Heparin-dependent and -independent anti-platelet factor 4 autoantibodies in patients with systemic lupus erythematosus

Objective. Antibodies that recognize complexes formed by platelet factor 4 (PF4) and heparin are involved in the pathogenesis of heparin-induced thrombocytopenia (HIT). This study was undertaken to investigate the prevalence and clinical correlations of anti-PF4 autoantibodies in patients with SLE. Methods. We studied 118 patients with SLE, 78 with primary immune thrombocytopenia (ITP), 27 with primary APS, 2 with HIT (as positive controls) and 47 healthy controls. Heparin-dependent and -independent anti-PF4 antibodies were measured with an ELISA. Antibody binding was confirmed to be heparin-dependent when inhibited by the presence of a high concentration of heparin. Pathogenic anti-PF4 antibody was assessed by serotonin-release assay. Results. Heparin-dependent anti-PF4 antibodies were detected in 11 SLE (9%) and 2 primary ITP (3%) patients, but at much lower levels than in HIT patients. In serotonin-release assays, only the HIT sera induced platelet activation in vitro. Heparin-independent anti-PF4 antibodies were detected in 17 SLE patients (14%). There was no correlation between the levels of heparin-dependent and -independent anti-PF4 antibodies. Cross-reactivity between these two antibodies was not detectable by ELISA competitive assay. Heparin-dependent anti-PF4 antibodies were associated with thrombocytopenia and IgM aCLs (P?=?0.007 for both comparisons), while heparin-independent anti-PF4 antibody levels were correlated with SLE disease activity index (P?=?0.0005). None of the SLE patients with anti-PF4 antibodies had previous heparin exposure. Conclusion. PF4 is an autoimmune target in SLE patients. Heparin-dependent and -independent anti-PF4 autoantibodies may be involved in different aspects of pathophysiology of SLE.     

Phase II study of liposome-encapsulated doxorubicin plus cyclophosphamide,followed by sequential trastuzumab plus docetaxel as primary systemic therapy for breast cancer patients with HER2 overexpression or amplification

Purpose of the studyTrastuzumab combined with sequential chemotherapy with taxanes and anthracyclines as primary systemic therapy achieved high rates of pathologic complete response (pCR). Non-pegylated liposome-encapsulated doxorubicin (NPLD) has shown equal efficacy but minor cardiotoxicity compared to doxorubicin. This phase II study aimed to evaluate the activity and safety of trastuzumab with sequential chemotherapy for early or locally advanced HER2 positive BC.MethodsPreoperative treatment included NPLD (60 mg/mq iv) plus cyclophosphamide (600 mg/mq iv) every 3 weeks for 4 cycles followed by docetaxel (35 mg/mq iv) plus trastuzumab (4 mg/mq loading dose iv, then 2 mg/mq iv) weekly for 16 weeks. Primary endpoint was pCR defined as the absence of residual invasive cancer both in the breast and regional nodes. Clinical staging was exploratory evaluated by CT-PET.Results43 pts were treated from december 2005 to September 2011, 39 of them were evaluable for the purpose of study. Median age was 53 years (range: 31–78), the majority of pts had tumour stage cT2 (63%), tumour grade 3 (86%), clinical nodes involvement N+ (77%), ER positive (56%) and Ki-67 ≥20% (77%). pCR was reported in 19 (49%) of 39 pts. There was an association between Ki-67 ≥20% at baseline and pCR (p = 0.018). No cardiac toxicity or discontinuation of trastuzumab was reported. CT-PET modified the clinical stage for 10 patients showing new loco-regional lymph nodes.ConclusionsThis study confirms that integrating anti-HER2 therapy in primary treatment for HER2 positive breast cancer is active. NPLD is a safe option to minimize cardiotoxicity.     

Ultrasound evaluation of fetal brain dysfunction based on behavioral patterns

To identify fetuses at high risk of poor neurological outcomes using a novel ultrasound evaluation system. We assessed an ultrasound evaluation system based on our previous findings, consisting of screening for decreased or lack of fetal movements, abnormal patterns of fetal heart rate, congenital CNS malformations, polyhydramnios of unknown cause, and a “brief ultrasound evaluation” of fetal brain functions, including movement of extremities, breathing movements, ultradian rhythm, REM period, and NREM period. We then assessed the correlation between fetal brain functions and neurological outcomes in infancy (MR, CP, and low Developmental Quotient). During screening, we prospectively evaluated 4978 fetuses receiving prenatal and intrapartum management between January 2000 and December 2009 in our hospital that were later delivered between 32 and 41 weeks’ gestation and identified 93 cases as suspicious for impairment. Of the 93 fetuses, 26 underwent the second step of brief ultrasound examination at 35–40 weeks’ gestation. Our findings revealed that this method was adequately sensitive (80%) and specific (88%) in identifying neurological impairment. We concluded that this method was mainly useful in the clinical setting for establishing the first indication for fetal CNS examination for functional impairment, rendering it suitable for clinical application.     

4′-[methyl-11C]-thiothymidine as a proliferation imaging tracer for detection of colorectal cancer: comparison with 18F-FDG

Annals of Nuclear Medicine - The novel radiotracer, 4′-[methyl-11C]-thiothymidine (11C-4DST), was developed based on the DNA incorporation method as a cell proliferation marker. This study...     

Genetic Analysis of UGT1A1 Polymorphisms Using Preserved Dried Umbilical Cord for Assessing the Potential of Neonatal Jaundice as a Risk Factor for Autism Spectrum Disorder in Children

Journal of Autism and Developmental Disorders - Neonatal jaundice has been suggested as a perinatal risk factor for autism spectrum disorder (ASD). We examined UGT1A1 polymorphisms to assess the...     

Safety of peritoneal dialysis catheter surgery under dexmedetomidine and local anesthesia for elderly patients in Japan: a single-center prospective cohort study

Clinical and Experimental Nephrology - The number of patients aged ≥ 75 years and who need renal replacement therapy is steadily increasing. The study aimed to determine...     

Impact of preoperative factors on catheter position in peritoneal dialysis: a prospective cohort study

Clinical and Experimental Nephrology - Peritoneal dialysis (PD) catheter malposition is one of the complications of renal replacement therapy. This study aimed to determine the preoperative factors...     

Chronic active EBV infection with features of granulomatosis with polyangiitis

Herein, we report the case of a 13‐year‐old boy with multiple recurrent ulcers on his legs. He developed severe sinusitis at 10 years of age and had significant weight loss (6 kg) in the 2 months prior to admission. Histology of tissue biopsied from the ulcer indicated small vessel vasculitis and granulomatous inflammation. Given that these findings met the diagnostic criteria for granulomatosis with polyangiitis (GPA), he was treated with immunosuppressive agents. Further pathology, however, indicated Epstein–Barr virus (EBV)‐encoded RNA (EBER) in most lymphocytes in the same sample. The EBER‐positive lymphocytes were mainly CD4‐positive T cells. The EBV‐DNA load in the peripheral blood was also abnormally increased (1.0 × 10⁴ copies/μg DNA). Thus, the diagnosis was established as chronic active EBV infection (CAEBV). This case illustrates the necessity of careful differential diagnosis of CAEBV owing to its clinical resemblance and pathological overlap with GPA.