[Ferritinemia, a complex marker of iron metabolism]. / La ferritinémie, un marqueur complexe du métabolisme du fer.

Ferritinemia is a basic analysis in the exploration of iron deficiency. However, its interpretation is difficult and limited due to the complexity of ferritin metabolism, which is still poorly understood, and its sensitivity to many factors, including inflammation. A more correct diagnostic approach can be obtained by combining ferritin measurement with other parameters, but at the expense of practicality. New markers should make it possible to refine the diagnosis of iron deficiency in the future.

La ferritinémie est une analyse de première ligne dans l'exploration de la carence en fer. Son interprétation est toutefois difficile et limitée en raison de la complexité du métabolisme de la ferritine, encore mal connu, et de sa sensibilité à de très nombreux facteurs dont l'inflammation. Une approche diagnostique plus correcte peut être obtenue en la combinant avec d'autres paramètres, au détriment de la praticabilité toutefois. De nouveaux marqueurs devraient permettre d'affiner le diagnostic de la carence en fer dans le futur.

Systemic versus Oral and Systemic Antibiotic Prophylaxis (SOAP) study in colorectal surgery: prospective randomized multicentre trial.

BACKGROUND: There is no consensus regarding the role of mechanical bowel preparation (MBP) and oral antibiotic prophylaxis (OABP) in reducing postoperative complications in colorectal surgery. The aim of this study was to examine the effect of OABP given in addition to MBP in the setting of a prospective randomized trial. METHODS: Patients awaiting elective colorectal surgery in four Hungarian colorectal centres were included in this multicentre, prospective, randomized, assessor-blinded study. Patients were randomized to receive MBP with or without OABP (OABP+ and OABP- groups respectively). The primary endpoints were surgical-site infection (SSI) and postoperative ileus. Secondary endpoints were anastomotic leak, mortality, and hospital readmission within 30 days. RESULTS: Of 839 patients assessed for eligibility between November 2016 and June 2018, 600 were randomized and 529 were analysed. Trial participation was discontinued owing to adverse events in seven patients in the OABP+ group (2.3 per cent). SSI occurred in eight patients (3.2 per cent) in the OABP+ and 27 (9.8 per cent) in the OABP- group (P = 0.001). The incidence of postoperative ileus did not differ between groups. Anastomotic leakage occurred in four patients (1.6 per cent) in the OABP+ and 13 (4.7 per cent) in the OABP- (P = 0.02) group. There were no differences in hospital readmission (12 (4.7 per cent) versus 10 (3.6 per cent); P = 0.25) or mortality (3 (1.2 per cent) versus 4 (1.4 per cent); P = 0.39). CONCLUSION: OABP given with MBP reduced the rate of SSI and AL after colorectal surgery with anastomosis, therefore routine use of OABP is recommended.

Evaluation of oxidative/nitrative stress and uterine artery pulsatility index in early pregnancy.

INTRODUCTION: Increased oxidative/nitrative stress is characteristic not only in pathologic, but also in healthy pregnancy. High uterine artery pulsatility index (UtAPI) at the end of the first trimester is associated with altered placentation and elevated risk for adverse pregnancy outcomes. We aimed to examine the relationship of systemic oxidative/nitrative stress and uterine artery pulsatility index in the first trimester and their correlation to pregnancy outcomes. MATERIAL AND METHODS: Healthy pregnant women were recruited at 12-13th gestational week ultrasound examination; UtAPI was determined by color Doppler ultrasound. Patients were divided into high (UtAPI ≥ 2.3) (n = 30) and low (n = 31) resistance groups, and pregnancies were followed until labor. Systemic oxidative/nitrative stress was estimated by measuring total peroxide level, total antioxidant capacity and nitrotyrosine level. RESULTS: Plasma total peroxide level was significantly lower (2,510 ± 39 µM vs. 2,285 ± 59 µM), total antioxidant capacity was higher (781 ± 16 mM CRE vs. 822 ± 13 mM CRE) in the high UtAPI group, which were accompanied by lower birth weight (3,317 ± 64 vs. 3,517 ± 77 g, P < 0.05). Plasma total peroxide level showed a negative correlation (by Pearson) to UtAPI (P < 0.01) and positive correlation to birth weight (P < 0.05). CONCLUSIONS: According to our results, lower systemic oxidative stress showed correlation with high UtAPI measured between the 12-13th weeks of gestation. We also found significant differences in the birth weight of healthy newborns; therefore it is worth examining this relationship in pathological pregnancies.

Integrated twin-screw wet granulation, continuous vibrational fluid drying and milling: A fully continuous powder to granule line.

Highly homogeneous low-dose (50 µg) tablets were produced incorporating perfectly free-flowing granules prepared by a fully integrated Continuous Manufacturing (CM) line. The adopted CM equipment consisted of a Twin-Screw Wet Granulator (TSWG), a Continuous Fluid Bed Dryer (CFBD) and a Continuous Sieving (CS) unit. Throughout the experiments a pre-blend of lactose-monohydrate and corn starch was gravimetrically dosed with 1 kg/h into the TSWG, where they were successfully granulated with the drug containing water-based PVPK30 solution. The wet mass was subsequently dried in the CFBD on a vibratory conveyor belt and finally sieved in the milling unit. Granule production efficiency was maximized by determining the minimal Liquid-to-Solid (L/S) ratio (0.11). Design of Experiments (DoE) were carried out in order to evaluate the influence of the drying process parameters of the CFBD on the Loss-on-Drying (LOD) results. The manufactured granules were compressed into tablets by an industrial tablet rotary press with excellent API homogeneity (RSD < 3%). Significant scale-up was realized with the CM line by increasing the throughput rate to 10 kg/h. The manufactured granules yielded very similar results to the previous small-scale granulation runs. API homogeneity was demonstrated (RSD < 2%) with Blend Uniformity Analysis (BUA). The efficiency of TSWG granulation was compared to High-Shear Granulation (HSG) with the same L/S ratio. The final results have demonstrated that both the liquid distribution and more importantly API homogeneity was better in case of the TSWG granulation (RSD 1.3% vs. 4.5%).

Effectiveness of the Gerundium Youth Educating Program in Hungary.

The acceptance of brain death and the legitimation of organ transplantation is very much dependent on the general knowledge of the society. In Hungary, the legislation of brain death is based on presumed consent. There is no structural education about the topic so far. AIM: The role of the Gerundium program is to educate high school students about the importance of transplantation and the meaning of brain death. The goal of this study was to evaluate the effectiveness of the Gerundium contemporary educational program in a pilot study. METHOD: The education was held by medical students who successfully completed a preparatory elective course consisting of relevant information in the topic. Medical students used simple language during the 45-minute presentations. Two tests with simple but representative questions created by experts were completed by high school students: one directly before contemporary education and another 5 to 6 weeks after the lecture. RESULTS: A total of 147 tests were completed: 78 before and 69 after the presentation in the city of Debrecen and 294 before the lecture in the city of Gyor. In Debrecen, the overall correct answers increased by 6.05% (P < .05; before vs after). The results show that the knowledge transfer is highly effective in this manner and the students know significantly more weeks after the lectures. CONCLUSION: There is much to do to broadly inform society about transplantation and brain death, but we will continue to increase the number of students and measure the dynamic change of the students' knowledge.

Altered dynamics may drift pathological fibrillization in membraneless organelles.

Protein phase transition can generate non-membrane bound cellular compartments, which can convert from liquid-like to solid-like states. While the molecular driving forces of phase separation have been largely understood, much less is known about the mechanisms of material-state conversion. We apply a recently developed algorithm to describe the weak interaction network of multivalent motifs, and simulate the effect of pathological mutations. We demonstrate that linker dynamics is critical to the material-state of biomolecular condensates. We show that linker flexibility/mobility is a major regulator of the weak, heterogeneous meshwork of multivalent motifs, which promotes phase transition and maintains a liquid-like state. Decreasing linker dynamics increases the propensity of amyloid-like fragments via hampering the motif-exchange and reorganization of the weak interaction network. In contrast, increasing linker mobility may compensate rigidifying mutations, suggesting that the meshwork of weak, variable interactions may provide a rescue mechanism from aggregation. Motif affinity, on the other hand, has a moderate impact on fibrillization. Here we demonstrate that the fuzzy framework provides an efficient approach to handle the intricate organization of membraneless organelles, and could also be applicable to screen for pathological effects of mutations.

Next-generation sequencing identifies novel mitochondrial variants in pituitary adenomas.

PURPOSE: Disrupted mitochondrial functions and genetic variants of mitochondrial DNA (mtDNA) have been observed in different human neoplasms. Next-generation sequencing (NGS) can be used to detect even low heteroplasmy-level mtDNA variants. We aimed to investigate the mitochondrial genome in pituitary adenomas by NGS. METHODS: We analysed 11 growth hormone producing and 33 non-functioning [22 gonadotroph and 11 hormone immunonegative] pituitary adenomas using VariantPro™ Mitochondrion Panel on Illumina MiSeq instrument. Revised Cambridge Reference Sequence (rCRS) of the mtDNA was used as reference. Heteroplasmy was determined using a 3% cutoff. RESULTS: 496 variants were identified in pituitary adenomas with overall low level of heteroplasmy (7.22%). On average, 35 variants were detected per sample. Samples harbouring the highest number of variants had the highest Ki-67 indices independently of histological subtypes. We identified eight variants (A11251G, T4216C, T16126C, C15452A, T14798C, A188G, G185A, and T16093C) with different prevalences among different histological groups. T16189C was found in 40% of non-recurrent adenomas, while it was not present in the recurrent ones. T14798C and T4216C were confirmed by Sanger sequencing in all 44 samples. 100% concordance was found between NGS and Sanger method. CONCLUSIONS: NGS is a reliable method for investigating mitochondrial genome and heteroplasmy in pituitary adenomas. Out of the 496 detected variants, 414 have not been previously reported in pituitary adenoma. The high number of mtDNA variants may contribute to adenoma genesis, and some variants (i.e., T16189C) might associate with benign behaviour.

[The Patient Blood Management]. / Le «Patient Blood Management¼ ou la «Gestion du Sang pour le Patient¼.

Patient Blood Management (PBM) is a comprehensive hospital approach to the anemic patient or at risk of becoming anemic, aimed at protecting and optimizing the patient's blood capital and resistance. The main aim of BPM is to combat the risk factors of anaemia, hemorrhage and blood transfusion. PBM involves transdisciplinary collaboration ranging from pre-hospital prevention to post-hospital follow-up. This combination of techniques and preventive actions considerably improves the medicosurgical prognosis and contributes to the drastic reduction in the use of blood transfusion. PBM is expanding worldwide and should eventually become an evolving treatment standard.

Le Patient Blood Management (PBM) est une approche hospitalière globale du patient anémique ou à risque de le devenir, visant à protéger et optimiser le capital sanguin et la résistance du patient. Le PBM vise essentiellement à lutter contre les facteurs de risques que sont l'anémie, l'hémorragie et la transfusion sanguine. Le PBM implique une collaboration transdisciplinaire qui va de la prévention pré-hospitalière au suivi post-hospitalier. Cette combinaison de techniques et d'actions préventives améliore considérablement le pronostic médico-chirurgical et contribue à la diminution drastique du recours à la transfusion sanguine. Le PBM est en extension dans le monde et devrait, à terme, devenir un standard de traitement évolutif.

Fibre Dissection and Sectional Study of the Major Porcine Cerebral White Matter Tracts.

White matter anatomy is the basis for numerous applications in neurology, neurosurgery and fundamental neuroscience. Although the porcine brain is frequently used as experimental model in these fields of research, the description of its white matter is not as thorough as in the human brain or other species. Thus, the aim of this study is to describe the porcine white matter tracts in a complex manner. Two stepwise dissection protocols adapted from human anatomy were performed on six adult pig brain hemispheres prepared according to the Klingler method. Other four hemispheres were sectioned along section planes that were chosen similar to the Talairach coordinate system. As a result, three commissural tracts, seven association tracts and one projection tract were identified: corpus callosum, fornix, commissura rostralis, the short-association tracts, fasciculus longitudinalis superior, fasciculus uncinatus, fasciculus longitudinalis inferior, fasciculus occipitofrontalis inferior, cingulum, tractus mamillothalamicus and capsula interna. They were described and illustrated from multiple points of view, focusing on their trajectory, position, dimensions and anatomical relations. All in all, we achieved a three-dimensional understanding of the major tracts. The results are ready to be applied in future imagistic or experimental studies.

Anatomical variations of the obturator veins and their surgical implications.

PURPOSE OF INVESTIGATION: The obturator veins and their network contribute to major bleeding complications during gynaecologic surgery. MATERIALS AND METHODS: The anatomical variations of the obturator veins were studied on 106 patients in which a thorough bilateral pelvic lymphadenectomy was performed. RESULTS: Symmetrical drainage on right and left sides was found in 75 cases: only in internal iliac vein in 32 cases, both in external iliac vein and internal in 41 cases, and only in external in two cases (so called "pubic vein"). In 31 procedures, asymmetric drainage was found between the two sides: one side in internal, the other side both in internal and external in 25 patients; in three patients, in external on one side and in both internal and external on the other; and in external on one side and in internal on the other side in one patient. CONCLUSIONS: Anatomical variations of the obturator veins appear quite often.

Abdominal radical trachelectomy (ART) performed during pregnancy: a case report.

PURPOSE OF INVESTIGATION: Cervical cancer is one of the most frequent malignant diseases diagnosed during pregnancy. Abdominal or vaginal radical trachelectomies are fertility-preserving alternatives to radical hysterectomy for young women with early-stage cervical cancer that can be performed during ongoing pregnancy. MATERIAL AND METHODS: The authors report a pregnancy complicated by cervical cancer treated by abdominal radical trachelectomy (ART) at 16-17 gestational weeks with preservation of the concurrent pregnancy. RESULTS: The pregnancy evolved normally and delivery occurred at 38-39 gestational weeks by elective caesarean section. CONCLUSIONS: Radical trachelectomy could be offered as an option for pregnant patients with early invasive cervical cancer. It may help women to avoid the triple losses of a desired pregnancy, fertility, and motherhood.

Within-group relationships and lack of social enhancement during object manipulation in captive Goffin's cockatoos (Cacatua goffiniana).

Different types of social relationships can influence individual learning strategies in structured groups of animals. Studies on a number of avian species have suggested that local and/or stimulus enhancement are important ingredients of the respective species' exploration modes. Our aim was to identify the role of enhancement during object manipulation in different social contexts. We used focal observations to identify a linear dominance hierarchy as well as affiliative relationships between individuals in a group of 14 Goffin's cockatoos (Cacatua goffiniana, formerly goffini). Thereafter, in an unrewarded object choice task, several pairs of subjects were tested for a possible influence of social enhancement (local vs. stimulus) in three conditions: dominance, affiliation, and kinship. Our results suggest strong individual biases. Whereas previous studies on ravens and kea had indicated that enhancement in a non-food-related task was influenced by the social relationship between a demonstrator and an observer (affiliated - nonaffiliated), we found no such effects in our study group. In this context, Goffin's cockatoos' object learning seems to take place more on an individual level, despite their generally high motivation to manipulate nonfood items.

Microarchitectural study of the augmented bone following ridge preservation with a porcine xenograft and a collagen membrane: preliminary report of a prospective clinical, histological, and micro-computed tomography analysis.

Socket preservation using a combination of porcine xenograft and collagen membrane maintains the vertical and horizontal dimensions of the ridge. The aim of this study was to evaluate the microarchitecture of the grafted area by histological analysis and micro-computed tomography. Patients in the test group (group 1; nine patients) underwent socket preservation, while the sockets in the control group (group 2; eight patients) were allowed to heal without preservation. After a 6-month healing period, bone core biopsy samples were obtained and implants were placed in the augmented sites in the test group (12 biopsy samples) and the non-augmented sockets of the control group (12 biopsy samples). Analysis of the biopsy samples obtained from group 1 revealed that particles of the graft were surrounded by newly formed bone in eight cases and by granulation tissue in four cases. Micromorphometric data showed statistically significant differences in several parameters between the microarchitecture of the native bone and the newly formed bone within the augmented sites, which suggests that the xenograft particles interfere with the bony healing of the alveoli.

Use of intravenous tigecycline in patients with severe Clostridium difficile infection: a retrospective observational cohort study.

There are only a limited number of antimicrobials for treating severe Clostridium difficile infection (sCDI). Tigecycline shows significant in vitro effect against C. difficile and is approved for management of complicated intra-abdominal infections. Our aim was to analyse the efficacy of tigecycline compared with standard therapy (oral vancomycin plus intravenous metronidazole) in adults treated for sCDI. A retrospective cohort study of such patients hospitalized at our department from January 2014 to December 2015 was performed. Patients receiving tigecycline monotherapy were compared with patients treated with standard therapy alone. Diagnosis and severity of CDI were determined according to guidelines of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Primary outcome was clinical recovery, secondary outcomes were in-hospital and 90-day all-cause mortality and relapse, colectomy, and complication rates. Of the 359 patients hospitalized for sCDI, 90 (25.0%) were included, 45 in each group. Patients treated with tigecycline had significantly better outcomes of clinical cure (34/45, 75.6% vs. 24/45, 53.3%; p 0.02), less complicated disease course (13/45, 28.9% vs. 24/45, 53.3%; p 0.02), and less CDI sepsis (7/45, 15.6% vs. 18/45, 40.0%; p 0.009) compared with patients receiving standard therapy. Tigecycline usage was not associated with adverse drug reactions or need for colectomy. Rates of ileus, toxic megacolon, mortality, and relapse were similar between the two groups. Favourable outcomes suggest that tigecycline might be considered as a potential candidate for therapeutic use in cases of sCDI refractory to standard treatment.

Left atrial thrombus under dabigatran in a patient with nonvalvular atrial fibrillation.

Dabigatran is a new direct competitive inhibitor of thrombin and is equally effective and safe as warfarin in the prevention of thromboembolism in patients with nonvalvular atrial fibrillation. We present a case of a 60-year-old man with persistent nonvalvular atrial fibrillation who switched from acenocoumarol to dabigatran 110 mg twice daily. After five months the patient developed a large atrial thrombus, occlusion of the tibial arteries of the right foot, cerebellar infarction and multiple infarctions in kidneys and spleen. Blood test showed a dabigatran concentration of 35 ng/ml six hours after intake, correlating with a low trough concentration of 24-27 ng/mL and significantly increased thromboembolic risk. Other risk factors for thromboembolism were excluded. The present case indicates that in selected patients, there might be an indication for dose adjustments based on serum levels of dabigatran to ensure patient efficacy (thromboembolic events) and safety (bleeding).

Psychological distress and personality factors in takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TCC) is a transient condition characterised by severe left ventricular dysfunction combined with symptoms and signs mimicking myocardial infarction. Emotional triggers are common, but little is known about the psychological background characteristics of TCC. This study examined whether patients with TTC have higher levels of psychological distress (depressive symptoms, perceived stress, general anxiety), illness-related anxiety and distinct personality factors compared with healthy controls and patients with heart failure. METHODS AND RESULTS: Patients with TCC (N = 18; mean age 68.3 ± 11.7 years, 77.8 % women) and two comparison groups (healthy controls: N = 19, age 60.0 ± 7.6, 68.4 % women and patients with chronic heart failure: N = 19, age 68.8 ± 10.1, 68.4 % women) completed standardised questionnaires to measure depression (PHQ­9), perceived stress (PSS-10), general anxiety (GAD-7), illness-related anxiety (WI-7) and personality factors (NEO-FFI and DS-14). Psychological measures were obtained at 23 ± 18 months following the acute TTC event. Results showed that patients with TCC had higher levels of depressive symptoms (5.2 ± 5.2 vs. 2.5 ± 2.4, p = 0.039) and illness-related anxiety (2.1 ± 1.7 vs. 0.7 ± 1.3, p = 0.005) compared with healthy controls. Patients with TCC did not display significantly elevated perceived stress (p = 0.072) or general anxiety (p = 0.170). Regarding personality factors, levels of openness were lower in TCC compared with healthy controls (34.2 ± 4.3 vs. 38.2 ± 5.6, p = 0.021). No differences between TCC and heart failure patients were found regarding the psychological measures. CONCLUSIONS: TCC is associated with higher levels of depressive symptoms, more illness-related anxiety and less openness compared with healthy controls. These data suggest that TCC is associated with adverse psychological factors that may persist well after the acute episode.

[Early experiences with the Sorin Perceval S arteficial biological valve]. / Kezdeti tapasztalatok a Sorin Perceval S aorta biológiai billentyu beültetésével.

OBJECTIVES: We examined the Sorin Perceval S artificial biological valve implantation techniques, and present the initial experiences in our unit. METHODS: In the last 1.5 years, 27 patients had been implanted with Sorin Perceval S biological arteficial valve due to aortic valve disease. The device was mainly used in high-risk patients, in reoperative circumstances, in cases of calcified aortic root, and in elderly patients. RESULTS: The valve implantation time, aortic cross clamp time is shorter, but the risk of the operation cannot be eliminated entirely, because of the high risk patients' severe comorbidities. Furthermore, we performed echocardiography in the postoperative period, which demonstrated that the valve function is excellent, the valve fitted tightly in the anulus, and there was no paravalvular leakage. CONCLUSIONS: The Sorin Perceval S biological arteficial aortic valve is safe to use in high risk patients, and the surgical procedure is easier in case of partial sternotomy, too.

The mandatory role of groin lymphadenectomy in clinical Stages IB and II vulvar cancer.

PURPOSE OF INVESTIGATION: To analyze the prevalence of inguinofemoral lymph nodes metastases in clinical Stages IB-II vulva cancer. MATERIALS AND METHODS: Twenty-two patients with FIGO Stages IB-II FIGO vulva cancer with no clinically and imagistic evidence of nodes metastases were treated in the present clinic. The surgical procedures consisted in radical vulvectomy plus inguinofemoral lym- phadenectomy. RESULTS: The final pathological result was squamous carcinoma in 20 patients, vulva melanoma in one, and carcinosar- coma in one. The prevalence of positive lymph nodes was 45.4%. The median number of harvested lymph nodes was 14.0 per groin (between four and 27). Twelve patients (54.5%) developed some wound complications, but all were resolved. At the present time, 20 patients are alive, but the follow-up period is short for many of them; two patients died of disease. CONCLUSION: The prevalence of groin metastases in Stages IB-II vulvar cancer is high. A thorough inguino-femoral dissection seems necessary, despite the high incidence of wound complications.

Comparative Study of the Major White Matter Tracts Anatomy in Equine, Feline and Canine Brains by Use of the Fibre Dissection Technique.

The spatial anatomy of the white matter tracts is a subject of growing interest not only for researchers but also for clinicians. Imagistic methods have some limitations so that they should be confronted with dissection studies. The aim of this paper was to provide a three-dimensional view of the major white matter tracts in equine, feline and canine brains by use of the fibre dissection technique. Twenty cerebral hemispheres (six equine, four feline and 10 canine brains) were prepared according to the Klingler method. Stepwise mediolateral and lateromedial blunt dissections were performed using wooden sticks and spatulas. The lateromedial dissection was followed by the opening of the lateral ventricle. The use of the same multi-stage procedures resulted in a comparable exposure of the major association, projection and commissural fibres and their spatial relation with the lateral ventricle. To conclude, the proposed techniques are reproducible in equine, feline and canine brains and they can be successfully used for teaching, training or research in the field of neurobiology.