Institutional Repository in Medical Sciences of Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
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Addressing artificial intelligence gaps in transplant medecine: a machine learning solution
Get PDFIntroduction: Artificial intelligence (AI) shows promise in transplant medicine, particularly in organ
matching and rejection prediction. However, gaps remain in personalized immunosuppression,
including optimal drug dosing, patient-specific data integration, and clinical implementation. This
study identifies these gaps and proposes a machine learning model to optimize immunosuppressive
therapy.
Material and Methods: A systematic review was conducted using PubMed, Scopus, and Web of
Science from 2010 to 2024 with keywords: "Artificial Intelligence," "Transplant Medicine," "Rejection
Prediction," and "Patient Care Optimization." Studies discussing AI applications in rejection prediction
or patient care in organ transplantation were included. Data on study design, AI methods, outcomes,
and limitations were extracted. Findings show most AI models rely on static predictors and fail to adapt
to real-time changes like infections and inflammation. Multi-omics data, crucial for drug metabolism
and immune response, are rarely integrated, reducing accuracy. Generalizability is also limited, as most
models are trained on small, single-center datasets further reducing accuracy. To address these gaps,
we propose a machine learning model using longitudinal transplant data. It will integrate electronic
health records, pharmacokinetics, genomics, and biomarkers to predict individualized dosing.
Recurrent neural networks or transformer-based architectures will update recommendations based on
patient-specific responses. Model performance will be validated using real-world clinical data and
benchmarked against traditional dosing protocols.
Results: The review included 68 articles, with 14 meeting inclusion criteria. While AI has been applied
to organ matching and rejection prediction, no existing models provide real-time, patient-specific
immunosuppression adjustments, impacting patient outcomes. The proposed model aims to bridge this
gap, potentially reducing rejection rates and improving outcomes.
Conclusions: This study identifies deficiencies in AI-driven immunosuppression management,
particularly in real-time dose adjustments, multi-omics integration, and model generalizability. The
proposed machine learning framework seeks to create an adaptive, personalized dosing system to
enhance transplant outcomes and minimize rejection risks
Specific features of the facial nerve trunk
Get PDFIntroduction: The facial nerve trunk (FNT) is vulnerable to iatrogenic injures in surgery of the
retromandibular region, particularly in mastoidectomy. Variation of the FNT number, topography and
course increase the risk of its iatrogenic injures. Our goal was to determine the length of the FNT
depending on the gender, laterality, cephalometric type, branching pattern and variant of branching.
Materials and Methods: The study was conducted on 75 formalized adult hemiheads (59 males and
16 females), dissected at the Department of Anatomy and Clinical Anatomy of Nicolae Testemitanu
State University of Medicine and Pharmacy. The length of the FNT was measured from the point of
its exit through the stylomastoid foramen until point of its division into primary branches. One-way
ANOVA, t-test and χ2 test were used for statistical analysis.
Results: In males the mean length of the FNT was 11.3 mm and in females it was 10.4 mm, p = 0.289.
Bilaterally the length of the FNT was equal to 11.1 mm, p = 0.981. The mean length of the FNT in
mesocephalic type was 10.9 ± 2.87 mm, in brachycephalic type it was 12.3 ± 3.54 mm and in
dolichocephalic type it was 10.9 ± 2.54 mm. The intergroup frequency variation (IGFV = 0.755); the
degree of freedom (df = 2); p = 0.474. Seven branching patterns of the extracranial portion of the facial
nerve were revealed in the current study. Depending on the branching pattern the length of the FNT
varied as follows: Type I (12.2 ± 3.33 mm); Type II (11.0 ± 2.54 mm); Type III (11.3 ± 2.93 mm);
Type IV (10.3 ± 3.85 mm); Type V (11.5 ± 2.08 mm); Type VI (10.1 ± 2.06 mm); Type NI-atypical
(11.5 ± 3.11 mm); IGFV = 0.794; df = 6; p = 0.578. In classic branching patterns the mean length of
the FNT was 11.4 mm, while in atypical variants, it was 10.6 mm; p = 0.258.
Conclusion: The length on the FNT was variable on four of the examined criteria. The FNT was longer
in males, in brachycephalic type, in Type I and in classic variant of branching
Ultramicroscopic study of the lateral tubule hybridization
No full textIntroducere. Stratul hibrid reprezintă partea de dentină aflată în contact strâns cu materialul restaurator,
demineralizată de acid și infiltrată de rășina adezivă. Fiind un biopolimer tridimensional de colagen-rășină,
determină o legătură continuă și stabilă între adeziv și substratul dentinar. Fenomenul de hibridizare tubulară
laterală este descris ca formarea unui strat hibrid în pereții ramurilor tubulilor dentinari laterali. Asigurarea
hibridizării adecvate și stabilitatea interfeței rășină-dentină sunt o cheie importantă în procesul adeziunii.
Scopul lucrării. Studierea ultramicroscopică a fenomenului de hibridizare dentinară tubulară laterală
la obturarea cavităților cu compozit prin tehnica de stratificare și injection-molding.
Material și metode. Pentru realizarea studiului au fost selectați molari de minte, lipsiți de carie, iar la
nivelul acestora au fost preparate cavități mezio-ocluzale. Dinții au fost repartizați în două loturi de cercetare:
lotul control cu cavități obturate prin tehnica convențională de stratificare și lotul experimental cu cavități
obturate prin tehnica injection-molding. A fost folosit adezivul universal Scotchbond Universal Adhesive, 3M
ESPE și compozitul Filtek One Bulk Fill Restorative, 3M ESPE. Dinții obturați au fost secționați pe direcție vestibulo-
orală cu ajutorul discurilor de almaz. Șlifurile dentare obținute au fost supuse studiului ultramicroscopic
al interfeței adezive prin microscopie electronică scanată (SEM).
Rezultate și discuții. În cadrul analizei șlifurilor dentare, fenomenul de hibridizare dentinară tubulară laterală
a fost mai des întâlnit în cazul tehnicii injection-molding de obturare cu compozit. Astfel se prezintă retenții
adiționale ca supliment al procesului de adeziune, fapt ce este determinat de injectarea unui material compozit
cu proprietăți de curgere, care prezintă elemente caracteristice unui proces hidrodinamic, și anume: viscozitatea
materialului ghidată de fluiditatea sa, aplicarea sub presiune și distribuția acesteia, viteza curgerii și fricțiunea.
Concluzii. Tehnica injection-molding de obturare cu compozit determină apariția la nivelul interfeței
adezive a fenomenului de hibridizare dentinară tubulară laterală, care contribuie la retenția suplimentară și
etanșeitatea adeziunii prin formarea micro-extensiilor laterale ramificate din tubii dentinari principali.Background. The hybrid layer represents the portion of dentin that is in close contact with the restorative
material, demineralized by acid, and infiltrated with adhesive resin. Being a three-dimensional collagen-
resin biopolymer, it determines a continuous and stable bond between the adhesive and the dentin substrate.
The phenomenon of lateral tubular hybridization is described as the formation of a hybrid layer within
the walls of the lateral branches of dentinal tubules. Ensuring proper hybridization and the stability of the
resin-dentin interface is a key factor in the adhesion process.
Objective of the study. The ultramicroscopic study of the lateral tubule hybridization in cavity filling
with composite by using the layering and injection-molding techniques.
Material and methods. For the study, free caries third molars were selected, and mesio-occlusal cavities
were prepared. The teeth were divided into two research groups: a control group with cavities restored
using the conventional layering technique and an experimental group with cavities restored using the injection-
molding technique. The Scotchbond Universal adhesive (3M ESPE) and Filtek One Bulk Fill Restorative
composite (3M ESPE) were used. The restored teeth were sectioned in the vestibulo-oral direction using diamond
discs. The obtained dental samples were subjected to an ultramicroscopic study of the adhesive interface
using scanning electron microscopy (SEM).
Results and discussions. In the analysis of dental samples, the phenomenon of lateral tubule hybridization
was more frequently observed when using the injection-molding composite filling technique. This results
in additional retention as a supplement to the adhesion process, which is determined by the injection of a
flowable composite material exhibiting characteristics of a hydrodynamic process, namely: the viscosity of the
material guided by its fluidity, application under pressure and its distribution, flow rate, and friction.
Conclusions. The injection-molding composite filling technique leads to the appearance of the lateral
tubule hybridization at the adhesive interface, which contributes to additional retention and adhesion sealing
by forming micro-resin-tugs that branch from the main dentinal tubules
Multifocal transcranial magnetic stimulation in migraine and epilepsy
No full textStructura tezei. Lucrarea este expusă pe 88 de pagini de text de bază; include 45 figuri, 6
tabele și 16 anexe; este compusă din introducere, 3 capitole dintre care 2 – conțin material propriu,
concluzii generale, recomandări practice, adnotare în limbile română, rusă și engleză și
bibliografie cu 297 referințe. Rezultatele cercetării au fost publicate în 18 lucrări ştiinţifice
Cuvinte-cheie: Stimulare magnetică transcraniană, stimulare theta burst, migrenă episodică,
epilepsie generalizată, prevenție, neuromodulare.
Scopul studiului. Aprecierea eficacității stimulării magnetice transcraniene multifocale în
profilaxia atacurilor de migrenă la pacienți cu migrenă episodică și a crizelor epileptice la pacienți
cu epilepsie generalizată.
Obiectivele studiului. (1) Evaluarea efectului stimulării magnetice transcraniene
multifocale asupra zilelor cu migrenă, frecvenței și intensității crizelor de migrenă la pacienți cu
migrenă episodică; (2) Determinarea impactului TMS multifocal asupra calității vieții la pacienți
cu migrenă episodică; (3) Aprecierea efectului stimulării theta burst (TBS) asupra frecvenței și
severității crizelor epileptice la pacienți cu epilepsie generalizată; (4) Analiza influenței TBS
asupra calității vieții la pacienții cu epilepsie generalizată; (5) Aprecierea profilului de siguranță și
tolerabilitate a protocoalelor experimentale de TMS (rTMS și TBS);
Originalitatea și noutatea științifică. A fost efectuat un studiu experimental care a debutat
paradigma de stimulare magnetică transcraniană multifocală cu examinarea impactului terapeutic
al acesteia în tratamentul preventiv al pacienților cu migrenă episodică și epilepsie generalizată.
Problema științifică rezolvată în teză constă în identificarea modalităților noi terapeutice
de modulare a activității rețelelor cerebrale cortico-subcorticale prin aplicarea stimulării magnetice
transcraniene multifocale, ceea ce va contribui la fundamentalizarea paradigmei multifocale de
neuromodulare în cercetările științifice ulterioare.
Semnificația teoretică și valoarea aplicativă. Prin implementarea unei metode moderne de
tratament neuromodulator a pacienților cu migrenă episodică și a celor cu epilepsie generalizată
din Republica Moldova, cercetarea efectuată a fundamentalizat viziunea contemporană în
algoritmul de evaluare și tratament complex la acești pacienți. Pe lângă aceasta, elaborarea și
utilizarea unui protocol multifocal de TMS, inovativ nu doar pe plan național dar și internațional,
a permis creșterea cunoștințelor în domeniul metodelor de neuromodulare în tratamentul
tulburărilor neurologice paroxismale precum migrena și epilepsia.
Impactul practic al prezentului studiu constă în implementarea în cadrul Laboratorului de
neurobiologie și genetică medicală, Universității de Stat de Medicină și Farmacie ”Nicolae
Testemițanu” și a departamentului de Neurologie, Epileptologie și Boli interne, IMSP IMU a
metodei inovative de neuromodulare a activității cerebrale la pacienți cu migrenă episodică și
epilepsie generalizată.Структура диссертации. Работа изложена на 88 страницах основного текста;
включает 45 фигур, 6 таблиц и 16 приложений; Состоит из введения, 3 глав с общими
выводами, практические рекомендации, аннотации на румынском, русском и английском
языках и библиографию с 297 ссылками. Результаты исследований опубликованы в 18
научных статьях.
Ключевые слова: транскраниальная магнитная стимуляция, тета-стимуляция,
эпизодическая мигрень, генерализованная эпилепсия, профилактика, нейромодуляция.
Цель исследования. Оценка эффективности мультифокальной транскраниальной
магнитной стимуляции в профилактики приступов мигрени у больных с эпизодической
мигренью и эпилептических припадков у больных с генерализованной эпилепсией.
Задачи исследования: (1) Оценка влияния мультифокальной транскраниальной
магнитной стимуляции на количество дней мигрени, частоту и интенсивность приступов
мигрени у пациентов с эпизодической мигренью; (2) Определение влияния
мультифокальной ТМС на качество жизни пациентов с эпизодической мигренью; (3)
Оценка влияния тета-стимуляции (TБС) на частоту и тяжесть эпилептических припадков у
пациентов с генерализованной эпилепсией; (4) Анализ влияния ТБС на качество жизни
пациентов с генерализованной эпилепсией; (5) Оценка профиля безопасности и
переносимости экспериментальных протоколов ТМС (рТМС и TБС);
Научная оригинальность и новизна. Проведено экспериментальное исследование,
дебютировавшее с парадигмой мультифокальной транскраниальной магнитной
стимуляции с изучением ее терапевтического воздействия в профилактическом лечении
пациентов с эпизодической мигренью и генерализованной эпилепсией.
Научная проблема, решаемая в диссертации, заключается в выявлении новых
терапевтических способов модуляции активности корково-подкорковых сетей головного
мозга путем применения мультифокальной транскраниальной магнитной стимуляции, что
может способствовать обоснованию парадигмы мультифокальной нейромодуляции в
дальнейших научных исследованиях.
Теоретическая значимость и прикладное значение. Внедряя современный метод
нейромодулирующего лечения пациентов с эпизодической мигренью и генерализованной
эпилепсией в Республики Молдова, проведенное исследование закрепило современное
видение алгоритма комплексного обследования и лечения этих пациентов. Помимо этого,
разработка и применение мультифокального протокола ТМС, инновационного не только на
национальном, но и на международном уровне, позволили расширить знания в области
методов нейромодуляции при лечении пароксизмальных неврологических расстройств,
какими являются мигрень и эпилепсия.
Практическая значимость настоящего исследования заключается во внедрении в
лаборатории нейробиологии и медицинской генетики Государственного медикофармацевтического университета им. Николае Тестемицану и Деапартамента неврологии,
эпилептологии и внутренних болезней Института Неотложной Медицины, инновационного
метода нейромодуляции у больных с эпизодической мигренью и генерализованной
эпилепсией.Structure of the thesis. The thesis is presented on 88 text pages; includes 45 figures, 6 tables
and 16 appendices; it is composed of introduction, 3 chapters of which 2 – contain own research
data, general conclusions, practical recommendations, annotation in Romanian, Russian and
English and 297 bibliographic references. The main results of the research were published in 18
scientific papers.
Keywords: Transcranial magnetic stimulation, theta burst stimulation, episodic migraine,
generalized epilepsy, prevention, neuromodulation.
The aim of study. Assesment of multifocal transcranial magnetic stimulation efficacy in
prevention of migraine attacks in patients with episodic migraine and epileptic seizures in patients
with generalized epilepsy.
Objectives of the study. (1) Assess the effect of multifocal transcranial magnetic
stimulation on migraine days, frequency and intensity of migraine attacks in patients with episodic
migraine; (2) Determine the impact of multifocal TMS on quality of life in patients with episodic
migraine; (3) Assess the effect of theta burst stimulation (TBS) on frequency and severity of
epileptic seizures in patients with generalized epilepsy; (4) Analysis of the influence of TBS on
quality of life in patients with generalized epilepsy; (5) Safety and tolerability profile assessment
of experimental multifocal TMS protocols (rTMS and TBS);
Scientific originality and novelty. An experimental study was conducted that debuted the
paradigm of multifocal transcranial magnetic stimulation with the examination of its therapeutic
impact in preventive treatment of patients with episodic migraine and generalized epilepsy.
The scientific problem solved in the thesis consists in identifying new therapeutic ways of
modulating the activity of cortico-subcortical brain networks by applying multifocal transcranial
magnetic stimulation, which will strengthen the foundation of the multifocal neuromodulation
paradigm in further scientific research.
Theoretical significance and applicative value. By implementing a modern method of
neuromodulatory treatment of patients with episodic migraine and those with generalized epilepsy
from the Republic of Moldova, the research conducted has fundamentalized the contemporary
vision in the complex evaluation and treatment algorithm for these patients. In addition, the
development and use of a multifocal TMS protocol, innovative not only nationally but also
internationally, allowed the increase of knowledge in the field of neuromodulation methods in the
treatment of paroxysmal neurological disorders such as migraine and epilepsy.
The practical impact of the present study consists in the implementation within the
Laboratory of Neurobiology and Medical Genetics, State University of Medicine and Pharmacy
"Nicolae Testemițanu" and the Department of Neurology, Epileptology and Internal Diseases,
Emergency Medicine Institute of the innovative method of neuromodulation of brain activity in
patients with episodic migraine and generalized epilepsy
Current events in liver transplatology
Get PDFBackground. Liver transplantation is a surgical procedure that involves removing a diseased liver and
replacing it with a healthy liver from another person, called a donor. This procedure is used when the
liver is unable to perform its normal functions (liver failure or end-stage liver disease). The types of
transplant are from a living donor (the right lobe of the liver is used) and from a deceased donor (the
entire liver of the donor is used along with the portal vein).
Materials and methods. To carry out the study, the selection and analysis of bibliographic sources
published in specialized medical scientific databases between 2018-2024 available online were carried
out.
Results Liver transplantation techniques are whole liver (from deceased donor), reduced liver (left
lobe or segments 2-3 compatible with the pediatric recipient), split liver (two grafts that can be used
for either an adult and a child, or for two adults), domino (sequential, where a young patient with a
metabolic disorder receives a liver from a deceased donor, and the young patient's liver is harvested
for donation to an older patient with end-stage liver disease), dual graft (2 grafts from 2 different
donors). For the highest possible success rate of liver transplantation, some basic principles must be
followed, such as high genetic compatibility, perfect harvesting and transplantation technique, and
careful postoperative care. The most common indications for liver transplantation are end-stage
chronic liver diseases, acute liver failure, non-resectable malignant liver diseases, and hereditarymetabolic liver diseases.
Conclusions The only hope for long-term survival of a person with liver failure is a liver transplant.
Liver transplant patients require clinical, biochemical, and instrumental monitoring to detect early
(acute rejection, early and late hepatic artery thrombosis, arterial stenosis, acute Budd Chiari syndrome,
anastomotic fistula) and late (chronic rejection, chronic Budd Chiari syndrome, portal vein thrombosis,
portal vein stenosis, recurrent sclerosing cholangitis, papillary stenosis, proximal hepatic duct stenosis)
complications. To increase the tolerability, safety and adherence of the therapy in the long term, the
patient will undergo treatment with immunosuppressants and antivirals
Bone graft use in internal fixation of proximal and diaphyseal humeral fractures and pseudoarthrosis
Get PDFIntroduction: This study explores the use of bone graft in combination with internal fixation for
treating fractures and pseudarthrosis of the proximal and diaphyseal humerus.
Materials and Methods: We retrospectively analyzed data collected for proximal and diaphyseal
humerus fractures between 2020-2024. The analysis focused on cases treated with open reduction and
internal fixation (ORIF), with or without bone graft utilization.
Results: Out of 584 cases analyzed, 65 (8.9%) were diagnosed with pseudarthrosis. In 12 cases post
ORIF treatment with implant stability of diaphyseal segment were applied mononuclear stem cell
apheresis (1.6%), and ORIF with T-plates or LCP for Neer 3-4 part fractures in 5 cases (0.6%) and
humeral diaphysis fractures in 13 cases (1.8%). Bone graft(alo-auto) was used in 35 (4.8%)
pseudarthrosis cases. 349 cases (47.6%) were extremity superior humerus fractures treated with ORIF
using T-plates or LCP for Neer 2-parts fractures in 92 cases (12.5%), Neer 3-4 parts fractures in 229
cases (31.2%), and Neer 3-4 parts fractures with diaphyseal extension in 22 cases (3.0%). Bone graft
was used in 6 (0.8%) of these cases. 170 cases (23.2%) were diaphysis humerus fractures treated with
ORIF using T-plates or LCP in the proximal 1/3 in 5 cases (0.7%), the middle 1/3 in 157 cases (21.4%),
and the distal 1/3 in 7 cases (1%). Bone graft was used in 1 (0.1%) of these cases.
Conclusions: The use of bone graft is frequent in the treatment of proximal and diaphyseal humerus
pseudarthrosis. Internal fixation with plates remains an essential method in managing these fracture
types. This has implications for future research in bone healing and fracture management
Cакрококцигеальная тератома у детей
Get PDFRezumat. Teratomul sacrococcigian este cel mai des întâlnit neoplasm
din perioada neonatală. În articol în baza unui caz clinic se analizează problema
recurenței teratomului sacrococcigian și importanța evaluării sechelelor
funcționale la diatanță.Summary. The sacrococcygeal teratoma is the most common neoplasm in neonatal
period. The article on the basis of a clinical case analyzes the problem of
recurrence of the sacrococcygeal teratoma and the importance of evaluation the
functional sequelae.Резюме. Cакрококцигеальная тератома является самым часто встречаемым
новообразованием в неонатальном периоде. В статье на базе одного
клинического случая анализируется проблема рецидива крестцовокопчиковой тератомы и важность исследования функциональных
результатов
