BACKGROUND Non-ST segment elevation myocardial infarction (NSTEMI) poses significant challenges in clinical management due to its diverse outcomes. Understanding the prognostic role of hematological parameters and derived ratios in NSTEMI patients could aid in risk stratification and improve patient care. AIM To evaluate the predictive value of hemogram-derived ratios for major adverse cardiovascular events (MACE) in NSTEMI patients, potentially improving clinical outcomes. METHODS A prospective, observational cohort study was conducted in 2021 at the Internal Medicine Clinic of the University Hospital in Tuzla, Bosnia and Herzegovina. The study included 170 patients with NSTEMI, who were divided into a group with MACE and a control group without MACE. Furthermore, the MACE group was subdivided into lethal and non-lethal groups for prognostic analysis. Alongside hematological parameters, an additional 13 hematological-derived ratios (HDRs) were monitored, and their prognostic role was investigated. RESULTS Hematological parameters did not significantly differ between non-ST segment elevation myocardial infarction (NSTEMI) patients with MACE and a control group at T1 and T2. However, significant disparities emerged in HDRs among NSTEMI patients with lethal and non-lethal outcomes post-MACE. Notably, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were elevated in lethal outcomes. Furthermore, C-reactive protein-to-lymphocyte ratio (CRP/Ly) at T1 (> 4.737) demonstrated predictive value [odds ratio (OR): 3.690, P = 0.024]. Both NLR at T1 (> 4.076) and T2 (> 4.667) emerged as significant predictors, with NLR at T2 exhibiting the highest diagnostic performance, as indicated by an area under the curve of 0.811 (95%CI: 0.727-0.859) and OR of 4.915 (95%CI: 1.917-12.602, P = 0.001), emphasizing its important role as a prognostic marker. CONCLUSION This study highlights the significant prognostic value of hemogram-derived indexes in predicting MACE among NSTEMI patients. During follow-up, NLR, PLR, and CRP/Ly offer important insights into the inflammatory processes underlying cardiovascular events.

Lumbar disc herniation (LDH) often results in significant pain and disability, and histopathologic evaluation of intervertebral discs offers critical insights into treatment outcomes. This prospective observational study explores histopathologic (HP) changes in intervertebral discs (IVD) and their association with clinical outcomes following surgical treatment for lumbar disc herniation (LDH). A cohort of 141 patients undergoing magnetic resonance imaging (MRI)-confirmed LDH surgery underwent HP evaluation using a semi-quantitative Histopathologic Degeneration Score (HDS). Preoperatively and at a six-month follow-up, comprehensive clinical assessment included the Oswestry Disability Index (ODI) and Visual Analog Scale (VAS), with a minimal clinically important difference (MCID) calculated from ODI and VAS. Results indicated significant associations between higher HDS and adverse clinical outcomes, including persistent pain and greater disability post-surgery. Specifically, HDS ≥ 7 was predictive (OR = 6.25, 95%CI: 2.56-15.23) of disability outcomes measured with MCID-ODI (AUC: 0.692, 95%CI: 0.609-0.767, P < 0.001), and HDS ≥ 8 was predictive (OR = 1.72, 95%CI: 1.04-2.77) of persistent pain measured with MCID-VAS (AUC: 0.628, 95%CI: 0.598-0.737, P = 0.008), highlighting the diagnostic potential of HDS in assessing postoperative recovery. This study underscores the potential of HP evaluation using HDS to provide valuable insights into disease progression and outcomes in LDH patients, complementing conventional radiologic methods. The findings support the application of personalized treatment strategies based on HP findings while acknowledging challenges in interpretation and clinical implementation.

Simple Summary This study explores hypoxia-inducible factors (HIFs) in glioblastoma development, progression, and treatment. Reviewing 104 relevant studies, it highlights diverse global contributions, with China leading at 23.1%. The most productive year was 2019, contributing 11.5% of the studies. Key factors studied included HIF1α, HIF2α, osteopontin, and cavolin-1, involving pathways such as GLUT1, GLUT3, VEGF, PI3K-Akt-mTOR, and ROS. HIF expression correlates with glioblastoma progression, survival, neovascularization, glucose metabolism, migration, and invasion. Overcoming treatment resistance and the lack of biomarkers is crucial for integrating HIF-related therapies into glioblastoma treatment to improve patient outcomes. Abstract Background: The study aims to investigate the role of hypoxia-inducible factors (HIFs) in the development, progression, and therapeutic potential of glioblastomas. Methodology: The study, following PRISMA guidelines, systematically examined hypoxia and HIFs in glioblastoma using MEDLINE (PubMed), Web of Science, and Scopus. A total of 104 relevant studies underwent data extraction. Results: Among the 104 studies, global contributions were diverse, with China leading at 23.1%. The most productive year was 2019, accounting for 11.5%. Hypoxia-inducible factor 1 alpha (HIF1α) was frequently studied, followed by hypoxia-inducible factor 2 alpha (HIF2α), osteopontin, and cavolin-1. Commonly associated factors and pathways include glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) receptors, vascular endothelial growth factor (VEGF), phosphoinositide 3-kinase (PI3K)-Akt-mechanistic target of rapamycin (mTOR) pathway, and reactive oxygen species (ROS). HIF expression correlates with various glioblastoma hallmarks, including progression, survival, neovascularization, glucose metabolism, migration, and invasion. Conclusion: Overcoming challenges such as treatment resistance and the absence of biomarkers is critical for the effective integration of HIF-related therapies into the treatment of glioblastoma with the aim of optimizing patient outcomes.

Introduction: Industrialization and urbanization led to a significant increase in the environment. Lead inhibits the activity of numerous enzymes, triggers oxidative stress, and causes protein biosynthesis dysregulation. Inhalation of lead particles is the most common route of intoxication associated with occupational exposure. This study aims to evaluate laboratory methods and biomarkers in the assessment of lead exposure. Methods: For non-experimental qualitative research, available scientific articles in English published in the relevant databases (MEDLINE and ScienceDirect) were used. The database search was performed using the keywords “Laboratory diagnostics”, “occupational exposure”, and “lead”. Results: Atomic absorption spectrometry (AAS) is the gold standard in laboratory monitoring of occupational lead exposure. Inductively coupled plasma with mass spectrometry is a commonly used method described as more sensitive than AAS due to its low detection limit. Lead concentrations can be determined in various samples, but blood and urine are the most commonly used in laboratory practice. The most important exposure biomarker is the enzyme δ-aminolevulinic acid dehydratase (ALAD) in the blood, which is characterized by progressive inactivation by lead and a negative correlation with its concentration. The concentration of urinary delta-aminolevulinic acid (δ-ALA-U) reflects the state of impaired enzyme function in heme biosynthesis. In addition, determining blood zinc protoporphyrin and urinary coproporphyrin levels significantly aids in assessing occupational lead exposure disorders. Conclusion: The availability of the laboratory methods used and the biomarker specificity and sensitivity play an important role in the adequacy of lead exposure monitoring. Accurate determination of ALAD and δ-ALA-U concentrations, along with other biomarkers, is critical for assessing individuals exposed to lead.

Uvod: Heterogena priroda akutne mijeloične leukemije (AML) iziskuje primjenu specifičnih i pouzdanih laboratorijskih testova pri postavljanju dijagnoze. Istraživanja ukazuju na određene nedostatke konvencionalnih morfoloških i imunofenotipskih metoda, ali i potrebu za imple-mentacijom kompleksnog dijagnostičkog algoritma koji uz navedene metode inkorporira citogenetičke i molekularno-genetičke analize u integrirani dijagnostički pristup. Cilj: Predstaviti prednosti i nedostatke integriranog dijagnostičkog pristupa u dijagnostici akutne mijeloične leukemije. Metode: Za potrebe neeksperimentalnog kvalitativnog istraživanja, pretražene su relevantne baze podataka (PubMed, Scopus i Web of Science). Pretraga baza u širem opsegu provedena je uz pomoć ključnih riječi acute myeloid leukemia, cytomorphology, flow cytometry, cytogenetic abnormalities i molecular diagnostics. Za konačnu analizu, odabrani su naučni radovi koji zadovoljavaju kriterije relevantnosti i povezanosti s postavljenim ciljem i temom istraživanja. Rezultati: Integracija dijagnostičkih modaliteta u AML predstavlja veliki izazov zbog kontinuriane složenosti i opterećenja za zdravstvene profesionalce. Kao značajne prednosti izdvajaju se mogućnost umrežavanja rezultata različitih dijagnostičkih modaliteta, te detekcija nespecifičnih i izazovnih slučajeva AML. Prijavljeni nedostaci se odnose na potrebu za jedinstvenim protokolima, nepredvidiv turnaround time, validaciju i potrebu za visoko specija-liziranim osobljem. Danas se sve više pažnje pridaje AI (engl. artifical intelligence) i njenoj sposobnosti da obradi podatke s ciljem pružanja brzih i preciznih dijagnostičkih i prognostičkih informacija što predstavlja obećavajući koncept u AML-u. Usvajanje ove paradigme znatno bi olakšalo trenutne pristupe i unaprijedilo koncept zdravstvene zaštite. Zaključak: Integrirani dijagnostički pristup ima za cilj poboljšati kvalitet pojedinačnih metoda primjenom dosadašnjih saznanja i paralelnim testiranjem novih mogućnosti. S razvojem precizne medicine, ovaj dijagnostički model će u budućnosti dobiti dodatni značaj. Neovisno od utvrđenih prednosti i nedostatka, dostupna istraživanja ukazuju na nužnost dodatnih napora i primjenu AI za uspostavljanje standardiziranog integriranog pristupa na globalnom nivou.

Introduction: Hypothyroidism is a common disorder of the endocrine system caused by insufficient biologically active hormones at the tissue level or the inability of the tissue to utilize thyroid hormones. Iron plays a crucial role in the synthesis and metabolism of thyroid hormones, and it is stored in the body as ferritin. We aimed to evaluate the correlation between serum ferritin (SF) levels and thyroid hormone panel levels in both hypothyroid and euthyroid subjects. Methods: In 2022, a matched case–control study was conducted. The study involved participants with hypothyroidism and a control group (n = 53). The levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and SF were measured using the chemiluminescence immunoassay on a Mindray Cl 900-i analyzer (Shenzhen Mindray Bio-Medical Electronics Co., China). Results: The hypothyroid group had TSH levels that were significantly higher (10.76 [8.54-18.76] vs. 1.76 [1.26-2.58]; p < 0.001) and SF concentrations that were significantly lower (39.08 [21.15-45.70] vs. 54.09 [41.41-71.82]; p < 0.001) compared to the control group. In both male and female subjects of the hypothyroid group, a strong negative correlation was found between SF concentration and TSH levels ([Rho = −0.855,p < 0.01]; [Rho = −0.747; p < 0.01]). In female subjects of the hypothyroid group, a weak positive correlation was found between SF concentration and fT3 (Rho = 0.488; p < 0.05). In the euthyroid group, a correlation of the same strength and direction was found for fT4 (Rho = 0.366; p < 0.05). Conclusion: Research results indicate a correlation between lower SF concentrations and hypothyroidism, which is of particular importance for understanding the etiopathogenesis, diagnosis, monitoring, and treatment modalities of patients with hypothyroidism.

Uvod: Povećanje koncentracije olova u okolišu posljedica je intenzivne industrijalizacije i urbanizacije. Toksična djelovanja olova zasnivaju se na inhibiciji aktivnosti velikog broja enzima, indukciji oksidativnog stresa i disregulaciji biosinteze proteina. Najčešći put unosa u općoj populaciji je ingestija kontaminirane hrane i vode, dok je inhalatorni put najčešće povezan sa profesionalnom izloženošću u različitim zanimanjima. Cilj istraživanja je evaluirati laboratorijske metode i biomarkere u procjeni izloženosti olovu. Materijal i metode: Za potrebe neeksperimentalnog kvalitativnog istraživanja korišteni su dostupni naučni članci publicirani na engleskom jeziku u relevantnim bazama podataka (MEDLINE i ScienceDirect). Pretraga baza provedena je upotrebom ključnih riječi: „laboratory diagnostics“, „occupational exposure“, „lead“. Rezultati: Najširu primjenu u laboratorijskoj dijagnostici kod procjene profesionalne izloženosti olovu imaju atomska apsorpciona spektrometrija (AAS) kao zlatni standard i induktivno spregnuta plazma sa masenom spektrometrijom, koja se zbog niske granice detekcije opisuje kao senzitivnija metoda u poređenju sa AAS. Koncentracija olova može se odrediti u brojnim biološkim uzorcima, ali se u laboratorijskoj praksi najčešće upotrebljavaju krv i urin. Kao najznačajniji biomarker u praćenju izloženosti koristi se enzim dehidrataza δ-aminolevulinske kiseline (ALAD) u krvi, kojeg karakterizira progresivna inaktivacija olovom i negativna korelacija sa koncentracijom olova. Također, koncentracija delta-aminolevulinske kiseline u urinu (δ-ALA-U) odražava stanje narušene funkcije enzima u biosintezi hema, te se smatra da dodatno određivanje cink protoporfirina u krvi i koproporfirina u urinu značajno doprinose u procjeni poremećaja izazvanih profesionalnom izloženošću olovu. Zaključak: Adekvatno praćenje izloženosti olovu ovisi o dostupnosti i karakteristikama primijenjenih laboratorijskih metoda, te specifičnosti i osjetljivosti biomarkera. Zbog toga, precizno određivanje koncentracije ALAD i δ-ALA-U, uz dodatne biomarkere, postaje imperativ za poboljšanu evaluaciju profesionalne izloženosti i omogućava pravovremeno poduzimanje preventivnih mjera.

Introduction: Insulin resistance (IR) is a complex pathophysiological condition multifactorial etiology characterized by diminished responsiveness of insulin target tissues. Today, various diagnostic approaches involving different laboratory parameters are available, but simple and non-invasive indices based on mathematical models are increasingly used in practice. This study aims to assess the effectiveness of various clinical surrogate indices in predicting IR across a population with varying body weights. Methods: The matched case-control study was conducted between January 2021 and December 2022. Secondary data extracted from the medical records of 129 subjects was analyzed, including demographic characteristics (age and gender), anthropometric measures (height and weight), and biochemical laboratory test results. y further divided into two subgroups based on body mass index (BMI): overweight (BMI between 25 and 29.9 kg/m2) and obese (BMI of 30 kg/m2 or higher). Using laboratory data values for six widely used clinical surrogate markers were calculated: Homeostatic model assessment for IR (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Mcauley index (MCAi), metabolic score for IR (METS-IR), Triglyceride to Glucose Index (TyG), and TyG to BMI (TyG-BMI). Results: Significant differences in HOMA-IR levels were observed between the groups (p < 0.001). A similar pattern was found for the TyG-BMI, with notable differences (p < 0.001). The obese participants had the highest mean levels for METS-IR and the TyG index while the control group had the highest mean values for the QUICKI and MCAi indices (p < 0.001). According to the analysis, three indices showed statistical significance in predicting IR independent of BMI (p < 0.05). Sensitivity and specificity were higher in the obese group (0.704 and 0.891) than in the overweight group (0.631 and 0.721). Conclusion: Given that IR is a multifactorial disease, using derived indices based on a combination of biochemical parameters and anthropometric indicators can significantly aid in predicting and mitigating numerous complications.

Background: Coronavirus disease 2019 (COVID-19) can cause a wide clinical spectrum, ranging from asymptomatic to severe disease with a high mortality rate. In view of the current pandemic and the increasing influx of patients into healthcare facilities, there is a need to identify simple and reliable tools for stratifying patients. Objective: Study aimed to analyze whether hemogram-derived ratios (HDRs) can be used to identify patients with a risk of developing a severe clinical form and admission to hospital. Methods: This cross-sectional and observational study included 500 patients with a confirmed diagnosis of COVID-19. Data on clinical features and laboratory parameters were collected from medical records and 13 HDRs were calculated and analyzed. Descriptive and inferential statistics were included in the analysis. Results: Of the 500 patients, 43.8% had a severe form of the disease. Lymphocytopenia, monocytopenia, higher C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were found in severe patients (p < 0.05). Significantly higher neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), neutrophil-to-platelet ratio (NPR), neutrophil-to-lymphocyte-to-platelet ratio (NLPR) and CRP-to-lymphocyte ratio (CRP/Ly) values were found in severe patients (p < 0.001). In addition, they have statistically significant prognostic potential (p < 0.001). The area under the curve (AUC) for CRP/Ly, dNLR, NLPR, NLR, and NPR were 0.693, 0.619, 0.619, 0.616, and 0.603, respectively. The sensitivity and specificity were 65.7% and 65.6% for CRP/Ly, 51.6% and 70.8 for dNLR, 61.6% and 57.3% for NLPR, 40.6% and 80.4% for NLR, and 48.8% and 69.1% for NPR. Conclusion: The results of the study suggest that NLR, dNLR, CRP/Ly, NPR, and NLPR can be considered as potentially useful markers for stratifying patients with a severe form of the disease. HDRs derived from routine blood tests results should be included in common laboratory practice since they are readily available, easy to calculate, and inexpensive.