Development of autonomic heart rate modulations during childhood and adolescence.

Autonomic control of heart rate is well known in adult subjects, but limited data are available on the development of the heart rate control during childhood and adolescence. Continuous 12-lead electrocardiograms were recorded in 1045 healthy children and adolescents (550 females) aged 4 to 19 years during postural manoeuvres involving repeated 10-min supine, unsupported sitting, and unsupported standing positions. In each position, heart rate was measured, and heart rate variability indices were evaluated (SDNN, RMSSD, and high (HF) and low (LF) frequency components were obtained). Quasi-normalized HF frequency components were defined as qnHF = HF/(HF + LF). These measurements were, among others, related to age using linear regressions. In supine position, heart rate decreases per year of age were significant in both sexes but lower in females than in males. In standing position, these decreases per year of age were substantially lowered. RMSSD and qnHF indices were independent of age in supine position but significantly decreased with age in sitting and standing positions. Correspondingly, LF/HF proportions showed steep increases with age in sitting and standing positions but not in the supine position. The study suggests that baseline supine parasympathetic influence shows little developmental changes during childhood and adolescence but that in young children, sympathetic branch is less responsive to vagal influence. While vagal influences modulate cardiac periods in young and older children equally, they are less able to suppress the sympathetic influence in younger children.

Does the articularis cubiti muscle really exist? Anatomical, histological, and magnetic resonance imaging study with a narrative review of literature.

Although the term articularis cubiti muscle is incorporated in the official anatomical nomenclature, only sparse data about its appearance are available. It is usually described as few fibres originating from the medial head of the triceps brachii muscle and inserting to the capsule of the elbow joint. However, the most recent observations regarding the morphological relations in the posterior elbow region point towards the absence of a well-defined muscle. Therefore, this study was designed to verify the existence of the articularis cubiti muscle in question and to compile more data on the topographical features of the subtricipital area near the posterior aspect of the elbow. To address these questions, 20 embalmed upper limbs were dissected, and seven samples were collected for histological analysis. The laboratory findings were then correlated with 20 magnetic resonance imaging (MRI) scans of the elbow. Consequently, a narrative review of literature was performed to gain more information on the discussed muscle in a historical context. Upon the anatomical dissection, muscular fibres running from the posterior aspect of the shaft of the humerus to the elbow joint capsule and olecranon were identified in 100% of cases. Histologically, the connection with the joint capsule was provided via winding bands of connective tissue. On MRIs, the muscular fibres resembled a well-demarcated thin muscle located underneath the medial head of the triceps brachii muscle. Combined with the review of literature, we concluded that the constant articularis cubiti muscle originates from the posterior shaft of the humerus and attaches indirectly to the posterior aspect of the elbow joint capsule and directly to the superior portion of the olecranon. The obtained results slightly differ from the modern description, but are in agreement with the original publication, which has become misinterpreted throughout time. Presumably, the misused description has led to questioning the existence of an independent muscle. Moreover, our findings attribute to the articularis cubiti muscle, a function in pulling on the posterior aspect of the elbow joint capsule to prevent its entrapment, and possibly also a minor role in extension of the forearm. The presented results should be taken into consideration when intervening with the posterior aspect of the elbow joint because the articularis cubiti muscle poses a consistently appearing landmark.

Current Approaches to Wound Repair in Burns: How far Have we Come From Cover to Close? A Narrative Review.

Burn injuries are a significant global health concern, with more than 11 million people requiring medical intervention each year and approximately 180,000 deaths annually. Despite progress in health and social care, burn injuries continue to result in socioeconomic burdens for victims and their families. The management of severe burn injuries involves preventing and treating burn shock and promoting skin repair through a two-step procedure of covering and closing the wound. Currently, split-thickness/full-thickness skin autografts are the gold standard for permanent skin substitution. However, deep burns treated with split-thickness skin autografts may contract, leading to functional and appearance issues. Conversely, defects treated with full-thickness skin autografts often result in more satisfactory function and appearance. The development of tissue-engineered dermal templates has further expanded the scope of wound repair, providing scar reductive and regenerative properties that have extended their use to reconstructive surgical interventions. Although their interactions with the wound microenvironment are not fully understood, these templates have shown potential in local infection control. This narrative review discusses the current state of wound repair in burn injuries, focusing on the progress made from wound cover to wound closure and local infection control. Advancements in technology and therapies hold promise for improving the outcomes for burn injury patients. Understanding the underlying mechanisms of wound repair and tissue regeneration may provide new insights for developing more effective treatments in the future.

Autologous Alternative Vein Grafts for Infrainguinal Bypass in the Absence of Single-Segment Great Saphenous Vein: A Single-Center Study.

BACKGROUND: Alternative autologous veins can be used as a conduit when adequate great saphenous vein is unavailable. We analyzed the results of our infrainguinal bypasses after adopting upper extremity veins in our practice. METHODS: This is a single-center observational study involving all patients whose infrainguinal bypass involved the use of upper extremity veins between April 2019, when we began using arm veins, and February 2023. RESULTS: During the study period, 49 bypasses were done in 48 patients; mean age 68.1 ± 9.8; men 32 (66.7%); body mass index 28.0 ± 4.8; indications for surgery: chronic limb threatening ischemia 41 (83.7%); acute limb ischemia 3 (6.1%); complications of previous prosthetic 3 (6.1%), or autologous 2 (4.1%) bypass grafts. Vein splicing was used in 43 (87.8%) bypasses with 3-segment grafts being the most common (26; 53.1%). There were 24 (49.0%) femorotibial, 11 (22.4%) femoropopliteal, 9 (18.4%) femoropedal, and 5 (10.2%) extension jump bypass procedures. Eighteen (36.7%) operations were redo surgeries. Twenty-one (42.9%) bypasses were formed using only arm veins. The median follow-up was 12.9 months (4.5-24.2). Two bypasses occluded during the first 30 postoperative days (2/49; 4.1%). Overall 30-day, 1-year, and 2-year primary patency rates were 93.7% ± 3.5%, 84.8% ± 5.9%, and 80.6% ± 6.9%, and secondary patency (SP) rates were 95.8% ± 2.9%, 89.2% ± 5.3%, and 89.2% ± 5.3%. One-segment grafts had better patencies than 2-, 3-, and 4-segment grafts (1-year SP 100% ± 0% vs 87.6% ± 6.0%). Two-year amputation-free survival was 86.8% ± 6.5%; 2-year overall survival was 88.2% ± 6.6%. CONCLUSIONS: Integration of arm vein grafts in infrainguinal bypass practice can be done safely with low incidences of perioperative graft failure. One-segment grafts had better patencies than spliced vein grafts. The achieved early patency and amputation-free survival rates strongly encourage their use. In the absence of a single-segment great saphenous vein, upper extremity vein grafts should be the preferred conduit choice.

Procalcitonin kinetics following abdominal aortic surgery and its value for postoperative intestinal ischaemia detection.

OBJECTIVE: The purpose of our study was to describe perioperative kinetics of procalcitonin (PCT) in patients undergoing aortic surgery, to compare the kinetics in the open abdominal aortic aneurysm (AAA) repair and aortobifemoral bypass for aortoiliac occlusive disease (AIOD), and to evaluate the ability of PCT to detect intestinal ischaemia. METHODS: A prospective non-randomized observational cohort study in 80 patients (62 men and 18 women) undergoing elective aortic surgery was performed. Serum PCT was measured at baseline and defined intraoperative and postoperative timepoints up to postoperative day 7. MRI contrast-enhanced imaging was used to detect intestinal ischaemia. RESULTS: The comparison of the AAA and AIOD cohort did not show any significant difference in PCT levels. Patients with intestinal ischaemia had higher serum PCT at multiple timepoints postoperatively. The most accurate timepoints for early diagnosis were postoperative day 3, followed by 24 h after declamping of the vascular reconstruction, and postoperative day 7. The sensitivity and negative predictive values were 100% in all mentioned timepoints. However, event at the best timepoint the specificity was 89% and the positive predictive value 43%. CONCLUSIONS: Procalcitonin levels in the postoperative period at proper timepoints might help to detect postoperative intestinal ischaemia. The limitation of this marker is its low specificity for intestinal ischaemia and low positive predictive value. The highest value of this marker is that it can rule out this complication because normal PCT levels mean that intestinal ischaemia is very unlikely.

QRS micro-fragmentation as a mortality predictor.

AIMS: Fragmented QRS complex with visible notching on standard 12-lead electrocardiogram (ECG) is understood to represent depolarization abnormalities and to signify risk of cardiac events. Depolarization abnormalities with similar prognostic implications likely exist beyond visual recognition but no technology is presently suitable for quantification of such invisible ECG abnormalities. We present such a technology. METHODS AND RESULTS: A signal processing method projects all ECG leads of the QRS complex into optimized three perpendicular dimensions, reconstructs the ECG back from this three-dimensional projection, and quantifies the difference (QRS 'micro'-fragmentation, QRS-µf) between the original and reconstructed signals. QRS 'micro'-fragmentation was assessed in three different populations: cardiac patients with automatic implantable cardioverter-defibrillators, cardiac patients with severe abnormalities, and general public. The predictive value of QRS-µf for mortality was investigated both univariably and in multivariable comparisons with other risk factors including visible QRS 'macro'-fragmentation, QRS-Mf. The analysis was made in a total of 7779 subjects of whom 504 have not survived the first 5 years of follow-up. In all three populations, QRS-µf was strongly predictive of survival (P < 0.001 univariably, and P < 0.001 to P = 0.024 in multivariable regression analyses). A similar strong association with outcome was found when dichotomizing QRS-µf prospectively at 3.5%. When QRS-µf was used in multivariable analyses, QRS-Mf and QRS duration lost their predictive value. CONCLUSION: In three populations with different clinical characteristics, QRS-µf was a powerful mortality risk factor independent of several previously established risk indices. Electrophysiologic abnormalities that contribute to increased QRS-µf values are likely responsible for the predictive power of visible QRS-Mf.

Treatment of knee cartilage by cultured stem cells and three dimensional scaffold: a phase I/IIa clinical trial.

PURPOSE: Damage of the knee cartilage is a common condition manifesting itself mainly by pain and/or swelling that may substantially reduce the quality of life while ultimately leading to osteoarthritis in affected patients. Here, we aimed to evaluate the safety and efficacy of cultured autologous bone marrow mesenchymal stem cells (BM-MSCs) attached to the 3D Chondrotissue® scaffold by autologous blood plasma coagulation (BiCure® ortho MSCp) in the treatment of knee cartilage defects. METHODS: The primary endpoint of this phase I/IIa clinical trial was to evaluate the safety of the treatment. The secondary objective was to determine the short-to-medium-term therapeutic outcomes by standardized scoring questionnaires including Lysholm Knee Scoring Scale (Lysholm score), Knee Injury and Osteoarthritis Outcome Score (KOOS), and pain Visual Analogue Scale (VAS) systems and imaging (X-ray and magnetic resonance imaging, MRI). A total of six patients were included and followed for 12 months after the surgery. RESULTS: BiCure® ortho MSCp was well tolerated with no adverse events associated with the investigational medicinal product. Significant improvements were observed in Lysholm scores and KOOS while X-ray showed no deterioration of the arthritis and MRI revealed a persistent filling of the chondral defects by the implant. CONCLUSION: Overall, our data demonstrate the safety of the tested investigational medicinal product. The function of the treated knee improved within one year after surgery in all enrolled patients. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: EudraCT No.: 2018-004,067-31; October 18 2018.

Mathematical model of electromigration allowing the deviation from electroneutrality.

The structure of the double layer on the boundary between solid and liquid phases is described by various models, of which the Stern-Gouy-Chapman model is still commonly accepted. Generally, the solid phase is charged, which also causes the distribution of the electric charge in the adjacent diffuse layer in the liquid phase. We propose a new mathematical model of electromigration considering the high deviation from electroneutrality in the diffuse layer of the double layer when the liquid phase is composed of solution of weak multivalent electrolytes of any valence and of any complexity. The mathematical model joins together the Poisson equation, the continuity equation for electric charge, the mass continuity equations, and the modified G-function. The model is able to calculate the volume charge density, electric potential, and concentration profiles of all ionic forms of all electrolytes in the diffuse part of the double layer, which consequently enables to calculate conductivity, pH, and deviation from electroneutrality. The model can easily be implemented into the numerical simulation software such as Comsol. Its outcome is demonstrated by the numerical simulation of the double layer composed of a charged silica surface and an adjacent liquid solution composed of weak multivalent electrolytes. The validity of the model is not limited only to the diffuse part of the double layer but is valid for electromigration of electrolytes in general.

Minoxidil decreases collagen I deposition and tissue-like contraction in clubfoot-derived cells: a way to improve conservative treatment of relapsed clubfoot?

AIM: Clubfoot is a congenital deformity affecting the musculoskeletal system, resulting in contracted and stiff tissue in the medial part of the foot. Minoxidil (MXD) has an inhibitory effect on lysyl hydroxylase, which influences the quality of extracellular matrix crosslinking, and could therefore be used to reduce the stiffness and to improve the flexibility of the tissue. We assessed the in vitro antifibrotic effects of minoxidil on clubfoot-derived cells. METHODS: Cell viability and proliferation were quantified by xCELLigence, MTS, and LIVE/DEAD assays. The amount of collagen I deposited into the extracellular matrix was quantified using immunofluorescence with subsequent image segmentation analysis, hydroxyproline assay, and Second Harmonic Generation imaging. Extracellular matrix contraction was studied in a 3D model of cell-populated collagen gel lattices. RESULTS: MXD concentrations of 0.25, 0.5, and 0.75 mM inhibited the cell proliferation in a concentration-dependent manner without causing a cytotoxic effect. Exposure to ≥0.5 mM MXD resulted in a decrease in collagen type I accumulation after 8 and 21 days in culture. Changes in collagen fiber assembly were observed by immunofluorescence microscopy and nonlinear optical microscopy (second harmonic generation). MXD also inhibited the contraction of cell-populated collagen lattices (0.5 mM by 22%; 0.75 mM by 28%). CONCLUSIONS: Minoxidil exerts an in vitro inhibitory effect on the cell proliferation, collagen accumulation, and extracellular matrix contraction processes that are associated with clubfoot fibrosis. This study provides important preliminary results demonstrating the potential relevance of MXD for adjuvant pharmacological therapy in standard treatment of relapsed clubfoot.

Increased Collagen Crosslinking in Stiff Clubfoot Tissue: Implications for the Improvement of Therapeutic Strategies.

Congenital clubfoot is a complex musculoskeletal deformity, in which a stiff, contracted tissue forms in the medial part of the foot. Fibrotic changes are associated with increased collagen deposition and lysyl oxidase (LOX)-mediated crosslinking, which impair collagen degradation and increase the tissue stiffness. First, we studied collagen deposition, as well as the expression of collagen and the amount of pyridinoline and deoxypyridinoline crosslinks in the tissue of relapsed clubfoot by immunohistochemistry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA). We then isolated fibroblast-like cells from the contracted tissue to study the potential inhibition of these processes in vitro. We assessed the effects of a LOX inhibitor, ß-aminopropionitrile (BAPN), on the cells by a hydroxyproline assay, ELISA, and Second Harmonic Generation imaging. We also evaluated the cell-mediated contraction of extracellular matrix in 3D cell-populated collagen gels. For the first time, we have confirmed significantly increased crosslinking and excessive collagen type I deposition in the clubfoot-contracted tissue. We successfully reduced these processes in vitro in a dose-dependent manner with 10-40 µg/mL of BAPN, and we observed an increasing trend in the inhibition of the cell-mediated contraction of collagen gels. The in vitro inhibitory effects indicate that BAPN has good potential for the treatment of relapsed and resistant clubfeet.

Toxocariasis as a Rare Parasitic Complication of a Transthoracic Spine Surgery Procedure.

Human toxocariasis is a helminthozoonosis caused by the migration of Toxocara species larvae through an organism. The infection in humans is transmitted either by direct ingestion of the eggs of the parasite, or by consuming undercooked meat infested with Toxocara larvae. This parasitosis can be found worldwide, but there are significant differences in seroprevalence in different areas, depending mainly on hot climate conditions and on low social status. However, the literature estimates of seroprevalence are inconsistent. Infected patients commonly present a range of symptoms, e.g., abdominal pain, decreased appetite, restlessness, fever, and coughing. This manuscript presents a case report of a polytraumatic patient who underwent a two-phase spinal procedure for a thoracolumbar fracture. After the second procedure, which was a vertebral body replacement via thoracotomy, the patient developed a pathologic pleural effusion. A microscopic cytology examination of this effusion revealed the presence of Toxocara species larvae. Although the patient presented no specific clinical symptoms, and the serological exams (Enzyme-linked immunosorbent assay (ELISA), Western blot) were negative, the microscopic evaluation enabled a timely diagnosis. The patient was successfully treated with albendazole, with no permanent sequelae of the infection.

Electrolysis phenomena in electrophoresis.

We present a new theoretical approach for calculating changes in the physico-chemical properties of BGEs for measurements by CZE due to the electrolysis in electrode vials (vessels). Electrolysis is an inevitable phenomenon in any measurement in CZE. Water electrolysis, which occurs in most measurements, can significantly alter the composition of the BGE in electrode vials and in the separation capillary and has a negative influence on the robustness and quality of separations. The ability to predict changes in the composition of the BGE is important for evaluation of the suitability of the BGEs for repeating electrophoretic runs. We compared theoretically calculated changes in the physico-chemical properties (pH, conductivity) with those measured using pH-microelectrode and contactless conductivity detection of the BGE after the electrophoretic run. We confirmed the validity of our theoretical approach with a common BGE composed of acid-base pair, where one constituent is fully dissociated while the second constituent is dissociated by only half, and with Good's buffer. As predicted by theoretical approach, the changes in the physico-chemical properties of the Good's buffer after the electrophoretic run were several times lower than in the case of a common BGE composed of a weak acid - strong base pair.

Problems with Bazett QTc correction in paediatric screening of prolonged QTc interval.

BACKGROUND: Bazett formula is frequently used in paediatric screening for the long QT syndrome (LQTS) and proposals exist that using standing rather than supine electrocardiograms (ECG) improves the sensitivity of LQTS diagnosis. Nevertheless, compared to adults, children have higher heart rates (especially during postural provocations) and Bazett correction is also known to lead to artificially prolonged QTc values at increased heart rates. This study assessed the incidence of erroneously increased QTc values in normal children without QT abnormalities. METHODS: Continuous 12-lead ECGs were recorded in 332 healthy children (166 girls) aged 10.7 ± 2.6 years while they performed postural manoeuvring consisting of episodes (in the following order) of supine, sitting, standing, supine, standing, sitting, and supine positions, each lasting 10 min. Detailed analyses of QT/RR profiles confirmed the absence of prolonged individually corrected QTc interval in each child. Heart rate and QT intervals were measured in 10-s ECG segments and in each segment, QTc intervals were obtained using Bazett, Fridericia, and Framingham formulas. In each child, the heart rates and QTc values obtained during supine, sitting and standing positions were averaged. QTc durations by the three formulas were classified to < 440 ms, 440-460 ms, 460-480 ms, and > 480 ms. RESULTS: At supine position, averaged heart rate was 77.5 ± 10.5 beat per minute (bpm) and Bazett, Fridericia and Framingham QTc intervals were 425.3 ± 15.8, 407.8 ± 13.9, and 408.2 ± 13.1 ms, respectively. At sitting and standing, averaged heart rate increased to 90.9 ± 10.1 and 100.9 ± 10.5 bpm, respectively. While Fridericia and Framingham formulas showed only minimal QTc changes, Bazett correction led to QTc increases to 435 ± 15.1 and 444.9 ± 15.9 ms at sitting and standing, respectively. At sitting, Bazett correction identified 51, 4, and 0 children as having the QTc intervals 440-460, 460-480, and > 480 ms, respectively. At sitting, these numbers increased to 118, 11, and 1, while on standing these numbers were 151, 45, and 5, respectively. Irrespective of the postural position, Fridericia and Framingham formulas identified only a small number (< 7) of children with QT interval between 440 and 460 ms and no children with longer QTc. CONCLUSION: During screening for LQTS in children, the use of Bazett formula leads to a high number of false positive cases especially if the heart rates are increased (e.g. by postural manoeuvring). The use of Fridericia formula can be recommended to replace the Bazett correction not only for adult but also for paediatric ECGs.

Increased Microvessel and Arteriole Density in the Contracted Side of the Relapsed Clubfoot.

BACKGROUND: Clubfoot deformity (pes equinovarus) is one of the most common birth defects, and its etiology is still unknown. Initial clubfoot treatment is based on the Ponseti method throughout most of the world. Despite the effectiveness of this therapy, clubfoot may relapse. Recent studies confirm the theory of active fibrotic remodeling processes in the extracellular matrix of the affected tissue. The aim of this study was to clarify whether relapses in clubfoot therapy are associated with altered angiogenesis and to suggest possible regulatory pathways of this pathologic process. METHODS: We compared microvessel density, arteriole density, and concentration of angioproliferative-related proteins found between tissues in the contracted, that is, the medial side (M-side), and noncontracted, that is, the lateral side (L-side) of the relapsed clubfeet. Tissue samples from 10 patients were analyzed. Histopathologic analysis consisted of immunohistochemistry and image analysis. Real-time polymerase chain reaction was used to study mRNA expression. RESULTS: An increase in microvessel and arteriole density was noted in contracted, relapsed clubfoot tissue. This was accompanied by a significant increase in the levels of the vascular endothelial growth factor, vascular endothelial growth factor receptor 2, ß catenin and active ß catenin. Vascular endothelial growth factor, vascular endothelial growth factor receptor 2, and CD31 overexpression was also seen with mRNA analysis. CONCLUSIONS: Increased microvessel and arteriole density in the contracted side of the relapsed clubfoot was noted. These processes are mediated by specific proangiogenic proteins that are overexpressed in the contracted tissue. These findings contribute to the etiology and the development of relapses in the treatment of clubfoot. LEVEL OF EVIDENCE: Level II-analytical and prospective.

Effects of noise-induced coherence on the fluctuations of current in quantum absorption refrigerators.

We investigate the effects of noise-induced coherence on average current and current fluctuations in a simple model of a quantum absorption refrigerator with degenerate energy levels. We describe and explain the differences and similarities between the system behavior when it operates in the classical regime, where the populations and coherences in the corresponding quantum optical master equation decouple in a suitably chosen basis, and in the quantum regime, where such a transformation does not exist. The differences between the quantum and the classical cases are observable only close to the maximum current regime, where the system steady-state becomes nonunique. This allows us to approximate the system dynamics by an analytical model based on a dichotomous process that explains the behavior of the average current both in the classical and in the quantum cases. Due to the nonuniqueness, the scaled cumulant generating function for the current at the vicinity of the critical point exhibits behavior reminiscent of the dynamical first-order phase transition. Unless the system parameters are fine-tuned to a single point in the parameter space, the corresponding current fluctuations are moderate in the quantum case and large in the classical case.

Present criteria for prophylactic ICD implantation: Insights from the EU-CERT-ICD (Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in EUrope) project.

BACKGROUND: The clinical effectiveness of primary prevention implantable cardioverter defibrillator (ICD) therapy is under debate. It is urgently needed to better identify patients who benefit from prophylactic ICD therapy. The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD) completed in 2019 will assess this issue. SUMMARY: The EU-CERT-ICD is a prospective investigator-initiated non-randomized, controlled, multicenter observational cohort study done in 44 centers across 15 European countries. A total of 2327 patients with heart failure due to ischemic heart disease or dilated cardiomyopathy indicated for primary prophylactic ICD implantation were recruited between 2014 and 2018 (>1500 patients at first ICD implantation, >750 patients non-randomized non-ICD control group). The primary endpoint was all-cause mortality, and first appropriate shock was co-primary endpoint. At baseline, all patients underwent 12­lead ECG and Holter-ECG analysis using multiple advanced methods for risk stratification as well as documentation of clinical characteristics and laboratory values. The EU-CERT-ICD data will provide much needed information on the survival benefit of preventive ICD therapy and expand on previous prospective risk stratification studies which showed very good applicability of clinical parameters and advanced risk stratifiers in order to define patient subgroups with above or below average ICD benefit. CONCLUSION: The EU-CERT-ICD study will provide new and current data about effectiveness of primary prophylactic ICD implantation. The study also aims for improved risk stratification and patient selection using clinical risk markers in general, and advanced ECG risk markers in particular.

Clinical value of different QRS-T angle expressions.

Aims: Increased spatial angle between QRS complex and T wave loop orientations has repeatedly been shown to predict cardiac risk. However, there is no consensus on the methods for the calculation of the angle. This study compared the reproducibility and predictive power of three most common ways of QRS-T angle assessment. Methods and results: Electrocardiograms of 352 healthy subjects, 941 survivors of acute myocardial infarction (MI), and 605 patients recorded prior to the implantation of automatic defibrillator [implantable cardioverter defibrillator (ICD)] were used to obtain QRS-T angle measurements by the maximum R to T (MRT), area R to T (ART), and total cosine R to T (TCRT) methods. The results were compared in terms of physiologic reproducibility and power to predict mortality in the cardiac patients during 5-year follow-up. Maximum R to T results were significantly less reproducible compared to the other two methods. Among both survivors of acute MI and ICD recipients, TCRT method was statistically significantly more powerful in predicting mortality during follow-up. Among the acute MI survivors, increased spatial QRS-T angle (TCRT assessment) was particularly powerful in predicting sudden cardiac death with the area under the receiver operator characteristic of 78% (90% confidence interval 63-90%). Among the ICD recipients, TCRT also predicted mortality significantly among patients with prolonged QRS complex duration when the spatial orientation of the QRS complex is poorly defined. Conclusion: The TCRT method for the assessment of spatial QRS-T angle appears to offer important advantages in comparison to other methods of measurement. This approach should be included in future clinical studies of the QRS-T angle. The TCRT method might also be a reasonable candidate for the standardization of the QRS-T angle assessment.

Hypersensitivity to material and environmental burden as a possible cause of late complications of cardiac implantable electronic devices.

Aims: To evaluate whether patients with late complications of pacemakers or implantable cardioverter-defibrillators have hypersensitivity reactions to some of the materials used in generators or in electrodes, or to environmental metal burden. Methods and results: The cohort consisted of 20 men and 4 women (mean age: 62.3 ± 17.2 years) who had a history of late complications of implanted devices. The control group involved 25 men and 8 women (mean age: 64.6 ± 14.0 years) who had comparable devices, but no history of late complications. Lymphocyte transformation test was used to evaluate hypersensitivity to eight metal pollutants (antimony, manganese, mercury, molybdenum, nickel, platinum, tin, and titanium) selected by results of questionnaires on environmental burden, and by material analysis of generators and electrode surfaces. Exposures to metal pollutants were approximately the same in patients and in controls. Titanium alloy used in generators contained at least 99.32% of titanium and trace levels of other metals; higher levels of tin and platinum were detected in electrode surfaces. Hypersensitivity reactions to mercury and tin were significantly more frequent in patients than in controls (patients and controls: mercury: 68.2 and 31.1%, respectively; P = 0.022; tin: 25.0 and 3.2%, respectively; P = 0.035). In contrast, hypersensitivity to manganese was significantly more frequent in controls than in patients (patients and controls: 13.6 and 50.0%, respectively; P = 0.008). Conclusion: Our findings suggest a possible relation between hypersensitivity to metals used in implantable devices or to environmental metal burden and the occurrence of their late complications.

Four-day pulse of sodium cromoglycate modulates pulmonary vessel wall remodeling during 21-day hypoxia in rats.

AIM OF THE STUDY: Remodeling of pulmonary resistance arteries in rats due to 4-day hypoxia could be successfully suppressed by sodium cromoglycate. In this study, we tested the difference in the suppression between two distinct time patterns of cromoglycate administration during 21-day hypoxia. In the experiment, we focused on some details in both smooth muscle cells and extracellular matrix of pulmonary arterial walls. METHODS: During 21-day hypoxia, rats were treated with sodium cromoglycate either in the first four days or in the last four days. The first four days were chosen to test efficiency of an initial pulse of cromoglycate to suppress pulmonary vascular remodeling. The last four-day administration tested possibility to block remodeling post hoc. RESULTS: Initial pulse reduced and modified remodeling in all levels of pulmonary arteries, which comprises neomuscularization of prealveolar arteries, asymmetrical hypertrophy of tunica media in muscular pulmonary arteries and hypertrophy of tunica media and tunica adventitia in large conduit arteries. Terminal pulse had only negligible effect. CONCLUSIONS: Only the initial cromoglycate therapy led to significant morphological suppression of remodeling. We therefore assume important role of initial remodeling influencing during long time hypoxia experiment.

Automation bias in medicine: The influence of automated diagnoses on interpreter accuracy and uncertainty when reading electrocardiograms.

INTRODUCTION: Interpretation of the 12­lead Electrocardiogram (ECG) is normally assisted with an automated diagnosis (AD), which can facilitate an 'automation bias' where interpreters can be anchored. In this paper, we studied, 1) the effect of an incorrect AD on interpretation accuracy and interpreter confidence (a proxy for uncertainty), and 2) whether confidence and other interpreter features can predict interpretation accuracy using machine learning. METHODS: This study analysed 9000 ECG interpretations from cardiology and non-cardiology fellows (CFs and non-CFs). One third of the ECGs involved no ADs, one third with ADs (half as incorrect) and one third had multiple ADs. Interpretations were scored and interpreter confidence was recorded for each interpretation and subsequently standardised using sigma scaling. Spearman coefficients were used for correlation analysis and C5.0 decision trees were used for predicting interpretation accuracy using basic interpreter features such as confidence, age, experience and designation. RESULTS: Interpretation accuracies achieved by CFs and non-CFs dropped by 43.20% and 58.95% respectively when an incorrect AD was presented (p < 0.001). Overall correlation between scaled confidence and interpretation accuracy was higher amongst CFs. However, correlation between confidence and interpretation accuracy decreased for both groups when an incorrect AD was presented. We found that an incorrect AD disturbs the reliability of interpreter confidence in predicting accuracy. An incorrect AD has a greater effect on the confidence of non-CFs (although this is not statistically significant it is close to the threshold, p = 0.065). The best C5.0 decision tree achieved an accuracy rate of 64.67% (p < 0.001), however this is only 6.56% greater than the no-information-rate. CONCLUSION: Incorrect ADs reduce the interpreter's diagnostic accuracy indicating an automation bias. Non-CFs tend to agree more with the ADs in comparison to CFs, hence less expert physicians are more effected by automation bias. Incorrect ADs reduce the interpreter's confidence and also reduces the predictive power of confidence for predicting accuracy (even more so for non-CFs). Whilst a statistically significant model was developed, it is difficult to predict interpretation accuracy using machine learning on basic features such as interpreter confidence, age, reader experience and designation.