Leukocyte-reduced transfusions in cardiac surgery results of an implementation trial

An implementation trial of leukocyte-reduced transfusions in cardiac surgery (primary coronary artery bypass graft and valve replacement) was performed from July to December 1998; comparisons were made with data from the same period in 1997. Patients from both periods were similar in important preoperative and intraoperative variables (age, sex, weight, number of units of RBCs transfused, ejection fraction). The mean total number of complications was statistically significantly decreasedfrom 0.26 complications per patient in the non-leukocyte-reduced to 0.19 in the leukocyte-reduced recipients. Overall, the mean +/- ISD costs of care per patient decreasedfrom 1997 ($27,615 +/- $33,973) to 1998 ($27,038 +/- $24,107). Mean costs decreased $1,700 per patient for recipients of leukocyte-reduced blood in 1998 compared with recipients of non-leukocyte-reduced blood in 1997 Mean costs increased $4,000 per patient in patients who did not receive transfusions in 1998 compared with 1997. Hospitalization costs decreased when leukocyte-reduced transfusions were implemented for patients undergoing cardiac surgery in our institution. Implementation of leukocyte reduction may be cost neutral or cost saving in at least some settings.     

Clinicopathological patterns of bladder carcinoma over 1 year: experience from University Hospital of Nepal

Purpose

To define the clinical and pathological patterns of urinary bladder carcinoma from the University Hospital of Nepal.

Methods

This is a retrospective analytical study. Patients with bladder mass who underwent surgery over 1 year and who had data record were included in the study. Demographic profile, type of surgery, findings on clinical examination, cystoscopy findings, histopathological report, tumor stage, and post-surgery adjuvant therapy were analyzed.

Results

Out of 86 patients who underwent transurethral resection of bladder tumor, 77 patients had biopsy-proven malignant bladder tumor. Urothelial cancer was present in 96.1%. Male were 78.6%. The mean age of diagnosis was 65.5?±?11.8 years. Non-muscle-invasive bladder cancer (NMIBC) was 3.7 times more common than muscle-invasive bladder cancer (MIBC). High-grade tumors (58.6%) were more common than low grade (41.4%). The detrusor muscle was present inthe biopsy specimen of 48 patients (64%). Re-TURBT within 2–6 weeks was considered based on histopathology reports for about half of the patients (45.3%). Upstaging and upgrading of the tumor was present in 5.8 and 5.8% of the patients, respectively. Residual tumor without upstaging and upgrading was present in 23.5%. One patient (1.3%) had Clavien–Dindo grade 1, three (4%) patients had grade 2 and two patients (2.7%) had grade 3b.

Conclusion

In the present study, patients with bladder cancer are younger than reported in other studies. Smokers are strongly predisposed. The histological pattern is similar to the Western and Asian populations. NMIBC and MIBC occur in proportion to that described as in other studies. We had a lower rate of recurrence, upstaging and upgrading. We had a lesser rate of acceptance for radical cystectomy in our patients.

     

Influence of the cardioprotective agent dexrazoxane on doxorubicin pharmacokinetics in the dog

Summary The influence of dexrazoxane on doxorubicin pharmacokinetics was investigated in four dogs using the two treatment sequences of saline/doxorubicin or dexrazoxane/doxorubicin. Intravenous doses of 1.5 mg/kg doxorubicin and 30 mg/kg (the 20-fold multiple) dexrazoxane were given separately, with doxorubicin being injected within 1 min of the dexrazoxane dose. Both doxorubicin and its 13-dihydro metabolite doxorubicinol were quantified in plasma and urine using a validated high-performance liquid chromatographic (HPLC) fluorescence assay. The doxorubicin plasma concentration versus time data were adequately fit by a three-compartment model. The mean half-lives calculated for the fast and slow distributive and terminal elimination phases in the saline/doxorubicin group were 3.0±0.5 and 32.2±12.8 min and 30.0±4.0 h, respectively. The model-predicted plasma concentrations were virtually identical for the saline and dexrazoxane treatment groups. Analysis of variance of the area under the plasma concentration-time curve (AUC_0–), terminal elimination rate (_Z), systemic clearance (CL _s), and renal clearance (CL _r) for the parent drug showed no statistically significant difference (P<0.05) between the two treatments. Furthermore, the doxorubicinol plasma AUC_0– value and the doxorubicinol-to-doxorubicin AUC_0– ratio showed no significant difference, demonstrating that dexrazoxane had no effect on the metabolic capacity for formation of the 13-dihydro metabolite. The total urinary excretion measured as parent drug plus doxorubicinol and the metabolite-to-parent ratio in urine were also unaffected by the presence of dexrazoxane. The myelosuppressive effects of doxorubicin as determined by WBC monitoring revealed no apparent difference between the two treatments. In conclusion, these results show that drug exposure was similar for the two treatment arms. No kinetic interaction with dexrazoxane suggests that its coadministration is unlikely to modify the safety and/or efficacy of doxorubicin.     

15th International Symposium on Pediatric Surgical Research

Pediatric Surgery International -     

Consensus guidelines on pediatric acute rheumatic fever and rheumatic heart disease

JUSTIFICATION: Acute rheumatic fever and rheumatic chronic valvular heart disease is an important preventable cause of morbidity and mortality in suburban and rural India. Its diagnosis is based on clinical criteria. These criteria need verification and revision in the Indian context. Furthermore, there are glaring differences in management protocols available in literature. These facts prompted Indian Academy of Pediatrics to review the management of rheumatic fever. PROCESS: Management of Rheumatic fever was reviewed and recommendation was formulated at national consultative meeting on 20th May 2007 at New Delhi. OBJECTIVES: To formulate uniform guidelines on management of acute rheumatic fever and rheumatic heart disease in the Indian context. Guidelines were formulated for the management of streptococcal pharyngitis, acute rheumatic fever and its cardiac complication as well as secondary prophylaxis for recurrent episodes. RECOMMENDATIONS: (1) Streptococcal eradication with appropriate antibiotics (Benzathine penicillin single dose or penicillin V oral or azithromycin). (2) Diagnosis of rheumatic fever based on Jones criteria. (3) Control inflammatory process with aspirin with or without steroids (total duration of treatment of 12 weeks). (4) Treatment of chorea according to severity (therapy to continue for 2-3 weeks after clinical improvement). (5) Protocol for managing cardiac complication like valvular heart disease, congestive heart failure and atrial fibrillation. (6) Secondary prophylaxis with benzathine penicillin and management of anaphylaxis.     

Disturbance of SHH signalling pathway during early embryogenesis in the cadmium-induced omphalocele chick model

Introduction

Administration of cadmium (Cd) after 60 h (H) incubation induces ventral body wall defect (VBWD) similar to the omphalocele phenotype in the chick embryo. In this model, the earliest histological changes have been observed in somites commencing at 4-h post-treatment (4H). The molecular mechanism by which Cd acts in this critical period of embryogenesis still remains unclear. Sonic hedgehog (SHH) signalling plays an important role in vertebrate development, including somitogenesis and thus ventral body wall formation. Patched (PTCH), a cell membrane receptor for SHH, is expressed in somites and Patched knockout mice display somite dysfunction. Another transmembrane receptor, Smoothened (SMO), is also expressed in somites and transduces the SHH signal regulated by PTCH. We designed this study to test the hypothesis that SHH signalling is downregulated during the critical period of early embryogenesis in the Cd-induced omphalocele chick model.

Methods

After 60 h of incubation, chicks were exposed to either chick saline or 50 μL of 50 μM cadmium acetate and divided into two groups: control and Cd (n = 24 for each group). Chicks were harvested 1, 4, and 8 h post-treatment. Real-time RT-PCR was performed to evaluate the relative mRNA expression level of SHH, PTCH and SMO. Immunofluorescence confocal microscopy was then performed to evaluate protein expression/distribution of SHH, PTCH and SMO.

Results

The relative mRNA expression levels of SHH, PTCH and SMO were significantly downregulated in the Cd group compared to controls at 4H post treatment, whereas, there were no significant differences at the other time points. Immunohistochemistry revealed that the intensity of SHH, PTCH and SMO was markedly diminished at 4 h in Cd-treated embryos compared to controls.

Conclusion

Disturbance of the SHH signalling pathway as evidenced by SHH, PTCH and SMO downregulation during the narrow window of early embryogenesis may result in somite maldevelopment, contributing to the omphalocele phenotype in the Cd chick model.     

Point-of-care hepatitis C screening with direct access referral to improve linkage to care among halfway house residents: a pilot randomised study

INTRODUCTIONLinkage to care among individuals with substance misuse remains a barrier to the elimination of the hepatitis C virus (HCV). We aimed to determine whether point-of-care (PoC) education, screening and staging for liver disease with direct access to hospitals would improve linkage to care among this group.METHODSAll participants were offered PoC education and HCV screening. HCV-positive participants were randomised to standard care (controls) or direct access, which provided a direct pathway to hospitals. Linkage to care was determined by reviewing electronic medical records. Linkage of care cascade was defined as attendance at the specialist clinic, confirmation of viraemia by HCV RNA testing, discussion about HCV treatment and initiation of treatment.RESULTS351 halfway house residents were screened. The overall HCV prevalence was 30.5% (n = 107), with 69 residents in the control group and 38 in the direct access group. The direct access group had a significantly higher percentage of cases linked to specialist review for confirmatory RNA testing (63.2% vs. 40.6%, p = 0.025), HCV treatment discussion (p = 0.009) and treatment initiation (p = 0.01) compared to the controls. Overall, only 12.6% (n = 13) had treatment initiation during follow-up. PoC HCV screening with direct access referral had significantly higher linkage to HCV treatment initiation (adjusted odds ratio 9.13, p = 0.005) in multivariate analysis.CONCLUSIONPoC HCV screening with direct access improves linkage to care and simplifies the HCV care cascade, leading to improved treatment uptake. PoC education, screening, diagnosis and treatment may be an effective strategy to achieving HCV micro-elimination in this population.     

Elucidation of the mechanism of mitochondrial iron loading in Friedreich's ataxia by analysis of a mouse mutant

We used the muscle creatine kinase (MCK) conditional frataxin knockout mouse to elucidate how frataxin deficiency alters iron metabolism. This is of significance because frataxin deficiency leads to Friedreich''s ataxia, a disease marked by neurologic and cardiologic degeneration. Using cardiac tissues, we demonstrate that frataxin deficiency leads to down-regulation of key molecules involved in 3 mitochondrial utilization pathways: iron-sulfur cluster (ISC) synthesis (iron-sulfur cluster scaffold protein1/2 and the cysteine desulferase Nfs1), mitochondrial iron storage (mitochondrial ferritin), and heme synthesis (5-aminolevulinate dehydratase, coproporphyrinogen oxidase, hydroxymethylbilane synthase, uroporphyrinogen III synthase, and ferrochelatase). This marked decrease in mitochondrial iron utilization and resultant reduced release of heme and ISC from the mitochondrion could contribute to the excessive mitochondrial iron observed. This effect is compounded by increased iron availability for mitochondrial uptake through (i) transferrin receptor1 up-regulation, increasing iron uptake from transferrin; (ii) decreased ferroportin1 expression, limiting iron export; (iii) increased expression of the heme catabolism enzyme heme oxygenase1 and down-regulation of ferritin-H and -L, both likely leading to increased “free iron” for mitochondrial uptake; and (iv) increased expression of the mammalian exocyst protein Sec15l1 and the mitochondrial iron importer mitoferrin-2 (Mfrn2), which facilitate cellular iron uptake and mitochondrial iron influx, respectively. Our results enable the construction of a model explaining the cytosolic iron deficiency and mitochondrial iron loading in the absence of frataxin, which is important for understanding the pathogenesis of Friedreich''s ataxia.     

Autochthonous hepatitis E in Southwest England: natural history, complications and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease

AIMS: To report the natural history of autochthonous hepatitis E and hepatitis E virus (HEV) IgG seroprevalence in Southwest England. METHODS: Patients with unexplained hepatitis were tested for hepatitis E and cases followed until recovery or death. Five hundred blood donors, 336 individuals over the age of 60 years and 126 patients with chronic liver disease were tested for HEV IgG. RESULTS: Forty cases of autochthonous hepatitis E (genotype 3) were identified. Hepatitis E was anicteric in 25% of cases and usually caused a self-limiting hepatitis predominantly in elderly Caucasian males. Six of 40 had a significant complication and three patients died, two of who had previously undiagnosed cirrhosis. Hepatitis E shows a seasonal variation with peaks in the spring and summer and no cases in November and December. HEV IgG prevalence increases with age, is more common in men and is 16% in blood donors, 13% in patients with chronic liver disease and 25% in individuals over 60 years. CONCLUSION: Autochthonous hepatitis E is more common than previously recognized, and should be considered in the differential diagnosis in patients with hepatitis, whatever their age or travel history. It carries a significant morbidity and when seen in the context of chronic liver disease carries an adverse prognosis.     

Prevention and reversal of LV remodeling with neurohormonal inhibitors

Opinion statement Left ventricular (LV) remodeling refers to alterations in ventricular mass, chamber size, and shape that result from myocardial injury, pressure, or volume overload. Numerous studies have demonstrated that LV remodeling correlates with the incidence of heart failure and death, supporting a causative role for remodeling in heart failure progression. Heart failure trials have shown that neurohormonal antagonists, including angiotensin-converting enzyme (ACE) inhibitors and β-adrenergic receptor blockers (β blockers), reduce remodeling in parallel with improved clinical outcomes. Existing data favor using angiotensin II type 1 (AT1) receptor antagonists (or “ARBs”), although their anti-remodeling effects are less well established. Recently, mineralocorticoid receptor antagonists have gained substantial interest based on favorable clinical trial results, although data regarding their effects on remodeling are limited. Thus, an optimal medical regimen to prevent or limit LV remodeling in patients with LV dysfunction should include both an ACE inhibitor and β-adrenergic receptor antagonist, irrespective of the degree of LV dysfunction and symptom status. For patients intolerant to ACE inhibitors, an AT1 receptor antagonist should be substituted. An aldosterone antagonist should be administered to patients with severe, New York Heart Association class III to IV heart failure who have normal or only mildly impaired renal function, or to those patients with depressed LV function following an acute myocardial infarction. Through the aggressive pharmacologic inhibition of both the renin-angiotensin-aldosterone and sympathetic nervous systems, progressive LV remodeling can be prevented or hindered, thereby favorably altering the natural history of the heart failure syndrome.