Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes

Valproic acid (VPA), an inhibitor of histone deacetylases, inhibits the growth of leukemia cells and induces their differentiation in vitro. In the present study, VPA in combination with two differentiating agents, 13-cis retinoic acid and 1,25-dihydroxyvitamin D3, was given to 19 previously untreated patients with MDS or CMML. Eight patients had to discontinue treatment before week 16 due to toxicity. According to international working group criteria, three patients (16%) responded to treatment. No correlation between VPA serum level, histone acetylation or clinical response was observed.     

Cell-free plasma DNA as a predictor of outcome in severe sepsis and septic shock

BACKGROUND: Increased concentrations of cell-free DNA have been found in plasma of septic and critically ill patients. We investigated the value of plasma DNA for the prediction of intensive care unit (ICU) and hospital mortality and its association with the degree of organ dysfunction and disease severity in patients with severe sepsis. METHODS: We studied 255 patients with severe sepsis or septic shock. We obtained blood samples on the day of study inclusion and 72 h later and measured cell-free plasma DNA by real-time quantitative PCR assay for the beta-globin gene. RESULTS: Cell-free plasma DNA concentrations were higher at admission in ICU nonsurvivors than in survivors (median 15 904 vs 7522 genome equivalents [GE]/mL, P < 0.001) and 72 h later (median 15 176 GE/mL vs 6758 GE/mL, P = 0.004). Plasma DNA values were also higher in hospital nonsurvivors than in survivors (P = 0.008 to 0.009). By ROC analysis, plasma DNA concentrations had moderate discriminative power for ICU mortality (AUC 0.70-0.71). In multiple regression analysis, first-day plasma DNA was an independent predictor for ICU mortality (P = 0.005) but not for hospital mortality. Maximum lactate value and Sequential Organ Failure Assessment score correlated independently with the first-day plasma DNA in linear regression analysis. CONCLUSIONS: Cell-free plasma DNA concentrations were significantly higher in ICU and hospital nonsurvivors than in survivors and showed a moderate discriminative power regarding ICU mortality. Plasma DNA concentration was an independent predictor for ICU mortality, but not for hospital mortality, a finding that decreases its clinical value in severe sepsis and septic shock.     

Long-term results of esophageal atresia: Helsinki experience and review of literature

Esophageal atresia (EA) affects one in 2,840 newborns, and over half have associated anomalies that typically affect the midline. After EA repair in infancy, gastroesophageal reflux (GER) and esophageal dysmotility and respiratory problems are common. Significant esophageal morbidity associated with EA extends into adulthood. Surgical complications, increasing age, and impaired esophageal motility predict the development of epithelial metaplasia after repair of EA. To date, worldwide, six cases of esophageal cancer have been reported in young adults treated for EA. According to our data, the statistical risk for esophageal cancer is not higher than 500-fold that of the general population. However, the overall cancer incidence among adults with repaired EA does not differ from that of the general population. Adults with repaired EA have had significantly more respiratory symptoms and infections, as well as more asthma and allergies than does the general population. Nearly half the patients have bronchial hyperresponsiveness. Thoracotomy-induced rib fusion and gastroesophageal reflux-associated columnar epithelial metaplasia are the most significant risk factors for the restrictive ventilatory defect that occurs in over half the patients. Over half the patients with repaired EA are likely to develop scoliosis. Risk for scoliosis is 13-fold after repair of EA in relation to that of the general population. Nearly half of the patients have had vertebral anomalies predominating in the cervical spine, and of these, most were vertebral fusions. The natural history of spinal deformities seems, however, rather benign, with spinal surgery rarely indicated.     

Bone health in patients with cloacal exstrophy and persistent cloaca after bladder augmentation

Purpose

In this study, the prevalence of osteoporosis was evaluated in patients operated on for cloacal exstrophy or persistent cloaca and who had undergone bladder augmentation.

Methods

Seven patients operated on because of cloacal exstrophy and 3 patients operated on because of persistent cloaca were evaluated. Patients were clinically assessed. Areal bone mineral density for the lumbar spine (L1-L4), femoral neck, and whole body was measured with dual-energy x-ray absorptiometry. Acid-base balance, plasma 25-hydroxyvitamin D (vitamin D), and gonadal function were determined and correlated with dual-energy x-ray absorptiometry results.

Results

The patients were small in height (median, −2.2 SD). According to areal bone mineral density measurements, 40% of the patients had significantly reduced BMD. When the values were adjusted for patient size, only 1 patient had slightly reduced bone mass. Half of the patients had low vitamin D values. The height-corrected bone mineral content values showed a positive correlation with vitamin D values (P = .0072) but were not different in patients with and without hypogonadism (P = .33).

Conclusions

Patients with cloacal exstrophy or complicated cloaca have many risk factors for osteoporosis. However, this study showed good overall bone health in affected adolescents.     

Are small hospitals with small intensive care units able to treat patients with severe sepsis?

Purpose  

To find out whether mortality from sepsis is influenced by the size of the hospital and of the intensive care unit (ICU).     

Patient Preference for Dissection of Sentinel Nodes Outside Level I-II of the Axilla

In this study patients' and female doctors' opinions about harvesting sentinel nodes outside the axilla are evaluated and patients' ability to understand the concept of sentinel node biopsy is investigated. Information leaflets and questionnaires were mailed to 100 patients with breast cancer who had undergone sentinel node biopsy and to 300 female doctors. Seventy-three (73%) patients and 148 (49%) female doctors returned the questionnaire. Fifty-eight (79%) breast cancer patients and 71 (48%) female doctors wanted harvesting to be done in order to determine whether the nodes were involved. Sixty-six (90%) patients and 128 (86%) female doctors wanted the procedure if it changed the treatment. Sixty (82%) patients understood the outcome of the sentinel node procedure. Patients with breast cancer seem to value the information gained by harvesting sentinel nodes outside the axilla and want the procedure if there is even the slightest possibility that it might change the adjuvant treatment.     

Synovial fluid acid phosphatase in seropositive and seronegative arthritides

Synovial fluid acid phosphatase was investigated in 82 arthritic patients with hydropsy in a knee joint. 39 of the patients were seropositive and 43 seronegative. 36 of the seropositive group had erosive rheumatoid arthritis. The mean synovial fluid acid phosphatase in the seropositive group, 11.6 U/l (SD +/- 8.4), was significantly higher (p less than 0.001) than in the seronegative group, 6.5 U/l (SD +/- 4.8).     

Mesoportal bypass using a constructed saphenous vein graft for extrahepatic portal vein obstruction--technique, feasibility, and outcomes

BackgroundThe internal jugular vein is routinely used as a graft for the Rex shunt. We analyzed results of mesoportal bypass using an alternative autologous graft.MethodsTwenty-one children with extrahepatic portal vein obstruction were treated with a Rex shunt constructed using both greater saphenous veins. Follow-up included ultrasound and blood count screening at 3, 6, and 12 months and annually thereafter.ResultsMedian age was 8.7 years (range, 3.6-14 years), and follow-up time, 5.3 years (range, 0.6-7.1 years). Occlusion or narrowing occurred in 6 patients after a median of 20 months (range, 2.6-52 months). In 2 cases, patency was restored, giving an overall success rate of 81%. During follow-up, no variceal bleeding occurred while hemoglobin, platelet count, and leukocyte levels increased (P ≤ .02 for all) and spleen size decreased (P = .001). Patients with occlusive shunt complications weighed less (P = .01), had higher preoperative platelet levels (P = .02), and tended to have a smaller spleen preoperatively (P = .06) than patients without shunt complications. Cumulative graft patency at 6 months, 1 year, 3 years, and 5 years was 100%, 89%, 82%, and 74%, respectively.ConclusionsRex shunt constructed using the greater saphenous veins is a valuable alternative to the internal jugular vein graft, allowing long-term reversal of portal hypertension, splenomegaly, and hypersplenism. Low patient weight and high platelet count predicted shunt occlusion.