Whole-Exome Sequencing Identified Two Novel Pathogenic Mutations in the PTCH1 Gene in BCNS.

Basal cell nevus syndrome (BCNS, OMIM 109400) is a familial cancer syndrome characterized by the development of numerous basal cell cancers and various other developmental abnormalities, including epidermal cysts of the skin, calcified dural folds, keratocysts of the jaw, palmar and plantar pits, ovarian fibromas, medulloblastomas, lymphomesenteric cysts, and fetal rhabdomyomas. BCNS shows autosomal dominant inheritance and is caused by mutations in the patched 1 (PTCH1) gene and the suppressor of the fused homolog (SUFU) gene. In a few cases, variants of patched 2 (PTCH2) have been found in patients who met the criteria for BCNS. In an investigation of 11 Hungarian families who fulfilled the diagnostic criteria for BCNS, whole-exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA) identified two novel pathogenic variants (c.2994C>A; p.Cys998Ter and c.814_818del; p.Asn272SerfsTer11), one recently identified variant (c.1737_1745del p.Val580_Val582del), and three recurrent disease-causing variants of the PTCH1 gene with a diagnosis rate of 63.6%. Disease-causing variants were not found for the SUFU and PTCH2 genes. These applied methods could not fully elucidate the genetic background of all the BCNS cases that we investigated. To uncover the missing heritability of BCNS, whole-genome sequencing or an epigenetic approach might be considered in the future.

Dealing with confounding in observational studies: A scoping review of methods evaluated in simulation studies with single-point exposure.

The aim of this article was to perform a scoping review of methods available for dealing with confounding when analyzing the effect of health care treatments with single-point exposure in observational data. We aim to provide an overview of methods and their performance assessed by simulation studies indexed in PubMed. We searched PubMed for simulation studies published until January 2021. Our search was restricted to studies evaluating binary treatments and binary and/or continuous outcomes. Information was extracted on the methods' assumptions, performance, and technical properties. Of 28,548 identified references, 127 studies were eligible for inclusion. Of them, 84 assessed 14 different methods (ie, groups of estimators that share assumptions and implementation) for dealing with measured confounding, and 43 assessed 10 different methods for dealing with unmeasured confounding. Results suggest that there are large differences in performance between methods and that the performance of a specific method is highly dependent on the estimator. Furthermore, the methods' assumptions regarding the specific data features also substantially influence the methods' performance. Finally, the methods result in different estimands (ie, target of inference), which can even vary within methods. In conclusion, when choosing a method to adjust for measured or unmeasured confounding it is important to choose the most appropriate estimand, while considering the population of interest, data structure, and whether the plausibility of the methods' required assumptions hold.

Tumor-infiltrating immune cells as potential biomarkers predicting response to treatment and survival in patients with metastatic melanoma receiving ipilimumab therapy.

Monoclonal antibodies targeting immune checkpoints are gaining ground in the treatment of melanoma and other cancers, and considerable effort is made to identify biomarkers predicting the efficacy of these therapies. Our retrospective study was performed on surgical tissue samples (52 lymph nodes and 34 cutaneous/subcutaneous metastases) from 30 patients with metastatic melanoma treated with ipilimumab. Using a panel of 11 antibodies against different immune cell types, intratumoral immune cell densities were determined and evaluated in relation to response to ipilimumab treatment and disease outcome. For most markers studied, median immune cell densities were at least two times higher in lymph node metastases compared to skin/subcutaneous ones; therefore, the prognostic and predictive associations of immune cell infiltration were evaluated separately in the two groups of metastases as well as in all samples as a whole. Higher prevalence of several immune cell types was seen in lymph node metastases of the responders compared to non-responders, particularly FOXP3+ cells and CD8+ T lymphocytes. In subcutaneous or cutaneous metastases, on the other hand, significant difference could be observed only in the case of CD16 and CD68. Associations of labeled cell densities with survival were also found for most cell types studied in nodal metastases, and for CD16+ and CD68+ cells in skin/s.c. metastatic cases. Our results corroborate the previous findings suggesting an association between an immunologically active tumor microenvironment and response to ipilimumab treatment, and propose new potential biomarkers for predicting treatment efficacy and disease outcome.

Prospective pre- and post-race evaluation of biochemical, electrophysiologic, and echocardiographic indices in 30 racing thoroughbred horses that received furosemide.

BACKGROUND: Exercise induced cardiac fatigue (EICF) and cardiac dysrhythmias are well described conditions identified in high-level human athletes that increase in frequency with intensity and duration of exercise. Identification of these conditions requires an understanding of normal pre- and post-race cardiac assessment values. The objectives of this study were to (1) characterize selected indices of cardiac function, electrophysiologic parameters, and biochemical markers of heart dysfunction prior to and immediately after high level racing in Thoroughbred horses receiving furosemide; and (2) create pre- and post-race reference values in order to make recommendations on possible screening practices for this population in the future. RESULTS: Thirty Thoroughbred horses were enrolled in the study with an age range of 3-6 years. All horses received furosemide prior to racing. Physical exams, ECGs, and echocardiograms were performed prior to racing (T0) and within 30-60 min following the race (T1). Blood samples were obtained at T0, T1, 4 h post-race (T4) and 24 h after the race (T24). Electrolytes, hematocrit, cardiac troponin I, and partial pressure CO2 values were obtained at all time points. Heart rate was significantly increased post-race compared to baseline value with a median difference of 49 bpm, 95% CI [31,58],(P < 0.0001). No dysrhythmias were noted during ECG assessment. Following the race, an increase in number of horses demonstrating regurgitation through the aorta and AV valves was noted. Systolic function measured by fractional shortening increased significantly with a mean difference of 7.9%, 95% CI [4.8, 10.9], (P < 0.0001). Cardiac troponin I was not different at pre- and immediately post-race time points, but was significantly increased at T4 (P < 0.001). Troponin returned to baseline value by T24. CONCLUSIONS: This study utilized a before and after study design where each horse served as its own control, as such the possible effect of regression to the mean cannot be ruled out. The reference intervals generated in this study may be used to identify selected echocardiographic and electrocardiographic abnormalities in racing horses receiving furosemide.

[Personnel and material conditions of the Hungarian intensive care units dealing with organ donation]. / Magyarországi intenzív osztályok szervdonációval kapcsolatos személyi és tárgyi feltételei.

INTRODUCTION: At the end of 2016, the number of patients on the domestic transplant waiting list was twice as much as the number of the organ transplantations accomplished that year. The institutional prerequisites for functional organ donation programs are the sufficient number of personnel and the adequate material conditions to be provided in relation to the needs. AIM: The goal of the current study was to evaluate the professional environment in Hungary. METHOD: The Organ Coordination Office at the Hungarian National Blood Transfusion Service compiled a questionnaire survey on the personnel and material conditions of the intensive care units (ICUs) in Hungary in regards to organ donations. The survey applied an online questionnaire including 43 questions. In addition to the number of beds and employees, we investigated the tools needed for the legal and the medical diagnosis of brain death as well as the accessibility of examinations on the donor information form. The data collection spanned from 12 December 2016 to 30 June 2017. RESULTS: 59 intensive care units completed the questionnaire; the investigation involved 640 hospital beds, 816 physicians and 1252 nurses. In the daytime shift, 0.25 doctors and 0.41 nurses work on a patient bed at an average, while in the night shift, the figures are 0.11 and 0.33, respectively. 51.7% of the doctors are registered to access the National Non-Donor Registry, and brain death diagnosis committee is available in 83% of the hospitals. Among the medical imaging methods (cranial, abdominal-thoracic), CT scan in 71-73%, abdominal ultrasound in 75%, transthoracic echocardiograpy (TTE) in 37%, transoesophageal echocardiography (TEE) in 4%, bronchoscopy in 49%, coronarography in 19% are non-stop available, with instant interpretation in 75% of the cases. Transcranial Doppler (TCD) in 30%, four-vessel angiography in 45% and SPECT in 14% of the cases are available. More than 90% of the laboratory examinations on the donor information form are available 24 hours a day. CONCLUSION: The number of doctors and nurses did not change compared to our 2008 survey (0.18 doctors, 0.37 nurses/ICU beds in 2008), but the care of potential donors needs more resources and time. The standby availability of personnel and material conditions is a prerequisite for organ donation programs in order to save lives. Orv Hetil. 2018; 159(33): 1360-1367.

[Hungarian Diet and Nutritional Status Survey - OTÁP2014. II. Energy and macronutrient intake of the Hungarian population]. / Országos Táplálkozás és Tápláltsági Állapot Vizsgálat ­ OTÁP2014. II. A magyar lakosság energia- és makrotápanyag-bevitele.

INTRODUCTION AND AIM: The aim of the study was to assess and monitor the dietary habits and nutrient intake of Hungarian adults. METHOD: Three-day dietary records were used for dietary assessment, the sample was representative for the Hungarian population aged ≥18ys by gender and age. RESULTS: The mean proportion of energy from fat was higher (men: 38 energy%, women: 37 energy%), that from carbohydrates was lower (men: 45 energy%, women: 47 energy%) than recommended, the protein intake is adequate. CONCLUSION: Unfavorable change compared to the previous survey in 2009 was the increase of fat and saturated fatty acid energy percent in women, the decrease in fruit and vegetable consumption, which explains the decreased fiber intake. An increasing trend in added sugar energy percent in each age groups of both genders was observed compared to 2009. Interventions focusing on the promotion of fruit and vegetable consumption and decreasing of saturated fat and added sugar intake are needed. Orv. Hetil., 2017, 158(15), 587-597.

Disseminated peritoneal leiomyomatosis after laparoscopic myomectomy - A case report.

INTRODUCTION AND IMPORTANCE: Disseminated peritoneal leiomyomatosis (DPL) is a rare benign disease, characterized by intraperitoneal dissemination of smooth-muscle tumor masses. CASE PRESENTATION: The patient, a 40-year-old, female - presented with complaints of periodic back pain. During the initial workup, a tumor mass was visualized in the pelvis on ultrasound. Further clinical workup included computer tomography (CT) scan and ultrasound-guided fine-needle biopsy. A tumor mass in the right adrenal gland was identified on CT. Pathological examination revealed no signs of malignancy. The multidisciplinary team decided on surgical treatment. Tumor masses were removed from the pelvic cavity, the anterior abdominal wall, and the projection of the right adrenal gland with preservation of the uterus and ovaries due to the patient's wishes. Pathological examination with immunohistochemistry of surgical specimen confirmed diagnosis of DPL. CLINICAL DISCUSSION: Due to the rarity of DPL there are no standard guidelines for diagnostics and treatment. In many cases, on initial workup, DPL may look like a malignant tumor with intraperitoneal spread, which may lead to an inappropriate choice of treatment. CONCLUSION: Differential diagnosis of DPL may be a challenge due to its appearance as a disseminated peritoneal malignancy on CT scans and at laparotomy. A multidisciplinary approach is key to choosing the right clinical course for such patients.

R-Baclofen Treatment Corrects Autistic-like Behavioral Deficits in the RjIbm(m):FH Fawn-Hooded Rat Strain.

The Fawn-hooded rat has long been used as a model for various peripheral and central disorders and the data available indicate that the social behavior of this strain may be compromised. However, a thorough description of the Fawn-hooded rat is unavailable in this regard. The objective of the present study was to investigate various aspects of the Fawn-hooded rat's social behavior in depth. Our results show that several facets of socio-communicational behavior are impaired in the RjIbm(m):FH strain, including defective ultrasonic vocalizations in pups upon maternal deprivation, reduced social play in adolescence and impaired social novelty discrimination in adulthood. In addition, Fawn-hooded rats exhibited heightened tactile sensitivity and hyperactivity. The defects observed were comparable to those induced by prenatal valproate exposure, a widely utilized model of autism spectrum disorder. Further on, the pro-social drug R-baclofen (0.25-1 mg/kg) reversed the autistic-like defects observed in Fawn-hooded rats, specifically the deficiency in ultrasonic vocalization, tactile sensitivity and social novelty discrimination endpoints. In conclusion, the asocial, hypersensitive and hyperactive phenotype as well as the responsivity to R-baclofen indicate this variant of the Fawn-hooded rat strain may serve as a model of autism spectrum disorder and could be useful in the identification of novel drug candidates.

Tumour regression predicts better response to interferon therapy in melanoma patients: a retrospective single centre study.

We hypothesise that regression may have an impact on the effectiveness of adjuvant IFN therapy, based on its role in the host immune response. Our purpose is to investigate regression and ulceration as prognostic factors in case of interferon-alpha (IFN)-treated melanoma patients. We followed 357 IFN-treated melanoma patients retrospectively, investigating progression-free survival (PFS) and overall survival (OS) depending on the presence of ulceration and regression. A Kaplan-Meier analysis was performed, and we used a Cox regression analysis to relate risk factors. The survival function of the Cox regression was used to measure the effect of regression and ulceration on PFS and OS depending on the Breslow thickness (T1-T4) of the primary tumour. Regression was significantly positively related to PFS ( P  = 0.0018, HR = 0.352) and OS ( P  = 0.0112, HR = 0.380), while ulceration showed a negative effect (PFS: P  = 0.0001, HR = 2.629; OS: P  = 0.0003, HR = 2.388). They influence survival independently. The most favourable outcome was measured in the regressed/non-ulcerated group, whereas the worse was in the non-regressed/ulcerated one. Of risk factors, Breslow thickness is the most significant predictor. The efficacy of regression is regardless of Breslow thickness, though the more favourable the impact of regression was in the thicker primary lesions. Our results indicate that regression is associated with a more favourable outcome for IFN-treated melanoma patients, whereas ulceration shows an inverse relation. Further studies are needed to analyse the survival benefit of regression in relation to innovative immune checkpoint inhibitors.

[Allopurinol-induced hypersensitivity syndrome]. / Allopurinol okozta hiperszenzitivitási szindróma.

UNLABELLED: Allopurinol is an effective urate lowering drug, which is usually well-tolerated with no adverse effects in most cases, but about 2% of the treated patients develop a skin rash, and patients may experience severe allopurinol-induced hypersensitivity syndrome. AIMS: The aim of the authors was to summarize and present the clinical manifestations of allopurinol-induced hypersensitivity in patients treated at the Department of Dermatology and Allergology, University of Szeged in order to identify potential associations with this syndrome. METHODS: Retrospective review of all patients who were referred to the department with allopurinol-induced hypersensitivity syndrome in the last four years. RESULTS: During four years, 11 patients were treated with allopurinol-induced hypersensitivity syndrome. The average age was 70.3 years. Before the initiation of allopurinol therapy, 36% of patients had already suffered from various degrees of renal impairment, and 72% of them had been taking thiazide diuretics. Cutaneous manifestations were mainly generalized, erythematous, maculopapular exanthemas (9 patients, 82%), and two patients showed signs of erythema multiforme (18%). Asymptomatic hyperuricemia was the indication for allopurinol therapy in all patients. CONCLUSIONS: Allopurinol-induced hypersensitivity syndrome is a severe, life-threatening disease. Administration of allopurinol should be initiated with clear indications in appropriate dose. Old age, underlying renal impairment and concomitant thiazide diuretic intake should be considered as potential risk factors for developing hypersensitivity syndrome.

Analysis of the acceptance practice of deceased donor kidneys in a single Hungarian transplant centre / A kadáverdonor-vesék elfogadási gyakorlatának vizsgálata a debreceni transzplantációs centrumban.

Összefoglaló. Bevezetés: A magyarországi vesetranszplantáció 2013 óta az Eurotransplant (ET) keretein belül zajlik. A debreceni vesetranszplantációs centrumhoz évente kb. 200 kadáverdonorvese-felajánlás érkezik, melyek 37%-a kerül a megismert adatok alapján elfogadásra. Nem minden elfogadott vese kerül beültetésre, aminek számos oka lehet. Célkituzés: A debreceni szakmai gyakorlat elemzése és bemutatása reprezentatív mintán. Módszer: A debreceni centrumhoz 2016. november és 2020. március között 624 vesefelajánlás érkezett. A felajánlott vesék 37%-a (n = 229) került elozetesen elfogadásra, késobb az elfogadott vesék 63%-a (n = 144) került beültetésre. Centrumunkban az ún. 'standard criteria', azaz tökéletes minoségu donorvesék szignifikánsan magasabb arányban kerültek elfogadásra, majd beültetésre, mint az 'extended criteria', azaz kompromisszummal vállalhatók. Az elfogadott és nem elfogadott veséket vizsgálva a KDPI (kidney donor profile index) és a KDRI (kidney donor risk index) értéke szignifikánsan magasabb volt az elutasított donorok esetében (p<0,001). Eredmények: Elemeztük, hogy a felajánlott, de a centrum által nem beültetett donorveséket más ET-centrumban elfogadták-e. Látható, hogy a felajánlott 624 donorvese közül 144 Debrecenben, 313 pedig más ET-centrumban került beültetésre, viszont 167 vese beültetése egyik ET-centrumban sem történt meg (discarded organ). A 36-85 KDPI-értékkel rendelkezo csoportból került beültetésre a legtöbb donorvese (180 vese) más ET-centrumban. A Debrecenben beültetett kadáverdonor-vesék KDPI- és KDRI-értéke szignifikánsan alacsonyabb volt a nekünk felajánlott, majd máshol beültetett vesékhez képest. Következtetés: Összességében elmondható, hogy a debreceni centrumban a magas rizikócsoportba tartozó donorszervek elutasításra kerültek, miközben más centrumban a nagy részüket beültették. Ez alapján a 36-85 KDPI-értéku csoport a transzplantációs esetszám bovítésének lehetséges forrása a recipiens ismeretében. Orv Hetil. 2021; 162(26): 1022-1028. INTRODUCTION: Kidney transplantation in Hungary is carried out via Eurotransplant (ET). Our centre in Debrecen receives around 200 kidney offers a year, of which 37% are accepted. Not all accepted kidneys are transplanted, which can be a result of a number of causes. Obejctive: A debreceni szakmai gyakorlat elemzése és bemutatása reprezentatív mintán. METHOD: Between November 2016 and March 2020, the centre of Debrecen received 624 kidney offers. 37% (n = 229) of the offered kidneys got preliminarily accepted, of which 63% (n = 144) were transplanted later. In our centre, standard criteria donor kidneys were accepted and transplanted in significantly higher rate, than extended criteria donor kidneys. Looking at accepted and rejected kidneys, KDPI and KDRI values were significantly higher in the case of the refused ones (p<0.001). RESULTS: Part of our assessment is to analyze whether kidneys offered to and refused by us got accepted in other transplant centres. In the examined period, of the 624 kidneys offered to our centre 144 were transplanted in Debrecen, 313 were transplanted in other ET centres, while 167 were not transplanted at all (discarded organ). The majority of transplanted kidneys in other ET centres had KDPI values between 36 and 85 (180 kidneys.) KDPI and KDRI values of kidneys transplanted in our centre were significantly lower than those that were offered to us, but got transplanted elsewhere. CONCLUSION: To summarize, we can say that high-risk donor organs are refused in the transplant centre of Debrecen, while the majority of them are being transplanted in other centres. Based on this, kidneys of KDPI value between 36 and 85 are a possible source of expanding the number of transplantations, with regards to the recipient. Orv Hetil. 2021; 162(26): 1022-1028.

Quality Assessment of Donor Kidneys and the Tendency of Kidney Acceptance: A Single-Center Experience.

PURPOSE: The increasing age of donors and the increasing tendency of comorbidities requires an extension in acceptance criteria. In this review, the tendency for acceptance and refusal was analyzed by examining reasons for declining donor kidneys at the kidney transplantation center in Debrecen. This analysis aimed to assess the quality of donor kidneys and indicate why two-thirds of donated organs were refused. METHOD: Our center in Debrecen received 535 kidney offers (based on exclusion criteria) between November 2016 and August 2019, which were retrospectively analyzed. Donor kidneys were evaluated using expanded criteria donor, kidney donor profile index (KDPI), and kidney donor risk index criteria systems. RESULTS: Thirty-five percent (n = 189) of the kidneys offered to the center in Debrecen had been approved in advance, and later 63% (n = 119) were transplanted. Using the KDPI system, 41% of donors had a KDPI above 85, of which 23% were accepted, while acceptance of kidneys with a KDPI of 0 to 35 was around 70%. When examining causes of donor kidney refusal, 90% of the organs had donor quality problems, 13% had logistical cause (long cold ischemic time, large age difference between donor and recipient), and 10.5% had immunologic cause. In 13% of cases, the refusal of donor organs was due to the coexistence of several problems. CONCLUSION: Our data showed that high-risk donor organs were being refused in our center; however, they are being transplanted at a higher rate in other Eurotransplant centers. The decision to refuse or accept donor organs depends on several factors, including expected waiting time, patient's clinical characteristics, and quality of life.

Reduced Level of Tear Antimicrobial and Immunomodulatory Proteins as a Possible Reason for Higher Ocular Infections in Diabetic Patients.

(1) Background: Diabetes mellitus is one of the most common metabolic disorders and a risk factor for bacterial ocular infections. Our aim was to examine the antibacterial activity of tears from patients with diabetes mellitus with and without diabetic retinopathy and to link this activity to the level of tear proteins. (2) Methods: Non-stimulated basal tears were collected from 39 eyes of 35 subjects. The antibacterial activity of tear pools was tested against pathogenic Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 26922 and Pseudomonas aeruginosa ATCC 27853 strains. The levels of 10 antimicrobial and immunomodulatory proteins were analyzed in the individual tear samples of the studied groups by SRM-based targeted mass spectrometry analysis. (3) Results: Disease stage-specific antimicrobial effect was observed in case of Staphylococcus aureus ATCC 29213 strain, and a non-disease specific inhibitory effect was observed in case of Pseudomonas aeruginosa ATCC 27853 strain. Changes in the levels of the studied antimicrobial and immunomodulatory proteins in the tears of the studied groups were also observed. (4) Conclusions: The higher ocular infection rate observed in diabetic patients may be the consequence of the decreased antimicrobial activity of tears possibly caused by the changes in the levels of antimicrobial and immunomodulatory proteins.

Dietary Sodium and Potassium Intake in Hungarian Elderly: Results from the Cross-Sectional Biomarker2019 Survey.

High sodium intake and inadequate potassium intake are associated with high blood pressure. The elderly are more salt sensitive than other age groups, yet a reliable estimate of the dietary sodium and potassium intake of this age group in Hungary is unavailable. The study aimed to estimate the sodium and potassium intakes in the Hungarian elderly from 24 h urine sodium and potassium excretion. In this cross-sectional study, participants were selected from patients of general practitioners practicing in western Hungary. The participants comprised 99 men and 90 women (mean age 67.1 (SD 5.4] years) who participated in the Biomarker2019 survey and returned a complete 24 h urine collection. We assessed dietary sodium and potassium by determining 24 h urinary sodium and potassium excretions and 3-day dietary records. The mean urinary sodium was 188.8 (73.5) mmoL/day, which is equivalent to 11.0 g of salt/day; and the mean urinary potassium was 65.8 (24.3) mmoL/day, which is equivalent to 3.03 g of potassium/day, after adjusting for non-urinary potassium losses. Only 7% of the subjects met the World Health Organization's recommended target of less than 5 g of salt/day, and 33% consumed at least the recommended potassium amount of 3.5 g/day, based on the estimates from 24 h urine excretion. For most elderly, sodium intake exceeds, and potassium does not reach, dietary recommendations. The results underline the need to intensify salt reduction efforts in Hungary.

Culturing and Scaling up Stem Cells of Dental Pulp Origin Using Microcarriers.

Ectomesenchymal stem cells derived from the dental pulp are of neural crest origin, and as such are promising sources for cell therapy and tissue engineering. For safe upscaling of these cells, microcarrier-based culturing under dynamic conditions is a promising technology. We tested the suitability of two microcarriers, non-porous Cytodex 1 and porous Cytopore 2, for culturing well characterized dental pulp stem cells (DPSCs) using a shake flask system. Human DPSCs were cultured on these microcarriers in 96-well plates, and further expanded in shake flasks for upscaling experiments. Cell viability was measured using the alamarBlue assay, while cell morphology was observed by conventional and two-photon microscopies. Glucose consumption of cells was detected by the glucose oxidase/Clark-electrode method. DPSCs adhered to and grew well on both microcarrier surfaces and were also found in the pores of the Cytopore 2. Cells grown in tissue culture plates (static, non-shaking conditions) yielded 7 × 105 cells/well. In shake flasks, static preincubation promoted cell adhesion to the microcarriers. Under dynamic culture conditions (shaking) 3 × 107 cells were obtained in shake flasks. The DPSCs exhausted their glucose supply from the medium by day seven even with partial batch-feeding. In conclusion, both non-porous and porous microcarriers are suitable for upscaling ectomesenchymal DPSCs under dynamic culture conditions.

The impact of the COVID‒19 pandemic on organ donation and transplantation in Hungary in 2020 / A COVID-19-járvány hatása a szervadományozásra és -átültetésre Magyarországon 2020-ban.

Összefoglaló. Bevezetés: A SARS-CoV-2-világjárvány terjedése drasztikus változásokat okozott a mindennapi betegellátásban, amelyek érintették a szervadományozás és -átültetés területét is, így csökkent az élo és az elhunyt donorokból történo donációk és transzplantációk száma világszerte. Az esetszám csökkenése mellett a transzplantált és egyben immunszupprimált betegek védelme érdekében további biztonsági intézkedéseket kellett bevezetni. Módszer: A vizsgálat célja a COVID-19-járvány hazai donációs és transzplantációs aktivitásra gyakorolt hatásának kimutatása volt 2020-ban, a megelozo évvel történo összehasonlításban. A magyar eredményeket összehasonlítottuk elsosorban az Eurotransplant, illetve az Európai Unió tagállamainak adataival is. Eredmények: A lakosságszámra súlyozott, regisztrált COVID-19-fertozöttség és -halálozás tekintetében nem igazoltunk 2020-ban kiemelkedo eltérést itthon az Eurotransplant-tagállamokhoz képest. A hazai szervdonációs potenciál nem csökkent a vizsgált idoszakban, ugyanakkor 38,33%-kal csökkent az agyhalott szervdonorok száma Magyarországon, míg az Eurotransplantban átlagosan 8,64%-kal és 23 adatközlo európai országban 17,55%-kal. Az elhunytból történt szervátültetések száma 29,27%-kal csökkent, különösen a szív- és a májátültetések esetén. A külföldrol kapott szervek száma 21,13%-kal és aránya 12,34%-kal emelkedett. Az élo donoros veseátültetések száma nem változott. 2020-ban 25%-kal kevesebb új beteget regisztráltak, mint 2019-ben, és a várólista-mortalitás 28%-kal növekedett az elozo évhez képest, kifejezetten a veseátültetésre várók között. Következtetés: A hazai szervátültetési program biztonságos: donoreredetu SARS-CoV-2-átvitel nem történt hazánkban. A szervdonációs potenciál és a COVID-19-járvány mellett a szervdonációs és -transzplantációs aktivitás jelentosen csökkent Magyarországon 2020. márciustól az év végéig. A legtöbb európai országban átmeneti és kisebb mértéku szervdonációs csökkenést regisztráltak. A szervátültetések száma nem csökkent olyan mértékben, mint a donorszám, mert az Eurotransplantból több donorszerv érkezett hazánkba, mint amennyit külföldre küldtünk. Orv Hetil. 2021; 162(23): 890-896. INTRODUCTION: The spread of the SARS-CoV-2 pandemic has resulted in drastic changes in day-to-day patient care, which has also affected the field of organ donation and transplantation, thus reducing the number of donations and transplants from living and deceased donors worldwide. In addition to the reduction in the number of cases, additional safety measures had to be introduced to protect transplanted and implicatively immunosuppressed patients. METHOD: The aim of the study was to demonstrate the impact of the COVID-19 epidemic on domestic donation and transplantation activity in 2020, compared to the previous year. We also compared the Hungarian results with the data of the Eurotransplant and the European Union member states. RESULTS: In terms of population-weighted, registered COVID-19 infection and mortality, we did not find a significant difference in Hungary in 2020 compared to the Eurotransplant member states. The national organ donation potential did not diminish in the period under review, however, the number of brain-dead organ donors decreased by 38.33% in Hungary, while in the Eurotransplant it did by 8.64% on average and in 23 reporting European countries by 17.55%. The number of organ transplants from the deceased decreased by 29.27%, especially regarding heart and liver transplants. Both the number and the proportion of organs received from abroad increased by 21.13% and 12.34%, respectively. The number of living donor kidney transplants did not change. In 2020, 25% fewer new patients were registered than in 2019 and the mortality on waiting list increased by 28% compared to the previous year, especially among those waiting for a kidney transplant. CONCLUSION: The national organ transplantation program is safe: donor-derived SARS-CoV-2 transmission did not occur in Hungary. In addition to the organ donation potential and the COVID-19 pandemic, organ donation and transplantation activity decreased significantly in Hungary from March 2020 until the end of the year. Transient and smaller reductions in organ donation rates have been reported in most European countries. The number of organ transplants did not decrease as much as the number of donors, because more donor organs arrived in Hungary from the Eurotransplant than we sent abroad. Orv Hetil. 2021; 162(23): 890-896.

The First 5 Years of the Newest Eurotransplant Member State: Hungarian Results of International Organ Exchange From 2014 to 2018.

INTRODUCTION: Hungary joined Eurotransplant International (ET) to improve the chance of transplantation for Hungarian patients and patient outcomes, including access and graft and patient survival. After 5 years of full membership, the evaluation of numbers and quality indicators is possible. METHOD: A comparison was made between 5 years prior to a preliminary cooperation agreement (2007-2011) and 5 years after full ET membership (2014-2018). During the 2 study periods, we analyzed numbers and circumstances of deceased organ donors, multiorgan donors, donated organs, and transplantations in Hungary and development of waiting lists along with international organ exchanges. RESULT: The number of actual organ donors increased by 22.09% (729 vs 890), an additional 823 organ removals represents an increase of 42.71% (1927 vs 2750). There were 46.51% more transplants managed in the selected periods (1561 vs 2287). The number of new patients on the waiting list increased (2305 vs 3247; 40.87%). The mean kidney mismatch number decreased from 3.21 to 2.96. CONCLUSION: Joining ET has been an effective and efficient in terms of increasing access to organs and the lives of patients on the Hungarian waiting list posttransplant. It is also a benefit for patients with special needs because the number of organ transplants is greater than the increased number of donors.

Meteoric smoke fallout over the Holocene epoch revealed by iridium and platinum in Greenland ice.

An iridium anomaly at the Cretaceous/Tertiary boundary layer has been attributed to an extraterrestrial body that struck the Earth some 65 million years ago. It has been suggested that, during this event, the carrier of iridium was probably a micrometre-sized silicate-enclosed aggregate or the nanophase material of the vaporized impactor. But the fate of platinum-group elements (such as iridium) that regularly enter the atmosphere via ablating meteoroids remains largely unknown. Here we report a record of iridium and platinum fluxes on a climatic-cycle timescale, back to 128,000 years ago, from a Greenland ice core. We find that unexpectedly constant fallout of extraterrestrial matter to Greenland occurred during the Holocene, whereas a greatly enhanced input of terrestrial iridium and platinum masked the cosmic flux in the dust-laden atmosphere of the last glacial age. We suggest that nanometre-sized meteoric smoke particles, formed from the recondensation of ablated meteoroids in the atmosphere at altitudes >70 kilometres, are transported into the winter polar vortices by the mesospheric meridional circulation and are preferentially deposited in the polar ice caps. This implies an average global fallout of 14 +/- 5 kilotons per year of meteoric smoke during the Holocene.

Comparison of Two Commercially Available Immunoassays for the Measurement of Bovine Cardiac Troponin I in Cattle With Induced Myocardial Injury.

Background: Multiple cardiac troponin I (cTnI) immunoassays are commercially available. Overall, assays have not been standardized, and inter-assay differences in the detection of the analyte cardiac troponin I can be clinically relevant. Objective: To compare the diagnostic accuracy of the commercially available Abbott i-STAT®1 cTnI immunoassay (i-STAT) and the previously validated ADVIA Centaur TnI-Ultra immunoassay (Centaur) in cattle. Hypothesis: There will be significant differences in bovine serum cTnI results measured by the Centaur and i-STAT methods. Animals: Ten dairy cows with experimentally induced myocardial injury due to monensin administration. Thirty apparently healthy dairy cows with no history of monensin exposure served as controls. Methods: Blood was collected at various time points after administration of a single dose of monensin (20 to 50 mg/kg) via orogastric tube. A total of 112 blood samples were collected. Cardiac TnI concentration was analyzed with the two methods and the association between methods analyzed via linear regression. Bland-Altman analysis to evaluate agreement between methods was performed on samples divided into groups (cTnI < 1.0 ng/mL and cTnI ≥ 1.0 ng/mL). Results: Analyzer results were linearly correlated with each other (R 2 = 0.931). Samples with cTnI concentrations <1.0 ng/mL had a bias of -0.13 ± 0.20 ng/mL and samples with cTnI concentrations >1.0 ng/mL had a bias of -9.81 ± 13.26 ng/mL. Conclusions and clinical importance: The results of this study reveal that cTnI concentrations determined with the i-STAT are systematically lower compared to the concentrations determined by the Centaur.

Steroid precursors, steroids, neuroactive steroids, and neurosteroids concentrations in serum and saliva of healthy neonatal heifer Holstein calves.

BACKGROUND: Persistence of high neurosteroid concentrations in blood is associated with neonatal encephalopathy and septicemia in foals. This has not been investigated in calves. OBJECTIVES: To determine concentrations of steroid compounds in serum and saliva within the first 48 hours after birth in healthy neonatal calves, identify potential markers for disease, and investigate the association between serum steroid compounds concentrations in calves and their respective dams within 2 hours after birth. ANIMALS: Twelve healthy neonatal heifer Holstein calves and their dams. METHODS: Prospective study. Serum and saliva were collected from calves at 2, 6, 24, and 48 hours after birth. Steroid compounds were analyzed using liquid chromatography-mass spectrometry. A nonlinear regression model was used to determine half-lives of the neurosteroids. Serum concentrations of neurosteroids between the cows and calves were compared using the Wilcoxon signed rank test. RESULTS: Half-lives (95% confidence intervals) of dehydroepiandrosterone (DHEA) and 17α,20α-dihydroxyprogesterone in calf serum were 2.9 (2.1, 4.3), and 2.1 (1.3, 3.0) hours, respectively. Pregnanediol in saliva had a half-life (95% confidence interval) of 24.5 (14.2, 66.5) hours. Serum DHEA (1718.7 ± 2313 vs 57.7 ± 44) and 17α,20α-dihydroxyprogesterone (207.8 ± 198.2 vs 43.5 ± 33.5) concentrations respectively were higher (P < .05) in calves compared to cows. CONCLUSIONS AND CLINICAL IMPORTANCE: Dehydroepiandrosterone, 17α,20α-dihydroxyprogesterone, and pregnanediol could be potential markers of disease in neonatal heifer calves with unexplained failure to thrive or encephalopathy. However, because of the wide 95% confidence interval of the half-life, pregnanediol in saliva might not be a potential marker.