Best practices in epidermal growth factor receptor T790M testing for advanced non-small-cell lung cancer in Hong Kong.

The T790M mutation in the epidermal growth factor receptor gene causes most acquired resistance to firstor second-line epidermal growth factor receptor-tyrosine kinase inhibitors in advanced non-small-cell lung cancer. The results of T790M testing can guide subsequent treatment. Despite the availability of guidelines from international organisations, T790M testing practices in Hong Kong must be streamlined and adapted to the Hospital Authority setting. To address this issue, a panel of experts in oncology and pathology met for discussion of key topics regarding T790M testing practices in Hong Kong, including the appropriate timing of testing and re-testing, as well as optimal testing methods. All panel members voted on the results of the discussion to achieve consensus. Items supported by a majority vote were adopted as consensus statements regarding current best practices for T790M testing in Hong Kong. Among the topics discussed, the panel agreed that T790M testing should be initiated upon radiological progression, including symptomatic disease progression or central nervous system-only progression. The experts also preferred initial testing with liquid biopsy, using the widely available digital polymerase chain reaction platform. This document provides the final consensus statements, as well as a testing and treatment workflow, for clinicians in Hong Kong to use as guidance in T790M testing.

Novel assay demonstrates that coronary artery disease patients have heightened procoagulant platelet response.

Essentials Procoagulant platelets can be detected using GSAO in human whole blood. Stable coronary artery disease is associated with a heightened procoagulant platelet response. Agonist-induced procoagulant platelet response is not inhibited by aspirin alone. Collagen plus thrombin induced procoagulant platelet response is partially resistant to clopidogrel. SUMMARY: Background Procoagulant platelets are a subset of highly activated platelets with a critical role in thrombin generation. Evaluation of their clinical utility in thrombotic disorders, such as coronary artery disease (CAD), has been thwarted by the lack of a sensitive and specific whole blood assay. Objectives We developed a novel assay, utilizing the cell death marker, GSAO [(4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid], and the platelet activation marker, P-selectin, to identify procoagulant platelets in whole blood by flow cytometry. Patients/Methods Using this assay, we characterized the procoagulant platelet population in healthy controls and a cohort of patients undergoing elective coronary angiography. Results In patients with CAD, compared with patients without CAD, there was a heightened procoagulant platelet response to thrombin (25.2% vs. 12.2%), adenosine diphosphate (ADP) (7.8% vs. 2.7%) and thrombin plus collagen (27.2% vs. 18.3%). The heightened procoagulant platelet potential in CAD patients was not associated with other markers of platelet function, including aggregation, dense granule release and activation of α2b ß3 integrin. Although dual antiplatelet therapy (DAPT) was associated with partial suppression of procoagulant platelets, this inhibitory effect on a patient level could not be predicted by aggregation response to ADP and was not fully suppressed by clopidogrel. Conclusions We report for the first time that procoagulant platelets can be efficiently detected in a few microliters of whole blood using the cell death marker, GSAO, and the platelet activation marker, P-selectin. A heightened procoagulant platelet response may provide insight into the thrombotic risk of CAD and help identify a novel target for antiplatelet therapies in CAD.

Nationwide benthic macroinvertebrate assemblage multimetric indices: identifying inconsistencies and limitations in reporting stream impairment status, USA.

The objective of this study was to identify the current status of stream water-quality assessment and reporting methods for four states in the Ohio River basin (Indiana, Ohio, Tennessee, and Virginia), as required by the 305(b) section of the United States (US) Clean Water Act. Specifically, we clarified the discrepancies that exist among stream-impairment status classified by benthic macroinvertebrate multimetric indices (MMIs) and depicted using Geographic Information Systems shapefiles. In addition, we provided guidance in solving some of the comparability problems that arise when developing state-specific MMIs and depicting stream-impairment status using Geographic Information Systems technology. The MMI variation among states and differences in shapefile formats resulted in a nationwide dataset, which cannot be directly compared. Incorporating the changes suggested in this study allow for a uniform assessment and reporting method nationwide. Successful implementation of these changes would strengthen the US Environmental Protection Agency efforts to identify impaired streams and sources of those impairments without the limitations of state-by-state .developed assessment methods.

Myotonic dystrophy and the heart: A systematic review of evaluation and management.

UNLABELLED: Myotonic dystrophy (MD) is a multisystem, autosomal dominant disorder best known for its skeletal muscle manifestations. Cardiac manifestations arise as a result of myocardial fatty infiltration, degeneration and fibrosis and present most commonly as arrhythmias or conduction disturbances. Guidelines regarding the optimal cardiac management of patients with MD are lacking. The present article provides a summary of the pathophysiology of cardiac problems in patients with MD and provides a practical approach to contemporary cardiac monitoring and management of these patients with a focus on the prevention of complications related to conduction disturbances and arrhythmias. METHODS: A literature search was performed using PubMed and Medline. The keywords used in the search included "myotonic dystrophy", "cardiac manifestations", "heart", "arrhythmia", "pacemaker" and "defibrillator", all terms were used in combination. In addition, "myotonic dystrophy" was searched in conjunction with "electrophysiology", "electrocardiogram", "echocardiograph", "signal averaged electrocardiograph", "magnetic resonance imaging" and "exercise stress testing". The titles of all the articles revealed by the search were screened for relevance. The abstracts of relevant titles were read and those articles which concerned the cardiac manifestations of myotonic dystrophy or the investigation and management of cardiac manifestations underwent a full manuscript review.

Non-invasive detection of significant coronary artery disease with multi-section computed tomography angiography in patients with suspected coronary artery disease.

AIM: The objective of this prospective study was to compare the accuracy of multi-section computed tomography (MSCT) coronary angiography with invasive selective coronary angiography in the detection of significant coronary stenosis (> or =50% lumen diameter narrowing). METHODS: Thirty consecutive patients (mean age 59+/-10 years) with suspected coronary artery disease underwent both invasive coronary angiography and MSCT using a 40-section multidetector row machine with temporal resolution of 53ms. Reconstruction images were performed in eight phases of the cardiac cycle. Images of MSCT and invasive coronary angiography were analysed using the 16-segment model of the American Heart Association. RESULTS: A total of 480 segments from 30 patients were evaluated. Coronary segments distal to a vessel occlusion and segments with coronary stent were not considered for analysis (20 segments in total). Ninety-four (20.4%) segments showed significant (> or =50%) stenosis by invasive coronary angiogram. The accuracy of coronary MSCT was computed on a per segment basis. Average sensitivity, specificity, positive predictive value, and negative predictive value of MSCT were 99, 98, 94, and 99%, respectively. CONCLUSION: This study demonstrated that MSCT is as reliable as coronary angiography at detecting significant obstructive coronary artery disease. In selected groups of patients, it may replace the more invasive and potentially more dangerous conventional coronary angiography.

Hwa-byung. A community study of Korean Americans.

One hundred nine Korean American community subjects were interviewed regarding their experiences with hwa-byung (HB), a Korean folk illness label commonly used by Koreans with a myriad of physiological and psychological complaints. During these interviews, standard instruments were also used to assess their depressive and somatic symptoms. The results indicated that a relatively high proportion (12%) of the subjects labeled themselves as having suffered from HB. While no apparent sociodemographic differences were found between HB and non-HB subjects, significantly more HB subjects fulfilled the diagnosis of DSM-III major depression and also had previous diagnoses of depression. The HB subjects also had significantly higher scores for the total, depressive, and somatic subscales and 16 of the 20 individual items of the Center for Epidemiologic Studies-Depression Scale. These data confirm previous observations of substantial overlap between HB and DSM-III major depression among Koreans and Korean Americans, and suggest that HB may be a culturally patterned way of expression for Koreans experiencing major depression and related conditions. The clinical and theoretical implications of these findings are also discussed.

Haloperidol and prolactin concentrations in Asians and Caucasians.

Serum haloperidol and prolactin concentrations were measured in 34 normal male volunteers (12 Caucasians, 11 American-born Asians, and 11 foreign-born Asians) over a 7-hour period after haloperidol administration (0.5 mg given intramuscularly or 1.0 mg given orally). The results were similar between the two Asian groups but significantly different between Caucasians and Asians. After controlling for body surface area, Caucasians still had lower serum haloperidol concentrations and less prominent prolactin responses than did Asians. Furthermore, the ethnic difference in prolactin responses could not be fully accounted for by the differences in serum haloperidol concentrations between the two ethnic groups. These results indicate that both pharmacokinetic factors, including absorption and hepatic first-pass metabolism, and pharmacodynamic factors (dopamine receptor-mediated responses) contribute to the difference in responses between Caucasians and Asians.

Comparison of alprazolam plasma levels in normal Asian and Caucasian male volunteers.

Single-dose pharmacokinetics of alprazolam was studied in 42 normal male volunteers (14 Caucasians, 14 American-born Asians, and 14 foreign-born Asians), after both oral and parenteral (IV) administration of a small dose (0.5 mg) of the test drug. Asians manifested significantly higher Cmax, larger AUC, slower CL and longer t1/2 under both testing situations. When body surface area was used as a covariate, these cross-ethnic differences remained statistically significant (except Cmax) after oral but not IV drug administration. There were no differences between the two Asian groups in any of these parameters examined in this study. These results confirmed previous observations of ethnic differences in the pharmacokinetic response between Asians and Caucasians and suggested that smaller doses of alprazolam may be required for Asians for similar clinical effects as compared to their Caucasian counterparts.

Long-term assessment of aortic valve replacement with autologous pulmonary valve.

Two hundred two autologous pulmonary valves were transplanted into the aortic position between 1967 and 1982 at the National Heart Hospital in London. The indication for operation was congenital or acquired aortic valve disease, and the patients were followed for periods from 1 to 4 years. The patients were not anti-coagulated, but the entire series has been completely free from thromboembolism or bleeding. The actuarial prediction of freedom from valve-related deaths was 82 +/- 6% at the end of the fourteenth year after operation; deaths were due to reoperations for technical failure and to infective endocarditis. Event-free survival of the autologous pulmonary valve in the aortic position was 73 +/- 6% after 14 years at risk. Valve failure resulted mainly from technical problems encountered during the early years of surgical experience. There was no macroscopic or histological evidence of calcification in any of the failed valves. The right ventricular outflow was reconstructed with an aortic homograft in the majority of patients; 81 +/- 5% of these homografts demonstrated event-free performance over a 12-year follow-up period. It is concluded that the long-term performance of a pulmonary autograft inserted for aortic valve disease is superior to that of any other valve substitute and that the operation offers an almost ideal means of aortic valve replacement in appropriate patients.

Surgical treatment of prosthetic endocarditis. Aortic root replacement using a homograft.

This article reports the successful surgical treatment of six patients who presented with prosthetic endocarditis and uncontrolled bacteremia. They were treated by replacement of the aortic root with a preserved homograft aortic valve. With this technique, ventricular-aortic continuity was established with a centrally flowing valve together with its attached aorta. The weakened aortic and the associated root abscess were thereby excluded from the high-anulus pressure systemic circulation. There were no operative deaths, and the longest postoperative survival time is 10 years. Two patients have conduction disturbance and symptoms relating to their malfunctioning aortic valves. The remaining four patients are all well at 5 years, 2 years, 9 months, and 6 months with no further evidence of infection. Homograft aortic root replacement is a suitable treatment for this potentially lethal condition.

An electron microscope study of the effects of acute ischaemia in the brain.

The structural changes in the CNS of cats subjected to periods of 10 and 20 min of eschaemia have been studied. After 10 min of ischaemia the neurons show loss of granular endoplasmic reticulum and vacuolation of the persisting endoplasmic reticulum. After 20 min of ischaemia there is neuronal cell death, some synaptic degeneration. Glial foot processes swell and occlude the lumen of vessels. The significance of these changes is discussed.

Head injury, spasticity, suxamethonium and hyperkalaemia.

Cardiac arrest due to hyperkalaemia following suxamethonium in a patient with generalized spasticity due to head injury is reported and discussed.