Cancer before and after the start of hemodialysis and association with mortality - an Eastern-European multicenter study.

INTRODUCTION: East-European data on cancer in patients undergoing hemodialysis (HD) are scarce. This study aimed to assess the pattern of cancer and related mortality in patients with end-stage kidney disease (ESKD) undergoing HD. METHODS: Retrospectively analyzing data from 7 HD centers, this study examined 1377 incident HD patients divided into three groups: no-cancers (NoC), cancers that occurred prior to HD initiation (CPI) and de novo cancer developed after HD initiation (DNC). Mortality risk and survival trends within groups were analyzed using Cox regression and Kaplan-Meier methods. RESULTS: In the cohort, 89.46% of the patients had no cancer (NoC group), 3.63% had cancer before (CPI group), and 6.89% had cancer after HD initiation (DNC group). The mean time from HD initiation to DNC diagnosis was 1 [2.75] years. Older age was associated with a higher risk of developing DNC (p < 0.001). Chronic tubulointerstitial nephritis (CTIN) is more prevalent in cancer patients. The most common cancer sites among DNC patients were the digestive (29.47%) and urinary tracts (18.95%), while those in CPI subjects were hematologic (22%) and digestive (20%). Cancer was an independent predictor of mortality risk (HR = 6.9, 95% [CI]:4.5-10.6, p < 0.001). CONCLUSIONS: East-European ESKD patients undergoing HD have a high incidence of de novo cancers whose primary cancer sites are the digestive and urinary tracts. Almost half of the HD patients with CPI have hematologic and digestive tract cancers. Age and CTIN were associated with cancer risk. Cancer is an independent risk factor for all-cause mortality in patients undergoing hemodialysis (HD).

The Approach of Artificial Intelligence in Neuroendocrine Carcinomas of the Breast: A Next Step towards Precision Pathology?-A Case Report and Review of the Literature.

Primary neuroendocrine tumors (NETs) of the breast are considered a rare and undervalued subtype of breast carcinoma that occur mainly in postmenopausal women and are graded as G1 or G2 NETs or an invasive neuroendocrine carcinoma (NEC) (small cell or large cell). To establish a final diagnosis of breast carcinoma with neuroendocrine differentiation, it is essential to perform an immunohistochemical profile of the tumor, using antibodies against synaptophysin or chromogranin, as well as the MIB-1 proliferation index, one of the most controversial markers in breast pathology regarding its methodology in current clinical practice. A standardization error between institutions and pathologists regarding the evaluation of the MIB-1 proliferation index is present. Another challenge refers to the counting process of MIB-1's expressiveness, which is known as a time-consuming process. The involvement of AI (artificial intelligence) automated systems could be a solution for diagnosing early stages, as well. We present the case of a post-menopausal 79-year-old woman diagnosed with primary neuroendocrine carcinoma of the breast (NECB). The purpose of this paper is to expose the interpretation of MIB-1 expression in our patient' s case of breast neuroendocrine carcinoma, assisted by artificial intelligence (AI) software (HALO-IndicaLabs), and to analyze the associations between MIB-1 and common histopathological parameters.

A Heart Rate Step Function Response Method for the Evaluation of Pulse Wave Velocity as a Predictor of Major Adverse Cardio-Vascular Events.

Background and Objectives: Cardiovascular diseases are the main cause of death worldwide, and pulse wave velocity (PWV) is considered a predictor of major adverse cardiovascular events. The study intended to be helpful in finding methods for the preliminary assessment of PWV in primary care units. Materials and Methods: The study group consisted of 36 subjects (considered healthy by their own statement) from the medical field (medicine students and residents) aged between 20 and 30 years: 33.3% males and 66.7% females. Two types of measurements were carried out successively: (a) measurements with the arteriograph and (b) measurements on a treadmill effort testing system, where heart rate (HR) was measured over time as a response to step function physical effort (PE). Results: The study allowed for the highlighting of some limits which, if exceeded, can be associated with high PWV values: (i) if after a moderate PE and a resting time of at least 6 min, the HR is larger than 80 b/min; (ii) if the relaxation time in a PE test of moderate intensity is larger than 1 min; (iii) if the HR measured after the subject is raised from the supine to orthostatic position is larger than 100 b/min, and (iv) if the resting HR is larger than 80 b/min. Conclusions: Steady-state HR correlates with PWV and may be used for the preliminary assessment of PWV.

Hypothyroidism and Heart Rate Variability: Implications for Cardiac Autonomic Regulation.

Thyroid hormones have a pivotal role in controlling metabolic processes, cardiovascular function, and autonomic nervous system activity. Hypothyroidism, a prevalent endocrine illness marked by inadequate production of thyroid hormone, has been linked to different cardiovascular abnormalities, including alterations in heart rate variability (HRV). The study included 110 patients with hypothyroid disorder. Participants underwent clinical assessments, including thyroid function tests and HRV analysis. HRV, a measure of the variation in time intervals between heartbeats, serves as an indicator of autonomic nervous system activity and cardiovascular health. The HRV values were acquired using continuous 24-h electrocardiogram (ECG) monitoring in individuals with hypothyroidism, as well as after a treatment period of 3 months. All patients exhibited cardiovascular symptoms like palpitations or fatigue but showed no discernible cardiac pathology or other conditions associated with cardiac disease. The findings of our study demonstrate associations between hypothyroidism and alterations in heart rate variability (HRV) parameters. These results illustrate the possible influence of thyroid dysfunction on the regulation of cardiac autonomic function.

Autonomic Dysfunction and Cardiac Performance in Pregnant Women with Hypertensive Disorders: A Comparative Study Using Heart Rate Variability and Global Longitudinal Strain.

(1) Background: Pregnancy induces significant physiological adaptations with substantial impacts on the cardiovascular system. Hypertensive disorders of pregnancy (HDPs) are connected to significant risks of maternal and fetal complications, contributing significantly to morbidity and mortality across the globe. This study focuses on evaluating autonomic dysfunction by analyzing heart rate variability (HRV) and assessing cardiac performance through global longitudinal strain (GLS) using speckle tracking echocardiography, as well as examining diastolic function in pregnant women with HDP compared to healthy pregnant controls. (2) Methods: A case-control study was conducted involving pregnant women diagnosed with gestational hypertension (GH), preeclampsia (PE), or severe preeclampsia (SPE) as the case group, and healthy pregnant women as the control group. HRV was measured to evaluate autonomic function, GLS was assessed using speckle tracking echocardiography, and diastolic function was evaluated through standard echocardiographic parameters. Data were analyzed to compare cardiac performance and autonomic regulation between the HDP and control group, as well as among the different HDP subgroups. (3) Results: The HDP group exhibited significantly reduced HRV parameters compared to healthy controls, indicating notable autonomic dysfunction. Speckle tracking echocardiography revealed lower GLS among women with HDP, particularly in those with SPE, compared to the control group. Diastolic dysfunction was also present in the HDP group. (4) Conclusions: HRV and GLS are valuable non-invasive tools for detecting autonomic dysfunction and cardiac performance impairments in pregnant women with hypertensive disorders. These findings suggest that autonomic and cardiac dysfunctions are prevalent in HDP.

Heart Rate Variability and Global Longitudinal Strain for Prognostic Evaluation and Recovery Assessment in Conservatively Managed Post-Myocardial Infarction Patients.

Background: Heart rate variability (HRV) is the fluctuation in the time intervals between adjacent heartbeats. HRV is a measure of neurocardiac function that is produced by dynamic autonomic nervous system (ANS) processes and is a simple measure that estimates cardiac autonomic modulation. Methods: The study included 108 patients admitted to the Coronary Intensive Care Unit with acute myocardial infarction (AMI) who did not undergo primary percutaneous transluminal coronary angioplasty (PTCA) or systemic thrombolysis and followed conservative management. All patients underwent detailed clinical, biological, and paraclinical assessments, including evaluation of HRV parameters and echocardiographic measurements. The analysis of RR variability in both time and frequency domains indicates that the negative prognosis of patients with AMI is associated with an overall imbalance in the neuro-vegetative system. The HRV parameters were acquired using continuous 24 h electrocardiogram (ECG) monitoring at a baseline, after 1 month, and 6 months. Results: Our analysis reveals correlations between alterations in HRV parameters and the increased risk of adverse events and mortality after AMI. The study found a significant improvement in HRV parameters over time, indicating better autonomic regulation post-AMI. The standard deviation of all RR intervals (SDNN) increased significantly from baseline (median 75.3 ms, IQR 48.2-100) to 1 month (median 87 ms, IQR 55.7-111) and further to 6 months (median 94.2 ms, IQR 67.6-118) (p < 0.001 for both comparisons). The root mean square of successive difference of RR (RMSSD) also showed significant increases at each time point, from baseline (median 27 ms, IQR 22-33) to 1 month (median 30.5 ms, IQR 27-38) and from 1 month to 6 months (median 35 ms, IQR 30-42) (p < 0.001 for all comparisons), indicating enhanced parasympathetic activity. Moreover, changes in HRV parameters have been associated with impaired left ventricle ejection fraction (LVEF) and global longitudinal strain (GLS), indicating a relationship between autonomic dysfunction and myocardial deformation. GLS values improved from a baseline median of -11% (IQR 5%) to -13% (IQR 4%) at 6 months (p < 0.001), reflecting better myocardial function. Conclusions: HRV parameters and cardiac performance analysis, especially using GLS, offer a solid framework for evaluating recovery and predicting adverse outcomes post-MI.

Development of a Framework for On-Demand Caesarean Section in Romania.

BACKGROUND: Caesarean section rates have continued to trend upward in most countries, including Romania, creating a number of economic challenges. In the public health system, there is no regulation for performing Caesarean sections on demand; it is often done unlawfully, and in private hospitals, it is a real business. Thus, this study aims to investigate the budgetary impact at a hospital level and the profit per procedure by introducing on-demand caesarean sections for a fee. METHODS: This study was conducted in one of the largest maternity units in Western Romania-the "Bega" Maternity Clinic of the Timisoara County Emergency Hospital. For the analysis, the difference between a proposed occupancy rate (between 50 and 85%, increasing every 5 percent) and the actual occupancy rate was calculated. Considering that this difference can be used to admit patients to receive Caesarean sections on demand for a fee, the profit that could be obtained during the study period was calculated. RESULTS: It is reported that between 238 (proposed occupancy rate of 50%) and 4683 patients (a proposed occupancy rate of 85%) could have benefited from on-demand caesarean section surgery in 2017-2019. Between RON 419,999 and RON 8,551,636 could be obtained in the 3 years of study by implementing caesarean section against payment. CONCLUSION: The implementation of a system of on-demand payment for caesarean sections in Romania would bring significant profits to the hospital budget.

Analysis of the Healthcare System in Romania: A Brief Review.

This manuscript provides a brief review and analysis of the healthcare system in Romania. This study aims to comprehensively analyse the healthcare system in Romania, evaluating its strengths, weaknesses, and impact on the population's access to quality healthcare services. Within the framework of the Romanian healthcare system, a multitude of pressing challenges endure. These encompass insufficient funding, shortages of medical personnel, and ineffectiveness in the provisioning of services. These impediments substantially hinder the accessibility of healthcare services, particularly in outlying and pastoral regions, thereby rendering the system susceptible and underserving certain demographics. Our investigation presents three hypotheses. The opening conjecture proposes that inadequate funding has a negative impact on the availability and standard of healthcare facilities in Romania. In addition, another hypothesis assumes that insufficient medical staff plays a considerable role in inequalities in access to and delivery of healthcare. Moreover, the existence of inadequacies in service provision serves as a significant barrier, obstructing the timely and efficient delivery of healthcare to those who need it. Our research encompasses a comprehensive analysis of key aspects of the Romanian healthcare system, ranging from healthcare infrastructure and financing mechanisms to service delivery and healthcare outcomes. Through a blend of qualitative and quantitative data sources, including government reports, academic studies, and statistical data, we have endeavoured to provide an in-depth evaluation. The analysis encompasses various aspects, including healthcare infrastructure, financing mechanisms, service delivery, and healthcare outcomes. Romania has a mixed healthcare system with both public and private providers. The primary level of care is delivered by family doctors, while hospitals and specialised medical centres provide secondary and tertiary care services. This research underlines the criticality of significant alterations being implemented in the healthcare system of Romania to address the issues arising from insufficient funding, a shortage of medical personnel, and shortcomings in service delivery. It is vital to tackle the obstacles presented by insufficient funding, the dearth of healthcare staff, and inadequacies in service delivery to attain impartial and reachable healthcare. By implementing these essential transformations, Romania can pave the way towards a healthcare system that efficaciously caters to the diverse requirements of its populace and guarantees the provision of prompt and superior healthcare services.

Chronic kidney disease in cancer patients, the analysis of a large oncology database from Eastern Europe.

INTRODUCTION: Kidney dysfunction is prevalent in oncology patients and has an impact on their treatment and quality of life. The aim of our study was to analyze the prevalence of CKD in a large cohort of several types of cancer patients in an East European Region. MATERIAL AND METHODS: We conducted an observational retrospective cohort study on 5831 consecutive, biopsy-diagnosed cancer patients between January 2019 -December 2020 in the largest oncology hospital and outpatient clinic in Western Romania. 4342 subjects were included in the statistical analysis. RESULTS AND DISCUSSION: From the 24 cancer types, the most prevalent cancers were represented by: breast (22.02%), lung (10.18%) and colonic cancer (9.51%). The prevalence of CKD (G3 -G5) was 12.27% after the first year of follow-up and 13.42 after the second year. The prevalence of CKD was higher in patients with renal (50%), urinary tract (33.6%) and pancreatic cancers (19.6%) and lower in patients with colonic cancers (5.3%) and brain tumors (2.5%). At the end of our 2-year survey period, 0,7% of the CKD cases had an eGFR around 6 ml/min/1.73m2 -an indication for renal replacement therapy. CONCLUSION: Oncology patients have a significantly higher prevalence of CKD compared to the general population, dependent of the age of the patients and the type of cancer. The prevalence of advanced CKD was surprisingly high (stages G4-G5 Pre-Dialysis 22.15%) one third of the CKD- G5 patients having indication for initiation of renal replacement therapy. An onco- nephrology team should be needed for the best medical care of these patients.

Acute Kidney Injury after Endoscopic Retrograde Cholangiopancreatography-A Hospital-Based Prospective Observational Study.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) represents a major pivotal point in gastrointestinal endoscopy. Little is known about acute kidney injury (AKI) post-ERCP. This study analyses the incidence, risk factors, and prognosis of post-ERCP AKI. Methods: A total of 396 patients were prospectively studied. AKI was defined by an increase in serum creatinine (SCr) ≥ 0.3 mg/dL or by an increase in SCr ≥ 50% in the first 48 h post-ERCP. Logistic regression analysis was used to identify the predictors of AKI and in-hospital mortality. A two-tailed p value < 0.05 was considered significant. Results: One hundred and three patients (26%) developed post-ERCP AKI. Estimated glomerular filtration rate (adjusted odds ratio (aOR) = 0.95, 95% confidence interval (CI): 0.94−0.96, p < 0.001), nonrenal Charlson Comorbidity Index (Aor = 1.19, 95% CI: 1.05−1.35, p = 0.006), choledocholithiasis (aOR = 4.05, 95% CI: 1.98−8.29, p < 0.001), and bilirubin (aOR = 1.1, 95% CI: 1.05−1.15, p < 0.001) were associated with post-ERCP AKI. Post-ERCP AKI was associated with longer hospital stay (p < 0.001) and with increased in-hospital mortality (7.76% versus 0.36%, p < 0.001). Moderate-to-severe (stage 2 and 3) AKI was independently associated with in-hospital mortality (aOR = 6.43, 95% CI: 1.48−27.88, p < 0.013). Conclusions: Post-ERCP AKI represented an important complication associated with longer hospital stay. Moderate-to-severe post-ERCP AKI was an independent risk factor for in-hospital mortality.

Diagnosis and Management of Dysgerminomas with a Brief Summary of Primitive Germ Cell Tumors.

Dysgerminoma represents a rare malignant tumor composed of germ cells, originally from the embryonic gonads. Regarding its incidence, we do not have precise data due to its rarity. Dysgerminoma occurs at a fertile age. The preferred treatment is the surgical removal of the tumor succeeded by the preservation of fertility. Even if a multidisciplinary team, founded in 2009 by a gynecologist, an oncologist, a pediatric oncologist and a pediatric surgeon, under the guidance of the Malignant Germ Cell International Consortium (MaGIC), studies this type of tumor, issues still remain related to the lack of a randomized study and to both the management and understanding of the concept of OMGCTs (ovarian malignant germ cell tumors). The aim of this review is to present from the literature the various approaches for this type of tumor, and, regarding innovative therapies or possible prevention, which can be applied in clinical practice. Multidisciplinarity and treatment in reference centers have proven their usefulness as well.

Exploring the relation between mortality and left ventricular structure and function in stable hemodialysis treated patients, a longitudinal multicenter cohort study.

Left ventricular (LV) structure and function anomalies are frequent during the CKD continuum and are associated with increased risk of mortality. Cross section and longitudinal ultrasound data are available for advanced CKD and transition to ESKD. Less information is available about LV changes during stable, long-term hemodialysis (HD) treatment. All stable HD patients from 9 HD centers (1034 patients, 671 males, age 58.71 ± 12.94 years) have been enrolled in January 2015. The cohort was followed-up for 4 years, kidney transplantation or death. Yearly, two-dimensional and M-mode continuous and Pulse Doppler echocardiography were performed. During the follow-up, the prevalence of cardiovascular comorbidities significantly increased (p < 0.0001), coronary artery disease (CAD) from 73.5 to 88.8%, peripheral artery disease (PAD) from 29 to 40.9%, cerebral vascular disease (CVD) from 20.4 to 30.8%, heart valves calcification (VC) from 65.6 to 89.3% and left ventricular hypertrophy (LVH) from 67.6 to 76.5%. The mortality risk increased with the presence of CAD (1.59-fold), PAD (1.61-fold), CVD (1.59-fold), and VC (1.77-fold). Mortality risk was increased in those with LVEF < 50% (LVEF 40-49% 1.5-fold and LVEF < 40% 2.3 fold). Among the survivors of the first year, LVEF varied (> 5% decrease, > 5% increase and ± 5% variations). More than 5% increase of LVEF was associated with higher mortality risk (crude 1.5-fold, adjusted 1.43-fold) compared to stationary EF (p = 0.001). Cardiovascular disease progresses during stable long-term HD therapy and increases mortality risk. HF becomes highly prevalent but only HF with decreased LVEF < 50% is associated with increased risk of mortality.

Arterial function in hypertensive pregnant women. Is arterial stiffness a marker for the outcomes in pregnancy?

AIMS: Hypertension (HTN) in pregnancy is a major cause of maternal, foetal and neonatal morbimortality in both developing and developed countries. Arterial stiffness is a predictor of cardiovascular events and can be assessed through augmentation index (AIx) and pulse wave velocity (PWV). This study was intended to analyse the arterial stiffness in three categories, hypertensive pregnant women vs. healthy women (both pregnant and non-pregnant). MAIN METHODS: Between 2018 and 2019, 150 women were prospectively included into three homogenous groups, of equal sizes (N = 50): pregnant women with HTN (group 1), pregnant women without HTN (group 2), and non-pregnant women (group 3). We assessed pregnant women 3 times (in all three trimesters) and six weeks postpartum, and the women from the control group once. KEY FINDINGS: Significant differences (p < 0.001) of the hemodynamic and arterial stiffness parameters and of the heart rate (HR) (p = 0.006) were observed between groups 1 and 2. Women with pregnancy-induced HTN had different values of arterial function parameters long time before the first signs of high blood pressure (BP) occurred. Also, body mass index (BMI) had a deleterious effect in all patients, but especially in pregnant HTN women. Significant differences (p < 0.001) between groups 2 and 3 were observed regarding the BP and aortic PWV (PWVao) and, as well, significant differences (p < 0.05) between BMI, aortic systolic BP (p = 0.02), brachial AIx (p = 0.01) and pulse pressure (PP) (p = 0.049) values. SIGNIFICANCE: The current study emphasizes the importance of the assessment of arterial function parameters and BMI as markers for future BP values and outcomes throughout gestation.

Clinical, ultrasound and histopathological correlation of clinically N0 neck nodes in patients with cancers of the pharynx and larynx.

BACKGROUND: The presence of metastatic cervical adenopathy is essential for treatment planning and prognosis assessment. Treatment of patients with head and neck cancer with clinically negative cervical lymphadenopathy (N0) remains controversial. Neck palpation, as the method used in tumor, node, metastasis (TNM) staging, has limitations and can provide false negative results in some cases. Lymph node metastases are associated with a reduced survival rate but at the same time, neck dissection for the patient with N0 neck is not without risks or complications. OBJECTIVES: In prospective study, we compared palpation, ultrasonography (US) examination of the neck and histopathological examination in patients with cancers of the pharynx and larynx. PATIENTS, MATERIALS AND METHODS: Forty-six patients with cancers of the pharynx and larynx that presented with a N0 neck were prospectively analyzed. They were divided in two groups: 23 patients operated with an external approach including the control of the lymph node areas, and a second group of 23 patients operated using endoscopy and carbon dioxide (CO2) laser, no neck dissection - "watchful waiting policy". All patients have had a flexible endoscopy of the pharynx and larynx, US of the neck and all received surgical treatment for their primary tumor. Imaging was performed in selected cases. All the removed lymph nodes were sent for histopathology. US was also used as a follow-up method. The US features of the examined lymph nodes were: diameters [longitudinal (L) and transverse (T)]; the ratio of the two diameters (L∕T); shape; lymph node area; central hypodensity; regular∕irregular margins; aspect (homogeneous or not). RESULTS: US has detected 25 lymph nodes in the open surgery group and intraoperatively, we excised 31 (sensitivity of 80.6%). Ten lymph nodes showed metastases, with 100% accuracy of US, which have been confirmed both pathologically and immunohistochemically. US in the second group - patients treated with CO2 laser - detected at four patients 10 cervical lymph nodes that did not presented any malignant features. At recurrence alone, the US confirmed 100% presence of nodes metastases. CONCLUSIONS: US was superior to palpation and this method can be recommended as a diagnostic tool in preoperative assessment of patients without palpable metastasis (N0).

Strain Elastography as a Valuable Diagnosis Tool in Intermediate Cytology (Bethesda III) Thyroid Nodules.

Fine needle aspiration (FNA) is considered the gold standard in the diagnostic of thyroid nodules. Using the recommended BETHESDA reporting system, up to 20% of results are classified as intermediate cytology. As there is no consensus whether ultrasound evaluation, lobectomy or surgery is the best treatment option, intermediate cytology results are considered a grey zone of the FNA. The main aim of our study was to evaluate the performance of combined advanced ultrasound techniques in the process of diagnosis and evaluation of the intermediate cytology cases after FNA. We evaluated 54 consecutive cases with intermediate cytology on FNA, using conventional B-mode ultrasound (2B), and strain elastography, using a linear multifrequency 6-13 MHz linear probe (Hitachi Prerius Machine, Hitachi Inc, Japan). All nodules were classified with our Thyroid Imaging Report and Data System (TI-RADS) proposed model, considering: vertical appearance, with antero-posterior diameter bigger than the transvers diameter, the so called taller than wide shape, irregular borders, intranodular inhomogeneity, marked hypoecogenicity, micro calcifications, the presence of suspect lymph nodes, and increased stiffness as suspicious for malignancy. The classification outcomes were compared with the pathology results, considered the gold standard diagnosis. The prevalence of cancer was 28.8%, with 13/45 cases having a clear diagnostic of cancer. Six cases were diagnosed with borderline follicular neoplasia, a category with unclear evolution, also considered as malignant in the analysis of the imaging results. In total, 16/19 cancer cases had increased stiffness on elastography. The cancer prevalence increased with TI-RADS category, being 25% in TI-RADS 4b category and 92.8% in TI-RADS 5 category. The AUROC (Area Under Receiver Operating Curve) of elastography alone, in differentiation of malignant thyroid nodules was 74.9%; the combination of elastographic and conventional ultrasound characteristics generated an even better AUROC, of 84.5%. The combined conventional ultrasound and elastography identified thyroid cancer in cases with intermediate cytology with a sensitivity of 89.5% with a specificity of 50%. High risk thyroid nodules, identified by combined high risk conventional ultrasound characteristics and increased stiffness, on strain elastography, are highly predictive for malignancy, in the intermediate cytology cases.