Comparison of nutritional and hydration status in patients undergoing twice and thrice-weekly hemodialysis: a silent drama in developing countries

International Urology and Nephrology - In low and middle- income countries, due to lack of financial resources, the number of patients receiving one or two hemodialysis (HD) sessions a week has...     

Protroca: A Noninterventional Study on Prophylactic Lipegfilgrastim against Chemotherapy-Induced Neutropenia in Nonselected Breast Cancer Patients

BackgroundProtroca evaluated the efficacy and safety of primary and secondary prophylaxis of neutropenia with lipegfilgrastim (Lonquex®) in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy (CT).Patients and MethodsOf the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients for the per-protocol set. Primary and secondary end points after lipegfilgrastim treatment were assessed.ResultsNine patients of the ITT set receiving lipegfilgrastim as primary prophylaxis (n = 222) had febrile neutropenia of grade 3–4 (5 patients) or infection of grade 3–4 (4 patients); 1/26 of those receiving secondary prophylaxis had an event. Dose reductions were performed in 9.5% of the patients. Postponement of cancer CT cycles for >3 days occurred in <15% of patients; 10.8% (92/851 AEs) and 8% (2/25 SAEs) of documented adverse events and serious adverse events, respectively, were related to lipegfilgrastim.ConclusionsApplication of lipegfilgrastim was effective as primary and secondary prophylaxis in the prevention of CT-induced neutropenia in breast cancer.     

Prevalence of rotavirus antibodies in a non-human primate colony

A total of 51 monkeys maintained in a colony at the Institute of Primate Research (Kenya) and housed in doors with natural lighting in a group cage were used in this study. Monkeys belonging to 3 species were selected at random and blood samples collected. The serum samples were screened for presence of neutralizing antibodies (VTN) to rhesus rotavirus (RRV) by virus neutralization assay. Virus neutralization was determined by 60% reduction in fluorescent focus units (ffu). 96% of the animals screened had naturally occurring antibodies to rhesus rotavirus. Another group of 11 lactating monkeys (5 baboons, 6 vervets) and their infants were screened further for presence of IgG and IgA antibodies in serum and breast milk (mothers). Overall, the mothers had higher titres of both IgG and IgA than the infants. Taken together, these results demonstrate rotavirus infection is endemic in this primate colony. This mimics the human situation, hence, captive non human primates (such as the baboons) could be a suitable model for testing rotavirus candidate vaccines and for investigating the possible application in humans of passive-active immunization strategy.     

Thrombocytopenia After Isolated Limb or Hepatic Perfusions with Melphalan: The Risk of Heparin-Induced Thrombocytopenia

Background: Three cases of heparin-induced thrombocytopenia (HIT) were observed in patients undergoing isolated limb perfusion (ILP) with melphalan. This occurrence prompted the discontinuation of prophylactic postoperative heparin in ILP patients and its avoidance in patients undergoing isolated hepatic perfusion (IHP). The need to reassess these decisions led to a review of thrombocytopenia in both patient populations.Methods: Records of all patients treated with ILP or IHP at our institution from July 1992 through November 1996, were reviewed. Nine IHP patients were tested prospectively for heparinrelated antibodies using serum samples obtained perioperatively and during the second postoperative week.Results: Thrombocytopenia (<100,000 platelets/L) developed postoperatively in 30% of 131 ILP patients and in 77% of 56 IHP patients. No cases of HIT were identified other than the three who had been previously diagnosed. The prevalence of HIT in heparinized ILP patients was 2.8% (3/108). All nine IHP patients developed heparin-related antibodies postoperatively.Conclusions: Because the prevalence of HIT following ILP is in the range observed in other clinical settings, postoperative heparin prophylaxis is an option. However, it probably should be limited to the first week, and daily platelet counts should be reviewed for a pattern of thrombocytopenia consistent with HIT. The prevalence of heparin-related antibodies after IHP is so high that prophylactic heparin should be avoided in this setting.     

Combined vascular endothelial growth factor and TP53 status predicts poor response to tamoxifen therapy in estrogen receptor-positive advanced breast cancer.

PURPOSE: In recent studies, we showed that TP53 gene mutation or high levels of cytosolic vascular endothelial growth factor (VEGF) in estrogen receptor (ER)-alpha-positive primary breast tumors predict a poor disease outcome for patients treated with first-line tamoxifen for advanced disease. Mutant TP53 may up-regulate VEGF, whereas, on the other hand, wild-type TP53 may decrease VEGF production. EXPERIMENTAL DESIGN: In the present study, we aimed to assess the combined predictive value of TP53 gene mutation and VEGF status of 160 advanced breast cancer patients with ER-positive tumors who were treated with tamoxifen (median follow-up from start of tamoxifen treatment, 64 months). To assess TP53 gene mutation status, the entire open reading frame was sequenced; for VEGF status, an ELISA was used. RESULTS: In univariate analysis, both TP53 gene mutation (28% of the tumors) and a VEGF level above the median value were significantly associated with a short progression-free survival, post-relapse overall survival, and a poor rate of response to tamoxifen. In Cox multivariate regression analysis including the traditional predictive factors, the addition of TP53 gene mutation and VEGF status, alone or in combination, significantly predicted a poor efficacy of tamoxifen treatment. When the two factors were combined, a significantly decreased odds ratio was seen for the rate of response (odds ratio, 0.27). Similarly, an increased hazard ratio (HR) was seen for progression-free survival (HR, 2.32) and post-relapse overall survival (HR, 1.68) in the group with mutant TP53 and high VEGF compared with the group with both risk factors absent. CONCLUSIONS: Combined TP53 gene mutation status and high VEGF levels of ER-positive primary breast tumors independently predict a poor course of the disease of patients with advanced breast cancer treated with tamoxifen. These patients, having unfavorable tumor characteristics, might benefit more from other types of (individualized) treatment protocols.     

High-dose methotrexate therapy of childhood acute lymphoblastic leukemia: lack of relation between serum methotrexate concentration and creatinine clearance.

BACKGROUND: The objectives of this study were: (1) to analyze the relation of serum methotrexate (MTX) concentration with creatinine clearance, (2) to compare the leucovorin rescue dose administered to the patients based on creatinine clearance, with the one calculated according to serum MTX levels, and (3) to determine MTX-related toxicity. PROCEDURE: Thirty children with high-risk non-B acute lymphoblastic leukemia (ALL) treated according to the national protocol (PINDA 92) based on ALL BFM 90, were randomized to receive consolidation with four doses of either 1 or 2 g/m(2) MTX as a 24-hr infusion, at 2-week intervals (group M1 and M2, respectively). Serum MTX concentrations were measured at 24, 42, and 48 hr after beginning the infusion and were analyzed retrospectively. The creatinine clearance was calculated after 12-hr intravenous hydration prior to each MTX dose. Leucovorin dosage was adjusted according to creatinine clearance. RESULTS: Serum MTX concentrations at 24, 42, and 48 hr after starting the infusion were not related to creatinine clearance in both treatment groups. Leucovorin rescue administered according to creatinine clearance was excessive in 43% in group M1 and in 51% in group M2, as compared to the dose calculated according to serum MTX levels. No serious clinical complications were observed. CONCLUSIONS: These results suggest that creatinine clearance is not a good parameter to calculate leucovorin rescue. MTX-related toxicity in this group of patients receiving a dose of 1 or 2 g/m(2) and rescued with leucovorin without monitoring serum MTX levels was acceptable.     

Pregnancy outcome of patients with pruritic urticarial papules and plaques of pregnancy.

OBJECTIVE: The study was designed to investigate obstetric risk factors and pregnancy outcome of patients with pruritic urticarial papules and plaques of pregnancy (PUPPP). METHODS: A population-based study comparing all pregnancies of women with and without PUPPP was conducted. Deliveries occurred during the years 1988-2002 at the Soroka University Medical Center. A multivariable logistic regression model was constructed in order to find independent risk factors associated with PUPPP. RESULTS: During a 15-year period, 159 197 deliveries took place. PUPPP complicated 42 (0.03%) of all pregnancies. Using a multivariable analysis, the following conditions were significantly associated with PUPPP: multiple pregnancies (odds ratio (OR) = 4.9, 95% confidence interval (CI) 1.7-14.1), hypertensive disorders (OR = 2.2, 95% CI 1.1-4.7), and induction of labor (OR = 7.6, 95% CI 4.0-14.5). Higher rates of 5-minute Apgar scores lower than 7 (OR = 8.0, 95% CI 4.4-14.9) and of cesarean deliveries (OR = 2.9, 95% CI 1.5-5.6) were noted in the PUPPP as compared to the comparison group. While investigating other perinatal outcome parameters such as oligohydramnios, intrauterine growth restriction, meconium-stained amniotic fluid and perinatal mortality, no significant differences were observed between the groups. CONCLUSION: Pruritic urticarial papules and plaques of pregnancy is a condition significantly associated with multiple pregnancies, hypertensive disorders, and induction of labor. Perinatal outcome is comparable to pregnancies without PUPPP.