Cardiac risk assessment with the Revised Cardiac Risk Index index before elective non-cardiac surgery: A retrospective audit from an Australian tertiary hospital.

Clinicians assessing cardiac risk as part of a comprehensive consultation before surgery can use an expanding set of tools, including predictive risk calculators, cardiac stress tests and measuring serum natriuretic peptides. The optimal assessment strategy is unclear, with conflicting international guidelines. We investigated the prognostic accuracy of the Revised Cardiac Risk Index for risk stratification and cardiac outcomes in patients undergoing elective non-cardiac surgery in a contemporary Australian cohort.We audited the records for 1465 consecutive patients 45 years and older presenting to the perioperative clinic for elective non-cardiac surgery in our tertiary hospital. We calculated individual Revised Cardiac Risk Index scores and documented any use of preoperative cardiac tests. The primary outcome was any major adverse cardiac events within 30 days of surgery, including myocardial infarction, pulmonary oedema, complete heart block or cardiac death.Myocardial perfusion imaging was the most common preoperative stress test (4.2%, 61/1465). There was no routine investigation of natriuretic peptide levels for cardiac risk assessment before surgery. Major adverse cardiac events occurred in 1.3% (18/1366) of patients who had surgery. The Revised Cardiac Risk Index score had modest prognostic accuracy for major cardiac complications, area under receiver operator curve 0.73, 95% confidence interval 0.60 to 0.86. Stratifying major adverse cardiac events by the Revised Cardiac Risk Index scores 0, 1, 2 and 3 or greater corresponded to event rates of 0.6% (4/683), 0.8% (4/488), 4.1% (6/145) and 8.0% (4/50), respectively.The Revised Cardiac Risk Index had only modest predictive value in our single-centre experience. Patients with a revised cardiac risk index score of 2 or more had an elevated risk of early cardiac complications after elective non-cardiac surgery.

Challenges of Using ICD-9-CM and ICD-10-CM Codes for Soft-Tissue Sarcoma in Databases for Health Services Research.

Objectives: Soft-tissue sarcoma (STS) is a heterogeneous group of rare solid tumors that arise from various soft tissues in the body, such as muscle, fat, nerves, and blood vessels. Current International Classification of Diseases (ICD) coding systems include a set of nonspecific codes for malignancies of connective and soft tissue (ICD-9-CM code 171 and ICD-10-CM code C49). The goal of this study was to evaluate the use of these codes for health services research involving patients with a diagnosis of this rare malignancy. Methods: Two databases were utilized to explore ICD coding for STS: claims data from Truven MarketScan and electronic medical records (EMRs) from Flatiron Health. Eligible patients from claims data were those with at least two ICD-9-CM codes of 171.x on two different days between July 1, 2004, and March 30, 2014. The treatment patterns of these cases were evaluated for consistency with known therapeutic approaches for STS. Eligible patients from the Flatiron EMR system were those who received olaratumab (a drug indicated only for use in patients diagnosed with STS) after its US Food and Drug Administration approval in October 2016 through the end of the data set (November 2017). ICD-10-CM codes were evaluated for this known STS cohort. Results: In claims data, 4,159 patients were eligible for inclusion. Although national treatment guidelines include only a limited number of drugs used to treat STS, 98 unique anticancer drugs were identified as being used to treat patients in a claims data cohort. Only 7.7 percent of patients had claims for doxorubicin-based therapy and 3.8 percent had claims for ifosfamide-based therapy as initial treatment for STS, despite these being a standard of care. In the EMR data, 350 patients were eligible; only 170 patients (48.6 percent) had any evidence in the database of a connective or soft-tissue ICD-10-CM malignancy code within 60 days before or after initiation of olaratumab. Conclusions: ICD coding for STS using the "Malignant neoplasm of connective and soft tissue" code is not reliable as a method to identify patients diagnosed with STS. Although codes reflecting the primary site of disease may have clinical relevance, lack of consistency in ICD coding for the diagnosis and treatment of this disease is a limiting factor in the ability to conduct real-world observational research of this rare disease. In the absence of consistent use of this code, an algorithm needs to be developed and validated to accurately identify patients with STS in these databases.

Hyperactivated PI3Kδ promotes self and commensal reactivity at the expense of optimal humoral immunity.

Gain-of-function mutations in the gene encoding the phosphatidylinositol-3-OH kinase catalytic subunit p110δ (PI3Kδ) result in a human primary immunodeficiency characterized by lymphoproliferation, respiratory infections and inefficient responses to vaccines. However, what promotes these immunological disturbances at the cellular and molecular level remains unknown. We generated a mouse model that recapitulated major features of this disease and used this model and patient samples to probe how hyperactive PI3Kδ fosters aberrant humoral immunity. We found that mutant PI3Kδ led to co-stimulatory receptor ICOS-independent increases in the abundance of follicular helper T cells (TFH cells) and germinal-center (GC) B cells, disorganized GCs and poor class-switched antigen-specific responses to immunization, associated with altered regulation of the transcription factor FOXO1 and pro-apoptotic and anti-apoptotic members of the BCL-2 family. Notably, aberrant responses were accompanied by increased reactivity to gut bacteria and a broad increase in autoantibodies that were dependent on stimulation by commensal microbes. Our findings suggest that proper regulation of PI3Kδ is critical for ensuring optimal host-protective humoral immunity despite tonic stimulation from the commensal microbiome.

TEXT messages to improve MEDication adherence and Secondary prevention (TEXTMEDS) after acute coronary syndrome: a randomised clinical trial protocol.

BACKGROUND: Identifying simple, low-cost and scalable means of supporting lifestyle change and medication adherence for patients following a cardiovascular (CV) event is important. OBJECTIVE: The TEXTMEDS (TEXT messages to improve MEDication adherence and Secondary prevention) study aims to investigate whether a cardiac education and support programme sent via mobile phone text message improves medication adherence and risk factor levels in patients following an acute coronary syndrome (ACS). STUDY DESIGN: A single-blind, multicentre, randomised clinical trial of 1400 patients after an ACS with 12 months follow-up. The intervention group will receive multiple weekly text messages that provide information, motivation, support to adhere to medications, quit smoking (if relevant) and recommendations for healthy diet and exercise. The primary endpoint is the percentage of patients who are adherent to cardioprotective medications and the key secondary outcomes are mean systolic blood pressure (BP) and low-density lipoprotein cholesterol. Secondary outcomes will also include total cholesterol, mean diastolic BP, the percentage of participants who are adherent to each cardioprotective medication class, the percentage of participants who achieve target levels of CV risk factors, major vascular events, hospital readmissions and all-cause mortality. The study will be augmented by formal economic and process evaluations to assess acceptability, utility and cost-effectiveness. SUMMARY: The study will provide multicentre randomised trial evidence of the effects of a text message-based programme on cardioprotective medication adherence and levels of CV risk factors. ETHICS AND DISSEMINATION: Primary ethics approval was received from Western Sydney Local Health District Human Research Ethics Committee (HREC2012/12/4.1 (3648) AU RED HREC/13/WMEAD/15). Results will be disseminated via peer-reviewed publications and presentations at international conferences. TRIAL REGISTRATION NUMBER: ACTRN12613000793718; Pre-results.

Assessment of cerebral blood flow in adult patients with aortic coarctation.

BACKGROUND: Survival into adult life in patients with aortic coarctation is typical following surgical and catheter-based techniques to relieve obstruction. Late sequelae are recognised, including stroke, hypertension, and intracerebral aneurysm formation, with the underlying mechanisms being unclear. We hypothesised that patients with a history of aortic coarctation may have abnormalities of cerebral blood flow compared with controls. METHODS: Patients with a history of aortic coarctation underwent assessment of cerebral vascular function. Vascular responsiveness of intracranial vessels to hypercapnia and degree of cerebral artery stiffness using Doppler-derived pulsatility indices were used. Response to photic stimuli was used to assess neurovascular coupling, which reflects endothelial function in response to neuronal activation. Patient results were compared with age- and sex-matched controls. RESULTS: A total of 13 adult patients (males=10; 77%) along with 13 controls underwent evaluation. The mean age was 36.1±3.7 years in the patient group. Patients with a background of aortic coarctation were noted to have increased pulse pressure on blood pressure assessment at baseline with increased intracranial artery stiffness compared with controls. Patients with a history of aortic coarctation had less reactive cerebral vasculature to hypercapnic stimuli and impaired neurovascular coupling compared with controls. RESULTS: Adult patients with aortic coarctation had increased intracranial artery stiffness compared with controls, in addition to cerebral vasculature showing less responsiveness to hypercapnic and photic stimuli. Further studies are required to assess the aetiology and consequences of these documented abnormalities in cerebral blood flow in terms of stroke risk, cerebral aneurysm formation, and cognitive dysfunction.

Multidisciplinary Assessment in Optimising Results of Percutaneous Patent Foramen Ovale Closure.

BACKGROUND: Percutaneous patent foramen ovale (PFO) closure is a therapeutic option to prevent recurrent cerebral ischaemia in patients with cryptogenic stroke and transient cerebral ischaemia (TIA). The apparent lack of benefit seen in previous randomised trials has, in part, reflected inclusion of patients with alternate mechanisms of stroke. The role of formal neurology involvement in accurately delineating the likely aetiology of stroke or TIA is crucial in appropriate identification of patients for device closure. Furthermore, as the benefits of device closure may accrue over time, long-term follow-up is essential to define the role of device closure in management of presumed cryptogenic stroke. METHODS: We retrospectively reviewed our experience with percutaneous PFO device closure since 2005. All subjects who underwent PFO closure at John Hunter and Lake Macquarie Private Hospitals were included in the study. All patients referred for device closure following cryptogenic stroke or TIA had first undergone formal neurology review with appropriate imaging and exclusion of paroxysmal atrial arrhythmia. Patients with a history of transient ischaemic attack (TIA) are frequently referred to a specialised clinic, aimed to identify patients with conditions not referable to cerebral ischaemia, with investigations initiated by the specialist clinic to elucidate an underlying aetiology. Outcome data was derived from the Hunter New England Area Local Health District Cardiac and Stroke Outcomes Unit, in addition to review of the medical record. The Cardiac and Stroke Outcomes Unit prospectively identified all patients presenting with stroke, TIA and atrial fibrillation. RESULTS: One hundred and twelve consecutive patients undergoing percutaneous patent foramen ovale closure between 2005 and 2015 were identified. The average age was 42.7 years and 57 (50.9%) patients were male. Cryptogenic stroke (68.8%) and transient cerebral ischaemia (23.2%) were the most common indications for PFO closure, with the Amplatzer device used in 83 cases (74.1%). Early residual shunting was visible in seven patients (6.3%), however on follow-up agitated saline study only two patients had residual shunt (1.8%). The annual risk of recurrent stroke or TIA was 0.21%. CONCLUSIONS: Percutaneous patent foramen ovale closure can be performed safely and effectively in patients with paradoxical embolism. In selected patients, following appropriate multidisciplinary specialist pre-procedural assessment, excellent long-term results with low incidence of recurrent events may be achieved.

Echocardiographic assessment of pulmonary artery systolic pressure following treadmill stress testing.

AIMS: The use of treadmill stress echocardiography (SE) for the diagnosis of nascent pulmonary hypertension (PH) has been hampered by a lack of well-defined, post-exercise pulmonary artery systolic pressure (PASP) values across representative age groups in a normal cohort. METHODS AND RESULTS: Five hundred and eleven subjects (mean age: 53 ±14, 68% female) with normal resting PASP were included in the study. All participants performed treadmill exercise using the Bruce protocol to a high level of perceived exertion. PASP was calculated before and immediately after exercise using Doppler assessment of tricuspid regurgitation. For the cohort, post-exercise PASP was 39 ± 7 mmHg (range: 23-64 mmHg) representing an increase of 11 ± 6 mmHg (44%) from resting values (P < 0.001). The 95th centile values for post-exercise PASP were calculated for the following age cohorts: <30 years; 46 mmHg, 31-50 years; 50 mmHg, 51-70 years; 52 mmHg, >70 years; 53 mmHg. There was a modest independent correlation between post-exercise PASP and (i) increasing age and (ii) resting PASP (r2 = 0.35 and 0.49, respectively, P = 0.01). CONCLUSION: An increase of post-exercise PASP was seen in all patients undergoing SE in this study. Age was directly correlated with post-exercise PASP. Using normative data from healthy controls, treadmill SE-derived post-exercise PASP may be a useful adjunct in the diagnosis of PH.

Abnormal pulmonary vascular responses in patients registered with a systemic autoimmunity database: Pulmonary Hypertension Assessment and Screening Evaluation using stress echocardiography (PHASE-I).

UNLABELLED: Patients with autoimmune disease, and in particular limited systemic sclerosis (CREST syndrome), are at risk of developing pulmonary artery hypertension (PAH) which is associated with a poor prognosis. With improvements in therapy offering improved survival and functional capacity, there has been an emphasis on screening to identify patients at risk. Assessment of patients during exercise may enable early identification of patients with this condition. AIMS AND METHODS: We aimed to assess the ability of exercise stress echocardiography to evaluate the change in pulmonary artery pressure in 51 patients with autoimmune disease (systemic lupus erythamatosus (SLE), limited systemic sclerosis (LSS or "CREST") and diffuse systemic sclerosis (DSS)). Systolic pulmonary artery pressure (sPAP) was estimated using interrogation of the tricuspid incompetence jet before and after exercise. PAH was classified as normal, mild, moderate or severe using echocardiographic assessment of sPAP. RESULTS: We were able to estimate pre-exercise and post-exercise sPAP in 92% and 90% of patients, respectively. Pulmonary pressures rose or remained unchanged in all screened individuals, with a mean rise during stress of 14.1mmHg (+/-1.1). Pulmonary artery pressure rose significantly in each of three subgroups (p<0.05). Stress echocardiography demonstrated PAH (using a cut-off of >35mmHg) in 59% of all individuals with systemic autoimmunity. CONCLUSION: Stress echocardiography is a useful tool in identifying individuals with autoimmune disease who may have underlying pulmonary arterial disease that may be amenable to therapy. We noted a consistent elevation in sPAP across all autoimmune subtypes, suggesting an abnormal pulmonary vascular response to exercise exists in these patients.