Brown Tumors: The Hidden Face of Primary and Renal Hyperparathyroidism Amid Real-Life Settings.

Brown tumors, an exceptional bone complication of severe primary (PHP) or renal (secondary) hyperparathyroidism (RHP), are caused by long-standing, elevated parathormone (PTH)-induced osteoclast activation causing multinucleated giant cell conglomerates with hemosiderin deposits in addition to the local production of cytokines and growth factors. We aim to present an adult case series including two females displaying this complication as part of a multidisciplinary complex panel in high PTH-related ailments. The approach was different since they had distinct medical backgrounds and posed a wide area of challenges amid real-life settings, namely, a 38-year-old lady with PHP and long-term uncontrolled hypercalcemia (with a history of pregnancy-associated PHP, the removal of a cystic jaw tumor, as well as a family and personal positive diagnosis of polycystic kidney disease, probably a PHP-jaw tumor syndrome), as well as, a 26-year-old woman with congenital single kidney and chronic renal disease-associated RHP who was poorly controlled under dialysis and developed severe anemia and episodes of metabolic acidosis (including one presentation that required emergency hemodialysis and was complicated with convulsive seizures, followed by resuscitated respiratory arrest). Both subjects displayed a severe picture of PHP/RHP with PTH levels of >1000 pg/mL and >2000 pg/mL and elevated serum bone turnover markers. Additionally, they had multiple brown tumors at the level of the ribs and pelvis (asymptomatically) and the spine, skull, and pelvis (complicated with a spontaneous cervical fracture). As an endocrine approach, the control of the underlying parathyroid disease was provided via surgery in PHP (for the postparathyroidectomy hungry bone syndrome) via medical intervention (with vitamin D analogs) in RHP. Additionally, in this case, since the diagnosis was not clear, a multidisciplinary decision to perform a biopsy was taken (which proved inconclusive), and the resection of the skull tumor to confirm the histological traits. This series highlights the importance of addressing the entire multidisciplinary panel of co-morbidities for a better outcome in patients with PHP/RHP-related brown tumors. However, in the instance of real-life medicine, poor compliance and reduced adherence to recommendations might impair the overall health status. Thus, sometimes, a direct approach at the level of cystic lesion is taken into consideration; this stands for a narrow frame of decision, and it is a matter of personalized decision. As seen here, brown tumors represent the hidden face of PHP/RHP, primarily the complex and severe forms, and awareness is essential even in the modern era.

N-Terminal Pro-Brain Natriuretic Peptide Correlates with Ghrelin and Acyl-Ghrelin in Pre-Dialysis Chronic Kidney Disease.

Pro-B amino-terminal natriuretic peptide (NT-proBNP) is a diagnostic marker for heart failure (HF), a severe complication of chronic kidney disease (CKD). However, its significance in CKD is not clear, as other factors, such as renal function, may also have an impact. Recent studies have shown that ghrelin treatment is effective in HF in the general population, but the impact of ghrelin on cardiac function in CKD patients is still unknown. Our study aimed to investigate the factors associated with NT-proBNP in pre-dialysis CKD patients and to evaluate the correlation between NT-proBNP and ghrelin and acyl-ghrelin, molecules determined using ELISA methods. In a cross-sectional observational study, we included 80 patients with pre-dialysis CKD, with a mean age of 68 years and 50% men. The median values for NT-proBNP were 351.8 pg/mL, for acyl ghrelin 16.39 pg/mL, and for ghrelin 543.32 pg/mL. NT-proBNP was correlated with ghrelin (p = 0.034, r = 0.24), acyl-ghrelin (p = 0.033, r = -0.24), estimated glomerular filtration rate (p = 0.027, r = -0.25), serum urea (p = 0.006, r = 0.31), and ferritin (p = 0.041, r = 0.28). In multivariate analysis, ghrelin (p = 0.040) and blood urea (p = 0.040) remained significant predictors for NT-proBNP levels. NT-proBNP was a significant predictor for acyl-ghrelin (p = 0.036). In conclusion, in pre-dialysis CKD patients, a high value of NT-proBNP was associated with a high value of total ghrelin and a low value of acyl-ghrelin.

Five-Year Trends of Vascular Disease-Related Amputations in Romania: A Retrospective Database Study.

Background/Objectives: Lower extremity amputations (LEAs) are a burdensome complication of peripheral artery disease (PAD) and/or arterial embolism and thrombosis (AET). We assessed the trends in PAD- and/or AET-related LEAs in Romania. Methods: This retrospective study (2015-2019) analyzed data on minor and major LEAs in hospitalized patients recorded in the National School for Public Health, Management, and Health Education database. The absolute numbers and incidences of LEAs were analyzed by diagnosis type, year, age, sex, and amputation level. Results: Of 38,590 vascular disease-related amputations recorded nationwide, 36,162 were in PAD and 2428 in AET patients. The average LEA incidence in the general population was 34.73 (minimum: 31.96 in 2015; maximum: 36.57 in 2019). The average incidence of major amputations, amputations above the knee, hip amputations, amputations below the knee, and minor amputations was 16.21 (15.62 in 2015; 16.84 in 2018), 13.76 (13.33 in 2015; 14.28 in 2018), 0.29 (0.22 in 2017; 0.35 in 2019), 2.15 (2.00 in 2015; 2.28 in 2019), and 18.52 (16.34 in 2015; 20.12 in 2019), respectively. Yearly PAD- and/or AET-related amputations were significantly higher in men versus women. The overall number of LEAs increased with age, particularly in patients ≥ 70 years. The increase in the total number of amputations was mainly due to a constant rise in minor amputations for both groups, regardless of gender. Conclusions: PAD- and/or AET-related LEAs in Romania increased from 2015 to 2019, with men having a greater incidence than women. Raising awareness and effective management strategies are needed to prevent LEAs.

Patients' Buying Behavior for Non-Reimbursed Off-Loading Devices Used in Diabetic Foot Ulcer Treatment-An Observational Study during COVID-19 Pandemic from a Romanian Physical Therapy Unit.

Diabetic foot ulcer non-reimbursed treatment depends on multiple factors, including the patient's buying behaviors. Factors affecting buying behaviors for the removable off-loading devices are not completely understood. The aim of this study was to investigate the patients' buying behaviors of the removable off-loading devices and their influence on the DFU treatment outcomes remotely monitored during the COVID-19 pandemic. In this prospective observational study, 45 patients affected by diabetic peripheral neuropathy, with/without peripheral arterial disease, with foot ulcers treated with removable devices were remotely monitored. Prefabricated removable cast walkers, insoles, and therapeutic footwear were the proposed off-loading methods. Patients affected by high blood pressure (p = 0.018), peripheral arterial disease (p = 0.029), past amputations (p = 0.018), and ulcer on the left foot (p = 0.007) bought removable cast walkers. Rural provenience (p = 0.011) and male (p = 0.034) did not buy a removable walker. The healing rate was 69.4%, while the median healing time was 20 weeks. High blood pressure negatively influenced healing time (p = 0.020). Patients who bought the most efficient treatment method for DFUs were females from urban provenience, with amputation in the past, with peripheral arterial disease, and with high blood pressure.

Association between Human Leukocyte Antigen and End-Stage Renal Disease in Patients from Transylvania, Romania.

End-stage renal disease (ESRD) is the final stage of chronic kidney disease. This study explored the association between human leukocyte antigen (HLA) and ESRD. The interaction between genetic and environmental factors may also play a role in the development of ESRD. The study included 2392 ESRD patients who were awaiting renal transplantation. Blood samples were genotyped by SSOP and SSP-PCR methods. Multivariate logistic regression analysis showed that HLA-A*11 (p = 0.027), HLA-A*34 (p = 0.017), HLA-A*69 (p = 0.012), HLA-B*41 (p < 0.001), HLA-B*50 (p = 0.004), HLA-DRB1*10 (p = 0.027), and HLA-DRB1*14 (p = 0.004) were positively associated with ESRD (OR > 1); HLA-DRB1*07 (p < 0.001), HLA-DRB1*08 (p = 0.005), and HLA-DRB1*13 (p < 0.001) were protective against ESRD (OR < 1); and the three-locus haplotype HLA-A*02-B*41-DRB1*03, containing one susceptible allele, was strongly associated with ESRD (p < 0.001, OR = 3.15). In conclusion, this retrospective analysis of HLA typing in patients with ESRD of various etiologies suggests that molecular data on the HLA polymorphism should be collected in order to identify high-risk ESRD patients and to improve graft survival after kidney transplantation.

Triiodothyronine and Protein Malnutrition Could Influence Pulse Wave Velocity in Pre-Dialysis Chronic Kidney Disease Patients.

Cardiovascular diseases (CVD) are the first cause of chronic kidney disease (CKD) mortality. For personalized improved medicine, detecting correctable markers of CVD can be considered a priority. The aim of this study was the evaluation of the impact of nutritional, hormonal and inflammatory markers on brachial-ankle Pulse Wave Velocity (PWV) in pre-dialysis CKD patients. A cross-sectional observational study was conducted on 68 pre-dialysis CKD patients (median age of 69 years, 41.2% with diabetes mellitus, 52.9% male). Laboratory data were collected, including levels of prolactin, triiodothyronine, TGF α, IL-6, and IL-1ß. The high values of brachial-ankle PWV were associated with reduced muscle mass (p = 0.001, r = -0.44), low levels of total cholesterol (p = 0.04, r = -0.26), triglycerides (p = 0.03, r = -0.31), triiodothyronine (p = 0.04, r = -0.24), and prolactin (p = 0.02, r = -0.27). High PWV was associated with advanced age (p < 0.001, r = 0.19). In the multivariate analysis, reduced muscle mass (p = 0.018), low levels of triiodothyronine (p = 0.002), and triglycerides (p = 0.049) were significant predictors of PWV, but age (p < 0.001) remained an important factor. In conclusion, reduced triiodothyronine together with markers of malnutrition and age were associated with PWV in pre-dialysis CKD patients.

Ultrasound Placental Remodeling Patterns and Pathology Characteristics in Patients with History of Mild SARS-CoV-2 Infection during Pregnancy.

Introduction: This research aims to describe a progressive pattern of ultrasound placental remodeling in patients with a history of SARS-CoV-2 infection during pregnancy. Materials and Methods: This was a longitudinal, cohort study which enrolled 23 pregnant women with a history of former mild SARS-CoV-2 infection during the current pregnancy. Four obstetricians analyzed placental ultrasound images from different gestational ages following COVID infection and identified the presence and degree of remodeling. We assessed the inter-rater agreement and the interclass correlation coefficients. Pathology workup included placental biometry, macroscopic and microscopic examination. Results: Serial ultrasound evaluation of the placental morphology revealed a progressive pattern of placental remodeling starting from 30-32 weeks of gestation towards term, occurring approximately 8-10 weeks after the SARS-CoV-2 infection. Placental changes-the "starry sky" appearance and the "white line" along the basal plate-were identified in all cases. Most placentas presented normal subchorionic perivillous fibrin depositions and focal stem villi perivillous fibrin deposits. Focal calcifications were described in only 13% of the cases. Conclusions: We identified two ultrasound signs of placental remodeling as potential markers of placental viral shedding following mild SARS-CoV-2. The most likely pathology correspondence for the imaging aspect is perivillous and, respectively, massive subchorionic fibrin deposits identified in most cases.

Lower Extremity Amputation and Peripheral Revascularisation Rates in Romania and Their Relationship with Comorbidities and Vascular Care.

(1) Background: This retrospective Romanian study aimed to calculate the rate of, and comparison between, amputation and revascularisation for patients with either cardiovascular or diabetic comorbidities. (2) Materials: In our hospital-based database, we analysed patient-level data from a series of 61 hospitals for 2019, which covers 44.9% of the amputation patients for that year. The national database is compiled by the national houses of insurance and was used to follow amputations and revascularisations between 2016 and 2021. (3) Results: During the six-year period, the mean number of amputations and revascularisations was 72.4 per 100,000 inhabitants per year for both groups. In this period, a decline in open-surgical revascularisation was observed from 58.3% to 47.5% in all interventions but was not statistically significant (r = -0.20, p = 0.70). The mean age of patients with amputation (hospital-based database) was 67 years. Of these patients, only 5.1% underwent revascularisation in the same hospital prior to amputation. The most common comorbidities in those undergoing amputations were peripheral arterial disease (76.8%), diabetes (60.8%), and arterial hypertension (53.5%). Most amputations were undertaken by general surgeons (73.0%) and only a small number of patients were treated by vascular surgeons (17.4%). (4) Conclusions: The signal from our data indicates that Romanian patients probably have a high risk of amputation > 5 years earlier than Western European countries, such as Denmark, Finland, and Germany. The prevalence of revascularisations in Romania is 64% lower than in the Western European countries.

Safety of Electrotherapy Treatment in Patients with Knee Osteoarthritis and Cardiac Diseases.

OBJECTIVE: To assess the safety of electrotherapy applied in the knee area in patients with known atrial arrhythmias or ischemic heart disease, as it is not known whether this treatment induces or aggravates arrhythmias during or immediately after therapy. MATERIAL AND METHODS: The analytical and transversal study involved 46 patients with degenerative knee osteoarthritis (OA), with or without cardiac diseases, from the Clinical Rehabilitation Hospital inpatient center, Cluj-Napoca, Romania. All patients underwent a 10-day physical therapy program for knee OA (electrotherapy, massage and kinesiotherapy). Heart rate and the total number of ventricular and supraventricular extrasystoles were evaluated before and after treatment, by 24 h Holter ECG monitoring. RESULTS: There was no significant increase in heart rate or in the number of ventricular or supraventricular extrasystoles before or after electrotherapy treatment, regardless of the positive or negative history of arrhythmia or ischemic heart disease (all p > 0.05). Mean values during day 1 were: 35.15 (95% CI [9.60−60.75]) for ventricular ones extrasystoles and 91.7 (95% CI [51.69−131.7]) for supraventricular ones, which during day 2 were 38.09 (95% CI [3.68−72.50]), 110.48 (95% CI [48.59−172.36]), respectively. CONCLUSION: One of the most important things to consider when dealing with an OA patient is that they are most likely older than 65 years, which increases the chance of having a cardiac disease. This raises the need for viable interventions regarding the management of this disease in patients that probably have multiple comorbidities, and where pharmacological and surgical management are not possible, limited or have multiple side effects. Electrotherapy used for treating knee OA did not cause a significant increase in heart rate or number of ventricular and supraventricular extrasystoles in this category of patients.

SUDOSCAN, an Innovative, Simple and Non-Invasive Medical Device for Assessing Sudomotor Function.

Diabetic autonomic neuropathy is probably the most undiagnosed but serious complication of diabetes. The main objectives were to assess the prevalence of peripheral and autonomic neuropathy in a population of diabetic patients, analyze it in a real-life outpatient unit scenario and determine the feasibility of performing SUDOSCAN tests together with widely used tests for neuropathy. A total of 33 patients were included in the study. Different scoring systems (the Toronto Clinical Neuropathy Score-TCNS; the Neuropathy Disability Score-NDS; and the Neuropathy Symptom Score-NSS) were applied to record diabetic neuropathy (DN), while the SUDOSCAN medical device was used to assess sudomotor function, detect diabetic autonomic neuropathy and screen for cardiac autonomic neuropathy (CAN). Fifteen (45.5%) patients had sudomotor dysfunction. The SUDOSCAN CAN risk score was positively correlated with the hands' electrochemical sweat conductance (ESC), diastolic blood pressure (DBP), the level of the glycated hemoglobin, as well as with the TCNS, NDS and NSS. Performing SUDOSCAN tests together with other tests for DN proved to be a feasible approach that could be used in daily clinical practice in order to screen for DN, as well as for the early screening of CAN, before more complex and time-consuming tests.

A Signal Processing Method for Assessing Ankle Torque with a Custom-Made Electronic Dynamometer in Participants Affected by Diabetic Peripheral Neuropathy.

Portable, custom-made electronic dynamometry for the foot and ankle is a promising assessment method that enables foot and ankle muscle function to be established in healthy participants and those affected by chronic conditions. Diabetic peripheral neuropathy (DPN) can alter foot and ankle muscle function. This study assessed ankle toque in participants with diabetic peripheral neuropathy and healthy participants, with the aim of developing an algorithm for optimizing the precision of data processing and interpretation of the results and to define a reference frame for ankle torque measurement in both healthy participants and those affected by DPN. This paper discloses the software chain and the signal processing methods used for voltage-torque conversion, filtering, offset detection and the muscle effort type identification, which further allowed for a primary statistical report. The full description of the signal processing methods will make our research reproducible. The applied algorithm for signal processing is proposed as a reference frame for ankle torque assessment when using a custom-made electronic dynamometer. While evaluating multiple measurements, our algorithm permits for a more detailed parametrization of the ankle torque results in healthy participants and those affected by DPN.

Predictive value of a novel sub-item mortality risk score derived from the Norfolk Quality of Life in Diabetic Neuropathy questionnaire in Romanian participants with diabetes mellitus.

AIMS: To evaluate whether the Norfolk Quality of Life in Diabetic Neuropathy (QOL-DN) questionnaire and the novel Norfolk Mortality Risk Score (NMRS), comprising Norfolk QOL-DN items, can identify 4-year mortality risk in individuals with diabetes. METHODS: Of 21,756 adults completing Norfolk QOL-DN in 2012, two groups of surviving and deceased patients were identified in 2016: Group 1, from a county capital and Group 2, from six small cities. NMRS was calculated in Group 1 using the 2012 scores of Norfolk QOL-DN items that discriminate between deceased and surviving participants (p < 0.05) and was subsequently applied to Group 2. RESULTS: 763 participants were included (Group 1: 481 [450 surviving, 31 deceased]; Group 2: 282 [218 surviving, 64 deceased]). Total Norfolk QOL-DN score was significantly higher (worse) in deceased participants than in survivors in both groups (p ≤ 0.008). Optimal cut-off for the 25-item NMRS was 11.5 in Group 1. Individuals in Groups 1 and 2 with NMRS≥ 11.5 in 2012 had a 4-year mortality risk ratio of 4.24 (95 % confidence interval [CI]: 1.65-10.84) and 2.33 (95 % CI: 1.33-4.07), respectively, corresponding to 8 and 16 additional deaths/100 persons/4 years (p = 0.001). CONCLUSION: Norfolk QOL-DN and NMRS can identify individuals with diabetes at risk of 4-year mortality.

Acute Effects of Sedentary Behavior on Ankle Torque Assessed with a Custom-Made Electronic Dynamometer.

Inactivity negatively influences general health, and sedentary behaviour is known to impact the musculoskeletal system. The aim of the study was to assess the impact of time spent in active and sedentary behaviour on foot muscle strength. In this observational study, we compared the acute effects of one day of prolonged sitting and one day of low-to-moderate level of activity on ankle torque in one group of eight healthy participants. Peak ankle torque was measured using a portable custom-made electronic dynamometer. Three consecutive maximal voluntary isometric contractions for bilateral plantar flexor and dorsiflexor muscles were captured at different moments in time. The average peak torque significant statistically decreased at 6 h (p = 0.019) in both static and active behaviours, with a higher average peak torque in the active behaviour (p < 0.001). Age, gender, body mass index and average steps did not have any significant influence on the average value of maximal voluntary isometric contraction. The more time participants maintained either static or active behaviour, the less force was observed during ankle torque testation. The static behaviour represented by the sitting position was associated with a higher reduction in the average peak ankle torque during a maximal voluntary isometric contraction when compared to the active behaviour.

A Custom-Made Electronic Dynamometer for Evaluation of Peak Ankle Torque after COVID-19.

The negative effects of SARS-CoV-2 infection on the musculoskeletal system include symptoms of fatigue and sarcopenia. The aim of this study is to assess the impact of COVID-19 on foot muscle strength and evaluate the reproducibility of peak ankle torque measurements in time by using a custom-made electronic dynamometer. In this observational cohort study, we compare two groups of four participants, one exposed to COVID-19 throughout measurements and one unexposed. Peak ankle torque was measured using a portable custom-made electronic dynamometer. Ankle plantar flexor and dorsiflexor muscle strength was captured for both feet at different ankle angles prior and post COVID-19. Average peak torque demonstrated no significant statistical differences between initial and final moment for both groups (p = 0.945). An increase of 4.8%, p = 0.746 was obtained in the group with COVID-19 and a decrease of 1.3%, p = 0.953 was obtained in the group without COVID-19. Multivariate analysis demonstrated no significant differences between the two groups (p = 0.797). There was a very good test−retest reproducibility between the measurements in initial and final moments (ICC = 0.78, p < 0.001). In conclusion, peak torque variability is similar in both COVID-19 and non-COVID-19 groups and the custom-made electronic dynamometer is a reproducible method for repetitive ankle peak torque measurements.

The Evaluation of the Four-Chamber Cardiac Dissection Method of the Fetal Heart as an Alternative to Conventional Inflow-Outflow Dissection in Small Gestational-Age Fetuses.

The examination of very small fetal hearts requires special equipment and a specialist that are not available in many general pathology laboratories. Compared to conventional examination, the four-chamber cardiac dissection (4CCD) method can be performed by any pathologist using instruments generally available in pathology services. The aim of this study is to evaluate the efficiency of the 4CCD method in the examination of small fetal hearts using post-mortem magnetic resonance imaging (pm-MRI) at 7T as the standard. Twelve fetuses with gestational ages between 13 and 19 weeks have been included in this study. All fetuses underwent pm-MRI examination prior to pathologic examination. The 4CCD method was used for the cardiac examination in all cases following the same guidelines for cardiac sectioning. The 4CCD was able to identify all cardiac anatomic structures as compared to pm-MRI at 7T, demonstrating a sensibility of 95.8% (95% CI, 94.5-95.8) and specificity of 100% (95% CI, 32.3-100). The overall accuracy in identifying cardiac anatomic structures was 95.8% (95% CI, 93.4-95.8). Additionally, the 4CCD method was able to detect cardiac anomalies with an overall diagnostic accuracy of 91% (95% CI, 85.8-94.2), sensibility of 67.6% (95% CI, 54.5-75.3), and specificity of 97% (95% CI, 93.7-99) as compared to pm-MRI at 7T. The four-chamber view dissection method can be considered as an alternative to the conventional inflow-outflow dissection method in selected cases.

Relationship between vascular cell adhesion molecule-1 (VCAM-1), soluble receptor for advanced glycation end products (sRAGE) and functional hemodynamic parameters of arteriovenous fistula.

BACKGROUND: The preferred vascular access for hemodialysis is represented by arteriovenous fistula (AVF) due to fewer complications and more prolonged survival. Considerable efforts have been made to identify biomarkers associated with AVF dysfunction, but results are conflicting. Vascular cell adhesion molecule (VCAM-1) and advanced glycation end products are involved in atherogenesis, vascular calcification, peripheral artery disease, and neointimal hyperplasia in renal and non-renal patients. The objective of this study was to evaluate whether there is an association between VCAM-1, soluble receptor for advanced glycation end products (sRAGE), NcarboxymethylLysine (CML), and arteriovenous fistula dysfunction (AVF). METHODS: VCAM-1, sRAGE, and CML were performed using the ELISA technique in 88 HD patients. Ultrasound assessment of AVF reports brachial artery blood flow (Qa), brachial resistivity index (RI), presence of calcification, and the diameter. AVF dysfunction was defined as a brachial artery Qa ⩽ 500 ml/min or RI ⩾ 0.5. RESULTS: The median level of VCAM-1 [2676.5(2206.8-4203.9) versus 2613.2(1885.7-3161.8), p 0.026] was significantly higher in patients with AVF dysfunction compared to the rest of the patients. sRAGE and CML were higher in this group but without statistical significance. In patients with AVF dysfunction, significant positive correlations were found between VCAM-1and sRAGE (r = 0.417, p = 0.001), RI (r = 0.313, p = 0.046), dialysis vintage (r = 0.540, p < 0.001), AVF vintage (r = 0.336, p = 0.032), intima-media thickness (r = 0.423, p = 0.006) and C-reactive protein (r = 0.315, p = 0.045). VCAM-1 correlated inversely with cholesterol (r = -0.312, p = 0.047), triglycerides (r = -0.358, p = 0.021), body mass index (r = -0.388, p = 0.012). In multivariate regression analysis, VCAM-1 (p = 0.013) and sRAGE (p = 0.01) remained significant predictors of RI and Qa. Logistic regression disclosed calcification, VCAM-1, as risks factors for AVF dysfunction. CONCLUSION: The results we obtained showed that patients with AVF dysfunction had a significantly higher level of VCAM-l. A positive correlation between VCAM-1 and sRAGE was identified in this group.

Arterial calcifications and osteoprotegerin in chronic hemodialysis patients: impact on 6-year survival.

AIM: The association between end-stage renal disease and cardiovascular mortality may be influenced through vascular alterations, in particular atherosclerosis and vascular calcification. The study goal was to assess the impact of each type of arterial intimal calcifications (AIC) and arterial medial calcifications (AMC), of osteoprotegerin (OPG), mineral metabolism markers and other features on all-cause and cardiovascular mortality in chronic hemodialysis patients. METHODS: Ultrasound was performed in 87 patients on the carotid and femoral arteries, and the severity of AIC and AMC was assessed calculating a score according to the extension of calcification. We analyzed the link between AIC, AMC, OPG, mineral markers and mortality after 6 years of follow-up. RESULTS: The cutoff value for OPG determined using ROC was 4.9 pmol/l for all-cause and cardiovascular mortality. Patients with higher serum OPG levels presented higher mortality rates. Our study revealed that AIC, high OPG, low ankle-arm index, presence of diabetes, smoking status, and lack of arteriovenous fistula are associated with all-cause and cardiovascular mortality in univariate regression analysis. Multivariate analysis identified AIC scoring based on the segmentation method as an independent predictor of all-cause and cardiovascular mortality, along with increased OPG levels. AMC scoring was not a predictor of mortality. CONCLUSIONS: Identifying and scoring AIC on ultrasound and measuring OPG levels, as a basis of the HD patient assessment may become valuable tools in clinical work, as these have an impact on death toll.

Hemodialysis Patients with Higher Serum Levels of Soluble Receptor for Advanced Glycation End Products Have an Increased Risk for Arteriovenous Fistula Failure.

BACKGROUND: Arteriovenous fistula (AVF) failure due to thrombosis is a major cause of morbidity in patients undergoing regular hemodialysis (HD). Advanced glycation end products (AGEs) and their receptor (RAGE) might contribute to inflammation, neointimal hyperplasia, and thrombosis. RAGE has a C-truncated secretory receptor form, called soluble RAGE (sRAGE). In this study, we aimed to evaluate the association of serum sRAGE with AVF failure due to thrombosis in HD patients. METHODS: Eighty-eight prevalent HD patients with functional AVF were included in the study. The presence of stenosis, clinical and laboratory data, and serum sRAGE was evaluated at inclusion. sRAGE concentration was measured by a competitive enzyme-linked immunosorbent assay, and stenosis was detected by ultrasound. Patients were prospectively followed up for 36 months. During this period, AVF failure (defined as the absence of blast or palpable thrill and impossible cannulation with 2 needles because of complete thrombosis) was noted and thrombosis was certified by ultrasound examination. RESULTS: During follow-up, 16 (18.18%) patients lost their vascular access due to thrombosis. In multivariate Cox regression analysis, sRAGE was a significant predictor of vascular access thrombosis (hazard ratio = 1.15, 95% confidence interval: 1.03-1.25, p = 0.012). Kaplan-Meier analysis showed a significantly lower AVF patency time in patients with sRAGE >16.78 ng/mL than those with sRAGE <16.78 ng/mL (p = 0.02). In the subgroup of patients with stenosis at baseline, sRAGE, serum albumin, obesity, and ischemic heart disease were associated with thrombosis. CONCLUSION: In our study, baseline, systemic sRAGE is associated with the occurrence of thrombosis of AVF, and this marker has a significant impact on AVF survival.

Diabetes-Related Lower Extremity Amputations in Romania: Patterns and Changes between 2015 and 2019.

Lower extremity amputations (LEAs) are a feared complication of diabetes mellitus (DM). Here we evaluated the recent trends in DM-related LEAs in Romania. We collected data from a national database regarding minor and major LEAs performed between 2015 and 2019 in patients with DM admitted to a public hospital. Absolute numbers of LEAs were presented by year, diabetes type, sex and age; incidence rates of LEAs in the general population were also calculated. Over the study period, 40,499 LEAs were recorded nationwide (83.16% in persons with type 2 DM [T2DM]); on average, the number of LEAs increased by 5.7%/year. This trend was driven by an increased number of LEAs in patients with T2DM; in patients with type 1 DM (T1DM), LEAs decreased over the study period. In patients with T2DM, the increase in minor LEAs was more pronounced than that in major LEAs. The overall number of LEAs showed an increasing trend with age (r = 0.72), which was most pronounced in patients aged ≥70 years. Men had a higher frequency of LEAs than women, regardless of DM type. These data support renewed efforts to prevent and decrease the burden of amputations among patients with DM.

Diagnostic value of virtual autopsy using pm-MRI at 3T on malformed second trimester fetuses vs classic autopsy.

OBJECTIVE: To determine the diagnostic value of virtual autopsy using post mortem-MRI (pm-MRI) at 3Tesla (T) compared to classic autopsy for the confirmation of fetal structural anomalies and secondly to establish which cases of termination of pregnancy would benefit mostly from a virtual autopsy. METHODS: In each of 32 fetuses included in the study, 32 anatomical structures were assessed, after termination of pregnancy in the second trimester. All cases were evaluated by prenatal ultrasonography, virtual autopsy and classic autopsy, and then divided into four groups: Cerebral Group, Cardiac Group, Renal Group and Other Group (miscellaneous group). The concordance of virtual autopsy with classic autopsy was calculated overall and for each group and each structural item. Also, the concordance between the two methods was assessed using a diagnostic error score (DgE_score), calculated as the absolute value of the difference between the number of malformations detected by classic autopsy per case (CA score) and the number of malformations detected at virtual autopsy per case (VA score). RESULTS: Overall virtual autopsy demonstrated a diagnostic sensitivity (Se) compared to classic autopsy of 67.33% [95% CI 57.28-76.33], with a specificity (Sp) of 98.37% [95% CI 97.33-99.09], a positive predictive value (PPV) of 81.93% [95% CI 71.95-89.52], a negative predictive value (NPV) of 96.49% [95% CI 95.11-97.57] achieving a diagnostic accuracy of 95.31% [95% CI 93.83-96.52]. Overall, no statistic significant correlation was demonstrated between DgE_score and the gestational age of the fetuses or between DgE_score and the weight of the fetuses, but a significant correlation was revealed between the virtual autopsy and classic autopsy score. The diagnostic utility of virtual autopsy using pm-MRI at 3 T as compared to classic autopsy for each category of termination of pregnancy revealed in the Cerebral Group a Se of 80.00% [95% CI 28.36-99.49], with a 96.30% [95% CI 81.03-99.91], a PPV of 80.00% [95% CI 35.75-96.64] a NPV of 96.30% [95% CI 81.81-99.34], with a diagnostic accuracy of 93.75% [95% CI 79.19% to 99.23] and a Cohen's Kappa coefficient of 0.76 [95% CI 0.4494-1.0765]; in the Renal Group a Se and Sp of 100%, but in the Cardiac Group the Se was only 60.00% [95% CI 26.24-87.84], Sp 75% [95% CI 34.91-96.81], the PPV 75.00% [95% CI 44.92-91.69], NPV 60% [95% CI 38.87-77.96], with a diagnostic accuracy of 66.67% [95% CI 40.99-86.66] and a Cohen's Kappa coefficient of 0.32 [95% CI -0.07-0.76]. CONCLUSIONS: The results support virtual autopsy using pm-MRI at 3T as a reliable alternative to classic autopsy for the non-forensic analysis of second trimester fetuses. Analyzing the diagnostic utility of virtual autopsy using pm-MRI at 3 T for the confirmation of prenatal ultrasound findings in second trimester fetuses as compared to classic autopsy, the best results were obtained in the Cerebral and Renal Group. Reserved results were found in the Cardiac Group. Therefore, for the pregnancies with termination of pregnancy for cerebral or renal abnormalities, virtual autopsy by pm-MRI at 3T can be taken into consideration as a first-line investigation to confirm the prenatal findings.