Overlap of proteomics biomarkers between women with pre-eclampsia and PCOS: a systematic review and biomarker database integration

Study question: Do any proteomic biomarkers previously identified for pre-eclampsia (PE) overlap with those identified in women with polycystic ovary syndrome (PCOS). Summary answer: Five previously identified proteomic biomarkers were found to be common in women with PE and PCOS when compared with controls. What is known already: Various studies have indicated an association between PCOS and PE; however, the pathophysiological mechanisms supporting this association are not known. Study design, size, duration: A systematic review and update of our PCOS proteomic biomarker database was performed, along with a parallel review of PE biomarkers. The study included papers from 1980 to December 2013. Participants/materials, setting, methods: In all the studies analysed, there were a total of 1423 patients and controls. The number of proteomic biomarkers that were catalogued for PE was 192. Main results and the role of chance: Five proteomic biomarkers were shown to be differentially expressed in women with PE and PCOS when compared with controls: transferrin, fibrinogen a, b and g chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. In PE, the biomarkers were identified in serum, plasma and placenta and in PCOS, the biomarkers were identified in serum, follicular fluid, and ovarian and omental biopsies. Limitations, reasons for caution: The techniques employed to detect proteomics have limited ability in identifying proteins that are of low abundance, some of which may have a diagnostic potential. The sample sizes and number of biomarkers identified from these studies do not exclude the risk of false positives, a limitation of all biomarker studies. The biomarkers common to PE and PCOS were identified from proteomic analyses of different tissues. Wider implications of the findings: This data amalgamation of the proteomic studies in PE and in PCOS, for the first time, discovered a panel of five biomarkers for PE which are common to women with PCOS, including transferrin, fibrinogen a, b and g chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. If validated, these biomarkers could provide a useful framework for the knowledge infrastructure in this area. To accomplish this goal, a well co-ordinated multidisciplinary collaboration of clinicians, basic scientists and mathematicians is vital

Proteomic biomarkers of preterm birth risk in women with polycystic ovary syndrome (PCOS): a systematic review and biomarker database integration.

BACKGROUND: Preterm Birth (PTB) is a major cause of neonatal mortality and morbidity. Women with Polycystic Ovary Syndrome (PCOS) are at high risk of PTB. There is a need for research studies to investigate the mechanisms linking PCOS and PTB, to facilitate screening, and develop novel preventative strategies. OBJECTIVE: To list all the proteomic biomarkers of PTB and integrate this list with the PCOS biomarker database to identify commonly expressed biomarkers of the two conditions. SEARCH STRATEGY: A systematic review of PTB biomarkers and update of PCOS biomarker database. All eligible published studies on proteomic biomarkers for PTB and PCOS identified through various databases were evaluated. SELECTION CRITERIA: For the identification of the relevant studies, the following search terms were used: "proteomics", "proteomic", "preterm birth", "preterm labour", "proteomic biomarker" and "polycystic ovary syndrome". This search was restricted to humans only DATA COLLECTION AND ANALYSIS: A database on proteomic biomarkers for PTB was created while an already existing PCOS biomarker database was updated. The two databases were integrated and biomarkers that were co-expressed in both women with PCOS and PTB were identified and investigated. RESULTS: A panel of six proteomic biomarkers was similarly differentially expressed in women with PTB and women with PCOS compared to their respective controls (normal age-matched women in the case of PCOS studies and women with term pregnancy in the case of PTB studies). These biomarkers include Pyruvate kinase M1/M2, Vimentin, Fructose bisphosphonate aldolase A, Heat shock protein beta-1, Peroxiredoxin-1 and Transferrin. CONCLUSIONS: These proteomic biomarkers (Pyruvate kinase M1/M2, Vimentin, Fructose bisphosphonate aldolase A, Heat shock protein beta-1, Peroxiredoxin-1 and Transferrin) can be potentially used to better understand the pathophysiological mechanisms linking PCOS and PTB. This would help to identify subgroups of women with PCOS at risk of PTB and hence the potential of developing preventative strategies

Atrial Fibrillation as a Rare Complication of the Use of Nifedipine as a Tocolytic Agent: A Case Report and Review of the Literature

Calcium channel blockers are commonly used tocolytic agents on Labor and Delivery units worldwide as part of the management of preterm labor. Despite their overall reassuring safety profile, rare cardiovascular complications have been reported. In this report, we describe the case of threatened preterm labor managed with nifedipine with subsequent development of atrial fibrillation. This type of cardiac arrhythmia may have considerable consequences for both the mother and the fetus. The aim of this case report and comprehensive review of the literature is to raise awareness

Management of a Splenic Artery Aneurysm in the Third Trimester of Pregnancy

Background. Splenic artery aneurysm (SAA) is a rare but potentially fatal complication associated with high maternal and fetal mortality when occurring during pregnancy. Case. A 29-year-old G4P3003 at 34 4/7 weeks of gestation was admitted with left upper quadrant pain and newly diagnosed SAA in the hilum. She was scheduled for embolization of the SAA but the night before went into labor. A multidisciplinary team discussion was held, and the patient underwent successful primary low transverse c-section via Pfannenstiel skin incision followed by laparoscopic splenectomy under general anesthesia. She delivered a male newborn with birth weight of 2855 and Apgar score of 8/5. Summary and Conclusion. Early diagnosis and management of SAA are key for improved maternal and fetal outcomes. Our case demonstrates that through a multidisciplinary approach and anticipation of the possible clinical scenarios, good outcomes can be achieved

The main characteristics of each study with the proteins affected in patients in PTL compared to normal individual.

<p> <b>Index:</b></p><p><b>(S)PTB = </b>(Spontaneous) Preterm birth.</p><p><b>1D-GE</b>  = 1D gel electrophoresis.</p><p><b>2D-CF</b>  = 2D chromatographic fractionation.</p><p><b>2D-LC</b>  = 2D liquid chromatography.</p><p><b>2D-DIGE</b> = Fluorescence two-dimensional differential gel electrophoresis.</p><p><b>2D-GE/2DE</b>  = 2D (gel) electrophoresis.</p><p><b>AF</b> = Amniotic fluid.</p><p><b>AFC</b> = Amniotic fluid culture.</p><p><b>AMBP</b> = Alpha-1-microglobulin/bikunin precursor.</p><p><b>APO</b>  = Apolipoprotein.</p><p><b>CF</b> = Cervical fluid.</p><p><b>cLC</b> = Capillary liquid chromatography.</p><p><b>CVF</b> = Cervical-vaginal fluid.</p><p><b>DSCR2</b> = Down syndrome critical region protein 2.</p><p><b>ELISAs</b> = Enzyme-linked immunosorbent assays.</p><p><b>EOI-TOFMS</b> = Electrospray-ionization, time-of-flight mass spectrometry.</p><p><b>ESI-IT MS</b> = Electrospray ionization-ion trap mass spectrometry.</p><p><b>FPLC</b> = Fast protein liquid chromatography.</p><p><b>HNP</b> = Human neutrophil protein.</p><p><b>HP8</b> =  Human peptide 8.</p><p><b>HPLC</b> = High performance liquid chromatography.</p><p><b>IAI</b> = Intra-amniotic infection/inflammation.</p><p><b>IGFBP-1</b> =  Insulin-like growth factor binding protein-1.</p><p><b>IL</b> = Interleukin.</p><p><b>ITIH4</b> =  Inter-alpha-trypsin inhibitor heavy chain 4.</p><p><b>iTRAQ</b> = Isobaric tag for relative and absolute quantitation.</p><p><b>LC-MS/MS</b> = Liquid chromatography – tandem mass spectrometry.</p><p><b>LTBP1</b> =  Latent-transforming growth factor β-binding protein isoform 1L.</p><p><b>LTF</b> = Growth-inhibiting protein 12/Lactoferrin.</p><p><b>MALDI-TOF</b> = Matrix-assisted laser desorption time-of-flight.</p><p><b>MHC</b> = Major histocompatibility complex.</p><p><b>MRM</b> = Multiple reaction monitoring.</p><p><b>MS</b> = Mass spectrometry.</p><p><b>N/A</b> =  Not Applicable.</p><p><b>N</b> = Number of participants.</p><p><b>OGN</b> = Mimecan precursor.</p><p><b>PANTHER</b> = Protein analysis through evolutionary relationships.</p><p><b>PPROM</b> = preterm premature/(pre-labour) rupture of membranes.</p><p><b>PT</b> = Placental tissue.</p><p><b>PTB</b> = Preterm birth.</p><p><b>PTL</b> = Preterm labour.</p><p><b>RBC</b> = Red blood cell.</p><p><b>RETN</b> = Resistin.</p><p><b>RP-HPLC</b> = Reversed-phase high performance liquid chromatography.</p><p><b>SCX chromatography column</b> = Strong cation exchange column.</p><p><b>SD</b> = Standard deviation.</p><p><b>SDS-PAGE</b> = Sodium dodecyl sulfate-polyacrylamide gel electrophoresis.</p><p><b>SELDI TOF</b> = Surface-enhanced laser desorption ionization time-of-flight.</p><p><b>SILAP</b> = Stable isotope labeled proteome.</p><p><b>SLPI</b> = Antileukoproteinase.</p><p><b>SRY</b> = Sex determining region Y.</p><p><b>TMSL3</b> =  Thymosin-like 3.</p><p><b>TPMsk1</b> =  Tropomyosin sk1 fragment.</p><p><b>WB</b> = Western nlotting.</p><p><b>WBC</b> = White blood cells.</p

According to QUADOMICS Tool the following methodological criteria were applied to this review.

<p>According to QUADOMICS Tool the following methodological criteria were applied to this review.</p

The proteins affected most frequently in the studies of women with PTB against women without PTB.

<p> <b>Index:</b></p><p><b>(S)PTB</b> = (Spontaneous) Preterm birth.</p><p><b>2D-CF</b>  = 2D chromatographic fractionation.</p><p><b>AF</b> = Amniotic fluid.</p><p>APO  = Apolipoprotein.</p><p><b>ELISA</b> = Enzyme-linked immunosorbent assays.</p><p><b>ESI-IT MS</b> = Electrospray ionization-ion trap mass spectrometry.</p><p><b>HPLC</b> = High performance liquid chromatography.</p><p><b>IAI</b> = Intra-amniotic Infection/Imflammation.</p><p><b>iTRAQ</b> = Isobaric tag for relative and absolute quantitation.</p><p><b>LC MS/MS</b> = Liquid chromatography – tandem mass spectrometry,</p><p><b>MALDI-TOF</b> = Matrix-assisted laser desorption time-of-flight,</p><p><b>MS</b> = Mass spectrometry,</p><p><b>PTB</b> =  Preterme birth.</p><p><b>PTL</b> = Preterm labour,</p><p><b>RP-HPLC</b> = Reversed-phase high performance liquid chromatography,</p><p><b>SCX chromatography column</b> = Strong cation exchange column,</p><p><b>SDS-PAGE</b> = Sodium dodecyl sulfate-polyacrylamide gel electrophoresis,</p><p><b>SELDI-TOF = </b>Surface-enhanced laser desorption ionization time-of-flight;</p><p><b>WB</b> = Western blotting.</p

A flow chart summarizing the selection process of the primary studies where proteomic methodologies were used for the identification of biomarkers in PTB.

<p>A flow chart summarizing the selection process of the primary studies where proteomic methodologies were used for the identification of biomarkers in PTB.</p

The Rising Triad of Cesarean Scar Pregnancy, Placenta Percreta, and Uterine Rupture: A Case Report and Comprehensive Review of the Literature

As the rate of cesarean sections continues to rapidly rise, knowledge of diagnosis and management of cesarean scar pregnancies (CSPs) is becoming increasingly more relevant. CSPs rest on the continuum of placental abnormalities which include morbidly adherent placenta (accreta, increta, and percreta). A CSP poses a clinical challenge which may have significant fetal and maternal morbidity. At this point, no clear management guidelines and recommendations exist. Herein we describe the case of a second trimester CSP with rapid diagnosis and management in a tertiary care center. The case underscores the need for well-coordinated mobilization of resources and a multidisciplinary approach. A review of the literature is performed and deficits in universal management principles are underscored