Contralateral Neck-shaft Angle Lower Than 130° Is Associated With Clinical Failure in Nongeriatric Individuals: Analysis of the National Femoral Neck Fracture Database of 1066 Patients.

BACKGROUND: Treatment of femoral neck fractures in patients who are nongeriatric (≤ 60 years) is challenging because of high failure rates. Anatomic parameters influence the biomechanical environment for fracture healing, but their associations with clinical prognosis remains unclear. QUESTIONS/PURPOSES: (1) Which anatomic parameter that is identifiable on pelvic radiographs shows a statistical correlation with a higher risk of clinical failure defined as nonunion, avascular necrosis (AVN), reoperation, and functional failure (decrease in Harris hip score reaching the minimum clinically important difference) in the screw fixation of femoral neck fractures among nongeriatric patients? (2) How does the influence of anatomic parameters on clinical prognosis manifest: directly or mediated by additional mechanisms? METHODS: This retrospective, multicenter study used a nationwide database in China. Between January 2014 and December 2020, we evaluated 1066 patients with femoral neck fractures with a median age of 53 years (interquartile range 46 to 56) and median follow-up period of 62 months. Anatomic parameters including femoral neck-shaft angle (NSA), femoral head radius, femoral neck width, femoral offset, acetabular center-edge angle, and acetabular sharp angle were variables of interest. The primary outcome was clinical failure including nonunion, AVN, reoperation, and functional failure (decrease in Harris hip score reaching the minimum clinically important difference). Risk factors for failure were first filtered using the Bayesian information criterion and then assessed with multiple regression adjusting for confounders. The mediation effect was further explored using model-based causal mediation analysis with a quasi-Bayesian Monte Carlo method. RESULTS: Of all anatomic parameters we assessed, the contralateral NSA was associated with clinical failure, after adjusting for all potential covariates and confounding variables (adjusted odds ratio 0.92 [95% confidence interval 0.89 to 0.95]; p < 0.001). The optimal threshold for the NSA was 130°, with the highest Youden index of 0.27. Patients with an NSA < 130° (41% [441 of 1066]) demonstrated an increased occurrence of nonunion (15% [68 of 441] versus 5% [33 of 625]; p < 0.001), AVN (32% [141 of 441] versus 22% [136 of 625]; p < 0.001), functional failure (25% [110 of 441] versus 15% [93 of 625]), and reoperations (28% [122 of 441] versus 13% [79 of 625]). The impact of an NSA less than 130° on clinical failure was direct and substantially mediated by the type of displaced fracture (mediation proportion: 18.7%). CONCLUSION: In our study of screw fixations for femoral neck fractures among nongeriatric patients, we identified that a contralateral NSA < 130° correlates with an increased risk of clinical failure including nonunion, AVN, functional failure, and reoperation. The effect is either direct or mediated through displaced fracture types. This is important for surgeons in order to recognize the elevated rate of clinical failure and nature of the challenging biomechanical environment, which should guide them in refining surgical details and selecting appropriate fixation and rehabilitation plans. Approaches to managing these fractures require further validation with large-scale clinical trials. LEVEL OF EVIDENCE: Level III, prognostic study.

Development of a risk-predicting score for hip preservation with bone grafting therapy for osteonecrosis.

Identification and differentiation of appropriate indications on hip preserving with bone grafting therapy remains a crucial challenge in the treatment of osteonecrosis of the femoral head (ONFH). A prospective cohort study on bone grafting therapy for ONFH aimed to evaluate hip survival rates, and to establish a risk scoring derived from potential risk factors (multivariable model) for hip preservation. Eight variables were identified to be strongly correlated with a decreased rate of hip survival post-therapy, and a comprehensive risk scoring was developed for predicting hip-preservation outcomes. The C-index stood at 0.72, and the areas under the receiver operating characteristics for the risk score's 5- and 10-year hip failure event predictions were 0.74 and 0.72, respectively. This risk score outperforms conventional methods in forecasting hip preservation. Bone grafting shows sustained benefits in treating ONFH when applied under the right indications. Furthermore, the risk scoring proves valuable as a decision-making tool, facilitating risk stratification for ONFH treatments in future.

Development and external validation of a prediction model for digit replantation failure after traumatic amputations based on a prospective multicenter cohort.

BACKGROUND: Failure of digit replantation after traumatic amputation is difficult to predict. The authors aimed to develop a prognostic model to better identify factors that better predict replantation failure following traumatic digit amputation. MATERIALS AND METHODS: In this multicenter prospective cohort, the authors identified patients who had received digit replantation between 1 January 2015 and 1 January 2019. Univariable and multivariable analyses were performed successively to identify independently predictive factors for failure of replanted digit. To reduce overfitting, the Bayesian information criterion was used to reduce variables in the original model. Nomograms were created with the reduced model after model selection. This model was then internally validated with bootstrap resampling and further externally validated in validation cohort. RESULTS: Digit replantation was failed in 101 of 1062 (9.5%) digits and 146 of 1156 digits (12.6%) in the training and validation cohorts, respectively. The authors found that six independent prognostic variables were associated with digit replantation failure: age, mechanism of injury, ischemia duration, smoking status, amputation pattern (complete or incomplete), and surgeon's experience. The prediction model achieved good discrimination, with concordance indexes of 0.81 (95% CI: 0.76-0.85) and 0.70 (95% CI: 0.65-0.74) in predicting digit failure in the training and validation cohorts, respectively. Calibration curves were well-fitted for both training and validation cohorts. CONCLUSIONS: The proposed prediction model effectively predicted the failure rate of digit replantation for individual digits of all patients. It could assist in selecting the most suitable surgical plan for the patient.

[Analysis of incidence and clinical characteristics of osteonecrosis of femoral head in patients with systemic lupus erythematosus treated with glucocorticoid: A descriptive study based on a prospective cohort].

Objective: To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure. Methods: Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described. Results: The age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences ( P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m 2 compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group. Conclusion: The incidence of ONFH after GC exposure in China's SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.

Glucagon-like peptide-1 receptor agonists as a disease-modifying therapy for knee osteoarthritis mediated by weight loss: findings from the Shanghai Osteoarthritis Cohort.

OBJECTIVE: Obesity is a risk factor for knee osteoarthritis (KOA) development and progression. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated for type 2 diabetes mellitus (T2DM) and obesity. However, whether KOA patients can benefit from GLP-1RA therapies has not been sufficiently investigated, especially in the long term. METHODS: The Shanghai Osteoarthritis Cohort study is a prospective, observational, multicentre study of >40 000 adults with clinically diagnosed osteoarthritis aged >45 years in Shanghai. We identified all KOA participants with comorbid T2DM enrolled from 1 January 2011 to 1 January 2017. Primary outcome was incidence of knee surgery after enrolment. Secondary outcomes included pain-relieving medication use, number of intra-articular therapies, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and medial femorotibial joint cartilage thickness. To evaluate the effects of GLP-1RA, we performed before-and-after comparison and comparison with participants who had no GLP-1RA exposure. RESULTS: For an intergroup comparison (non-GLP-1RA vs GLP-1RA), more weight loss (adjusted mean difference in weight change from baseline -7.29 kg (95% CI -8.07 to -6.50 kg), p<0.001) and lower incidence of knee surgery (93/1574 (5.9%) vs 4/233 (1.7%), adjusted p=0.014) were observed in the GLP-1RA group. Statistically significant differences in mean change from baseline for the WOMAC total and pain subscale scores were observed (adjusted mean difference in WOMAC total score -1.46 (95% CI -2.84 to -0.08), p=0.038; adjusted mean difference in WOMAC pain subscore -3.37 (95% CI -5.79 to -0.94), p=0.007). Cartilage-loss velocity of the medial femorotibial joint was significantly lower in the GLP-1RA group postadjustment for baseline characteristics (adjusted mean difference -0.02 mm (95% CI -0.03 to -0.002 mm), p=0.004). For the before-and-after comparison within the GLP-1RA group, we observed a significant decrease of symptom-relieving medication consumption and cartilage loss velocity of medial femorotibial joint (after-treatment vs before-treatment: -0.03±0.05 vs -0.05±0.07 mm/year, p<0.001). The association between GLP-1RA exposure and decreased incidence of knee surgery was mediated by weight reduction (mediation proportion: 32.1%), instead of glycaemic control (too small to calculate). CONCLUSION: With sufficient treatment duration, GLP-1RA therapies might be disease-modifying for KOA patients with comorbid T2DM, possibly mediated by weight loss. Further investigation is needed to elucidate effects of GLP-1RA on disease process, joint structure and patient-reported outcomes of osteoarthritis.

In-hospital waiting time to surgery and functional outcomes in geriatric hip fractures: a directed acyclic graph-based preplanned analysis from a prospective multicenter cohort study.

BACKGROUND: The early recovery of hip function after hip fracture surgery values more attention, especially for patients with delayed surgery of longer than 48 h. We aim to evaluate the associations of in-hospital surgical waiting time with the functional outcomes [Harris Hip Score (HHS), Parker Mobility Score (PMS), and EuroQol 5 dimensions VAS (visual analogue scale) score (EQ-5D VAS)] in elderly patients who sustained hip fractures. MATERIALS AND METHODS: Data on sociodemographic and clinical factors were prospectively collected using a multicenter hip fracture registry system. Participants in the cohort underwent a 12-month follow-up investigation. After adjusting potential confounders identified by the directed acyclic graphs, the associations between surgical waiting time longer than 48 h and functional outcomes were estimated by log-binomial regression and multivariable linear regression models with generalized estimating equations. RESULTS: Of 863 survival participants with available functional data at 12 months after surgery, an increased risk was obtained from receiving surgery after 48 h and the poor functional outcomes (HHS<80: relative risk (RR)=1.56, 95% CI: 1.00-2.51; PMS<7: RR=1.49, 95% CI: 1.13-2.01; EQ-5D VAS<80: RR=1.97, 95% CI: 1.57-2.47). In-hospital waiting time greater than 48 h were time-invariantly associated with lower PMS during recovery (-0.44 units 95% CI: -0.70 to -0.18). In addition, delayed surgery was time-varying associated with HHS and EQ-5D VAS. CONCLUSIONS: The associations between in-hospital waiting time and postoperative functional score suggest that delayed surgery can lead to poor functional outcomes, especially in patients waiting longer than 72 h from injury. Delayed surgery mainly impacted hip function and mobility recovery with a slower speed in early recovery of the first 3 months. More attention should be paid to mechanisms behind the associations between delayed surgery on general healthy status.

The Impact of COVID-19 on SARSCoV-2-Negative Elderly Patients with Hip Fractures: A Single-Center Retrospective Study from Shanghai, China.

Purpose: Coronavirus disease 2019 (COVID-19) has brought an unprecedented change in wellbeing globally. The spread of the pandemic reportedly reduced the incidence of activity-related trauma, while that of fragility fractures remained stable. Here, we aimed to identify the risk factors associated with the prognosis of SARS-CoV-2 negative elderly patients with hip fractures. Patients and Methods: This retrospective study included elderly patients with hip fractures between 1st January and 9th May during the COVID-19 pandemic (Experiment group) and the same period from 2017 to 2019 (Control group). Perioperative mortality, complications, and functional recovery were compared between two groups of different time frame in the total cohort and patients who received surgical treatment. Multiple linear regression was carried out to identify the risk factors influencing the prognosis of COVID-negative elderly patients with hip fractures. Results: The proportion of patients with admission time less than 24 hours and the 6-month postoperative Parker score were significantly decreased during COVID-19 compared with the pre-COVID-19 period (p < 0.001). Multiple linear regression demonstrated that TTA (defined as time from injury to admission), rehabilitation after discharge and outpatient follow-up were associated with the 6-month Parker score in the total population (p < 0.001) and in patients who received surgical treatment (p < 0.001). Conclusion: Elderly patients with hip fractures had a poorer prognosis in epidemic period despite being COVID-19 negative. Factors including timely admission, postoperative follow-up, and rehabilitation could optimize safety and significantly improve the prognosis of elderly COVID-19 negative patients with hip fractures, even during a pandemic.

Contribution of revision amputation vs replantation for certain digits to functional outcomes after traumatic digit amputations: A comparative study based on multicenter prospective cohort.

BACKGROUND: Traumatic digit amputations can result in significant impairment. Optimal surgical treatment is unclear for certain digits in various amputation patterns. Our aim was to compare the contribution of revision amputation vs replantation for each particular digit to functional outcomes. MATERIALS AND METHODS: Prospective cohort study at three tertiary hospitals was conducted in China. Eligible participants were 3192 patients with traumatic digit amputations enrolled from January 1, 2014, to January 1, 2018. The primary outcome was Michigan Hand Outcomes Questionnaire (MHQ) scores 2 years after initial surgery. Secondary outcome was score on the Disabilities of the Arm, Shoulder, and Hand (DASH). RESULTS: Of 3192 enrolled patients, 2890 completed the study. Main-effect linear regression showed that participants with replantation of thumb, index, long, and ring (proximal to the proximal interphalangeal [PIP] joint) fingers had significantly better MHQ scores compared to participants with the corresponding finger revision amputation. DASH results were comparable. Finger-finger interaction analyses conducted with multifactor dimensionality reduction (MDR) revealed that the small finger and ring finger had the smallest and greatest interactions with other fingers, respectively. After stratification by amputation level of thumb, index finger, or long finger, linear regression showed that replantation of the ring finger distal to the PIP joint resulted in better MHQ and DASH when the thumb or long finger was also traumatically amputated proximal to the IP/PIP joint. CONCLUSIONS: Replantation of the thumb, index, long, and ring (proximal to PIP joint) fingers is preferable to revision amputation, regardless of amputation pattern. Replantation of the ring finger amputated distal to PIP was beneficial only when the thumb or long finger was amputated proximal to IP/PIP joint. Replantation or revision amputation of the small finger was indistinguishable in terms of functional outcome. Future investigations and clinical decisions should take into account the role of finger-finger interactions.

Enhanced interfragmentary stability and improved clinical prognosis with use of the off-axis screw technique to treat vertical femoral neck fractures in nongeriatric patients.

BACKGROUND: The optimal internal fixation strategy for vertical femoral neck fractures (VFNFs) in nongeriatric patients remains uncertain. Therefore, the purpose of this study was to compare the clinical prognoses and underlying mechanical characteristics of a novel off-axis screw technique with dynamic hip screws (DHSs) and three traditional parallel screws. METHODS: This study included a clinical investigation and a patient-specific finite element analysis (FEA). In the clinical investigation, VFNF patients were grouped by fixation type: (1) use of three parallel screws (G-TRI); (2) augmentation with an off-axis screw (G-ALP); and (3) DHS with an anti-rotational screw (G-DHS). Fixation failures (nonunion, femoral neck shortening (FNS), varus deformation, screw cut-out) and avascular necrosis (AVN) consequent to the three types of fixations were compared. In the FEA, twenty-four fixation models with the three fixation types were created based on the data of eight healthy volunteers. Models were assessed under walking conditions. Stiffness, interfragmentary motion (IFM), and implant stress were evaluated. RESULTS: In the clinical investigation, the fixation failure rate was significantly (p < 0.05) lower in G-ALP (18.5%) than in G-DHS (37.5%) and G-TRI (39.3%). No significant difference in AVN was observed among the three fixation groups. In the FEA, stiffness and implant stress in the G-DHS models were significantly (p < 0.05) higher, and the IFM of G-ALP was significantly (p < 0.05) lower among the groups. CONCLUSIONS: Among fixation types for VFNFs, the off-axis screw technique exhibited better interfragmentary stability (lowest IFM) and a lower fixation failure rate (especially FNS). Analyzing interfragmentary stability in biomechanical experiments is more consistent with clinical prognosis than construct stability for VFNFs, suggesting that internal fixations should aim for this outcome.

Long-term differences in clinical prognosis between crossed- and parallel-cannulated screw fixation in vertical femoral neck fractures of non-geriatric patients.

BACKGROUND AND PURPOSE: Vertical femoral neck fractures (VFNFs) are one of the most difficult fractures to stabilize, with high non-union (17%), avascular necrosis (AVN, 21%), and femoral neck shortening (FNS, 29.0%) rates. The objective of this investigation was to directly compare the long-term clinical complication rates of VFNFs repaired by crossed (Alpha fixation) or parallel screws in non-geriatric patients. PATIENTS AND METHODS: We conducted a retrospective comparative study of VFNFs in patients (<60 years) between January 2014 and December 2017, with at least 2 years of follow-up. VFNFs were fixed with either three parallel screws (G-TRI) or augmented with a crossed screw (G-ALP). Confounding variables included age, gender, initial displacement, ISS (Injury Severity Score), general comorbidities, combined fractures, Pauwels angle, reduction quality. Complications, including non-union, AVN of the femoral head and FNS were compared as outcome indicators. Risk factors associated with these variables were further analysed using multivariate analysis. RESULTS: A total of 157 patients (97 G-TRI; 60 G-ALP) met inclusion criteria. G-ALP had a significantly lower rate of FNS (8.3% vs. 28.9%, p = 0.039) than that of G-TRI. non-union (3.3% vs. 11.3%), AVN (21.7% vs. 25.8%), and reoperation rates (21.7% vs. 23.7%) were lower in G-ALP than G-TRI but was not statistically significant. Multivariate analyses showed significant relationships between NU and unacceptable reduction quality (OR=7.610; 1.823-31.770, adjusted-p = 0.015); between AVN and initial displacement (Garden III and IV) (OR=7.885; 1.739-35.744, adjusted-p = 0.021); and between FNS and screw configuration (OR=5.713; 1.839-17.743, adjusted-p = 0.009). CONCLUSION: For the treatment of VFNFs, satisfactory reduction still remains the key surgical goal that prevents NU, while the incidence of AVN strongly depends on the initial displacement at the time of injury. Crossed screws were associated with a markedly lower FNS rate than parallel screws, which promote further randomised controlled trials to establish a guideline for optimal fixation selection in VFNFs.

Associations between glucocorticoids, antiphospholipid antibodies and femur head necrosis in patients with SLE: a directed acyclic graph-based multicentre study.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) remains a major cause of disability in patients with systemic lupus erythematosus (SLE) and seriously impairs quality of life. This study aimed to investigate associations between glucocorticoids (GCs), antiphospholipid antibodies (aPLs), and ONFH in patients with SLE. METHODS: We conducted a multicentre cohort study on patients with SLE and used a directed acyclic graph-based analysis strategy. Details of GC therapy, aPLs status, other drug administration and other SLE-related characteristics were collected. ONFH occurrence during follow-up was determined by magnetic resonance imaging. Multivariable logistic regression and generalized estimating equation models were performed to assess their effects on ONFH, and a simplified scoring system comprising these factors for short- and medium-term SLE-ONFH prediction was developed by receiver operating characteristic curve analysis. RESULTS: Of 449 SLE patients with a median follow-up duration of 5.3 years, 41 (9.1%) developed ONFH. Independently risk factors of SLE-ONFH including: average daily GC dose with an adjusted odds ratio (aOR) of 1.1 and 95% confidence interval (CI) of 1.0-1.1; GC therapy duration (3-5 years: aOR 3.3, 95% CI 1.4-7.8; >5 years: aOR 8.0, 95% CI 3.3-19.4); initial intravenous GC (aOR 4.4, 95% CI 1.9-10.1); positive aPLs (aOR 2.8, 95% CI 1.4-5.8); and Arterial hypertension secondary to GC usage (aOR 5.2, 95% CI 1.4-19.1). And we successfully developed the simplified scoring system (SCORE model) with an area under the curve of 0.88 (95% CI 0.82-0.94). CONCLUSION: Based on the risk factors involved in the development of SLE-ONFH, a novel SCORE model was developed, which might be helpful for risk stratification of SLE-ONFH in clinical practice.

Overt and occult hepatitis B infection after neonatal vaccination: mother-to-infant transmission and HBV vaccine effectiveness.

OBJECTIVES: Overt and occult hepatitis B infection (HBI) among mothers and infants were investigated, and the effectiveness of vaccination against HBI was evaluated based on transmission types. METHODS: A hospital-based cohort was built with 2,734 mothers and 330 mother-infant pairs. Their demographic data were collected. Serological HBV markers, nested-PCR for HBV genes, viral load detection, and phylogenetic analysis were done. RESULTS: The overall prevalence of HBI among mothers was 12.1% (330/2,734), with 10.4% for the overt type and 1.8% for the occult type. In 330 out of 1,650 (20%) mother-infant pairs, the overall, type-I (from overt mother to overt infant), type-II (from overt mother to occult infant), and type-Ⅲ (from occult mother to occult infant) transmissions were 1.9% (1/54), 5.6% (3/54) and 0.0% (0/7). The refinement of HBI classification improved the estimate of vaccine effectiveness against HBI from 74.4%-80.9% to 94.4%, which was more prominent for type-II. One mother-infant pair with type-II transmission shared nearly identical complete sequences. However, the high rate of lost-to-follow-up could not be ignored. CONCLUSIONS: During the transition period, HBV is mainly transmitted from the overt type of HBI mother to infant. Intensive prenatal screening for mothers is vital.

The Associations of Serum Vitamin D and Bone Turnover Markers with the Type and Severity of Hip Fractures in Older Women.

PURPOSE: Vitamin D (25[OH]D) status and bone turnover markers (BTMs) are considered important determinants of bone quality, which is associated with the risk of hip fractures, including both femoral neck and intertrochanteric fractures, in older adults; however, the exact relationship of 25(OH)D and BTMs with the type and severity of hip fractures remains unclear and the present study aimed to identify any specific associations. PATIENTS AND METHODS: According to the inclusion and exclusion criteria, 441 older female patients with hip fractures from 2015 to 2020 and 215 women without hip fractures were included in this cross-sectional study. According to Garden and AO/OTA classifications for femoral neck and intertrochanteric fractures, patients were divided into less severe (Garden I and Garden II; 31A1) and more severe (Garden III and Garden IV; 31A2 and 31A3) fracture groups. Levels of the serum osteoblast indicator, N-terminal/mid region (N-MID); the osteoclast indicator, beta-carboxy terminal telopeptide (ß-CTX); and 25(OH)D were analyzed. RESULTS: For patients with less severe fractures, mean 25(OH)D levels were significantly higher than those with more severe fractures (17.67 vs 15.30 ng/mL, p = 0.006). Higher 25(OH)D levels were also observed in patients with less severe intertrochanteric fractures (p = 0.01). After adjustments for confounders, 25(OH)D remained a risk factor for patients with more severe fractures (p = 0.01), particularly those with intertrochanteric fractures (p = 0.011). No significant differences in BTMS were found between patients with less severe and more severe fractures. CONCLUSION: Levels of 25(OH)D were significantly associated with the severity of intertrochanteric, but not femoral neck, fractures. Neither 25(OH)D nor BTMs were associated with the type of hip fracture in older women. Separate consideration of intertrochanteric and femoral neck fractures may be appropriate when investigating the clinical association between 25(OH)D and the severity of hip fractures in older women.

Maternal HBsAg carriers and adverse pregnancy outcomes: A hospital-based prospective cohort analysis.

It is not clear whether chronic hepatitis B virus (HBV) infection during pregnancy can increase the risk of adverse pregnancy outcomes for both mothers and neonates. We conducted a hospital-based prospective cohort study on pregnant women (PW) and used an analysis strategy that was guided by directed acyclic graphs (DAGs). Maternal characteristics and major adverse pregnancy outcomes were collected both from questionnaires and hospital-based electronic medical records. Serum hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) status were determined. In total, 3329 of the 3416 pregnant women who received routine antenatal care in a hospital setting at baseline, including 346 HBsAg carriers, were available for analysis. Maternal HBsAg carrier status was associated with an increased risk of intrahepatic cholestasis pregnancy [aOR (adjusting odds ratio) = 1.70; 95% CI (confidence interval) = 1.16-2.49], premature rupture of the membranes (aOR = 1.38; 95% CI = 1.00-1.89) and large for gestational age birth aOR = 1.67; 95% CI = 1.17-2.39). The risk of intrahepatic cholestasis remained in pregnant women with either HBeAg-positive (aOR = 2.96; 95% CI = 1.33-6.62) or HBeAg-negative (aOR = 1.52; 95% CI =1.00-2.32)] status; notably, only maternal HBeAg-negative status was associated with a higher risk of large for gestational age birth (aOR = 1.91; 95% CI = 1.33-2.76). Our results implied that chronic HBV infection during pregnancy may increase the risk of intrahepatic cholestasis of pregnancy, premature rupture of membranes and large for gestational age pregnancies.

Placental and cord blood brain derived neurotrophic factor levels are decreased in nondiabetic macrosomia.

PURPOSE: To measure levels of placental brain derived neurotrophic factor (BDNF) gene expression and umbilical cord blood BDNF in neonates with nondiabetic macrosomia and determine associations between these levels and macrosomia. METHODS: This case-control study included 58 nondiabetic macrosomic and 59 normal birth weight mother-infant pairs. Data were collected from interviews and our hospital's database. BDNF gene expression was quantified in placental tissues using quantitative real-time polymerase chain reaction (n = 117). Umbilical cord blood BDNF levels were measured by enzyme-linked immunosorbent assay (n = 90). Multivariate logistic regression models were used to evaluate associations between BDNF levels and macrosomia. RESULTS: Placental BDNF gene expression (P = 0.026) and cord blood BDNF (P = 0.008) were lower in neonates with nondiabetic macrosomia than in normal birth weight controls. Cord blood BDNF was significantly lower in vaginally delivered macrosomic neonates than vaginally delivered controls (P = 0.014), but cord BDNF did not differ between vaginal and cesarean section delivery modes in macrosomic neonates. Cord blood BDNF was positively associated with gestational age in control neonates (r = 0.496, P < 0.001), but not in macrosomic neonates. Cord blood BDNF was positively associated with placental BDNF relative expression (r s = 0.245, P = 0.02) in the total group. Higher cord blood BDNF levels were independently associated with protection against nondiabetic macrosomia (adjusted odds ratio 0.992; 95% confidence interval 0.986-0.998). CONCLUSIONS: Both placental BDNF gene expression and cord blood BDNF were downregulated in neonates with nondiabetic macrosomia compared with normal birth weight neonates. Cord BDNF may partly derive from BDNF secreted by the placenta. Higher cord plasma BDNF levels protected against nondiabetic macrosomia.

Decreased miR-143 and increased miR-21 placental expression levels are associated with macrosomia.

Macrosomia, a birth weight ≥ 4,000 g, is associated with maternal and infant health problems. The dysregulation of microRNAs (miRNAs) in the placenta is associated with adverse birth outcomes, yet whether aberrantly expressed placental miRNAs are associated with macrosomia remains unknown. The aim of the current study was to characterize the expression of three placental miRNAs (miR­6, ­21 and ­143) and evaluate their association with macrosomia. The miRNA expression in placental tissues from 67 macrosomic pregnancies and 64 normal pregnancies were analyzed using reverse transcription­quantitative polymerase chain reaction. The expression of miR­21 was observed to be elevated in macrosomic placenta compared with control samples, while miR­143 expression was significantly lower than in control placenta (P<0.05). No significant differences were identified in the miR­16 expression levels between the groups (P=0.955). Following division of miRNA expression levels by quartile, logistic regression models demonstrated that the odds of macrosomia increased with miR­21 expression quartile: Q2, odds ratio (OR)=6.67 [95% confidence interval (CI), 1.39­32.05]; Q3, OR=4.10 (95% CI, 0.88­19.11); Q4, OR=16.19 (95% CI, 2.46­106.68). Conversely, higher levels of miR­143 expression were protective against macrosomia: Q2, OR=0.22 (95% CI, 0.049­0.98); Q3, OR=0.11 (95% CI, 0.024­0.55), and Q4, OR=0.16 (95% CI, 0.032­0.79). Thus, statistical analysis demonstrated that high levels of miR­21 expression and low levels of miR­143 expression predict the risk for macrosomia, indicating an interaction between the two miRNAs. Bioinformatic analysis suggested that they are likely to function in the mitogen­activated protein kinases signaling pathway to influence the risk of macrosomia. The results of the present study provide evidence that placental miR-21 and -143 are important in the formation of macrosomia.

Birth weight is associated with placental fat mass- and obesity-associated gene expression and promoter methylation in a Chinese population.

OBJECTIVE: To explore the relationship between birth weight and fat mass- and obesity-associated (FTO) gene expression and promoter methylation status in the Chinese population. METHODS: Seventy-five neonates and their mothers were recruited from Yuying Children's Hospital of Wenzhou Medical University. Subjects were divided into three groups by birth weight: low (< 3,500 g, n = 20), medium (3,500-3,999 g, n = 30) and high (≥ 4,000 g, n = 25). Placental FTO transcript levels and promoter methylation were determined by quantitative PCR and Sequenom MassARRAY®. RESULTS: Placental FTO mRNA expression was significantly increased in the high- and medium-weight groups compared to the low-weight group (p = 0.023). Methylation rates of CpG11 sites were significantly decreased in high-birth weight newborns (p = 0.018). Multiple linear regressions showed placental FTO mRNA, maternal pre-pregnancy body mass index (BMI) and CpG11 methylation rate were independently associated with increased fetal birth weight. Additionally, FTO mRNA expression was negatively associated with CpG6.7.8.9 methylation in mothers that underwent C-section. CONCLUSIONS: High placental FTO expression is associated with increased birth weight in Chinese neonates, and FTO promoter methylation level at a specific CpG site is negatively associated with birth weight. Further work is needed to determine the functionality of this CpG site in placentas.