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Article ; Online: High sensitivity and specificity in fetal gender identification in the first trimester, using ultrasound and Noninvasive Prenatal Screening (NIPS) in twin pregnancies, a prospective study.

Svirsky, Ran / Sharabi-Nov, Adi / Sagi, Tal / Meiri, Hamutal / Adi, Orenstein / Kugler, Nadav / Maymon, Ron

2023 Volume 23, Issue 1, Page(s) 812

Abstract: Introduction: Determination of the fetal gender in the first trimester is important in twin pregnancy cases of familial X-linked genetic syndromes and helps determine chorionicity. We assessed and compared the accuracy of first-trimester ultrasound ... ...

Abstract	Introduction: Determination of the fetal gender in the first trimester is important in twin pregnancy cases of familial X-linked genetic syndromes and helps determine chorionicity. We assessed and compared the accuracy of first-trimester ultrasound scans, and cell-free fetal DNA (CfDNA) in determining fetal gender in the first trimester of twin pregnancies. Methods: Women with twin pregnancies were recruited prospectively during the first trimester. Fetal gender was determined using both ultrasound scans and CfDNA screening. Both results were compared to the newborn gender after delivery. Results: A total of 113 women with twin pregnancies were enrolled. There was 100% sensitivity and specificity in Y chromosome detection using CfDNA. Gender assignment using ultrasound in any first-trimester scans was 79.7%. Accuracy level increased from 54.2% in CRL 45-54 mm to 87.7% in CRL 55-67 mm and 91.5% in CRL 67-87 mm. Male fetuses had significantly higher chances of a gender assignment error compared to female fetuses, odds ratio = 23.574 (CI 7.346 - 75.656). Conclusions: CfDNA is highly sensitive and specific in determining the presence of the Y chromosome in twin pregnancies in the first trimester. Between CRL 55-87 mm, ultrasound scanning offers a highly accurate determination of fetal gender in twin pregnancies.
MeSH term(s)	Female ; Humans ; Infant, Newborn ; Male ; Pregnancy ; Cell-Free Nucleic Acids ; Crown-Rump Length ; Noninvasive Prenatal Testing ; Pregnancy Trimester, First ; Pregnancy, Twin ; Prospective Studies ; Retrospective Studies ; Ultrasonography, Prenatal/methods
Chemical Substances	Cell-Free Nucleic Acids
Language	English
Publishing date	2023-11-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2059869-5
ISSN	1471-2393 ; 1471-2393
ISSN (online)	1471-2393
ISSN	1471-2393
DOI	10.1186/s12884-023-06133-z
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Article ; Online: MiR-155 and other microRNAs downregulate drug metabolizing cytochromes P450 in inflammation.

Kugler, Nicole / Klein, Kathrin / Zanger, Ulrich M

Biochemical pharmacology

2019 Volume 171, Page(s) 113725

Abstract: In conditions of acute and chronic inflammation hepatic detoxification capacity is severely impaired due to coordinated downregulation of drug metabolizing enzymes and transporters. Using global transcriptome analysis of liver tissue from donors with ... ...

Abstract	In conditions of acute and chronic inflammation hepatic detoxification capacity is severely impaired due to coordinated downregulation of drug metabolizing enzymes and transporters. Using global transcriptome analysis of liver tissue from donors with pathologically elevated C-reactive protein (CRP), we observed comparable extent of positive and negative acute phase response, where the top upregulated gene sets included immune response and defense pathways while downregulation occurred mostly in metabolic and catabolic pathways including many important drug metabolizing enzymes and transporters. We hypothesized that microRNAs (miRNA), which usually act as negative regulators of gene expression, contribute to this process. Microarray and quantitative real-time PCR analyses identified differentially expressed miRNAs in liver tissues from donors with elevated CRP, cholestasis, steatosis, or non-alcoholic steatohepatitis. Using luciferase reporter constructs harboring native and mutated 3'-untranslated gene regions, several predicted miRNA binding sites on RXRα (miR-130b-3p), CYP2C8 (miR-452-5p), CYP2C9 (miR-155-5p), CYP2C19 (miR-155-5p, miR-6807-5p), and CYP3A4 (miR-224-5p) were validated. HepaRG cells transfected with miRNA mimics showed coordinate reductions in mRNA levels and several cytochrome P450 enzyme activities particularly for miR-155-5p, miR-452-5p, and miR-6807-5p, the only miRNA that was deregulated in all four pathological conditions. Furthermore we observed strong negative correlations between liver tissue miRNA levels and hepatic CYP phenotypes. Since miR-155 is well known for its multifunctional roles in immunity, inflammation, and cancer, our data suggest that this and other miRNAs contribute to coordinated downregulation of drug metabolizing enzymes and transporters in inflammatory conditions.
MeSH term(s)	Cell Line, Tumor ; Cytochrome P-450 CYP2C19/genetics ; Cytochrome P-450 CYP2C19/metabolism ; Cytochrome P-450 CYP2C8/genetics ; Cytochrome P-450 CYP2C8/metabolism ; Cytochrome P-450 CYP2C9/genetics ; Cytochrome P-450 CYP2C9/metabolism ; Cytochrome P-450 CYP3A/genetics ; Cytochrome P-450 CYP3A/metabolism ; Cytochrome P-450 Enzyme System/genetics ; Cytochrome P-450 Enzyme System/metabolism ; Down-Regulation ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Humans ; Inactivation, Metabolic ; Inflammation/enzymology ; Inflammation/genetics ; Inflammation/metabolism ; Liver/enzymology ; Liver/metabolism ; MicroRNAs/genetics ; Neoplasms/enzymology ; Neoplasms/genetics ; Neoplasms/metabolism
Chemical Substances	MIRN155 microRNA, human ; MicroRNAs ; Cytochrome P-450 Enzyme System (9035-51-2) ; Cytochrome P-450 CYP2C9 (EC 1.14.13.-) ; Cytochrome P-450 CYP2C19 (EC 1.14.14.1) ; Cytochrome P-450 CYP2C8 (EC 1.14.14.1) ; Cytochrome P-450 CYP3A (EC 1.14.14.1)
Language	English
Publishing date	2019-11-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2019.113725
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Article ; Online: Open versus endovascular repair of penetrating non-aortic arterial injuries: A systematic review and meta analysis.

Al Tannir, Abdul Hafiz / Biesboer, Elise A / Pokrzywa, Courtney / Golestani, Simin / Kukushliev, Vasil / Jean, Xavier / Harding, Eric / de Moya, Marc A / Morris, Rachel / Kugler, Nathan / Schellenberg, Morgan / Murphy, Patrick B

Injury

2024 Volume 55, Issue 3, Page(s) 111368

Abstract: Background: Non-aortic arterial injuries are common and are associated with high morbidity and mortality. Historically, open surgical repair (OSR) was the conventional method of repair. With recent advancements in minimally invasive techniques, ... ...

Abstract	Background: Non-aortic arterial injuries are common and are associated with high morbidity and mortality. Historically, open surgical repair (OSR) was the conventional method of repair. With recent advancements in minimally invasive techniques, endovascular repair (ER) has gained popularity. We sought to compare outcomes in patients undergoing endovascular and open repairs of traumatic non-aortic penetrating arterial injuries. Methods: A systematic review and meta-analysis was conducted using MEDLINE (OVID), Web of Science, Cochrane Library, and Scopus Database from January 1st, 1990, to March 20th, 2023. Titles and abstracts were screened, followed by full text review. Articles assessing clinically important outcomes between OSR and ER in penetrating arterial injuries were included. Exclusion criteria included blunt injuries, aortic injuries, pediatric populations, review articles, and non-English articles. Odds ratios (OR) and Cohen's d ratios were used to quantify differences in morbidity and mortality. Results: A total of 3770 articles were identified, of which 8 met inclusion criteria and were included in the review. The articles comprised a total of 8369 patients of whom 90 % were male with a median age of 28 years. 85 % of patients were treated with OSR while 15 % underwent ER. With regards to injury characteristics, those who underwent ER were less likely to present with concurrent venous injuries (OR: 0.41; 95 %CI: 0.18, 0.94; p = 0.03). Regarding hospital outcomes, patients who underwent ER had a lower likelihood of in-hospital or 30-day mortality (OR: 0.72; 95 %CI: 0.55, 0.95; p = 0.02) and compartment syndrome (OR: 0.29, 95 %CI: 0.12, 0.71; p = 0.007). The overall risk of bias was moderate. Conclusion: Endovascular repair of non-aortic penetrating arterial injuries is increasingly common, however open repair remains the most common approach. Compared to ER, OSR was associated with higher odds of compartment syndrome and mortality. Further prospective research is warranted to determine the patient populations and injury patterns that most significantly benefit from an endovascular approach. Level of evidence: Level III, Systematic Reviews & Meta-Analyses.
MeSH term(s)	Child ; Humans ; Male ; Adult ; Female ; Endovascular Procedures/methods ; Arteries/surgery ; Odds Ratio ; Probability ; Vascular System Injuries/surgery ; Vascular System Injuries/etiology ; Compartment Syndromes/etiology ; Treatment Outcome ; Risk Factors ; Blood Vessel Prosthesis Implantation/adverse effects
Language	English
Publishing date	2024-01-19
Publishing country	Netherlands
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	218778-4
ISSN	1879-0267 ; 0020-1383
ISSN (online)	1879-0267
ISSN	0020-1383
DOI	10.1016/j.injury.2024.111368
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Zs.A 778: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Caesarean scar pregnancy: is there a light in the end of the tunnel?

Shiber, Yair / Maymon, Ron / Gal-Kochav, Maayan / Kugler, Nadav / Pekar-Zlotin, Marina / Smorgick, Noam / Vaknin, Zvi

Archives of gynecology and obstetrics

2022 Volume 307, Issue 4, Page(s) 1057–1064

Abstract: Purpose: To summarize and present a single tertiary center's 25 years of experience managing patients with caesarean scar pregnancies and their long-term reproductive and obstetric outcomes.: Methods: A 25-year retrospective study included women ... ...

Abstract	Purpose: To summarize and present a single tertiary center's 25 years of experience managing patients with caesarean scar pregnancies and their long-term reproductive and obstetric outcomes. Methods: A 25-year retrospective study included women diagnosed with CSP from 1996 to 2020 in one tertiary center. Data were retrieved from the medical records and through a telephone interview. Diagnosis was made by sonography and color Doppler. Treatments included methotrexate, suction curettage, hysteroscopy, embolization and wedge resection by laparoscopy or laparotomy as a function of the clinical manifestations, the physicians' decisions, patient counseling, and parental requests. Results: Analysis of the records recovered 60 cases of CSP (two of whom were recurrent). All patients had complete resolution with no indication for hysterectomy. Thirty-five patients had a long-term follow-up, of whom 24 (68.6%) attempted to conceive again and 22 (91.6%) succeeded. There were 17/22 (77.3%) patients with at least one live birth, 3/22 (13.6%) spontaneous miscarriages and 2/22 (9%) recurrent CSP. The obstetric complications included abnormal placentation 5/19 (26.3%), premature rupture of membranes 2/19 (10.5%), preterm delivery 4/19 (21%) and abnormality of the uterine scar 2/19 (10.5%). There was one case of neonatal death due to complications of prematurity 1/19 (5.2%). Conclusion: CSP treatment focusing on reducing morbidity and preserving fertility has encouraging long-term reproductive and obstetric outcomes. In subsequent pregnancies, we recommend performing an early first trimester vaginal scan to map the location of the new pregnancy, followed by close monitoring given the obstetric complications mentioned above.
MeSH term(s)	Pregnancy ; Infant, Newborn ; Humans ; Female ; Cicatrix/complications ; Cicatrix/drug therapy ; Retrospective Studies ; Cesarean Section/adverse effects ; Pregnancy, Ectopic/diagnostic imaging ; Pregnancy, Ectopic/etiology ; Pregnancy, Ectopic/surgery ; Methotrexate/therapeutic use ; Live Birth
Chemical Substances	Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2022-12-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	896455-5
ISSN	1432-0711 ; 0932-0067
ISSN (online)	1432-0711
ISSN	0932-0067
DOI	10.1007/s00404-022-06888-4
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Article ; Online: Impact of the COVID-19 Pandemic on Excess Perinatal Mortality and Morbidity in Israel.

Mor, Matan / Kugler, Nadav / Jauniaux, Eric / Betser, Moshe / Wiener, Yifat / Cuckle, Howard / Maymon, Ron

American journal of perinatology

2020 Volume 38, Issue 4, Page(s) 398–403

Abstract: Objective: The 2020 COVID-19 pandemic has been associated with excess mortality and morbidity in adults and teenagers over 14 years of age, but there is still limited evidence on the direct and indirect impact of the pandemic on pregnancy. We aimed to ... ...

Abstract	Objective: The 2020 COVID-19 pandemic has been associated with excess mortality and morbidity in adults and teenagers over 14 years of age, but there is still limited evidence on the direct and indirect impact of the pandemic on pregnancy. We aimed to evaluate the effect of the first wave of the COVID-19 pandemic on obstetrical emergency attendance in a low-risk population and the corresponding perinatal outcomes. Study design: This is a single center retrospective cohort study of all singleton births between February 21 and April 30. Prenatal emergency labor ward admission numbers and obstetric outcomes during the peak of the first COVID-19 pandemic of 2020 in Israel were compared with the combined corresponding periods for the years 2017 to 2019. Results: During the 2020 COVID-19 pandemic, the mean number of prenatal emergency labor ward admissions was lower, both by daily count and per woman, in comparison to the combined matching periods in 2017, 2018, and 2019 (48.6 ± 12.2 vs. 57.8 ± 14.4, Conclusion: The COVID-19 pandemic stay-at-home policy combined with patient fear of contracting the disease in hospital could explain the associated higher rate of stillbirth. This collateral perinatal damage follows a decreased in prenatal emergency labor ward admissions during the first wave of COVID-19 in Israel. Key points: · Less obstetrical ER attendance is observed during the pandemic.. · There is a parallel increase in stillbirth rate.. · Stillbirth cases tested negative for COVID-19.. · Lockdown and pandemic panic are possible causes..
MeSH term(s)	COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19/psychology ; Communicable Disease Control/methods ; Communicable Disease Control/organization & administration ; Delayed Diagnosis/psychology ; Delayed Diagnosis/statistics & numerical data ; Delivery, Obstetric/methods ; Delivery, Obstetric/statistics & numerical data ; Emergency Medical Services/methods ; Emergency Medical Services/statistics & numerical data ; Female ; Humans ; Infant, Newborn ; Israel/epidemiology ; Obstetrics/methods ; Obstetrics/organization & administration ; Obstetrics/trends ; Perinatal Mortality ; Pregnancy ; Pregnancy Complications/diagnosis ; Pregnancy Complications/epidemiology ; Prenatal Care/methods ; Prenatal Care/statistics & numerical data ; Retrospective Studies ; SARS-CoV-2 ; Stillbirth/epidemiology
Language	English
Publishing date	2020-12-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	605671-4
ISSN	1098-8785 ; 0735-1631
ISSN (online)	1098-8785
ISSN	0735-1631
DOI	10.1055/s-0040-1721515
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Article: [SINGLE UTERINE PUNCTURE THROUGH THE INTERTWIN MEMBRANE IN TWIN PREGNANCY AMNIOCENTESIS: A DESCRIPTIVE STUDY OF OUR 9 YEARS' EXPERIENCE AT "SHAMIR" ("ASSAF HAROFEH") MEDICAL CENTER].

Segall, Hila / Shirazian-Bracha, Shirin / Melcer, Yaakov / Kugler, Nadav / Maymon, Ron

Harefuah

2020 Volume 159, Issue 4, Page(s) 242–246

Abstract: Introduction: Obstetrics Gynecology Department, "Shamir" ("Assaf Harofeh") Medical Center, Tzrifin There are 2 methods to perform amniocentesis in twin pregnancy. The widespread method is the two-punctures technique (1 for each sac). The other is a ... ...

Abstract	Introduction: Obstetrics Gynecology Department, "Shamir" ("Assaf Harofeh") Medical Center, Tzrifin There are 2 methods to perform amniocentesis in twin pregnancy. The widespread method is the two-punctures technique (1 for each sac). The other is a single uterine puncture through the intertwin membrane. No method is known to be superior. The main procedure-related complications are increased risk for fetal loss, amniotic fluid leakage and infection. The information regarding complications in twin pregnancy is limited and the method is not described. Objectives: To demonstrate whether a single uterine puncture is an acceptable alternative to the double uterine puncture method. Methods: A retrospective cohort study of 112 twin pregnancies which underwent amniocentesis by a single operator at "Shamir" ("Assaf Harofeh") Medical Center between the years 2010-2018. We compared a single uterine puncture (intervention group) to a double uterine puncture (control group). Results: Eighty-six patients (76.7%) underwent a single uterine puncture and 26 (23.3%) underwent a double uterine puncture. Most pregnancies were uncomplicated in both groups (80.2% vs. 76.9% respectively); no statistical difference was seen in any complication. The most common complication was seeking medical help due to bleeding or contraction (12.8% in single puncture group vs 19.2% in double puncture group). PPROM, infection and loss of pregnancy were rare. Conclusions: Only a few studies have related to the method of amniocentesis and compared the results of these 2 methods. A single uterine puncture does not bear an increased risk of complications compared to the double puncture.
MeSH term(s)	Amniocentesis ; Female ; Humans ; Pregnancy ; Pregnancy Trimester, Second ; Pregnancy, Twin ; Punctures ; Retrospective Studies ; Twins
Language	Hebrew
Publishing date	2020-04-19
Publishing country	Israel
Document type	Journal Article
ZDB-ID	953872-0
ISSN	0017-7768
ISSN	0017-7768
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Article ; Online: Oligohydramnios: how severe is severe?

Zilberman Sharon, Nataly / Pekar-Zlotin, Marina / Kugler, Nadav / Accart, Zohar / Nimrodi, Maya / Melcer, Yaakov / Cuckle, Howard / Maymon, Ron

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians

2021 Volume 35, Issue 25, Page(s) 5754–5760

Abstract: Objective: To investigate whether the severity of isolated oligohydramnios at term is associated with increased rates of adverse perinatal outcome.: Study design: A retrospective study conducted in a single medical center from 2017 to 2019. All low- ... ...

Abstract	Objective: To investigate whether the severity of isolated oligohydramnios at term is associated with increased rates of adverse perinatal outcome. Study design: A retrospective study conducted in a single medical center from 2017 to 2019. All low-risk pregnancies with incidental isolated oligohydramnios at term were included. The degree of oligohydramnios was arbitrarily classified into mild (AFI = 41-50 mm), moderate (AFI = 21-40 mm) and severe (AFI = 0-20 mm). Result: A total of 610 women were included: 202 with a mild (33.1%), 287 moderate (47.0%), and 121 severe oligohydramnios (19.8%). Non-reassuring monitor requiring immediate delivery and worse composite neonatal outcome were more common among severe than mild or moderate oligohydramnios (14.0% and 6.4%, 7.3% respectively; Conclusion: Low-risk pregnancies with isolated severe oligohydramnios at term have a higher tendency toward non-reassuring fetal monitoring requiring prompt delivery and adverse neonatal outcomes, this calls for close intrapartum surveillance.
MeSH term(s)	Pregnancy ; Infant, Newborn ; Female ; Humans ; Oligohydramnios/epidemiology ; Retrospective Studies ; Amniotic Fluid ; Pregnancy Outcome/epidemiology ; Fetal Monitoring
Language	English
Publishing date	2021-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2077261-0
ISSN	1476-4954 ; 1057-0802 ; 1476-7058
ISSN (online)	1476-4954
ISSN	1057-0802 ; 1476-7058
DOI	10.1080/14767058.2021.1892068
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Zs.A 3510: Show issues

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Article ; Online: Comparison between a prenatal sonographic scoring system and a clinical grading at delivery for Placenta Accreta Spectrum disorders.

Pekar-Zlotin, Marina / Maymon, Ron / Eliassi Revivo, Perry / Ezratty, Jody / Melcer, Yaakov / Kugler, Nadav / Jauniaux, Eric

2021 Volume 35, Issue 25, Page(s) 8810–8816

Abstract: Objective: Placenta Accreta Spectrum (PAS) disorders have become a major iatrogenic obstetric complication worldwide. Data on the accuracy of ultrasound examination diagnosis are limited by incomplete confirmation and variability in the description of ... ...

Abstract	Objective: Placenta Accreta Spectrum (PAS) disorders have become a major iatrogenic obstetric complication worldwide. Data on the accuracy of ultrasound examination diagnosis are limited by incomplete confirmation and variability in the description of the different grades of PAS at delivery. The aim of this study was to compare our prenatal routine sonographic screening and diagnostic scoring system with a standardized clinical grading system at birth in patient at risk of PAS. Study design: This is a retrospective cohort study of 607 pregnant patients with at least one prior cesarean delivery between December 2013 and December 2018. All patients were assessed for PAS using our institutional prenatal sonographic scoring system and the corresponding ultrasound findings were compared with those of a standardized clinical intra-operative macroscopic grading system of the degree of accreta placentation at vaginal birth or laparotomy. Results: PAS was diagnosed clinically at birth in 50 (8.2%) cases, 17 of which were confirmed by histopathology. A low (score ≤ 5), medium (score 6-7), high (score ≥ 8) probability for PAS was reported in 502, 61 and 44 cases, respectively. The probability score increased significantly ( Conclusions: Both ends of the spectrum of accreta placentation remain difficult to diagnose antenatal and clinically at birth, in particular when no histopathologic confirmation is available. There is a need to develop ultrasound accuracy score systems that can differentiate between the different grades of PAS and which are validated by standardized clinical and pathology protocols.
MeSH term(s)	Infant, Newborn ; Female ; Humans ; Pregnancy ; Placenta Accreta/diagnostic imaging ; Placenta Accreta/pathology ; Placenta Previa ; Retrospective Studies ; Placenta/pathology ; Ultrasonography, Prenatal
Language	English
Publishing date	2021-11-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2077261-0
ISSN	1476-4954 ; 1057-0802 ; 1476-7058
ISSN (online)	1476-4954
ISSN	1057-0802 ; 1476-7058
DOI	10.1080/14767058.2021.2005563
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Article: Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis: A Failed Concept.

Kugler, Nathan / Patel, Parag J / Lee, Cheong Jun

Vascular specialist international

2015 Volume 31, Issue 1, Page(s) 11–14

Abstract: In 2009 Paolo Zamboni et al. implicated that chronic cerebral venous congestion lead to the development of multiple sclerosis. In this review, we examined the role of chronic cerbrospinal venous insufficiency in multiple sclerosis and the proposed ... ...

Abstract	In 2009 Paolo Zamboni et al. implicated that chronic cerebral venous congestion lead to the development of multiple sclerosis. In this review, we examined the role of chronic cerbrospinal venous insufficiency in multiple sclerosis and the proposed therapy entailing venous angioplasty and stenting of extracranial veins with available evidence to date.
Language	English
Publishing date	2015-03-31
Publishing country	Korea (South)
Document type	Journal Article ; Review
ISSN	2288-7970
ISSN	2288-7970
DOI	10.5758/vsi.2015.31.1.11
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Article: Sterben, Tod und Trauer. Ein Gespräch mit Norbert Kugler von Eva Kolbinger

Kugler, Norbert / Kolbinger, Eva

Homöopathie-Zeitschrift

2015 Volume -, Issue 3, Page(s) 74

Language	German
Document type	Article
ZDB-ID	1199315-7
ISSN	0943-6839
Database	Current Contents Medicine

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