Search Results (547)

Background: Pancreatic solid pseudopapillary neoplasms (SPNs) are rare exocrine tumours with predominance in young women. These tumours are of low malignant potential, become considerably large before causing symptoms and are associated with good prognosis. This study aimed to present and analyse clinicopathological features and surgical outcome of SPNs. Methods: A retrospective analysis of 22 patients who underwent pancreatic surgery for SPNs in a single high-volume surgical centre in 2014–2023 was performed. Results: SPN was the most frequent in females (n = 21, 95.45%) in a mean age of 34 ± 11.09 (18–55) years. Fourteen (63.64%) patients were asymptomatic, and eight (36.36%) presented with symptoms. The most common clinical symptom was abdominal pain (n = 7, 31.82%). The majority of tumours were located in the pancreatic body (n = 8, 36.36%), and most patients underwent distal pancreatectomy (n = 11, 50%). The median tumour size was 3.6 cm (IQR = 4.9; range: 1.3–14). The median duration of hospitalisation was 12.5 days, and the postoperative complication rate was 40.91%. R0 resection was achieved in 18 (81.82%) patients. Postpancreatectomy acute pancreatitis (PPAP) was the most common postoperative complication. No adjuvant therapy in any patient was needed. One-year overall survival (OS) equalled 100% and five-year OS reached 85%. None of the patients developed diabetes or signs of impaired pancreatic secretion in the follow-up period. Histopathology showed features like perineural invasion in 72.73% of cases, pseudocapsule (59.09%), haemorrhage (45.45%), vascular invasion (40.91%), mucosal metaplasia (40.91%), necrosis (31.82%), and calcification in the capsule (31.82%). Ki67 did not exceed 7%. In one case (4.55%), metastasis to a lymph node was found. Clinical suspicion agreed with histopathological results in only 10 (45.45%) cases. Conclusions: SPN most often occurs in young females. The majority of cases are asymptomatic accidental findings. The final diagnosis of SPN can be based just on analysis of histopathological examination results. Full article

In end-stage renal disease (ESRD), the accumulation of solutes normally excreted by the kidneys contributes to multiple complications, including vascular calcification (VC), a key factor in the heightened cardiovascular risk seen in these patients. Among VC drivers, hyperphosphatemia and the uremic milieu are major contributors. Kynurenine, a tryptophan metabolite classified as a uremic toxin, may further exacerbate this process. This study investigated whether kynurenine amplifies high phosphate (Pi)-induced calcification in human aortic endothelial cells (HAEC). Cells were treated with Pi and kynurenine for up to seven days. Kynurenine increased Pi-induced calcium deposition by 36%, accompanied by enhanced endothelial-to-mesenchymal transition (EndMT) and osteoblastic differentiation. Mechanistically, kynurenine activated the aryl hydrocarbon receptor (AhR) pathway, and pharmacological inhibition of AhR partially attenuated this effect. These findings suggest that kynurenine contributes to VC in ESRD by potentiating phosphate-induced endothelial dysfunction via AhR signaling. Full article

Background/Objectives: We analyzed clinical and radiological characteristics and prognostic factors specific to young patients with breast cancer (YBC) aged <30 years. Methods: This retrospective study included 132 women aged <30 years who underwent breast surgery between 2008 and 2013. The clinical and radiological findings of the patients were examined and compared according to recurrence or death status at follow-up. Disease-free survival (DFS) and overall survival (OS) rates were also assessed. Results: Most patients (mean age, 27.1 years) presented with palpable lesions (85.6%). Hormone receptor-positive/human epidermal growth factor receptor-negative cancer was the most common molecular subtype (59.8%), followed by triple-negative breast cancer (28.0%), with high Ki-67 expression (62.1%). Mammography and ultrasound detected abnormalities in 90.1% and 97.3% of patients, respectively, whereas magnetic resonance imaging detected abnormalities in all patients. During the follow-up period (8–10 years), 28.5% of the patients experienced recurrence and 11.5% died. The calculated DFS and OS at 5 years were 80.8% and 69.8% and 91.3% and 87.8% at 10 years, respectively. Statistically significant factors associated with DFS/OS included the BRCA1 gene mutation, with preoperative neoadjuvant chemotherapy, no hormone therapy, larger tumor size, negative hormone receptor status, high Ki-67 expression, and some radiological findings, including asymmetry with calcifications on mammography, no sonographic echogenic rind of mass, and mild vascularity on Doppler study. Conclusions: Our study highlights the aggressive nature of breast cancer in YBC aged <30 years, with relatively high rates of recurrence and mortality. Significant factors affecting prognosis may guide personalized treatment approaches and predict the prognosis. Full article

Chronic kidney disease (CKD) is associated with a significantly elevated mortality rate, primarily due to cardiovascular disease (CVD), highlighting a complex bidirectional relationship between the two conditions. Life-threatening cardiovascular events occur despite control of the traditional risk factors, emphasizing the underlying role of non-traditional risk factors. CKD, causing mineral imbalance and the accumulation of uremic toxins due to a compromised ability to excrete waste products, imposes extra pressure on the cardiovascular system. The retention of mineral and uremic toxins, in turn, aggravates the progression of CKD. This review aims to elucidate the pathophysiological connections between CKD and CVD, with a particular focus on the metabolic regulatory mechanisms influenced by minerals such as calcium and phosphate, as well as uremic toxins. We review how these factors contributed to accelerated multi-organ damage through mechanisms such as inflammation, endothelial dysfunction, oxidative stress, and vascular calcification. In addition, we discuss the therapeutic strategies for specific uremic toxins and proposed directions for future investigations. This review provides insights into the complex interplay between metabolic dysregulation and cardiovascular outcomes in CKD patients, promoting the development of innovative therapeutic interventions, ultimately improving the prognosis and quality of life for patients affected by these interconnected conditions. Full article

Early stages of chronic kidney disease (CKD) are closely associated with vascular remodeling and coronary artery calcification. The aim of this study is to determine whether adropin is associated with asymptomatic coronary calcification in patients in the early stages of CKD. This study enrolled 337 individuals fulfilling the inclusion criteria of the early stages of CKD (G1–2, A1–3) and divided them into two subgroups with (n = 196) and without (n = 141) asymptomatic coronary artery calcification. Native coronary multi-detector computed tomography angiography was conducted to determine coronary artery calcification, which was stratified into four grades according to the Agatston method. Serum levels of adropin were measured by ELISA. The patients with known asymptomatic coronary artery calcification had significantly lower levels of adropin than those without this condition. The levels of adropin in individuals with mild (130–199 HU), moderate (200–299 HU), severe (300–399 HU) and very severe (≥400 HU) calcification were 3.13 (95% CI = 1.92–4.21) ng/mL, 2.3 (95% CI = 1.45–3.6) ng/mL, 2.1 (95% CI = 1.22–3.25) ng/mL and 1.26 (95% CI = 1.13–1.98) ng/mL, respectively. In multivariate logistic regression low adropin (<2.95 ng/mL), a presence of hypertension, type 2 diabetes mellitus (T2DM) exerted their independent potencies to predict asymptomatic coronary calcification. Moreover, adropin demonstrated better discriminative potency than concomitant hypertension and T2DM. Conclusions: Low levels of circulating adropin significantly predicted a risk of coronary artery calcification in patients in the early stages of CKD. Full article

Aging is associated with aortic stiffening (AoSt), a condition characterized by diminished aortic elasticity that predisposes individuals to cognitive decline, including Alzheimer’s disease (AD). Emerging evidence implicates medin, which is derived from milk fat globule-EGF factor 8 protein (MFG-E8), as a key link between AoSt and AD. Medin aggregates into aortic medial amyloid (AMA), which is found in approximately 97% of Caucasian individuals aged 50 and above, contributing to vascular inflammation, calcification, and loss of arterial elasticity. These changes may promote hyperpulsatile cerebral blood flow and impair glymphatic clearance, resulting in increased deposition of neurotoxic proteins, such as amyloid-β (Aβ) and possibly medin, which colocalizes with vascular Aβ in the brain. Medin enhances Aβ aggregation, generating heterologous fibrils, and thereby contributes to cerebrovascular dysfunction and neuroinflammation. This interaction (cross-seeding) may deteriorate amyloid pathology in both the vasculature and the parenchyma in AD. Furthermore, medin per se causes endothelial dysfunction, increases oxidative stress, and activates glial cells, promoting the development of a pro-inflammatory environment that enhances cognitive decline. In this manuscript, we contend that medin might act as a bridge connecting the age-related increase in aortic stiffness to AD, and therefore, medin might present a novel therapeutic target within this context. This hypothesis deserves experimental and clinical validation. Full article

Background/Objectives: Nowadays, intravascular lithotripsy (IVL) has emerged as a novel technique for treatment of vascular calcifications, first in coronary and then in peripheral arteries. In the current literature there is little evidence that describes IVL as an effective and safe solution in treating severe aortic and aorto-iliac calcifications. The aim of this study is to report current available data about the use of IVL in treating aortic and aorto-iliac calcified lesions and its application in facilitating other endovascular procedures. Methods: the present review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Guidelines. Preliminary searches were conducted on MEDLINE and Pubmed from January 2015 to February 2025. Studies were divided into 3 main categories depending on the location of calcifications and the type of treatment: IVL in visceral and infrarenal obstructive disease (group 1), IVL in aorto-iliac obstructive disease (group 2), IVL used to facilitate other endovascular procedures. Main primary outcomes in the perioperative period were technical and clinical successes and perioperative complications. Primary outcomes at 30 days and mid-term (2 years) were overall survival, limb salvage rate, primary patency, primary assisted patency, secondary patency, and residual stenosis. Results: Sixteen studies were identified for a total of 1674 patients. Technical and clinical successes were 100%, with low rates of perioperative complications. Dissection rate reaches up to 16.1% in some studies, without any differences compared to plain old balloon angioplasty (POBA) alone (22.8%; p = 0.47). At 30 days, limb salvage and survival rates were 100%. At 2 years, primary patency, assisted primary patency, and secondary patency were 95%, 98%, and 100%, respectively, with no difference compared to IVL + stenting. Conclusions: IVL has emerged as a novel approach to treat severe calcified lesions in visceral and aorto-iliac atherosclerotic disease and to facilitate other endovascular procedures. This technique seems to offer satisfactory early and mid-term outcomes in terms of primary, primary assisted patency, and secondary patency with low complication rates. Full article

A healthy vasculature with well-regulated perfusion and pulsatility is essential for the brain. One vascular structure that has received little attention is the carotid siphon. The proximal portion of the siphon is stiff due to the narrow location in the skull base, whilst the distal portion is highly flexible. This flexible part in combination with the specific curves lead to lower pulsatility at the cost of energy deposition in the arterial wall. This deposited energy contributes to damage and calcification. Severe siphon calcification stiffens the distal part of the siphon, leading to less damping of the pulsatility. Increased blood flow pulsatility is a possible cause of stroke and cognitive disorders. In this review, based on comprehensive multimodality imaging, we first describe the anatomy and physiology of the carotid siphon. Subsequently, we review the in vivo imaging data, which indeed suggest that the siphon attenuates pulsatility. Finally, the data as available in the literature are shown to provide convincing evidence that severe siphon calcifications and the calcification pattern are linked to incident stroke and dementia. Interventional studies are required to test whether this association is causal and how an assessment of pulsatility and the siphon calcification pattern can improve personalized medicine, working to prevent and treat brain disease. Full article

Background: Delirium is a common, underdiagnosed neuropsychiatric syndrome in older adults, associated with high mortality and functional decline. Given its multifactorial nature and overlap with frailty, radiological markers may improve risk stratification in the emergency department (ED). Methods: We conducted a retrospective study on a small sample of 30 patients diagnosed with delirium in the emergency department who had recently undergone brain, thoracic, or abdominal CT scans for unrelated clinical indications. Using post-processing software, we analyzed radiological markers, including coronary artery calcifications (to estimate vascular age), cerebral atrophy (via the Global Cortical Atrophy scale), and cachexia (based on abdominal fat and psoas muscle volumetry). Results: Five domains were identified as significant predictors of 12-month mortality in univariate Cox regression: vascular age, delirium etiology, cerebral atrophy, delirium subtype (hyperactive vs. hypoactive), and cachexia. Based on these domains, we developed an exploratory 10-point delirium score. This score demonstrated acceptable diagnostic accuracy for mortality prediction (sensitivity 0.93, specificity 0.73, positive predictive value 0.77, negative predictive value 0.91) in this limited cohort. Conclusions: While preliminary and based on a small, retrospective sample of 30 patients, this multidimensional approach integrating clinical and radiological data may help improve risk stratification in elderly patients with delirium. Radiological phenotyping, particularly in terms of vascular aging and sarcopenia/cachexia, offers objective insights into patient frailty and could inform more personalized treatment pathways from the ED to safe discharge home, pending further validation. Full article

Background and Objectives: Galectin-3 (Gal-3), a pro-inflammatory cytokine, has been implicated in atherosclerosis and adverse cardiovascular outcomes. While its role in coronary artery disease (CAD) is increasingly recognized, its association with systemic atherosclerosis remains underexplored. Objective: To investigate serum Gal-3 levels in patients with CAD and evaluate correlations between CAD severity and extra-coronary atherosclerotic involvement (carotid, femoral, and radial territories). Materials and Methods: We prospectively enrolled 56 patients with CAD undergoing coronary angiography (42.8% with acute-ACS; 57.2% with chronic coronary syndromes-CCS). Gal-3 levels were measured within 24 h of admission. Atherosclerosis severity was assessed angiographically and through vascular ultrasound of the carotid, femoral, and radial arteries. Patients were stratified by median Gal-3 levels, and clinical follow-up was performed at 1 and 3 months. Results: Gal-3 levels were significantly higher in CAD vs. controls (20.7 vs. 10.1 ng/mL; p < 0.00001) and in ACS vs. CCS (22.18. vs. 17.93 ng/mL; p = 0.019). Gal-3 correlated positively with culprit lesion diameter stenosis (DS) (R = 0.30; p = 0.023) and maximum severity of additional treated lesions (R = 0.62; p = 0.006). Gal-3 also correlated positively with carotid plaque thickness (R = 0.32; p = 0.016), while patients with Gal-3 levels above the median showed increased median values for femoral plaque thickness (32.4 vs. 26.45 mm, p = 0.046). No correlation was found with radial artery calcification. Gal-3 showed moderate discrimination for ACS (AUC = 0.685; cut-off 20.18 ng/mL). On multivariate analysis age, DS, and ACS presentation were independent predictors of Gal-3 above 19.07 ng/mL. Conclusions: Gal-3 levels are elevated in ACS and correlate with atherosclerotic burden, particularly in coronary, carotid, and femoral territories. These findings support Gal-3 as a potential marker of lesion severity and systemic vascular involvement, highlighting its possible role in risk stratification and the monitoring of atherosclerotic disease progression. This study provides integrated insights into the impact of Gal-3 across multiple vascular beds by assessing them concurrently within the same patient cohort. Full article

Background/Objectives: Bisphosphonates may influence vascular calcification and atheroma formation via farnesyl pyrophosphate synthase inhibition in the mevalonate pathway regulating bone and lipid metabolism. However, the clinical impact of NCB use on cardiovascular outcomes remains uncertain, largely due to methodological heterogeneity in prior studies. We aimed to evaluate the association between nitrogen-containing bisphosphonate (NCB) therapy and coronary artery calcium (CAC) progression, as well as the incidence of cardiovascular disease (CVD) and coronary heart disease (CHD) events. Methods: From 6814 participants in MESA Exam 1, we excluded males (insufficient male NCB users in the MESA cohort), pre-menopausal women, baseline NCB users, and users of hormone replacement therapy, raloxifene, or calcitonin. Among 166 NCB initiators and 1571 non-users with available CAC measurements, propensity score matching was performed using the available components of FRAX, namely age, race, BMI, LDL cholesterol, alcohol, smoking, and steroid use, and baseline CAC yielded 165 NCB initiators matched to 473 non-users (1:3 ratio). Linear mixed-effects models evaluated CAC progression, and Cox models analyzed incident CVD and CHD events. Results: In the overall cohort, NCB use was not significantly associated with CAC progression (annual change: −0.01 log Agatston units; 95% CI: −0.05 to 0.01). However, among participants with a baseline estimated glomerular filtration rate (eGFR) < 65 mL/min/1.73 m², NCB use was associated with attenuated CAC progression compared with non-users (−0.06 log Agatston units/year; 95% CI: −0.12 to −0.007). No significant association was observed between NCB use and incident CVD events in the overall cohort (HR: 0.90; 95% CI: 0.60−1.36) or within kidney function subgroups. Conclusions: Incident NCB use among postmenopausal women with mild or no CAC at baseline was associated with reduced CAC progression only in women with impaired kidney function. However, this association did not correspond to a decreased risk of subsequent cardiovascular events, suggesting that the observed imaging benefit may not translate into meaningful clinical association. Full article

Vascular calcification significantly contributes to cardiovascular complications and limb loss in chronic kidney disease (CKD). To establish an optimal rat model for vascular calcification, we tested varying adenine concentrations and feeding durations in Sprague–Dawley rats (n = 72), divided into six groups (n = 12 each). The control group received a standard diet for 18 weeks. Group 1 was given 0.5% adenine for 4 weeks, followed by a standard diet. Group 2 received 0.5% adenine for 4 weeks, then 0.25% for 14 weeks. Group 3A received 0.5% adenine for 12 weeks and then standard diet; group 3B received 0.5% adenine for 12 weeks, followed by 0.25% for 6 weeks; group 3C received 0.5% adenine for 18 weeks. At week 18, vascular calcification was absent in the control and group 1. Groups 2 and 3A showed low incidence (12.5%), while groups 3B and 3C showed high incidence (66.7%). However, survival rates differed: 75.0% in 3B and 50.0% in 3C after 12 wk. Thus, 0.5% adenine for 12 weeks followed by 0.25% for 6 weeks effectively induced vascular calcification while maintaining acceptable survival, providing a practical model for studying CKD-related vascular pathology. Full article

Background and Objectives: Sclerostin and dickkopf-1 (DKK1), which are Wnt inhibitors, are involved in vascular calcification and atherosclerosis. Atherosclerotic peripheral artery disease (PAD) is highly prevalent, particularly in patients with hypertension. This study aimed to explore the association between serum concentrations of Wnt pathway inhibitors and PAD in patients with hypertension. Materials and Methods: This cross-sectional trial recruited 92 patients with hypertension. PAD was defined as an ankle-brachial index < 0.9. The levels of sclerostin, DKK1, C-reactive protein (CRP), and other biochemical markers were assessed using fasting blood samples. Univariate and multivariate logistic regression and receiver operating characteristic curve analyses were conducted. Results: Patients with PAD (15.2%) had significantly higher serum sclerostin (p < 0.001) and CRP (p = 0.001) levels than those without PAD. However, the two groups did not significantly differ in terms of the DKK1 levels. Based on the multivariate analysis, sclerostin was an independent predictor of PAD (odds ratio: 1.054 per 1 pmol/L increase, 95% confidence interval: 1.019–1.090, p = 0.002) after adjusting for body mass index, fasting glucose levels, diabetes, smoking, and CRP levels. Sclerostin had a strong discriminatory power for diagnosing PAD according to the receiver operating characteristic curve analysis (area under the curve: 0.806, p < 0.001), with the best cutoff value of 71.5 pmol/L (sensitivity: 71.4%, specificity: 78.2%). Further, sclerostin was negatively associated with the ankle-brachial index, renal function, and dyslipidemia markers. Conclusions: Serum sclerostin levels are independently related to an increased risk for PAD in patients with hypertension. Therefore, it can be a potential biomarker for risk stratification and early diagnosis. Full article

Zinc is an essential trace element involved in diverse physiological processes in humans. Zinc deficiency is common in patients with chronic kidney disease (CKD), including those undergoing hemodialysis. This narrative review synthesizes both experimental and clinical findings on zinc status in CKD patients. Literature was primarily retrieved from PubMed using the keywords “zinc” AND (“CKD” OR “hemodialysis”) AND at least one of the following: “cardiovascular disease (CVD)”, “vascular calcification”, “anemia”, “blood pressure”, OR “infection”. In vitro, studies have shown that zinc suppressed phosphate-induced vascular calcification while zinc deficiency directly promoted calcification. Clinically, serum zinc levels were positively correlated with calcification propensity in patients with CKD. In vivo zinc deficiency has been implicated in elevated blood pressure, Moreover, zinc supplementation enhanced erythropoiesis and improved responsiveness to erythropoiesis-stimulating agents in both animal models and humans. We recently reported that low serum zinc levels are associated with increased mortality in hemodialysis patients with hypoalbuminemia. Previous randomized controlled trials (RCTs) suggest a daily dose of approximately 45 mg of zinc for 2 months mitigates inflammation, oxidative stress, and malnutrition in patients undergoing hemodialysis. Emerging evidence suggests that vascular calcification, hypertension, and renal anemia are newly recognized features of zinc deficiency and are established risk factors for CKD progression, CVD, and mortality. However, the impact of zinc supplementation on these clinical outcomes remains inconclusive. Further RCTs are required to establish zinc supplementation as an effective therapeutic strategy for improving various outcomes in patients with CKD including hemodialysis. Full article

Background/Objectives: Patients with chronic kidney disease (CKD) are associated with a significantly elevated cardiovascular risk. The incidence and prevalence of mediated cardiac disorders and major adverse cardiac events (MACEs), such as heart failure, arrhythmias, acute coronary syndrome (ACS) based on coronary artery disease (CAD), stroke, venous thromboembolism, and peripheral artery disease, are significantly higher in CKD patients as compared with the general population. Methods: This narrative review summarizes the current clinical understanding, the pathophysiological mechanisms, and the clinical consequences in the context of cardiovascular risk and disease in CKD. Results: The impact of CKD on mediated cardiovascular disorders and elevated MACE prevalence is complex and multifactorial. The underlying mechanisms involve various traditional cardiovascular risk factors, such as arterial hypertension, smoking, dyslipidemia, and diabetes. Furthermore, CKD-specific molecular and pathophysiological factors, such as chronic inflammation and associated oxidative stress and endothelial cell dysfunction, pro-coagulatory status, uremic toxins and uremic lipids, progressive vascular calcification, and alterations in the regulation of the renin–angiotensin–aldosterone system (RAAS) and sympathetic activation cause an increased cardiovascular risk. Conclusions: Understanding the complex disease mechanisms between CKD and elevated cardiovascular risk might contribute to optimizing individual patients’ risk stratification and result in individualized diagnostic and treatment strategies via appropriate clinical biomarker application and individualized anti-inflammatory approaches. Full article