Search Results (101)

Background: Behçet’s disease (BD) and granulomatosis with polyangiitis (GPA) are distinct vasculitides. PR3-ANCA is considered specific for GPA, yet rare BD cases demonstrate positivity, creating diagnostic dilemmas. Case Presentation: We describe a young man fulfilling criteria for BD, presenting with recurrent oral and genital ulcers, ocular inflammation, catastrophic jejunal perforations, pulmonary embolism, and myocardial infarction with non-obstructive coronary arteries. Despite strong PR3-ANCA positivity, the global phenotype was consistent with BD. Management required a complex, multimodal immunosuppressive regimen that included corticosteroids, cyclophosphamide, therapeutic plasma exchange, and rituximab. Conclusions: PR3-ANCA positivity may represent a severe BD phenotype rather than true GPA overlap, underscoring the need for individualized treatment strategies. Full article

Background: Dynamic whole-body (D-WB) FDG PET/CT is a novel technique that enables the direct reconstruction of multiparametric images representing the FDG metabolic uptake rate (MR_FDG) and “free” FDG (DV_FDG). Applying complementary parameters with distinct characteristics compared to static SUV images, the aims of this study are as follows: (1) to determine the threshold values of SUV, MR_FDG, and DV_FDG for malignant and benign lesions; (2) to compare the specificity of MR_FDG and DV_FDG images with static SUV_bw images; and (3) to assess whether any of the dynamic imaging parameters correlate more significantly with malignancy or non-malignancy in the examined lesions based on the measured values obtained from D-WB FDG PET/CT. Methods: The study was a retrospective analysis of D-WB PET/CT data from 43 patients (23 males and 20 females) included both in the context of primary staging as well as imaging performed due to suspicion of post-therapeutic relapse or recurrence. Standard scanning was performed using a multiparametric PET acquisition protocol on a Siemens Biograph Vision 600 PET/CT scanner. Pathological findings were manually delineated, and values for SUV_bw, MR_FDG, and DV_FDG were extracted. The findings were classified and statistically evaluated based on their was histological verification of a malignant or benign lesion. Multinomial and binomial logistic regression analyses were used to find parameters for data classification in different models, employing various combinations of the input data (SUV_bw, MR_FDG, DV_FDG). ROC curves were generated by changing the threshold p-value in the regression models to compare the models and determine the optimal thresholds. Results: Patlak PET parameters (MR_FDG and DV_FDG) combined with mean SUV_bw achieved the highest diagnostic accuracy of 0.82 (95% CI 0.75–0.89) for malignancy detection (F1-score = 0.90). Sensitivity reached 0.85 (95% CI 0.77–0.91) and specificity 0.93 (95% CI 0.87–0.98). Classification accuracy in tumors was 0.86 (95% CI 0.78–0.92) and in lymph nodes 0.81 (95% CI 0.73–0.88). Relative contribution analysis showed that DV_FDG accounted for up to 65% of the classification weight. ROC analysis demonstrated AUC values above 0.8 for all models, with optimal thresholds achieving sensitivities of around 0.85 and specificities up to 0.93. Thresholds for malignancy detection were, for mean values, SUV_bw > 5.8 g/mL, MR_FDG > 0.05 µmol/mL/min, DV_FDG > 68%, and, for maximal values, SUV_bw > 8.7 g/mL, MR_FDG > 0.11 µmol/mL/min, DV_FDG > 202%. Conclusions: The D-WB [¹⁸F]FDG PET/CT images in this study highlight the potential for improved differentiation between malignant and benign lesions compared to conventional SUV_bw imaging in patients with locally advanced head and neck cancers presenting with cervical lymphadenopathy and carcinoma of unknown primary origin (CUP). This observation may be particularly relevant in common diagnostic dilemmas, especially in distinguishing residual or recurrent tumors from post-radiotherapy changes. Further validation in larger cohorts with histopathological confirmation is warranted, as the small sample size in this study may limit the generalizability of the findings. Full article

Therapeutics involving small interfering RNA (siRNA) have enormous potential for treating a number of diseases, but their effective delivery to target cells remains a major challenge. We studied the influence of the structure and combination of targeted (folate conjugated, F13) and shield lipoconjugates (P1500, diP1500) on the ability of cationic liposomal formulations based on the 2X3-DOPE system to deliver siRNA into cells in vitro and in vivo. The loop-structured PEG lipoconjugate equipped with two hydrophobic anchor groups (diP1500) demonstrated superior performance across multiple evaluation criteria. The F13/diP1500 composition maintained a compact particle size (126.0 ± 23.0 nm), while F13/P1500 with the same PEG chain equipped with one anchor group maintained an increased particle size of 241.8 ± 65.7 nm. Most critically, F13/diP1500 preserved substantial positive surface charges (21.6–30.5 mV) across all N/P ratios, demonstrating superior ability in avoid the “PEG dilemma”, whereas F13/P1500 suffered substantial charge neutralization (3.9–9.1 mV). Competitive inhibition with free folate confirmed receptor-mediated cellular accumulation of siRNA mediated by F13 containing liposomal compositions. In vivo biodistribution revealed statistically significant circulation advantages: DSPE-PEG2000/diP1500 achieved the highest plasma concentration at 15 min (1.84 ± 0.01 pmol/mL), representing the first direct in vivo comparison of compositions with PEG lipoconjugates of the same length, but formed different structures in the liposomes due to the presence of one or two anchor groups. Our findings provide critical insights for the rational design of targeted liposomal delivery systems, highlighting the importance of balanced optimization between folate targeting functionality and PEG shielding for effective siRNA delivery both in vitro and in vivo. Full article

Background: Transcatheter aortic valve implantation (TAVI) is an established treatment for severe aortic stenosis in elderly and high-risk patients. However, prosthetic valve endocarditis (PVE) remains a rare but devastating complication. Its diagnosis is often delayed due to atypical clinical manifestations and the frequent occurrence of culture-negative endocarditis. Case Presentation: We report the case of a 68-year-old woman with a prior TAVI who presented with sacroiliitis, initially interpreted as a localized musculoskeletal infection. Subsequent evaluation revealed infective endocarditis involving the prosthetic aortic valve and the native mitral valve. Blood cultures remained negative, most likely due to prior antibiotic therapy, which complicated timely diagnosis. During hospitalization, the patient developed acute ST-segment elevation myocardial infarction (STEMI), caused by coronary septic embolization. Discussion: Distinguishing septic emboli from thrombotic occlusion in the setting of STEMI complicating endocarditis is extremely challenging but essential, as therapeutic approaches diverge. While percutaneous coronary intervention is the standard treatment for thrombotic occlusion, it carries major risks of septic embolization, including stent infection, mycotic aneurysm, and uncontrolled sepsis. Conclusions: This case highlights the need for high clinical suspicion of PVE in atypical presentations, the diagnostic challenges of culture-negative endocarditis, and the therapeutic dilemmas posed by acute coronary complications without clear guideline-based solutions. Full article

Cardiorenal syndrome (CRS) reflects the intricate and bidirectional interplay between cardiac and renal dysfunction, commonly resulting in diagnostic uncertainty, therapeutic dilemmas and poor outcomes. While traditional biomarkers like serum creatinine (Cr) and natriuretic peptides remain widely used, their limitations in specificity, timing and contextual interpretation often hinder optimal management. This narrative review synthesizes the current evidence on established and emerging biomarkers in CRS, with emphasis on their clinical relevance, integration into real-world practice, and potential to inform precision therapy. Markers of glomerular filtration rate beyond creatinine—such as cystatin C—offer more accurate assessment in frail or sarcopenic patients, while tubular injury markers such as NGAL, KIM-1, and urinary L-FABP (uL-FABP) provide early signals of structural renal damage. The FDA-approved NephroCheck^® test—based on TIMP-2 and IGFBP7— enables risk stratification for imminent AKI up to 24 h before functional decline. Congestion-related markers such as CA125 and bio-adrenomedullin outperform natriuretic peptides in certain CRS phenotypes, particularly in right-sided heart failure or renally impaired patients. Fibrosis and inflammation markers (galectin-3, sST2, GDF-15) add prognostic insights, especially when combined with NT-proBNP or troponin. Rather than presenting biomarkers in isolation, this review proposes a framework that links them to specific clinical contexts—such as suspected decongestion-related renal worsening or persistent congestion despite therapy—to support actionable interpretation. A tailored, scenario-based, multi-marker strategy may enhance diagnostic precision and treatment safety in CRS. Future research should prioritize prospective biomarker-guided trials and standardized pathways for clinical integration. Full article

Background: Deficient mismatch repair rectal cancer represents approximately 10% of rectal malignancies and demonstrates exceptional responsiveness to immune checkpoint inhibitors, achieving unprecedented complete response rates approaching 100%. This creates a novel clinical dilemma: should patients achieving complete response undergo standard surgical resection or pursue organ preservation through watch-and-wait management? Methods: We conducted a comprehensive literature review of clinical trials and retrospective studies published through 2025, focusing on response assessment strategies, decision-making frameworks, oncological outcomes, and quality of life assessments. Results: Landmark studies demonstrated remarkable efficacy with dostarlimab achieving 100% clinical complete response, while surgical cohorts achieved 68–92% pathological complete response rates. Response assessment challenges included pseudoprogression and pseudoresidue phenomena that complicated conventional imaging interpretation and required specialised multimodal evaluation protocols. Comparative analyses suggest equivalent oncological outcomes between surgical and non-surgical approaches in complete responders, achieving 100% disease-free survival at 2–3 years across multiple studies. The watch-and-wait approach offered significant advantages by preserving organ integrity and avoiding surgical morbidity, including permanent colostomy (15.4%) and perioperative complications (19.3%). Conversely, surgical management provided distinct benefits through definitive tissue confirmation and anxiety relief from intensive surveillance requirements and potential recurrence concerns. Conclusions: The surgery versus watch-and-wait dilemma represents a choice between equally effective oncological approaches with different quality of life implications. Evidence supports individualised decision-making weighing functional preservation benefits against patient preferences and institutional capabilities in this evolving therapeutic landscape. Full article

This article shows how “reasons of state” can sometimes influence end-of-life care decisions made by top politicians. Drawing on Ivan Illich’s concept of “medical nemesis” and the myth of Tithonus and Eos, it argues that the success of medicine in prolonging life can, paradoxically, increase suffering and raise ethical dilemmas, particularly when medicine is used to ensure the continuity of power. Through the analysis of four historical cases—Franklin D. Roosevelt, Francisco Franco, Josip Broz Tito, and François Mitterrand—the article highlights some issues related to the concealment or deliberate manipulation of information about the health of political leaders, invasive and disproportionate medical interventions, and various conflicts that can arise between clinical goals and political objectives. The article then adopts the doctrine of the “king’s two bodies”, revived in contemporary times by Ernst Kantorowicz, to interpret these dynamics as attempts to merge the leader’s mortal body with an eternal political body, generating a dangerous identification that fuels therapeutic excess. By decoupling the natural body from the political body, the study calls for transparent and ethically grounded frameworks capable of balancing privacy, continuity of government, and limits on the use of medical care. Full article

Breast cancer is the most prevalent malignant tumor in women. However, its clinical management is severely hindered by three interconnected challenges that limit long-term survival: treatment resistance, metastatic dissemination, and immunological evasion. Ferroptosis, an iron-dependent form of regulated cell death, is emerging as a novel strategy to overcome these obstacles. Furthermore, it demonstrates significant potential in inhibiting tumor metastasis and modifying the anti-tumor immune microenvironment, which provides a novel approach to address the core dilemma of breast cancer. Natural products have emerged as significant sources of ferroptosis inducers owing to their distinctive chemical variety, multi-target regulatory capabilities, and acceptable safety profile. Data increasingly indicates that several natural compounds can function as effective inducers or sensitizers of ferroptosis cell death. This review provides a thorough evaluation of current progress in harnessing natural ingredients to trigger ferroptosis for breast cancer treatment. It also elucidates the fundamental molecular mechanisms. Furthermore, it encapsulates therapeutic efficacy in preclinical models. Ultimately, it rigorously evaluates existing constraints and delineates potential and barriers for clinical translation. Full article

Background: Hydatid disease, caused by the larval form of Echinococcus granulosus, is a rare but potentially life-threatening condition during pregnancy, with an estimated incidence of 1 in 20,000 to 30,000 gestations. Physiological immunosuppression and increased placental steroid levels during pregnancy may promote cyst growth, elevating the risk of rupture, which can result in anaphylactic shock, sepsis, or widespread peritoneal dissemination. Diagnostic imaging, particularly ultrasonography, plays a central role in detection, while treatment decisions are complicated by the lack of standardized guidelines and the need to balance maternal–fetal safety. Methods: This case report describes a 29-year-old pregnant woman at 22 weeks’ gestation who was incidentally diagnosed with two large hepatic hydatid cysts during a routine ultrasound. Results: Given the high rupture risk, she underwent successful laparoscopic surgery in the second trimester, followed by careful monitoring and elective cesarean delivery at term. A third retroperitoneal cyst, initially managed conservatively, was excised postpartum. Conclusions: This case highlights the critical importance of individualized, multidisciplinary management in achieving favorable maternal and neonatal outcomes in complex presentations of hydatid disease during pregnancy. Full article

Background/Objectives: The use of opioid drugs in the elderly population is characterized by an increased risk of sedation and respiratory depression, and in the immediate postoperative period, it is associated with a higher incidence of postoperative delirium. The dilemma of opioid use as an element of acute postoperative pain therapy is crucial in elderly patients. Methods: This study was conducted in 80 patients qualified for laparoscopic cholecystectomy under general combined anesthesia. Two methods of analgesia were performed—Low-Opioid Analgesia (LOA) and Opioid-Based Analgesia (OBA)—and pain intensity based on the Numerical Rating Scale (NRS) was assessed at 0–2, 2–6, 6–12, and 12–24 h after surgery. The mean NRS in LOA and OBA was compared in age categories. Pain trajectory in patients over 60 years old was compared between LOA and OBA. Results: The trajectory of analgesia presented a negative slope in LOA for patients over 60 years of age, with reductions in pain intensity of 33%, 25%, and 66%. In OBA, a positive slope trajectory was noted, and pain intensity was higher within 12–24 h after surgery than within 0–2 and 2–6 h. Conclusions: Opioid analgesia in patients over 60 years of age presented a better effect in the immediate postoperative period. Non-opioid analgesia is indicated for patients over 60 years old in the later postoperative period. The model of combined minimal opioid anesthesia and non-opioid postoperative analgesia presents a favorable therapeutic effect for patients over 60 years old. Full article

Background: Statin intolerance is a serious therapeutic dilemma in secondary cardiovascular prevention (e.g., ESC/EAS Guidelines 2023). This is especially true when confirmed by genetic predisposition and complicated by rhabdomyolysis. Although several non-statin agents have become available in recent years, evidence regarding their combined use in high-risk statin-intolerant patients remains limited. Furthermore, the pharmacokinetics of statins in toxic concentrations are poorly characterized in clinical settings. Case Presentation: We present two cases of genetically confirmed statin-induced rhabdomyolysis, both accompanied by severe acute kidney injury requiring renal replacement therapy. In both patients, serial measurements of rosuvastatin plasma concentrations revealed markedly delayed elimination, with detectable levels persisting for several weeks despite ongoing dialysis. Estimated half-lives exceeded 7 days in both cases, far beyond the known therapeutic range. Genetic testing identified SLCO1B1, ABCB1, and CYP2C9 polymorphisms linked to reduced hepatic uptake and impaired drug clearance. Following biochemical recovery, both patients were initiated on a triple non-statin lipid-lowering regimen consisting of ezetimibe, bempedoic acid, and inclisiran. The combination was well tolerated, with no recurrence of muscle-related symptoms or biochemical toxicity. LDL-C levels were reduced from 3.05 to 1.59 mmol/L and from 4.99 to 1.52 mmol/L, respectively, with sustained response over 12 and 40 weeks. Full lipid profiles demonstrated favorable changes across all parameters. Conclusions: These two cases suggest that the combination of ezetimibe, inclisiran, and bempedoic acid may serve as a safe and effective therapeutic option in patients with severe statin intolerance. Pharmacogenetic testing and serial pharmacokinetic assessment may guide personalized lipid-lowering strategies and improve outcomes in this challenging patient population. Full article

Managing nephrolithiasis in chronic kidney disease (CKD) poses a therapeutic challenge: preventing stone recurrence while preserving kidney function. Standard urological interventions and preventive strategies, such as high fluid intake, thiazides, and potassium citrate, cut recurrence by 50–60% in healthy kidneys but risk fluid overload, hyperkalemia, and diminished efficacy in CKD as glomerular filtration rate (GFR) declines. Often, stone prevention and CKD care are addressed separately, leaving clinicians without unified guidance for this rising patient group. This review explores the bidirectional relationship between nephrolithiasis and CKD, integrating pathophysiology and therapeutic strategies into a practical, decision-oriented framework. It offers tailored interventions based on GFR category, stone type, and comorbid conditions, emphasizing the potential for dual-purpose therapies. Going beyond previous reviews, it connects clinical practice with existing research gaps, offering tools to balance outcomes and guide future studies. Full article

Desmoid tumors are rare, locally invasive soft-tissue tumors with unpredictable clinical behavior. Imaging plays a crucial role in their diagnosis, measurement of disease burden, and assessment of treatment response. However, desmoid tumors’ unique imaging features present challenges to conventional imaging metrics. The heterogeneous nature of these tumors, with a variable composition (fibrous, myxoid, or cellular), complicates accurate delineation of tumor boundaries and volumetric assessment. Furthermore, desmoid tumors can demonstrate prolonged stability or spontaneous regression, and biologic quiescence is often manifested by collagenization rather than bulk size reduction, making traditional size-based response criteria, such as Response Evaluation Criteria in Solid Tumors (RECIST), suboptimal. To overcome these limitations, advanced imaging techniques offer promising opportunities. Functional and parametric imaging methods, such as diffusion-weighted MRI, dynamic contrast-enhanced MRI, and T2 relaxometry, can provide insights into tumor cellularity and maturation. Radiomics and artificial intelligence approaches may enhance quantitative analysis by extracting and correlating complex imaging features with biological behavior. Moreover, imaging biomarkers could facilitate earlier detection of treatment efficacy or resistance, enabling tailored therapy. By integrating advanced imaging into clinical practice, it may be possible to refine the evaluation of disease burden and treatment response, ultimately improving the management and outcomes of patients with desmoid tumors. Full article

Background: Syringomyelia is a complex neurological disorder characterized by a fluid-filled cavity (syrinx) within the spinal cord, frequently resulting from altered cerebrospinal fluid (CSF) dynamics. While its clinical manifestations are diverse, orthopedic complications such as scoliosis, pes cavus, and Charcot arthropathy may represent early diagnostic clues yet are often under-recognized. Methods: This comprehensive review synthesizes the current literature on the pathophysiology, clinical presentation, diagnostic strategies, and management approaches of syringomyelia, with a specific emphasis on its orthopedic manifestations. Additionally, we present a detailed case of neuropathic shoulder arthropathy associated with advanced syringomyelia. Results: Orthopedic involvement in syringomyelia includes progressive spinal deformities and neurogenic joint destruction, particularly affecting the shoulder and elbow. Scoliosis is frequently observed, especially in association with Chiari malformations, and may precede neurologic diagnosis. Charcot joints result from impaired proprioception and protective sensation. The case presented illustrates the diagnostic challenges and therapeutic dilemmas in managing advanced neuro-orthopedic complications in syringomyelia. Conclusions: Syringomyelia should be considered in the differential diagnosis of atypical musculoskeletal presentations. Early recognition and multidisciplinary management are essential to prevent irreversible orthopedic sequelae. Conservative treatment remains the mainstay in stable cases, while surgery is reserved for progressive disease. Orthopedic assessment plays a pivotal role in the diagnostic pathway and long-term care of affected patients. Full article

Background: Advancements in pharmacogenomics, artificial intelligence (AI), and CRISPR gene-editing technology are revolutionizing precision medicine by enabling highly individualized therapeutic strategies. Artificial intelligence-driven computational techniques improve biomarker discovery and drug optimization while pharmacogenomics helps to identify genetic polymorphisms affecting medicine metabolism, efficacy, and toxicity. Genetically editing based on CRISPR presents a precise method for changing gene expression and repairing damaging mutations. This review explores the convergence of these three fields to enhance improved precision medicine. Method: A methodical study of the current literature was performed on the effects of pharmacogenomics on drug response variability, artificial intelligence, and CRISPR in predictive modeling and gene-editing applications. Results: Driven by artificial intelligence, pharmacogenomics allows clinicians to classify patients and select the appropriate medications depending on their DNA profiles. This reduces the side effect risk and increases the therapeutic efficacy. Precision genetic modifications made feasible by CRISPR technology improve therapy outcomes in oncology, metabolic illnesses, neurological diseases, and other fields. The integration of artificial intelligence streamlines genome-editing applications, lowers off-target effects, and increases CRISPR specificity. Notwithstanding these advances, issues including computational biases, moral dilemmas, and legal constraints still arise. Conclusions: The synergy of artificial intelligence, pharmacogenomics, and CRISPR alters precision medicine by letting customized therapeutic interventions. Clinically translating, however, hinges on resolving data privacy concerns, assuring equitable access, and strengthening legal systems. Future research should focus on refining CRISPR gene-editing technologies, enhancing AI-driven pharmacogenomics, and developing moral guidelines for applying these tools in individualized medicine going forward. Full article