University Hospital Centre Zagreb Research Articles

Pulmonary vein isolation by cryoablation on patients with paroxysmal atrial fibrillation

Aim: Atrial fibrillation is just one of many arrhythmias that affects the cardiac rhythm and the heart as a pump which consequently increases the chance of an embolic insult. Due to the electric stimuli that originate from pulmonary vein ostia and their lumen, an isolation procedure is initiated, mostly by cryoablation. The main goals of this study were to investigate the relationship between measured nadir temperatures during cryoablation of each individual pulmonary vein and to compare the success of first-time cryoablation between left and right pulmonary veins. Participants and methods: The study involved 40 participants who underwent pulmonary vein isolation by cryoablation due to paroxysmal atrial fibrillation, irrespective of gender and age. The procedures were carried out throughout the year 2022 at the University Hospital Centre Zagreb, where the data were collected. All necessary patient data were permanently recorded and saved in a separate cryoconsole used to dictate the entire procedure. Results: Given the 40 participants in the study, a total of 160 pulmonary veins were analyzed. The t-test shows that the left upper pulmonary vein was the most advantageous vein to isolate, and the lower right pulmonary vein was the least advantageous. p-value analysis has also shown significant differences between left and right pulmonary veins, with that difference being lower in value between the left-sided pulmonary veins. Additionally, the chi-squared test confirmed a statistically significant difference between successful cryoablations of left-sided and right-sided pulmonary veins. This has shown that the left-sided pulmonary veins are easier to isolate on first cryoablation, rather than their right-sided counterparts. Conclusion: Pulmonary vein isolation by cryoablation is an excellent proof of incorporating fundamental physical principles in medicinal purposes. This study keeps the doors open for further research into optimal approaches in atrial fibrillation treatment. Therefore, comparing our study with recent publications and literature suggests higher success in isolating left pulmonary veins compared to right pulmonary veins.

Co-occurrence of triple carbapenemase genes, bla VIM-2, bla NDM-1, and bla OXA-48 in Enterobacter hormaechei clinical isolates –first report from Croatia

Two Enterobacter hormaechei isolates harbouring three carbapenemase genes each, were isolated from two patients from different ICUs at University Hospital Centre Zagreb, Croatia, which is to our knowledge, the first report of triple carbapenemase (bla VIM-2, bla NDM-1, and bla OXA-48 ) co-existence in E. hormachei strains and also among Enterobacterales members in Croatia. Antimicrobial susceptibility testing showed susceptibility only to colistin and amikacin. The production of carbapenemases was phenotypically tested by immunochromatographic assay and confirmed by PCR. Detailed analysis by Whole Genome Sequencing (WGS) of short reads by Illumina and long reads by Oxford Nanopore Technologies (ONT) was additionally performed and showed that both isolates belonged to ST200. They were separated by 98 Single Nucleotide Polymorphisms (SNPs) having variations in the number of bla VIM-2 genes on the chromosome, the number of bla NDM-1 genes on the plasmid, non-identical bla NDM-1 plasmids, different plasmid content in general, and only one isolate carried a 94 kb prophage.

Dentist Involvement in the Treatment of Radiation-Induced Oral Mucositis-A Pilot Cross-Sectional Study.

Objectives: Oral mucositis (OM) occurs in more than 95% of patients irradiated in the head and neck area. This paper aims to determine the occurrence and characteristics of OM in patients with head and neck cancer (HNC), as well as the involvement of dentists/oral medicine specialists in treating such patients. Methods: This study was conducted at the Department of Otorhinolaryngology and Department of Oral Medicine, University Hospital Center Zagreb, from April to August 2022, on patients irradiated in the head and neck area. A unique OM questionnaire was created on the incidence, characteristics, oral care, and involvement of dentists in the overall care. Results: Thirty patients filled out the questionnaire. Of the 22 patients who had developed OM, 14 had grade-three OM. Ten patients were treated for OM in line with the instructions of an oral medicine specialist, eight based on the instructions of a specialist responsible for monitoring of the underlying disease, and four were not treated at all. Sixteen patients had not been referred to a dentist before the start of RT. Conclusions: These results showed insufficient care and treatment of OM, as well as insufficient involvement of dentists in the oncology team.

Abstract PO3-05-04: Characteristics and clinical outcome of patients with HR positive HER2 low metastatic breast cancer treated with CDK 4/6 inhibitors

Abstract Introduction Breast cancer (BC) is a disease characterized by significant intra- and intertumoral heterogeneity. Hence, it is not surprising that new subtypes with distinct biological features are being discovered, even among previously well-defined BC groups. Recently, HER2-low BC emerged as a new entity with specific clinical behavior, response to treatment and prognosis. HER2-low is a subset of HER2-negative BC, with HER2 immunohistochemical (IHC) score of 1+ or 2+, without HER2 gene amplification measured by in situ hybridization (ISH). As new therapeutic options become available for HER2-low patients, the best treatment sequence is yet to be determined. Furthermore, it is important to distinguish whether there is a difference in the response to standard treatment lines, such as CDK 4/6 inhibitors in metastatic HR positive BC patients, depending on HER2-low status. Methods A retrospective study of 369 metastatic BC (mBC) cases who started CDK 4/6 inhibitor therapy from January 2018 through December 2022 at University Hospital Centre Zagreb was conducted, with prior Ethics Committee approval. All patients with HR positive HER2 negative mBC, determined by standard IHC and ISH, were included in the research. Patient demographics and clinical presentation, tumor characteristics and treatment information were collected. Progression-free survival (PFS) analysis was done with the final data cut-off date being June 1st, 2023. Type 1 right censoring was performed. The data was analyzed using the Kaplan-Meier method and Cox proportional-hazards regression for clinically relevant covariates (age, line of treatment, de novo metastatic disease, endocrine resistance, liver metastases, and detected PIK3CA mutation). Results Median follow-up was 23 months. Of the 283 patients included, 146 (51.59%) had HER2-low disease. A change in HER2 expression between primary tumor and metastasis was found in 16.96% (N=48) patients. Of them,10.25% (N=29) who were initially HER2-low, were found to be HER2-0 in metastatic disease. Meanwhile, 6.71% (N=19) of patients had a change in HER2 expression from 0 to low upon becoming metastatic. In the HER2-low group, 47.06% (N=45) patients had a PIK3CA mutation as opposed to 33.33% (N=30) in the HER2-0 group. Odds ratio for a PIK3CA mutation in HER2-low patients was 1.86 (95% confidence interval (CI): 1.01-3.43, p-value 0.046). Median PFS in the HER2-low group was 18 months (95% confidence interval (CI): 14-24) versus 23 (95% CI: 18-30) in the HER2-0 group. Using multivariable analysis an adjusted hazard ratio of 1.15 (95% CI:0.84-1.57; p-value 0.389) was calculated. Covariates associated with a statistically significant increased risk of disease progression were a higher line of therapy (HR 1.39, 95% CI 1.36-1.71, p-value 0.002) and the presence of liver metastases (HR 2.17, 95% CI 1.42-3.32, p-value 0.0004). A covariate associated with a statistically significant longer PFS was de novo metastatic disease (HR 0.63, 95% CI 0.41-0.97, p-value 0.034). Conclusion There was a trend toward worse PFS in HER2-low mBC that did not reach statistical significance. HER2-low patients were more likely to harbor PIK3CA mutations than HER2-0 patient group. Longer follow-up and a larger cohort are needed in order to make definitive conclusions. Citation Format: Katarina Čular, Kristina Kanceljak, Ana Magdalena Glas, Dora Gudelj, Marija Križić, Marina Popović, Natalija Dedić Plavetić, Maja Sirotković-Skerlev, Stjepko Pleština, Tajana Silovski. Characteristics and clinical outcome of patients with HR positive HER2 low metastatic breast cancer treated with CDK 4/6 inhibitors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-04.

Abstract PO4-02-09: Clinical outcomes of neoadjuvant chemotherapy in HER2-low early breast cancer

Abstract BACKGROUND: According to immunohistochemistry (IHC) expression of HER2 receptor, breast cancer (BC) can be classified as either IHC score 0, 1+, 2+ or 3+. Until recently, two distinct BC subtypes were recognized depending on the HER2 IHC expression and in situ hybridization (ISH) score: HER2 positive (IHC 3+ or IHC 2+ ISH-amplified) and HER2 negative (IHC 0, 1+ or 2+ ISH negative). More recently a new BC entity termed HER2-low was acknowledged, defined as either HER2 IHC 1+ or 2+ ISH-negative. Given that no treatment benefit was observed in HER2-low group of patients in the pivotal trastuzumab studies, many years had to pass before the discovery of antibody-drug conjugates such as trastuzumab deruxtecan, that led to a significant improvement in the clinical outcome of HER2-low BC, compared to standard therapy options. It is still debated whether HER2-low BC represents a distinct biological subtype. The aim of this study was to determine whether there is an impact of HER2-low status on the effect of neoadjuvant chemotherapy (NACT) and its primary indicator - the rate of the pathologic complete response (pCR). METHODS: A retrospective study of 363 BC cases who received NACT between January 2020 and December 2022 at University Hospital Centre Zagreb, Croatia, was conducted with prior Ethics Committee approval. Histopathological characteristics of tumours available from the hospital information system (BIS), including hormone receptor status (ER, PR), HER2 status and Ki-67 at the time of diagnosis and after neoadjuvant treatment, as well as pCR rates, were analysed. pCR rates were calculated for HER2-low and HER2 0 cases. Chi square test was used to analyse association between pCR rate and HER2 status. RESULTS: After exclusion of HER2 positive BC cases, as well as cases with missing data, a total of 215 patients were included in the analysis. Of those, 101 (47%) were HER2-low, and 114 (53%) were HER2 negative. The majority of patients (N=151, 70.2%) had luminal BC, while 64 (29.8%) patients had triple negative BC (TNBC). In the luminal group, 86 cases (57%) were HER2-low, and 65 (43%) were HER2 0. In the TNBC group, 15 cases (23.4%) were HER2-low and 49 (76.6%) were HER2 0. The rate of pCR among luminal subtypes was 6.2% for HER2-low tumours, and 15.4% for HER2 0 tumours (p=.051559), approaching statistical significance. In the TNBC group, the pCR rate for HER2-low group was 60%, compared to 40% in the HER2 0 group, trending towards, but not reaching statistical significance (p=.191564). CONCLUSION: A trend toward higher pCR rates after neoadjuvant chemotherapy was observed in the luminal HER2 0 group compared to HER2-low luminal BC, almost reaching statistical significance. Interestingly, in TNBC there was a trend towards higher pCR rates among the HER2-low group, although a small number of patients precludes any definitive conclusions. Further trials that include novel targeted therapies are needed, as that might lead to significant changes in therapeutic approach, as well as clinical outcome of HER2-low BC patients. Citation Format: Dora Gudelj, Katarina Čular, Lea Toula, Marija Križić, Marina Popović, Natalija Dedić Plavetić, Ana Kelečić, Gordana Ivanac, Majana Soče, Iva Kukal Gjergjaj, Tajana Silovski. Clinical outcomes of neoadjuvant chemotherapy in HER2-low early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-02-09.

Decision day – A retrospective analysis of COVID-19 patients treated with high PEEP non-invasive ventilation

Background and objectives. This retrospective analysis investigates the effect of high levels of Positive End-Expiratory Pressure (PEEP) during Non-Invasive Ventilation (NIV) in patients with COVID 19 Acute Respiratory Distress Syndrome (ARDS). Materials and methods. In the University Hospital Center Zagreb from October 2021 to February 2022, the study analyzed data from 97 patients who received NIV for acute respiratory support during ICU stay. The effect of NIV on survival, the length of stay in the ICU as well as the duration of the support itself was investigated. Results. Results show that despite low mortality in patients with NIV support, mortality is quite high in patients who required intubation. There is also a divergence of the respiratory support level parameter after the 3rd day on NIV, which suggests that moment as pivotal for assessing the continuation of NIV support. Conclusions. The results show that high level PEEP is a viable option for starting respiratory support in ARDS, but also the importance of timely assessment to optimize patient outcomes.

Impact of anthracycline-based chemotherapy on RB1 gene methylation in peripheral blood leukocytes and biomarkers of oxidative stress and inflammation in sarcoma patients.

We investigated the impact of anthracycline-based chemotherapy on methylation status of RB1 gene in peripheral blood leukocytes together with parameters of oxidative stress and inflammation in sarcoma patients. Blood samples were collected from 51 consecutive newly diagnosed sarcoma patients admitted to University Hospital Center Zagreb (Zagreb, Croatia) for first-line chemotherapy before the first cycle and post-chemotherapy. Methylation and copy number variation (CNV) of leukocyte RB1 gene were assessed using MS-MLPA probes. In addition, in blood samples, parameters of oxidative stress (ROS, MDA, SOD, and GSH) and inflammation (CRP, WBC, and NBC) were followed. In pre-chemotherapy samples, no CNVs and aberrant methylation of CpG106 promoter region of RB1 gene were detected; however, one patient had hypermethylation (by approximately 10%) of imprinted locus CpG85 in intron 2 of RB1 gene. In addition, a very good correlation of the tumor burden and CRP and tumor burden and GSH was found. The anthracycline-based chemotherapy reverts methylation of RB1 gene-imprinted locus CpG85 to normal level. Moreover, inflammation and oxidative stress parameters such as CRP, WBC, ROS, and MDA were significantly decreased in post-chemotherapy samples. This single-centered study on a cohort of consecutive sarcoma patients indicates that sarcoma patients can have aberrant germline DNA methylation and confirms the relationship of tumor burden with inflammation and oxidative stress. The applied chemotherapy protocols reverted RB1 gene methylation to normal level and decreased the level of inflammation and oxidative damage, thus indicating chemotherapy benefit to the patient's health status.

Bacteriuria in Paediatric Oncology Patients: Clinical Features, Distribution and Antimicrobial Susceptibility of Bacterial Pathogens at University Hospital Centre Zagreb, Croatia over a 4-Year Period.

Bacteriuria in paediatric oncology patients have not been well studied. This retrospective study analysed clinical features, distribution and antimicrobial susceptibility of bacterial pathogens cultured from urine in paediatric oncology patients over a 4-year period (2019-2022). A total of 143 episodes of bacteriuria were documented in 74 patients. Neutropenia was present in 17.5% (25/143), symptoms in 25.9% (37/143) and urinary catheter in 7.0% (10/143) episodes. Symptomatic bacteriuria episodes were statistically significantly more frequent in patients with neutropenia (p = 0.0232). The most common bacterial pathogens were Escherichia coli (n = 49; 32.2%), Klebsiella spp. (n = 34; 22.4%), Pseudomonas aeruginosa (n = 22; 14.5%) and Enterococcus spp. (n = 21; 13.8%). Extended-spectrum β-lactamases-producing (ESBL) Enterobacterales were found in 11 episodes (11/143; 7.7%) with the highest proportion among Klebsiella pneumoniae isolates (n = 7/34; 20.6%). No carbapenem-resistant Enterobacterales, multidrug-resistant P. aeruginosa or vancomycin-resistant Enterococcus spp. were found. The most important novelties are demonstrating P. aeruginosa as one of the prominent bacteriuria pathogens in this patient population, presence of ESBL isolates and carbapenem-resistant P. aeruginosa later during hospitalization highlights the need for appropriate antimicrobial treatment. However, because of the small number of symptomatic patients, further studies are needed to clarify the importance of including urine culture in the diagnostic process in patients with febrile neutropenia.

Bloodstream Infections in Pediatric Oncology Patients: Bacterial Pathogen Distribution and Antimicrobial Susceptibility at the University Hospital Centre Zagreb, Croatia-A 5-Year Analysis.

The epidemiology of bacterial pathogens causing bloodstream infections (BSIs) in pediatric hematology/oncology patients is changing and resistance to antimicrobial agents is globally spread. We retrospectively assessed demographic, clinical, and microbiologic data of BSIs during a 5-year period at a pediatric hematology/oncology unit from January 1, 2017, to December 31, 2021, at the University Hospital Centre Zagreb, Zagreb, Croatia. In 66 pediatric patients with malignancies, 93 BSI episodes were registered and 97 bacterial isolates were cultured. The Gram-positive versus Gram-negative ratio was 67 (69.1%) versus 30 (30.9%). Coagulase-negative staphylococci (48; 49.6%) were the most frequent isolates, followed by Enterobacterales (17; 17.5%) and Staphylococcus aureus (6; 6.2%). Multidrug resistance isolates included extended spectrum β-lactamase producers (n=3). Resistance rates to piperacillin/tazobactam, cefepime, and meropenem in Gram-negative isolates were 15.4%, 14.3%, and 0.0%, respectively. Gram-positive bacteria are the most common cause of BSI in our patients. Resistance rates to piperacillin/tazobactam and cefepime in Gram-negative isolates make meropenem a better choice for empirical antimicrobial treatment. As national and hospital data may differ, the surveillance of pathogen distribution and antimicrobial susceptibility in pediatric hematology/oncology wards is necessary to adjust empirical treatment accordingly.

A Multicentric Verification of Hereditary and Acquired Thrombophilia Coagulation Assays

Aims: With an ever-growing number of patients being admitted to our University Hospital Sveti Duh (Zagreb, Croatia), there was a need to positively respond to clinicians' demands about hereditary and acquired thrombophilia testing.
 Study Design: An extensive and multicentric verification of coagulation assays included in thrombophilia testing was performed on the BCS XP coagulation analyzer (Siemens Healthineers, Marburg, Germany): antithrombin activity (AT) (Innovance Antithrombin), protein C activity (PC) (Berichrom Protein C), protein S activity (PS) (Protein S Ac), free protein S antigen (free PS:Ag) (Innovance Free PS Ag), activated protein C resistance (APCR) (ProC Ac R and ProC Global + Coagulation Factor V Deficient Plasma), lupus anticoagulant (LA) screening (LA1 and activated partial thromboplastin time by using Dade Actin FSL as reagent) and confirmation test (LA2), factor VIII activity (FVIII) (Dade Actin FS and coagulation FVIII Deficient Plasma).
 Place and Duration of Study: Department of Medical Laboratory Diagnostics, University Hospital Sveti Duh, Zagreb, Croatia, between January 2020 and December 2021.
 Methodology: Verification protocol included: the precision study (CLSI EP15-A3 protocol), trueness estimation by comparison of seventy remnant plasma samples with two large Croatian hospital laboratories with established thrombophilia testing, and verification of reference intervals and cut-off values (CLSI EP28-A3C and CLSI HA-60 guidelines).
 Results: All of the obtained imprecision CVs were within the manufacturer's claims (<5/10/15%). While the observed bias for PC (+1.9%) was within the EFLM performance specifications (6.7%), the average bias for AT was higher than acceptance criteria (+10.8% vs 3.2% allowed). P&B regression revealed a significant positive proportional difference (slope=1.14). Comparison of PS activity yielded a high negative bias (-33.4%) that exceeded the acceptance criteria of 8.1%. Regarding LA testing, the diagnostic accuracy was 99% when compared to Sestre milosrdnice UHC (N=70) and 95% when compared to University Hospital Centre Zagreb (N=19). All manufacturer's reference intervals and cut-offs were verified.
 Conclusion: The verification study confirmed all manufacturer's claims, except for PS which has been replaced with free PS:Ag determinations.

Exploring adherence in patients with advanced breast cancer: focus on CDK4/6 inhibitors.

Treatment adherence is crucial for optimal outcomes in advanced breast cancer, but can be challenging due to various factors, i.e. patients' attitudes and behavior upon diagnosis, and complex therapies with high adverse effect rates. Our aim was to explore the adherence to oral anticancer medications (OAM) in women with advanced breast cancer, focusing on cyclin-dependent kinase 4 and 6 inhibitors (CDKI), and identify factors associated with the adherence. We conducted a cross-sectional study at the University Hospital Centre Zagreb, Croatia, involving women with stage IV advanced breast cancer receiving OAM. Data collection included a questionnaire assessing socio-demographic and clinical information, Beck Depression Inventory-II for depressive symptoms, Medication Adherence Report Scale (MARS-5) for adherence to OAM, and Beliefs about Medicines Questionnaire. Plasma concentrations of CDKI were confirmed by LC-MS/MS in three randomly selected participants. A total of 89 women were included. The most prescribed OAMs were anti-estrogen (71.3 %) and CDKI (60.9 %). MARS-5 scores (mean: 24.1 ± 1.6) correlated with CDKI plasma concentrations. Forgetfulness was the primary reason for non-adherence (25.9 %). Women receiving CDKI (p = 0.018), without depressive symptomatology (p = 0.043), and with more positive beliefs about medicines were more adherent (p < 0.05). This study enhances understanding of medication adherence in advanced breast cancer and identifies influential factors.

Challenges of the COVID-19 pandemic – perfusionists experience at University Hospital Centre Zagreb

Challenges of the COVID-19 pandemic – perfusionists experience at University Hospital Centre Zagreb

Transplantation of cardiovascular tissue from University Hospital Centre Zagreb tissue banks

Transplantation of cardiovascular tissue from University Hospital Centre Zagreb tissue banks

Monocyte related haematological indices in acute exacerbations of COPD - a new biomarker?

C-reactive protein (CRP) and leukocyte count are standard tools for recognising inflammation in COPD patients. This study aimed to find if there is a pattern in monocyte related haematological indices - monocyte to neutrophil ratio (MNR) and monocyte to lymphocyte ratio (MLR) - which could be helpful in differentiating COPD patients in need for hospitalization due to acute exacerbation of COPD or differentiating frequent COPD exacerbators from non-frequent COPD exacerbators. The study included 119 patients with COPD and 35 control subjects, recruited at the Clinic for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, Croatia. Complete blood count was performed on Sysmex XN-1000, CRP on Cobas c501, and Fbg on BCS XP analyser. Data were analysed with MedCalc statistical software. The COPD patients were divided into three groups - frequent exacerbators (FE), non-frequent exacerbators (NFE), patients hospitalized for acute COPD exacerbations (HAE) and the control group were healthy smokers (HS). A statistically significant difference was found in the values of MNR while comparing these groups of patients: FE vs HAE (p<0.000), NFE vs HAE (p<0.000) and HS vs HAE (p<0.001); and for the values of MLR: FE vs HAE (p<0.022), NFE vs HAE (p<0.000) and HS vs HAE (p<0.000). As MLR and MNR have shown the statistical difference comparing the group of HAE to NFE, FE and HS, MLR and MNR could be valuable and available markers of acute COPD exacerbations and need for hospitalization.

The Transcatheter Mitral Valve Replacement program at the University Hospital Centre Zagreb – a case series

The Transcatheter Mitral Valve Replacement program at the University Hospital Centre Zagreb – a case series

Senhance robotic radical prostatectomy: A single-centre, 3-year experience.

Senhance Surgical System is a novel robotic platform used in University Hospital Centre Zagreb since February 2019. In this study, we present our 3-year experience with this platform. Data were prospectively collected for 200 patients who underwent extraperitoneal robotic radical prostatectomy (RRP) from May 2019 to March 2022. The median age of the patients was 65years, and the prostate-specific antigen was 6.9ng/mL. Clinically, most of the patients had T1c stage. The estimated blood loss was 250mL, and there were 6 conversions to laparoscopic and 2 to open prostatectomy. There were 15 early postoperative complications, 11 Clavien-Dindo classification grade I, 3 grade II and 1 grade IV. Functional outcomes in the first 150 patients: 140 patients (93.3%) had good urinary control. Thirteen patients underwent additional oncological treatment. RRP performed with the Senhance robotic platform is a feasible and safe procedure with good initial results.

Genetic and Clinical Characterization of Patients with HNF1B-Related MODY in Croatia.

Mutation of the gene encoding Hepatocyte Nuclear transcription Factor-1 Beta (HNF1B) causes a rare monogenetic subtype of Maturity-Onset Diabetes of the Young (MODY). HNF1B-related MODY results in the dysfunction of multiple organ systems. However, genetic analysis enables personalized medicine for patients and families. To understand the clinical characteristics and explore the gene mutations in Croatian patients. This was a retrospective observational study of individuals (and their relatives) who were, due to the clinical suspicion of MODY, referred to the Department of Laboratory Diagnostics at the University Hospital Centre Zagreb for genetic testing. A total of 118 participants, 56% females, were screened. Seven patients (three females) from five families were identified to have HNF1B-related MODY. The median age at diagnosis was 31 (11-45) years, the median c-peptide was 0.8 (0.55-1.39) nmol/L, the median HbA1c was 9.1 (5.7-18.4)%, and the median BMI was 22.9 kg/m2 (17-24.6). Patients had a variety of clinical manifestations; kidney disease was not as frequent as liver lesions, neuropsychiatric symptoms, hyperlipidemia, hyperuricemia, and hypomagnesemia. We identified two new pathogenic mutations (c.1006C > G protein p.His336Asp on exon 4 and c.1373T > G p protein Val458Gly on exon 7). In a study involving Croatian patients, new genetic (two previously unknown mutations) and clinical (diverse range of clinical presentations) aspects of HNF1B-related MODY were found.

Significance of immunohematologic testing in mother and newborn ABO incompatibility.

The aim of this study was to define risk factors for jaundice and anemia in newborns with a positive direct antiglobulin test (DAT) and/or with an incompatible crossmatch due to ABO incompatibility between mother and newborn. ABO incompatibility has become a more significant cause of hemolytic disease of the fetus and newborn since the introduction of effective anti-D prophylaxis. The condition is common and, if clinically significant at all, causes only mild jaundice, which can be treated with phototherapy (PT). However, rare and serious presentations, requiring transfusion therapy, have been noted. Clinical, laboratory, and immunohematologic data were collected retrospectively from medical records of ABO-incompatible newborns and their mothers over a 5-year period (2016-2020) from University Hospital Centre Zagreb. Two groups of newborns were compared: those who needed medical intervention because of hyperbilirubinemia or anemia and those who did not. Within the group of newborns requiring intervention, we also compared those with A and B blood groups. Over the 5-year period, 72 of 184 (39%) newborns required treatment. The treatment was PT in 71 (38%) newborns and erythrocyte transfusion in 2 (1%). In 112 (61%) newborns, ABO incompatibility was an accidental finding while performing blood group typing; these newborns did not require any therapy. In conclusion, we found a statistical, but not clinically significant, difference between the groups of treated and untreated newborns, related to the mode of delivery and DAT positivity within hours of delivery. There were no statistically significant differences in characteristics between the groups of treated newborns, except for two newborns with blood group A who received erythrocyte transfusions.

Influence of ovarian function supression on quality of life in breast cancer survivors during adjuvant endocrine therapy.

560 Background: Adding ovarian function suppression to adjuvant endocrine therapy (AET) lowers the disease recurrence rates among premenopausal women with hormone receptor-positive (HR+) early breast cancer (EBC). However, a detrimental effect on endocrine symptoms burden (ESB) is expected. Therefore, this study aimed to investigate differences in Quality of life (QoL) and endocrine symptoms in premenopausal women prescribed AET, with/without gonadotropin-releasing hormone agonist (GnRH). Methods: This cross-sectional study included women, with HR+ EBC, premenopausal at diagnosis, treated with AET for more than 3 months, with and without GnRH. The research was conducted with institutional Ethics Committee approval at the University Hospital Centre Zagreb, General Hospital Šibenik, and with online survey. A validated instrument, the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES), was used. The collected data were analysed using SPSS v. 29 (p≤0.05). Results: Overall, 314 eligible BC survivors with a median age of 45 years (22-65) and a median duration of AET of 2 years (3 months -12 years) responded to FACT-ES and were included in the analysis. Altogether 45.2% (n=142) of participants were prescribed tamoxifen (TAM), 25.8% (n=81) GnRH+TAM, and 29% (n=91) GnRH+aromatase inhibitor (AI); exemestane (9%), letrozole (13.6%) and anastrozole (6.4%). The total QoL (FACT-ES) score was higher in patients treated with TAM as opposed to patients treated with AI+GnRH (p=0.01). Adding GnRH to TAM did not significantly change QoL when compared to TAM alone or AI+GnRH. In addition, patients on AI+GnRH had lower physical well-being (PWB) score than patients on TAM+GnRH (p=0.03) or TAM alone (p=0.05) and lower endocrine subscale score (ESS-19) than patients on TAM (p=0.01), indicating more endocrine symptoms in premenopausal women treated with AI+GnRH. Among patients treated with AI+GnRH letrozole had lower PWB (p=0.03) and ESS-19 score (p=0.01) than exemestane. Conclusions: This study showed that GnRH+AI in premenopausal women with HR+ EBC results in greater ESB and lower QoL compared to patients treated with TAM or GnRH+TAM. Therefore, interventions helping decrease the ESB in patients treated with AI+GnRH should be explored and developed to help patients adhere to and persist in AET. [Table: see text]

Clinical characteristics and outcome of PIK3CA mutated hormone receptor positive (HR+), human epidermal growth factor 2 negative (HER2-), advanced breast cancer (BC) treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i): Real world data.

e13078 Background: BC is the most common malignant disease and leading cancer-related cause of death in women. Despite significant achievements in the treatment, advanced BC (aBC) is still an incurable disease. HR+/HER2- subtype accounts for 70% of all BC. One of the most common mutations in BC is the PIK3CA gene mutation which can induce endocrine and chemo- resistance. In early BC, patients (pts) with PIK3CA mutations mostly have better, but in aBC worse prognosis. Standard first-line treatment for HR+/HER2- aBC is a combination of CDK4/6i and endocrine therapy. PIK3CA status is most often assessed in this group of pts and combination of alpelisib - PIK3CA inhibitor and fulvestrant is second-line treatment option in PIK3CA mutated pts. Methods: Medical records of HR+/HER2- aBC pts who started CDK4/6i therapy between 01.08.2018. and 01.10.2020. were analyzed with prior University Hospital Center Zagreb Ethics Committee approval. Demographics, tumor characteristics, clinical presentation and therapy information were collected. Molecular analysis of PIK3CA mutations was performed on tumor tissue samples. Time to treatment failure (TTF) was analyzed using the Kaplan-Meier method and the data cut-off was 31.12.2022. Results: Of the 103 pts with determined PIK3CA status, 45 (43.7%) had a detectable mutation. Median follow-up was 35 months. CDK4/6i were first line therapy in 31 (68.9%) pts with and 29 (50%) pts without PIK3CA mutation. Endocrine resistance, de novo metastatic disease and bone marrow infiltration were more common in PIK3CA mutated subgroup. The incidence of visceral metastases was similar in both groups, whereas liver metastases were more common in the unmutated group. Disease progression was observed in 69 (67%) pts, 28 (40.6%) of whom were PIK3CA mutated. Median TTF in mutated subgroup was 24 months (95% CI 21-33) and 25 months in unmutated subgroup (95% CI 19-36). During the follow-up period, 35 (34%) pts died, 14 (40%) of whom were PIK3CA mutated. Odds ratios in pts with a PIK3CA mutation. Conclusions: There was no relevant difference in TTF between two groups. However, PIK3CA mutated subgroup had more aggressive clinical features - more often presented with bone marrow infiltration and de novo aBC, statistically relevant OR 5.158 and 2.323 respectively, which is related to lower quality of life and highlights the importance of treatment improvement for this subgroup of pts. [Table: see text]