Search Results (4,894)

This brief report addresses intraclonal heterogeneity in multiple myeloma (MM) through a laboratory-based exploratory approach. We conducted a retrospective study of 49 patients with intact immunoglobulin MM and abnormal serum free light chain (sFLC) ratio at diagnosis, evaluating the molar relationship between sFLC and monoclonal protein (MP). The relative excess of sFLC showed wide variability, and higher values were associated with a trend toward less favorable outcomes, although not statistically significant. These findings suggest that the sFLC-to-MP relationship may reflect underlying biological features related to intraclonal heterogeneity and provide additional insight beyond conventional assessment. Full article

Background: The combined prognostic value of the fibrinogen-to-albumin ratio (FAR) and uric acid-to-albumin ratio (UAR) in acute kidney injury patients undergoing continuous renal replacement therapy remains unclear. Methods: This retrospective cohort study utilized the MIMIC-IV database. Adult patients with AKI receiving CRRT were included and stratified into four groups based on optimal FAR and UAR cut-offs. Multivariable Cox proportional hazards regression and restricted cubic spline analyses were employed to examine associations with 30-, 90-, and 360-day all-cause mortality. Results: Patients with high FAR/high UAR had the poorest survival (log-rank p < 0.001). After multivariable adjustment, high FAR/high UAR was associated with higher 30-day (HR = 2.17, 95%CI: 1.61–2.92) and 360-day mortality (HR = 1.50, 95%CI: 1.18–1.90) vs. low FAR/low UAR. The association was stronger in patients with an SOFA score >12 or vasopressin use (interaction p < 0.05). Conclusions: In critically ill AKI patients undergoing CRRT, the combined assessment of the FAR and UAR is associated with elevated mortality risk. These readily obtainable composite markers may support risk stratification in clinical practice. Full article

Background: Malnutrition and systemic inflammation are increasingly recognized as important determinants of prognosis in patients with heart failure. Several immunonutritional indices, including the Prognostic Nutritional Index (PNI), the Controlling Nutritional Status (CONUT) score, and the C-reactive protein–albumin–lymphocyte (CALLy) index, have been proposed as markers of nutritional and inflammatory status. However, their prognostic value in elderly patients with heart failure with preserved ejection fraction (HFpEF) remains incompletely defined. This study aimed to evaluate the prognostic significance of these immunonutritional indices in elderly patients with HFpEF over a long-term follow-up period. Methods: This retrospective observational study included 200 elderly patients hospitalized with HFpEF (mean age 86.6 ± 6.5 years). Clinical, laboratory, and echocardiographic parameters were collected at admission. Nutritional status was assessed using PNI, CONUT score, and CALLy index. Patients were followed for mortality during long-term follow-up. Survival analyses were performed using Cox regression models, receiver operating characteristic (ROC) curves, and Kaplan–Meier analysis. Median follow-up was 3.8 years (IQR 2.1–5.9). Results: During follow-up, 123 patients (61.5%) died, while 77 patients (38.5%) were alive at the end of observation. In univariate analysis, PNI, CONUT score, left ventricular ejection fraction (LVEF), and the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure (TAPSE/sPAP) ratio were significantly associated with mortality. In multivariate analysis, the CONUT score, LVEF, and the TAPSE/sPAP ratio remained independent predictors of mortality. ROC analysis showed strong prognostic performance for the TAPSE/sPAP ratio (AUC 0.932), CONUT score (AUC 0.925), and LVEF (AUC 0.897). Optimal cut-off values for mortality prediction were CONUT ≥ 6, LVEF ≥ 65%, and TAPSE/sPAP ≤ 0.55 mm/mmHg. Kaplan–Meier analysis confirmed significantly reduced survival among patients with higher CONUT scores, higher LVEF, and an impaired TAPSE/sPAP ratio. Conclusions: In elderly patients with HFpEF, nutritional status and cardiopulmonary functional parameters are important determinants of long-term prognosis. The CONUT score emerged as the most informative immunonutritional index, while echocardiographic parameters reflecting ventricular function and right ventricular–pulmonary arterial coupling provided additional prognostic information. Integrating nutritional assessment with echocardiographic evaluation may improve risk stratification in elderly patients with HFpEF. Full article

Background: Risk stratification of patients with mitral regurgitation (MR), including both primary (degenerative) and secondary (functional) forms, remains challenging, particularly in asymptomatic or minimally symptomatic stages, as clinical assessment and resting echocardiography may underestimate disease severity and functional impairment. Exercise stress echocardiography (ESE) enables dynamic evaluation of regurgitation severity, ventricular performance, and cardiopulmonary response, potentially improving prognostic assessment. Methods: A systematic review was conducted according to PRISMA guidelines. PubMed, Scopus, and EMBASE were searched from inception to March 2026. Studies including adult patients with primary or secondary MR undergoing exercise-based stress echocardiography and reporting clinical outcomes were selected. Studies using exclusively pharmacological stress were excluded. Data were qualitatively synthesized, and continuous variables were summarized as weighted medians and interquartile ranges. In addition, emerging and non-conventional prognostic markers, including anatomical indices such as the modified Haller index (MHI), were explored to provide a more comprehensive risk stratification framework. Results: Nineteen studies were included, encompassing a heterogeneous population in terms of MR etiology, severity, and clinical presentation. During follow-up, a substantial proportion of patients experienced adverse events, including heart failure, mitral valve intervention, or death. Exercise-derived parameters consistently showed strong prognostic value. In particular, exercise-induced worsening of MR severity (increase in effective regurgitant orifice area and regurgitant volume), absence of contractile reserve, elevated filling pressures (E/e’), and exercise-induced pulmonary hypertension were associated with worse outcomes. Reduced functional capacity and impaired right ventricular–pulmonary arterial coupling provided additional prognostic information. Emerging markers, including chest wall configuration assessed by MHI, appeared to further refine risk stratification in selected patient subsets. In contrast, resting parameters were less consistently predictive. Conclusions: ESE provides incremental prognostic information in patients with MR by identifying dynamic abnormalities not evident at rest. Its integration into clinical evaluation, together with novel anatomical and functional markers, may improve risk stratification and support earlier identification of high-risk patients who could benefit from timely intervention. Further studies are needed to standardize methodologies and define clinically relevant thresholds. Full article

Background: Risk stratification of patients with asymptomatic aortic stenosis (AS) remains challenging, as symptom-based assessment may underestimate disease severity. Exercise stress echocardiography (ESE) provides a comprehensive evaluation of valvular, ventricular, and cardiopulmonary responses under physiological stress and may improve prognostic assessment. Methods: A systematic review was conducted according to PRISMA guidelines to evaluate the prognostic value of ESE in asymptomatic moderate and severe AS. Electronic databases (PubMed, Scopus, and EMBASE) were searched from inception to March 2026. Studies were included if they assessed adult patients with asymptomatic moderate or severe AS undergoing exercise-based stress echocardiography and reported clinical outcomes. Studies using exclusively pharmacological stress or lacking outcome data were excluded. Data were extracted and synthesized qualitatively. Continuous variables were summarized as weighted medians and interquartile ranges. Results: A total of 11 studies were included, encompassing a heterogeneous population of patients with moderate-to-severe and severe AS. During follow-up, a substantial proportion of patients experienced adverse events, including symptom onset, aortic valve replacement, or death. Across studies, exercise-derived parameters consistently showed strong prognostic value. In particular, exercise-induced increases in mean transvalvular gradient, an elevated E/e’ ratio, the development of pulmonary hypertension, and reduced functional capacity emerged as the most reproducible predictors of adverse outcomes. Notably, thresholds such as an increase in mean transvalvular gradient ≥ 18–20 mmHg, peak exercise E/e’ ≥ 15, and systolic pulmonary artery pressure ≥ 60 mmHg were consistently associated with a higher risk across multiple studies. Myocardial deformation parameters and biomarkers such as exercise-induced BNP further contributed to risk stratification in selected studies. In contrast, resting parameters alone were less consistently predictive. Conclusions: ESE provides incremental prognostic information in asymptomatic moderate and severe AS by unmasking subclinical hemodynamic and myocardial abnormalities. The integration of stress-derived parameters, including reproducible threshold values, into clinical assessment may improve risk stratification and support more individualized management strategies. Further studies are needed to validate these cut-offs and define their role in guiding clinical decision-making. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) remains a major malignancy with high incidence and mortality, in part due to its diverse etiology and intratumoral heterogeneity, which contributes to drug resistance and frequent recurrence. SALL1 (Spalt-Like Transcription Factor 1), a zinc-finger transcription factor, was reported to function as a tumor suppressor in several cancers, including breast cancer and glioma, and accumulating evidence support its involvement in tumor biology. In this study, the role of SALL1 in HCC was examined. Methods: Public RNA and protein databases derived from human HCC were interrogated. Western blotting quantification of clinical HCC for SALL1 levels was carried out. Cell culture and xenograft studies were performed using genetically modified HCC tumor cells. Results: As revealed by pubic RNA and protein database analysis and further western blotting quantification of clinical samples of HCC, SALL1 is decreased in human HCC. The effect of reduced SALL1 expression on the tumorigenic properties and transcriptional regulation in HCC was then examined. Knockdown of SALL1 in the HCC cell lines Huh7 and Hep3B, enhanced cell proliferation in vitro and accelerated tumor growth in a xenograft mouse model, suggesting that lower SALL1 expression increases cell proliferation and tumorigenesis in HCC. RNA-seq and ChIP analyses further identified three novel candidate target genes (SLC6A14, GABRG1, and AKR1B10), suggesting that SALL1 may exert a tumor-suppressive effect, at least in part, through negative regulation of these genes. Conclusions: These findings establish SALL1 as a possible tumor suppressor and provide new insights into the biological significance of SALL1 downregulation in HCC. SALL1 could be a candidate prognostic marker and a potential therapeutic target. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) is a tumor characterized by heterogeneous clinical behavior and prognosis. The tumor immune microenvironment plays a significant role in tumor progression and patient prognosis. p16 expression has been investigated as a surrogate biomarker in certain subtypes of head and neck squamous cell carcinomas, but its prognostic significance in oral squamous cell carcinoma remains incompletely elucidated. Methods: A retrospective cohort of 59 patients diagnosed with primary oral squamous cell carcinoma was analyzed. Tumor samples were evaluated for p16 expression and immunohistochemical markers associated with immune cell populations. Associations between immune microenvironment features, p16 status, and clinical outcomes such as recurrence and survival rate were analyzed. Results: p16-positive tumors were predominantly associated with immunotype A and exhibited higher densities of CD8+ cytotoxic T lymphocytes and natural killer (NK) cells. In contrast, immunotype B tumors showed similar characteristics regardless of p16 status, with no significant differences between p16-positive and p16-negative cases. Distinct immune profiles were variably associated with clinicopathological features and patient outcomes. Conclusions: These findings suggest that the immunological phenotype of oral squamous cell carcinoma may represent a potential prognostic factor. Full article

Background: Sarcopenia is increasingly recognized as a prognostic factor in surgical populations. This study evaluated the association between cranial CT-based markers of sarcopenia and neurological outcomes in patients undergoing surgery for chronic subdural hematoma (CSDH). Methods: This retrospective case–control study included 82 patients who underwent surgery for unilateral CSDH. Demographic data, comorbidities, use of anticoagulant and antiplatelet therapy, postoperative complications and length of hospital stay were collected from patients’ medical records. Radiological parameters of sarcopenia, including temporal muscle thickness, temporal muscle area, and occipital fat pad thickness, as well as standard radiological features of CSDH, were measured preoperatively on the initial CT scan. Neurological outcome 3 months after surgery was assessed using the Glasgow Outcome Scale, with scores ≥ 4 defined as favourable and scores 1–3 as poor. Results: Demographic and clinical characteristics, including age, sex, comorbidities, hematoma thickness and intracranial midline shift, did not differ significantly between outcome groups. Temporal muscle thickness (4.7 vs. 2.8 mm, p < 0.001), temporal muscle area (160 vs. 106 mm², p = 0.04), and occipital fat pad thickness (4.7 vs. 3.4 mm, p = 0.04) were significantly greater in patients with favourable neurological outcomes. After corrections for age and comorbidities, multivariate logistic regression with temporal muscle thickness, area and density, temporal bone thickness and density, and occipital fat pad thickness demonstrated that temporal muscle thickness was the only independent predictor of good neurological recovery (OR 3.20, 95% CI 1.37–7.46, p = 0.007). ROC analysis showed good discriminatory power of temporal muscle thickness (AUC 0.812, 95% CI 0.695–0.930, p < 0.001), with a cut-off value of ≥3.37 mm for its ability to predict favourable neurological outcome. Conclusions: Temporal muscle thickness is a reliable, non-invasive imaging biomarker for predicting good neurological recovery after CSDH surgery and may aid in risk stratification, particularly in elderly or frail patients. Full article

Background and Aim: Anti-epidermal growth factor receptor (EGFR) therapy is commonly associated with skin toxicity, which may reflect treatment response. This study evaluated the prognostic significance of anti-EGFR-related skin toxicity in patients with RAS wild-type metastatic colorectal cancer (mCRC) receiving palliative chemotherapy. Materials and Methods: We retrospectively analyzed 256 RAS wild-type mCRC patients treated with anti-EGFR monoclonal antibodies at Erciyes University, Kayseri, Turkey (June 2011–February 2024). Survival was estimated using the Kaplan-Meier method with log-rank comparisons. A landmark analysis at 2 months was performed to address guarantee-time bias. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. Results: The median PFS was 17 months in patients with grade ≥ 2 skin toxicity versus 8 months in those with grade < 2 skin toxicity (p < 0.001). The median OS was 32 and 21 months, respectively (p < 0.001). In the landmark-adjusted multivariate analysis, grade ≥ 2 skin toxicity was an independent prognostic factor for both PFS (HR 0.52, 95% CI 0.39–0.70, p < 0.001) and OS (HR 0.50, 95% CI 0.37–0.68, p < 0.001). Additional independent factors for OS included albumin, LDH, peritoneal metastasis, age, tumor sidedness, and BMI. The objective response rates were 53.9% and 11.3% in the grade ≥ 2 and grade < 2 groups, respectively (p < 0.001). Conclusions: Grade ≥ 2 skin toxicity was significantly associated with longer PFS, OS, and a higher response rate, and was confirmed as an independent prognostic factor in multivariate analysis. These findings suggest that skin toxicity may serve as a non-invasive marker of treatment efficacy. Prospective studies with time-dependent methodologies are needed to validate these results. Full article

Background/Objectives: Clear cell renal cell carcinoma is the most common subtype of kidney cancer and exhibits marked biological heterogeneity, even among tumors of the same histological grade. Although tumor grade remains a key prognostic parameter, the molecular alterations associated with tumor differentiation are not fully understood. This study aimed to evaluate grade-dependent tissue-level expression patterns of proteins involved in cellular stress response, growth regulation, stemness, and apoptosis in clear cell renal cell carcinoma. Methods: Protein expression of heat shock protein 70, insulin-like growth factor 1, octamer-binding transcription factor 4, and apoptosis-inducing factor were analyzed in human clear cell renal cell carcinoma samples and normal renal cortex. Low-grade and high-grade tumors were compared using immunofluorescence staining combined with semi-quantitative and quantitative image analysis. The proportion of positive signals and the number of positive cells were assessed across tissue compartments. In addition, publicly available transcriptomic data from The Cancer Genome Atlas kidney renal clear cell carcinoma cohort were analyzed to explore associations between gene expression levels and overall survival. Results: Distinct grade-dependent expression patterns were observed for all investigated proteins. Heat shock protein 70, insulin-like growth factor 1, and octamer-binding transcription factor 4 showed a higher expression in normal renal tissue with a progressive reduction across tumor grades. In contrast, apoptosis-inducing factor exhibited increased expression in tumor tissue, particularly in low-grade tumors, with a relative decrease in high-grade carcinomas. Stromal compartments of tumor tissue showed minimal or no expression for most markers. Transcriptomic survival analysis did not reveal significant differences in overall survival between high- and low-expression groups for any of the investigated genes. Grade-stratified transcriptomic analysis of the TCGA KIRC cohort revealed consistent patterns for HSP70 family members and OCT4, with progressive grade-dependent mRNA reduction toward higher grades, while IGF1 showed an inverse mRNA trend and AIFM1 showed a uniform reduction across all tumor grades without a clear inter-grade pattern. Conclusions: The findings demonstrate that stress response, growth-related, stemness-associated, and apoptotic proteins display distinct grade-dependent tissue-level expression patterns in clear cell renal cell carcinoma, with the expression profiles of high-grade tumors being of particular translational interest given the aggressive clinical behavior and therapeutic resistance characteristic of this disease stage. These alterations appear to reflect tumor differentiation and biological behavior rather than independent prognostic value, highlighting the complexity of molecular regulation in renal tumorigenesis. Full article

Background: Older adults hospitalized with acute heart failure frequently present with multimorbidity, frailty, and reduced physiological reserve. This makes accurate prognostic assessment particularly challenging in internal medicine. Traditional heart failure risk models often fail to capture this multidimensional vulnerability. The PROFUND index, developed to estimate medium-term mortality in multimorbid patients, and serum albumin, an established biomarker of nutritional and inflammatory status, may provide complementary prognostic information. This formed the aim of the present study. This study’s objective is to evaluate the individual and combined prognostic value of the PROFUND index and serum albumin for one-year mortality in patients admitted with AHF. Methods: We conducted a prospective, multicenter cohort study within the PROFUNDIC registry. We included consecutive adults hospitalized with AHF or decompensated chronic heart failure who met European Society of Cardiology diagnostic criteria and had NT-proBNP levels >1500 pg/mL. PROFUND scores were obtained at admission, and hypoalbuminaemia was dichotomized as ≤3.5 g/dL. The primary outcome was one-year mortality, analyzed using Kaplan–Meier survival estimates, Cox proportional hazards models, and time-dependent ROC curves. Results: Among 544 included patients (mean age 85 years; 60% women), high PROFUND scores (>7) were present in 39% and hypoalbuminaemia in 55%. Both variables independently predicted one-year mortality, with the highest risk observed in patients presenting both high PROFUND scores (HR 2.26; 95% CI 1.66–3.09; p < 0.001) and hypoalbuminaemia (HR 1.70; 95% CI 1.18–2.46; p = 0.0046). The combined use of these markers modestly improved discriminatory performance compared with the PROFUND index alone (HR 2.83; 95% CI 1.72–4.64; p < 0.000). Conclusions: These findings suggest that integrating clinical complexity, assessed by the PROFUND index, with serum albumin provides a simple and clinically meaningful approach to early risk stratification in very elderly multimorbid patients treated in internal medicine wards. Full article

Background: Liver biopsy remains the gold standard for staging chronic hepatitis B (CHB), yet it is invasive, costly, and associated with potential complications. There is a critical need for non-invasive, cost-effective biomarkers to monitor disease progression. This study aimed to evaluate the correlation between the Prognostic Nutritional Index (PNI) and Systemic Immune–Inflammatory Index (SII) with histological fibrosis stages and the Histological Activity Index (HAI) in patients with CHB. Methods: This retrospective study analyzed 274 patients diagnosed with CHB (HBsAg positivity > 6 months) who underwent liver biopsy at the University of Health Sciences, Kanuni Sultan Süleyman Training and Research Hospital between February 2016 and February 2022. Histopathological findings were staged using the Ishak fibrosis score and HAI. PNI and SII were calculated from peripheral blood parameters. Statistical discrimination power was assessed using Area Under the Receiver Operating Characteristic (AUROC) curves. Results: The cohort comprised 119 females (43.4%) and 155 males (56.6%), with a mean age of 45.25 ± 11.2 years. Mean values were 55.83 ± 5.33 for PNI and 494.37 ± 336.86 for SII. Fibrosis distribution showed 56.2% at stages F0–F1 and 43.8% at ≥F2. For fibrosis staging, SII demonstrated statistically significant but limited predictive ability for Ishak scores ≥F2, while PNI was significant for identifying advanced fibrosis (≥F4) (p < 0.05). SII showed moderate diagnostic performance for severe inflammation (HAI ≥12; AUROC = 0.848), although this finding should be interpreted cautiously. For lower HAI thresholds (≥6), both PNI and SII demonstrated poor discriminative ability (AUROC 0.5–0.6). Conclusions: Both indices were associated with histological parameters but showed limited overall diagnostic performance. SII appeared relatively better; however, this was descriptively observed without formal statistical comparison. These markers may provide complementary information but should not be used as standalone diagnostic tools. Full article

Background: Actinic keratoses (AKs) are considered early in situ forms of cutaneous squamous cell carcinoma (cSCC). However reliable histopathological or molecular markers for predicting the risk of progression are still lacking. The aim of this study was to investigate the relationship between immunohistochemical markers and basal proliferation patterns of AKs in order to identify histopathological associations that may be relevant for malignant transformation. Methods: A total of 97 AK samples from facial and scalp areas were retrospectively analyzed and classified according to their basal proliferation pattern (Pro I: non-proliferative and Pro III: proliferative). Immunohistochemical staining was performed for Ki-67, p53, p16 and podoplanin. In addition, histopathological parameters such as Röwert-Huber grade, inflammatory infiltrate, parakeratosis, elastosis and the presence of acantholysis were evaluated. Results: Pro III lesions were significantly more frequently associated with higher Röwert-Huber grades (AK III: 47.9% vs. 14.3%; p = 0.0004) and with acantholysis (p = 0.0004). No significant differences between the groups were found for Ki-67, p53 and p16. Podoplanin expression, however, was significantly higher in Pro III lesions (93.7% vs. 57.1%, p < 0.0001) and was predominantly localized basally. The combination of a PRO III pattern and podoplanin positivity identified a distinct histopathological subgroup associated with features linked to progression. Conclusions: Podoplanin expression, especially in combination with PRO III pattern and acantholysis, characterizes a histologically and biologically distinct AK subgroup. In contrast, Ki-67, p53 and p16 showed no additional discriminative value in this cohort. Podoplanin could therefore be a useful addition to existing classification systems and in the future support risk-adapted treatment decision. However, prospective longitudinal studies are required to determine its prognostic value. Full article

Sepsis-associated acute kidney injury (SA-AKI) remains a major diagnostic challenge in critically ill patients, as conventional functional criteria—serum creatinine and urine output—often detect AKI after clinically relevant pathophysiological derangement has already evolved. Increasing evidence suggests that SA-AKI reflects a heterogeneous process characterized by early cellular stress, microcirculatory dysfunction, inflammation-associated injury, and maladaptive repair preceding overt functional decline. In this context, biomarker-based approaches have been investigated to improve early risk stratification, phenotypic characterization, and prognostic assessment in septic patients. This narrative review synthesizes current evidence on established and emerging biomarkers relevant to SA-AKI, encompassing stress markers ([TIMP-2]•[IGFBP7]), tubular injury markers (e.g., NGAL, KIM-1, IL-18), functional markers (e.g., proenkephalin/penKid, cystatin C), and exploratory molecular signatures such as circulating microRNAs (miRNAs). We examine their temporal dynamics, performance estimates, and context-dependent applicability in sepsis, and discuss limitations related to heterogeneity, assay variability, and threshold standardization. Particular attention is given to multimodal and longitudinal strategies integrating biomarkers with KDIGO criteria and clinical phenotyping. Finally, we outline a stratified framework for biomarker interpretation in SA-AKI anchored to pathophysiological windows and clinical decision points. While available evidence supports the potential of selected biomarkers for short-term risk stratification and trajectory assessment, implementation requires prospective validation demonstrating incremental value beyond established models and measurable impact on patient-centered outcomes. Full article