Outcomes Following Percutaneous Coronary Intervention in Renal Transplant Recipients: A Binational Collaborative Analysis

ObjectiveTo investigate the clinical and procedural characteristics in patients with a history of renal transplant (RT) and compare the outcomes with patients without RT in 2 national cohorts of patients undergoing percutaneous coronary intervention (PCI).Patients and MethodsData from the National Inpatient Sample (NIS) and British Cardiovascular Intervention Society (BCIS) were used to compare the clinical and procedural characteristics and outcomes of patients undergoing PCI who had RT with those who did not have RT. The primary outcome of interest was in-hospital mortality.ResultsOf the PCI procedures performed in 2004-2014 (NIS) and 2007-2014 (BCIS), 12,529 of 6,601,526 (0.2%) and 1521 of 512,356 (0.3%), respectively, were undertaken in patients with a history of RT. Patients with RT were younger and had a higher prevalence of congestive cardiac failure, hypertension, and diabetes but similar use of drug-eluting stents, intracoronary imaging, and pressure wire studies compared with patients who did not have RT. In the adjusted analysis, patients with RT had increased odds of in-hospital mortality (NIS: odds ratio [OR], 1.90; 95% CI, 1.41-2.57; BCIS: OR, 1.60; 95% CI, 1.05-2.46) compared with patients who did not have RT but no difference in vascular or bleeding events. Meta-analysis of the 2 data sets suggested an increase in in-hospital mortality (OR, 1.79; 95% CI, 1.40-2.29) but no difference in vascular (OR, 1.24; 95% CI, 0.77-2.00) or bleeding (OR, 1.21; 95% CI, 0.86-1.68) events.ConclusionThis large collaborative analysis of 2 national databases revealed that patients with RT undergoing PCI are younger, have more comorbidities, and have increased mortality risk compared with the general population undergoing PCI.     

Spectrum and outcome of pancreatic trauma.

BACKGROUND AND AIMS: Pancreatic trauma is associated with high morbidity and mortality. Diagnosis is often difficult and surgery poses a formidable challenge. METHOD: Data from 17 patients of pancreatic trauma gathered from a prospectively maintained database were analysed and the following parameters were considered: mode of injury, diagnostic modalities, associated injury, grade of pancreatic trauma and management. Pancreatic trauma was graded from I through IV, as per Modified Lucas Classification. RESULTS: The median age was 39 years (range 19-61). The aetiology of pancreatic trauma was blunt abdominal trauma in 14 patients and penetrating injury in 3. Associated bowel injury was present in 4 cases (3 penetrating injury and 1 blunt trauma) and 1 case had associated vascular injury. 5 patients had grade I, 3 had grade II, 7 had grade III and 2 had grade IV pancreatic trauma. Contrast enhanced computed tomography scan was used to diagnose pancreatic trauma in all patients with blunt abdominal injury. Immediate diagnosis could be reached in only 4 (28.5%) patients. 7 patients responded to conservative treatment. Of the 10 patients who underwent surgery, 6 required it for the pancreas and the duodenum. (distal pancreatectomy with splenectomy-3, pylorus preserving pancreatoduodenectomy-1, debridement with external drainage-1, associated injuries-duodenum-1). Pancreatic fistula, recurrent pancreatitis and pseudocyst formation were seen in 3 (17.05%), 2 (11.7%) and 1 (5.4%) patient respectively. Death occurred in 4 cases (23.5%), 2 each in grades III and IV pancreatic trauma. CONCLUSIONS: Contrast enhanced computed tomography scan is a useful modality for diagnosing, grading and following up patients with pancreatic trauma. Although a majority of cases with pancreatic trauma respond to conservative treatment, patients with penetrating trauma, and associated bowel injury and higher grade pancreatic trauma require surgical intervention and are also associated with higher morbidity and mortality.     

Alterations of humoral, cell mediated and antibody dependent cell mediated cytotoxic responses during the course of amoebic infection in guinea pigs.

The cellular and antibody dependent cellular cytotoxic (ADCC) responses of splenic lymphocytes and peritoneal macrophages obtained from animals at variable intervals after inoculation were studied against trophozoites of axenic E histolytica (NIH:200). Cytotoxic responses of effector cells from infected animals were compared with those of effector cells from vaccine stimulated and unstimulated uninfected control animals. Cellular and antibody-dependent cellular cytotoxic responses of the effector cells from animals during the establishment and acute phase of infection were significantly suppressed, compared with unstimulated uninfected and vaccinated (FI amoebic proteins stimulated) effector cells. The effector cells from animals recovered from infection showed enhanced cytotoxic responses against trophozoites of E histolytica. The suppressed cytotoxic response was accompanied by impairment of cytotoxic cell activities and lack, or very low level of anti-FI antibodies in the sera of animals during the establishment phase of infection. With the rise in anti-FI antibodies in the sera of animals ADCC could be induced effectively against trophozoites of E histolytica, which seem to result in clearance of amoebic infection.     

Lentivirus-mediated overexpression of angiotensin-(1-7) attenuated ischaemia-induced cardiac pathophysiology

Myocardial infarction (MI) results in cell death, development of interstitial fibrosis, ventricular wall thinning and ultimately, heart failure. Angiotensin-(1-7) [Ang-(1-7)] has been shown to provide cardioprotective effects. We hypothesize that lentivirus-mediated overexpression of Ang-(1-7) would protect the myocardium from ischaemic injury. A single bolus of 3.5 × 10(8) transducing units of lenti-Ang-(1-7) was injected into the left ventricle of 5-day-old male Sprague-Dawley rats. At 6 weeks of age, MI was induced by ligation of the left anterior descending coronary artery. Four weeks after the MI, echocardiography and haemodynamic parameters were measured to assess cardiac function. Postmyocardial infarction, rats showed significant decreases in fractional shortening and dP/dt (rate of rise of left ventricular pressure), increases in left ventricular end-diastolic pressure, and ventricular hypertrophy. Also, considerable upregulation of cardiac angiotensin-converting enzyme (ACE) mRNA was observed in these rats. Lentivirus-mediated cardiac overexpression of Ang-(1-7) not only prevented all these MI-induced impairments but also resulted in decreased myocardial wall thinning and an increased cardiac gene expression of ACE2 and bradykinin B2 receptor (BKR2). Furthermore, in vitro experiments using rat neonatal cardiac myocytes demonstrated protective effects of Ang-(1-7) against hypoxia-induced cell death. This beneficial effect was associated with decreased expression of inflammatory cytokines (tumour necrosis factor-α and interleukin-6) and increased gene expression of ACE2, BKR2 and interleukin-10. Our findings indicate that overexpression of Ang-(1-7) improves cardiac function and attenuates left ventricular remodelling post-MI. The protective effects of Ang-(1-7) appear to be mediated, at least in part, through modulation of the cardiac renin-angiotensin system and cytokine production.     

Cardiovascular surgical outcomes in patients with the antiphospholipid syndrome--a case-series

BACKGROUND: Patients with the antiphospholipid syndrome (APLS) have severe involvement of the cardiovascular apparatus and often need surgical interventions to correct these manifestations. Few studies that have looked at the outcomes of cardiothoracic surgeries in APLS patients have reported high rates of perioperative mortality and thromboembolic events. OBJECTIVE: Our goal was to examine the outcomes of adult APLS patients undergoing coronary artery bypass surgery (CABG) and/or valvular surgery. We also wanted to determine whether aggressive anticoagulation therapy could prevent life threatening thromboembolic complications in these patients. METHODS: We retrospectively reviewed medical records of nine patients with primary APLS undergoing cardiothoracic surgery between 1985 and 2005 at our institution. Patient demographics, operative procedures and one-year clinical outcomes were obtained. RESULTS: Forty-five percent of our patients had more than three cardiovascular risk factors other than APLS. There were no mortalities in our case series. However, 89% of our patients developed major complications. Despite aggressive anticoagulation, 37.5% developed thromboembolic events including cerebrovascular accidents, myocardial infarctions and vena caval thrombosis. Other complications included heparin-induced thrombocytopenia, redo of CABG surgery and sepsis. CONCLUSION: Despite aggressive anticoagulation and lack of significant pre-operative co-morbidities, APLS patients undergoing cardiothoracic surgery appear to have high rates of post-operative clinical events.     

Surgical results in bronchiectasis: analysis of 149 patients

Bronchiectasis remains a serious problem in developing countries. We reviewed the morbidity, mortality, and functional outcome of surgical treatment for bronchiectasis in our institution. Between 1992 and 2003, 149 patients (105 males, 44 females) underwent pulmonary resection for bronchiectasis. Their mean age was 33.7 years (range, 5-66 years). The indications for surgery were failure of conservative treatment in 59 (40%) patients, recurrent hemoptysis in 53 (36%), bronchial obstruction by a tumor in 9 (6%), and destroyed lung in 28 (19%). Bilateral disease was seen in 24 (16%) patients. Surgical treatment included pneumonectomy in 55 (37%) patients, lobectomy in 55 (37%), bilobectomy in 37 (25%), and lobectomy and/or segmentectomy in 2 (1%). There was one operative death (mortality, 0.67%) and morbidity occurred in 22 (14.8%) patients. Follow-up was complete in 94 patients, for a mean of 4.8 years (range, 3 months to 12 years). After surgery, 51 (34%) patients were asymptomatic. Surgical treatment for bronchiectasis can achieve good results with acceptable morbidity and mortality, not only in localized disease but also in extensive disease, if complete resection can be achieved.     

Evaluation of pharmaceutical excipients as cosolvents in 4-methyl umbelliferone glucuronidation in human liver microsomes: applications for compounds with low solubility

Standard incubation procedures for carrying out microsomal assays involve the use of less than 1% w/v organic solvents to minimize the potential inhibitory effects of organic solvents on metabolic activity. This presents a practical limitation for poorly soluble xenobiotics, which cannot be incubated at concentrations high enough to obtain a V(max), and therefore subsequent values for K(m) and Cl(int) cannot be calculated. Our goal was to study the application of a variety of pharmaceutical excipients to aid the solubilization of compounds in vitro in glucuronidation incubations, without affecting the reaction kinetics. In vitro glucuronidation incubations were carried out in human liver microsomes with 4-methylumbelliferone (4-MU) and the kinetics of 4-MU glucuronidation in the presence of excipients were compared to that in control incubations without any excipients. In addition, IC(75) values were calculated for each excipient. We observed that HPBCD (Hydroxypropyl-β-cyclodextrin) may be employed in in vitro glucuronidation incubations up to 0.5% w/v without affecting the Cl(int) of 4-MU. Although NMP (N-methyl-2-pyrrolidone) and DMA (N,N-dimethylacetamide); showed low IC(75) values approximately 0.1% w/v each, neither excipients altered the Cl(int) of 4-MUG (4-methylumbelliferyl-β-D-glucuronide) formation. Our studies point toward possible applications of pharmaceutical excipients to carry out in vitro glucuronidation of substrates with poor aqueous solubility, in order to estimate Cl(int) and subsequently scaled organ clearance values.