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INTRODUCTION: Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics. METHODS: A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints. RESULTS: Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents ( P = 0.047) and of late VTE with vedolizumab ( P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00). DISCUSSION: Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy.
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Produtos Biológicos , Colectomia , Colite Ulcerativa , Piperidinas , Complicações Pós-Operatórias , Pirimidinas , Humanos , Colite Ulcerativa/cirurgia , Colite Ulcerativa/tratamento farmacológico , Masculino , Feminino , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Readmissão do Paciente/estatística & dados numéricos , Pirróis/uso terapêutico , Pirróis/efeitos adversos , Tromboembolia Venosa/epidemiologia , Reoperação/estatística & dados numéricos , Infecção da Ferida Cirúrgica/epidemiologia , IdosoRESUMO
BACKGROUND Computer-aided design (CAD) has been used in the Nuss procedure to determine the bar length and shape. Despite computer aid, the shape and design remain quite intuitive. We tested a new algorithm to determine the optimal bar shape. MATERIAL AND METHODS The normal sterno-vertebral distance was defined on computed tomography (CT) scans of patients without pectus excavatum (PEx) at the same level where the deepest depression was found on CT scans of 97 patients with PEx. Four points were marked on the CT scan of 60 patients with PEx at the deepest deformity: P1: edge of the vertebra; P2: edge of the deformity; P3: the expected contact point of the bar and the rib; and P4: the expected end of the bar. The algorithm generated 3 circles upon these points, and the fusion of the arcs drew the line of the ideal bar. Corrected and normal sterno-vertebral distance values were compared with the Mann-Whitney U test. Ten bars were bent manually guided by a 1: 1 printout of the designed bar and were implanted in 10 adolescents. RESULTS The shortest sterno-vertebral distance was 3 cm below the intermammillary line in PEx patients. The normal mean sterno-vertebral distance at this level was 10.16±1.35 cm in non-PEx patients. The mean virtually corrected sterno-vertebral distance was 10.28±1.27 cm. No significant difference was found (P=0.44). The bars were seamless and were successfully implanted. No bar needed adjustment, the operation time was shorter, and the patient satisfaction score was 9.4/10. CONCLUSIONS With our new algorithm, an optimal Nuss bar can be designed.
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Algoritmos , Desenho Assistido por Computador , Tórax em Funil , Tomografia Computadorizada por Raios X , Humanos , Tórax em Funil/cirurgia , Tórax em Funil/diagnóstico por imagem , Adolescente , Masculino , Feminino , Tomografia Computadorizada por Raios X/métodos , Criança , Esterno/diagnóstico por imagemRESUMO
Circular dichroism (CD) spectroscopy is widely used to characterize the secondary structure composition of proteins. To derive accurate and detailed structural information from the CD spectra, we have developed the Beta Structure Selection (BeStSel) method (PNAS, 112, E3095), which can handle the spectral diversity of ß-structured proteins. The BeStSel webserver provides this method with useful accessories to the community with the main goal to analyze single or multiple protein CD spectra. Uniquely, BeStSel provides information on eight secondary structure components including parallel ß-structure and antiparallel ß-sheets with three different groups of twist. It overperforms any available method in accuracy and information content, moreover, it is capable of predicting the protein fold down to the topology/homology level of the CATH classification. A new module of the webserver helps to distinguish intrinsically disordered proteins by their CD spectrum. Secondary structure calculation for uploaded PDB files will help the experimental verification of protein MD and in silico modelling using CD spectroscopy. The server also calculates extinction coefficients from the primary sequence for CD users to determine the accurate protein concentrations which is a prerequisite for reliable secondary structure determination. The BeStSel server can be freely accessed at https://bestsel.elte.hu.
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Proteínas Intrinsicamente Desordenadas , Estrutura Secundária de Proteína , Simulação por Computador , Análise Espectral , Dicroísmo CircularRESUMO
INTRODUCTION: The apnea test (AT) is a crucial procedure in determining brain death (BD), with detection of spontaneous breathing efforts serving as a key criterion. Numerous national statutes mandate complete disconnection of the patient from the ventilator during the procedure to open the airway directly to the atmosphere. These regulations mandate visual observation as an exclusive option for detecting breathing efforts. However, reliance on visual observation alone can pose challenges in identifying subtle respiratory movements. CASE PRESENTATION: This case report presents a 55-year-old morbidly obese male patient with suspected BD due to cerebral hemorrhage undergoing an AT. The AT was performed with continuous electrical impedance tomography (EIT) monitoring. Upon detection of spontaneous breathing movements by both visual observation and EIT, the AT was aborted, and the patient was reconnected to the ventilator. EIT indicated a shift in ventilation distribution from the ventral to the dorsal regions, indicating the presence of spontaneous breathing efforts. EIT results also suggested the patient experienced a slow but transient initial recovery phase, likely due to atelectasis induced by morbid obesity, before returning to a steady state of ventilatory support. CONCLUSION: The findings suggest EIT could enhance the sensitivity and accuracy of detecting spontaneous breathing efforts, providing additional insights into the respiratory status of patients during the AT.
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Apneia , Morte Encefálica , Impedância Elétrica , Obesidade Mórbida , Tomografia , Humanos , Masculino , Morte Encefálica/diagnóstico , Morte Encefálica/fisiopatologia , Pessoa de Meia-Idade , Apneia/diagnóstico , Apneia/fisiopatologia , Tomografia/métodos , Obesidade Mórbida/complicações , Obesidade Mórbida/fisiopatologia , Respiração , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/complicações , Hemorragia Cerebral/fisiopatologiaRESUMO
Diagnostic imaging techniques provide a new aspect of the ante-mortem and post-mortem diagnostics in fish medicine. Ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) can provide more information about the internal organs and pathognomic lesions. The authors used diagnostic imaging techniques to evaluate and describe the neoplastic malformation in a 3-year-old female rainbow trout (Oncorhynchus mykiss). The fish was examined with Siemens Somatom Definition AS + CT scanner and Siemens Biograph mMR scanner. The animal was lethargic and showed anorectic signs and muscular dystrophy. During the post-mortem investigation, histopathology and immunohistochemistry were also performed allowing us to identify the neoplasms. The results showed a large soft tissue mass in the first mid-intestine segment, which proved to be an adenocarcinoma. This subsequently led to digestion problems and absorption disorders. Immunohistochemically, neoplastic cells of carcinoma revealed E-cadherin and pancytokeratin positivity. This is the first study to report the use of MRI and CT for studying gastrointestinal adenocarcinoma in rainbow trout.
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Adenocarcinoma , Doenças dos Peixes , Imageamento por Ressonância Magnética , Oncorhynchus mykiss , Animais , Adenocarcinoma/veterinária , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Feminino , Doenças dos Peixes/diagnóstico por imagem , Doenças dos Peixes/patologia , Imageamento por Ressonância Magnética/veterinária , Tomografia Computadorizada por Raios X/veterinária , Ultrassonografia/veterináriaRESUMO
A preliminary clinical report of implant placements with 2 immersive reality technologies is described: augmented reality with head mounted display and mixed reality with a tablet PC. Both immersive realities are promising and could facilitate innovative dental applications. However, mixed reality requires further development for clinical optimization.
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BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators. METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment. RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia. CONCLUSIONS: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).
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Produtos Biológicos , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Feminino , Humanos , Estudos de Coortes , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Fatores Imunológicos/efeitos adversos , Imunossupressores , Doenças Inflamatórias Intestinais/induzido quimicamente , Necrose , Estudos Prospectivos , Fator de Necrose Tumoral alfaRESUMO
Within the predator-prey relationship, predator behavior is less studied. Even in natural populations, it shows great diversity, and the factors influencing this are even less known. Among these factors, the personality type of the individual, (including exploration, and neophilia) and the practice significantly influence the success of adapting to a changing environment and switching to new prey types. In the present study, we investigated the first five consecutive foraging trials on live fish prey in naïve pikeperch individuals, which previously consumed or refused pelleted food. We hypothesized that individuals which were willing to consume alternative (pelleted) food would also show higher foraging success on living prey and that the practice would influence the learning process. Our results show that the timing of prey detection is influenced by exploratory behavior, the latency of the first attack by the aptitude for consuming pellets, and both traits by the individual's practice. However, neither of the factor affects the latency and success rate of capturing the prey, suggesting that predation is an independent behavioral trait.
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Percas , Comportamento Predatório , Animais , Comportamento Exploratório , AptidãoRESUMO
BACKGROUND: According to the European Society of Gastrointestinal Endoscopy guidelines, self-expandable metal stents (SEMSs) are preferable to plastic stents (PSs) in the management of pancreatic cancer, regardless of cancer stage. The aim of this study was to compare the therapeutic efficacy and treatment costs of SEMS and PS in the management of malignant biliary obstruction. METHODS: One hundred and thirty-five patients who underwent endoscopic stent placement were retrospectively enrolled and divided into PS (41 patients), primary SEMS (39 patients) and secondary SEMS (55 patients) groups. We determined the technical and functional success rate, stent patency, and cumulative treatment cost. RESULTS: A total of 111 SEMSs and 153 PSs were placed with similar technical (100% vs. 98.69%) and functional success rate (90.10% vs. 86.27%) but with different stent patency (10.28 vs. 22.16 weeks; p < 0.001). Multiple PS implantations and larger stent diameter increased the length of stent patency compared to 7-Fr PSs (10.88 vs. 10.55 vs. 7.63 weeks, respectively). The cumulative treatment cost of patients with different survival times did not differ significantly between groups, however, among patients surviving 2-4 months it was higher in PS group than primary SEMS and secondary SEMS groups (2888 vs. 2258 vs. 2144, respectively, p = 0.3369) due to increased number of biliary reintervention (2.08 ± 1.04 vs. 1.20 ± 0.42 vs. 1.50 ± 0.53; p < 0.0274) and longer hospital stay (15.77 ± 10.14 vs. 8.70 ± 7.70 vs. 8.50 ± 6.17 days, p = 0.0527). CONCLUSIONS: In view of treatment costs, the consequences of illness, and the processes of the health care system, SEMS implantation is recommended regardless of patients' life expectancy.
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Colestase , Neoplasias Pancreáticas , Stents Metálicos Autoexpansíveis , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Colestase/etiologia , Colestase/cirurgia , Stents , Neoplasias Pancreáticas/complicações , Custos de Cuidados de Saúde , PlásticosRESUMO
In synapses that show signs of local apoptosis and mitochondrial stress and undergo neuro-immunological synapse pruning, an increase in the levels of the presynaptic protein, neuronal-specific septin-3 can be observed. Septin-3 is a member of the septin GTPase family with the ability to form multimers and contribute to the cytoskeleton. However, the function of septin-3 remains elusive. Here, we provide evidence that septin-3 is capable of binding the most-studied autophagy protein Atg8 homolog microtubule-associated protein 1 light chain 3B (LC3B), besides another homolog, GABA receptor-associated protein-like 2 (GABARAPL2). Moreover, we demonstrate that colocalization of septin-3 and LC3B increases upon chemical autophagy induction in primary neuronal cells. Septin-3 is accumulated in primary neurons upon autophagy enhancement or blockade, similar to autophagy proteins. Using electron microscopy, we also show that septin-3 localizes to LC3B positive membranes and can be found at mitochondria. However, colocalization results of septin-3 and the early mitophagy marker PTEN-induced kinase 1 (PINK1) do not support that binding of septin-3 to mitochondria is mitophagy related. We conclude that septin-3 correlates with synaptic/neuronal autophagy, binds Atg8 and localizes to autophagic membranes that can be enhanced with chemical autophagy induction. Based on our results, elevated septin-3 levels might indicate enhanced or impeded autophagy in neurons.
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Autofagossomos , Septinas , Autofagossomos/metabolismo , Autofagia , Proteínas Associadas aos Microtúbulos/metabolismo , Mitofagia , Neurônios/metabolismo , Septinas/metabolismoRESUMO
BACKGROUND & AIMS: Tools for stratification of relapse risk of Crohn's disease (CD) after anti-tumor necrosis factor (TNF) therapy cessation are needed. We aimed to validate a previously developed prediction model from the diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressants (STORI) trial, and to develop an updated model. METHODS: Cohort studies were selected that reported on anti-TNF cessation in 30 or more CD patients in remission. Individual participant data were requested for luminal CD patients and anti-TNF treatment duration of 6 months or longer. The discriminative ability (concordance-statistic [C-statistic]) and calibration (agreement between observed and predicted risks) were explored for the STORI model. Next, an updated prognostic model was constructed, with performance assessment by cross-validation. RESULTS: This individual participant data meta-analysis included 1317 patients from 14 studies in 11 countries. Relapses after anti-TNF cessation occurred in 632 of 1317 patients after a median of 13 months. The pooled 1-year relapse rate was 38%. The STORI prediction model showed poor discriminative ability (C-statistic, 0.51). The updated model reached a moderate discriminative ability (C-statistic, 0.59), and included clinical symptoms at cessation (hazard ratio [HR], 2.2; 95% CI, 1.2-4), younger age at diagnosis (HR, 1.5 for A1 (age at diagnosis ≤16 years) vs A2 (age at diagnosis 17 - 40 years); 95% CI, 1.11-1.89), no concomitant immunosuppressants (HR, 1.4; 95% CI, 1.18-172), smoking (HR, 1.4; 95% CI, 1.15-1.67), second line anti-TNF (HR, 1.3; 95% CI, 1.01-1.69), upper gastrointestinal tract involvement (HR, 1.3 for L4 vs non-L4; 95% CI, 0.96-1.79), adalimumab (HR, 1.22 vs infliximab; 95% CI, 0.99-1.50), age at cessation (HR, 1.2 per 10 years younger; 95% CI, 1-1.33), C-reactive protein (HR, 1.04 per doubling; 95% CI, 1.00-1.08), and longer disease duration (HR, 1.07 per 5 years; 95% CI, 0.98-1.17). In subanalysis, the discriminative ability of the model improved by adding fecal calprotectin (C-statistic, 0.63). CONCLUSIONS: This updated prediction model showed a reasonable discriminative ability, exceeding the performance of a previously published model. It might be useful to guide clinical decisions on anti-TNF therapy cessation in CD patients after further validation.
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Doença de Crohn , Inibidores do Fator de Necrose Tumoral , Adalimumab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Infliximab/uso terapêutico , Necrose , Recidiva , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
PENELOP (Paramagnetic Equilibrium vs Nonequilibrium magnetization Enhancement or LOss Perturbation) is the presented nuclear magnetic resonance (NMR) approach to identify at once the location of proteins' exposed surface, hindered accessibility, and exchange processes occurring on a µs-ms time scale. In addition to mapping the protein surface accessibility, the application of this method under specific conditions makes it possible to distinguish conformational mobility and chemical exchange processes, thereby providing an alternative to characterization by more demanding techniques (transverse relaxation dispersion, saturation transfer, and high-pressure NMR). Moreover, its high sensitivity enables studying samples at low, physiologically more relevant concentrations. Association, dynamics, and oligomerization are addressed by PENELOP for a component of SARS-CoV-2 replication transcription complex and an amyloidogenic protein.
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COVID-19 , Agregados Proteicos , Humanos , Conformação Molecular , Ressonância Magnética Nuclear Biomolecular/métodos , SARS-CoV-2RESUMO
Colorectal cancer (CRC) is the third most common malignant tumor and resection remains the key element in its treatment. The correction of preoperative malnutrition reduces morbidity and mortality. Our study demonstrates a nutritional state mass screening protocol to steer nutritional support. Two hundred fifty-nine patients with planned colorectal resection were prospectively enrolled. Preoperative telemedicinal assessment determined the risk of malnutrition using Nutritional Risk Screening 2002 (NRS 2002) score. Patients with a score ≥3 were offered optimized oral nutritional supplement. Three groups were investigated. Group I (NRS 2002 < 3, n = 98) received no supplement. Group II- (NRS 2002 ≥ 3, n = 118) was offered but did not finally receive clinical nutrition. Group II+ (NRS 2002 ≥ 3, n = 43) accepted and received adequate clinical nutrition. 98 patients (37.8%) had no risk, 154 patients (59.5%) had increased risk and 7 (2.7%) had severe malnutrition. Severe complications (Clavien-Dindo >2) rate was similar in Group I (2%) and Group II+ (2.3%) with no mortality. Severe complications more often occurred in Group II- (5.1%) along with 1.7% mortality (p > 0.05). Length of stay was the highest in Group II- while the lowest in Group II+ (p < 0.01). Preoperative telemedicinal screening is applicable in identifying patients with malnutrition. NRS 2002 used by a nutritional team reduces length of stay.
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Cirurgia Colorretal , Desnutrição , Humanos , Tempo de Internação , Desnutrição/etiologia , Programas de Rastreamento/métodos , Avaliação Nutricional , Estado Nutricional , Estudos Prospectivos , Medição de RiscoRESUMO
BACKGROUND: Health care professionals in endoscopic labs have an elevated risk for COVID-19 infection, therefore, we aimed to determine the effect of current pandemic on the workflow and infection prevention and control strategies of endoscopy units in real-life setting. METHODS: All members of Hungarian Society of Gastroenterology were invited between 7 and 17 April 2020 to participate in this cross-section survey study and to complete an online, anonymous questionnaire. RESULTS: Total of 120 endoscopists from 83 institutes were enrolled of which 35.83% worked in regions with high cumulative incidence of COVID-19. Only 33.33% of them had undergone training about infection prevention in their workplace. 95.83% of endoscopists regularly used risk stratification of patients for infection prior endoscopy. While indications of examinations in low risk patients varied widely, in high-risk or positive patients endoscopy was limited to gastrointestinal bleeding (95.00%), removal of foreign body from esophagus (87.50%), management of obstructive jaundice (72.50%) and biliary pancreatitis (67.50%). Appropriate amount of personal protective equipment was available in 60.85% of endoscopy units. In high-risk or positive patients, surgical mask, filtering facepiece mask, protective eyewear and two pairs of gloves were applied in 30.83%, 76.67%, 90.00% and 87.50% of cases, respectively. Personal protective equipment fully complied with European guideline only in 67.50% of cases. CONCLUSIONS: Survey found large variability in indications of endoscopy and relative weak compliance to national and international practical recommendations in terms of protective equipment. This could be improved by adequate training about infection prevention.
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COVID-19/prevenção & controle , Endoscopia Gastrointestinal , Gastroenterologia/organização & administração , Unidades Hospitalares/organização & administração , Controle de Infecções/organização & administração , Fluxo de Trabalho , COVID-19/epidemiologia , COVID-19/transmissão , Estudos Transversais , Humanos , Hungria , Seleção de Pacientes , Equipamento de Proteção IndividualRESUMO
The aquaculture industry is growing and includes the farming and breeding of more than 580 aquatic species worldwide. The rainbow trout (Oncorhynchus mykiss, Walbaum 1792) is the most commonly bred trout species in Hungary. As broodfish form the basis of most fish farms, investigation into tumours occurring in trout, although under-researched, has proven to be a valuable and necessary field of study. During our investigation, we examined a broodstock of 3- to 6-year-old rainbow trouts (800) affected with idiopathic intestinal tumours (3%) which had consequentially led to ileus (40%). While performing necropsy, initial pathological observations showed intussusceptions. Tumours were discovered upon opening the body cavity, as well as metastasis forming in the livers and in the vessels of the gills. Histopathological and immunohistochemical tests allowed us to identify the neoplasms. The primary adenocarcinoma was found to have been developed within the intestines of the fish. The tumour tissue broke through the basal membrane and infiltrated the propria, protruding asymmetrically into the lumen of the mid-intestines, causing it to narrow significantly. This subsequently led to passage disorders, invagination of the intestinal segment and finally the emaciation of the fish. Histopathological and immunohistochemical inspection of the tumour cells displayed a high mitotic index, confirming malignancy.
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Adenocarcinoma/veterinária , Doenças dos Peixes/etiologia , Neoplasias Intestinais/veterinária , Intussuscepção/veterinária , Oncorhynchus mykiss , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Animais , Doenças dos Peixes/patologia , Pesqueiros , Hungria , Neoplasias Intestinais/complicações , Neoplasias Intestinais/patologia , Intussuscepção/etiologiaRESUMO
BACKGROUND: There are contradictory results about the effect of magnesium citrate plus sodium picosulfate bowel cleansing agents on the fluid and electrolyte balance. Therefore, this study aimed to determine the efficacy, tolerability and safety of this medication in colonoscopy preparation. METHODS: 233 patients were enrolled in this phase IV prospective observational study. The effectiveness of bowel cleansing was assessed using the Boston Bowel Preparation Scale (BBPS). Adequate cleansing was defined as BBPS ≥ 6 and excellent cleansing as BBPS > 7. Tolerability was examined using a standardized questionnaire. In the safety analysis, the change of serum electrolytes levels and renal function during bowel cleansing was assessed. RESULTS: Adequate and excellent bowel cleansing were achieved 94.85% and 72.96% of cases, respectively. None or very mild symptoms were reported in 47.21% of cases. Statistically significant changes occurred in serum potassium (4.38±0.43 vs. 4.25±0.43 mmol/L, p<0.0001), urea (4.86±1.37 vs. 3.84±1.43 mmol/L, p<0.0001) and creatinine (male: 81.07±16.02 vs. 84.54±15.11 µmol/L; female: 69.32±12.22 vs. 72.96±12.11 µmol/L, p<0.0001) levels during the colonoscopy preparation. However, the number of patients with values outside of the normal range increased significantly only in the case of serum urea (3.95% vs. 26.97%, p<0.0001). CONCLUSION: Magnesium citrate with sodium picosulfate is outstandingly effective, well tolerated and a safe agent in colonoscopy preparation. It caused significant, but non-clinically relevant changes in serum electrolytes levels and renal function.
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Catárticos , Compostos Organometálicos , Catárticos/efeitos adversos , Citratos/efeitos adversos , Ácido Cítrico , Colonoscopia , Feminino , Humanos , Masculino , Compostos Organometálicos/efeitos adversos , Picolinas/efeitos adversos , PolietilenoglicóisRESUMO
Controlling the balance of pro-inflammatory M1 versus anti-inflammatory M2 macrophages may have paramount therapeutic benefit in cardiovascular diseases, infections, cancer and chronic inflammation. The targeted depletion of different macrophage populations provides a therapeutic option to regulate macrophage-mediated functions. Macrophages are highly sensitive to necroptosis, a newly described regulated cell death mediated by receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain like pseudokinase. Antagonists of inhibitors of apoptosis proteins (SMAC mimetics) block RIPK1 ubiquitination, while TGF-activated kinase 1 (TAK1) inhibitors prevent the phosphorylation of RIPK1, resulting in increased necroptosis. We compared the sensitivity of monocyte-derived human M1 and M2 cells to various apoptotic and necroptotic signals. The two cell types were equally sensitive to all investigated stimuli, but TAK1 inhibitor induced more intense necroptosis in M2 cells. Consequently, the treatment of co-cultured M1 and M2 cells with TAK1 inhibitor shifted the balance of the two populations toward M1 dominance. Blockage of either Aurora Kinase A or glycogen synthase kinase 3ß, two newly described necroptosis inhibitors, increased the sensitivity of M1 cells to TAK1-inhibitor-induced cell death. Finally, we demonstrated that in vitro differentiated tumor-associated macrophages (TAM-like cells) were as highly sensitive to TAK1 inhibitor-induced necroptosis as M2 cells. Our results indicate that at least two different necroptotic pathways operate in macrophages and the targeted elimination of different macrophage populations by TAK1 inhibitor or SMAC mimetic may provide a therapeutic option to regulate the balance of inflammatory/anti-inflammatory macrophage functions.
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Lactonas/farmacologia , MAP Quinase Quinase Quinases/antagonistas & inibidores , Macrófagos/efeitos dos fármacos , Necroptose/efeitos dos fármacos , Resorcinóis/farmacologia , Humanos , Macrófagos/metabolismoRESUMO
The aim of our study was to examine the possible effect of steatosis and fibrosis on the blunt force vulnerability of human liver tissue. 3.5 × 3.5 × 2-cm-sized liver tissue blocks were removed from 135 cadavers. All specimens underwent microscopical analysis. The tissue samples were put into a test stand, and a metal rod with a square-shaped head was pushed against the capsular surface. The force (Pmax) causing liver rupture was measured and registered with a Mecmesin AFG-500 force gauge. Six groups were formed according to the histological appearance of the liver tissue: intact (group 1), mild steatosis (group 2), moderate steatosis (group 3), severe steatosis (group 4), fibrosis (group 5), and cirrhosis (group 6). The average Pmax value was 34.1 N in intact liver samples (range from 18.1 to 60.8 N, SD ± 8.7), 45.1 N in mild steatosis (range from 24.2 to 79.8 N SD ± 12.6), 55.4 N in moderate steatosis (range from 28.9 to 92.5 N, SD ± 16.0), 57.6 N in severe steatosis (range from 39.8 to 71.5 N, SD ± 11.9), 63.7 N in fibrosis (range from 37.8 to 112.2 N, SD ± 19.5), and 87.1 N in the case of definite cirrhosis (range from 52.7 to 162.7 N, 30.3). The Pmax values were significantly higher in samples with visible structural change than in intact liver sample (p = 0.023, 0.001, 0.009, 0.0001, 0.0001 between group 1 and groups 2 to 6 respectively). Significant difference was found between mild steatosis (group 2) and cirrhosis (group 6) (p = 0.0001), but the difference between mild, moderate, and severe steatosis (groups 2, 3, and 4) was not significant. Our study demonstrated that contrary to what is expected as received wisdom dictates, the diseases of the parenchyma (steatosis and presence of fibrosis) positively correlate with the blunt force resistance of the liver tissue.
Assuntos
Fígado Gorduroso/patologia , Fibrose/patologia , Cirrose Hepática/patologia , Fígado/lesões , Fígado/fisiopatologia , Ferimentos não Penetrantes/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Patologia Legal , Humanos , Pessoa de Meia-Idade , Estresse MecânicoRESUMO
BACKGROUND: Diagnostic accuracy and quality of smears obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are influenced by characteristics of suction and examined organ. AIMS AND METHODS: Efficiency of EUS-FNA and quality of smears obtained by slow-pull (SP) and standard suction (SS) techniques was prospectively compared in the sampling of pancreatic (N = 56) and extrapancreatic (N = 145) tumors. RESULTS: SS technique resulted in a higher number of smear pairs both in pancreatic (1.74 vs. 3.19; p < 0.001) and extrapancreatic tumors (1.62 vs. 3.28; p < 0.001); however, it decreased the proportion of diagnostic smears (46.69% vs. 36.52%; p = 0.002 and 49.17% vs. 30.67%; p < 0.001) and increased the bloodiness (1.51 vs. 2.07; p < 0.001 and 1.48 vs. 2.05; p < 0.001). In pancreatic cancers, no difference was observed in terms of diagnostic accuracy (81.38% vs. 83.45%) and cellularity (1.44 vs. 1.27; p = 0.067); however, they were substantially higher in extrapancreatic tumors using SP technique (71.41% vs. 60.71% and 1.34 vs. 0.77; p < 0.001). Only SP technique resulted in a significant difference between examiners in terms of technical success rate and quality of smears without any decrease of diagnostic accuracy. CONCLUSIONS: SP technique yields better quality smears independently from tumors characteristics; however, it shows significant examiner-dependency. SS technique reduces the diagnostic accuracy of sampling in extrapancreatic tumors.
Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Estudos Prospectivos , Sensibilidade e Especificidade , SucçãoRESUMO
Porcine reproductive and respiratory syndrome (PRRS) causes significant losses to the swine industry worldwide, which leads to launching eradication programmes. The PRRS eradication programme in Hungary is based on the territorial principle, and it is obligatory for each swine farm irrespective of the number of animals kept there. Hungary has an exceptionally large herd size in large-scale pig farms. Large fattening farms operate as all-in/all-out or continuous flow systems. The large-scale breeding herds are predominantly farrow-to-finish types. In large-scale breeding farms, PRRS eradication was carried out by the depopulation-repopulation method in 33 farms, of which 23 received state compensation, 18 farm units either finished production or changed to producing fatteners only. Two farms used the test and removal method for eradication. One farm was classified as 'vaccinated free'. At this farm the breeding animals are vaccinated continuously but there is no vaccination of the progeny at any age, and the PRRS-free status of the farm is strictly controlled and monitored. By 31 December 2019, all pigs in five euroregions of Hungary had become free from PRRS virus, while the PRRS eradication process is still ongoing in the remaining two regions.