Impact of Antenatal Care Modifications on Gestational Diabetes Outcomes During the COVID-19 Pandemic.

BACKGROUND: Many of the adverse outcomes of gestational diabetes mellitus (GDM) are linked to excessive fetal growth, which is strongly mediated by the adequacy of maternal glycemic management. The COVID-19 pandemic led to a rapid adoption of virtual care models. We aimed to compare glycemic management, fetal growth, and perinatal outcomes before and during the COVID-19 pandemic. METHODS: A retrospective cohort study was conducted between 2017 and 2020. Singleton pregnancies complicated by GDM were included in the study. The cohort was stratified into "before" and "during" COVID-19 subgroups, using March 11, 2020, as the demarcation time point. Women who began their GDM follow-up starting March 11, 2020, and thereafter were allocated to the COVID-19 era, whereas women who delivered before the demarcation point served as the pre-COVID-19 era. The primary outcome was the rate of large-for-gestational-age (LGA) neonates. Secondary outcomes included select maternal and neonatal adverse outcomes. RESULTS: Seven hundred seventy-five women were included in the analysis, of which 187 (24.13%) were followed during the COVID-19 era and 588 (75.87%) before the COVID-19 era. One hundred seventy-one of the 187 women (91.44%) followed during COVID-19 had at least 1 virtual follow-up visit. No virtual follow-up visits occurred before the COVID-19 era. There was no difference in the rate of LGA neonates between groups on both univariate (5.90% vs 7.30%, p=0.5) and multivariate analyses, controlling for age, ethnicity, parity, body mass index, gestational weight gain, chronic hypertension, smoking, and hypertensive disorders in pregnancy (adjusted odds ratio [aOR] 1.11, 95% confidence interval [CI] 0.49 to 2.51, p=0.80). In the multivariate analysis, there was no difference in composite neonatal outcome between groups (GDM diet: aOR 1.40, 95% CI 0.81 to 2.43, p=0.23; GDM medical treatment: aOR 1.20, 95% CI 0.63 to 2.43, p=0.5). CONCLUSIONS: After adjusting for differences in baseline variables, the combined virtual mode of care was not associated with a higher rate of LGA neonates or other adverse perinatal outcomes in women with GDM. Larger studies are needed to better understand the specific impact of virtual care on less common outcomes in pregnancies with GDM.

The surgical destabilization of the abductor muscle leads to development of instability-associated hip osteoarthritis in mice.

Osteoarthritis (OA) of the hip is a common and debilitating painful joint disease. However, there is paucity of surgically induced hip OA models in small animals that allow scientists to study the onset and progression of the disease. A growing body of evidence indicates a positive association between periarticular myotendinous pathology and the development of hip OA. Thus, in the current study, we aimed to establish a novel mouse instability-associated hip OA model via selective injury of the abductor complex around the hip joint. C57BL6/J mice were randomized to sham surgery or abductor injury, in which the myotendinous insertion at the third trochanter and greater trochanter were surgically detached. Mice were allowed free active movement until they were sacrificed at either 3 weeks or 20 weeks post-injury. Histologic analyses and immunohistochemical staining of the femoral head articular cartilage were performed, along with microCT (µCT) analysis to assess subchondral bone remodeling. We observed that mice receiving abductor injury exhibited significantly increased instability-associated OA severity with loss of proteoglycan and type II collagen staining compared to sham control mice at 20 weeks post-surgery, while comparable matrix metalloproteinase 13 expression was observed between injury and sham groups. No significant differences in subchondral bone remodeling were found after 3 or 20 weeks following injury. Our study further supports the link between abductor dysfunction and the development of instability-associated hip OA. Importantly, this novel surgically induced hip OA mouse model may provide a valuable tool for future investigations into the pathogenesis and treatment of hip OA.

A Novel, Simple Rapid Reverse-Phase HPLC-DAD Analysis, for the Simultaneous Determination of Phenolic Compounds and Abscisic Acid Commonly Found in Foodstuff and Beverages.

A novel, simple, rapid, 7-minute HPLC-DAD method for the determination of 10 phenolic compounds and abscisic acid commonly found in teas, wines, fruit and honey was successfully developed and validated according to the International Council of Harmonization (ICH) guidelines. This reverse-phase (RP) HPLC-DAD method boasts rapid separation and excellent resolution while introducing green chemistry techniques. The Agilent 1200 series diode array detector SL coupled with a reverse-phase Advanced Materials Technology Halo C18 column (100 × 3.0 mm i.d., 2.7 µm) contributed to the rapid analyses. This, together with a 0.1% formic acid in water (v/v) and methanol mobile phase, a flow rate of 0.8 mL/min and the utilization of a meticulous gradient elution resulted in a validated method for the determination of 10 phenolic compounds and abscisic acid commonly found in various foodstuffs. The resulting method proved to be rapid, accurate, precise and linear with sensitive detection limits from 0.025 µg/mL to 0.500 µg/mL and percentage recoveries of 98.07%-101.94%. Phenolic compounds have been acknowledged throughout literature for their therapeutic properties, interalia, antioxidant, anti-inflammatory and antiaging due to free radical scavenging potentials. However, resulting analysis, can be frequently complicated and long and very often discounts green chemistry techniques. The developed and validated method successfully and rapidly analyses, gallic acid, caffeic acid, trans-p-coumaric acid, rutin, myricetin, abscisic acid, trans-cinnamic acid, quercetin, luteolin, kaempferol and chrysin with excellent resolution and precision.

Irrigation and Debridement with Chronic Antibiotic Suppression Is as Effective as 2-Stage Exchange in Revision Total Knee Arthroplasty with Extensive Instrumentation.

BACKGROUND: Extraction of implants because of periprosthetic infection (PJI) following complex revision total knee arthroplasty (rTKA) with extensive instrumentation is a daunting undertaking for surgeon and patient alike. The purpose of the present study was to evaluate whether infections following complex rTKA are better treated with 2-stage exchange or irrigation and debridement (I&D) with modular component exchange and antibiotic suppression in terms of infection control, reoperation, and function. METHODS: We reviewed rTKAs that had been performed for the treatment of PJI from 2005 to 2016. Extensive instrumentation was defined as the presence ≥1 of the following: metaphyseal cones/sleeves, distal femoral replacement, periprosthetic fracture instrumentation, or fully cemented stems measuring >75 mm. Cases were categorized according to the initial treatment (I&D with antibiotic suppression or initiation of 2-stage exchange). RESULTS: Eighty-seven patients with PJI and extensive instrumentation were identified: 56 patients who were managed with I&D with suppression and 31 who were managed with the initiation of 2-stage exchange. The rate of success (defined as no reoperation for infection) was similar for the 2 groups (62.5% the I&D group compared with 67.7% for the 2-stage group; p = 0.62). The rate of mortality was also similar (39.3% for the I&D group compared with 38.7% for the 2-stage group; p = 0.96). Of the 31 patients in the 2-stage group, 18 (58.1%) underwent reimplantation with a revision replacement. Of those 18 patients, 13 were still infection-free at the time of the most recent follow-up; however, when the analysis was expanded to all 31 patients in the 2-stage group, only 13 (41.9%) both had a successful reimplantation and did not require additional surgery for infection. Nine (29.0%) of the 31 patients in the 2-stage group never underwent the second stage, and 4 (12.9%) of the 31 required arthrodesis at the second stage. In contrast, 35 (62.5%) of the 56 patients in the I&D group were successfully managed, without additional surgery for the treatment of infection. At the time of the latest follow-up (mean, 3.2 years; range, 2 to 13 years), more patients in the I&D group were ambulatory (76.8% in the I&D group compared with 54.8% in the 2-stage group; p = 0.05) and maintained a functional bending knee joint (85.7% in the I&D group compared with 45.2% in the 2-stage group; p < 0.001). CONCLUSIONS: In the treatment of periprosthetic infection of rTKA with extensive instrumentation, I&D with chronic antibiotic suppression was as effective as 2-stage exchange in terms of preventing reoperation for infection and was more effective in terms of maintaining function. These data apply to rTKA with extensive periarticular instrumentation and should not be extrapolated to primary or simple revision implants. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

The Effects of Different Smoking Patterns in Pregnancy on Perinatal Outcomes in the Southampton Women's Survey.

Maternal smoking during pregnancy has established associations with poor perinatal outcomes. Among continuing pregnant smokers, harm-reduction strategies have been suggested, including temporary cessation of smoking during pregnancy, also known as partial quitting. Support for this strategy, however, remains limited. Six hundred and ninety-seven women in the Southampton Women's Survey who smoked at their last menstrual period were categorised into sustained quitters, partial quitters (quit in either the first or third trimester but not both) or sustained smokers (continued to smoke throughout pregnancy). In regression models, compared with infants born to sustained smokers, infants born to sustained quitters and partial quitters were heavier at birth by ß = 0.64 standard deviations (SD) (WHO z-score) (95% CI: 0.47-0.80) and 0.48 SD (WHO z-score) (95% CI: 0.24-0.72) respectively, adjusted for confounders, with similar patterns seen for other anthropometric measures (head circumference and crown-heel length). Sustained quitters had longer gestations by ß = 3.5 days (95% CI: 1.8-5.2) compared with sustained smokers, but no difference was seen for partial quitters. While sustained quitting remains the most desired outcome for pregnant smokers, partial quitting should be explored as a strategy to reduce some of the harmful effects of smoking on offspring in those who cannot achieve sustained quitting.

Complications Following Transosseous Repair of Zone I Flexor Tendon Injuries.

PURPOSE: Multiple techniques are described for repair of zone I flexor tendon injuries, many of which are fraught with complications. This study evaluated the clinical complications after a transosseous repair technique. METHODS: A retrospective review of a single institutional database identified all zone I flexor digitorum profundus (FDP) injuries repaired using a transosseous technique. In this technique, 2 nonabsorbable sutures were passed from volar to dorsal through transosseous tunnels and tied dorsally over the distal phalanx proximal to the germinal matrix. Demographics, injury characteristics, operative details, and complications were reviewed. RESULTS: Eight patients met the inclusion criteria. Average age was 31 years (range, 15-66 years) and all patients were male. Eight fingers were included: ring (4), small (3), and middle (1). Seven injuries were closed and one was open. Average time between injury and surgery was 13 days (range, 4-34 days). Five patients experienced complications, including osteomyelitis, chronic draining granuloma, and abnormal nail growth. Three patients required an additional operative procedure for management of complications. CONCLUSIONS: Transosseous repair of zone I flexor digitorum profundus injuries with a buried dorsal suture is associated with a high rate of clinical complications. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Why Do Revision Total Knee Arthroplasties Fail? A Single-Center Review of 1632 Revision Total Knees Comparing Historic and Modern Cohorts.

BACKGROUND: Utilization of revision total knee arthroplasty (TKA) has been increasing, and reasons for failure are less understood than those of primary TKA. The purpose of this study is to identify the rates and mechanisms of failure of revision TKA, and compare those between a historic (1986-2005) and modern (2006-2015) cohort. METHODS: All revision TKAs performed at a single institution between 1986 and 2015 were reviewed, with minimum 2-year follow-up. Failure was defined as a second revision surgery in which any component was exchanged. Diagnosis at the time of index and any re-revision procedure was determined. RESULTS: In total, 1632 revision TKAs in 1560 patients were reviewed. The average age was 65.1 and the average follow-up was 61.4 months. Overall failure rate was 22.8%, with no significant differences between the historic and modern cohort (25.1% vs 22.0%, P = .19). The leading cause for failure was infection in 38.5% of failures. The next most common causes for failure were aseptic loosening (20.9%) and instability (14.2%). Failure rate among revision TKAs for infection was 33%, with 67.2% failing due to repeat infection. Multivariate analysis found that septic index revision (odds ratio [OR] 1.91, 95% confidence interval [CI] 1.47-2.48), male gender (OR 1.41, 95% CI 1.11-1.78), and age less than 65 (OR 1.56, 95% CI 1.23-1.97) were independent risk factors for failure. CONCLUSION: There remains a high rate of failure in revision TKA, with infection being the most common reason for failure. Rates and primary reasons for failure have not changed significantly in the past decade.

Is a full component revision necessary for isolated tibial loosening?

AIMS: Aseptic loosening of the tibial component is a frequent cause of failure in primary total knee arthroplasty (TKA). Management options include an isolated tibial revision or full component revision. A full component revision is frequently selected by surgeons unfamiliar with the existing implant or who simply wish to "start again". This option adds morbidity compared with an isolated tibial revision. While isolated tibial revision has a lower morbidity, it is technically more challenging due to difficulties with exposure and maintaining prosthetic stability. This study was designed to compare these two reconstructive options. METHODS: Patients undergoing revision TKA for isolated aseptic tibial loosening between 2012 and 2017 were identified. Those with revision implants or revised for infection, instability, osteolysis, or femoral component loosening were excluded. A total of 164 patients were included; 88 had an isolated tibial revision and 76 had revision of both components despite only having a loose tibial component. The demographics and clinical and radiological outcomes were recorded. RESULTS: The patient demographics were statistically similar in the two cohorts. The median follow-up was 3.5 years (interquartile range (IQR) 1 to 12.5). Supplementary femoral metaphyseal fixation was required in five patients in the full revision cohort. There was a higher incidence of radiological tibial loosening in the full component revision cohort at the final follow-up (8 (10.5%) vs 5 (5.7%); p = 0.269). Three patients in the full component revision cohort developed instability while only one in the isolated tibial cohort did. Three patients in the full revision cohort developed a flexion contracture greater than 5° while none in the isolated tibial cohort did. CONCLUSION: Isolated tibial revision for aseptic tibial loosening has statistically similar clinical and radiological outcomes at a median follow-up of 3.5 years, when compared with full component revision. Substantial bone loss can occur when removing a well-fixed femoral component necessitating a cone or sleeve. Femoral component revision for isolated tibial loosening can frequently be avoided provided adequate ligamentous stability can be obtained. Cite this article: Bone Joint J 2020;102-B(6 Supple A):123-128.

Complications in the treatment of prosthetic joint infection.

AIMS: Two-stage exchange arthroplasty is the most common definitive treatment for prosthetic joint infection (PJI) in the USA. Complications that occur during treatment are often not considered. The purpose of this study was to analyze complications in patients undergoing two-stage exchange for infected total knee arthroplasty (TKA) and determine when they occur. METHODS: We analyzed all patients that underwent two-stage exchange arthroplasty for treatment of PJI of the knee from January 2010 to December 2018 at a single institution. We categorized complications as medical versus surgical. The intervals for complications were divided into: interstage; early post-reimplantation (three months); and late post-reimplantation (three months to minimum one year). Minimum follow-up was one year. In total, 134 patients underwent a first stage of a two-stage exchange. There were 69 males and 65 females with an mean age at first stage surgery of 67 years (37 to 89). Success was based on the new Musculoskeletal Infection Society (MSIS) definition of success reporting. RESULTS: Overall, 70 (52%) patients experienced a complication during the planned two-stage treatment, 36 patients (27%) experienced a medical complication and 47 (41%) patients experienced a surgical complication. There was an 18% mortality rate (24/134) at a mean of 3.7 years (0.09 to 8.3). During the inter-stage period, 28% (37/134) of patients experienced a total of 50 complications at a median of 47 days (interquartile range (IQR) 18 to 139). Of these 50 complications, 22 were medical and 28 required surgery. During this inter-stage period, four patients died (3%) and an additional five patients (4%) failed to progress to the second stage. While 93% of patients (125/134) were reimplanted, only 56% (77/134) of the patients were successfully treated without antibiotic suppression (36%, 28/77) or with antibiotic suppression (19%, 15/77) at one year. CONCLUSION: Reported rates of success of two stage exchanges for PJI have not traditionally considered complications in the definition of success. In our series, significant numbers of patients experienced complications, more often after reimplantation, highlighting the morbidity of this method of treatment. Cite this article: Bone Joint J 2020;102-B(6 Supple A):145-150.

Thumb Metacarpophalangeal Ulnar and Radial Collateral Ligament Injuries.

Thumb metacarpophalangeal collateral ligament injuries are common in athletes and occur via forced abduction or hyperextension. Management primarily depends on the grade of ligamentous injury and the presence of a Stener lesion or large avulsion fracture. Surgeons should consider the athlete's position, hand dominance, duration of season remaining, and goals. Shared decision making regarding timing of surgery is imperative. Acutely, primary ligamentous repair with or without augmentation is achievable. Chronic collateral ligament injuries are effectively treated with ligament reconstruction. Numerous surgical techniques have been described without 1 showing superiority. Postoperative rehabilitation protocols vary based on repair quality and sports-specific considerations.

The relationship between maternal body mass index and pregnancy outcomes in twin compared with singleton pregnancies.

OBJECIVE: Women with twins have an a priori increased risk for many of the complications associated with maternal obesity. Thus, the impact of maternal obesity in twins may differ from that reported in singletons. In addition, given the increased metabolic demands in twin pregnancies, the impact of maternal underweight may be greater in twin compared with singleton gestations. Our objective was to test the hypothesis that the relationship between maternal pre-pregnancy body mass index (BMI) and adverse pregnancy outcomes differ between twin and singleton gestations. METHODS: This was a retrospective population-based study of all women who had a singleton or twin hospital birth in Ontario, Canada, between April 2012 and March 2016. Data were obtained from the Better Outcomes Registry & Network (BORN) Ontario. The relationship between maternal BMI category and pregnancy complications was assessed separately in twin and singleton gestations. The primary outcome was a composite variable that included any of the following complications: preeclampsia, gestational diabetes, or preterm birth before 320/7 weeks. Relative risk (aRR) and 95% confidence intervals (CI) for adverse outcomes for each BMI category as defined by WHO (using normal weight category as reference) were generated using modified Poisson regression, adjusting for maternal age, nulliparity, smoking, previous preterm birth, and fetal sex. RESULTS: A total of 487,870 women with singleton (n = 480,010) and twin (n = 7860) pregnancies met the inclusion criteria. The risk of the composite primary outcome, preeclampsia, gestational diabetes, and cesarean delivery increased with high maternal BMI in both singleton and twin gestations, but these associations were weaker in twin compared with singleton gestations (association of BMI ≥ 40.0 kg/m2 with primary outcome: aRR = 3.10, 95%-CI 2.96-3.24 in singletons compared with aRR = 1.74, 95%-CI 1.37-2.20 in twins). In singleton pregnancies the risk of preterm birth at < 320/7 weeks increased with maternal BMI, mainly due to an increased risk of provider-initiated preterm birth. In twin gestations, however, underweight (but not overweight or obesity) was associated with the greatest risk of preterm birth at < 32 weeks (aRR 1.67, 95%-CI 1.17-2.37), mainly due to an increased risk of spontaneous preterm birth (aRR 2.10, 95%-CI 1.44-3.08). CONCLUSION: In healthy women with twin pregnancies, underweight is associated with the greatest risk for preterm birth, while the association of maternal obesity with adverse pregnancy outcomes is weaker than that observed in singletons.

Contemporary Issues in Women's Health.

Should we be performing routine salpingectomy as a preventative approach to reduce the risk of ovarian cancer? Machine Learning in Women's Health. Women who undergo cesarean delivery in many parts of Africa are at high risk of severe maternal morbidity and mortality.

Gestational diabetes mellitus is associated with adverse outcomes in twin pregnancies.

BACKGROUND: Among singleton pregnancies, gestational diabetes mellitus is associated with adverse outcomes. In twin pregnancies, this association may be attenuated, given the higher rate of prematurity and the a priori increased risk of some of these complications. OBJECTIVE: Our aim was to test the hypothesis that gestational diabetes mellitus is less likely to be associated with adverse pregnancy outcomes in twin compared with singleton gestations. METHODS: This retrospective cohort study comprised all twin and singleton live births in Ontario, Canada, 2012-2016. Pregnancy outcomes were compared between women with vs without gestational diabetes mellitus, analyzed separately for twin and singleton births. Adjusted risk ratios and 95% confidence intervals were generated using modified Poisson regression, adjusting for maternal age, nulliparity, smoking, race, body mass index, preexisting hypertension, and assisted reproductive technology. RESULTS: A total of 270,843 women with singleton (n = 266,942) and twin (n = 3901) pregnancies met the inclusion criteria. In both the twin and singleton groups, gestational diabetes mellitus was associated with (adjusted risk ratio, [95% confidence interval]) cesarean delivery (1.11 [1.02-1.21] and 1.20 [1.17-1.23], respectively) and preterm birth at <370/7 weeks (1.21 [1.08-1.37] and 1.48 [1.39-1.57]) and at <340/7 weeks (1.45 [1.03-2.04] and 1.25 [1.06-1.47]). In singletons, but not twins, gestational diabetes mellitus was associated with gestational hypertension (1.66 [1.55-1.77]) and preeclampsia. With respect to neonatal outcomes, gestational diabetes mellitus was associated with birthweight greater than the 90th percentile in both twins and singletons, with the risk being 2-fold higher in twins (2.53 [1.52-4.23] vs 1.18 [1.13-1.23], respectively, P = .004). Gestational diabetes mellitus was associated with jaundice in both twins (1.56 [1.10-2.21]) and singletons (1.49 [1.37-1.62) but was associated with the following complications only in singletons: neonatal intensive care unit admission (1.44 [1.38-1.50]), respiratory morbidity (1.09 [1.02-1.16]), and neonatal hypoglycemia (3.20 [3.01-3.40]). CONCLUSION: In contrast to singleton pregnancies, gestational diabetes mellitus in twins was not associated with hypertensive complications and certain neonatal morbidities. Still, the current study highlights that gestational diabetes mellitus is associated with some adverse pregnancy outcomes including accelerated fetal growth also in twin pregnancies.

Is Activity Tracker-Measured Ambulation an Accurate and Reliable Determinant of Postoperative Quality of Recovery? A Prospective Cohort Validation Study.

BACKGROUND: Quality of recovery (QOR) instruments measure patients' ability to return to baseline health status after surgery. Whether, and the extent to which, postoperative ambulation contributes to QOR is unclear, in part due to the lack of valid tools to measure ambulation in clinical settings. This cohort study of the cesarean delivery surgical model examines the accuracy and reliability of activity trackers in quantifying early postoperative ambulation and investigates the correlation between ambulation and QOR. METHODS: A prospective cohort of 200 parturients undergoing cesarean delivery between July 2015 and June 2017 was fitted with wrist-worn activity trackers immediately postpartum. The trackers were collected 24 hours later, along with QOR assessments (QoR-15 scale). The relationship between QOR and various covariates, including ambulation, was explored using multivariable linear regression and Spearman correlation (ρ). Forty-eight parturients fitted with 2 trackers also completed a walk exercise accompanied by a step-counting assessor, to evaluate accuracy, inter-, and intradevice reliability using interclass correlation (ICC). RESULTS: Compared to step counting, activity trackers had high accuracy (ICC = 0.93) and excellent inter- and intradevice reliability (ICC = 0.98 and 0.96, respectively). Correlation analysis suggested that early ambulation is moderately correlated with postcesarean QoR-15 scores, with a ρ (95% confidence interval) equivalent to 0.56 (0.328-0.728). Regression analysis suggested that ambulation is a determinant of postcesarean QoR-15 scores, with an effect estimate (95% confidence interval) equivalent to 0.002 (0.001-0.003). Ambulation was also associated with all QoR-15 domains, except psychological support. The patient's acceptable symptom state (subjective threshold for good ambulation) in the first 24 hours was 287 steps. CONCLUSIONS: This study demonstrated the accuracy and reliability of activity trackers in measuring ambulation in clinical settings and suggested that postoperative ambulation is a determinant of postoperative QOR. A hypothetical implication of our findings is that interventions that improve ambulation may also help to enhance QOR, but further research is needed to establish a causal relationship.

No. 364-Antenatal Corticosteroid Therapy for Improving Neonatal Outcomes.

OBJECTIVE: To assess the benefits and risks of antenatal corticosteroid therapy for women at risk of preterm birth or undergoing pre-labour Caesarean section at term and to make recommendations for improving neonatal and long-term outcomes. OPTIONS: To administer or withhold antenatal corticosteroid therapy for women at high risk of preterm birth or women undergoing pre-labour Caesarean section at term. OUTCOMES: Perinatal morbidity, including respiratory distress syndrome, intraventricular hemorrhage, bronchopulmonary dysplasia, infection, hypoglycemia, somatic and brain growth, and neurodevelopment; perinatal mortality; and maternal morbidity, including infection and adrenal suppression. INTENDED USERS: Maternity care providers including midwives, family physicians, and obstetricians. TARGET POPULATION: Pregnant women. EVIDENCE: Medline, PubMed, Embase, and the Cochrane Library were searched from inception to September 2017. Medical Subject Heading (MeSH) terms and key words related to pregnancy, prematurity, corticosteroids, and perinatal and neonatal mortality and morbidity were used. Statements from professional organizations including that of the National Institutes of Health, the American College of Obstetricians and Gynecologists, the Society for Maternal Fetal Medicine, the Royal College of Obstetricians and Gynaecologists, and the Canadian Pediatric Society were reviewed for additional references. Randomized controlled trials conducted in pregnant women evaluating antenatal corticosteroid therapy and previous systematic reviews on the topic were eligible. Evidence from systematic reviews of non-experimental (cohort) studies was also eligible. VALIDATION METHODS: This Committee Opinion has been reviewed and approved by the Maternal-Fetal Medicine Committee of the SOGC and approved by SOGC Council. BENEFITS, HARMS, AND/OR COSTS: A course of antenatal corticosteroid therapy administered within 7 days of delivery significantly reduces perinatal morbidity/mortality associated with preterm birth between 24 + 0 and 34 + 6 weeks gestation. When antenatal corticosteroid therapy is given more than 7 days prior to delivery or after 34 + 6 weeks gestation, the adverse effects may outweigh the benefits. Evidence on long-term effects is scarce, and potential neurodevelopment harms are unquantified in cases of late preterm, term, and repeated exposure to antenatal corticosteroid therapy. GUIDELINE UPDATE: Evidence will be reviewed 5 years after publication to evaluate the need for a complete or partial update of the guideline. If important evidence is published prior to the 5-year time point, an update will be issued to reflect new knowledge and recommendations. SPONSORS: The guideline was developed with resources provided by the Society of Obstetricians and Gynaecologists of Canada with support from the Canadian Institutes of Health Research (APR-126338). SUMMARY STATEMENTS: RECOMMENDATIONS: Gestational Age Considerations Agents, Dosage, Regimen, and Target Timing Subpopulations and Special Consideration.

Development and internal validation of the multivariable CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) clinical risk prediction model.

BACKGROUND: Intensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care. METHODS: A retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries. Women admitted to an ICU for more than 24 h during pregnancy or less than 6 weeks post-partum from 2000 to 2012 were included in the cohort. A composite primary outcome was defined as maternal death or need for organ support for more than 7 days or acute life-saving intervention. Model development involved selection of candidate predictor variables based on prior evidence of effect, availability across study sites, and use of LASSO (Least Absolute Shrinkage and Selection Operator) model building after multiple imputation using chained equations to address missing data for variable selection. The final model was estimated using multivariable logistic regression. Internal validation was completed using bootstrapping to correct for optimism in model performance measures of discrimination and calibration. RESULTS: Overall, 127 out of 769 (16.5%) women experienced an adverse outcome. Predictors included in the final CIPHER model were maternal age, surgery in the preceding 24 h, systolic blood pressure, Glasgow Coma Scale score, serum sodium, serum potassium, activated partial thromboplastin time, arterial blood gas (ABG) pH, serum creatinine, and serum bilirubin. After internal validation, the model maintained excellent discrimination (area under the curve of the receiver operating characteristic (AUROC) 0.82, 95% confidence interval (CI) 0.81 to 0.84) and good calibration (slope of 0.92, 95% CI 0.91 to 0.92 and intercept of -0.11, 95% CI -0.13 to -0.08). CONCLUSIONS: The CIPHER model has the potential to be a pragmatic risk prediction tool. CIPHER can identify critically ill pregnant women at highest risk for adverse outcomes, inform counseling of patients about risk, and facilitate bench-marking of outcomes between centers by adjusting for baseline risk.

Obesity/Type II diabetes alters macrophage polarization resulting in a fibrotic tendon healing response.

Type II Diabetes (T2DM) dramatically impairs the tendon healing response, resulting in decreased collagen organization and mechanics relative to non-diabetic tendons. Despite this burden, there remains a paucity of information regarding the mechanisms that govern impaired healing of diabetic tendons. Mice were placed on either a high fat diet (T2DM) or low fat diet (lean) and underwent flexor tendon transection and repair surgery. Healing was assessed via mechanical testing, histology and changes in gene expression associated with collagen synthesis, matrix remodeling, and macrophage polarization. Obese/diabetic tendons healed with increased scar formation and impaired mechanical properties. Consistent with this, prolonged and excess expression of extracellular matrix (ECM) components were observed in obese/T2DM tendons. Macrophages are involved in both inflammatory and matrix deposition processes during healing. Obese/T2DM tendons healed with increased expression of markers of pro-inflammatory M1 macrophages, and elevated and prolonged expression of M2 macrophages markers that are involved in ECM deposition. Here we demonstrate that tendons from obese/diabetic mice heal with increased scar formation and increased M2 polarization, identifying excess M2 macrophage activity and matrix synthesis as a potential mechanism of the fibrotic healing phenotype observed in T2DM tendons, and as such a potential target to improve tendon healing in T2DM.

Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses.

BACKGROUND: Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at-risk fetus in both intrauterine growth restriction and the appropriate-for-gestational-age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain-sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort. OBJECTIVE: The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight <10th centile. The objective of this secondary analysis was to evaluate if normalizing cerebroplacental ratio predicts adverse perinatal outcome. STUDY DESIGN: In all, 1116 consecutive singleton pregnancies with intrauterine growth restriction completed the study protocol over 2 years at 7 centers, undergoing serial sonographic evaluation and multivessel Doppler measurement. Cerebroplacental ratio was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Abnormal cerebroplacental ratio was defined as <1.0. Adverse perinatal outcome was defined as a composite of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death. RESULTS: Data for cerebroplacental ratio calculation were available in 881 cases, with a mean gestational age of 33 (interquartile range, 28.7-35.9) weeks. Of the 87 cases of abnormal serial cerebroplacental ratio with an initial value <1.0, 52% (n = 45) of cases remained abnormal and 22% of these (n = 10) had an adverse perinatal outcome. The remaining 48% (n = 42) demonstrated normalizing cerebroplacental ratio on serial sonography, and 5% of these (n = 2) had an adverse perinatal outcome. Mean gestation at delivery was 33.4 weeks (n = 45) in the continuing abnormal cerebroplacental ratio group and 36.5 weeks (n = 42) in the normalizing cerebroplacental ratio group (P value <.001). CONCLUSION: The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect was significantly associated with an adverse perinatal outcome in our intrauterine growth restriction cohort. It was hypothesized that a normalizing cerebroplacental ratio would be a further predictor of an adverse outcome due to the loss of this compensatory mechanism. However, in this subanalysis we did not demonstrate an additional poor prognostic effect when the cerebroplacental ratio value returned to a value >1.0. Overall, this secondary analysis demonstrated the importance of a serial abnormal cerebroplacental ratio value of <1 within the <34 weeks' gestation population. Contrary to our proposed hypothesis, we recognize that reversion of an abnormal cerebroplacental ratio to a normal ratio is not associated with a heightened degree of adverse perinatal outcome.