Volume 41 (2020): Edition 2 (September 2020)

Stress, as a kind of emotion, is inevitable in everyday life. In psychosomatic medicine stress represents a powerful link in the pathophysiological chain of disorder. Having evidence about the power of stress on the body, the interest in medicine was how to measure it in appropriate, fast way and with minimal cost. Electrodermal activity seems to be available for this purpose.

The galvanic skin response (GSR) is an objective, transient indication of autonomic nervous system arousal in response to a stimulus. It refers to changes in sweat gland activity that are reflective of the intensity of our emotional arousal.

In this article we discuss physiological specifics of skin conductance/resistance and how it is measured in practice. The most used application of GSR is in biofeedback methodology. Biofeedback assessment and training exactly uses skin reaction to different stimuli and aims to gain voluntary control over this autonomic response. The aim of this article is to show effectiveness of this method in paediatric practice.

EEG can determine changes in brain activity that might be useful in diagnosing different brain disorders as well as some mental states. Many advantages of this record have been the reason for resurrect the EEG in current clinical practice and research. More sophisticated form, the Q-EEG comprises a procedure that processes the recorded EEG activity from a multi-electrode recording using a computer, where data is processed with various algorithms, such as the Fourier or Wavelet analysis. Q-EEG data are important as a marker for many psychophysiological disorders.

Neurofeedback (NF) is a form of behavioural training aimed at developing skills for self-regulation of brain activity. It is a treatment method for altering brain functioning by the use of signals provided to a patient that reflect the moment-to-moment changes in the patient’s electroencephalogram.

This article summarizes some of our large experience with neurofeedback training in different groups of disorders in children and adolescents. Positive outcome is promising for more expansive use of this non-pharmacological, cost-benefit methodology in paediatric and general population.

Summary: Anaplastic lymphoma kinase (ALK) rearrangement is identified in approximately 3-7% of all metastatic non-small cell lung cancer (NSCLC) patients, and ALK tyrosine kinase inhibitors (TKIs) have revolutionized the management of this subset of lung cancer cases.

Purpose: This study aims to show alectinib (TKI) effectiveness and safety with focus on alectinib intracranial efficacy for ALK+ NSCLC patients.

Case presentation: Patient 1 was a 46-year-old woman diagnosed with non-small cell lung cancer with an echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene (ALK+). She presented with intracranial and liver metastases and poor performance status of ECOG 3. Alectinib was initiated as a second line therapy, after whole brain irradiation and discontinuation of first line chemotherapy after two cycles, due to the central nervous system progression and liver metastases. Good response was consequently achieved, characterized with improved overall performance and without significant adverse events.

Patient 2 was a 53-year old man with left sided lung adenocarcinoma surgically treated in 2017. Post-operative pTNM stage was IIB with a positive resection margin- R1. He received adjuvant chemotherapy and radiotherapy. In 2019, after two and half years of being disease free, he presented with severe cerebral symptoms leading to poor performance status. CT scan of the brain showed multiple brain metastases. He was treated with first line alectinib after completion of whole brain radiotherapy. In 5 months period he got significantly better and able for work again.

Conclusions: We recommend alectinib as a first and second line treatment approach for ALK+ NSCLC patients, in particular the ones with brain metastases at the time of diagnosis and poor PS.

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. This study was designed to determine the clinical, biological features and outcomes among children with ALL treated at the only pediatric hematology-oncology center in North Macedonia.

Patients and methods: Seventy four consecutive children age 1 to 14 years, diagnosed with ALL between January 1, 2010 and October 31, 2017 and treated according to ALL IC BFM 2002 protocol were retrospectively evaluated.

Results: The median age at diagnosis was 5 years and males were predominant (60.8%). Precursor B-cell ALL was diagnosed in 81.1% of patients, while 18.9% had T cell ALL. CNS involvement at the time of diagnoses was present in 6.8% of patients. Complete remission was achieved in 93.2% of patients. The induction death rate was 5.4%. The rate of death during first complete remission was 4.1%. Relapse occurred in 13.5% of patients. After a median observation time of 44 months, the 5-year overall survival (OS) and event-free survival (EFS) rates (± standard error) were 79.4% ± 5.2% and 74% ± 5.7%, respectively. The 5-year EFS rate for patients categorized as standard risk by NCI criteria was significantly higher than for high risk patients (83.3% versus 46.7%; P<0.001). Patients with precursor B-cell ALL and negative minimal residual disease (MRD) status at the end of induction had the best prognoses.

Conclusion: Our study demonstrated that the treatment results of childhood ALL in North Macedonia are comparable to those obtained in the ALL IC BFM 2002 trial.

Aim: Data on the use of novel anticoagulant drugs (NOACc) in renal transplant recipients is scarce. The aim of our study was to investigate the safety and efficacy of NOACs in renal transplant recipients.

Materials and Methods: In a single-centre retrospective cohort study we assessed adverse reactions, thromboembolic events, and interactions of calcineurin inhibitors in patients treated with NOACs.

Results: Twenty-three renal transplant recipients were treated with NOACs (70% male), mean age of 65.8 ± 1.8 years. Fourteen (61%) patients were treated with rivaroxaban, apixaban was given to 8 (35%) of our patients, and dabigatran to one patient (4%). The main indications for NOAC therapy was atrial fibrillation in 61% and deep venous thrombosis in 23% of patients. Bleeding occurred in 2 patients (1 treated with rivaroxaban and 1 with dabigatran). None of our patients developed thrombosis while treated with NOAC. During the median follow-up of 24 months graft function, as well as hematological parameters, remained stable in patients that were treated with rivaroxaban and apixaban, while dabigatran was ceased after a month of therapy due to a bleeding event.

Conclusion: Our results show that both rivaroxaban and apixaban are safe and efficient oral anticoagulant drugs in renal transplant patients. Additional studies are needed to prove these results.

Metastasis of renal cell carcinoma (RCC) to the pancreas is a rare entity accounting only 0.25–3% of all pancreatic tumors. We present a rare case of isolated three focal pancreatic metastases from RCC, occurring 15 years after the left nephrectomy. The majority of the pancreatic metastases are asymptomatic, as it was in case of our patient excluding the weight loss for the last three months. We demonstrate the importance of the medical history, radiological examinations, histological and immunohistochemical analysis in making a definitive diagnosis.

Introduction: Seasonal influenza, although often presented as a mild, self-limiting disease, is frequently accompanied by complications that lead to the development of a severe clinical presentation and a fatal outcome. The most common are respiratory complications, with secondary bacterial pneumonia being the leading cause.

Aim: The aim of this study is to determine the impact of pneumonia on the severity of the clinical presentation and outcome in patients with seasonal influenza.

Materials and Methods: This research is comparatively group-based and has been conducted at the University Clinic for Infectious Diseases and Febrile Conditions during a three-year period. The analysis consists of 122 adult patients with clinically and laboratory-confirmed influenza. Based on the severity of the clinical picture, the patients are divided into two groups, severe (n=87) and mild (n=35) forms of the disease. The study included demographic, general data, clinical symptoms, and signs as well as complications.

Results: Of 122 patients with seasonal influenza, complications were registered among 108(88.52%), with a significantly more frequent emergence among the group with severe influenza 93.1% vs 77.14% (p=0.012). Pneumonia was the most common 98(80.33%) and had a significant effect on disease severity (p=0.002). Complications from the types of ABI 8(6.56%), ARDS 7(5.74%), sepsis 5(4.1%), DIC 4 (3.28%) and otitis 2(1.64%) were reported only in the group with severe influenza. Acute meningoencephalitis was registered among 5(4.1%), gastroenterocolitis among 3(2.46%), and hepatic damage among 14(11.47%) of patients.

Conclusion: Pneumonia as the most common complication among patients with seasonal influenza significantly impacts the clinical course and outcome of the illness.

Background: The surgical treatment of chronic patellar tendinopathy could be open or arthroscopic. A general agreement on the best surgical treatment option is still lacking.

Purpose: The aim of our study was to evaluate the clinical results after a minimally invasive arthroscopic treatment of chronic patellar tendinopathy including a resection of the lower patellar pole.

Methods: The study included 14 patients with a mean age of 26 years and chronic patellar tendinopathy refractory to non-operative treatment of more than 6 months. All patients underwent arthroscopic debridement of the adipose tissue of the Hoffa’s body posterior to the patellar tendon, debridement of abnormal patellar tendon and resection of the lower patellar pole. Preoperative and postoperative evaluation was undertaken using clinical examination, magnetic resonance imaging (MRI) and the Lysholm and Victorian Institute of Sport Assessment-Patella (VISA-P) scores. Return to sports and postoperative complications were also assessed. The mean follow-up was 12.2 ± 0.9 months.

Results: All 14 patients continued with sport activities, but only 12 of them (85.7%) achieved their presymptom sporting level. The median time to return to preinjury level of activity was 3.9 ± 0.8 months. Patients showed a major improvement in the mean Lysholm score from 51.1 ± 3.8 to 93.4 ± 4.2 (p=0.001) and in the mean VISA-P score from 42.1 ± 3.5 to 86.7 ± 8.4 (p=0.001) There were no postoperative complications.

Conclusion: We found that this arthroscopic technique gives reduced morbidity and satisfactory outcome resulting in significantly faster recovery and return to sports in patients with chronic patellar tendinopathy.

Autism spectrum disorder (ASD) comprises a group of complex lifelong neurodevelopmental disorders, characterized with symptoms related to the difficulty of communication and interaction with other people, as well as restricted interests and repetitive behaviors. These symptoms affects the person’s ability to function properly in school, work, and other areas of life.

For better understanding the needs and challenges of families the survey developed by Autism Speaks in collaboration with the National Coordinators for Autism from nine Balkan countries was established. The aim of this research is to obtain an overview of some important data for children with some form of autistic disorder.

The same questionnaire was used in two different periods of time (during 2015 and at the beginning of 2020) including samples of 60 and 140 parents respectively.

The questionnaire comprises 57 questions in the following four domains: demographic characteristics, index child characteristics, service encounters and parent/caregiver perceptions. Results are compared and discussed.

The survey results underscore that parents and families of children with ASD in our country carry a heavy burden. They face significant financial difficulties and need improved services from the health, educational and social sectors.

It was concluded that there is a critical need to strengthen national capacity in caring for children, young people and adults with ASD and other neurodevelopmental disorders.

Neonatal hypoglycemia (HG) can cause neurologic damage, epilepsy, mental retardation, behavioral and personality disorders and death. The longest the HG lasts and the greatest the glucose nadir the consequences are more pronounced.

Comorbidities are rather important in development of neurological damage. Hypoxemia and ischemia can cause permanent brain damage. Small for gestational age (SGA), large for gestational age (LGA), intrauterine growth restriction, gestational age bellow the 37th week, low Apgar score, sepsis, children whose mothers have toxemia, diabetes or chorioamnionitis are all newborns with increased HG risk.

Comparing 34 patients with NH and 34 children without NH with similar GA, BW, BL, the Apgar score, we found statistically significant differences in motor and mental development using the Griffith scale. Children with neonatal HG fared significantly worse than those without neonatal HG. Therefore, CBG measurements and early recognition of neonatal HG is of significant importance in preventing motor and mental damage in children. A larger and well-balanced cohort of patients followed for a longer period is also necessary to clarify and discern in detail the importance of neonatal HG and other perinatal factors in neurodevelopmental damage.

COVID-19 pandemic has provoked a huge change in daily functioning in millions of people worldwide. The epidemiological measures in prevention of possible infection have increased the possible risks on the mental and physical health.

We have conducted a survey in order to investigate the needs and challenges of families with children with chronic respiratory diseases. In this order, we have created a questionnaire with general information about the family, general information about the child with chronic respiratory disease, overall physical and mental health before and during the pandemic, needs and mental health condition of the parents/caregivers.

This survey showed that this group of families of children with respiratory disorders have suffered financially in significant way and has changed the way they perform professional and educational patterns due to the pandemic. Most of the children were stable in their physical health, but their mental health has deteriorated. This is probably due to the regular contact with the medical staff, but not with the mental health professionals. This group of children has a significant reduction in their physical activity and increase the hours in front of TV screens. The further effect on the physical and mental health is to be investigated.

Prof. Dr. Dimitar T. Hrisoho was born on June 11, 1924 in Bitola, R. Macedonia. He died in Struga on September 22, 1986, and was buried in Skopje.

He completed primary and secondary education in Bitola. He graduated from the Medical Faculty in Belgrade in 1951 as one of the best students of his generation (average grade of 9.75). In 1953 he was employed at the Internal Clinic of the Medical Faculty in Skopje, where in 1955 he passed the specialist exam in internal medicine. He successfully defended his habilitation “Polyarthritis chronica evolutiva” and his doctoral dissertation “Clinical features of Vitina nephropathy”. The doctoral dissertation indicates that Vitina nephropathy is a new site of the Balkan Endemic Nephropathy entity and that more genetic testing of patients were needed. Based on numerous clinical and scientific researches published in over 200 papers, he was elected a Full Professor of internal medicine at the Medical Faculty of the Ss. Cyril and Methodius University in Skopje in 1971. In 1970, he formed the nephrology section of the Macedonian Medical Association (MMA), which grew into the nephrology Association of MMA. Through the Association, the education of the medical staff from the field of nephrology was performed. He also set up a bio-cybernetics association.

He achieved his vision and desire to transfer and apply the achievements of modern nephrology in the diagnosis and treatment of kidney patients in Macedonia at the Clinic of Nephrology of the Medical Faculty in Skopje, which was the first specialized institution established for examination and treatment of kidney patients in the former Yugoslavia and the Balkans. The Clinic educated nephrological staff and examined and treated kidney patients with new methods and drugs that positively affected the development of nephrology as a subspecialty of the internal medicine. D. Hrisoho was actively involved in the introduction of new methods for examination of kidney patients, as well as in the treatment of patients with acute and chronic renal insufficiency with dialysis since 1965. He also participated in the first two kidney transplantations from living donors performed in 1977. He wrote a chapter on “kidney examination”, printed in the book of Prof. A. J. Ignjatovski “Fundamentals of Internal Propedeutics” Part III, published by “Prosvetno delo”, 1963, in Skopje. This is the first text to investigate a patient with kidney disease published in a textbook in R. Macedonia. In 1984 he published the textbook “Clinical Nephrology” printed by the University of the Ss. Cyril and Methodius University in Skopje.

Prof. D. Hrisoho organized the First Scientific Meeting of Yugoslav Nephrologists with international participation, from 26 to 28 September 1977, in Struga, R. Macedonia. The meeting was attended by prominent nephrologists from the former Yugoslavia, the Balkans, Europe and the United States, among them: J.S. Cameron from UK, J.L. Funck-Brentano from France, M. Burg and P. Ivanovich from the USA, R. Kluthe from Germany and A. Puchlev from Bulgaria. The scientific meeting was the largest nephrology event until then organized in the former Yugoslavia. The meeting provided an exchange of experiences with world-renowned nephrologists. D. Hrisoho presented the paper Artificial intelligence in nephrology. The author tried to apply bio-cybernetics in nephrology. Prof. D. Hrisoho was Vice Dean of the Medical Faculty in Skopje in the period 1963-1965 and Vice Rector of the University of the Ss. Cyril and Methodius University in Skopje in the period 1974-1975. Prof. Hrisoho was also active in socio-political organizations. For his medical, educational and scientific activities he received several awards and recognitions in the country and abroad. Thus, the work of Prof. D. Hrisoho was permanently embedded in the nephrology of R. Macedonia.