Enhancement of Vascularization and Ovarian Follicle Survival Using Stem Cells in Cryopreserved Ovarian Tissue Transplantation-A Systematic Review.

The increase in cancer survival rates has put a focus on ensuring fertility preservation procedures for cancer patients. Ovarian tissue cryopreservation presents the only option for prepubertal girls and patients who require immediate start of treatment and, therefore, cannot undergo controlled ovarian stimulation. We aimed to provide an assessment of stem cells' impact on cryopreserved ovarian tissue grafts in regard to the expression of growth factors, angiogenesis promotion, tissue oxygenation, ovarian follicle survival and restoration of endocrine function. For this systematic review, we searched the Scopus and PubMed databases and included reports of trials using murine and/or human cryopreserved ovarian tissue for transplantation or in vitro culture in combination with mesenchymal stem cell administration to the grafting site. Of the 1201 articles identified, 10 met the criteria. The application of stem cells to the grafting site has been proven to support vascular promotion and thereby shorten the period of tissue hypoxia, which is reflected in the increased number of remaining viable follicles and faster recovery of ovarian endocrine function. Further research is needed before implementing the use of stem cells in OT cryopreservation and transplantation procedures in clinical practice. Complex ethical dilemmas make this process more difficult.

Bloodstream Infections by AmpC-Producing Enterobacterales: Risk Factors and Therapeutic Outcome.

Bloodstream infections associated with AmpC-producing Enterobacterales are severe medical conditions which, without prompt and effective treatment, may have dire ramifications. This study aimed to assess whether certain comorbidities and previous surgical procedures coincide with resistance determinants of AmpC-producing Enterobacterales associated with bloodstream infections. Antibiotic resistance patterns and therapy outcome were also determined. The patients' data obtained revealed that the prevalence of recent surgical procedures, solid organ tumors, metabolic diseases, kidney and liver failure, and hematological malignancies do not differ between resistant and susceptible isolates of AmpC-producing Enterobacterales. Furthermore, no difference was reported in mortality rates. Regarding antibiotic resistance, 34.52% of isolates were confirmed to be resistant (AmpC hyperproduction, ESBL, or carbapenemase). More than one in five AmpC hyperproducers were reported amid Providencia spp., K. aerogenes, E. cloacae, and C. freundii. strains. Carbapenemases were mostly noted in Providencia spp. followed by M. morganii and K. aerogenes strains. Serratia marcescens had the highest proportion of ESBLsof ESBLs. Resistance to expanded-spectrum cephalosporins of Providencia spp. and K. aerogenes strains exceeded 50%, and resistance to meropenem over 10% was observed only in C. freundii strains. Enterobacterales' ever-growing resistance to antibiotics is becoming quite a challenge for clinicians and new treatment options are required.

Typical course of cystinuria leading to untypical complications in pregnancy: A case report and review of literature.

Cystinuria is a rare genetic disorder inherited by an autosomal recessive pattern which affects the transmembrane transporter for the base amino acid cystine. It has a general prevalence of 1 in 7000 with demographic variations. Patients with cystinuria have excessive urinary excretion of cystine, which can lead to the formation of stones. Up to 70% of patients will develop chronic kidney disease that can progress even to end-stage renal disease. Symptoms usually start in the first two decades of life with a typical presentation consisting of flank pain and renal colic, usually accompanied by urinary tract infection and deterioration of kidney function. Men are typically affected twice as often as women and have a more severe clinical course. Diagnosis is made by spectrophotometric analysis of the stones that are collected after spontaneous expulsion or medical intervention. Genetic testing is not mandatory but is recommended in uncertain cases or as a part of genetic counseling. Treatment consists of diet modification, alkalization of urine, and thiol-based therapies if other measures fail to prevent stone formation. In pregnancy, cystinuria with the formation of cystine stones represents a therapeutic challenge and requires a multidisciplinary approach consisting of an uro-nephrology team and a gynecologist. We present the case of a 34-year-old woman with cystinuria on whom the diagnosis was made by analysis of the expulsed stone. While her previous pregnancies were without complications, her third pregnancy was accompanied by frequent urinary tract infections, acute worsening of kidney function, and urological interventions during pregnancy due to the formation of new stones. Despite the complicated course, the pregnancy was successfully carried to term with the delivery of a healthy female child.

Maternity Blues among Croatian Mothers - A Single-Center Study.

BACKGROUND: Maternity blues is a transient change of mood that occurs within the first few days after delivery. Some of the most common symptoms include mood swings, tearfulness, irritability, loss of appetite, fatigue. The aim of the study was to investigate the relationship between maternity blues, psychological, demographic and obstetrics risk factors. SUBJECTS AND METHODS: A cross-sectional study was conducted between October 2019 and February 2020 at the University Hospital Center Zagreb, Croatia. Final analysis included 227 mothers. Participants were assessed with Stein's Maternity Blues Scale, Connor-Davidson Resilience Scale (CD-RISC), Multidimensional Scale of Perceived Support (MSPSS) and Brennan's Experiences in Close Relationship Scale, as well as demographic and obstetric data. RESULTS: The prevalence of maternity blues in our study was 19.9%. Higher result on Stein's Maternity Blues Scale was associated with anxious attachment style (r=0.425, p<0.01), oxytocin (r=0.308, p<0.01), lower birth weight (r=-0.242), lower resilience (r=-0.252) and less perceived social support from family and significant other (p<.01). CONCLUSIONS: This report presents the very first study assessing maternity blues occurence among Croatian mothers and in Croatian cultural environment. We believe that our report will address importance of employing adequate screening methods in preventing and timely recognizing maternity blues and subsequent postpartum depression in Croatian population.

Endometriosis, Pain and Mental Health.

BACKGROUND: Endometriosis is a chronic and progressive disease which can significantly affect a woman's personal, as well as intimate and professional aspects of life. The aim of this study was to asses health-related quality of life and mental health status in patients with endometriosis, investigating also their relationship with endometriosis-related comorbid symptoms and conditions, such as pain and infertility. SUBJECTS AND METHODS: An observational cross-sectional study involved 79 women with endometriosis. All patients filled the Endometriosis Health Profile (EHP-5), the Depression Anxiety Stress Scales (DASS-21) and the Visual Analogue Scale (VAS). Their medical data were retrieved from medical records. Data was analyzed using the SPSS 23.0 (IBM Corp., Armonk, NY). RESULTS: Of all the patients evaluated in our study, 44.3% presented depressive symptoms and 25.3% presented anxiety, while 31.7% reported stress symptoms. Moderate correlations were found between results on EHP-5 and depression (r=0.515), stress (r=0.558) and VAS score (r=0.565). Furthermore, weak positive relationship was observed between EHP-5 and anxiety (r=0.295) and infertility (r=0.267). Additionally, moderate correlation was found between depression and infertility (r=0.519), while there was weak association between VAS score and stress (r=0.236). CONCLUSIONS: This study showed complex relationships between symptoms and conditions manifesting in patients with endometriosis. Due to diversity of symptoms, potentially including mental health issues, it is important to emphasize the need for combined personalized treatment for these patients, taking into account both physical and psychological aspect of the disease.

Detection and characterisation of extended-spectrum and plasmid-mediated AmpC ß-lactamase produced by Escherichia coli isolates found at poultry farms in Bosnia and Herzegovina.

Extended-spectrum ß-lactamases (ESBLs) hydrolyse extended-spectrum cephalosporins (ESC) and aztreonam. As ESBL-producing organisms have been identified in food producing animals, the aim of our study was to detect and analyse such Escherichia coli isolates from poultry. Antibiotic susceptibility of the isolates was determined with disk-diffusion and broth microdilution methods. ESBLs were detected with the double-disk synergy and inhibitor-based test with clavulanic acid. The transferability of cefotaxime resistance was determined with conjugation experiments, and genes encoding ESBLs, plasmid-mediated AmpC ß-lactamases, and quinolone resistance determinants identified by polymerase chain reaction. The study included 108 faecal samples (cloacal swabs) from 25 different poultry farms in the Zenica-Doboj Canton, Bosnia and Herzegovina. Of these, 75 (69.4 %) were positive for E. coli, of which 27 were resistant to cefotaxime, amoxicillin, cefazoline, and cefriaxone, and susceptible to imipenem, meropenem, ertapenem, and amikacin. All 27 cefotaxime-resistant isolates were positive in double-disk synergy and combined disk tests. Eighteen isolates transferred cefotaxime resistance to E. coli recipient. Twenty-one isolates were positive for the bla CTX-M-1 cluster genes and seven for bla CTX-M-15. Fourteen were positive for the bla TEM genes. The most frequent plasmid incompatibility group was IncFIB, whereas IncFIA and Inc HI1 were present in only a few isolates. Two different sequence types (STs) were identified: ST117 and ST155. The emergence of ESBL-producing E. coli in farm animals presents a public health threat, as they can colonise the intestine and cause infections in humans.

Pregnancy-Onset Acute Severe Colitis after in vitro Fertilization Embryo Transfer.

Inflammatory bowel diseases (IBD) usually affect women in their fertile years and, therefore, have implications for their fertility and pregnancy. The presence of IBD during pregnancy has been shown to adversely affect pregnancy outcomes, and increased rates of preterm delivery and of spontaneous abortion have been reported. An onset of acute severe colitis in pregnancy has rarely been seen. We present the case of a 42-year-old woman who conceived after 9 attempts of in vitro fertilization and whose pregnancy was the result of a donated oocyte. Shortly after conception, she was diagnosed with severe active ulcerative colitis, and biologic therapy was introduced in the 28th week of pregnancy. Although therapy for IBD in pregnancy is considered safe for most drugs, this was not very well known in 2015. We also consider our case exceptional because we now have a 5-year follow-up of our patient and her child after having begun biologic therapy during late pregnancy.

Extended-spectrum beta-lactamases and plasmid diversity in urinary isolates of Escherichia coli in Croatia: a nation-wide, multicentric, retrospective study.

In recent years, a dramatic increase in the prevalence of Escherichia coli strains producing extended-spectrum ß-lactamases (ESBLs) has been observed - both in the community and in healthcare settings. This multicentric study aimed to characterize ESBLs produced by E. coli isolates causing hospital-onset and community urinary tract infections, as well as to compare their antimicrobial sensitivity patterns, ß-lactamase content and plasmid types. Phenotypic tests for the detection of ESBLs and plasmid-mediated AmpC ß-lactamases were initially pursued, followed by molecular detection of resistance genes, plasmid characterization, genotyping with pulsed-field gel electrophoresis and whole genome sequencing (WGS). The isolates exhibited high level of resistance to expanded-spectrum cephalosporins (ESC) and carried CTX-M (cefotaximase-Munich) or TEM (Temoniera) ß-lactamases. All six representative isolates subjected to WGS belonged to the widespread clone ST131. In conclusion, our study demonstrated dissemination of group 1 CTX-M positive E. coli in different geographic regions of Croatia, but also different components of the health care systems (hospitals, nursing homes and the community) and confirmed the switch from SHV-2 (suphydril variant) and SHV-5 ESBLs to the nation-wide predominance of group 1 CTX-M ß-lactamases. Different plasmids were shown to be associated with the dissemination of blaCTX-M genes in different geographic regions of Croatia.

THE IMPACT OF ANTIEPILEPTIC TREATMENT IN PREGNANCY ON PERINATAL OUTCOME IN CROATIA - A SINGLE-CENTER STUDY.

Pregnancy can alter the natural course of epilepsy and affect pharmacokinetic profile of antiepileptic drugs (AEDs) making therapeutic management more demanding. Since there is no relevant population-based study in Croatia to date, we conducted this research with the aim to observe antiepileptic treatment policy in pregnancy and to determine if the number of AEDs affects pregnancy outcomes. The study included all women with epilepsy with singleton pregnancy exposed to one or more AEDs divided into two groups (group 1: one AED and group 2: more than one AED used). Data were collected retrospectively at the Department of Obstetrics and Gynecology, Zagreb University Hospital Centre, Zagreb, Croatia, and included 153 women from January 2010 to December 2018. Primary outcomes included rates of preterm delivery, major fetal malformations, gestational hypertension, cesarean section rate, and appearance of seizures during pregnancy. We found higher rates of all pregnancy complications examined than in the general population, while comparison of the two study groups yielded significant differences. Preterm labor was detected in 30% of deliveries in polytherapy group compared to 16.6% in monotherapy group (p=0.03). Gestational hypertension was recorded in 20% of women in polytherapy group vs. 4.90% in monotherapy group (p=0.009). There was also a high rate of cesarean deliveries in polytherapy group (27.5%). Seizures during pregnancy occurred in 48.4% of patients in polytherapy group, which was significantly higher than the rate recorded in monotherapy group (p=0.015). In this single-center retrospective study, women with epilepsy using AEDs during pregnancy had a higher rate of gestational hypertension and preterm delivery than the general population of pregnant women. To the best of our knowledge, this is the first study in Croatia observing antiepileptic treatment policy in pregnancy with regards to AED regimen and perinatal outcome.

Fetal-maternal complications and their association with gestational thrombocytopenia.

OBJECTIVES: Thrombocytopenia is defined as a platelet count of < 150 × 109/L. It is a common hematologic abnormality during pregnancy. Evaluation and treatment of gestational thrombocytopenia can be both, expensive and invasive, and may result in an adverse outcome. The aim of our study was to investigate the incidence of perinatal complications in pregnancies complicated with gestational thrombocytopenia and to determine if the severity of maternal gestational thrombocytopenia implicates unfavorable perinatal outcome. MATERIAL AND METHODS: Over a period of three years, we identified 50 patients with gestational thrombocytopenia: 38 with platelet count between 50-100 × 109/L - classified as moderate thrombocytopenia, and 12 with platelet count of < 50 × 109/L - classified as severe thrombocytopenia. Fifty women with normal platelet count constituted the control group. Maternal complications and neonatal outcomes were compared. RESULTS: Neonatal thrombocytopenia occurred more often in pregnancies complicated with gestational thrombocytopenia (p = 0.041). Thrombocytopenia in previous pregnancy seems to be an important predicting factor for disease severity in the current pregnancy (p = 0.01). CONCLUSIONS: Gestational thrombocytopenia, even if severe, is not associated with adverse maternal or neonatal outcome. Moderate neonatal thrombocytopenia is more common in pregnancies complicated with severe gestational thrombocytopenia. The incidence of severe gestational thrombocytopenia is higher in patients with thrombocytopenia in previous pregnancy.

Emergence of multidrug-resistant Proteus mirabilis in a long-term care facility in Croatia.

BACKGROUND: An increased frequency of Proteus mirabilis isolates resistant to expanded-spectrum cephalosporins was observed recently in a long-term care facility in Zagreb (Godan). The aim of this study was the molecular characterization of resistance mechanisms to new cephalosporins in P. mirabilis isolates from this nursing home. METHODS: Thirty-eight isolates collected from 2013-2015 showing reduced susceptibility to ceftazidime were investigated. Antibiotic susceptibilities were determined by broth microdilution method. Inhibitor-based tests were performed to detect extended-spectrum (ESBLs) and AmpC ß-lactamases. AmpC ß-lactamases were characterized by polymerase chain reaction (PCR) followed by sequencing of bla ampC genes. Quinolone resistance determinants (qnr genes) were characterized by PCR. Genotyping of the isolates was performed by repetitive element sequence (rep)-PCR and pulsed-field gel electrophoresis (PFGE). RESULTS: Presence of an AmpC ß-lactamase was confirmed in all isolates by combined-disk test with phenylboronic acid. All isolates were resistant to amoxicillin alone and combined with clavulanate, cefotaxime, ceftriaxone, cefoxitin, and ciprofloxacin; but susceptible to cefepime, imipenem, and meropenem. PCR followed by sequencing using primers targeting bla ampc genes revealed CMY-16 ß-lactamase in all but one strain. Bla cmy-16 was carried by a non-conjugative plasmid which did not belong to any known plasmid-based replicon typing (PBRT) group. Rep-PCR identified one large clone consisting of 15 isolates, three pairs or related isolates, one triplet, and four singletons. PFGE confirmed the clonality of the isolates. CONCLUSIONS: This is the first report of multidrug resistant P. mirabilis in a nursing home in Croatia. Cephalosporin resistance was due to plasmid-mediated AmpC ß-lactamase CMY-16.

[EVOLUTION OF BETA-LACTAM ANTIBIOTIC RESISTANCE IN ENTEROBACTER SPP. IN CROATIA].

Enterobacter spp. develops resistance to expanded-spectrum cephalosporins by induction or derepression of chromosomal AmpC ß-lactamase, or production of extended-spectrum ß-lactamases (ESBLs) or carbapenemases. The aim of the study was to analyze the mechanisms of resistance to expanded-spectrum cephalosporins and the evolution of resistance mechanism during the study period (2008­2011) on a collection of 58 randomly collected Enterobacter spp. strains from three hospital centers in Croatia and Bosnia and Herzegovina during 2008-2010. The antibiotic susceptibility was determined by broth microdilution method according to CLSI. Resistance genes were determined by PCR. Plasmids were characterized by PCR-based replicon typing (PBRT). The hypothesis of the study was that there will be multiple mechanisms of ceftazidime resistance involved, from inducible and derepressed AmpC ß-lactamases to extended-spectrum ß-lactamases and carbapenemases at the end of the study. The isolates from different centers were expected to express different phenotypes and mechanisms of resistance. The study showed the predominance of derepressed AmpC ß-lactamases combined with ESBLs belonging to CTX-M family as a mechanism of resistance to expanded-spectrum cephalosporins. The emergency of MBLs was reported in the last year of the study in University Hospital Center Zagreb. The plasmids encoding ESBLs belonged to different incompatibility groups. This points out to the evolution of ß-lactam resistance in Enterobacter spp. from derepressed AmpC ß-lactamases and ESBL to carbapenemases.

[Hormone replacement therapy and venous thromboembolism]. / Hormonsko nadomjesno lijecenje I venske tromboembolije.

Venous thromboembolism (VTE) is the most important side effect of using hormone replacement therapy (HRT). Biological and epidemiological studies have shown that oral administration of estrogen is associated with an increased risk of VTE compared to transdermal route of administration. Addition of progestogen to estrogen further increases the risk of VTE. Different pharmacological classes of progestogens differently contribute to the risk of VTE. Observational studies observed that the application of micronized progesterone and didrogesteron are safer regarding the risk of VTE compared to other progestins. These results should be further confirmed in the randomized studies. A personal or family history of VTE, existence of hereditary thrombophilia or/and multiple risk factors for VTE represent a strong contraindication to oral HRT use. In such persons the application of transdermal estrogen can be considered after careful individual evaluation of the benefits and risks. Transdermal estrogen should be also the first choice in overweight/obese women requiring HRT.

Maternal group B streptococcus infection, neonatal outcome and the role of preventive strategies.

To determine the newborn infection rate with group B streptococcus infection (GBS) before and after American Academy of Pediatrics Protocol (AAP) implementation in Croatia, antenatal risk factors, neonatal outcome and necessity for introducing national policy for intrapartum chemoprophylaxis. To evaluate the role of intrapartum chemoprophylaxis in preterm labor at < 37 weeks of gestation, premature rupture of membranes at < 37 weeks of gestation, fever during labor, ruptures of membranes > 18 hours before delivery and previous delivery of a sibling with GBS disease. A total of 784 neonates admitted to the Neonatal Intensive Care Unit, from 1 January 2005 to 31 December 2005. 60 (10/1000 live born) developed early-onset infection (EOGBS). The dominant presentation for EOGBS was sepsis (65%), pneumonia (32.2%) and meningitis (3%). Mean gestational age was 34.5 (+/- 5.3) weeks. There were 2 neonatal deaths (3%) in EOGBS, both preterm. EOGBS disease was associated with following risk factors: rupture of the membranes > 12 hours (49.3%), chorioamnionitis (11.9%), status post cerclage (10.4%), diabetes mellitus (4.5%), delivery out of hospital (3%), uroinfection (1.5%). After AAP implementation the incidence of GBS infection decreased from 15/1000 to 10/1000 of live born infants. The mortality from EOGBS dropped from 5% to 3%. The incidence of GBS infection in our study was considerably higher than in all current reports. Reasons for that can be inadequate perinatal screen in some parts of the country and no established policy for intrapartum antibiotic treatment of women with risk factors. Our results documented that intrapartum chemo-prophylaxis for GBS infection significantly reduces perinatal mortality due to neonatal infection and sepsis.

Maternal and fetal outcome in elective versus emergency caesarean section in a developing country.

As the other major European countries, Croatia has also seen a marked increase in the rate of caesarean sections. The aim of this study was to determine the most common reasons for caesarean section, to compare emergency and elective caesarean section in regard to intraoperative and postoperative complications in both mother and child, and to assess the decision-to-delivery interval (DDI) in our clinic in comparison to current recommendations. Analyzing the results of our research we can say that the new-borns in the group with the elective caesarean section had considerably better Apgar index score in the first minute (p = 0.00056) and in the fifth minute (p = 0.054) than the children born in the group with emergency caesarean section. Children from the group with elective caesarean section had also less frequent asphyxia (p = 0.02315) and considerably less frequent resuscitation (p = 0.0143) than the children from the group with emergency caesarean sections. Only 39.73% of the emergency caesarean sections were performed within the "golden standard" period of 30 minutes. Regarding the data from the literature our results are similar with the ones from developed countries and 30 minute current standard seem to be not achievable.