Iatrogenic inner ear dehiscence associated with lateral skull base surgery: a systematic analysis of drilling injuries and their causal factors.

PURPOSE: Drilling injuries of the inner ear are an underreported complication of lateral skull base (LSB) surgery. Inner ear breaches can cause hearing loss, vestibular dysfunction, and third window phenomenon. This study aims to elucidate primary factors causing iatrogenic inner ear dehiscences (IED) in 9 patients who presented to a tertiary care center with postoperative symptoms of IED following LSB surgery for vestibular schwannoma, endolymphatic sac tumor, Meniere's disease, paraganglioma jugulare, and vagal schwannoma. METHODS: Utilizing 3D Slicer image processing software, geometric and volumetric analysis was applied to both preoperative and postoperative imaging to identify causal factors iatrogenic inner ear breaches. Segmentation analyses, craniotomy analyses, and drilling trajectory analyses were performed. Cases of retrosigmoid approaches for vestibular schwannoma resection were compared to matched controls. RESULTS: Excessive lateral drilling and breach of a single inner ear structure occurred in 3 cases undergoing transjugular (n=2) and transmastoid (n=1) approaches. Inadequate drilling trajectory breaching ≥1 inner ear structure occurred in 6 cases undergoing retrosigmoid (n=4), transmastoid (n=1), and middle cranial fossa approaches (n=1). In retrosigmoid approaches the 2-cm visualization window and craniotomy limits did not provide drilling angles to the entire tumor without causing IED in comparison to matched controls. CONCLUSIONS: Inappropriate drill depth, errant lateral drilling, inadequate drill trajectory, or a combination of these led to iatrogenic IED. Image-based segmentation, individualized 3D anatomical model generation, and geometric and volumetric analyses can optimize operative plans and possibly reduce inner ear breaches from lateral skull base surgery.

Peripheral Arterial Disease in Patients With Acute Coronary Syndrome: Results From a Large Real-World Registry.

BACKGROUND: Limited data exist regarding the significance of peripheral arterial disease (PAD) in patients with acute coronary syndrome (ACS). METHODS: We evaluated 16,922 consecutive ACS patients who were prospectively included in a national ACS registry. The co-primary endpoint included 30 days major adverse cardiovascular event (MACE) (re-infarction, stroke, and/or cardiovascular death) and 1-year mortality. RESULTS: PAD patients were older (70±11 vs 63±13; p<0.01), male predominance (80% vs 77%; p=0.01), and more likely to sustain prior cardiovascular events. PAD patients were less likely to undergo coronary angiography (69% vs 83%; p<0.001) and revascularisation (80% vs 86%; p<0.001). Patients with PAD were more likely to sustain 30-day MACE (22% vs 14%; p<0.001) and mortality (10% vs 4.4%; p<0.001), as well as re-hospitalisation (23% vs 19%; p=0.001). After adjusting for potential confounders, PAD remained an independent predictor of 30-day MACE (odds ratio [OR], 1.6 [95% confidence interval (CI), 1.24-2.06]). Patients with compared to those without PAD had 2.5 times higher 1-year mortality rate (22% vs 9%; p<0.001). Co-existence of PAD remained an independent predictor of 1-year mortality after adjustment for potential confounders by multivariable regression analysis (OR, 1.62; 95% CI, 1.4-1.9). PAD was associated with a significant higher 1-year mortality rate across numerous sub-groups of patients including type of myocardial infarction (ST-elevation myocardial infarction vs non-ST-elevation myocardial infarction), and whether the patient underwent revascularisation. CONCLUSIONS: Acute coronary syndrome with concomitant PAD represents a high-risk subgroup that warrants special attention and a more tailored approach.

Temporal trends in prognosis of patients with acute coronary syndrome complicated by ventricular tachyarrhythmia.

OBJECTIVES: To evaluate clinical characteristics and prognosis of patients presented with acute coronary syndrome (ACS) that developed ventricular tachyarrhythmia VTA and to analyse it according to the period of presentation. BACKGROUND: VTA is an infrequent yet serious complication of ACS. There is limited data regarding the incidence and prognostic implications of VTA in the last decade as compared with the previous decade. METHODS: We evaluated clinical characteristics, major adverse cardiovascular events, short and long- term mortality of patients hospitalised with ACS who were enrolled in the Acute Coronary Syndrome Israeli Survey (ACSIS) during the years 2000-2016. Patients were classified into three groups: no VTA, early VTA (≤48 hours of onset) and late VTA (>48 hours of onset). Data were analysed according to the period of presentation: early vs late period (years 2000-2006 and 2008-2016 accordingly). RESULTS: The study population comprised 15,200 patients. VTA occurred in 487 (3.2%) patients. Early VTA presented in 373/487 (77%) patients and late VTA in 114/487 (23%) patients. VTA's, occurring in ACS patients were associated with increased risk of in-hospital, 30-days, 1-year and 5-year mortality rates during both early and late periods compared with no VTA. Moreover, late VTA was associated with the highest mortality rate with up to 65% in 5-year follow up (P < .001). Nevertheless, late VTA was associated with a lower mortality rate in the late period compared with the early period. CONCLUSIONS: Any VTA following ACS was associated with high short- and long-term mortality rate. However, over the late period, there has been a significant improvement in survival rates, especially in patients with late VTA. This may be attributed to early and invasive reperfusion therapy, implantable cardioverter-defibrillator implantation and better medical treatment.

The impact of diabetes mellitus on the clinical phenotype of hypertrophic cardiomyopathy.

AIMS: Diabetes mellitus (DM) aggravates the clinical features of ischaemic and hypertensive heart diseases and worsens the prognosis of heart failure patients. Hypertrophic cardiomyopathy (HCM) and diabetes coexist fairly frequently in elderly patients but the impact of DM on the clinical phenotype of HCM is yet unknown. We sought to describe if predominant features of heart failure in DM patients exist independently in HCM. METHODS AND RESULTS: We reviewed clinical characteristics of 937 patients, age ≥40, diagnosed with HCM, from two tertiary medical centres in Spain and Israel. A propensity score matched cohort of 294 patients was also analysed. Our cohort comprised 102 HCM patients with diabetes (8.7%). Patients with DM were older at diagnosis {median 56 [interquartile range (IQR) 47-67] vs. 53 (IQR 43-63), P = 0.02} and had a higher prevalence of comorbidities. Hypertrophic cardiomyopathy patients with DM had a higher prevalence of diastolic dysfunction, pulmonary hypertension, significant mitral regurgitation, and pacemaker implantation. Hypertrophic cardiomyopathy patients with DM had a higher New York Heart Association (NYHA) class (P < 0.001) and lower exercise capacity [7.0 METS (IQR 5.0-10.0) vs. 9.0 METS (IQR 6.6-11.0), P = 0.002]. These findings were independent of age, gender, country of origin, hypertension, and coronary artery disease. Patients with diabetes had a significantly higher 15-year mortality (22% vs. 15%, P = 0.03), with no differences in sudden cardiac death, appropriate implanted cardioverter-defibrillator therapy, or heart transplantation. CONCLUSION: Hypertrophic cardiomyopathy patients with diabetes are older and have a higher cardiovascular risk profile. They have a lower functional capacity and more heart failure symptoms due to diastolic dysfunction.

CHA2DS2-VASc score performance to predict stroke after acute decompensated heart failure with and without reduced ejection fraction.

AIMS: To validate the utility of CHA2DS2-VASc score to predict the annual risk of stroke in patients admitted with acute heart failure, comparing those with preserved ejection fraction (HF-presEF) and reduced ejection fraction (HF-redEF). METHODS AND RESULTS: We investigated 2922 patients with known atrial fibrillation who were admitted to the Sheba Medical Center for acute decompensated heart failure (HF). Anticoagulation therapy was prescribed based on CHA2DS2-VASc score or physician's discretion. Subjects were divided into four pre-specified groups based on HF type and median CHA2DS2-VASc score: HF-presEF with CHA2DS2-VASc <5(N = 731), HF-presEF with CHA2DS2-VASc ≥5 (N = 1102), HF-redEF with CHA2DS2-VASc <5 (N = 563), and HF-redEF with CHADS2-VASc ≥5 (N = 526). The primary endpoint was an ischaemic stroke at 1 year. Mean age of the study population was 79 ± 11 years, of whom more than half were women. The median CHA2DS2-VASc score for the entire study population was 5.0 (interquartile range 25-75%: 4-6). Stroke rate for the entire study population was 6.6%. Multivariate Cox regression proportional hazards regression analysis revealed that in both HF-redEF and HF-presEF patients, each one-point increment in CHA2DS2-VASc was associated with a corresponding 28% increase in stroke risk (P < 0.001). The Kaplan-Meier's survival analysis revealed that in the same CHADS2-VASc category (high vs. low), no difference was found between HF-redEF and HF-presEF with regards to the risk of stroke. CONCLUSION: Our key finding is that the CHA2DS2-VASc score is a valid and powerful predictor of subsequent stroke among patients admitted with acute heart failure decompensation regardless of heart failure type.

Developing a risk score to predict mortality in the first year after implantable cardioverter defibrillator implantation: Data from the Israeli ICD Registry.

INTRODUCTION: Life expectancy of less than 1 year is usually a contraindication for implantable cardioverter defibrillator (ICD) implantation. The aim was to identify patients at risk of death during the first year after implantation. METHODS AND RESULTS: Data were derived from a prospective Israeli ICD Registry. Two groups of patients were compared, those who died and those who were alive 1 year after ICD implantation. Factors associated with 1-year mortality were identified on a derivation cohort. A risk score was established and validated. A total of 2617 patients have completed 1 year of follow-up after ICD or cardiac resynchronization therapy defibrillator (CRT-D) implantation. Age greater than 75 years (hazard ratio [HR], 2.7; 95% confidence interval [95% CI], 1.6 to 4.4), atrial fibrillation (AF; HR, 1.9; 95% CI, 1.12 to 3.17), chronic lung disease (HR, 2.0; 95% CI, 1.1 to 3.76), anemia (HR, 2.3; 95% CI, 1.3 to 3.93) and chronic renal failure (CRF; HR, 3.4; 95% CI, 1.74 to 6.6) were independent risk factors for 1-year mortality. We propose a simple AAACC ("triple A double C") score for prediction of 1-year mortality after ICD implantation: Age greater than 75 years (3 points(pts)), anemia (2 pts), AF (1 pt), CRF (3 pts) and chronic lung disease (1 pt). Mortality risk increased with rising number of points (from 1% with 0 pts to 12.5% with >4 pts). The risk score was evaluated with receiver operating characteristic curve and the area under the curve of the validation curve is 0.71 (95% CI, 0.66 to 0.76). CONCLUSIONS: Age greater than 75, AF, chronic lung disease, anemia, and CRF were independent risk factors for 1-year mortality. AAACC risk score identifies patients at high risk of death during 1 year after ICD implantation.

Antithrombotic Treatment Prior to Intracerebral Hemorrhage: Analysis in the National Acute Stroke Israeli Registry.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is the most disastrous stroke subtype. Prognosis is considered worse with prior antithrombotic treatment. Our aim was to evaluate the association of prior antithrombotic treatment on the radiological and clinical outcome after ICH in a subgroup of patients included in a national registry. METHODS: Based on the National Acute Stroke Israeli (NASIS) registry during 2004, 2007, 2010, and 2013 (2-month periods), characteristics, volumetric parameters, and prognosis of a subgroup of patients with ICH were analyzed. RESULTS: Among the 634 patients with ICH in the NASIS registry, 310 (49%) were not treated previously with antithrombotic medications, 232 (37%) were treated with an antiplatelet agent, and 92 (14.5%) patients were on oral anticoagulant therapy, of them 30 patients (33%) with an international normalised ratio (INR) value below 2, 33 (36%) patients with an INR value of 2-3, and 29 patients (31%) with an INR value above 3 upon admission. Patients with deep hemorrhage on prior anticoagulants treatment had the highest probability for poor outcome at hospital discharge. Patients with low bleeding volume (0-30 cm3), were likely to have admission National Institute of Health Stroke Scale < 10 (62%), while those with higher volumes (30-59 cm3 and > 60 cm3), had only 16.7% and 14.3% chance, respectively. We did not observe a significant difference between prior antithrombotic treatment and functional outcome at discharge, yet prior anticoagulant treatment was associated with higher long-term mortality rates. CONCLUSIONS: Our findings, based on a national registry, support the high mortality and poor outcome of anticoagulant related ICH.

Risk of early, intermediate, and late rejection following heart transplantation: Trends over the past 25 years and relation to changes in medical management. Tertiary center experience: The Sheba Heart Transplantation Registry.

AIM: To explore the trends in the risk for rejection following heart transplantation (HT) over the past 25 years, and their relation to changes in medical management. METHODS: The study population comprised 216 HT patients. Rejection periods were defined as follows: 0-3 months (early), 3-12 months (intermediate), and 12+ months (late). HT era was dichotomized as follows: 1991-1999 (remote era) and 2000-2016 (recent era). Medication combination was categorized as newer (TAC, MMF, and everolimus) vs older therapies (AZA, CSA). RESULTS: Multivariate analysis showed that patients who underwent HT during the recent era experienced a significant reduction in the risk for major rejection. These findings were consistent for early (OR = 0.44 [95% CI 0.22-0.88]), intermediate (OR = 0.02 [95% CI 0.003-0.11]), and late rejections (OR = 0.18 [95% CI 0.05-0.52]). Using the year of HT as a continuous measure showed that each 1-year increment was independently associated with a significant reduction in the risk for early, intermediate, and late rejections (5%, 21%, 18%, respectively). In contrast, the risk reduction associated with newer types of immunosuppressive therapies was not statistically significant after adjustment for the treatment period. CONCLUSIONS: Major rejection rates following HT have significantly declined over the past 2 decades even after adjustment for changes in immunosuppressive therapies, suggesting that other factors may also play a role in the improved outcomes of HT recipients.

Early aspirin initiation following heart transplantation is associated with reduced risk of allograft vasculopathy during long-term follow-up.

AIM: Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality after heart transplantation (HT). Enhanced platelet reactivity is a contributing factor. We aimed to investigate the association between early initiation of aspirin therapy post-HT and the 15-year risk of the development of CAV. METHODS: We studied 206 patients who underwent HT between 1991 and 2016. Multivariate Cox proportional hazards regression modeling was employed to evaluate the association between early aspirin initiation and the long-term risk of CAV. RESULTS: Ninety-seven patients (47%) received aspirin therapy. At 15 years of follow-up, the rate of CAV was lowered by sixfold in patients treated with aspirin compared with the non-treated patients: 7% vs 37% (log-rank P-value<.001). The corresponding rates of the combined end-point of CAV or death were also lower in patients treated with aspirin, compared with the non-treated patients: 42% vs 78% (log-rank P < .001). Consistently, multivariate analysis showed that early aspirin therapy was associated with a significant 84% (P < .001) reduction in CAV risk, and with a corresponding 68% (P < .0001) reduction in the risk of the combined end-point of CAV or death. We further validated these results using a propensity score-adjusted Cox model. CONCLUSIONS: Early aspirin initiation is independently associated with a significant reduction in the risk of CAV.

Morbidity and mortality with cardiac resynchronization therapy with pacing vs. with defibrillation in octogenarian patients in a real-world setting.

AIMS: Cardiac resynchronization therapy (CRT) with a defibrillator (CRT-D) has downsides of high cost and inappropriate shocks compared to CRT without a defibrillator (CRT-P). Recent data suggest that the survival benefit of implantable cardioverter defibrillator (ICD) therapy is attenuated in the older age group. We hypothesized that, among octogenarians eligible for cardiac resynchronization therapy, CRT-P confers similar morbidity and mortality benefits as CRT-D. METHODS AND RESULTS: We compared morbidity and mortality outcomes between consecutive octogenarian patients eligible for CRT therapy who underwent CRT-P implantation at Barzilai MC (n = 142) vs. those implanted with CRT-D for primary prevention indication who were prospectively enrolled in the Israeli ICD Registry (n = 104). Among the 246 study patients, mean age was 84 ± 3 years, 74% were males, and 66% had ischaemic cardiomyopathy. Kaplan-Meier survival analysis showed that at 5 years of follow-up the rate of all-cause mortality was 43% in CRT-P vs. 57% in the CRT-D group [log-rank P = 0.13; adjusted hazard ratio (HR) = 0.79, 95% CI 0.46-1.35, P = 0.37]. Kaplan-Meier analysis also showed no significant difference in the rates of the combined endpoint of heart failure or death (46 vs. 60%, respectively, log-rank P = 0.36; adjusted HR was 0.85, 95% CI 0.51-1.44, P = 0.55). A Cox proportional hazard with competing risk model showed that re-hospitalizations for cardiac cause were not different for the two groups (adjusted HR 1.35, 95% CI 0.7-2.6, P = 0.37). CONCLUSION: Our data suggest that, in octogenarians with systolic heart failure, CRT-P therapy is associated with similar morbidity and mortality outcomes as CRT-D therapy.

Real-World Use of Novel P2Y12 Inhibitors in Patients with Acute Myocardial Infarction: A Treatment Paradox.

OBJECTIVE: To assess the real-world use, clinical outcomes, and adherence to novel P2Y12 inhibitors. METHODS: We evaluated 1,093 consecutive acute myocardial infarction patients undergoing a percutaneous intervention. Patients were derived from a prospective, multicenter, nationwide registry and were followed for 30 days; 381 patients (35%) received clopidogrel, 468 (43%) received prasugrel, and 244 (22%) received ticagrelor. Patients treated with clopidogrel were older and more likely to suffer from chronic renal failure and stroke and/or present with non-ST-elevation myocardial infarction (NSTEMI) (p < 0.01 for all). Independent predictors of undertreatment with novel P2Y12 inhibitors included: older age (OR 0.17; 95% CI 0.1-0.27, p < 0.0001), a prior stroke (OR 0.41; 95% CI 0.2-0.68, p = 0.008), and NSTEMI (OR 0.37; 95% CI 0.26-0.54, p < 0.0001). RESULTS: Novel P2Y12 inhibitors were associated with a lower incidence of cardiovascular events, major bleeding, and/or death (7.6 vs.11%, HR 0.67; 95% CI 0.43-1, p = 0.05). However, after a multivariate analysis this trend was not statistically significant. Patients discharged with ticagrelor versus thienopyridines demonstrated a higher rate of crossover to other P2Y12 inhibitors (11 vs. 5%, p = 0.03). CONCLUSIONS: In a real-world cohort, there was an underutilization of novel P2Y12 inhibitors which was more pronounced in higher-risk subsets that might benefit from novel P2Y12 inhibitors at least as much as other patients.

Primary Percutaneous Coronary Intervention Versus In-hospital thrombolysis as Reperfusion Therapy in Early-Arriving Low-risk STEMI Patients.

BACKGROUND: Trials have shown superiority of primary percutaneous intervention (PPCI) over in-hospital thrombolysis in ST-elevation myocardial infarction (STEMI) patients treated within 6-12 hours from symptom onset. These studies also included high-risk patients not all of whom underwent a therapeutic intervention. OBJECTIVES: To compare the outcome of early-arriving stable STEMI patients treated by thrombolysis with or without coronary angiography to the outcome of PPCI-treated STEMI patients. METHODS: Based on six biannual Acute Coronary Syndrome Israeli Surveys comprising 5474 STEMI patients, we analyzed the outcome of 1464 hemodynamically stable STEMI patients treated within 3 hours of onset. Of these, 899 patients underwent PPCI, 383 received in-hospital thrombolysis followed by angiography (TFA), and 182 were treated by thrombolysis only. RESULTS: Median time intervals from symptom onset to admission were similar while door-to-reperfusion intervals were 63, 45 and 52.5 minutes for PPCI, TFA and thrombolysis only, respectively (P < 0.001). The 30-day composite endpoint of death, post-infarction angina and myocardial infarction occurred in 77 patients of the PPCI group (8.6%), 64 patients treated by TFA (16.7%), and 36 patients of the thrombolysis only group (19.8%, P < 0.001), with differences mostly due to post-infarction angina. One-year mortality rate was 27 (3%), 13 (3.4%) and 11 (6.1%) for PPCI, TFA and thrombolysis only, respectively (P = 0.12). CONCLUSIONS: PPCI was superior to thrombolysis in early-arriving stable STEMI patients with regard to 30-day composite endpoint driven by a decreased incidence of post-infarction angina. No 1 year survival benefit for PPCI over thrombolysis was observed in early-arriving stable STEMI patients.

Bezafibrate for the treatment of dyslipidemia in patients with coronary artery disease: 20-year mortality follow-up of the BIP randomized control trial.

BACKGROUND: Recent data support the renewed interest in hypertriglyceridemia as a possible important therapeutic target for cardiovascular risk reduction. This study was designed to address the question of all-cause mortality during extended follow-up of the BIP trial in patients stratified by baseline triglyceride levels. METHODS: In the BIP trial 3090 patients with proven coronary artery disease were randomized to bezafibrate 400 mg/day or placebo. All-cause mortality data after 20 years of follow-up, were obtained from the National Israeli Population Registry. Patients with hypertriglyceridemia (triglycerides ≥200 mg/dL, n = 458) were equally distributed among the study groups (15 % in both placebo and bezafibrate groups). RESULTS: During follow-up 1869 patients died (952 in placebo vs. 917 in bezafibrate group). Following multivariate adjustment allocation to bezafibrate was associated with small but significant 10 % mortality risk reduction (HR 0.90; 95 % CI 0.82-0.98, p = 0.026). Variables associated with significantly increased mortality risk were history of a past MI, NYHA class, diabetes, age, higher BMI and glucose level. In patients with hypertriglyceridemia multivariate analysis demonstrated a 25 % all-cause mortality risk reduction associated with allocation to bezafibrate (HR 0.75, CI 95 % 0.60-0.94; p = 0.012). In patients without hypertriglyceridemia bezafibrate had no significant effect on long-term mortality. CONCLUSIONS: During long-term follow-up bezafibrate-allocated patients experienced a modest but significant 10 % reduction in the adjusted risk of mortality. This effect of bezafibrate was more prominent among patients with baseline hypertriglyceridemia (25 % mortality risk reduction).

Metabolic syndrome is independently associated with increased 20-year mortality in patients with stable coronary artery disease.

BACKGROUND: Data regarding long-term association of metabolic syndrome (MetS) with adverse outcomes are conflicting. We aim to determine the independent association of MetS (based on its different definitions) with 20 year all-cause mortality among patients with stable coronary artery disease (CAD). METHODS: Our study comprised 15,524 patients who were enrolled in the Bezafibrate Infarction Prevention registry between February 1, 1990, and October 31, 1992, and subsequently followed-up for the long-term mortality through December 31, 2014. MetS was defined according to two definitions: The International Diabetes Federation (IDF); and the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP). RESULTS: According to the IDF criteria 2122 (14%) patients had MetS, whereas according to the NCEP definition 7446 (48%) patients had MetS. Kaplan-Meier survival analysis showed that all-cause mortality was significantly higher among patients with MetS defined by both the IDF (67 vs. 61%; log rank-p < 0.001) as well as NCEP (67 vs. 54%; log rank-p < 0.001) criteria. Multivariate adjusted mortality risk was 17% greater [Hazard Ratio (HR) 1.17; 95% Confidence Interval (CI) 1.07-1.28] in patients with MetS according to IDF and 21% (HR 1.21; 95% CI 1.13-1.29) using the NCEP definition. Subgroup analysis demonstrated that long-term increased mortality risk associated with MetS was consistent among most clinical subgroups excepted patients with renal failure (p value for interaction < 0.05). CONCLUSIONS: Metabolic syndrome is independently associated with an increased 20-year all-cause mortality risk among patients with stable CAD. This association was consistent when either the IDF or NCEP definitions were used. Trial registration retrospective registered.

The proxy of renal function that most accurately predicts short- and long-term outcome after acute coronary syndrome.

AIMS: The aim of this study is to determine the most accurate renal function formula that predicts short- and long-term mortality in a wide spectrum of acute coronary syndrome (ACS) patients. METHODS AND RESULTS: We analyzed 8,726 consecutive patients (46.3% ST-elevation myocardial infarction [STEMI] and 53.7% non-ST-elevation ACS [NSTE-ACS]) enrolled in the ACS survey in Israel. Renal function, assessed using 5 formulas as proxies of creatinine clearance or estimated glomerular filtration rate (Cockcroft-Gault, modification of diet in renal disease [MDRD], Chronic Kidney Disease Epidemiology Collaboration, Mayo quadratic, and inulin clearance based), varied in applying the different formulas. For both STEMI and NSTE-ACS patients, the Mayo formula yielded the highest mean value (88.9 ± 27.7 and 81.4 ± 29.2 mL/min per 1.73 m(2), respectively) and Chronic Kidney Disease Epidemiology Collaboration the lowest (73.0 ± 23.1 and 67.0 ± 24.1 mL/min per 1.73 m(2), respectively). Using multivariate analysis, worse renal function was independently associated with increased mortality risk by 30% to 40% for each decrement of 10 U of creatinine clearance or estimated glomerular filtration rate in STEMI patients and by 25% to 30% for NSTE-ACS patients, using all 5 formulas. The only formula that more accurately predicted 1-year mortality than the MDRD formula was the Mayo quadratic formula with a 1-year net reclassification index of 0.26 and 0.14 for STEMI and NSTE-ACS patients, respectively, after multivariable adjustment. CONCLUSION: Worse renal function was an independent predictor for short- and long-term mortality using all 5 formulas in a broad spectrum of ACS patients, but only the Mayo quadratic formula had better accuracy in predicting mortality relative to the MDRD, suggesting that it may be the preferred prognosticator among ACS patients.

Inner Ear Breaches from Vestibular Schwannoma Surgery: Revisiting the Incidence of Otologic Injury from Retrosigmoid and Middle Cranial Fossa Approaches.

OBJECTIVE: To assess the rate of iatrogenic injury to the inner ear in vestibular schwannoma resections. STUDY DESIGN: Retrospective case review. SETTING: Multiple academic tertiary care hospitals. PATIENTS: Patients who underwent retrosigmoid or middle cranial fossa approaches for vestibular schwannoma resection between 1993 and 2015. INTERVENTION: Diagnostic with therapeutic implications. MAIN OUTCOME MEASURE: Drilling breach of the inner ear as confirmed by operative note or postoperative computed tomography (CT). RESULTS: 21.5% of patients undergoing either retrosigmoid or middle fossa approaches to the internal auditory canal were identified with a breach of the vestibulocochlear system. Because of the lack of postoperative CT imaging in this cohort, this is likely an underestimation of the true incidence of inner ear breaches. Of all postoperative CT scans reviewed, 51.8% had an inner ear breach. As there may be bias in patients undergoing postoperative CT, a middle figure based on sensitivity analyses estimates the incidence of inner ear breaches from lateral skull base surgery to be 34.7%. CONCLUSIONS: A high percentage of vestibular schwannoma surgeries via retrosigmoid and middle cranial fossa approaches result in drilling breaches of the inner ear. This study reinforces the value of preoperative image analysis for determining risk of inner ear breaches during vestibular schwannoma surgery and the importance of acquiring CT studies postoperatively to evaluate the integrity of the inner ear.

Left Atrial Appendage Occlusion versus Novel Oral Anticoagulation for Stroke Prevention in Atrial Fibrillation-One-Year Survival.

Aim To compare the 1-year survival rate of patients with atrial fibrillation (AF) following left atrial appendage occluder (LAAO) implantation vs. treatment with novel oral anticoagulants (NOACs). METHODS: We have conducted an indirect, retrospective comparison between LAAO and NOAC registries. The LAAO registry is a national prospective cohort of 419 AF patients who underwent percutaneous LAAO between January 2008 and October 2015. The NOACs registry is a multicenter prospective cohort of 3138 AF patients treated with NOACs between November 2015 and August 2018. Baseline patient characteristics were retrospectively collected from coded diagnoses of hospitalization and outpatient clinic notes. Follow-up data was sorted from coded diagnoses and the national civil registry. Subjects were matched according to propensity score. Baseline characteristics were compared using Chi-Square and student's t-test. Survival analysis was performed using Kaplan-Meier survival curves, log-rank test, and multivariable Cox regression, adjusting for possible confounding variables. RESULTS: This study included 114 subjects who underwent LAAO implantation and 342 subjects treated with NOACs. The mean age of participants was 77.9 ± 7.44 and 77.1 ± 11.2 years in the LAAO and NOAC groups, respectively (p = 0.4). The LAAO group had 70 (61%) men compared to 202 (59%) men in the NOAC group (p = 0.74). No significant differences were found in baseline comorbidities, renal function, or CHA2DS2-VASc score. One-year mortality was observed in 5 (4%) patients and 32 (9%) patients of the LAAO and NOAC groups, respectively. After adjusting for confounders, LAAO was significantly associated with a lower risk for 1-year mortality (HR 0.38, 95%CI 0.14-0.99). In patients with impaired renal function, this difference was even more prominent (HR 0.21 for creatinine clearance (CrCl) < 60 mL/min). CONCLUSIONS: In a pooled analysis of two registries, we found a significantly lower risk for 1-year mortality in patients with AF who were implanted with LAAO than those treated with NOACs. This finding was more prominent in patients with impaired renal function. Future prospective direct studies should further investigate the efficacy and adverse effects of both treatment strategies.

Hajek and Hirsch: Otolaryngology Pioneers of Endonasal Transsphenoidal Pituitary Surgery.

OBJECTIVE: To evaluate the historical descriptive origins of the extracranial transnasal transsphenoidal route to the sphenoid sinus and sella turcica focusing on the works of two otolaryngologists: Markus Hajek (1861-1941) and Oskar Hirsch (1877-1965). DATA SOURCES: A collection of primary references of author publications, and contemporary references and textbooks. REVIEW METHODS: Primary references were reviewed with specific focus on surgical routes to the sphenoid sinus and sella turcica. Chronology was cross-referenced with contemporary publications by contemporaries. Translations from German were conducted by author AM when necessary. RESULTS: Markus Hajek elegantly described the surgical approach to the posterior ethmoids and sphenoid sinus in 1904 using a transnasal route. Building on this foundation, Oskar Hirsch described the fully extracranial endonasal transethmoid transsphenoidal approach in 1909. He was first to describe surgical entrance to the sella using this exclusively unilateral endonasal route, which he demonstrated on a cadaver. He reports performing this procedure on a live patient in April, 1910, under local anesthesia in stages over 5 weeks. For better exposure, Hirsch consolidated his method with Killian's submucosal window resection of the posterior nasal septum allowing for bilateral access to the sphenoid sinus and sella, and completed a single stage procedure on a patient in June 1910. CONCLUSION: Oskar Hirsch was the first to describe and perform a stepwise surgical approach to the sella using an exclusively extracranial, endonasal, transethmoid, and transsphenoidal approach. He built upon his mentor Markus Hajek's approaches to the posterior ethmoid cells and sphenoid sinus. LEVEL OF EVIDENCE: NA: Background information, synthesis from multiple sources emphasizing factual information Laryngoscope, 133:807-813, 2023.

Reducing the foreign body response on human cochlear implants and their materials in vivo with photografted zwitterionic hydrogel coatings.

The foreign body response to implanted materials often complicates the functionality of sensitive biomedical devices. For cochlear implants, this response can reduce device performance, battery life and preservation of residual acoustic hearing. As a permanent and passive solution to the foreign body response, this work investigates ultra-low-fouling poly(carboxybetaine methacrylate) (pCBMA) thin film hydrogels that are simultaneously photo-grafted and photo-polymerized onto polydimethylsiloxane (PDMS). The cellular anti-fouling properties of these coatings are robustly maintained even after six-months subcutaneous incubation and over a broad range of cross-linker compositions. On pCBMA-coated PDMS sheets implanted subcutaneously, capsule thickness and inflammation are reduced significantly in comparison to uncoated PDMS or coatings of polymerized poly(ethylene glycol dimethacrylate) (pPEGDMA). Further, capsule thickness is reduced over a wide range of pCBMA cross-linker compositions. On cochlear implant electrode arrays implanted subcutaneously for one year, the coating bridges over the exposed platinum electrodes and dramatically reduces the capsule thickness over the entire implant. Coated cochlear implant electrode arrays could therefore lead to persistent improved performance and reduced risk of residual hearing loss. More generally, the in vivo anti-fibrotic properties of pCBMA coatings also demonstrate potential to mitigate the fibrotic response on a variety of sensing/stimulating implants. STATEMENT OF SIGNIFICANCE: This article presents, for the first time, evidence of the in vivo anti-fibrotic effect of zwitterionic hydrogel thin films photografted to polydimethylsiloxane (PDMS) and human cochlear implant arrays. The hydrogel coating shows no evidence of degradation or loss of function after long-term implantation. The coating process enables full coverage of the electrode array. The coating reduces fibrotic capsule thickness 50-70% over a broad range of cross-link densities for implantations from six weeks to one year.

Poor outcome among patients undergoing myocardial perfusion imaging with intermediate-zone troponin.

BACKGROUND: Intermediate zone troponin elevation is defined as one to five times the upper limit of normal. Approximately half the patients presenting with chest pain to the emergency department have initial intermediate zone troponin. OBJECTIVES: We aimed to investigate the long-term outcome of patients hospitalized with chest pain and intermediate zone troponin elevation. METHODS: We investigated 8269 patients hospitalized in a tertiary center with chest pain. All patients had serial measurements of troponin during hospitalization. Patients were divided into three groups based on their initial troponin levels: negative troponin (N = 6112), intermediate zone troponin (N = 1329) and positive troponin (N = 828). All patients underwent myocardial perfusion imaging (MPI) as part of the initial evaluation. RESULTS: Mean age of the study population was 68 ± 11, of whom 36% were women. Patients with an intermediate zone troponin were older, more likely to be males, and with significantly more cardiovascular co-morbidities. Multivariate analysis adjusted for age, gender, cardiovascular risk factors, and abnormal MPI result found that patients with intermediate zone troponin had a 70% increased risk of re-hospitalization at 1 year (HR 1.70, 95%CI 1.48-1.96, p-value < 0.001) and 5.3 times higher risk of total mortality at 1-year (HR 5.33, 95%CI 3.65-7.78, p-value < 0.001). sub-group analysis found that among the intermediate zone troponin group, patients with double intermediate zone troponin had the poorest outcome. CONCLUSIONS: Intermediate zone troponin elevation is an independent risk factor associated with adverse outcomes and therefore patients with an initial value in this range should be closely monitored and aggressively managed.