Volumen 43 (2022): Heft 2 (July 2022)

Background/aim: Hematological parameters are the starting point in COVID-19 severity classification. The aim of this study was to analyze oxidative stress in hospitalized COVID-19 patients and to determine its association with D-dimer, neutrophil to lymphocyte ratio (NLR), and platelets to lymphocyte ratio (PLR) as markers for disease progression.

Materials and methods: 52 patients with moderate and severe forms of COVID-19 were enrolled. A hematological and coagulation profile was performed for each patient. PAT (total antioxidant power, iron-reducing) and d-ROMs (plasma peroxides) were determined in serum at admission and 7 days after hospitalization.

Results: The severe group presented parameters that indicated a poor prognosis. Patients that recovered had a significant reduction in d-ROM (t-test, p<0.01) and improvement in oxidative stress index (t-test, p<0.05). Patients that died had significantly decreased PAT (p<0.01) resulting in an increase in oxidative stress. Except for d-ROM vs PLR in both groups and d-ROM vs D-dimer in the severe group, a good correlation between oxidative stress parameters and D-dimer, PLR, and NLR was demonstrated (p<0.01).

Conclusion: Our results show that oxidative stress markers can be used as a tool for disease progression in COVID-19. This analysis is easily accessible and affordable in addition to conventional hematological parameters performed for severity classification.

The current COVID-19 pandemic has raised significant mental health consequences across the world. Even though healthcare workers provide psychological services, the mental health of the overall population often is cause for concern. Psychosocial stressors of the population play a critical role in impacting both the spread of the disease and the occurrence of emotional distress and psychological disorder, during and after an infectious disease outbreak.

The inability to plan, to anticipate future events, and to exert control, at least partially, over external variables inevitably generate stress and tension. Subsequently, this condition can generate more or less discomfort depending on the subjective evaluation of the individual, an evaluation which is influenced by the individual’s stable personality traits. In fact, subjective experiences are never unique: stimuli endowed with the same stressful power do not necessarily cause these reactions in different individuals, while stressful conditions of varying degrees can induce the same response in different people.

The aim of this research was to evaluate some aspects of mental health using answers related to this pandemic of a group young people, selected by chance.

Results showed important changes in quality of life, insecurity, changes in mood and behaviour as well as not optimistic view for the future life.

Discussion confirmed similar finding about young people opinions from other counties.

Additionally, some mediating measures are proposed.

Childhood obesity is assuredly one of the most important health challenges of the 21st century, particularly regarding long-term metabolic complications. In the last four decades, there has been a tenfold increase in childhood and adolescence obesity.

This cross-sectional study aimed to show the prevalence of overweight and obesity compared by age, sex, and ethnicity in n=1034 healthy male and female children, aged 6-13 years in North Macedonia.

Out of the total 1034 children included in the study, 589 (57.0%) were observed with normal weight, 202 (19.5%) children were obese, 140 (13.5%) children were overweight and, 103 (10.0%) children underweight. The study presents an insight that 33% of primary school children are at >85th percentile overweight; or at ≥95th percentile with increased weight due to obesity. The data show that boys have a higher prevalence of obesity and overweight with 37.1%, compared to girls with 29.1%. Also, all age groups demonstrate an exponential increase of the prevalence of overweight: in 6-7 years (5.8%); 8-9 years (12%); 10-11 years (15%); and, 12-13 years old with 19.5%. A jump of prevalence of overweight and obesity between the age groups of 6-7 years, and 8-9 years was observed (17.9% to 25.4% obese and 5.8% to 12.0% overweight). The onset of puberty may be the possible cause.

According to the Global Atlas of Childhood Obesity, North Macedonia is graded with a risk index of 7/11; i.e. it is expected that in the next decade until 2030 the obesity rate will rise to 52.5% for children aged 5-19 years old.

It is with utmost importance to emphasize that continuous monitoring of children’s nutritional status and their risk of obesity is essential, as to further prevent obesity and overweight in the pediatric population.

Background: Genetic factors play an important role in deep vein thrombosis (DVT). The duration of anticoagulation therapy in patients with verified genetic inheritance and previous events of DVT is still questionable.

Case reports: We present three cases of siblings (two brothers and one sister) with verified Venous thromboembolism (VTE) and genetic inheritance. The first case is a 33 y.o. male who was admitted with bilateral massive pulmonary thromboembolism and DVT of the right femoral vein. He had an episode of DVT 4 years ago. Fibrinolytic therapy was introduced immediately. Afterwards, unfractionated heparin was introduced, and then switched to enoxaparin and acenocoumarol. Because of inappropriate INR, it was switched then to rivaroxaban. The imaging methods showed significant improvement, and the patient was discharged from the hospital with rivaroxaban at 2x15 mg/day for another 2 weeks and was instructed to continue 20 mg/day until his next control. In the meantime, the second case, a 36 y.o. male, brother to the first patient, came with vein thrombosis of vena saphena magna of the left leg. Treatment with Acenocoumarol was started and continued for 2 years until complete resolution of the thrombi, and then it was changed to Aspirin. The third case is the sister of the first 2 cases, a 38 y.o female with symptoms and findings almost similar to those in the second case. She was treated with Acenocoumarol for 6 months. Doppler ultrasound showed complete resolution of the thrombosis and anticoagulation therapy was stopped. Genetic investigations for mutation showed presence of homozygous gene mutation for Prothrombin (PTB G20210A) in the first patient, his brother (the second case) was compound heterozygote for PTB and for MTHFR C677T, and his sister (third case) was heterozygous only for the PTB mutation. According to the clinical (recurrent unprovoked DVT with thromboembolic complications) and genetic testing (homozygous gene mutation for PTB) in the first patient, we decided to continue the secondary thromboprophylaxis with rivaroxaban 10 mg/day indefinitely.

Conclusion: Testing for genetically inherited thrombophilia should be included in the risk assessment for recurrence, and performed in all patients under 50 y.o. who have a first, non-provoked episode of thrombosis, in order to determine the duration of anticoagulation therapy.

Background: The administration of high doses of opioids during surgery can lead to higher postoperative pain scores at rest and when coughing. Multimodal analgesia may lower the need for opioids during surgery and the suffering of postoperative pain. Multimodal analgesia can be achieved by providing non-opioid drugs (lidocaine, ketamine, and magnesium sulfate), three different types of drugs. Each of these drugs as different analgesic effects and they belong to three different pharmacological groups. The aim of this study is to develop a better understanding of the effects of each drug (lidocaine, ketamine, and magnesium sulfate) on postoperative analgesia, the needs for rescue analgesics, and analyze the total amount of fentanyl during the intraoperative period in patients undergoing laparoscopic cholecystectomy.

Methods: 120 patients were enrolled in this randomized controlled study. They were classified as ASA 1 and 2 and were scheduled for laparoscopic cholecystectomy. They were further divided into 3 groups. Group 1, or the lidocaine group, had received lidocaine at 1 mg/kg and a continuous intravenous infusion with lidocaine at 2 mg/kg/h. Group 2, or the ketamine group, received ketamine at 0.5 mg/kg. Group 3, or the magnesium sulfate group, received a continuous intravenous infusion of magnesium sulfate at 1.5 gr/kg. The intensity of postoperative pain was assessed using a VAS score at rest and when coughing, with evaluation at 1, 4, 8, 12, and 24 hours, postoperatively. Also, the needs for rescue analgesics and the total amount of fentanyl during the intraoperative period in all groups was also followed.

Results: The patients from the lidocaine group had the highest scores of pain in the postoperative period at rest and when coughing, and the ketamine group had the lowest pain scores. Rescue analgesia was given the most to lidocaine group, and less so in the magnesium group. The magnesium group received the highest dose of fentanyl during surgery and the lowest dose was received by patients from the lidocaine group.

Conclusion: Multimodal analgesia can lower the need for opioids in the intra- and postoperative period after laparoscopic cholecystectomy.

Background: Multimodal anesthesia represents a technique that can improve analgesia and lower the occurrence of opioid side effects in the postoperative period, such as postoperative nausea and vomiting (PONV). It can be achieved by providing different types of medication during the intraoperative period which can decrease the need for opioids. PONV happens more often in patients who have received large amounts of opioids during laparoscopic cholecystectomy. In this study, our aim was to observe the occurrence of PONV between three different groups of patients who received lidocaine, ketamine and magnesium sulfate in combination with fentanyl in the intraoperative period. We also observed any additional nausea and vomiting in the three groups as well as the amount of fentanyl given to these groups during operation.

Materials and methods: 120 patients aged 20-65 years old were included in this randomized and prospective study, ASA classification 1 and 2, scheduled for laparoscopic cholecystectomy. Patients were classified into three groups randomly: Group 1 (lidocaine group-LG), these patients received lidocaine at 1 mg/kg during induction to general anesthesia and 2 mg/kg/h after intubation in continuous intravenous infusion; Group 2 (ketamine group-KG) these patients received ketamine at 0.5 mg/kg during induction to general anesthesia; and Group 3 (magnesium group-MG) these patients received magnesium sulfate at 1.5 gr/hr as a continuous intravenous infusion after intubation. In all three groups, patients additionally received bolus doses of fentanyl. Postoperative nausea and vomiting were monitored in all three groups at 1, 4, 8, 12, and 24 hours after surgery as a primary objective, and if patients had complainant of vomiting, they were treated with 10 mg of metoclopramid. Between the five control time points, additional nausea and vomiting was recorded as well, as a secondary objective. The third objective was to measure of the total amount of fentanyl given in the intraoperative period.

Results: Patients from the lidocaine group experienced less PONV and they received less fentanyl compared to patients of ketamine and magnesium groups. Patients from the ketamine group had more nausea than other groups. In the magnesium group, the rate of vomiting was higher, and they received higher amounts of fentanyl during surgery. Additional nausea and vomiting occurred in 3 patients in the LG, 2 in the KG, and 3 in the MG between the five control time points. The patients from the magnesium group received the highest dose of fentanyl during surgery (307.50 ± 130.4), followed by the patients from the ketamine group (292.50 ± 60.5), and then patients from the lidocaine group (258.75 ± 60.9). The doses of fentanyl that patients received during surgery in all three groups were not statistically significant.

Conclusion: Multimodal anesthesia has been shown to lower PONV 24 hours after laparoscopic cholecystectomy and can lower need for opioids during laparoscopic cholecystectomy.

Aim: To determine and define the advantages of the laparoscopic appendectomy in the treatment of complicated appendicitis by comparing it with the open appendectomy.

Material and Methods: In this prospective interventional clinical study we compared the intraoperative data and the postoperative outcome of 77 patients presented with complicated appendicitis, operated with open and laparoscopic appendectomy within a period of 20 months. One surgeon performed all of the laparoscopic procedures and two other senior surgeons performed the open procedures.

Results: Operative time was shorter in the laparoscopic group (p = 0.033). Conversion rate was 2.3%. Overall postoperative morbidity was 25.97%. There was one operative revision due to postoperative small bowel obstruction in the laparoscopic group. Appendicular stump leakage occurred in one patient in the open group. One intra-abdominal abscess occurred in the laparoscopic group (p = 0.38). Wound infection occurred only in the open group (p = 0.018). Length of stay was shorter in the laparoscopic group (p = 0.0052). One patient from the laparoscopic group was readmitted.

Conclusions: Laparoscopy is a reliable method in the treatment of complicated appendicitis. It offers a shorter operative time, low conversion rate, an acceptable rate of major postoperative complications and a shorter length of stay.

After more than a decade, an accurate description of the current state of pediatric inguinal hernia repair still an issue of contention. Improvement of techniques together with patient-entered intervention that account for the experiences related to individual disease characteristics have become an important factor of which the surgeon must be aware. Therefore, the aim of this study is to analyze a potential treatment for metachronous contralateral inguinal hernia (MCIH) in children during laparoscopic assisted percutaneous internal inguinal ring suturing (PIRS). In a prospective clinical study, carried out at the University Clinic for Pediatric Surgery in Skopje, Republic of North Macedonia, we analyzed the data from 49 female children, aged 1-14 years old, with clinically diagnosed congenital inguinal hernia treated via PIRS. The position of hernias on the right side was 29 (59.2%) on the left side was 19 (38.8%) and on both sides was 1 (2.0%). With intraoperative assessment, it was determined that in 33 (67.3%) participants there was no presence of a hidden hernia, while in 16 (32.7%), there was indeed the presence of a hidden hernia. Of the hidden hernias determined laparoscopically [16 (100%)], 8 (50%) were left and right hidden hernias, all treated laparoscopically. The PIRS technique is a procedure where the basic advanced treatment is exploration. This also included the adequate treatment of other pathologies, such as the prophylactic closure of a contralateral patent processus vaginalis with simultaneous treatment as there is the potential for hernia in future, therefore reducing the number of metachronous inguinal hernias.

Background: The frequency of ABO, Rh and Kell blood group antigens differs among populations of different ethnic ancestry. There are low-frequency antigens (<1%) and high-frequency antigens (>90%). A rare blood group is defined as the absence of a high-frequency antigen in the general population, as well as absence of multiple frequent antigens within a single or multiple blood group systems.

Aim: To perform red blood cell typing and to calculate the antigen and phenotype frequencies, in order to identify rare blood group donors within the clinically most important АВО, Rh and Kell systems.

Material and Methods: АВО, Rh (D, C, E, c, e) and Kell (K) antigen typing was performed using specific monoclonal sera and microplate technique, while Cellano (k) typing was performed with a monoclonal anti-k, antihuman globulin and column agglutination technique. Weak ABO subgroups were determined using the absorption elution method or molecular genotyping (PCR-SSP).

Results: ABO antigen frequency is: A (40.89%), O (34.22%), B (16.97%), AB (7.92%) and weak ABO subgroups (0, 009 %). The established genotypes were AxO1 (0, 0026%) and AxB (0, 001%). Rh antigen frequency is: D (85.79%), C (71.7%), c (76.0%), E (26.0%) and е (97.95%). The most common Rh pheno-type is the DCcee (32.7%) while the rarest phenotype is the DCCEE phenotype (0. 003%). The prevalence of K and k antigen is 7.5% and 99.94%, respectively. The frequency of the rare phenotype K+k- is 0.06%.

Conclusion: Large scale phenotyping of blood group antigens enables the identification of blood donors with rare blood groups for patients with rare phenotypes or with antibodies to high-frequency antigens and to frequent antigens within one or more blood group systems.

Background: In arterial hypertension, left ventricular relaxation is affected early on in relation to a chronic difference in peak left ventricular afterload with early development of HF.

Objective: in ascending compares to descending thoracic aortic stenosis, resulting in chronic late and early LV afterload increase, to assess the left ventricular isovolumic relaxation pressure decay constant through regression analysis, a parameter of left ventricular relaxation on the 4th and 8th week period from invasive left ventricular pressure measurements.

Methods: fourteen pigs underwent posterolateral thoracotomy for ascending aortic stenosis, resulting in chronic early left ventricular afterload increase (EL = 6], or descending thoracic aortic stenosis creating chronic late systolic left ventricular load (LL = 8]. Exponential regression with nonzero asymptote for τ assessment, with linear and nonlinear regression were performed on isovolumic relaxation pressure decay from the left ventricular invasive pressure measurements on 4th and 8th week. Two-way repeated measurement ANOVA, post-hoc Tukey test and linear regression were performed for statistical analysis. Results presented are mean ± SEM or median (quartiles], with significance is at p < 0.05.

Results: The ascending aortic stenosis associated with prolonged biexponential asynchronous τ, compared to the descending thoracic aorta stenosis, resulted in data that were different at the 8^th week in presence of respirations (interaction p < 0.05]. Monoexponential and linear τ were not different in either respiration being preserved or suspended transitionally and in preload reduction. Preload sensitive response of τ was found in ascending compared to descending thoracic aortic banding that reduced in EL and in LL it increased with load reduction (p < 0.05]. These results indicated that τ is not different in and between LV afterloading conditions in a chronic setting, although it indicates that myocardial ischemia is present and that it is greater in ascending aortic banding, compared to descending thoracic aorta banding at the 8th week.

Conclusion: In different sequence of the left ventricular afterload, ventricular relaxation is affected early on, having in EL compared to LL prolonged biexponential asynchronous left ventricular relaxation constant, thus indicating the development left ventricular myocardial ischemia and different elastic recoil in an invasive left ventricular hemodynamic assessment.

Introduction: In centers with limited resources, a high flow nasal cannula is not available, thus we assess if preoxygenation with 15L flow of O2 available from anesthesia machines can prolong the safety period of induction of anesthesia before intubation and provide more time for securing the airway. Moreover, we compared the preoxygenation with standard 6L vs. 15L O2 through a facemask or a nasal cannula.

Material and methods: Patients were allocated into four groups. Group I patients were preoxygenated with a nasal cannula on 6L of oxygen, patients in group II were preoxygenated with a nasal cannula on 15L of oxygen, patients in group III were preoxygenated with a facemask on 6L of oxygen, and patients in group IV were preoxygenated with a facemask on 15L of oxygen. The primary endpoint was time to desaturation and intubation. The secondary endpoints were PaO2, PaCO2, Sat% and ETCO2.

Results: The groups with 15L preoxygenation had a statistically significant prolonged time to desaturation and intubation. Patients allocated to group II have a statistically significant greater PaO2 and lesser ETCO2 compered with group I. However, between patients in group III and IV there is a difference only in PaCO2, and although this effect is significant, both groups have values within the normal range.

Conclusion: In centers with limited resources, preoxygenation with the maximum available oxygen flow from anesthesia machines (15L/min) are useful. This prolongs the safety period for securing the airway. We suggest the use of the maximum available amount of oxygen flow from anesthesia machines in clinical settings.

Objective: Left ventricular hypertrophy in aortic stenosis, arterial hypertension or coarctation of the aorta is risk factor for early development of HF. In chronic late compared to early left ventricular afterload increases resulting from descending thoracic оr ascending aorta stenosis, we assess the left ventricular stroke work, pressure-volume area for О₂ demand and effective work on the 4^th and 8^th weeks. It is suggested that reduced proximal thoracic aortic compliance presents with myocardial ischemia. However, development of adverse left ventricular hypertrophic remodeling and HF in different peak of LV afterload increase is understood poorly.

Methods: Fourteen domestic male pigs (28 ± 3 kg) underwent descending thoracic or ascending aortic stenosis through posterior lateral thoracotomy, with cMRI and an invasive left ventricular pressure-volume loops’ аrea assessment (Millar 5Fr pig-tailed conductance catheter) on the 4^th and 8^th weeks. Left ventricular stroke work and pressure-volume area PVA, parameter for LV O₂ demand, were assessed in hypertrophic left ventricular remodeling, resulting from different peaks in LV afterload (late vs. early LV afterload) increase and we thus defined early adverse LV hypertrophic remodeling in linear and nonlinear end-systolic pressure-volume regression analysis. For this we used special software. Data was compared with two-way repeated measures ANOVA. Results presented are means ± (SEM) or medians and significance is set at p < 0.05.

Results: The left ventricular nonlinear PVA was not different, in LL compared to EL on the 8^th week and when using the linear regression analysis. Stroke work was not different. The linear and nonlinear potential energy were not different between LL vs. the EL group. Nonlinear bLVO₂ demand was not different, being higher in LL compared to EL in the 8^th week. Indexed PVA parameters were not different or changed between the 4^th and 8^th weeks, when being normalized for body surface-area (m²) or 100 grams of LV mass.

Conclusion: The left ventricular potential energy, PVA with effective work and LVO2 demands are not different in hypertrophic LV remodeling in LL vs. EL group at the 8^th week. Difference is not present when end-systolic pressure-volume relation is assessed from indexed LV volumes for m² BSA or 100 grams of LV mass. EL is as important as LL in increased LV afterloads based on LV work and mechanical coupling in this hypertensive heart failure model having preserved EF.

Aims: This study assessed the effects of individualized dialysis sodium prescription on changes of echo-cardiography in hemodialysis (HD) patients.

Methods: 77 chronic hemodialysis patients were analysed. In the first phase all patients underwent dialysis with standard dialysate sodium of 138 mmol/L followed by the second phase where dialysis was performed with individualized dialysate sodium concentration according to average pre HD serum sodium concentration. After the first phase, the subjects were divided into 3 groups: normotensive, hypertensive and hypotensive based on the average pre-HD systolic BP during the first phase. In all patients echocardiography was performed at the end of the first and second phase.

Results: Patients had no statistical significant change in blood pressure compared with standard dialysate sodium, only statistical significant change in interdialytic weight gain (IDWG). By dividing the patients, sodium individualization resulted in significantly lower blood pressure and IDWG (p=0.018) in hyper-tensive patients, whereas normotensive patients showed only significant decrease in IDWG (p=0,004). Hypertensive patients had significant highest sodium gradient compared to other patients (p<0.05), followed by significant increase of 0,6% IDWG confirmed with univariate regression analysis. In all patients, echocardiography analysis showed an increase of 2.04 mm of LVDD by increasing the sodium gradient for 1 mmol/L and significantly increased LVM of 35.69 gr by 1 kg increase in IDWG.

Conclusions: A reduction of the dialysate sodium concentration based on the pre HD serum sodium level of the patient, reduced the SBP, DBP and IDWG and decreased the volume overload upon the heart and consequently heart hypertrophy assessed by echocardiography.

Objectives: Olanzapine is an atypical antipsychotic that is approved across Europe, the USA, and in many other countries for oral treatment of schizophrenia and acute manic episodes in patients with bipolar disorder as well as for maintenance therapy to prevent recurrence in responders. The objective of the present study was to compare the pharmacokinetics of two 10 mg tablet formulations of Olanzapine following a single oral dose in healthy volunteers under fasting conditions, as per the European Medicine Agency (EMA) guidelines to grant marketing authorization.

Methods: This study was a randomized, open-label, two-treatment, two-period, two-sequences, single-dose, cross-over design with a washout period of 14 days. Both the test and the reference products were administered as 10 mg tablets with 240 mL of water after an overnight fast in each study period. A total of twenty blood samples were collected before dosing and within 144 hours after drug administration. Adverse events were monitored, recorded, and evaluated by investigators throughout the study.

Results: Of the 24 healthy adult male subjects enrolled, all of them completed both study periods. The geometric mean ratio 90% confidence intervals (CI) for fasting Cmax, AUC0-t, and AUC0-infinity were 94.83-113.71%, 95.04-105.69% and 95.94-107.00%, respectively. The 90% CI for the ratios of the three primary pharmacokinetic parameters (using log-transformed data) were within the range of 80-125%, meeting the regulatory criteria for bioequivalence.

Conclusions: The generic Olanzapine was bioequivalent to the reference formulation. It was well tolerated and provides an acceptable alternative to the reference drug.

Background: The comprehensive management of patients with Hodgkin’s lymphoma (HL) is a success story in contemporary oncology. Over the past decades, the survival rate of patients with HL has significantly improved. The objective of this analysis is to evaluate and document the progress in the management of Hodgkin’s lymphoma in patients in our country, reflected in their vital statistics, over time periods defined by the respective standard of treatment.

Material and methods: The present study is designed as a retrospective-prospective study. We analyzed different modalities of treatment and compared 5 and 10-year overall survival rates in a total of 588 Hodgkin’s lymphoma patients treated at the University Clinic for Hematology in Skopje during two consecutive time periods, before 2000 and after 2000. The entire observation period is from 1980 to 2020. All patients are above the age of 14, with a documented histopathological diagnosis of Hodgkin’s lymphoma and with evaluable medical documentation, including clinical and laboratory data on their initial condition, the administered therapy, as well as the clinical follow-up of the patients.

Results: The basic clinical features of the analyzed population across the two periods correlate with those reported in the relevant medical literature, with only slight deviations. Ten-year overall survival rates improved by 31.7% through the two calendar periods. During the last two decades of the previous century (1980-2000) the initial treatment options were COPP and COPP-like regimens for the vast majority of patients (94.7%), leading to disease remission in 80% of them. After 2000, 95.8% of de novo diagnosed patients have been treated with ABVD chemotherapy as a frontline choice and the complete response rate is 88.4%. We confirmed the superiority of ABVD in terms of efficacy, improved tumor and disease control, as well as its long-term clinical outcome. While in the past we had very limited options for relapsed/refractory HL patients, the analysis of the results of HL patients treated with various therapeutic approaches in the latter period, defines BEACOPP as the preferred choice. High-dose chemotherapy, followed by autologous hematopoietic stem cell graft, as a strategy for our R/R patients in the timeframe after 2000, ensures a 5-year overall survival for 51% of them, whereas 45% of the patients survive more than 10 years.

Conclusion: This analysis from our Hodgkin’s lymphoma database illustrates that there has been tremendous improvement in the long-term survival rates since the turn of this century. At our institution we strive to implement positive trends in practice, as suggested by relevant guidelines, regarding the evolution and progress in the diagnostic workup, treatment, and the overall management of patients with Hodgkin’s disease. The objective would be to secure favorable vital statistics for our patient population, now reaching 83.5% at 10 years, which closely correlates with the data of more developed countries and centers. In future clinical trials we will also evaluate the efficacy of brentuximab-vedotin and new PD-1 blocking antibodies.

Alström syndrome (ALMS) is an autosomal recessive disorder characterized by multiple organ involvement, including progressive cone-rod dystrophy, sensorineural hearing loss, childhood obesity, and type 2 diabetes mellitus. Pathogenic variants in the ALMS1 gene are the known cause for the occurrence of this devastating condition.

Here we report on a 12 year old boy referred to the University Clinic with early signs of impaired hearing and vision, obesity, and scoliosis. Central vision was first affected, followed by peripheral vision. In addition, his weight began increasing after the age of two years, reaching 78 kg at a height of 157 cm (BMI 31.64). No polydactyly was present. His mental development was normal in spite of his hearing and vision impairments. There was acanthosis nigricans on the neck. ECG and the cardiac ultrasound were normal. At the age of 12 years, his testicles are 12 ml and his pubertal status is P2 A2. OGTT revealed impaired glucose tolerance with elevated insulin concentrations 121ulU/mL (reference range 2,00-29,1 ulU/mL). Renal function was unaffected, liver functions were normal. Uric acid and lipids were within normal plasma concentrations. A Whole Exome Sequencing was performed and a homozygous ALMS1 pathogenic, frameshift gene variant (LRG_741t1(ALMS1):c.4156dup; p.Thr1386AsnfsTer15) was determined as the cause of the disease. Both parents were carriers for the variant. The absence of mental retardation and polydactyly differentiates Alström and Bardet-Biedle syndrome.