Intra-articular depletion of macrophages increases acute synovitis and alters macrophage polarity in the injured mouse knee.

OBJECTIVE: Acute synovial inflammation following joint trauma is associated with posttraumatic arthritis. Synovial macrophages have been implicated in degenerative changes. In this study, we sought to elucidate the role of intra-articular macrophages in the acute inflammatory response to fracture in the mouse knee. METHOD: A closed articular fracture was induced in two models of synovial macrophage depletion: genetically-modified MaFIA mice administered AP20187 to induce programmed macrophage apoptosis, and wild-type C57BL/6 mice administered clodronate liposomes, both via intra-articular injection. Synovial inflammation, bone morphology, and levels of F4/80+ macrophages, NOS2+ M1 macrophages, and CD206+ M2 macrophages were quantified 7 days after fracture using histology and micro-computed tomography. RESULTS: Intra-articular macrophage depletion with joint injury did not reduce acute synovitis or the number of synovial macrophages 7 days after fracture in either macrophage-depleted MaFIA mice or in clodronate-treated C57BL/6 mice. In macrophage-depleted MaFIA mice, macrophage polarity shifted to a dominance of M1 macrophages and a reduction of M2 macrophages in the synovial stroma, indicating a shift in M1/M2 macrophage ratio in the joint following injury. Interestingly, MaFIA mice depleted 2 days prior to fracture demonstrated increased synovitis (P = 0.003), reduced bone mineral density (P = 0.0004), higher levels of M1 macrophages (P = 0.013), and lower levels of M2 macrophages (not statistically significant, P=0.084) compared to control-treated MaFIA mice. CONCLUSION: Our findings indicate that macrophages play a critical immunomodulatory role in the acute inflammatory response surrounding joint injury and suggest that inhibition of macrophage function can have prominent effects on joint inflammation and bone homeostasis after joint trauma.

Essential variables for reporting research studies on fetal growth restriction: a Delphi consensus.

OBJECTIVE: To determine, by expert consensus using a Delphi procedure, a minimum reporting set of study variables for fetal growth restriction (FGR) research studies. METHODS: A panel of experts, identified based on their publication record as lead or senior author of studies on FGR, was asked to select a set of essential reporting study parameters from a literature-based list of variables, utilizing the Delphi consensus methodology. Responses were collected in four consecutive rounds by online questionnaires presented to the panelists through a unique token-secured link for each round. The experts were asked to rate the importance of each parameter on a five-point Likert scale. Variables were selected in the three first rounds based on a 70% threshold for agreement on the Likert-scale scoring. In the final round, retained parameters were categorized as essential (to be reported in all FGR studies) or recommended (important but not mandatory). RESULTS: Of the 100 invited experts, 87 agreed to participate and of these 62 (71%) completed all four rounds. Agreement was reached for 16 essential and 30 recommended parameters including maternal characteristics, prenatal investigations, prenatal management and pregnancy/neonatal outcomes. Essential parameters included hypertensive complication in the current pregnancy, smoking, parity, maternal age, fetal abdominal circumference, estimated fetal weight, umbilical artery Doppler (pulsatility index and end-diastolic flow), fetal middle cerebral artery Doppler, indications for intervention, pregnancy outcome (live birth, stillbirth or neonatal death), gestational age at delivery, birth weight, birth-weight centile, mode of delivery and 5-min Apgar score. CONCLUSIONS: We present a list of essential and recommended parameters that characterize FGR independent of study hypotheses. Uniform reporting of these variables in prospective clinical research is expected to improve data quality, study consistency and ultimately our understanding of FGR. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Linking databases on perinatal health: a review of the literature and current practices in Europe.

BACKGROUND: International comparisons of perinatal health indicators are complicated by the heterogeneity of data sources on pregnancy, maternal and neonatal outcomes. Record linkage can extend the range of data items available and thus can improve the validity and quality of routine data. We sought to assess the extent to which data are linked routinely for perinatal health research and reporting. METHODS: We conducted a systematic review of the literature by searching PubMed for perinatal health studies from 2001 to 2011 based on linkage of routine data (data collected continuously at various time intervals). We also surveyed European health monitoring professionals about use of linkage for national perinatal health surveillance. RESULTS: 516 studies fit our inclusion criteria. Denmark, Finland, Norway and Sweden, the US and the UK contributed 76% of the publications; a further 29 countries contributed at least one publication. Most studies linked vital statistics, hospital records, medical birth registries and cohort data. Other sources were specific registers for: cancer (70), congenital anomalies (56), ART (19), census (19), health professionals (37), insurance (22) prescription (31), and level of education (18). Eighteen of 29 countries (62%) reported linking data for routine perinatal health monitoring. CONCLUSION: Research using linkage is concentrated in a few countries and is not widely practiced in Europe. Broader adoption of data linkage could yield substantial gains for perinatal health research and surveillance.

[Customized and non-customized French intrauterine growth curves. II - Comparison with existing curves and benefits of customization]. / Courbes de croissance in utero ajustées et non ajustées adaptées à la population française. II - Comparaison à des courbes existantes et apport de l'ajustement.

OBJECTIVES: Our aim is to compare the new French EPOPé intrauterine growth curves, developed to address the guidelines 2013 of the French College of Obstetricians and Gynecologists, with reference curves currently used in France, and to evaluate the consequences of their adjustment for fetal sex and maternal characteristics. POPULATION AND METHODS: Eight intrauterine and birthweight curves, used in France were compared to the EPOPé curves using data from the French Perinatal Survey 2010. The influence of adjustment on the rate of SGA births and the characteristics of these births was analysed. RESULTS: Due to their birthweight values and distribution, the selected intrauterine curves are less suitable for births in France than the new curves. Birthweight curves led to low rates of SGA births from 4.3 to 8.5% compared to 10.0% with the EPOPé curves. The adjustment for maternal and fetal characteristics avoids the over-representation of girls among SGA births, and reclassifies 4% of births. Among births reclassified as SGA, the frequency of medical and obstetrical risk factors for growth restriction, smoking (≥10 cigarettes/day), and neonatal transfer is higher than among non-SGA births (P<0.01). CONCLUSION: The EPOPé curves are more suitable for French births than currently used curves, and their adjustment improves the identification of mothers and babies at risk of growth restriction and poor perinatal outcomes.

What about the mothers? An analysis of maternal mortality and morbidity in perinatal health surveillance systems in Europe.

OBJECTIVE: To assess capacity to develop routine monitoring of maternal health in the European Union using indicators of maternal mortality and severe morbidity. DESIGN: Analysis of aggregate data from routine statistical systems compiled by the EURO-PERISTAT project and comparison with data from national enquiries. SETTING: Twenty-five countries in the European Union and Norway. POPULATION: Women giving birth in participating countries in 2003 and 2004. METHODS: Application of a common collection of data by selecting specific International Classification of Disease codes from the 'Pregnancy, childbirth and the puerperium' chapter. External validity was assessed by reviewing the results of national confidential enquiries and linkage studies. MAIN OUTCOME MEASURES: Maternal mortality ratio, with distribution of specific obstetric causes, and severe acute maternal morbidity, which included: eclampsia, surgery and blood transfusion for obstetric haemorrhage, and intensive-care unit admission. RESULTS: In 22 countries that provided data, the maternal mortality ratio was 6.3 per 100,000 live births overall and ranged from 0 to 29.6. Under-ascertainment was evident from comparisons with studies that use enhanced identification of deaths. Furthermore, routine cause of death registration systems in countries with specific systems for audit reported higher maternal mortality ratio than those in countries without audits. For severe acute maternal morbidity, 16 countries provided data about at least one category of morbidity, and only three provided data for all categories. Reported values ranged widely (from 0.2 to 1.6 women with eclampsia per 1000 women giving birth and from 0.2 to 1.0 hysterectomies per 1000 women). CONCLUSIONS: Currently available data on maternal mortality and morbidity are insufficient for monitoring trends over time in Europe and for comparison between countries. Confidential enquiries into maternal deaths are recommended.

Obstetric interventions for babies born before 28 weeks of gestation in Europe: results of the MOSAIC study.

OBJECTIVE: To describe obstetric intervention for extremely preterm births in ten European regions and assess its impact on mortality and short term morbidity. DESIGN: Prospective observational cohort study. SETTING: Ten regions from nine countries participating in the 'Models of Organising Access to Intensive Care for Very Preterm Babies in Europe' (MOSAIC) project. POPULATION: All births from 22 to 29 weeks of gestation (n = 4146) in 2003, excluding terminations of pregnancy. METHODS: Comparison of three obstetric interventions (antenatal corticosteroids, antenatal transfer and caesarean section for fetal indication) rates at 22-23, 24-25 and 26-27 weeks to that at 28-29 weeks and the association of the level of intervention with pregnancy outcome. MAIN OUTCOME MEASURES: Use of antenatal corticosteroids, antenatal transfer and caesarean section by two-week gestational age groups as well as a composite score of these three interventions. Outcomes included stillbirth, in-hospital mortality and intraventricular haemorrhage (IVH) grades III and IV and/or periventricular leucomalacia (PVL) and bronchopulmonary dysplasia (BPD). RESULTS: There were large differences between regions in interventions for births at 22-23 and 24-25 weeks. Differences were most pronounced at 24-25 weeks; in some regions these babies received the same care as babies of 28-29 weeks, whereas elsewhere levels of intervention were distinctly lower. Before 26 weeks and especially at 24-25 weeks, there was an association between the composite intervention score and mortality. No association was observed at 26-27 weeks. For survivors at 24-25 weeks, the intervention score was associated with higher rates of BPD, but not with IVH or PVL. CONCLUSIONS: There are large differences between European regions in obstetric practices at the lower limit of viability and these are related to outcome, especially at 24-25 weeks.

Are risk factors the same for small for gestational age versus other preterm births?

OBJECTIVES: This article explores whether the impact of social and demographic risk factors for preterm birth differs for small for gestational age preterm births versus other preterm births. STUDY DESIGN: This was a European case control study of the determinants of preterm birth (4700 cases and 6460 controls). Small for gestational age and non-small for gestational age preterm births were compared with a control group of term births; relationships were explored further by stratifying preterm births into subgroups by mode of onset, the presence of hypertension, and gestational age. RESULTS: Of the social and demographic risk factors for preterm birth identified in this sample, high maternal age, smoking, and low and high maternal body mass index have a stronger effect on small for gestational age preterm births. In contrast, obstetric history, maternal education, and marital status have similar effects regardless of birth weight. Hypertension during pregnancy is strongly associated with small for gestational age preterm birth and contributes to an explanation of observed differences. CONCLUSIONS: These results underline the importance of considering fetal growth restriction in the analysis of risk factors for preterm birth.

Nasal and sinus manifestations of sarcoidosis.

Nasal and sinus diseases are considered uncommon manifestations of sarcoidosis. We evaluated 159 consecutive patients with sarcoidosis for nasal symptoms. Sixty-three patients (39%) denied any nasal symptoms. Thirty-six patients (23%) had intermittent symptoms that lasted less than three weeks and required continuous intervention with nasal steroids or normal saline. Sixty patients (38%) were treated with nasal steroids and antibiotics for symptoms that lasted more than three weeks. Thirty-three patients (21%) had resolution of their symptoms after treatment with nasal steroids and antibiotics. Twenty-seven patients (17%) had symptoms that were unresponsive to three weeks of oral antibiotics and nasal steroids, and underwent CT scan. Based on the CT results, five patients underwent biopsy, which confirmed sarcoidosis. An additional patient who had a normal CT scan underwent a biopsy that was consistent with sarcoidosis. A retrospective review of 733 sarcoidosis patients was then performed, and an additional 12 patients were identified with biopsy-proven sarcoidosis. All of these patients required long-term therapy with prednisone (14 patients), methotrexate (13 patients), and/or azathioprine (8 patients). Our clinical study reveals a higher incidence of nasal and sinus disease in patients with sarcoidosis than has previously been described, and the recalcitrance of sarcoidosis when there is sinus involvement.

HPV detection using "hot start" polymerase chain reaction in patients with oral cancer: a clinicopathological study of 64 patients.

We examined the incidence of human papillomavirus (HPV) in intraoral cancers from 64 patients as determined by the highly sensitive technique of "hot start" polymerase chain reaction (PCR) in formalin-fixed paraffin-embedded tissues. Polymerase-chain-reaction-amplified HPV DNA was detected in the carcinomas of 16 patients (25%). The percentage of men in the HPV-positive (HPV+) group was greater than that in the HPV-negative (HPV-) group (86% versus 68%), but the difference was not statistically significant. There was no intraoral site preference for the HPV+ tumors. The mean age of viral-positive and -negative groups was similar (55 versus 53.8 yr). Three of 16 HPV+ patients (19%) had never smoked cigarettes; however, 16% of the HPV- group had also never smoked. Of interest, 38% of patients interviewed had occupation-related exposures that may have contributed to their carcinogenesis, and a disproportionate percentage of these patients (57%) were from the HPV+ group. There were no statistically significant differences between HPV+ and HPV- cases regarding T stage, clinical stage, and tumor differentiation. The disease-free interval did not differ significantly for HPV+ and HPV- patients in total nor when patients were stratified for tumor stage and clinical stage. The only group that showed some difference in outcome was that of the stage III/IV patients with oral cancer. We observed a shorter survival time for the HPV+ patients as compared with the HPV- patients (P = 0.09). We conclude that, in general, HPV is associated with a minority of intraoral cancers and its presence is not predictive of patient outcome.