Publications by authors named "Antonella Iannaccone"

14 Publications

  • Page 1 of 1

Abnormal expression of the costimulatory molecule B7-H4 in placental chorionic villous and decidual basalis tissues of patients with preeclampsia and HELLP syndrome.

Am J Reprod Immunol 2021 09 6;86(3):e13430. Epub 2021 May 6.

Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany.

Background: B7-H4, a checkpoint molecule of the B7 family, regulates a broad spectrum such as T-cell activation, cytokine secretion, tumour progression, and invasion capacities. Our previous data revealed that soluble B7-H4 (sB7-H4) blood serum levels are elevated in women at high risk for the hypertensive pregnancy disorder preeclampsia (PE) in the first trimester, as well as in patients with confirmed early/late-onset PE.

Aim: We here aim to investigate the expression pattern of B7-H4 in placental tissues of PE and HELLP Syndrome versus control group.

Methods: B7-H4 protein expression and localization were investigated by immunoblotting and co-immunohistochemistry in placental chorionic villous and decidual basalis tissues.

Results: B7-H4 protein was prominently expressed at the cell membrane, in the cytoplasm of the syncytiotrophoblast (STB) and interstitial extravillous trophoblast (EVT). B7-H4 protein levels in placental chorionic villous tissue were significantly higher in women with early-onset/late-onset PE and HELLP, while it was decreased in decidual basalis tissues of early-onset PE and HELLP compared with controls.

Conclusion: B7-H4 was inversely expressed in placental chorionic villous and decidual basalis tissues of PE and HELLP patients. The increase in B7-H4 in the STB in PE and HELLP may lead to excessive apical expression and release of soluble B7-H4 in the maternal circulation. In contrast, the decrease in B7-H4 in decidual basalis tissues could be related to the decrease in invasion ability of the EVT in PE. Thus, the current results strongly suggest that B7-H4 is involved in the pathogenesis of PE and HELLP.
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http://dx.doi.org/10.1111/aji.13430DOI Listing
September 2021

Uterine Artery Embolization in the Twentieth Week of Pregnancy in Abnormally Invasive Placenta with Live Birth.

J Vasc Interv Radiol 2021 03;32(3):339-342

Institute for Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany. Electronic address:

An abnormally invasive placenta is an increasing and potentially life-threatening pregnancy complication. The case presented herein is a heterotopic dichorial pregnancy with implantation of 1 placenta within the isthmocervical area, which caused vaginal bleeding during the 20th week of pregnancy, requiring a blood transfusion. To stop the bleeding, a bilateral embolization of the cervical branches of the uterine arteries was performed. The embolization was well tolerated and resulted in the abrupt and lasting cessation of bleeding for more than 10 weeks, resulting in the live birth of 1 child.
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http://dx.doi.org/10.1016/j.jvir.2020.12.002DOI Listing
March 2021

Bi-allelic loss of function variants in SLC30A5 as cause of perinatal lethal cardiomyopathy.

Eur J Hum Genet 2021 May 5;29(5):808-815. Epub 2021 Feb 5.

Institute of Human Genetics, University Medical Center Leipzig, Leipzig, Germany.

Perinatal mortality is a heavy burden for both affected parents and physicians. However, the underlying genetic causes have not been sufficiently investigated and most cases remain without diagnosis. This impedes appropriate counseling or therapy. We describe four affected children of two unrelated families with cardiomyopathy, hydrops fetalis, or cystic hygroma that all deceased perinatally. In the four patients, we found the following homozygous loss of function (LoF) variants in SLC30A5 NM_022902.4:c.832_836del p.(Ile278Phefs*33) and NM_022902.4:c.1981_1982del p.(His661Tyrfs*10). Knockout of SLC30A5 has previously been shown a cardiac phenotype in mouse models and no homozygous LoF variants in SLC30A5 are currently described in gnomAD. Taken together, we present SLC30A5 as a new gene for a severe and perinatally lethal form of cardiomyopathy.
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http://dx.doi.org/10.1038/s41431-020-00803-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110774PMC
May 2021

Further evidence for POMK as candidate gene for WWS with meningoencephalocele.

Orphanet J Rare Dis 2020 09 9;15(1):242. Epub 2020 Sep 9.

Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.

Background: Walker-Warburg syndrome (WWS) is a rare form of alpha-dystroglycanopathy characterized by muscular dystrophy and severe malformations of the CNS and eyes. Bi-allelic pathogenic variants in POMK are the cause of a broad spectrum of alpha-dystroglycanopathies. POMK encodes protein-O-mannose kinase, which is required for proper glycosylation and function of the dystroglycan complex and is crucial for extracellular matrix composition.

Results: Here, we report on male monozygotic twins with severe CNS malformations (hydrocephalus, cortical malformation, hypoplastic cerebellum, and most prominently occipital meningocele), eye malformations and highly elevated creatine kinase, indicating the clinical diagnosis of a congenital muscular dystrophy (alpha-dystroglycanopathy). Both twins were found to harbor a homozygous nonsense mutation c.640C>T, p.214* in POMK, confirming the clinical diagnosis and supporting the concept that POMK mutations can be causative of WWS.

Conclusion: Our combined data suggest a more important role for POMK in the pathogenesis of meningoencephalocele. Only eight different pathogenic POMK variants have been published so far, detected in eight families; only five showed the severe WWS phenotype, suggesting that POMK-associated WWS is an extremely rare disease. We expand the phenotypic and mutational spectrum of POMK-associated WWS and provide evidence of the broad phenotypic variability of POMK-associated disease.
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http://dx.doi.org/10.1186/s13023-020-01454-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488248PMC
September 2020

Fetal subdural hematoma, sickle cell disease and storage pool disease: A case report.

Case Rep Womens Health 2020 Apr 20;26:e00183. Epub 2020 Feb 20.

Department of Obstetrics and Gynecology, University Hospital, University of Duisburg-Essen, Essen, Germany.

A fetal subdural hematoma (SDH) was diagnosed in a patient with sickle cell disease (SCD) during a routine ultrasound exam in the 30th week of pregnancy. A scan performed a few days earlier had revealed no abnormalities. After interdisciplinary consultation with neurosurgeons and neonatologists, a cesarean section was performed since acute subdural bleeding was hypothesized and the mother's condition was critical. After surgery, the diagnostic procedures revealed that the child and the mother had also suffered from thrombocytopathy, which probably jointly contributed to causing the bleeding; in general, anemia and hypoxia may also play an important role. The newborn had a good neurological outcome. Ultrasound features do not reflect the underlying cause and therefore predicting the prognosis is challenging. In most cases, prenatal counseling is difficult because of the unknown underlying cause and because there are no ultrasound or magnetic resonance imaging criteria to define which cases can benefit from delivery or expectant management. Where there is acute bleeding, the child could benefit from delivery and surgical evacuation of the hematoma. Further investigation to identify the cause of the bleeding can improve management and prognosis.
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http://dx.doi.org/10.1016/j.crwh.2020.e00183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057149PMC
April 2020

Afamin predicts gestational diabetes in polycystic ovary syndrome patients preconceptionally.

Endocr Connect 2019 May;8(5):616-624

Division of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.

Background: Patients suffering from polycystic ovary syndrome (PCOS) are often insulin resistant and at elevated risk for developing gestational diabetes mellitus (GDM). The aim of this study was to explore afamin, which can be determined preconceptionally to indicate patients who will subsequently develop GDM. Serum concentrations of afamin are altered in conditions of oxidative stress like insulin resistance (IR) and correlate with the gold standard of IR determination, the HOMA index.

Methods: Afamin serum concentrations and the HOMA index were analyzed post hoc in 63 PCOS patients with live births. Patients were treated at Essen University Hospital, Germany, between 2009 and 2018. Mann-Whitney U test, T test, Spearman's correlation, linear regression models and receiver-operating characteristic (ROC) analyses were performed for statistical analysis.

Results: Patients who developed GDM showed significantly higher HOMA and serum afamin values before their pregnancy (P < 0.001, respectively). ROCs for afamin concentrations showed an area under the curve of 0.78 (95% confidence interval (CI) 0.65-0.90) and of 0.77 (95% CI 0.64-0.89) for the HOMA index. An afamin threshold of 88.6 mg/L distinguished between women who will develop GDM and those who will not with a sensitivity of 79.3% and a specificity of 79.4%. A HOMA index of 2.5 showed a sensitivity of 65.5% and a specificity of 88.2%.

Conclusion: The HOMA index and its surrogate parameter afamin are able to identify pre-pregnant PCOS patients who are at risk to develop GDM. Serum afamin concentrations are independent of fasting status and therefore an easily determinable biomarker.
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http://dx.doi.org/10.1530/EC-19-0064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510713PMC
May 2019

Soluble B7-H4 blood serum levels are elevated in women at high risk for preeclampsia in the first trimester, as well as in patients with confirmed preeclampsia.

Am J Reprod Immunol 2018 09 24;80(3):e12988. Epub 2018 May 24.

Department of Obstetrics and Gynecology, University Hospital of Essen, Essen, Germany.

Problem: B7-H4 negatively regulates T-cell-mediated immunity and might play an important role in preeclampsia (PE). Here, we have investigated the association between PE and maternal soluble B7-H4 (sB7-H4) serum levels and B7-H4 mRNA expression in the placenta.

Method Of Study: Maternal serum levels of sB7-H4 were determined by enzyme-linked immunosorbent assay in women between 11 and 13 weeks' gestation with elevated risk for PE (n = 48) and women without elevated risk for PE (n = 47). In the third trimester, sB7-H4 serum levels (n = 166) and B7-H4 mRNA expression in the placenta (n = 54) were determined in women with early-onset PE, late-onset PE, fetal growth restriction (FGR), and in healthy controls.

Results: In the first trimester, significant higher levels of sB7-H4 were detected in women at elevated risk for PE compared to women without risk for PE (P < .0001). sB7-H4 has some predictive ability to identify cases with an elevated risk of developing PE with area under the curve (AUC) value of 0.88 (95% CI 0.8-0.94). Using a specificity of 90.0% led to a sensitivity of 47.9% and a threshold of 3.63 ng/mL. In the third trimester, the highest serum levels of sB7-H4 and B7-H4 mRNA expression in the placenta were observed in early-onset PE. Significant higher serum levels of sB7-H4 and B7-H4 mRNA expression in the placenta were observed in women with early-onset PE (P = .01 and P = .006, respectively) and late-onset PE (P = .03 and P = .004, respectively) compared to healthy controls, but not compared to FGR.

Conclusion: sB7-H4 is involved in the regulation of immune tolerance in women with PE in the third trimester. In the first trimester of pregnancy, sB7-H4 might serve as a predictive immunological biomarker for women who are at elevated risk of developing PE.
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http://dx.doi.org/10.1111/aji.12988DOI Listing
September 2018

Vasospasm-related complications after subarachnoid hemorrhage: the role of patients' age and sex.

Acta Neurochir (Wien) 2018 07 27;160(7):1393-1400. Epub 2018 Apr 27.

Department of Neurosurgery, University Hospital, University of Duisburg-Essen, 45147, Essen, Germany.

Background: Outcome of aneurysmal subarachnoid hemorrhage (SAH) depends strongly on occurrence of symptomatic vasospasm (SV) leading to delayed cerebral ischemia (DCI). Various demographic, radiographic, and clinical predictors of SV have been reported so far, partially with conflicting results. The aim of this study was to analyze the role of patients' age and sex on SV/DCI risk, especially to identify age and sex-specific risk groups.

Methods: All patients admitted with acute SAH during a 14-year-period ending in 2016 were eligible for this study. The study endpoints were the following: SV requiring spasmolysis, occurrence of DCI in follow-up computed tomography scans and unfavorable outcome at 6 months (modified Rankin scale > 2).

Results: Nine hundred ninety-four patients were included in this study. The majority was female (666; 67%). SV, DCI, and unfavorable outcomes were observed in 21.5, 21.8, and 43.6% of the patients, respectively. Younger age (p < 0.001; OR = 1.03 per year decrease) and female sex (p = 0.025; OR = 1.510) were confirmed as independent predictors of SV. Regarding the sex differences, there were three age groups for SV/DCI risk ≤ 54, 55-74, and ≥ 75 years. Male patients showed earlier decrease in SV risk (at ≥ 55 vs. ≥ 75 years in females). Therefore, SAH females aged between 55 and 74 years were at the highest risk for DCI and unfavorable outcome, as compared to younger/older females (p = 0.001, OR = 1.77/p = 0.001, OR = 1.80). In contrast, their male counterparts did not show these risk alterations (p = 0.445/p = 0.822).

Conclusion: After acute SAH, female and male patients seem to show different age patterns for the risk of SV and DCI. Females aged between 55 and 74 years are at particular risk of vasospasm-related SAH complications, possibly due to onset of menopause.

Clinical Trial Registration Number: DRKS, Unique identifier: DRKS00008749.
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http://dx.doi.org/10.1007/s00701-018-3549-1DOI Listing
July 2018

Embryologically based radical hysterectomy as peritoneal mesometrial resection (PMMR) with pelvic and para-aortic lymphadenectomy for loco-regional tumor control in endometrial cancer: first evidence for efficacy.

Arch Gynecol Obstet 2016 07 23;294(1):153-60. Epub 2015 Nov 23.

Department of Gynaecology and Obstetrics, West-German Tumour Center, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany.

Objective: To evaluate the feasibility and efficacy of embryologically based compartmental surgery for locoregional tumor control in intermediate and high risk endometrial cancer: peritoneal mesometrial resection with therapeutic pelvic and para-aortic lymphadenectomy by robotically assisted laparoscopy.

Methods: 75 consecutive surgically treated patients with uterine malignancies have been analyzed. 68 patients with histologically proven endometrial cancer and complete robotically assisted surgery have been included in this study on morbidity and oncological outcome. 56 % of the patients were at intermediate/high risk with either stage IAG3 or IB (n = 22) or stage II-IV (n = 16). Adjuvant EBRT was offered to three patients only (4 %), whereas five received isolated vaginal brachytherapy (7 %). Indocyanine-green (ICG) fluorescence lymphography is demonstrated being useful for additional intraoperative visualization of the compartment borders and lymphatic drainage to the postponed lymph compartments.

Results: After a mean follow-up of 32 months, there were only two loco-regional recurrences (2.9 %). Both recurrences were apparently cured by salvage therapy. 9 patients died; 6 (8.8 %) from metastatic disease (5) or unknown cause (1), 3 (4.4 %) from intercurrent disease without evidence of disease. One patient (1.4 %) experienced a peritoneal carcinosis and is alive. There were 8/68 perioperative complications (12 %). No perioperative mortality was observed.

Conclusions: Embryologically defined compartmental surgery by robotically assisted laparoscopy seems to be feasible and safe in endometrial cancer. The low loco-regional recurrence rate of 2.9 % in spite of a very low percentage of adjuvant radiotherapy and 56 % of intermediate/high risk tumors should stimulate to initiate a multicentre trial to evaluate the value of compartmental surgery for prevention of locoregional recurrence in endometrial cancer.
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http://dx.doi.org/10.1007/s00404-015-3956-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908154PMC
July 2016

Definition of compartment-based radical surgery in uterine cancer: radical hysterectomy in cervical cancer as 'total mesometrial resection (TMMR)' by M Höckel translated to robotic surgery (rTMMR).

World J Surg Oncol 2013 Aug 26;11:211. Epub 2013 Aug 26.

Department of Gynecology and Obstetrics, West German Cancer Center, University Clinic Essen, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.

Background: Radical hysterectomy has been developed as a standard treatment in Stage I and II cervical cancers with and without adjuvant therapy. However, there have been several attempts to standardize the technique of radical hysterectomy required for different tumor extension with variable success. Total mesometrial resection as ontogenetic compartment-based oncologic surgery - developed by open surgery - can be standardized identically for all patients with locally defined tumors. It appears to be promising for patients in terms of radicalness as well as complication rates. Robotic surgery may additionally reduce morbidity compared to open surgery. We describe robotically assisted total mesometrial resection (rTMMR) step by step in cervical cancer and present feasibility data from 26 patients.

Methods: Patients (n = 26) with the diagnosis of cervical cancer were included. Patients were treated by robotic total mesometrial resection (rTMMR) and pelvic or pelvic/periaortic robotic therapeutic lymphadenectomy (rtLNE) for FIGO stage IA-IIB cervical cancer.

Results: No transition to open surgery was necessary. No intraoperative complications were noted. The postoperative complication rate was 23%. Within follow-up time (mean: 18 months) we noted one distant but no locoregional recurrence of cervical cancer. There were no deaths from cervical cancer during the observation period.

Conclusions: We conclude that rTMMR and rtLNE is a feasible and safe technique for the treatment of compartment-defined cervical cancer.
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http://dx.doi.org/10.1186/1477-7819-11-211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765976PMC
August 2013

Definition of compartment-based radical surgery in uterine cancer: modified radical hysterectomy in intermediate/high-risk endometrial cancer using peritoneal mesometrial resection (PMMR) by M Höckel translated to robotic surgery.

World J Surg Oncol 2013 Aug 16;11:198. Epub 2013 Aug 16.

Background: The technique of compartment-based radical hysterectomy was originally described by M Höckel as total mesometrial resection (TMMR) for standard treatment of stage I and II cervical cancer. However, with regard to the ontogenetically-defined compartments of tumor development (Müllerian) and lymph drainage (Müllerian and mesonephric), compartments at risk may also be defined consistently in endometrial cancer. This is the first report in the literature on the compartment-based surgical approach to endometrial cancer. Peritoneal mesometrial resection (PMMR) with therapeutic lymphadenectomy (tLNE) as an ontogenetic, compartment-based oncologic surgery could be beneficial for patients in terms of surgical radicalness as well as complication rates; it can be standardized for compartment-confined tumors. Supported by M Höckel, PMMR was translated to robotic surgery (rPMMR) and described step-by-step in comparison to robotic TMMR (rTMMR).

Methods: Patients (n = 42) were treated by rPMMR (n = 39) or extrafascial simple hysterectomy (n = 3) with/without bilateral pelvic and/or periaortic robotic therapeutic lymphadenectomy (rtLNE) for stage I to III endometrial cancer, according to International Federation of Gynecology and Obstetrics (FIGO) classification. Tumors were classified as intermediate/high-risk in 22 out of 40 patients (55%) and low-risk in 18 out of 40 patients (45%), and two patients showed other uterine malignancies. In 11 patients, no adjuvant external radiotherapy was performed, but chemotherapy was applied.

Results: No transition to open surgery was necessary. There were no intraoperative complications. The postoperative complication rate was 12% with venous thromboses, (n = 2), infected pelvic lymph cyst (n = 1), transient aphasia (n = 1) and transient dysfunction of micturition (n = 1). The mean difference in perioperative hemoglobin concentrations was 2.4 g/dL (± 1.2 g/dL) and one patient (2.4%) required transfusion. During follow-up (median 17 months), one patient experienced distant recurrence and one patient distant/regional recurrence of endometrial cancer (4.8%), but none developed isolated locoregional recurrence. There were two deaths from endometrial cancer during the observation period (4.8%).

Conclusions: We conclude that rPMMR and rtLNE are feasible and safe with regard to perioperative morbidity, thus, it seems promising for the treatment of intermediate/high-risk endometrial cancer in terms of surgical radicalness and complication rates. This could be particularly beneficial for morbidly obese and seriously ill patients.
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http://dx.doi.org/10.1186/1477-7819-11-198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751733PMC
August 2013

Definition of compartment based radical surgery in uterine cancer-part I: therapeutic pelvic and periaortic lymphadenectomy by Michael höckel translated to robotic surgery.

ISRN Obstet Gynecol 2013 25;2013:297921. Epub 2013 Mar 25.

Department Gynecology and Obstetrics University Clinic Essen, West German Cancer Center, University Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.

Objective. To define compartment based therapeutic pelvic and periaortic lymphadenectomy in cervical and endometrial cancer. Compartment based oncologic surgery appears to be favorable for patients in terms of radicality as well as complication rates, and the same appears to be true for robotic surgery. We describe a method of robotically assisted compartment based lymphadenectomy step by step in uterine cancer and demonstrate feasibility data from 35 patients. Methods. Patients with the diagnosis of endometrial (n = 16) or cervical (n = 19) cancer were included. Patients were treated by rTMMR (robotic total mesometrial resection) or rPMMR (robotic peritoneal mesometrial resection) and pelvic or pelvic/periaortic rtLNE (robotic therapeutic lymphadenectomy) with cervical cancer FIGO IB-IIA or endometrial cancer FIGO I-III. Results. No transition to open surgery was necessary. Complication rates were 13% for endometrial cancer and 21% for cervical cancer. Within follow-up time median (22/20) month we noted 1 recurrence of cervical cancer and 2 endometrial cancer recurrences. Conclusions. We conclude that compartment based rtLNE is a feasible and safe technique for the treatment of uterine cancers and is favorable in aspects of radicality and complication rates. It should be analyzed in multicenter studies with extended followup on the basis of the described technique.
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http://dx.doi.org/10.1155/2013/297921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621289PMC
April 2013
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