Periventricular hemorrhagic infarction in preterm neonates: Etiology and time of development.

BACKGROUND: To find the obstetrical and delivery associated risk factors of antenatal and postnatal grade III intraventricular hemorrhage (IVH) or periventricular hemorrhagic infarction (PVHI) in preterm neonates. METHODS: A retrospective study of obstetric and delivery associated risk factors included neonates (<35 gestational weeks) with severe IVH/PVHI (n = 120) and a prospectively collected control group (n = 50). The children were divided into: (1) antenatal onset group (n = 27) with insult visible on cerebral ultrasonography within the first 12 hours of birth or periventricular cystic changes visible in PVHI within the first 3 days; (2) neonatal onset group (n = 70) with insult diagnosed after initial normal findings or I-II grade IVH, and (3) unknown time-onset group (n = 23) with insult visible at > 12 h of age. RESULTS: The mothers of the antenatal onset group had significantly more bacterial infections before delivery compared to the neonatal onset group: 20/27 (74.1%) versus 23/69 (33.3%), (odds ratio (OR) 5.7 [95% confidence interval 2.1-16]; p = 0.0008) or compared to the control group (11/50 (22%); OR 11 [2.8-42]; p = 0.0005). Placental histology revealed chorioamnionitis more often in the antenatal compared to the neonatal onset group (14/21 (66.7%) versus 16/42 (38.1%), respectively; OR 3.7 [1.18-11]; p = 0.025). Neonates with neonatal development of severe IVH/PVHI had significantly more complications during delivery or intensive care. CONCLUSIONS: Bacterial infection during pregnancy is an important risk factor for development of antenatal onset severe IVH or PVHI. In neonates born to mothers with severe bacterial infection during pregnancy, cerebral ultrasonography is indicated for early detection of severe IVH or PVHI.

New insights into the natural course of knee osteoarthritis: early regulation of cytokines and growth factors, with emphasis on sex-dependent angiogenesis and tissue remodeling. A pilot study.

OBJECTIVE: This study was conducted to identify cytokine profiles associated with radiographic phenotypes of knee osteoarthritis (rKOA) with a focus on early stage of the disease. METHODS: The pilot population study involved 60 middle-aged patients (mean age 50 ± 7.3y.). Standardized weight-bearing anteroposterior and axial radiographs were used to assess rKOA severity in tibiofemoral (TFJ) of patellofemoral joint (PFJ) by grading system (grades 0-3). Luminex (xMAP®) technology was used to simultaneously assess 60 biomarkers (BMs). RESULTS: Several pathways of angiogenic (CXCL10/IP-10, FGF1/2, PDGF-AA/BB, ANG1, RANTES), tissue remodeling/fibrosis (MMP1/3, TIMP2/3/4, TGFß), and fat tissue (leptin) BMs associated with rKOA severity already in very early phase (grade 1). We identified several sets of cytokines as key markers of early knee osteoarthritis (KOA) predicting radiographic features in logistic-regression models (AUC = 0.80-0.97). Marked sex-specificity of rKOA course was detected: upregulation of angiogenesis dominated in females, whereas the activation of tissue remodeling was dominant in males. Several of these shifts, e.g., decrease of CXCL10/IP-10, took place only in grade 1 KOA and disappeared or reversed in later stages. OA of different knee-joint compartments has distinct profiles of cytokines. A broad list of BMs (TIMP2/3/4, MMP1/3, TGFß1/2, vWF-A2, sE-selectin and leptin) associated with OA in the PFJ. CONCLUSION: Our results demonstrate that substantial and time-limited shifts in the angiogenic and TIMP/MMP systems occur in the early stage of KOA. Our study findings highlight the sex-, grade- and compartment-dependent shifts in above processes. The data may contribute to the individualized prevention of KOA in the future.

Diagnostic and prognostic value of bone biomarkers in progressive knee osteoarthritis: a 6-year follow-up study in middle-aged subjects.

OBJECTIVE: To determine the value of bone markers in early-stage progressive knee osteoarthritis (OA), a population-based cohort of middle-aged subjects with chronic knee complaints was followed over 6 years (two consecutive two 3-year periods). METHODS: Tibiofemoral (TF) and patellofemoral (PF) radiographs were graded in 128 subjects (mean age at baseline 45 ± 6.2 years) in 2002, 2005 and 2008. Bone formation was assessed by the serum concentration of procollagen type I amino-terminal propeptide (sPINP); bone resorption by the level of the C-terminal cross-linked telopeptides of type I collagen (sCTx-I); and bone mineralization by the values of osteocalcin (sOC) by electrochemiluminescence immunoassay. A novel marker of bone resorption, urinary osteocalcin midfragments (uMidOC), was assayed using enzyme linked immunosorbent assay (ELISA). RESULTS: Several diagnostic associations were found between the bone markers (PINP, OC, MidOC) and progressive OA expressed by TF osteophytosis. The increasing output of MidOC demonstrated several-fold higher risk for progressive TF osteophytosis [odds ratio (OR) 5.32; 95% confidence interval (CI) 1.41-20.06, P = 0.014] than other bone markers. The values of PINP had prognostic value for subsequent more severely expressed knee OA progression [r(s) = 0.460, P = 0.005]. CONCLUSIONS: Bone metabolism is activated in early-stage knee OA. OA progression was preceded by the enhanced bone formation (by PINP) and accompanied by the activation of bone formation (by PINP), non-collagenous bone resorption (by MidOC), as well as by changes in mineralization (by OC). All three bone markers had diagnostic value, and one of them, PINP, had also a predictive value for knee OA progression, especially for progressive osteophytosis.

Association of ADAM12-S protein with radiographic features of knee osteoarthritis and bone and cartilage markers.

ADAM12 (A disintegrin and metalloprotease) is one of the candidate genes demonstrating susceptibility to osteoarthritis. The purpose of this study was to investigate the relationship between ADAM12-S protein and radiographic knee osteoarthritis (KOA) and its correlation to several bone and cartilage biomarkers. The ADAM12-S protein was measured in 276 subjects (60% women, aged 32-60 years), including 181 individuals with and 95 without radiographic KOA features. The radiographs were obtained from both tibiofemoral (TF) and patellofemoral (PF) joints. The serum levels of ADAM12-S protein were measured by DELFIA1/AutoDELFIA research kit. The ADAM12-S protein was found in detectable ranges in 43 subjects (16 men), without statistical difference between the two genders. In the whole group, the ADAM12-S was related to radiographic KOA grades in TF (P = 0.004) as well in PF joint (P = 0.003). We also found a correlation between ADAM12-S protein and osteophytes in TF and/or PF joints (P = 0.003). No correlations were found between serum levels of S-CTx-I (C-terminal cross-linked telopeptides of type I collagen) or S-PINP (type I procollagen N-terminal propeptide) and ADAM12-S. Similarly, in the whole group, the ADAM12-S protein was not correlated with U-CTx-II (urinary C-telopeptide fragments of type II collagen); however, in the female group, trend to positive correlation between the investigated biomarkers (P = 0.019) was observed. The ADAM12-S protein could be elevated in some KOA cases, and this elevation correlates with the grades of the disease, mostly owning to development of osteophytes. This finding suggests the possible involvement of the ADAM12-S protein in the pathogenesis of KOA.

Patient doses in paediatric CT: feasibility of setting diagnostic reference levels.

Despite the fact that doses to paediatric patients from computed tomography (CT) examinations are of special concern, only few data or studies for setting of paediatric diagnostic reference levels (DRLs) have been published. In this study, doses to children were estimated from chest and head CT, in order to study the feasibility of DRLs for these examinations. It is shown that for the DRLs, patient dose data from different CT scanners should be collected in age or weight groups, possibly for different indications. For practical reasons, the DRLs for paediatric chest CT should be given as a continuous DRL curve as a function of patient weight. For paediatric head CT, DRLs for a few age groups could be given. The users of the DRLs should be aware of the calibration phantom applied in the console calibration for different paediatric scanning protocols. The feasibility of DRLs should be re-evaluated every 2-3 y.

Missense single nucleotide polymorphism of the ADAM12 gene is associated with radiographic knee osteoarthritis in middle-aged Estonian cohort.

OBJECTIVE: One of the recognized candidate genes of osteoarthritis (OA) is the ADAM metallopeptidase domain 12 (meltrin alpha) gene. We investigated the potential role of two single nucleotide polymorphisms (SNP) of the ADAM12 gene in susceptibility to radiographic knee OA and its progression in an Estonian cohort. METHODS: The rs3740199 and rs1871054 polymorphisms were genotyped according to restriction fragment polymorphism in a population-based cohort consisting of 189 subjects selected from the age group 32-55 years. The radiological features of OA were measured in the tibio- and patellofemoral joints (PFJ). The X-ray investigation was repeated 3 years later for estimation of OA progression. RESULTS: We found statistically significant association between rs3740199 polymorphism and patellofemoral OA in male patients (P=0.014), genetic risk was mostly related to CC homozygosity. The same SNP also affected the presence of advanced grade (II+III) osteophytes in the whole group (P=0.042) and the occurrence of osteophytes on the patellar margins in the PFJ (P=0.046). In OA progression the most significant association was found between joint space narrowing of the tibiofemoral joint and rs3740199 SNP in women (P=0.018). The rs1871054 polymorphism was not related to OA susceptibility or to progression traits. In our study the haplotype GC (rs3740199/rs1871054) was associated with reduced risk for development of osteophytes in the PFJ (P=0.041). CONCLUSIONS: We conclude that rs3740199 polymorphism may affect occurrence of knee OA and its progression. We also hypothesize that the genetic contribution of ADAM12 to OA is remarkably gender-dependent and anatomical site-specific.

Cerebral blood-flow velocities in predicting outcome of asphyxiated newborn infants.

AIM: To evaluate the role of early (up to 12 h) changes in cerebral blood-flow (CBF) velocity in predicting the severity of hypoxic-ischaemic encephalopathy (HIE) and long-term outcome in asphyxiated term infants. METHODS: CBF velocities were investigated by colour Doppler ultrasonography in 81 healthy and 60 asphyxiated term infants at least three times during the first 5 d of life. The psychomotor development of infants was followed up to 18 mo. RESULTS: No differences in CBF velocities were found at the age of 2-6 h between infants with severe and mild-moderate HIE, mean CBF velocity [mean (95% CI of mean CBF velocity)] in anterior cerebral artery [14.9 (1.4-28.4)cm/s] and [13.9 (11.1-16.7) cm/s], respectively, and between infants with poor outcome (death or severe disability) and with normal development/mild impairments. By the age of 12 h infants with mild-moderate HIE and infants with normal development/mild impairments had decreased CBF velocity in the anterior cerebral artery, and infants with severe HIE or poor outcome had increased mean CBF velocity in anterior, medial cerebral and basilar artery compared to the control group. CONCLUSION: The value of CBF velocity changes to predict poor outcome in asphyxiated infants is low 2-6 h after asphyxia, but increases by the age of 12 ho.