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.

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.

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.

The predictive value of creatinine clearance for mortality in patients undergoing revascularization.

BACKGROUND: Renal function plays a significant role in the prognosis and management of patients with multi-vessel coronary artery disease (CAD) referred for revascularization. Current data lack precise risk stratification using estimated glomerular filtration rate (eGFR) and creatinine clearance. METHODS: This prospective study includes a three-year follow-up of 1112 consecutive patients with multi-vessel CAD enrolled in the 22 hospitals in Israel that perform coronary angiography. RESULTS: The Mayo formula yielded the highest mean eGFR (90 ± 26 mL/min per 1.73m2) and chronic kidney disease-epidemiology collaboration (CKD-EPI) the lowest (76 ± 24 mL/min per 1.73m2). Consequently, the Mayo formula classified more patients (56%) as having normal renal function. There was a significant and strong correlation between the values obtained from all five formulas using Cockcroft-Gault as the reference formula: Mayo: r = 0.80, p < 0.001; CKD-EPI: r = 0.87, p < 0.001; modification of diet in renal disease (MDRD): r = 0.84, p < 0.001; inulin clearance-based: r = 0.99, p < 0.001). Multivariable analysis demonstrated that decreased renal function is an independent predictor of 3-year mortality in all five formulas, with risk increasing by 15-25% for each 10-unit decrease in eGFR. Despite the similarities between the formulas, the ability to predict mortality was highest in the Mayo formula and lowest in MDRD. CONCLUSIONS: Our data suggest that while the Mayo formula is not currently recommended by any nephrology guidelines, it may be an alternative formula to predict mortality among patients with multivessel CAD, including to the widely used MDRD formula.

Outcome of patients with prior coronary bypass surgery admitted with an acute coronary syndrome.

BACKGROUND: Patients with prior coronary artery bypass graft surgery (CABG) are at increased risk for recurrent cardiovascular ischaemic events. Advances in management have improved prognosis of patients with acute coronary syndrome (ACS), yet it is not known whether similar trends exist in patients with prior CABG. AIM: Examine temporal trends in the prevalence, treatment and clinical outcomes of patients with prior CABG admitted with ACS. METHODS: Time-dependent analysis of patients with or without prior CABG admitted with an ACS who enrolled in the ACS Israeli Surveys between 2000 and 2016. Surveys were divided into early (2000-2008) and late (2010-2016) time periods. Outcomes included 30 days major adverse cardiac events (30d MACE) (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularisation) and 1-year mortality. RESULTS: Among 15 152 patients with ACS, 1506 (9.9%) had a prior CABG. Patients with prior CABG were older (69 vs 63 years), had more comorbidities and presented more with non-ST elevation-ACS (82% vs 51%). Between time periods, utilisation of antiplatelets, statins and percutaneous interventions significantly increased in both groups (p<0.001 for each). The rate of 30d MACE decreased in patients with (19.1%-12.4%, p=0.001) and without (17.4%-9.5%, p<0.001) prior CABG. However, 1-year mortality decreased only in patients without prior CABG (10.5% vs 7.4%, p<0.001) and remained unchanged in patients with prior CABG. Results were consistent after propensity matching. CONCLUSIONS: Despite an improvement in the management and prognosis of patients with ACS in the last decade, the rate of 1-year mortality of patients with prior CABG admitted with an ACS remained unchanged.

Outcomes of different revascularization strategies among patients presenting with acute coronary syndromes without ST elevation.

OBJECTIVE: To compare short- and long-term outcomes of patients hospitalized with non-ST-segment myocardial infarction (NSTEMI) or unstable angina (UA) who were referred for revascularization by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in a real-world national cohort. METHODS: This observational study included 5112 patients, who underwent either CABG or PCI, admitted for NSTEMI or UA and were enrolled in the Acute Coronary Syndrome Israeli Survey between 2000 and 2016. Propensity score-matching analysis compared early outcomes and all-cause mortality in patients who underwent revascularization by PCI with revascularization by CABG. RESULTS: Of the 5112 patients, 4327 (85%) underwent PCI and 785 (15%) CABG. Following propensity score analysis, 447 pairs were chosen (1:1). Independent predictors for CABG referral included 3-vessel CAD (odds ratio [OR], 5.5; 95% confidence interval [CI], 4.5-6.7, P < .001), absence of on-site cardiac surgery (OR, 1.3; 95% CI, 1.1-1.6, P = .004), no previous PCI (OR, 1.5; 95% CI, 1.2-1.9, P = .002) and no previous myocardial infarction (OR, 1.3; 95% CI, 1-1.7, P = .022). The 10-year mortality risk was significantly lower among those who underwent CABG compared with PCI (20.4% vs 28.4%, P = .006). Consistent with these findings, multivariable analysis showed that referral to CABG was independently associated with a significant 65% reduction in the risk of 10-year mortality (P < .001). This long-term advantage was seen among male patients (P < .001) and not female patients (P = .910). CONCLUSIONS: In a real-life setting, revascularization by CABG provides excellent long-term outcomes in patients with NSTEMI or UA. The advantage of CABG over PCI was seen only in male patients.

Association of Bezafibrate Treatment With Reduced Risk of Cancer in Patients With Coronary Artery Disease.

OBJECTIVE: To evaluate the association between bezafibrate, a drug used to treat hypertriglyceridemia, and long-term cancer incidence in patients with coronary artery disease (CAD). PATIENTS AND METHODS: The study comprised 2980 patients with CAD (mean age, 60 years; 2729 [91.6%] men) who were free of cancer and were enrolled in the Bezafibrate Infarction Prevention study, a double-blind trial conducted between May 1, 1990, and January 31, 1993, in 18 cardiology departments in Israel. Patients randomized to receive 400 mg of bezafibrate (n=1486) or placebo (n=1494) daily for a median of 6.2 years (range, 4.7-7.6 years) were followed up for incidence of cancer through the Israeli National Cancer Registry and all-cause death through the Population Registry of the State of Israel until December 31, 2013. Cox proportional hazards and Fine and Gray survival models were used to assess the bezafibrate-cancer association. RESULTS: Clinical characteristics and laboratory values were well balanced between the 2 groups at the study entry. Over a median follow-up of 22.5 years (range, 21.2-23.9 years), cancer developed in 753 patients. With death considered a competing event, the cumulative incidence of cancer at the end of the follow-up was lower in the bezafibrate vs the placebo group (23.9%; 95 CI, 21.9%-26.1% vs 27.2%; 95 CI, 25.1%-29.4%; P=.04). The hazard ratio for cancer in the bezafibrate vs placebo groups was 0.86 (95% CI, 0.74-0.99). In mediation analysis, the association between bezafibrate treatment and cancer incidence was not sensitive to adjustment for on-trial lipid levels but was attenuated on adjustment for on-trial fibrinogen levels. CONCLUSION: Bezafibrate treatment is associated with reduced risk of cancer among patients with CAD. Fibrinogen, but not lipid lowering, is linked to this association.

Characteristics and outcomes of patients with cancer presenting with acute myocardial infarction.

BACKGROUND: Limited data are available regarding the optimal management of patients with cancer in the acute myocardial infarction (AMI) setting. PATIENTS AND METHODS: We studied consecutive patients with AMI included in a national registry (years 2010, 2016) with the diagnosis of past or active malignancy and followed them for 1 year. RESULTS: Our cohort consisted of 2937 cancer-naive patients and 152 patients with cancer, of whom 35% presented with active malignancies. Compared with cancer-naive patients, patients with cancer were older, with female predominance, and presented more often with a history of hypertension and chronic kidney disease (P<0.001 for all comparisons). The rate of ST-elevation AMI was comparable (P=0.067). GRACE score more than 140 was more common in the cancer group (P<0.001). Most patients with cancer were referred to coronary angiography, though less than cancer-naive patients (87 vs. 93%; P=0.004). The rate of percutaneous coronary intervention was similar (P=0.265). Propensity score matching demonstrated similar rates of in-hospital complications between groups, and no mortality or major cardiac adverse event differences were noted at 30 days. Moreover, short-term mortality was similar between patients with active versus past malignancies, and between patients with solid and nonsolid tumors. However, cancer in patients with AMI was found to predict an increased mortality risk at 1 year by multivariable analysis (hazard ratio=2.52; P<0.001). CONCLUSION: Patients with cancer and AMI have a more complicated clinical presentation, yet their short-term prognosis is similar to cancer-naive patients. Nevertheless, 1-year outcome is worse.

Real-world referral pattern and outcomes of diabetic patients who undergo revascularization: data from the prospective Multi-vessel Coronary Artery Disease (MULTICAD) Israeli Registry†.

OBJECTIVES: Diabetes mellitus patients with multivessel coronary artery disease present with a poor prognosis. We aimed to explore real-life clinical outcomes of diabetic patients who were referred for coronary revascularization. METHODS: We used data from the Multi-vessel Coronary Artery Disease (MULTICAD) Israeli Registry. Using descriptive statistics, Kaplan-Meier, Cox and logistic regression, we described a revascularization referral pattern, short-term outcomes and long-term survival among 475 diabetic patients with multivessel and/or left main disease, 48% of whom underwent surgical and 52% percutaneous revascularization. RESULTS: Factors independently associated with referral for surgery included the presence of left main stenosis [odds ratio (OR) 1.89; P = 0.030] and a higher Syntax score (OR 1.15 per point increment; P < 0.001), whereas an older age (OR 1.03 per 1-year increment in age; P = 0.019), prior percutaneous coronary intervention (OR 1.83; P = 0.009) and the presence of renal impairment (OR 2; P = 0.026) were associated with percutaneous coronary intervention referral. At 7 months of follow-up, multivariable analysis did not reveal any difference in mortality risk between the surgical and percutaneous revascularization groups [hazard ratio (HR) 1.23, 95% confidence interval (CI) 0.5-3.04; P = 0.649], whereas after 7 months, surgical revascularization was associated with a significant survival benefit (HR 2.24, 95% CI 1.03-4.87; P = 0.042). CONCLUSIONS: Our observation suggests that in a real-world setting, only approximately one-half of diabetic patients with multivessel disease are referred to surgical revascularization despite guideline indications. Surgical compared to percutaneous revascularization in this population was associated with improved long-term survival that became evident 7 months after the revascularization procedure.

Impact of Self-Reported Family History of Premature Cardiovascular Disease on the Outcomes of Patients Hospitalized for Acute Coronary Syndrome (from the Acute Coronary Syndrome Israel Survey [ACSIS] 2000 to 2013).

Family history of premature cardiovascular disease (FHpCVD) is a well-established risk factor for development of coronary artery disease. However, little is known about the impact of FHpCVD on the outcome of patients presenting with acute coronary syndrome (ACS). We therefore aimed to evaluate the outcomes of ACS patients grouped by the presence and/or absence of FHpCVD. All patients ≤65 at admission who had an ACS event and were enrolled in the national ACS Israel Survey registry from 2000 to 2013 were included. Patients were grouped by the presence or absence of self-reported FHpCVD. Nearest neighbor propensity score matching was applied to create an evenly matched cohort of patients. Outcomes included 30-day MACE (defined as the composite of death, unstable angina pectoris, myocardial infarction, stroke, stent thrombosis, and urgent revascularization) and its individual components. Of 7,173 ACS patients, 33.9% reported FHpCVD. These patients were younger, with lower prevalence of diabetes, previous cerebrovascular and kidney diseases, but had higher prevalence of smoking and hyperlipidemia (p <0.001 for each). The propensity score-matching cohort included 1,793 pairs of evenly matched patients. The rate of 30-day MACE did not differ in the groups, as well as 1-year mortality (2.4% vs 2.2%, with vs without FHpCVD, respectively). During long-term follow-up (median 7.6 years), mortality rate was lower in the FHpCVD group (hazard ratio 0.82, 95% confidence intervals 0.69 to 0.99). In conclusion, we observed no differences in short- and intermediate-term outcomes based on the presence and/or absence of FHpCVD. However, patients with FHpCVD had better long-term survival.

Comparison of patients with multivessel disease treated at centers with and without on-site cardiac surgery.

BACKGROUND: The regional needs and consolidation of cardiac surgery services (CSS) result in an increased number of stand-alone interventional cardiology units. We aimed to explore the impact of a heart team on the decision making and outcomes of patients with multivessel coronary artery disease referred for coronary revascularization in stand-alone interventional cardiology units. METHODS: This prospective study included 1063 consecutive patients with multivessel disease enrolled between January and April 2013 from all 22 hospitals in Israel that perform coronary angiography and percutaneous coronary intervention (PCI), with or without on-site CSS. RESULTS: Of the 1063 patients, 487 (46%) underwent coronary artery bypass grafting (CABG) and 576 (54%) underwent PCI. A higher proportion of patients underwent PCI in hospitals without on-site CSS compared with those with on-site CSS (65% vs 46%; P < .001). Furthermore, patients referred to CABG from hospitals without on-site CSS had a significantly higher mean SYNTAX score compared with those who underwent CABG in centers with on-site CSS (29 vs 26; P = .018). Multivariate logistic regression analysis consistently showed that the absence of on-site cardiac surgery and a heart team was independently associated with a 2.5-fold increased likelihood for predicting the referral of PCI rather than CABG (odds ratio, 2.54; 95% confidence interval, 1.8-3.6). CONCLUSIONS: Patients with multivessel coronary artery disease treated in centers without on-site cardiac surgery services receive a lower rate of appropriate guideline-based intervention with CABG. These findings suggest that a heart team approach should be mandatory even in centers with stand-alone interventional cardiology units.

Metformin therapy reduces the risk of malignancy after heart transplantation.

BACKGROUND: Malignancy and diabetes mellitus (DM) cause significant morbidity and mortality after heart transplantation (HTx). Metformin, one of the most commonly used anti-diabetic drugs worldwide, has also been shown to exhibit anti-tumor activity. We therefore investigated the association between metformin therapy and malignancy after HTx. METHODS: The study population comprised 237 patients who underwent HTx between 1991 and 2016 and were prospectively followed-up. Clinical data were recorded on prospectively designed forms. The primary outcome was any cancer recorded during 15 years of follow-up. Treatment with metformin and the development of DM after HTx were assessed as time-dependent factors in the analyses. RESULTS: Of the 237 study patients, 85 (36%) had diabetes. Of the DM patients, 48 (56%) were treated with metformin. Kaplan-Meier survival analysis showed that, at 15 years after HTx, malignancy rate was 4% for DM patients treated with metformin, 62% for those who did not receive metformin and 27% for non-DM patients (log-rank test, p < 0.0001). Consistently, multivariate analysis showed that for DM patients, metformin therapy was independently associated with a significant 90% reduction (hazard ratio = 0.10; 95% confidence interval 0.02 to 0.40; p = 0.001) in the risk of the development of a malignancy. DM patients who were treated with metformin had a markedly lower risk (65%; p = 0.001) for the development of a malignancy or death after HTx as compared with non-DM patients. CONCLUSIONS: Our findings suggest that metformin therapy is independently associated with a significant reduction in the risk of malignancy after HTx.

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.

Prior chronic clopidogrel therapy is associated with increased adverse events and early stent thrombosis.

Despite the growing use of clopidogrel, limited data exist regarding the prognostic significance of chronic clopidogrel therapy in patients sustaining acute coronary syndrome (ACS). Our aim was to determine whether patients sustaining ACS while on chronic clopidogrel therapy have a worse prognosis than clopidogrel-naïve patients. A total of 5,386 consecutive ACS patients were prospectively characterised and followed-up for 30 days. Of them, 680 (13%) were treated with clopidogrel prior to the index ACS. Major adverse cardiovascular events (MACE) were defined as death, recurrent ACS, stroke and/or stent thrombosis. Compared with clopidogrel-naïve, chronic clopidogrel-treated patients were older (66 ± 12 vs 63 ± 13, respectively; p<0.01), suffered more from diabetes mellitus, hypertension, dyslipidaemia, prior cardiovascular history, including prior myocardial infarction, revascularisation, coronary artery bypass graft and stroke (p<0.01 for all), and were less likely to present with ST-elevation myocardial infarction (21% vs 45%; respectively; p < 0.001). Prior clopidogrel therapy was associated with a two-fold increase in in-hospital (1.6% vs 0.6%, respectively; p =0.006) as well as 30-day stent thrombosis (2.2% vs 1.0%, respectively; p=0.007). MACE at 30 days was also higher among chronic clopidogrel-treated compared with clopidogrel-naïve patients [12.3% vs 9.4%, respectively; p<0.01]. In multivariate log regression analysis chronic clopidogrel treatment was an independent predictor of stent thrombosis [OR=2.6 (95%CI 1.2-5.6), p=0.001]. Patients sustaining ACS while on chronic clopidogrel treatment are at higher risk for in-hospital and 30-day adverse outcomes, including stent thrombosis.