Institutional Repository in Medical Sciences of Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
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Сопутствующие заболевания при подагре: изучение клинического полиморфизма, диагностика, стратегии лечения и прогноз
Structura tezei. Lucrarea a fost expusă pe 256 de pagini de text electronic și se compartimentează în:
introducere, 5 capitole, discuții, 8 concluzii și 12 recomandări, indice bibliografic (240 de titluri), 36 de figuri,
45 de tabele, 13 anexe. Rezultatele cercetării au fost prezentate în 62 de publicații.
Cuvinte-cheie: acid uric, hiperuricemie, gută, boli metabolice, comorbidități, diagnostic, scorul de severitate.
Domeniul de studiu. Reumatologie
Scopul studiului. Evaluarea comorbidității pacienților de diferite vârste afectați de gută cu argumentarea
clinică și economică privind îmbunătățirea managementului de evaluare clinico-paraclinică în acordarea
asistenței medicale acestor pacienți.
Obiectivele studiului. 1. Evaluarea statutului comorbid la pacienții suferinzi de gută de diferite vârste.
2. Analiza evoluției procesului inflamator și a progresiei bolii la pacienții cu gută prin prisma diferitor decade
ale vârstei. 3. Specificarea modificărilor patologice ale organelor interne și a particularităților evolutive ale
afectărilor extraarticulare la pacienții cu gută. 4. Determinarea factorilor provocatori și a influenței lor asupra
debutului, caracteristicilor și evoluției gutei la persoanele vârstnice. 5. Analiza posibilității corecției factorilor
provocatori la pacienții vârstnici prin ajustarea tratamentului non-farmacologic și farmacologic.
6. Determinarea fezabilității economice exprimate prin analiza costurilor medicale directe în funcție de vârstă
și comorbiditate, cu elaborarea principiilor de eficientizare a cheltuielilor. 7. Analiza economică a costurilor
unui caz tratat staționar, cu elaborarea principiilor de eficientizare a cheltuielilor în funcție de evoluție.
8. Elaborarea recomandărilor pentru eficientizarea managementului clinic și fezabilității economice de
acordare a asistenței medicale pacienților vârstnici cu gută.
Noutatea și originalitatea științifică. În cadrul unui studiu observațional, descriptiv, transversal, pacienții cu
gută au fost cercetați multidimensional. Au fost evaluate factorii provocatori, debutul și evoluția, frecvența
comorbidităților la pacienții vârstnici cu gută în comparație cu indicatorii similari ai pacienților din alte grupuri
de vârstă. A fost efectuată o evaluare a conformității „practicii tipice” de gestionare a pacienților vârstnici cu
gută într-un cadru spitalicesc, ținând cont de recomandările internaționale valabile pentru perioada studiului. Sa demonstrat importanța factorilor controlabili dobândiți care afectează severitatea gutei la pacienții vârstnici,
dintre care: administrarea diureticelor și dozelor mici de acidul acetilsalicilic, obezitatea, respectarea dietei și
consumul excesiv de alcool. S-au analizat recomandările pentru îmbunătățirea metodologiei de analiză clinică
și economică a costurilor de acordare a asistenței medicale pacienților vârstnici cu gută, luând în considerare
corectarea contextului comorbid, acestea fiind fundamentate și testate științific.
Problema științifică importantă soluționată în teză. Pe baza analizei factorilor provocatori care cauzează
guta la vârstnici, au fost identificate principalele metode de abordare optimă a prevenirii și tratamentului
acesteia, care includ medicamente (diuretice, acidul acetilsalicilic), nerespectarea regimului alimentar,
consumul de alcool și prezența sindromului metabolic. În baza datelor obținute, a fost determinat rolul
semnificativ al comorbidităților în formarea costurilor pentru furnizarea de asistență medicală pacienților
vârstnici cu gută. În special, prezența HTA, CPI, BCR crește semnificativ aceste costuri. Sunt prezentate
recomandări metodice pentru optimizarea metodologiei de modelare a costurilor de acordare a îngrijirilor
medicale unui pacient vârstnic cu gută, ținând cont de comorbidități, care includ revizuirea numărului de
examinări, atât de laborator, cât și instrumentale, pentru fiecare boală comorbidă.
Semnificația teoretică. Datele epidemiologice obținute privind distribuția frecvenței factorilor provocatori de
gută la pacienții vârstnici vor permite stratificarea determinată științific a riscurilor la anumiți pacienți și vor fi
utilizate în mod activ la crearea recomandărilor pentru prevenirea și tratamentul bolii. Caracteristicile
debutului și ale evoluției gutei la pacienții vârstnici identificați pe parcursul studiului în comparație cu
pacienții de vârstă medie vor optimiza desfășurarea măsurilor diagnostice și terapeutice la pacienții din acest
grup de vârstă.
Valoarea aplicativă. Analizându-se factorii provocatori pentru dezvoltarea gutei la vârstnici, au fost
identificate principalele cauze care afectează lipsa unei abordări optime a prevenirii și tratamentului acesteia.
În baza datelor obținute, a fost determinat un rol semnificativ al patologiei comorbide în formarea costurilor
pentru furnizarea de asistență medicală pacienților vârstnici cu gută. Sunt prezentate recomandări metodice
pentru optimizarea metodologiei de modelare a costurilor de acordare a îngrijirilor medicale unui pacient
vârstnic cu gută, ținând cont de patologia concomitentă.
Implementarea rezultatelor. Rezultatele studiului au fost incluse în Protocolul Clinic Național „Guta la
adult”, se aplică în procesul didactic al Departamentului Medicină Internă, în practica Disciplinei de
reumatologie și nefrologie a IP USMF „Nicolae Testemițanu” și în secția de Artrologie a IMSP SCR „Timofei
Moșneaga”.Thesis structure. The work was exposed on 256 pages of electronic text and is divided into: introduction, 5
chapters, discussions, 8 conclusions and 12 recommendations, bibliographic index (240 titles), 36 figures, 45
tables, 13 annexes. The results of the research were presented in 62 publications.
Keywords: uric acid, hyperuricemia, gout, metabolic diseases, comorbidities, diagnosis, severity score.
Domain of research. Rheumatology
Aim of the study. Assessment of the comorbidity of patients of different ages affected by gout with clinical
and economic rationale for improving the management of clinical-paraclinical assessment in providing care to
these patients.
Study objectives. 1. Assessment of comorbid status in gout patients of different ages. 2. Analysis of the
evolution of the inflammatory process and disease progression in patients with gout in the different decades of
age. 3. Specify the pathological changes of internal organ pathology and the evolutionary peculiarities of extraarticular damage in patients with gout. 4. Determine the triggering factors and their influence on the onset,
characteristics and evolution of gout in the elderly. 5. Analysis of the possibility of correcting modifiable risk
factors in elderly patients by adjusting non-pharmacological and pharmacological treatment. 6. Determination
of economic feasibility expressed by analysis of direct medical costs according to age and comorbidity, with
elaboration of principles of cost efficiency. 7. Economic cost analysis of an inpatient case, with development
of cost efficiency principles according to evolution. 8. Development of recommendations for streamlining
clinical management and economic feasibility of providing care to elderly patients with gout.
Scientific novelty and originality. In an observational, descriptive, cross-sectional study, patients with gout
were investigated multidimensionally. Challenging factors, onset and progression, frequency of comorbidities
in elderly patients with gout were assessed in comparison with similar indicators of patients in other age
groups. An assessment of the compliance of the „typical practice” management of elderly patients with gout in
a hospital setting was performed, taking into account the international guidelines valid for the study period.
The importance of acquired controllable factors affecting the severity of gout in elderly patients was
demonstrated, including: the administration of diuretics and low doses of acetylsalicylic acid, obesity, dietary
compliance and excessive alcohol consumption. Recommendations for improving the methodology of clinical
and economic cost analysis of healthcare delivery for elderly patients with gout, taking into account the
correction of the comorbid context, have been reviewed and are scientifically substantiated and tested.
The scientific problem solved in the thesis. Based on the analysis of the factors that cause gout in the elderly,
the main methods of optimal approach to its prevention and treatment have been identified, which include
drugs (diuretics, acetylsalicylic acid), dietary non-compliance, alcohol consumption and the presence of
metabolic syndrome. Based on the data obtained, the significant role of comorbidities in shaping the costs of
providing care to elderly patients with gout was determined. In particular, the presence of ischemic heart
disease, chronic heart failure, chronic renal failure significantly increases these costs. Methodological
recommendations are presented for optimizing the methodology for modeling the costs of providing health
care to an elderly patient with gout, taking into account comorbidities, which include reviewing the number of
examinations, both laboratory and instrumental, for each comorbid disease.
Theoretical significance. The epidemiological splints obtained on the distribution of the frequency of gout
risk factors in elderly patients will allow scientifically determined stratification of risks in certain patients and
will be actively used to create recommendations for the prevention and treatment of the disease. The
characteristics of the onset and development of gout in elderly patients identified during the study compared to
middLe-aged patients will optimize the conduct of diagnostic and therapeutic measures in patients in this age
group.
Applicative value of the study. When analyzing the factors that cause the development of gout in elderly, the
main causes affecting the lack of an optimal approach to its prevention and treatment have been identified.
Based on the data obtained, a significant role of comorbid pathology in the formation of costs for the provision
of medical care to elderly patients with gout was determined. Methodical recommendations are presented for
optimizing the methodology for modeling the costs of providing medical care to an elderly patient with gout,
taking into account the concomitant pathology.
Results implementation. The results of the study were included in the National Clinical Protocol „Gout in
adult”, is applied in the didactic process of the Department of Internal Medicine, in the practice Department of
Rheumatology and Nephrology of „Nicolae Testemitanu” SMPhU and in the Clinical Department of
Arthrology of Republican Clinical Hospital „Timofei Moşneaga”.Структура диссертации. Работа представлена на 256 страницах электронного текста и состоит из:
введения, 5 глав, обсуждение, 8 выводов, 12 практических рекомендаций, библиографии (240 источника), 36
рисунков, 45 таблиц, 13 приложений. Результаты исследования были опубликованы в 62 научных работах.
Ключевые слова: мочевая кислота, гиперурикемия, подагра, метаболические заболевания, сопутствующие
заболевания, диагностика, оценка тяжести.
Область исследования. Ревматология
Цель исследования. Оценка коморбидности пациентов разного возраста, страдающих подагрой, с клиникоэкономическим обоснованием для улучшения управления клинико-параклинической оценкой при оказании
помощи этим пациентам.
Задачи исследования. 1. Оценка коморбидного статуса у больных подагрой разного возраста. 2. Анализ
эволюции воспалительного процесса и прогрессирования заболевания у пациентов с подагрой в разных
возрастных категориях. 3. Уточнить патологические изменения внутренних органов и эволюционные
особенности внесуставного поражения у больных подагрой. 4. Определить триггерные факторы и их
влияние на возникновение, характеристики и эволюцию подагры у пожилых людей. 5. Анализ возможности
коррекции модифицируемых факторов риска у пациентов пожилого возраста путем корректировки
нефармакологического и фармакологического лечения. 6. Определение экономической целесообразности,
выраженной в анализе прямых медицинских затрат в зависимости от возраста и коморбидности, с
разработкой принципов экономической эффективности. 7. Анализ экономических затрат на стационарный
случай с разработкой принципов эффективности затрат в зависимости от эволюции. 8. Разработка
рекомендаций по оптимизации клинического менеджмента и экономической целесообразности оказания
помощи пожилым пациентам с подагрой.
Научная новизна. В обсервационном, описательном, перекрестном исследовании пациентов с подагрой
были комплексно обследованы. Были оценены провоцирующие факторы, дебют и эволюция заболевания,
частота сопутствующих заболеваний у пожилых пациентов с подагрой в сравнении с аналогичными
показателями пациентов других возрастных групп. Проведена оценка соответствия „типичной практики”
ведения пожилых пациентов с подагрой в условиях стационара с учетом международных рекомендаций,
действующих на период исследования. Показана важность приобретенных контролируемых факторов,
влияющих на тяжесть подагры у пожилых пациентов, в том числе: прием диуретиков и низких доз
ацетилсалициловой кислоты, ожирение, соблюдение диеты и чрезмерное употребление алкоголя.
Рассмотрены и научно обоснованы рекомендации по совершенствованию методологии анализа клиникоэкономических затрат на оказание медицинской помощи пожилым пациентам с подагрой с учетом
коррекции коморбидных заболеваний.
Важность решенной научной проблемы. На основе анализа факторов, вызывающих подагру у пожилых,
определены основные методы оптимального подхода к ее профилактике и лечению, к которым относятся
лекарственные препараты (диуретики, ацетилсалициловая кислота), несоблюдение диеты, употребление
алкоголя и наличие метаболического синдрома. На основании полученных данных, была определена
значительная роль сопутствующих заболеваний в формировании затрат на оказание помощи пожилым
пациентам с подагрой. В частности, наличие ишемической болезни сердца, хронической сердечной
недостаточности, хронической почечной недостаточности значительно увеличивает эти затраты.
Представлены методические рекомендации по оптимизации методики моделирования затрат на оказание
медицинской помощи пожилому пациенту с подагрой с учетом коморбидных заболеваний, которые
включают пересмотр количества обследований по каждому коморбидному заболеванию.
Теоретическая значимость. Полученные эпидемиологические данные по распределению частоты
провоцирующих факторов при подагре у пациентов пожилого возраста позволили определить
стратификацию рисков у отдельных пациентов и были использованы для создания рекомендаций по
профилактике и лечению заболевания. Выявленные в ходе исследования особенности возникновения и
развития подагры у пациентов пожилого возраста по сравнению с пациентами среднего возраста позволили
оптимизировать проведение диагностических и лечебных мероприятий у пациентов этой возрастной
группы.
Прикладная значимость. При анализе провоцирующих факторов развития подагры в старческом возрасте
выявлены основные причины, влияющие на отсутствие оптимального подхода к ее профилактике и
лечению. На основании полученных данных определена значительная роль коморбидной патологии в
формировании затрат на оказание медицинской помощи пожилым пациентам с подагрой. Представлены
методические рекомендации по оптимизации методики моделирования затрат на оказание медицинской
помощи пожилому пациенту с подагрой с учетом сопутствующей патологии.
Внедрение в практику. Результаты исследования были включены в Национальный Клинический Протокол
„Подагра у взрослых”, были внедрены в дидактическом процессе и в практику Дисциплины ревматологии и
нефрологии, Департамента Внутренних Болезней, ГУМФ „Николае Тестемицану” и в отделении
Артрологии Республиканской Клинической Больницы „Тимофей Мошняга”
Analysis of clinical-biological markers and scoring of patients with liver cirrhosis in the liver transplant program: Summary of doctoral thesis in medical sciences: 321.24 – Transplantology
Actuality and importance of the researched problem: Although recent years have seen
a steady increase in the incidence of liver disease, which is a serious problem in modern
medicine, viral liver cirrhosis is still certainly underestimated both nationally and globally.
Currently, worldwide 844 million people are registered with chronic liver disease, with a
mortality rate of 2 million deaths per year, including 1 million deaths due to complications of
cirrhosis and 1 million due to viral hepatitis and hepatocellular carcinoma [1].
Liver disease is becoming more and more common lately and more alarming worldwide,
as well as in the Republic of Moldova, 75% of deaths caused by pathology of the digestive
system are due to liver cirrhosis [2].
Epidemiological analysis of viral liver cirrhosis showed a 3-fold increase in morbidity in
2019 compared to 2000. As a result of which, the number of patients with liver cirrhosis of viral
etiology increased in 2019 to 5482 patients. Also, in the case of chronic viral hepatitis, the
majority of patients were detected with hepatitis B virus. In the multi-year dynamics the
prevalence index of HBV morbidity increased from 655 cases (15.3 cases per 100 thousand
inhabitants) in 2000 to 2422 cases (68.32 cases per 100 thousand inhabitants) in 2019. The
prevalence rate in liver cirrhosis caused by C virus increased practically 9-fold, from 229 cases
(5.4 cases per 100 thousand inhabitants) in 2000 to 2240 cases (63.19 cases per 100 thousand
inhabitants) in 2019. Viral liver cyonoses, other etiologies and those not specified, showed a
slight decrease from 522 cases (12.2 cases per 100 thousand inhabitants) in 2000 to 420 cases
(11.85 cases per 100 thousand inhabitants) in 2019 [3].
Thus, at this stage, viral liver cirrhosis and primary liver cancer represent one of the most
serious problems for the population, due to their global spread, increased morbidity and
mortality, and the high degree of disability caused by the rapid progression of these pathologies.
Globally, approximately 257 million people are infected with chronic viral hepatitis B, while 71
million people are infected with chronic viral hepatitis C, mainly in less developed countries. In
2019, 10 thousand patients with liver cirrhosis were registered in the Republic of Moldova, as a
result of which 70% of patients with cirrhosis developed primary liver cancer. Morbidity for
viral etiology liver cirrhosis, caused by virus D, increased from 183 cases (4.3 cases per 100
thousand inhabitants) in 2000 to 400 cases (11.28 cases per 100 thousand inhabitants) in 2019.
What denotes a higher prevalence for the Republic of Moldova is HDV viral liver cirrhosis,
which has a more aggressive and rapid evolution compared to other viral liver cirrhosis [3].
Over the past two decades, efforts have focused on reducing mortality on the liver
transplant waiting list without compromising post-transplant outcomes. However, it can be
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difficult to identify candidates who are too ill for HT to prevent unnecessary transplants [39].
The implementation of the MELD score was the first and most important change in liver
allocation, redirecting donor organs to the sickest patients and aiming to reduce waiting list
mortality [4].
Notwithstanding the fact, that there is a need for continuous consolidation and
development of new prognostic scores for the end-stage liver disease population on the waiting
list for liver transplantation in the Republic of Moldova, the validation of new scores and in fact
what defines the research problem at hand, which is predestined to improve and prolong the
quality of life of patients on the waiting list within the national liver transplantation system.
Thus, based on the above, the aim of the scientific work is to: study the clinical-biological
landmarks and analyze different prognostic scores on the population with viral liver cirrhosis
from the waiting list for liver transplantation in the Republic of Moldova.
The following general research objectives were stipulated to achieve the aim:
1. Evaluation of clinical-biological landmarks in patients on the waiting list for liver
transplantation
2. Analysis of prioritization factors of recipients for liver transplant waiting list
3. Comparison of predictive accuracy between MELD score, MELD Na, MESO-index on
mortality in the first 3 months after liver transplant listing
4. Validation of the MELD 3.0 prognostic score for mortality in the first 3 months of recipients
on the liver transplant waiting list
5. Development of the algorithm for enrolling patients with decompensated viral liver cirrhosis
on the liver transplant waiting list based on the validated maximum predictive accuracy
prognostic score
Scientific research methodology
The present work represents a stepwise, retrospective and analytical clinical study
focused on the evaluation of clinical parameters, results of instrumental methods of diagnosis
and monitoring of 265 patients with viral liver cirrhosis included in the waiting list for liver
transplantation. With the application of prognostic scores to predict mortality rate in the first 90
days after listing for liver transplantation.
Statistical analysis was performed using SPSS software, version 23.0. Data are reported
as mean±SD. Gaussian normal distribution was tested by applying normality tests (ShapirkoWilk test); and homogeneity of variance was checked by Levene's test. Differences between
groups were detected by performing the independent t-test for normally distributed homogeneous
values and the Welch test for non-homogeneous normally distributed values. The Mann-Whitney
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U test was applied for non-parametric data or for parametric data not following the normal
distribution. Differences were considered significant at a p-value less than 0.05.
The PhD scientific project was favourably approved by the Research Ethics Committee
of the IP USMF "Nicolae Testemitanu" (no. 47 of 17.06.2019).
Novelty and scientific originality of the results obtained: Taking into account the
increasing number of patients on the waiting list with viral liver cirrhosis, the long waiting time,
the rapid progression of the disease with increased mortality rate of patients, for the first time an
interdisciplinary clinical and paraclinical study was conducted, with a complex evaluation of
prognostic scores predicting mortality in the first 90 days of listing, with the creation of a
monitoring system validated and adapted for the Republic of Moldova. Careful monitoring and
re-evaluation of candidates at regular intervals has been implemented which can improve the
success of the liver transplant programme and the overall patient outcome.
Scientific and practical problem solved
The scientific-practical problem solved in the research is the development of the rational
algorithm for evaluation and triage of patients with liver cirrhosis of viral aetiology from the
waiting list in various clinical situations and greater accessibility in the view of the liver
transplant coordinator team.
Theoretical importance and applicative value of the study
The applicative value of the study is reflected in the scientific work - the analysis of the
concepts of scientists in the country and abroad, the hypotheses and problematizations made, as
well as the knowledge we have gained through our PhD research, will broaden the horizon of
research of clinical-paraclinical features in patients with liver cirrhosis of viral etiology and the
assessment of prognostic scores of short-term mortality risk for patients included in the waiting
list for liver transplantation. New scores have been proposed that exceed the predictive value of
the MELD score and would facilitate the inclusion of patients on the liver transplant waiting list
depending on the severity of the disease, so that patients with end-stage liver disease in severe
disease are given priority for liver transplantation. Also in teaching activity - the conclusions and
recommendations presented in the paper can be used in the training process of students/residents;
practical activity - the acquired knowledge and the proposed recommendations will improve the
work of clinics.
Implementation of research results.
The practical impact of the present study is the external validation of the new MELD 3.0
score on the population with viral liver cirrhosis from the waiting list for liver transplantation in
the Scientific Surgical Laboratory ,,Reconstructive Surgery of the Digestive Tract'' Nicolae
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Testemitanu State University of Medicine and Pharmacy, Chisinau, Republic of Moldova. In
addition, the results obtained (validation of the new prognostic mortality score in the first 90
days after listing) were presented to medical students during the classes at the Department of
Surgery No. 2.
Approval of scientific results. The results obtained were discussed and presented at the
following scientific forums: the National Congress of Surgery, Sinaia, 2022, the National
Congress of the Romtransplant Association, edition 2022, the scientific-practical conference with
international participation ,,Hepatobiliary-pancreatic surgery, abdominal parietal defects,
advanced laparoscopic surgery'', Chisinau, 2022, the annual scientific conference ,,Research in
biomedicine and health: Quality, Excellence and Performance'' dedicated to the 77th anniversary
of the founding of Alma Mater. National Conference ,,Days of the CF Clinical Hospital Iasi'',
edition 2022, Scientific Conference with international participation dedicated to the Medical
Days of the Municipal Clinical Hospital ,,Saint Archangel Michael'' 1st edition, 21.11.2022,
International Scientific Conference ,,Tissue and Cell Transplantation. Actualități și perspective'',
National Scientific Conference on BPH Surgery, 20.04.2023 - 23.04.2023, Bucharest, Congress
Balkan Medical Week, XXXVII edition Perspectives of Balkan Medicine in the post COVID-19
era, 7-9 June 2023, Chisinau, Republic of Moldova, National Congress of Surgery. The XIVth
Congress of the Association of Surgeons ,,Nicolae Anestiadi'' of the Republic of Moldova. 21-23
September 2023.
Publications on the research topic. 29 scientific papers have been published on the
subject of the thesis, of which: 10 articles in scientific journals, 9 theses, 1 abstract in SCOPUS
journal. 1 patent, active participations in national and international scientific conferences and
congresses in total 10 participations confirmed by programs and certificates of participation. Of
which, international communications - 2, national - 8.
Thesis structure. Thesis includes annotations in Romanian, Russian and English, list of
abbreviations, introduction, 4 chapters with general conclusions, practical recommendations. The
paper is followed by the list of bibliographical references with 222 sources and the author's CV.
The introduction part of the paper reflects the topicality and scientific-practical importance of the
problem addressed in the thesis, the aim, objectives, scientific novelty, theoretical importance
and applied value of the research, approval of the results of the study
Cartografierea consumului de antibiotice în Republica Moldova
Introduction. Antibiotic consumption represents a crucial aspect of modern healthcare.
Abuse and inappropriate use of antibacterial agents contribute to the phenomenon of bacterial resistance. The aim of the study was to determine antibiotic consumption in hospital
conditions and map the results in order to highlight regions in the country with the highest
levels of antibiotic consumption and the classes of antibiotics used.
Material and methods. Antibiotic consumption in hospitals (64 facilities) over a 4-year period (2018-2021) was determined using the defined daily dose (DDD) as the unit of measurement. The quantity of antibiotics consumed was expressed in DDD/1000 patient-days (hospitalization days), followed by mapping the results.
Results. A "very high" level of antibiotic consumption, expressed in DDD/1000 patient-days,
was observed in the Falesti district, while a "medium" level of antibacterial agent consumption was observed in the Taraclia, Comrat, Ialoveni, Singerei, Glodeni, and Donduseni
districts. The total consumption per antibiotic class revealed an increased use of Cephalosporins, Imidazole derivatives, Macrolides, Tetracyclines, Fluoroquinolones, and Aminoglycosides.
Conclusions. Mapping antibiotic consumption is an efficient tool in highlighting administrative-territorial regions with high antibiotic consumption and identifying the most frequently used antibiotic classes. Providing this information is useful for developing policies
aimed at optimizing antibiotic use and minimizing resistance.Introducere. Consumul de antibiotice reprezintă un aspect crucial al asistenței medicale moderne. Abuzul și utilizarea necorespunzătoare a preparatelor antibacteriene favorizează fenomenul de rezistență bacteriană. Scopul studiului a fost determinarea consumului de antibiotice în condiții de staționar în Republica Moldova și cartografierea rezultatelor obținute.
Material și metode. În acest studiu a fost determinat consumul de antibiotice în condiții de
staționar (64 de spitale), pe o perioadă de patru ani (2018-2021), folosind ca unitate de măsură doza zilnică definită (DDD). Cantitatea de antibiotice consumată a fost exprimată în
DDD/1000 zile-pacient (zile de spitalizare), ulterior fiind efectuată cartografierea rezultatelor.
Rezultate. Rezultatele înregistrate atestă un nivel „foarte mare” de consum de antibiotice
exprimat în DDD/1000 zile de spitalizare în raionul Fălești și un nivel „mediu” de consum de
preparate antibacteriene în raioanele Taraclia, Comrat, Ialoveni, Sîngerei, Glodeni, Dondușeni. Consumul total per clase de antibiotice a scos în evidență un consum sporit de cefalosporine, de derivați de imidazol, de macrolide, de tetracicline, de fluorochinolone și de aminoglicozide.
Concluzii. Cartografierea consumului de antibiotice reprezintă un instrument eficient de
evidențiere a regiunilor administrativ-teritoriale în care consumul de antibiotice este ridicat, și a claselor de antibiotice cel mai frecvent utilizate. Aceste informații sunt utile pentru
elaborarea de politici menite să optimizeze utilizarea antibioticelor și să minimizeze
rezistența acestora
Immunostimulation of local immunity in the complex treatment of chronic tonsillitis in children
Background. After healing the palatine tonsils in the complex conservative treatment of chronic
tonsillitis, an important role is the stimulation of local immunity by applying autologous mononuclear
cells. This is done by introducing these activated cells into the peritonsillar space. The application of
this method does not produce immune conflict, transmission is excluded hemotransmissible
pathologies, the bioethical problem is missing.
Objective. To examine the effect of applying local immunostimulation with activated autocells in
chronic tonsillitis in children without complications at the distance.
Materials and methods. Clinical and immunological studies of the treatment of children with chronic
tonsillitis without complications of other organs and (74 children) were investigated in the IP Mother
and Child Center, Emilian Cotaga Clinic, ENT Department. The method of local immunostimulation
(autologous mononuclear cells) was developed in the Tissue Engineering and Cell Cultures Laboratory
of Nicolae Testemițanu SUMPh.
Results. After more than 2 months of treatment were highlighted decreases in IgE content, decreases
in sensitization of T lymphocytes to Streptococcus pyogenes and pneumococcal antigens, decreases in
IgG titers, decreases in the level of pro-inflammatory cytokines TNF-alpha, IL-1-8 beta, increases in
cytokines anti-inflammatory Il-4. The presence of Streptococcus pyogenes in tonsillar surface smears
was significantly reduced after treatment. Over the course of a year, the number of acute respiratory
infections decreased in these children, as well as indications for antibiotic therapy, signs of chronic
inflammation of the palatine tonsils (caseous masses in the hollows, hyperemia of the tonsil pillars,
etc)
Conclusion. The method of local immunostimulation (with autologous mononuclear cells) in the case
of chronic tonsillitis has a positive clinical impact, exerting a positive complex action on the reactivity
of immune indices
Autolog tranplantation of platelet rich fibrin in inguinal hernia repair in liver cirrhosis
Background. The objective of this study is to provide autologous platelet-rich fibrin transplantation
in inguinal hernia repair in liver cirrhosis with ascites.
Materials and methods. A study was conducted on 28 patients with inguinal hernia combined with
liver cirrhosis and massive ascites-peritonitis.
Group I: 14 patients with inguinal hernia associated with liver cirrhosis and massive ascites peritonitis
underwent Lichtenstein type hernioplasty. Group II: 14 patients with inguinal hernia associated with
liver cirrhosis and massive ascites peritonitis underwent Lichtenstein type hernioplasty with the
application of autologous fibrin transplantation rich in platelets. All patients in both groups underwent
laparoscopic lavage of the abdominal cavity with antibacterials and postoperative drainage with lavage.
Results. Seroma wounds postoperative wounds I group 3 cases, II group 0 cases. Postoperative wound
suppuration I group 1 case, In group II – 0 cases. Recurrence of the hernia at 1 year was not observed
in both groups. Mortality consists of 2 patients, who developed liver failure after 2 months of
hospitalization, 1 patient from group I.
Conclusion. In patients with inguinal hernia and liver cirrhosis and ascites-peritonitis, the application
of Lichtenstein-type surgical treatment with the application of autologous platelet-rich fibrin
transplantation ensures safe local results, without postoperative complications in the postoperative
wound (lack of seromaler and wound suppuration). Postoperative mortality does not determine a
significant difference, being caused by liver reserves and liver failure. Surgical treatment without the
application of autologous platelet-rich fibrin transplantation has an increased incidence of
postoperative complications
Organizarea asistenței medicale victimelor violenței sexuale
Scopul: Evaluarea practicilor de organizare a asistenței medicale victimelor violenței
sexuale pentru elaborarea recomandărilor menite să îmbunătățească structura și procesele
instituționale în domeniu.
Obiective: Analiza practicilor internaționale și naționale privind organizarea asistenței
medicale victimelor violenței sexuale; evaluarea practicilor existente de organizare a serviciilor
medicale și medico-legale pentru victimele violenței sexuale; identificarea barierelor și
provocărilor în organizarea asistenței medicale victimelor violenței sexuale; elaborarea unor
recomandări privitor la îmbunătățirea serviciilor medicale și medico-legale acordate victimelor
violenței sexuale.
Material și metode: Tipul de studiu: transversal, descriptiv, mixt (cantitativ și calitativ),
efectuat prin chestionarea a 240 de medici ginecologi și interviuri în profunzime cu diferite categorii de profesioniști, precum: manageri de spitale, șef Centru Perinatal, reprezentant al
Inspectoratului de Poliție, medic-legist. Datele au fost colectate în perioada noiembrie 2022-
martie 2023. Chestionarul a fost realizat în Google Forms și distribuit online. Metodele studiului
– grafică, statistică, sociologică.
Rezultate obținute: În studiul cantitativ, caracteristicile social-demografice ale
respondenților sunt după cum urmează: 165 (68,70%) sunt femei și 75 (31,30%) bărbați; stagiul
de muncă de 5 ani a fost indicat de 6,2%, 10-15 ani – 12,5%, peste 20 de ani – 81,3 %. După
regiunea geografică a țării, din centru au răspuns 18,8%, sud – 37,4%, nord – 43,8%. Datele
studiului relatează că medicii ginecologi în proporție de 100% sunt total de acord că serviciile de
sănătate acordate victimelor violenței sexuale trebuie să fie furnizate concomitent cu serviciile
medico-legale, în același loc și timp. Medicii ginecologi din cadrul spitalului, de altfel, foarte rar
participă la expertiza medico-legală efectuată de către medicul legist în UPU, deoarece nu este
solicitat/invitat. Cu faptul că fenomenul de violență sexuală este o problemă majoră de sănătate
publică au fost de acord jumătate din respondenți, total de acord au fost 31,3% și nu sunt de
acord – 18,7%. Frecvența fenomenului violenței sexuale în practica medicului ginecolog se
întâlnește rar conform opiniei a 37,5%, frecvent – 25%, foarte rar – 25%, iar pentru opțiunea
greu de răspuns optează 12,5% dintre respondenți. Răspunsul sistemului de sănătate la cazurile
de violență sexuală este fragmentar și sunt oferite de diferite unități în cadrul spitalului (UPU,
AMSA, cât și centrele de sănătate). Conform datelor studiului, în 37,5% din cazuri asistența
medicală este acordată în cadrul spitalelor și în 25% – AMSA. Medicii din UPU și medicii
obstetricieni ginecologi au acces la contracepție de urgență care se oferă 100% datorită donațiilor
din partea UNFPA. Formarea profesională a medicilor implicați în acordarea asistenței medicale
victimelor violului a inclus instruiri sporadice în managementul cazurilor de viol. În cadrul
cursurilor de educație continuă nu există cursuri tematice dedicate exclusiv gestionării cazurilor
de violență sexuală. Conform datelor studiului au beneficiat de instruiri 68,8%, pe când 31,3%
nu au beneficiat. Oferirea suportului psihosocial victimei este deosebit de importantă la adresarea
în instituția medicală. Nevoia de instruire a furnizorilor de servicii cu privire la ajutorul
psihosocial și consiliere pentru victimele violenței sexuale a fost raportat de 87,5% din
respondenți, pe când doar 31,2% au beneficiat de asemenea instruiri. Frecvent în instituțiile
medicale se încalcă principiul de confidențialitate, dreptul de a primi îngrijiri și tratament într-un
mediu privat și sigur. Rezultatele studiului calitativ confirmă că răspunsul sistemului de sănătate
la cazurile de violență sexuală nu corespunde „standardului de aur” al OMS, care prevede
acordarea serviciilor medicale și medico-legale victimelor violului concomitent. Majoritatea
specialiștilor optează pentru o comunicare mai eficientă care va fi posibilă prin formarea
centrelor/serviciilor multidisciplinare de asistență a victimelor violenței sexuale.
Concluzii: La momentul actual, în pofida existenței cadrului legal în domeniu, acordarea
asistenței medicale victimelor violenței sexuale este fragmentară și neuniformă. Un rol important
revine acțiunilor de informare și prevenire. Instruirea personalului implicat nu este suficientă
pentru o schimbare durabilă, fiind necesar de a îmbunătăți infrastructura, comunicarea între
diferiți actori, elaborarea procedurilor standard operaționale și a procedurilor de confidențialitate,
mobilizare comunitară. Se constată necesitatea creării unui serviciu specializat multidisciplinar
amplasat cât mai aproape de beneficiari, ce va permite examinarea medicală și medico-legală,
consiliere psihologică, servicii sociale și asistență juridică sub același acoperiș
Complications associated with fixation method of orthopedic constructions on implant support
Rezumat. Articolul examinează complicațiile asociate cu metodele de fixare a construcțiilor protetice pe
suport implantar, comparând cimentarea și înșurubarea. Studiul a relevat că fixarea prin cimentare prezintă
un risc mai mare de complicații biologice, cum ar fi
periimplantita și pierderea osoasă, în timp ce fixarea
prin înșurubare este asociată cu un risc crescut de
complicații tehnice, cum ar fi slăbirea sau fracturarea
șuruburilor. Ambele metode au avantaje și dezavantaje
distincte, dar necesită luarea în considerare a complicațiilor posibile pentru a alege metoda optimă.Abstract. The article examines the complications
associated with methods of fixing prosthetic constructions on implant support, comparing cementation and
screwing. The study revealed that cementation fixation
presents a higher risk of biological complications, such
as peri-implantitis and bone loss, while screw fixation
is associated with an increased risk of technical complications, such as screw loosening or fracturing. Both
methods have distinct advantages and disadvantages,
but require consideration of possible complications to
choose the optimal method
Osteo-cellular graft in the wrist instability. Clinical case
Background. The wrist or carpal instability means any disturbance of the static and dynamic balance
of forces at the wrist under the conditions of daily living [Linscheid, 1972]. The cause of wrist
instability in 95% is of post-traumatic origin, the most of cases are around scaphoid bone [Watson,
1984]. The instability of the wrist joint causes the deforming osteoarthritis of the joint which in turn
leads to chronic pain and disability [AzÛcar, 2021]. Wrist arthrodesis is a procedure performed in
advanced arthritis with painful movement in wrist joint [Chhabra, 2010]. This surgery is a rescue one,
and is made in order to remove the pain syndrome and increase the strength of the hand [Gelberman,
2000]. Aim of study was presentation the clinical case of scaphoid pseudarthrosis with deforming
osteoarthritis of the wrist joint treated by arthrodesis using osteo-cellular graft (OCG).
Material and methods. Anamnesis, clinical and paraclinical data were taken from the hospital patient
record. Were analyzed the laboratory examinations, radiography and MRI of the wrist joint of the
patient.
Results. A 39-year-old man suffered repetitive fall trauma in the left hand: first time it was about 20
years ago and was performed conservative treatment, but 6 years later the pains started to appear. After
another trauma 5 years ago, it was diagnosed scaphoid pseudarthrosis, but it was neglected. Now the
patient presented at the Clinical Hospital of Traumatology and Orthopedics with severe pain, limitation
of movements and deformity of the left wrist joint, he was admitted to the Division of Hand Surgery.
The patient’s radiological images and MRI reports - Scaphoid pseudarthrosis of the left hand with 2nd
degree deforming osteoarthritis of the wrist joint. Together with patient it was decided to perform
surgical treatment – scaphoidectomy and arthrodesis using osteo-cellular graft (OCG). Before surgery,
harvesting of autologous mesenchymal stem cells and enrichment by tissue-engineering was carried
out, which were combined with demineralized allograft obtaining OCG. According to preoperative
planning, scaphoidectomy and 4-corner arthrodesis (capitate-lunate and triquetrum-hamatum) using
OCG was performed. Remote imaging and clinical examinations showed a satisfactory outcome. The
patient completely got rid of pain and began to work again.
Conclusion. The use of osteo-cellular graft in arthrodesis of wrist instability is a safe method with
good results, the clinical study of this topic is imperative and needs to be researched further
The use of autotransplanted and homotransplanted septal cartilage in rhinoplasty and rhinoseptoplasty surgeries
Background. Surgical interventions for nasal reshaping, such as rhinoplasty and rhinoseptoplasty,
have gained significant popularity among the population. Currently, these procedures are increasingly
performed using both autotransplants and homotransplants. These surgical procedures are now
enhanced through the use of advanced surgical techniques, specialized equipment, and high-
performance instruments. Rhinoplasty surgeons have embraced a modern approach, abandoning
traditional methods of dorsum nasi bone resection with chisel and hammer. Instead, a piezotome is
used to perform median and lateral osteotomies, allowing for controlled fracturing of nasal bones along
the greenstick fracture lines to obtain mobile fragments without displacement, and adjusting only the
insertion angle. These aspects are crucial moments that previously presented multiple difficulties for
surgeons. In many cases, it is necessary to fill depressions or tissue deficiencies on the nasal pyramid
or adjust the position of the nasal tip using cartilaginous tissues. In such cases, nasal septal cartilage is
a valuable resource. Rhinoplasty surgeons prefer to use the patient's own nasal septal cartilage
whenever possible, but it is not always sufficient or may be absent, especially after previous nasal
septal surgeries. In these cases, rib cartilage can be used, but some patients may refuse its harvesting
or there may be contraindications. Consequently, the question arises regarding the use of
homotransplanted nasal septal cartilage.This technique is well-known and successfully used by
rhinoplasty surgeons. To benefit from homotransplanted cartilage, collaboration with a specialized
tissue bank for human tissue transplants is necessary.
The aim of the study. Is to conduct comprehensive literature studies regarding the use of
autotransplanted and homotransplanted nasal septal cartilage in rhinoplasty and rhinoseptoplasty
surgeries. Materials and methods. In the analysis process, a total of 50 sources of information were
evaluated, including those available on medical platforms such as Medlife, PubMed, Google Scholar,
and ResearchGate. Among the highly relevant sources, several were highlighted, considered
significant for this research domain, providing varied and detailed perspectives on the use of nasal
septal cartilage in nasal aesthetic surgery and contributing to the comprehensive analysis of the subject.
To achieve an advanced selection of bibliographic sources, several filters and criteria were applied.
Full-text articles published in English and Russian between 2000 and 2024 were sought. After a
preliminary analysis of the titles, original articles, editorials, and narrative, systematic, and meta-
analysis synthesis articles were selected. These types of articles were chosen because they provide
relevant information and contemporary concepts regarding the use of autotransplanted and
homotransplanted nasal septal cartilage in rhinoplasty and rhinoseptoplasty surgeries.
Additionally, a supplementary search was conducted in the bibliographic reference lists of the initially
identified sources to find additional relevant publications not included in the consulted databases.
Information from the publications included in the bibliography was gathered, classified, evaluated, and
synthesized to highlight the main aspects of contemporary views on the practices mentioned in the
field of using nasal septal cartilage in aesthetic and reconstructive nasal surgeries. This approach
allowed for exhaustive and updated research in the field of rhinoplasty and rhinoseptoplasty.
Results and discussions. According to the results obtained in these studies, in rhinoplasty and
rhinoseptoplasty interventions, it was found that autotransplanted nasal septal cartilage was most
commonly used, while homotransplanted cartilage, collected from other patients, and previously
preserved at a human tissue bank for transplantation, was used less frequently. Overall, the results were promising, with good integration and revitalization observed in both
autotransplants and homotransplants.
Conclusions. The use of transplants, both autotransplants and homotransplants, represents the most
efficient and commonly used method in rhinoplasty and rhinoseptoplasty surgeries. In rhinoplasty and
rhinoseptoplasty surgeries, it was found that nasal septal cartilage is most frequently used compared to
other types of transplants, such as auricular cartilage or costal cartilage. These transplants have the
advantage of not being resorbed, maintaining their shape over time, and not causing inflammatory or
allergic reactions, contributing to the success and durability of surgical interventions in these areas
Hepatic veins in anatomical-surgical aspect
Background. Currently, complex liver pathology has imposed an increased need for surgical
interventions at this level, which has required a detailed knowledge of hepatic blood circulation. An
important place in this study belongs to the efferent venous circulation. Under normal conditions, the
liver accumulates about 20% of the circulating blood volume and directs up to 1,200 ml of blood per
minute into the inferior vena cava, which represents 50% of the breast volume returned through this
vein. The advances made lately in knowing the anatomical distribution of the components of the
hepatic, arterial and venous vascular tree have allowed a systematization of knowledge in the field of
liver segmentation.The purpose of the present paper is to study the anatomical and surgical peculiarities
of hepatic veins.
Material and methods. To establish the morphology of hepatic veins, the study was performed on a
number of 11 macroscopic liver preparations. Macropreparations were taken from cadavers of both
sexes who died at different ages, in which no diseases of the hilar or cavale area of the liver.
As working methods were used: plastic injection, which has solvent dust and green, yellow, blue and
red paint, and corrosion step in hydrochloric acid solution.
Results. The trunks of the hepatic veins in all given cases are located intraorganically and flow into
the inferior vena cava in its subdiaphragmatic portion. Depending on the size of the veins, large hepatic
veins with a diameter of 7-18 mm and small diameters of 2-6 mm can be highlighted. The number of
hepatic veins flowing into the inferior vena cava is variable.
Conclusions. The casts of the venous elements of the liver, obtained by polychrome injection and
corrosion are very informative