Malignant insulinoma: Can we predict the long-term outcomes?

Insulinomas are the most frequent type of functional pancreatic neuroendocrine tumors with a variety of neuroglycopenic and autonomic symptoms and well-defined diagnostic criteria; however, prediction of their clinical behavior and early differentiation between benign and malignant lesions remain a challenge. The comparative studies between benign and malignant cases are limited, suggesting that short clinical history, early hypoglycemia during fasting, high proinsulin, insulin, and C-peptide concentrations raise suspicion of malignancy. Indeed, malignant tumors are larger with higher mitotic count and Ki-67 proliferative activity, but there are no accurate histological criteria to distinguish benign from malignant forms. Several signaling pathways have been suggested to affect the pathophysiology and behavior of insulinomas; however, our knowledge is limited, urging a further understanding of molecular genetics. Therefore, there is a need for the identification of reliable markers of metastatic disease that could also serve as therapeutic targets in patients with malignant insulinoma. This opinion review reflects on current gaps in diagnostic and clinical aspects related to the malignant behavior of insulinoma.

Human pegivirus infection after transplant: Is there an impact?

The microbiome's role in transplantation has received growing interest, but the role of virome remains understudied. Pegiviruses are single-stranded positive-sense RNA viruses, historically associated with liver disease, but their path-ogenicity is controversial. In the transplantation setting, pegivirus infection does not seem to have a negative impact on the outcomes of solid-organ and hematopoietic stem cell transplant recipients. However, the role of pegiviruses as proxies in immunosuppression monitoring brings novelty to the field of virome research in immunocompromised individuals. The possible immunomodulatory effect of pegivirus infections remains to be elucidated in further trials.

Hepatitis E virus in professionally exposed: A reason for concern?

The zoonotic risk of hepatitis E virus (HEV) is well established. The HEV seroprevalence rates vary according to geographical region, assays used, and study cohorts. HEV infection is still underdiagnosed, implying the need to evaluate the disease's burden in the general population and specific risk groups, such as professionally exposed. Close contact with various animal reservoirs such as pigs, rabbits, sheep, dogs, wild boars, and deer has been associated with higher anti-HEV seroprevalence as a part of occupational exposure. While exact transmission routes remain to be determined, some general preventive measures such as proper hand hygiene, the usage of personal protective equipment, and the thermal processing of food before consumption should be followed. A "One-Health" multisectoral approach should be implemented to achieve optimal health and well-being outcomes, recognizing the interconnections between humans, animals, plants, and their shared environment, in which a vaccine against the zoonotic genotypes 3 and 4 and swine vaccination should be considered as a possible public health measure. This opinion review comprehensively addresses the HEV burden of professional exposure for butchers, slaughterhouse workers, veterinarians, farmers, hunters, and forestry workers delineates the current limits of protective work measures, and tackles future directions.

Hepatitis E Virus in Croatia in the "One-Health" Context.

Hepatitis E virus (HEV) is the most common cause of viral hepatitis globally. The first human case of autochthonous HEV infection in Croatia was reported in 2012, with the undefined zoonotic transmission of HEV genotype 3. This narrative review comprehensively addresses the current knowledge on the HEV epidemiology in humans and animals in Croatia. Published studies showed the presence of HEV antibodies in different population groups, such as chronic patients, healthcare professionals, voluntary blood donors and professionally exposed and pregnant women. The highest seroprevalence in humans was found in patients on hemodialysis in a study conducted in 2018 (27.9%). Apart from humans, different studies have confirmed the infection in pigs, wild boars and a mouse, indicating the interspecies transmission of HEV due to direct or indirect contact or as a foodborne infection. Continued periodical surveys in humans and animals are needed to identify the possible changes in the epidemiology of HEV infections.

Computed tomography colonography and radiation risk: How low can we go?

Computed tomography colonography (CTC) has become a key examination in detecting colonic polyps and colorectal carcinoma (CRC). It is particularly useful after incomplete optical colonoscopy (OC) for patients with sedation risks and patients anxious about the risks or potential discomfort associated with OC. CTC's main advantages compared with OC are its non-invasive nature, better patient compliance, and the ability to assess the extracolonic disease. Despite these advantages, ionizing radiation remains the most significant burden of CTC. This opinion review comprehensively addresses the radiation risk of CTC, incorporating imaging technology refinements such as automatic tube current modulation, filtered back projections, lowering the tube voltage, and iterative reconstructions as tools for optimizing low and ultra-low dose protocols of CTC. Future perspectives arise from integrating artificial intelligence in computed tomography machines for the screening of CRC.

The expression of osteopontin and vascular endothelial growth factor in correlation with angiogenesis in monoclonal gammopathy of undetermined significance and multiple myeloma.

Several studies have shown a gradual increase in the extent of bone marrow angiogenesis in various stages of proliferative plasma cell disorders, from monoclonal gammopathy of undetermined significance (MGUS) to active multiple myeloma (MM). The main aim of this study was to evaluate tumor angiogenesis parameters in detail and to correlate them with the expression of osteopontin (OPN) and vascular endothelial growth factor (VEGF) in the bone marrow of patients with MGUS and MM. In addition, we wanted to determine their prognostic significance in active MM. Ninety-five patients were enrolled in the study: 14 diagnosed with MGUS, 13 with asymptomatic myeloma (AMM) and 68 with active MM. Computer assisted image analysis was used to determine the angiogenesis parameters, the quantity of microvessels per 1mm(2) (MVD), the area occupied by microvessels per 1mm(2) and the percentage of microvessel area in total section area (TVA). Double immunohistochemical methods CD138+VEGF and CD138+OPN were used to evaluate expression of these proteins in plasma cells, and OPN was also analyzed for its interstitial expression (iOPN). A significant positive correlation was determined between VEGF and iOPN with angiogenic parameters in the MGUS stage of the disease. In advanced stages of the disease, a significant negative correlation was recorded between OPN and iOPN with parameters of angiogenesis. Overall survival was significantly shorter for patients with negative iOPN (p=0.002) and higher angiogenic parameters, MVD (p=0.009), TVA (p=0.008) and area of microvessels per 1mm(2) (p=0.02). Positive VEGF expression in our model predicted a better three-year survival of patients with active MM (OR: 5.25, p=0.03; HR: 0.44, p=0.04). The results of our study suggested a possible key role of VEGF and OPN in the induction of angiogenesis in early-stage disease.

[SATISFACTION OF YOUNG DOCTORS IN CROATIA: ARE WE HEADING IN THE RIGHT DIRECTION]? / ZADOVOLJSTVO MLADIH LIJECNIKA U REPUBLICI HRVATSKOJ: IDEMO LI U PRAVOM SMJERU?

Introduction: The satisfaction of junior medical doctors is primarily associated with the training they receive during the residency period and working conditions. Given a considerable brain-drain of medical doctors from the Republic of Croatia, the present research focused on the evaluation of the satisfaction of junior medical doctors. Methodology: The Junior Doctors Committee of the Croatian Medical Chamber prepared a questionnaire on the satisfaction of junior doctors. The relevant questionnaire was available for filling in online in the period from February 1 to March 20, 2016. Results: The questionnaire was completed by 1,531 persons aged between 29 and 35 (mean age 32) of which 67% were females. A 58% of respondents would leave the Republic of Croatia if offered an opportunity. The main reasons for leaving the country include better working conditions (74%), well-regulated healthcare system (64%) and higher wages (64%). In case of staying in the country, their future professional status and development would remain unaltered (44%). Conclusion: The questionnaire results show a high level of dissatisfaction with the healthcare system, some segments of the specialist training and the mentor role. The analysis of factors affecting the satisfaction of junior doctors will facilitate the preparation and adoption of measures aiming to mitigate the above-mentioned trend.

Transcranial Doppler ultrasound assessment of intracranial hemodynamics in patients with type 2 diabetes mellitus.

BACKGROUND: Diabetics have a 3-fold risk for cardiovascular diseases compared with non-diabetics. This study was designed to evaluate cerebral hemodynamic changes related to type 2 diabetes mellitus (DM) with transcranial Doppler ultrasonography (TCD). TCD is a highly sensitive and specific method of quick bedside assessment of cerebrovascular circulation hemodynamics. PATIENTS AND METHODS: In a prospective study, we compared a group of 100 patients with the diagnosis of type 2 diabetes mellitus (aged 48 to 67 years) and an age- and sex-matched control group of 100 healthy subjects without diabetes mellitus. We measured flow velocities (Vm) and the Gosling pulsatility index (PI) of the middle cerebral artery (MCA). RESULTS: The rate of TCD abnormalities was significantly higher in diabetic patients than in healthy control subjects (55% vs. 11%, P < 0.05). The PI was significantly higher in diabetic patients than in healthy controls (P < 0.001). Atherosclerotic changes were found in 34.0% and 71.4% of patients suffering from diabetes for <5 and > or =5 years, respectively. CONCLUSION: This study suggests that TCD is a useful marker for the detection of diabetic cerebrovascular changes. The duration and type of diabetes were found to have an impact on the development of pathologic cerebrovascular changes.

Antioxidant enzymes activity in patients with peripheral vascular disease, with and without presence of diabetes mellitus.

The study evaluated antioxidant status in patients with peripheral vascular disease (PVD), with and without concomitant diabetes mellitus (DM). 211 participants were divided into standardized 4 groups: patients with PVD and DM (PVD+DM+), patients with PVD without DM (PVD+DM-), patients without PVD with DM (PVD-DM+) and patients without PVD and DM (PVD-DM-). The diagnosis of PVD was established by Doppler sonography analysis, including determination of the ankle brachial index (ABI), partial pressures along the leg, and CW Doppler sonography at typical locations. Antioxidant status has been evaluated through the colorimetrically assessed serum activity of key antioxidant enzymes: superoxide dismutase (SOD), catalase, and glutathione peroxidase (GLPX) as well as through total antioxidant status (TAS) determination. In PVD+DM- group, as well as PVD-DM+ group, a significantly lower activity of the GLPX, catalase and TAS was found, whereas activity of SOD was significantly higher. There was no statistically significant difference between PVD+DM+ and PVD-DM+ group. Likewise, there was no statistically significant difference between PVD+DM- and PVD-DM-group. This study has shown that there is statistically significant difference in activity of antioxidant enzymes between diabetic and non-diabetic patients, irrespectively of PVD presence. Furthermore, PVD present alone does not alter key antioxidant enzymes activity in comparison with healthy subjects.