Pulmonary artery systolic hypertension is common and associated with increased mortality among adult sickle cell disease (SCD) patients in the United States. Although the prevalence of SCD is highest in subSaharan Africa, the frequency of pulmonary artery systolic hypertension and the risk factors for the development of pulmonary hypertension have not been reported from Africa. We studied 208 hydroxyurea naïve Nigerian SCD patients at steady state and 94 healthy controls. Pulmonary artery systolic hypertension was defined prospectively as tricuspid regurgitant jet velocity ≥2.5 m/sec. Results were compared with a previously published US prospective SCD cohort. Only 7% of Nigerians compared with 46% of US adults with SCD were >35 years. Tricuspid regurgitant jet velocity was ≥2.5 m/sec in 25% of Nigerian SCD patients. Higher jet velocity was associated with greater serum globulin (P 5 0.002), blood urea nitrogen (P 5 0.019) and lactate dehydrogenase concentrations (P 5 0.026) and with inability to walk >300 m in 6 min (P 5 0.042). Compared with the US cohort, Nigerian patients had more hemolysis as indicated by lower hemoglobin and higher lactate dehydrogenase concentrations (P ≤ 0.003). Pulmonary hypertension is common among Nigerian SCD patients. The public health implication of this finding is significant considering the potential number of individuals at risk for this complication. Better understanding of the long term outcome of pulmonary hypertension and causes of death in SCD and the institution of preventive measures are major public health challenges for Africa. The inclusion of African sites in sickle cell pulmonary hypertension clinical trials should be encouraged. Am. J. Hematol. 83:485-490, 2008. V

Secondary pulmonary hypertension (PAH) has been shown to have a prevalence of 30% in patients with sickle cell disease (SCD) with mortality rates of 40% at 40 months after diagnosis in the United States. The burden of SCD is highest in sub-Saharan Africa, especially in Nigeria (West Africa), where approximately 6 million people are afflicted. The true global incidence, prevalence, and burden of SCD and its associated end organ complications however remain unknown. Chronic hemolysis represents a prominent mechanistic pathway in the pathogenesis of SCD-associated pulmonary hypertension via a nitric oxide (NO) scavenging and abrogation of NO salutatory effects on vascular function, including smooth muscle relaxation, downregulation of endothelial adhesion molecules and inhibition of platelet activation. Many known infectious risk factors for PAH are also hyperendemic in Africa, including Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS), chronic hepatitis B and C, and possibly malaria. Interactions between these infectious complications and SCD-related hemolysis could yield an even higher prevalence of pulmonary hypertension and compound the existing global health systems challenges in managing SCD. Indeed, our preliminary analysis of African immigrants currently in the United States suggests that pulmonary hypertension represents a significant complication of SCD in the African subcontinent. There is clearly a need to include Africa and other parts of the world with high SCD prevalence in future comprehensive studies on the epidemiology and treatment of end organ complications of an aging SCD population world-wide. Am.

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BackgroundPatients with Chuvash polycythemia, (homozygosity for the R200W mutation in the von Hippel Lindau gene (VHL)), have elevated levels of hypoxia inducible factors HIF-1 and HIF-2, often become iron-deficient secondary to phlebotomy, and have elevated estimated pulmonary artery pressure by echocardiography. The objectives of this study were to provide a comprehensive echocardiographic assessment of cardiovascular physiology and to identify clinical, hematologic and cardiovascular risk factors for elevation of tricuspid regurgitation velocity in children and adults with Chuvash polycythemia. Design and MethodsThis cross-sectional observational study of 120 adult and pediatric VHL R200W homozygotes and 31 controls at outpatient facilities in Chuvashia, Russian Federation included echocardiography assessment of pulmonary artery pressure (tricuspid regurgitation velocity), cardiac volume, and systolic and diastolic function, as well as hematologic and clinical parameters. We determined the prevalence and risk factors for elevation of tricuspid regurgitation velocity in this population and its relationship to phlebotomy. ResultsThe age-adjusted mean ± SE tricuspid regurgitation velocity was higher in VHL R200W homozygotes than controls with normal VHL alleles (2.5±0.03 vs. 2.3±0.05 m/sec, P=0.005). The ageadjusted left ventricular diastolic diameter (4.8±0.05 vs. 4.5±0.09 cm, P=0.005) and left atrial diameter (3.4±0.04 vs. 3.2±0.08 cm, P=0.011) were also greater in the VHL R200W homozygotes, consistent with increased blood volume, but the elevation in tricuspid regurgitation velocity persisted after adjustment for these variables. Among VHL R200W homozygotes, phlebotomy therapy was associated with lower serum ferritin concentration, and low ferritin independently predicted higher tricuspid regurgitation velocity (standardized beta=0.29; P=0.009). ConclusionsChildren and adults with Chuvash polycythemia have higher estimated right ventricular systolic pressure, even after adjustment for echocardiography estimates of blood volume. Lower ferritin concentration, which is associated with phlebotomy, independently predicts higher tricuspid regurgitation velocity (www.clinicaltrials.gov identifier NCT00495638).Key words: pulmonary hypertension, tricuspid regurgitation velocity, ferritin, VHL, hypoxia inducible factor.Citation: Sable CA, Aliyu ZY, Dham N, Nouraie M, Sachdev V, Sidenko S, Miasnikova GY, Polyakova LA, Sergueeva AI, Okhotin DJ, Bushuev V, Remaley AT, Niu X, Castro OL, Gladwin MT, Kato GJ, Prchal10 JT, and Gordeuk VR. Pulmonary artery pressure and iron deficiency in patients with upregulation of hypoxia sensing due to homozygous VHLR200W mutation (Chuvash polycythemia). Haematologica 2012;97(2):193-200. doi:10.3324/haematol.2011

Low maternal age appears to be a risk factor for low birth weight and very preterm birth among gastroschisis-affected fetuses. This information is potentially useful for planning by care providers and in counseling affected parents.

BackgroundA variable decision in managing community acquired pneumonia (CAP) is the initial site of care; in-patient versus outpatient. These variations persist despite comprehensive practice guidelines. Patients with a Pneumonia Severity Index (PSI) score lower than seventy have low risk for complications and outpatient antibiotic management is recommended in this group. These patients are generally below the age of fifty years, non-nursing home residents, HIV negative and have no major cardiac, hepatic, renal or malignant diseases.MethodsA retrospective analysis of 296 low-risk CAP patients evaluated within a year one period at St. Agnes Hospital, Baltimore, Maryland was undertaken. All patients were assigned a PSI score. 208 (70%) were evaluated and discharged from the emergency department (E.D.) to complete outpatient antibiotic therapy, while 88 (30%) were hospitalized. Patients were sub-stratified into classes I-V according to PSI. A comparison of demographic, clinical, social and financial parameters was made between the E.D. discharged and hospitalized groups.ResultsStatistically significant differences in favor of the hospitalized group were noted for female gender (CI: 1.46-5.89, p= 0.0018), African Americans (CI: 0.31-0.73, p= 0.004), insurance coverage (CI: 0.19-0.63, p= 0.0034), temperature (CI: 0.04-0.09, p= 0.0001) and pulse rate (CI: 0.03-0.14, p= 0.0001). No statistically significant differences were observed between the two groups for altered mental status, hypotension, tachypnea, laboratory/radiological parameters and social indicators (p>0.05). The average length of stay for in-patients was 3.5 days at about eight time's higher cost than outpatient management. There was no difference in mortality or treatment failures between the two groups. The documentation rate and justifications for hospitalizing low risk CAP patients by admitting physicians was less than optimal.ConclusionsHigh fever, tachycardia, female gender, African- American race and medical insurance coverage are determinants for hospitalization among low risk CAP patients in our study. The average length of stay for in-patients was 3.5 days (3 to 5 days). The cost of in-patient care was about eight times higher than outpatient management. This study supports the recommendation of using the PSI for E.D evaluation of patients in appropriate social settings.

Survival among pre-viable fetuses is increasing in the United States. This raises ethical, legal and medical issues concerning the defined viability status of these babies, which is currently described as "non-viable".

Saw palmetto is a frequently used botanical agent in benign prostatic enlargement (BPH). Although it has been reported to cause cholestatic hepatitis and many medical conditions, Saw palmetto has not been implicated in acute pancreatitis. We report a case of a probable Saw palmetto induced acute hepatitis and pancreatitis. A 55-year-old reformed alcoholic, sober for greater than 15 years, presented with severe non-radiating epigastric pain associated with nausea and vomiting. His only significant comorbidity is BPH for which he intermittently took Saw palmetto for about four years. Physical examination revealed normal vital signs, tender epigastrium without guarding or rebound tenderness. Cullen and Gray Turner signs were negative. Complete blood count and basic metabolic profile were normal. Additional laboratory values include a serum amylase: 2,152 mmol/L, lipase: 39,346 mmol/L, serum triglyceride: 38 mmol/L, AST: 1265, ALT: 1232 and alkaline phosphatase was 185. Abdominal ultrasound and magnetic resonance cholangiography revealed sludge without stones. A hepatic indole diacetic acid scan was negative. Patient responded clinically and biochemically to withdrawal of Saw palmetto. Two similar episodes of improvements followed by recurrence were noted with discontinuations and reinstitution of Saw Palmetto. Simultaneous and sustained response of hepatitis and pancreatitis to Saw palmetto abstinence with reoccurrence on reinstitution strongly favors drug effect. "Natural" medicinal preparations are therefore not necessarily safe and the importance of detailed medication history (including "supplements") cannot be over emphasized.