Publications by authors named "Marios Marcou"

7 Publications

  • Page 1 of 1

Blunt renal trauma-induced hypertension in pediatric patients: a single-center experience.

J Pediatr Urol 2021 Jun 30. Epub 2021 Jun 30.

Clinic of Urology and Pediatric Urology, University Hospital Erlangen, Germany. Electronic address:

Purpose: Children have a greater chance of sustaining a renal injury than adults and higher odds of having a high-grade renal injury. Hypertension is a rare complication of blunt renal trauma, with risk being higher in cases of major renal trauma. We reviewed the cases of pediatric blunt renal trauma-induced hypertension in our tertiary referral center in an attempt to better understand this rare condition.

Study Design: A retrospective evaluation of children under the age of 18 who were admitted to our department during the last 20 years and were diagnosed with blunt renal trauma.

Results: Twenty-three children presented with blunt renal trauma, one of whom was treated with emergency nephrectomy. Four children (18%) developed post-traumatic hypertension. All four cases were associated with a reduction in blood flow to the kidney, either through injury to the renal artery (in three cases) or through extrinsic compression of the kidney by a large perirenal hematoma (Page kidney; in one case). The Page kidney case developed hypertension during the initial hospitalization, and it resolved spontaneously after five months through the gradual resorption of the perirenal hematoma. Among the three cases of renal artery injury, hypertension during the initial hospitalization was only observed in one case, with hypertension in the other two cases manifesting after two months and four years, respectively. All three cases of renal artery injury resulted in a complete loss of function of the injured kidney, and two cases were treated with nephrectomy. Following nephrectomy, the blood pressure level returned to normal within a few days.

Discussion: Development of hypertension following a blunt renal trauma can be heterogenous, with the time of manifestation stretching between days after the accident and years thereafter. Children have a higher risk of renal trauma and, according to published data out of the National Trauma Data Bank, a 20-times higher risk of renal artery injury in comparison to the adult population. Large multicenter studies are required to answer the question of whether children are therefore more prone to blunt renal trauma-induced hypertension than adults.

Conclusions: Our study highlights the importance of blood pressure monitoring in children following blunt renal trauma, as post-traumatic hypertension can develop even years after the accident. In cases of a poorly functioning kidney, nephrectomy may be regarded as a curative therapy.
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http://dx.doi.org/10.1016/j.jpurol.2021.06.026DOI Listing
June 2021

The European Academy of Andrology (EAA) ultrasound study on healthy, fertile men: clinical, seminal and biochemical characteristics.

Andrology 2020 09 1;8(5):1005-1020. Epub 2020 Jun 1.

Andrology, Female Endocrinology and Gender Incongruence Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.

Background: Infertility affects 7%-12% of men, and its etiology is unknown in half of cases. To fill this gap, use of the male genital tract color-Doppler ultrasound (MGT-CDUS) has progressively expanded. However, MGT-CDUS still suffers from lack of standardization. Hence, the European Academy of Andrology (EAA) has promoted a multicenter study ("EAA ultrasound study") to assess MGT-CDUS characteristics of healthy, fertile men to obtain normative parameters.

Objectives: To report (a) the development and methodology of the "EAA ultrasound study," (b) the clinical characteristics of the cohort of healthy, fertile men, and (c) the correlations of both fertility history and seminal features with clinical parameters.

Methods: A cohort of 248 healthy, fertile men (35.3 ± 5.9 years) was studied. All subjects were asked to undergo, within the same day, clinical, biochemical, and seminal evaluation and MGT-CDUS before and after ejaculation.

Results: The clinical, seminal, and biochemical characteristics of the cohort have been reported here. The seminal characteristics were consistent with those reported by the WHO (2010) for the 50th and 5th centiles for fertile men. Normozoospermia was observed in 79.6% of men, while normal sperm vitality was present in almost the entire sample. Time to pregnancy (TTP) was 3.0[1.0-6.0] months. TTP was negatively correlated with sperm vitality (Adj.r =-.310, P = .011), but not with other seminal, clinical, or biochemical parameters. Sperm vitality and normal morphology were positively associated with fT3 and fT4 levels, respectively (Adj.r = .244, P < .05 and Adj.r = .232, P = .002). Sperm concentration and total count were negatively associated with FSH levels and positively, along with progressive motility, with mean testis volume (TV). Mean TV was 20.4 ± 4.0 mL, and the lower reference values for right and left testes were 15.0 and 14.0 mL. Mean TV was negatively associated with gonadotropin levels and pulse pressure. Varicocoele was found in 33% of men.

Conclusions: The cohort studied confirms the WHO data for all semen parameters and represents a reference with which to assess MGT-CDUS normative parameters.
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http://dx.doi.org/10.1111/andr.12808DOI Listing
September 2020

Increased Soluble CMG2 Serum Protein Concentration is Associated with the Progression of Prostate Carcinoma.

Cancers (Basel) 2019 Jul 26;11(8). Epub 2019 Jul 26.

Center for Reproductive Medicine and Andrology, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany.

Prostate carcinoma (PCa) is one of the leading causes of cancer-related death in males, but biomarkers for the prognosis are rare. Capillary morphogenesis gene 2 (CMG2) is a modulator of extracellular matrix remodeling during angiogenesis. Four isoforms of CMG2 have been described so far, one secreted in the serum as soluble CMG2 (sCMG2). The aim of this study was to evaluate the sCMG2 serum concentrations in 179 PCa patients and 163 age-matched control subjects by ELISA and correlate it to clinical and demographic parameters. We observed that sCMG2 concentration is increased in the serum of PCa patients with metastases, while no significant differences in the concentrations were detected between the control subjects and patients with localized PCa. Furthermore, elevated sCMG2 concentrations were significantly associated with the highest T stage. Increased sCMG2 serum concentrations tended to be associated with a worsened overall and disease-specific survival of the PCa patients. In conclusion, sCMG2 may be an interesting additive biomarker for the prediction of the progression of PCa and the patients' outcome.
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http://dx.doi.org/10.3390/cancers11081059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721319PMC
July 2019

Expression of GP88 (progranulin) in serum of prostate cancer patients is associated with Gleason scores and overall survival.

Cancer Manag Res 2018 5;10:4173-4180. Epub 2018 Oct 5.

Department of Urology and Pediatric Urology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany,

Background: GP88/Progranulin is a well-recognized cell growth promoter in different cancers, and elevated serum GP88 levels have been described as negative prognostic factor in breast cancer. However, serum levels in prostate cancer (PCa) patients have not yet been studied.

Material And Methods: We analyzed serum GP88 levels by enzyme immunosorbent assay and correlated them with clinicopathological parameters in PCa patients. PCa patients were separated into two groups based on the serum GP88 median level (low ≤44.56 ng/mL or high >44.56 ng/mL) and according to their median age (younger ≤66 years or elder patients >66 years).

Results: Low serum GP88 levels were more often detected in younger patients and high levels in elder patients (=0.018; Fisher's exact test). PCa patients were separated into three groups, Gleason score (GS) ≤6; GS=7; and GS≥8. In receiver operating characteristic analyses, we could distinguish GS≤6 from GS=7 [area under the curve (AUC): 0.646; =0.018] and GS≤6 from GS≥8 (AUC: 0.629; =0.048) but not GS=7 from GS≥8. For survival analysis, GP88 levels were separated into two groups by an optimized cutoff value of 36.92 ng/mL. Using this GP88 stratification, all PCa patients and younger patients with a low serum GP88 level had a significantly better overall survival compared with patients with higher serum GP88 levels (log-rank test =0.010 and =0.024).

Conclusion: Serum GP88 levels are significantly different depending on age and GS, and they are associated with the prognosis of PCa patients.
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http://dx.doi.org/10.2147/CMAR.S172069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178934PMC
October 2018

Serum levels of miR-320 family members are associated with clinical parameters and diagnosis in prostate cancer patients.

Oncotarget 2018 Feb 30;9(12):10402-10416. Epub 2017 Dec 30.

Department of Urology and Pediatric Urology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

We studied the association of the serum levels of the microRNA family members miR-320a/-b/-c with clinico-pathological data to assess their applicability as diagnostic biomarker in prostate cancer (PCa) patients. The levels of miR-320a/-b/-c in 3 groups were evaluated by qRT-PCR (145 patients with PCa, 31 patients with benign prostatic hyperplasia (BPH) and 19 healthy controls). The levels of the three family members of miR-320 were directly correlated within each group ( < 0.001), but they differed significantly among the three groups ( < 0.001). The serum levels of the miR-320 family members were significantly increased in older patients compared to younger patients (≤ 66 years vs. > 66 years, ≤ 0.001). In addition, the levels of all three miR-320 family members were significantly different in patients with low tumor stage compared with those with high tumor stage (miR-320a: = 0.034; miR-320b: = 0.006; miR-320c: = 0.007) and in patients with low serum PSA compared with those with high serum PSA (≤ 4 ng vs. > 4 ng; miR-320a: = 0.003; miR-320b: = 0.003; miR-320c: = 0.006). The levels of these miRNAs were inversely correlated with serum PSA levels. Detection in the serum samples of PCa patients with or without PSA relapse revealed higher levels of miR-320a/-b/-c in the group without PSA relapse before/after radical prostatectomy than in that with PCa relapse. In summary, the differences among the PCa/BPH/healthy control groups with respect to miR-320a/-b/-c levels in conjunction with higher levels in patients without a PSA relapse than in those with a relapse suggest the diagnostic potential of these miRNA-320 family members in PCa patients.
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http://dx.doi.org/10.18632/oncotarget.23781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828216PMC
February 2018

Treatment with human, recombinant FSH improves sperm DNA fragmentation in idiopathic infertile men depending on the FSH receptor polymorphism p.N680S: a pharmacogenetic study.

Hum Reprod 2016 09 20;31(9):1960-9. Epub 2016 Jun 20.

Center for Reproductive Medicine and Andrology, Martin Luther University Halle-Wittenberg, Halle, Germany.

Study Question: Does the sperm DNA fragmentation index (DFI) improve depending on the FSH receptor (FSHR) genotype as assessed by the nonsynonymous polymorphisms rs6166 (p.N680S) after 3 months of recombinant FSH treatment in men with idiopathic infertility?

Summary Answer: FSH treatment significantly improves sperm DFI only in idiopathic infertile men with the p.N680S homozygous N FSHR.

What Is Known Already: FSH, fundamental for spermatogenesis, is empirically used to treat male idiopathic infertility and several studies suggest that DFI could be a candidate predictor of response to FSH treatment, in terms of probability to conceive. Furthermore, it is known that the FSHR single nucleotide polymorphism (SNP) rs6166 (p.N680S) influences ovarian response in women and testicular volume in men.

Study Design, Size And Duration: A multicenter, longitudinal, prospective, open-label, two-arm clinical trial was performed. Subjects enrolled were idiopathic infertile men who received 150 IU recombinant human FSH s.c. every other day for 12 weeks and were followed-up for a further 12 weeks after FSH withdrawal. Patients were evaluated at baseline, at the end of treatment and at the end of follow-up.

Participants/materials, Setting, Methods: Eighty-nine men with idiopathic infertility carrier of the FSHR p.N680S homozygous N or S genotype, FSH ≤ 8 IU/l and DFI >15%, were enrolled. A total of 66 patients had DFI analysis completed on at least two visits. DFI was evaluated in one laboratory by TUNEL/PI (propidium iodide) assay coupled to flow cytometry, resolving two different fractions of sperm, namely the 'brighter' and 'dimmer' sperm DFI fractions.

Main Results And The Role Of Chance: Thirty-eight men (57.6%) were carriers of the p.N680S homozygous N and 28 (42.4%) of the homozygous S FSHR. Sperm concentration/number was highly heterogeneous and both groups included men ranging from severe oligozoospermia to normozoospermia. Total DFI was significantly lower at the end of the study in homozygous carriers of the p.N680S N versus p.N680S S allele (P = 0.008). Total DFI decreased significantly from baseline to the end of the study (P = 0.021) only in carriers of the p.N680S homozygous N polymorphism, and this decrease involved the sperm population containing vital sperm (i.e. brighter sperm) (P = 0.008). The dimmer sperm DFI fraction, including only nonvital sperm, was significantly larger in p.N680S S homozygous patients than in homozygous N men (P = 0.018). Total DFI was inversely related to total sperm number (P = 0.020) and progressive sperm motility (P = 0.014). When patients were further stratified according to sperm concentration (normoozospermic versus oligozoospermic) or -211G>T polymorphism in the FSHB gene (rs10835638) (homozygous G versus others), the significant improvement of sperm DFI in FSHR p.N680S homozygous N men was independent of sperm concentration and associated with the homozygous FSHB -211G>T homozygous G genotype.

Limitations, Reasons For Caution: The statistical power of the study is 86.9% with alpha error 0.05. This is the first pharmacogenetic study suggesting that FSH treatment induces a significant improvement of total DFI in men carriers of the p.N680S homozygous N FSHR; however, the results need to be confirmed in larger studies using a personalized FSH dosage and treatment duration.

Wider Implications Of The Findings: The evaluation of sperm DFI as a surrogate marker of sperm quality, and of the FSHR SNP rs6166 (p.N680S), might be useful to predict the response to FSH treatment in men with idiopathic infertility.

Study Funding/competing Interests: The study was supported by an unrestricted grant to M.S. and H.M.B. from Merck Serono that provided the drug used in the study. MS received additional grants from Merck Serono and IBSA as well as honoraria from Merck Serono. The remaining authors declare that no conflicts of interest are present.

Trial Registration Number: EudraCT number 2010-020240-35.
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http://dx.doi.org/10.1093/humrep/dew167DOI Listing
September 2016

The combined serum levels of miR-375 and urokinase plasminogen activator receptor are suggested as diagnostic and prognostic biomarkers in prostate cancer.

Int J Cancer 2015 Sep 18;137(6):1406-16. Epub 2015 Mar 18.

Department of Urology, Universitätsklinikum Erlangen, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.

This study aimed to assess the applicability of miR-375 in combination with the soluble urokinase plasminogen activator receptor (suPAR) protein as a diagnostic and/or prognostic biomarker for prostate cancer (PCa) patients. miR-375 levels by qRT-PCR and suPAR levels by ELISA were evaluated in serum samples from 146 PCa patients, 35 benign prostate hyperplasia (BPH) patients and 18 healthy controls. Antigen levels of suPAR differed between healthy controls and PCa or BPH patients, whereas miR-375 levels differed between PCa and BPH patients or healthy controls (p < 0.001). Additionally, suPAR levels differed between the Gleason sum groups GS = 7 versus GS > 7, with higher levels in the latter group (p = 0.011), and miR-375 levels were higher in the tumor stage group T3-T4 compared with the T1-T2 group (p = 0.039). A high concentration of suPAR was associated with a poor disease-specific survival (DSS; p = 0.039). The combination of suPAR and miR-375 levels identified a patient group possessing high levels for both parameters. This was associated with a poorer 10-year overall survival (OS) and DSS, with a 6.38-fold increased risk of death and a 7.68-fold increased risk of tumor-related death (p = 0.00026 and p = 0.014; univariate Cox's regression analysis). In a multivariate Cox's regression analysis PCa patients with high levels of suPAR and miR-375 showed a 5.72-fold increased risk of death in OS (p = 0.006). In summary, the differences between the PCa/BPH/healthy control cohorts for either suPAR and miR-375 levels in conjunction with the association of combined high suPAR/miR-375 levels with a poor prognosis suggest a diagnostic and prognostic impact for PCa patients.
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http://dx.doi.org/10.1002/ijc.29505DOI Listing
September 2015
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