Efficacy of adjuvant capecitabine in residual triple negative breast cancer: a multicenter observational Turkish Oncology Group (TOG) study.

BACKGROUND: Triple negative breast cancer (TNBC) is characterized by high rates of recurrence, especially in patients with residual disease after neoadjuvant chemotherapy (NAC). Capecitabine is being used as standard adjuvant treatment in residual TNBC. We aimed to investigate the real-life data regarding the efficacy of capecitabine in residual TNBC. DESIGN AND METHODS: In this retrospective multicenter study, TNBC patients with residual disease were evaluated. Patients, who received standard anthracycline and taxane-based NAC and adjuvant capecitabine were eligible. Overall survival (OS), disease free survival (DFS) and toxicity were analyzed. RESULTS: 170 TNBC patients with residual disease were included. Of these, 62.9% were premenopausal. At the time of analysis, the recurrence rate was 30% and death rate was 18%. The 3-year DFS and OS were 66% and 74%, respectively. In patients treated with adjuvant capecitabine, residual node positive disease stood out as an independent predictor of DFS (p = 0.024) and OS (p = 0.032). Undergoing mastectomy and the presence of T2 residual tumor was independent predictors of DFS (p = 0.016) and OS (p = 0.006), respectively. CONCLUSION: The efficacy of capecitabine was found lower compared to previous studies. Selected patients may have further benefit from addition of capecitabine. The toxicity associated with capecitabine was found lower than anticipated.

Peptide-conjugated Nanoparticle Platforms for Targeted Delivery, Imaging, and Biosensing Applications.

Peptides have become an indispensable tool in engineering of multifunctional nanostructure platforms for biomedical applications such as targeted drug and gene delivery, imaging and biosensing. They can be covalently incorporated into a variety of nanoparticles (NPs) including polymers, metallic nanoparticles, and others. Using different bioconjugation techniques, multifunctional peptide-modified NPs can be formulated to produce therapeutical and diagnostic platforms offering high specificity, lower toxicity, biocompatibility, and stimuli responsive behavior. Targeting peptides can direct the nanoparticles into specific tissues for targeted drug and gene delivery and imaging applications due to their specificity towards certain receptors. Furthermore, due to their stimuli-responsive features, they can offer controlled release of therapeutics into desired sites of disease. In addition, peptide-based biosensors and imaging agents can provide non-invasive detection and monitoring of diseases including cancer, infectious diseases, and neurological disorders. In this review, we covered the design and formulation of recent peptide-based NP platforms, as well as their utilization in in vitro and in vivo applications such as targeted drug and gene delivery, targeting, sensing, and imaging applications. In the end, we provided the future outlook to design new peptide conjugated nanomaterials for biomedical applications.

The safety and efficacy of first-line atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma: A multicenter real-world study from Turkey.

The aim of the study was to evaluate the real-world clinical outcomes of atezolizumab and bevacizumab (Atez/Bev) as the initial therapy for advanced hepatocellular carcinoma (HCC). We retrospectively analyzed 65 patients treated with Atez/Bev for advanced HCC from 22 institutions in Turkey between September 2020 and March 2023. Responses were evaluated by RECIST v1.1 criteria. The median progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Cox regression model was employed to conduct multivariate analyses. The median age was 65 (range, 22-89) years, and 83.1% of the patients were male. A total of 1.5% achieved a complete response, 35.4% had a partial response, 36.9% had stable disease, and 26.2% had progressive disease. The disease control rate was 73.8% and associated with alpha-fetoprotein levels at diagnosis and concomitant antibiotic use. The incidence rates of any grade and grade ≥ 3 adverse events were 29.2% and 10.7%, respectively. At a median follow-up of 11.3 (3.4-33.3) months, the median PFS and OS were 5.1 (95% CI: 3-7.3) and 18.1 (95% CI: 6.2-29.9) months, respectively. In univariate analyses, ECOG-PS ≥ 1 (relative to 0), Child-Pugh class B (relative to A), neutrophil-to-lymphocyte ratio (NLR) > 2.9 (relative to ≤ 2.9), and concomitant antibiotic use significantly increased the overall risk of mortality. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 2.69, P = .02), NLR > 2.9 (HR: 2.94, P = .017), and concomitant antibiotic use (HR: 4.18, P = .003) were independent predictors of OS. Atez/Bev is an effective and safe first-line therapy for advanced-stage HCC in a real-world setting. The survival benefit was especially promising in patients with a ECOG-PS score of 0, Child-Pugh class A, lower NLR, and patients who were not exposed to antibiotics during the treatment.

Discrepancy among microsatellite instability detection methodologies in non-colorectal cancer: Report of 3 cases.

BACKGROUND: Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy. The tumor-agnostic nature of MSI makes it a denominator for immunotherapy in several solid tumors. It can be assessed using next-generation sequencing (NGS), fluorescent multiplex PCR, and immunohistochemistry (IHC). CASE SUMMARY: Here, we report 3 cases with discordant MSI results detected using different methods. A cholangiocellular carcinoma case revealed proficient mismatch repair (MMR) by IHC but high MSI (MSI-H) by liquid NGS. A cervical cancer case revealed deficient MMR by IHC, microsatellite stable by PCR, and MSI-H by NGS. Lastly, an endometrial cancer case revealed proficient MMR by IHC but MSI-H by NGS. CONCLUSION: IHC for MMR status is the first choice due to several advantages. However, in cases of indeterminate IHC results, molecular testing by MSI-PCR is preferred. Recently, NGS-based MSI assays are being widely used to detect MSI-H tumors. All three methods have high accuracy; however, the inconsistencies between them may lead to misdiagnosis.

Current trends in perioperative treatment of resectable gastric cancer.

In the last few decades, the treatment strategy for locally advanced resectable gastric cancer (GC) has shifted to a multimodal approach, which potentially decreases recurrence risk and improves survival rates. Perioperative therapy leads to downstaging, increased curative resection rates, and prolonged disease-free and overall survival, by preventing micrometastases in patients with resectable GC. Application of neoadjuvant therapy provides information about tumor biology and in vivo sensitivity. A consensus regarding the therapeutic approach for non-metastatic GC does not exist, and many clinical trials aim to clarify this aspect. Advances in precision medicine and the role of immunotherapy have been the focus of research in GC treatment. Herein, the current status and possible future developments of perioperative therapy for locally advanced resectable GC are reviewed, based on the most recent randomized clinical trials.

Intramural Component of Venous, Lymphatic, and Perineural Invasion in Colon Cancer: A Threat or an Illusion?

Background: Extramural venous invasion is an independent predictor of poor outcome in colorectal cancer, whereas the significance of the intramural component of venous and lymphatic and perineural invasion is unclear. Aims: To evaluate the prognostic impact of intramural components for venous, lymphatic, and perineural invasions and the relation of these invasion patterns with clinicopathological features in patients with colon cancer. Study Design: A retrospective cross-sectional study. Methods: The analysis included 626 patients with colon cancer in stages II and III. All patients were divided into four categories (no invasion, intramural invasion only, extramural invasion only, or both intramural and extramural invasions) for vascular invasion, lymphatic invasion and perineural invasion. The primary outcomes were 5-year disease-free and overall survival. Results: Right-sided (for vascular invasion, 24.7% vs. 33.9%, p = 0.007; for perineural invasion, 34.5% vs. 41.5%, p = 0.034) and dMMR tumors (for vascular invasion, 13.5% vs. 33.5, p < 0.001; for perineural invasion, 25% vs. 41.4%, p = 0.004) exhibited less venous and perineural invasion. Compared with no invasion, presence of intramural invasion only, did not exert any effect on disease-free or overall survival for vascular invasion, lymphatic invasion, and perineural invasion. Multivariate analyses revealed that the presence of both intramural and extramural invasion was independently associated with poor disease-free and overall survival for venous (hazard ratios: 2.39, p = 0.001; hazard ratios: 2.46, p = 0.001), lymphatic (hazard ratios: 2.456, p < 0.001; hazard ratios: 2.13, p = 0.02) and perineural invasion (hazard ratios: 2.99, p < 0.001; hazard ratios: 2.68, p < 0.001), respectively. Conclusion: Our data strongly advocates the importance of reporting intramural and extramural components of invasion since the presence of intramural invasion alone may not be considered as a high-risk factor for systemic recurrence.

First detection and molecular characterization of Dientamoeba fragilis in cattle.

Dientamoeba fragilis is a flagellated protozoan with amoeba-like morphology that inhabits the human gastrointestinal tract. It is endemic in a vast geography around the world, including developed countries. There are limited studies on non-human hosts of the parasite, and suitable hosts have not been clarified. The parasite has been detected in non-human primates, pigs, cats, dogs and rats. There is no study in the literature investigating and detecting the presence of this parasite in cattle. In this study, stool samples taken from 163 different cattle and calves from 11 different farms between March 2017 and May 2022 were examined for the detection of D. fragilis via PCR. Trichrome staining was performed on all PCR-positive samples. The isolates with the expected amplicon size were sequenced using the 18S ribosomal RNA region, and their genotypes were determined by BLAST analysis. Sequences were analysed with the most similar and reference sequences in the literature, forming a phylogenetic tree. We detected D. fragilis in 31 (19.01%) of the 163 stool samples. D. fragilis cysts/trophozoites were detected by trichrome staining method in six of 31 samples. All PCR products selected for molecular analysis from positive samples had the same nucleotide sequence. As a result of BLAST analysis, all sequences were determined to belong to D. fragilis genotype 1. This study determined for the first time that cattle are suitable hosts for D. fragilis. Furthermore, the parasite subtype we detected belongs to genotype 1, which is the most common type in humans, suggesting that the parasite may have a zoonotic character. Our result is important in terms of the epidemiology of the parasite, as the mode of transmission is controversial, and available data on its suitable hosts are limited.

Predictors of left ventricular ejection function decline in young patients with ST-segment elevation myocardial infarction

SUMMARY OBJECTIVE: A decrease in the left ventricular ejection fraction (≤40%) in the setting of ST-segment elevation myocardial infarction is a significant predictor of mortality in the young ST-segment elevation myocardial infarction population. In this study, we aimed to investigate the predictors of left ventricular ejection fraction reduction and evaluate the long-term mortality rates in young ST-segment elevation myocardial infarction patients with or without decreased left ventricular ejection fraction. METHODS: We enrolled retrospectively 411 consecutive ST-segment elevation myocardial infarction patients aged 45 years or below who underwent primary percutaneous coronary intervention. Young ST-segment elevation myocardial infarction patients were divided into two groups according to their left ventricular ejection fraction (≤40%, n=72 and >40%, n=339), which were compared with each other. RESULTS: Statin use, white blood cell count, C-reactive protein, peak creatine kinase-MB, prolonged ischemia time, left anterior descending artery-related infarction, proximally/ostial located lesion, and no-reflow were independently associated with low left ventricular ejection fraction. Additionally, long-term mortality was considerably higher in the left ventricular ejection fraction ≤40% group than those in the left ventricular ejection fraction>40% group (18.1% versus 2.4%; p<0.001). CONCLUSIONS: In young ST-segment elevation myocardial infarction patients, lesion properties (left anterior descending lesion, proximally located lesion), no-reflow, and prolonged ischemia time appeared to be important determinants for the left ventricular ejection fraction decline, rather than coronary disease severity or demographic and hematological parameters. Statin use may be preventive in the development of left ventricular ejection fraction decline in young ST-segment elevation myocardial infarction patients.

Computational Analysis of the Inhibition Mechanism of NOTUM by the ONIOM Method.

Notum is a member of serine hydrolyses that cleaves the palmitoleate moiety from Wingless-related integration site (Wnt) ligands. This enzyme plays crucial functions through modulating the Wnt signaling pathway. Inhibition of Notum carries therapeutic effects against a number of maladies including osteoporosis, cancer, and Alzheimer's disease. Recently, a class of irreversible inhibitors based on esters of 4-(indolin-1-yl)-4-oxobutanoic acid have been reported. Using the crystal structures of enzyme-4-(indolin-1-yl)-4-oxobutanoate adduct and 4-(indolin-1-yl)-4-oxobutanoic acid-enzyme complex, we studied computationally the proposed inhibition mechanism using model systems based on the own n-layered integrated molecular orbital and molecular mechanics (ONIOM) method. In the first place, model systems were formulated to investigate the transesterification between the catalytic serine residue, Ser-232, and the methyl ester of 4-(indolin-1-yl)-4-oxobutanoate. In the second place, the hydrolysis mechanism of the resultant enzyme-inhibitor adduct was studied. The energetics of these steps were analyzed using a density functional theory functional in the ONIOM method. In addition, the roles of active-site residues during these steps were highlighted. It was found that the hydrolysis of the covalent adduct is highly endergonic corroborating the irreversible inhibition mechanism. These results will shed light not only on the inhibition mechanism but also on the catalytic mechanism.

Computational Analysis of Histone Deacetylase 10 Mechanism by the ONIOM Method: A Complementary Approach to X-ray and Kinetics Studies.

Histone deacetylase 10 (HDAC 10) catalyzes deacetylation of N8-acetylspermidine into spermidine in the cytosolic region of eukaryotic cells. Inhibition of HDAC 10 has clinical importance in certain types of cancers. Recently, X-ray crystal structures corresponding to the substrate-bound, tetrahedral intermediate-bound, and product-bound enzymes have been resolved using variant forms of humanized HDAC 10. Based on these structures, it was proposed that Y307 residue polarizes the carbonyl of the acetyl group in N8-acetylspermidine together with a zinc atom, which is coordinated by D174, H176, D267, and an H2O molecule. The H2O molecule undergoes nucleophilic addition to the carbonyl carbon of N8-acetylspermidine to form the tetrahedral intermediate. During this process, it is suggested that H136 acts as a general base to deprotonate the H2O molecule. It is further proposed that the protonation of the amide N atom of the tetrahedral intermediate by H137 causes the deacetylation forming the final products, spermidine and acetate ion. In this study, computational models based on the ONIOM method were employed to study the proposed mechanism for the two steps of the deacetylation process based on the crystal structure of the substrate-bound enzyme. The energy profiles of each step as well as the roles of the active site residues were investigated for the catalysis. The calculated activation barrier is in good agreement with the reported kcat value.

Tailored total neoadjuvant therapy for locally advanced rectal cancer: One size may not fit for all!

While current neoadjuvant protocols have proven benefits on local control for majority of patients with locally advanced rectal cancer, there are certain clinical conditions that require future advances for improving the outcomes. Total neoadjuvant therapy incorporates systemic chemotherapy planned within standard neoadjuvant protocols either before or after radiotherapy for locally advanced rectal cancer as a whole. Enhanced compliance with planned oncological therapy, tumour downstaging, administration of chemotherapy at the earliest time in the disease course to help assessing chemosensitivity are the proposed benefits of total neoadjuvant therapy in patients with locally advanced rectal cancer. Patient selection criteria for administration of total neoadjuvant therapy in the recent guidelines are unclear. Since current literature is inconclusive for the optimal sequence and type of radiotherapy and chemotherapy, premature incorporation of total neoadjuvant therapy for all locally advanced rectal cancers may result in overtreatment and subsequently toxicity. This article aims to discuss the current literature and to propose a future perspective by considering real-life scenarios reflecting patients' needs for treatment of locally advanced rectal cancer.

Liver and Pancreatic Injury in Response to ALK Inhibitors in a Patient with Primary Signet Ring Cell Carcinoma of the Lung: A Case Report.

We report a patient with stage IV anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (primary lung signet ring cell adenocarcinoma) who received serial crizotinib, chemotherapy, and lorlatinib over more than 4 years. The patient discontinued crizotinib after approximately 4 months due to crizotinib-associated hepatotoxicity. Twenty-five days later, when transaminases had normalized, crizotinib was resumed. However, the patient's liver enzymes rapidly increased again, and crizotinib was discontinued. After 6 cycles of platinum-based chemotherapy, lorlatinib was initiated. Hepatotoxicity did not recur with lorlatinib, a next-generation ALK inhibitor, but grade 4 hypertriglyceridemia and acute pancreatitis were induced by lorlatinib after 4 months. To our knowledge, this is the first case report of acute pancreatitis with lorlatinib. Additionally, stereotactic body radiation therapy (SBRT) was performed for residual small primary lesions in the lung without stopping lorlatinib. Given the rarity of radiation pneumonitis, especially with the relatively small fields treated by SBRT, we suspect that lorlatinib enhanced the pulmonary toxicity. Physicians should be aware that ALK inhibitors, such as lorlatinib and crizotinib, have potentially lethal side effects.

Mechanistic study of L-6-hydroxynicotine oxidase by DFT and ONIOM methods.

L-6-Hydroxynicotine oxidase (LHNO) is a member of monoamine oxidase (MAO) family and catalyzes conversion of (S)-6-hydroxynicotine to 6-hydroxypseudooxynicotine during bacterial degradation of nicotine. Recent studies indicated that the enzyme catalyzes oxidation of carbon-nitrogen bond instead of previously proposed carbon-carbon bond. Based on kinetics and mutagenesis studies, Asn166, Tyr311, and Lys287 as well as an active site water molecule have roles in the catalysis of the enzyme. A number of studies including experimental and computational methods support hydride transfer mechanism in MAO family as a common mechanism in which a hydride ion transfer from amine substrate to flavin cofactor is the rate-limiting step. In this study, we formulated computational models to study the hydride transfer mechanism using crystal structure of enzyme-substrate complex. The calculations involved ONIOM and DFT methods, and we evaluated the geometry and energetics of the hydride transfer process while probing the roles of active site residues. Based on the calculations involving hydride, radical, and polar mechanisms, it was concluded that hydride transfer mechanism is the only viable mechanism for LHNO.

GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients.

Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. METHODS: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. RESULTS: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK(+) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 ±â€¯1.6 months and median overall survival (mOS) was 89.1 ±â€¯19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 ±â€¯2.5 months and mOS of 90.3 ±â€¯24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. CONCLUSION: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 ±â€¯19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ±â€¯24 months is unprecedented for ROS1(+) NSCLC.

Retrospective Analysis of Cystic Echinococcosis Results in Aydin Adnan Menderes University Training and Research Hospital Parasitology Laboratory Between 2005 and 2017

Objective: Echinococcus granulosus is the causative helminth of cystic echinococcosis (CE). The parasite is known to form fluid-filled cysts that grow slowly in the internal organs, particularly the liver and/or lungs. This disease is still important in terms of public health and economically in Turkey and other countries where animal husbandry is widespread. The aim of our study was to retrospectively evaluate the cases that were admitted to the Adnan Menderes University, Training and Research Hospital Parasitology laboratory on suspicion of CE between January 2005 and January 2017. Methods: Totally, 3446 sera (from 2019 female and 1427 male) were tested with an in-house ELISA for the presence of E. granulosus specific IgG antibodies at the timeswhen they were sent. Socio-demographic characteristics (age, gender, residence, and dog ownership), positivity titers, and cyst locations of pathologically confirmed CE patients were analyzed retrospectively. Results: The ages of patients varied between 4-87 years. It was found that 1104 (32%) of the 3446 sera were positive, and of them, 642 (58.1%) were female and 462 (41.9%) were male. Patients who had pathologically confirmed CE diagnosis constituted 247 (22.3%) of the total seropositive sera. Liver was the most commonly affected organ (81.8%), followed by lungs (6.1%). Conclusion: CE remains an important public health problem in our city; therefore, it is once again emphasized that preventive studies should be planned.

Association of Serum Osmolarity With Contrast-Induced Nephropathy in Patients With ST-Segment Elevation Myocardial Infarction.

Contrast-induced nephropathy (CIN) is a prevalent and serious complication after primary percutaneous coronary intervention (pPCI). Although the association between serum osmolarity and chronic kidney disease is well established, its relation to CIN in patients with ST-segment elevation myocardial infarction (STEMI) undergoing pPCI needs to be elucidated. We evaluated the predictive value of serum osmolarity for CIN development in patients with STEMI (n = 768) undergoing pPCI. Serum osmolarity on admission was calculated. The study population was divided into 2 groups according to CIN development, and both groups were compared according to clinical, laboratory, and demographic features, including the serum osmolarity. Serum osmolarity was significantly higher in patients with CIN than in those without CIN (278 [8] vs 284 [9]; P = .024). Serum osmolarity (odds ratio: 1.052; 95% confidence interval: 1.018-1.086; P = .002), hemoglobin, contrast media volume, creatinine on admission, basal SYNergy between PCI with TAXus and cardiac surgery II score, and left ventricular ejection fraction were found to be independent predictors of CIN. Serum osmolarity (given the simple calculation of this parameter on admission) can be useful to define patients with STEMI undergoing pPCI who are more likely to develop CIN.

Prognostic factors for survival in metastatic renal cell carcinoma patients with brain metastases receiving targeted therapy.

BACKGROUND: The primary objective of our study was to examine the clinical outcomes and prognosis of patients with metastatic renal cell carcinoma (mRCC) with brain metastases (BMs) receiving targeted therapy. PATIENTS AND METHODS: Fifty-eight patients from 16 oncology centers for whom complete clinical data were available were retrospectively reviewed. RESULTS: The median age was 57 years (range 30-80). Most patients underwent a nephrectomy (n = 41; 70.7%), were male (n = 42; 72.4%) and had clear-cell (CC) RCC (n = 51; 87.9%). Patients were treated with first-line suni-tinib (n = 45; 77.6%) or pazopanib (n = 13; 22.4%). The median time from the initial RCC diagnosis to the diagnosis of BMs was 9 months. The median time from the first occurrence of metastasis to the development of BMs was 7 months. The median overall survival (OS) of mRCC patients with BMs was 13 months. Time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months; p = 0.001), histological subtype (non-CC; p<0.05) and number of BMs (>2; p<0.05) were significantly associated with OS in multivariate analysis. There were no cases of toxic death. One mRCC patient with BMs (1.7%) experienced treatment-related cerebral necrosis. All other toxicities included those commonly observed with VEGF-TKI therapy. CONCLUSIONS: The time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months), a non-CC histological subtype, and a greater number of BMs (>2) were independent risk factors for a poor prognosis.

Association among tenascin-C and NT-proBNP levels and arrhythmia prevalence in heart failure.

PURPOSE: Tenascin-C (TN-C) and amino-terminal fragment of the B-type natriuretic peptide (NT-proBNP) are the important predictors in prognosis of heart failure (HF). The aim of this study was to analyze the relationship of TN-C and NT-proBNP levels with the frequency and severity of ventricular arrhythmia. MATERIALS AND METHODS: Our study included 107 HF patients with EF < 45%. According to Holter analysis, the patients were divided into two groups as malignant arrhythmia group (n=29) with Lown Class 4a and 4b arrhythmia and benign arrhythmia group(n=78) with Lown Class 0-3b arrhythmia. The groups were compared with respect to levels of TN-C and NT-proBNP. The relationship of TN-C and NT-proBNP levels with frequency of ventricular premature beat (VPB) was also analyzed. FINDINGS: NT-proBNP (5042.1±1626 versus 1417.1±1711.6 pg/ml) and TN-C (1089±348.6 versus 758.5±423.9 ng/ml) levels were significantly higher in the malignant arrhythmia group than that of the benign arrhythmia group (p.