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We present a case of hypoglycemia in a young patient without diabetes mellitus who presented initially with enlarging neck mass and weight loss, and was found to have aggressive melanoma with metastasis to multiple organs and diffuse lymphadenopathy. He had presented to the emergency room two times with neuroglycopenic symptoms that required admission and intravenous dextrose continuously. Evaluation of hypoglycemia included C-peptide, insulin levels, insulin-like growth factor (IGF) -I and -II, and ß- hydroxybutyrate. Insulin levels were suppressed appropriately during hypoglycemia, however, IGF-II:IGF-I ratio was high, suggesting non-islet tumour induced hypoglycemia. The presence of IGF-II produced by large tumors results in a low hepatic glucose output and increased uptake by skeletal muscle, resulting in hypoglycemia especially in a patient with extremely low appetite such as our patient. Treating the culprit malignancy leads to resolution of hypoglycemia, but corticosteroids have been used to suppress IGF-II levels and alleviate symptoms.

OBJECTIVE The objective of this study was to determine the frequency with which brain biopsy for presumed CNS relapse of systemic hematological malignancies yields new, actionable diagnostic information. Hematological malignancies represent a disparate group of genetic and histopathological disorders. Proclivity for brain involvement is dependent on the unique entity and may occur synchronously or metasynchronously with the systemic lesion. Diffuse large B-cell lymphomas (DLBCLs) have a high propensity for brain involvement. Patients in remission from systemic DLBCL may present with a lesion suspicious for brain relapse. These patients often undergo brain biopsy. The authors’ a priori hypothesis was that brain biopsy in patients with a history of systemic DLBCL and a new brain MRI lesion would have lower diagnostic utility compared with patients with non-DLBCL systemic malignancies. METHODS The authors performed a retrospective review of patients who underwent brain biopsy between 2000 and 2019. Inclusion criteria were patients ≥ 18 years of age with a prior systemic hematological malignancy in remission presenting with a new brain MRI lesion concerning for CNS relapse. Patients with a history of any CNS neoplasms, demyelinating disorders, or active systemic disease were excluded. The main outcome was the proportion of patients with a distinct histopathological brain diagnosis compared with the systemic malignancy. The authors secondarily assessed overall survival, procedure-related morbidity, and 30-day mortality. RESULTS Sixty patients met inclusion criteria (40 males and 20 females); the median age at brain biopsy was 67 years (range 23–88 years). The median follow-up was 8.5 months (range 0.1–231 months). Thirty-nine (65.0%) patients had DLBCL and 21 (35%) had non-DLBCL malignancies. Thirty-five of 36 (97.2%) patients with prior systemic DLBCL and a diagnostic biopsy had histopathological confirmation of the original systemic disease versus 0 of 21 patients with non-DLBCL systemic malignancies (p < 0.001). Morbidity and 30-day mortality were 8.3% and 10.0%, respectively; 2 of 6 30-day mortalities were directly attributable to the biopsy. The median overall survival following brain biopsy was 10.8 months. CONCLUSIONS Patients with a history of systemic DLBCL and presumed CNS relapse gained minimal clinical benefit from brain biopsy but were at high risk of morbidity and mortality. In patients with a history of non-DLBCL systemic malignancies, brain biopsy remained critical given the high likelihood for discovery of distinct diagnostic entities. It was determined that patients with a prior systemic DLBCL and presumed brain relapse should likely receive empirical therapy obviating treatment delay and the risks of brain biopsy.

Type 2 diabetes is a disease characterized by impaired insulin secretion and defective glucagon suppression in the postprandial period. We examined the effect of impaired glucagon suppression on glucose concentrations and endogenous glucose production (EGP) at different degrees of insulin secretory impairment. The contribution of anthropometric characteristics, peripheral, and hepatic insulin action to this variability was also examined. To do so, we studied 54 nondiabetic subjects on two occasions in which endogenous hormone secretion was inhibited by somatostatin, with glucagon infused at a rate of 0.65 ng/kg/min, at 0 min to prevent a fall in glucagon (nonsuppressed day) or at 120 min to create a transient fall in glucagon (suppressed day). Subjects received glucose (labeled with [3-(3)H]-glucose) infused to mimic the systemic appearance of 50-g oral glucose. Insulin was infused to mimic a prandial insulin response in 18 subjects, another 18 received 80% of the dose, and the remaining 18 received 60%. EGP was measured using the tracer-dilution technique. Decreased prandial insulin resulted in greater % increase in peak glucose but not in integrated glucose concentrations attributable to nonsuppressed glucagon. The % change in integrated EGP was unaffected by insulin dose. Multivariate regression analysis, adjusted for age, sex, weight, and insulin dose, did not show a relationship between the EGP response to impaired suppression of glucagon and insulin action as measured at the time of screening by oral glucose tolerance. A similar analysis for hepatic insulin action also did not show a relationship with the EGP response. These data indicate that the effect of impaired glucagon suppression on EGP is independent of anthropometric characteristics and insulin action. NEW & NOTEWORTHY In prediabetes, anthropometric characteristics as well as insulin action do not alter the hepatic response to glucagon. The postprandial suppression or lack of suppression of glucagon secretion is an important factor governing postprandial glucose tolerance independent of insulin secretion.

INTRODUCTION We examined national Google Trends and local healthcare utilization after 3 high-impact gastroenterology publications. METHODS Changes in US Google Trends and Olmsted County health utilization were studied. RESULTS Publication views within 30 days were 51,458 (Imperiale), 49,759 (Pimentel), and 18,750 (Gomm). Colonoscopy searches (P = 0.04) and Cologuard tests performed (P < 0.01) increased while colonoscopies decreased (P < 0.01). Searches for rifaximin (P = 0.05), irritable bowel syndrome (P < 0.01), diarrhea (P < 0.01), and rifaximin prescriptions (P = 0.02) increased. Increase in hydrogen-2 blocker searches (P = 0.02) and prescriptions (P < 0.01) and gastroesophageal reflux disease (P < 0.01) and dementia office visits (P < 0.01) occurred. DISCUSSION High-impact gastroenterology publications influence Google searches and local population-based healthcare utilization.

Undiagnosed dilated cardiomyopathy (DC) can be asymptomatic or present as sudden cardiac death, therefore pre-emptively identifying and treating patients may be beneficial. Screening for DC with echocardiography is expensive and labor intensive and standard electrocardiography (ECG) is insensitive and non-specific. The performance and applicability of artificial intelligence-enabled electrocardiography (AI-ECG) for detection of DC is unknown. Diagnostic performance of an AI algorithm in determining reduced left ventricular ejection fraction (LVEF) was evaluated in a cohort that comprised of DC and normal LVEF control patients. DC patients and controls with 12-lead ECGs and a reference LVEF measured by echocardiography performed within 30 and 180 days of the ECG respectively were enrolled. The model was tested for its sensitivity, specificity, negative predictive (NPV) and positive predictive values (PPV) based on the prevalence of DC at 1% and 5%. The cohort consisted of 421 DC cases (60% males, 57±15 years, LVEF 28±11%) and 16,025 controls (49% males, age 69 ±16 years, LVEF 62±5%). For detection of LVEF≤45%, the area under the curve (AUC) was 0.955 with a sensitivity of 98.8% and specificity 44.8%. The NPV and PPV were 100% and 1.8% at a DC prevalence of 1% and 99.9% and 8.6% at a prevalence of 5%, respectively. In conclusion AI-ECG demonstrated high sensitivity and negative predictive value for detection of DC and could be used as a simple and cost-effective screening tool with implications for screening first degree relatives of DC patients.

The use of activated charcoal in poisoning remains both a pillar of modern toxicology and a source of debate. Following the publication of the joint position statements on the use of single-dose and multiple-dose activated charcoal by the American Academy of Clinical Toxicology and the European Association of Poison Centres and Clinical Toxicologists, the routine use of activated charcoal declined. Over subsequent years, many new pharmaceuticals became available in modified or alternative-release formulations and additional data on gastric emptying time in poisoning was published, challenging previous assumptions about absorption kinetics. The American Academy of Clinical Toxicology, the European Association of Poison Centres and Clinical Toxicologists and the Asia Pacific Association of Medical Toxicology founded the Clinical Toxicology Recommendations Collaborative to create a framework for evidence-based recommendations for the management of poisoned patients. The activated charcoal workgroup of the Clinical Toxicology Recommendations Collaborative was tasked with reviewing systematically the evidence pertaining to the use of activated charcoal in poisoning in order to update the previous recommendations.The main objective was: Does oral activated charcoal given to adults or children prevent toxicity or improve clinical outcome and survival of poisoned patients compared to those who do not receive charcoal? Secondary objectives were to evaluate pharmacokinetic outcomes, the role of cathartics, and adverse events to charcoal administration. This systematic review summarizes the available evidence on the efficacy of activated charcoal.A medical librarian created a systematic search strategy for Medline (Ovid), subsequently translated for Embase (From 22,950 titles originally identified, the final data set consisted of 296 human studies, 118 animal studies, and 145This systematic review found heterogenous data. The higher GRADE data was focused on a few select poisonings, while studies that addressed patients with unknown and or mixed ingestions were hampered by low rates of clinically meaningful toxicity or death. Despite these limitations, they reported a benefit of activated charcoal beyond one hour in many clinical scenarios.

Background As the uncertainty surrounding the future of U.S. health care policy intensifies, political advocacy and campaign contributions have become increasingly relevant. This study describes the trends of political contributions of U.S. neurosurgeons from the years 2003–2019. Methods Individual contribution data from 2003–2019 were obtained from the Federal Election Commission website. Contributions were filtered for occupation lines matching either “neurosurg,” “neurologic surgeon,” or “neurological surgeon.” Each contribution is designated to a recipient committee associated with a political candidate or group. The party designations of these committees were used to catalogue donations as “Republican,” “Democratic,” or “Independent.” Results From 2003–2019 a total of 9242 political donations were made by self-identified neurosurgeons amounting to $8,469,121. Most of these contribution dollars were directed to Independent committees (47.9%). Of all Independent contribution dollars from 2005–2019, 95.9% were directed to the American Association of Neurological Surgeons Political Action Committee. The total number of unique contributions increased from 442 contributions in 2003 to 650 in 2019. Democrats experienced the most substantial increase in support, from 4.8% of all contribution dollars in 2003 to 26.3% in 2019. Republican support was noted to be more widespread across the United States compared with Democratic support. Conclusions Political contributions from U.S. neurosurgeons have increased steadily over time. Donations were largely Independent but became increasingly partisan in recent years. Overall, this displays an increase in political involvement among the neurosurgeon community. Future studies are warranted into how this involvement translates to representative health policy.

Objectives The aim of this study was to examine the effect of CYP2C19 genotype on clinical outcomes in patients with coronary artery disease (CAD) who predominantly underwent percutaneous coronary intervention (PCI), comparing those treated with ticagrelor or prasugrel versus clopidogrel. Background The effect of CYP2C19 genotype on treatment outcomes with ticagrelor or prasugrel compared with clopidogrel is unclear. Methods Databases through February 19, 2020, were searched for studies reporting the effect of CYP2C19 genotype on ischemic outcomes during ticagrelor or prasugrel versus clopidogrel treatment. Study eligibility required outcomes reported for CYP2C19 genotype status and clopidogrel and alternative P2Y12 inhibitors in patients with CAD with at least 50% undergoing PCI. The primary analysis consisted of randomized controlled trials (RCTs). A secondary analysis was conducted by adding non-RCTs to the primary analysis. The primary outcome was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia. Meta-analysis was conducted to compare the 2 drug regimens and test interaction with CYP2C19 genotype. Results Of 1,335 studies identified, 7 RCTs were included (15,949 patients, mean age 62 years; 77% had PCI, 98% had acute coronary syndromes). Statistical heterogeneity was minimal, and risk for bias was low. Ticagrelor and prasugrel compared with clopidogrel resulted in a significant reduction in ischemic events (relative risk: 0.70; 95% confidence interval: 0.59 to 0.83) in CYP2C19 loss-of-function carriers but not in noncarriers (relative risk: 1.0; 95% confidence interval: 0.80 to 1.25). The test of interaction on the basis of CYP2C19 genotype status was statistically significant (p = 0.013), suggesting that CYP2C19 genotype modified the effect. An additional 4 observational studies were found, and adding them to the analysis provided the same conclusions (p value of the test of interaction Conclusions The effect of ticagrelor or prasugrel compared with clopidogrel in reducing ischemic events in patients with CAD who predominantly undergo PCI is based primarily on the presence of CYP2C19 loss-of-function carrier status. These results support genetic testing prior to prescribing P2Y12 inhibitor therapy.

Introduction Plasma thrombin generation kinetics as measured by the calibrated automated thrombogram (CAT) assay is a predictor of symptomatic venous thromboembolism after trauma. We hypothesized that data from a new prototype assay for measurement of thrombin generation kinetics in fresh whole blood (near patient testing of thrombin generation), will correlate with the standard CAT assay in the same patients, making it a potential tool in the future care of trauma patients. Methods Patients were enrolled from June 2018 to February 2020. Within 12 hours of injury, blood samples were collected simultaneously for both assays. Variables compared and correlated between assays were lag time, peak height, time to peak, and endogenous thrombin potential. Data are presented as median with interquartile range (IQR). Spearman and Pearson correlations were estimated and tested between both assays; a P value of

Objective Pulsatile insulin secretion is impaired in diseases such as type 2 diabetes that are characterized by insulin resistance. This has led to the suggestion that changes in insulin pulsatility directly impair insulin signaling. We sought to examine the effects of pulse characteristics on insulin action in humans, hypothesizing that a decrease in pulse amplitude or frequency is associated with impaired hepatic insulin action. Methods We studied 29 nondiabetic subjects on two occasions. On 1 occasion, hepatic and peripheral insulin action was measured using a euglycemic clamp. The deuterated water method was used to estimate the contribution of gluconeogenesis to endogenous glucose production. On a separate study day, we utilized nonparametric stochastic deconvolution of frequently sampled peripheral C-peptide concentrations during fasting to reconstruct portal insulin secretion. In addition to measuring basal and pulsatile insulin secretion, we used approximate entropy to measure orderliness and Fourier transform to measure the average, and the dispersion of, insulin pulse frequencies. Results In univariate analysis, basal insulin secretion (R2 = 0.16) and insulin pulse amplitude (R2 = 0.09) correlated weakly with insulin-induced suppression of gluconeogenesis. However, after adjustment for age, sex, and weight, these associations were no longer significant. The other pulse characteristics also did not correlate with the ability of insulin to suppress endogenous glucose production (and gluconeogenesis) or to stimulate glucose disappearance. Conclusions Overall, our data demonstrate that insulin pulse characteristics, considered independently of other factors, do not correlate with measures of hepatic and peripheral insulin sensitivity in nondiabetic humans.

Background Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response after Percutaneous Coronary Intervention (TAILOR-PCI) is the largest cardiovascular genotype-based randomized pragmatic trial (NCT#01742117) to evaluate the role of genotype-guided selection of oral P2Y12 inhibitor therapy in improving ischemic outcomes after PCI. The trial has been extended from the original 12- to 24-month follow-up, using study coordinator-initiated telephone visits. TAILOR-PCI Digital Study tests the feasibility of extending the trial follow-up in a subset of patients for up to 24 months using state-of-the-art digital solutions. The rationale, design, and approach of extended digital study of patients recruited into a large, international, multi-center clinical trial has not been previously described. Methods A total of 930 patients from U.S. and Canadian sites previously enrolled in the 5,302 patient TAILOR-PCI trial within 23 months of randomization are invited by mail to the Digital Study website ( http://tailorpci.eurekaplatform.org ) and by up to 2 recruiting telephone calls. Eureka, a direct-to-participant digital research platform, is used to consent and collect prospective data on patients for the digital study. Patients are asked to answer health-related surveys at fixed intervals using the Eureka mobile app and or desktop platform. The likelihood of patients enrolled in a randomized clinical trial transitioning to a registry using digital technology, the reasons for nonparticipation and engagement rates are evaluated. To capture hospitalizations, patients may optionally enable geofencing, a process that allows background location tracking and triggering of surveys if a hospital visit greater than 4 hours is detected. In addition, patients answer digital hospitalization surveys every month. Hospitalization data received from the Digital Study will be compared to data collected from study coordinator telephone visits during the same time frame. Conclusions The TAILOR-PCI Digital Study evaluates the feasibility of transitioning a large multicenter randomized clinical trial to a digital registry. The study could provide evidence for the ability of digital technology to follow clinical trial patients and to ascertain trial-related events thus also building the foundation for conducting digital clinical trials. Such a digital approach may be especially pertinent in the era of COVID-19.

Acute invasive fungal sinusitis (AIFS) is a potentially life-threatening diagnosis in immunocompromised patients. Identifying patients who could benefit from evaluation and intervention can be challenging for referring providers and otolaryngologists alike. We aimed to develop and validate an accessible diagnostic tool to estimate the probability of AIFS.Retrospective chart review from 1999 to 2017 identified all patients evaluated for possible AIFS at a tertiary care center. AIFS was diagnosed by pathologic confirmation of fungal tissue angioinvasion. Stepwise selection and univariate logistic regression were used to screen risk factors for a multivariable predictive model. Model performance was assessed using Tukey's goodness-of-fit test and the area under the receiver operator characteristic curve (AUC). Model coefficients were internally validated using bootstrapping with 1000 iterations.A total of 283 patients (244 negative controls, 39 with AIFS) were included. Risk factors in our final diagnostic model included: fever ≥38°C (log-odds ratio [LOR] 1.72; 95% CI, 0.53 to 2.90), unilateral facial swelling, pain, or erythema (LOR 2.84; 95% CI, 1.46 to 4.23), involvement of the orbit or pterygopalatine fossa on imaging (LOR 3.02; 95% CI, 1.78 to 4.26), and mucosal necrosis seen on endoscopy (LOR 5.52; 95% CI, 3.81 to 7.24), with p0.01 for all factors. The model had adequate goodness of fit (p0.05) and discrimination (AUC = 0.96).We present an internally validated diagnostic tool to stratify the risk for AIFS. The estimated risk may help determine which patients can be observed with serial nasal endoscopy, which ones could be biopsied, and which ones would benefit from immediate surgical intervention.

Whether cardiovascular (CV) disease is associated with clinical outcomes in cancer patients receiving immunotherapy is unknown. We reviewed the Mayo Clinic database for all cancer patients who received an immune checkpoint inhibitor (ICI). Multivariate logistic regression analysis, survival analyses, and Cox proportional-hazards models were formulated. Between March, 2010 and July, 2019, 3,326 patients received ICI. Mean patient age was 63.5 years (range: 16 to 96 years). In a Cox proportional-hazards model, obesity (hazard ratio [HR] 0.65, 95% confidence level [CI] 0.55 to 0.77, p < 0.001) and hypercholesterolemia (HR 0.80, 95% CI 0.72 to 0.89, p < 0.001) were associated with lower all-cause mortality while hypertension (HR 1.32, 95% CI 1.17 to 1.49, p < 0.001) and smoking (HR 1.17, 95% CI 1.06 to 1.29, p = 0.002) were associated with higher overall mortality. Among patients with lung cancer, multivariable-adjusted hazard ratios for death from any cause for beta blocker users, as compared with patients who had never used a beta blocker, were 1.39 (95% CI 1.10 to 1.76, p = 0.006). A total of 80 patients (2.4%) experienced CV immune-related adverse events. Event-related morality for ICI-induced myocarditis was 41.7% (5/12). Multivariable-adjusted hazard ratios for ICI-induced myocarditis were 5.2 (95% CI 1.4 to 18.7, p = 0.01) for history of heart failure, 4.06 (95% CI 1.15 to 14.3, p = 0.03) for history of acute coronary syndrome, and 1.07 (per each 1-year increase, 95% CI 1.01 to 1.14, p = 0.02) for age. In conclusion, our study shows that CV factors are associated with clinical outcomes in cancer patients receiving ICI and could be used to predict mortality. In patients with lung cancer, pretreatment beta blocker use is associated with higher all-cause mortality. Three clinical factors-history of heart failure, history of acute coronary syndrome, and age greater than 80 years-help identify patients at higher risk of ICI-induced myocarditis who might benefit from more intensive cardiac surveillance.

BACKGROUND Studies demonstrate an association between aortic hemodynamics and cognitive function. The impact of pregnancy history on this association is unknown. METHODS Postmenopausal women (age 59 ± 5 years; years since last pregnancy 35 ± 3) with either a history of preeclampsia (PE; n = 34) or a history of a normotensive pregnancy (NP; n = 30) underwent cognitive testing: Letter-Number Sequencing, Digit Span, Trail Making Test, and letter and category fluency. Applanation tonometry was used to derive aortic systolic and diastolic blood pressure and augmentation index. RESULTS Distribution of cognitive scores and aortic hemodynamic measures was similar between the PE and NP groups. Principal component (PC) analysis was used to reduce the 3 aortic hemodynamic measures and the 5 cognitive variables to single summary indices, each representing a weighted average of their respective constituent variables. Using a multivariable linear model based on these PCs that adjusted for pregnancy history and body mass index, the composite index of aortic hemodynamics was associated with the summary cognitive index, whether taking into account a potential interaction with pregnancy history (P = 0.035) or not (P = 0.026) (interaction P = 0.178). Multivariable modeling of individual cognitive tests revealed a differential association for letter fluency by pregnancy history (test for interaction P = 0.023); this score correlated with the aortic hemodynamic index in the PE (partial R2 = 0.20), but not the NP (partial R2 = 0.00) group. CONCLUSIONS Elevated aortic hemodynamics may negatively impact cognitive function in postmenopausal women with specific executive functions, such as letter fluency, being impacted more by a pregnancy history of PE.

Primary central nervous system lymphoma is an aggressive form of non-Hodgkin lymphoma arising in the eyes, meninges, spinal cord, or brain. Treatment of primary CNS lymphoma with a combination of high-dose chemotherapy and autologous stem cell transplantation has been shown to have high rates of remission which is frequently sustained for multiple years. Recurrence of primary CNS lymphoma generally presents with one or multiple contrast enhancing lesions on MRI. In rare cases, lymphoma cells may proliferate diffusely within the brain parenchyma without mass formation, a pattern termed lymphomatosis cerebri. Lymphomatosis cerebri presents a significant diagnostic challenge, and has not been reported to present with parkinsonism. Here, we present a case of initially mass forming, contrast-enhancing primary CNS lymphoma which remitted following chemotherapy and autologous stem cell transplantation, and recurred 7 years post-transplant with symptoms of parkinsonism and a lack of typical lesions on imaging, with lymphomatosis cerebri confirmed at autopsy.

Skull base paragangliomas are highly vascular tumors that are often embolized before surgical resection; however, the safety and efficacy of preoperative embolization using an ethylene vinyl alcohol copolymer (Onyx; Medtronic, Dublin, Republic of Ireland) in these tumors is unknown. This retrospective cohort study evaluated patient outcomes after preoperative embolization of skull base paragangliomas using Onyx. We retrospectively analyzed data from all patients with skull base paragangliomas who underwent preoperative Onyx embolization at our institution (January 01, 2005–December 31, 2017). Patient, tumor, embolization, and outcomes data were extracted by reviewing inpatient and outpatient clinical and imaging records. Seven patients were studied (5/7 [71%] female), 6 with glomus jugulares and 1 with a glomus vagale. The median age was 52 years, and the most common presenting symptom was cranial neuropathy (6/7 [86%]). The tumor vascular supply was from the ascending pharyngeal artery in all 7 cases (100%) with additional feeders including the occipital artery in 5 (71%); internal carotid artery in 3 (43%); middle meningeal, vertebral, and internal maxillary artery each in 2 (29%); and posterior auricular artery in 1 (14%). The median postembolization tumor devascularization was 80% (range, 64–95%). The only postembolization complication was a facial palsy in 1 patient. Preoperative embolization with Onyx affords excellent devascularization for the majority of skull base paragangliomas, and it may facilitate resection of these hypervascular lesions. The advantages provided by Onyx with respect to penetration of intratumoral vessels must be weighed against the risk of cranial neuropathy.

Supplemental Digital Content is available in the text, Objective: Development of white matter hyperintensities (WMH) in the brain is associated with blood thrombogenicity in recently menopausal women. This study examined the influence of menopausal hormone treatments (MHTs) on this association. Methods: Measures of blood thrombogenicity were examined in women of the Kronos Early Estrogen Prevention Study (n = 95) who had brain magnetic resonance imaging before and during the 48 months of randomization to transdermal 17β-estradiol (n = 30), oral conjugated equine estrogen (n = 29) both with progesterone for 12 days per month or placebo pills and patch (n = 36). Principal components (PCs) analysis was used to reduce the dimensionality of 14 markers of platelet activation and blood thrombogenicity. The first 5 PCs were assessed for association with treatment and changes in WMH. Within-person slopes were obtained to capture the extent of WMH change for each woman. Results: WMH increased in all groups over the 48 months (P = 0.044). The partial effect of PC1, representing an average of six thrombogenicity variables (microvesicles derived from endothelium, leukocytes, and monocytes, and positive for tissue factor and adhesion molecules) on WMH was significant (P = 0.003). PC3, reflecting a contrast of platelet microaggregates and adenosine triphosphate secretion versus total platelet count, differed across groups (P = 0.006) with higher scores in the oral conjugated equine estrogen group. The global association between PCs and WMH increase, however, did not differ significantly by MHT (P = 0.207 for interaction between MHT and PC's). Conclusion: In recently menopausal women, the type of MHT did not significantly influence the association of markers of blood thrombogenicity with development of WMH in the brain.

The purpose of this study is to evaluate monetary trends from 2000 to 2018 in Medicare reimbursement rates for the most common general surgery procedures.A complete understanding of financial trends in general surgery in the United States is lacking. As such, an evaluation of trends in reimbursement rates in general surgery is important for defining the specialty's current and future financial health.The Physician Fee Schedule Look-Up Tool from the Centers for Medicare and Medicaid Services was queried for each of the 20 top codes top in general surgery. The total raw percent change in Medicare reimbursement rate for each procedure from 2000 to 2018 was calculated and averaged. All data was corrected for inflation. Both average annual and total percentage change were calculated based on these adjusted trends. Compound annual growth rate was calculated using the adjusted data.After adjusting all data for inflation, the reimbursement rate for all included procedures decreased by an average of 24.4% throughout the study period. During this time, the adjusted reimbursement rate decreased by an average of 1.4% each year with an average compound annual growth rate of -1.6%.After adjusting for inflation, Medicare reimbursement rates in general surgery have steadily decreased from 2000 to 2018. It is important that these trends are understood and considered by surgeons, healthcare administrators, and policy-makers in order to develop and implement agreeable models of reimbursement while ensuring access to quality general surgery care in the United States.

AimTo provide a contemporary analysis of incidence trends of infective endocarditis (IE) with its changing epidemiology over the past two decades in Europe.MethodsA systematic review was conducted at the Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus and Web of Science were searched for studies published between 1 January 2000 and 30 November 2020. All studies were independently reviewed by four referees and those that included a population-based incidence of IE in patients, irrespective of age, in Europe were included. Least squares regression was used to estimate pooled temporal trends in IE incidence.ResultsOf 9138 articles screened, 18 studies were included in the review. Elderly men predominated in all studies. IE incidence increased 4.1% per year (95% CI 1.8% to 6.4%) in the pooled regression analysis of eight studies that included comprehensive and consistent trends data. When trends data were weighted according to population size of individual countries, an increase in yearly incidence of 0.27 cases per 100 000 people was observed. Staphylococci and streptococci were the most common pathogens identified. The rate of surgical intervention ranged from 10.2% to 60.0%, and the rate of inpatient mortality ranged from 14.3% to 17.5%. In six studies that examined the rate of injection drug use, five of them reported a rate of less than 10%.ConclusionBased on findings from our systematic review, IE incidence in Europe has doubled over the past two decades in Europe. Multiple factors are likely responsible for this striking increase.Trial registeration numberCRD42020191196.

Background The objective of this paper was to examine temporal changes of infective endocarditis (IE) incidence and epidemiology in North America. Methods A systematic review was conducted at Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science were searched for studies published between January 1, 2000, and May 31, 2020. Four referees independently reviewed all studies, and those that reported a population-based incidence of IE in patients aged 18 years and older in North America were included. Results Of 8588 articles screened, 14 were included. Overall, IE incidence remained largely unchanged throughout the study period, except for 2 studies that demonstrated a rise in incidence after 2014. Five studies reported temporal trends of injection drug use (IDU) prevalence among IE patients with a notable increase in prevalence observed. Staphylococcus aureus was the most common pathogen in 7 of 9 studies that included microbiologic findings. In-patient mortality ranged from 3.7% to 14.4%, while the percentage of patients who underwent surgery ranged from 6.4% to 16.0%. Conclusions The overall incidence of IE has remained stable among the 14 population-based investigations in North America identified in our systematic review. Standardization of study design for future population-based investigations has been highlighted for use in subsequent systematic reviews of IE.

Objective:Clinical trials, which are mainly conducted in urban medical centers, may be less accessible to rural residents. Our aims were to assess participation and the factors associated with participation of rural residents in clinical trials.Methods:Using geocoding, the residential address of participants enrolled into clinical trials at Mayo Clinic locations in Arizona, Florida, and the Midwest between January 1, 2016, and December 31, 2017, was categorized as urban or rural. The distance travelled by participants and trial characteristics was compared between urban and rural participants. Ordinal logistic regression analyses were used to evaluate whether study location and risks were associated with rural participation in trials.Results:Among 292 trials, including 136 (47%) cancer trials, there were 2313 participants. Of these, 731 (32%) were rural participants, which is greater than the rural population in these 9 states (19%,P P= 0.004) and travelled further to the medical center (103 ± 104 vs 68 ± 88 miles,P P Conclusions:Approximately one in three clinical trial participants were rural residents versus one in five in the population. Rural residents travelled further to access clinical trials. The study-associated risks were not associated with the distribution of rural and urban participants in trials.

Background Hypertriglyceridemia is associated with increased risk of coronary heart disease but the association is often attributed to concomitant metabolic abnormalities. We investigated the epidemiology of primary isolated hypertriglyceridemia (PIH) and associated cardiovascular risk in a population‐based setting. Methods and Results We identified adults with at least one triglyceride level ≥500 mg/dL between 1998 and 2015 in Olmsted County, Minnesota. We also identified age‐ and sex‐matched controls with triglyceride levels P = 0.022). There was no statistically significant association between PIH and cerebrovascular disease (HR, 1.06; 95% CI, 0.65‐1.73, P = 0.813), peripheral artery disease (HR, 1.27; 95% CI, 0.43‐3.75; P = 0.668), or the composite end point of all 3 (HR, 1.28; 95% CI, 0.92‐1.80; P =0.148) in adjusted models. Conclusions PIH was associated with incident coronary heart disease events (although there was attenuation after adjustment for conventional risk factors), supporting a causal role for triglycerides in coronary heart disease. The condition is relatively prevalent but awareness and control are low.

Fasting plasma glucose (FPG) concentration is a major predictor of a person’s risk of developing diabetes mellitus (DM). However, we sought to examine characteristics of individuals who develop DM despite a baseline FPG of ≤ 80mg/dL. The Rochester Epidemiology Project (REP) links the medical records of virtually all persons who have resided in Olmsted County, MN, USA between 1966 and present. Electronic laboratory data are available from 2005. Using REP, we identified individuals with ≥ 2 FPG tests from 2005-17, after excluding people who met criteria for DM on/before their first FPG. Those who developed DM (FPG > 125mg/dL) were assigned an event date as the date of their first diagnostic value. Subjects who did not develop DM were censored at their last FPG value on/before Dec 31, 2017. The entire cohort consisted of 44,815 individuals, of whom 3689 (8.2%) developed DM. Although higher baseline FPG was strongly related to development of DM, 2315 had a baseline FPG of ≤ 80mg/dL with 130 (5.6%) developing DM. Within this subset, those who progressed were older at baseline (40 ± 11 vs. 36 ± 12 years, p Disclosure A. M. Egan: None. C. Wood-wentz: None. K. R. Bailey: None. A. Vella: Research Support; Self; Novo Nordisk. Funding National Institutes of Health (DK78646, DK116231, DK126206, K12HD065987)

Time-resolved luminescence lifetime measurements are an important photophysical technique. However, access to this technique at the undergraduate level is limited by the expense of the instrumentat...

Foldable origami structures have been implemented into robotics as a way of compacting joints and circuitry into smaller structures. This technique is especially useful in minimally invasive surgical instruments, where the goal is to create slimline devices that can be inserted through small incisions. Origami also has the potential to cut costs by reducing the amount of material required for assembly. Origami devices are especially suitable for MRI-guided procedures, where instruments must be nonmagnetic because origami is more suitable for flexible, non-metallic materials. MR conditional surgical instruments enable intraoperative MRI procedures that provide superior imaging capabilities to physicians to allow for safer procedures. This work presents an MR conditional joint developed using origami techniques that reduces costs by eliminating assembly of various components and has potential applications in endoscopy. The joint is a compliant rolling-contact element that employs curved-folding origami techniques. A chain of these joints can be constructed from a single sheet of material, eliminating assembly of numerous materials to produce a final product, which is specifically advantageous for constructing low-cost, disposable surgical devices. The prototype contains a degree of bending of ±9 degrees per joint, a response time of less than 4 seconds and an actuation force of 0.5 N using a 1.25 A current. The MRI results showed a minimal artifact of less than 1 mm measured from the boundary of the joint chain and a SNR reduction of less than 10%.

BACKGROUND Interindividual variability in blood pressure (BP) response to antihypertensives has been reported. Although plasma renin activity (PRA) is a potential biomarker for personalizing antihypertensive therapy in European American (EA) and African American (AA) hypertensives, clinical utility of PRA-guided prescribing is incompletely understood. METHODS Using systematic-phased approach, PRA’s clinical utility was assessed. After categorizing by baseline PRA, clinic systolic BP (SBP) responses to metoprolol and chlorthalidone were compared in 134 EAs and 102 AAs enrolled in the Pharmacogenomics Evaluation of Antihypertensive Responses-2 (PEAR-2) trial. Receiver operating characteristic (ROC) analysis was conducted in EAs. Data from PEAR-2 AAs were used to estimate an optimal PRA cut point using multivariable linear regression models. The derived cut point in AAs was tested in a meta-analysis of 2 independent AA cohorts, and its sensitivity and specificity were assessed. RESULTS EAs with PRA < 0.65 ng/ml/hour had a greater decrease in SBP to chlorthalidone than metoprolol (by –15.9 mm Hg, adjusted P < 0.0001), whereas those with PRA ≥ 0.65 ng/ml/hour had a greater decrease in SBP to metoprolol than chlorthalidone (by 3.3 mm Hg, adjusted P = 0.04). Area under ROC curve (0.69, P = 0.0001) showed that PRA can predict SBP response among EAs. However, we observed no association between PRA and SBP response in PEAR-2 AAs. Among independent AA cohorts, those with PRA ≥ 1.3 ng/ml/hour (PEAR-2-derived cut point) responded better to atenolol/candesartan than hydrochlorothiazide (meta-analysis P = 0.01). However, sensitivity of the derived cut point was 10%. CONCLUSIONS PRA at the previously established 0.60–0.65 ng/ml/hour cut point is an effective predictive biomarker of BP response in EAs. However, we were unable to identify PRA cut point that could be used to guide antihypertensive selection in AAs. TRIAL REGISTRATION NCT01203852, NCT00246519, NCT00005520.

Objective:Little is known regarding the progression of preclinical atherosclerosis upon cessation of menopausal hormone therapy (MHT). This study evaluated changes in carotid artery intima-media thickness (CIMT) in a subgroup of participants during 4 years and 3 years after the Kronos Early

Background Over the last 30 years, public opinion and state level legislation regarding the concealed-carry of firearms have shifted dramatically. Previous studies of potential effects have yielded mixed results, making policy recommendations difficult. We investigated whether liberalization of state level concealed-carry legislation was associated with a change in the rates of homicide or other violent crime. Study Design Data on violent crime and homicide rates were collected from the US Department of Justice Uniform Crime Reporting Program (UCR) and the Centers for Disease Control and Prevention (CDC) over 30 years, from 1986 to 2015. State level concealed-carry legislation was evaluated each study year on a scale including "no carry," "may issue," "shall issue," and "unrestricted carry." Data were analyzed using general multiple linear regression models with the log event rate as the dependent variable, and an autoregressive correlation structure was assumed with generalized estimating equation (GEE) estimates for standard errors. Results During the study period, all states moved to adopt some form of concealed-carry legislation, with a trend toward less restrictive legislation. After adjusting for state and year, there was no significant association between shifts from restrictive to nonrestrictive carry legislation on violent crime and public health indicators. Adjusting further for poverty and unemployment did not significantly influence the results. Conclusions This study demonstrated no statistically significant association between the liberalization of state level firearm carry legislation over the last 30 years and the rates of homicides or other violent crime. Policy efforts aimed at injury prevention and the reduction of firearm-related violence should likely investigate other targets for potential intervention.

Sarcoidosis is a systemic granulomatous disease that frequently involves the myocardium. Unfortunately, the sentinel manifestations of cardiac sarcoidosis are often potentially fatal bradyarrhythmia and tachyarrhythmia. Advanced imaging modalities such as cardiac magnetic resonance have allowed for increased diagnosis of cardiac involvement. The current review article explores diagnosis and treatment strategies for arrhythmias in patients with cardiac sarcoidosis.

Arteriovenous malformations (AVMs) are a highly complex array of abnormal arteries and veins that directly fistulize without intervening capillary beds. 1 As AVMs can differ in size, location, and morphology, specific clinical management is determined for each individual patient, in conjunction with their specific goals and needs. 2 This Video demonstrates the resection of an AVM located in the language area of eloquent cortex of a 38-year-old opera singer. The patient presented to the emergency department with a new-onset seizure. Magnetic resonance imaging including task-based functional imaging demonstrated a left post temporal AVM with associated hemosiderin-stained white matter and language activation just posterior to the lesion. Awake microsurgical resection was recommended given her career as an opera singer and the high-risk location of the AVM in proximity to eloquent language cortex, with additional goals of preventing further risk of hemorrhage and reduction in the risk of epilepsy. The patient underwent a left temporoparietal craniotomy with direct electrical stimulation-based language mapping and monitoring along with microsurgical resection of the AVM with image guidance, confirmed with intraoperative indocyanine green angiography. Postoperative angiography demonstrated no residual AVM with preservation of normal arterial and venous anatomy. At follow-up, the patient was clinically intact, seizure free, and off all antiepileptic medications. At 3 months, she resumed her career as an opera singer. Awake resection with intraoperative functional mapping can be used for select small AVMs to avoid injury to functional tissue and allow more aggressive resection of potentially epileptogenic tissue.

Background Desoxycorticosterone pivalate (DOCP) is a commonly used mineralocorticoid replacement for dogs with primary hypoadrenocorticism (HA), but manufacturer-recommended dosing protocols can be cost-prohibitive. Recent reports also have raised concerns that label dose protocols could be excessive. Objective To investigate the relative efficacy and adverse effects of 2 DOCP dosages in dogs with primary glucocorticoid and mineralocorticoid deficient HA. Animals Thirty-seven dogs, including 19 test population dogs and 18 controls. Methods Randomized controlled double-blinded clinical trial. Dogs with newly diagnosed primary HA were assigned to standard (2.2 mg/kg q30d, control population) or low-dose (1.1 mg/kg q30d, test population) DOCP treatment. Clinical and laboratory variables were assessed 10 to 14 days and approximately 30 days after each DOCP treatment for 90 days. Results Mean serum sodium to potassium ratios at reevaluations were ≥32 in both populations throughout the study. No dog developed electrolyte abnormalities warranting medical treatment, although hypokalemia occurred on at least 1 occasion in 9 controls and 6 test population dogs. Urine specific gravities (median, interquartile range) were lower in control dogs (1.022, 1.016-1.029) as compared to test population dogs (1.033, 1.023-1.039; P = .006). Plasma renin activity was overly suppressed on 84 of 104 (80.8%) assessments in control dogs whereas increased renin activity occurred on 23 of 112 (20.5%) assessments in test population dogs. Conclusions and clinical importance Low-dose DOCP protocols appear to be safe and effective for treatment of HA in most dogs. Standard-dose protocols are more likely to result in biochemical evidence of overtreatment.

High-definition (HD) mapping with the Advisor HD Grid and HD Wave Solution software offers unparalleled resolution in mapping complex arrhythmias. The unique shape of a HD Grid (16 electrodes in a 4 × 4 pattern) allows for the mapping of orthogonal electrograms (EGMs). In so doing, the HD Grid catheter virtually eliminates the issue of 'bipolar blindness', a phenomenon seen when a wavefront of propagation is traveling perpendicular to a bipole pair. By improving the accuracy of the 3D electroanatomical map, HD Grid offers the potential of shorter procedure times, safer ablations and higher success rates. The following article explores the role of HD Grid in mapping a variety of arrhythmias including supraventricular tachycardias, atrial fibrillation and ventricular tachycardia. In addition, the authors explore the role of HD Grid in more recently described substrate-based advanced mapping techniques.Lay abstract Cardiac mapping is a minimally invasive procedure carried out in patients with abnormal heart rhythm arrhythmias. The procedure identifies and produces a map of the electrical activity of the heart. The unique shape of the Advisor HD Grid offers an advantage when mapping complex arrhythmias as it allows for a more detailed map of electrical activity in the heart. By improving the accuracy of the heart map, HD Grid could shorten procedure times, improve safety and increase success rates. The following article explores the role of HD Grid in mapping a variety of arrhythmias. In addition, the authors explore the role of HD Grid in more recently described substrate-based advanced mapping techniques.

AIMS. Gastric emptying is of limited utility for predicting the severity of symptoms in patients with diabetes mellitus and gastrointestinal symptoms. We evaluated the extent to which symptoms recorded during a (13)C-spirulina-based gastric emptying breath test (GEBT) or scintigraphy predicted the severity of daily symptoms in diabetes mellitus. METHODS. Gastric emptying, symptoms during a gastric emptying study, either scintigraphy (n=38) or GEBT (n=111), and daily gastrointestinal symptoms were evaluated in 149 patients with diabetes mellitus and variably severe gastrointestinal symptoms. KEY RESULTS. Gastric emptying was normal, delayed, and rapid in 37%, 52%, and 9% measured with the GEBT and 55%, 34%, and 11% of patients measured with scintigraphy; differences between GEBT and scintigraphy were not significant. Daily symptoms were moderately severe or more intense in 58% and 21% of patients undergoing scintigraphy and GEBT (P < 0.0001). Symptoms during the GEBT (46%) and emptying t(half) (3%) explained 50% of the variance in daily symptoms in the GEBT group. In the scintigraphy group, symptoms explained 29% of this variance; the t(half) was insignificant. Among patients who reported that one or more symptoms were more severe than the others during the GE study, were more likely (OR 3.98, 95% CI 2.16, 7.33) to report the same symptom(s) as being the most severe in the daily diary. CONCLUSIONS. Symptoms during a GEBT and to a lesser extent during scintigraphy, but not gastric emptying predict the severity of daily symptoms and may serve as a biomarker in patients with diabetes mellitus.

Objective To estimate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in health care personnel. Methods The Mayo Clinic Serology Screening Program was created to provide a voluntary, two-stage testing program for SARS-CoV-2 antibodies to health care personnel. The first stage used a dried blood spot screening test initiated on June 15, 2020. Those participants identified as reactive were advised to have confirmatory testing via a venipuncture. Venipuncture results through August 8, 2020, were considered. Consent and authorization for testing was required to participate in the screening program. This report, which was conducted under an institutional review board–approved protocol, only includes employees who have further authorized their records for use in research. Results A total of 81,113 health care personnel were eligible for the program, and of these 29,606 participated in the screening program. A total of 4284 (14.5%) of the dried blood spot test results were "reactive" and warranted confirmatory testing. Confirmatory testing was completed on 4094 (95.6%) of the screen reactive with an overall seroprevalence rate of 0.60% (95% CI, 0.52% to 0.69%). Significant variation in seroprevalence was observed by region of the country and age group. Conclusion The seroprevalence for SARS-CoV-2 antibodies through August 8, 2020, was found to be lower than previously reported in other health care organizations. There was an observation that seroprevalence may be associated with community disease burden.

BackgroundVon Willebrand factor (VWF) is an acute phase reactant synthesized in the megakaryocytes and endothelial cells. VWF forms ultra-large multimers (ULVWF) which are cleaved by the metalloprotease ADAMTS-13, preventing spontaneous VWF–platelet interaction. After trauma, ULVWF is released into circulation as part of the acute phase reaction. We hypothesized that trauma patients would have increased levels of VWF and decreased levels of ADAMTS-13 and that these patients would have accelerated thrombin generation.MethodsWe assessed plasma concentrations of VWF antigen and ADAMTS-13 antigen, the Rapid Enzyme Assays for Autoimmune Diseases (REAADS) activity of VWF, which measure exposure of the platelet-binding A1 domain, and thrombin generation kinetics in 50 samples from 30 trauma patients and an additional 21 samples from volunteers. Samples were analyzed at 0 to 2 hours and at 6 hours from the time of injury. Data are presented as median (IQR) and Kruskal-Wallis test was performed between trauma patients and volunteers at both time points.ResultsREAADS activity was greater in trauma patients than volunteers both at 0 to 2 hours (190.0 (132.0–264.0) vs. 92.0 (71.0–114.0), pDiscussionTrauma patients have increased exposure of the VWF A1 domain and decreased levels of ADAMTS-13 compared with healthy volunteers. This suggests that the VWF burst after trauma may exceed the proteolytic capacity of ADAMTS-13, allowing circulating ULVWF multimers to bind platelets, potentially contributing to trauma-induced coagulopathy.Level of evidenceProspective case cohort study.

The coronavirus disease 2019 (COVID-19) pandemic created an extremely disruptive challenge for health care leaders that required a rapid, dynamic, and innovative response. The purpose of this manuscript is to share the leadership actions and decisions at Mayo Clinic in Florida during the first 6 months of the pandemic (February to July 2020). We note 4 strategies that contributed to an effective response: (1) leverage experience with disaster preparedness and mobilize regional and national networks; (2) use surge models to anticipate and to address supply chain issues as well as practical and financial effects of the pandemic; (3) adapt creatively to establish new safety and procedural protocols in various areas for various populations; and (4) communicate timely information effectively and be the common source of truth. Mayo Clinic in Florida was able to address the surges of patients with COVID-19, to provide ongoing tertiary care, and to restore function within the first 6 months with new, strengthened practices and protocols.

Drug overdose and poisoning are leading causes of emergency department visits and hospital admissions in the United States, accounting for more than 500,000 emergency department visits and 11,000 deaths each year. This chapter discusses the approach to the patient with poisoning or drug overdose, beginning with the initial stabilization period in which the physician proceeds through the ABCDs (airway, breathing, circulation, dextrose, decontamination) of stabilization. The management of some of the more common complications of poisoning and drug overdose are summarized and include coma, hypotension and cardiac dysrhythmias, hypertension, seizures, hyperthermia, hypothermia, and rhabdomyolysis. The physician should also perform a careful diagnostic evaluation that includes a directed history, physical examination, and the appropriate laboratory tests. The next step is to prevent further absorption of the drug or poison by decontaminating the skin or gastrointestinal tract and, possibly, by administering antidotes and performing other measures that enhance elimination of the drug from the body. The diagnosis and treatment of overdoses of a number of specific drugs and poisons that a physician may encounter, as well as food poisoning and smoke inhalation, are discussed. Tables present the ABCDs of initial stabilization of the poisoned patient; mechanisms of drug-induced hypotension; causes of cardiac disturbances; drug-induced seizures; drug-induced hyperthermia; autonomic syndromes induced by drugs or poison; the use of the clinical laboratory in the initial diagnosis of poisoning; methods of gastrointestinal decontamination; methods of and indications for enhanced drug removal; toxicity of common beta blockers; common stimulant drugs; corrosive agents; dosing of digoxin-specific antibodies; poisoning with ethylene glycol or methanol; manifestations of excessive acetylcholine activity; common tricyclic and other antidepressants; seafood poisonings; drugs or classes that require activated charcoal treatment; and special circumstances for use of activated charcoal. This review contains 3 figures, 22 tables, and 198 references.

Introduction: The impact of beta blocker use on surgical outcomes of cancer patients receiving immunotherapy is unknown. Hypothesis: Beta blocker use is associated with lower post-operative mortality in cancer patients on immunotherapy. Methods: We used an institutional Advanced Cohort Explorer to identify all patients who underwent any surgical procedure less than 90 days after receiving immunotherapy. Data on the procedure performed as well as the post-operative outcome were collected and analyzed per the pre-operative beta blocker use status. Results: A total of 233 patients underwent surgery between 09/2011-06/2019. Mean age was 64.7 years (range: 16-92). The most common cancer diagnoses were lung (48, 44.4%), melanoma (49, 45.4%) and kidney (11, 10.2%). Immunotherapy medications were pembrolizumab ( 127, 54.5%), nivolumab (51, 21.9%), ipilimumab (43, 18.5%), atezolizumab (11, 4.7%) and avelumab (1, 0.43%). Pre-operative beta blocker use was documented in 140 (60.1%) patients. Most common surgical procedures were skin resection (75, 32.1%), wound repair (47, 20.2%), vascular procedures (36, 15.5%), urethral procedures 16 (6.9%) and sentinel lymph node biopsies (10, 4.3%). The 30-day mortality rate was 10.3% (24 deaths). In a multi-variable logistic regression analysis, pre-operative use of beta blockers was associated with a lower risk of death within 30 days from surgery (OR 0.34, CI 0.13-0.87, P=0.024). 30-day mortality rates were higher in patients undergoing vascular (50%, 17 of 34) versus non-vascular (3.5%, 7 of 199) procedures (P Conclusions: Beta blocker use is associated with a lower 30-day mortality rate after surgical procedures in cancer patients treated with immunotherapy. Further investigation is warranted.

Introduction: Atrial natriuretic peptide (ANP) plays an important role in blood pressure (BP) regulation via the second messenger cGMP. ANP also induces lipolysis by increasing plasma levels of non-esterified fatty acids (NEFA). MANP is a new Mayo Clinic designed ANP analog consisting of the native ANP with a novel 12-amino-acid C-terminus extension. In experimental models, MANP is more potent than ANP in reducing BP and inducing natriuresis. These actions are mediated by the activation of the pGC-A receptor and generation of cGMP. To date, the BP pressure lowering, cGMP generating and lipolytic actions of MANP remain unexplored along with its safety and tolerability in subjects with hypertension (HTN) associated with metabolic disease. Hypothesis: In subjects with HTN, obesity and metabolic syndrome (MS), MANP administration is safe, well tolerated, activates cGMP and exerts BP lowering and lipolytic properties. Methods: Double-blind, placebo-control clinical trial in 22 subjects (17 receiving MANP) with HTN, obesity and MS involving a single subcutaneous (SQ) injection of MANP (2.5 μg/Kg) or placebo. Subjects were monitored and cardiovascular, cGMP and metabolic parameters were collected during 24 hours after the injection. Results: In all subjects, MANP was safe and well-tolerated with no serious adverse side effects. MANP increased mean cGMP plasma levels after 30 minutes (delta: 4.8 ± 2.0 pmol/mL, p=0.02) and 1 hour (delta: 2.9 ±1.3 pmol/mL, p=0.03) when compared to baseline. Six hours after MANP injection systolic BP decreased by 5.7 ± 2.9 mmHg (p=0.06) whereas subjects receiving placebo had no decrease in blood pressure values compared to baseline. During fasting period, one hour after the administration of MANP, NEFA plasma levels increased by 108.2 ± 37.4 μM (p=0.01). Conclusions: In subjects with HTN, obesity and MS, SQ MANP is safe, well tolerated and activates the pGC-A receptor as measured by a significant increase in the second messenger cGMP. Subjects receiving MANP showed a borderline significant decrease in systolic BP and a significant increase in NEFA circulating levels supporting anti-hypertensive and lipolytic properties. Our findings support MANP as a potential novel therapy for HTN associated with metabolic disease.

BACKGROUND Trends in Medicare billing and procedural reimbursement for outpatient office visits remain unclear within the field of neurosurgery. OBJECTIVE To analyze financial trends of neurosurgeon reimbursement for Medicare office visits in 2010 compared to 2018. METHODS The 2010 and 2018 physician/supplier files from the Centers for Medicare and Medicaid Services website were utilized. All payments submitted by neurosurgeons (provider ID 14) were included. Trends in office visit Current Procedural Terminology codes 99201 to 99205 and 99211 to 99215 were analyzed. RESULTS Neurosurgeons billed for 1 109 979 office visits (463 611 h) in 2010 and Medicare denied 63 704 payments (totaling $11 205 283). Neurosurgeons billed for 1 189 046 office visits (508 526 h) in 2018 and Medicare denied 57 048 payments (totaling $15 103 879). This is a 7.1% increase in total neurosurgery office visits billed to Medicare, 9.7% increase in total office hours, and 34.8% increase in the payment amounts denied over 8 yr. Furthermore, after adjusting for inflation, the average amount paid to physicians by Medicare decreased by 8.3% per office visit. Additionally, Medicare paid 36.1% of the total neurosurgeon submitted charge amount for all office visits in 2010 but paid only 27.8% in 2018 (-8.3%). CONCLUSION Neurosurgeons are performing more office visits and billing for more time with patients. Meanwhile, Medicare has been paying physicians less per office visit, denying higher amounts of payments and reimbursing a decreasing percentage of submitted charges for office visits. An understanding of these trends is necessary to ensure continued equity and quality access to neurosurgical care in the United States.

Background Practice consolidation in health care has widespread consequences for providers and patients. Although many studies describe this phenomenon in various medical specialties, no such analysis has been performed in neurosurgery specifically. The goal of this study was to assess the trends in the size of U.S. neurosurgery practices over a 5-year period. Methods Neurosurgery practice characteristics were obtained from the Medicare Physician Compare database from March 2014 through October 2019 on the Centers for Medicare & Medicaid Services Web site. Neurosurgeons were separated on the basis of their practice size. Group practice sizes ranged from solo practitioner practice to large multispecialty groups and health organizations. Eight groups were identified (1 or 2, 3–9, 10–24, 25–49, 50–99, 100–499, 500–999, and ≥1000 members). Additionally, neurosurgery practices were analyzed across the 4 U.S. geographical regions to understand changes in practice size and distribution. Results The percentage of neurosurgeons in smaller practices of 1 or 2 members decreased, from 20.09% to 13.05%; 3–9 members, from 17.79% to 9.41%; and 10–24 members, from 10.53% to 8.0%. The largest increase was seen in health organizations of 1000 members or more, with an increase from 9.85% to 22.84%. Conclusions This study shows that over the past 5 years, a substantial trend toward increasing practice sizes has evolved. The effect of the differences in practice size should be examined to determine the large-scale impacts on patient care, payment models, and health care access, in addition to neurosurgeon compensation, and satisfaction.

Background Recent investigations suggest that inflammation and autoimmunity might have a role in the pathophysiology of atrial fibrillation (AF). Given that abnormal ventriculovascular coupling often coexists with AF, we hypothesize that autoimmune vasculitis plays a significant role in the pathogenetic mechanism of AF. Methods and Results A standardized retrospective population‐based case–control study was conducted to evaluate the association between autoimmune vasculitis and AF, and all‐cause mortality. The study included 8459 patients with a new diagnosis of AF and 8459 age‐, sex‐, and registration calendar year–matched controls in Olmsted County, Minnesota, between January 1, 1980 and December 31, 2010. The association of each clinical characteristic, diagnosis, and treatment was assessed using conditional logistic regression to account for the matched case–control study design. Cox proportional hazards regression models and Kaplan‐Meier curves were used to detect independent predictors of mortality and examine cumulative survival. Of a total of 16 918 patients (mean age 72.3+14.4 years; 48.7% women), 320 (1.9%) were diagnosed with autoimmune vasculitis before the index date during the 30‐year period. Among the cases, the prevalence of any autoimmune vasculitis was 2.3%, whereas the frequency of autoimmune vasculitis in controls was 1.5% ( P P =0.03). Patients with AF and autoimmune vasculitis had worse 5‐year survival than those without autoimmune vasculitis or AF (44.7% versus 77.2%; log‐rank P Conclusions Autoimmune vasculitis is significantly associated with AF and independently confers worse survival. These observations may represent one mechanism linking autoimmunity and inflammation to the pathogenesis and prognosis of AF.

Objective We sought to determine the proportion and number of female neurosurgeons in the workforce at different stages of practice. Methods The Physician Compare National Downloadable File data set was obtained from the Centers for Medicare & Medicaid Services for physicians who indicated “neurosurgery” as their primary specialty. Physician duplicates, physicians with no listed medical school graduation year, and physicians expected to be in residency (graduation years 2013–2019) were removed, yielding 4956 neurosurgeons. Five-year intervals were used to measure the number of male and female neurosurgeons by different stages of their careers. For example, graduates from years 2008–2012 were expected to be in their first 1–5 years of practice. Results There were 405 female (8.2%) and 4551 male (91.8%) neurosurgeons. At 1–5 years of practice, 13.8% (105/760) were women; 6–10 years, 11.5% (94/820) women; 11–15 years, 8.9% (64/720) women; 16–20 years, 8.7% (59/682) women; 21–25 years, 7.4% (46/619) women; 26–30 years, 3.8% (20/520) women; 31–35 years, 3.6% (15/413) women; and 36 years or more, 0.5% women (2/422). The number of female neurosurgeons varied among states, ranging from 0 in Hawaii to 53 in California. The states with the lowest percentage of female neurosurgeons were Hawaii (0%), Oklahoma (3.1%), and Nevada (3.6%). The states with the highest percentage of female neurosurgeons were New Hampshire (20.0%), Vermont (16.7%), and Rhode Island (15.8%). Conclusions The number of practicing female neurosurgeons within the United States is increasing, as shown by the growing percentage of women who are earlier in their surgical careers.

Importance After percutaneous coronary intervention (PCI), patients withCYP2C19*2or*3loss-of-function (LOF) variants treated with clopidogrel have increased risk of ischemic events. Whether genotype-guided selection of oral P2Y12 inhibitor therapy improves ischemic outcomes is unknown. Objective To determine the effect of a genotype-guided oral P2Y12 inhibitor strategy on ischemic outcomes inCYP2C19LOF carriers after PCI. Design, Setting, and Participants Open-label randomized clinical trial of 5302 patients undergoing PCI for acute coronary syndromes (ACS) or stable coronary artery disease (CAD). Patients were enrolled at 40 centers in the US, Canada, South Korea, and Mexico from May 2013 through October 2018; final date of follow-up was October 2019. Interventions Patients randomized to the genotype-guided group (n = 2652) underwent point-of-care genotyping.CYP2C19LOF carriers were prescribed ticagrelor and noncarriers clopidogrel. Patients randomized to the conventional group (n = 2650) were prescribed clopidogrel and underwent genotyping after 12 months. Main Outcomes and Measures The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia at 12 months. A secondary end point was major or minor bleeding at 12 months. The primary analysis was in patients withCYP2C19LOF variants, and secondary analysis included all randomized patients. The trial had 85% power to detect a minimum hazard ratio of 0.50. Results Among 5302 patients randomized (median age, 62 years; 25% women), 82% had ACS and 18% had stable CAD; 94% completed the trial. Of 1849 withCYP2C19LOF variants, 764 of 903 (85%) assigned to genotype-guided therapy received ticagrelor, and 932 of 946 (99%) assigned to conventional therapy received clopidogrel. The primary end point occurred in 35 of 903CYP2C19LOF carriers (4.0%) in the genotype-guided therapy group and 54 of 946 (5.9%) in the conventional therapy group at 12 months (hazard ratio [HR], 0.66 [95% CI, 0.43-1.02];P = .06). None of the 11 prespecified secondary end points showed significant differences, including major or minor bleeding inCYP2C19LOF carriers in the genotype-guided group (1.9%) vs the conventional therapy group (1.6%) at 12 months (HR, 1.22 [95% CI, 0.60-2.51];P = .58). Among all randomized patients, the primary end point occurred in 113 of 2641 (4.4%) in the genotype-guided group and 135 of 2635 (5.3%) in the conventional group (HR, 0.84 [95% CI, 0.65-1.07];P = .16). Conclusions and Relevance AmongCYP2C19LOF carriers with ACS and stable CAD undergoing PCI, genotype-guided selection of an oral P2Y12 inhibitor, compared with conventional clopidogrel therapy without point-of-care genotyping, resulted in no statistically significant difference in a composite end point of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia based on the prespecified analysis plan and the treatment effect that the study was powered to detect at 12 months. Trial Registration ClinicalTrials.gov Identifier:NCT01742117

Idiopathic normal pressure hydrocephalus (iNPH) is a progressive neurological disorder characterized by gait apraxia, cognitive decline, and urinary incontinence. It can be difficult to diagnose iNPH as the symptoms may overlap with other neurodegenerative diseases including ​cervical spondylotic myelopathy. Cervical spondylotic myelopathy is a progressive degenerative disease in which compression of the cervical spinal cord causes gait disturbances and imbalance, loss of dexterity and strength in the hands, and, at late stages, urinary dysfunction. As with iNPH, increased age is associated with higher incidence and prevalence. Surgical decompression of the cervical spinal cord is the treatment of choice in patients with progressive myelopathy. Accordingly, iNPH and cervical myelopathy may both present with progressive gait impairment and incontinence, especially in the elderly. The case presented here demonstrates that both iNPH and cervical myelopathy may present simultaneously and result in gait disturbances and imbalance in some patients. For patients with suspected iNPH and myelopathic findings on examination, it is prudent to obtain a cervical spine MRI to assess for cervical stenosis. Moreover, cervical stenosis can mask the effect of cerebrospinal fluid diversion in patients with comorbid iNPH and cervical myelopathy. Therefore, the differential for patients who have symptomology suggestive of iNPH should include cervical spine myelopathy, with considerations for possible cervical decompression in addition to placement of a ventriculoperitoneal shunt.

The study of quality of life (QOL) in patients with asymptomatic diseases receiving interventional treatment provides an essential metric for the assessment of procedural benefits in the surgical patient population. In this study, we analyzed QOL data collected from patients with unruptured intracranial aneurysms (UIAs) before and after endovascular coiling in the HEAT Trial, alongside a systematic review on QOL in unruptured brain aneurysms.HEAT was a randomized controlled trial comparing recurrence rates in aneurysms treated with either bare platinum coils or hydrogel coils. Patients enrolled in this trial completed a short form-36 (SF-36) QOL questionnaire before treatment and at the 3- to 12- and 18- to 24-month follow-ups. The change in QOL before and after treatment was assessed. Regression analysis evaluated the effect of select baseline characteristics on QOL change.A total of 270 patients were eligible for analysis. There was an increase in the role physical (P = 0.043), vitality (P = 0.022), and emotional well-being (P0.001) QOL components at the 18- to 24-month follow-up compared with baseline scores. Regression analysis showed that age younger than 60 and absence of serious adverse events were associated with improved social functioning and vitality. The literature review showed a mixed effect of intervention on QOL in patients with UIAs.Our analysis has revealed that patients with 3- to 14-mm UIAs had improvements in some physical and emotional components of QOL at 18-24 months following aneurysm coiling in the HEAT study. The literature remains indeterminate on this issue. Further studies are needed to better understand the effects of the diagnosis of UIAs and their treatment on QOL.