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- Heparin-induced thrombocytopenia in a patient with colon cancer. [Journal Article]
- Indian J Med Paediatr Oncol 2013 Oct; 34(4):336-7.
- Multicenter Phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple negative breast cancer. [JOURNAL ARTICLE]
- Int J Cancer 2014 Mar 6.
Apatinib is an oral, highly potent tyrosine-kinase inhibitor targeting VEGFR2. Phase I study showed the recommended dose of 750 mg/d with substantial antitumor activity. This phase II study aims to evaluate the optimum dose level for the efficacy and safety of apatinib monotherapy in heavily pretreated patients with metastatic triple negative breast cancer (mTNBC) in China. Phase IIa was first performed among 25 patients previously treated with anthracycline and/or taxane. All patients received apatinib 750 mg/d p.o. in a 4-week cycle. Subsequently, a phase IIb study of 59 patients was activated, with the endpoint progression-free survival (PFS). The dosage of drug for the Phase IIb was determined according to safety, tolerability and efficacy from the phase IIa study. As a result of toxicity associated with the 750 mg dose in phase IIa, the recommended initial dose of apatinib in the phase IIb was 500mg/d. In phase IIb, grade 3/4 hematologic toxicities were thrombocytopenia (13.6%), leukopenia (6.8%), neutropenia (3.4%) and anemia (1.7%). The most frequent grade 3/4 non-hematologic toxicities were hand-foot syndrome, proteinuria, hypertension, and increased ALT. In the 56 evaluable patients, overall response rate and clinical benefit rate (CBR) were 10.7% and 25.0%, respectively. Median PFS and overall survival were 3.3 (95 % CI, 1.7-5.0) and 10.6 (95 % CI, 5.6-15.7) months, respectively. Our results indicate that apatinib dose of 500 mg rather than 750 mg is the recommended starting dose for the heavily pretreated mTNBC patients with measurable rate of PR and PFS. © 2014 Wiley Periodicals, Inc.
- A phase I study of the human monoclonal anti-NRP1 antibody MNRP1685A in patients with advanced solid tumors. [JOURNAL ARTICLE]
- Invest New Drugs 2014 Mar 7.
The human monoclonal antibody MNRP1685A targets the VEGF binding domain of neuropilin-1 (NRP1), a multi-domain receptor necessary for neural development and blood vessel maturation. In nonclinical studies, MNRP1685A prevents vascular maturation by keeping blood vessels in an immature, highly VEGF-dependent state. We explored the safety and tolerability of MNRP1685A in patients with advanced solid tumors. Patients were treated with MNRP1685A given intravenously every 3 weeks using a 3 + 3 dose-escalation design with 7 dose-escalation cohorts. Twenty-four of 35 patients (69 %) experienced drug-related adverse events (AEs) of infusion-related reaction on the day of MNRP1685A administration. With premedication including dexamethasone, infusions were well-tolerated with main symptoms of pruritus and rash. Outside the day of infusion, most common (≥ 2 patients) related AEs were fatigue (17 %), pruritus (9 %), myalgia and thrombocytopenia (both 6 %) (all were Grade 1-2). MNRP1685A-related Grade ≥ 3 AEs consisted of one dose-limiting toxicity of Grade 3 upper gastrointestinal bleeding and one related Grade 3 thrombocytopenia, coinciding with unrelated Grade 3 fungemia and duodenal obstruction. MNRP1685A showed nonlinear PK with more-than-dose proportional increases in exposure, consistent with broad target expression. Transient platelet count reductions (≥ 30 % from predose) were observed in 56 % of evaluable patients. Nine patients were on study for ≥ 4 cycles, one colorectal cancer patient for one year. MNRP1685A was generally well-tolerated. The primary MNRP1685A-related AE was infusion-related reaction, which were attenuated by premedication including dexamethasone. Transient platelet count reductions were frequent but did not impact MNRP1685A dosing.
- Ludwig's angina after severe thrombocytopenic purpura associated with dengue fever. [JOURNAL ARTICLE]
- Rev Soc Bras Med Trop 2014 Jan-Feb; 47(1):116-118.
Here, we report a case of Ludwig's angina, which required surgery because of toothache. The patient had dengue and severe thrombocytopenia as confirmed by clinical and laboratory diagnoses. However, dengue is not included among the predisposing factors for Ludwig's angina.
- Risk factors associated with hantavirosis fatality: a regional analysis from a case-control study in Brazil. [Journal Article]
- Rev Soc Bras Med Trop 2014 Jan-Feb; 47(1):47-51.
Introduction: In Brazil, hantavirus cardiopulmonary syndrome (HCPS) has a high lethality rate that varies by region. This study aimed to identify the risk factors associated with fatal hantavirosis.
Methods:This study was a case-control study that included all laboratory confirmed cases of hantavirosis. The cases were stratified by the different Brazilian regions using data from the Notifiable Diseases Information System. "Cases" were patients who progressed to death, whereas "controls" were patients who were cured. The odds ratio (OR) and the adjusted OR were calculated.
Results:Overall, 158 cases and 281 controls were included in this study. In the Midwest region, the cases were 60% less likely to present with flank pain, and the time between the beginning of symptoms and death was shorter than the time between the beginning of symptoms and a cure. In the Southeast region, the cases were 60% less likely to present with thrombocytopenia or reside in rural areas compared to those who progressed to a cure. Additionally, the cases sought medical assistance, notification and investigation more quickly than the controls. In the Southern region, the cases that died were 70% less likely to be male compared to the controls.
Conclusions:HCPS manifests with nonspecific symptoms, and there are few published studies related to the condition, so determining a patient's therapeutic strategy is difficult. This study presents findings from different Brazilian regions and highlights the need for further investigations to improve comprehension about regional risk factors associated with hantavirosis and to reduce morbimortality.
- [Analysis of risk factors for secondary cytopenia after allogeneic hematopoietic stem cell transplantation]. [English Abstract, Journal Article]
- Zhonghua Xue Ye Xue Za Zhi 2014 Jan; 35(1):4-8.
To investigate the incidence and risk factors for secondary cytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).The clinical data of a total of 260 patients received allo-HSCT between Jan 1, 2006 to Jan 1, 2008 were retrospectively analyzed for the incidence and risk factors of secondary cytopenia. According to the hematopoietic reconstitution after transplantation, the patients were divided into (1) secondary neutropenia group; (2) secondary thrombocytopenia group and (3)secondary poor graft function group.During the 100 days after allo-HSCT, the secondary neutropenia (38.8% vs 18.0%, P=0.0005) or secondary thrombocytopenia (25% vs 12%, P=0.01) occurred in haploidentical HSCT (haplo-HSCT) patients were more often than that in HLA-matched group. Poor graft function showed no significant difference between the above two groups (5.6% vs 2.0%, P=0.21). Multivariate analyses revealed that cytomegalovirus (CMV) infection significantly increased the risk of secondary neutropenia. GVHD and CMV infection were independent risk factors for secondary thrombocytopenia. Meanwhile, CMV infection was an independent risk factor for secondary poor graft function.Secondary cytopenia remains a serious complication following allo-HSCT, especially in haplo-HSCT. Higher occurrence of GVHD and CMV infection may lead to higher incidence of secondary cytopenia in haplo-HSCT.
- Effect of Thrombopoietin-Receptor Agonists on APRIL Plasma Levels in Patients with Immune Thrombocytopaenia. [LETTER]
- Br J Clin Pharmacol 2014 Mar 6.
- Treatment of five haemodynamically stable dogs with immune-mediated thrombocytopenia using mycophenolate mofetil as single agent. [JOURNAL ARTICLE]
- J Small Anim Pract 2014 Mar 7.
Five dogs were presumptively diagnosed with immune-mediated thrombocytopenia. As they had all been chronically treated with non-steroidal anti-inflammatory drugs, administration of immunosuppressive doses of corticosteroids was considered contraindicated. Non-steroidal anti-inflammatory drugs were temporarily discontinued in all the dogs and mycophenolate mofetil was introduced as first-line single immunomodulatory therapy. This treatment protocol resulted in complete remission of immune-mediated thrombocytopenia in all the dogs, and mycophenolate mofetil was discontinued after several months of therapy in four of the five dogs with no relapses, even when non-steroidal anti-inflammatory drug administration was resumed. The remaining dog required continued mycophenolate mofetil therapy to avoid relapse. One dog experienced diarrhoea, and another dog had diarrhoea and decreased appetite.
- Hepatic impairment induced by scrub typhus is associated with new onset of renal dysfunction. [Journal Article]
- Clin Lab 2014; 60(1):63-8.
Scrub typhus is a potentially fatal infectious disease caused by Orientia tsutsugamushi. There is little attention given to hepatic impairment in the adults with scrub typhus. This study investigated the incidence and the prognostic implications of hepatic impairment in patients with scrub typhus.We retrospectively reviewed a total of 143 adult patients with scrub typhus who were admitted between January 1999 and December 2010 in Guangdong province, China. The patients were divided into three groups, e.g., normal, mild, and moderate to severe groups based on the elevated serum ALT and/or total bilirubin levels. Furthermore, clinical characteristics and prognosis of the patient groups were compared.109 patients (76.2%) had abnormal liver function. Among the patients with hepatic impairment 45 cases (31.4%), 54 cases (37.8%), and 10 cases (7.0%) had mild, moderate, and severe hepatic damage, respectively. The moderate to severe hepatic impairment group had higher levels of serum creatinine compared with that of normal hepatic function. The incidence of new onset of renal dysfunction - defined as peak serum creatinine > or = 176 micromol/L during hospital stay with no evidence of renal disease prior hospitalization - was 0% in the mild hepatic impairment group, 8.9% in the moderate hepatic impairment group, and 21.9% in the severe hepatic impairment group, (p = 0.005 for trend). Additionally, the patients with hepatic impairment (n = 109) had higher incidences of episodes of thrombocytopenia (45.9% vs. 8.82%, p < 0.001), hypoalbuminemia (50.5% vs. 11.8%, p < 0.001), new onset of renal dysfunction (16.5% vs. 0.0%, p = 0.011), and electrocardiogram abnormality (28.4% vs. 8.82%, p = 0.019) than the patients without hepatic impairment.The degree of hepatic impairment induced by scrub typhus is associated with new onset of renal dysfunction.
- Heparin-induced thrombocytopenia. [Journal Article]
- Medsurg Nurs 2013 Nov-Dec; 22(6):399, 397.