Incidence, clinical features and perinatal outcome in anomalous fetuses with late-onset growth restriction: cohort study.

OBJECTIVE: To describe the incidence, clinical features and perinatal outcome of late-onset fetal growth restriction (FGR) associated with genetic syndrome or aneuploidy, structural malformation or congenital infection. METHODS: This was a retrospective multicenter cohort study of patients who attended one of four tertiary maternity hospitals in Italy. We included consecutive singleton pregnancies between 32 + 0 and 36 + 6 weeks' gestation with either fetal abdominal circumference (AC) or estimated fetal weight < 10th percentile for gestational age or a reduction in AC of > 50 percentiles from the measurement at an ultrasound scan performed between 18 and 32 weeks. The study group consisted of pregnancies with late-onset FGR and a genetic syndrome or aneuploidy, structural malformation or congenital infection (anomalous late-onset FGR). The presence of congenital anomalies was ascertained postnatally in neonates with abnormal findings on antenatal investigation or detected after birth. The control group consisted of pregnancies with structurally and genetically normal fetuses with late-onset FGR. Composite adverse perinatal outcome was defined as the presence of at least one of stillbirth, 5-min Apgar score < 7, admission to the neonatal intensive care unit (NICU), need for respiratory support at birth, neonatal jaundice and neonatal hypoglycemia. The primary aims of the study were to assess the incidence and clinical features of anomalous late-onset FGR, and to compare the perinatal outcome of such cases with that of fetuses with non-anomalous late-onset FGR. RESULTS: Overall, 1246 pregnancies complicated by late-onset FGR were included in the study, of which 120 (9.6%) were allocated to the anomalous late-onset FGR group. Of these, 11 (9.2%) had a genetic syndrome or aneuploidy, 105 (87.5%) had an isolated structural malformation, and four (3.3%) had a congenital infection. The most frequent structural defects associated with late-onset anomalous FGR were genitourinary malformations (28/105 (26.7%)) and limb malformation (21/105 (20.0%)). Compared with the non-anomalous late-onset FGR group, fetuses with anomalous late-onset FGR had an increased incidence of composite adverse perinatal outcome (35.9% vs 58.3%; P < 0.01). Newborns with anomalous, compared to those with non-anomalous, late-onset FGR showed a higher frequency of need for respiratory support at birth (25.8% vs 9.0%; P < 0.01), intubation (10.0% vs 1.1%; P < 0.01), NICU admission (43.3% vs 22.6%; P < 0.01) and longer hospital stay (median, 24 days (range, 4-250 days) vs 11 days (range, 2-59 days); P < 0.01). CONCLUSIONS: Most pregnancies complicated by anomalous late-onset FGR have structural malformations rather than genetic abnormality or infection. Fetuses with anomalous late-onset FGR have an increased incidence of complications at birth and NICU admission and a longer hospital stay compared with fetuses with isolated late-onset FGR. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Third-trimester ultrasound for antenatal diagnosis of placenta accreta spectrum in women with placenta previa: results from the ADoPAD study.

OBJECTIVE: To evaluate the performance of third-trimester ultrasound for the diagnosis of clinically significant placenta accreta spectrum disorder (PAS) in women with low-lying placenta or placenta previa. METHODS: This was a prospective multicenter study of pregnant women aged ≥ 18 years who were diagnosed with low-lying placenta (< 20 mm from the internal cervical os) or placenta previa (covering the internal cervical os) on ultrasound at ≥ 26 + 0 weeks' gestation, between October 2014 and January 2019. Ultrasound suspicion of PAS was raised in the presence of at least one of these signs on grayscale ultrasound: (1) obliteration of the hypoechogenic space between the uterus and the placenta; (2) interruption of the hyperechogenic interface between the uterine serosa and the bladder wall; (3) abnormal placental lacunae. Histopathological examinations were performed according to a predefined protocol, with pathologists blinded to the ultrasound findings. To assess the ability of ultrasound to detect clinically significant PAS, a composite outcome comprising the need for active management at delivery and histopathological confirmation of PAS was considered the reference standard. PAS was considered to be clinically significant if, in addition to histological confirmation, at least one of these procedures was carried out after delivery: use of hemostatic intrauterine balloon, compressive uterine suture, peripartum hysterectomy, uterine/hypogastric artery ligation or uterine artery embolization. The diagnostic performance of each ultrasound sign for clinically significant PAS was evaluated in all women and in the subgroup who had at least one previous Cesarean section and anterior placenta. Post-test probability was assessed using Fagan nomograms. RESULTS: A total of 568 women underwent transabdominal and transvaginal ultrasound examinations during the study period. Of these, 95 delivered in local hospitals, and placental pathology according to the study protocol was therefore not available. Among the 473 women for whom placental pathology was available, clinically significant PAS was diagnosed in 99 (21%), comprising 36 cases of placenta accreta, 19 of placenta increta and 44 of placenta percreta. The median gestational age at the time of ultrasound assessment was 31.4 (interquartile range, 28.6-34.4) weeks. A normal hypoechogenic space between the uterus and the placenta reduced the post-test probability of clinically significant PAS from 21% to 5% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 9% in the subgroup with previous Cesarean section and anterior placenta. The absence of placental lacunae reduced the post-test probability of clinically significant PAS from 21% to 9% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 36% in the subgroup with previous Cesarean section and anterior placenta. When abnormal placental lacunae were seen on ultrasound, the post-test probability of clinically significant PAS increased from 21% to 59% in the whole cohort and from 62% to 78% in the subgroup with previous Cesarean section and anterior placenta. An interrupted hyperechogenic interface between the uterine serosa and bladder wall increased the post-test probability for clinically significant PAS from 21% to 85% in women with low-lying placenta or placenta previa and from 62% to 88% in the subgroup with previous Cesarean section and anterior placenta. When all three sonographic markers were present, the post-test probability for clinically significant PAS increased from 21% to 89% in the whole cohort and from 62% to 92% in the subgroup with previous Cesarean section and anterior placenta. CONCLUSIONS: Grayscale ultrasound has good diagnostic performance to identify pregnancies at low risk of PAS in a high-risk population of women with low-lying placenta or placenta previa. Ultrasound may be safely used to guide management decisions and concentrate resources on patients with higher risk of clinically significant PAS. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Guidelines for Perioperative Care in Elective Colorectal Surgery: Enhanced Recovery After Surgery (ERAS®) Society Recommendations: 2018.

BACKGROUND: This is the fourth updated Enhanced Recovery After Surgery (ERAS®) Society guideline presenting a consensus for optimal perioperative care in colorectal surgery and providing graded recommendations for each ERAS item within the ERAS® protocol. METHODS: A wide database search on English literature publications was performed. Studies on each item within the protocol were selected with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohorts and examined, reviewed and graded according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: All recommendations on ERAS® protocol items are based on best available evidence; good-quality trials; meta-analyses of good-quality trials; or large cohort studies. The level of evidence for the use of each item is presented accordingly. CONCLUSIONS: The evidence base and recommendation for items within the multimodal perioperative care pathway are presented by the ERAS® Society in this comprehensive consensus review.

Untangling Neolithic and Bronze Age mitochondrial lineages in South Asia.

Two key moments shaped the extant South Asian gene pool within the last 10 thousand years (ka): the Neolithic period, with the advent of agriculture and the rise of the Harappan/Indus Valley Civilisation; and Late Bronze Age events that witnessed the abrupt fall of the Harappan Civilisation and the arrival of Indo-European speakers. This study focuses on the phylogeographic patterns of mitochondrial haplogroups H2 and H13 in the Indian Subcontinent and incorporates evidence from recently released ancient genomes from Central and South Asia. It found signals of Neolithic arrivals from Iran and later movements in the Bronze Age from Central Asia that derived ultimately from the Steppe. This study shows how a detailed mtDNA phylogeographic approach, combining both modern and ancient variation, can provide evidence of population movements, even in a scenario of strong male bias such as in the case of the Bronze Age Steppe dispersals.

Cervical-length measurement in mid-gestation to predict spontaneous preterm birth in asymptomatic triplet pregnancy.

OBJECTIVE: To assess the predictive value of sonographic cervical-length (CL) measurement in mid-gestation for spontaneous preterm birth (PTB) in asymptomatic triplet pregnancy. METHODS: This was a retrospective study of asymptomatic triplet pregnancies followed at five Italian tertiary referral centers, between 2002 and 2015. CL was measured transvaginally between 18 and 24 weeks' gestation. Pregnancies with medically indicated PTB were excluded. Demographic and pregnancy characteristics of pregnancies complicated by PTB were analyzed and the distributions of CL measurements in these patients were calculated. Logistic regression analysis was performed to assess the association between CL and PTB, adjusted for confounders. Performance of CL measurement in prediction of PTB < 28, < 30 and < 32 weeks of gestation was assessed. RESULTS: A total of 120 triplet pregnancies were included in the final analysis. Median CL was 35 (interquartile range (IQR), 29-40) mm measured at a median gestational age of 20 + 2 (IQR, 20 + 0 to 23 + 4) weeks. Overall, 23 (19.2%), 17 (14.2%) and eight (6.7%) patients had a CL < 25, < 20 and < 15 mm, respectively. Spontaneous PTB < 32 weeks occurred in 41 (34.2%) cases, < 30 weeks in 23 (19.2%) and < 28 weeks in 12 (10%) cases. CL < 15 mm was significantly more frequent in the group of patients who delivered < 28 (P = 0.03) and < 30 (P = 0.01) weeks' gestation, compared with those who delivered after 28 and after 30 weeks, respectively, while CL < 20 mm was more common in triplet pregnancies with delivery < 32 weeks compared with those delivered ≥ 32 weeks (P = 0.03). Logistic regression analysis was possible only for PTB < 32 weeks due to the small number of cases that delivered < 30 and < 28 weeks. After adjustment for confounders, CL was not significantly associated with PTB < 32 weeks (adjusted odds ratio, 0.97; 95% CI, 0.94-1.01). CL measurement had an area under the receiver-operating characteristics curve of 0.41 (95% CI, 0.20-0.62), 0.41 (95% CI, 0.26-0.56) and 0.42 (95% CI, 0.31-0.54) for the prediction of spontaneous PTB < 28, < 30 and < 32 weeks, respectively. CONCLUSION: CL assessed in mid-gestation is a poor predictor of PTB < 28, < 30 and < 32 weeks' gestation in asymptomatic triplet pregnancy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Early prediction of twin-to-twin transfusion syndrome: systematic review and meta-analysis.

OBJECTIVE: To assess the role of first- and early second-trimester markers in the prediction of twin-to-twin transfusion syndrome (TTTS) in monochorionic twin pregnancies. METHODS: Electronic databases MEDLINE, EMBASE and ClinicalTrials.gov were searched from inception to April 2014, using the MeSH term 'fetofetal transfusion' in combination with phrases 'predictive value', 'sensitivity', 'specificity', 'false positive', 'false negative', 'screening', 'accuracy' and 'ROC'. Study quality was assessed using the PRISMA guidelines and QUADAS-2 tool. A meta-analysis was planned for the following predictive factors: intertwin nuchal translucency (NT) discrepancy; NT > 95th percentile in at least one twin; intertwin crown-rump length (CRL) discrepancy as a percentage of the larger CRL; abnormal ductus venosus (DV) flow in at least one twin. The outcome assessed was TTTS, defined according to the presence of a twin oligohydramnios-polyhydramnios sequence. The diagnostic performance of the predictive factors was evaluated for each included study. RESULTS: The electronic search identified 152 records, of which 23 were assessed in full for eligibility. We identified 13 eligible studies that reported the predictive accuracy of ultrasound parameters, measured before 16 weeks, for the development of TTTS, including a total of 1991 pregnancies, of which 323 developed TTTS. An increased risk of TTTS was associated with: intertwin NT discrepancy (positive likelihood ratio (LR+), 1.92 (95% CI, 1.25-2.96); negative likelihood ratio (LR-), 0.65 (95% CI, 0.50-0.84)); NT > 95th percentile (LR+, 2.63 (95% CI, 1.51-4.58); LR-, 0.85 (95% CI, 0.75-0.96)); CRL discrepancy > 10% (LR+, 1.80 (95% CI, 1.05-3.07); LR-, 0.92 (95% CI, 0.81-1.05)); abnormal DV flow (LR+, 4.77 (95% CI, 1.33-17.04; LR-, 0.49 (95% CI, 0.17-1.41)). The highest sensitivities were observed for intertwin NT discrepancy (52.8% (95% CI, 43.8-61.7%)) and abnormal DV flow (50.0% (95% CI, 33.4-66.6%)). CONCLUSION: Monochorionic twin pregnancies with intertwin NT discrepancy, NT > 95th percentile, intertwin CRL discrepancy > 10% or abnormal DV flow on first-trimester ultrasound examination are at significantly increased risk of developing TTTS. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Cervical length at mid-gestation in screening for preterm birth in twin pregnancy.

OBJECTIVE: Short cervical length (CL) in mid-gestation is considered predictive of spontaneous preterm birth (PTB). The medical literature suggests 20 mm as the cut-off for high risk in twin pregnancies. Our objective was to assess the predictive value of CL for spontaneous PTB < 32 weeks' gestation in twin pregnancies and to calculate the cut-off point with the best sensitivity and specificity. METHODS: This was a single-center retrospective cohort study of women in whom CL had been measured by transvaginal ultrasound at 18-23 weeks' gestation. Pregnancies complicated by twin-to-twin transfusion syndrome, those requiring intrauterine therapy or those with indicated PTB were excluded. The predictive value of CL for PTB < 32 weeks was assessed. The distribution of CL measurements and the optimal cut-off in patients with PTB were calculated and logistic regression analysis was performed to assess the association between pregnancy characteristics and PTB. RESULTS: A total of 940 twin pregnancies were included. CL showed an area under the receiver-operating characteristics curve of 0.65 (95% CI, 0.58-0.71) for the prediction of PTB < 32 weeks. The optimal cut-off value for predicting PTB was 36 mm (sensitivity, 64.1%; specificity, 62.8%; positive predictive value, 13.5%; negative predictive value, 95.1%; accuracy, 62.9%). The relative risk of PTB with CL ≤ 36 mm was 2.35 (95% CI, 1.53-3.60; P < 0.001). After adjusting for confounders in logistic regression analysis, only CL (adjusted odds ratio (aOR), 0.94 (95% CI, 0.90-0.99); P = 0.03), and not monochorionicity (aOR 4.14 (95% CI, 0.89-19.25); P = 0.07), was independently associated with PTB. More than one-third (36%) of PTB cases delivering < 32 weeks had a normal CL in mid-gestation. This proportion rose to 85% when considering the 20-mm cut-off suggested by the medical literature. CONCLUSIONS: This study shows that, despite the weak independent association, CL assessed in mid-gestation is a poor predictor of PTB < 32 weeks' gestation in asymptomatic twin pregnancies. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Intertwin discrepancy in middle cerebral artery peak systolic velocity and third-trimester fetal growth restriction in monochorionic-diamniotic twin pregnancy.

OBJECTIVES: To assess the role of intertwin discrepancy in middle cerebral artery peak systolic velocity (MCA-PSV) for the prediction of late selective intrauterine growth restriction (sIUGR) at birth and birth weight discrepancy of > 25% (BW-25) in otherwise uncomplicated monochorionic-diamniotic (MCDA) twin pregnancies. METHODS: This was a cohort study including all MCDA pregnancies followed in a tertiary fetal medicine unit between 2008 and 2013. Exclusion criteria were referral after first trimester, abnormal karyotype, structural anomalies, twin-to-twin transfusion syndrome, twin anemia-polycythemia sequence and sIUGR detected before 28 weeks. MCA-PSV values of both twins measured in the second trimester (18-24 weeks) and early third trimester (26-32 weeks) were converted in multiples of the median (MoM). sIUGR was defined as birth weight < 5(th) centile. The relationship between MCA-PSV discrepancy, sIUGR and BW-25 was assessed by logistic regression analysis. Receiver-operating characteristics (ROC) curves were used to ascertain the predictive value of MCA-PSV discrepancy for such complications. RESULTS: In total, 136 MCDA twin pregnancies were included in the analysis. Thirty (22.1%) were complicated with sIUGR at birth and 12 (8.8%) were complicated with BW-25. Logistic regression analysis identified MCA-PSV discrepancy as an independent predictor for sIUGR. ROC curves identified third-trimester MCA-PSV discrepancy as the best predictor for both sIUGR (area under ROC curve (AUC), 0.73 (95% CI, 0.62-0.85)) and BW-25 (AUC, 0.79 (95% CI, 0.65-0.93)). The optimal cut-off point for MCA-PSV discrepancy was 0.30 MoM (sensitivity, 70% and specificity, 69% for sIUGR; sensitivity, 83% and specificity, 72% for BW-25). CONCLUSION: In MCDA twin pregnancies, MCA-PSV discrepancy is associated with both sIUGR at birth and BW discordance. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Fetal cardiac parameters for prediction of twin-to-twin transfusion syndrome.

OBJECTIVES: To assess myocardial performance index measured by conventional Doppler (MPI) and by tissue Doppler imaging (MPI') at 18 weeks' gestation in monochorionic diamniotic twins for the prediction of twin-to-twin transfusion syndrome (TTTS). METHODS: This was a single-center observational study of 100 uncomplicated monochorionic diamniotic twin pregnancies attending the twin pregnancy clinic at the University Hospital Spedali Civili of Brescia from 2009 to 2012. MPI and MPI' were obtained from the left (LV) and right (RV) ventricles of each twin at around 18 weeks of gestation (range, 17 + 1 to 19 + 4 weeks) and fortnightly thereafter. Cases which later developed TTTS formed the study group, and the remaining controls were subdivided into those continuing as uncomplicated pregnancies and those which later developed selective intrauterine growth restriction (sIUGR). Data were analyzed by receiver-operating characteristics curve analysis and univariate and multivariable logistic regression. RESULTS: Of the 100 pregnancies, 88 were controls (84 uncomplicated and four developed sIUGR) and 12 developed TTTS. RV-MPI and LV-MPI, and LV-MPI' were significantly higher in future TTTS recipients than in controls, while RV-MPI' was significantly lower in donors. RV-MPI and LV-MPI and LV-MPI' were found to be predictive indicators in pregnancies that had not yet developed TTTS. Their negative predictive values were > 90%, and their specificities > 80%. The best performing index was LV-MPI', with a sensitivity of 91.7% and specificity of 88.6%. CONCLUSIONS: Before diagnosis of TTTS, the cardiac function (as assessed by MPI and MPI') of the future donor twin is not grossly abnormal, but that of the recipient is abnormal. We identified cardiac indices predictive of the subsequent development of TTTS, and suggest a possible role of these indices in planning the follow-up of monochorionic diamniotic twin pregnancies.

Poor glycaemic control and ectopic fat deposition mediates the increased risk of non-alcoholic steatohepatitis in high-risk populations with type 2 diabetes: Insights from Bayesian-network modelling.

Background: An estimated 55.5% and 37.3% of people globally with type 2 diabetes (T2D) will have concomitant non-alcoholic fatty liver disease (NAFLD) and the more severe fibroinflammatory stage, non-alcoholic steatohepatitis (NASH). NAFLD and NASH prevalence is projected to increase exponentially over the next 20 years. Bayesian Networks (BNs) offer a powerful tool for modelling uncertainty and visualising complex systems to provide important mechanistic insight. Methods: We applied BN modelling and probabilistic reasoning to explore the probability of NASH in two extensively phenotyped clinical cohorts: 1) 211 participants with T2D pooled from the MODIFY study & UK Biobank (UKBB) online resource; and 2) 135 participants without T2D from the UKBB. MRI-derived measures of visceral (VAT), subcutaneous (SAT), skeletal muscle (SMI), liver fat (MRI-PDFF), liver fibroinflammatory change (liver cT1) and pancreatic fat (MRI-PDFF) were combined with plasma biomarkers for network construction. NASH was defined according to liver PDFF >5.6% and liver cT1 >800ms. Conditional probability queries were performed to estimate the probability of NASH after fixing the value of specific network variables. Results: In the T2D cohort we observed a stepwise increase in the probability of NASH with each obesity classification (normal weight: 13%, overweight: 23%, obese: 36%, severe obesity: 62%). In the T2D and non-T2D cohorts, elevated (vs. normal) VAT conferred a 20% and 1% increase in the probability of NASH, respectively, while elevated SAT caused a 7% increase in NASH risk within the T2D cohort only. In those with T2D, reducing HbA1c from the 'high' to 'low' value reduced the probability of NASH by 22%. Conclusion: Using BNs and probabilistic reasoning to study the probability of NASH, we highlighted the relative contribution of obesity, ectopic fat (VAT and liver) and glycaemic status to increased NASH risk, namely in people with T2D. Such modelling can provide insights into the efficacy and magnitude of public health and pharmacological interventions to reduce the societal burden of NASH.

Current laparoscopic management of inflammatory bowel disease.

Since the introduction of laparoscopic surgery in the management of colorectal disease in the early '90s, minimally invasive techniques have gained popularity. While good quality studies have been published in the literature on laparoscopy for colorectal cancer, evidence supporting the use of minimally invasive surgery for inflammatory bowel disease is lacking. This patient population represents a challenge to the colorectal surgeon even in conventional open surgery and this has limited the widespread application of minimally invasive techniques especially in Crohn's disease. Laparoscopic ileocecal resection for Crohn's disease is the most performed minimally invasive procedure in the field of inflammatory bowel disease, with promising short-term outcomes but with still some concerns related to prolonged operative times and overall costs. For ulcerative colitis the magnitude of restorative procedures has also restricted the use of minimally invasive approaches to highly specialized tertiary referral centers. The benefits of performing restorative procedures laparoscopically for ulcerative colitis are less obvious based on the limited reports available in the literature with adequate follow-up for assessing long-term outcomes, and controversies still remains about the need for a staged approach in the era of biologic therapy. Nevertheless, surgeons are actively working in an effort to obviate to the current technical limitations of laparoscopy, and to further minimize surgical trauma. In this manuscript we will present the current evidence supporting the use of laparoscopy and minimally invasive techniques in inflammatory bowel disease and present the future direction of development and research.

Disparities in Emergent Colectomy for Colorectal Cancer Contribute to Inequalities in Postoperative Morbidity and Mortality in The US Health Care System.

BACKGROUND AND AIMS: Colorectal cancer is the third most common cancer among both men and women in the United States. We aimed to determine racial and socioeconomic disparities in emergent colectomy rates for colorectal cancer in the US Health Care system. MATERIAL AND METHODS: We performed a retrospective analysis of the National Inpatient Sample including adult patients (⩾18 years) diagnosed with colorectal cancer, and who underwent colorectal resection while admitted between 2008 and 2015. Multivariable logistic and linear regression were used to assess the association between emergent admissions, compared to elective admissions, and postoperative outcomes. RESULTS: A total of 141,641 hospitalizations were included: 93,775 (66%) were elective admissions and 47,866 (34%) were emergent admissions. Black patients were more likely to undergo emergent colectomy, compared to white patients (42% vs 32%, p < 0.0001). Medicaid and Medicare patients were also more likely to have an emergent colectomy, compared to private insurance (47% and 36% vs 25%, respectively, p < 0.0001), as were patients with low household income, compared to highest (38% vs 31%, p < 0.0001). Emergent procedures were less likely to be laparoscopic (19% vs 38%, p < 0.0001). Patients undergoing emergent colectomy were significantly more likely to have postoperative venous thromboembolism, wound complications, infection, bleeding, cardiac failure, renal failure, respiratory failure, shock, and inpatient mortality. CONCLUSION: There are significant racial and socioeconomic disparities in emergent colectomy rates for colorectal cancer. Efforts to reduce this disparity in colorectal cancer surgery patients should be prioritized to improve outcomes.