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BACKGROUND - Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care.
METHODS - In this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct.
RESULTS - A total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04).
CONCLUSIONS - Regular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.).
The HIV epidemic in higher-income nations is driven by receptive anal intercourse, injection drug use through needle/syringe sharing, and, less efficiently, vaginal intercourse. Alcohol and noninjecting drug use increase sexual HIV vulnerability. Appropriate diagnostic screening has nearly eliminated blood/blood product-related transmissions and, with antiretroviral therapy, has reduced mother-to-child transmission radically. Affected subgroups have changed over time (e.g., increasing numbers of Black and minority ethnic men who have sex with men). Molecular phylogenetic approaches have established historical links between HIV strains from central Africa to those in the United States and thence to Europe. However, Europe did not just receive virus from the United States, as it was also imported from Africa directly. Initial introductions led to epidemics in different risk groups in Western Europe distinguished by viral clades/sequences, and likewise, more recent explosive epidemics linked to injection drug use in Eastern Europe are associated with specific strains. Recent developments in phylodynamic approaches have made it possible to obtain estimates of sequence evolution rates and network parameters for epidemics.
AIM - To evaluate the relationship between liver stiffness and duration of infection in blood transfusion-associated hepatitis C virus (HCV) patients with or without hepatocellular carcinoma (HCC).
METHODS - Between December 2006 and June 2008, a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled. Liver stiffness was obtained noninvasively by using Fibroscan (Echosens, Paris, France). The date of blood transfusion was obtained by interview. Duration of infection was derived from the interval between the date of blood transfusion and the date of liver stiffness measurement (LSM). Patients were stratified into four groups based on the duration of infection (17-29 years; 30-39 years; 40-49 years; and 50-70 years). The difference in liver stiffness between patients with and without HCC was assessed in each group. Multiple linear regression analysis was used to determine the factors associated with liver stiffness.
RESULTS - A total of 524 patients underwent LSM. Eight patients were excluded because of unsuccessful measurements. Thus 516 patients were included in the current analysis (225 with HCC and 291 without). The patients were 244 men and 272 women, with a mean age of 67.8 ± 9.5 years. The median liver stiffness was 14.3 kPa (25.8 in HCC group and 7.6 in non-HCC group). The patients who developed HCC in short duration of infection were male dominant, having lower platelet count, with a history of heavier alcohol consumption, showing higher liver stiffness, and receiving blood transfusion at an old age. Liver stiffness was positively correlated with duration of infection in patients without HCC (r = 0.132, P = 0.024) but not in patients with HCC (r = -0.103, P = 0.123). Liver stiffness was significantly higher in patients with HCC than in those without in each duration group (P < 0.0001). The factors significantly associated with high liver stiffness in multiple regression were age at blood transfusion (P < 0.0001), duration of infection (P = 0.0015), and heavy alcohol consumption (P = 0.043).
CONCLUSION - Although liver stiffness gradually increases over time, HCC develops in patients with high stiffness value regardless of the duration of infection.
Iron overload is a major toxicity of chronic transfusions. Myocardial iron overload is associated with cardiac dysfunction. Cardiac and liver magnetic resonance imaging (MRI) was performed on 14 chronically transfused sickle cell disease (SCD) and non-sickle cell disease (non-SCD) patients seen at Vanderbilt Children's Hospital from 1 January 2000 to 10 March 2010. Retrospective review was conducted to assess cardiac T2*, liver T2*, ventricular dimensions and function, echocardiogram, length of transfusion, hemoglobin, and ferritin measurements. Ten patients had SCD and 4 had non-SCD, including α-thalassemia, β-thalassemia, and Diamond-Blackfan anemia. Cardiac T2* was normal in all SCD patients (mean 39 ± 12 ms), but abnormal in 3 of 4 non-SCD patients (mean 11.8 ± 2.4 ms). Liver T2* was similar between SCD (mean 6.2 ± 1.6 ms) and non-SCD patients (mean 5.9 ± 1.9 ms), and did not correlate with serum ferritin. Comparing SCD and non-SCD patients with similar transfusion duration, SCD patients had normal cardiac T2* and non-SCD patients had abnormal cardiac T2*. No patients had cardiomyopathy, but ventricular dilatation was common among SCD patients. Chronically transfused pediatric SCD patients are relatively spared of myocardial iron overload, which is unlikely to be due to lower total body iron burden in SCD patients than non-SCD patients.
BACKGROUND AND OBJECTIVES - Acute kidney injury (AKI) is a frequent complication in critically ill patients and sepsis is the most common contributing factor. We aimed to determine the risk factors associated with AKI development in patients with septic shock.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS - Observational cohort study consisted of consecutive adults with septic shock admitted to a medical intensive care unit (ICU) of a tertiary care academic hospital from July 2005 to September 2007. AKI was defined according to RIFLE criteria (urine output and creatinine criteria). Demographic, clinical, and treatment variables were reviewed. Main outcomes measured were AKI occurrence, all-cause hospital mortality, and hospital and ICU length of stay.
RESULTS - Three hundred ninety patients met inclusion criteria, of which 237 (61%) developed AKI. AKI development was independently associated with delay to initiation of adequate antibiotics, intra-abdominal sepsis, blood product transfusion, use of angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker, and body mass index (kg/m²). Higher baseline GFR and successful early goal directed resuscitation were associated with a decreased risk of AKI. Hospital mortality was significantly greater in patients who developed AKI (49 versus 34%).
CONCLUSIONS - In a contemporary cohort of patients with septic shock, both patient and health care delivery risk factors seemed to be important for AKI development.
BACKGROUND - Risk factors for the development of acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) include positive fluid balance, high tidal volumes (TVs), high airway pressures, and transfusion of blood products. However, research examining intraoperative factors such as fluid resuscitation, mechanical ventilation strategies, and blood administration on the postoperative development of ARDS is lacking.
METHODS - We assessed patients admitted to the ICU with postoperative hypoxemic respiratory failure requiring mechanical ventilation for the development of ARDS in the first 7 postoperative days using established clinical and radiological criteria. Data on risk factors for ARDS were obtained from the electronic anesthetic and medical records. Logistic regression was used to examine the independent association between fluid resuscitation, TV per ideal body weight, and number of blood products transfused during surgery and the postoperative development of ARDS, adjusting for important clinical covariates.
RESULTS - Of the 89 patients with postoperative respiratory failure, 25 developed ARDS. Compared with those who received <10 mL/kg/h fluid resuscitation in the operating room, patients receiving >20 mL/kg/h fluid resuscitation had a 3.8 times higher adjusted odds of developing ARDS (P = 0.04), and those receiving 10 to 20 mL/kg/h had a 2.4 times higher adjusted odds of developing ARDS (P = 0.14). TV per ideal body weight and the number of blood units transfused were not associated with ARDS development in this study.
CONCLUSIONS - This cohort study provides evidence to suggest a relationship between intraoperative fluid resuscitation and the development of ARDS. Larger prospective trials are required to confirm these findings.
Graft-versus-host disease (GVHD), a common complication of hematopoietic stem cell transplantation, is a clinical syndrome that requires synthesis of clinical, laboratory, and histopathologic findings for diagnosis. The gastrointestinal (GI) tract is commonly affected, and pathologists must recognize subtle morphologic alterations in GI mucosal biopsies to make the diagnosis and to rule out other causes of GI dysfunction such as cytomegalovirus infection and drug effects. This review summarizes the histopathologic features of GVHD in the GI tract and outlines recent recommendations for reporting of GI biopsies with suspected GVHD.
RATIONALE - Acute lung injury (ALI) that develops 6 hours after transfusion (TRALI) is the leading cause of transfusion-related mortality. Several transfusion characteristics have been postulated as risk factors for TRALI, but the evidence is limited to retrospective studies.
OBJECTIVES - To compare patient and transfusion risk factors between patients who do and do not develop ALI.
METHODS - In this prospective cohort study, consecutive transfused critically ill patients were closely observed for development of ALI. Donor samples were collected from the transfusion bags. Risk factors were compared between patients who developed ALI after transfusion and transfused control patients, matched by age, sex, and admission diagnosis.
MEASUREMENTS AND MAIN RESULTS - Seventy-four of 901 transfused patients developed ALI within 6 hours of transfusion (8%). Compared with transfused control subjects, patients with ALI were more likely to have sepsis (37 vs. 22%, P = 0.016) and a history of chronic alcohol abuse (37 vs. 18%, P = 0.006). When adjusted for patient characteristics, transfusion of plasma from female donors (odds ratio [OR], 5.09; 95% confidence interval [95% CI], 1.37-18.85) rather than male donors (OR, 1.60; 95% CI, 0.76 to 3.37), number of pregnancies among the donors (OR, 1.19; 95% CI, 1.05 to 1.34), number of donor units positive for anti-granulocyte antibodies (OR, 4.85; 95% CI, 1.32-17.86) and anti-HLA class II antibodies (OR, 3.08; 95% CI, 1.15-8.25), and concentration of lysophosphatidylcholine in the donor product (OR, 1.69; 95% CI, 1.10 to 2.59) were associated with the development of ALI.
CONCLUSIONS - Both patient and transfusion risk factors determine the probability of ALI after transfusion. Transfusion factors represent attractive targets for the prevention of ALI.
OBJECTIVES - Primary hemorrhagic stroke is an uncommon complication of sickle cell disease, with reported mortality rates of 24% to 65%. Most reported cases are in adults; little is known about its occurrence in children. Proposed risk factors include previous ischemic stroke, aneurysms, low steady-state hemoglobin, high steady-state leukocyte count, acute chest syndrome, and hypertransfusion. We performed a retrospective case-control study to evaluate risk and prognostic factors for primary hemorrhagic stroke among children with sickle cell disease.
PATIENTS AND METHODS - Case subjects (sickle cell disease and primary hemorrhagic stroke) and control subjects (sickle cell disease and ischemic stroke) were identified at 2 children's hospitals from January 1979 to December 2004 by reviewing divisional records and the discharge databases.
RESULTS - We identified 15 case subjects (mean age: 10.4 +/- 1.3 years) and 29 control subjects (mean age: 5.2 +/- 0.4 years). An increased risk of hemorrhagic stroke was associated with a history of hypertension and recent (in the last 14 days) transfusion, treatment with corticosteroids, and possibly nonsteroidal antiinflammatory drugs. Average blood pressures at well visits (adjusted for age and gender) were similar between the 2 groups, suggesting that hypertension was intermittent.
CONCLUSIONS - In this group of children with sickle cell disease, hemorrhagic stroke was associated with a history of hypertension or antecedent events including transfusion or treatment with corticosteroids. Improved understanding of risk and prognostic factors, especially those that are modifiable, may help prevent this devastating complication in children with sickle cell disease.
OBJECTIVE - To describe the HIV/AIDS epidemic in mainland China.
METHODS - We review the magnitude of the HIV/AIDS epidemic and the social characteristics and geographic distribution of at-risk groups in China based on published literature and unpublished official data.
RESULTS - Injection drug use has been the dominant route for HIV infection in China, and will continue to be a major risk factor with increasing numbers of new drug users and needle sharing. Commercial plasma donation with unhygienic re-infusion of red blood cells was common in rural communities in the early 1990s. While this is unlikely to constitute a major factor for future HIV spread, those already infected represent a formidable treatment challenge. Huge seasonal work migration facilitates disease spread across regions. Many homosexual men have unprotected sex with men, women, or both, and may contract or spread HIV. Though commercial sex workers have contributed to a small proportion of the reported epidemic thus far, flourishing commercial sex is of growing concern and may have a bridging role in transmitting HIV from core groups to the general population.
CONCLUSION - Increasing numbers of sex workers and drug users, internal migration, high risk behaviours, and low condom use suggest a future upward trend for HIV/AIDS and underscore the urgency of scaling up interventions in China.