Background Acute cholecystitis (AC) is one of the most common surgical emergencies with a wide range of clinical outcomes. Early identification of patients at risk for postoperative complications is essential for optimizing surgical decision-making and resource allocation. Hemogram-derived indices such as the systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR), in addition to biochemical markers, may provide prognostic value beyond traditional risk factors. Materials and methods This retrospective single-center study included 210 patients admitted to the University Clinical Center Tuzla with AC between January 2024 and January 2025. Demographic, clinical, and laboratory data were collected. Receiver operating characteristic (ROC) analysis was performed to identify optimal cut-off values for predicting complications. Multivariate logistic regression was adjusted for age, sex, diabetes mellitus, hypertension, and other baseline comorbidities, in addition to SII, NLR, glucose, and creatinine. Results Four variables emerged as independent predictors of complications: SII > 950 remained an independent predictor after full adjustment (p = 0.002) with a sensitivity of 78% and specificity of 72%. It yielded the highest discriminatory accuracy among the evaluated markers, with an area under the curve (AUC) of 0.81 (95% confidence interval (CI) 0.75-0.87). No formal comparison with TG18 grading was performed. In contrast, baseline comorbidities such as diabetes mellitus and hypertension did not retain significance after adjustment. Conclusion SII, NLR, glucose, and creatinine independently predicted complications in AC, with SII emerging as the strongest predictor among the evaluated variables. These findings suggest that incorporating hemogram-derived indices into preoperative assessment may enhance risk stratification. However, the retrospective single-center design and potential confounding related to the surgical approach warrant cautious interpretation.

Clear Cell Sarcoma (CCS) are ultra-rare fusion-translocated soft-tissue tumours occurring mainly in young adults with poor prognosis. Their aggressiveness and resistance to conventional chemotherapy, especially in a metastatic setting, characterize these tumours. A functional drug screen consisting of 80 drugs was performed on patient derived CCS cell lines. Top candidates were validated in 3D cell culture and in vivo models, allowing comparison of drug responses among CCS cell lines, including one matched pair (MUG Lucifer cell lines) representing primary and metastatic disease from the same patient. Underlying mechanisms were evaluated with RNA Seq, fluorescence/luminescence based assays, western blot and IHC. In vitro experiments in CCS spheroids highlighted the transcription inhibitor lurbinectedin to be the best overall candidate which was further confirmed in mouse xenografts, albeit to a lesser extent than observed in vitro, especially in the metastatic CCS model. Transcriptional and functional analyses revealed heterogeneous drug responses and differences in cell death mechanisms across CCS lines, reflecting patient-specific variability. Furthermore, we explored combinational treatment of lurbinectedin with selinexor. Synergistic effects were confirmed in a novel autologous co-culture model incorporating cancer-associated fibroblasts, providing a more physiologically relevant system for drug testing. This study identified promising therapeutic avenues by highlighting key vulnerabilities in CCS, considering both inter tumour heterogeneity, tumour plasticity and the stromal influence on drug response.

Bacterial cell poles play a fundamental role in several cellular processes, such as cell cycle, chemotaxis, cell differentiation, development, growth, and structure of the bacterial cell, as well as protein localization. Using a set of bioinformatics tools, we evaluated the probability of 19 bacterial cell pole-related proteins to be disordered and undergo spontaneous liquid-liquid phase separation (LLPS). Our analysis revealed that11 cell pole-related proteins are predicted to be highly disordered, 7 proteins are moderately disordered, and only one protein is expected to be highly ordered. Furthermore, this intrinsic disorder propensity is mostly evolutionary conserved. Most of the analyzed 19 cell pole-related proteins were found to be associated with the LLPS process, with TipN, PopZ, and PBP2A being capable of spontaneous phase separation, RacA, Noc, PBP1A/1B, ParB, PBP3, PBP2B, FtsZ, MipZ, MinD, and MreB being expected to potentially serve as droplet clients, and with the remaining proteins (DivIVA, ComN, Maf, PBP4, MinC, and MinJ) being predicted to be unrelated to LLPS. The results suggested that FtsZ, DivIVA, and MiPZ serve as the main regulatory proteins, being well-known for their role in forming the septum and chromosomal segregation. Furthermore, PopZ and TipN proteins contribute to high stress resistance. Clarifying the function and effects of each mechanism gives insight into the organization of bacterial cells and some strategies for antimicrobial targets.

Three novel unsymmetrically substituted 2,2'-bipyridine ligands were prepared by introducing a 2-hydroxyphenyl group at the 6-position and either a 4-methoxyphenyl, 3,4-dimethoxyphenyl or 3,4-methylenedioxyphenyl group at the 4-position, using a modified Kröhnke protocol. Their corresponding rhenium(I) tricarbonyl iodido complexes, fac-[Re(L)(CO)3I], 1-3, were synthesized and comprehensively characterized by single-crystal X-ray diffraction (SCXRD), 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, cyclic voltammetry (CV), high-resolution mass spectrometry (HRMS), and elemental analysis. The common 6-(2-hydroxyphenyl) moiety predominantly influences the spectroscopic and redox properties of the complexes. SCXRD confirms the facial arrangement of the fac-[Re(CO)3N2I] core in all three cases, although solid-state conformational isomerism was observed only in complex 1. In contrast, two NMR-distinguishable isomers are observed in solution for all three complexes. The cytotoxicity of 1-3 was evaluated by MTT assay after 48 h of continuous exposure in several human tumor cell lines (HeLa, PANC-1, MDA-MB-231, A549) and in non-malignant human lung fibroblasts (MRC-5). Notably, all three complexes displayed low-micromolar IC50 values comparable to cisplatin, with the highest activity observed in HeLa cells (5.11-7.45 μM). However, significant activity was also recorded in MRC-5 cells (IC50 = 8.19-8.95 μM), suggesting higher overall toxicity and weaker selectivity compared to cisplatin. Analysis in HeLa cells using bright-field microscopy confirmed a substantial antiproliferative effect.

microRNA-27a is a promising candidate for miRNA mimic therapy to combat obesity, but its clinical application is hindered by enzymatic degradation and low membrane permeability. To address these challenges, we developed cationic nanostructured lipid carriers (cNLCs) via high-pressure homogenization as non-viral carriers for miRNA-27a. However, the formation of a protein corona in biologically-relevant media altered the particle size and surface charge, significantly reducing cellular uptake. To mitigate this issue, we hypothesized that coating miRNA/cNLC complexes with human serum albumin (HSA) will prevent protein corona formation and enhance cellular uptake. The HSA-coated miRNA/cNLC complexes, termed albuplexes, were characterized for particle size, zeta potential, morphology, and stability in various media. The integrity of the HSA coat was assessed using circular dichroism and UV/Vis spectroscopy. We also evaluated the biocompatibility and cellular uptake of albuplexes in 3T3-L1 cells. The biological effects of miRNA-27a on adipocyte development were analyzed through light microscopy and absorbance measurements of Oil-red-O dye in lipid droplets. Results indicated that albuplexes possess favourable physicochemical properties and enhanced stability in serum. Notably, albuplexes were rapidly taken up by 3T3-L cells via endocytosis, although 20 % HSA in the culture medium completely inhibited uptake. Furthermore, albuplexes exhibited an anti-adipogenic effect by reducing the lipid droplet accumulation, suggesting their potential as a therapeutic strategy for miRNA replacement in obesity treatment.

Background and Clinical Significance: Concomitant severe aortic stenosis (AS) and abdominal aortic aneurysm (AAA) in elderly patients presents a significant therapeutic challenge. While transcatheter aortic valve replacement (TAVR) and endovascular aneurysm repair (EVAR) have become established minimally invasive treatments for high-risk patients, simultaneous management of both conditions remains rare. Case Presentation: We report the first documented case in Serbia of a simultaneous TAVR and EVAR in a 75-year-old male with severe symptomatic AS and AAA. The patient had a history of hypertension, diabetes mellitus, atrial fibrillation, prior radiofrequency pulmonary vein ablation, and pacemaker implantation. Echocardiography demonstrated severe AS with a transvalvular gradient of 116/61 mmHg, an aortic valve area of 0.6 cm2, and a left ventricular ejection fraction of 30–35%. Coronary angiography revealed 50–60% stenosis of the right coronary artery. Following evaluation by a multidisciplinary Heart and Vascular Team, a combined procedure was performed under general anesthesia via bilateral femoral access. TAVR with a Medtronic Evolut R valve was successfully deployed, followed by EVAR with satisfactory stent graft positioning and angiographic results. The patient’s postoperative course was uneventful, and he was discharged on the ninth day. At six-month follow-up, echocardiography showed optimal valve function, and CT identified a type II endoleak, which was managed conservatively. Conclusions: This case demonstrates the feasibility and safety of simultaneous TAVR and EVAR in a high-risk elderly patient, emphasizing the importance of careful preoperative planning and a coordinated multidisciplinary approach. Further studies are warranted to establish standardized guidelines for the management of patients with coexisting severe AS and AAA.

Dexketoprofen/tramadol is a fixed-dose multimodal combination analgesic that significantly controls multiple acute pain states, and may have an important clinical application in providing pain control adequate to prevent the transition from acute to chronic postsurgical and low back pain. A consensus is needed to quantify and define the actual burden of postsurgical pain (PSP) and low back pain (LBP), which can support efforts toward effective approaches to manage potential pain chronification. This study utilized a modified Delphi approach. A Scientific Committee set forth 28 statements on six themes about the burden of acute PSP and LBP, their potential transition to chronic pain, their pathophysiology, therapeutic approaches to stop this transition, and the role of multimodal analgesia in this context, specifically a fixed-dose combination oral product of dexketoprofen/tramadol. An international panel of healthcare professionals from various regions and relevant medical specialties participated in a Delphi study and were surveyed for consensus on a 5-point Likert scale with consensus defined as > 70% concordance. A round of online voting lasting 3 months and using an online survey platform was permitted for each participant. A total of 100 experts completed the Delphi survey. All the 28 proposed statements reached consensus > 70% in the first round of voting. A fixed-dose combination product, specifically dexketoprofen/tramadol was recognized as a multimodal analgesic which could effectively relieve acute pain and act to prevent its transition to chronic pain. The high global burden of chronic PSP (CPSP) and chronic LBP (CLBP) was identified as well. Healthcare professionals who deal with pain recognize the burden of acute pain, the risks of acute pain transitioning to chronic pain, and inspire to avert the transition by providing effective multimodal control of acute pain. The role of fixed-dose combination analgesics, in particular dexketoprofen/tramadol, was recognized by consensus as an efficacious and safe therapy option for these acute pain syndromes. 7KDL7wDHZ5GDvGppW1iD89 A Video Abstract is available for this article. To view, please see the online version of the manuscript or follow the ‘Digital Features’ link. A Video Abstract for The Role of Dexketoprofen/Tramadol in Multimodal Therapy to Prevent Acute Postsurgical and Acute Low Back Pain from Developing into Chronic Pain: A Delphi Consensus Study (MP4 112565 KB) A Video Abstract is available for this article. To view, please see the online version of the manuscript or follow the ‘Digital Features’ link. A Video Abstract for The Role of Dexketoprofen/Tramadol in Multimodal Therapy to Prevent Acute Postsurgical and Acute Low Back Pain from Developing into Chronic Pain: A Delphi Consensus Study (MP4 112565 KB)

In heart failure, hyperuricemia is common, and higher serum uric acid levels are associated with poorer clinical outcomes. Additionally, hyperuricemia can cause gout, which is difficult to manage and can prolong hospitalization in patients with heart failure. In this context, agents that lower UA have even been investigated as potential treatments for heart failure because of their potential effect on SUA. Among patients with chronic heart failure, our study aimed to determine whether SGLT2 inhibitor empagliflozin influences SUA levels and whether empagliflozin has therapeutic efficacy related to SUA, particularly their effect on reducing mortality, preventing hospitalization, and improving clinical status. In 164 patients, the association between SUA and cardiovascular death or hospitalization for worsening HF and all-cause mortality was investigated. The treatment effect of empagliflozin was studied in relation to SUA as continuous variable, to clinical hyperuricemia (SUA >5.7 mg/dL for women, >7.0 mg/dL for men). Hyperuricemia was prevalent in 61% of patients with no sex differences. Elevated SUA (mean SUA 9.42 ± 1.53 mg/dL) was associated with advanced severity of HF and with worst outcome [composite outcome, hazard ratio (HR) 1.67 (95% confidence interval, CI 1.26–2.14); cardiovascular mortality, HR 1.96 (95% CI 1.32–2.89); all-cause mortality, HR 1.8 (95% CI 1.31–2.44). The reduction of SUA after initiating therapy with empagliflozin was observed rapidly (i.e. at 4 weeks) and was maintained throughout the follow-up period. The beneficial effect of empagliflozin on the primary endpoint was independent of baseline SUA [HR 0.78 (95% CI 0.69–0.90), P < 0.001) and of the change in SUA at 4 weeks [HR 0.84 (95% CI 0.71–0.94), P = 0.014]. Hyperuricemia is common in HF and is a strong indicator of advanced disease severity and increased mortality. The administration of empagliflozin resulted in rapid and sustained reductions in SUA levels and hyperuricemia-related clinical events. The benefit of empagliflozin on the primary outcome was observed independently of SUA. Patients with elevated SUA levels experienced a significant reduction in cardiovascular mortality and all-cause mortality, whereas patients with lower SUA levels did not experience this reduction. Empagliflozin was most effective in lowering SUA levels in patients with the highest SUA levels at baseline who also showed the highest mortality risks.Treatment effect of empagliflozin  Cumulative incidence of hyperur. events