Post‐Procedural Bivalirudin Infusion Following Primary PCI to Reduce Stent Thrombosis

Background

Prolonging infusions may abrogate the acute stent thrombosis (ST) associated with bivalirudin use during primary PCI but at an increased cost. We hypothesized that continuing the bivalirudin infusion commenced during the procedure at the PCI recommended dose until infusion end would prevent excess early ST.

Methods

Baseline demographics, procedural data and outcomes were gathered prospectively on 1395 consecutive patients undergoing primary PCI. The choice of bivalirudin versus heparin was at the cardiologist's discretion. Local protocol recommended continuation of the procedural bivalirudin at the PCI dose until infusion end.

Results

Patients' mean age was 62.8 ± 13.1years with 11.4% presenting with shock. The majority of patients underwent PCI using bivalirudin with fewer using heparin (87.7 vs. 12.3%, P < 0.0001). Glycoprotein inhibitor bailout rates were 6.1% with bivalirudin and 36.3% with heparin (P < 0.0001). Calculated on an individual patient basis the median intra‐procedure duration of the bivalirudin infusion was 30(IQR 21‐43) minutes and post‐procedure 49(32–66) minutes. The acute (<24‐hours) ST rates were 4/1224 with bivalirudin ± GPI (0.3%) and 0/171 with heparin ± GPI (0%, P = 0.41). The sub‐acute (24‐hours to 30‐days) ST rates were 3/1224 for bivalirudin ± GPI (0.3%) and 2/171 with heparin ± GPI (1.2%, P = 0.11). In total the early (<30‐days) ST rates were 7/1224 for bivalirudin ± GPI (0.6%) and 2/171 with heparin ± GPI (1.2%, P = 0.31). Acute ST was significantly more likely to occur in clopidogrel‐loaded patients than prasugrel/ticagrelor patients (2.7 vs. 0.5%, P = 0.003).

Conclusion

Continuing the bivalirudin infusion commenced during the procedure at the PCI recommended dose until infusion end combined with potent P₂Y12 inhibitors ameliorates excess early stent thrombosis. (J Interven Cardiol 2016;29:129–136)

     

Endogenous methyl palmitate modulates nicotinic receptor-mediated transmission in the superior cervical ganglion

Nitric oxide (NO) is identified as the endothelium-derived relaxing factor and a neurotransmitter with a superfusion bioassay cascade technique. By using a similar technique with rat superior cervical ganglion (SCG) as donor tissue and rabbit endothelium-denuded aortic ring as detector tissue, we report here that a vasodilator, which is more potent than NO, is released in the SCG upon field electrical stimulation (FES) or addition of nicotine. Release of this vasodilator was enhanced by arginine analogs, including N^ω-nitro-l-arginine (a NO synthase inhibitor), suggesting that it is not NO. Analysis by gas chromatography/mass spectrometry identified 2 saturated fatty acids, palmitic acid methyl ester (PAME) and stearic acid methyl ester (SAME), being released from the SCG upon FES in the presence of arginine analogs. Exogenous PAME but not SAME induced significant aortic dilation (EC₅₀ = 0.19 nM), indicating that PAME is the potent vasodilator. Release of PAME and SAME was significantly diminished in chronically decentralized SCG but not denervated SCG, suggesting the preganglionic origin. Furthermore, release of both fatty acids was calcium- and myosin light chain kinase-dependent, suggesting that both were released from axoplasmic vesicular stores. Electrophysiological studies further demonstrated that PAME but not SAME inhibited nicotine-induced inward currents in cultured SCG and the α7-nicotinic acetylcholine receptor-expressing Xenopus oocytes. Endogenous PAME appears to play a role in modulation of the autonomic ganglionic transmission and to complement the vasodilator effect of NO.     

Nutrient intakes; biochemical and risk indices associated with Type 2 diabetes and glycosylated haemoglobin, in the British National Diet and Nutrition Survey of people aged 65 years and over.

AIMS: To characterize nutritional differences between survey participants diagnosed with Type 2 diabetes; those without diabetes, and those with "undiagnosed diabetes" based on glycosylated haemoglobin (HbA(1c)). SUBJECTS AND METHODS: The 1994/5 British National Diet and Nutrition Survey, of people aged 65 years and over (mean age 78 years), included 73 respondents with diagnosed Type 2 diabetes [mean (sd) HbA(1c) = 7.06 (2.05)%], and 30 with "undiagnosed diabetes" (defined as HbA(1c) > 6.3%; mean (sd) HbA(1c) = 7.40 (1.66)%], among a representative sample of 1038 with anthropometry; 4-day weighed diet; blood and urine status measurements. RESULTS: The prevalence of Type 2 diabetes (diagnosed + undiagnosed) was 10%. In subjects without diagnosis of diabetes, those with HbA(1c) > 6.3% had on average a significantly higher body weight (73.6 vs. 67.9 kg), higher waist circumference (99.8 vs. 91.8 cm), higher body mass index (28.6 vs. 25.9 kg/m(2)) and higher white cell counts (7.64 vs. 7.09 x 10(9)/l), than those with mean HbA(1c) < or = 6.3%. Diagnosed diabetic subjects had significantly higher energy-adjusted intakes of protein, fibre, vitamins and minerals than those not in this category (P < 0.01). In contrast, those with undiagnosed diabetes (HbA(1c) > 6.3%) were nutritionally "at risk", having low plasma concentrations of lycopene (0.13 vs. 0.24 micromol/l) and high density lipoprotein cholesterol (0.99 vs. 1.27 micromol/l) and a trend towards low vitamin C (24 vs. 36 micromol/l) which was significant (P < 0.01) for men. HbA(1c) was positively correlated with white cell count, plasma fasting triglycerides, plasma alkaline phosphatase and homocysteine (all P < 0.01 overall), being particularly striking amongst men. CONCLUSIONS: Among older British citizens, those with diagnosed diabetes had healthier nutritional profiles than those undiagnosed with high HbA(1c). Important health-promoting benefits are therefore predicted following early diagnosis and nutritional advice for people with Type 2 diabetes.     

CT imaging characteristics of oncocytic adrenal neoplasms (OANs): comparison with adrenocortical carcinomas

Objective

Oncocytic adrenal neoplasms (OANs) are rare, but are an important subtype of adrenal tumors that is being diagnosed with increasing frequency. Unfortunately, the imaging characteristics of this tumor have not been well described. Our purpose was to identify CT features to differentiate OANs from adrenocortical carcinomas (ACC).

Materials and methods

From 1991 to 2012, 18 patients with OANs were identified from our institution’s pathology database. Twelve had CT examinations available for review. CT characteristics of five benign and seven malignant OANs were reviewed by two abdominal radiologists, and compared to ACC (n = 10). Morphologic characteristics and density measurements were recorded for each imaging phase. Absolute contrast washout was calculated and compared.

Results

Benign OANs were smaller [mean size 3.7 cm (range 2.6–5.3)] and more homogeneous than malignant OANs and demonstrated greater washout [mean washout percentage 72.3% (range 61–88)]. Malignant OANs demonstrated features similar to ACCs, including size [mean 9.4 cm (range 5.2–9.8)] and internal necrosis (n = 6). Mean enhancement washout percentage for malignant OANs was 12% (range ?8 to 32).

Conclusion

Benign OANs (oncocytomas) may be distinguished from lipid-rich adenomas on non-contrast CT but may be indistinguishable from lipid-poor adenomas. Malignant oncocytic neoplasms can demonstrate features similar to ACCs, including larger size, internal necrosis, and lower percentage enhancement washout.     

Low‐dose anti‐CD20 veltuzumab given intravenously or subcutaneously is active in relapsed immune thrombocytopenia: a phase I study

Low doses of the humanized anti‐CD20 monoclonal antibody, veltuzumab, were evaluated in 41 patients with immune thrombocytopenia (ITP), including 9 with ITP ≤1 year duration previously treated with steroids and/or immunoglobulins, and 32 with ITP >1 year and additional prior therapies. They received two doses of 80–320 mg veltuzumab 2 weeks apart, initially by intravenous (IV) infusion (N = 7), or later by subcutaneous (SC) injections (N = 34), with only one Grade 3 infusion reaction and no other safety issues. Thirty‐eight response‐assessable patients had 21 (55%) objective responses (platelet count ≥30 × 10⁹/l and ≥2 × baseline), including 11 (29%) complete responses (CRs) (platelet count ≥100 × 10⁹/l). Responses (including CRs) occurred with both IV and SC administration, at all veltuzumab dose levels, and regardless of ITP duration. Responders with ITP ≤1 year had a longer median time to relapse (14·4 months) than those with ITP >1 year (5·8 months). Three patients have maintained a response for up to 4·3 years. SC injections resulted in delayed and lower peak serum levels of veltuzumab, but B‐cell depletion occurred after first administration even at the lowest doses. Eight patients, including 6 responders, developed anti‐veltuzumab antibodies following treatment (human anti‐veltuzumab antibody, 19·5%). Low‐dose SC veltuzumab appears convenient, well‐tolerated, and with promising clinical activity in relapsed ITP.( Clinicaltrials.gov identifier: NCT00547066.)     

Implementation of a protocol for integrated management of pain,agitation, and delirium can improve clinical outcomes in the intensive care unit: A randomized clinical trial

Background

Inappropriate diagnosis and treatment of pain, agitation, and delirium (PAD) in intensive care settings results in poor patient outcomes. We designed and used a protocol for systematic assessment and management of PAD by the nurses to improve clinical intensive care unit (ICU) outcomes.

Materials and Methods

A total of 201 patients admitted to 2 mixed medical-surgical ICUs were randomly allocated to protocol and control groups. A multidisciplinary team approved the protocol. Pain was assessed by Numerical Rating Scale and Behavioural Pain Scale, agitation by Richmond Agitation Sedation Scale, and delirium by Confusion Assessment Method in ICU. The Persian version of the scales was prepared and tested for validity, reliability, and feasibility in a preliminary study. The patients in the protocol group were managed pharmacologically according to the protocol, whereas those in the control group were managed according to the ICU routine.

Results

The median (interquartile range) for the duration of mechanical ventilation in the protocol and control groups was 19 (9.3-67.8) and 40 (0-217) hours, respectively (P = .038). The median (interquartile range) length of ICU stay was 97 (54.5-189) hours in the protocol group vs 170 (80-408) hours in the control group (P < .001). The mortality rate in the protocol group was significantly reduced from 23.8% to 12.5% (P = .046).

Conclusion

The current randomized trial provided evidence for a substantial reduction in the duration of need to ventilatory support, length of ICU stay, and mortality rates in ICU-admitted patients through protocol-directed management of PAD.     

Acid base balance in seriously ill surgical cases and its prognostic significance

Acid base changes are common in surgical patients. The present study was conducted in 50 seriously ill surgical patients over a period of 56 hours. A wide range of pH was observed with 72% observations outside the normal limits. Alkalosis was observed in 44% of total observations while acidosis was noted in 28%. A higher mortality was seen in cases with alkalosis.     

Correlation of breast tumour aromatase activity and response to aromatase inhibition with aminoglutethimide

Tumour aromatase, oestrogen (E) and progesterone (P) receptor (R) measurements were carried out in biopsies from 29 patients with advanced or recurrent breast cancer. Patients were then treated with aminoglutethimide according to one of two dosage regimens: (a) aminoglutethimide 1000 mg/day + hydrocortisone 20 mg/day, and (b) aminoglutethimide 250 mg/day. Tumour aromatase values varied from 0.05 to 2.07 pmol ER produced/mg protein/h and ER and PR values from less than 1 to 249 and less than 1 to 132 fmol of steroid bound/mg protein, respectively. There was no correlation between aromatase values and either ER or PR and also no correlation between ER and PR and response to aminoglutethimide. Tumour aromatase values did however correlate with response to treatment. Mean aromatase levels for responders (1.18 +/- 0.64 pmol E produced/mg protein/h) were significantly higher than those of non-responders (0.34 +/- 0.27) (t = 5.20, DF 27; p less than 0.005). Ten out of fourteen patients with aromatase values greater than 0.5 pmol ER produced/mg protein/h responded, whereas 0 out of 15 patients with tumour aromatase values less than this responded. Responses were seen at both dosages of aminoglutethimide. It is concluded that tumour aromatisation will be a useful measurement in predicting response to aromatase inhibitors.     

ANGIOTENSIN CONVERTING ENZYME INHIBITOR, CAPTOPRIL, INHIBITS CARDIAC HYPERTROPHY WITHOUT CHANGING COLLAGEN TYPES AND CONCENTRATION IN SPONTANEOUSLY HYPERTENSIVE RATS

1. The effects of the ACE inhibitor, captopril, on collagen metabolism in spontaneously hypertensive rats (SHR) with cardiac hypertrophy was examined. Captopril (100 mg/kg per day) was administered in drinking water to 20 week old male SHR for 12 weeks. Collagen concentration was calculated from hydroxyproline content, and relative proportions of types I, III and V collagen were determined by non-interrupted SDS-polyacrylamide gel electrophoresis (SDS-PAGE). These parameters were examined in age and sex matched Wistar-Kyoto (WKY) rats, as well as in non-treated SHR, and compared with those of captopril-treated SHR. 2. Captopril significantly reduced both blood pressure (191 ± 12.1 vs 146 ± 11.2 mmHg, P < 0.01), and the ratio of left ventricular (LV) weight to bodyweight (BW; 2.38 ± 0.17 vs 2.05 ± 0.12 mg/g, P < 0.01). There were no significant differences in collagen concentration among WKY rats, captopril-treated SHR and non-treated 32 week old SHR. However, total collagen content in captopril-treated SHR reduced significantly compared with non-treated 32 week old SHR (16.8 ± 2.0 vs 21.3 ± 0.8 mg, P < 0.01). The relative proportion of type V collagen was significantly higher in both captopril-treated (58.6 ± 3.4 vs 46.8 ± 1.3%, P < 0.01) and non-treated 32 week old SHR (59.9 ± 3.1 vs 46.8 ± 1.3%, P < 0.01) compared with WKY rats. However, there were no significant differences between captopril-treated SHR and non-treated 32 week old SHR. 3. The data from this study showed that captopril reduced cardiac hypertrophy, as reported previously, but did not change collagen types and concentration of the hypertrophied myocardium in SHR.