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Dan Valean has a total of 132 co-authors. Here are the top co-authors by number of shared publications:


Latest Publications

  • Open Access

    Risk Factors and Predictive Biomarkers for Postoperative Complications in Crohn’s Disease Surgery: Systematic Review

    by Bobuțac Eduard, Zaharie Delia Roxana, Vălean Dan, Emil Moiș, Călin Popa, Andra Ciocan, Nadim Al-Hajjar, Florin Zaharie

    Surgical intervention in Crohn’s disease remains a significant contributor to patient morbidity, with postoperative complication rates reported between 20% and 50%. These complications include a broad spectrum of adverse outcomes, such as surgical site infections, intra-abdominal abscesses, and anastomotic leakage, all of which can substantially impact recovery, healthcare costs, and long-term prognosis. Although several clinical and perioperative risk factors have been identified, accurate prediction of postoperative outcomes remains challenging, highlighting the need for improved risk stratification strategies. In recent years, the evolution of biological therapies has transformed the management of Crohn’s disease, raising important questions regarding their influence on surgical outcomes and postoperative healing. Consequently, a more nuanced understanding of the interplay between medical and surgical approaches is required to optimize patient care. This systematic review aims to evaluate established and emerging predictive biomarkers associated with postoperative complications in Crohn’s disease surgery. Particular emphasis is placed on inflammatory markers, nutritional parameters, and novel molecular signatures. Furthermore, the review explores the growing role of multiomics approaches—including genomics, proteomics, and metabolomics—as well as the integration of machine learning models to enhance predictive accuracy. By synthesizing current evidence, this study underscores the potential of combining biomarkers with advanced analytical tools to support personalized risk assessment and guide clinical decision-making in Crohn’s disease surgery.

  • Open Access

    Exploratory Serum-Based Surface-Enhanced Raman Spectroscopy Analysis in Crohn’s Disease: A Pilot Cross-Sectional Study

    by Dan Vălean, Roxana Zaharie, Valentin Toma, Anca Onaciu, Rareș-Mario BorșA, Rareș-Ionuț Știufiuc, Alin Fetti, Beata Dohi, Călin Popa, Emil Moiș, et al.

    Crohn’s disease (CD) is a chronic inflammatory bowel disease requiring accurate and timely diagnosis. Current diagnostic tools may be invasive, costly, or insufficiently specific. Surface-enhanced Raman spectroscopy may enable rapid, minimally invasive detection of disease-associated biochemical alterations in serum. This cross-sectional pilot study included age- and sex-matched patients with Crohn’s disease and healthy controls. Serum samples were analyzed using surface-enhanced Raman spectroscopy. Spectral data were preprocessed and analyzed using principal component analysis-linear discriminant analysis and partial least squares-discriminant analysis. Classification performance was evaluated using leave-one-out cross-validation. Variable importance in projection scores was used to identify discriminatory vibrational bands. Fifty-four participants fulfilled the clinical inclusion criteria, while 51 participant-level spectra were retained for final classification analysis. PCA-LDA differentiated CD from healthy controls with a sensitivity of 85.19%, specificity of 91.67%, accuracy of 88.24%, and AUC of 0.881. PLS-DA showed slightly higher performance, with a sensitivity of 88.89%, specificity of 95.83%, accuracy of 92.16%, and AUC of 0.937. Relevant discriminatory bands were observed at 498, 639, 728, 813, 1136, 1205, 1443, 1579, and 1657 cm−1, suggesting alterations in purine metabolism, protein structure, lipid composition, and nucleic acid-associated signals. Serum-based SERS combined with multivariate analysis showed promising ability to distinguish patients with CD from healthy controls in this pilot cohort. Larger multicenter studies are required to validate these findings and assess clinical applicability.

  • Open Access

    Benefits of Surgical Management in Ileocecal Crohn’s Disease: A Review of the Past Decade (2020–2026)

    by Ion Balint, Roxana Zaharie, Vălean Dan, Emil Moiș, Călin Popa, Andra Ciocan, Nadim Al-Hajjar, Florin Zaharie

    Background and Objectives: The management of localized ileocecal Crohn’s disease (CD) is undergoing a significant paradigm shift from traditional “step-up” medical escalation toward proactive early surgical intervention. With the evolution of surgical therapies as well as various minimally invasive procedures, as well as a better understanding of inflammatory bowel diseases, surgery is playing a more important role in the treatment of inflammatory bowel disease. One of the most common occurrences in Crohn’s disease, the ileocecal localization can present with a lot of dilemmas regarding the optimal treatment in both adult patients and pediatric patients alike. One of the biggest challenges remains the decision between early surgery and continuous biological treatment, which can prove a challenge from multiple standpoints ranging from cost-efficiency to recurrence rate. This review highlights the latest changes in surgical management in ileocecal Crohn’s disease, focusing primarily on the anastomotic type, comparison with biological therapy, early aggressive surgery and pediatric surgery. Materials andMethods: After respecting the review criteria, 16 articles were included in our study, which emphasize the importance and the recent trends in the surgical management of the ileocecal disease. Results: All 16 articles met criteria for good quality, suggesting a low risk of bias, focusing primarily on early surgery, the role of Kono-S anastomosis as well as pediatric considerations. Conclusions: While the choice of the Kono-S anastomosis remains debatable, significant progress has been made in terms of early surgery which improves the long-term outcomes in patients while minimizing the risk of morbidity and mortality.

  • Open Access

    Differential Metabolic Dysregulations in Hepatocellular Carcinoma and Cirrhosis: Insights into Lipidomic Signatures

    by Cristina-Paula Ursu, Luminița Elena Furcea, Bogdan Procopeț, Răzvan Alexandru Ciocan, Ștefan Ursu, Claudia Diana Gherman, Dan Vălean, Rodica Sorina Pop, Emil Ioan Moiș, Horia Ștefănescu, et al.

    Hepatocellular carcinoma (HCC), the most common primary liver malignancy, usually develops in patients with cirrhosis, yet the metabolic mechanisms that distinguish the two conditions remain poorly understood. This study aimed to explore metabolic dysregulations in HCC compared with cirrhosis and to identify potential biomarkers, especially lipids, with diagnostic and prognostic value. We prospectively studied 81 patients—41 with HCC and 40 with cirrhosis—using high-resolution UHPLC-QTOF-ESI+-MS to characterize their serum lipidome. Across both groups, 322 metabolites were identified, but their distribution was strikingly different. Patients with HCC showed higher levels of sphingolipids, glycerophospholipids, diglycerides, sterols, and certain fatty acids, reflecting tumor-related metabolic rewiring. In contrast, cirrhotic patients had increased D-glucose, 5-hydroxymethyluracil, lysophospholipids, acylcarnitines, and specific fatty acid derivatives. Several lipids, such as CerPE(d16:2/24:1(2OH)), SM(d18:0/14:0), PA(36:6), and GlcCer(d18:1/12:0), displayed excellent discriminative accuracy, highlighting their role as putative biomarkers. These findings underscore the importance of lipid metabolic reprogramming in HCC, characterized by membrane remodeling, energy adaptation, and oxidative stress resistance. Integrating lipidomic profiling into clinical practice could improve early detection and risk stratification in cirrhotic patients. Larger, multicenter studies are needed to validate these biomarkers and assess their therapeutic implications.


  • Open Access

    Multitargeted Effects of Plantago ovata Ethanol Extract in Experimental Rat Streptozotocin-Induced Diabetes Mellitus and Letrozole-Induced Polycystic Ovary Syndrome

    by Lia-Oxana Usatiuc, Raluca Maria Pop, Surd Adrian, Marcel Pârvu, Mădălina Țicolea, Ana Uifălean, Dan Vălean, Laura-Ioana Gavrilaș, Szabo Csilla-Enikő, Loredana Florina Leopold, et al.

    Polycystic ovary syndrome (PCOS), a common and multifactorial endocrine disorder in reproductive-aged women, is strongly associated with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), and also affects up to one in four women with type 1 diabetes mellitus (T1DM). The current study explored the potential of Plantago ovata (P. ovata) seed ethanol extract (POEE) to modulate oxidative stress (OS), inflammatory responses, metabolic profiles, and hormonal levels in rat Streptozotocin (STZ)-induced DM and Letrozole (LET)-induced PCOS. Phytochemical analysis measured total phenolic content (TPC) and total flavonoid content (TFC) using HPLC-DAD-ESI MS for compound identification. POEE’s antioxidant activity was evaluated in vitro through DPPH, H2O2, FRAP, and NO scavenging assays. Rats received POEE, metformin, or Trolox (TX) for 10 days. PCOS confirmation was achieved via ultrasound and histopathology. Serum levels of OS markers (TOS, TAC, OSI, MDA, AOPP, 8-OHdG, NO, 3-NT, AGEs, and SH), inflammatory markers (NF-κB, IL-1β, IL-18, Gasdermin D, and IL-10), metabolic parameters (fasting blood glucose, lipid profile, and liver enzymes), and hormone levels (LH, FSH, estrogen, testosterone, and insulin) were assessed. Additionally, the Triglyceride–Glucose index (TyG) and HOMA-IR were calculated. POEE had a medium content of polyphenols and a good in vitro antioxidant effect. In vivo, POEE administration in diabetic rats led to a reduction in OS markers and an increase in antioxidant levels, alongside decreases in inflammatory cytokines, blood glucose levels, and transaminase activity and improvements in lipid profile. In the PCOS model, POEE treatment effectively reduced total OS and lowered levels of LH, FSH, and testosterone, while elevating estrogen concentrations and reducing insulin resistance. These therapeutic effects were dose-dependent, with higher doses producing more pronounced outcomes, comparable to those observed with metformin and TX treatment.


  • Open Access

    Electrocardiographic Changes in Patients with Type 2 Diabetes Mellitus—A Meta-Analysis

    by Teodora-Gabriela Alexescu, Antonia Nechita, Paula-Viorica Alexander, Mirela-Georgiana Perné, Mircea-Vasile Milaciu, George Ciulei, Ioana Para, Vasile Negrean, Ana-Florica Chiș, Doina-Adina Todea, et al.

    Background: Diabetes mellitus (DM) is a chronic metabolic disorder significantly associated with cardiovascular complications. Electrocardiographic (ECG) abnormalities are common in patients with type 2 diabetes (T2DM) and can serve as early markers for cardiovascular risk. Objective: This meta-analysis aims to evaluate the impact of T2DM on electrocardiographic changes, focusing on major ECG abnormalities, fragmented QRS (fQRS) complexes, and prolonged corrected QT (QTc) intervals. Materials and Methods: A systematic review of observational studies published between 2017 and 2022 was conducted using databases such as PubMed, Web of Science, Cochrane Library, Embase, and ClinicalTrials.gov. The inclusion criteria required studies to focus on patients with T2DM and report ECG changes. A total of 13 studies comprising 25,530 participants met the criteria and were included in the meta-analysis. The statistical analysis was performed using RevMan 5.4 with a random-effects model. Results: T2DM patients were 1.74 times more likely to develop major ECG abnormalities than non-diabetic individuals (crude OR = 1.74, 95% CI = 1.17–2.57, p = 0.006). The prevalence of fQRS complexes was significantly higher among T2DM patients (crude OR = 2.48, 95% CI = 2.09–2.957, p < 0.00001). Additionally, T2DM patients exhibited a higher likelihood of QTc interval prolongation (crude OR = 1.38, 95% CI = 1.09–1.74, p = 0.008). Conclusions: This meta-analysis demonstrates that T2DM patients have a significantly higher risk of ECG abnormalities, including major changes, fQRS complexes, and prolonged QTc intervals. Regular ECG monitoring is essential for early detection and management of cardiovascular risks in T2DM patients.


  • Open Access

    Continuous Non-Invasive Hemodynamic Monitoring in Cirrhotic Patients—Friend or Foe?

    by Mirela Crihan, Alexandru Leonard Alexa, Dan Valean, Daniela Ionescu

    Background and Objectives: Liver cirrhosis leads to significant hemodynamic changes, particularly portal hypertension and a hyperdynamic circulatory state. Traditional invasive methods for hemodynamic monitoring, while accurate, carry risks such as infection and hemorrhage in a patient predisposed to these conditions. This study evaluates the accuracy of non-invasive continuous hemodynamic monitoring compared to a minimally invasive method in patients with decompensated liver cirrhosis. Materials and Materials and Methods: The study enrolled 51 patients with decompensated liver cirrhosis requiring continuous hemodynamic monitoring in the ICU. Patients underwent simultaneous monitoring via the minimally invasive FloTrac system and continuous non-invasive ClearSight sensor over 24 h, with measurements registered at 6 h intervals. Hemodynamic parameters measured included cardiac output (CO), cardiac index (CI), stroke volume (SV), stroke volume variation (SVV), systemic vascular resistance (SVR), and mean arterial pressure (MAP). Results: Significant discrepancies were observed between the two monitoring methods for most parameters, particularly CO, CI, and MAP, at most time intervals. However, SVV measurements showed no significant differences, indicating similar efficacy in assessing fluid responsiveness between the devices. Conclusions: The ClearSight system, although a valuable non-invasive alternative, demonstrated lower accuracy compared to the FloTrac system for hemodynamic measurements in patients with decompensated liver cirrhosis. Its effectiveness in assessing fluid responsiveness, particularly by SVV, suggests it could play a role in the monitoring of these patients, especially when invasive techniques have increased risks.


  • Open Access

    Current Approaches to the Management of Postoperative Fistulas in Gastric Cancer Surgery: Experience of a Tertiary Center

    by Alin Fetti, Roxana Zaharie, Vlad Radu Puia, Dan Valean, Roman Taulean, Vlad Nechita, Florin Zaharie, Ioan Catalin Bodea, Oana Moșincat, Nadim Al-Hajjar

    Background: Gastric cancer remains a leading global health challenge, despite advances in surgical techniques and perioperative care. Patients with gastric cancer present with a degree of postoperative complications, most notably anastomotic fistulas, which can lead to a high level of morbidity and mortality. Although significant advances have been made in their management by implementing less invasive methods, issues and debate remain regarding their early detection and treatment decisions. The purpose of this study was to emphasize the particularities of the treatment of postoperative fistulas in gastric cancer surgery, focusing on risk factors as well as management strategies. Methods: This retrospective study analyzed risk factors, diagnostic methods, and treatment strategies for anastomotic fistulas in 527 patients undergoing curative gastric cancer surgery over the span of five years, highlighting postoperative complication rates, the management of postoperative complications, and the primary risk factors for developing fistulas. Results: Conservative treatment combined with minimally invasive interventions achieved a primary success rate of over 65%, with surgical intervention being reserved for severe cases. The primary risk factors identified were an advanced tumor stage, total gastrectomy, type II diabetes mellitus, and a high number of transfusions required, as well as hypoalbuminemia. Conclusions: Although further research is required to standardize treatment protocols and reduce the morbidity and mortality associated with postoperative fistulas, understanding the primary elements of its causation can prove helpful in choosing the correct treatment.


  • Open Access

    Influence of SARS-CoV2 Pandemic on Colorectal Cancer Diagnosis, Presentation, and Surgical Management in a Tertiary Center: A Retrospective Study

    by Roman Taulean, Roxana Zaharie, Dan Valean, Lia Usatiuc, Mohammad Dib, Emil Moiș, Calin Popa, Andra Ciocan, Alin Fetti, Nadim Al-Hajjar, et al.

    Background: Oncological surgery during the COVID-19 pandemic was performed only in carefully selected cases, due to variation in the allocation of resources. The purpose of this study was to highlight the impact of the pandemic lockdown on the presentation, diagnosis, and surgical management of colorectal cancers as well as the post-pandemic changes in this area. Material and methods: This single center, retrospective comparative study contained 1687 patients, divided into three groups with equal time frames of two years, consisting of a pre-pandemic, pandemic, and post-pandemic period, in which preoperative and perioperative as well as postoperative parameters were compared. Results: Statistically significant differences regarding environment, type of admission, and ASA score, as well as a more advanced tumoral stage, increased number of important postoperative complications, and a lower minimally invasive surgical approach, were highlighted within the pandemic group. Statistically significant differences regarding emergency diagnosis as well as late diagnosis were highlighted. There were no significant differences regarding the tumor location, postoperative 30-day mortality, or hospitalization duration. Conclusions: COVID-19 significantly impacted the surgical timing in colorectal cancer, as well as addressability for the rural population, with a marked decrease in elective cases as well as an increased number of cases diagnosed in an emergency setting, with locally advanced tumors. However, no significant changes in postoperative mortality or hospitalization duration were highlighted. In addition, most of the changes highlighted were reverted in the post-pandemic period. Further studies are required to observe the long-term effects in terms of morbidity and mortality, regarding the delay of diagnosis and oncological treatment.


  • Open Access

    Assessing the Anti-Inflammatory and Antioxidant Activity of Mangiferin in Murine Model for Myocarditis: Perspectives and Challenges

    by Alexandra Popa, Lia-Oxana Usatiuc, Iuliu Calin Scurtu, Raluca Murariu, Alexandra Cofaru, Romelia Pop, Flaviu Alexandru Tabaran, Luciana Madalina Gherman, Dan Valean, Alexandru Cristian Bolundut, et al.

    Myocarditis is a major cause of heart failure and death, particularly in young individuals. Current treatments are mainly symptomatic, but emerging therapies focus on targeting inflammation and fibrosis pathways. Natural bioactive compounds like flavonoids and phenolic acids show promising anti-inflammatory and antioxidant properties. Corticosteroids are frequently employed in the treatment of autoimmune myocarditis and appear to lower mortality rates compared to conventional therapies for heart failure. This study aims to explore the effects of Mangiferin on pro-inflammatory cytokine levels, nitro-oxidative stress markers, histopathological alterations, and cardiac function in experimental myosin-induced autoimmune myocarditis. The effects were compared to Prednisone, used as a reference anti-inflammatory compound, and Trolox, used as a reference antioxidant. The study involved 30 male Wistar–Bratislava rats, which were randomly divided into five groups: a negative control group (C−), a positive control group with induced myocarditis using a porcine myosin solution (C+), three groups with induced myocarditis receiving Mangiferin (M), Prednisone (P), or Trolox (T) as treatment. Cardiac function was evaluated using echocardiography. Biochemical measurements of nitro-oxidative stress and inflammatory markers were conducted. Finally, histopathological changes were assessed. At echocardiography, the evaluation of the untreated myocarditis group showed a trend toward decreased left ventricular ejection fraction (LVEF) but was not statistically significant, while all treated groups showed some improvement in LVEF and left ventricular fraction shortening (LVFS). Significant changes were seen in the Mangiferin group, with lower end-diastolic left ventricular posterior wall (LVPWd) by day 21 compared to the Trolox group (p < 0.001). In the first week of the experiment, levels of interleukins (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α were significantly higher in the myosin group compared to the negative control group (p < 0.001, p < 0.001, p < 0.01), indicating the progression of inflammation in this group. Treatment with Mangiferin, Prednisone, and Trolox caused a significant reduction in IL-1β compared to the positive control group (p < 0.001). Notably, Mangiferin resulted in a superior reduction in IL-1β compared to Prednisone (p < 0.05) and Trolox (p < 0.05). Furthermore, Mangiferin treatment led to a statistically significant increase in total oxidative capacity (TAC) (p < 0.001) and a significant reduction in nitric oxide (NOx) levels (p < 0.001) compared to the negative control group. Furthermore, when compared to the Prednisone-treated group, Mangiferin significantly reduced NOx levels (p < 0.001) and increased TAC levels (p < 0.001). Mangiferin treatment significantly lowered creatine kinase (CK) and aspartate aminotransferase (AST) levels on day 7 (p < 0.001 and p < 0.01, respectively) and reduced CK levels on day 21 (p < 0.01) compared to the untreated group. In the nontreated group, the histological findings at the end of the experiment were consistent with myocarditis. In the group treated with Mangiferin, only one case exhibited mild inflammatory infiltrates, represented by mononucleated leukocytes admixed with few neutrophils, with the severity graded as mild. Statistically significant correlations between the grades (0 vs. 1–2) and the study groups have been highlighted (p < 0.005). This study demonstrated Mangiferin’s cardioprotective effects in autoimmune myocarditis, showing reduced oxidative stress and inflammation. Mangiferin appears promising as a treatment for acute myocarditis, but further research is needed to compare its efficacy with other treatments like Trolox and Prednisone.