Alterations in body composition are highly prevalent in older adults with chronic kidney disease (CKD) and may contribute to adverse health outcomes. In particular, the coexistence of sarcopenia and obesity-referred to as sarcopenic obesity-has emerged as a potentially high-risk nutritional phenotype. However, it remains unclear whether sarcopenia and obesity exert synergistic or merely additive effects on estimated geriatric risk in older adults with CKD. This cross-sectional study included 222 older adults (aged ≥ 70 years) with CKD (defined as estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and/or albuminuria ≥ 30 mg/g) who underwent comprehensive geriatric assessment and multimodal body composition evaluation. Sarcopenia was defined according to EWGSOP2 criteria using muscle strength and muscle mass assessed by bioelectrical impedance analysis and computed tomography. Obesity was defined as body mass index ≥ 30 kg/m2. Participants were classified into four body composition phenotypes: no sarcopenia/no obesity, obesity only, sarcopenia only, and sarcopenic obesity. Estimated 10-year mortality and disability risks were calculated using validated geriatric risk indices. Outcomes represent estimated risk scores rather than observed clinical events. Sarcopenia-related phenotypes were associated with higher estimated mortality risk (p < 0.001) and disability risk (p = 0.046). In multivariable analyses, lower eGFR, lower serum albumin, sarcopenia, and obesity were each independently associated with higher estimated mortality risk, whereas the interaction between sarcopenia and obesity was not significant, suggesting additive rather than synergistic effects. For disability risk, serum albumin was the only independent predictor; sarcopenia was not independently associated with estimated disability risk in the adjusted model. In this cross-sectional study of older adults with CKD, sarcopenia and obesity were independently associated with higher estimated mortality risk scores, with sarcopenia showing a stronger association. These exploratory findings support further evaluation of muscle-centered nutritional assessment beyond BMI in older adults with CKD, though prospective studies with observed clinical outcomes are needed to confirm these associations.

Obesity and type 2 diabetes mellitus are increasingly recognized as important risk factors for cancer development and progression, including cancers of the digestive system. Indeed, epidemiologic evidence demonstrated that both conditions increase the risk of digestive system cancer incidence and mortality, although with sex-specific and ethnic variations for certain associations with specific types of cancers. While these associations were quite consistent, study design and quality differences, lack of uniform adjustment for confounding factors, heterogeneity and various biases require caution when interpreting the results. The intricate processes by which these two closely related metabolic diseases contribute to carcinogenesis involve increased substrate availability and metabolic dysregulation that create a cellular microenvironment permissive to the activation of multiple signaling pathways that contribute to tumor growth and proliferation. This review thoroughly explores the complex interplay of metabolic and inflammatory mechanisms underlying these processes, including hyperglycemia, insulin resistance, altered insulin‑like growth factor-1 signaling, dysregulated adipokines, hormonal imbalance, gut dysbiosis, chronic inflammation and altered immune response, altered mitochondrial function and oxidative stress, circadian rhythm disruption, altered autophagy. Nevertheless, most mechanistic evidence derives from in vitro systems or non-human animal models which may not fully replicate human pathophysiology and disease, and thus extrapolation to human cancer risk should be made cautiously. Given this complex mechanistic interplay, it is evident that obesity and T2DM-associated metabolic alterations play an important role in carcinogenesis, highlighting the need for targeted prevention strategies in high-risk populations, such as weight management and glycemic control, to mitigate cancer burden.

Background: Vitamin D deficiency is highly prevalent in older adults and has been increasingly recognised as a potential contributor to cognitive decline, depressive symptomatology, and functional impairment. However, the clinical significance of specific 25-hydroxyvitamin D thresholds in relation to this multidomain geriatric phenotype remains incompletely characterised. Methods: We conducted a cross-sectional study of 1438 consecutive patients aged 65 years or older admitted for comprehensive geriatric assessment at a tertiary centre in Cluj-Napoca, Romania, between January 2023 and November 2025. Serum 25-hydroxyvitamin D [25(OH)D] was categorised as deficient (<20 ng/mL), insufficient (20-30 ng/mL), or sufficient (≥30 ng/mL). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), depressive symptoms using the Geriatric Depression Scale (GDS-30 and GDS-SF), and functional status using Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL). Multivariable linear regression analyses were adjusted for age, body mass index, serum albumin, and estimated glomerular filtration rate (eGFR). Results: Suboptimal vitamin D status was highly prevalent in this geriatric cohort, with 43.3% of participants meeting criteria for frank deficiency (<20 ng/mL). Lower 25(OH)D concentrations were significantly associated with worse cognitive performance, greater depressive symptom burden, and higher functional dependency. Serum 25(OH)D correlated positively with MoCA and MMSE scores and inversely with ADL, IADL, and GDS scores. In adjusted models, vitamin D remained independently associated with MoCA, IADL, and GDS. Stratified analyses suggested that the main clinical deterioration occurred below 20 ng/mL, while the 20-30 ng/mL range behaved as an intermediate phenotype closer to sufficiency than to frank deficiency. Conclusions: In this large cohort of hospitalised older adults, serum 25(OH)D deficiency below 20 ng/mL was independently associated with poorer cognition, more depressive symptoms, and greater functional impairment. These findings support routine vitamin D assessment in geriatric practice and suggest that the <20 ng/mL threshold identifies a clinically relevant high-risk phenotype.

Background: Sarcopenia is highly prevalent in older adults and in individuals with impaired kidney function, where it is associated with adverse clinical outcomes. A creatinine-cystatin C-based sarcopenic index has been proposed as a surrogate marker of muscle status; however, its association with sarcopenia as defined by the EWGSOP2 framework, particularly in the context of renal dysfunction, remains uncertain. Methods: Older adults were classified according to EWGSOP2 criteria into probable, confirmed, and severe sarcopenia. Associations between the sarcopenic index and sarcopenia phenotypes were examined using group comparisons and multivariable logistic regression analyses in the overall cohort and in a subgroup of participants with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2). Results: The sarcopenic index was not independently associated with probable, confirmed, or severe sarcopenia. In contrast, age emerged as the strongest independent correlate of probable sarcopenia (OR 1.12; 95% CI 1.05-1.19, p = 0.001), while body mass index was independently associated with confirmed sarcopenia (OR 0.91; 95% CI 0.86-0.96, p < 0.001). Similar patterns were observed in participants with reduced kidney function. Conclusions: Within the present analytical framework, the sarcopenic index did not show a meaningful association with EWGSOP2-defined probable sarcopenia, the most uniformly assessable EWGSOP2 stage, in older adults, including those with reduced kidney function. Exploratory analyses of more advanced sarcopenia stages did not reveal additional associative information. These findings should be interpreted within a descriptive and associative framework rather than a formal assessment of diagnostic or clinical decision-making performance.

Background/Objectives: Sarcopenia is a progressive decline in skeletal muscle strength and mass, leading to decreased functionality, metabolic disorders, morbidity, and mortality. There are a number of sarcopenia screening tools, such as the SARC-F questionnaire (that includes noting strength, assistance with walking, ability to raise from the chair, climb stairs, and falls), with its augmented forms that have added calf circumference (SARC-CalF), BMI and age (SARC-F + EBM), and the Ishii score, which show variable performance across populations. However, these were developed and validated mostly in Asian cohorts. To evaluate the diagnostic accuracy of these tools for the European Working Group on Sarcopenia in Older People (EWGSOP2), as well as define sarcopenia in hospitalized East European older adults, with sex and obesity stratification. Methods: Sarcopenia was diagnosed using the EWGSOP2. ROC analyses with DeLong tests assessed SARC-F, SARC-CalF, SARC-F + EBM, and the Ishii score in 278 Romanian inpatients (probable sarcopenia n = 201/278, 72.3%; confirmed n = 77/278, 27.7%). Results: Probable sarcopenia was noted as good-excellent discrimination against across all tools (AUCs 0.764-0.812); confirmed sarcopenia was noted as SARC-CalF superior (AUC = 0.743), followed by SARC-F + EBM (0.697), the Ishii score as moderate (0.667), and SARC-F was limited (0.591; p < 0.001 vs. augmented). SARC-CalF optimal cut-offs varied significantly: 4-6 (probable) vs. ≥11 (confirmed). Sex-stratified outcomes had excellent probable detection in both sexes, and this was confirmed to be superior in men. The Ishii score thresholds were 152/244 vs. Asian ≥ 105/120. Obesity required higher cut-offs with high NPVs (77-100%), confirming rule-out utility and SARC-F + EBM performing the best, both in the obesity and sarcopenic obesity subgroups (AUCs 0.742, 0.964). Conclusions: Augmented SARC-F scores outperformed the original SARC-F for confirmed sarcopenia in multimorbid Europeans, with SARC-F CalF having the best performance overall. Population-specific (sex/obesity) data-driven thresholds are essential, especially for the Ishii score, as this first Romanian validation reveals limitations of Asian norms in European cohorts, thus advocating for European recalibration.

BACKGROUND/OBJECTIVES:Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous condition shaped by metabolic dysfunction, adipose tissue distribution, inflammatory activation, and body composition. Understanding how these factors interact across distinct clinical phenotypes is essential for improving diagnostic accuracy and risk stratification. This study aimed to compare metabolic, inflammatory, and elastographic profiles between MASLD subgroups defined by adipose tissue dysfunction (ATD) and obesity, and to identify pathways linking metabolic dysregulation to hepatic fibrosis. METHODS:We conducted a cross-sectional observational study including 178 adult participants evaluated clinically, biochemically, and by bioimpedance and shear wave elastography. Participants ranged in age from 19 to 82 years. Patients were stratified into a non-MASLD control group and two MASLD subgroups: MASLD with ATD (G1) and MASLD with obesity (G2). Anthropometric data, lipid profile, glycemic markers, cytokines (IL-6, IL-10, TNF-α), liver stiffness, and non-invasive fibrosis indices were compared across groups using standard statistical testing. RESULTS:Patients with MASLD showed higher liver stiffness, triglycerides, and IL-6/IL-10 levels than controls. Between MASLD phenotypes, the ATD group (G1) exhibited a more inflammatory and dysmetabolic profile, with significantly higher triglycerides, IL-6 levels, neutrophil counts, and creatinine, alongside trends suggesting early sarcopenic changes. In contrast, the obese phenotype (G2) demonstrated greater hepatic structural involvement, including higher liver stiffness and BMI, AST/ALT ratio and Diabetes (BARD) scores, despite more favorable inflammatory parameters. Several associations between liver stiffness, IL-6, and glycemic control approached but did not reach statistical significance. CONCLUSIONS:MASLD progression appears to follow two complementary but distinct mechanisms: an inflammatory, adipose dysfunction pathway dominated by IL-6 activation and early anabolic decline, and a metabolic-overload pathway driven by obesity. Phenotype-specific evaluation integrating inflammatory markers, metabolic indices, and elastographic parameters may improve risk stratification and inform personalized therapeutic strategies.

Background:The global population is rapidly aging, and an epidemic increase in chronic kidney disease (CKD) has been reported. As the presence of malnutrition in elderly CKD patients can pose serious health problems, the aim of our study was to identify, using different assessment tools, the relationship between nutrition with kidney function and albuminuria in elderly patients. Methods: The study included 793 hospitalized patients aged 65 years and older. A comprehensive assessment of nutritional status and renal involvement was performed, and the relationship between malnutrition and kidney issues was tested. Results: CKD was highly prevalent in our geriatric population, with 39.84% having CKD G3a–5. Malnutrition, determined according to the Mini Nutritional Assessment (MNA) score, was identified in 34.6% of patients. With an increase in albuminuria, we observed worse nutrition indicators: low serum albumin; lower body fat (p = 0.002) and visceral fat (p = 0.001), assessed via bioimpedance; and lower MNA (p = 0.04) and geriatric nutritional risk index (GNRI) (p = 0.002) scores. Elderly patients with CKD G3a–5 had lower HDL-cholesterol (p < 0.001), higher triglycerides (p < 0.001), lower albumin (p = 0.011), and a lower MNA score (p = 0.001). Conclusions: Malnutrition was found to be common and more severe with increased albuminuria and decreased eGFR. Our study sheds light on a novel relationship between malnutrition, albuminuria, and renal function in a geriatric population.

BACKGROUND AND AIMS:Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer-related mortality, a figure that is on the rise. The shared hallmark of different etiologies, progression, and HCC survival is chronic inflammation, making it a significant field of interest for prognostic and therapeutic strategies. We aimed to evaluate the prognostic accuracy of several inflammation-based scores in HCC. METHODS:A consecutive series of patients at their first HCC diagnosis were enrolled during a 5-year timespan in a prospectively maintained multicentric database. Demographic, clinical, biological, and imagistic data were collected. Representative inflammation-based prognostic scores, including the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic immune inflammation index (SII), prognostic nutritional index (PNI), albumin-to-bilirubin index (ALBI), platelet-albumin-bilirubin-index (PALBI), AST-to-lymphocyte ratio (ALRI), AST/ALT, AST-to-platelet ratio (APRI) were assessed for prediction of overall survival (OS) in a scenario-based setting, using Kaplan-Meier curves, univariate and multivariate analyses. RESULTS:A total of 467 patients from five tertiary-care hospitals were enrolled in this study. The median age was 64.94 years, and the most frequent etiology of the liver disease was hepatitis C (50%). During a median of 14.85 (35) months of follow-up, the cumulative mortality was 84.8%. In the univariate analysis, PNI (HR=2.414; p=0.021), ALBI grade (HR=2.023; p<0.001), and PALBI grade (HR=2.022; p<0.001) demonstrated the highest prognostic accuracies for OS in HCC, regardless of the clinical scenario. Moreover, PLR (HR=1.635; p=0.002), ALRI (HR=1.555; p<0.001), NLR (HR=1.461; p=0.007), AST/ALT (HR=1.420; p=0.012), and APRI (HR=1.356; p=0.009) were also significant prognostic factors for OS. The multivariate analysis showed that only ALBI grade (HR=1.974; p<0.001), SII (HR=1.487; p=0.009), and PLR (HR=1.647; p=0.014) were independently associated with OS. CONCLUSIONS:Inflammation-based scores allow for an accurate prediction of survival in HCC. Their ability to predict the response to treatment and complications merits further investigation.

The connections between sarcopenia and various chronic conditions, including type 2 diabetes (T2DM), metabolic syndrome (MetS), and liver disease have been highlighted recently. There is also a high occurrence of sarcopenia in metabolic dysfunction-associated steatotic liver disease (MASLD) patients, who are often disregarded. Both experimental and clinical findings suggest a complex, bidirectional relationship between MASLD and sarcopenia. While vitamin D, testosterone, and specific drug therapies show promise in mitigating sarcopenia, consensus on effective treatments is lacking. Recent focus on lifestyle interventions emphasizes dietary therapy and exercise for sarcopenic obesity in MASLD. Challenges arise as weight loss, a primary MASLD treatment, may lead to muscle mass reduction. The therapeutic approach to sarcopenia in morbidly obese MASLD patients also includes bariatric surgery (BS). BS induces weight loss and stabilizes metabolic imbalances, but its impact on sarcopenia is nuanced, underscoring the need for further research. Our aim is to provide a comprehensive review of the interplay between sarcopenia and MASLD and offer insight into the most recent therapeutic challenges and discoveries, as sarcopenia is often overlooked or unrecognized and poses significant challenges for managing these patients.

Background/Objectives: Colorectal cancer (CRC) represents one of the most prevalent forms of cancer, with high mortality rates. The aim of this study was to observe and understand the metabolic changes in CRC through targeted metabolomics. Methods: Samples collected from 58 CRC patients and 35 healthy individuals have been analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), targeting two classes of metabolites: amino acids and acylcarnitines. Results: Statistical analysis revealed 26 significantly modified (p-value < 0.01; |FC| > 1.2) metabolites in CRC patients compared to the control group and 22 between colon cancer and control, whereas 8 metabolites differed only significantly between rectal cancer and healthy patients. Some of these significantly modified metabolites characterize cancer-specific adaptations, such as increased energy demand, increased tumor invasiveness, capabilities to promote amino acid synthesis, and tumor resistance against acute immune response. Moreover, receiver operator characteristic (ROC) analysis revealed that a set of two acylcarnitines (C6DC and C4-OH) can differentiate between CRC patients and healthy individuals with a high degree of confidence (AUC 0.837). Conclusions: By implementing a metabolomics approach targeting amino acids and acylcarnitines, several metabolic alterations induced by CRC have been highlighted. Even though these modifications are not specific enough to act as disease markers, they might prove useful for evaluating patient status.

Objectives: To evaluate the individual and combined impact of sarcopenia (SARC) and heart failure (HF) on functional performance, systemic biomarkers, and structural cardiac changes in hospitalized older adults. A total of 598 patients aged ≥65 years admitted to a geriatric unit between January 2023 and December 2024, stratified into four groups based on the presence or absence of sarcopenia and HF. Methods: Muscle strength (handgrip), gait speed, SPPB score, and calf circumference were assessed, along with inflammatory/nutritional markers and echocardiographic parameters. Sarcopenia was diagnosed according to EWGSOP2 criteria and HF was diagnosed according to ESC 2021 guidelines. Results: Functional impairment was the most severe in the SARC+/HF+ group, with significantly lower handgrip strength, gait speed, and SPPB scores (p < 0.001). Sarcopenia alone was associated with greater functional decline than HF alone. Serum hemoglobin and albumin levels were reduced in sarcopenic groups, while NT-proBNP and cardiac remodeling indices (IVS and LVEDD) were highest in patients with both conditions. Conclusions: Sarcopenia exerts a significant impact on physical performance in older adults, surpassing that of HF in isolation. The coexistence of sarcopenia and HF amplifies vulnerability and clinical decline, supporting the need for integrated assessment and early muscle-targeted interventions in geriatric cardiology.

This study investigates the association between the Functional Health Pattern Assessment Screening Tool (FHPAST) and frailty in hospitalized geriatric patients. One hundred and forty patients (mean age 78.2 years, age range 65–90) were screened for frailty using the Frail Scale during hospitalization in the geriatric unit. Among them, 57 patients were identified as prefrail (40.7%), and 83 were identified as frail (59.3%). A comparative analysis between groups in terms of the FHPAST components covering health risk, general well-being, and health promotion was performed. Correlations between FHAPST components, socio-demographic data, frailty criteria, as well as logistic regression to identify variables that better predict frailty were also sought. Frailty was mainly associated with difficulty urinating, limitations in performing activities of daily living and walking, physical discomfort, less positive feelings in controlling one’s own life, lower compliance with recommendations from the healthcare provider, and engagement in seeking healthcare services. Patients with difficulty urinating and walking had a probability of 4.38 times (OR = 4.38, CI 95% [1.20–15.94]), p = 0.025) and 65.7 times (OR = 65.7, CI 95% [19.37–223.17], p < 0.001) higher of being frail rather than prefrail. The relationship between frailty and prefrailty in hospitalized geriatric patients and components of nursing Functional Health Patterns (FHP) has yet to be explored. This study provides evidence of the most prevalent needs of frail geriatric patients in hospital settings.

Background: Europe’s largest ethnic minority, the Roma, are often confronted with substantial obstacles that result in health disparities. Research indicates that there are elevated rates of both communicable and non-communicable diseases, such as metabolic syndrome (MetS), among Roma communities, often linked to living conditions, limited education, or poverty. This study centers on remote rural Roma settlements in Romania, evaluating the prevalence of metabolic dysfunction, obesity, and liver steatosis while considering socio-economic and lifestyle factors. Methods: Over a period of 36 months, local visits to a total of 25 rural Roma communities were conducted, where a medical team gathered information through a standardized questionnaire and conducted a physical exam on every participant. Liver steatosis was also recorded with the help of a portable wireless ultrasound device. Results: Our study included 343 participants, with a predominance of female subjects, representing 72.5% (n = 249) of the patients. The prevalence of obesity, defined by a body mass index (BMI) above 30 kg/m2, was 32.2% (n = 111). Arterial hypertension was found to have a prevalence of 54.1% (n = 185), with de novo hypertension being observed in 19.2% patients (n = 66). Type 2 diabetes mellitus was found in 28.9% patients (n = 99), with 19.5% being de novo cases. The prevalence of hepatic steatosis was 57.2% (n = 111/194). A positive association between metabolic features and at-risk behaviors was found. Conclusions: This study underscores the transition from infectious to metabolic diseases in vulnerable communities and highlights the urgency of targeted public health strategies tailored to the unique needs of rural Roma populations, aiming to mitigate health disparities and promote equitable healthcare access.

Background and Objectives: The global demographic trend of population aging is evident across all regions, with a notable increase in the proportion of elderly individuals. Romania exemplifies this phenomenon, as 17% of its population is currently aged 65 years or older—a figure projected to rise to 25% by 2050. This demographic shift underscores the pressing need for comprehensive measures to address the health and social requirements of this growing population segment. This study aims to assess the prevalence of frailty among older adults in Romania and explore its relationship with socioeconomic factors. Materials and Methods: We employed a quantitative approach, by using cross-sectional data from patients hospitalized at the geriatrics ward of the Municipal Clinical Hospital in Cluj-Napoca, Romania. Frailty scores were calculated through established frailty assessment tools, allowing for a comprehensive evaluation of frailty status. In addition, we compared the socioeconomic characteristics of frail and non-frail patients to identify potential disparities. Statistical analyses were performed to assess associations between frailty and socioeconomic factors, providing insight into the relationship between these variables within the patient population. Results: The prevalence of frailty in our sample is, depending on the frailty scale used, 55% to 79%, which is in line with figures from specialized geriatric wards in other studies. There is moderate to substantial agreement between the scales we compared, and all six scales seem to concurrently agree on the frailty diagnostic in 55% of cases. Additionally, frail patients are more likely to have a low socioeconomic status. Conclusions: A significant limitation in European frailty research has been the absence of comparative frailty prevalence data across several European countries, especially those with lower economic development. Our study fills this gap by providing data on frailty prevalence in the north-western region of Romania.

More than half of patients hospitalized with liver cirrhosis are dealing with an episode of acute kidney injury; the most severe pattern is hepatorenal syndrome due to its negative prognosis. The main physiopathology mechanisms involve renal vasoconstriction and systemic inflammation. During the last decade, the definition of hepatorenal syndrome changed, but the validated criteria of diagnosis are still based on the serum creatinine level, which is a biomarker with multiple limitations. This is the reason why novel serum and urinary biomarkers have been intensively studied in recent years. Meanwhile, the imaging studies that use shear wave elastography are using renal stiffness as a surrogate for an early diagnosis. In this article, we focus on the physiopathology definition and highlight the novel tools used in the diagnosis of hepatorenal syndrome.

Heart failure (HF) with preserved ejection fraction (HFpEF) is an increasingly frequent form and is estimated to be the dominant form of HF. On the other hand, HFpEF is a syndrome with systemic involvement, and it is characterized by multiple cardiac and extracardiac pathophysiological alterations. The increasing prevalence is currently reaching epidemic levels, thereby making HFpEF one of the greatest challenges facing cardiovascular medicine today. Compared to HF with reduced ejection fraction (HFrEF), the medical attitude in the case of HFpEF was a relaxed one towards the disease, despite the fact that it is much more complex, with many problems related to the identification of physiopathogenetic mechanisms and optimal methods of treatment. The current medical challenge is to develop effective therapeutic strategies, because patients suffering from HFpEF have symptoms and quality of life comparable to those with reduced ejection fraction, but the specific medication for HFrEF is ineffective in this situation; for this, we must first understand the pathological mechanisms in detail and correlate them with the clinical presentation. Another important aspect of HFpEF is the diversity of patients that can be identified under the umbrella of this syndrome. Thus, before being able to test and develop effective therapies, we must succeed in grouping patients into several categories, called phenotypes, depending on the pathological pathways and clinical features. This narrative review critiques issues related to the definition, etiology, clinical features, and pathophysiology of HFpEF. We tried to describe in as much detail as possible the clinical and biological phenotypes recognized in the literature in order to better understand the current therapeutic approach and the reason for the limited effectiveness. We have also highlighted possible pathological pathways that can be targeted by the latest research in this field.

Background and Aims: Hepatocellular carcinoma (HCC) is a significant public health issue, with an increasing incidence and prevalence and a high incidence-to-mortality ratio. The prognosis of HCC depends on two competing factors, tumor burden and underlying liver disease severity, encompassed in the Barcelona Clinic Liver Cancer (BCLC) classification. To assess HCC staging and the way staging affects eligibility for treatment at the time of the first diagnosis in Romania in the setting of opportunistic diagnosis, in the absence of a national HCC screening policy. Methods: Data regarding HCC staging, underlying liver disease, and eligibility for treatment at the time of diagnosis was analyzed using a prospectively maintained multicentric database, which included patients from the five largest tertiary care hepatology units in the country between June 2016 and February 2020. Results: A consecutive series of 477 patients was included. The distribution within BCLC classes was as follows: very early (0) 7.1%, early (A) 34.3%, intermediate (B) 19.4%, advanced (C) 14.2%, terminal (D) 24.7%. At the time of the diagnosis, 198 (41.5%) were eligible for a curative intent treatment, while 359 (75.2%) were eligible for a disease-modifying therapy. 228 patients (47.8%) had decompensated liver disease at the time of diagnosis, the most common decompensating event being ascites (78.1%). Conclusions: A large proportion of HCC cases are diagnosed at the time of a decompensating event, severely restricting the therapeutic potential. Proactive diagnostic strategies should be implemented to improve the rate of actionable diagnosis.

Previously, we showed that skin-derived ABCB5+mesenchymal stem cells (MSCs) upon exposure with infection mimicking lipopolysaccharide (LPS) fundamentally shift their transcriptome with high expression and the release of neutrophil activating chemokines. This adaptive response resulted in a significant increase in neutrophil expulsed DNA traps (NETs) and proteolytic enzymes which guarantees the defense from bacterial attack. Wound healing decreases with age and the propensity for infection dramatically increases. We here set out to address the question whether skin-derived MSCs from old healthy donors (> 60 years) unlike young healthy donors (< 30 years) may change their adaptive response upon LPS exposure towards a reduced microbicidal response. Young and old LPS primed MSCs revealed profound differences of NF-κB translocation from the cytoplasm to the nucleus where it transactivates neutrophil activating target genes among others. By contrast to young MSCs, old MSCs depicted a significantly delayed back-regulation of NF-κB. This correlates with p-p65 expression, indicative of NF-κB activation and the prolonged higher expression of NF-κB target genes like IL-6 in MSCs from elderly individuals. Notably, LPS primed young MSCs revealed high concentrations of IL-8 and GCP-2,neutrophil activating peptides, an increase in the anti-microbial peptide LL-37 and increased expulsion of NETs as opposed to old MSCs. Collectively, we here uncovered a previously unreported, dysregulated anti-bacterial response in LPS-primed MSCs from old individuals with an impressively reduced killing ability of gram negative bacteria like E.coli, P. aeruginosa and the gram-positive S. aureus. These findings highlight dysregulated MSCs from old individuals to distinctly contribute to higher susceptibility for severe local and systemic infections in elderly.