Objective: To summarize the existing knowledge about adrenal gland abscesses, including etiology, clinical presentation, common laboratory and imaging findings, management and overall morbidity and mortality. Design: Systematic literature review. Methods: We performed a search in the PubMed database using search terms: ‘abscess and adrenal glands’, ‘adrenalitis’, ‘infection and adrenal gland’, ‘adrenal abscess’, ‘adrenal infection’ and ‘infectious adrenalitis’. Articles from 2017 to 2022 were included. We found total of 116 articles, and after applying exclusion criteria, data from 73 articles was included in the final statistical analysis. Results: Of 84 patients included in this review, 68 were male (81%), with a mean age of 55 years (range: 29 to 85 years). Weight loss was the most frequent symptom reported in 58.3% patients, followed by fever in 49%. Mean duration of symptoms was 4.5 months. The most common laboratory findings were low cortisol (51.9%), elevated ACTH (43.2%), hyponatremia (88.2%) and anemia (83.3%). Adrenal cultures were positive in 86.4% cases, with Histoplasma capsulatum (37.3%) being the leading causative agent. Blood cultures were positive in 30% of patients. The majority of the adrenal infections occurred through secondary dissemination from other infectious foci and abscesses were more commonly bilateral (70%). A total of 46.4% of patients developed long-term adrenal insufficiency requiring treatment. Abscess drainage was performed in 7 patients (8.3%) and adrenalectomy was performed in 18 (21.4%) patients. The survival rate was 92.9%. Multivariate analysis showed that the only independent risk factor for mortality was thrombocytopenia (p = 0.048). Conclusion: Our review shows that adrenal abscesses are usually caused by fungal pathogens, and among these, Histoplasma capsulatum is the most common. The adrenal glands are usually involved in a bilateral fashion and become infected through dissemination from other primary sources of infection. Long-term adrenal insufficiency develops in 46% of patients, which is more common than what is observed in non-infectious etiology of adrenal gland disorders. Mortality is about 7%, and the presence of thrombocytopenia is associated with worse prognosis. Further prospective studies are needed to better characterize optimal testing and treatment duration in patients with this relatively rare but challenging disorder.

Objectives: Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipid metabolism characterized by high levels of low-density lipoprotein (LDL). This study aimed to identify variants in the LDLR, APOB, PCSK9 and LDLRAP1 genes and to identify the genotype–phenotype correlation in Serbian FH patients. Method: This study included a total of 101 patients suspected of having FH based on clinical criteria. Genetic analysis was performed by the next-generation sequencing (NGS) method. Results: An overall mutation detection rate of 43.6% was achieved. Thirteen distinct variants were detected in the LDLR gene (93.2%). The most frequently observed variant was c.858C>A p.(Ser286Arg), which was present in 26% of the LDLR-positive patients. Additional variants were detected in the APOB gene. No pathogenic variants were detected in the PCSK9 or LDLRAP1 genes. Comparing genetically FH-positive and FH-negative patients, statistical significance was observed in terms of age (p < 0.001), total cholesterol (TC) (p < 0.001), low-density-lipoprotein cholesterol (LDL-C) (p < 0.001) and triglyceridemia (p < 0.001). Conclusions: This study represents the first insight into the genetic basis of FH in Serbia. Taking into consideration that variants were detected in more than one gene and that the variants in the LDLR gene were distributed across nearly all exons, the FH diagnostics in Serbia ought to be based on NGS methodology.

Background: Familial hypercholesterolemia (FH) is characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels and an increased risk of premature cardiovascular disease. The present study aimed to investigate the genetic background, associated biochemical profiles, clinical manifestations, and therapeutic response in patients with clinically suspected FH in Serbia. Methods: A total of 101 patients with clinically suspected FH were recruited from the Clinic for Endocrinology, Diabetes and Metabolic Diseases in Serbia between 2015 and 2023. Clinical diagnosis was established using the Dutch Lipid Clinic Network (DLCN) criteria. Genetic profiles of all patients were previously determined using next-generation sequencing. Fasting serum lipids, apolipoprotein A-I [ApoA-I], apolipoprotein B [ApoB], and lipoprotein(a) (Lp(a)) were measured enzymatically. Levels of serum lipids were compared between genetically FH-positive (carriers of variants in LDLR, APOB, PCSK9 and LDLRAP1 genes) and FH-negative patients. Therapeutic response was assessed by achieving the LDL-C target level. Statistical analyses were conducted in SPSS (version 30.0). Results: Genetically confirmed FH patients exhibited significantly higher levels of ApoB (p=0.001) compared with variant-negative individuals, while ApoA-I (p=0.413) and Lp(a) (p=0.421) levels did not differ significantly between groups. Patients with pathogenic FH-associated variants were less likely to reach target LDL-C levels after therapy than those without identified variants. Conclusions: This study demonstrates biochemical diversity in familial hypercholesterolemia associated with genetic background in the Serbian population. Pathogenic FH mutations were associated with higher ApoB levels, underscoring the importance of combining genetic testing with lipid profiling for precise diagnosis and management.

Nogo (RTN4) proteins and their receptors have emerged as candidate mediators of metabolic regulation and vascular pathology relevant to type 2 diabetes (T2D). The primary objective of this PRISMA-guided systematic review was to evaluate the clinical and cohort evidence for RTN4/RTN4R as potential biomarkers of T2D progression and vascular complications. A secondary objective was to synthesize preclinical mechanistic evidence on the effects of Nogo axis modulation on pathways relevant to the pathogenesis of T2D. We performed a PRISMA-guided systematic review. The protocol was not prospectively registered in PROSPERO. To ensure reproducibility, we provide complete search keywords, the screening log and the full-text exclusion table. PubMed/MEDLINE, EMBASE and Web of Science were searched for studies published 2000–2025; full search keywords are provided in the main text. The search strategy combined and free-text terms with Boolean operators. We included original preclinical and clinical studies, cohort/proteomic analyses, meta-analyses, and mechanistic papers reporting expression, function, signaling, or clinical associations of Nogo proteins/receptors in metabolic or vascular outcomes. Exclusion criteria: non-English articles, unclear methods, studies outside 2000–2025, and studies lacking primary data. Two reviewers independently screened records; conflicts were resolved by consensus. Study quality was appraised using established tools (SYRCLE for animal studies, Newcastle–Ottawa Scale for cohort/case-control studies). Preclinical evidence supports tissue-specific roles for RTN4 isoforms and receptors in the regulation of insulin secretion, proGCG → GLP-1 processing, ER homeostasis, and vascular permeability through the Src/PI3K/Akt and RhoA/ROCK axes. Cohort and proteomic analyses report associations between RTN4/RTN4R or serum NogoB and faster progression of T2D or vascular complications, but genetic assessment of causality (Mendelian randomization) has so far provided limited support in available data sets. Findings are heterogeneous with respect to directionality and tissue localization. RTN4 signaling exhibits tissue-specific mechanisms relevant to glucose regulation and vascular biology and warrants further translational study. However, heterogeneity across studies and limited genetic support for causality indicate that isoform-specific quantitative validation, longitudinal cohorts and integrated genetic–functional analyses are required before RTN4/RTN4R can be considered as clinical biomarkers.

Despite significant advances in lowering LDL cholesterol, a substantial residual risk for atherosclerotic cardiovascular disease (ASCVD) persists, largely driven by triglyceride-rich lipoproteins (TRLs). This narrative review emphasizes the importance of hypertriglyceridemia in the development of atherosclerotic cardiovascular disease and acute pancreatitis and clarifies the diagnostic dilemmas and current therapeutic options. This narrative review explores the pathophysiology, diagnostic criteria, and epidemiological impact of hypertriglyceridemia. TRLs, including chylomicrons and VLDL, contribute to atherosclerosis through the accumulation of cholesterol-rich "remnant particles" and apolipoprotein B (Apo B) in the subendothelial space. Recent epidemiological data, including findings from the Copenhagen General Population Study and the SIMETAP-HTG study, confirm that mild-to-moderate hypertriglyceridemia (1.7-5.6 mmol/L) is prevalent in approximately 25% of the population and is strongly associated with increased risks of myocardial infarction, heart failure, and multiorgan diseases such as diabetes and MASLD. Conversely, severe hypertriglyceridemia (≥10 mmol/L) significantly elevates the risk of acute pancreatitis. Current guidelines emphasize measuring fasting triglycerides, though non-fasting levels are increasingly recognized for screening. The paper concludes that secondary causes must be ruled out upon diagnosis and highlights non-HDL cholesterol as a critical secondary therapeutic target for comprehensive cardiovascular risk management. The final part of the review is focused on novel therapeutic options and emerging therapies for increased TRL.

Cardiovascular disease is the leading cause of death worldwide, accounting for one-third of the total global mortality. Dyslipidemia is one of the most common risk factors and plays a cardinal role in the development and progression of atherosclerotic cardiovascular disease. Since statin therapy is often insufficient, or cardiovascular disease continues to develop despite achieving target lipid levels, current attention is focused on new therapeutic options with significantly greater efficacy. The reduction in LDL cholesterol levels with PCSK-9 inhibitors is about 60% when used as monotherapy and as much as 85% when combined with high-intensity statins and/or other lipid-lowering therapies. Alirocumab and evolocumab are two monoclonal antibodies that effectively bind to the LDL receptor, interfering with its degradation. Inclisiran is a small interfering RNA that interferes with the synthesis of PCSK-9 molecules and effectively reduces LDL-C. Indications for PCSK-9 inhibitors usage are increasingly expanding due to the discovery of their pleiotropic effects. Additionally, the focus is on discovering new mechanisms of PCSK-9 inhibition that would open the door to the development of new therapeutic agents. Studies on the efficacy and safety of oral PCSK9 inhibitors are ongoing, along with early-stage clinical trials exploring gene-editing strategies for the treatment of dyslipidemias. The purpose of this review article is to provide an overview of the current knowledge on the application of PCSK-9 inhibitors.