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Urszula Szydełko-Paśko,1 Joanna Przeździecka-Dołyk,1,2 Rafał Małecki,3 Andrzej Szuba,3 Marta Misiuk-Hojło1 1Department of Ophthalmology, Wroclaw Medical University, Wrocław, Poland; 2Department of Optics and Photonics, Wroclaw University of Science and Technology, Wrocław, Poland; 3Department of Angiology, Systemic Hypertension and Diabetology, Wroclaw Medical University, Wrocław, PolandCorrespondence: Urszula Szydełko-Paśko, Department of Ophthalmology, Wroclaw Medical University, Borowska 213, Wrocław, 50-556, Poland, Tel +48 71 736 43 00, Email u.szydelko@gmail.comAbstract: Buerger’s disease, also known as thromboangiitis obliterans, is a disorder of primarily small and medium arteries and veins of the arms and legs. We have failed to find a comprehensive review discussing a possible link between the disease and the eyes. The aim of this study is to review current knowledge on the topic of ocular manifestations in the course of Buerger’s disease. The Medline and Web of Science databases were searched without a time or language limit. We have managed to review 13 articles, describing the involvement of the eyes in thromboangiitis obliterans. It appears that patients suffering from Buerger’s disease may develop non-arteritic anterior ischemic optic neuropathy (NAION), occlusive retinal vasculitis and periphlebitis, papillophlebitis, central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), normal tension glaucoma (NTG), uveitis, chorioretinal atrophy, retinitis, papillitis, optic atrophy, changes typical for hypertensive retinopathy. Additionally the abnormalities in electroretinography might be present. The treatment options and the possible outcome depend on the type of ocular manifestations, so it seems impossible to propose a universal therapy. We would like to raise awareness of the possible ocular manifestations in the course of Buerger’s disease.Keywords: Buerger’s disease, anterior ischemic optic neuropathy, central retinal artery occlusion, normal tension glaucoma, uveitis

Hypothenarhammersyndrome (HHS) jest rzadko występującym zespołem, w którym powtarzające się tępe urazy okolicy kłębika prowadzą do niedokrwienia palców ręki związanego z rozwojem przetrwałego skurczu, zakrzepicy lub powikłań zatorowych tętniaka tętnicy łokciowej. Zespół ten najczęściej rozwija się u mężczyzn zawodowo narażonych na przewlekły uraz mechaniczny, w którym okolica kłębika poddawana jest silnym wibracjom, pośredniczy w chwytaniu przedmiotów lub też używana jest jako narzędzie w charakterze „młotka". Chorobę opisywano również u sportowców. Klinicznie w HHS występują objawy neurologiczne będące następstwem ucisku lub uszkodzenia nerwu łokciowego w kanale Guyona oraz jednostronne niedokrwienie palców ręki oszczędzające kciuk. W zaawansowanych postaciach mogą pojawić się bóle spoczynkowe i zmiany troficzne skóry, a nawet zgorzel. Z uwagi na rzadkość występowania HHS może nastręczać trudności w diagnostyce różnicowej z innymi, częstszymi przyczynami niedokrwienia kończyn górnych. Właściwa identyfikacja czynników ryzyka i wczesne wdrożenie leczenia może uchronić pacjenta przed martwicą zagrażającą amputacją palców. Objawy HHS nierzadko pojawiają się z dużym opóźnieniem w stosunku do ekspozycji na czynniki uszkadzające, co wymaga od lekarza szczególnej uwagi w zbieraniu wywiadu chorobowego. Przedstawiono przypadek 48-letniego instruktora sportów walki, u którego wystąpiły objawy krytycznego niedokrwienia palca IV i V dominującej ręki. Dane z wywiadu wskazywały, że pacjent od wielu lat uprawiał sporty urazowe (karate i boks), co było przyczyną powtarzających się urazów wyniosłości kłębika. W toku postępowania diagnostycznego (badania serologiczne w kierunku choroby układowej i systemowego zapalenia naczyń, USG serca, badanie duplex-dopplerowskie tętnic kończyn górnych kodowane kolorem, kapilaroskopia, arteriografia prawej kończyny górnej) ustalono rozpoznanie HHS. W wyniku zastosowanego leczenia enoksaparyną, alprostadilem, pentoksyfiliną i preparatami przeciwpłytkowymi uzyskano znaczącą poprawę ukrwienia ręki, ustąpienie dolegliwości bólowych i wygojenie zmian martwiczych w ciągu 5 tygodni obserwacji. [ABSTRACT FROM AUTHOR]

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Background: Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis., Methods: PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin-angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850., Findings: Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6-110) was -2·7 mL/min per 1·73 m 2 per year versus -3·8 mL/min per 1·73 m 2 per year (difference 1·1 mL/min per 1·73 m 2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1-week 110) was -2·9 mL/min per 1·73 m 2 per year versus -3·9 mL/min per 1·73 m 2 per year (difference 1·0 mL/min per 1·73 m 2 per year, 95% CI -0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (-42·8%, 95% CI -49·8 to -35·0, with sparsentan versus -4·4%, -15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals., Interpretation: Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function., Funding: Travere Therapeutics., Competing Interests: Declaration of interests BHR reports consulting fees from Alexion Pharmaceuticals, Alpine Pharma, BioCryst Pharmaceuticals, Calliditas Therapeutics, Novartis, Q32 Bio, Omeros, Otsuka Pharmaceuticals, Travere Therapeutics, and Vera Therapeutics; and has a leadership role at NephroNet, Lupus ABC/LRA, and Lupus Foundation of America. JB reports a research grant and consulting fees from Travere Therapeutics. HJLH reports honoraria from Travere Therapeutics for membership of the DUPLEX clinical trial steering committee; grants for clinical trials and clinical research from AstraZeneca, Boehringer Ingelheim, Janssen, and Novo Nordisk paid to his institution; consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, CLS Behring, Chinook Therapeutics, Dimerix, Lilly, Gilead Sciences, Janssen, Mitsubishi Tanabe Pharma, Novartis, Novo Nordisk, and Travere Therapeutics paid to his institution; honoraria from AstraZeneca, Bayer, and Novo Nordisk; and travel support from AstraZeneca and Lilly. CEA reports consulting fees from Travere Therapeutics and honoraria from Travere Therapeutics for membership of the DUPLEX clinical trial steering committee. SB, UAD, JKI, RK, PP, and WER are employees and stockholders of Travere Therapeutics. JF reports consulting fees and honoraria from AstraZeneca, Boehringer Ingelheim, Calliditas Therapeutics, Chinook Therapeutics, CSL Vifor, Novartis, Omeros, STADApharm, Travere Therapeutics, and Vera Therapeutics, and serves on a data safety monitoring or advisory board for Novo Nordisk and Visterra. LG reports grant support from ABIONYX Pharma and Sanofi to his institution; has been a member of advisory boards for AstraZeneca, Baxter, Chinook Therapeutics, CSL Vifor, GSK, Mundipharma, Novartis, PharmaDoc, Roche, Sanofi, and Travere Therapeutics; and has been an invited speaker at meetings supported by AstraZeneca, Astellas Pharma, Estor, Fresenius, GSK, Medtronic, Travere Therapeutics, and Werfen. DEK reports consulting fees from AstraZeneca, Chinook Therapeutics, and Travere Therapeutics, and honoraria from Chinook Therapeutics and Travere Therapeutics. LAK is a principal investigator for studies sponsored by Akebia Therapeutics, AstraZeneca, Boehringer Ingelheim, Cara Therapeutics, Chinook Therapeutics, CSL Behring, Galderma, Omeros, Otsuka Pharmaceuticals, Reata Pharmaceuticals, Sanifit Therapeutics, Travere Therapeutics, and Visterra. RL reports research grants and consulting fees from Alexion Pharmaceuticals, Amgen, BeiGene, Calliditas Therapeutics, Chinook Therapeutics, Novartis, Omeros, Otsuka Pharmaceuticals, Roche, Travere Therapeutics, and Vera Therapeutics, and travel support from Calliditas Therapeutics and Novartis. RM reports honoraria from AstraZeneca, Bayer, Berlin-Chemie Menarini, Boehringer Ingelheim, Fresenius Kabi, Novartis, Novo Nordisk, and Lilly, and travel support from Aurovitas Pharma and Menarini. AM reports consulting fees from HI-Bio, Travere Therapeutics, and Vera Therapeutics. ILN reports grants and consulting fees from George Clinical; honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, and Lilly; and travel support from AstraZeneca. MP reports consulting fees from Alexion Pharmaceuticals, Apellis Pharmaceuticals, CSL Vifor, GSK, Novartis, Otsuka Pharmaceuticals, Sanofi, and Travere Therapeutics. JR reports grant funding for clinical trials from Travere Therapeutics paid to his institution; consulting fees from Travere Therapeutics; advisory board membership for Travere Therapeutics; and a leadership role at KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. MNR reports funding for clinical trials by Travere Therapeutics paid to her institution; grants from Akebia Therapeutics, Chinook Therapeutics, the US Department of Defense, the US National Institute of Diabetes and Digestive and Kidney Diseases, Reata Pharmaceuticals, River 3 Renal, and Sanofi paid to her institution; consulting fees from ENYO Pharma, Visterra, and Walden Biosciences; membership of the data safety monitoring board of Advicenne; and leadership roles at #NephJC, Pediatric Nephrology Research Consortium, and Women in Nephrology. SCWT reports honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, GSK, and Novartis, and has leadership roles at Asian Pacific Society of Nephrology and KDIGO. VT reports consulting fees from AstraZeneca, Boehringer Ingelheim, Calliditas Therapeutics, Novartis, Omeros, Otsuka Pharmaceuticals, and Travere Therapeutics, and had a leadership role at the International Society of Nephrology. HTra reports loyalties or licenses from UpToDate; consulting fees from Aclipse Therapeutics, Boehringer Ingelheim, Maze Therapeutics, Natera, Otsuka Pharmaceuticals, PhaseV, Travere Therapeutics, and Walden Biosciences; honoraria from the US National Kidney Foundation; travel support from Travere Therapeutics; membership of a data safety and monitoring or advisory board for ChemoCentryx, Otsuka Pharmaceuticals, and Travere Therapeutics; and leadership roles at Alport Syndrome Foundation, Glomerular Diseases, Kidney Health Initiative, and Pediatric Nephrology. HTri reports grants from AstraZeneca, Bayer, BioCryst Pharmaceuticals, Calliditas Therapeutics, Chinook Therapeutics, Dimerix, George Clinical, Novartis, Omeros, Otsuka Pharmaceuticals, and Vera Therapeutics; consulting fees from AstraZeneca, BioCryst Pharmaceuticals, Calliditas Therapeutics, Chinook Therapeutics, Dimerix, George Clinical, Novartis, Omeros, Travere Therapeutics, and Vera Therapeutics; honoraria from AstraZeneca, BioCryst Pharmaceuticals, Calliditas Therapeutics, Chinook Therapeutics, George Clinical, Novartis, and Travere Therapeutics; travel support from BioCryst Pharmaceuticals, Calliditas Therapeutics, and Chinook Therapeutics; and membership of a data safety monitoring or advisory board for AstraZeneca, BioCryst Pharmaceuticals, Calliditas Therapeutics, Chinook Therapeutics, Novartis, and Travere Therapeutics. JAT reports grants, consulting fees, and honoraria from Travere Therapeutics. MGW reports grants as a member of clinical trial steering committees for Alpine Pharma, CSL Behring, Eledon Pharma, Kira Pharma, Travere Therapeutics, Otsuka Pharmaceuticals, and TESTING trials; consulting fees from George Clinical via Travere Therapeutics; honoraria from AstraZeneca, Amgen, Baxter, Boehringer Ingelheim, and Travere Therapeutics; travel support from Amgen, Baxter, Chinook Therapeutics, George Clinical, Otsuka Pharmaceuticals, and Travere Therapeutics; membership of the data safety monitoring boards for the ARGX-133 and HFpEF Polypill trials and the advisory board of Alpine Pharma, Eledon Pharma, and Kira Pharma; and leadership roles at the Australia New Zealand Society of Nephrology and Asia Pacific Society of Nephrology. VP serves as Board Director for St Vincents Health Australia and several medical research institutes; has led or served on the steering committees of trials funded by AbbVie, Bayer, Boehringer Ingelheim, Chinook Therapeutics, Gilead Sciences, GSK, Janssen, Lilly, Novartis, Novo Nordisk, Otsuka Pharmaceuticals, Pfizer, Travere Therapeutics, and Tricida; and reports honoraria for steering committee roles, scientific presentations, or advisory board attendance from AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Chinook Therapeutics, Gilead Sciences, GSK, Janssen, Lilly, Merck, Mitsubishi Tanabe Pharma, Mundipharma, Novartis, Novo Nordisk, Otsuka Pharmaceuticals, Pfizer, Travere Therapeutics, and Tricida. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Treatment of essential thrombocythemia (ET) is particularly challenging in pregnancy due to the increased risk of thromboembolic complications. Therefore, the use of antithrombotic regimens are recommended in pregnant women with ET. Methods: The study included 52 pregnancies in 27 patients diagnosed with ET, who were treated in Department of Haematology. The influence of anticoagulant, antiplatelet and cytoreductive therapy on the course and outcome of pregnancy was analysed. This study also examined if there was any correlation between molecular and clinical features such as mutational profile, blood count, presence of acquired von Willebrand syndrome (AvWS), the International Prognostic Score for Essential Thrombocythemia (IPSET) risk group and the IPSET-thrombosis risk group and pregnancy outcome. Results: Study participants who received antithrombotic therapy were significantly more likely to give birth to a healthy child. The best outcomes were observed in patients who received low dose acetylsalicylic acid (ASA) together with low-molecular-weight heparin (LMWH). There was a statistically significant correlation between classification to the high-risk group according to the IPSET-thrombosis score and incidence of miscarriage. Cytoreductive treatment with interferon-α2, as well as the presence of AvWS did not increase the likelihood of pregnancy loss. Blood counts and presence of specific gene mutations profile were also not found to be significant determinants of pregnancy outcome. Conclusion: To our best knowledge, this is the first clinical study investigating the correlation between risk group (according to IPSET and IPSET-thrombosis) and pregnancy outcome in women with ET.

The COVID-19 pandemic has significantly affected the lives and mental health of people around the world, and it has become clinically essential to define risk factors in order to provide adequate prevention and support. The aim of the study was to describe coping strategies in Polish women related to the COVID-19 pandemic using the balance model, one of the most important concepts of positive psychotherapy (PPT after Peseschkian since 1977). The analysis included 735 women at the mean age of 39.61 years. The survey was conducted using the questionnaire form on the website. Based on Beck’s depression test, depressive disorders were disclosed in 32.65%, and both the presence and severity of depressive syndromes were inversely correlated with age. Using a cluster analysis, three adaptation strategies could be identified, related to the different prevalence of depressive disorders. Relationships proved the most crucial area of the balance model, responsible for the effectiveness of the coping strategy. Based on the obtained results, it has to be concluded that preventive measures should primarily concern women aged < 25 years old and focus on strengthening the relationships area.

BACKGROUND Giant cell arteritis (GCA) is an inflammation of large vessels that affects the lining of the arteries and leads to vessel swelling and the eventual reduction of blood flow. This can result in ischemia of the optic nerve, which is known as arteritic anterior ischemic optic neuropathy (AAION). The present case seems noteworthy because the patient developed GCA with the ocular manifestation of AAION shortly after having COVID-19. CASE REPORT A 69-year-old woman was admitted to the Clinic of Ophthalmology after having COVID-19. She reported vision loss in the left eye, which appeared 2.5 weeks after a positive SARS-CoV-2 test. While in the hospital, she was diagnosed with AAION and GCA. The patient was treated with enoxaparin sodium, prednisone, and methotrexate. Three months after the hospitalization, the visual acuity of the left eye was limited to light perception, and optic nerve atrophy was reported. CONCLUSIONS We would like to emphasize the role of SARS-CoV-2 infection as a possible risk factor for the onset of GCA and its ocular manifestations, such as AAION. However, further research is needed to determine the relationship between SARS-CoV-2 infection and GCA. Because some symptoms of the 2 diseases are similar, the diagnosing process might be long and challenging. The diagnosis of GCA should be made as soon as possible to avoid serious complications, such as bilateral vision loss.

Background: The genetic backgrounds of diabetic kidney disease (DKD) and end-stage kidney disease (ESKD) have not been fully elucidated., Aim: To examine the individual and cumulative effects of single-nucleotide polymorphisms (SNPs) previously associated with DKD on the risk for ESKD of diabetic etiology and to determine if any associations observed were specific for DKD., Methods: Fourteen SNPs were genotyped in hemodialyzed 136 patients with diabetic ESKD (DKD group) and 121 patients with non-diabetic ESKD (NDKD group). Patients were also re-classified on the basis of the primary cause of chronic kidney disease (CKD). The distribution of alleles was compared between diabetic and non-diabetic groups as well as between different sub-phenotypes. The weighted multilocus genetic risk score (GRS) was calculated to estimate the cumulative risk conferred by all SNPs. The GRS distribution was then compared between the DKD and NDKD groups as well as in the groups according to the primary cause of CKD., Results: One SNP (rs841853; SLC2A1) showed a nominal association with DKD ( P = 0.048; P > 0.05 after Bonferroni correction). The GRS was higher in the DKD group (0.615 ± 0.260) than in the NDKD group (0.590 ± 0.253), but the difference was not significant ( P = 0.46). The analysis of associations between GRS and individual factors did not show any significant correlation. However, the GRS was significantly higher in patients with glomerular disease than in those with tubulointerstitial disease ( P = 0.014) and in those with a combined group (tubulointerstitial, vascular, and cystic and congenital disease) ( P = 0.018)., Conclusion: Our results suggest that selected SNPs that were previously associated with DKD may not be specific for DKD and may confer risk for CKD of different etiology, particularly those affecting renal glomeruli., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing financial interests. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Diagnosis of pheochromocytomas and paragangliomas in patients receiving hemodialysis is troublesome. The aim of the study was to establish optimal conditions for blood sampling for mass spectrometric measurements of normetanephrine, metanephrine and 3-methoxytyramine in patients on hemodialysis and specific reference intervals for plasma metanephrines under the most optimal sampling conditions. Blood was sampled before and near the end of dialysis, including different sampling sites in 170 patients on hemodialysis. Plasma normetanephrine concentrations were lower (P < 0.0001) and metanephrine concentrations higher (P < 0.0001) in shunt than in venous blood, with no differences for 3-methoxytyramine. Normetanephrine, metanephrine and 3-methoxytyramine concentrations in shunt and venous blood were lower (P < 0.0001) near the end than before hemodialysis. Upper cut-offs for normetanephrine were 34% lower when the blood was drawn from the shunt and near the end of hemodialysis compared to blood drawn before hemodialysis. This study establishes optimal sampling conditions using blood from the dialysis shunt near the end of hemodialysis with optimal reference intervals for plasma metanephrines for the diagnosis of pheochromocytomas/paragangliomas among patients on hemodialysis., (© 2021. The Author(s).)

The aim of our study was to evaluate if endothelial-dysfunction (ED) occurs in patients with primary Sjogren syndrome (pSS) and whether it is associated with the disease characteristics and activity. A total of 46 patients with pSS and 30 controls, without known cardiovascular disease, were enrolled in this study. A flow-mediated-dilation (FMD) of the brachial artery, plasma concentrations of the nitric oxide (NO) metabolic pathway (ADMA, L-arginine, SDMA, cGMP), and markers of endothelial inflammatory function (PAI-1, sE-selectin) and angiogenesis (angiostatin, VEGF) were analyzed. The FMD was significantly lower in pSS patients (7.56 ± 3.08 vs. 10.91 ± 1.02%, p = 0.043) and positively correlated with the Ro/SS-A-antibodies ( r = 0.34, p = 0.03), pulmonary involvement ( r = 0.52, p = 0.001) and inversely with ADMA ( r = -0.35, p = 0.04). Plasma ADMA, L-arginine and angiostatin levels were significantly higher in pSS patients (0.39 ± 0.08 vs. 0.36 ± 0.06 µmol/L, p = 0.05; 29.07 ± 6.7 vs. 25.4 ± 5.23 µmol/L, p = 0.01; 152.25 ± 60.99 vs. 120.07 ± 38.7 pg/mL, p = 0.0, respectively). ADMA was associated with ESSDAI ( r = 0.33, p = 0.02), SCORE ( r = 0.57, p = 0.00003) and focus score ( r = 0.38, p = 0.04). In the multiple regression analysis, the ESSDAI was significantly and independently associated with plasma ADMA levels ( β = 0.24, p = 0.04). Moreover, plasma cGMP concentrations were negatively correlated with the disease duration ( r = -0.31, p = 0.03). Endothelial function is impaired in patients with pSS and associated with the measures of disease activity, which supports the key-role of inflammation in developing and maintaining accelerated atherosclerosis.

Aims: Infection in diabetic foot syndrome (DFS) represents serious medical problem, and the annual risk of DFS in diabetic patients is 2.5%. More than half of the patients with DFS have symptoms of extremity ischemia (peripheral arterial disease (PAD)). The aim of the present study was to analyze the frequency of particular bacterial strains in people with DFS, analyze the impact of arterial ischemia on the occurrence of a given pathogen, and evaluate the antibacterial treatment based on the results of bacterial culture., Methods: The analysis included 844 bacterial strains obtained from 291 patients with DFS hospitalized in the Department of Angiology in years 2016-2019., Results: The most common isolates were Staphylococcus aureus , Enterococcus faecalis , Enterobacter cloacae , Pseudomonas aeruginosa , and Acinetobacter baumannii . Nearly 20% of the species were found to have at least one resistance mechanism. In patients with PAD, Gram-negative species were isolated more commonly than in people without PAD. The most useful drugs in DFS in hospitalized patients are penicillins with beta-lactamase inhibitors, 3rd- to 5th-generation cephalosporins (with many exceptions), carbapenems, aminoglycosides, and tigecycline., Conclusions: Bacterial strains isolated from ischemic DFS are more resistant to commonly used antibacterial agents, i.e., penicillins (including penicillins with beta-lactamase inhibitors), cephalosporins (except for the 4 th and 5 th generations), glycopeptides, and linezolid. When planning treatment of hospitalized patients with DFS, the presence of ischemia in DFS should always be taken into consideration. It determines the occurrence of particular bacterial species and the choice of antibacterial agent and may determine the rate of treatment success., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Rafał Małecki et al.)

Introduction: Patients with type 2 diabetes represent 50% of all sudden cardiac deaths. Disseminated arteriosclerotic lesions are the cause of vascular incidents that cause permanent disability resulting from lower limb amputations., Objectives: Our study was designed to investigate the relationship between asymmetrical dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) plasma concentration and intima-media thickness (IMT) in subjects with diabetes mellitus without vascular complications (group A) and a group of diabetic patients diagnosed with diabetes micro- and macroangiopathy (group B)., Patients and Method: The experimental groups included 42 diabetic patients. Group A - 22 patients (9 W and 13 M), free from vascular complications (mean age 55.83±7.37 years), group B - 20 patients (6 W, 14 M) with accompanying micro- and macropathic changes (mean age 63.80±8.79 years). Group C (n=22), the control group, consisted of healthy volunteers (12 W and 10 M), between the ages of 40 to 60 (mean age 51.16±6.39), selected in reference to the age and sex of the research group. The carotid artery intima-media complex thickness (IMT) was evaluated with the use of a duplex ultrasound., Conclusions: There was no correlation between ADMA and the maximal or mean intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA). We demonstrated a correlation between symmetric dimethylarginine (SDMA) concentration and CCA IMT. The results suggest that ICA IMT may serve as a marker of vascular complication among patients with diabetes.

Background and Purpose: When choosing a cytoreduction method for patients suffering from essential thrombocythemia (ET), it is important to know the safety profile of the medicine used. Few articles have been published about the effects of hydroxycarbamide (hydroxyurea, HU) and anagrelide (ANA) on renal function in ET patients. This study is the largest analysis of nephrotoxicity of cytoreductive drugs used in ET therapy so far, which additionally includes risk factors for the progression of kidney disease and coexisting genetic mutation., Experimental Approach: The retrospective study included 310 patients diagnosed with ET. Demographic data, comorbidities, Cr, and estimated glomerular filtration rate (eGFR) were all taken into account prior to diagnosis and after 6 months of HU and ANA treatment., Key Results: A statistically significant difference was found between Cr and eGFR levels at baseline and after 6 months of treatment (p < 0.001). The applied treatment (HU and ANA) had the greatest impact on kidney function. ANA significantly increased the risk of worsening renal function in contrary to hydroxycarbamide after 6 months of treatment (eGFR change: median +1 mL/min/1.73 m2 [interquartile range (IQR) (-4)-(+7)] in the HU group vss. median -13 mL/min/1.73 m2 [IQR (-18)-(-6)] in the ANA group, odds ratio [OR] 7.92 95% confidence interval [95% CI] [4.17-15.08], p < 0.001). Lowering of eGFR <60 mL/min/1.73 m2 occurred in 31 patients (31.0%) from the ANA group and 10 people (4.8%) treated with HU (p = 0.000). In 1 patient from the ANA group, >50% decrease in eGFR was observed. The chance for an increase in Cr levels was higher in people with pre-existing arterial hypertension (OR 1.92 CI = 95% [1.21-3.05], p = 0.006). Sex, type of mutation found (JAK2 V617F or CALR), and previous renal impairment did not affect renal function after 6 months of treatment. In addition, there was no difference in the efficacy of ET treatment between HU and ANA (p = 0.998)., Conclusions and Implications: The observations indicate that ANA should be used in patients with ET with great caution and taking into account the risk of worsened kidney function., (© 2021 S. Karger AG, Basel.)

Purpose: The usefulness of FRAX in predicting major bone fractures in patients with end-stage kidney disease on maintenance hemodialysis treatment has been confirmed in previous studies. For meaningful clinical use, the prognostic and intervention FRAX thresholds need to be established., Methods: The primary aim of our study was to calculate the optimal cut-off point of FRAX for the best prediction of an increased bone fracture risk in dialysis patients and additionally, to propose its intervention threshold, indicating the need for antifracture pharmacological treatment. The study included 718 hemodialysis patients, who were followed up for two years. Thirty low-energy major bone fractures were diagnosed during the study period. We used the Polish version of FRAX (without the DXA examination) and some particular variables of the FRAX calculator. The optimal cut-off point for prediction of an increased major bone fracture risk was based on the analysis of the sensitivity and specificity curves of FRAX., Results: The analysis revealed FRAX >5% (sensitivity of 70.0%, specificity of 69.8%) as the prognostic threshold for major bone fractures. Its sensitivity for bone fracture prediction was significantly higher, but specificity lower than those of FRAX ≥10%, used in general Polish population. The reason for this can be an underestimation of bone fracture risk with FRAX in dialysis patients., Conclusions: We conclude that the FRAX prognostic threshold for identification of an increased risk of major bone fractures in hemodialysis patients is >5%. We propose to use this specific value of FRAX as an intervention threshold for pharmacological antifracture treatment in hemodialysis patients., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A significant number of patients with essential thrombocythemia (ET) complain of symptoms including distal parts of the extremities (e.g., paresthesias or Raynaud's phenomenon). The aim of the present study was to examine peripheral circulation in the upper extremities of individuals with ET. The study included 45 ET patients and 30 control subjects. All participants were subjected to thermography, photoplethysmography, impedance plethysmography, and applanation tonometry pulse wave analysis. The patients with ET differed significantly from the control subjects in terms of 3rd finger skin temperature (mean 31.04 vs. 32.45°C), skin temperature gradient (mean 1.82 vs. 0.11°C), photoplethysmographic amplitude (median 0.25 vs. 0.74%), and pulse waveform in the radial artery (more frequent occurrence of type B waveform). Pulse wave parameters correlated with the skin temperature gradient. The study findings imply the altered regulation of peripheral circulation in ET, including a decreased flow and an increased resistance., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Patients with increased thromboembolic risk tend to form denser fibrin clots which are relatively resistant to lysis. We sought to investigate whether essential thrombocythemia (ET) is associated with altered fibrin clot properties in plasma. Ex vivo plasma fibrin clot permeability coefficient (Ks), turbidimetry and clot lysis time (CLT) were measured in 43 consecutive patients with ET (platelet count from 245 to 991 × 10(3)/µL) and 50 control subjects matched for age, sex and comorbidities. Fibrinolysis proteins and inhibitors together with platelet activation markers were determined. Reduced Ks (-38%, p < 0.0001) and prolonged CLT (+34%, p < 0.0001) were observed in ET. The differences remained significant after adjustment for fibrinogen and platelet count. ET was associated with a slightly shorter lag phase (-5%, p = 0.01) and higher maximum absorbency of the turbidimetric curve (+6%, p < 0.001). The ET patients had higher plasma P-selectin by 193% (p < 0.00001) and platelet factor 4 (PF4) by 173% (p < 0.00001), with higher P-selectin observed in 19 (44%) patients with JAK-2 gene V617F mutation. Higher t-PA (+20%, p < 0.001), 23% higher plasminogen activator inhibitor-1, PAI-1 (+23%, p < 0.01) and unaltered thrombin-activatable fibrinolysis inhibitor, plasminogen and α2-antiplasmin activity were found in the ET group. Ks inversely correlated with fibrinogen, PF4 and C-reactive protein. CLT positively correlated only with PAI-1. Patients with ET display prothrombotic plasma fibrin clot phenotype including impaired fibrinolysis, which represents a new prothrombotic mechanism in this disease.

Background: Patients with rheumatoid arthritis (RA) have a shortened lifespan compared to the general population. The high rate of premature mortality in the RA population can be attributed to cardiovascular disease (CVD)., Objectives: The aim of the study was to look for non-classic risk factors that can at least partially explain the enhanced cardiovascular (CV) risk in patients with RA., Material and Methods: This was an observational study with 37 RA patients and 24 healthy volunteers as controls. The participants' medical history was taken, and systematic coronary risk evaluation (SCORE) and carotid ultrasonography examinations were performed on all the participants. Laboratory tests included antibodies anti-cyclic citrullinated peptide (anti-CCP), inflammatory markers, lipid level, oxidized low-density lipoprotein (oxLDL) level and the level of anti-oxLDL antibodies., Results: Both SCORE and oxLDL fraction were elevated in RA patients as compared to the healthy controls (3.1 ± 3.7 vs. 0.8 ± 1.2, p = 0.005; and 0.029 ± 0.033% vs. 0.014 ± 0.006%, p = 0.04, respectively). In the RA group, the presence of anti-CCP was associated with thickening of the carotid intima-media complex and SCORE elevation. In the RA group, significant correlations were found between SCORE and mean carotid intima-media thickness (IMT; RP = 0.34, p = 0.040), disease activity score (RP = 0.42, p = 0.011), erythrocyte sedimentation rate (ESR; RP = 0.35, p = 0.036), and disease duration (RP = 0.52, p = 0.002). In RA patients with carotid plaques, the oxLDL fraction was significantly elevated in comparison to those without plaques (0.055 ± 0.070% vs. 0.022 ± 0.018%, p = 0.033). In the RA group, there was a significant negative correlation between mean carotid IMT and the serum concentration of anti-oxLDL antibodies (RP = -0.38, p = 0.02). No association was noted between the presence of rheumatoid nodules and SCORE or carotid IMT., Conclusions: Among RA patients, disease activity, ESR, disease duration, the presence of anti-CCP antibodies, the oxLDL fraction and the level of anti-oxLDL antibodies influence CV risk.

Thromboangiitis obliterans (TAO) is a rare disease of unknown etiology that results in the occlusion of limb arteries located distally to the elbow and knee. Despite the fact that more than one hundred years have passed since its first description, knowledge on the pathogenesis of TAO and precipitating factors is still limited. Due to a lack of decisive noninvasive diagnostic methods and geographical differences in the prevalence of this condition, data on TAO epidemiology also remains sparse. This review presents important evidence on the pathogenesis and the course of the condition, as well as diagnostic modalities, with a focus on differential diagnosis. Theories on the pathogenesis of TAO include the theory of an infectious disease, coagulation disorders and injury to vascular endothelium resulting in activation of the inflammatory response. Differential diagnosis should exclude thoracic outlet syndrome, blue toe syndrome, infectious endocarditis, popliteal entrapment syndrome, Takayasu disease, primary and secondary systemic vasculitis, antiphospholipid syndrome, infection with the anaerobic Clostridium sp. bacilli and some less common conditions.

Urological consultation is an important step in the procedure of a patient's preparation before placing him/her on a waiting list for a renal transplant. Urological work-up aims to diagnose, treat, and optimize any preexisting urological disease. In the present paper we present the review of the literature together with the authors' conclusions based on literature and their experience. There is not enough data in current literature and urology manuals on the adequate sequence of the urological management with patients qualified for renal transplant and the literature needs an update. This study presents the crucial steps of the qualification and emphasizes the urge for a more standardized urological approach in patients qualified for a kidney transplantation.

Background: Insufficiency of blood vessels supplying a limb allograft may lead to loss of the extremity. Thus, a regular evaluation of perfusion of transplants seems a reasonable approach. The purpose of the present study was assessment of allograft perfusion by means of non-invasive methods., Material/methods: Six hand allografts transplanted in 5 patients were included in the study group. The transplant procedure occurred on average 45 months before. The study group comprised 2 allografts at forearm level, 2 transplants of the arm, and 1 bilateral transplant of the forearm. Parameters of blood flow using Doppler ultrasonography, impedance plethysmography, Doppler measurement of segmental pressures, optical pulse oscillography (OPO), and thermography were performed in all participants., Results: DUS revealed increased resistive index in ulnar arteries of transplant hands compared to native hands and an altered blood supply was confirmed by IP. Flow-mediated dilatation within the transplanted extremity was abnormal in most patients and was inversely correlated with number of episodes of acute rejection. Analysis of oscillographic spectrum revealed flattening of the dicrotic notch in transplant hands. A tendency for lower temperature of the skin of transplanted hands compared to native extremities was also observed., Conclusions: In asymptomatic patients after limb transplantation, non-invasive methods disclosed discreet abnormalities of graft perfusion. Thus, regular measurement of perfusion parameters using these methods appears to be a promising approach to detect early and potentially reversible disturbances of blood supply. Further observational studies are required to determine its clinical significance.

Background: Diabetic foot syndrome (DFS) represents one of the most frequent reasons for lower limb amputation in developed countries. In most cases, it is associated with bacterial infection, requiring optimal antibiotic therapy., Objectives: The aim of this study was to identify the most frequent pathogens responsible for infections associated with DFS, establish the optimal protocol of empirical therapy, and ascertain the clinical variables that may determine the choice of the appropriate antibacterial agent., Material and Methods: The analysis included hospital records of patients treated at the Department between 2008 and 2010. A total of 102 individuals were identified; their material was cultured and tested for antibiotic susceptibility., Results: A total of 199 bacterial strains were isolated. There was a predominance of Gram-positive bacteria, particularly Staphylococcus aureus, Staphylococcus coagulase-negative strains, and Enterococcus faecalis. Of note was the high percentage of E. faecalis infection (16.08%). One can speculate on the potential etiological factors in the case of some bacteria, e.g. patients infected with S. aureus were characterized by higher monocytosis and lymphocytosis as compared to other patients. Analysis of drug susceptibility revealed that ciprofloxacin has the highest (but still only 44%) efficacy of all agents tested as monotherapy, and a combination of piperacillin and tazobactam or amoxicillin and clavulanate with aminoglycosides is particularly beneficial., Conclusions: Staphylococcus spp. predominates amongst the etiological factors of DFS infection; however, the rate of E. faecalis infection is alarmingly high. Monotherapy enables effective treatment in a minority of cases; therefore, at least two-drug protocols should be implemented from the very beginning of the therapy.

Skin ischemia is one of the crucial phenomena during chronic lower limb ischemia in patients with peripheral arterial occlusive disease and/or diabetes. However, risk stratification for development of ischemic ulceration and/or skin necrosis in those patients is not easy, mostly due to the complex structure of the dermal vascular bed and limited possibilities for studying the skin capillaries in everyday practice. All definitions of critical limb ischemia thus far have considered mostly the clinical symptoms and the degree of macrocirculatory impairment. Despite the fact that the reduction of absolute dermal perfusion and improper distribution of perfusion in ischemic feet, primarily diminished perfusion or even a complete loss of blood flow in nutritional capillaries, rather than arterial occlusion per se, is the eventual reason for critical limb ischemia symptoms, the vessels of the microcirculation are not routinely assessed in clinical practice. Monitoring of microcirculatory parameters, as a part of integrated diagnostic approach, may have a considerable value in the evaluation of risk, progression of the disease and the effectiveness of therapeutic intervention in individual patients. Relative simplicity and availability of different non-invasive methods, including video capillaroscopy and laser Doppler fluxmetry, should constitute a premise to their wider application in clinical management of chronic limb ischemia.

Thrombotic complications of unknown etiology remain a serious diagnostic and therapeutic problem. Occurrence of the inherited polymorphisms of genes encoding proteins involved in the coagulation cascade is one of the possible causes of these complications. In recent years, protein Z (PZ) and PZ-dependent protease inhibitor (ZPI) have been added to the list of prothrombotic factors. PZ is a glycoprotein serving as a cofactor of ZPI, which is responsible for the inhibition of prothrombinase. Expression of the PZ gene is under the control of many transcriptional factors; several polymorphisms alternate the rate of gene expression. The present article describes the significance of the ZPI-PZ system in venous and arterial thrombosis, adverse pregnancy outcomes and antiphospholipid syndrome complications.

Thromboangiitis obliterans (TAO) is a relatively rare disease of peripheral blood vessels, affecting small and medium sized arteries and veins. Although the first description of the disease was given by Winiwarter almost 130 years ago, etiology of TAO remains not elucidated. Smoking is considered as a precipitating factor of the disease. We emphasised some particular features of the new face of TAO - significant decrease in incidences, increased disease prevalence among women and coexistence of other than smoking atherosclerotic risk factors (especially disturbances of glucose metabolism). Contemporary methods of treatment were also discussed.

The relationship between plasma lipid levels and mortality from cardiovascular diseases has been shown in many studies, but there has been far less investigation into their relationship to non-cardiovascular diseases. The aim of this study was to investigate the lipid profile of individuals with hematological malignancies and its relationship to disease activity. 238 patients were included in the study: 84 with acute leukemia, 62 with non-Hodgkin lymphoma, 35 with Hodgkin's lymphoma, 32 with multiple myeloma, and 25 with myeloproliferative syndrome. The HDL cholesterol level of the patients differed to that of the individuals in the control group in the active disease period for all the analyzed disorders, but only remained statistically significant in the acute leukemia and non-Hodgkin lymphoma groups during the remission period. Smaller differences were observed for the remaining lipid fractions, except for the triglyceride level, which increased in the active disease period in all the analyzed disorders except non-Hodgkin lymphoma. The most pronounced changes in the lipid fractions occurred in the HDL cholesterol level, and were the most remarkable for acute leukemia.

Among patients with chronic renal failure 10-20 times higher cardiovascular mortality than in the control group is observed. It increases further among dialyzed patients. The occurrence of the traditional risk factors only partially explains this phenomenon. Increasing evidence suggests that disturbances in the complex system of cytokine network, matrix metalloproteinases and oxidative stress may cause acceleration of the course of atherosclerosis. The activation of immunological response (partially as a result of infections) leads to exceeded expresion of proinflammatory cytokines, dysregulation of matrix metalloproteinases and their inhibitors system and increased synthesis of neopterine. These processes induce in turn oxidative stress and separately result in atherosclerosis progression. New possibilities of therapeutic interventions seem to appear, e.g. involving cytokine network. They may bring us closer to the aim, which is improvement of prognosis in chronic renal insufficiency.

The pathomechanism of acute complications of atheromatosis, i.e. arterial thrombosis, still remains unclear. Conventional cardiovascular risk factors can explain only about 50% of cases of arterial thrombosis. The activation of intrinsic and extrinsic pathways of the coagulation system on damaged atherosclerotic plaque is one of the most important mechanisms. The role of clotting factors in the development of arterial thrombosis is also considered. From among a few clotting factors (V, VIII, XIII), factor VIII arouses interest due to the well-known observation that the morbidity for cardiovascular reasons is less among hemophiliacs than in the general population. A high factor VIII level predicts the occurrence of episodes of venous thromboses, but its role in the pathogenesis of arterial thromboses is still unclear. In clinical studies, a high factor VIII level predicts episodes of stroke, myocardial infarct, and acute lower-limb ischemia over a short period of observation. A high factor VIII level may the cause of about 5% of all episodes of arterial thrombosis. The reasons for elevated factor VIII levels in some persons remain unclear. Although heritability can play an important role, the influence of other factors (e.g. activation of the sympathetic nervous system) has been reported. The pathomechanism is the subject of investigation as well. An explanation for the occurrence of severe complications of arterial thrombosis in patients without significant risk factors may result in the development of methods of detection and prevention.

Artery calcification occurring in atherosclerosis is connected with a high risk of cardiovascular events. Quantitative calcification evaluation using electron beam tomography indicated a correlation between artery calcification and well-known cardiovascular risk factors, i.e. smoking, obesity, and hyperlipidemia. Elevated calcium scores are especially observed in diabetic patients, which may even explain the higher mortality in this group. Calcification leads to increased blood vessel rigidity and, consequently, elevated arterial vascular resistance and left ventricular hypertrophy. An increased risk of plaque rupture in relation to calcium-rich atherosclerotic lesions was not proved. Plaque rupture and thromboembolitic complications are probably higher in the case of lipid-rich lesions. Atherosclerotic calcification is an active process in which many cells (monocytes/macrophages, vascular smooth muscle cells, and endothelial cells) participate. Many substances and transcription factors normally participating in the bone remodeling process are found in calcified atherosclerotic lesions (e.g. Cbfa-1, osteocalcin, alkaline phosphatase, BMP-2, osteopontin, osteoprotegrin, and RANKL). On monocytes, cells playing an important role in atherosclerosis progression, the presence of a calcium-sensing receptor (CaR) has been demonstrated. Increase in monocyte chemotaxis and increased interleukin 6 secretion in response to extracellular calcium were observed. Monocytes also directly and indirectly enhance vascular calcification. Immune cells and cytokines participating in vascular calcification are connected in one pathogenetic mechanism, i.e. atherosclerosis as an inflammatory disease and calcification.

In Europe, 20% of the populations is over 65 years of age. About 5% of the older adults have heart failure. Heart failure (HF) in the elderly is an increasing public health problem, leading cause of hospitalization in older patients and a major cause of morbidity and mortality. Prognosis has improved only slightly during the past decade. Typically, heart failure occurs when ventricles do not fill (diastolic heart failure - DHF) or empty blood (systolic heart failure - SHF) properly. Transthoracic echocardiography is the key investigation to confirm the underlying structural and functional abnormalities of the heart. Patients with heart failure due to left ventricular systolic dysfunction should be treated with a diuretic, an angiotensin converting enzyme inhibitor, and a beta-blocker (unless contraindicated). Several epidemiologic studies have recently shown that more than 50% of older patients who present with symptoms of HF have DHF. While numerous large trials have established specific therapies for SHF, such trials are lacking for DHF. The finding of similar key pathophysiologic abnormalities in DHF and SHF suggests the possibility that therapies that have been successful for SHF may have a role in therapy for DHF. A recent survey showed that despite physicians' awareness of the benefits of beta-blocker therapy, only minority of patients with heart failure are treated with beta-blocker or combination of ACE inhibitors and beta-blocker.

The case of 53-year-old man who suffered from chronic lymphocytic leukemia since 1993 was presented. In the 6th year of treatment fludarabine was administered. Few days after administration of drug the patient developed watery diarrhoea not responding to treatment. We excluded both infectious etiological factors and infiltration of intestine in course of chronic lymphocytic leukemia. Histopathological examination with monoclonal antibodies and periodic acid-Schiff stain (PAS) revealed Whipple's disease as the reason of enteropathy. During 6 months diarrhoea caused extreme dyselectrolitemia, renal insufficiency and finally death of the patient.

T-cell interactions with endothelium and the extracellular matrix proteins were studied in vitro in a patient with Takayasu arteritis. Markedly enhanced spontaneous adhesiveness to cultured endothelium and collagen IV and fibronectin were found to be paralleled by abolished responses to the costimulating action of collagens I and IV and fibronectin. Those abnormalities were partly corrected by immunosuppressive therapy. Aberrant interactions of T cells with endothelium and the extracellular matrix proteins may underlay the pathogenesis of some forms of vasculitis.

The aim of this paper is to present the advantages of performing a vascular access in two steps in uremic patients requiring urgent hemodialysis. In 15 patients age 28-68 yrs. (mean 50 yrs.) with end stage renal disease the Quinton-Scribner shunt linking radial artery with cephalic vein was placed on a forearm, and dialysis was started on the same day. After 18-35 days (mean 26 day) in 12 patients depending on efferent vein arterialization the second step operation of creating Cimino-Brescia fistula was performed on the same vessels. The fistula was immediately good for punction with standard needles. In 3 patients, due to low arterial output the vein condition did not allow for the second step operation. The results of our observations show an efficiency of the proposed method in establishing an acute and chronic vascular access which was as effective as routinely constructed shunts. Our patients avoided complications of central vein cannulation and the hospitalization period was shortened.

Recent findings suggest that recombinant human erythropoietin (rhEpo) may have an immunomodulating action. We have studied the in vitro and in vivo effects of rhEpo on immune functions in man. Low pharmacological concentrations of the hormone inhibit T-cell activation and proliferation, while higher ones are without that effect. The same Epo concentrations inhibit mitogen- and alloantigen-driven B-cell differentiation and immunoglobulin synthesis and, to a lesser extent, B-cell proliferation. In vivo treatment with rhEpo causes an initial inhibition of T- and B-cell proliferation, but with prolonged administration improved responsiveness is observed. Our data support the notion that rhEpo can regulate immune functions, a fact of potential clinical application.

A patient with mesangio-proliferative glomerulopathy with advanced nephrotic syndrome (proteinuria 20 g/day) received bolus doses of corticosteroids (5 x 1.0 g iv) but renal function continued to deteriorate. A 11-day course of nitrogranulogen (0.01 mg/kg/day) with prednisone (0.5 mg/kg) caused complete disappearance of proteinuria with improvement in renal function. This observation supports our earlier findings indicating that treatment with low dose nitrogranulogen may be efficacious in some forms of glomerulopathies.