Pan-cancer analysis of CDKN2A alterations identifies a subset of gastric cancer with a cold tumor immune microenvironment.

BACKGROUND: Although CDKN2A alteration has been explored as a favorable factor for tumorigenesis in pan-cancers, the association between CDKN2A point mutation (MUT) and intragenic deletion (DEL) and response to immune checkpoint inhibitors (ICIs) is still disputed. This study aims to determine the associations of CDKN2A MUT and DEL with overall survival (OS) and response to immune checkpoint inhibitors treatment (ICIs) among pan-cancers and the clinical features of CDKN2A-altered gastric cancer. METHODS: This study included 45,000 tumor patients that underwent tumor sequencing across 33 cancer types from four cohorts, the MSK-MetTropism, MSK-IMPACT, OrigiMed2020 and TCGA cohorts. Clinical outcomes and genomic factors associated with response to ICIs, including tumor mutational burden, copy number alteration, neoantigen load, microsatellite instability, tumor immune microenvironment and immune-related gene signatures, were collected in pan-cancer. Clinicopathologic features and outcomes were assessed in gastric cancer. Patients were grouped based on the presence of CDKN2A wild type (WT), CDKN2A MUT, CDKN2A DEL and CDKN2A other alteration (ALT). RESULTS: Our research showed that CDKN2A-MUT patients had shorter survival times than CDKN2A-WT patients in the MSK MetTropism and TCGA cohorts, but longer OS in the MSK-IMPACT cohort with ICIs treatment, particularly in patients having metastatic disease. Similar results were observed among pan-cancer patients with CDKN2A DEL and other ALT. Notably, CDKN2A ALT frequency was positively related to tumor-specific objective response rates to ICIs in MSK MetTropism and OrigiMed 2020. Additionally, individuals with esophageal carcinoma or stomach adenocarcinoma who had CDKN2A MUT had poorer OS than patients from the MSK-IMPACT group, but not those with adenocarcinoma. We also found reduced levels of activated NK cells, T cells CD8 and M2 macrophages in tumor tissue from CDKN2A-MUT or DEL pan-cancer patients compared to CDKN2A-WT patients in TCGA cohort. Gastric cancer scRNA-seq data also showed that CDKN2A-ALT cancer contained less CD8 T cells but more exhausted T cells than CDKN2A-WT cancer. A crucial finding of the pathway analysis was the inhibition of three immune-related pathways in the CDKN2A ALT gastric cancer patients, including the interferon alpha response, inflammatory response, and interferon gamma response. CONCLUSIONS: This study illustrates the CDKN2A MUT and DEL were associated with a poor outcome across cancers. CDKN2A ALT, on the other hand, have the potential to be used as a biomarker for choosing patients for ICI treatment, notably in esophageal carcinoma and stomach adenocarcinoma.

Trends in cardiovascular health among US adults by glycemic status based on Life's Essential 8.

OBJECTIVE: We aimed to assess the secular trends in cardiovascular health (CVH) among U.S. adults with different glycemic statuses based on the Life's Essential 8 (LE8). METHODS: This cross-sectional study used nationally representative data from 6 cycles of the National Health and Nutrition Examination Surveys between 2007 and 2018. Survey-weighted linear models were used to assess time trends in LE8 scores. Stratified analyses and sensitivity analyses were conducted to validate the stability of the results. RESULTS: A total of 23,616 participants were included in this study. From 2007 to 2018, there was no significant improvement in overall CVH and the proportion of ideal CVH among participants with diabetes and prediabetes. We observed an opposite trend between health behavior and health factors in the diabetes group, mainly in increasing physical activity scores and sleep scores (P for trend<0.001), and declining BMI scores [difference, -6.81 (95% CI, -12.82 to -0.80)] and blood glucose scores [difference, -6.41 (95% CI, -9.86 to -2.96)]. Dietary health remained at a consistently low level among participants with different glycemic status. The blood lipid scores in the prediabetes group improved but were still at a lower level than other groups. Education/income differences persist in the CVH of participants with diabetes or prediabetes, especially in health behavior factors. Sensitivity analyses of the absolute difference and change in proportion showed a consistent trend. CONCLUSIONS: Trends in CVH among participants with diabetes or prediabetes were suboptimal from 2007 to 2018, with persistent education/income disparities.

The Windshield Wiper Sign Is an Instability-Related Osteochondral Defect of the Anterolateral Femoral Head.

PURPOSE: To investigate a radiographic sign believed to be indicative of hip instability and acetabular suction seal disruption in the native hip, coined the "windshield wiper" (WSW) sign. METHODS: A retrospective review was performed for patients who underwent periacetabular osteotomy (PAO) with the senior author between March 2021 and September 2023. A WSW sign was identified on plain films as a concave or flat osteochondral defect on the anterolateral femoral head extending medial to the head-neck junction with resultant loss of femoral head sphericity in the native hip. Every patient underwent a standardized series of radiographs, as well as computed tomography and magnetic resonance imaging. All patients underwent arthroscopy before PAO to address intra-articular pathology and other indicated procedures. The osteochondral defect and resultant suction seal disruption were verified during arthroscopy. These patients were then compared with a control group of arthroscopically treated hips without hip instability. RESULTS: Of 250 patients reviewed, a total of 19 hips in 17 patients (prevalence of 7.6%) demonstrated radiographic evidence of the WSW sign. All patients with a WSW sign presented with symptomatic clinical hip instability requiring a PAO. The mean patient age was 31.2 years, with a mean lateral center-edge angle (LCEA) of 14.3°. There were 13 hips (68.4%) with dysplasia, 4 (21.1%) with borderline dysplasia, and 2 (10.5%) with a normal LCEA. All patients with a WSW sign and LCEA ≥ 20° displayed significant femoral antetorsion abnormalities. All arthroscopic videos and images demonstrated a compromised suction seal. Of the 50 control group hips reviewed, the WSW sign was not identified. CONCLUSIONS: The WSW sign is an uncommon radiographic finding in patients with hip instability. When identified, it can be predictive of substantial instability, especially in cases which are otherwise considered borderline dysplasia or normal based on LCEA. LEVEL OF EVIDENCE: Level III, retrospective comparative case control study.

Risk of intrapartum cesarean delivery in twin pregnancies: A retrospective cohort study.

OBJECTIVE: To compare the risk of intrapartum cesarean delivery (CD) between patients with twin and singleton pregnancies undergoing a trial of labor and identify risk factors for intrapartum CD in twin pregnancies. METHODS: The present study was a retrospective cohort study of patients with a twin or singleton pregnancy who underwent a trial of labor at ≥340/7 weeks in a single center (2015-2022). The primary outcome was the rate of intrapartum CD. In twin pregnancies, this outcome was limited to CD of both twins. The association of plurality with intrapartum CD was estimated using multivariable Poisson regression. RESULTS: A total of 20 754 patients met the study criteria, 669 of whom had a twin pregnancy. Patients with twins had a greater risk of intrapartum CD (of both twins) than those with singleton pregnancies (22.1% vs 15.9%, respectively; aRR 1.38 [95% CI: 1.15-1.66]), primarily due to a greater risk of failure to progress. In addition, 4.1% of the twin pregnancies had a CD for the second twin, resulting in an overall CD rate in twin pregnancies of 26.2%. Variables associated with intrapartum CD in twin pregnancies included nulliparity (aOR 3.50, 95% CI: 2.34-5.25), birthweight discordance >20% (aOR 2.47, 95% CI: 1.27-4.78), and labor induction (aOR 1.64, 95% CI: 1.07-2.53). The rate of intrapartum CD was highest when all three risk factors were present (67% [95% CI: 41%-87%]). CONCLUSION: Twin pregnancies are associated with a greater risk of intrapartum CD than singleton pregnancies. Information on the individualized risk of intrapartum CD may be valuable when counseling patients with twins regarding mode of delivery.

Patients Undergoing Postless Hip Arthroscopy Demonstrate Significantly Better Patient-Reported Outcomes and Clinically Significant Outcomes Compared to Conventional Post-Assisted Hip Arthroscopy at Short-Term Follow-Up.

PURPOSE: To prospectively compare the short-term clinical outcomes of patients undergoing hip arthroscopy with versus without the use of a perineal post. METHODS: A prospective, single-surgeon cohort study was performed on a subset of patients undergoing hip arthroscopy between 2020 and 2022. A post-free hip distraction system was used at 1 center at which the senior author operates, and a perineal post was used at another surgical location. An electronic survey of patient-reported outcome measures (PROMs) was completed by each patient at a minimum of 1 year postoperatively. PROMs included a visual analog scale for pain; University of California, Los Angeles (UCLA) Activity Scale; modified Harris Hip Score (mHHS); Hip Outcome Score-Sports-Specific Subscale (HOS-SSS); and a Single Assessment Numeric Evaluation. Postoperative scores and clinically significant outcomes, including the minimal clinically important difference, substantial clinical benefit, and patient acceptable symptom state, for each PROM were compared between groups. RESULTS: Sixty-nine patients were reached for follow-up (41 post, 28 postless) of 87 patients eligible for the study (79%). No significant differences were found between groups in terms of sex (post: 61% female, postless: 54% female, P = .54), age (post: 34 years, postless: 29 years, P = .11), body mass index (post: 26, postless: 24, P = .23), or follow-up duration (post: 24.4 months, postless: 21.3 months, P = .16). There was a significantly higher visual analog scale (3.1 vs 1.4, P = .01), a significantly lower UCLA Activity Scale score (7.0 vs 8.4, P = .02), and a significantly lower mHHS (73.7 vs 82.2, P = .03) in the post-assisted group. A significantly higher proportion of patients in the postless group achieved a patient acceptable symptom state for the UCLA (89.3% vs 68.3%, P = .04), mHHS (84.6% vs 61.0%, P = .04), and HOS-SSS (84.0% vs 61.0%, P = .048) and a substantial clinical benefit for HOS-SSS (72.0% vs 41.5%, P = .02). One patient (2.6%) in the post group underwent revision hip arthroscopy, and another was indicated for total hip arthroplasty by the time of follow-up. CONCLUSIONS: Postless hip arthroscopy may result in better clinical outcomes compared with post-assisted hip arthroscopy. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Arthroscopic Femoral Head Allograft With Proximal Femoral/Periacetabular Osteotomies for Sequelae of Perthes: A Case Report.

CASE: We describe the unique case of a 20-year-old man with a history of Legg-Calve-Perthes disease, hip dysplasia, and osteochondral fragmentation of the medial femoral head. We performed arthroscopic femoroplasty and femoral head allografting, followed by a valgus-producing derotational femoral osteotomy (DFO) and periacetabular osteotomy (PAO). At 1-year follow-up, the patient achieved osseous union and complete femoral head healing with return to his active hobbies. CONCLUSION: We describe the successful utilization of arthroscopic allografting for medial femoral head osteochondral fragmentation. To our knowledge, this is the first report on femoral head arthroscopic allografting before DFO and PAO.

The Everted Acetabular Labrum: Outcomes of Surgical Management.

BACKGROUND: An everted acetabular labrum (EL) is a pathologic variant in which the labrum is flipped to the capsular side of the acetabular rim. An iatrogenic EL is a known complication of a poorly executed labral repair, and a recent study described the native acetabular EL. PURPOSE: To analyze surgical outcomes after advancement or reconstruction of an EL in a native hip. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This was a multicenter retrospective review of prospectively collected data on primary hip arthroscopic surgeries performed between 2013 and 2023. An EL was identified arthroscopically as a labrum-femoral head gap while off traction in the native hip. All patients with EL who were analyzed in this study underwent arthroscopic labral repair and advancement or labral augmentation or reconstruction. Patients with hip dysplasia also underwent periacetabular osteotomy with or without a derotational femoral osteotomy. Patient-reported outcomes (PROs) were assessed using the 12-item International Hip Outcome Tool (iHOT-12) and the Nonarthritic Hip Score. PROs were obtained preoperatively and up to 24 months after surgery. PROs were compared with those of a case-matched control cohort in a 1:2 ratio. Only patients with PROs available at ≥1 year postoperatively were included in the outcome analysis. RESULTS: A total of 111 patients (129 hips) with EL during the study period were identified, with PROs available in 96 hips. The mean age of patients with EL was 30.5 years, and women made up 87% of the cohort. Of the 129 hips with an EL, an isolated diagnosis of an EL was present in 11.6% of hips. Deficient acetabular coverage (lateral center-edge angle <25°) was seen in 40.6% of EL hips. No difference was seen in iHOT-12 scores between EL and control groups at 12- or 24-month follow-up (P = .18 and .94, respectively). Patients with EL reported a significant improvement of PROs at latest follow-up (P < .001 for iHOT-12 and Nonarthritic Hip Score). CONCLUSION: Surgical management of a native EL with restoration of the labral seal on the femoral head and correction of concomitant pathologies resulted in significant clinical improvement, with postoperative outcome scores comparable to those of patients without an EL. These findings provide evidence supporting surgical intervention for a native EL.

Bridging the notch: quantification of the end diastolic notch to better predict fetal growth restriction.

PURPOSE: We aimed to evaluate several quantitative methods to describe the diastolic notch (DN) and compare their performance in the prediction of fetal growth restriction. MATERIALS AND METHODS: Patients who underwent a placental scan at 16-26 weeks of gestation and delivered between Jan 2016 and Dec 2020 were included. The uterine artery pulsatility index was measured for all of the patients. In patients with a DN, it was quantified using the notch index and notch depth index. Odds ratios for small for gestational age neonates (defined as birth weight <10th and <5th percentile) were calculated. Predictive values of uterine artery pulsatility, notch, and notch depth index for fetal growth restriction were calculated. RESULTS: Overall, 514 patients were included, with 69 (13.4%) of them delivering a small for gestational age neonate (birth weight<10th percentile). Of these, 20 (20.9%) had a mean uterine artery pulsatility index >95th percentile, 13 (18.8%) had a unilateral notch, and 11 (15.9%) had a bilateral notch. 16 patients (23.2%) had both a high uterine artery pulsatility index (>95th percentile) and a diastolic notch. Comparison of the performance between uterine artery pulsatility, notch, and notch depth index using receiver operating characteristic curves to predict fetal growth restriction <10th percentile found area under the curve values of 0.659, 0.679, and 0.704, respectively, with overlapping confidence intervals. CONCLUSION: Quantifying the diastolic notch at 16-26 weeks of gestation did not provide any added benefit in terms of prediction of neonatal birth weight below the 10th or 5th percentile for gestational age, compared with uterine artery pulsatility index.

During Postless Hip Arthroscopy, Male Patients, High Body Mass Index, Low Beighton Scores, and Limited Range of Motion Require High Traction Force.

PURPOSE: To determine the effects of demographic and anatomic factors on traction force required during postless hip arthroscopy. METHODS: A prospectively collected database was retrospectively analyzed on patients undergoing hip arthroscopy by the senior author, including patient sex, age, body mass index (BMI), Beighton Hypermobility Score, hip range of motion in clinic and under anesthesia, hip dysplasia, acetabular version, and femoral version. All patients underwent postless hip arthroscopy under general anesthesia. At the initiation of hip arthroscopy, the traction force required to distract the hip joint was measured before and following interportal capsulotomy. Multiple regression analysis was performed to determine the effects of demographic and anatomic factors on measured distraction force. RESULTS: In total, 352 hips (114 male, 238 female) were included with a mean age of 32.6 years and a mean BMI of 24.1 kg/m2. Mean initial traction force was 109 lbs and decreased to 94.3 lbs following capsulotomy (P < .0001). The starting traction force was significantly greater in male patients (P < .001), patients with a lack of hypermobility (Beighton Hypermobility Score of 0-2) (P = .026), and in patients with lower abduction (P < .001), lower internal rotation (P = .002), and lower external rotation (P = .012) on multiple regression analysis. When performing a subanalysis divided by sex, male patients with elevated BMI required significantly greater starting traction force (P = .014). Lateral center edge angle, sourcil angle, and the presence of hip dysplasia did not demonstrate a significant correlation with traction force. CONCLUSIONS: Male patients, patients with reduced preoperative hip range of motion, patients with a lack of joint hypermobility, and male patients with an elevated BMI require greater initial traction force during postless hip arthroscopy. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Neuron-derived exosomes mediate sevoflurane-induced neurotoxicity in neonatal mice via transferring lncRNA Gas5 and promoting M1 polarization of microglia.

Sevoflurane exposure during rapid brain development induces neuronal apoptosis and causes memory and cognitive deficits in neonatal mice. Exosomes that transfer genetic materials including long non-coding RNAs (lncRNAs) between cells play a critical role in intercellular communication. However, the lncRNAs found in exosomes derived from neurons treated with sevoflurane and their potential role in promoting neurotoxicity remain unknown. In this study, we investigated the role of cross-talk of newborn mouse neurons with microglial cells in sevoflurane-induced neurotoxicity. Mouse hippocampal neuronal HT22 cells were exposed to sevoflurane, and then co-cultured with BV2 microglial cells. We showed that sevoflurane treatment markedly increased the expression of the lncRNA growth arrest-specific 5 (Gas5) in neuron-derived extracellular vesicles, which inhibited neuronal proliferation and induced neuronal apoptosis by promoting M1 polarization of microglia and the release of inflammatory cytokines. We further revealed that the exosomal lncRNA Gas5 significantly upregulated Foxo3 as a competitive endogenous RNA of miR-212-3p in BV2 cells, and activated the NF-κB pathway to promote M1 microglial polarization and the secretion of inflammatory cytokines, thereby exacerbating neuronal damage. In neonatal mice, intracranial injection of the exosomes derived from sevoflurane-treated neurons into the bilateral hippocampi significantly increased the proportion of M1 microglia, inhibited neuronal proliferation and promoted apoptosis, ultimately leading to neurotoxicity. Similar results were observed in vitro in BV2 cells treated with the CM from HT22 cells after sevoflurane exposure. We conclude that sevoflurane induces the transfer of lncRNA Gas5-containing exosomes from neurons, which in turn regulates the M1 polarization of microglia and contributes to neurotoxicity. Thus, modulating the expression of lncRNA Gas5 or the secretion of exosomes could be a strategy for addressing sevoflurane-induced neurotoxicity.

A prediction tool for mode of delivery in twin pregnancies-a secondary analysis of the Twin Birth Study.

BACKGROUND: One of the controversies regarding the management of twin gestations relates to the mode of delivery. Currently, counseling regarding the mode of delivery and the chance of successful vaginal twin delivery is based on the average risk for intrapartum cesarean delivery in the general population of twin pregnancies. Decision support tools that provide an individualized risk for intrapartum cesarean delivery based on the unique characteristics of each patient can improve counseling and decision-making regarding the choice of mode of delivery in twin pregnancies. OBJECTIVE: This study aimed to develop and validate a prediction model to determine the risk for intrapartum cesarean delivery in twin pregnancies. STUDY DESIGN: In this secondary analysis of the Twin Birth Study, a multicenter randomized controlled trial, we considered the subgroup of individuals who underwent a trial of vaginal delivery. Candidate predictors included maternal age, parity, previous cesarean delivery, conception method, chorionicity, diabetes and hypertension in pregnancy, gestational age at birth, the onset of labor, presentation of the second twin, sonographic fetal weight estimation, and fetal sex. The co-primary outcomes were overall intrapartum cesarean delivery and cesarean delivery of the second twin. Multivariable logistic regression models were used to estimate the probability of the study outcomes. Model performance was evaluated using measures of discrimination (the area under the receiver operating characteristic curve), calibration, and predictive accuracy. Internal validation was performed using the bootstrap resampling technique. RESULTS: A total of 1221 individuals met the study criteria. The rate of overall intrapartum cesarean delivery and cesarean delivery for the second twin was 25.4% and 5.7%, respectively. The most contributory predictor variables were nulliparity, term birth (≥37 weeks), a noncephalic presentation of the second twin, previous cesarean delivery, and labor induction. The models for overall intrapartum cesarean delivery and cesarean delivery of the second twin had good overall discriminatory accuracy (area under the receiver operating characteristic curve, 0.720; 95% confidence interval, 0.688-0.752 and 0.736; 95% confidence interval, 0.669-0.803, respectively) and calibration (as illustrated by the calibration plot and Brier scores of 0.168; 95% confidence interval, 0.156-0.180 and 0.051; 95% confidence interval, 0.040-0.061, respectively). The models achieved good specificity (66.7% and 81.6%, respectively), high negative predictive value (86.0% and 96.9%, respectively), and moderate sensitivity (68.1% and 57.1%, respectively). CONCLUSION: The prediction models developed in this study may assist care providers in counseling individuals regarding the optimal timing and mode of delivery in twin pregnancies by providing individualized estimates of the risk for intrapartum cesarean delivery.

Low-dose ethanol consumption inhibits neutrophil extracellular traps formation to alleviate rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Ethanol consumption has been reported to reduce morbidity in RA patients, but the mechanism behind it remains unclear. Our results showed that Muribaculaceae was predominant in the gut microbiota of mice after ethanol treatment, and the levels of microbiota metabolite acetate were increased. Acetate reduced arthritis severity in collagen-induced arthritis (CIA) mice, which was associated with a decrease in the articular neutrophils and the myeloperoxidase-deoxyribonucleic acid complex in serum. Meanwhile, in vitro experiments confirmed that acetate affected neutrophil activity by acting on G-protein-coupled receptor 43, which reduced endoplasmic reticulum stress in neutrophils and inhibited neutrophil extracellular traps formation. Furthermore, exogenous acetate reversed CIA mice with exacerbated gut microbial disruption, further confirming that the effect of gut microbial metabolite acetate on neutrophils in vivo is crucial for the immune regulation. Our findings illuminate the metabolic and cellular mechanisms of the gut-joint axis in the regulation of autoimmune arthritis, and may offer alternative avenues to replicate or induce the joint-protective benefits of ethanol without associated detrimental effects.

The smaller firstborn: exploring the association of parity and fetal growth.

PURPOSE: To investigate the association of parity with a range of neonatal anthropometric measurements in a cohort of uncomplicated term singleton pregnancies. METHODS: Retrospective cohort study of patients with a singleton term birth at a single tertiary center (2014-2020) was carried out. The primary exposure was parity. The following neonatal anthropometric measures were considered: birthweight, head circumference, length, ponderal index, and neonatal body mass index (BMI). RESULTS: A total of 8134 patients met the study criteria, 1949 (24.0%) of whom were nulliparous. Compared with multiparous patients, infants of nulliparous patients had a lower mean percentile for birthweight (43.1 ± 26.4 vs. 48.3 ± 26.8 percentile, p < 0.001), head circumference (44.3 ± 26.4 vs. 48.1 ± 25.5 percentile, p < 0.001), length (52.6 ± 25.1 vs. 55.5 ± 24.6 percentile, p < 0.001), ponderal index (34.4 ± 24.0 vs. 37.6 ± 24.2 percentile, p < 0.001), and BMI (39.1 ± 27.1 vs. 43.9 ± 27.3 percentile, p < 0.001). In addition, infants of nulliparous patients had higher odds of having a small (< 10th percentile for gestational age) birthweight (aOR 1.32 [95% CI 1.12-1.56]), head circumference (aOR 1.54 [95% CI 1.29-1.84]), length (aOR 1.50 [95% CI 1.16-1.94]), ponderal index (aOR 1.30 [95% CI 1.12-1.51]), and body mass index (aOR 1.42 [95% CI 1.22-1.65]). Most neonatal anthropometric measures increased with parity until a parity of 2, where it seemed to reach a plateau. CONCLUSION: Parity has an independent impact on a wide range of neonatal anthropometric measures, suggesting that parity is associated with both fetal skeletal growth and body composition. In addition, the association of parity with fetal growth does not follow a continuous relationship but instead reaches a plateau after the second pregnancy.

Maternal First-Trimester Alpha-Fetoprotein and Placenta-Mediated Pregnancy Complications.

BACKGROUND: Maternal serum markers used for trisomy 21 screening are associated with placenta-mediated complications. Recently, there has been a transition from the traditional first-trimester screening (FTS) that included PAPP-A (pregnancy-associated plasma protein-A) and beta-hCG (human chorionic gonadotropin), to the enhanced FTS test, which added first-trimester AFP (alpha-fetoprotein) and PlGF (placental growth factor). However, whether elevated first-trimester AFP has a similar association with placenta-mediated complications to that observed for elevated second-trimester AFP remains unclear. Our objective was to estimate the association of first-trimester AFP with placenta-mediated complications and compare it with the corresponding associations of second-trimester AFP and other first-trimester serum markers. METHODS: Retrospective population-based cohort study of women who underwent trisomy 21 screening in Ontario, Canada (2013-2019). The association of first-trimester AFP with placenta-mediated complications was estimated and compared with that of the traditional serum markers. The primary outcome was a composite of stillbirth or preterm placental complications (preeclampsia, birthweight less than third centile, or placental abruption). RESULTS: A total of 244 990 and 96 167 women underwent FTS and enhanced FTS test screening, respectively. All markers were associated with the primary outcome, but the association for elevated first-trimester AFP (adjusted relative risk [aRR], 1.57 [95% CI, 1.37-1.81]) was weaker than that observed for low PAPP-A (aRR, 2.48 [95% CI, 2.2-2.8]), low PlGF (aRR, 2.28 [95% CI, 1.97-2.64]), and elevated second-trimester AFP (aRR, 1.97 [95% CI, 1.81-2.15]). When the models were adjusted for all 4 enhanced FTS test markers, elevated first-trimester AFP was no longer associated with the primary outcome (aRR, 0.77 [95% CI, 0.58-1.02]). CONCLUSIONS: Unlike second-trimester AFP, elevated first-trimester AFP is not an independent risk factor for placenta-mediated complications.

Survival differences between the USA and an urban population from China for all cancer types and 20 individual cancers: a population-based study.

Background: The systematic comparison of cancer survival between China and the USA is rare. Here we aimed to assess the magnitude of survival disparities and disentangle the impact of the stage at diagnosis between a Chinese metropolitan city and the USA on cancer survival. Methods: We included 11,046 newly diagnosed cancer patients in Dalian Cancer Registry, China, 2015, with the follow-up data for vital status until December 2020. We estimated age-standardised 5-year relative survival and quantified the excess hazard ratio (EHR) of death using generalised linear models for all cancers and 20 individual cancers. We compared these estimates with 17 cancer registries' data from the USA, using the Surveillance, Epidemiology, and End Results database. We further estimated the stage-specific survival for five major cancers by region. Findings: Age-standardised 5-year relative survival for all patients in Dalian was lower than that in the USA (49.9% vs 67.9%). By cancer types, twelve cancers with poorer prognosis were observed in Dalian compared to the USA, with the largest gap seen in prostate cancer (Dalian: 55.8% vs USA: 96.0%). However, Dalian had a better survival for lung cancer, cervical cancer, and bladder cancer. Dalian patients had a lower percentage of stage Ⅰ colorectal cancer (Dalian: 17.9% vs USA: 24.2%) and female breast cancer (Dalian: 40.9% vs USA: 48.9%). However, we observed better stage-specific survival among stage Ⅰ-Ⅱ lung cancer patients in Dalian than in the USA. Interpretation: This study suggests that although the overall prognosis for patients was better in the USA than in Dalian, China, survival deficits existed in both countries. Improvement in cancer early detection and cancer care are needed in both countries. Funding: National Key R&D Program (2021YFC2501900, 2022YFC3600805), Major State Basic Innovation Program of the Chinese Academy of Medical Sciences (2021-I2M-1-010, 2021-I2M-1-046), and Talent Incentive Program of Cancer Hospital of Chinese Academy of Medical Sciences.

Guideline No. 440: Management of Monochorionic Twin Pregnancies.

OBJECTIVE: This guideline reviews the evidence-based management of normal and complicated monochorionic twin pregnancies. TARGET POPULATION: Women with monochorionic twin or higher order multiple pregnancies. BENEFITS, HARMS, AND COSTS: Implementation of these recommendations should improve the management of both complicated and uncomplicated monochorionic (and higher order multiple) twin pregnancies. They will help users monitor monochorionic twin pregnancies appropriately and identify and manage monochorionic twin complications optimally in a timely manner, thereby reducing perinatal morbidity and mortality. These recommendations entail more frequent ultrasound monitoring of monochorionic twins compared to dichorionic twins. EVIDENCE: Published literature was retrieved through searches of PubMed and the Cochrane Library using appropriate MeSH headings (Twins, Monozygotic; Ultrasonography, Prenatal; Placenta; Fetofetal Transfusion; Fetal Death; Fetal Growth Retardation). Results were restricted to systematic reviews, randomized controlled clinical trials, and observational studies. There were no date limits, but results were limited to English or French language materials. VALIDATION METHODS: The content and recommendations were drafted and agreed upon by the principal authors. The Board of the SOGC approved the final draft for publication. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Maternal-fetal medicine specialists, obstetricians, radiologists, sonographers, family physicians, nurses, midwives, residents, and other health care providers who care for women with monochorionic twin or higher order multiple pregnancies. TWEETABLE ABSTRACT: Canadian (SOGC) guidelines for the diagnosis, ultrasound surveillance and management of monochorionic twin pregnancy complications, including TTTS, TAPS, sFGR (sIUGR), acardiac (TRAP), monoamniotic twins and intrauterine death of one MC twin. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 440 : Prise en charge de la grossesse gémellaire monochoriale.

OBJECTIF: Cette directive clinique passe en revue les données probantes sur la prise en charge de la grossesse gémellaire monochoriale normale et compliquée. POPULATION CIBLE: Les femmes menant une grossesse gémellaire ou multiple de haut rang. BéNéFICES, RISQUES ET COûTS: L'application des recommandations de cette directive devrait améliorer la prise en charge des grossesses gémellaires (ou multiples de haut rang) monochoriales compliquées et non compliquées. Ces recommandations aideront les fournisseurs de soins à surveiller adéquatement les grossesses gémellaires monochoriales ainsi qu'à détecter et prendre en charge rapidement les complications associées de façon optimale afin de réduire les risques de morbidité et mortalité périnatales. Ces recommandations impliquent une surveillance échographique plus fréquente en cas de grossesse monochoriale qu'en cas de grossesse bichoriale. DONNéES PROBANTES: La littérature publiée a été colligée par des recherches dans les bases de données PubMed et Cochrane Library au moyen de termes MeSH pertinents (Twins, Monozygotic; Ultrasonography, Prenatal; Placenta; Fetofetal Transfusion; Fetal Death; Fetal Growth Retardation). Les résultats ont été restreints aux revues systématiques, aux essais cliniques randomisés et aux études observationnelles. Aucune date limite n'a été appliquée, mais les résultats ont été limités aux contenus en anglais ou en français. MéTHODES DE VALIDATION: Les auteurs principaux ont rédigé le contenu et les recommandations et ils se sont entendus sur ces derniers. Le conseil d'administration de la SOGC a approuvé la version définitive aux fins de publication. Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations Assessment, Development and Evaluation). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: Spécialistes en médecine fœto-maternelle, obstétriciens, radiologues, échographistes, médecins de famille, infirmières, sages-femmes, résidents et autres fournisseurs de soins de santé qui s'occupent de femmes menant une grossesse gémellaire ou multiple de haut rang. RéSUMé POUR TWITTER: Directive canadienne (SOGC) pour le diagnostic, la surveillance échographique et la prise en charge des complications de la grossesse gémellaire monochoriale (p. ex., STT, TAPS, retard de croissance sélectif, cojumeau acardiaque, monoamnionicité et mort d'un jumeau). DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Accuracy in predicting soft tissue changes of orthodontic class III cases using Dolphin® software.

OBJECTIVES: The prediction of posttreatment outcomes is conducive to the final determination of ideal therapeutic options. However, the prediction accuracy in orthodontic class III cases is unclear. Therefore, this study conducted exploration on prediction accuracy in orthodontic class III patients using the Dolphin® software. MATERIALS AND METHODS: In this retrospective study, lateral cephalometric radiographs of pre- and posttreatment were collected from 28 angle class III adults who received completed non-orthognathic orthodontic therapy (8 males, 20 females; mean age = 20.89 ± 4.26 years). The values of 7 posttreatment parameters were recorded and inserted into the Dolphin® Imaging software to generate a predicted outcome, and then the prediction radiograph and actual posttreatment radiograph were superimposed and compared in terms of soft tissue parameters and landmarks. RESULTS: The prediction showed significant differences with the actual outcomes in nasal prominence (the difference between the prediction and the actual value was - 0.78 ± 1.82 mm), the distance from the lower lip to the H line (0.55 ± 1.11 mm), and the distance from the lower lip to the E line (0.77 ± 1.62 mm) (p < 0.05). Point subnasale (Sn) (an accuracy of 92.86% in the horizontal direction and 100% in the vertical direction in 2 mm) and point soft tissue A (ST A) (an accuracy of 92.86% in the horizontal direction and 85.71% in the vertical direction in 2 mm) were proven to be the most accurate landmarks, while the predictions in the chin region were relatively inaccurate. Furthermore, the predictions in the vertical direction were of higher accuracy compared to the horizontal direction except for the points around the chin. CONCLUSIONS: The Dolphin® software demonstrated acceptable prediction accuracy in midfacial changes in class III patients. However, there were still limitations for changes in the chin and lower lip prominence. CLINICAL RELEVANCE: Clarifying the accuracy of Dolphin® software in predicting soft tissue changes of orthodontic class III cases will facilitate physician-patient communication and clinical treatment.

Prediction of birthweight and risk of macrosomia in pregnancies complicated by diabetes.

BACKGROUND: Antenatal detection of accelerated fetal growth and macrosomia in pregnancies complicated by diabetes mellitus is important for patient counseling and management. Sonographic fetal weight estimation is the most commonly used tool to predict birthweight and macrosomia. However, the predictive accuracy of sonographic fetal weight estimation for these outcomes is limited. In addition, an up-to-date sonographic fetal weight estimation is often unavailable before birth. This may result in a failure to identify macrosomia, especially in pregnancies complicated by diabetes mellitus where care providers might underestimate fetal growth rate. Therefore, there is a need for better tools to detect and alert care providers to the potential risk of accelerated fetal growth and macrosomia. OBJECTIVE: This study aimed to develop and validate prediction models for birthweight and macrosomia in pregnancies complicated by diabetes mellitus. STUDY DESIGN: This was a completed retrospective cohort study of all patients with a singleton live birth at ≥36 weeks of gestation complicated by preexisting or gestational diabetes mellitus observed at a single tertiary center between January 2011 and May 2022. Candidate predictors included maternal age, parity, type of diabetes mellitus, information from the most recent sonographic fetal weight estimation (including estimated fetal weight, abdominal circumference z score, head circumference-to-abdomen circumference z score ratio, and amniotic fluid), fetal sex, and the interval between ultrasound examination and birth. The study outcomes were macrosomia (defined as birthweights >4000 and >4500 g), large for gestational age (defined as a birthweight >90th percentile for gestational age), and birthweight (in grams). Multivariable logistic regression models were used to estimate the probability of dichotomous outcomes, and multivariable linear regression models were used to estimate birthweight. Model discrimination and predictive accuracy were calculated. Internal validation was performed using the bootstrap resampling technique. RESULTS: A total of 2465 patients met the study criteria. Most patients had gestational diabetes mellitus (90%), 6% of patients had type 2 diabetes mellitus, and 4% of patients had type 1 diabetes mellitus. The overall proportions of infants with birthweights >4000 g, >4500 g, and >90th percentile for gestational age were 8%, 1%, and 12%, respectively. The most contributory predictor variables were estimated fetal weight, abdominal circumference z score, ultrasound examination to birth interval, and type of diabetes mellitus. The models for the 3 dichotomous outcomes had high discriminative accuracy (area under the curve receiver operating characteristic curve, 0.929-0.979), which was higher than that achieved with estimated fetal weight alone (area under the curve receiver operating characteristic curve, 0.880-0.931). The predictive accuracy of the models had high sensitivity (87%-100%), specificity (84%-92%), and negative predictive values (84%-92%). The predictive accuracy of the model for birthweight had low systematic and random errors (0.6% and 7.5%, respectively), which were considerably smaller than the corresponding errors achieved with estimated fetal weight alone (-5.9% and 10.8%, respectively). The proportions of estimates within 5%, 10%, and 15% of the actual birthweight were high (52.3%, 82.9%, and 94.9%, respectively). CONCLUSION: The prediction models developed in the current study were associated with greater predictive accuracy for macrosomia, large for gestational age, and birthweight than the current standard of care that includes estimated fetal weight alone. These models may assist care providers in counseling patients regarding the optimal timing and mode of delivery.