Medicine and Pharmacology

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Review
Medicine and Pharmacology
Oncology and Oncogenics

Vehary Sakanyan

Abstract: Science has made significant progress in detecting reactive oxygen species (ROS) in tobacco smoke, which is an important step for precision cancer therapy. An important advance is also the understanding that superoxide can be produced by electrophilic molecules. The dual action of hydrogen peroxide, directly or via electrophilic molecules, in the development of oxidative stress allows the identification of target proteins that can potentially stop unwanted signals in cancer development. However, despite advances in proteomics, reliable inhibitors to stop ROS-associated cancer progression have not yet been proposed for the treatment of tobacco cigarette smokers. This is likely due to an imperfect understanding of the diversity of molecular mechanisms of anti-ROS action. Fluorescent protein detection in living cells, called in-gel, offers a direct route to a better understanding of the rapid interaction of ROS and electrophilic compounds with targeted proteins. It seemed that the traditional paradigm of pharmaceutical innovation "one drug, one disease" did not solve the problem of tobacco smoking causing cancer. However, among the various therapeutic treatments for tobacco smokers, the best way to combat cancer today is smoking cessation, which fits into the “one-cure” paradigm.
Article
Medicine and Pharmacology
Obstetrics and Gynaecology

Sandugash Yerkenova,

Vyacheslav Lokshin,

Аlmagul Kurmanova,

Sharapat Moiynbayeva,

Galiya Alikeyeva,

Gulnara Kalibekova,

Tamara Abdirova,

Zamira Zhantenova,

Kuralay Shaikova,

Alla Mireeva

+1 authors
Abstract: Background/Objectives: The long-term impact of COVID-19 on female reproductive health remains poorly understood. This study aimed to assess structural and endocrine alterations in women of reproductive age who had recovered from SARS-CoV-2 infection, compared to uninfected controls. Materials and Methods: A total of 150 women aged 18–45 years were enrolled in a comparative study: 75 with a confirmed history of COVID-19 and 75 without. All participants underwent ultrasound examinations of the pelvic organs and mammary glands, along with laboratory assessment of reproductive hormones and inflammatory markers. Statistical analysis was performed using the Mann–Whitney U-test and odds ratio calculations. Results: Structural abnormalities in the pelvic organs were observed in 53.5% of the post-COVID group versus 12.0% in the control group (p< 0.001), with oophoritis showing a statistically significant association (OR = 11.38; 95% CI: 1.42–91.36; p = 0.009). Non-significant but elevated frequencies were also found for uterine fibroids and breast cysts. Biochemically, post-COVID participants demonstrated higher serum ferritin, estradiol, and fibrinogen levels, along with lower TSH and AMH levels, suggesting potential endocrine disruption and persistent inflammation. Conclusions: Women with a history of COVID-19 may be at increased risk of developing structural and hormonal abnormalities, highlighting the importance of post-infection gynecological and endocrine monitoring. Further longitudinal studies are required to elucidate the long-term effects and underlying mechanisms of these alterations.
Review
Medicine and Pharmacology
Other

Marco Pradella

Abstract: This review recalls some ISO 15189:2022 requirements for the management of examination results and emerging alternatives for internal quality control (IQC), in relation to Italian Society of Clinical Pathology and Laboratory Medicine (SIPMeL) Recommendations Q19. We have observed phenomena of contrasting “metrological,” or rather “tracealogic,” and “statistical” approaches. SIPMeL Recommendation Q19 picks up IQC with moving average from ISO 15189, which provides for the use of moving average of patient sample results (MA). In the veterinary field the procedure of QC with repeat testing on patient samples (RPT-QC) has met with some success. The “bayesian approach” of IQC making use of the distinction between a priori probability, evidential probability (data) and a posteriori probability (IQC rules). SIPMeL recommendations Q19 strictly adhere to ISO 15189:2022 document. SIPMeL Q19 calls for abandoning the 1-2s rule, using appropriate computer tools, not only control charts, and trying to reduce false positives to very low frequencies. The alternatives to IQC with patient results and Bayesian approach are compatible with ISO 15189 and SIPMeL Q19. In contrast, the alternative with material designed for traceability, with assigned value, is not compatible with ISO standard.
Article
Medicine and Pharmacology
Other

Pierpaolo Biondetti,

Francesco Cicchetti,

Gaetano Valerio Davide Amato,

Velio Ascenti,

Niccolò Finardi,

Jacopo Tintori,

Francesco Ugo Iovino,

Salvatore Alessio Angileri,

Carolina Lanza,

Pierluca Torcia

+4 authors
Abstract: Background: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Percutaneous thermal ablation is an effective treatment, but standard ultrasound (US) guidance is limited in cases of inconspicuous nodules. Ultrasound fusion imaging (USFI), which overlays cross-sectional imaging onto real-time U is an emerging tech-nique which improves tumor visibility and technical feasibility. This study reports re-al-life outcomes of USFI-guided microwave ablation (MWA) for HCC in two Italian centres. Materials and Methods: In this multicentric retrospective study, 56 patients with 73 poorly or non-visible HCC nodules underwent USFI-guided percutaneous MWA with no visibility or poor visi-bility on B-mode US. Technical success, complications, and local tumor control were evaluated, with follow-up imaging at 1 month and every 3 months thereafter. Results: Complete response (CR) at 1 month was observed in 78.1% of nodules, with residual disease (RD) more common in poorly visible nodules than non-visible nodules (18.1% vs. 4.2%, p=0.019). During a median 13-month follow-up, local tumor progression (LTP) occurred in 9.6% of patients. No significant association was found with difficult tumor location. Conclusion: USFI-guided MWA is a safe and effective option for treating HCC nodules not ade-quately visualized with conventional US, expanding eligibility to complex cases.
Article
Medicine and Pharmacology
Pediatrics, Perinatology and Child Health

Ralf-Bodo Tröbs,

Grigore Cernaianu,

Andreas Lipphaus,

Matthias Nissen

Abstract: Background: Recurrent vomiting in infantile hypertrophic pyloric stenosis (IHPS) leads to metabolic alkalosis and a respiratory driven compensatory hypercapnia. Alkalosis has been identified as the main causal factor for respiratory depression on admission. The value of contribution of hemoglobin and carbon dioxide partial pressure to this phenomenon will be evaluated. Materials and methods: A retrospective cohort study was conducted on 105 infants with IHPS. The acid-base status, including levels of hemoglobin, sodium and lactate, were recorded. The U-test, correlation analysis, linear regression and multivariate regression analysis was applied. Results: Twelve (11.4%) infants had hypercapnia, and six (5.7%) low hemoglobin. Hypercapnia was associated with increased sodium (p = 0.033) and mean corpuscular hemoglobin concentration (p = 0.029). A positive correlation was found between pCO2 and hemoglobin (p = 0.042). The multivariate linear regression analysis showed that pCO₂ is dependent on the pH (p < 0.001) and on hemoglobin (p = 0.002), among other factors. Increased pCO2 was found in infants with low hemoglobin (p = 0.056). Conclusion: Increased carbon dioxide levels directly stimulate- respiratory drive, but in higher concentrations, elicid a depressant effect on respiratory drive. The extent to which low levels of hemoglobin and strongly increased pCO2 contribute to respiratory depression needs to be further investigated.
Review
Medicine and Pharmacology
Cardiac and Cardiovascular Systems

Antoine AbdelMassih,

Fatema Mohamed,

Fatmah Almesmari,

Maryam Alfalasi,

Mohamed Al Ali,

Noora Alattar,

Rahaf AbuGhosh,

Rosul Makkiyah,

Salma Alfalasi

Abstract: Echocardiography is vital in diagnosing and managing congenital heart disease (CHD), particularly in the pediatric population, necessitating detailed structural and functional assessments. Artificial intelligence (AI) has revolutionized echocardiographic analysis, particularly in functional assessments and the detection of valvular lesions. While convolutional neural networks (CNNs) dominate image-based tasks, emerging vision language models (VLMs) are transforming report generation by integrating multimodal data. This review explores the current state of AI in echocardiography, emphasizing the potential of VLMs to provide comprehensive reports and image-specific diagnoses. Despite significant advancements, several challenges hinder the development of holistic AI software for diagnosing complex congenital heart disease (CXCHD). These challenges include the heterogeneity of CHD, limited access to high-quality labeled datasets, variability in imaging techniques, and the need for expertise in image annotation. This review highlights the necessity for robust algorithms, standardized protocols, and diverse training datasets to fully realize the potential of AI in complex CHD diagnosis.
Article
Medicine and Pharmacology
Dermatology

Jesús Gay-Mimbrera,

Macarena Aguilar-Luque,

Pedro Jesús Gómez-Arias,

Irene Rivera-Ruiz,

Francisco Gómez-García,

Miguel Juan-Cencerrado,

Carmen Mochón-Jiménez,

Esmeralda Parra-Peralbo,

José Liñares-Blanco,

Pedro Carmona-Saez

+2 authors
Abstract: Background: Alopecia areata (AA) is a chronic immune-mediated skin disease that causes non-scarring hair loss. While most cases are mild, a subset of patients progress to severe forms such as alopecia totalis or universalis. Current severity assessments have limitations in predicting disease evolution and require invasive procedures. Objective: To identify circulating microRNAs (miRNAs) associated with severe AA and evaluate their potential as non-invasive biomarkers for diagnosis and stratification. Methods: We performed plasma miRNA profiling in a discovery cohort using TaqMan OpenArray and validated the findings by RT-qPCR in an independent cohort including patients with AA, psoriasis, atopic dermatitis, vitiligo, and healthy controls. Results: We identified 19 miRNAs significantly downregulated in severe AA. Ten miRNAs were technically and clinically validated, showing high specificity for AA compared to other skin conditions. A machine learning model based on the top four miRNAs achieved high classification accuracy (AUC = 0.94). Pathway enrichment and drug repurposing analyses revealed dysregulated immune, metabolic, and signal transduction pathways, identifying potential therapeutic targets including kinase inhibitors and antioxidants. Conclusions: Our study defines a circulating miRNA signature for severe AA, distinguishing it from other inflammatory skin diseases and offering a basis for non-invasive biomarkers and future therapeutic strategies.
Article
Medicine and Pharmacology
Surgery

Cheng-Hsun Lin,

Tsai-Wang Huang,

Hsian-He Hsu,

Wen-Chiuan Tsai,

Kai-Hsiung Ko

Abstract: Background and Objectives: The needle path is crucial for preoperative localization of deep thoracic pulmonary nodules using CT-guided patent blue dye (PBD) injection. This study aimed to evaluate the efficacy and safety of four categorized needle approach paths tailored to the anatomical location of the nodules. Materials and Methods: We retrospectively evaluated data from 50 consecutive patients (50 deep pulmonary nodules), who underwent CT-guided localization with PBD injection, between November 2015 and May 2023 at our hospital. The nodules could be divided into four categories: (1) perifissural nodules (2) paravertebral nodules, (3) paramediastinal nodules, and (4) deep parenchymal nodules, according to the location relative to the thoracic organs and the visceral pleura. The needle approach methods and the needle pathway lengths were recorded. Clinical and radiological features, technical information, pathological results and procedure-related complications were analyzed. Results: All 50 dyes were successfully identified by thoracoscopy and then resected without major complication. The mean nodule diameter and the nodular depth were 10.3 (range, 4.7–21.0) mm, and 16.1 (range, 0.1–52.2) mm. The needle pathway length was 7.7 (range, 4.5–11.7) cm. The mean procedure time was 16 (range, 8–26) minutes. Asymptomatic pneumothorax developed in 24 patient (48.0%), and focal parenchymal hemorrhage occurred in 4 patients (8.0%) after localization. No patients required chest tube insertion or resuscitation. Conclusions: Strategic needle approach paths provide precise localization of deep thoracic pulmonary nodules with minimal complications. These methods offer a practical framework for improving thoracoscopic surgery in challenging deep thoracic cases.
Case Report
Medicine and Pharmacology
Hematology

Svetlana Lebedeva,

Ekaterina Mikhailova,

Sophia Bogacheva,

Dmitry Abramov,

Svetlana Kashpor,

Alexander Druy,

Alexandra Semchenkova,

Marina Gaskova,

Olga Lotonina,

Ilya Sidorov

+6 authors
Abstract: Acute megakaryoblastic leukemia (AMKL) is a heterogeneous form of acute myeloid leukemia (AML) and is significantly more common in children than in adults. In non-Down syndrome children with AMKL, inv(16)(p13q24)/CBFA2T3::GLIS2 is the most frequent genetic aberration. Pediatric CBFA2T3::GLIS2-positive AMKL is strongly associated with a poor prognosis and a high cumulative incidence of relapse. One of the key laboratory signs of CBFA2T3::GLIS2-positive AMKL is the RAM immunophenotype, which includes dim to negative CD45 and CD38 expression, extremely bright CD56 and a lack of HLA-DR on leukemic cells. This immunophenotype looks very similar to that of solid tumor bone marrow (BM) infiltration. For this reason, in cases of isolated extramedullary involvement of CBFA2T3::GLIS2-positive AMKL, excluding solid tumors may be challenging. The differential diagnosis between extramedullary AMKL relapse and secondary tumors is especially difficult. We report a case of a 3.5-year-old girl with isolated extramedullary CBFA2T3::GLIS2-positive AMKL relapse, which was misdiagnosed as secondary Ewing sarcoma. The morphological differential diagnosis between Ewing sarcoma and AMKL presents significant challenges owing to their overlapping histological features (small round blue cell morphology and similar growth patterns). The tumor cells immunophenotype was completely mirrored that at the initial diagnosis of AMKL. Additional cytogenetic and molecular studies confirmed the presence of the CBFA2T3::GLIS2 fusion, but no Ewing sarcoma-specific EWSR1 fusion transcripts were found. Thus, extramedullary CBFA2T3::GLIS2-positive AMKL relapse was confirmed. The patient’s clinical condition gradually worsened, and the patient died 5 months after diagnosis. The presented case demonstrates difficulties in the differential diagnosis between AMKL relapse and the development of a secondary tumor.
Review
Medicine and Pharmacology
Neuroscience and Neurology

Shailendra Mohan Tripathi,

Porimita Chutia,

Alison D Murray

Abstract: Alzheimer’s disease accounts for approximately 50% to 80% of all causes of dementia. Co-existence of AD with other diseases causing dementia poses a diagnostic challenge as we are still far from diagnosing AD accurately and hence to manage it appropriately. Neuroimaging techniques, not only help diagnose AD but also consistently features in diagnostic and research criteria for AD as biomarkers. Molecular biomarkers including Positron emission tomography (PET) and Single Photon emission computed tomography (SPECT) and structural biomarkers including Magnetic Resonance Imaging (MRI) have been used in various therapeutic and prognostic studies in AD. This review highlights the recent advances in the neuroimaging biomarkers including molecular biomarkers (PET and SPECT) and structural biomarkers (MRI) for AD. For the purpose of this review, molecular biomarkers have been further subcategorized into non-specific radiotracers (FDG-PET and SPECT) and specific amyloid and tau related radiotracers. The aim of this review is to discuss the recent advances and evidences on molecular and structural biomarkers of AD.
Article
Medicine and Pharmacology
Medicine and Pharmacology

Razvan Septimiu Zdrehus,

Teodora Mocan,

Lavinia Ioana Sabau,

Cristian Tudor Matea,

Flaviu Tăbăran,

Teodora Pop,

Cristian Delcea,

Ofelia Mosteanu,

Lucian Mocan

Abstract: Background and aim. The efficacy of cancer vaccines depends on the development of safe and effective delivery systems that can improve antigen stability, facilitate targeted uptake by immune cells, and promote efficient intracellular processing. Gold nanopar-ticles offer an attractive platform due to their biocompatibility, stability, and modifiable surfaces. Functionalizing gold nanoparticles with tumor-associated antigens such as car-cinoembryonic antigen (CEA) peptides may enhance antigen presentation and stimulate immune activation. This study aimed to evaluate the cytocompatibility, cellular inter-nalization, and antigen-processing capabilities of CEA-functionalized gold nanoparticles (CEA-AuNPs) as a potential nanovaccine candidate in vitro. Materials and Methods. CEA peptides were conjugated to gold nanoparticles and characterized using UV-VIS spec-troscopy and dynamic light scattering to confirm functionalization and assess particle size distribution. In vitro assays were performed on macrophage cell cultures to evaluate cytotoxicity (via viability and caspase-3 expression), nanoparticle uptake (by reflectance microscopy), and antigen processing (via fluorescence intensity analysis). Results. Spectral analysis confirmed successful functionalization, with a broadened absorbance plateau between 510–700 nm and a size increase from 20 nm (bare AuNPs) to ~80 nm (CEA-AuNPs). Viability assays demonstrated cytologyc viability above 85% at all tested concentrations. Caspase-3 activity, suggested controlled apoptotic signaling in response to the nanoconstruct. Reflective imaging and fluorescence microscopy confirmed efficient cellular uptake, localized predominantly in the perinuclear region, and enhanced pro-teasomal activity in macrophages treated with the CCEA-AuNPs, indicating effective antigen processing. Discussion. Functionalization of gold nanoparticles with a CEA peptide resulted in stable, biocompatible nanostructures capable of efficient uptake by antigen-presenting cells. Enhanced intracellular processing, evidenced by increased ubiquitin-proteasome pathway activity, highlights the immunogenic potential of the construct. Low cytotoxicity supports its suitability for further preclinical development. Conclusion CEA-functionalized gold nanoparticles exhibit high cytocompatibility, tar-geted cellular uptake, and promote intracellular antigen processing—highlighting their promise as a nanovaccine platform in cancer immunotherapy. These results support further preclinical evaluation toward translational application.
Article
Medicine and Pharmacology
Dietetics and Nutrition

Natalia Mudarra-García,

Marina Pérez-Mudarra,

Ismael Ortuño-Soriano,

Raquel Badía-Iborra,

María Jesús Vicente-Galán,

Ignacio Zaragoza-García,

Fernando Roque-Rojas,

Francisco Javier García-Sánchez

Abstract: Bad dietary habits and sedentary lifestyles alter body composition, increasing disease risk. We conducted a prospective, comparative, longitudinal observational study among nursing students (n=72, 79.2% female, mean age 21.94 years) from Complutense University of Madrid. Data were collected at two periods: before exams (January 2024) and during exams (May 2024). Body composition was assessed via bioimpedance (Beurer BF 1000), dietary habits through modified Kidmed survey, and physical activity using IPAQ. During exam preparation, fat mass significantly increased (25.43% to 28.79%, p=0.016), muscle mass significantly decreased (39.70% to 36.20%, p&lt;0.001), and visceral fat rose notably (2.34 to 3.52, p&lt;0.001). Students exhibiting poor dietary quality increased (54.2% to 80.0%, p&lt;0.001), vigorous physical activity dramatically decreased (84.7% to 11.1%, p&lt;0.001), and sedentary time increased significantly (408.24 to 543.61 minutes/day, p&lt;0.001). Our findings suggest dietary deterioration and reduced physical activity during exams adversely affect students’ body composition.
Article
Medicine and Pharmacology
Pharmacy

Matthias Frei,

Ricky Wirawan,

Thomas Wein,

Franz Bracher

Abstract: Selective and potent inhibitors of the NAD+-dependent deacetylase Sirt2 represent a valuable epigenetic approach for the treatment of hitherto incurable diseases such as Parkinson's disease, Huntington’s disease, Alzheimer's disease and multiple sclerosis. Guided by docking studies, a lead structure-based hybridization concept was developed, resulting in a series of very effective Sirt2 inhibitors. With RW-93 we present a highly potent and selective Sirt2 inhibitor (IC50 = 16 nM), which as a next generation SirReal-type inhibitor significantly surpasses established Sirt2 inhibitors and extends current structure-activity relationships. The structural modification strategy employed in this study proved to be a highly promising approach, resulting in the identification of the most potent low-molecular Sirt2 inhibitors reported to date.
Review
Medicine and Pharmacology
Medicine and Pharmacology

Doni Dermawan,

Nasser Alotaiq

Abstract: Background/Objectives: Artificial intelligence (AI) is transforming drug discovery and development by enhancing the speed and precision of identifying drug candidates and optimizing their efficacy. This review evaluates the application of AI in various stages of drug discovery, from hit identification to lead optimization, and its impact on clinical outcomes. The objective is to provide insights into the role of AI across therapeutic areas and assess its contributions to improving clinical trial efficiency and pharmaceutical outcomes. Methods: A systematic review followed PRISMA guidelines to analyze studies published between 2015 and 2025, focusing on AI in drug discovery and development. A comprehensive search was performed across multiple databases to identify studies employing AI techniques. Studies were categorized based on AI methods, clinical phase, and therapeutic area. Percentages of AI methods used, clinical phase stages, and the therapeutic regions were analyzed to identify trends. Results: AI methods included machine learning (ML) at 40.9%, molecular modeling and simulation (MMS) at 20.7%, and deep learning (DL) at 10.3%. Oncology accounted for the majority of studies (72.8%), followed by dermatology (5.8%) and neurology (5.2%). In clinical phases, 39.3% of studies were in the preclinical stage, 23.1% in Clinical Phase I, and 11.0% in the transitional phase. Clinical outcome reporting was observed in 45% of studies, with 97% reporting industry partnerships. Conclusions: AI significantly enhances drug discovery and development, improving drug efficacy and clinical trial outcomes. Future work should focus on expanding AI applications into underrepresented therapeutic areas and refining models to handle complex biological systems.
Review
Medicine and Pharmacology
Neuroscience and Neurology

Uwe Windhorst,

Payam Dibaj

Abstract: Pain is – a pain in the neck, isn´t it? Yes and no. Yes, it hurts. Yet, it helps. At least do acute and transient pain. Acute pain resulting from an acute event is a fundamental condition for survival, insofar as it warns against imminent or actual tissue damage, a potentially life-endangering threat. The importance of the physiological, protective role of nociceptive pain is underscored by cases, in which a failure to sense pain such as in the case of congenital insensitivity often leads to self-mutilation, bone fractures, joint deformities, amputations, and even early death. While the goal of acute pain based on nociception thus appears to be clear, its implementation is anything but that because to achieve this goal calls for a number of requirements to be fulfilled. The first is the identification of a noxious stimulus, including its intensity and location on the body surface or within the body. The second is the orchestration of counter-measures, including arousal, emotional and various motor reactions. The third is the mobilization of the required energy as well as cardio-vascular and respiratory responses. All this implies multi-dimensional activations of diverse neural and neuro-muscular systems. This review attempts to describe the structures and mechanisms underlying nociception and pain in quite some detail to emphasize their complexity. It starts with a structural description of the nociceptive and pain system in an ascending order, from peripheral nociceptors to supraspinal structures involved in nociceptive and pain processing. This is followed by a description of the systems organizing descending pain modulation. The focus will here be on acute pain. It turns out that even acute nociception and pain and the underlying neural systems are very complex. There are many reasons for this complexity. First, many neuronal nodes receive multifarious inputs and send multiple outputs to other nodes, which often have additional functions other than nociception and pain. This constitutes an extended, multi-functional, multiple input-multiple output network. Second, individual nodes often have an inhomogeneous structure chracterized by diverse neuron groups and inter-connections. Third, sub-cellular processes are complex, but will not be treated here. It comes as no surprise, then, that we face difficulties in dealing with pain and its clinical consequences, and find appropriate treatments. It will not suffice to manipulate a single screw or only a few.
Review
Medicine and Pharmacology
Oncology and Oncogenics

Daniela Sambataro,

Giuseppina Scandurra,

Linda Scarpello,

Vittorio Gebbia,

Ligia Dominguez,

Maria Rosaria Valerio

Abstract: Magnesium (Mg2+) has gained oncologists’ attention due to its wide range of biological functions and frequent use as a complementary or integrative agent. This review outlines Mg's actions, its complex role in carcinogenesis and tumor risk, and clinical issues. Mg2+ is essential in numerous biochemical processes, including adenosine triphosphate production, cellular signal transduction, DNA, RNA and protein synthesis, and bone formation. The authors conducted a literature review on MEDLINE, PubMed, EMBASE, and the Web of Science to report the relationship between Mg2+ and cancer. Pertinent full-text articles were thoroughly examined, and the most relevant ones were selected for inclusion in this review. Mg2+ alterations are associated with cancer risk variably since scientific evidence is not univocal, except for colorectal cancer. Chronic Mg2+ deficiency leads to immune dysfunctions and enhanced baseline inflammation associated with oxidative stress related to various age-associated morbidities and cancer. On the other hand, Mg2+ deficiency is associated with several clinical settings, such as drug or chemotherapy-related hypomagnesemia, postoperative pain, cachexia, opioid-induced constipation, normal tissue protection from radiation damage, and prevention of nephrotoxicity. The issue of Mg2+ supplementation is also analyzed. A balanced diet usually provides sufficient Mg2+, but supplementation may be necessary in some clinical settings. Excessive supplementation can negatively impact immune function and should be avoided.
Article
Medicine and Pharmacology
Oncology and Oncogenics

Marija Gjorgoska,

Angela E. Taylor,

Spela Smrkolj,

Tea Lanišnik Rižner

Abstract: Objective: To evaluate the diagnostic and prognostic potential of preoperative serum steroid levels in endometrial cancer (EC) alone and in combination with clinical pa-rameters and biomarkers CA125 and HE4. Methods: This single-center observational study included 62 patients with EC and 70 controls with benign uterine conditions who underwent surgery between June 2012 and February 2020. Preoperative serum levels of classic androgens, 11-oxyandrogens, glucocorticoids, and mineralocorticoids were measured using liquid chromatog-raphy-tandem mass spectrometry (LC-MS/MS). Machine learning was used to assess their diagnostic and prognostic value alone and combined with clinical parameters and biomarkers. Results: Patients with EC had significantly higher serum levels of classic androgens (androstenedione, testosterone), 11-oxyandrogens (11β-hydroxy-androstenedione, 11β-hydroxy-testosterone), and glucocorticoids (17α-hydroxy-progesterone, 11-deoxycortisol) compared to controls. While individual steroids had limited diagnostic value, a multivariate model including classic androgens, CA125, HE4, BMI, and parity achieved an AUC 0.87, 79.1% sensitivity and 74.7% specificity in distinguishing EC from benign uterine condition. This model outperformed our previously published model based on CA125, HE4, and BMI (AUC: 0.81, p < 0.0001). Prognostically, HE4 was the strongest marker for lymphovascular space invasion (LVSI) (AUC: 0.79) and deep myometrial invasion (MI) (AUC: 0.71). Among steroids, androstenedione was the most predictive of LVSI (AUC: 0.67), while 11β-hydroxy-testosterone was the strongest predictor of deep MI (AUC: 0.64). Conclusions: Patients with EC exhibit distinct steroid hormone profiles. While steroids alone offer modest diagnostic and prognostic value, integrating them into multivariate models improves diagnostic accuracy.
Article
Medicine and Pharmacology
Pediatrics, Perinatology and Child Health

Thi Thuy Hong Nguyen,

Khanh Minh Le,

Thi Anh Thuong Tran,

Khanh Ngoc Nguyen,

Thi Bich Ngoc Can,

Phuong Thao Bui,

Tien Dat Tran,

Chi Dung Vu

Abstract: Background/Objectives: Children with congenital adrenal hyperplasia (CAH) face significant risks of impaired growth and metabolic disturbances despite standard glucocorticoid therapy. This cross-sectional study aimed to evaluate growth outcomes, nutritional status, and associated factors among children with CAH treated in a Viet-namese tertiary pediatric center. Methods: We assessed 201 children aged 1.1–16.5 years in a tertiary pediatric center in Vietnam for anthropometric parameters, biochemical markers (calcium, phosphate, 25-hydroxyvitamin D), and clinical features. Growth status was evaluated using WHO standards, and bone age was assessed radiographically. Statistical analyses explored associations between growth outcomes and clinical, bio-chemical, and treatment-related factors. Results: Stunting was present in 16.4% of chil-dren, while 53.3% were overweight or obese. Bone age advancement occurred in 51.7% of cases. Vitamin D insufficiency or deficiency was detected in 85.6%, and hypocalcemia in 95% of patients. Overweight/obesity, vitamin D deficiency, and bone age advancement were associated with older age, prolonged corticosteroid therapy, higher androgen levels, and clinical features of treatment imbalance (e.g., Cushingoid appearance, hyperpig-mentation). Female sex was significantly associated with higher rates of stunting. Con-clusions: Growth impairment, nutritional deficiencies, and skeletal maturation dis-turbances are prevalent among children with CAH in Vietnam. Early identification of risk factors and tailored management strategies addressing both endocrine and nutritional health are crucial for optimizing long-term outcomes.
Article
Medicine and Pharmacology
Obstetrics and Gynaecology

Mihai Stanca,

Henrietta Becze,

Alexandra Maria Pop,

Dan Mihai Căpîlna,

Szilard Leo Kiss,

Mihai Emil Căpîlna

Abstract: Despite the relatively high incidence of vulvar cancer, there is a noticeable lack of studies in Ro-mania and other Eastern European countries focused on evaluating the long-term oncological outcomes and Quality of Life (QoL) for patients with this condition. Methods: A total of 91 pa-tients were included in the study. The first objective was to evaluate the 5-year overall survival (OS) in patients with vulvar cancer at FIGO stages IA-IVA who underwent surgery, ± adjuvant radiotherapy (RT). Additionally, the study aimed to identify prognostic factors that could either positively or negatively influence survival outcomes in these patients. The second objective was to assess the QoL, conducted using validated questionnaires issued by the European Organization for Research and Treatment of Cancer, specifically the QLQ-CX30 and QLQ-VU34. Results: The patients had an average age of 67.7 years (38-91). At the time of assessment, 51.6% of the patients were alive. Additionally, the 5-year OS was reported at 45%. The multivariate analysis indicated that age ≤ 50 years (p < 0.03), FIGO stage IB (p < 0.007), and tumor differentiation grade I (p < 0.01) were associated with improved survival rates. Conversely, age > 80 years (p < 0.05), FIGO stages IIIB (p < 0.01) and IIIC (p < 0.06), tumor size > 5 cm (p < 0.02), positive resection margins (p < 0.03), lymph node metastasis (p < 0.06), and pelvic exenteration (p < 0.002) were identified as independent negative prognostic factors. Of the 47 living patients, 32 fulfilled the QoL question-naires. The respondents reported a decent overall QoL score of 65.3. However, treatment-specific symptoms, such as vulvar scarring, vulvar swelling, groin lymphedema, and leg lymphedema, had a negative impact on QoL. Consequently, functional symptoms like fatigue, pain, and sleep disturbances persisted, leading to a body image perception score of 33.7 on a scale from 0 to 100. Conclusions: This study highlights decent OS and QoL outcomes. It is important to note that vulvar cancer primarily affects older women. In this study, 51.6% of patients were over 70 years old at the time of surgery. Consequently, the 5-year OS of 45% could not be attributed solely to oncological factors, as most of these patients did not die from recurrences but rather from associ-ated comorbidities. The findings of this study provide a foundation for future randomized con-trolled trials aimed at further enhancing vulvar cancer patients care and outcomes.
Review
Medicine and Pharmacology
Pediatrics, Perinatology and Child Health

Aikaterini Agrafiotou,

Evdoxia Sapountzi,

Angeliki Margoni,

Lampros Fotis

Abstract: Kawasaki disease (KD) is a systematic inflammatory condition that results in vasculitis and possible progression to the development of coronary artery lesions if left untreated. Disease pathogenesis is not fully understood, and diagnosis is based on clinical symp-toms, with limited reliability considering that KD progression is time sensitive. This is further complicated by the shared clinical characteristics with other febrile diseases. Early diagnosis and prompt treatment start are associated with good prognosis in most patients. However, up to 20% of patients are resistant to available therapeutic agents and would benefit from alternative regimens. Therefore, identification of biomarkers that can pro-vide insights on disease pathogenesis are necessary to enable early diagnosis and initi-ation of treatment, as well as to predict treatment responses. To this end, immunophe-notyping, most commonly by flow cytometry, has been crucial in identifying central factors in KD pathogenesis. The available literature on such factors is vast and may in-clude contradictory findings. Therefore, we aimed to summarize the available literature of the last decade on the immunophenotype of KD, focusing on biomarkers associated with disease pathogenesis and those associated with treatment response. Our review high-lights the role of cells of both the innate and adaptive immune system in disease path-ogenesis, as well as the role of various secreted and cell surface proteins, including in-flammatory cytokines, chemokines, complement receptors, and chemoattractants both in KD pathogenesis and in treatment response.

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