Unveiling Health Inequalities: Exploring Metabolic Dysfunction in Rural Roma Communities.

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.

Increased type-I interferon level is associated with liver damage and fibrosis in primary sclerosing cholangitis.

BACKGROUND: The level of type-I interferons (IFNs) in primary sclerosing cholangitis (PSC) was investigated to evaluate its association with disease activity and progression. METHODS: Bioactive type-I IFNs were evaluated in a murine model of PSC and human patients' sera using a cell-based reporter assay and ELISA techniques. In total, 57 healthy participants, 71 PSC, and 38 patients with primary biliary cholangitis were enrolled in this study. RESULTS: Bioactive type-I IFNs were elevated in the liver and serum of multidrug resistance protein 2-deficient animals and showed a correlation with the presence of CD45+ immune cells and serum alanine transaminase levels. Concordantly, bioactive type-I IFNs were elevated in the sera of patients with PSC as compared to healthy controls (sensitivity of 84.51%, specificity of 63.16%, and AUROC value of 0.8267). Bioactive IFNs highly correlated with alkaline phosphatase (r=0.4179, p<0.001), alanine transaminase (r=0.4704, p<0.0001), and gamma-glutamyl transpeptidase activities (r=0.6629, p<0.0001) but not with serum bilirubin. In addition, patients with PSC with advanced fibrosis demonstrated significantly higher type-I IFN values. Among the type-I IFN subtypes IFNα, ß and IFNω could be detected in patients with PSC with IFNω showing the highest concentration among the subtypes and being the most abundant among patients with PSC. CONCLUSIONS: The selectively elevated bioactive type-I IFNs specifically the dominating IFNω could suggest a novel inflammatory pathway that might also have a hitherto unrecognized role in the pathomechanism of PSC.

Don't Judge a Book by Its Cover: The Role of Statins in Liver Cancer.

Statins, which are inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, are an effective pharmacological tool for lowering blood cholesterol levels. This property makes statins one of the most popular drugs used primarily to prevent cardiovascular diseases, where hyperlipidemia is a significant risk factor that increases mortality. Nevertheless, studies conducted mainly in the last decade have shown that statins might prevent and treat liver cancer, one of the leading causes of cancer-related mortality worldwide. This narrative review summarizes the scientific achievements to date regarding the role of statins in liver tumors. Molecular biology tools have revealed that cell growth and proliferation can be inhibited by statins, which further inhibit angiogenesis. Clinical studies, supported by meta-analysis, confirm that statins are highly effective in preventing and treating hepatocellular carcinoma and cholangiocarcinoma. However, this effect may depend on the statin's type and dose, and more clinical trials are required to evaluate clinical effects. Moreover, their potential hepatotoxicity is a significant caveat for using statins in clinical practice. Nevertheless, this group of drugs, initially developed to prevent cardiovascular diseases, is now a key candidate in hepato-oncology patient management. The description of new drug-statin-like structures, e.g., with low toxicity to liver cells, may bring another clinically significant improvement to current cancer therapies.

PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for patients with intrahepatic cholangiocarcinoma.

Cholangiocarcinoma, the second most common liver malignancy, after hepatocarcinoma is highly aggressive and usually diagnosed in advanced cases. In the era of personalized medicine, targeted therapy protocols are limited for cholangiocarcinoma and the only potential curative treatment, surgical resection, is seldom applicable.This retrospective study included all cases with pathology-confirmed intrahepatic cholangiocarcinoma admitted in a tertiary healthcare facility during a 10-year timeframe. Clinical information, laboratory values, imaging studies, and survival data were retrieved, and PD-L1 immunostaining was performed on representative pathology slides, for each case. From the total of 136 included cases (49 surgical resections and 87 liver biopsies), 38.97% showed PD-L1 positivity on tumoral cells, 34.8% on tumor infiltrating immune cells, 10.11% on epithelial cells within the peritumoral area and 15.95% on immune cells from the peritumoral area. Overall survival was significantly higher in the first two scenarios. However, after adjusting for age, tumor number, tumor size, and tumor differentiation in a multivariate analysis, only PD-L1 positivity on tumor infiltrating immune cells remained a favorable prognostic for survival. High immune cell counts also correlated with increased overall survival.Our study demonstrated that PD-1/PD-L1 checkpoint pathway in the microenvironment of intrahepatic cholangiocarcinoma bears prognostic significance. PD-L1 expression on immune cells, in both resection and biopsy specimens, might be a strong independent predictor for a favorable outcome.

Carbon Nanotubes-Based Assays for Cancer Detection and Screening.

Carbon nanotubes (CNTs) were considered a potential cargo for cancer therapy and diagnosis following researchers' shared goal of finding a new delivery system to enhance the pharmacological performance of the administered drugs. To date, several excellent reviews have focused on the role of CNTs as drug delivery systems, although there is currently no existing study that gathers all the advances in research-connected carbon nanotubes-based assay development for the early detection of cancer. In this review article, we will focus on the emerging role of CNTs as anticancer detection agents.

Basic cardiovascular risk assessment in naïve patients with colon cancer.

Cardiovascular assessment of oncological patients suggests that cancer can lead to subclinical damage of the heart. The aim of the present study was to analyze the value of baseline cardiovascular biomarkers in patients with newly diagnosed colon cancer prior to treatment. Additionally, another aim was to establish baseline cut-off alert values for this low-intensity neoplastic damage. A total of 51 patients with newly diagnosed colon cancer, without history of cardiac disease, were enrolled in a prospective, cross-sectional study. All patients underwent clinical, biochemical and basic echocardiographic evaluation before starting treatment. Patients were assessed for myocardial damage using high-sensitivity troponin T (hs-TnT), creatine kinase-MB (CK-MB) and N-terminal-pro B-type natriuretic peptide (NT-proBNP). A group of 28 healthy controls was included for comparison. Cardiac ultrasound revealed similar left ventricular (LV) ejection fraction but enlarged LV chambers compared with the control group (LV at end systole, 29.50 vs. 26.00 mm; LV at end diastole, 44.50 vs. 38.00 mm; P<0.001 in both cases). The levels of cardiovascular biomarkers of myocardial damage were higher in the patients than in the control group (CK-MB, 17.00 vs. 11.00 IU/l, P<0.001; hs-TnT, 8.20 vs. 3.00 ng/l, P<0.001; NT-proBNP, 155.40 vs. 48.50 pg/ml, P=0.001). In multivariate analysis, CK-MB and hs-TnT retained statistical significance (P=0.004 and P=0.045, respectively). Moreover, it was demonstrated that new cut-offs for hs-TnT (8.00 ng/l) and NT-proBNP (220.00 pg/ml) can identify cardiac damage in patients ≥65 years old. Thus, the present study confirmed the hypothesis that a basic cardiovascular assessment of treatment-naïve patients with colon cancer can identify important pre-treatment myocardial impact. Adapted cut-off values should be set for cardiovascular biomarkers in the cancer population, different from those currently accepted for acute coronary syndromes or heart failure.

Gastrointestinal Manifestations and Treatment Options in Fabry Disease Patients. A Systematic Review.

BACKGROUND AND AIMS: Fabry disease (FD) is a rare chronic genetic disorder that presents under a paucity of symptoms. Gastrointestinal (GI) involvement is a common event and can sometimes be debilitating, but relatively often it is overlooked. We aimed to provide a systematic review of main GI symptoms in FD patients and treatment possibilities. METHODS: We completed a systematic review of literature, using the MeSH terms: "Fabry disease", "gastrointestinal", "gastrointestinal", "digestive", "manifestations", "symptoms", "clinical", "treatment", "therapy" and the supplementary concepts "enzyme replacement", "chaperone", "Migalastat", in different combinations, with defined inclusion and exclusion criteria. RESULTS: From 221 initial studies identified, through our selection process we included a final date base of 51 articles on GI signs and symptoms and their treatment. The primary GI manifestations of the disease consist of abdominal pain, bowel movement disorders or nausea and vomiting. Less frequent manifestations such as diverticular bowel disease, gastroesophageal reflux or achalasia have also been described. Main treatment options in FD are represented by enzyme replacement therapy and chaperone treatment. Patients presenting with GI symptoms unfortunately do not always respond to enzyme replacement, necessitating symptomatic relief. CONCLUSION: Fabry disease is a rare disease that often involves the GI tract, affecting patients' quality of life and burdening the healthcare system. Physicians must be aware of the multitude of manifestations in this category of patients, to promptly recognize and treat them.

Digestive Toxicities Secondary to Immune Checkpoint Inhibition Therapy - Reports of Rare Events. A Systematic Review.

BACKGROUND AND AIMS: While immune checkpoint inhibitors therapy (ICI) is exceedingly effective, these drugs are associated with various immune-related adverse effects. As gastrointestinal, hepatic or pancreatic toxicity becomes more common, various reports of rare adverse effects have emerged, leading to a significant clinical and prognostic impact. We aimed to provide a systematic review of mainly case-reports on rare events, to help physicians to make an accurate and fast diagnosis. METHODS: We performed a systematic review of the literature, using established MeSH terms: "immune checkpoint inhibitors", "gastrointestinal tract", "gastrointestinal diseases", "liver", "pancreas", "nivolumab", "ipilimumab", the subheadings "adverse effects", "toxicity" and the supplementary concepts "pembrolizumab", "tremelimumab", "atezolizumab", "avelumab", "durvalumab", with defined inclusion criteria. RESULTS: From 419 manuscripts initially selected, 74 reports of rare adverse events were included in our review. Special cases of neutrophilic gastritis, hemorrhagic gastritis, or even perforations were described at upper digestive tract. Different types of colitis were found secondary to ICI such as pseudomembranous, granulomatous, collagenous and microscopic colitis or even inflammatory bowel disease. In terms of liver toxicity, we found rare reports of cholangitis, granulomatous hepatitis, lipodystrophy and hepatic sinusoidal obstruction syndrome. Pancreas toxicity was rarely reported as severe pancreatitis, exocrine failure and diabetes mellitus. CONCLUSION: Although a complete check-up of every organ at every routine visit may not be practical, focus on symptoms, targeted laboratory and imaging testing may reveal rare organ damage. Raising awareness of the uncommon toxicities related to the immunotherapy is essential, as some rare events can lead to fatal outcomes.

Tetraspanins: Physiology, Colorectal Cancer Development, and Nanomediated Applications.

Tetraspanins are transmembrane proteins expressed in a multitude of cells throughout the organism. They contribute to many processes that surround cell-cell interactions and are associated with the progress of some diseases, including cancer. Their crucial role in cell physiology is often understated. Furthermore, recent studies have shown their great potential in being used as targeting molecules. Data have suggested the potential of tetraspanins as a targeting vector for nanomediated distribution and delivery for colorectal cancer applications. Our aim is to provide a review on the important part that tetraspanins play in the human organism and highlight their potential use for drug delivery systems using nanotechnology.

Recent Advances in Nanoparticle-Mediated Diagnosis and the Treatment of Pancreatic Cancer.

Pancreatic cancer (PC), one of the most lethal solid tumors in humans, has a five-year survival rate of only 4%. Surgical treatment is the only accepted therapy with curative intent because the vast majority of these tumors are chemoresistant. Unfortunately, due to the aggressive nature of these tumors, fewer than 20% are resectable when the first symptoms occur. Novel therapies are required to overcome all these therapeutic issues, and the development of active nanocarriers represents an exciting opportunity to improve PC outcomes. The present review focuses on recent advances in the field of nanotechnology with application in PC treatment.

Biomarkers in Pancreatic Cancer as Analytic Targets for Nanomediated Imaging and Therapy.

As the increase in therapeutic and imaging technologies is swiftly improving survival chances for cancer patients, pancreatic cancer (PC) still has a grim prognosis and a rising incidence. Practically everything distinguishing for this type of malignancy makes it challenging to treat: no approved method for early detection, extended asymptomatic state, limited treatment options, poor chemotherapy response and dense tumor stroma that impedes drug delivery. We provide a narrative review of our main findings in the field of nanoparticle directed treatment for PC, with a focus on biomarker targeted delivery. By reducing drug toxicity, increasing their tumor accumulation, ability to modulate tumor microenvironment and even improve imaging contrast, it seems that nanotechnology may one day give hope for better outcome in pancreatic cancer. Further conjugating nanoparticles with biomarkers that are overexpressed amplifies the benefits mentioned, with potential increase in survival and treatment response.

Liver Injury and Elevated FIB-4 Define a High-Risk Group in Patients with COVID-19.

Liver involvement in Coronavirus Disease 2019 (COVID-19) has been widely documented. However, data regarding liver-related prognosis are scarce and heterogeneous. The current study aims to evaluate the role of abnormal liver tests and incidental elevations of non-invasive fibrosis estimators on the prognosis of hospitalized COVID-19 patients. We conducted a retrospective cohort study to investigate the impact of elevated liver tests, non-invasive fibrosis estimators (the Fibrosis-4 (FIB-4), Forns, APRI scores, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio), and the presence of computed tomography (CT)-documented liver steatosis on mortality in patients with moderate and severe COVID-19, with no prior liver disease history. A total of 370 consecutive patients were included, of which 289 patients (72.9%) had abnormal liver biochemistry on admission. Non-survivors had significantly higher FIB-4, Forns, APRI scores, and a higher AST/ALT ratio. On multivariate analysis, severe FIB-4 (exceeding 3.25) and elevated AST were independently associated with mortality. Severe FIB-4 had an area under the receiver operating characteristic (AUROC) of 0.73 for predicting survival. The presence of steatosis was not associated with a worse outcome. Patients with abnormal liver biochemistry on arrival might be susceptible to a worse disease outcome. An FIB-4 score above the threshold of 3.25, suggestive of the presence of fibrosis, is associated with higher mortality in hospitalized COVID-19 patients.

Epidermal Growth Factor Receptor and Its Role in Pancreatic Cancer Treatment Mediated by Nanoparticles.

Pancreatic adenocarcinoma (PDAC) is a disease with a high incidence and a dreary prognosis. Its lack of symptomatology and late diagnosis contribute to the dearth and inefficiency of therapeutic schemes. Studies show that overexpressed epidermal growth factor receptor (EGFR) is a common occurrence, linking this to the progression of pancreatic cancer, although the association between its expression and the survival rate is rather controversial. EGFR-targeted therapy has not shown the results expected, leaving at hand more questions than answers; clearly, there is a need for a better understanding of the molecular pathways involved. Nanoparticles have been used in trying to improve the efficacy of antitumor treatment; thus, using EGFR's ligand, EGF, for nanoconjugation, showed promising results in increasing the cellular uptake mechanisms and apoptosis of the targeted cells.