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Minimalistic Approach for Transcatheter Aortic Valve Implantation (TAVI): Open Vascular Vs. Fully Percutaneous Approach

Abstract

Background: Aortic stenosis (AS) is the most common valvular heart disease in elderly people. Transcatheter aortic valve implantation (TAVI) has emerged as a revolutionary treatment for elderly patients with symptomatic severe aortic stenosis. The authors present the first experiences with transcatheter aortic valve implantation treatment in Macedonia and compare their findings in regard to differences between open vascular vs. minimalistic transfemoral TAVI approach.

Methods: The procedure was performed in 54 patients with severe and symptomatic AS in the period from December 2014 until February 2018. All patients were deemed having high surgical risk or were denied surgery. Pre-procedural screening included detailed clinical and echocardiographic evaluation, coronary, peripheral and carotid angiography and computed tomography scan of the aortic root. A self-expandable aortic valve (Core Valve/Evolut R, Medtronic, USA) was implanted in all patients.

Results: Mean patient age was 75 ± 7.2 years, 28 (52%) were female, 26 patients (48%) male. All interventions were successfully performed through right transfemoral approach with 100% implantation success. Ancillary right radial and ulnar approach was used for correct valve positioning and control. 22(40%) cases were performed under general anesthesia and open vascular access to the femoral artery. All other 32(60%) cases were performed with minimalistic approach (local anaesthesia and analgosedation of the patients, access site was closed with closure devices). Patients in the minimalistic approach group were older, with more chronic conditions as anaemia, chronic kidney disease, poor mobility and peripheral vascular disease (p<0.0001). Also 4(12.5%) patients in the minimalistic group had bicuspid valve TAVI implantation (p<0.0001). Procedural time and contrast amount spent were shorter in this group with 97± 38 vs. 121± 38.3(p<0.0001) and 287± 122 vs. 330± 115 ml, while fluoroscopy time was similar in both groups. Immediate hemodynamic improvement was obtained in all patients. Echocardiographic peak gradient decreased from 85 ± 25 to 17 ± 8 mmHg (p < 0.001) and mean pressure gradient from 49 ± 26 to 8.3 ± 4.2 mmHg, (p < 0.001). Effective valve orifice area was 1.8±0.4 cm2 after intervention. None of the patients had significant aortic regurgitation after implantation. After intervention 7(12%) patients developed a permanent heart block and required implantation of a permanent pacemaker. There was a larger Hgb drop after intervention with open vs. minimalistic approach 1,9±0.9 vs. 0.7±0,2 g/dL (p<0.0001). 3 (13% vs.0%) patients from the open vascular access group had a major bleeding complication with 2 requiring transfusion after intervention (p<0.0001). Mortality was 5.5%, 2 with open-vascular and 1 with minimalistic approach. MACCE rate that included MI, Stroke, Major bleeding and Death rate, was recorded in 5(18%) patients with open vascular approach vs. 1(3.1%) in minimalistic approach (p<0.0001). Hospital discharge was 8.7±3.1 vs. 4±3.1 days respectively (p<0.0001). All TAVI patients with minimalistic approach were discharged the following day after intervention. All discharged patients had a good neurological condition, which was assessed based on the CPC-1 (Cerebra Performance Categories Scale). After median follow up of 26 months, the survival rate was 95% with clinical improvement in all patients.

Conclusion: Percutaneous aortic valve implantation can be successfully conducted with high success rate and low rate of complications in patients with severe aortic stenosis. Using a less invasive approach with local anaesthesia and analgosedation is associated with shorter length of stay and a decrease in post-procedural complication rates and MACCE.

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Prof. Aleksandar Josifovich Ignjatovski, Founder and First Director of the Clinic for Internal Medicine and the First Head of the Department of Internal Medicine at the Faculty of Medicine in Skopje, R. Macedonia

Abstract

Aleksandar J. Ignjatovski was born in the Smolensk Region, Russia, on 18.03.1875. He graduated from the Faculty of Medicine in St. Petersburg in 1899 where he started specialization in internal medicine and continued in Berlin, Heidelberg, Munich and Paris. In 1905 he was elected assistant professor in St. Petersburg, continued as an associate professor in Odessa in 1908 and a full-time professor in 1912 in Warsaw. During the October Revolution, he was the Head of the Internal Clinic in Rostov, and in 1920 he emigrated to Belgrade. In 1922 he was appointed full professor and Director of the First Internal Clinic at the Faculty of Medicine in Belgrade, which he established, developed and managed until his retirement in 1946. In 1948 he moved to Skopje as a full professor and first Director of the Internal Clinic at the Faculty of Medicine in Skopje. He studied the pathogenesis of arteriosclerosis and first proved it experimentally, and published a paper in 1908, indicating that it was associated with higher blood cholesterol level. He also dealt with immunobiology and infectious diseases, in particular tuberculosis and tetanus. Prof. A. Ignjatovski was an excellent clinician, teacher and scientist, who published over 80 papers. His most important textbooks are “Clinical Semiotics and Symptomatic Therapy”, in two editions, in Russian (1919) and in Serbian (1929-37), and “The Basics of Internal Propedeutics” in three volumes, published in Skopje in 1952, 1954 and 1963. The work of Prof. A. Ignjatovski, as a leading clinician and a great teacher and scientist, is embedded in the development of internal medicine, and medicine in general, in Russia, Serbia and Macedonia. The bright memorial of the founder and first director of the Internal Medicine Clinic and the first Head of the Department of Internal Medicine at the Faculty of Medicine in Skopje has been permanently incorporated in the history of medicine in R. Macedonia. Prof. A. Ignjatovski died on 18.08.1955.

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Quality of the Clinical Maternal and Neonatal Healthcare Assessment in a Tertiary Public Maternity Hospital in R. Macedonia

Abstract

Introduction: Maternal and neonatal infections can be prevented, but they are still common in low and middle-developed countries. There is a connection between childbirth on one hand and postpartum and newborn care on the other. Globally, several efforts are being made to improve quality of childbirth by providing initial assessment of procedures, risk prevention and continuous monitoring of childbirth process and possible complications. The World Health Organization has developed Checklists for Safe Delivery with procedures to be implemented as routine care, in order to promptly detect and manage complications related to childbirth.

Material and Methods: A retrospective study was conducted in the University Clinic of Gynecology and Obstetrics in Skopje, a maternity hospital in R. Macedonia from the tertiary level of the public health care system. In this study 300 obstetric and 307 neonatal histories from childbirths in February and March 2018 have been analyzed. The collected data refers to the care of the prepartum, intrapartum, early postpartum and early neonatal periods.

Results: An initial assessment at admission proved that 14.7% of pregnant women had existing infection, in 93% of them the body temperature was measured and in only 9.3% urine analysis was made, 10.3% of the women had arterial hypertension, and 66.5% of them with hypertension had a headache. In the continuous monitoring and prevention of potential risk, arterial tension was measured in 33% of all mothers. In all women the placenta quality was checked up, as well as vaginal bleeding, application of oxytocin and hemoglobin level before discharge.

Conclusion: The quality and quantity of documented data in the maternity hospital medical histories is high. There were no standard protocols for assessment of pregnant women. Certain procedures are conducted in every woman during childbirth. Standardized procedures are needed to be applied during every childbirth.

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A Rare Case of Superior Gluteal Artery Pseudo Aneurysm after Blunt Trauma

Abstract

Prevailing over in rotationally unstable pelvic fractures, acetabular fractures or hip dislocations, superior gluteal artery pseudo aneurysm imperceptibly could be found after blunt force trauma of the pelvic region. We present a case of superior gluteal artery pseudo aneurysm after blunt force trauma that became gradually symptomatic in two months following the prime malevolence. Non-resolving gluteal hematoma presented two months after the incident, disregarding standard treatment methods led the diagnosis to plausible entity of pseudo aneurysm. Standard protocol was followed. CT angiography was indicated and it confirmed the suspected diagnosis. Upon indication a treatment plan was established with correspondent angioembolization of the pathologic substrate. Pseudo aneurism of the superior gluteal artery should be considered as differential diagnosis for unexplained hematomas in the posterior pelvic region following a trauma regardless of its nature.

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Special Conditions in Venous Thrombembolism – Case Series

Abstract

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a preventable cause of in-hospital death, and one of the most prevalent vascular diseases. There is a lack of knowledge with regards to contemporary presentation, management, and outcomes of patients with VTE. Many clinically important subgroups (including the elderly, those with recent bleeding, renal insufficiency, disseminated malignancy or pregnant patients) have been under-represented in randomized clinical trials. We still need information from real life data (as example RIETE). The paper presents case series with VTE in special conditions, including cancer associated thrombosis, malignant homeopathies, as well in high risk population.

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Transmission Electron Microscopy: Novel Application of Established Technique in Characterization of Nanoparticles as Drug Delivery Systems

Abstract

Nanotechnology presents a modern field of science that in the last twenty-five years plays a dominant role in the biomedicine. Different analytical methods are used for evaluation of the physico-chemical properties of nanoparticles including chromatography, electrophoresis, X-ray scattering, spectroscopy, mass spectrometry, zeta potential measurement and microscopy on which this article will focus.

Herein, we present novel application of the long-established TEM technique that is focused on characterization and evaluation of various nanoparticles in development of drug delivery systems.

Transmission electron microscopy images were taken of samples from native nanoparticles, nanoparticles labeled using stannous chloride labeling procedure, inorganic silica nanoparticles loaded with budesonide and native micelles and micelles carrier of anticancer drug camptothecin. In the case of radiolabeled nanoparticles, beside for nanoparticle characterization, TEM technique was used to confirm the stability of the nanoparticles after radiolabeling. Furthermore, the porous structure of hybrid silica particles loaded with budesonide was examined under TEM.

Transmission electron microscopy technique offers exceptional benefits for nanoparticle characterization. Additionally, the necessity of ultrastructural analysis demonstrates the potential of TEM in the field of nanomedicine. Hence, the long-established and well-known TEM has been only partially exploited and offer researchers very detailed images of specimens at microscopic and nano scale.

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Treatment of Acetabular Defects with Porous Metal Augments in Revision Hip Surgery

Abstract

Porous metal augments have been used successfully for management of large acetabular defects during revision hip arthroplasty. This study analyzes and compares the clinical and radiographic outcomes of porous metal augments in cemented and uncemented acetabular revisions, all performed at the same institution. In the period 2015-2017, 36 patients with 37 large acetabular defects were treated with porous metal augments in cemented and uncemented acetabular revisions. Postoperatively, patients were monitored for two years on average period of 24-36 months.

Acetabular augments were used when preoperative and intraoperative findings indicated the presence of large acetabular defects that can hinder the stability of the revision implants. We used lateral approach, 36 mm femoral head, and cementless or cemented acetabular cup depending on local bone quality. Postoperatively, all patients followed total hip arthroplasty precautions, with weight bearing as tolerated regimen with use of crutches during 6 weeks after surgery. The follow-up was radiological and clinical. We used HHS. At a mean follow-up of two years (range 24-36 months) one patient had reinfection and one patient had infection. None of the patients shown signs of aseptic augment or acetabular cup loosening. Porous metal augments show comparable excellent radiographic and clinical short-term outcomes, when combined with cemented or uncemented cups in revision hip arthroplasty. They allow good bone ingrowth, adequate implant contact and good stability. Complications were related to infection and not related to the augments itself.

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Brain Rate Parameter in Children with General Anxiety Disorder

Abstract

Introduction: Brain rate is parameter correlated to brain electric and metabolic activity.

Aim: The aim of this study was to analyze the results obtained for brain rate parameter as an indicator for general mental arousal in anxious patients and to compare them with results of healthy young people matched in age and gender, as well as with anorectic and hyperactive children.

Material and Methods: The diagnosis for all examinees was made according two statistic manuals (DMSIV- R and ICD-10), medical history, neuropsychological assessment, biochemical analysis and QEEG. In this study we examined the spectra power of the brain waves through quantified EEG (QEEG). The obtained results were exported to brain rate software and then calculated for each region separately. The QEEG spectra power data and the brain rate data were analyzed using Statistica software.

Results: According to sagittal and lateral topography maximal values of brain rate parameter were obtained in group of healthy individuals and in group of anorectic patients. The lowest results were obtained in group of hyperactive children for all three regions.

Conclusions: The general conclusion will be that pathological conditions in childhood, analyzed in this research, can be defined as conditions of hypoarausal and this can be specific sign of brain dysfunction.

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Comparison Between HPV DNA Testing and HPV E6/E7 MRNA Testing in Women with Squamous Cell Abnormalities of the Uterine Cervix

Abstract

Introduction: The aim of the study was to compare the results of two human papillomavirus (HPV) diagnostic techniques: human papillomavirus deoxyribonucleic acid (HPV DNA) testing and human papillomavirus E6/E7 messenger ribonucleic acid (HPV E6/E7 mRNA) testing in women with squamous cell abnormalities of the uterine cervix.

Material and Methods: Comparative prospective study, conducted in the period from January 2016 to June 2017 of 128 sexually active women, age groups of 20 to 59 years (40.50 ± 10.85) with squamous cell abnormalities on the cervical cytology. All patients were subject to: HPV DNA testing, HPV E6/E7 mRNA testing and colposcopic cervical biopsy with endocervical curettage for histopathologycal analysis. HPV DNA testing was done using multiplex polymerase chain reaction (PCR) and reverse hybridization methods. HPV E6/E7 mRNA testing was done using real-time PCR method.

Results: Data analysis showed an association between the results of HPV DNA testing and HPV E6/E7 mRNA testing (p˂0.0001). The concordance between the results of both tests was moderate (55.47%). The results show that HPV E6/E7 mRNA testing had a higer specificity 88.89% and positive predictive value (PPV) 93.59% for HSIL + invasive squamous cell carcinoma compared to HPV DNA testing that had specificity of 55.56% and PPV 84.61%, respectively.

Conclusion: The results of our study suggested that HPV E6/E7 mRNA testing is more specific and has a higher positive predictive value than HPV DNA testing and that viral oncoproteins E6 and E7 are superior biomarkers for the detection of high-risk HPV-associated squamous intraepithelial lesions of the uterine cervix.

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Different Clinical Expression of Anxiety Disorders in Children and Adolescents: Assessment and Treatment

Abstract

Background: Fearful and anxious behaviour is especially common in children, when they come across new situations and experiences. The difference between normal worry and an anxiety disorder is in the severity and in the interference with everyday life and normal developmental steps. Many longitudinal studies in children suggest that anxiety disorders are relatively stable over time and predict anxiety and depressive disorders in adolescence and adulthood. For this reason, the early diagnostic and treatment are needed.

Researchers supposed that anxiety is a result of repeated stress. Additionally, some genetic, neurobiological, developmental factors are also involved in the aetiology.

Methods and subjects: The aim of this article is to summarize and to present our own results obtained with the assessment and treatment of different forms of anxiety disorders in children and adolescents such as: Posttraumatic Stress Disorder (PTSD), Obsessive Compulsive Disorder (OCD), Dental anxiety, General Anxiety Disorder (GAD), and Anxious-phobic syndrome. Some results are published separately in different journals.

a) Post Traumatic Stress Disorder (PTSD) in 10 young children aged 9 ± 2, 05 y. is evaluated and discussed concerning the attachment quality.

b) The group with OCD comprises 20 patients, mean age 14,5 ± 2,2 years, evaluated with Eysenck Personality Questionnaire (EPQ), Child behaviour Checklist (CBCL), K-SADS (Schedule for Affective Disorders and Schizophrenia for School age children), Beck Depression Inventory (BDI), SCWT (Stroop Colour Word task), WCST (Wisconsin Card Scoring test).

c) Dental stress is evaluated in a group of 50 patients; mean age for girls 11,4 ± 2,4 years; for boys 10,7 ± 2,6 years, evaluated with (General Anxiety Scale (GASC), and Eysenck Personality Questionnaire (EPQ).

d) Minnesota Multiphasic Personality Inventory (MMPI) profiles obtained for General Anxiety Disorder in 20 young females and 15 males aged 25,7± 5,35 years, and a group with Panic attack syndrome N=15 aged 19,3±4,9 years are presented and discussed by comparison of the results for healthy people.

e) Heart Rate Variability (HRV) was applied for assessment and treatment in 15 anxious-phobic patients, mean age 12, 5±2,25 years and results are compared with other groups of mental disorder.

Results: Children with PTSD showed a high level of anxiety and stress, somatization and behavioural problems (aggression, impulsivity, non-obedience and nightmares), complemented by hypersensitive and depressed mothers and misattachment in the early period of infancy. Consequently, the explanation of the early predisposition to PTSD was related to be the non-developed Right Orbital Cortex. The later resulted from insecure attachment confirmed in all examined children.

The obtained neuropsychological profile of children with OCD confirmed a clear presence of obsessions and compulsions, average intellectual capacities, but the absence of depressive symptoms. Executive functions were investigated through Event Related Potentials on Go/NoGo tasks. Results showed that no significant clinical manifestations of cognitive dysfunction among children with OCD in the early stage of the disorder are present, but it could be expected to be appearing in the later stage of the disorder if it is no treated.

In a study of 50 children randomly selected, two psychometric instruments were applied for measuring general anxiety and personal characteristics. It was confirmed that there was presence of significant anxiety level (evaluated with GASC) among children undergoing dental intervention. The difference in anxiety scores between girls and boys was also confirmed (girls having higher scores for anxiety). Results obtained with EPQ showed low psychopathological traits, moderate extraversion and neuroticism, but accentuated insincerity (L scale). L scales are lower by increasing of age, but P scores rise with age, which can be related to puberty. No correlation was found between personality traits and anxiety except for neuroticism, which is positively correlated with the level of anxiety.

The obtained profiles for MMPI-201 in a group of patients with general anxiety are presented as a figure. Females showed only Hy peak, but in the normal range. However, statistics confirmed significant difference between scores in anxiety group and control (t= 2, 25164; p= 0, 038749). Males showed Hs-Hy-Pt peaks with higher (pathological) scores, related to hypersensitivity of the autonomic nervous system, as well as with manifested anxiety. Calculation confirmed significant difference between control and anxiety in men (t= 15.13, p=0.000).

Additionally, MMPI profiles for patients with attack panic syndrome are also presented as a figure. Control scales for females showed typical V form (scales 1 and 3) related to conversing tendencies. In addition, females showed peaks on Pt-Sc scales, but in normal ranges. Pathological profile is obtained in males, with Hy-Sc peaks; this profile corresponds to persons with regressive characteristics, emotionally instable and with accentuated social withdraw.

Heart rate variability (HRV) is a measure of the beat to beat variability in heart rate, related to the work of autonomic nervous system. It may serve as a psychophysiological indicator for arousal, emotional state and stress level. We used HRV in both, the assessment and biofeedback training, in a group of anxious-phobic and obsessive-compulsive school children. Results obtained with Eysenck Personality Questionnaire showed significantly higher psychopathological traits, higher neuroticism and lower lie scores. After 15 session HRV training very satisfying results for diminishing stress and anxiety were obtained.

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