0.001) and lower morbidity risk compared to SURPAS for high-risk patients (ASA class 5, 37.6% vs 69.8%, P < 0.001). This trend also occurred in high-risk patients for mortality (ASA 5, 11.1% vs 44.3%, P < 0.001). C-indices for SURPAS vs surgeons were 0.84 vs 0.76 (P = 0.3) for morbidity and 0.98 vs 0.85 (P = 0.001) for mortality. Brier scores for SURPAS vs surgeons were 0.1579 vs 0.1986 for morbidity (P = 0.03) and 0.0409 vs 0.0543 for mortality (P = 0.006). ICCs showed that surgeons had moderate risk agreement for morbidity (ICC = 0.654) and mortality (ICC = 0.507). Thoracic surgeons and patients could benefit from using a surgical risk calculator to better estimate patients' surgical risks during the informed consent process.

Outcomes of incidentally detected ovarian cancers diagnosed at time of risk-reducing salpingo-oophorectomy in BRCA mutation carriers.

OBJECTIVE: Prior data suggested that women with incidentally detected occult invasive ovarian cancer (OIOC) at the time of risk-reducing salpingo-oophorectomy (RRSO) for BRCA mutation may have poorer prognoses than would be expected based on disease stage. We sought to evaluate prevalence and outcomes of patients with OIOC in a tertiary referral center. METHODS: Patients with BRCA mutation undergoing RRSO from 01/2005 to 05/2017 were identified, and their records reviewed. Women with incidentally detected OIOC were included; those with clinical features raising preoperative suspicion for malignancy were excluded. RESULTS: 548 patients with BRCA mutation who underwent RRSO were identified. 26 (4.7%) had an OIOC (median age 55 years; range 42-75); 15(58%) patients, BRCA1; 9(34%), BRCA2; 2(8%) had a mutation in both genes. All OIOCs were high-grade serous: 10 (38%) Stage I; 8 (31%) Stage II; 8(31%) Stage III. 24(92%) patients received adjuvant platinum/taxane therapy. Of Stage III patients, 4 (50%) were identified intraoperatively; the remaining 4 (50%) had microscopic nodal disease on final pathology only. At median follow-up of 67.3 months (28-166) no Stage I patients have recurred; 2 Stage II and 6 Stage III patients recurred. 5-year progression-free survival (PFS) was 72% (95%CI, 50.2-85.7%); median PFS for the cohort was 129 months (95%CI, 75.3-not estimable). 5-year disease-specific survival (DSS) was 96% (95%CI, 76-99%); median DSS not reached. CONCLUSION: Consistent with prior reports, almost 5% of patients had an OIOC at RRSO. The majority with early-stage disease had excellent PFS and DSS outcomes, as would be expected based on disease stage.

Fumarate hydratase FH c.1431_1433dupAAA (p.Lys477dup) variant is not associated with cancer including renal cell carcinoma.

Fumarate hydratase (FH) mutations underpin the autosomal recessive syndrome. FH deficiency and the autosomal dominant syndrome hereditary leiomyomatosis and renal cell carcinoma (HLRCC). The FH c.1431_1433dupAAA (p.Lys477dup) genomic alteration has been conclusively shown to contribute to FH deficiency when occurring with another FH germline alteration. However, a sufficiently large dataset has been lacking to conclusively determine its clinical significance to cancer predisposition in the heterozygous state. We reviewed a series of 7,571 patients with cancer who received germline results through MSK-IMPACT testing at the Memorial Sloan Kettering Cancer Center. The FH c.1431_1433dupAAA (p.Lys477dup) variant was detected in 24 individuals, none of whom was affected with renal cancer. Eleven of the 372 patients with renal cancer were identified to carried pathogenic FH variants associated with HLRCC. None of these 372 patients with renal cancer carried the FH c.1431_1433dupAAA variant. Our data indicate the FH c.1431_1433dupAAA is not associated with cancer including renal cell carcinoma.

Validation of the olfactory disorders questionnaire for English-speaking patients with olfactory disorders.

OBJECTIVES: To adapt the existing German language olfactory disorders questionnaire for use with English-speaking patients. To validate the adapted version for routine clinical use. DESIGN: The translated version of the original German questionnaire was revised with a patient and a clinician to reflect British language and culture. Patients attending an olfactory dysfunction clinic were recruited to perform the adapted questionnaire on two occasions at least 1 month apart. Additional online participants completed the questionnaire via the charity Fifth Sense. MAIN OUTCOME MEASURES: Retest reliability of the English olfactory disorders questionnaire (eODQ) in affected patients including potential for redundancy in any of the included questions. Correlation of eODQ scores with Sniffin' Sticks scores. RESULTS: Eighty-seven patients reporting olfactory dysfunction were recruited and had a mean age of 48 with 35% of them being male; 50 datasets were available for analysis. A total of 957 members of the charity entered responses into the online questionnaire; 699 responses could be scored with participants' mean age of 55 years and with 69% reporting as female. The eODQ score and Sniffin' Sticks threshold, discrimination and identification score at timepoint 1 were correlated to assess for concurrent validity, (r = -0.15, P = 0.17) and showed no significant correlation. Female participants had a significantly higher mean total eODQ score than men, 55.75 compared to 52.28 (P = 0.001). The average score was 54.7 (SD 13.5) with a range from 26 to 87. The internal consistency of the questionnaire was good with a Cronbach's alpha of 0.90 (confidence intervals 0.89, 0.91). CONCLUSIONS: The results of this study support the use of the eODQ in a native English-speaking population and highlight the different distinctions between "objective" testing of olfaction with the Sniffin' Sticks test, and the patient reported impact of olfactory dysfunction on daily life. These two types of assessment can be easily administered in an outpatient setting and used in the assessment and management of olfactory dysfunction.

Understanding inherited risk in unselected newly diagnosed patients with endometrial cancer.

PURPOSE: Mutations in DNA mismatch repair (MMR) genes and PTEN, diagnostic of Lynch and Cowden syndromes, respectively, represent the only established inherited predisposition genes in endometrial cancer to date. The prevalence of other cancer predisposition genes remains unclear. We sought the prevalence of pathogenic germline variants in unselected patients with endometrial cancer attending for surgical consultation. PATIENTS AND METHODS: Patients were prospectively consented (4/2016-5/2017) to an IRB-approved protocol of tumor-normal sequencing via a custom next-generation sequencing panel (MSK-IMPACT) with return of germline results for >75 cancer predisposition genes. Tumors were assessed for microsatellite instability (MSI). Per institutional standards, all tumors underwent Lynch syndrome screening via IHC for MMR proteins. RESULTS: Of 156 patients who consented to germline genetic testing, 118 (76%) had stage I disease. Tumors were endometrioid in 104 (67%), of which 60 (58%) were grade 1. Twenty-four pathogenic germline variants were identified in 22 patients (14%)-7 (4.5%) with highly penetrant cancer syndromes and 15 (9.6%) with variants in moderate-, low-penetrance, or recessive genes. Of these, 5 (21%) were in Lynch syndrome genes (2 MSH6, 2 PMS2, and 1 MLH1). All 5 tumors had concordant IHC staining; 2 (40%) were definitively MSI-high by next-generation sequencing. One patient had a known BRCA1 mutation; 1 had SMARCA4 deletion. The remaining 17 variants (71%) were incremental findings in moderate- and low-penetrance variants or genes associated with recessive disease. CONCLUSION: In unselected patients with predominantly low-risk, early-stage endometrial cancer, germline multi-gene panel testing identifies cancer predisposition gene variants in 14%. This finding may have implications for future cancer screening and risk-reduction recommendations. Universal IHC screening for Lynch syndrome successfully identifies the majority (71%) of high-penetrance germline mutations.

Prevalence of Germline Mutations in Cancer Susceptibility Genes in Patients With Advanced Renal Cell Carcinoma.

Importance: Identification of patients with hereditary renal cell carcinoma (RCC) is important for cancer screening and, in patients with advanced disease, for guiding treatment. The prevalence of cancer-related germline mutations in patients with advanced RCC and the phenotypes associated with some rare mutations are unknown. Objectives: To examine the prevalence of germline mutations in both known RCC predisposition genes and other cancer-associated genes and to identify clinical and pathologic factors associated with germline mutations. Design, Setting, and Participants: In this cohort study conducted from October 1, 2015, to July 31, 2017, 254 of 267 patients with advanced (American Joint Committee on Cancer stage III or IV) RCC who were seen in medical oncology or urology clinics agreed to germline sequencing and disclosure of results under an institutional protocol of matched tumor-germline DNA sequencing. Main Outcomes and Measures: Mutation prevalence and spectrum in patients with advanced RCC were determined. Clinical characteristics were assessed by mutation status. Results: Of the 254 patients (median age [range], 56 [13-79] years; 179 [70.5%] male; 211 [83.1%] non-Hispanic white), germline mutations were identified in 41 (16.1%); 14 (5.5%) had mutations in syndromic RCC-associated genes (7 in FH, 3 in BAP1, and 1 each in VHL, MET, SDHA, and SDHB). The most frequent mutations were CHEK2 (n = 9) and FH (n = 7). Of genes not previously associated with RCC risk, CHEK2 was overrepresented in patients compared with the general population, with an odds ratio of RCC of 3.0 (95% CI, 1.3-5.8; P = .003). Patients with non-clear cell RCC were significantly more likely to have an RCC-associated gene mutation (9 [11.7%] of 74 vs 3 [1.7%] of 177; P = .001), and 8 (10.0%) had a mutation in a gene that could guide therapy. Of patients with mutations in RCC-associated genes, 5 (35.7%) failed to meet current clinical guidelines for genetic testing. Conclusions and Relevance: Of patients with non-clear cell RCC, more than 20% had a germline mutation, of which half had the potential to direct systemic therapy. Current referral criteria for genetic testing did not identify a substantial portion of patients with mutations, supporting the role of a more inclusive sequencing approach.

Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing.

Importance: Guidelines for cancer genetic testing based on family history may miss clinically actionable genetic changes with established implications for cancer screening or prevention. Objective: To determine the proportion and potential clinical implications of inherited variants detected using simultaneous sequencing of the tumor and normal tissue ("tumor-normal sequencing") compared with genetic test results based on current guidelines. Design, Setting, and Participants: From January 2014 until May 2016 at Memorial Sloan Kettering Cancer Center, 10 336 patients consented to tumor DNA sequencing. Since May 2015, 1040 of these patients with advanced cancer were referred by their oncologists for germline analysis of 76 cancer predisposition genes. Patients with clinically actionable inherited mutations whose genetic test results would not have been predicted by published decision rules were identified. Follow-up for potential clinical implications of mutation detection was through May 2017. Exposure: Tumor and germline sequencing compared with the predicted yield of targeted germline sequencing based on clinical guidelines. Main Outcomes and Measures: Proportion of clinically actionable germline mutations detected by universal tumor-normal sequencing that would not have been detected by guideline-directed testing. Results: Of 1040 patients, the median age was 58 years (interquartile range, 50.5-66 years), 65.3% were male, and 81.3% had stage IV disease at the time of genomic analysis, with prostate, renal, pancreatic, breast, and colon cancer as the most common diagnoses. Of the 1040 patients, 182 (17.5%; 95% CI, 15.3%-19.9%) had clinically actionable mutations conferring cancer susceptibility, including 149 with moderate- to high-penetrance mutations; 101 patients tested (9.7%; 95% CI, 8.1%-11.7%) would not have had these mutations detected using clinical guidelines, including 65 with moderate- to high-penetrance mutations. Frequency of inherited mutations was related to case mix, stage, and founder mutations. Germline findings led to discussion or initiation of change to targeted therapy in 38 patients tested (3.7%) and predictive testing in the families of 13 individuals (1.3%), including 6 for whom genetic evaluation would not have been initiated by guideline-based testing. Conclusions and Relevance: In this referral population with selected advanced cancers, universal sequencing of a broad panel of cancer-related genes in paired germline and tumor DNA samples was associated with increased detection of individuals with potentially clinically significant heritable mutations over the predicted yield of targeted germline testing based on current clinical guidelines. Knowledge of these additional mutations can help guide therapeutic and preventive interventions, but whether all of these interventions would improve outcomes for patients with cancer or their family members requires further study. Trial Registration: clinicaltrials.gov Identifier: NCT01775072.

Patient Participation at Health Care Conferences: Engaged Patients Increase Information Flow, Expand Propagation, and Deepen Engagement in the Conversation of Tweets Compared to Physicians or Researchers.

BACKGROUND: Health care conferences present a unique opportunity to network, spark innovation, and disseminate novel information to a large audience, but the dissemination of information typically stays within very specific networks. Social network analysis can be adopted to understand the flow of information between virtual social communities and the role of patients within the network. OBJECTIVE: The purpose of this study is to examine the impact engaged patients bring to health care conference social media information flow and how they expand dissemination and distribution of tweets compared to other health care conference stakeholders such as physicians and researchers. METHODS: From January 2014 through December 2016, 7,644,549 tweets were analyzed from 1672 health care conferences with at least 1000 tweets who had registered in Symplur's Health Care Hashtag Project from 2014 to 2016. The tweet content was analyzed to create a list of the top 100 influencers by mention from each conference, who were then subsequently categorized by stakeholder group. Multivariate linear regression models were created using stepwise function building to identify factors explaining variability as predictor variables for the model in which conference tweets were taken as the dependent variable. RESULTS: Inclusion of engaged patients in health care conference social media was low compared to that of physicians and has not significantly changed over the last 3 years. When engaged patient voices are included in health care conferences, they greatly increase information flow as measured by total tweet volume (beta=301.6) compared to physicians (beta=137.3, P<.001), expand propagation of information tweeted during a conference as measured by social media impressions created (beta=1,700,000) compared to physicians (beta=270,000, P<.001), and deepen engagement in the tweet conversation as measured by replies to their tweets (beta=24.4) compared to physicians (beta=5.5, P<.001). Social network analysis of hubs and authorities revealed that patients had statistically significant higher hub scores (mean 8.26×10-4, SD 2.96×10-4) compared to other stakeholder groups' Twitter accounts (mean 7.19×10-4, SD 3.81×10-4; t273.84=4.302, P<.001). CONCLUSIONS: Although engaged patients are powerful accelerators of information flow, expanders of tweet propagation, and greatly deepen engagement in conversation of tweets on social media of health care conferences compared to physicians, they represent only 1.4% of the stakeholder mix of the top 100 influencers in the conversation. Health care conferences that fail to engage patients in their proceedings may risk limiting their engagement with the public, disseminating scientific information to a narrow community and slowing flow of information across social media channels.