Improving Outcome of Thalassemia with Hematopoetic Stem Cell Transplantation: An Experience of Gujarat Cancer Research Institute

Total 26 children of thalassemia underwent hematopoetic stem cell transplantation from September 2006 to December 2014. Out of these 17 were matched sibling transplantation (MST) and 9 were unrelated umbilical cord blood transplantation (UCT). Median age was 4 years. At a median follow up of 46.5 months, 12 of 17 (70 %) MST and 3 out of 9 (33.33 %) UCT were cured of thalassemia. Three (11.53 %) patients died due to transplant related mortality. Average cost of MST was 6 lakhs and that of UCT was 20 lakhs.     

Unmanipulated Stem Cell Boost for Mixed Chimerism in Transfusion Dependent Thalassemia

Early mixed chimerism (MC) can lead to secondary graft rejection post allogeneic hematopoietic stem cell transplantation in transfusion dependent thalassemia (TDT) patients. Reduction of immunosuppression and donor lymphocyte infusions is the mainstay for treating MC. We report our experience of administering unmanipulated stem cell boost (SCB) in reversing progressive early MC. There were 70 transplants done for 69 TDT patients at our center between September 2005 and January 2020. Mixed chimerism was defined by > 5% recipient cells and the severity was assigned according to the proportion of recipient cells as level 1 =  < 10%, level 2 = 10–25%, level 3 =  > 25%. For patients developing MC level 2 and 3, we administered unmanipulated SCB and analyzed its safety and efficacy. Out of 70 transplants 7 (10%) had MC level 2 (3/7) and 3 (4/7). These patients received unmanipulated SCB at a median CD34 cell dose of 4.5 × 10⁶/kg (range—3.5 × 10⁶/kg–5.5 × 10⁶/kg). Overall Response (stable MC and/or transfusion independency) to unmanipulated SCB was seen in 5 patients (71.4%). Five patients (71.4%) developed acute graft versus host disease (GVHD) of which 1 patient expired due to severe GVHD. SCB infusion was well tolerated by majority of our patients. The 3 year overall survival and thalassemia free survival was 85.7% (6/7) and 57.1% (4/7) respectively. Timely monitoring of chimerism is important for detecting early MC. Development of acute GVHD is common after administration of unmanipulated SCB and requires vigilance and prompt management. Unmanipulated SCB is a feasible modality for treating progressive MC and salvaging the graft especially in resource-constrained settings.     

Different Interleukin-1β Converting Enzyme (ICE) Family Protease Requirements for the Apoptotic Death of T Lymphocytes Triggered by Diverse Stimuli

Two cell permeable peptide fluoromethyl ketone inhibitors of Interleukin-1β converting enzyme (ICE) family proteases were tested as inhibitors of apoptotic cell death of T lymphocytes at various stages of differentiation. The CPP-32–like protease activity in apoptotic cell lysates was blocked by both the ICE inhibitor Cbz-Val-Ala-Asp(OMe)-fluoromethyl ketone (ZVADFMK) as well as its truncated analog Boc-Asp(OMe)-fluoromethyl ketone (BD-FMK), which failed to block ICE. In vitro apoptotic death in murine thymocytes triggered by the independent agents dexamethasone, etoposide, radiation, anti-Fas, and anti-CD3 was blocked equally well by BD-FMK and ZVAD-FMK, but not by the control reagent Cbz-Phe-Ala-fluoromethyl ketone. In activated T cell blasts, while anti-CD3/ Fas-induced death was almost completely inhibited by both ZVAD-FMK and BD-FMK, death induced by dexamethasone, etoposide, or irradiation was more sensitive to inhibition by BD-FMK. In the murine T cell line CTLL-2, apoptotic death induced by IL-2 withdrawal, etoposide, or dexamethasone was inhibited by BD-FMK, while ZVAD-FMK was without effect. These data indicate that ICEfamily proteases comprise a common functional step in distinct T cell apoptotic death pathways, but suggest that different family members are likely to be critical in various differentiated T cell types, even when triggered by the same stimulus.     

Preserved or slightly depressed ejection fraction and outcomes after myocardial infarction

BACKGROUND Left ventricular ejection fraction (EF) in post-myocardial infarction (MI) patients is a strong predictor of adverse cardiovascular events. Although resting EF as measured by transthoracic echocardiography (TTE), contrast ventriculography (CNV), and radionuclide angiography (RNA) exhibit high correlation, there is only modest agreement between these modalities. This study sought to explore whether modality of EF assessment influences prognostication of post-MI patients with normal or slightly reduced EF. METHODS AND RESULTS The National Heart, Lung, and Blood Institute (NHLBI) limited access dataset of the Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial (1996-2003, n=8290) comparing trandolapril versus placebo was used. The cohort was partitioned into TTE (n=2582), RNA (n=816), and CNV (n=1155) groups based on modality of EF assessment. EF was a significant predictor of cardiovascular mortality (HR 0.97, 95% CI 0.95 to 0.98; p<0.005) and all cause mortality (HR 0.98, 95% CI 0.97 to 0.99; p=0.0002) on multivariate analysis in this population with preserved or mildly depressed EF. Although CNV, TTE, and RNA groups differed significantly in terms of baseline variables, no appreciable differences were noted between RNA (HR 1.13, 95% CI 0.85 to 1.50; ns) and CNV (HR 1.13, 95% CI 0.99 to 1.27; ns) groups, compared with TTE for all cause mortality. Similarly, no significant differences were observed for cardiovascular mortality between RNA (HR 1.23, 95% CI 0.82 to 1.84; p=0.31) and CNV (HR 1.14, 95% CI 0.78 to 1.67, p=0.49) versus TTE. CONCLUSION EF is a significant predictor of all-cause mortality and cardiovascular mortality in patients with preserved or mildly depressed EF. Modalities of EF measurement are interchangeable and do not play a significant role in prognostication in a post-MI population.     

The PDA as a reference tool: libraries' role in enhancing nursing education

"The PDA as a Reference Tool: The Libraries' Role in Enhancing Nursing Education" is a pilot project funded by the University of Massachusetts President's Office Information Technology Council through their Professional Development Grant program in 2004. The project's goal is to offer faculty and students in nursing programs at two University of Massachusetts campuses access to an array of medical reference information, such as handbooks, dictionaries, calculators, and diagnostic tools, on small handheld computers called personal digital assistants. Through exposure to the variety of information resources in this digital format, participants can discover and explore these resources at no personal financial cost. Participants borrow handhelds from the University Library's circulation desks. The libraries provide support in routine resynchronizing of handhelds to update information. This report will discuss how the projects were administered, what we learned about what did and did not work, the problems and solutions, and where we hope to go from here.     

Japanese Encephalitis: A Persistent Threat

Japanese encephalitis virus (JEV) belongs to arthropod-borne virus family, which are infectious agents transmitted by blood-sucking arthropods. They multiply in the tissues of the arthropod without evidence of disease or damage. The principal vector is Culex mosquito, most important being C. tritaenorhynchus, which is a rural mosquito, breeding extensively in rice fields and bites large domestic animals. In temperate zones, this vector is present in greatest density from June to November. The natural cycle of JEV consists of pig?Cmosquito?Cpig or bird?Cmosquito?Cbird cycle. Pigs serve as most important biological amplifiers and reservoirs. JEV is transmitted to humans through the bites of infected mosquitoes. Humans are accidental, dead-end hosts as they do not develop a level of viraemia sufficient to infect mosquitoes. The infection with JEV ranges from nonspecific febrile illness to a severe meningoencephalomyelitis illness. The risk for Japanese encephalitis varies by local ecology and season. In temperate areas of Asia, human disease usually peaks in summer and falls down after that and these seasonal epidemics can be explosive with thousands of cases occurring over a period of several months; whereas, in the subtropics and tropics, transmission can occur throughout the year, with disease at a peak during rainy season. A detailed study has been done on geographic distribution of JEV and incidence and burden of disease in India. Vaccination proves to be the best measure to protect the individual against any disease. So, large scale immunization of susceptible human population is highly important to prevent this deadly infection. In India, vaccinations against Japanese encephalitis are administered in areas where the disease is hyperendemic.