Doxorubicin-induced cardiotoxicity in adult Indian patients on chemotherapy

BACKGROUND: Doxorubicin-induced cardiotoxicity is widely known to occur at cumulative doses exceeding 450 mg/m(2). However, very few studies have reported incidence of cardiac dysfunction in patients on chemotherapy with lower cumulative doses. To the best of our knowledge, there is no study carried out so far that has reported the incidence of cardiac dysfunction in adult Indian patients receiving doxorubicin. This study was undertaken to determine the incidence of doxorubicin-induced cardiotoxicity by serial resting echocardiography in patients on chemotherapy and identify risk factors associated with cardiotoxicity. MATERIALS AND METHODS: Patients that were started on doxorubicin-based chemotherapy in the period from January 2000 to June 2001 and had completed at least 300 mg/m(2) cumulative dose were taken in the study. Electrocardiography, chest X-ray and echocardiography were done at baseline, at 300 mg/m(2) and at 450 mg/m(2) cumulative doses of doxorubicin. All patients were evaluated for the presence of the following risk factors: Age>70 years, female sex, preexisting cardiac disease, hypertension, chest wall irradiation, body mass index (BMI)<20 kg/m(2) , Karnofsky performance status, combination chemotherapy with cyclophosphamide and presence of liver disease. Subclinical cardiac dysfunction was defined as ejection fraction fall greater than 10% on follow-up echocardiography. RESULTS: Thirty patients satisfied the criterion for being considered for evaluation. One (3%) patient developed congestive cardiac failure, while 8 (27%) patients developed subclinical cardiac dysfunction. Concomitant use of cyclophosphamide significantly increased the risk of cardiac dysfunction (P = 0.048), while low BMI (<20 kg/m(2)) and preexisting cardiac disease showed a trend towards increased risk of cardiac dysfunction (P = 0.07 for both). CONCLUSION: Twenty-seven percent of the patients developed subclinical cardiac dysfunction in the cumulative dose range of 300-450 mg/m(2) . This entails regular monitoring for cardiac dysfunction by echocardiography during treatment

Late-onset hepatic veno-occlusive disease post autologous peripheral stem cell transplantation successfully treated with oral defibrotide

Hepatic veno-occlusive disease (VOD) remains one of the commonest and most serious complications after myeloablative hematopoietic stem cell transplantation (HSCT). Clinical diagnosis of hepatic VOD is based on the finding of the triad of painful hepatomegaly, hyperbilirubinemia, and unexplained fluid retention occurring within 21 days of the transplant. However, the uncommon clinical entity of late-onset VOD can occur even beyond 20 days and should be considered in the differential diagnosis of any liver disease of more than 3 weeks\u2032 duration. While mild cases usually resolve spontaneously, severe VOD is associated with a grim prognosis. Defibrotide, a polydisperse mixture of single-stranded oligonucleotide with antithrombotic and fibrinolytic effects on microvascular endothelium, has emerged as an effective and safe therapy for patients with severe VOD. We describe a patient who presented 55 days post transplant with clinical features suggestive of VOD. Upon treatment with oral defibrotide, he showed complete resolution of the VOD

Introduction of Situation, Background, Assessment, Recommendation into Nursing Practice: A Prospective Study

Objective: The aim of the study was to introduce and evaluate the compliance to documentation of situation, background, assessment, recommendation (SBAR) form. Methods: Twenty nurses involved in active bedside care were selected by simple random sampling. Use of SBAR was illustrated thru self-instructional module (SIM). Content validity and reliability were established. The situation, background, assessment, recommendation (SBAR) form was disseminated for use in a clinical setting during shift handover. A retrospective audit was undertaken at 1 st week (A1) and 16 th week (A2), post introduction of SIM. Nurse′s opinion about the SBAR form was also captured. Results : Majority of nurses were females (65%) in the age group 21-30 years (80%). There was a significant association (P = 0.019) between overall audit scores and graduate nurses. Significant improvement (P = 0.043) seen in overall scores between A1 (mean: 23.20) and A2 (mean: 24.26) and also in "Situation" domain (P = 0.045) as compared to other domains. There was only a marginal improvement in documentation related to patient′s allergies and relevant past history (7%) while identifying comorbidities decreased by 40%. Only 70% of nurses had documented plan of care. Most (76%) of nurses expressed that SBAR form was useful, but 24% nurses felt SBAR documentation was time-consuming. The assessment was easy (53%) to document while recommendation was the difficult (53%) part. Conclusions: SBAR technique has helped nurses to have a focused and easy communication during transition of care during handover. Importance and relevance of capturing information need to be reinforced. An audit to look for reduced number of incidents related to communication failures is essential for long-term evaluation of patient outcomes. Use of standardized SBAR in nursing practice for bedside shift handover will improve communication between nurses and thus ensure patient safety

Study of stem cell homing & self-renewal marker gene profile of ex vivo expanded human CD34+ cells manipulated with a mixture of cytokines & stromal cell-derived factor 1

Background & objectives: Next generation transplantation medicine aims to develop stimulating cocktail for increased ex vivo expansion of primitive hematopoietic stem and progenitor cells (HSPC). The present study was done to evaluate the cocktail GF (Thrombopoietin + Stem Cell factor + Flt3-ligand) and homing-defining molecule Stromal cell-derived factor 1 (SDF1) for HSPC ex vivo expansion. Methods: Peripheral blood stem cell (n=74) harvests were analysed for CD34hiCD45lo HSPC. Immunomagnetically enriched HSPC were cultured for eight days and assessed for increase in HSPC, colony forming potential in vitro and in vivo engrafting potential by analyzing human CD45+ cells. Expression profile of genes for homing and stemness were studied using microarray analysis. Expression of adhesion/homing markers were validated by flow cytometry/ confocal microscopy. Results: CD34hiCD45lo HSPC expansion cultures with GF+SDF1 demonstrated increased nucleated cells (n=28, P< 0.001), absolute CD34+ cells (n=8, P=0.021) and increased colony forming units (cfu) compared to unstimulated and GF-stimulated HSPC. NOD-SCID mice transplanted with GF+SDF1-HSPC exhibited successful homing/engraftment (n=24, P< 0.001). Microarray analysis of expanded HSPC demonstrated increased telomerase activity and many homing-associated genes (35/49) and transcription factors for stemness/self-renewal (49/56) were significantly upregulated in GF+SDF1 stimulated HSPC when compared to GF-stimulated HSPC. Expression of CD44, CXCR4, CD26, CD14, CD45 and soluble IL-6 in expanded cultures were validated by flow cytometry and confocal microscopy. Interpretation & conclusions: Cocktail of cytokines and SDF1 showed good potential to successfully expand HSPC which exhibited enhanced ability to generate multilineage cells in short-term and long-term repopulation assay. This cocktail-mediated stem cell expansion has potential to obviate the need for longer and large volume apheresis procedure making it convenient for donors