Abstract Background and Aims Membranous nephropathy (MN) is the most prevalent cause of nephrotic syndrome in adult population. Our aim was to assess long term renal outcome of primary membranous ...nephropathy patients. Method In this retrospective study adult patients with biopsy proven membranous nephropathy from 2000 till 2015 with follow up of at least 5 years from UHC Zagreb were included. Extensive clinical workup was done to exclude patients with secondary MN. Except otherwise stated, data are shown as N (%) or median with interquartile range (IQR) and accompanied p levels. Results Between 2000 and 2015, 48 patients were diagnosed to have idiopathic/primary membranous nephropathy, out of which 33 (68%) MN patients had follow up of at least 5 years and where further analyzed. They were predominantly male 20 (60.6%) of average age of 52 years (min – max 19 - 76). High risk MN patient 25 (75%) were treated with immunosuppressive therapy, dominantly with cyclophosphamide and corticosteroids. During the median follow up of 10 (7 – 14) years, 19 (57%) accomplished complete remission and 11 (33%) partial remission. One (3%) patient did not achieve remission and 2 (6.1%) were in relapse of nephrotic syndrome at last follow up. Proteinuria significantly decreased (6.2 (3.3 – 10.9) vs. 0.2 (0.14 – 0,90); p < 0.001) and there was no significant change in creatinine level (87 (42.8 – 101.5) vs. 93 (68.5 – 140.5; p = 0.332)). In follow up there were 5 (15%) carcinomas detected; one of each origin (colon, pancreas, lung, prostate, lymph nodes) approximately 7,8 years after the diagnose of MN. Limitation of this study could be selection bias but there was no difference in renal function at presentation of all MN patients and those who had at least 5 years follow up. Conclusion Renal long-term outcome of patients with idiopathic MN in our cohort was excellent. Nevertheless, there is high prevalence of cancer and therefore regular screening for cancer disease should take place in this population of patients. Also, drugs with cancerogenic potential should be avoided, as well as bear in mind cumulative dose of drugs applied.
Abstract Background and Aims Standard of care of high-risk idiopathic membranous nephropathy patients is immunosuppressive treatment with cyclophosphamide and corticosteroids or rituximab. Our aim ...was to assess outcome and safety of rituximab therapy in COVID19 era in comparison to modified Ponticelli protocol. Method In this retrospective study all adult patients with biopsy proven membranous nephropathy treated with rituximab as a first line therapy from 2020 till 2022 were enrolled and compared with MN patients treated with modified Ponticelli protocol from 2013 till 2020. Renal outcome was defined as composite of partial and complete remission defined according KDIGO guidelines. Except otherwise stated, data are shown as N (%) or median with interquartile range (IQR) and accompanied p levels. Results During the COVID 19 era, between 2020 and 2022, 8 MN patients were treated with rituximab as a first line therapy. One was lost from follow up and one had allergic infusion reaction and therefore was excluded from further analysis. Ten patients were treated with modified Ponticelli protocol. There was no difference in age (60 vs. 59 years; p = 0.669), gender (M 57.1 vs. 60%), BMI (26.3 vs. 29.1cm/kg; p = 0.906), systolic (140. vs. 150 mmHg; p = 0.161) or diastolic (90 vs. 91.5 mmHg; p = 0.230) blood pressure between rituximab and cyclophosphamide treated group. Also, there was no difference in proteinuria between rituximab and cyclophosphamide treated group (16.2 (5.7–31.3) vs. 8.7 (6.5–12.5) g/dU; p = 0.201) Patients treated with cyclophosphamide had lower eGFR compared with patients treated with rituximab (51 (34-79) vs. 93 (72-98) ml/min/1,73 m²; p = 0.005). At 6 months follow up only 2 (28.6%) in rituximab group and 6 (60%) in cyclophosphamide group achieved outcome defined as composite of complete and partial remission. At one year follow up, there was no difference in outcome between groups and all patients from rituximab group compared to 8 patients (88.9%) from cyclophosphamide group accomplished composite favorable renal outcome (p = 398). At the end of follow up, one year after cyclophosphamide therapy eGFR was better (57 (43-96) vs. 51 (34-79) ml/min/1,73 m²). Rituximab was safe in our cohort. Three (50%) of patients acquired SARS CoV2 infection and there was no adverse outcome regarding COVID 19 disease. Conclusion Cyclophosphamide is faster than rituximab in accomplishing remission of nephrotic syndrome and improves deteriorated kidney function. Nevertheless, at 1 year follow up rituximab efficiency is proven to be excellent. Cyclophosphamide should be reserved for MN patients with nephrotic syndrome with reduced glomerular filtration rate.
U savremenoj Srbiji pripadnici političkih i ekonomskih elita sistematski krše zakone i za to ne bivaju kažnjeni. U ovom tekstu nudimo objašnjenje ove pojave oslanjajući se na nalaze iz oblasti pravne ...teorije, sociologije i političke nauke. Delovanje zvaničnika u savremenoj Srbiji može se objasniti analizom složenih interakcija izmedu državnog prava i neformalnih normi koje nastaju na neformalnim institucijama klijentelizma i korupcije. Te norme čine zasebni neformalni ili paralelni normativni poredak koji čine (1) neformalne norme i zajednička očekivanja u pogledu njihovog poštovanja (koja mogu imati oblik sankcija). (2) U njegovoj osnovi stoje odnosi društvene i političke moći koji osnažuju i neformalne institucije i sistem neformalnih pravila. (2) Norme ovog poretka regulišu ponašanje aktera i (3) medusobno su uskladene, a u njihovom središtu nalazi se norma lojalnosti. (4) Paralelni normativni sistem suspenduje državno pravo za političke i ekonomske aktere koji poštuju neformalna pravila (5) Istovremeno, paralelni normativni sistem koristi mehanizme, pravila i resurse državno-pravnog normativnog poretka naročito u pogledu sankcionisanja težih kršenja neformalnih pravila koja se shvataju kao temeljna. Odnos izmedu formalnog i neformalnog normativnog poretka je konfliktan, kompetitivan i parazitirajući. Da bi obrazložili ove teze, mi najpre objašnjavamo pojmove neformalnih pravila, institucija i poredaka, i izlažemo i analiziramo tipologije odnosa izmedu formalnih i neformalnih poredaka i institucija. Zatim prikazujemo i analiziramo niz empirijskih istraživanja o korupciji i klijentelizmu, da bi na kraju, na osnovu postavljenog teorijskog okvira i raspoloživih podataka, utvrdili da se u Srbiji može govoriti o ustanovljavanju i održavanju paralelnog normativnog poretka.
Frequent episodes of nasal symptoms are the usual clinical manifestations (CM) of allergic rhinitis (AR) and have a significant negative impact on health-related quality of life (HRQoL) in ...adolescents. The purpose of this cross-sectional study was to test the hypothesis that cytokines in nasal mucus may be associated with HRQoL in adolescents with AR.
European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L), "The Adolescent Rhinoconjunctivitis Quality of Life Questionnaire" (AdolRQLQ) and the Total 4 Symptom Score (T4SS) scoring system were administered to 113 adolescents with AR, nonallergic rhinitis (NAR) and to healthy control subjects. Nasal secretions were sampled and tested for 13 cytokines using a multiplex flow cytometric bead assay.
The AR group had significantly lower EQ-5D-3L (0.661 ± 0.267 vs. 0.943 ± 0.088;
< 0.001) and higher AdolRQLQ total scores (2.76 ± 1.01 vs. 1.02 ± 0.10;
< 0.001) compared to the control group. The AR group had higher concentrations of IL-1β (
= 0.002), IL-6 (
= 0.031), IL-8 (
< 0.001), IL17-A (
= 0.013) and IL-18 (
= 0.014) compared to the control group, and IL-1β, IL-6, IL17-A and IL-18 were significantly (
< 0.050) increased with disease progression. Cytokines IL-1β, IL-6, as well as severe CM, were identified as significant predictors of lower HRQoL in adolescents with AR.
This study identified IL-1β, IL-6, as well as severe CM, as predictors of lower HRQoL in adolescents with AR. However, these results should only serve as a starting point for additional confirmation research.
Abstract
Background and Aims
Nephrotic syndrome (NS) is a rare complication of haematopoietic stem cell transplantation (HSCT). When it occurs, it usually develops after cessation of ...immunosuppressive therapy, which is why it is commonly denominated as a renal form of chronic graft-versus-host disease. Membranous nephropathy (MN) is the most common pathological finding. The protocadherin FAT1 antigen is a novel antigen identified only in patients with MN who have undergone allogeneic HSCT. PLA2R and NELL1 antigens can also be found, even though they are rare and not specific to HSCT-associated MN. The aim of this study was to present a case series of allogeneic HSCT-associated MN, the treatment, outcomes and presence of a novel antigen specifically detected in this population.
Method
All patients with full blown NS due to MN after HSCT in UHC Zagreb were enrolled. Kidney biopsy was performed and examined by light, immunofluorescence and electron microscopy. Biopsy samples were sent to Renal Pathology Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic for detection of FAT1 antigen in biopsy tissue samples
Results
In last 30 years there had been 1302 HSCT in UHC Zagreb and three of them developed MN. The first two patients were treated with allogeneic HSCT for acute myeloid leukaemia (AML). Both developed NS after cessation of GVHD prophylaxis, after 1 and 8 months respectively. The first patient's kidney function was preserved, while the second patient's was reduced. Kidney biopsy showed MN. Thorough examination found no secondary cause of the disease. In the first patient, complete remission (CR) was achieved after 5 months of steroids, 2 boluses of cyclophosphamide (CP) and cyclosporine treatment. The second patient reached partial remission (PR) after 6 months of steroid treatment and oral CP. Immunosuppression was terminated due to infectious complications. CR was achieved after an additional 8 months while the patient was not taking immunosuppressants. Both patients remained in CR during the follow-up period.
The third patient with acute lymphoblastic leukaemia (ALL) underwent a related peripheral blood HSCT. Sixteen years later, he developed NS with preserved renal function and was diagnosed with MN. Apart from thyroid disease, no secondary cause was detected and he was treated with rituximab. Partial remission (PR) was achieved after 24 months of therapy.
Anti-PLA2R antibodies were negative in all three cases. Tissue samples from patients 1 and 2 were positive for FAT1 antigen using laser microdissection and tandem mass spectrometry (MS/MS) of glomeruli. The third patient was negative for FAT1. Clinical and biopsy findings in our cohort of HSCT-associated MN are summarised in Tables 1 and 2.
Conclusion
MN can occur at different points in time, sometimes even years, after HSCT. It can be successfully treated with steroids and immunosuppressants, achieving long-term remission. Most patients with HSCT-associated MN are FAT1-positive, although it is not the only antigen associated with MN in HSCT patients. In the future, serum testing for anti-FAT1 antibodies in patients with HSCT could be of similar significance in diagnosing FAT1-associated MN as PLA2R antibodies are for PLA2R-associated MN.
Icelandic topsoil sediments, as confirmed by numerous scientific studies, represent the largest and the most important European source of mineral dust. Strong winds, connected with the intensive ...cyclonic circulation in the North Atlantic, induce intense emissions of mineral dust from local sources all year and carry away these fine aerosol particles for thousands of kilometers. Various impacts of airborne mineral dust particles on local air quality, human health, transportation, climate and marine ecosystems motivated us to design a fully dynamic coupled atmosphere–dust numerical modelling system in order to simulate, predict and quantify the Icelandic mineral dust process including: local measurements and source specification over Iceland. In this study, we used the Dust Regional Atmospheric Model (DREAM) with improved Icelandic high resolution dust source specification and implemented spatially variable particle size distribution, variable snow cover and soil wetness. Three case studies of intense short- and long-range transport were selected to evaluate the model performance. Results demonstrated the model’s capability to forecast major transport features, such as timing, and horizontal and vertical distribution of the processes. This modelling system can be used as an operational forecasting system, but also as a reliable tool for assessing climate and environmental Icelandic dust impacts.
The Integrated Agrometeorological Prediction System (IAPS) was a two-year project for the development of the long term forecast (LRF) for agricultural producers. Using LRF in decision-making, to ...reduce the risks and seize the opportunities, represents short-term adaptation to climate change. High-resolution ensemble forecasts (51 forecasts) were made for a period of 7 months and were initiated on the first day of each month. For the initial testing of the capacity of LRF to provide useful information for producers, 2017 was chosen as the test year as it had a very hot summer and severe drought, which caused significant impacts on agricultural production. LRF was very useful in predicting the variables which bear the memory of the longer period, such are growing degree days for the prediction of dates of the phenophases’ occurrences and the soil moisture of deeper soil layers as an indicator for the drought. Other project activities included field observations, communication with producers, web portal development, etc. Our results showed that the selected priority forecasting products were also identified by the producers as being the highest weather-related risks, the operational forecast implementation with the products designed for the use in agricultural production is proven to be urgent and necessary for decision-making, and required investments are affordable. The total cost of the full upgrade of agrometeorological climate services to meet current needs (including monitoring, seamless forecasting system development and the development of tools for information dissemination) was found to be about three orders of magnitude lower than the assessed losses in agricultural production in the two extreme years over the past decade.
Around 8000 years ago, throughout the Neolithic world a new type of artefact appeared, small spoons masterly made from cattle bone, usually interpreted as tools, due to their intensive traces of use. ...Contrary to those interpretations, the small dimensions of spoons and presence of intensive traces of use led us to the assumption that they were used for feeding babies. In order to test that assumption we compared 2230 marks on three spoons from the Neolithic site of Grad-Starčevo in Serbia (5800-5450 cal BC) with 3151 primary teeth marks produced experimentally. This study has shown that some of the marks on spoons were made by primary teeth, which indicate their usage in feeding babies. The production of a new type of artefact to feed babies is probably related to the appearance of a new type of weaning food, and the abundance of spoons indicates that new baby gruels became an important innovation in prehistoric baby-care.
Abstract
Background and Aims
Membranous nephropathy (MN) can be associated with tumor and present a paraneoplastic condition. Recently, development of tumors during the course of follow up is more in ...focus. It is especially interested whether patient with MN are prone to tumors, or tumors are condition indipendent of membranous nephropathy or consequence of imunosupressive therapy (IS).
Method
Retrospective data of all adult patients diagnosed with MN from 1987 to 2017 at the Department of Nephrology of University Hospital Centre Zagreb were analysed. Medical data regarding antropometric measeures and preexsisting comorbid disease at presentation and during follow up were derived from medical records and hospital informatic system. Furthermore, data regarding kidney function were used, namely serum creatinine (SCr), proteinuria. Renal function was assessed using CKD-EPI equation. CKD stages, partial and complete remission were defined according to KDIGO guidelines.
Results
From 1987 till 2017 a total of 122 patients were diagnosed with MN. Eighty nine (72.9%) were treated with imunosupressive therapy. Most commonly prescribed initial therapy was combination of corticosteroids and cyclophosphamide (N=66; 74%). Three (0,02%) patients had history of tumor with median of 3y (min – max 1-4 y) before glomerular disease presentation, two solid tumor, adenocarcinoma pulmonum and carcinoma prostatae, and one condition after allogenic haematopoetic transplantation due to acute myeloid leukemia. There was no difference in clinical presentation between those with positive history of malignant disease and others (proteinura 11.7 g/du (25-75C 3.4-15.7) vs. 5.8 g/dU (25-75C 3.4 – 8.5); p=0.232 and eGFR 57 ml/min/1,73m2 (25C-75C 14 – 59) vs. 81 ml/min/1.73m2 (25-75C 54 – 100); p=0.066). During follow up 11 (9%) patients developed tumor, median age of pts 67 y (min – max 59 – 71); nine solid tumors most comonly of gastrointestinal origin (pancreas, colon N=5 (45%)), then pulmonum (N=2(18%)) and urogenithal origin (ca renis and prostate N=2 18%). Also two hematological malignancies (B-ALL, B-NHL) occurred. Median time till confirmed malignant disease was 9 y (min – max 5 -24). At the time of detecting the tumor six (54%) patients were in complete and partial remission (4 and 2) and 2 (18%) patients had nephrotic syndrome. No difference was observed in proteinuria between those with malignant condition and other MN patients (1,4 g/dU (25 – 75C 0.2 – 5.6) vs. 0,29 g/dU (25 – 75C 0.13 – 0.74); P=0.154). MN patients with malignant disease during follow up had lower estimated glomerular filtration rate (eGFR 45 ml/min/1,73m2 (25 – 75C 22 – 70) vs. 77 (25 – 75C 58 – 92); p=0.010). There was no difference in cummulative dose of cyclophosphamide between those who developed tumor with others (24 g(25 – 75C13.5 – 30) vs. 27 g(25 – 75C 15 – 38)p=0.592).
Conclusion
Our data emphasize the need for long term follow up of patients with membranous nephropathy despite accomplishing remission of MN and period screening for malignant disease, especially in those with deteriorating kidney function.
On 2 June 2014, at about 13 UTC, a dust storm arrived in Tehran as a severe hazard that caused injures, deaths, failures in power supply, and traffic disruption. Such an extreme event is not ...considered as common for the Tehran area, which has raised the question of the dust storm’s origin and the need for increasing citizens’ preparedness during such events. The analysis of the observational data and numerical simulations using coupled dust-atmospheric models showed that intensive convective activity occurred over the south and southwest of Tehran, which produced cold downdrafts and, consequently, high-velocity surface winds. Different dust source masks were used as an input for model hindcasts of the event (forecasts of the past event) to show the capability of the numerical models to perform high-quality forecasts in such events and to expand the knowledge on the storm’s formation and progression. In addition to the proven capability of the models, if engaged in operational use to contribute to the establishment of an early warning system for dust storms, another conclusion appeared as a highlight of this research: abandoned agricultural areas south of Tehran were responsible for over 50% of the airborne dust concentration within the dust storm that surged through Tehran. Such a dust source in the numerical simulation produced a PM10 surface dust concentration of several thousand μm/m3, which classifies it as a dust source hot-spot. The produced evidence indivisibly links issues of land degradation, extreme weather, environmental protection, and health and safety.
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