Management Of High-risk Patients Research Articles

Influence of Lp(a) and systemic inflammation on all-cause mortality in a primary prevention population: data from our clinic database

Abstract Background Epidemiological, pathophysiological, and genetic studies have established Lp(a) as a causal risk factor for development of cardiovascular (CVD) and valvular heart disease. However, there is controversy about how inflammation can modulate Lp(a) risk and major adverse cardiovascular events. We aim to investigate the influence of elevated Lp(a) and systemic inflammation on all-cause mortality in a primary prevention setting. Method We analyzed data obtained from the Preventive Cardiology Information System (PreCis), a database of clinical and laboratory information on 8,136 primary prevention patients seen at our clinic preventive cardiology clinic between 1st Jan 1999-12th Dec 2018. Primary prevention was defined as having no history of coronary artery disease (CAD), coronary and peripheral arterial revascularization, nor atherosclerosis. Lp(a) ≥50 mg/dL was considered as clinically elevated. The association between Lp(a) and the demographic and clinical variables of interest was examined using the student’s t-test or Chi-squared test. All-cause mortality was assessed using Kaplan-Meier estimates, and adjusted Cox proportional hazards models. All statistical analyses were conducted using SAS version 9.4. Result In the overall primary prevention population (n=8,136), the median age was 54 years, with 56.9% women and 84.8% being Caucasian. In this cohort, 21% had hypertension, and 5.5% had diabetes. The median Lp(a) was 21 mg/dL (interquartile interval 7-57 mg/dL). Lp(a) was ≥50 mg/dL in 29% of the population. Of those with elevated Lp(a) (n=2,368), 1,751 (73.9%) patients had hsCRP drawn. In this group, 782 patients (44.7%) had hsCRP <2 mg/L and 969 (55.3%) had hsCRP ≥2 mg/L. The all-cause mortality rate in individuals with elevated Lp(a) and hsCRP ≥2mg/L was 9.2% compared to 4.2% in those with elevated Lp(a) and hsCRP <2mg/L. In a multivariable Cox proportional hazard regression model adjusted for age and gender, in patients with elevated Lp(a), hsCRP ≥2 mg/L was significantly associated with all-cause mortality (HR 2.35, 95% CI (1.57-3.53), p>0.001) (Figure 1). Conclusion In a primary prevention population without established atherosclerosis, elevated Lp(a), increased systemic inflammation was associated with increased all-cause mortality. This finding supports the need for risk classification and targeted primary prevention management of higher risk patients with elevated Lp(a).

The Impact of Accelerated Diagnostic Protocol Implementation on Chest Pain Observation Unit Utilization.

Data evaluating the impact of the history, ECG, age, risk factors, and troponin (HEART) Pathway on observation unit (OU) use is limited. The objective of this study is to determine how HEART Pathway implementation affects OU use. An analysis of OU registry data from October 2012 to October 2016, 2 years before and after HEART Pathway implementation at an academic medical center, was conducted. Adult patients placed in the OU for chest pain were included. The proportion of patients placed in the OU chest pain protocol per total OU volume and hospitalization and myocardial infarction (MI) rates were determined. Proportions before versus after implementation were compared using χ2 tests and age was compared using a Mann-Whitney U test. During the study period, 1688 patients with chest pain before HEART Pathway implementation and 1692 after were included. The proportion of chest pain patients in the OU per total OU volume decreased following implementation from (57% [1688/2968] to 43.6% [1692/3882]; P < 0.001). Before HEART Pathway implementation, the hospitalization rate was 10.4% (175/1688) versus 12.4% (210/1692) after (P = 0.07). More patients were diagnosed with MI following implementation (0.8% [14/1665] vs. 2.0% [33/1686]; P = 0. 008). Median age was older postimplementation (52 years [IQR: 45-59 years] vs. 54 years [IQR: 48-64 years]; P < 0. 001). HEART Pathway implementation resulted in management of higher risk patients in the OU. Following implementation, OU chest pain patients were older and were more likely to be hospitalized or diagnosed with MI.

Hip Fracture Management Using External Fixation—A Systematic Review

Patients with significant comorbidities have high general anaesthetic risks and are often thought to be undesirable candidates for general anaesthesia and, therefore, surgery. External fixation uses local or regional anaesthesia, and allows patients with significant comorbidities to avoid the risks of general anaesthesia. It has been described to be successful in the management of high-risk patients with intertrochanteric fractures. However, published data have been derived from small case series, and no published literature has attempted to analyse them in totality. This review aims to pool together these case series, and to evaluate the outcomes and complications of external fixation when performed in high-risk patients with intertrochanteric fractures. The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRSIMA) guidelines. All studies that reported the outcomes of external fixation for intertrochanteric fractures of high-risk patients were included. A total of 13 publications, involving 687 patients, were included in the review. All the studies reported postoperative radiological reduction and complete fracture healing with reduction of limb length discrepancy. One study using parallel placement of proximal fixation screws showed shorter operative duration as compared to convergent placement. Another study mentioned that there was no significant difference in mortality rates between patients with stable fractures and those with unstable fractures who underwent external fixation. All the studies reported a decrease in postoperative immobility, reduction in pain and improvement in clinical outcome hip scores. External fixation is promising and useful especially in the management of high-risk patients with intertrochanteric fractures. The procedure can help with radiological reduction of the fracture, reduction of limb length discrepancy, reduction of operative duration, decrease in postoperative immobility, reduction in pain and improvement in clinical outcome hip scores. The procedure is versatile and seems to be able to accommodate both stable and unstable fractures. However, unstable fractures may be associated with greater postoperative morbidity, and it may be worthwhile to prognosticate based on the stability of the patients' fracture for better risk-benefit analysis preoperatively. Shorter operative times can also be achieved through parallel proximal pin placement, without impact on mortality or morbidity.

P2757Embolic risk stratification and prognostic impact of early surgery in left-sided infective endocarditis

Abstract Background Surgery is performed in 50% to 60% of infective endocarditis. In patients with definite surgical indication for hearth failure and with large vegetation, early surgery prevents embolic events. The optimal timing of surgery for other indications is still debated. Moreover, patients with large vegetation as unique indication to surgery, have a weak class of recommendation to it. Accurate risk stratification for embolic events is desirable to optimize selection of surgical candidates. Materials and methods We retrospectively analyzed 195 consecutive patients (72 women and 123 men) admitted to our department between 2013 and 2017 with definite IE according to modified Duke University criteria. Transesophageal echocardiography and blood cultures were performed in all patients for confirmation of diagnosis. Systemic embolism was soughton admission clinically and with imaging techniques (Brain and chest CT plus abdominal CT or US scan). Seventy-seven percent of patients underwent surgery (valve repair or replacement). Outcome following discharge was systematically assessed by structured telephone interviews. Results Of the 195 patients with left sided IE, 151 underwent surgery, 29 were low risk and treated medically, 5 refused surgery and 10 were not operated due to high surgical risk. Overall survival was 78% at 4 years. Patients excluded from surgery had the worst prognosis, while operated patients with high-risk IE showed comparable survival to non-complicated infections treated medically. Early surgery (&lt;2 weeks from diagnosis) was associated with similar survival compared to later intervention. Euroscore II was the main predictor of mortality when above a threshold of 7 before 2015 and 16 after 2015, reflecting surgical management of higher risk patients over time.In left sided IE, mean vegetation length was 11.1 mm; embolic events before diagnosis occurred in 35% of cases and Staphylococcus aureus etiologywas the main risk factor associated with embolism (OR 4, p&lt;0.05). Vegetation size &gt;10 mm was also independently associated with embolic risk (p=0.033) whereas renal failure, age, sex, endocarditis location (mitral or aortic), type of valve (native or prosthetic), perivalvular extension and degree of valveregurgitation were not. Conclusions Compared to low-risk IE patients treated medically, those at high-risk showed comparable survival when managed surgically, whereas a conservative approach was associated with adverse prognosis. In patients with left sided IE and intermediate vegetation length, S. aureus infection was the best independent predictor of systemic embolic events. Our data support extensive surgical referral in high risk IE and suggest that its etiology represents an important factor in decision-making.

Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)

▪Background: Rigosertib (RIG) is a RAS-mimetic interacting with the RAS-binding domains of RAF kinases, preventing their binding to RAS and inhibiting the RAS-RAF-MEK pathway. Rigosertib also binds to the RAS-binding domains of Ral-GDS and PI3Ks (Athuluri-Divakar, et al, Cell 165:643, 2016). Mutations of RAS are involved in proliferative processes important in neoplastic transformation (Gil-Bazo, et.al, Cancer Biology and Therapy 17:719, 2016).As of May 2016, 557 patients with MDS or AML received IV (N=335) or oral (N=222) rigosertib. All IV rigosertib was administered as monotherapy. Oral rigosertib was administered as monotherapy (N=168) or in combination with injectable azacitidine (AZA; N=54). Safety results across this rigosertib development program have not been presented.Methods: We reviewed all treatment-emergent adverse events (TEAEs) among patients with MDS/AML treated with rigosertib IV monotherapy, rigosertib oral monotherapy, or in combination therapy, overall and by grade of severity, and serious TEAEs and TEAEs leading to discontinuation. Due to the unexpected observation of urinary AEs, including occasional gross hematuria, we analyzed urinary AEs in greater detail.Results: Rigosertib IV monotherapy: The most common TEAEs were fatigue (33%), nausea (33%), diarrhea (27%), constipation (25%), anaemia (24%) and pyrexia (24%). The most common ≥Grade 3 AEs were anaemia (21%), febrile neutropenia (13%), pneumonia (12%) and thrombocytopenia (11%). The most common serious AEs were febrile neutropenia (10%), pneumonia (9%), and sepsis (7%). The most common AEs leading to discontinuation of IV rigosertib were sepsis and pneumonia (3% each) (Table 1).Rigosertib oral monotherapy: The most common TEAEs were pollakiuria (increased urinary frequency) (35-%), fatigue (32%), diarrhoea (26%), dysuria (29%) and haematuria (24%). The most common ≥Grade 3 AEs were anaemia (17%), thrombocytopenia (5%), haematuria (4%) and urinary tract infection (4%). The most common serious AE was pneumonia (6%). The most common AEs leading to discontinuation of patients receiving oral rigosertib as monotherapy were (dysuria [8%], urinary tract pain [7%], haematuria [5%] and urinary frequency [5%] (Table 2).Rigosertib oral in combination with azacitidine (AZA): The most common TEAEs were nausea (41%), fatigue (39%), diarrhea (37%), constipation (37%) and dysuria (28%). The most common serious AEs were pneumonia (11%) and febrile neutropenia (7%). The most common AEs leading to discontinuation were AML (4%) and pneumonia (4%) (Table 3).In patients fully evaluable for gross hematuria the cause of bleeding was bladder inflammation. Urinary and plasma concentration of RIG were examined to assess dose relationship.According to the azacitidine package insert, the incidence of gross hematuria of any grade with single agent azacitidine is 6.3 % and Grade 3-4 of 2.3%.Evaluations performed of hematuria among 5 studies of oral rigosertib (4 monotherapy and 1 in combination with AZA) in patients with MDS/AML (Table 4).Conclusions: Rigosertib IV or oral formulations were generally well tolerated in clinical trials in over 500 patients with MDS/AML. Gastrointestinal AEs were most frequently reported with IV rigosertib and genitourinary AEs were seen more often with oral than IV dosing. The greater rate of urinary AEs in the oral than in the IV studies indicates a need for close monitoring of these patients and proactive risk management, such as adequate hydration, timing of administration of the second dose, and bladder emptying prior to sleep. Studies are being designed to optimize dosing and schedule to maximize efficacy and minimize hematuria of single agent oral rigosertib. A randomized trial of oral rigosertib/azacitidine versus azacitidine will be required to optimize the clinical benefit and safety in the management of higher-risk patients with MDS. [Display omitted] [Display omitted] [Display omitted] DisclosuresFenaux:Celgene: Honoraria, Research Funding; Janssen: Research Funding; Novartis: Honoraria, Research Funding; Astex: Research Funding; Teva: Honoraria, Research Funding. Al-Kali:Celgene: Research Funding; Onconova Therapeutics, Inc.: Research Funding. Navada:Onconova Therapeutics, Inc.: Research Funding. Roboz:Agios, Amgen, Amphivena, Astex, AstraZeneca, Boehringer Ingelheim, Celator, Celgene, Genoptix, Janssen, Juno, MEI Pharma, MedImmune, Novartis, Onconova, Pfizer, Roche/Genentech, Sunesis, Teva: Consultancy; Cellectis: Research Funding. Santini:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Onconova: Consultancy; Amgen: Consultancy; Astex: Consultancy. Platzbecker:Onconova, Teva, Celgene, Janssen, Novartis, Amgen: Honoraria, Research Funding. Petrone:Onconova Therapeutics, Inc.: Employment. Brownstein:Onconova Therapeutics, Inc.: Consultancy. Zbyszewski:Onconova Therapeutics, Inc.: Employment. Maniar:Onconova Therapeutics, Inc.: Employment. Silverman:Onconova Therapeutics, Inc.: Patents & Royalties: Co-Patent holder for the combination of azacitidine and rigosertib, Research Funding.

Diagnosis and clinical management of melanoma patients at higher risk of a new primary melanoma: A population-based study in New South Wales, Australia.

To describe the method of diagnosis, clinical management and adherence to clinical practice guidelines for melanoma patients at high risk of a subsequent primary melanoma, and compare this with melanoma patients at lower risk. The Melanoma Patterns of Care study was a population-based, observational study based on doctors' reported clinical management of melanoma patients in New South Wales, Australia, diagnosed with in situ or invasive melanoma over a 12-month period from October 2006. Of 2605 patients with localised melanoma, 1019 (39%) were defined as at higher risk due to the presence of one or more of the following factors: a family history of melanoma (11%), multiple primary melanomas (17%), or many naevi (24%). Compared to patients at lower risk, high risk patients were more likely to receive their initial care from a primary care physician (56% vs 50%, P = 0.002), have their melanoma detected during a routine skin check (40% vs 33%, P < 0.001), have their lesion assessed with dermoscopy (63% vs 56%, P = 0.002), and be encouraged to have skin surveillance (84% vs 77%, P < 0.001) and skin self-examination (87% vs 83%, P = 0.03). Higher socioeconomic status and urban residence were associated with patients at higher risk receiving initial treatment from a specialist doctor. Clinical management of higher risk patients was more likely to conform to clinical practice guidelines for diagnosis and skin surveillance than to melanoma patients at lower risk.

Long-Term Survival After Open Repair and Thoracic Endovascular Aortic Repair for Descending Thoracic Aortic Aneurysms

Thoracic endovascular aortic repair (TEVAR) for descending thoracic aortic aneurysms (DTAs) was first reported by Dake et al1 in 1994. The advent of TEVAR was clinically relevant because open DTA repair had long been associated with operative mortality rates ranging from ≈5% to 7% at centers of excellence2,3 to as high as 20% to 22% in real-world practice.4,5 The favorable results6 of TEVAR with nearly 75% reduction in operative mortality in early industry-sponsored device trials led to US Food and Drug Administration approval for first commercial use in 2005 and subsequent device approvals in 2008.7,8 The operative mortality and morbidity benefits of TEVAR highlighted by numerous single-center reports,9–11 device registries,12,13 and device trials6–8 have led to widespread public and surgeon acceptance of this less invasive modality for the management of DTA in contemporary practice. As such, TEVAR has supplanted open surgical repair in the majority of patients with DTA.14,15 Article see p 2661 In the current issue of Circulation , Goodney et al16 reviewed the long-term survival of patients treated for DTA by the use …

Assessment of a scoring system for predicting complications after esophagectomy

Complications occur frequently after esophagectomy. Identifying the risk of complications preoperatively may help in patient selection and postoperative management. We performed a retrospective review of patients who underwent esophagectomy between 1980 and 2009. A previously reported scoring system was used to estimate risk, and its ability to predict complications was assessed. A total of 514 patients (382 men; 74%) with a mean age of 59.0 ± 12.5 years underwent esophagectomy for cancer (398; 77%) or benign disease. Minor complications occurred in 224 patients (44%) and severe complications occurred in 134 patients (26%). The calculated risk score was based on weighted values for age, coronary artery disease, cerebrovascular disease, type of operation, and forced expiratory volume in the first second expressed as a percent of predicted (FEV1%). Increasing risk score was associated with a linear increase in the incidence of complications (P < 0.001 for either severe complications or any complications). The scoring system predicted severe complications with an accuracy of 65.3% (P < 0.001). Score groups identified an incremental risk of severe complications (0 to 6 = 12%; 7 to 13 = 18%; 14 to 20 = 28%; 21 to 27 = 36%; >27 = 52%; P < 0.001). Complications are frequent after esophagectomy and can be predicted using a previously reported scoring system. This scoring system may assist in patient selection for esophagectomy and in providing appropriate resources for postoperative management of higher risk patients.

A national cardiac surgery database: Why, how and when?

As users of large amounts of public funding, surgeons are increasingly being required to justify their activities. The provision of accurate risk-stratified data on cardiac surgical procedures and their outcomes allows for government review while also providing a means of achieving potential improvements to strategies for the management of higher risk patients. In addition, accurate data will allow for the appropriate assessment of results that fall outside acceptable benchmark standards. A management strategy may then be implemented, following peer-review processes, to examine the outlying results on an anonymous basis. The dataset currently employed in the Victorian Database is derived from USA and UK models, and it will be used for the development of a national database. This project has Federal Government support in principle, and, it is hoped, its eventual financial backing.