Herman Haller

Bio: Herman Haller is an academic researcher from University of Rijeka. The author has contributed to research in topics: Decidua & Trophoblast. The author has an hindex of 18, co-authored 66 publications receiving 872 citations.

SUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer

Abstract: Background Minimally invasive surgery in cervical cancer has demonstrated in recent publications worse outcomes than open surgery. The primary objective of the SUCCOR study, a European, multicenter, retrospective, observational cohort study was to evaluate disease-free survival in patients with stage IB1 (FIGO 2009) cervical cancer undergoing open vs minimally invasive radical hysterectomy. As a secondary objective, we aimed to investigate the association between protective surgical maneuvers and the risk of relapse. Methods We obtained data from 1272 patients that underwent a radical hysterectomy by open or minimally invasive surgery for stage IB1 cervical cancer (FIGO 2009) from January 2013 to December 2014. After applying all the inclusion-exclusion criteria, we used an inverse probability weighting to construct a weighted cohort of 693 patients to compare outcomes (minimally invasive surgery vs open). The first endpoint compared disease-free survival at 4.5 years in both groups. Secondary endpoints compared overall survival among groups and the impact of the use of a uterine manipulator and protective closure of the colpotomy over the tumor in the minimally invasive surgery group. Results Mean age was 48.3 years (range; 23–83) while the mean BMI was 25.7 kg/m2 (range; 15–49). The risk of recurrence for patients who underwent minimally invasive surgery was twice as high as that in the open surgery group (HR, 2.07; 95% CI, 1.35 to 3.15; P=0.001). Similarly, the risk of death was 2.42-times higher than in the open surgery group (HR, 2.45; 95% CI, 1.30 to 4.60, P=0.005). Patients that underwent minimally invasive surgery using a uterine manipulator had a 2.76-times higher hazard of relapse (HR, 2.76; 95% CI, 1.75 to 4.33; P Conclusions Minimally invasive surgery in cervical cancer increased the risk of relapse and death compared with open surgery. In this study, avoiding the uterine manipulator and using maneuvers to avoid tumor spread at the time of colpotomy in minimally invasive surgery was associated with similar outcomes to open surgery. Further prospective studies are warranted.

Characteristics of Perforin Expressing Lymphocytes Within the First Trimester Decidua of Human Pregnancy

Abstract: PROBLEM: The number of perforin (P)-positive cells in decidua of pregnancy is larger than that observed in any other pathological condition. The aim was to investigate the distribution and the phenotype of P + cells. METHOD: Decidual tissue was obtained from the first trimester vaginal termination of pregnancy. Tissue distribution of P + cells was analyzed by immunohistochemistry. The method for simultaneous measurement of P and cell surface is presented. RESULTS: There is no difference in number and distribution of P + cells between decidua basalis (DB) and decidua parietalis (DP). The percentage of P + decidual lymphocytes (DL) is two times higher than in peripheral blood lymphocytes (PBL) (55% vs. 27%), and the prevalent phenotype is CD3 - CD4 - CD8 - CD2 + (95%) CD11c + (68%) and CD56 + (82%). CD56 bright+ DL are also P bright+ and this is the largest DL subpopulation (42.4% DL). Two different subpopulations of CD8 + DL exist: 1) CD8 bright+ , which are CD3 + CD56 - P - and 2) CD8 dim+ , which are CD3 - CD56 + P + . CONCLUSION: P expressing DL are prevalently nonclassical NK cells (CD16 - ) with low cytolytic activity but fully equipped with potent cytolytic machinery (P bright+ ). There are no classical cytotoxic lymphocytes (CTL) (CD3 + CD8 + P + ) in the decidua, and all CD8 + P + cells are CD3 - CD56 + . The number of P + cells is even higher in DP in the vicinity of noninvasvie trophoblast, than in DB

Decidual natural killer cell tuning by autologous dendritic cells.

Abstract: Problem Dendritic cells (DC)/natural killer (NK) cells interactions in the deciduas of early human pregnancies were analyzed in vitro. Method of study Phenotype, cytokine expression and/or cytolytic mediators' expression were measured by flow cytometry in NK and DC from the freshly isolated decidual mononuclear cells or after their purification and co-culture in vitro. Proliferation of 5(6)-Carboxyfluorescein diacetate N-succinimidyl ester (CFSE)-labeled CD56(+) cells was analyzed by flow cytometry after the co-culture with CD1a(+) or CD83(+) DC. Results Decidual CD1a(+) cells show less mature phenotype with no expression of CD197, lower expression of CD80 and CD86 and higher expression of CD206 and CD195 in comparison to CD83(+) cells. Interleukin (IL)-15, interferon-gamma and tumor necrosis factor-alpha productions were higher in immature than mature DC, whereas IL-10 and IL-18 were equally produced in both subpopulations. Immature DC increase perforin, FasL and TRAIL protein expression and proliferation of NK cells, but decrease their intracellular IL-15 production. Mature DC caused less efficient proliferation of NK cells, and did not affect cytokine and cytolytic mediator expression. Conclusion These results suggest that decidual CD1a(+) cells regulate and shape NK cell function more profoundly than CD83(+) cells in decidua.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

Latest advances in understanding preeclampsia.

Abstract: Preeclampsia is a relatively common pregnancy disorder that originates in the placenta and causes variable maternal and fetal problems. In the worst cases, it may threaten the survival of both mother and baby. We summarize recent work on the causes of preeclampsia, which reveals a new mode of maternal immune recognition of the fetus, relevant to the condition. The circulating factors derived from the placenta, which contributes to the clinical syndrome, are now better understood. This brief review on preeclampsia does not cover all aspects of this intriguing condition but focuses on some new and interesting findings.

Macrophage plasticity and polarization in tissue repair and remodelling.

Abstract: Mononuclear phagocyte plasticity includes the expression of functions related to the resolution of inflammation, tissue repair and remodelling, particularly when these cells are set in an M2 or an M2-like activation mode. Macrophages are credited with an essential role in remodelling during ontogenesis. In extraembryonic life, under homeostatic conditions, the macrophage trophic and remodelling functions are recapitulated in tissues such as bone, mammary gland, decidua and placenta. In pathology, macrophages are key components of tissue repair and remodelling that occur during wound healing, allergy, parasite infection and cancer. Interaction with cells bearing stem or progenitor cell properties is likely an important component of the role of macrophages in repair and remodelling. These properties of cells of the monocyte-macrophage lineage may represent a tool and a target for therapeutic exploitation.

Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies

Abstract: Objective To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia. Design Systematic review and meta-analysis of cohort studies. Data sources PubMed and Embase databases, 2000-15. Eligibility criteria for selecting studies Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation. Data extraction Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. Results There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors. Conclusions There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.

Actions of Placental and Fetal Adrenal Steroid Hormones in Primate Pregnancy

Abstract: It is clear that steroid hormones of placental and fetal adrenal origin have critically important roles in regulating key physiological events essential to the maintenance of pregnancy and development of the fetus for extrauterine life Thus, progesterone has suppressive actions on lymphocyte proliferation and activity and on the immune system to prevent rejection of the developing fetus and placenta (see Fig 9) Progesterone also suppresses the calcium-calmodulin-MLCK system and thus activity of uterine smooth muscle, thereby promoting myometrial quiescence to ensure the maintenance of pregnancy Estrogen enhances uteroplacental blood flow and possibly placental neovascularization to provide optimal gas exchange and the nutrients required for the rapidly developing fetus and placenta In turn, estrogen has specific stimulatory effects on the receptor-mediated uptake of LDL by, and P-450scc activity within, syncytiotrophoblasts, thus promoting the biosynthesis of progesterone Moreover, there is an estrogen-dependent developmental regulation of expression of the LDL receptor and NAD-dependent 11 beta-HSD in the placenta, processes reflecting functional/biochemical differentiation of the trophoblast cells with advancing gestation The increase in 11 beta-HSD causes a change in transplacental corticosteroid metabolism, which results in activation of the HPAA in the fetus As a result of this cascade of events, there is an increase in expression of pituitary POMC/ACTH and key enzymes, eg 3 beta-HSD and P-450 17 alpha-hydroxylase, important for de novo cortisol formation by, and consequently maturation of, the fetal adrenal gland In turn, cortisol has well defined actions on surfactant biosynthesis and consequently fetal lung maturation, as well as effects on placental CRH/POMC release, which may be important to the initiation of labor At midgestation, estrogen also selectively feeds back on the fetal adrenal to suppress DHA and maintain physiologically normal levels of estrogen Preparation of the breast for lactation and nourishment of the newborn appears to involve a multifactorial system of regulation that includes estrogen It is apparent, therefore, that autocrine/paracrine, as well as endocrine, systems of regulation are operative within the fetoplacental unit during primate pregnancy A major goal of this review has been to illustrate the critically close functional communication existing between the developing placenta and fetus in the biosynthesis and the actions of steroid hormones during primate pregnancy The functional interaction of the human fetal adrenal and placenta with respect to the biosynthesis of estrogen was demonstrated many years ago However, the recent studies presented in this review show that the endocrine interaction between the fetus and placenta is more extensive, involving complex physiological regulatory mechanisms Thus, as illustrated in Fig 9, estrogen, acting via its receptor within the placenta and other reproductive tissues, orchestrates the dynamic interchange between the placenta and fetus responsible for the developmental regulation of the biosynthesis of the various steroid and peptide hormones and their receptors necessary for the maintenance of pregnancy and development of a live newborn It would appear, therefore, that the immediate and long range challenges in this area of reproductive endocrinology are to employ in vitro molecular and in vivo experimental approaches simultaneously to elucidate the nature of these complex interactions and define the cellular and molecular mechanisms underlying these important regulatory events