Volume 41 (2020): Edition 3 (November 2020)

Introduction: Minimal residual disease (MRD) assessment in acute myeloid leukemia (AML) cases is a complex, multi-modality process and, though much of its clinical implications at different points are extensively studied, it remains even now a challenging area. It is a disease the biology of which governs the modality of MRD assessment; in patients harboring specific molecular targets, high sensitivity techniques can be applied. On the other hand, relapse is considered as the leading cause of treatment failure in AML patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT).

Materials and methods: Since November 2018 until June 2020, 10 AML patients underwent matched unrelated donor (MUD) HSCT at the University Clinic of Hematology-Skopje, Republic of North Macedonia. Molecular markers were identified in a total of 4 patients; 3 patients expressed chimeric fusion transcripts; two RUNX-RUNX1T1 and one for CBFB-MYH11. One patient harbored mutation in the transcription factor CCAAT/enhancer binding protein α (CEBPA). Post-transplant MRD kinetics was evaluated by using quantitative polymerase chain reaction (RT-qPCR) or multiplex fluorescent-PCR every three months during the first two years after the transplantation.

Results: MRD negativity was achieved in three pre-transplant MRD positive patients by the sixth month of HSCT. They sustained hematological and molecular remission for 19, 9 and 7 months, respectively. The fourth patient died due to transplant-related complications.

Conclusion: According to our experience, when molecularly-defined AML patients undergo HSCT, regular MRD monitoring helps predict impending relapse and direct future treatment strategies.

Aim: The aim of this study was to develop quantiative criteria for defining visceral obesity and to establish dual-energy X-ray absorptiometric (DXA) diagnostic cut-off points (CP) for normal and abnormal values of the central obesity indexes (COI) that best differentiate extreme visceral obesity in Cushing’s syndrome (CS) from non CS obese and non obese women.

Material and Methods: COI_1–4 values calculated as a ratio of android to gynoid tissue mass, fat mass and their % were determined in 4 groups, each consisting of 18 women: 1^st group of CS, 2nd group of obese women (O₁) not different according to their age and BMI from CS, 3^rd group of obese women (O2) with BMI of 35 ± 1.2 kg and 4^th group of non obese healthy women (C) with normal BMI. Diagnostic accuracy (DG) of CP values of COI_1m-4m indexes of abdominal obesity and CP values of COI_1n-4n indexes of normal body fat distribution (BFD) was determined.

Results: COI_1-4 indexes values were highly significantly different among the 4 examined groups and were significantly highest in CS patients and lowest in group C (p < 0.0001). COI1m-4m CP values differentiated extreme visceral, abdominal obesity in CS with highest DG as well as COI1n-4n CP values differentiated normal BFD in group C. COI_1m CP of 0.55 best differentiated CS from O1 for DG of 100%. COI2n of 0.38 best differentiated C from CS and O₂ for highest DG of 100% compared to O1 because of the significantly higher BMI and COI_1n-4n values in O₂ that were associated with more pronounced abdominal obesity and highly significantly positive correlation with BMI.

Conclusions: DXA cut-off point values of indexes COI_1m-4m and COI_1n-4n were established as diagnostic indexes and criteria useful in discovering extreme abdominal and normal BFD. COI_1m CP value of 0.55 was discovered as a diagnostic criterion of extreme abdominal obesity and COI_2n of 0.38 as a diagnostic criterion of normal BFD that excluded abdominal obesity. The other indexes COI_1m-4m and COI_1n-4n CP values had also high DG in discovering abdominal and normal body fat distribution.

Rotavirus is highly contagious factor with dominant feces-oral transmission. Because it is stable in external environment, transmission clusters are possible by close contact, ingestion of contaminated water or food or contact with contaminated surfaces. It survives within hours and days on hands and contaminated surfaces. This makes it the most common enteric and nosocomial pathogen in the world, especially in early childhood. In addition to the rapid dehydration with pronounced electrolyte disturbances, numerous extraintestinal possibilities have been recorded in the clinical picture, which emphasizes the need for prevention of this disease.

In the period from 1.02.2018 to 31.01.2020 at the Clinic for Infectious diseases were treated 1060 patients with diarrheal disease, of which 502 children (47.36%). Rotavirus etiology was confirmed in 23.30% of the children. According to the protocols, laboratory and biochemical investigations were done to all 117 children, with tracking parameters and their dynamics of admission and discharge from the hospital. Most of the children, 84 (82.0 6%) are from urban areas, with a more confirmed epidemiological survey of 59 (42.00%). The average age of the children was 8 months, with a small percentage of children on maternal food (breastfed 25, i.e. 21.37%), with high febrile admission in 99% of children with an average temperature of 38.5oC and an average febrile duration of 4 days, with an average of 7 (+ 2.49) of stools and 5 (+ 2.12) of vomiting. There was a significant difference in hematocrit, leukocyte, electrolyte, glycaemia, and CRP values on admission and discharge. There was predominant isonatremic dehydration, and the compensatory mechanisms followed by the values of the electrolytes ABS, Ph, BE showed a tendency to maintain within the physiological limits. The clinical picture of extraintestinal manifestations included bronchitis, mesenteric lymphadenitis, upper respiratory infections and rash.

Rotavirus infection is a serious health and economic problem in our country, so it needs continuous prevention and monitoring in order to reduce the incidence, and thus the need for hospitalization and cure of rotavirus disease.

Introduction: Speech communication is a complex process based on the function of the central nervous system, and also on the speech mechanisms conditioned and controlled by auditory perception, verbal memory, intellectual activity and peripheral speech apparatus.

The aim of this study was to determine the prevalence of the most common phonological articulation disorders in preschool children, from 4-6 years old.

Materials and methods: A cross-sectional study was conducted during 2018, on a representative sample of 550 preschool children aged 4 - 6 years, who attend preschool institutions-kindergartens in the city of Skopje. The study used standardized articulation tests: The Global Articulation Test (GAT) and the Triple Test (vocals, plasia, affricative, fricative, nasal, and lateral), and a questionnaire filled out by a social worker at the kindergarten about the socioeconomic status and the child’s health condition.

Results: Using GAT, we found that 260 (47.3%) children didn’t manifest any phonological articulation disorders, but 290 (52.7%) had disorders. The analysis of gender-based data showed a higher percentage of speech disorders in 57% of boys and 46.9% of girls. The highest percentage of speech disorder is sigmatism with 24.5% in boys and 20.4% in girls, rhotacismus was found in 17.8% in boys and 16.5% in girls. Lambdacism with 8.3% was found in boys and 4.2% in girls. A mixed form (sigmatism, rotacism, and lambdacism) was also found in 2.4% of boys and 3.5% of girls.

Conclusions: The calculated prevalence of phonological articulation disorders in preschool children aged 4-6 years is 52.7%, (57.9% in boys and 46.9% in girls), or every second child in kindergarten has some form of speech disorder. These findings indicate that the treatment of speech disorders should begin in the appropriate services as soon as possible, because the early detection and treatment of speech disorders enable child’s normal intellectual development. The treatment should be started in the preschool period, to allow the start of the educational process without any speech problems.

Introduction: Pancreatic cancer is malignancy with poor prognosis for quality of life and overall survival. The incidence is variant, 7.7/100,000 in Europe, 7.6/100,000 in the USA, 2.2/100.000 in Africa. The only real benefit for cure is surgery, duodenopancreatectomy. The key points for this procedure are radicality, low morbidity and low mortality, the follow up and the expected overall survival. The benchmark of the procedure is the pancreaticojejunoanastomosis, with its main pitfall, postoperative pancreatic fistula B or C. Subsequently, the manner of creation of pancreaticojejunoanastomosis defines the safety, thus the postoperative morbidity and mortality. Finally, this issue remarkably depends on the surgeon and the surgical technique creating the anastomosis. We used 2 techniques with interrupted sutures, dunking anastomosis and duct-to-mucosa double layer technique. The objective of the study was to compare these 2 suturing techniques we applied, and the aim was to reveal the risk benefit rationale for dunking either duct to mucosa anastomosis.

Material and method: In our last series of 25 patients suffering pancreatic head carcinoma we performed a standard dodenopancreatectomy. After the preoperative diagnosis and staging with US, CICT, tumor markers, they underwent surgery. Invagination-dunking anastomosis was performed in 15, whereas, duct-to-mucosa, double layer anastomosis was performed in 10. In the first group with dunking anastomosis, we had 6 patients with soft pancreas and 8 with narrow main pancreatic duct, less than 3 mm. In the duct-to-mucosa group there were 5 patients with soft pancreas and 4 with narrow main pancreatic duct. All other stages of surgery were unified, so the only difference in the procedure remained on the pancreatojejunoanastomosis. The onset of the postoperative pancreatic fistula was estimated with revelation of 3 fold serum level of alfa amylases from the third postoperative day in the drain liquid.

Results: In the duct to mucosa group there wasn’t a clinically relevant postoperative pancreatic fistula, while in the dunking anastomosis group we had 4 postoperative pancreatic fistula B, 26 %. One of these 4 patients experienced intraabdominal collection – abscess, conservatively managed with lavation through the drain. Comparing the groups, there was no significant difference between the groups concerning the appearance of postoperative pancreatic fistula: p>0.05, p=0.125. From all 25 patients, in 21 patients biliary stent was installed preoperatively to resolve the preoperative jaundice. All 21 suffered preoperative and postoperative reflux cholangitis, extending the intra-hospital stay.

Conclusion: So far, there have been many trials referring to opposite results while comparing these 2 techniques in creation of the pancreticojejunoanastomosis. In our study, the duct to mucosa anastomosis prevailed as a technique, proving its risk benefit rationale. However, further large randomized clinical studies have to be conducted to clarify which of these procedures would be the prime objective in the choice of the surgeon while creating pancreatojejunoanastomosis.

Plants that are primarily used as a food source commonly have undervalued biological properties beyond the basic supply of nutrients. One important example of this are the antimicrobial properties of plants. Inclusion of natural and food grade antimicrobial ingredients in recipes to prevent food spoilage and disease transmission, or in cosmetic products to prevent transient and pathogenic bacteria would have world-wide public health implications. A patented natural polyphenol rich sugar cane extract (PRSE), is marketed as a high anti-oxidant and polyphenol ingredient, but its anti-microbial activity has not been reported previously. We determined the anti-bacterial properties of PRSE on common human pathogens relating to a range of diseases including food poisoning, tooth decay, acne and severe skin infections using disc/well diffusion experiments. Our findings indicate that PRSE is an efficient antimicrobial, which could be included at differing dosages to target a range of food borne and environmental pathogens.

Predicting the outcome of neonatal critical patients remains elusive. The multiple factors of maternal state of health (infections, diabetes, gestosis), the placental situation (premature rupture of membranes) as well as multiple factors from the baby (small for gestational age, low Apgar score, low birth infections, mechanical ventilation, hypoglycaemia hyperglycamiea) render the approach to treatment of each patient individual and the outcome uncertain. Several approaches and scales are developed in order to assess the mortality risk in those rather complicated situations.

We used the CRIB-II scale to assess the mortality risk in 80 patients delivered in a large tertiary level hospital with more than 4,000 deliveries yearly. The patients were stratified according to all the neonatal risk factors and comorbidities. The CRIB-II scale identified well the mortality rates, but not the outcomes. A large and well-balanced cohort of patients followed for a longer period is required to discern in detail the importance of CRIB-II scale in predicting outcomes in high-risk new-borns. This could serve as an assistance to personalized approach to severely sick children. In addition, it is a valuable method in comparing outcomes in different NICUs and outcomes in different times in the same NICU, thus rendering possible improvements in the same unit and among several NICU departments.

Aneurysms of the thoracic aorta involving the distal arch and the proximal descending aorta have traditionally been treated with two open procedures. During the first stage, the aortic arch pathology has been addressed through a median sternotomy. Several weeks or months later, a second stage followed and included completing the repair of the descending aorta through a lateral thoracotomy.

We, herein, report a single stage repair of an aneurysm involving the distal aortic arch and the proximal descending aorta using the frozen elephant trunk operative technique. Vascular hybrid stent graft prosthesis, specifically designed for treatment of extensive aortic aneurysms, has been used to replace the arch component and exclude the descending aorta component of the aneurysm through a median sternotomy, using bilateral antegrade cerebral perfusion and mild systemic hypothermia for intraoperative organ protection.

Cat scratch disease (CSD) is the main clinical manifestation caused by Bartonella henselae in immuno-competent patients. The bacterium is transmitted to humans from cats via scratches or bites. In this case report, we are presenting to our knowledge the first etiologically confirmed case of CSD in our country. Here we describe the case of a previously healthy adult female patient presenting with fever and axillar lymphadenopathy over 1-month period. She underwent numerous clinical and paraclinical investigations for potential etiologies associated with lymphadenopathy and fever. Finally, serological testing for B.henselae was performed with titers for IgG 1:1024 and 1:160 for IgM, which confirmed the diagnosis. Five-day treatment with azithromycin resulted with good clinical response and complete recovery. We proved that CSD is a reality in our country and this report should raise awareness in medical doctors, especially infectious disease specialist. Also, CSD should be included in differential diagnosis in patients with fever of unkown origin (FUO), who are presenting with regional lymphadenopathy, with or without history of cat contact.

Artificial Organs 2000 Satellite Symposium of European Society for Artificial Organs (ESAO) was organized by the Macedonian Society for Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO) and the Macedonian Academy of Sciences and Arts (MASA) on November 25-26, 2000 on the occasion of the 25th Anniversary of the Department of Nephrology of the Ss. Cyril and Methodius University, Skopje, R. Macedonia.

The main topics of this symposium were: Blood-purification techniques, Artificial Kidney, Metabolic- and Cardiac-Assist Systems as well as Biomaterials to be used for Artificial Organs.

H. Klinkmann (Glasgow, United Kingdom), D. Falkenhagen (Krems, Austria), U. Baurmeister (Wuppertal, Germany), V. Bonomini, S. Stefoni (Bologna, Italy), R. Vanholder (Ghent, Belgium), S. Stiller (Aachen, Germany), H. Mann, H. Melzer (Aachen, Germany), J. Pop-Jordanov, N. Pop-Jordanova (Skopje, R. Macedonia), B. Stegmayr (Umea, Sweden), M. Mydlik, K. Derzisova, O. Racz, A. Sipulova, J. Boldizsar, E. Lovasova, M. Hribikova (Kosice, Slovak Republic), A. Jörres (Berlin, Germany), M. Polenakovic (Skopje, R. Macedonia), J. Vienken (Bad Homburg, Germany), S. Bowry (Bad Homburg, Germany), E. Piskin (Ankara, Turkey), J. Klinkmann, W. Schimmelpfennig, H. Lantow, W. Rigger. (Teterow, Germany), A. Sikole (Skopje, R. Macedonia), A. Oncevski, P. Dejanov, V. Gerasimovska, M. Polenakovic (Skopje, R. Macedonia), J. Wojcicki (Warsaw, Poland), K. Affeld (Berlin, Germany), G. Rakhorst et al. (Groningen, The Netherlands), Z. Mitrev (Skopje, R. Macedonia), S. Kedev, G. Guagliumi, O. Valsecchi, M. Tespili (Skopje, R. Macedonia, Bergamo, Italy) have presented their papers at the Symposium. The presentations provoked a fruitful discussion and it was concluded that they should be published.

The papers were published in the International Journal of Artificial Organs of the European Society for Artificial Organs (ESAO) as a special issue on “Artificial Organs 2000 ESAO Satellite Symposium -Skopje, R. Macedonia”, Guest Editors: M. H. Polenakovic, Skopje and J. Vienken, Bad Homburg; Vol. 25, No. 5, 2002.

On the occasion of the celebration of the 40th anniversary of the Macedonian Academy of Sciences and Arts (MASA) the Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO) organized a one day symposium titled: “Artificial Organs Today: From in vitro assessment to human therapies”, on September 28, 2007 at the Macedonian Academy of Sciences and Arts. The following sessions were held: Artificial Organs in Front of the Ageing Populations; System Requirements for Artificial Organ Technology; Tools for Artificial Organ Technology; Extracorporeal Blood Circuits in Organ Replacement Therapies; Treatment Options for Blood Purification Therapies. Presentation were delivered by: Horst Klinkmann, Germany; Jörg Vienken, Germany; Jens Hartmann, Austria; Udo Losert, Austria; Jan Wojcicki, Poland; Helmut Mann and Siegfried Stiller, Germany; Beat Walpoth, Switzerland; Juan F. del Cañizo, Spain; Borce Georgievski, Macedonia; Bernd Stegmayr, Sweden; Momir Polenakovic, Macedonia; Petar Kes, Croatia; Aleksandar Sikole, Macedonia; Wolfgang Ramlow, Germany; Dieter Falkenhagen, Austria. These meetings are significant for the application and development of the artificial organs in patients.

The Macedonian Society for Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO) was established on September 1, 1992 in order to stimulate the development of nephrology and to unite experts from all professions interested in the research and treatment of kidney patients. Momir H. Polenakovic was elected President of MSNDTAO.

The First congress of MSNTAO was held in Ohrid from October, 7 to 10, 1993 in hotel “Desaret” under the auspices of the first President of R. Macedonia, Kiro Gligorov. During the Congress, the Balkan Cities Association of Nephrology, Dialysis, Transplantation and Artificial Organs (BANTAO) was formed on October 9, 1993. The idea of cooperation with the Department of Nephrology from the Ege University, Izmir, R. Turkey was promoted. Some of the presented papers were published in the Proceedings “Nephrology ’93” as a supplement to the Macedonian medical review. The “Doctrine for performing nephrological activity in the Republic of Macedonia” was also promoted.

The Second congress of MSNDTAO was held in Struga, R. Macedonia from September, 6 to 10, 1997 together with the Second BANTAO Congress. Selected papers were printed in the Macedonian Medical Review.

The Third congress of MSNDTAO was held from May, 30 to June 2, 2001 in Skopje, at the Macedonian Academy of Sciences and Arts (MASA). Proceedings of papers was also published.

In 2011 M. H. Polenakovic was elected Honorary President of MSNDTAO for life, and Goce Spasovski was elected the current President of MSNDTAO.

The Fourth congress of MSNDTAO was held in Ohrid from June, 21 to 24, 2012 together with the Fourth Meeting of the South-Eastern European Pediatric Nephrology Working Group (SEEPNWG).

The Fifth congress of MSNDTAO was held from June, 9 to 12, 2016 in Skopje, at MASA together with the 6th Southeastern European Pediatric Nephrology Working Group (SEPNWG) Meeting and IPNA (International Pediatric Nephrology Association) Teaching Course. The VIII Macedonian-Croatian Nephrology Days were also held during the Congress.

The Sixth congress of MSNDTAO was held from September, 26 to 29, 2019 along with the 15th BANTAO Congress, in Skopje, at MASA. The Congress also marked the 80th anniversary of the birth of M. H. Polenakovic.

Apart from the participants from R. Macedonia, the congress was attended by renowned nephrologists from Europe and the world.

A novelty of the last congresses was the organization of 9 CME (Continuing Medical Education) courses with famous lecturers. CME courses supported by the ERA-EDTA and / or the ISN were as follows: 2005 - Ohrid (BANTAO), 2006 - Skopje (MSNDTAO), 2009 - Skopje (MSNDTAO), 2010 - Skopje (ERA-EDTA - ESAO), 2011 Skopje (ERA-EDTA - EUTox group), 2012 - Ohrid (MSNDTAO), 2014 -Skopje (MSNDTAO), 2016 - Skopje (MSNDTAO), 2018 - Skopje (MSNDTAO - ERA-EDTA & ISN), 2019 - Skopje (BANTAO - ISN & ERA-EDTA).

In addition to the congresses, MSNDTAO has held meetings with nephrological associations from the neighboring countries as Croatia, Serbia, Albania and Kosovo.

The congresses of MSNDTAO contributed to the introduction and education of doctors in the diagnosis and treatment of kidney patients. They were a strong stimulus for the development of nephrology in R. Macedonia and beyond.