Echocardiographic abnormalities in patients with sickle cell disease (SCD) were determined, and pulmonary arterial systolic pressure (PASP) was estimated. Clinical data and echocardiograms of 38 adult hospitalized patients with SCD at two tertiary care hospitals were reviewed. Fisher's exact test was performed to determine correlation between pulmonary hypertension and various clinical variables. Pulmonary hypertension was the most common abnormality identified in 22 (58%) patients. The estimated mean PASP was 37.5¯± 10.9 mmHg. Older age and prior history of acute chest syndrome were significantly correlated with an increased prevalence of pulmonary hypertension (P < 0.05). Patients with hemoglobin levels <8 g/dL had PASP 43.2¯± 0.5 compared to a mean PASP of 33.3¯± 6.0 in patients with hemoglobin ‡8 g/dL (P = 0.01). Eight (21%) patients had evidence of a hyperdynamic left ventricle. Left heart abnormalities included dilated atrium in 14 (37%), dilated ventricle in 5 (13%), ventricle hypertrophy in 5 (13%), and ventricle dysfunction in 3 (9%) patients. Right heart abnormalities included dilated atrium in 9 (24%), dilated ventricle in 6 (16%), and ventricle dysfunction in 3 (9%) patients. Despite an increased incidence of abnormal flow across the valves on Doppler analysis, no patient had structurally abnormal valves. A majority of patients with SCD had evidence of pulmonary hypertension, which correlated with older age and history of acute chest syndrome. Other structural and functional echocardiographic abnormalities were less common. Am.

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Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crisis. The vascular occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestations of the disease. Abdominal pain is an important component of vaso-occlusive painful crisis and may mimic diseases such as acute appendicitis and cholecystitis. Acute pancreatitis is rarely included as a cause of abdominal pain in patients with sickle cell disease. When it occurs it may result form biliary obstruction, but in other instances it might be a consequence of microvessel occlusion causing ischemia. In this series we describe four cases of acute pancreatitis in patients with sickle cell disease apparently due to microvascular occlusion and ischemic injury to the pancreas. All patients responded to conservative management. Acute pancreatitis should be considered in the differential diagnosis of abdominal pain in patients with sickle cell disease. Am. J. Hematol. 73:190-193, 2003.

The composition of the plasma membrane (PM)-associated proteome of tumor cells determines cell–cell and cell–matrix interactions and the response to environmental cues. Whether the PM-associated proteome impacts the phenotype of Medulloblastoma (MB) tumor cells and how it adapts in response to growth factor cues is poorly understood. Using a spatial proteomics approach, we observed that hepatocyte growth factor (HGF)-induced activation of the receptor tyrosine kinase c-MET in MB cells changes the abundance of transmembrane and membrane-associated proteins. The depletion of MAP4K4, a pro-migratory effector kinase downstream of c-MET, leads to a specific decrease of the adhesion and immunomodulatory receptor CD155 and of components of the fast-endophilin–mediated endocytosis (FEME) machinery in the PM-associated proteome of HGF-activated MB cells. The decreased surface expression of CD155 or of the fast-endophilin–mediated endocytosis effector endophilin-A1 reduces growth and invasiveness of MB tumor cells in the tissue context. These data thus describe a novel function of MAP4K4 in the control of the PM-associated proteome of tumor cells and identified two downstream effector mechanisms controlling proliferation and invasiveness of MB cells.

Peritoneal metastasis (PM) originating from gastrointestinal cancer was considered a terminal disease until recently. The advent of better systemic treatment, a better understanding of prognostic factors, and finally, the advent of novel loco-regional therapies, has opened the door for the multimodal treatment of PM. These strategies, including radical surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) showed surprisingly good results, leading to the prolonged survival of patients with peritoneal metastasis. This has triggered a significant body of research, leading to the molecular characterization of PM, which may further help in the development of novel treatments. This review summarizes current evidence on peritoneal metastasis and explores potential novel mechanisms and therapeutic approaches to treat patients with peritoneal metastasis.

Patients with SCD during vaso-occulsive painful crisis have an elevated D-dimer level. Low-dose anticoagulation treatment is associated with a significant reduction in the D-dimer levels.

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Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve the survival of selected patients with peritoneal metastasis. A major cause of treatment-related morbidity after CRS/HIPEC is infection and sepsis. HIPEC alters the diagnostic sensitivity and specificity of blood and serum markers and therefore has an impact on early diagnosis of postoperative complications. This study aimed to assess the sensitivity and specificity of blood and serum markers after CRS/HIPEC. Methods Patients from two centers, operated between 2009 and 2017, were enrolled in this study. Perioperative blood samples were analyzed for white blood cells (WBC), C-reactive protein (CRP), and procalcitonin (PCT); postoperative complications were graded according to Clavien-Dindo and infectious complications according to CDC criteria. Results Overall, n=248 patients were included with peritoneal metastasis from different primary tumors treated by CRS/HIPEC. Depending on the applied HIPEC protocol, patients presented a suppressed WBC response to infection. In addition, a secondary and unspecific CRP elevation in absence of an underlining infection, and pronounced after prolonged perfusion for more than 60 min. PCT was identified as a highly specific — although less sensitive — marker to diagnose infectious complications after CRS/HIPEC. Discussion/conclusion Sensitivity and specificity of WBC counts and CRP values to diagnose postoperative infection are limited in the context of HIPEC. PCT is helpful to specify suspected infection. Overall, diagnosis of postoperative complications remains a clinical diagnosis, requiring surgical expertise and experience.