Depiction of Branched-Chain Amino Acids (BCAAs) in Diabetes with a Focus on Diabetic Microvascular Complications.

Type 2 diabetes mellitus (T2DM) still holds the title as one of the most debilitating chronic diseases with rising prevalence and incidence, including its complications such as retinal, renal, and peripheral nerve disease. In order to develop novel molecules for diagnosis and treatment, a deep understanding of the complex molecular pathways is imperative. Currently, the existing agents for T2DM treatment target only blood glucose levels. Over the past decades, specific building blocks of proteins-branched-chain amino acids (BCAAs) including leucine, isoleucine, and valine-have gained attention because they are linked with insulin resistance, pre-diabetes, and diabetes development. In this review, we discuss the hypothetical link between BCAA metabolism, insulin resistance, T2DM, and its microvascular complications including diabetic retinopathy and diabetic nephropathy. Further research on these amino acids and their derivates may eventually pave the way to novel biomarkers or therapeutic concepts for the treatment of diabetes and its accompanied complications.

Transient hepatic attenuation difference (THAD) or fat sparing? Aberrant right gastric vein (ARGV) determining a pseudolesion at the border of the IInd/IIIrd liver segments. Review of developmental concepts.

The aberrant right gastric vein (ARGV) is a rare anatomical variation. It can be responsible for unexplained hyperdensities in the hepatic parenchyma on CT scans, also known as third inflow effects. We present two cases sharing similar vascular pattern and slightly different imagistic findings on ultrasound and computer-tomography performed studies. Both ultrasonographies showed a nodular-geographic hypoechoic area within a hyperechogenic fatty liver. Further CT evaluation showed in both cases a hyperattenuating homogenous area clearly visible on all four phases at the border of the IInd/IIIrd hepatic segment, that enhance especially on the portal venous phase, with no slow-fill, wash-out, central scar or rim-like features. The areas were considered to be focal fat sparing areas in diffuse fatty liver or a perfusion disorder due to the presence of an aberrant right gastric vein. The aim of this paper is to discuss the embryological aspects which are the groundwork for this vascular anomaly and to correlate the findings with imagistic aspects. These two ARGV produced pseudolesions, understood as focal fat sparing areas within diffuse fatty livers. These pseudolesions mimic liver tumours, therefore it is important to look for such an aberrant vessel in order to rule out other diagnoses.

Compassion fatigue and compassion satisfaction among Romanian emergency medicine personnel.

Background: Contemporary scientific literature has emphasized two specific aspects of healthcare professionals: compassion satisfaction and compassion fatigue. In the context of the COVID-19 pandemic, which has placed significant strain on health systems and healthcare workers, the Russian-Ukrainian crisis appears to have a magnifying effect, particularly on mental health. Methods: The aim of the present study was to investigate the relationship between threat perception, daily worries, and professional quality of life in a sample of Emergency Medicine Personnel during two major events mentioned above. The sample included 372 participants (56.7% nurses and 43.3% physicians) from emergency units in five county hospitals in the Eastern region of Romania. Results: The study revealed that threats related to the pandemic were positively linked to secondary traumatic stress, and daily worries were positively linked to both secondary traumatic stress and burnout. Threats generated by the war did not manifest a direct relation with any of the indicators of professional quality of life, but daily worries generated by war positively predicted both secondary traumatic stress and burnout. Conclusion: Both the pandemic, which involved cumulative exposure, and the war, which involved a lower and more distant level of exposure, had the potential to generate worries and predict a low quality of life. However, our results did not reveal any association between threats, worries, and compassion satisfaction. As a result, this positive indicator of quality of life remained stable despite the presence of threats and worries.

Age, blood tests and comorbidities and AIMS65 risk scores outperform Glasgow-Blatchford and pre-endoscopic Rockall score in patients with upper gastrointestinal bleeding.

BACKGROUND: Upper gastrointestinal (GI) bleeding is a life-threatening condition with high mortality rates. AIM: To compare the performance of pre-endoscopic risk scores in predicting the following primary outcomes: In-hospital mortality, intervention (endoscopic or surgical) and length of admission (≥ 7 d). METHODS: We performed a retrospective analysis of 363 patients presenting with upper GI bleeding from December 2020 to January 2021. We calculated and compared the area under the receiver operating characteristics curves (AUROCs) of Glasgow-Blatchford score (GBS), pre-endoscopic Rockall score (PERS), albumin, international normalized ratio, altered mental status, systolic blood pressure, age older than 65 (AIMS65) and age, blood tests and comorbidities (ABC), including their optimal cut-off in variceal and non-variceal upper GI bleeding cohorts. We subsequently analyzed through a logistic binary regression model, if addition of lactate increased the score performance. RESULTS: All scores had discriminative ability in predicting in-hospital mortality irrespective of study group. AIMS65 score had the best performance in the variceal bleeding group (AUROC = 0.772; P < 0.001), and ABC score (AUROC = 0.775; P < 0.001) in the non-variceal bleeding group. However, ABC score, at a cut-off value of 5.5, was the best predictor (AUROC = 0.770, P = 0.001) of in-hospital mortality in both populations. PERS score was a good predictor for endoscopic treatment (AUC = 0.604; P = 0.046) in the variceal population, while GBS score, (AUROC = 0.722; P = 0.024), outperformed the other scores in predicting surgical intervention. Addition of lactate to AIMS65 score, increases by 5-fold the probability of in-hospital mortality (P < 0.05) and by 12-fold if added to GBS score (P < 0.003). No score proved to be a good predictor for length of admission. CONCLUSION: ABC score is the most accurate in predicting in-hospital mortality in both mixed and non-variceal bleeding population. PERS and GBS should be used to determine need for endoscopic and surgical intervention, respectively. Lactate can be used as an additional tool to risk scores for predicting in-hospital mortality.

Cisplatin and AKI: an ongoing battle with new perspectives-a narrative review.

Acute kidney injury (AKI) is a growing global health problem with increased mortality and morbidity. Cisplatin is achemotherapy drug first introduced in 1978, and since then, it became one of the most widely used and successful anti-cancer medication. However, there are risks associated with cisplatin administration, such as nephrotoxicity. Mechanisms of nephrotoxicity include proximal tubular injury, DNA damage, apoptosis, inflammation, oxidative stress, and vascular injury. Although various protocols are being used in clinical practice in nephrotoxicity prevention due to cisplatin, there are no clear guidelines regarding this approach. Most recommendations include hydration and avoiding additional nephrotoxic drugs. To prevent nephrotoxicity, future perspectives could rely on natural products, such as flavonoids or saponins or pharmacological products, such as aprepitant, but data are scarce in this direction. Repetitive administration of cisplatin could cause subclinical kidney injury, which over time, leads to chronic kidney disease (CKD). Therefore, more studies are needed to determine possible ways to prevent nephrotoxicity and avoid the burden of CKD worldwide.

General Health among Eastern Romanian Emergency Medicine Personnel during the Russian-Ukrainian Armed Conflict.

(1) Background: The aim of the current study is to identify the relations between worries, threat perceptions, anxiety states, and general health in a sample of Emergency unit staff during the Russian Ukrainian armed conflict. The sample consisted of 372 Emergency Care staff (M age = 39.41; 77.2% women), physicians, and nurses from North-eastern Romania. (2) Methods: Participants completed an online survey including scale measuring worries, recent anxiety symptoms, and general health. The survey was distributed and completed in the next month after the outbreak of the war. (3) Results: The results showed that the worries, perceived threats, and anxiety symptoms during the last period are negatively related to general health. Women presented higher levels of worries, perceived threats, and anxiety symptoms, compared to men, while for general health, women presented lower scores. Concerning the differences between different professional categories, the results showed that trainees presented higher scores on worries, perceived threats, and anxiety symptoms, as well as lower scores on general health. The implications of these results for improving health and quality of life are discussed. (4) Conclusions: The level of stress increases beyond the borders where the war takes place, thus indirectly affecting the Emergency Care staff involved in the care of victims. Clinical implications of these results for interventions designed to monitor quality of life and to prevent unwanted consequences of exposure to traumatic life events are discussed.

Salt, Not Always a Cardiovascular Enemy? A Mini-Review and Modern Perspective.

Dietary salt intake is a long-debated issue. Increased sodium intake is associated with high blood pressure, leading to salt-sensitive hypertension. Excessive salt intake leads to arterial stiffness in susceptible individuals via impaired nitric oxide action and increased endothelin-1 expression, overactivity of the renal sympathetic nervous system and also via aldosterone-independent activation of the mineralocorticoid receptor. Salt restriction in such individuals reduces blood pressure (BP) values. The optimal level of salt restriction that leads to improved cardiovascular outcomes is still under debate. Current BP and dietary guidelines recommend low sodium intake for the general population. However, a specific category of patients does not develop arterial hypertension in response to sodium loading. In addition, recent research demonstrates the deleterious effects of aggressive sodium restriction, even in heart failure patients. This mini review discusses current literature data regarding the advantages and disadvantages of salt restriction and how it impacts the overall health status.

Aqueous Humor Cytokines in Non-Proliferative Diabetic Retinopathy.

Background and Objectives: Cytokines are cell-signaling proteins whose identification may serve as inflammatory markers or early indicators for progressive disease. The aim of our study was to quantify several cytokines in aqueous humor (AH) and their correlations with biochemical parameters in diabetic eyes with non-proliferative diabetic retinopathy (NPDR). Materials and Methods: A total of 62 eyes from 62 patients were included in the study: 37 eyes from nondiabetic patients (group 1), 13 diabetic eyes with no retinopathy changes (group 2) and 12 diabetic eyes with early and moderate NPDR (group 3). AH samples were collected during uneventful cataract surgery. The cytokines IL-1ß, IL-6, IL-8, IL-10, IL-12, IP-10, MCP-1, TNF-α and VEGF were quantified using multiplex bead-based immunoassay. Due to unreliable results, IL-1ß, TNF-α, IL-10 and IL-12 were excluded. Concentrations were compared between groups. Biochemical parameters (fasting blood sugar, glycated hemoglobin, C-reactive protein) and the duration of diabetes were recorded. Results: VEGF levels were significantly different between groups (p = 0.001), while levels of IL-6, IL-8, IP-10 and MCP-1 were comparable across all groups (p > 0.05). IL-6 concentration correlated with VEGF in group 1 (rho = 0.651, p = 0.003) and group 3 (rho = 0.857, p = 0.007); no correlation could be proved between IL-6, IL-8, IP-10, MCP-1 or VEGF and biochemical parameters. Duration of diabetes was not correlated with the cytokine levels in groups 2 and 3. The receiver operating characteristic (ROC) curve revealed that VEGF concentrations could discriminate early and moderate NPDR from diabetes, with an area under the curve (AUC) of 0.897 (p = 0.001, 95% CI = 0.74−1.0). Conclusions: Diabetes mellitus induces significant intraocular changes in the VEGF expression in diabetic patients vs. normal subjects, even before proliferative complications appear. VEGF was increasingly expressed once the diabetes progressed from no retinopathy to early or moderate retinopathy.

Choroidal Assessment in Patients with Type 2 Diabetes Mellitus and Non-Proliferative Diabetic Retinopathy by Swept-Source Ocular Coherence Tomography and Image Binarization.

Background and Objectives: The aim of this study was to evaluate choroidal structure and vascularity indices in patients with non-proliferative diabetic retinopathy (NPDR). Materials and Methods: Sixty-three eyes from sixty-three patients were evaluated: 21 from healthy subjects, 20 with diabetes mellitus (DM) and no diabetic retinopathy (DR), and 22 with DM and non-proliferative diabetic retinopathy without diabetic macular edema (DME). Each patient underwent ocular examination, macular swept-source ocular coherence tomography (SS-OCT) imaging, glycemic control, and systemic high blood pressure (HBP) evaluation. Subfoveal choroidal thickness (SF-CT) was manually assessed on a line scan. Line scan OCT images were exported to ImageJ program. The areas under a 1.5, 3 and 6 mm horizontal line centered on the fovea were assessed by converting the OCT images to binary images, and total choroidal area (TCA), luminal area (LA), stromal area (SA), LA:SA ratio, and choroidal vascularity index (CVI) were evaluated. SF-CT and choroidal parameters were compared between groups, and correlations with ocular and systemic factors were analyzed. Results: SF-CT, TCA, LA, and SA were similar between groups. CVIs were significantly different between groups for all three studied areas (CVI-1.5: 66.21% vs. 66.06% vs. 63.74%, p = 0.003; CVI-3: 65.88% vs. 66.46% vs. 63.79%, p = 0.008; CVI-6: 64.79% vs. 65.40% vs. 63.61%, p = 0.032). NPDR patients had significantly lower CVIs compared to DM patients (p < 0.05). No association of choroidal parameters with glycemic control, DM duration and HBP was found significant (p < 0.05). Conclusions: Choroidal assessment by SS-OCT and image binarization in healthy subjects, subjects with DM without DR, and subjects with DM and NPDR indicated that CVI changes were identifiable and significant in early DR. The lack of association with ocular and systemic factors suggest that CVIs are reliable assessment parameters of choroidal vascular structure.

Immune Thrombocytopenic Purpura as a Hemorrhagic Versus Thrombotic Disease: An Updated Insight into Pathophysiological Mechanisms.

Immune thrombocytopenic purpura (ITP) is a blood disorder characterized by a low platelet count of (less than 100 × 109/L). ITP is an organ-specific autoimmune disease in which the platelets and their precursors become targets of a dysfunctional immune system. This interaction leads to a decrease in platelet number and, subsequently, to a bleeding disorder that can become clinically significant with hemorrhages in skin, on the mucous membrane, or even intracranial hemorrhagic events. If ITP was initially considered a hemorrhagic disease, more recent studies suggest that ITP has an increased risk of thrombosis. In this review, we provide current insights into the primary ITP physiopathology and their consequences, with special consideration on hemorrhagic and thrombotic events. The autoimmune response in ITP involves both the innate and adaptive immune systems, comprising both humoral and cell-mediated immune responses. Thrombosis in ITP is related to the pathophysiology of the disease (young hyperactive platelets, platelets microparticles, rebalanced hemostasis, complement activation, endothelial activation, antiphospholipid antibodies, and inhibition of natural anticoagulants), ITP treatment, and other comorbidities that altogether contribute to the occurrence of thrombosis. Physicians need to be vigilant in the early diagnosis of thrombotic events and then institute proper treatment (antiaggregant, anticoagulant) along with ITP-targeted therapy. In this review, we provide current insights into the primary ITP physiopathology and their consequences, with special consideration on hemorrhagic and thrombotic events. The accumulated evidence has identified multiple pathophysiological mechanisms with specific genetic predispositions, particularly associated with environmental conditions.

Reply to Campbell et al. Comment on "Hogas et al. Salt, Not Always a Cardiovascular Enemy? A Mini-Review and Modern Perspective. Medicina 2022, 58, 1175".

We thank Campbell et al. for their comment [...].

Posterior choroidal boundary morphology and segmentation errors influence on choroidal thickness assessment in diabetic patients - a swept-source OCT study.

Objective: to evaluate the choroidal morphology and choroidal thickness (CT) in normal and diabetic subjects and to compare the differences between automated segmentation (AS) and manual segmentation (MS) of the choroid. Methods: in this observational cross-sectional study we included 48 eyes: 24 normal eyes (group 1), 9 eyes with DM without diabetic retinopathy (DR) (group 2) and 15 eyes with DM and DR (group 3). Swept-source OCT line scans images were analyzed for the presence of the suprachoroidal layer (SCL), choroidal morphology and the CT was measured manually subfoveal and at 750 µ both nasal and temporal to the fovea after AS and MS. SCL was not included in the CT evaluation. CT values were compared between the groups and between the three points of evaluation. Results: SCL was visualized in 21 eyes (43.8%). In diabetic patients, SCL was visible in 11 (45.83%) cases and in nondiabetic patients, in 10 eyes (41.66%). There was a good AS of Bruch's membrane, which was not further corrected manually. There were statistically significant differences between AS and MS at the level of CSJ for all three locations in all three groups (P ≤ 0.01). After MS, the choroid was statistically significantly thicker. Group 2 and group 3 showed a higher CT thickness. There were no statistically significant differences in the CT between groups in all three locations. Conclusions: Defining posterior choroidal boundary and the applied segmentation method can result in differences in CT measurements. Diabetic patients have altered CT and choroidal morphology. Abbreviations: CT = choroidal thickness, AS = automated segmentation, MS = manual segmentation, CSJ = choroidoscleral junction, SCL = suprachoroidal layer, SCS = suprachoroidal space, DM = diabetes mellitus, DR = diabetic retinopathy, RPE = retinal pigmented epithelium, BM = Buch's membrane.

A TODAY VICTIM OF SECOND WORLD WAR.

Emergency medicine as a medical specialty has to deal with all kind of emergency situations, from medical to post traumatic acute eyents and from new born to the elderly persons, but also with particular situations like explosions. In Romania nowadays these are accidental explosions and rare like frequency, but may be dramatic due to numbers of victims and multisystem injury that may occur. We present a case of a single victim of accidental detonated bomb, a projectile from the Second World War, which unfortunately still may be found in some areas. The management of the case from first call to 112 until the victim is discharge-involves high professional team work. We use these opportunity to make a brief review of the mechanism through the lesions may appear and also to renew the fact that the most impressive lesion may not be the most severe, and we have to examine carefully in order to find the real life threatening injury of the patient.

Digital microscopy assessment of angiogenesis in different breast cancer compartments.

BACKGROUND/AIM: Tumour angiogenesis defined by microvessel density (MVD) is generally accepted as a prognostic factor in breast cancer. However, due to variability of measurement systems and cutoffs, it is questionable to date whether it contributes to predictive outline. Our study aims to grade vascular heterogeneity by comparing clear-cut compartments: tumour associated stroma (TAS), tumour parenchyma, and tumour invasive front. MATERIAL AND METHODS: Computerized vessel area measurement was performed using a tissue cytometry system (TissueFAXS) on slides originated from 50 patients with breast cancer. Vessels were marked using immunohistochemistry with CD34. Regions of interest were manually defined for each tumour compartment. RESULTS: Tumour invasive front vascular endothelia area was 2.15 times higher than that in tumour parenchyma and 4.61 times higher than that in TAS (P < 0.002). Worth to mention that the lymph node negative subgroup of patients show a slight but constant increase of vessel index in all examined compartments of breast tumour. CONCLUSION: Whole slide digital examination and region of interest (ROI) analysis are a valuable tool in scoring angiogenesis markers and disclosing their prognostic capacity. Our study reveals compartments' variability of vessel density inside the tumour and highlights the propensity of invasive front to associate an active process of angiogenesis with potential implications in adjuvant therapy.