Optic nerve sheath diameter in severe preeclampsia with neurologic features versus controls.

BACKGROUND: Optic nerve sheath diameters (ONSD) have been validated as an accurate screening tool to detect elevated intracranial pressure in hypertensive encephalopathy. The neurologic manifestations of preeclampsia and/or eclampsia mimic those of hypertensive encephalopathy. This study was performed to assess the incidence of elevated optic nerve sheath diameters of patients with severe preeclampsia and neurologic criteria compared to non-preeclamptic patients. The secondary objective was to determine baseline optic nerve sheath diameters in patients with severe preeclampsia without neurologic criteria and preeclampsia without severe features. METHODS: Single site cohort study including 62 pregnant women 18 years or older and 20 weeks or further gestation. Patients with preeclampsia without severe features, preeclampsia with severe features by non-neurologic criteria, preeclampsia with severe features with neurologic criteria, and patients without preeclampsia were enrolled via convenience sampling. One blinded reviewer measured sheath diameters; baseline demographics and pregnancy data were collected by chart review. Statistical analysis was completed with STATA/IC 16. Categorical variables were compared by the χ2 test. Continuous variables were presented as mean ± standard deviation, and discrete variables were presented as medians and compared by Kruskal-Wallis testing. Normality was confirmed by Shapiro-Wilk testing. Linear and logistic regression were used to test the association between the preeclampsia groups and optic nerve sheath diameters. Models were presented as unadjusted and adjusted for BMI, gestation, hypertension, diabetes, parity, and gravidity. RESULTS: The incidence of optic nerve sheath diameters > 5.8 mm was 43.8% in the severe preeclampsia with neurologic features cohort, and 42.1% in the control cohort, with a relative risk of 1.04. Patients with severe preeclampsia without neurologic features had sheath diameters of 5.75 mm ± 1.09 mm; non-severe preeclampsia patients had sheath diameters of 5.54 mm ± 1.26 mm. CONCLUSIONS: We did not find a significant elevated optic nerve sheath diameter relative risk between severe preeclampsia patients with neurologic features and non-preeclampsia control patients. This is the first study to assess a North American population utilizing ACOG criteria for severe and non-severe preeclampsia, with severe cohorts additionally stratified by neurologic criteria.

Fetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis.

OBJECTIVE: To evaluate the clinical safety of antenatal and postnatal N-acetylcysteine (NAC) as a neuroprotective agent in maternal chorioamnionitis in a randomized, controlled, double-blinded trial. STUDY DESIGN: Twenty-two mothers >24 weeks gestation presenting within 4 hours of diagnosis of clinical chorioamnionitis were randomized with their 24 infants to NAC or saline treatment. Antenatal NAC (100 mg/kg/dose) or saline was given intravenously every 6 hours until delivery. Postnatally, NAC (12.5-25 mg/kg/dose, n = 12) or saline (n = 12) was given every 12 hours for 5 doses. Doppler studies of fetal umbilical and fetal and infant cerebral blood flow, cranial ultrasounds, echocardiograms, cerebral oxygenation, electroencephalograms, and serum cytokines were evaluated before and after treatment, and 12, 24, and 48 hours after birth. Magnetic resonance spectroscopy and diffusion imaging were performed at term age equivalent. Development was followed for cerebral palsy or autism to 4 years of age. RESULTS: Cardiovascular measures, cerebral blood flow velocity and vascular resistance, and cerebral oxygenation did not differ between treatment groups. Cerebrovascular coupling was disrupted in infants with chorioamnionitis treated with saline but preserved in infants treated with NAC, suggesting improved vascular regulation in the presence of neuroinflammation. Infants treated with NAC had higher serum anti-inflammatory interleukin-1 receptor antagonist and lower proinflammatory vascular endothelial growth factor over time vs controls. No adverse events related to NAC administration were noted. CONCLUSIONS: In this cohort of newborns exposed to chorioamnionitis, antenatal and postnatal NAC was safe, preserved cerebrovascular regulation, and increased an anti-inflammatory neuroprotective protein. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00724594.

Diagnostic accuracy of fundal height and handheld ultrasound-measured abdominal circumference to screen for fetal growth abnormalities.

OBJECTIVE: We sought to compare fundal height and handheld ultrasound-measured fetal abdominal circumference (HHAC) for the prediction of fetal growth restriction (FGR) or large for gestational age. STUDY DESIGN: This was a diagnostic accuracy study in nonanomalous singleton pregnancies between 24 and 40 weeks' gestation. Patients underwent HHAC and fundal height measurement prior to formal growth ultrasound. FGR was defined as estimated fetal weight less than 10%, whereas large for gestational age was defined as estimated fetal weight greater than 90%. Sensitivity and specificity were calculated and compared using methods described elsewhere. RESULTS: There were 251 patients included in this study. HHAC had superior sensitivity and specificity for the detection of FGR (sensitivity, 100% vs 42.86%) and (specificity, 92.62% vs 85.24%). HHAC had higher specificity but lower sensitivity when screening for LGA (specificity, 85.66% vs 66.39%) and (sensitivity, 57.14% vs 71.43%). CONCLUSION: HHAC could prove to be a valuable screening tool in the detection of FGR. Further studies are needed in a larger population.

Impact of dosing schedule on uptake of neuroprotective magnesium sulfate.

Background: Preterm delivery <32-week gestation is associated with significant neurodevelopmental morbidity ranging from mild delay to profound disability. Several randomized trials have shown that magnesium sulfate (MgSO4) is an effective neuroprotectant, demonstrating reduced rates of cerebral palsy, death, and gross motor dysfunction for the neonate or infant. Dosing was not consistent among the major trials and the onus was placed on institutions by ACOG to develop and implement protocols with respect to MgSO4 as a neuroprotectant. A recent study demonstrated that MgSO4 exposure <12 h prior to delivery was associated with a decrease in CP compared to more remote exposure.Objective: To assess impact of dosing schedule on uptake of neuroprotective MgSO4 in patients delivering <32 weeks gestational age.Study design: A retrospective cohort study of all deliveries occurring <32 weeks' gestation at a single academic center between March-December 2014 and March-December 2015 was conducted. Institutional policy shifted in 2015 from MgSO4 bolus with continuous infusion based on the BEAM trial to a single bolus dose based on the PREMAG trial. Patients with preeclampsia, known fetal anomalies, and/or stillbirth were excluded from this analysis. Patients were identified through query of the Medical University of South Carolina Perinatal Information System (PINS) database with respect to whether or not they had received MgSO4 within 12 h of delivery. Chi-squared analysis was performed to compare the overall rate of MgSO4 exposure and MgSO4 exposure <12 h prior to delivery between groups. Fisher's exact test was used to evaluate maternal, obstetric, and neonatal variables among those receiving MgSO4 within 12 h of delivery in each cohort. Binary logistic regression analysis was performed to control for co-linear or potential confounding variables.Results: A total of 224 patients were identified, 115 delivered between March-December 2014 and 109 delivered between March-December 2015. With respect to MgSO4 exposure prior to delivery, 27 (23.5%) received MgSO4 in the 2014 cohort compared to 44 (40.4%) in the 2015 cohort (OR: 2.2, p < .01). Of those being exposed within 12 h of delivery, there were 16 (13.9%) maternal exposures in the 2014 cohort versus 28 (26.7%) in the 2015 cohort (OR: 2.15, p = .02). Of the 18 neonates delivered in 2014 there were four cases of grade III or IV intraventricular hemorrhage versus one case among the 36 neonates (2.7%) born in 2015 (0.04). This finding holds after controlling for race, preterm labor, gestational age, corticosteroid, birthweight, and indomethacin exposure.Conclusions: Dosing of neuroprotective MgSO4 according to PREMAG trial specifications was associated with a significantly greater percentage of patients having received neuroprotective magnesium at any point prior to delivery or within the 12 h prior to delivery when compared to dosing according to BEAM trial specifications.

D-transposition of the great arteries with right-sided pulmonary hypoplasia.

Unilateral pulmonary agenesis or aplasia (UPA) in combination with congenital heart defects is rare and has not been reported in connection with transposition of the great arteries. This case demonstrated dextroposition of the fetal heart, and subsequent scans could not clearly visualize the right pulmonary artery. UPA should be considered in the workup and counseling for a family in the setting of fetal heart malposition, as there is a significant clinical impact.

Effect of Antibiotic Treatment of Amniotic Fluid Sludge.

BACKGROUND: Amniotic fluid sludge refers to the sonographic presence of echogenic, free-floating aggregates of debris located within the amniotic cavity near the internal cervical os of women with intact membranes. Clinically, it is independently associated with increased obstetric, infectious, and neonatal morbidity, including: short cervix, chorioamnionitis, and an increased risk of preterm birth. It is thought to be infectious in nature and has been described as an intrauterine bacterial biofilm. There is little evidence on the impact of treatment with antibiotics on outcome. OBJECTIVE: To determine whether outpatient antibiotics administered to women with amniotic fluid sludge would reduce preterm birth risk compared to no antibiotic treatment. MATERIALS AND METHODS: This was a retrospective cohort study of all patients diagnosed with amniotic fluid sludge by transvaginal sonography between 15 and 25 weeks' gestation in the outpatient ultrasound unit at a single academic center between 2010 and 2017. Patients were segregated according to whether they were treated with oral antibiotics at the time of diagnosis. Women with multiple gestation, fetal anomalies, preterm rupture of membranes prior to initial diagnosis of amniotic fluid sludge, and active preterm labor placenta previa and/or suspected accreta were excluded from analysis. Primary outcome of preterm birth at less than 37 weeks' gestation was compared by univariate and regression analysis to control for potential co-linear and/or confounding variables. Additional outcomes were compared by univariate analysis. RESULTS: A total of 181 patients were initially identified, and 97 patients met inclusion criteria. Of these patients, 51 were treated with oral antibiotics (46 azithromycin and 5 moxifloxacin), and 46 were not treated. The overall incidence of preterm birth at <37 weeks was 49.4 % (48 of 97) and preterm birth <28 weeks was 22.7% (22 of 97). There was no significant difference in preterm birth, either at <37 weeks (P = .47) or <28 weeks (P = .83) between the treated and untreated women. After adjusting for race, body mass index, tobacco use, cervical length, and preterm birth history, antibiotic treatment did not reduce the risk of preterm birth (adjusted odds ratio, 1.3; confidence interval, 0.77-1.9). No differences were seen in the incidence of preterm premature rupture of membranes (P = .94) or median latency from diagnosis to delivery (P = .47). Birthweight (P = .99), sepsis (P = .53), intraventricular hemorrhage (P = .95), and neonatal intensive care unit (NICU) admission (P = .08) were not affected by antibiotic treatment. Antibiotic treatment did not affect the incidence of either clinical or histologic chorioamnionitis (P = .92 and .14, respectively) or histologic stage 2-3 maternal or fetal inflammation (P = .94 and 0.58, respectively). Sonographic resolution of amniotic fluid sludge on first subsequent scan was seen in 34% of antibiotic-treated women and 43% of untreated women (P = .42). There was no difference in latency from diagnosis to delivery or mean gestational age at delivery according to whether sludge resolved or persisted at the first subsequent scan (P = .14 for each). CONCLUSION: Antibiotic treatment of amniotic fluid sludge is not associated with a reduction in premature birth. Likewise, antibiotic treatment of amniotic fluid sludge was not associated with improvement in other obstetric, neonatal, or pathologic variables. These findings suggest that the presumed infectious nature of sludge and subsequent adverse outcomes are not treated or improved by administration of azithromycin following midtrimester sonographic diagnosis.

A comparison of placental pathology between small for gestational age infants at < 5 % versus 5-9.

INTRODUCTION: Among SGA newborns, those < 5th % for GA are more likely to have adverse outcomes than those at 5-9th %. The differential morbidity and mortality may be due to abnormal placental pathology between groups. Our purpose was to compare placental pathology characteristics and composite placental pathology among SGA infants with birth weights <5th % vs. 5-9th %. METHODS: This study is a secondary analysis of a multicenter, retrospective cohort study. Placental pathological variables and composite placental pathology (CPP) among SGA infants <5th % and 5-9th % were compared. Multivariable logistic regression was used to model the probability of an infant's birth weight being classified as <5th % based on pathology characteristics. RESULTS: Of 11,487 live singleton births, 925 SGA infants met inclusion criteria. Placental pathology was available for review in 407 (44 %) SGA infants: 210 (51.6 %) <5th % and 197 (48.4 %) 5-9th %. A decreased placental weight for GA, was more common in the <5th % group compared to the 5-9th % group (p = 0.0019). No significant differences in the distribution of pathological variables or in CPP (p = 0.3) was observed between the two centile groups. A decreased placental weight was the only reliable predictor of an infant's birth weight centile group (p = 0.0018). CONCLUSIONS: Placental hypoplasia, reflected by a decreased placental weight for GA, was significantly more common among SGA infants < 5th % compared to the 5-9th %. There was no difference in placental pathological features or CPP between the two centile groups of SGA infants.

Duplex criteria for native superior mesenteric artery stenosis overestimate stenosis in stented superior mesenteric arteries.

OBJECTIVES: Superior mesenteric artery (SMA) duplex scanning is utilized to screen for high-grade (>or=70%) SMA stenosis (peak systolic velocity [PSV] >or=275 cm/second) and for follow-up of SMA bypass grafts and stents. Expected duplex scan findings in SMA bypass grafts have been recently reported. There is, however, little information correlating duplex scans from stented SMAs to procedural angiograms in patients treated for high-grade (>or=70%) SMA stenosis. We report validation of duplex scan criteria for high-grade native artery SMA stenosis, and also duplex scan examined results after SMA stent placement correlated with angiograms and angiographic measured pressure gradients pre- and post-SMA stent placement. METHODS AND RESULTS: Thirty-five patients with symptoms consistent with mesenteric ischemia were treated with SMA stents. Pre-intervention angiography demonstrated >70% SMA stenosis or SMA occlusion in all but 3 patients. Pre-intervention pressure gradients were obtained in 20 stenotic but patent SMAs and averaged 57 +/- 38 mm Hg; range, 15 to 187 mm Hg. Eighteen of the patients had SMA duplex scan prior to angiography, and 17 demonstrated an SMA PSV >or=275 cm/second or no flow, (mean 450 +/- 152 cm/second in patent arteries; range, 256 to 770 cm/second). Post-stent placement angiography demonstrated <30% SMA stenosis in all 35 patients. Post-stent pressure gradients were obtained in 22 patients and averaged 11 +/- 13 mm Hg; range, 0 to 45 mm Hg, (P < .001 compared to pre-stent pressure gradients in a paired test) and were elevated in patients with >or=60% celiac artery stenosis compared with those with <60% celiac artery stenosis (P < .006). Mean early post-stent duplex PSV scans obtained in 13 patients, were 336 +/- 45 cm/second; range, 279 to 416 cm/second (P = .011 compared to pre-stent PSVs). CONCLUSION: SMA stenting provides good anatomic results and significantly reduces measured pressure gradients. Duplex scans measured SMA PSVs are reduced post-stent placement but despite good angiographic results remain above criteria predicting high-grade native artery SMA stenosis. Duplex scan criteria developed to identify high-grade native artery SMA stenosis accurately predict high-grade native artery SMA stenosis but overestimate stenosis in stented SMAs. New duplex scan criteria are required to predict high-grade stenosis in stented SMAs.

The use of blunt needles does not reduce glove perforations during obstetrical laceration repair.

OBJECTIVE: The objective of the study was to compare the rate of glove perforation for blunt and sharp needles used during obstetrical laceration repair. A secondary aim was to assess physician satisfaction with blunt needles. STUDY DESIGN: This was an institutional review board-approved, randomized, prospective trial. Patients with obstetric lacerations were randomized to repair with either blunt or sharp needles. Patient demographics, operator experience, and other clinical variables were collected. Physicians reported any percutaneous injuries and were surveyed regarding satisfaction with the assigned needles. Glove perforation was determined using a validated water test method. RESULTS: There were 438 patients enrolled in the trial: 221 in the control group and 217 in the study group. There was no statistical difference between groups in patient demographics, clinical variables, severity of laceration, or experience level of the surgeon. There was no difference in the glove perforation rate between blunt and sharp needles (risk ratio, 0.79; 95% confidence interval, 0.2-2.95). There was poor correlation between reported perforations and those detected by water test (R(2) = 0.33). The physicians reported that blunt needles were more difficult to use than sharp needles (P = .0001). CONCLUSION: There was no difference in the rate of surgical glove perforation for blunt, compared with sharp, needles used during vaginal laceration repair. Physicians also reported increased difficulty performing the repair with blunt needles.

The evaluation of esophageal adenocarcinoma using dynamic contrast-enhanced magnetic resonance imaging.

Although neoadjuvant chemoradiation eradicates esophageal adenocarcinoma in a substantial proportion of patients, conventional imaging techniques cannot accurately detect this response. Dynamic contrast-enhanced magnetic resonance imaging is an emerging approach that may be well suited to fill this role. This pilot study evaluates the ability of this method to discriminate adenocarcinoma from normal esophageal tissue. Patients with esophageal adenocarcinoma and control subjects underwent scanning. Patients treated with neoadjuvant therapy underwent pre- and postchemoradiation scans. Parameters were extracted for each pixel were Ktrans (equilibrium rate for transfer of contrast reagent across the vascular wall), ve (volume fraction of interstitial space), and taui (mean intracellular water lifetime). Five esophageal adenocarcinoma patients and two tumor-free control subjects underwent scanning. The mean Ktrans value was 5.7 times greater in esophageal adenocarcinoma, and taui is 2.0 times smaller, than in the control subjects. Ktrans decreased by 11.4-fold after chemoradiation. Parametric maps qualitatively demonstrate a difference in Ktrans. DCE MRI of the esophagus is feasible. Ktrans, a parameter that has demonstrated discriminative ability in other malignancies, also shows promise in differentiating esophageal adenocarcinoma from benign tissue. The determination of Ktrans represents an in vivo assay for endothelial permeability and thus may serve as a quantitative measure of response to induction chemoradiation.

Second-trimester angiogenic factors as biomarkers for future-onset preeclampsia.

OBJECTIVE: The purpose of this study was to determine whether second-trimester soluble fms-like tyrosine kinase-1 and placenta growth factor (PlGF) are altered in patients who have preeclampsia develop compared with controls. Furthermore, soluble fms-like tyrosine kinase-1 and placenta growth factor levels in patients with chronic hypertension are described. STUDY DESIGN: With the use of a research database, 21 patients who had severe preeclampsia develop, 34 controls, and 9 patients with chronic hypertension were enrolled. Placenta growth factor and soluble fms-like tyrosine kinase-1 serum levels were determined by enzyme-linked immunosorbent assay. Appropriate statistical tests were used and results were reported as median (quartile 1-quartile 3) in picograms per milliliter. RESULTS: Placenta growth factor was significantly lower in patients in the second trimester who later had severe preeclampsia develop but soluble fms-like tyrosine kinase-1 was unchanged compared with healthy pregnancies. In patients with chronic hypertension, placenta growth factor and soluble fms-like tyrosine kinase-1 levels were not different compared with controls. CONCLUSION: Second-trimester placenta growth factor levels are altered in patients who had severe preeclampsia develop.

Incorporation of Nissen fundoplication in a rat model of duodenoesophageal reflux.

BACKGROUND: Few in vivo models of esophageal reflux and fundoplication suitable for the study of the pathogenesis of Barrett's esophagus and esophageal cancer exist. We describe a modification of a rat model of duodenoesophageal reflux that incorporates Nissen fundoplication and uses it to study the role of fundoplication in ameliorating esophageal reflux. METHODS: A previously described rat model of duodenoesophageal reflux was modified to include Nissen fundoplication. Reflux threshold (RT), defined as the gastric pressure required to cause gastroesophageal reflux during transgastric instillation of saline, was measured in 12 Sprague-Dawley rats at baseline, after cardiomyotomy with esophagogastroduodenal anastomosis (EGDA), after subsequent Nissen fundoplication, and, finally, after takedown of Nissen fundoplication (NF). RESULTS: Cardiomyotomy with EGDA induced no significant change in RT compared with baseline (mean RT +/- SD: 4.0 +/- 1.9 mmHg and 6.0 +/- 2.5 mmHg, respectively, p = 0.741). Nissen fundoplication led to a 14-fold increase in RT (56.4 +/- 18.2 mmHg) compared with cardiomyotomy. RT pressure reverted to baseline levels after NF takedown (4.7 +/- 2.9 mmHg, p < 0.001). Antegrade esophageal flow was demonstrated without an increase in distal esophageal pressure after NF. CONCLUSIONS: Nissen fundoplication creates a one-way antireflux mechanism that eliminates gastroesophageal reflux in this rat model. This modification of an in vivo model of duodenoesophageal reflux represents a unique opportunity to investigate the effect of NF on cardiomyotomy-induced reflux and distal esophageal exposure to duodenogastric refluxate, and could be useful in the study of the role of NF in preventing progression to BE and ECA.

Simplifying minimally invasive transhiatal esophagectomy with the inversion approach: Lessons learned from the first 20 cases.

HYPOTHESIS: The laparoscopic transhiatal esophagectomy can be simplified and performed safely and effectively by using a novel esophageal inversion technique. DESIGN: Case series describing technique, initial experience, and learning curve with laparoscopic inversion esophagectomy. SETTING: Tertiary care university hospital and veteran's hospital. PATIENTS: Twenty consecutive patients with high-grade dysplasia (n = 16) and esophageal adenocarcinoma (n = 4). INTERVENTION: Laparoscopic inversion esophagectomy, a totally laparoscopic approach to transhiatal esophagectomy that incorporates distal to proximal inversion to improve mediastinal exposure and ease of dissection. MAIN OUTCOME MEASURES: Perioperative end points and complications, compared between the first and second groups of 10 patients. RESULTS: There were 19 men and 1 woman. Median operative time was 448 minutes. Median blood loss was 175 cm3. Median intensive care unit stay was 4 days, and median total hospital stay was 9 days. Overall anastomotic leak rate was 20%. Five patients developed an anastomotic stricture, all successfully managed with endoscopic dilation. There were 2 recurrent laryngeal nerve injuries, which resolved. There was no intraoperative or 30-day mortality. Between the first 10 consecutive cases and last 10 procedures, the incidence of anastomotic leak and stricture formation decreased from 30% to 10% and 40% to 10%, respectively. During this period, the number of lymph nodes harvested increased 9-fold, and duration of intensive care unit stay decreased from 8.00 to 2.50 days. CONCLUSIONS: Laparoscopic inversion esophagectomy is a safe procedure. The learning curve for the inversion approach is approximately 10 operations in the hands of esophageal surgeons with advanced laparoscopic expertise.

Evaluation of placenta growth factor and soluble Fms-like tyrosine kinase 1 receptor levels in mild and severe preeclampsia.

OBJECTIVE: The purpose of this study was to determine if maternal serum concentrations of placenta growth factor (PlGF) and soluble Fms-like tyrosine kinase 1 receptor (s-Flt1) are more abnormal in patients with severe preeclampsia compared with mild preeclampsia. STUDY DESIGN: Serum samples were collected from 32 control patients and 80 patients with mild or severe preeclampsia. PlGF and s-Flt1 concentrations were quantitated by enzyme-linked immunosorbent assay (ELISA). Results are expressed as median (Q1-Q3) unless stated otherwise. After normalization, serum markers were compared using one-way analysis of covariance (ANCOVA). RESULTS: Patients with preeclampsia had decreased levels of PlGF (75.1 +/- 14 vs 391 +/- 54 pg/mL, P < .0001) and elevated s-Flt1 concentration (1081 +/- 108 vs 100.1 +/- 26.9 pg/mL, P < .0001) compared with the respective controls (mean +/- SEM). PlGF concentration was lower in patients with mild preeclampsia compared with severe, respectively (67 pg/mL [39-158] vs 24 pg/mL [4-57], P < .02). s-Flt1 was not different between mild and severe preeclampsia (674 pg/mL [211-1297] vs 1015 pg/mL [731-1948], P = .08). CONCLUSION: PlGF and s-Flt1 serum levels are abnormal in patients with preeclampsia compared with controls, but only PlGF is more abnormal in severe preeclampsia compared with mild preeclampsia.

Outcomes of breast cancer in patients who use alternative therapies as primary treatment.

BACKGROUND: Some breast cancer patients opt for alternative treatments in place of conventional treatments. The lack of published data on the outcome of this strategy may contribute to this trend. METHODS: A chart review was performed of breast cancer patients who refused or delayed standard surgery, chemotherapy, and/or radiation therapy. Prognosis was calculated for recommended and actual therapy. RESULTS: Thirty-three patients were included in the analysis. Of 11 patients who initially refused surgery, 10 developed disease progression. Of 3 patients who refused adequate nodal sampling, 1 developed nodal recurrence. Of 10 patients who refused local control procedures, 2 developed local recurrences and 2 died of metastatic disease. By refusing chemotherapy, 9 patients increased their estimated 10-year mortality rate from 17% to 25%. CONCLUSIONS: Alternative therapies used as primary treatment for breast cancer are associated with increased recurrence and death. Homeopathy instead of surgery resulted in disease progression in most patients. These data may aid patients who are considering alternative therapies.

The evaluation and treatment implications of isolated pulmonary nodules in patients with a recent history of breast cancer.

BACKGROUND: Breast cancer patients with pulmonary lesions are often assumed to have metastatic disease and treated palliatively. We evaluated the proportion of these patients who actually have primary lung tumor (PLT) and assessed their outcome. METHODS: We performed a 10-year retrospective review of the cancer registry in a community hospital system. RESULTS: Among 54 breast cancer patients with pulmonary nodules, biopsy was pursued in 30. Although metastatic breast cancer (MBC) was presumed in 24, biopsy showed MBC in 9 patients and PLT in 21. The two groups differed in age, stage, breast tumor size, nodal involvement, and estrogen receptor (ER) positivity. However, no variable excluded the possibility of PLT. Of those with PLT, 11 had early-stage lung disease; 9 underwent curative resection. CONCLUSIONS: Women with breast cancer and 1 or more pulmonary lesions without evidence of other metastatic disease require work-up of pulmonary lesions. Aggressive evaluation can afford treatment of lung cancer and impact survival.

A prospective analysis of microsatellite instability as a molecular marker in colorectal cancer.

BACKGROUND: Microsatellite instability (MSI) may be a molecular marker of colorectal tumor biology. We sought to evaluate the incidence and significance of MSI in an unselected colorectal cancer population. METHODS: Colorectal cancer cases from a community health system were prospectively evaluated for MSI and patient outcomes monitored. RESULTS: Of 240 eligible, 140 underwent testing; 43 (31%) had high-frequency MSI (MSI-H). Those with MSI-H tumors presented with earlier disease stage (P = .014) and lymphocytic infiltration (P < .001). Stage III MSI-H patients trended toward improved disease-free survival (P = .065). MSI-H patients were more likely to have other primary malignancies. CONCLUSIONS: Prevalence of MSI-H in the general colorectal cancer population is higher than previously reported. MSI testing of colorectal cancers is useful as part of a molecular profile to stratify patients for prognosis, treatment, and further study. Patients with MSI-H tumors are more likely to have other primary malignancies, suggesting a role for heightened screening.

Placental Nkx2-5 and target gene expression in early-onset and severe preeclampsia.

OBJECTIVE: Preeclampsia (PE) affects 2-8% of pregnancies worldwide and is a significant source of maternal and neonatal morbidity and mortality. However, the mechanisms underlying PE are poorly understood and major questions regarding etiology and risk factors remain to be addressed. Our objective was to examine whether abnormal expression of the cardiovascular developmental transcription factor, Nkx2-5, was associated with early onset and severe preeclampsia (EOSPE). METHODS: Using qPCR and immunohistochemical assay, we examined expression of Nkx2-5 and target gene expression in EOSPE and control placental tissue. We tested resulting mechanistic hypotheses in cultured cells using shRNA knockdown, qPCR, and western blot. RESULTS: Nkx2-5 is highly expressed in racially disparate fashion (Caucasians > African Americans) in a subset of early EOSPE placentae. Nkx2-5 mRNA expression is highly correlated (Caucasians > African Americans) to mRNA expression of the preeclampsia marker sFlt-1, and of the Nkx2-5 target and RNA splicing factor, Sam68. Knockdown of Sam68 expression in cultured cells significantly impacts sFlt-1 mRNA isoform generation in vitro, supporting a mechanistic hypothesis that Nkx2-5 impacts EOSPE severity in a subset of patients via upregulation of Sam68 to increase sFlt-1 expression. Expression of additional Nkx2-5 targets potentially regulating metabolic stress response is also elevated in a racially disparate fashion in EOSPE. CONCLUSIONS: Expression of Nkx2-5 and its target genes may directly influence the genesis and racially disparate severity, and define a mechanistically distinct subclass of EOSPE.

Costs and clinical outcomes of noninvasive fetal RhD typing for targeted prophylaxis.

OBJECTIVE: To examine the cost and clinical outcomes of noninvasive RhD typing with cell-free fetal DNA to selectively deliver antenatal and postnatal prophylaxis with anti-D immune globulin for prevention of alloimmunization in RhD-negative women. METHODS: We developed a decision tree to compare the costs and clinical outcomes of three strategies in an RhD-negative nonalloimmunized population as follows: 1) routine antenatal anti-D immune globulin prophylaxis and postpartum prophylaxis guided by cord blood typing (the current approach in most of the United States); 2) noninvasive fetal RhD typing with prophylaxis guided by test results; and 3) no screening or prophylaxis. Costs were estimated for testing and treatment algorithms using hospital billing records and information from the manufacturer of the fetal RhD genotyping test. Probability estimates were derived from published literature. The decision tree and sensitivity analyses were constructed and performed with Microsoft Excel. RESULTS: We estimated the cost of the current approach to prevention of alloimmunization to be $351 per pregnancy, and we estimated the cost of noninvasive determination of fetal RhD status to be $682. Assuming essentially perfect test performance, threshold analysis found the cost must decrease to $119 to break even. The gap widened in favor of routine prophylaxis in most other circumstances (increased false-negative test rate and decreasing prevalence of RhD negativity). CONCLUSION: Unless the cost of noninvasive fetal RhD typing is reduced substantially, routine antenatal anti-D immune globulin prophylaxis with postpartum prophylaxis guided by cord blood typing is less costly than noninvasive determination of fetal RhD status.

N-acetylcysteine prevents preterm birth by attenuating the LPS-induced expression of contractile associated proteins in an animal model.

OBJECTIVE: Intrauterine infection is associated with maternal immune activation (MIA) leading to preterm birth through upregulation of contractile associated proteins (CAPs). We hypothesized that N-acetylcysteine would decrease NF-κB activation and CAP expression in a MIA model for preterm birth. METHODS: Pregnant CD-1 mice were given intrauterine LPS or saline on day 15/20. They received NAC or saline prior to injection and were monitored until delivery. The rate of preterm birth in the control, LPS, and LPS + NAC animals was determined. In another group, animals were sacrificed 6 h after treatment and myometrium was collected. COX-2, connexin 43, and oxytocin receptor expression was determined. RESULTS: LPS administration resulted in preterm birth and this effect was attenuated by NAC. LPS increased COX-2, connexin 43, and oxytocin receptor expression. NAC significantly decreased COX-2 expression. LPS increased NF-κB activation; this was attenuated by NAC. CONCLUSION: NAC may be beneficial in prevention of MIA-related preterm birth through attenuation of NF-κB activation and COX-2 upregulation.