Noninvasive ventilation (NIV) has been found to be beneficial for respiratory failure in many disease states; however, limited data are available supporting its use in acute asthma exacerbation. A retrospective chart analysis of adult patients admitted for acute asthma exacerbation and treated with NIV between January 2007 and December 2009 at a tertiary care community hospital was done. Ninety-eight patient encounters were identified. Mean age of the patients was 48.3 years, and 46% were male. Nineteen patients failed NIV and required invasive ventilation. There was no significant difference in the mean age, sex, race, and initial blood gas between patients with successful versus failed NIV. Usage of drugs, smoking, and history of past hospital or intensive care unit admission or intubation did not significantly influence the rate of failure of NIV. Patients who needed higher initial FiO2 were more likely to get intubated during their hospital stay (46.2 vs. 20.4%, P = 0.019). Patients who failed NIV were found to have longer duration of hospital stay (6.8 vs. 3.9 days, P= 0.016) and longer intensive care unit stay (4 vs. 0.9 days, P = 0.002). Use of inhalers and other medications was not found to significantly influence the rate of failure of NIV. NIV can be used initially in patients with acute asthma exacerbation, as it is associated with shorter duration of hospital stay and can prevent the morbidity of mechanical intubation. Patients with initial requirement of higher FiO2 were more likely to fail NIV and should be carefully monitored.

The purpose of this meta-analysis was to compare postprocedural mortality and major adverse cardiovascular and cerebrovascular events between transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) for severe aortic stenosis. Seventeen studies (n = 4,659) comparing TAVI (n = 2,267) and SAVR (n = 2,392) were included. End points were baseline logistic European System for Cardiac Operative Risk Evaluation score, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, transient ischemic attack, and major bleeding events. Mean differences or risk ratios with 95% confidence intervals were computed, and p values <0.05 were considered significant. The population was matched for risk between the 2 groups on the basis of logistic European System for Cardiac Operative Risk Evaluation score for all outcomes except 30-day all-cause mortality, which had a high-risk population in the TAVI group (p = 0.02). There was no significant difference found in all-cause mortality at 30 days (p = 0.97) and at an average of 85 weeks (p = 0.07). There was no significant difference in cardiovascular mortality (p = 0.54) as well as the incidence of myocardial infarction (p = 0.59), stroke (p = 0.36), and transient ischemic attack (p = 0.85) at averages of 86, 72, 66, and 89 weeks, respectively. Compared with patients who underwent TAVI, those who underwent SAVR had a significantly higher frequency of major bleeding events (p <0.0001) at mean follow-up of 66 weeks. In conclusion, TAVI has similar cardiovascular and all-cause mortality to SAVR at early and long-term follow-up. TAVI is superior to SAVR for major bleeding complications and noninferior to SAVR for postprocedural myocardial infarctions and cerebrovascular events. TAVI is a safe alternative to SAVR in selected high-risk elderly patients with severe aortic stenosis.

Background: The recent literature has shown that triple antiplatelet therapy with cilostazol in addition to the standard dual antiplatelet therapy with aspirin and clopidogrel may reduce platelet reactivity and improve clinical outcomes following percutaneous coronary intervention. The purpose of this meta-analysis is to compare the efficacy of triple antiplatelet therapy and dual antiplatelet therapy in regard to on-treatment platelet reactivity. Methods: Nine studies (n = 2179) comparing on-treatment platelet reactivity between dual antiplatelet therapy (n = 1193) and triple antiplatelet therapy (n = 986) in patients undergoing percutaneous coronary intervention were included. Primary end points were P2Y12 reaction unit (PRU) and platelet reactivity index (PRI). Secondary end points were platelet aggregation with adenosine diphosphate (ADP) 5 and 20 µmol/L and P2Y12% inhibition. Mean difference (MD) and 95% confidence intervals (CI) were computed and 2-sided α error <.05 was considered as a level of significance. Results: Compared to dual antiplatelet therapy, triple antiplatelet therapy had significantly lower maximum platelet aggregation with ADP 5 µmol/L (MD: −14.4, CI: −21.6 to −7.2, P < .001) and 20 µmol/L (MD: −14.9, CI: −22.9 to −6.8, P < .001), significantly lower PRUs (MD: −45, CI: −59.4 to −30.6, P < .001) and PRI (MD: −26, CI: −36.8 to −15.2, P < .001), and significantly higher P2Y12% inhibition (MD: 18.5, CI: 2.3 to 34.6, P = .025). Conclusion: Addition of cilostazol to conventional dual antiplatelet therapy significantly lowers platelet reactivity and may explain a decrease in thromboembolic events following coronary intervention; however, additional studies evaluating clinical outcomes will be helpful to determine the benefit of triple antiplatelet therapy.

N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) is the enzyme that removes sulfate groups from the N-acetylgalactosamine-4-sulfate residue at the non-reducing end of chondroitin-4-sulfate (C4S) and dermatan sulfate (DS). Previous studies demonstrated reduction in cell-bound high molecular weight kininogen in normal rat kidney (NRK) epithelial cells when chondroitin-4-sulfate content was reduced following overexpression of ARSB activity, and chondroitinase ABC produced similar decline in cell-bound kininogen. Reduction in the cell-bound kininogen was associated with increase in secreted bradykinin. In this report, we extend the in vitro findings to in vivo models, and present findings in Dahl salt-sensitive (SS) rats exposed to high (SSH) and low salt (SSL) diets. In the renal tissue of the SSH rats, ARSB activity was significantly less than in the SSL rats, and chondroitin-4-sulfate and total sulfated glycosaminoglycan content were significantly greater. Disaccharide analysis confirmed marked increase in C4S disaccharides in the renal tissue of the SSH rats. In contrast, unsulfated, hyaluronan-derived disaccharides were increased in the rats on the low salt diet. In the SSH rats, with lower ARSB activity and higher C4S levels, cell-bound, high-molecular weight kininogen was greater and urinary bradykinin was lower. ARSB activity in renal tissue and NRK cells declined when exogenous chloride concentration was increased in vitro. The impact of high chloride exposure in vivo on ARSB, chondroitin-4-sulfation, and C4S-kininogen binding provides a mechanism that links dietary salt intake with bradykinin secretion and may be a factor in blood pressure regulation.

We report a rare clinical scenario of chronic mesenteric ischemia (CMI) patient with obstruction of all the three major gut vessels including celiac, superior mesenteric artery (SMA), and inferior mesenteric artery (IMA) with a sole artery supplying the collaterals through marginal artery of left colon (the "wandering artery of Drummond"). A 70-year-old man was presented to hospital with acute onset of dyspnea, diaphoresis, severe epigastric pain, nausea, and vomiting that started after lunch. Initially, patient was diagnosed and treated for non-ST elevation myocardial infarction (NSTEMI). Furthermore, work-up, including computed tomographic scan of abdomen followed by angiogram, revealed 100% obstruction of celiac and SMA, whereas inferior IMA had 90% ostial lesion with poststenotic dilatation and collaterals supplying to entire colon. Subsequently, IMA ostial lesion was stented through percutaneous intervention and patient noted significantly improved symptoms and quality of life. To conclude, percutaneous endovascular treatments confer favorable strategy for CMI, and it may either be curative or allow nutritional optimization before definitive surgery.

Background: Dual antiplatelet therapy with aspirin and clopidogrel is the cornerstone of treatment to prevent major adverse cardiovascular events (MACE) in patients following percutaneous coronary intervention (PCI). In high-risk patients requiring long-term anticoagulant, the current literatures have controversial results in preventing MACE and bleeding events with the use of triple therapy with aspirin, clopidogrel and warfarin compared to dual antiplatelet therapy following PCI. The purpose of this meta-analysis was to compare the safety and efficacy of triple therapy with dual therapy following PCI in high-risk patients requiring long term anticoagulation. Methods: A literature search identified 4 prospective and 4 retrospective studies with total of 2439 patients requiring long term anticoagulation undergoing PCI. End points measured were bleeding events, deaths, ischemic stroke, myocardial infarction, stent thrombosis and MACE. The odds ratios (OR) with 95% confidence intervals (CI) were computed and two sided alpha error <0.05 considered as a level of significance. Results: In contrast to dual antiplatelet therapy, patients on triple therapy with anticoagulant had significantly lower stent thrombosis (OR: 0.45, CI: 0.21-0.94, p=0.03) and ischemic stroke (OR: 0.30, CI: 0.16-0.56, p<0.001) (Fig 1 - Zone A is dual therapy group, zone B is triple therapy group). No significant difference was found between two groups in overall bleeding events (OR: 1.57, CI: 0.87-2.85, p=0.14), major bleeding events(OR:1.21, CI: 0.57-2.59, p=0.62), deaths (OR:0.89, CI: 0.5-1.58, p=0.69), myocardial infarction (OR:1.31, CI: 0.85-2.02, p=0.22) and MACE (OR:0.61, CI:0.20-1.82, p=0.37). Conclusions: Our meta-analysis suggests that the triple therapy with anticoagulant does not increase bleeding compared to dual antiplatelet therapy. Moreover, triple therapy decreases stent thrombosis and ischemic stroke following PCI in patients requiring long-term anticoagulants. Our study did not show any difference in mortality between two groups. Triple therapy may be a favorable strategy following PCI in high-risk patients requiring long-term anticoagulation. The randomized control clinical trials are needed for further evaluation of long-term outcomes.

Background: Studies evaluating intracoronary administration of adenosine for prevention of microvascular dysfunction and ischemic-reperfusion injury in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) have yielded mixed results. Therefore, we performed a meta-analysis of these trials to evaluate the safety and efficacy of intracoronary adenosine administration in patients with AMI undergoing primary PCI. Methods: A total of seven prospective randomized controlled trials were analyzed. The endpoints extracted were post-procedure residual stent thrombosis (ST) segment elevation and ST segment resolutions (STRes), difference in peak creatine kinase (CK-MB) concentration, thrombolysis in myocardial infarction (TIMI) grade III flow (TIMI 3 flow), myocardial blush grade (MBG) 3, mean difference in post-PCI ejection fraction (EF), all-cause mortality, cardiovascular mortality, heart failure (HF) and major adverse cardiovascular event (MACE). Safety endpoints analyzed were bradycardia, second-degree atrioventricular block (AVB), ventricular tachycardia (VT), ventricular fibrillation (VF) and recurrence of chest pain (CP). The endpoints were analyzed by standard methods of meta-analysis. Results: Intracoronary adenosine therapy led to significantly more post-PCI STRes [relative risk (RR) 1.39, 95% confidence interval (CI) 1.01–1.90; p = 0.04] and reduction in residual ST segment elevation (RR 0.82, CI 0.69–0.99; p = 0.04) but did not improve TIMI 3 flow (RR 1.09, CI 0.94–1.27; p = 0.25), MBG3 (RR 1.04, CI 0.65–1.69; p = 0.88), peak CK-MB concentration (mean difference −39.43, CI −120.223 to 41.371; p = 0.339) and post-PCI EF (mean difference 1.238, CI −5.802 to 8.277; p = 0.730). There was a trend towards improvement and MACE (RR 0.64, CI 0.40–1.03; p = 0.06), incidence of HF (RR 0.47, CI 0.19–1.12; p = 0.08) and CV mortality (RR 0.15, CI 0.02–1.23; p = 0.08) that did not reach statistical significance but no difference in all-cause mortality (RR 0.77, CI 0.25–2.34; p = 0.64). Safety analysis showed no significant difference in CP events (RR 1.26, CI 0.55–2.86; p = 0.58), bradycardia (RR 2.19, CI 0.24–0.38; p = 0.49), VT (odds ratio 0.61, CI 0.08–4.90; p = 0.64) and VF (RR 0.49, CI 0.13–1.90; p = 0.30), but significantly more second-degree AVB (RR 7.88, CI 4.15–14.9; p < 0.01) in the adenosine group compared with the placebo group. Conclusion: Intracoronary adenosine administration was well tolerated and significantly improved electrocardiographic outcomes with a tendency towards improvement in MACE, HF and CV mortality that could not reach statistical significance.

BACKGROUND:Studies evaluating CYP2C19*2 and ABCB1-C3435T polymorphisms have shown conflicting results. We performed this meta-analysis to evaluate role of clinical testing for these polymorphisms in CAD patients on clopidogrel.METHODS:19,601 patients from 14 trials were analyzed. The endpoints were major adverse cardiovascular events (MACE), cardiovascular (CV) death, stent thrombosis (ST), myocardial infarction (MI), stroke and major bleeding. Combined relative risks (RR) with 95% confidence intervals (CI) were computed for each outcome by using standard methods of meta-analysis and test parameters were computed.RESULTS:CYP2C19*2 polymorphism was associated with higher risk of MACE [RR: 1.28, CI: 1.06-1.54; p=0.009], CV death [RR: 3.21, CI: 1.65-6.23; p=0.001], MI [RR: 1.36, CI: 1.12-1.65; p=0.002], ST [RR: 2.41, CI: 1.69-3.41; p<0.001]. No difference was seen in major bleeding events [RR: 1.02, CI: 0.86-1.20; p=0.83]. Subgroup analysis showed similar results for elective PCI [RR: 1.34, CI: 1.01-1.76; p=0.03], and PCI with DES [RR: 1.53, CI: 1.029-1.269; p=0.03]. CYP2C19*2 polymorphism has very low sensitivity (28-58%), specificity (71-73%), positive predictive value (3-10%) but good negative predictive value (92-99%). ABCB1-C3435T polymorphism analysis revealed similar MACE [RR: 1.13, CI: 0.99-1.29; p=0.06], ST [RR: 0.88, CI: 0.52-1.47; p=0.63] and major bleeding [RR: 1.04, CI: 0.87-1.25; p=0.62] in both groups.CONCLUSION:In CAD patients on clopidogrel therapy, CYP2C19*2 polymorphism is associated with significantly increased adverse cardiovascular events. However, due to the low positive predictive value, routine genetic testing cannot be recommended at present.

Controversy persists regarding the incidence of very late stent thrombosis (VLST) with bare metal stents (BMS) compared to drug eluting stents (DES) after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). We performed a meta-analysis of

Background: Recent studies have suggested association of vitamin D with cardiovascular events. The relationship of vitamin D deficiency with cardiovascular fitness level (CVF) has not been studied in current literatures. Demographic variation of this association is also unclear. The primary objective of our study was to assess the relationship of vitamin D level to CVF and evaluate the demographic variation of this association in young adults. The secondary objective of this study was to assess the relationship of vitamin D level with the other cardiovascular risk factors. Methods: We evaluated 5388 adults from National Health and Nutrition Examination Survey 2001-2004. The associations of serum 25-hydroxy vitamin D level with CVF and cardiovascular risk factors such as systolic/diastolic blood pressure (SBP/DBP), low density lipoprotein (LDL), high density lipoprotein (HDL), and glycohemoglobin (HbA1c) levels in young adults aged 20-49 years were evaluated. Adults with vitamin D deficiency (≤30 mg/dL) and normal vitamin D level (>30 mg/dL) were compared. The CVF was assessed with peak oxygen uptake on treadmill test (VO2 max <20 percentile= low CVF, VO2 max ≥60 percentile= high CVF). Chi square analysis and odds ratio were calculated to assess the association of vitamin D deficiency with CVF. Pearson correlation was measured for the secondary analysis of association of vitamin D level with cardiovascular risk factors. The alpha error ≤0.05 was used as a level of significance. Results: Total of 85.4% (n=4603/5388) young adults had vitamin D deficiency. Vitamin D level was positively associated with CVF (p<0.001). In comparison to normal vitamin D level, vitamin D deficiency was significantly associated with low CVF (Odds ratio 2.01, confidence interval 1.64-2.46, p<0.001). In contrast to normal vitamin D level, vitamin D deficiency was significantly associated with low CVF in subgroups of males (p<0.01), females (p<0.01), age group of 20-29 years (p<0.01) and age group of 30-49 years (p<0.01). In contrast to normal vitamin D level, vitamin D deficiency was significantly associated with low CVF only in Caucasians (p=0.001). This association was not significant in Mexican-Hispanics (p=0.35), other Hispanics (p=0.095), African Americans (p=0.061) and other races (p=0.206). In comparison to normal vitamin D level, vitamin D deficiency was significantly associated with low CVF among normal BMI (p<0.001), overweight BMI (p<0.001) and obese adults (p=0.019) but not in underweight BMI adults (p=0.48). Vitamin D level was inversely associated with SBP (p<0.001), and HbA1c (p<0.001) and positively associated with HDL (p<0.001). There was no significant association found between vitamin D level and DBP (p=0.66) or LDL (p=0.79). Conclusions: The results of our study demonstrate that vitamin D deficiency may decrease CVF in Caucasian young adults. Surprisingly it may not affect CVF in other races and underweight adults. Vitamin D deficiency is also associated with increase in cardiovascular risk factors such as low HDL, high SBP and HbA1c. The large population based clinical trials are needed for evaluation of this relationship and long-term consequences on cardiovascular outcomes.

Immune dysregulation is the hallmark of all autoimmune diseases. It is extremely interesting to study the associations and pathogenesis of the various autoimmune diseases, like the link between the AIHA and CLL. This link is well established and is based on the fact that there is loss of tolerance to the self-antigen, which in turn leads to immunebased hemolytic anemia. Around 30% of the patients with CLL are at the risk of developing AIHA, and 11% eventually develop AIHA. Whether there is any definite linkup between the corrupted immune system and "acute" leukemias/lymphomas is yet to be established. Needless to say, if there was an association between the pathogenesis of the ALLs and AIHA, it would be a landmark in the field of oncology as it would enforce early diagnosis and treatment for the disease which is much more aggressive and found in a comparatively younger age group (predominantly in children and a mean age of 40 years in adults) as compared to its chronic counterparts. The AIHA would serve as a "tip to the underlying iceberg" in these situations, warning us of the cryptic diagnosis.

Background: Majority of the transradial procedures are performed by using right radial approach (RRA). The left radial approach (LRA) has anatomical advantage of being direct access to the ascendin...