Danica Marković

Beyond the Limits: Clinical Utility of Novel Cardiac Biomarkers

Preoperative assessment of cardiovascular risk is essential when it comes to extensive noncardiac surgery procedures. Therefore, accurate and timely diagnosis of myocyte damage is vital. In modern medical practice it is believed that the so-called “multimarker” approach is the most appropriate and most accurate, but new research points out that there are novel biomarkers which could be used independently. Studies that evaluate miRNA, H-FABP, and MR-PAMP give encouraging results. When it comes to miRNA clinical studies show high statistical significance, especially in the case of acute myocardial infarction (P = 0.001). Statistical significance of P = 0.007 was found in acute coronary syndrome, when H-FABP was measured. Biochemical marker MR-PAMP showed statistical significance of P < 0.0001 in most clinical studies.

Addition of biomarker panel improves prediction performance of American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) calculator for cardiac risk assessment of elderly patients preparing for major non-cardiac surgery: a pilot study

BackgroundNumber of elderly patients subjected to extensive surgical procedures in the presence of cardiovascular morbidities is increasing every year. Therefore, there is a need to make preoperative diagnostics more accurate.AimsTo evaluate the usefulness of American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) calculator as a predictive tool in preoperative assessment of cardiovascular risk in elderly patients.MethodsThis prospective pilot study included 78 patients who were being prepared for extensive non-cardiac surgeries under general anaesthesia. Their data have been processed on the interactive ACS NSQIP calculator. Blood sampling has been performed 7 days prior to surgery, and serum has been separated. Clinical, novel, and experimental biomarkers [hsCRP, H-FABP, and Survivin (BIRC5)] have been measured in specialized laboratories.ResultsMean age of included patients was 71.35 ± 6.89 years. In the case of heart complications and mortality prediction, hsCRP and ACS NSQIP showed the highest specificity and sensitivity with AUC, respectively, 0.869 and 0.813 for heart complications and 0.883 and 0.813 for mortality. When combined with individual biomarkers AUC of ACS NSQIP raised, but if we combined all three biomarkers with ACS NSQIP, AUC reached as much as 0.920 for heart complications and 0.939 for mortality.DiscussionACS NSQIP proved to reduce inaccuracy in preoperative assessment, but it cannot be used independently, which has already been proved by other authors.ConclusionsOur results indicate that ACS NSQIP represents an accurate tool for preoperative assessment of elderly patients, especially if combined with cardiac biomarkers.

Mutations in Sodium Channel Gene SCN9A and the Pain Perception Disorders

Voltage-gated sodium channels (NaV) play a crucial role in development and propagation of action potentials in neurons and muscle cells. NaV1.7 channels take a special place in modern science since it is believed that they contribute to nerve hyperexcitability. Mutations of the gene SCN9A, which codes the α subunit of NaV1.7 channels, are associated with pain perception disorders (primary erythermalgia, congenital analgesia, and paroxysmal pain disorder). It is considered that the SCN9A gene mutations may cause variations in sensitivity to pain, from complete insensitivity to extreme sensitivity. Further research of the SCN9A gene polymorphism influence on pain sensitivity is essential for the understanding of the pathophysiology of pain and the development of the appropriate targeted pain treatment.

Clinical Utility of Survivin (BIRC5), Novel Cardiac Biomarker, as a Prognostic Tool Compared to High-Sensitivity C-Reactive Protein, Heart-Type Fatty Acid Binding Protein and Revised Lee Score in Elderly Patients Scheduled for Major Non-Cardiac Surgery: A Prospective Pilot Study

Summary Background: Recent studies indicate that survivin (BIRC5) is sensitive to the existence of previous ischemic heart disease, since it is activated in the process of tissue repair and angiogenesis. The aim of this study was to determine the potential of survivin (BIRC5) as a new cardiac biomarker in the preoperative assessment of cardiovascular risk in comparison with clinically accepted cardiac biomarkers and one of the relevant clinical risk scores. Methods: We included 79 patients, female (41) and male (38), with the mean age of 71.35±6.89. Inclusion criteria: extensive non-cardiac surgery, general anesthesia, age >55 and at least one of the selected cardiovascular risk factors (hypertension, diabetes mellitus, hyperlipidemia, smoking and positive family history). Exclusion criteria: emergency surgical procedures and inability to understand and sign an informed consent. Blood sampling was performed 7 days prior surgery and levels of survivin (BIRC5), hsCRP and H-FABP were measured. Results: Revised Lee score was assessed based on data found in patients’ history. Levels of survivin (BIRC5) were higher in deceased patients (P<0.05). It showed AUC=0.807 (95% CI, P<0.0005, 0.698–0.917), greater than both H-FABP and revised Lee index, and it increases the mortality prediction when used together with both biomarkers and revised Lee score. The determined cut-off value was 4 pg/mL and 92.86% of deceased patients had an increased level of survivin (BIRC5), (P=0.005). Conclusions: Survivin (BIRC5) is a potential cardiac biomarker even in elderly patients without tumor, but it cannot be used independently. Further studies with a greater number of patients are needed.

Enhanced Recovery in Thoracic Surgery: A Review

The main goal of enhanced recovery program after thoracic surgery is to minimize stress response, reduce postoperative pulmonary complications, and improve patient outcome, which will in addition decrease hospital stay and reduce hospital costs. As minimally invasive technique, video-assisted thoracoscopic surgery represents an important element of enhanced recovery program in thoracic surgery. Anesthetic management during preoperative, intraoperative and postoperative period is essential for the enhanced recovery. In the era of enhanced recovery protocols, non-intubated thoracoscopic procedures present a step forward. This article focuses on the key elements of the enhanced recovery program in thoracic surgery. Having reviewed recent literature, the authors highlight potential procedures and techniques that might be incorporated into the program.

Enhanced Recovery after Vascular Surgery

The beginnings of the enhanced recovery after surgery (ERAS) program were first developed for patients in colorectal surgery, and after it was established as the standard of care in this surgical field, it began to be applied in many others surgical areas. This is multimodal, evidence-based approach program and includes simultaneous optimization of preoperative status of patients, adequate selection of surgical procedure and postoperative management. The aim of this program is to reduce complications, the length of hospital stay and to improve the patients outcome. Over the past decades, special attention was directed to the postoperative management in vascular surgery, especially after major vascular surgery because of the great risk of multiorgan failure, such as: respiratory failure, myocardial infarction, hemodynamic instability, coagulopathy, renal failure, neurological disorders, and intra-abdominal complications. Although a lot of effort was put into it, there is no unique acceptable program for ERAS in this surgical field, and there is still a need to point out the factors responsible for postoperative outcomes of these patients. So far, it is known that special attention should be paid to already existing diseases, type and the duration of the surgical intervention, hemodynamic and fluid management, nutrition, pain management, and early mobilization of patients.

Genetic Variability of Tumor Necrosis Factor Receptors Type I and II in Lymphoproliferative Diseases in the Serbian Population

Summary TNF-alpha and LT-alpha are involved in the pathogenesis of established lymphoproliferative diseases. Both molecules bind to TNFRI and TNFRII. TNFRI is the major mediator of the TNF pro-apoptotic and proliferative effects and TNFRII might enhance these effects. TNF receptors I and II are normally present on hematopoetic cells. TNFR II is characteristic only on immune cells, especially on peripheral leukocytes. Neoplastic B cells and activated B lymphocytes have increased expression of surface TNFR I. In this study, we have analyzed polymorphisms in the TNFRI gene (TNFRI+36A/G SNP) and polymorphism in the TNFRII gene (TNFRII + 676 T/G). All these polymorphisms were studied in patients with chronic lymphocytic leukemia (CLL), patients with non-Hodkin’s lymphoma (NHL) and in healthy controls. The present study was undertaken to investigate the genetic association of these polymorphisms with lymproproliferative disease development. A total of 68 patients (49-CLL, 19-HNL) were diagnosed at the Clinic of Hematology, Clinical centre Niš, Serbia, using clinical findings and conventional morphological, cytochemical and immunological tests. Genomic DNA was isolated from isolated lymphocytes by proteinase K/phenol/chloroform method, and genotyped for TNFR I (A36G) and TNFR II (T676G) using the PCR-RFLP method. No significant differences in allele frequencies of TNFR1 polymorphism were found between the patients with lymphoproliferative disease and healthy individuals. In a group of healthy individuals, the study has revealed for the first time significantly higher TNFRI G/G genotype compared to the patients with lymphoproliferative disease (χ22 = 5.66; p = 0.017). Also, we reported the implication of TNFRII T allele in NHL pathogenesis, respectively (χ22 = 10.77; p = 0.001; Mantel-Haenszel: χ22 = 10.64; p = 0.0011). Our data showed that TNFRII T676G polymorphisms have an important role in NHL pathogenesis but not in CLL patients. A/A polymorphism in TNFRI was not associated with CLL and NHL patients in the Serbian population. Investigated polymorphisms on TNFR genes in leukemic cells of CLL and NHL patients have not showed a correlation with increased proliferation of B lymphocytes and increased expression of TNF R II on B CLL lymphocytes.

Response: “Commentary: Peripartum Cardiomyopathy in Intensive Care Unit: An Update”

We are very glad that our work got the attention of Dr. Biteker, and we wish to thank him for mentioning PPCM definition by ESC.