Opioid Use Disorder is Associated With Complications and Increased Length of Stay After Major Abdominal Surgery.

OBJECTIVE: The objective of this study was to determine the impact of opioid use disorder (OUD) on perioperative outcomes after major upper abdominal surgeries. SUMMARY OF BACKGROUND DATA: OUD, defined as dependence/abuse, is a national health epidemic. Its impact on outcomes after major abdominal surgery has not been well characterized. METHODS: Patients who underwent elective esophagectomy, total/partial gastrectomy, major hepatectomy, and pancreatectomy were identified using the National Inpatient Sample (2003-2015). Propensity score matching by baseline characteristics was performed for patients with and without OUD. Outcomes measured were in-hospital complications, mortality, length of stay (LOS), and discharge disposition. RESULTS: Of 376,467 patients, 1096 (0.3%) had OUD. Patients with OUD were younger (mean 53 vs 61 years, P < 0.001) and more often male (55.1% vs 53.2%, P < 0.001), black (15.0% vs 7.6%, P < 0.001), Medicaid beneficiaries (22.0% vs 6.4%, P < 0.001), and in the lowest income quartile (32.6% vs 21.3%, P < 0.001). They also had a higher rate of alcohol (17.2% vs 2.8%, P < 0.001) and nonopioid drug (2.2% vs 0.2%, P = 0.023) dependence/abuse. After matching (N = 1077 OUD, N = 2164 no OUD), OUD was associated with a higher complication rate (52.9% vs 37.3%, P < 0.001), including increased pain [odds ratio (OR) 3.5, P < 0.001], delirium (OR 3.0, P = 0.004), and pulmonary complications (OR 2.0, P = 0.006). Additionally, OUD was associated with increased LOS (mean 12.4 vs 10.6 days, P = 0.015) and nonroutine discharge (OR 1.6, P < 0.001). In-hospital mortality did not differ (OR 2.4, P = 0.10). CONCLUSION: Patients with OUD more frequently experienced complications and increased LOS. Close postoperative monitoring may mitigate adverse outcomes.

Patterns of Metastasis in Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a propensity for regional and distant spread. Because of the relative infrequency of this disease, the patterns of metastasis in MCC are understudied. METHODS: Patients with American Joint Committee on Cancer (8th edition) stage I-IV MCC treated at our institution were identified (1/1/2008-2/28/2018). The first site of metastasis was classified as regional [regional lymph node (LN) basin, in-transit] or distant. Distant metastasis-free (DMFS) and MCC-specific (MSS) survival were estimated. RESULTS: Of 133 patients, 64 (48%) had stage I, 13 (10%) stage II, 48 (36%) stage III, and 8 (6%) stage IV disease at presentation. The median follow-up time in patients who remained alive was 36 (interquartile range 20-66) months. Regional or distant metastases developed in 78 (59%) patients. The first site was regional in 87%, including 73% with isolated LN involvement, and distant in 13%. Thirty-seven (28%) patients eventually developed distant disease, which most commonly involved the abdominal viscera (51%) and distant LNs (46%) first. The lung (0%) and brain (3%) were rarely the first distant sites. Stage III MCC at presentation was significantly associated with worse DMFS (hazard ratio 4.87, P = 0.001) and stage IV disease with worse MSS (hazard ratio 6.30, P = 0.002). CONCLUSIONS: Regional LN metastasis is the most common first metastatic event in MCC, confirming the importance of nodal evaluation. Distant disease spread appears to have a predilection for certain sites. Understanding these patterns could help to guide surveillance strategies.

Gastric Neuroendocrine Tumors: Reappraisal of Type in Predicting Outcome.

BACKGROUND: Type I gastric neuroendocrine tumors (GNETs) are typically managed either expectantly or endoscopically. In contrast, locoregional surgery has been recommended for patients with type III GNETs because of the risk of metastasis. This study aimed to identify predictors of outcome independent of type in a contemporary cohort of GNET patients. METHODS: A single-institution retrospective cohort study of 121 patients with a pathologic diagnosis of primary GNET between January 2009 and June 2019 was performed. GNETs were designated as type 1 (n = 74) if atrophic gastritis was present, or as type III (n = 47) in the absence of atrophic gastritis. Demographic, clinical, and histopathologic factors were examined using Kaplan-Meier and multivariable Cox regression to assess the impact of various factors on recurrence and overall survival. RESULTS: Median follow-up for the entire cohort was 62.7 months. While there was no difference in OS in patients with different GNET types (p = 0.10), higher tumor grade (p = 0.02) and presence of nodal or distant metastases (p = 0.02) predicted worse survival on multivariable analysis. Among type III GNET patients, those with small (< 0.5 cm), grade 1 lesions ("low-risk") were less likely to develop metastases (0% versus 33%, p < 0.01) and more likely to survive (100% versus 67%, p < 0.01) at 5 years. CONCLUSIONS: Size and tumor grade predict recurrence and survival in patients with GNETs irrespective of type. Small, low-grade type III GNETs are associated with minimal risk of progression and may be managed accordingly.

Long-lasting attenuation of amygdala-kindled seizures after convection-enhanced delivery of botulinum neurotoxins a and B into the amygdala in rats.

Botulinum neurotoxins (BoNTs) are well recognized to cause potent, selective, and long-lasting neuroparalytic actions by blocking cholinergic neurotransmission to muscles and glands. There is evidence that BoNT isoforms can also inhibit neurotransmission in the brain. In this study, we examined whether locally delivered BoNT/A and BoNT/B can attenuate kindling measures in amygdala-kindled rats. Male rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully kindled animals received a single infusion of vehicle or BoNT/A or BoNT/B at doses of 1, 3.2, or 10 ng over a 20-minute period by convection-enhanced delivery. Electrographic (EEG) and behavioral kindling measures were determined at selected times during the 3- to 64-day period after the infusion. BoNT/B produced a dose-dependent elevation in after-discharge threshold and duration and a reduction in the seizure stage and duration of behavioral seizures that lasted for up to 50 days after infusion. BoNT/A had similar effects on EEG measures; behavioral seizure measures were also reduced, but the effect did not reach statistical significance. The effects of both toxins on EEG and behavioral measures progressively resolved during the latter half of the observation period. Animals gained weight normally, maintained normal body temperature, and did not show altered behavior. This study demonstrates for the first time that locally delivered BoNTs can produce prolonged inhibition of brain excitability, indicating that they could be useful for the treatment of brain disorders, including epilepsy, that would benefit from long-lasting suppression of neurotransmission within a circumscribed brain region.

Optical coherence tomography guided neurosurgical procedures in small rodents.

The delivery of therapeutic agents directly to targets deep within the brain is becoming an important tool in the treatment of a variety of neurological disorders. Currently, the standard method to accomplish this is by using stereotactic procedures. While this existing method is adequate for many experimental situations, it is essentially a blind procedure that cannot provide real-time feedback on whether the actual location deviated from the intended location or whether the therapeutic agent was actually delivered. Here we describe an optical guidance technique that is designed to work in conjunction with existing stereotactic procedures to provide the needed real-time feedback for therapeutic delivery in live animals. This real-time feedback is enabled by a technology called catheter-based optical coherence tomography (OCT). In this study we show that OCT can provide real-time position feedback based on microanatomic landmarks from the live rodent brain. We show that OCT can provide the necessary guidance to perform microsurgery such as the selective transection of the Schaffer collateral inputs to the CA1 region of the hippocampus with minimal perturbation of overlying structures. We also show that OCT allows visual monitoring of the successful delivery of viral vectors to specific subregions of the hippocampus.

Trends in practice patterns and outcomes: A decade of sarcoma care in the United States.

BACKGROUND: Soft tissue sarcomas (STS) represent a rare and heterogeneous group of tumors. We sought to characterize national trends in referral patterns, treatment strategies, and overall survival (OS) over the course of a decade. METHODS: Adult patients with extra-abdominal STS were identified using the National Cancer Database and categorized by diagnosis year (2005-2009 and 2010-2014). High-volume hospitals (HVH) were defined as those >90th percentile in volume of STS patients treated, and others were defined as low-volume hospitals (LVH). Standard statistical methods were used to compare treatment strategies and OS by diagnosis period. RESULTS: Of 55,212 patients, 25,469 (46.1%) were diagnosed in 2005-2009 and 29,743 (53.9%) in 2010-2014. Despite increased utilization of neoadjuvant radiation therapy (26.6% vs. 34.8%, P < 0.001), the rate of R0 resections did not change (75.0% vs. 74.8%, P = 0.067). Furthermore, at a national level, OS did not improve over time (HR 0.99, 95% CI 0.96-1.01). When outcomes were stratified by volume, treatment at HVH compared to LVH was associated with improved rates of R0 resection (OR 1.27, 95% CI 1.20-1.35) and OS (HR 0.92, 95% CI 0.89-0.95). Moreover, there was a modest improvement in OS at HVH (HR 0.95, 95% CI 0.91-1.00), but not at LVH (HR 1.01, 95% CI 0.97-1.04). However, referral to HVH did not change over time (40.7% vs. 40.7%, P = 0.91). CONCLUSION: OS for STS did not change at a national level over the course of a decade, although it improved at HVH. Further outcome improvements will likely require more effective systemic therapies.

Rapid aneuploidy testing (knowing less) versus traditional karyotyping (knowing more) for advanced maternal age: what would be missed, who should decide?

OBJECTIVES: The application of rapid aneuploidy testing as a stand-alone approach in prenatal diagnosis is much debated. The major criticism of this targeted approach is that it will not detect other chromosomal abnormalities that will be picked up by traditional karyotyping. This study aimed to study the nature of such chromosomal abnormalities and whether parents would choose to terminate affected pregnancies. DESIGN: Retrospective study on a cytogenetic database. SETTING: Eight public hospitals in Hong Kong. PARTICIPANTS: The karyotype results of 19 517 amniotic fluid cultures performed for advanced maternal age (>or=35 years) from 1997 to 2002 were classified according to whether they were detectable by rapid aneuploidy testing. The outcomes of pregnancies with abnormal karyotypes were reviewed from patient records. RESULTS: In all, 333 (1.7%) amniotic fluid cultures yielded abnormal karyotypes; 175 (52.6%) of these were detected by rapid aneuploidy testing, and included trisomy 21 (n=94, 28.2%), trisomy 18 or 13 (n=21, 6.3%), and sex chromosome abnormalities (n=60, 18.0%). The other 158 (47.4%) chromosomal abnormalities were not detectable by rapid aneuploidy testing, of which 63 (18.9%) were regarded to be of potential clinical significance and 95 (28.5%) of no clinical significance. Pregnancy outcomes in 327/333 (98.2%) of these patients were retrieved. In total, 143 (42.9%) of these pregnancies were terminated: 93/94 (98.9%) for trisomy 21, 20/21 (95.2%) for trisomy 18 or 13, 19/60 (31.7%) for sex chromosome abnormalities, and 11/63 (17.5%) for other chromosomal abnormalities with potential clinical significance. There were no terminations in the 95 pregnancies in which karyotyping results were regarded to be of no clinical significance. CONCLUSIONS: 'Knowing less' by the rapid aneuploidy stand-alone testing could miss about half of all chromosomal abnormalities detectable by amniocentesis performed for advanced maternal age. Findings from two fifths of the latter were of potential clinical significance, and the parents chose to terminate one out of six of the corresponding pregnancies. If both techniques are available, parents could have enhanced autonomy to choose.

Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to Chemotherapy.

Bone metastasis is a major health threat to breast cancer patients. Tumor-derived Jagged1 represents a central node in mediating tumor-stromal interactions that promote osteolytic bone metastasis. Here, we report the development of a highly effective fully human monoclonal antibody against Jagged1 (clone 15D11). In addition to its inhibitory effect on bone metastasis of Jagged1-expressing tumor cells, 15D11 dramatically sensitizes bone metastasis to chemotherapy, which induces Jagged1 expression in osteoblasts to provide a survival niche for cancer cells. We further confirm the bone metastasis-promoting function of osteoblast-derived Jagged1 using osteoblast-specific Jagged1 transgenic mouse model. These findings establish 15D11 as a potential therapeutic agent for the prevention or treatment of bone metastasis.

Optical coherence tomography in the diagnosis and treatment of neurological disorders.

Optical contrast is often the limiting factor in the imaging of live biological tissue. Studies were conducted in postmortem human brain to identify clinical applications where the structures of interest possess high intrinsic optical contrast and where the real-time, high-resolution imaging capabilities of optical coherence tomography (OCT) may be critical. Myelinated fiber tracts and blood vessels are two structures with high optical contrast. The ability to image these two structures in real time may improve the efficacy and safety of a neurosurgical procedure to treat Parkinson's disease called deep brain stimulation (DBS). OCT was evaluated as a potential optical guidance system for DBS in 25 human brains. The results suggest that catheter-based OCT has the resolution and contrast necessary for DBS targeting. The results also demonstrate the ability of OCT to detect blood vessels with high sensitivity, suggesting a possible means to avoid their laceration during DBS. Other microscopic structures in the human brain with high optical contrast are pathological vacuoles associated with transmissible spongiform encephalopathy (TSE). TSE include diseases such as Mad Cow disease and Creutzfeldt-Jakob disease (CJD) in humans. OCT performed on the brain from a woman who died of CJD was able to detect clearly the pathological vacuoles.

Cystic hygroma detected in the first trimester scan in Hong Kong.

OBJECTIVE: To investigate the outcome of fetuses with cystic hygroma (CH) diagnosed at the first trimester from a general population in Hong Kong. METHOD: This was a prospective study of 30 fetal cystic hygroma detected at 11 to 13 + 6 weeks' gestation in 8835 sequential unselected pregnancies. Fetal cystic hygroma was categorized as isolated cystic hygroma (ICH) or associated cystic hygroma (ACH) according to the presence of associated multiple congenital structural abnormalities (MCA). RESULTS: There were 10 cases of ICH and 20 cases of ACH. The karyotypes were obtained in 29 cases. In the ICH, 30% (3/10) were associated with chromosomal abnormalities. In the ACH, 65% (13/20) were associated with major chromosomal abnormalities. CONCLUSION: This study suggests that the prognosis of cystic hygroma detected in the first trimester is guarded, with high incidence of MCA (66.7%, 20/30) and chromosomal abnormalities (53.3%, 16/30). The findings support detailed ultrasound examination and invasive prenatal diagnosis for cystic hygroma.

Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study.

OBJECTIVES: To validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling. DESIGN: Diagnostic accuracy validated against full karyotyping, using prospectively collected or archived maternal plasma samples. SETTING: Prenatal diagnostic units in Hong Kong, United Kingdom, and the Netherlands. PARTICIPANTS: 753 pregnant women at high risk for fetal trisomy 21 who underwent definitive diagnosis by full karyotyping, of whom 86 had a fetus with trisomy 21. Intervention Multiplexed massively parallel sequencing of DNA molecules in maternal plasma according to two protocols with different levels of sample throughput: 2-plex and 8-plex sequencing. MAIN OUTCOME MEASURES: Proportion of DNA molecules that originated from chromosome 21. A trisomy 21 fetus was diagnosed when the z score for the proportion of chromosome 21 DNA molecules was >3. Diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were calculated for trisomy 21 detection. RESULTS: Results were available from 753 pregnancies with the 8-plex sequencing protocol and from 314 pregnancies with the 2-plex protocol. The performance of the 2-plex protocol was superior to that of the 8-plex protocol. With the 2-plex protocol, trisomy 21 fetuses were detected at 100% sensitivity and 97.9% specificity, which resulted in a positive predictive value of 96.6% and negative predictive value of 100%. The 8-plex protocol detected 79.1% of the trisomy 21 fetuses and 98.9% specificity, giving a positive predictive value of 91.9% and negative predictive value of 96.9%. CONCLUSION: Multiplexed maternal plasma DNA sequencing analysis could be used to rule out fetal trisomy 21 among high risk pregnancies. If referrals for amniocentesis or chorionic villus sampling were based on the sequencing test results, about 98% of the invasive diagnostic procedures could be avoided.

Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing.

Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due to the lack of data from a large sample set. We studied 392 pregnancies, among which 25 involved a trisomy 13 fetus and 37 involved a trisomy 18 fetus, by massively parallel sequencing. By using our previously reported standard z-score approach, we demonstrated that this approach could identify 36.0% and 73.0% of trisomy 13 and 18 at specificities of 92.4% and 97.2%, respectively. We aimed to improve the detection of trisomy 13 and 18 by using a non-repeat-masked reference human genome instead of a repeat-masked one to increase the number of aligned sequence reads for each sample. We then applied a bioinformatics approach to correct GC content bias in the sequencing data. With these measures, we detected all (25 out of 25) trisomy 13 fetuses at a specificity of 98.9% (261 out of 264 non-trisomy 13 cases), and 91.9% (34 out of 37) of the trisomy 18 fetuses at 98.0% specificity (247 out of 252 non-trisomy 18 cases). These data indicate that with appropriate bioinformatics analysis, noninvasive prenatal diagnosis of trisomy 13 and trisomy 18 by maternal plasma DNA sequencing is achievable.

Feasibility and efficacy of a church-based intervention to promote physical activity in children.

BACKGROUND: This study evaluated the feasibility and preliminary efficacy of a church-based intervention to promote physical activity (PA) in children. METHODS: The study was conducted in 4 churches located in 2 large metropolitan areas and 2 regional towns in Kansas. Churches in the intervention condition implemented the "Shining Like Stars" physical activity curriculum module during their regularly scheduled Sunday school classes. Churches in the control condition delivered the same content without integrating physical activity into the lessons. In addition to the curriculum, the intervention churches completed a series of weekly family devotional activities designed to promote parental support for PA and increase PA outside of Sunday school. RESULTS: Children completing the Shining Like Stars curriculum exhibited significantly greater amounts of MVPA than those in the control condition (20 steps/min vs. 7 steps/min). No intervention effects were observed for PA levels outside of Sunday school or parental support for PA; however, relative to controls, children in the intervention churches did exhibit a significant reduction in screen time. CONCLUSION: The findings confirm that the integration of physical activity into Sunday school is feasible and a potentially effective strategy for promoting PA in young children.

The anticonvulsant activity of acetone, the major ketone body in the ketogenic diet, is not dependent on its metabolites acetol, 1,2-propanediol, methylglyoxal, or pyruvic acid.

BACKGROUND: Acetone, one of the principal ketone bodies elevated during treatment with the ketogenic diet, exhibits anticonvulsant properties that may contribute to the seizure protection conferred by the diet. The anticonvulsant mechanism of acetone is unknown, but it is metabolized to several bioactive substances that could play a role. METHODS: Acetone and its major metabolites-acetol, 1,2-propanediol, methylglyoxal, and pyruvic acid-were assessed for anticonvulsant activity in two mouse seizure models. Various doses of the substances administered intraperitoneally were characterized for their ability to elevate the threshold for clonic seizures induced by intravenous infusion of pentylenetetrazol (PTZ) and for protection against tonic seizures induced by subcutaneous bolus administration of 4-aminopyridine (4-AP). The inverted-screen test was used to assess acute neurological toxicity. RESULTS: Acetone (1-32 mmol/kg, i.p.), in a dose-dependent fashion, elevated the PTZ threshold and conferred protection against 4-AP seizures (ED(50), 26.3 mmol/kg). Effective doses of acetone (10-32 mmol/kg) did not cause motor impairment in the inverted-screen test (TD(50), 45.7 mmol/kg). In doses 10-fold greater than the minimally effective dose of acetone (3.2 mmol/kg), the metabolites acetol, 1,2-propanediol, and pyruvic acid were inactive in the PTZ model. At higher doses that produced motor impairment, acetol and 1,2-propanediol (but not pyruvic acid) did elevate the PTZ threshold. Methylglyoxal had both proconvulsant and anticonvulsant actions, and had substantial toxicity, producing respiratory distress, motor impairment, and death. None of the acetone metabolites protected against 4-AP seizures. CONCLUSIONS: This study confirms the broad-spectrum anticonvulsant properties of acetone and indicates that the seizure protection conferred is unlikely to result from its major metabolic products.

First-trimester examination of fetal nasal bone in the Chinese population.

OBJECTIVES: Absence of the nasal bone in fetuses with trisomy 21 is a potential ultrasound marker for Down syndrome from the first trimester onwards. Racial differences in fetal nasal bone length have been reported. There was no reference range for the first-trimester fetal nasal bone length (NBL) in the Chinese population. METHODS: From January 2002 to February 2005, we investigated the reference range of NBL in 2169 singleton fetuses whose parents were Chinese with normal pregnancy outcome. Ultrasound measurements of NBL were performed on a midsagittal plane at 12-14 weeks' gestation. RESULTS: The nasal bone length measurement showed a significant increase with gestational age (GA) (p < 0.05). A linear relationship between nasal bone length and gestational age (NBL = -3.3462 x GA + 0.627, R(2) = 0.30, p < 0.001) as well as a linear relationship between nasal bone length and crown-rump length (CRL) (NBL = 0.3741 x CRL + 0.284, R(2) = 0.30, P < 0.001) was established. CONCLUSION: The measurement of nasal bone length was feasible in the first trimester. The reference range of NBL in normal Chinese fetuses in the first-trimester of pregnancy was established. This formed a basis for further study on the use of fetal nasal bone measurement in the screening for aneuploidy in the Chinese population.

The effect of ethnic origin on nuchal translucency at 10-14 weeks of gestation.

INTRODUCTION: Fetal nuchal translucency (NT) increases with gestation and is affected by fetal posture and fetal gender. A recent report suggested that there might also be ethnic differences. We investigated the effect of ethnic origin on NT in an Asian population. METHODS: NT was measured at 10-14 weeks. The measurements were converted into multiples of the median (MoM) for gestational day. The risk of Down syndrome was calculated by combining NT and maternal age. Cases affected by chromosomal and major structural abnormalities were excluded. NT measurements of different ethnic groups were compared. RESULTS: Between January 1997 and October 2001, 16 981 pregnancies with known ethnic origin and normal fetal outcome were analysed. Median NT MoM (95% CI) of the Filipinos was 1.07 (1.04-1.11). This was significantly higher than that of the Chinese, 1.01 (1.01-1.02); other Asians (Indians, Pakistanis and Nepalese), 0.96 (0.94-0.99), and Caucasians, 0.98 (0.93-1.06) (p<0.05, respectively; Mann-Whitney U-test). An NT risk cut-off of 1:180 would classify 5% of the Chinese, 4.6% of the Caucasians, 5.6% of the Filipinos and 4.2% of the other Asians as screen-positive. There were no statistically significant differences between these screen-positive rates (p>0.05, Chi-square test). CONCLUSIONS: Although there were statistically significant differences in NT measurements between different ethnic groups, it was clinically insignificant, as reflected by similar screen-positive rates.

Comparison and integration of first trimester fetal nuchal translucency and second trimester maternal serum screening for fetal Down syndrome.

BACKGROUND: It is uncertain whether first trimester nuchal translucency (NT) is more effective than the well-established second trimester serum screening for fetal Down syndrome or whether their combination works best. We report data from a large multicentre non-interventional trial in which all subjects underwent both first and second trimester screening. METHODS: All women who attended the obstetric clinic before 15 weeks' gestation were recruited. An ultrasound examination was performed at 10 to 14 weeks to measure the NT. The nuchal measurements were not acted upon unless the fetus showed gross features of hydrops fetalis. All women had serum alpha-fetoprotein (AFP) and human chorionic gonadotrophin (hCG) assay at 15 to 20 weeks. The Down syndrome risk assigned by serum screening was disclosed and amniocentesis was offered if this assigned risk was >or=1:250 or if the women were 35 years and older. The efficacy of different combinations of screening markers was compared. RESULTS: Between January 1997 and August 2000, 17 590 women were recruited (19% >or=35 years old). After excluding subjects who miscarried, defaulted the serum test and other reasons, 16 237 pregnancies were analysed. Of these, 35 pregnancies were affected by Down syndrome (2.2 cases per 1000 pregnancies). At a false-positive rate of 5%, the detection rate of Down syndrome by NT alone, NT and age, serum hCG, AFP and age, and NT, hCG, AFP and age were 61%, 69%, 73% and 86%, respectively. CONCLUSION: Integration of NT and second trimester serum AFP and hCG assay yielded the best screening efficacy for Down syndrome.