Maternal pre-pregnancy body mass index and risk of preterm birth: a collaboration using large routine health datasets.

BACKGROUND: Preterm birth (PTB) is a leading cause of child morbidity and mortality. Evidence suggests an increased risk with both maternal underweight and obesity, with some studies suggesting underweight might be a greater factor in spontaneous PTB (SPTB) and that the relationship might vary by parity. Previous studies have largely explored established body mass index (BMI) categories. Our aim was to compare associations of maternal pre-pregnancy BMI with any PTB, SPTB and medically indicated PTB (MPTB) among nulliparous and parous women across populations with differing characteristics, and to identify the optimal BMI with lowest risk for these outcomes. METHODS: We used three UK datasets, two USA datasets and one each from South Australia, Norway and Denmark, together including just under 29 million pregnancies resulting in a live birth or stillbirth after 24 completed weeks gestation. Fractional polynomial multivariable logistic regression was used to examine the relationship of maternal BMI with any PTB, SPTB and MPTB, among nulliparous and parous women separately. The results were combined using a random effects meta-analysis. The estimated BMI at which risk was lowest was calculated via differentiation and a 95% confidence interval (CI) obtained using bootstrapping. RESULTS: We found non-linear associations between BMI and all three outcomes, across all datasets. The adjusted risk of any PTB and MPTB was elevated at both low and high BMIs, whereas the risk of SPTB was increased at lower levels of BMI but remained low or increased only slightly with higher BMI. In the meta-analysed data, the lowest risk of any PTB was at a BMI of 22.5 kg/m2 (95% CI 21.5, 23.5) among nulliparous women and 25.9 kg/m2 (95% CI 24.1, 31.7) among multiparous women, with values of 20.4 kg/m2 (20.0, 21.1) and 22.2 kg/m2 (21.1, 24.3), respectively, for MPTB; for SPTB, the risk remained roughly largely constant above a BMI of around 25-30 kg/m2 regardless of parity. CONCLUSIONS: Consistency of findings across different populations, despite differences between them in terms of the time period covered, the BMI distribution, missing data and control for key confounders, suggests that severe under- and overweight may play a role in PTB risk.

Simulating drifting fish aggregating device trajectories to identify potential interactions with endangered sea turtles.

Purse-seine fishers using drifting fish aggregating devices (dFADs), mainly built with bamboo, plastic buoys, and plastic netting, to aggregate and catch tropical tuna, deploy 46,000-65,000 dFADs per year in the Pacific Ocean. Some of the major concerns associated with this widespread fishing device are potential entanglement of sea turtles and other marine fauna in dFAD netting; marine debris and pollution; and potential ecological damage via stranding on coral reefs, beaches, and other essential habitats for marine fauna. To assess and quantify the potential connectivity (number of dFADs deployed in an area and arriving in another area) between dFAD deployment areas and important oceanic or coastal habitat of critically endangered leatherback (Dermochelys coriacea) and hawksbill (Eretmochelys imbricata) sea turtles in the Pacific Ocean, we conducted passive-drift Lagrangian experiments with simulated dFAD drift profiles and compared them with known important sea turtle areas. Up to 60% of dFADs from equatorial areas were arriving in essential sea turtle habitats. Connectivity was less when only areas where dFADs are currently deployed were used. Our simulations identified potential regions of dFAD interactions with migration and feeding habitats of the east Pacific leatherback turtle in the tropical southeastern Pacific Ocean; coastal habitats of leatherback and hawksbill in the western Pacific (e.g., archipelagic zones of Indonesia, Papua New Guinea, and Solomon Islands); and foraging habitat of leatherback in a large equatorial area south of Hawaii. Additional research is needed to estimate entanglements of sea turtles with dFADs at sea and to quantify the likely changes in connectivity and distribution of dFADs under new management measures, such as use of alternative nonentangling dFAD designs that biodegrade, or changes in deployment strategies, such as shifting locations.

Simulación de las trayectorias de dispositivos de concentración de peces a la deriva para identificar las interacciones potenciales con las tortugas marinas en peligro de extinción Resumen Los pescadores que usan redes de cerco con dispositivos de concentración de peces a la deriva (dFADs), hechos principalmente con bambú, boyas de plástico y redes de plástico, para concentrar y capturar atún, instalan entre 46,000 y 65,000 dFADs al año en el Océano Pacífico. Algunas de las problemáticas principales asociadas con este dispositivo de pesca de uso extenso son el enredamiento potencial de tortugas marinas y otras especies marinas en las redes de los dFADs; los desechos marinos y la contaminación; y el potencial daño ecológico por el varamiento en los arrecifes de coral, playas y otros hábitats esenciales para la fauna marina. Realizamos experimentos lagrangianos de deriva pasiva con la simulación de perfiles de deriva de los dFADs y los comparamos con áreas conocidas de importancia para las tortugas marinas. Esto fue con el objetivo de evaluar y cuantificar la conectividad potencial (número de dFADs instalados en un área que llegan a otra área) entre las áreas de instalación de dFADs y los hábitats oceánicos o costeros importantes para la tortuga laúd (Dermochelys coriacea) y la tortuga de carey (Eretmochelys imbricata), ambas en peligro crítico de extinción, en el Océano Pacífico. Hasta el 60% de los dFADs de las áreas ecuatoriales llegaron a los hábitats esenciales para las tortugas marinas. La conectividad fue menor sólo cuando se usaron áreas en donde actualmente hay dFADs instalados. Nuestras simulaciones identificaron regiones potenciales de interacción entre los dFADs y los hábitats de migración y alimentación de la tortuga laúd en el sureste tropical del Océano Pacífico; los hábitats costeros de ambas especies en el Pacífico occidental (p. ej.: zonas de archipiélagos en Indonesia, Papúa Nueva Guinea y en las Islas Salomón); y en el hábitat de forrajeo de la tortuga laúd en una gran área ecuatorial al sur de Hawái. Se requiere de mayor investigación para estimar el enredamiento de las tortugas marinas con los dFADs en el mar y para cuantificar los cambios probables en la conectividad y la distribución de los dFADs bajo nuevas medidas de manejo, como el uso alternativo de diseños que eviten el enredamiento y sean biodegradables, o cambios en las estrategias de instalación, como la reubicación.

Improved responsiveness to change in joint space width over 24-month follow-up: comparison of 3D JSW on weight-bearing CT vs 2D JSW on radiographs in the MOST study.

OBJECTIVE: Radiographic joint space width (JSW) has been a standard for measuring knee osteoarthritis (OA) structural change. Limitations in the responsiveness of this approach might be overcome by instead measuring 3D JSW on weight-bearing CT (WBCT). This study compared the responsiveness of 3D JSW measurements using WBCT with the responsiveness of radiographic 2D JSW. DESIGN: Standing, fixed-flexion knee radiographs (XR) and WBCT were acquired ancillary to the 144- and 168-month Multicenter Osteoarthritis Study visits. Tibiofemoral JSW was measured on both XR and WBCT. Responsiveness to change was defined by the standardized response mean (SRM) for change in JSW (1) at predetermined mediolateral locations (JSWx) on both modalities and (2) in the following subregions measured on WBCT images: central medial and lateral femur (CMF/CLF) and tibia (CMT/CLT), and anterior and posterior tibia (AMT/ALT, PMT/MLT). RESULTS: Baseline and 24-month follow-up JSWx measurements were completed for 265 participants (58.1% women). Responsiveness of 3D JSWx for medial tibiofemoral compartment on coronal WBCT (SRM range: -0.18, -0.24) exceeded that for 2D JSWx (-0.10, -0.16). Responsiveness of 3D JSW subregional mean (-0.06, -0.36) and maximal (-1.14, -1.75) CMF and CMT and maximal CLF/CLT 3D JSW changes were statistically significantly greater in comparison with respective medial and lateral 2D JSWx (P ≤ 0.002). CONCLUSIONS: Subregional 3D JSW on WBCT is substantially more responsive to 24-month changes in tibiofemoral joint structure compared to radiographic measurements. Use of subregional 3D JSW on WBCT could enable improved detection of OA structural progression over a 24-month duration in comparison with measurements made on XR.

Prevalence of intra-articular mineralization on knee computed tomography: the multicenter osteoarthritis study.

OBJECTIVE: The aim of this work was to report the prevalence of computed tomography (CT)-detected intra-articular mineralization. DESIGN: We included participants from the Multicenter Osteoarthritis (MOST) Study. At the 12th year visit of the MOST study, bilateral knee CTs were first obtained. All participants also had posteroanterior and lateral radiographs of bilateral knees and completed standard questionnaires. Knee radiographs were assessed for Kellgren & Lawrence grade (KLG) and radiographic evidence of intra-articular mineralization. CT images were scored using the Boston University Calcium Knee Score (BUCKS) for cartilage, menisci, ligaments, capsule, and vasculature. Prevalence of intra-articular mineralization was computed for the total sample, and stratified by age, sex, race, Body Mass Index (BMI), presence of frequent knee pain, and KLG. We also determined distribution of mineralization in the cartilage and meniscus, and co-localization. RESULTS: 4140 bilateral knees from 2070 participants were included (56.7% female, mean age 61.1 years, mean BMI: 28.8 kg/m2). On radiographs 240 knees (5.8%) had intraarticular mineralization, while CT-detected mineralization was present in 9.8% of knees. Prevalence of hyaline articular and meniscus mineralization increased with age and KL grade, and was similar by sex, BMI categories, and comparable in subjects with and without frequent knee pain. Mineralization tended to be ubiquitous in the joint, most commonly involving all three (medial/lateral tibiofemoral and patellofemoral) compartments (3.1%), while the patellofemoral compartment was the most involved compartment in isolation (1.4%). CONCLUSIONS: CT of the knee provides greater visualization of intra-articular mineralization than radiographs and allows better localization of the crystal deposition within the joint. Further studies should focus on the co-localization of intra-articular crystal deposition and corresponding magnetic resonance imaging (MRI)-features of knee osteoarthritis (OA).

Clinical value of weight-bearing CT and radiographs for detecting patellofemoral cartilage visualized by MRI in the MOST study.

OBJECTIVE: The patellofemoral joint is frequently affected by osteoarthritis (PFOA) and is incompletely imaged on radiographs (XR). Weight-Bearing CT (WBCT) could offer advantages for visualization. This study determined the sensitivity, specificity, and accuracy of axial WBCT and lateral XR for detection of PFOA features in comparison with cartilage damage on MRI. DESIGN: A convenience sample of 60 right knees from the MOST cohort were analyzed. WBCT and XR were read for OARSI JSN score and MRI for MOAKS cartilage score by two experienced musculoskeletal radiologists blinded to participant. Using MOAKS scoring on MRI (referent standard), the sensitivity, specificity and accuracy of patellofemoral OARSI JSN scores based on WBCT and XR were compared. RESULTS: The mean ± SD age and BMI for the participants included (66.7% women) were 67.6 ± 9.8 years and 30.0 ± 5.3 kg/m2 respectively. WBCT demonstrated significantly greater sensitivity (0.85-0.97 on WBCT vs 0.47-0.57 on XR) and accuracy (0.85-0.92 on WBCT vs 0.48-0.57 on XR) for all parameters except lateral full-thickness cartilage loss (McNemar's test p-values all <0.001). There was moderate-to-strong and low-to-moderate agreement between PFOA findings on WBCT and XR, respectively, and semi-quantitative scores of PF cartilage on MRI. Inter-rater reliability for XR JSN [weighted kappa = 0.83 (0.64, 1.0)], WBCT JSN [kappa = 0.60 (0.48, 0.72)] and MRI MOAKS-CM [kappa = 0.70 (0.61, 0.79)] readings were good. CONCLUSION: WBCT demonstrates significantly greater sensitivity and accuracy than radiographs for identification of PFOA. Given the same Relative Radiation Level as XR and improved visualization, WBCT holds promise to improve understanding of the weight-bearing patellofemoral joint.

Elective labor induction vs expectant management of pregnant women at term and children's educational outcomes at 8 years of age.

OBJECTIVE: To estimate the effect of elective induction of labor at 39 weeks' gestation on children's educational outcomes as measured using the Australian National Assessment Program-Literacy and Numeracy (NAPLAN) tests in school year 3 (∼8 years of age), compared with expectant management. METHODS: We merged perinatal data on all infants born in South Australia from 1999 to 2008 with children's school assessment data from NAPLAN. The study population included all singleton infants born without a malformation at 39-42 weeks in vertex presentation. Children who had undertaken the NAPLAN test in school year 3 were included. We excluded births to women who had a contraindication to vaginal delivery and those with a condition possibly justifying elective delivery before 39 weeks. The outcome of interest was children's educational outcome as measured using NAPLAN, which includes five learning domains (reading, writing, spelling, grammar and numeracy). Each domain was categorized according to performance at or below vs above the national minimum standard (NMS). Average treatment effects (ATEs) of elective induction of labor at 39 weeks compared with expectant management on the proportion of children performing at/below the NMS for each domain were estimated using the augmented inverse-propensity-weighted estimator, accounting for potential confounders. RESULTS: Of 53 843 children born at 39-42 weeks in vertex presentation from 1999 to 2008 and who were expected to participate in the year-3 NAPLAN from 2008 to 2015, a total of 31 120 had at least one year-3 NAPLAN domain. Of these, 1353 children were delivered after elective induction of labor at 39 weeks while 29 767 children were born following expectant management. The ATEs (mean differences) of elective induction of labor at 39 weeks compared with expectant management on the proportion of children scoring at/below the NMS on each domain were 0.01 (95% CI, -0.02 to 0.03) for reading, 0.02 (95% CI, 0.00-0.04) for writing, 0.01 (95% CI, -0.01 to 0.04) for spelling, 0.02 (95% CI, -0.01 to 0.04) for grammar and 0.03 (95% CI, 0.00-0.05) for numeracy. CONCLUSION: Elective induction of labor at 39 weeks did not affect children's standardized literacy and numeracy testing outcomes at 8 years of age when compared with expectant management. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Reliability of a new scoring system for intraarticular mineralization of the knee: Boston University Calcium Knee Score (BUCKS).

BACKGROUND: The role of intra-articular mineralization in osteoarthritis (OA) is unclear. Its understanding may potentially advance our knowledge of knee OA pathogenesis. We describe and assess the reliability of a novel computed tomography (CT) scoring system, the Boston University Calcium Knee Score (BUCKS) for evaluating intra-articular mineralization. METHODS: We included subjects from the most recent study visit of the Multicenter Osteoarthritis Study (MOST) Study, a NIH-funded longitudinal cohort of community-dwelling older adults with or at risk of knee OA. All subjects underwent CT of bilateral knees. Each knee was scored at 28 scored locations (14 for cartilage, 6 for menisci, 6 for ligaments, 1 for joint capsule, and 1 popliteal-tibial vessels). A single musculoskeletal radiologist scored cartilage and meniscus subregions, as well as vascular calcifications assigning to each a score ranging from 0 to 3. The joint capsule, medial and lateral posterior meniscal roots, anterior cruciate ligament (ACL)/posterior cruciate ligament (PCL) and 2 collateral ligaments [medial collateral ligament (MCL)/lateral collateral ligament (LCL)] were each scored 0 or 1 for absence or presence of mineralization. To assess reliability, 31 subject CTs were reread 12 weeks later by the same reader and by a second reader and agreement was evaluated using a weighted kappa. RESULTS: The intra-reader reliability ranged from 0.92 for ligaments to 1.0 for joint capsule. The inter-reader reliability ranged from 0.94 for cartilage and ligaments, to 1.0 for joint capsule. CONCLUSION: BUCKS demonstrated excellent reliability and is a potentially useful CT-based tool for studying the role of calcium crystals in knee OA.

The morphology of proximal tibiofibular joint (PTFJ) predicts incident radiographic osteoarthritis: data from Osteoarthritis Initiative.

OBJECTIVE: To determine whether the morphology of proximal tibiofibular joint (PTFJ) is associated with increased risk of incident radiographic osteoarthritis (iROA) over 4 years in the OA Initiative (OAI) study. METHODS: A nested matched case-control study design was used to select participants from OAI study. Case knees were defined as those with iROA. Control knees were matched one-to-one by sex, age and radiographic status with case knees. T2-weighted MR images were assessed at P0 (the visit when incident ROA was found on radiograph), P1 (1 year prior to P0) and at OAI baseline. The contacting area of PTFJ (S) and its projection areas onto the horizontal (load-bearing area, Sτ), sagittal (lateral stress-bolstering area, Sφ) and coronal plane (posterior stress-bolstering area, Sυ) were assessed, respectively. RESULTS: 354 case knees and 354 matched control knees were included, with a mean age of 60 and a mean body mass index (BMI) of 28 kg/m2. Baseline PTFJ morphological parameters (S, Sτ and Sυ) were significantly associated with iROA over 4 years, and these associations remained unchanged after adjustment for BMI, number of knee bending activities, self-reported knee injury and surgery. S, Sτ and Sυ were also significantly associated with iROA at P1 and P0. In subgroup analysed, S, Sτ and Sυ were associated with risks of incident joint space narrowing in the medial, but not the lateral tibiofemoral compartment. CONCLUSION: Greater contacting area, load-bearing area and posterior stress-bolstering area of PTFJ were associated with increased risks of iROA, largely in the medial tibiofemoral compartment.

MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES).

PURPOSE: Our aim was to introduce a simplified MRI instrument, Rapid OsteoArthritis MRI Eligibility Score (ROAMES), for defining structural eligibility of patients for inclusion in disease-modifying osteoarthritis drug trials using a tri-compartmental anatomic approach that enables stratification of knees into different structural phenotypes and includes diagnoses of exclusion. We also aimed to define overlap between phenotypes and determine reliability. METHODS: 50 knees from the Foundation for National Institutes of Health Osteoarthritis Biomarkers study, a nested case-control study within the Osteoarthritis Initiative, were selected within pre-defined definitions of phenotypes as either inflammatory, subchondral bone, meniscus/cartilage, atrophic or hypertrophic. A focused scoring instrument was developed covering cartilage, meniscal damage, inflammation and osteophytes. Diagnoses of exclusion were meniscal root tears, osteonecrosis, subchondral insufficiency fracture, tumors, malignant marrow infiltration and acute traumatic changes. Reliability was determined using weighted kappa statistics. Descriptive statistics were used for determining concordance between the a priori phenotypic definition and ROAMES and overlap between phenotypes. RESULTS: ROAMES identified 43 of 50 (86%) pre-defined phenotypes correctly. Of the 50 participants, 27 (54%) had no additional phenotypes other than the pre-defined phenotype. 18 (36%) had one and 5 (10%) had two additional phenotypes. None had three or four additional phenotypes. All features of ROAMES showed almost perfect agreement. One case with osteonecrosis and one with a tumor were detected. CONCLUSIONS: ROAMES is able to screen and stratify potentially eligible knees into different structural phenotypes and record relevant diagnoses of exclusion. Reliability of the instrument showed almost perfect agreement.

Crotonaldehyde-induced vascular relaxation and toxicity: Role of endothelium and transient receptor potential ankyrin-1 (TRPA1).

INTRODUCTION: Crotonaldehyde (CR) is an electrophilic α,ß-unsaturated aldehyde present in foods and beverages and is a minor metabolite of 1,3-butadiene. CR is a product of incomplete combustion, and is at high levels in smoke of cigarettes and structural fires. Exposure to CR has been linked to cardiopulmonary toxicity and cardiovascular disease. OBJECTIVE: The purpose of this study was to examine the direct effects of CR in murine blood vessels (aorta and superior mesenteric artery, SMA) using an in vitro system. METHODS AND RESULTS: CR induced concentration-dependent (1-300 µM) relaxations (75-80%) in phenylephrine (PE) precontracted aorta and SMA. Because the SMA was 20× more sensitive to CR than aorta (SMA EC50 3.8 ± 0.5 µM; aorta EC50 76.0 ± 2.0 µM), mechanisms of CR relaxation were studied in SMA. The CR-induced relaxation at low concentrations (1-30 µM) was inhibited by: 1) mechanically-impaired endothelium; 2) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME); 3) guanylyl cyclase (GC) inhibitor (ODQ); 4) transient receptor potential ankyrin-1 (TRPA1) antagonist (A967079); and, 5) by non-vasoactive level of nicotine (1 µM). Similarly, a TRPA1 agonist, allyl isothiocyanate (AITC; mustard oil), stimulated SMA relaxation dependent on TRPA1, endothelium, NO, and GC. Consistent with these mechanisms, TRPA1 was present in the SMA endothelium. CR, at higher concentrations (100-300 µM), induced tension oscillations (spasms) and irreversibly impaired contractility (a vasotoxic effect enhanced by impaired endothelium). CONCLUSIONS: CR relaxation depends on a functional endothelium and TRPA1, whereas vasotoxicity is enhanced by endothelium dysfunction. Thus, CR is both vasoactive and vasotoxic along a concentration continuum.

Children and adolescents with type 1 and type 2 diabetes mellitus in the Pediatric Diabetes Consortium Registries: comparing clinical characteristics and glycaemic control.

AIM: To compare the characteristics of children and adolescents with type 1 vs. type 2 diabetes in the Pediatric Diabetes Consortium (PDC) registries. METHODS: Participants were 10 to < 21 years of age at diagnosis; there were 484 with type 1 diabetes and 1236 with type 2 diabetes. RESULTS: Children and adolescents with type 2 diabetes were more likely to be female, overweight/obese, and from low-income, minority ethnic families. Children and adolescents with type 1 diabetes were more likely to present with diabetic ketoacidosis and have higher mean HbA1c levels at diagnosis. More than 70% in both cohorts achieved target HbA1c levels < 58 mmol/mol (< 7.5%) within 6 months, but fewer participants with type 1 than type 2 diabetes were able to maintain target HbA1c levels after 6 months consistently throughout 3 years post diagnosis. Of the 401 participants with type 2 diabetes with ≥ 24 months diabetes duration on enrolment in the registry, 47% required no insulin treatment. Median C-peptide levels were 1.43 mmol/l in the subset of participants with type 2 diabetes in whom it was measured, but only 0.06 mmol/l in the subset with type 1 diabetes. CONCLUSIONS: Although families of children and adolescents with type 2 diabetes face greater socio-economic obstacles and risk factors for poor diabetes outcomes, the greater retention of residual endogenous insulin secretion likely contributes to the increased ability of children and adolescents with type 2 diabetes to maintain target HbA1c during the first 3 years of diabetes diagnosis.

From smartphone to bed-side: exploring the use of social media to disseminate recommendations from the National Tracheostomy Safety Project to front-line clinical staff.

Traditional methods used to disseminate educational resources to front-line healthcare staff have several limitations. Social media may increase the visibility of these resources among targeted groups and communities. Our project aimed to disseminate key clinical messages from the National Tracheostomy Safety Project to those caring for patients with tracheostomies or laryngectomies. We commissioned an external media company to design educational material and devise a marketing strategy. We developed videos to communicate recommendations from the safety project and used Facebook, Twitter, YouTube and LinkedIn to deliver these to our target users. We recorded 629,270 impressions over a paid 12-week campaign. Our YouTube channel registered more than a five-fold increase in views and watch time during the campaign as compared with the previous year. Around two-thirds of views across all platforms were from peer-to-peer sharing. We spent £4140 on social media advertising, with each view and click costing £0.02 and £0.67, respectively. This intelligence-led approach using social media is an effective and efficient method to disseminate knowledge on the principles of safe tracheostomy care to front-line clinical staff. Similar strategies may be effective for other patient safety topics, especially when targeting groups that do not use medical journals or other traditional means of dissemination.

Reversible cerebral vasoconstrictive syndrome preceded by minor head trauma.

Reversible cerebral vasoconstriction syndrome is a heterogeneous and under-recognised neurovascular disorder. Our knowledge with regards to specific syndrome triggers and optimal management is limited. The delay in diagnosis can be deleterious to the patient due to intracerebral sequelae causing temporary or permanent morbidity. Prompt identification of this syndrome is vital to reverse neurological deficits while appropriately managing and supporting patient recovery.

Caesarean section and risk of type 1 diabetes: whole-of-population study.

AIM: A hypothesized mechanism for increased type 1 diabetes risk among caesarean births is lack of exposure to the vaginal microbiota. Children born by prelabour caesarean are not exposed to the vaginal microbiota, whereas caesarean births during labour (intrapartum) may be exposed. The aim of this study was to estimate type 1 diabetes risk among children born by caesarean compared with normal vaginal delivery. METHODS: This whole-of-population study linked routinely collected, de-identified administrative data from the South Australian Early Childhood Data Project for all births from 1999 to 2013. Type 1 diabetes cases were identified using inpatient hospitalizations from 2001 to 2014 (ICD-10-AM codes E10-E109). Type 1 diabetes risk for caesarean was assessed by Cox regression using two models: (i) caesarean vs. vaginal and (ii) prelabour or intrapartum caesarean vs. vaginal. Analyses were adjusted for confounding and multiple imputation was used to address missing data. RESULTS: A total of 286 058 children born between 1999 and 2013 contributed to 2 200 252 person-years, of which 557 had type 1 diabetes. Of all births, 90 546 (31.7%) were caesarean, and of these 53.1% were prelabour and 46.9% intrapartum caesarean. Compared with vaginal delivery, the adjusted hazard ratio for type 1 diabetes was 1.05 [95% confidence interval (CI) 0.86-1.28) for caesarean, 1.02 (95% CI 0.79-1.32) for prelabour caesarean and 1.08 (95% CI 0.82-1.41) for intrapartum caesarean. CONCLUSION: There may be a small increased type 1 diabetes risk following caesarean, but confidence intervals included the null. The lower estimate for prelabour compared with intrapartum caesarean, and the potential for unmeasured confounding suggest that neonatal vaginal microbiota might not be involved in type 1 diabetes.

The Prognostic Importance of Bronchoalveolar Lavage Fluid CXCL9 During Minimal Acute Rejection on the Risk of Chronic Lung Allograft Dysfunction.

The clinical significance and treatment strategies for minimal acute rejection (grade A1), the most common form of acute rejection (AR), remain controversial. In this retrospective single-center cohort study of 441 lung transplant recipients, we formally evaluate the association between minimal AR and chronic lung allograft dysfunction (CLAD) and test a novel hypothesis using bronchoalveolar lavage (BAL) CXCL9 concentration during minimal AR as a biomarker of subsequent CLAD development. In univariable and multivariable models adjusted for all histopathologic injury patterns, minimal AR was not associated with CLAD development. However, minimal AR with elevated BAL CXCL9 concentrations markedly increased CLAD risk in a dose-response manner. Minimal AR with CXCL9 concentrations greater than the 25th, 50th, and 75th percentile had adjusted hazard ratios (HRs) for CLAD of 1.1 (95% confidence interval [CI] 0.8-1.6), 1.6 (95% CI 1.1-2.3), and 2.2 (95% CI 1.4-3.4), respectively. Thus we demonstrate the utility of BAL CXCL9 measurement as a prognostic biomarker that allows discrimination of recipients at increased risk of CLAD development after minimal AR. BAL CXCL9 measurement during transbronchial biopsies may provide clinically useful prognostic data and guide treatment decisions for this common form of AR, as a possible strategy to minimize CLAD development.

Quantitative measurement of cartilage volume is possible using two-dimensional magnetic resonance imaging data sets.

PURPOSE: 3D Magnetic resonance imaging (MRI) scans are generally used for quantitative cartilage measurements in knee osteoarthritis. However, a great deal of MRI data is from 2D scans, often thought to be unsuitable for quantitative cartilage assessment. The goal of our study was to demonstrate that mLACS, a modified version of the Local Area Cartilage Segmentation (LACS) method, could be used to measure cartilage volume on 2D MRI images. METHODS: We studied 301 randomly selected subjects from the OA Biomarkers Consortium FNIH Study, a nested case-control study within the Osteoarthritis Initiative (OAI). The study comprised four subgroups based on radiographic and pain progression. We compared mLACS applied to 2D TSE scans to LACS on 3D DESS data. The Pearson's correlation coefficient was used to establish agreement between LACS and mLACS, standardized response means (SRMs) for responsiveness, and intra-class correlation coefficients (ICCs) to measure reader precision. Logistic regression in a case/control analysis was used to compare the clinical validity between the two methods. RESULTS: We found R2 = 0.76 for the correlation between LACS and mLACs. For LACS, the responsiveness was SRM = 0.49 compared to 0.39 for mLACS. The odds ratios (OR) for the primary case/control analyses were 1.62 for LACS and 1.78 for mLACS. The intra and inter reader reproducibility values for mLACS were ICC = 0.90 and 0.86, respectively. CONCLUSION: This study has demonstrated that a reproducible, responsive, and clinically valid quantitative measurement of cartilage volume can be made using 2D TSE scans with a modest loss of responsiveness compared to 3D scans.

Signal intensity alteration within infrapatellar fat pad predicts knee replacement within 5 years: data from the Osteoarthritis Initiative.

OBJECTIVE: To investigate whether infrapatellar fat pad (IPFP) signal intensity (SI) alteration predicts the occurrence of knee replacement (KR) in knee osteoarthritis (OA) patients over 5 years. DESIGN: The subjects were selected from Osteoarthritis Initiative (OAI) study. Case knees (n = 127) were defined as those who received KR during 5 years follow-up visit. They were matched by gender, age and radiographic status with control knees (n = 127). We used T2-weighted MR images to measure IPFP SI alteration using a newly developed algorithm in MATLAB. The measurements were assessed at baseline (BL), T0 (the visit just before KR) and 1 year before T0 (T-1). Conditional logistic regression was used to analyse the associations between IPFP SI alterations and the risk of KR. RESULTS: Participants were mostly female (57%), with an average age of 63.7 years old and a mean body mass index (BMI) of 29.5 kg/m2. In multivariable analysis, the standard deviation (SD) of IPFP SI [sDev (IPFP)] and the ratio of high SI region volume to whole IPFP volume [Percentage (H)] measured at BL were significantly associated with increased risks of KR after adjustment for covariates. IPFP SI alterations measured at T-1 including sDev (IPFP), Percentage (H) and clustering effect of high SI [Clustering factor (H)] were significantly associated with higher risks of KR. All measurements were significantly associated with higher risks of KR at T0. CONCLUSIONS: IPFP SI is associated with the occurrence of KR suggesting it may play a role in end-stage knee OA.

Associations between molecular biomarkers and MR-based cartilage composition and knee joint morphology: data from the Osteoarthritis Initiative.

OBJECTIVE: The purpose of this study was to assess the associations between serum/urine biomarkers for osteoarthritis and magnetic resonance (MR) imaging measures of cartilage composition and joint structure (cartilage, meniscus, and bone marrow), using MR imaging data from the Osteoarthritis Initiative (OAI). DESIGN: 141 subjects with Kellgren Lawrence (KL) grades 0-3 in the right knee and with available serum/urine biomarker assays were selected from the OAI. Cartilage magnetic resonance imaging (MRI) T2 measurements were performed in the medial femur, lateral femur, medial tibia, lateral tibia, and patella compartments. Compartment-specific knee morphologic grading [whole-organ magnetic resonance imaging score (WORMS)] in the cartilage, meniscus, and bone marrow was also performed. We focused on associations of serum hyaluronan (sHA), serum cartilage oligomeric matrix protein (sCOMP), serum matrix metalloproteinase-3 (sMMP3), and Urine Carboxy-Terminal Telepeptides of Type II Collagen (uCtX-II)) with MRI parameters (T2, WORMS), assessed using partial correlations adjusted for age, gender, body mass index (BMI), KL grade in both knees, and diabetes status. RESULTS: Higher levels of sHA, sMMP3 and sCOMP were correlated (P < 0.05) with T2 of the lateral femur (r = 0.18 to 0.32) and lateral tibia (r = 0.17 to 0.23), and with average T2 of all knee regions (r = 0.23). uCTXII was correlated with patellar T2 (r = 0.19, P = 0.04). Among the morphologic measures, sHA and sMMP3 was positively correlated (r = 0.17 to 0.21, P < 0.05) with meniscal damage. CONCLUSIONS: This study suggests weak, but statistically significant, correlations between serum biomarkers of OA (sHA, sCOMP, and sMMP3) and MRI T2 measures of cartilage extra-cellular matrix degeneration.

Impact of Allograft Injury Time of Onset on the Development of Chronic Lung Allograft Dysfunction After Lung Transplantation.

The impact of allograft injury time of onset on the risk of chronic lung allograft dysfunction (CLAD) remains unknown. We hypothesized that episodes of late-onset (≥6 months) allograft injury would produce an augmented CXCR3/ligand immune response, leading to increased CLAD. In a retrospective single-center study, 1894 transbronchial biopsy samples from 441 lung transplant recipients were reviewed for the presence of acute rejection (AR), lymphocytic bronchiolitis (LB), diffuse alveolar damage (DAD), and organizing pneumonia (OP). The association between the time of onset of each injury pattern and CLAD was assessed by using multivariable Cox models with time-dependent covariates. Bronchoalveolar lavage (BAL) CXCR3 ligand concentrations were compared between early- and late-onset injury patterns using linear mixed-effects models. Late-onset DAD and OP were strongly associated with CLAD: adjusted hazard ratio 2.8 (95% confidence interval 1.5-5.3) and 2.0 (1.1-3.4), respectively. The early-onset form of these injury patterns did not increase CLAD risk. Late-onset LB and acute rejection (AR) predicted CLAD in univariable models but lost significance after multivariable adjustment for late DAD and OP. AR was the only early-onset injury pattern associated with CLAD development. Elevated BAL CXCR3 ligand concentrations during late-onset allograft injury parallel the increase in CLAD risk and support our hypothesis that late allograft injuries result in a more profound CXCR3/ligand immune response.

The relationship between meniscal pathology and osteoarthritis depends on the type of meniscal damage visible on magnetic resonance images: data from the Osteoarthritis Initiative.

OBJECTIVE: To determine the association of different types of meniscal pathology with knee pain, bone marrow lesion (BML) volume, and end-stage knee osteoarthritis (esKOA). DESIGN: Participants were selected from an ancillary project to the Osteoarthritis Initiative (OAI) who had at least one knee with symptomatic osteoarthritis. Baseline magnetic resonance images (MRI) were evaluated for meniscal pathology using a modified International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine (ISAKOS) classification system. We collapsed 10 types of meniscal pathology into five categories: normal, intrameniscal signal, morphological deformity/extrusion (altered meniscal shape and/or extrusion but no apparent substance loss), tear, and maceration. Outcomes included Western Ontario and McMaster Universities osteoarthritis index (WOMAC) knee pain and BML volume at baseline and after 2 years. We defined the prevalence of esKOA based on a validated algorithm. We performed logistic regression and adjusted for age, sex, and body mass index (BMI). RESULTS: The 463 participants (53% male) included in the analysis had mean age 63 (9.2) years, BMI 29.6 (4.6) kg/m2, and 71% had Kellgren-Lawrence grade ≥2. Morphological deformity/extrusion and maceration, but no other types of meniscal pathology, were associated with BML volume (morphological deformity/extrusion odds ratio [OR] = 2.47, 95% CI: 1.49, 4.09, maceration OR = 5.85, 95% CI: 3.40, 10.06) and change in BML volume (morphological deformity/extrusion OR = 2.17, 95% CI: 1.37, 3.45, maceration OR = 3.12, 95% CI: 1.87, 5.19). Only maceration was associated with baseline WOMAC knee pain (OR = 2.82, 95% CI: 1.79, 4.43) and prevalence of esKOA (OR = 7.53, 95% CI: 4.25, 13.31). CONCLUSIONS: Based on MRI, morphologic deformity/extrusion and maceration rather than intrameniscal signal or tear were associated with osteoarthritis severity and progression, which highlights the importance of differentiating distinct types of meniscal pathology.