Amantadine in unvaccinated patients with early, mild to moderate COVID-19: A randomized, placebo-controlled, double-blind trial.

BACKGROUND AND PURPOSE: Adamantanes were listed as an interesting option as an early intervention against COVID-19. We aimed to evaluate the effectiveness of amantadine in preventing the progression of COVID-19 and its neurological sequelae. METHODS: Unvaccinated patients with confirmed SARS-CoV-2 infection within 5 days were enrolled. Subjects were randomized (50:50) to amantadine (AMD; 100 mg twice daily) or placebo (PLB) for 14 days. The Ordinal Scale for Clinical Improvement of the World Health Organization (OSCI-WHO) was the primary measure. Secondary endpoints included assessment for fatigue; depression, disorders of smell and taste, and sleepiness on Days 1 and 15. RESULTS: We enrolled 99 patients (49 AMD and 50 PLB). Disease progression (OSCI-WHO = 4) was observed in 6% (AMD) and 8% (PLB) patients (p > 0.05) with further deterioration (OSCI-WHO〉4) in 0% (AMD) and 8% (PLB) patients (p > 0.05). Complete recovery on Day 15 was 60% higher in the AMD compared with the PLB group (p = 0.025). There was improvement in taste (AMD: p = 0.003; PLB: p = 0.0001) and smell (AMD: p = 0.005; PLB: p = 0.0004) but not in fatigue in both groups. Improvement was observed in the AMD (p = 0.010) but not in the PLB group (p = 0.058) when assessing depression as well as sleepiness (AMD: p = 0.0002; PLB: p = 0.341). There was one death in the PLB group (2.0%) and none in the AMD group (p > 0.05) until Day 210. Overall, the drug was well tolerated. CONCLUSION: The central effects of amantadine on the nervous system with reduction of sleepiness and depression might have had a supportive effect on faster recovery in early COVID-19 patients.

FT-Raman spectra in combination with machine learning and multivariate analyses as a diagnostic tool in brain tumors.

Brain tumors are one of the most dangerous, because the position of these are in the organ that governs all life processes. Moreover, a lot of brain tumor types were observed, but only one main diagnostic method was used - histopathology, for which preparation of sample was long. Consequently, a new, quicker diagnostic method is needed. In this paper, FT-Raman spectra of brain tissues were analyzed by Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), four different machine learning (ML) algorithms to show possibility of differentiating between glioblastoma G4 and meningiomas, as well as two different types of meningiomas (atypical and angiomatous). Obtained results showed that in meningiomas additional peak around 1503 cm-1 and higher level of amides was noticed in comparison with glioblastoma G4. In the case of meningiomas differentiation, in angiomatous meningiomas tissues lower level of lipids and polysaccharides were visible than in atypical meningiomas. Moreover, PCA analyses showed higher distinction between glioblastoma G4 and meningiomas in the FT-Raman range between 800 cm-1 and 1800 cm-1 and between two types of meningiomas in the range between 2700 cm-1 and 3000 cm-1. Decision trees showed, that the most important peaks to differentiate glioblastoma and meningiomas were at 1151 cm-1 and 2836 cm-1 while for angiomatous and atypical meningiomas - 1514 cm-1 and 2875 cm-1. Furthermore, the accuracy of obtained results for glioblastoma G4 and meningiomas was 88 %, while for meningiomas - 92 %. Consequently, obtained data showed possibility of using FT-Raman spectroscopy in diagnosis of different types of brain tumors.

miRNA Signature of Urine Extracellular Vesicles Shows the Involvement of Inflammatory and Apoptotic Processes in Diabetic Chronic Kidney Disease.

BACKGROUND: The aim of this study was to investigate the role of urine-derived extracellular vesicles (uEVs) in diabetic kidney disease (DKD) in patients diagnosed with type 2 diabetes mellitus (T2DM). METHODS: UEVs were characterized by size distribution and microRNA content by next-generation small RNA sequencing and quantitative reverse transcription PCR. RESULTS: A subset of sixteen miRNAs enriched in T2DM patients with DKD, including hsa-miR-514a-5p, hsa-miR­451a, hsa-miR-126-3p, hsa-miR-214, or hsa-miR­503 was identified. Eight miRNAs as hsa-miR-21-3p, hsa-miR-4792, hsa-miR­375, hsa-miR-1268a, hsa-miR-501-5p, or hsa-miR-582 were downregulated. Prediction of potential target genes and pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) confirmed possible functions related to cellular processes such as apoptosis, inflammation, and tissue remodeling, that promote diabetic complications, such as DKD. Among them, hsa-miR-375, hsa-miR-503, and hsa-miR-451a make important contribution. Additionally, downregulated hsa-miR-582-5p has not been reported so far in any diabetes-related pathways. CONCLUSIONS: This study revealed the most significant miRNAs in uEVs of patients with T2DM. However, as this is a bioinformatic prediction that we performed based on the putative targets of the identified miRNAs. Thus, further in vitro functional studies are needed to confirm our findings. Knowing the fact that EVs are crucial in transferring miRNAs, there is a great need toto discover their involvement in the pathomechanism of T2DM-related kidney disease.

Raman spectroscopy of urinary extracellular vesicles to stratify patients with chronic kidney disease in type 2 diabetes.

In this study, we verified the hypothesis that Raman signature of urinary extracellular vesicles (UEVs) can be used to stratify patients with diabetes at various stages of chronic kidney disease (CKD). Patients with type 2 diabetes diagnosed with different stages of CKD and healthy subjects were enrolled in the study. UEVs were isolated using low-vacuum filtration followed by ultracentrifugation. Correlation analysis, multiple linear regression and principal component analysis were used to find differences between spectral fingerprints of UEVs derived from both groups of patients. Electron microscopy and nanoparticle tracking analysis were applied to characterize the size and morphology of UEVs. We observed significant correlations between selected Raman bands measured for UEVs and clinical parameters. We found significant differences in the area under the specific bands originating mainly from proteins and lipids between the study groups. Based on the tryptophan and amide III bands, we were able to predict the estimated glomerular filtration rate (eGFR). Principal component analysis, partial least squares regression (PLSR) and correlation analysis of the UEV Raman spectra supported the results obtained from the direct analysis of Raman spectra. Our analysis revealed that PLSR and a regression model including tryptophan and amide III bands allows to estimate the value of eGFR.

Safety and tolerability of therapeutic plasma exchange in autoimmune neurological diseases - a retrospective single-centre analysis.

CLINICAL RATIONALE FOR STUDY: The sudden onset of autoimmune neurological diseases often threatens life. In such clinical situations, fast, effective and safe treatment is needed. Therapeutic plasma exchange (TPE) is an option in the treatment of autoimmune disorders. AIM OF STUDY: The aim was to assess the tolerability and safety of membrane-based therapeutic plasma exchange (mTPE) in patients with autoimmune neurological diseases. MATERIALS AND METHODS: A total of 410 TPE treatments were performed in 91 adult patients. The main reasons for performing TPE were: Guillain-Barre syndrome (39.56%), chronic inflammatory demyelinating polyradiculoneuropathy (20.88%), and myasthenia gravis (17.58%). RESULTS: A total of 183 (44.6%) mTPE treatments were performed without complications. In 18 (19.8%) patients, there were no complications observed in any of the mTPE procedures (a total of 83 procedures). Serious and life-threatening complications occurred during four (0.97%) mTPEs. The most common abnormality in laboratory tests was hypocalcaemia. In patients with a fibrinogen c oncentration ≥ 2 .63 g /L, m easured before the second plasmapheresis, coagulation in the TPE filter was more f requently o bserved (p = 0 .04). CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study proves that the use of plasmapheresis conducted by filtration in the treatment of autoimmune neurological diseases is safe and well tolerated.

Markers of Glomerular and Tubular Damage in the Early Stage of Kidney Disease in Type 2 Diabetic Patients.

Diabetic kidney disease develops in half of genetically predisposed patients with type 2 diabetes (T2DM). Early diagnosis of kidney damage and nephroprotective treatment are the ways of preventing the disease progression. Our aim was to evaluate selected laboratory markers of glomerular and tubular damage in T2DM patients with early stages of chronic kidney disease (G1/G2, A1/A2) for their associations with A2 albuminuria and early decline in the estimated glomerular filtration rate (eGFR). Among 80 T2DM patients with median eGFR of 92.4 ml/min/1.73 m2 and median urinary albumin to creatinine ratio (uACR) of 4.69 mg/g, 19 had uACR > 30 mg/g (A2). Higher serum cystatin C, serum and urine neutrophil gelatinase associated lipocalin (NGAL), urine kidney injury molecule 1 (KIM-1), detectable urine transferrin and IgG, and lower serum uromodulin significantly predicted A2 albuminuria, urine KIM-1/creatinine ratio, and IgG being the best predictors. Albuminuria, urine NGAL/creatinine, and IgG correlated with diabetes duration. Albuminuria, urine NGAL, transferrin, IgG, and uromodulin correlated with diabetes control. In a subgroup of 29 patients, retrospective data were available on changes in eGFR and uACR over one year. Decline in eGFR was observed in 17 patients and increase in uACR in 10 patients. Serum and urine NGAL correlated with eGFR changes. Higher urine NGAL, KIM-1/creatinine ratio, and detectable IgG were significantly associated with the increase in uACR. Widely available markers, serum cystatin C, urine IgG, transferrin, and NGAL, may help in early assessment of kidney disease in T2DM patients; however, large prospective studies are needed to confirm the conclusion.

Serum Uromodulin Levels in Prediction of Acute Kidney Injury in the Early Phase of Acute Pancreatitis.

In health, uromodulin is the main protein of urine. Serum uromodulin concentrations (sUMOD) have been shown to correlate with kidney function. Acute kidney injury (AKI) is among the main complications of severe acute pancreatitis (AP). No reports exist on sUMOD in patients with AP, including the diagnostic usefulness for early prediction of AP severity. We measured sUMOD during first 72 h of AP. Sixty-six adult patients with AP were recruited at the surgical ward of the District Hospital in Sucha Beskidzka, Poland. AP was diagnosed according to the Revised Atlanta Classification. Blood samples were collected at 24, 48 and 72 h of AP, and sUMOD concentrations were measured with enzyme-linked immunosorbent test. sUMOD decreased non-significantly during the study. Patients with severe AP had non-significantly lower sUMOD concentrations than those with mild disease. Significant positive correlation was observed between sUMOD and estimated glomerular filtration rate on each day of the study and negative correlations were shown between sUMOD and age, serum creatinine, cystatin C and urea. Patients with AKI tended to have lower sUMOD. Although sUMOD correlated significantly with kidney function in the early phase of AP, measuring sUMOD did not allow to reliably predict AP severity or development of AKI.

[Membranous nephropathy - the most commonly diagnosed glomerulopathy in patients who underwent renal biopsy in the Department of Internal Medicine, Nephrology and Endocrinology St. Queen Jadwiga Clinical District Hospital No. 2 in Rzeszow].

We retrospectively analysed the results of 120 renal biopsy, performed in 52 women, 62 men and 6 children hospitalized mainly in the Department of Internal Medicine, Nephrology and Endocrinology St. Queen Jadwiga Clinical District Hospital No. 2 in Rzeszów from 2013 to 2016. The average age of patients on whom renal biopsy was performed amounts to 44 (7-78) years. The most common indications for renal biopsy were nephrotic syndrome in 47 patients (37.3%), non-nephrotic proteinuria in 31 patients (24.6%), worsening renal function in 22 patients (17.5%), coexistence proteinuria with hematuria in 16 patients (12.7%), nephritic syndrome in 9 patients (7.1%) as well as an isolated hematuria in 1 patient (0.8%). Membranous glomerulonephritis was the most common histological diagnosis observed in biopsies, and was diagnosed in 19 patients (15.1%). In 14 patients we diagnosed lupus nephritis (11.1%). With the same frequency we diagnosed focal glomerulosclerosis, and mesangioproliferative glomerulonephritis (11 patients, 8,7%). Membraneproliferative glomerulonephritis was diagnosed in 10 patients (7.9%). Other nephropathy accounted for less than 8% of all diagnoses. Most patients with membranous nephropathy (8 patients, 61%) had antibodies against phospholipase A2 receptor. All patients with a diagnosis of membranous nephropathy received the renin- angiotensin-aldosterone system blockade, and 13 patients (68.4%) received immunosuppressive therapy. Complete remission was achieved in 11 patients (64.7%) with primary membranous nephropathy. In 35 patients (27.8%) of all patients who underwent renal biopsy they had complications after procedure in the form of small and clinically insignificant perirenal hematomas. Hematuria was observed in 7 cases (5.56%). In one case, due to retroperitoneal bleeding, the patient required a transfusion of blood products.

Angiopoietin-2 Is an Early Indicator of Acute Pancreatic-Renal Syndrome in Patients with Acute Pancreatitis.

Within the first week of the disease, acute kidney injury (AKI) is among the most common causes of mortality in acute pancreatitis (AP). Recently, serum angiopoietin-2 (Ang-2) has been associated with hyperdynamic state of the systemic circulation. The aim of this study was to examine the associations between Ang-2 and the clinical AP severity during the first 72 hours of the disease, and organ disfunction, including AKI. Methods. Study included patients admitted to the surgery ward, diagnosed with AP. AKI was diagnosed according to KDIGO guidelines and renal failure according to modified Marshall scoring system. Ang-2 was determined in serum with ELISA. Results. AP was classified as mild (MAP) in 71% of patients, moderately severe (MSAP) in 22%, and severe (SAP) in 8%. During the first 72 hours of AP, 11 patients developed AKI and 6 developed renal failure. Ang-2 at 24, 48, and 72 hours following the onset of AP symptoms significantly predicted SAP and MSAP, as well as AKI and renal failure. Also, Ang-2 significantly correlated with acute phase proteins as well as with the indicators of renal disfunction. Conclusions. Serum Ang-2 may be a relevant predictor of AP severity, in particular of the development of AP-renal syndrome.

Determination of serum neutrophil gelatinase-associated lipocalin at the early stage of acute pancreatitis.

AIM: e aim of the study was to assess the diagnostic value of serum concentrations of neutrophil gelatinase-associated lipocalin (sNGAL) for the determination of the severity of acute pancreatitis (AP) at the early stage of the disease. MATERIALS AND METHOD: The study group consisted of 65 patients(34 men and 31 women),aged 62.2 ± 16.0, admitted to the Surgery Department of the District Hospital in Sucha Beskidzka, Poland, with the diagnosis of AP according to the revised Atlanta classification (2012). sNGAL was measured with ELISA at 24, 48 and 72 hours following the onset of AP symptoms. The correlations were analyzed between sNGAL and clinical, as well as laboratory parameters, used for the assessment of AP severity. RESULTS: Severe AP was associated with higher sNGAL at 24, 48 and 72 hours, while moderately severe AP was associated with higher sNGAL at 48 and 72 hours as compared to mild disease. The BISAP score ≥3 during the first 24 hours of hospital stay, and the duration of hospital stay were significantly correlated with sNGAL. Also, sNGAL positively correlated with white blood cells, C-reactive protein and fibrinogen and negatively with albumin throughout the study. The diagnostic accuracy of sNGAL for the differentiation between mild AP and more severe disease was 75%, 77% and 85% at 24, 48 and 72 hours, respectively. CONCLUSIONS: Serum NGAL concentrations are associated with inflammatory markers, BISAP score and the severity of AP. sNGAL may serve as an additional prognostic biomarker in the early assessment of AP severity.

Urine NGAL is useful in the clinical evaluation of renal function in the early course of acute pancreatitis.

INTRODUCTION: Acute Kidney Injury (AKI) is a serious early complications in patients with acute pancreatitis (AP) that signifcantly increases mortality rates compared to patients without AKI. The early diagnosis of AKI during its treatable phases and implementation of appropriate treatment protocols can improve outcomes for this group of patients. A promising biomarker for AKI is neutrophil gelatinase-associated lipocalin (NGAL). AIM: This study evaluated the diagnostic value of NGAL concentrations in serum and in urine for patients developing AKI as an early complication of AP compared to AP patients without AKI. MATERIAL AND METHODS: The study group composed of 65 patients (34 men and 31 women) with a mean age of 62.2 ± 16 years with AP and hospitalized in the Surgery Department of the Direct Hospital in Sucha Beskidzka, Poland between January and December 2014. Serum NGAL (sNGAL) levels were measured with the BioVendor ELISA kit, and urine NGAL (uNGAL) with the Abbott ARCHITECT Analyzer. RESULTS: In the early phase of AP, 11 patients (17%) developed AKI, including 10 patients with stage 1 and one with stage 2. AKI was associated with more severe AP, higher BISAP scores, the need for more intensive treatment, longer hospital stays and higher mortality. Both serum and urine NGAL concentrations were signifcantly higher in patients with AKI throughout the study and signifcantly predicted AKI in simple and multiple logistic regression adjusted for age, sex and comorbidities. Serum and urine NGAL concentrations were signifcantly correlated with levels of serum urea, creatinine, urine albumin, and the maximum change in serum creatinine. Serum and urine NGAL levels also correlated positively with direct neutrophil counts and CRP concentrations throughout the study. CONCLUSIONS: The measurement of NGAL levels, particularly in urine, is simple, easy to interpret, routinely available, and clinically useful in the assessment of dynamic changes in kidney function for patients with AP.

Blood vessels of the shin - posterior tibial artery - anatomy - own studies and review of the literature.

Anatomy of the vascular system of the leg was studied using classical anatomical dissection methods. Based also on literature we have reviewed the current knowledge on the vascularization of the lower leg and its embryological background with special respect toward the posterior tibial artery and its branches.

[Urinalysis in patients at the early stage of acute pancreatitis]. / Badanie ogólne moczu u chorych z ostrym zapaleniem trzustki we wczesnej fazie rozwoju choroby.

Urinalysis is a routine and cheap laboratory test that provides clinically useful information in patients with acute abdominal conditions, including acute pancreatitis. The aim of the study was to assess the relationships between the results of urinalysis and the course of the disease among 65 patients with acute pancreatitis (34 men and 31 women, mean age 61 ± 19 years) at the early phase of the disease, i.e. during the first 72 hours from the onset of symptoms. Mild acute pancreatitis was diagnosed in 47 patients, moderately severe in 13 and severe in 5. The most prevalent abnormalities were proteinuria (43% of patients), high urinary bilirubin (20%), erythrocytes (18%), glucose (18%) and leukocytes (17%). High urinary protein and low specific gravity were associated with more severe acute disease and with acute kidney injury. The severity of bilirubinuria and proteinuria were positively correlated with urine concentrations of neutrophil gelatinase associated lipocalin (NGAL). Urinalysis should be routinely performed in patients with acute pancreatitis.

Renal interstitial mast cell count is significantly higher in membranoproliferative glomerulonephritis than in class IV lupus nephritis.

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus; in LN class IV morphologic lesions may be similar to the lesions in primary membranoproliferative glomerulonephritis (MPGN). The aim of the study was to compare the counts of tryptase-positive and chymase-positive mast cells between LN class IV and MPGN. The material consisted of 61 renal biopsies: 32 with lupus nephritis class IV, and 29 with membranoproliferative glomerulonephritis. Chymase- and tryptase-positive cells were stained by immunohistochemistry and subsequently counted. The mean count of chymase-positive mast cells was 21.94 for the whole group, 12.66 for LN class IV and 32.18 for MPGN. The mean count of tryptase-positive cells was 34.94 hpf for the entire group, 22.98 for LN class IV and 48. 13 for MPGN. The differences between lupus nephritis and membranoproliferative glomerulonephritis were significant both for chymase- and tryptase-positive cells. Both chymase-positive MC counts and tryptase-positive MC counts correlated with relative interstitial volume (RIV) (R=0.35 and R=0.28, respectively) and with creatinine level (R=0.35 and R=0.43, respectively). There was also a significant correlation between age, creatinine level and RIV (R=0.28 and R=0.26, respectively).

Role of new biomarkers for the diagnosis of nephropathy associated with diabetes type 2.

In twenty first century, the incidence of type 2 diabetes mellitus (DMt2) dramatically increases, followed by the number of patients suffering from its complications. Currently, diabetic kidney disease (DKD) is the leading cause of renal replacement therapy. Often, DMt2 is diagnosed after several years of duration, and irreversible organ damage can develop during that period. On the other hand, the early diag- nosis of DKD in the preclinical phase, when glomerular filtration rate (GFR) is still maintained and there are no evident changes in urinalysis, gives the possibility of implementing the nephroprotective treatment that can significantly delay the progression of the disease. However, the diagnostic tests available in clinical practice, i.e. serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria have important limitations. There is a need for new, early and non-invasive biomarkers specific for kidney injury, allowing for differentiation between glomerular and tubular injury, and changing dynamically in response to the degree of kidney damage. Hereby, we review the current knowledge about the novel and emerging biomarkers of kidney injury and their used for the diagnosis of DKD.

Numerical analysis of blood flow in the abdominal aorta under simulated weightlessness and earth conditions.

Blood flow through the abdominal aorta and iliac arteries is a crucial area of research in hemodynamics and cardiovascular diseases. To get in to the problem, this study presents detailed analyses of blood flow through the abdominal aorta, together with left and right iliac arteries, under Earth gravity and weightless conditions, both at the rest stage, and during physical activity. The analysis were conducted using ANSYS Fluent software. The results indicate, that there is significantly less variation in blood flow velocity under weightless conditions, compared to measurement taken under Earth Gravity conditions. Study presents, that the maximum and minimum blood flow velocities decrease and increase, respectively, under weightless conditions. Our model for the left iliac artery revealed higher blood flow velocities during the peak of the systolic phase (systole) and lower velocities during the early diastolic phase (diastole). Furthermore, we analyzed the shear stress of the vessel wall and the mean shear stress over time. Additionally, the distribution of oscillatory shear rate, commonly used in hemodynamic analyses, was examined to assess the effects of blood flow on the blood vessels. Countermeasures to mitigate the negative effects of weightlessness on astronauts health are discussed, including exercises performed on the equipment aboard the space station. These exercises aim to maintain optimal blood flow, prevent the formation of atherosclerotic plaques, and reduce the risk of cardiovascular complications.

[Performance neutrophil gelatinase-associated lipocalin in clinical settings]. / Oznaczanie lipokaliny zwiazanej z zelatynazq neutrofili (NGAL) w praktyce klinicznej.

Acute kidney injury (AKI) is largely asymptomatic, and establishing the diagnosis in thisin creasingly common disorder currently hinges on functional biomarkers such as serum creatinine. Early neutrophil gelatinase-associated lipocalin (NGAL) measurements can identify patients with sub-clinical AKI who have an increased risk of adverse outcomes, even in the absence of diagnostic increases in serum creatinine. NGAL is emerging as an excellent biomarker in the urine and plasma, for the early prediction of AKI, for monitoring clinical trials in AKI, and for the prognosis of AKI in several common clinical scenarios. Also numerous studies have also demonstrated that NGAL may be a potential biomarker for the diagnosis, prediction, prevention, and prognosis of non-AKI diseases such as chronic kidney diseases, vascular disorders, cancer, preeclampsia, and allergies. The current status of the most promising of novel biomarkers in medicin as NGAL is appraised in this review.

Secondary hyperparathyroidism in chronic kidney disease: pathomechanism and current treatment possibilities.

Secondary hyperparathyroidism (SHPT) is one of the most common metabolic complications resulting from chronic kidney disease (CKD). The complexity of calcium and phosphate disorders associated with CKD is defined by the Kidney Disease Improvement Global Outcomes (KDIGO) working group as CKD-related mineral and bone disorders (CKD-MBD). The last update of the KDIGO guidelines on the conduct in CKD-MBD was published in 2017. The treatment of SHPT is based on 2 strategies: counteracting hyperphosphataemia and suppressing parathyroid hormone (PTH) secretion. Therapy should be based on optimally selected drugs, taking into account additional effects to reduce the risk of chronic complications and side effects. The creation of new drugs with a better safety profile, significant reduction of side effects, and greater efficiency in achieving target serum phosphorus and PTH values forces the gradual replacement of existing treatment with new pharmacotherapies. The aim of this study is to discuss the latest issues (in connection with the latest KDIGO guidelines) regarding the pathomechanism of secondary hyperparathyroidism and the current directions of the therapy in these disorders.