Defibrotide for the treatment of hepatic veno-occlusive disease: results of the European compassionate-use study

Severe hepatic veno-occlusive disease (VOD) is a recognized complication of autologous and allogeneic stem cell transplantation (SCT) that is often fatal. Defibrotide (DF) is a polydeoxyribonucleotide that has been found to have anti-thrombotic, anti-ischaemic and thrombolytic properties without causing significant anticoagulation. Preliminary studies have demonstrated activity for DF in the treatment of VOD, with minimal associated toxicity. In the present study, 40 patients who fulfilled established criteria for VOD were treated with DF on compassionate grounds in 19 European centres; 28 patients met risk criteria predicting progression of VOD and fatality or had evidence of multiorgan failure (MOF), and were defined as 'poor-risk'. DF was commenced intravenously at a median of 14 d (range, -2 d to 53 d) post SCT at doses ranging from 10 to 40 mg/kg. The median duration of therapy was 18 d (range, 2--71 d). Twenty-two patients showed a complete response (CR) (bilirubin < 34.2 micromol/l and resolution of signs/symptoms of VOD and end-organ dysfunction) [CR = 55%, confidence interval (CI) 40--70%] and 17 patients (43%) are alive beyond d +100. Ten poor-risk patients showed a complete response (CR = 36%, CI 21--51%). These results demonstrate that DF is an active treatment for VOD following SCT and a randomized trial is now underway in order to further evaluate its role.     

In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation

A novel nonmyeloablative conditioning regimen was investigated in 44 patients with hematologic malignancies. The median patient age was 41 years. Many of the patients had high-risk features, including 19 patients with a previous failed transplant. Recipient conditioning consisted of CAMPATH-1H, 20 mg/day on days -8 to -4; fludarabine, 30 mg/m(2) on days -7 to -3; and melphalan, 140 mg/m(2) on day -2. Thirty-six recipients received unmanipulated granculocyte colony-stimulating factor-mobilized peripheral blood stem cells from HLA-identical siblings, and 8 received unmanipulated marrow from matched unrelated donors. GVHD prophylaxis was with cyclosporine A alone for 38 patients and cyclosporine A plus methotrexate for 6 sibling recipients. Forty-two of the 43 evaluable patients had sustained engraftment. Results of chimerism analysis using microsatellite polymerase chain reaction indicate that 18 of 31 patients studied were full-donor chimeras while the other patients were mixed chimeras in one or more lineages. At a median follow-up of 9 months (range 3 to 29 months), 33 patients remain alive in complete remission or with no evidence of disease progression. Seven patients relapsed or progressed post-transplantation, and 4 of them subsequently died. Four patients died of regimen-related complications. There were no cases of grades III-IV acute GVHD. Only 2 patients developed grade II acute GVHD, and only 1 had chronic GVHD. The estimated probability of nonrelapse mortality was 11%. Although longer follow-up is needed to establish the long-term remission rates, this study demonstrates that this nonmyeloablative preparative regimen is associated with durable engraftment, minimal toxicity, and low incidence of GVHD.     

Left internal mammary artery to pulmonary vasculature fistulae closed with particle embolizaton: new form of percutaneous intervention

The left internal mammary artery is frequently employed as a conduit in coronary bypass surgery. We report a 42-year-old male post-coronary artery bypass grafting patient with, angina on exertion who was found to have multiple atrioventricular fistulae arising from left internal mammary artery to pulmonary vasculature leading to coronary steal and positive stress thallium in left anterior descending territory. These fistulae were selectively embolized with polymer particles leading to improved flow in distal left anterior descending artery. Postintervention, the patient has been asymptomatic for more than 8 months.     

Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4- hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL.     

Every death counts: use of mortality audit data for decision making to save the lives of mothers, babies, and children in South Africa

South Africa is one of the few developing countries with a national confidential inquiry into maternal deaths. 164 health facilities obtain audit data for stillbirths and neonatal deaths, and a new audit network does so for child deaths. Three separate reports have been published, providing valuable information about avoidable causes of death for mothers, babies, and children. These reports make health-system recommendations, many of which overlap and are intertwined with the scarcity of progress in addressing HIV/AIDS. The leaders of these three reports have united to prioritise actions to save the lives of South Africa's mothers, babies, and children. The country is off-track for the health-related Millennium Development Goals. Mortality in children younger than 5 years has increased, whereas maternal and neonatal mortality remain constant. This situation indicates the challenge of strengthening the health system because of high inequity and HIV/AIDS. Coverage of services is fairly high, but addressing the gaps in quality and equity is essential to increasing the number of lives saved. Consistent leadership and accountability to address crosscutting health system and equity issues, and to prevent mother-to-child transmission of HIV, would save tens of thousands of lives every year. Audit is powerful, but only if the data lead to action.     

Comparative evaluation of 2-point vs 3-point fixation in the treatment of zygomaticomaxillary complex fractures – A systematic review

BackgroundThe zygomaticomaxillary complex (ZMC) functions as the main buttress for the lateral portion of the middle third of the facial skeleton and because of its prominent position & convex shape, it is frequently fractured, alone or along with other bones of the midface. The management of the ZMC fractures is debatable as the literature is saturated with various theories. A number of techniques, from closed reduction to open reduction and internal fixation can be effectively used to manage these fractures. Controversies lie right from the amount of fixation (1-, 2-, 3- or 4- point fixation) required to the ideal approach, and there is no conclusive view on its ideal line of management.ObjectiveTo compare Malar asymmetry after 2-point vs 3-point fixation in the treatment of zygomaticomaxillary complex fractures.Data sourceElectronic search of Pub Med, Google Scholar, Institutional Library, Email to authors and manual search of various journals.Study eligibility criteriaThe following criteria were used to select the studies on 2- point and 3-point fixation methods in Zygomaticomaxillary complex fractures. Inclusion criteria had articles that included clinical studies published in the English language or those having sufficient data in English on 2-point or 3-point fixation in the treatment of zygomaticomaxillary complex fractures between the period of 1st January 2008 to 30th September 2018. While exclusion criteria were articles not published in the English language before 1st January 2008 and after 30th September 2018, any reviews, abstracts, letters to editors, editorials and in vitro studies were excluded. Studies that included patients with craniofacial and secondary deformities were also excluded.InterventionOpen reduction and internal fixation using 2-point and 3-point fixation methods in the treatment of Zygomaticomaxillary complex fractures.ResultsPreliminary screening consisted of 757 studies and additional records identified through other sources of 272 studies. Amongst these 1029 studies, 837 studies were excluded after reviewing the titles. A review of abstract further excluded 71 studies, so 34 studies that remained were evaluated to fit the eligibility criteria. On the basis of information on fixation methods and parameters of evaluation of fixation method, 26 studies were further excluded. Thus 8 studies with a total of 823 estimates were included in qualitative synthesis.LimitationsParameters assessed by all the authors varied and hence a standardisation for comparison could not be done.ConclusionFive out of eight studies showed that the use of 3-point fixation in the treatment of zygomaticomaxillary complex fractures was superior than 2-point fixation for the same. Hence it can be concluded that 3-point fixation is superior than 2-point fixation in reducing malar asymmetry in zygomaticomaxillary complex fractures.Future implicationsFuture studies with uniform parameters being assessed can be done. 3-point fixation can be used as a standard treatment modality in the effective management of Zygomaticomaxillary complex fractures.