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Background : In recent years, cardiac dysfunction in childhood cancer survivors has become an important issue. Studies are focusing on identifying means for the early identification of patients at risk. Considering this, our study aims to investigate 24-hour Holter electrocardiogram (ECG) repolarization changes throughout doxorubicin (DOX) and cyclophosphamide (CPM) administration in pediatric patients treated for acute lymphoblastic leukemia (ALL). Methods : This was an investigator-driven, single-center, prospective, observational study. Enrolled children had a baseline bedside ECG examination performed before starting chemotherapy (T0). Serial Holter ECG examinations were conducted at three moments during their treatment protocol: day 8 (T1), day 29 (T2), and day 36 (T3). This study evaluated several ECG repolarization parameters, such as the QT interval, corrected QT interval (QTc), and QTc dispersion, as well as ST segment variations. Results : We evaluated 37 children diagnosed with ALL. The T0 examination revealed that over a third of patients had a resting heart rate (HR) outside the normal range for their age and sex. During chemotherapy, statistically significant increases in both HR as well as QT and QTc dispersion values were noticed, especially during the first DOX administration. What is more, a significant increase in the percentage of patients with ST segment depression from T1 to T2 and T3 was noticed. Rhythm disturbances were rare in the study population, with only a few patients presenting ventricular or supraventricular extrasystoles. Conclusions : This study reveals silent repolarization changes occurring early during anticancer treatment in children treated for ALL. These findings could aid in a better understanding of the cardiac toxicity mechanism, and they could potentially improve cardiac risk stratification for oncologic patients. Because of the small number of patients, our results need to be validated by larger studies.

Wolf-Parkinson-White (WPW) syndrome is a disorder characterized by the presence of at least one accessory pathway (AP) that can predispose people to atrial/ventricular tachyarrhythmias and even sudden cardiac death. It is the second most common cause of paroxysmal supraventricular tachycardia in most parts of the world, affecting about 0.1-0.3% of the general population. Most patients with WPW syndrome have normal anatomy, but it may be associated with concomitant congenital heart disease or systemic diseases. Although many individuals are asymptomatic, during supraventricular arrhythmia episodes, they may experience severe symptoms, including syncope or even sudden cardiac death (mainly due to pre-excited atrial fibrillation over rapidly conducting AP). In addition to arrhythmia-related symptoms, for some specific locations of the APs with overt anterograde conduction, there might be a reduction in exercise capacity mediated by a reduction in LV systolic performance due to anomalous LV depolarization. Although it is typically diagnosed through electrocardiography (ECG), additional tests are necessary for risk assessment. Management of WPW syndrome may be quite challenging and can vary from only acknowledging the presence of the accessory pathway to pharmacological treatment or radiofrequency ablation. Early diagnosis, risk assessment, and appropriate treatment are critical steps in the management of WPW syndrome, aiming to improve the quality of life and reduce the risk of life-threatening arrhythmias.

Acute myocardial infarction is one of the most serious cardiovascular pathologies, impacting patients' long-term outcomes and health systems worldwide. Significant effort is directed toward the development of biosensing technologies, which are able to efficiently and accurately detect an early rise of cardiac troponin levels, the gold standard in detecting myocardial injury. In this context, this work aims to develop a microfluidic plasmonic chip for the fast and accurate real-time detection of the cardiac troponin I biomarker (cTnI) via three complementary detection techniques using portable equipment. Furthermore, the study focuses on providing a better understanding of the thermoplasmonic biosensing mechanism taking advantage of the intrinsic photothermal properties of gold nanoparticles. Specifically, a plasmonic nanoplatform based on immobilized gold nanobipyramids was fabricated, exhibiting optical and thermoplasmonic properties that promote, based on a sandwich-like immunoassay, the "proof-of-concept" multimodal detection of cTnI via localized surface plasmon resonance, surface enhanced Raman spectroscopy and thermoplasmonic effects under simulated conditions. Furthermore, after the integration of the plasmonic nanoplatform in a microfluidic channel, the determination of cTnI in 16 real plasma samples was successfully realized via thermoplasmonic detection. The results are compared with a conventional high-sensitivity enzyme-linked immunosorbent clinical assay (ELISA), showing high sensitivity (75%) and specificity (100%) as well as fast response features (5 minutes). Thus, the proposed portable and miniaturized microfluidic plasmonic chip is successfully validated for clinical applications and transferred to clinical settings for the early diagnosis of cardiac diseases, leading towards the progress of personalized medicine.

The implementation of metal enhanced fluorescence (MEF) as an efficient detection tool, especially in the near-infrared region of the electromagnetic spectrum, is a rather new direction for diagnostic analytical technologies. In this context, we propose a novel microfluidic plasmonic design based on paper for efficient MEF detection of the "proof-of-concept" biotin-streptavidin recognition interaction. Our design made use of the benefits of gold nanobipyramids (AuBPs), considering the strong enhanced electromagnetic field present at their sharp tips, and filter paper to operate as a natural microfluidic channel due to excellent wicking abilities. The calligraphed plasmonic paper, obtained using a commercial pen filled with AuBPs, was integrated in a robust sandwich optically transparent polydimethylsiloxane chip, exhibiting portability and flexibility while preserving the chip's properties. To place the Alexa 680 fluorophore at an optimal distance from the nanobipyramid substrate, the human IgG-anti-IgG-conjugated biotin sandwich reaction was employed. Thus, upon the capture of Alexa 680-conjugated streptavidin by the biotinylated system, a 1.3-fold average enhancement of the fluorophore's emission was determined by bulk fluorescence measurements. However, the local enhancement factor was considerably higher with values spanning from 5 to 6.3, as proven by mapping the fluorescence emission under both re-scan microscopy and fluorescence lifetime imaging, endorsing the proposed chip's feasibility for bulk MEF biosensing as well as high-resolution MEF bioimaging. Finally, the versatility of our chip was demonstrated by adapting the biosensing protocol for cardiac troponin I biomarker detection, validated using 10 plasma samples collected from pediatric patients and corroborated with a conventional ELISA assay.

Anthracycline treatments are known to cause cardiotoxic long-term side effects in cancer survivors. Recently, a decrease in heart rate variability (HRV) has been identified in these patients, signaling autonomic dysfunction and altered cardiac fitness. This study aimed at evaluating changes in HRV in children treated with anthracyclines. A total of 35 pediatric patients with acute lymphoblastic leukemia were evaluated by means of a 24 h Holter ECG, at baseline and after reaching half the total cumulative dose of doxorubicin equivalent (120 mg/m 2 ). Parameters of HRV were assessed, as well as any arrhythmic episodes, bradycardia and tachycardia percentages. The results showed a significant decrease in both time-domain and frequency-domain HRV parameters, following anthracycline treatment. The low-frequency (LF) to high-frequency (HF) parameters' ratio also displayed a significant difference ( p = 0.035), suggestive of early cardiac autonomic dysfunction. Of note, none of the patients presented symptoms of heart disease or elevated troponins, and only two patients presented echocardiographic signs of diastolic dysfunction. The present study showed that cardiac autonomic nervous system regulation is compromised in children treated with anthracyclines even before reaching the total cumulative dose. Therefore, HRV parameters could be the first indicators of subclinical cardiac toxicity, making Holter ECG monitoring of the oncological patient a necessity.

Background/aim: Catastrophic antiphospholipid syndrome (CAPS) may be the first manifestation ("de novo") of antiphospholipid syndrome (APS) or a complication in the clinical course of patients known to have this syndrome. Approximately 40% of patients had an associated autoimmune disease, mainly, systemic lupus erythematosus (SLE). The trigger can be one of the following: infections, surgical interventions, neoplasms, pregnancy, discontinuation of anticoagulant treatment, and others. CAPS is a medical emergency in which early identification and prompt initiation of aggressive therapy is extremely important. According to the Guidelines for the use of Therapeutic Apheresis in Clinical Practice developed by the American Society for Apheresis (ASFA), last updated in April 2023, in CAPS, the indication for therapeutic plasma exchange (TPE) is category I, grade 2C., Case Report: We present a case of probable CAPS secondary to systemic lupus erythematosus (SLE) in an elderly patient in whom clinical and biological improvement was achieved through a multidisciplinary approach and prompt initiation of TPE. Because TPE is considered first-line therapy in CAPS, we initiated the procedure as soon as the attending rheumatologist raised this suspicion. Four plasmapheresis sessions were performed in the Intensive Care Unit. We used TPE by membrane filtration. Following the therapeutic intervention with TPE, corticotherapy (Solumedrol in puls-therapy), cyclophosphamide and anticoagulant treatment, the evolution was favourable, with clinical and biological improvement., Conclusion: The prompt initiation of TPE, because of the suspicion of CAPS, increases the chances of a favourable evolution., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Acute myocardial infarction (AMI) is considered as one of the main causes of death, threating human lives for decades. Currently, its diagnosis relies on electrocardiography (ECG), which has been proven to be insufficient. In this context, the efficient detection of cardiac biomarkers was proposed to overcome the limitations of ECG. In particular, the measurement of troponins, specifically cardiac troponin I (cTnI) and cardiac troponin T (cTnT), has proven to be superior in terms of sensitivity and specificity in the diagnosis of myocardial damage. As one of the most life-threatening conditions, specific and sensitive investigation methods that are fast, universally available, and cost-efficient to allow for early initiation of evidence-based, living-saving treatment are desired. In this review, we aim to present and discuss the major breakthroughs made in the development of cTnI and cTnT specific biosensor designs and analytical tools, highlighting the achieved progress as well as the remaining challenges to reach the technological goal of simple, specific, cheap, and portable testing chips for the rapid and efficient on-site detection of cardiac cTnI/cTnT biomarkers in order to diagnose and treat cardiovascular diseases at an incipient stage.

Background/aim: Convalescent plasma collected from COVID-19 survivors contains antibodies against receptor binding domains with potent antiviral activity. The use of this therapy for COVID-19 is still under investigation, as the pathophysiological and immunological mechanisms responsible for the evolution of the disease have not been fully identified., Patients and Methods: In this retrospective observational study, we included all patients with a confirmed SARS-Cov-2 infection based on positive RT-PCR testing, who received convalescent plasma treatment in addition to standard therapy, between 17.05.2020 and 27.11.2020, following hospitalization in the Anaesthesia and Intensive Care Unit of the Sibiu County Emergency Clinical Hospital, Romania., Results: Convalescent plasma therapy of patients with SARS-Cov-2 infection and severe forms of the disease (requiring only high-flow oxygen therapy or non-invasive ventilation) significantly improved inflammatory markers (CRP, fibrinogen) and ventilatory parameters (SaO2, paO2, paO2/FiO2) reducing the need of supplemental oxygen delivery (p<0.05). Other factors that had a significant influence on the outcome were age and comorbidity., Conclusion: Inflammatory markers and ventilatory parameters were significantly improved and the need of supplemental oxygen delivery was reduced in COVID-19 patients treated with convalescent plasma., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The use of high-sensitivity cardiac troponin (hs-cTn) assays has become part of the daily practice in most of the laboratories worldwide in the initial evaluation of the typical chest pain. Due to their early surge, the use of hs-cTn may reduce the time needed to recognise myocardial infarctions (MI), which is vital for the patients presenting in the emergency departments for chest pain. The latest European Society of Cardiology Guidelines did not only recognise their central role in the diagnosis algorithm but also recommended their use for rapid rule-in/rule-out of MI. High-sensitivity cardiac troponins are also powerful prognostic markers for long-term events and mortality, not only in a wide spectrum of other cardiovascular diseases (CVD) but also in several non-CVD pathologies. Moreover, these biomarkers became a powerful tool in special populations, such as paediatric patients and, most recently, COVID-19 patients. Although highly investigated, the assessment and interpretation of the hs-cTn changes are still challenging in the patients with basal elevation such as CKD or critically ill patients. Moreover, there are still various analytical characteristics not completely understood, such as circadian or sex variability, with major clinical implications. In this context, the present review focuses on summarizing the most recent research in the current use of hs-cTn, with a main consideration for its role in the diagnosis of MI but also its prognostic value. We have also carefully selected the most important studies regarding the challenges faced by clinicians from different specialties in the correct interpretation of this biomarker. Moreover, future perspectives have been proposed and analysed, as more research and cross-disciplinary collaboration are necessary to improve their performance., Competing Interests: All authors declare that they have no conflict of interest., (Copyright © 2022 Diana Raluca Lazar et al.)

Background: In 2018 and 2019, paediatric vision screening was implemented in Cluj County, Romania, where universal paediatric vision screening does not yet exist. We report on the preparation and the first year of implementation., Methods: Objectives, target population and screening protocol were defined. In cities, children were screened by kindergarten nurses. In rural areas, kindergartens have no nurses and children were screened by family doctors' nurses, initially at the doctors' offices, later also in rural kindergartens. CME-accredited training courses and treatment pathways were organised. Implementation was assessed through on-site observations, interviews, questionnaires and analysis of screening results of referred children., Results: Out of 12,795 eligible four- and five-year-old children, 7,876 were screened in 2018. In the cities, kindergarten nurses screened most children without difficulties. In Cluj-Napoca 1.62x the average annual birth rate was screened and in the small cities 1.64x. In the rural areas, however, nurses of family doctors screened only 0.49x the birth rate. In 51 out of 75 rural communes, no screening took place in the first year. Of 118 rural family doctors' nurses, 51 had followed the course and 26 screened children. They screened only 41 children per nurse, on average, as compared to 80 in the small cities and 100 in Cluj-Napoca. Screening at rural kindergartens met with limited success. These are attended by few children because of low population density, parents working abroad or children being kept at home in case of bad weather and road conditions., Conclusions: Three times fewer children were screened in rural areas as compared to urban areas. Kindergartens in rural areas are too small to employ nurses and family doctors' nurses do not have easy access to many children and have competing healthcare priorities: there are 1.5x as many family doctors in urban areas as compared to rural areas. For nationwide scaling-up of vision screening, nurses should be enabled to screen a sufficient number of children in rural areas., (© 2021. The Author(s).)

It is a new and exciting time for acute lymphoblastic leukemia (ALL). While nearly 50 years ago, only one in nine children with ALL survived with chemotherapy, nowadays nearly 90% of children have a chance of long-term survival. Adults with ALL, as well as the special category of adolescents and young adult (AYA) patients, are catching up with the new developments seen in children, but still their prognosis is much worse. A plethora of factors are regarded as responsible for the differences in treatment response, such as age, ethnicity, disease biology, treatment regimens and toxicities, drug tolerance and resistance, minimal residual disease evaluation, hematopoietic stem cell transplantation timing and socio-economic factors. Taking these factors into account, bringing pediatric-like protocols to adult patient management and incorporating new agents into frontline treatment could be the key to improve the survival rates in adults and AYA.

Purpose: The outbreak of COVID-19 pandemic has changed the provision of medical services worldwide. We assessed the impact of the pandemic on the oncological patients' visits to a tertiary cancer centre., Methods: We analysed registrations from the administrative data system of in- and outpatients in all of the departments of the Cluj-Napoca Oncology Institute, during March-October 2020, and compared to the same 7-month period of the previous year., Results: The decrease during March-October 2020 was 40.2% for new referrals overall (with the most significant drop in April, of 80%), 52.5% for medical oncology inpatients, 39% for paediatric oncology department inpatients, 69% for radiotherapy inpatients, 34.9% for surgical interventions and 31% decrease of issued pathology reports. The decrease was less important for outpatients: only 10% for medical oncology outpatient department, 33% for radiotherapy and 27% for breast cancer unit outpatients. Imaging investigations were only slightly influenced by the pandemic (reduction of 5% for MRI scans, 19% for mammograms,whereas performed CT scans were even more after the outbreak of COVID-19)., Conclusion: Our results show a decrease in the number of patients during the period after the outbreak of the COVID-19 pandemic, more for inpatients and less significant for outpatient departments, probably because of the internal circuits reorganization but also because of health care measures taken nationally and locally to limit the spread of the pandemic.

Colorectal cancer remains one of the most frequent malignancies (third place at both genders) worldwide in the last decade, owing to significant changes in modern dietary habits. Approximately half of the patients develop metastases during the course of their disease. The available therapeutic armamentarium is constantly evolving, raising questions regarding the best approach for improving survival. Bevacizumab remains one of the most widely used therapies for treating metastatic colorectal cancer and can be used after progression. This study aimed to identify the best chemotherapy partner for bevacizumab after progression. We performed a retrospective analysis of patients with metastatic colorectal cancer who were treated with bevacizumab as first- and second-line chemotherapy. Data were collected for 151 patients, 40 of whom were treated with double-dose bevacizumab after the first progression. The two standard chemotherapy regimens combined with bevacizumab were FOLFIRI/CAPIRI and FOLFOX4/CAPEOX. The initiation of first-line treatment with irinotecan-based chemotherapy improved progression-free survival and time to treatment failure but not overall survival. After the first progression, retreatment with the same regimen as that used in the induction phase was the best approach for improving overall survival (median overall survival: 46.5 vs. 27.0 months for the same vs. switched strategy, respectively). No correlations were observed between the dose intensity of irinotecan, oxaliplatin, 5-fluorouracil, or bevacizumab and the overall survival, progression-free survival in the first-/second-line treatment, and time to treatment failure. Interaction between an irinotecan-based regimen as a second-line treatment and double-dose bevacizumab after progression was associated with an improved overall survival (p = 0.06). Initiating systemic treatment with an irinotecan-based regimen in combination with bevacizumab improved the progression-free survival in the first-line treatment and time to treatment failure. In terms of overall survival, bevacizumab treatment after the first progression is better partnered with the same regimen as that used in the induction phase., Competing Interests: The authors have declared that no competing interests exist.

Gastric cancer represents one of the most severe cancers with poor overall survival. Despite the availability of published data on the efficacy of adjuvant treatment, the actual percentage of treated patients remains low. The toxicity of radiotherapy or chemotherapy regimens differ and clinicians need accessible tools in order to better select candidates for adjuvant treatment. In this review, we present published data from clinical trials and cancer registries that might be useful for properly balancing the efficacy and toxicity of adjuvant treatment in gastric cancer patients who underwent surgery with curative intent.

Cancer is one of the most difficult diseases to be treated. The particularities regarding the tumors' occurrence mechanism, their evolution under chemotherapy, disease-free interval, but also the increasing number of patients make cancer an intensively studied health domain. Although introduced in therapy since the early 80s, platinum derivatives play an essential role in anticancer therapy. Their use in therapy resulted in improving the patient quality of life and prolonging disease-free interval, which makes them still a benchmark for other anticancer compounds. However, adverse reactions and allergic reactions are a major impediment in therapy with platinum derivatives. This paper summarizes data about platinum derivatives through a multidisciplinary approach, starting from a chemical point of view and on to their mechanism of action, mechanism of cellular resistance, predictive factors for the outcome of chemotherapy such as micro RNAs (miRNAs), tumor suppressor protein p53, and the excision repair cross-complementing 1 protein (ERCC1).

Background and Aim: Endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) are considered good tools for the diagnosis of pancreatic cancer and for obtaining material for cytology or histology. The accuracy of EUS-FNA can rise to 85-95%, but it is lower in cases with a chronic pancreatitis background or with previous biliary stenting. We aimed to establish the diagnostic yield of the visible length of the core biopsy samples in pancreatic cancer by using one single type of standard 22G needle and to evaluate the factors which can influence the results., Method: EUS-FNA was performed by using a 22G standard needle on patients prospectively recruited with the suspicion of pancreatic masses on transabdominal ultrasound or CT scan over a period of eight months. The number of passes was limited by the length of the core obtained. The final diagnosis was based on EUS-FNA or hepatic biopsy for their metastasis or by follow up every three month by imaging methods., Results: The study included 118 patients. Previous stents were present in 10 patients and chronic pancreatitis features were found in 3 patients. The procedure sensitivity was 89% and the global accuracy was 89%. The presence of biliary stents did not impede the accuracy of results. The number of passes did not influence the results., Conclusions: The diagnostic rate of core biopsy by using 22G needles had a high accuracy and it is safe when the length of core dictates the number of passes. The presence of biliary stents did not influence the results.

Purpose: The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen., Methods: Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj-Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonald's trial., Results: In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS., Conclusion: The proposed treatment is not less effective compared with the McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS.

Purpose: Platinum derivatives play a very important role in cancer therapy. Despite their outstanding results in the treatment of tumors with different locations, the occurrence of hypersensitivity reactions raises issues when it comes to therapy decision, because the changing of chemotherapy line could influence the tumor's evolution. Over the years the scientific community has paid particular attention to the mechanism by which this occurs and to identification of predictive factors. The purpose of this case-control, retrospective study was to find new predictive markers for the occurrence of allergic reactions to platinum derivatives., Methods: We identified 59 cases of allergic reactions to platinum derivatives in the Oncology Institute "Prof. Dr. Ion Chiricuta" from Cluj-Napoca city in 2013. Blood tests data were analyzed before the administration of the cycle on which the allergic reaction occurred, along with the mandatory analyses for the patients and we focused on the values of neutrophils, lymphocytes, monocytes, eosinophils and basophils., Results: When these values were compared with the values of the control group (,which was made at a ratio of 1:2 or 1:3, matched for age, tumor location and chemotherapy cycle) we found that each increase of lymphocytes or doses of platinum and each drop in monocytes number increased the risk for allergic reactions to occur., Conclusion: These findings are of a great value for the physicians and represent a starting point for more detailed studies.

Ivemark syndrome (IS) is a rare embryological disorder which results from failure of development of the left-right asymmetry of organs. It is often associated with cardiac and other organ abnormalities, which are the usual causes of death in early neonatal life. We report a 3 months old girl with IS with dextrocardia, transposition of the great vessels, atrio-ventricular connection, total anomalous pulmonary venous drainage, a right atrial and right pulmonary isomerism, a midline liver, a midline gallbladder, asplenia, intestinal malrotation and vena cava anomalies. To our knowledge, complete right heterotaxia syndrome has been rarely described in literature. Lateralization defects such as situs inversus, asplenia or polysplenia due to defective left-right axis development are considered as defects of the primary developmental field. Therefore, additional malformations in IS can be synchronic defects in the primary developmental field rather than causally independent malformations.