Accuracy of High-Resolution Manometry in Hiatal Hernia Diagnosis in Primary and Revision Bariatric Surgery.

PURPOSE: There is a complex association between obesity, hiatal hernia (HH), and reflux. There is a deficiency of literature on the accuracy of preoperative high-resolution manometry (HRM) in detecting HH before both primary and revision bariatric surgery. MATERIALS AND METHODS: A retrospective analysis of a prospective database of all HRM performed before bariatric surgery from 2014 to 2019. An electronic medical records review was conducted. Sensitivity, specificity, and global diagnostic test accuracy were calculated. RESULTS: Sixty-seven patients with HRM (mean age of 44.0 ± 11.3 years, body mass index 40.8 ± 6.9 kg/m2) were eligible. Intraoperative diagnosis of HH was made in 37 patients (55.2% prevalence). The HRM sensitivity was 48.7% (95% confidence interval (CI) 31.9-65.6%), specificity 90.0% (95% CI 73.5-97.9%), and accuracy was 67.2% (95% CI 54.6-78.2%). Comparing primary (28) and revision (39) surgery, the sensitivity (37.5% vs 57.1%), specificity (75.0% vs 100%), and diagnostic accuracy (54.3% vs 76.3%) were comparable, with overlapping 95% CI. Endoscopy performed in 30 patients had a sensitivity of 25.5% (95% CI 6.8-49.9%), specificity of 100% (95% CI 75.3-100%), and accuracy of 57.8% (95% CI 38.5-75.5%) and was comparable to HRM. CONCLUSION: High-resolution manometry for the detection of HH before bariatric surgery has a high specificity and maintains a high accuracy in both primary and revision bariatric surgery.

S-glutathionylation of the Na+-K+ Pump: A Novel Redox Mechanism in Preeclampsia.

CONTEXT: Reduced Na+-K+ pump activity is widely reported in preeclampsia and may be caused by a reversible oxidative modification that is a novel pathological feature of preeclampsia. OBJECTIVE: This work aims to determine whether ß 1 subunit (GSS-ß 1) protein glutathionylation of the Na+-K + pump occurs in preeclampsia. METHODS: The GSS-ß1 of the Na+-K+ pump and its subunit expression in human placentas were compared between women with healthy pregnancies and women with preeclampsia. Human placental samples of pregnant women with preeclampsia (n = 11, mean gestational age 36.5 weeks) were used to examine the GSS-ß 1 of the Na+-K+ pump, compared to healthy pregnancies (n = 11, mean gestational age 39 weeks).The potential pathogenetic role of GSS-ß 1-mediated Na+-K+ pump dysfunction in preeclampsia was investigated. RESULTS: Protein expression of the ß 1 subunit was unchanged in placentas from women with preeclampsia vs those with normotensive pregnancies. Preeclamptic placentas had a significantly increased GSS-ß 1 of the Na+-K+ pump compared to those from healthy pregnancies, and this was linked to a decrease in α 1/ß 1 subunit coimmunoprecipitation. The cytosolic p47phox nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase subunit and its coimmunoprecipitation with the α 1 Na+-K+ pump subunit was increased in preeclamptic placentas, thus implicating NADPH oxidase-dependent pump inhibition. CONCLUSIONS: The high level of ß 1 pump subunit glutathionylation provides new insights into the mechanism of Na+-K+ pump dysfunction in preeclampsia.

Accuracy of hiatal hernia diagnosis in bariatric patients: Preoperative endoscopy versus intraoperative reference.

BACKGROUND AND AIM: Obesity is becoming increasingly prevalent in Asia. Bariatric surgery in the region is growing in popularity to reflect increasing demand. Hiatal hernia (HH) is common among the obese population. There is a lack of evidence comparing preoperative endoscopy against intraoperative findings as a standard of reference for HH diagnosis. METHODS: This was a retrospective analysis of a bariatric procedure database from a single tertiary teaching hospital and high-volume endoscopy center. Electronic medical records were reviewed. Endoscopy results were compared to intraoperative findings, and subgroup analysis of >2 cm hernias was performed. Sensitivity, specificity, predictive values, likelihood ratios, and global diagnostic test accuracy were calculated. RESULTS: A total of 434 patients were eligible for this study, of which HH was detected in 37 patients (prevalence rate 8.55%). Mean age was 41.51 ± 11.07 years, and body mass index was 39.37 ± 5.67 kg/m2. Endoscopy sensitivity was 75.68% (95% confidence interval, 58.80-88.23%) and specificity 91.44% (88.24-94.00%). Positive likelihood ratio was 8.53 (6.11-12.79) and negative likelihood ratio 0.27 (0.15-0.47). Positive predictive value was 45.16% (36.27-54.38%) and negative predictive value 97.58% (95.80-98.62%). Accuracy of endoscopy for preoperative HH diagnosis was 90.09% (86.89-92.74%). CONCLUSION: Endoscopy can have a high diagnostic accuracy of preoperative HH diagnosis in obese Asian patients using intraoperative diagnosis as the reference standard.

The 15-Epilipoxin-A4 Pathway with Prophylactic Aspirin in Preventing Preeclampsia: A Longitudinal Cohort Study.

INTRODUCTION: The benefit of aspirin in preventing preeclampsia is increasingly recognized; however, its mechanism of action remains unclear. Nonobstetric studies have described an anti-inflammatory effect of aspirin through the 15-epilipoxin-A4 pathway (aspirin-triggered lipoxin [ATL]). However, the anti-inflammatory mechanism of aspirin in the prevention of preeclampsia remains unknown. OBJECTIVE/HYPOTHESIS: To examine (1) the difference in longitudinal endogenous lipoxin-A4 (En-Lipoxin-A4) concentration in low-risk (LR) and high-risk (HR) pregnancies, and (2) the effect of aspirin on endogenous ATL concentration and the associated effect on cytokine profile of HR women. METHODS: Plasma from 220 HR women was collected at 12, 16, 20, 24, 28, 32, and 36 weeks of gestation. Adherence to aspirin was biochemically verified. Plasma En-Lipoxin-A4 and ATL concentrations were analyzed using liquid chromatography mass spectrometry, and cytokines, interleukin (IL)-10, tumor necrosis factor-α, interferon-γ, IL-8, and IL-1ß, with the high-sensitivity multibead Luminex® assay. RESULTS: HR women have up to 70% lower plasma concentration of En-Lipoxin-A4 (P < 0.001) than LR women. HR women with adequate aspirin adherence (HR-AA) (n = 82) had higher plasma concentration of ATL (P < .001), lower concentration of IL-8 from 16 to 36 weeks of gestation (P < .001), and increased IL-10 concentration from 16 to 28 weeks of gestation (P = .03) compared with high-risk women who were not on aspirin (HR-NA). HR-AA who did not develop preeclampsia had higher plasma En-lipoxin-A4 (P < .001), ATL (P = .02), and IL-10 concentrations (P < .001) with lower IL-8 concentration (P = .004) than HR women who developed preeclampsia. DISCUSSION: Plasma concentration of En-Lipoxin-A4 is lower in HR women than in LR controls. Adequate adherence with aspirin results in an increase in ATL and IL-10 with reduced IL-8 plasma concentration. This study suggests a potential anti-inflammatory role of aspirin through the ATL pathway with prophylactic aspirin in HR pregnant women.

Calcium deficient placental growth restriction is mediated by an increase in non-invasive integrin α5 and ß4 phenotype.

OBJECTIVES: Integrins are cell adhesion receptors that participated in endovascular invasion by cytotrophoblasts in preeclampsia. This study aimed to investigate the effect of calcium on cellular pathways influencing the trophoblast integration into endothelial cellular networks in vitro. STUDY DESIGN: Red fluorescent-labelled human uterine myometrial microvascular endothelial cells (UtMVECs) were seeded on Matrigel. Green fluorescent-labelled HTR-8/SVneo trophoblast cells were then co-cultured with endothelial cells in different concentrations of calcium for 24 h. MAIN OUTCOME MEASURES: The calcium effects on HTR-8/SVneo cell integration were quantified by Image J. Quantitative PCR was performed to measure mRNA expression of integrins α1, α5, α6, ß1 and ß4. The concentrations of interleukin IL-6, matrix metalloproteinase-2 (MMP-2), MMP-9, PlGF and sFlt-1 in the conditioned medium were measured by ELISA while levels of cytokines IL-1ß, IL-8, IL-10, TNF-α and INF-γ were assessed by magnetic Luminex assays™. RESULTS: Both calcium depletion (0.4 mM) and low calcium (1.8 mM) groups demonstrated inhibited integration of trophoblast cells into endothelial cellular networks, compared with the normal calcium group (2.4 mM). The IL-6 production was reduced from conditioned media in both calcium depletion and low calcium groups. In calcium depletion group, mRNA expression of integrin α5 and ß4 in trophoblasts was increased while integrin α1 was decreased. CONCLUSIONS: The in vitro trophoblast cell integration into endothelial cellular networks could be modified by altering media calcium through integrin switch away from integrins α5 and ß4 and towards integrin α1 which may be required for healthy early trophoblast integration.

Effect of placental growth factor in models of experimental pre-eclampsia and trophoblast invasion.

Placental growth factor (PlGF) is decreased in early gestation of pregnant women who subsequently develop pre-eclampsia. In this study, pre-emptive treatment with PlGF to prevent pre-eclampsia was evaluated in an in vivo rodent model of experimental pre-eclampsia (EPE) induced by TNF-α and in an in vitro model of human first-trimester trophoblast invasion. Pregnant C57/BL6 mice were treated with recombinant mouse placental growth factor-2 (rmPlGF-2) 100 µg/kg/day IP from gestational day (gd) 10. Animals had EPE induced by continuous TNF-α infusion on gd 13 and were subject to either continuous blood pressure monitoring by radiotelemetry throughout pregnancy or live placenta T2 -weighted magnetic resonance imaging (MRI) to demonstrate placental function on gd 17. There was no difference in BP (P > .99), proteinuria (P = .9) or T2 values on MRI (P = .9) between control and rmPlGF-2-treated animals. On gd 13, animals treated with rmPlGF-2 demonstrated increased placenta PlGF (P = .01) and Toll-like receptor-3 (P = .03) mRNA expression as compared with controls. Fluorescent-labelled human uterine microvascular endothelial cells and HTR8/SVNeo cells were co-cultured on Matrigel™ and treated with recombinant human PlGF (rhPlGF) (10 ng/mL) and/or TNF-α (0.5 ng/mL). Trophoblast integration into endothelial networks was reduced by added TNF-α (P = .006), as was rhPlGF concentration in conditioned media (P < .0001). Cell integration was not ameliorated by addition of rhPlGF (P > .9). Although TNF-α-induced EPE was not reversed with pre-emptive rmPlGF-2, a further trial of pre-emptive rhPlGF in vivo is required to determine whether the absence of effect of rhPlGF demonstrated in vitro precludes PlGF as a preventative therapy for pre-eclampsia.

Adolescent Perinatal Outcomes in South West Sydney, Australia.

OBJECTIVE: To compare perinatal outcomes, blood pressures throughout pregnancy, rates of hypertensive disorders of pregnancy, preeclampsia, gestational diabetes mellitus, and immediate obstetric outcomes in adolescents younger than 20 years at delivery and those in the 20- to 34-year age group. PATIENTS AND METHODS: Questionnaires were administered to pregnant women at Campbelltown and Liverpool hospitals within South West Sydney, Australia, as part of a broader study of sleep-disordered breathing in pregnancy between February 1, 2009, and February 28, 2013. Data collected included demographic data, blood pressure readings, pregnancy complications, delivery type, and neonatal outcomes. Adolescents were compared with older women using Student t tests and χ2 statistics. RESULTS: A total of 103 adolescents were compared with 2291 women aged 20 to 34 years. Adolescents were more likely to be primiparous, had longer average gestations, and had lower pre-pregnancy body mass index. Adolescents had lower rates of cesarean section delivery and gestational diabetes mellitus. There was no significant difference in smoking rates, perinatal mortality rate, small for gestational age, intrauterine growth restriction, Apgar score of less than 7 at 5 minutes, admission to special care nursery, or hypertensive disorder of pregnancy rates. Adolescents had lower booking systolic and diastolic blood pressures, and their highest antenatal systolic blood pressures were lower. CONCLUSION: Adolescents have birth outcomes to similar to those of their older counterparts. Adolescents had lower booking blood pressures. This may have implications for the screening and diagnosis of hypertensive disorders of pregnancy in adolescents.

CD83 is a new potential biomarker and therapeutic target for Hodgkin lymphoma.

Chemotherapy and hematopoietic stem cell transplantation are effective treatments for most Hodgkin lymphoma patients, however there remains a need for better tumor-specific target therapy in Hodgkin lymphoma patients with refractory or relapsed disease. Herein, we demonstrate that membrane CD83 is a diagnostic and therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node biopsies. CD83 from Hodgkin lymphoma tumor cells was able to trogocytose to surrounding T cells and, interestingly, the trogocytosing CD83+T cells expressed significantly more programmed death-1 compared to CD83-T cells. Hodgkin lymphoma tumor cells secreted soluble CD83 that inhibited T-cell proliferation, and anti-CD83 antibody partially reversed the inhibitory effect. High levels of soluble CD83 were detected in Hodgkin lymphoma patient sera, which returned to normal in patients who had good clinical responses to chemotherapy confirmed by positron emission tomography scans. We generated a human anti-human CD83 antibody, 3C12C, and its toxin monomethyl auristatin E conjugate, that killed CD83 positive Hodgkin lymphoma cells but not CD83 negative cells. The 3C12C antibody was tested in dose escalation studies in non-human primates. No toxicity was observed, but there was evidence of CD83 positive target cell depletion. These data establish CD83 as a potential biomarker and therapeutic target in Hodgkin lymphoma.

Risk factors associated with hypertensive disorders of pregnancy within an urban indigenous population in south western Sydney.

BACKGROUND: The prevalence of hypertensive disorders of pregnancy (HDP) in Australia's urban indigenous women is unknown. AIM: To explore the risk factors associated with HDP for a cohort of urban indigenous women in South-Western Sydney, Australia. METHODS: This study was conducted in partnership with the Tharawal Aboriginal Medical Service. Women (18-45 years) were recruited at the clinic and community events. The quantitative questionnaire included obstetric history, personal and family history of hypertension. Anthropometric measurements and blood pressure were conducted. Rates were compared with Australian Bureau of Statistics (ABS) national rates. RESULTS: Eighty-three participants completed the questionnaire. The rate of ever having HDP in a pregnancy was 36.1%. The overall ABS rate was 9.8% and for indigenous women, 14%. The mean maternal age at first pregnancy was 20.8 years (SD 3.7 years). The mean body mass index (BMI) of the sample population (n = 81) was 32.2 kg/m2 (SD 9.5 kg/m2 ) and BMI was not related to HDP (P = 0.197). Of those questioned, 25.3% had an individual history and 63.9% had a family history of hypertension. The effect of family history of hypertension (P = 0.020) (odds ratio (OR) 4.29; 95% confidence interval (CI); 1.42-12.93) and individual history of hypertension (P < 0.001) (OR 15.69; 95% CI; 4.50-54.76) were associated with HDP. CONCLUSION: There was a higher rate of HDP in urban indigenous women compared to the national indigenous prevalence. The family history, or individual history of hypertension was the most significant risk factors and BMI was not identified as a risk factor for HDP in this population.

The effect of acetyl salicylic acid (Aspirin) on trophoblast-endothelial interaction in vitro.

Early administration of low dose acetyl salicylic acid (Aspirin) in high risk women reduces the risk of early onset preeclampsia. This study aims to investigate the effect of aspirin on trophoblast integration and the its effect on angiogenic and invasive pathways in an in-vitro model of preeclampsia. Red fluorescent-labeled human uterine myometrial microvascular endothelial cells (UtMVECs) were seeded on matrigel to form endothelial networks. Green fluorescent-labeled trophoblastic HTR-8/SVneo cells were co-cultured with the endothelial networks with/without TNF-a (0.5ng/mL) and/or aspirin (0.1mM) for 24h. Fluorescent images were captured and quantified by Image J to examine the effects of TNF-a and aspirin on the trophoblast-endothelial integration. Conditioned media were collected to measure free VEGF, PlGF and sFlt-1 by ELISA and PGF1a by Enzyme immunoassay (EIA). Cells were retrieved to examine mRNA expression of angiogenic factors (VEGF, PlGF and sFlt-1), invasion markers (MMP-2 and TIMP-1), endothelial cell activation markers (E-selectin and VCAM), eNOS and cyclooxygenase (COX)-2 by quantitative PCR. Aspirin reversed the inhibitory effect of TNF-a on trophoblast cell integration into endothelial cellular networks. TNF-a increased PGF1a production (128±11%, p<0.05), whilst aspirin reversed the TNF-a effect on PGF1a production (19±4%, p<0.01). TNF-a decreased the mRNA expression of PlGF, eNOS, MMP-2 and TIMP-1, and stimulated COX2, E-selectin and VCAM mRNA expression. Aspirin did not reverse the TNF-a effect on these molecules. Aspirin improves trophoblast cell integration into endothelial cellular networks by inhibiting the effect of TNF-a via PGI2 with no significant effect on antiangiogenic, invasive or endothelial activation markers.