Several molecular clonality assays have been developed to assess canine B cell proliferations. These assays were based on different sequence data, utilized different assay designs and employed different testing strategies. This has resulted in a complex body of literature and complicates evidence-based selection of primer sets. In addition, further refinement of primer sets is difficult because it is unknown how well current primer sets cover the expressed sequence repertoire. The objectives of this study were 1) to provide an overview of published IGH clonality assays that highlights key differences in assay design and testing strategy and 2) to propose a novel method for optimizing primer sets that leverages large-scale sequencing data. A review of previously published assays highlighted confounding factors that hamper a direct comparison of performance metrics between studies. These findings illustrate the need for a multi-institutional effort to harmonize veterinary clonality testing. A novel in silico analysis of primer sequences using a large dataset of expressed sequences identified shortfalls of existing primer sets and was used to guide primer optimization. Three optimized primer sets were tested and yielded qualitative sensitivity values between 80-90%. The qualitative sensitivity ranged from 1% to over 50% and was dependent on the size of the neoplastic clone and the sample DNA used. These findings illustrate that inclusion of high-throughput sequencing data for primer design can be a useful tool to guide primer design and optimization. This strategy could be applied to other antigen receptor loci or species to further improve veterinary clonality assays.
- MeSH
- B-Lymphocytes cytology MeSH
- Clone Cells * MeSH
- DNA Primers * MeSH
- Dogs genetics immunology MeSH
- Immunoglobulin Heavy Chains genetics MeSH
- Animals MeSH
- Check Tag
- Dogs genetics immunology MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Radiologists utilize pictures from X-rays, magnetic resonance imaging, or computed tomography scans to diagnose bone cancer. Manual methods are labor-intensive and may need specialized knowledge. As a result, creating an automated process for distinguishing between malignant and healthy bone is essential. Bones that have cancer have a different texture than bones in unaffected areas. Diagnosing hematological illnesses relies on correct labeling and categorizing nucleated cells in the bone marrow. However, timely diagnosis and treatment are hampered by pathologists' need to identify specimens, which can be sensitive and time-consuming manually. Humanity's ability to evaluate and identify these more complicated illnesses has significantly been bolstered by the development of artificial intelligence, particularly machine, and deep learning. Conversely, much research and development is needed to enhance cancer cell identification-and lower false alarm rates. We built a deep learning model for morphological analysis to solve this problem. This paper introduces a novel deep convolutional neural network architecture in which hybrid multi-objective and category-based optimization algorithms are used to optimize the hyperparameters adaptively. Using the processed cell pictures as input, the proposed model is then trained with an optimized attention-based multi-scale convolutional neural network to identify the kind of cancer cells in the bone marrow. Extensive experiments are run on publicly available datasets, with the results being measured and evaluated using a wide range of performance indicators. In contrast to deep learning models that have already been trained, the total accuracy of 99.7% was determined to be superior.
- MeSH
- Algorithms MeSH
- Deep Learning * MeSH
- Bone Marrow diagnostic imaging pathology MeSH
- Humans MeSH
- Bone Neoplasms pathology diagnostic imaging diagnosis MeSH
- Neural Networks, Computer * MeSH
- Image Processing, Computer-Assisted methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Ciele. V predošlých výskumoch boli dokumentované rôzne dopady pandémie COVID-19 na mentálne zdravie. Menej pozornosti však bolo venovanej tomu, ktoré faktory tu môžu zohrávať protektívnu rolu. Otázky a hypotézy. Predkladaná štúdia sa zaoberá tým, akú rolu zohrávali tri druhy pozitívnych očakávaní (optimizmus, nádej a sebaúčinnosť) v rámci subjektívnej pohody a prežívanej úzkosti počas nástupu prvej vlny pandémie COVID-19 na Slovensku. Súbor a metódy. Výskum bol realizovaný po tom, ako bol na Slovensku vyhlásený núdzový stav (N = 1011). Autori zisťovali sme subjektívnu pohodu, aktuálne prežívanú úzkosť, tri druhy očakávaní (nádej, optimizmus a všeobecnú sebaúčinnosť) a to, do akej miery vnímali účastníci výskumu koronavírus ako nebezpečný. Druhý zber dát sa konal po celoštátnom lockdowne (N = 391). Tu sa autori zamerali na stratégie zvládania. Analýzy. V rámci analýzy dát boli využité dva postupy. Prvý bol reprezentovaný lineárnou regresiou pracujúcou s viacerými modelmi (Bayesiánsky prístup), druhý mediačnou analýzou (Frekventistický prístup). Výsledky. V hlavnej časti (N = 1011), realizovanej krátko povyhlásení núdzového stavu, sa ako dôležitý prediktor ukázal predovšetkým optimizmus. Pozitívne predikoval subjektívnu pohodu a negatívne prežívanú úzkosť. Zmienený vzťah bol sprostredkovaný tým, do akej miery považovali účastníci výskumu koronavírus za nebezpečný. Okrem toho, sebaúčinnosť negatívne predikovala prežívanú úzkosť a subškály nádeje predikovali subjektívnu pohodu. V nadväzujúcom zbere dát (N = 391), uskutočnenom po prvom lockdowne, sa autori zamerali na rolu stratégii zvládania ako potenciálneho mediátora vo vzťahu medzi očakávaniami a kritérialnými premennými. Tu sa ako jeden z potenciálne dôležitých mechanizmov ukázali predovšetkým dysfunkčné stratégie zvládania stresu. Limity. Medzi limity možno zaradiť príležitostný výber výskumného súboru a to, že otázka, týkajúca sa toho, do akej miery tu šlo o vzťah špecifický pre pandémiu, zostáva aj naďalej otvorená. Okrem toho je nevyhnutné, aby výzkumníci zostali pri vyjadrovaní sa k otázke kauzality nanajvýš opatrní.
Objectives. Although various mental health-related consequences of the COVID-19 pandemic have been documented, there has been far less attention given to potential protective factors. Questions and hypotheses. In the present study, authors examined the role of three types of positive expectancies - optimism, hope, and self-efficacy - as predictors of well-being and anxiety. Furthermore, authors examined the role of coping strategies as a potential mediator between expectancies and criterion variables. Sample and settings. The present study was conducted during the COVID-19 outbreak in Slovakia after a national emergency was declared (N=1011). Additionally, longitudinal follow up was conducted after a national lockdown (N=391). Statistical analysis. Multi-model linear regression (the Bayesian approach) and simple mediation analysis (the Frequentist approach) were used to answer research questions. Results. In the main study with N=1011 participants sampled after a national emergency was declared, the role of optimism in predicting anxiety and well-being was corroborated. Moreover, this finding was replicated after a national lockdown and the degree to which Coronavirus was considered dangerous served as a potential mediator. Besides optimism, self-efficacy negatively predicted anxiety, and subscales of hope predicted well-being. Additionally, the role of coping strategies as potential mediator was examined. In follow up with N=391 respondents who decided to participate after the national lockdown, authors found an indirect effect of optimism on well-being and anxiety through dysfunctional coping. Limitations. The present study has some limitations that should be reflected upon. For example, convenience sampling was used. Moreover, interpretations related to causality should be avoided and the specificity of the effect in relation to a pandemic situation should be further examined in future research.
BACKGROUND: COVID-19 was declared a global health emergency. Since children are less than 1% of reported cases, there is limited information to develop evidence-based practice recommendations. The objective of this study was to rapidly gather expert knowledge and experience to guide the care of children with chronic kidney disease during the COVID-19 pandemic. METHODS: A four-round multi-center Delphi exercise was conducted among 13 centers in 11 European countries of the European Pediatric Dialysis Working Group (EPDWG) between March, 16th and 20th 2020. Results were analyzed using a mixed methods qualitative approach and descriptive statistics. RESULTS: Thirteen COVID-19 specific topics of particular need for guidance were identified. Main themes encompassed testing strategies and results (n = 4), changes in use of current therapeutics (n = 3), preventive measurements of transmission and management of COVID-19 (n = 3), and changes in standard clinical care (n = 3). Patterns of center-specific responses varied according to regulations and to availability of guidelines. CONCLUSIONS: As limited quantitative evidence is available in real time during the rapid spread of the COVID-19 pandemic, qualitative expert knowledge and experience represent the best evidence available. This Delphi exercise demonstrates that use of mixed methodologies embedded in an established network of experts allowed prompt analysis of pediatric nephrologists' response to COVID-19 during this fast-emerging public health crisis. Such rapid sharing of knowledge and local practices is essential to timely and optimal guidance for medical management of specific patient groups in multi-country health care systems such as those of Europe and the US.
- MeSH
- Renal Insufficiency, Chronic complications therapy MeSH
- Delphi Technique MeSH
- Renal Dialysis * MeSH
- Child MeSH
- Infant MeSH
- Infection Control MeSH
- Coronavirus Infections complications prevention & control therapy MeSH
- Humans MeSH
- Evidence-Based Medicine MeSH
- Adolescent MeSH
- Pandemics prevention & control MeSH
- Child, Preschool MeSH
- Pneumonia, Viral complications prevention & control therapy MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Europe MeSH
OBJECTIVE: To assess the value of preoperative albumin to globulin ratio for predicting pathologic and oncological outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy in a large multi-institutional cohort. MATERIALS AND METHODS: Preoperative albumin to globulin ratio was assessed in a multi-institutional cohort of 2492 patients. Logistic regression analyses were performed to assess the association of the albumin to globulin ratio with pathologic features. Cox proportional hazards regression models were performed for survival endpoints. RESULTS: The optimal cut-off value was determined to be 1.4 according to a receiver operating curve analysis. Lower albumin to globulin ratios were observed in 797 patients (33.6%) compared with other patients. In a preoperative model, low preoperative albumin to globulin ratio was independently associated with nonorgan-confined diseases (odds ratio 1.32, P = 0.002). Patients with low albumin to globulin ratios had worse recurrence-free survival (P < 0.001), cancer-specific survival (P = 0.001) and overall survival (P = 0.020) in univariable and multivariable analyses after adjusting for the effect of standard preoperative prognostic factors (recurrence-free survival: hazard ratio (HR) 1.31, P = 0.001; cancer-specific survival: HR 1.31, P = 0.002 and overall survival: HR 1.18, P = 0.024). CONCLUSIONS: Lower preoperative albumin to globulin ratio is associated with locally advanced disease and worse clinical outcomes in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma. As it is difficult to stage disease entity, low preoperative serum albumin to globulin ratio may help identify those most likely to benefit from intensified care, such as perioperative systemic therapy, and the extent and type of surgery.
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Urinary Bladder Neoplasms blood mortality pathology surgery MeSH
- Nephroureterectomy MeSH
- Preoperative Period MeSH
- Prognosis MeSH
- Proportional Hazards Models MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Serum Globulins analysis MeSH
- Serum Albumin analysis MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
Cíl: Cílem této práce bylo zhodnotit úspěšnost perkutánní drenáže při léčbě těžké akutní pankreatitidy s multiorgánovým selháváním. Materiál a metoda: V období 1998-2003 bylo na naší klinice vyšetřeno 441 pacientů S diagnózou akutní pankreatitidy. Jedno sto patnáct (27 %) pacientů mělo těžkou akutní pankreatitidu, z tohoto počtu bylo léčeno nouze drenáží 55 nemocných (47,8 %), 34 (29,6 %) mělo provedenu drenáž i operaci a 26 (22,6 %) pacientů bylo léčeno konzervativně. Osmnáct pacientů mělo multiorgánové selhávání, 26 septické teploty. Byl jim zaveden drén buď 18 G pig tail (Optimed) nebo 20-26 G Mallecot (Boston Scientific). Hodnocení úspěšnosti bylo provedeno na základě dotazníků, které byly rozeslány na pracoviště, kde pacienti byli léčeni s akutní pankreatitidou. Bylo rozesláno 115 dotazniků. Výsledky: Ze 115 zaslaných dotazníků se vrátilo 51 (44,3 %). Třicet devět (76,4 %) z 51 vrácených dotazníků hodnotilo drenáž jako metodu, která zlepšila zdravotní stav pacienta. Dvanáct z dotázaných (23,4 %) odpovědělo, že zdravotní stav se nezlepšil nebo naopak zhoršil. Pět pacientů (9,8 % z 51) zemřelo, dva na krvácení, jeden na iktus mozku, jeden na septický stav a jeden na respirační insuficienci. Dvanáct pacientů (66,6 %) z 18 s multiorgánovým selháním bylo drénováno a operováno, 6 nemocných (33,4 %) bylo pouze drénováno. Tři z těchto 18 nemocných (16 %) zemřeli na krvácení a respirační insuficienci, všichni patří do skupiny 12 pacientů, kteří byli operováni a drénováni. Drenáž byla u těchto pacientů provedena, když nekrotické solidní hmoty byly bez známek jejich zkapalnění. Výrazné zlepšení bylo zaznamenáno u 12, zhoršení u 3 nemocných. Dvacet šest pacientů mělo septické teploty, pět z těchto nemocných bylo operováno a drénováno, ostatní byli pouze drénováni. Závěr: Perkutánní drenáž těžké akutní pankreatitidy byla hodnocena dotazy na chirurgy a anesteziology, zda tato technika zlepšila zdravotní stav pacienta. Metoda se ukázala jako bezpečná a úspěšná při léčbě těžké akutní pankreatitidy i u pacientů s multiorgánovým selháváním, kteří mají nekrotické, solidní hmoty.
Objective: The study evaluated efficiency of percutaneous drainage in the therapy of severe acute pancreatitis with multi-organ failure. Material and methods: In the period of 1998-2000 the authors examined 441 patients with the diagnosis of acute pancreatitis. The diagnosis of severe acute pancreatitis was established in 115 patients (27%), 55 of them treated with drainage only (47.8% of the subset), 34 patients (29.6% of the subset) with drainage and surgery, and 26 patients (22.6% of the subset) were treated conservatively. Eighteen patients suffered from multi-organ failure, 26 patients had septic temperature. They were inserted drain, either 18 G pig tail (Optimed) or 20-26 G Mallecot (Boston Scientific). The successfulness was evaluated by questionnaires, which were sent out to workplaces, where the patients with acute pancreatitis were treated. There were 115 questionnaires on the whole. Results: Fifty one of the 115 forwarded questionnaires (44.3%) returned. Thirty nine of them (76.4%) evaluated drainage as a method which improved the health state of the patient. Twelve of the interviewed physicians (23.4%) declared that the health state of the patients had not improved or actually deteriorated. Five patients (9.8%) died, two of them from bleeding, one from ictus, one from septic state and one from respiratorv insufficiency. Twelve patients (66.6%) out of 18 with multi-organ failure were drained and operated on, and six patients (33.4%) were drained only. Three patients out of these 18 subjects (16%) died from bleeding and respiratory insufficiency, all of them belonging to the group of 12 patients who had been operated on and drained. The drainage in these patients was performed when the necrotic solid matter was without sings of becoming liquefied. A marked improvement was noted in 12 patients, deterioration in three patients. Twenty six patients suffered from septic temperature, five of them were operated on and drained, the other subjects were drained only. Conclusion: Percutaneous drainage of severe acute pancreatitis was evaluated by interviewing the surgeons and anesthesiologists, whether this technique improved the health state of the patients. The method proved to be safe and successful in the therapy of severe acute pancreatitis and in patients with multi-organ failure who had neerotíc solid matter.
There is a raising demand for sensitive and high throughput MS based methods for screening purposes especially tailored to the detection of allergen contaminants in different food commodities. A challenging issue is represented by complex food matrices where the antibody-based kits commercially available might encounter objective limitations consequently to epitope masking phenomena due to a multitude of interfering compounds arising from the matrix. The performance of a method duly optimized for the extraction and simultaneous detection of soy, egg and milk allergens in a cookie food matrix by microHPLC-ESI-MS/MS, is herein reported. Thanks to the innovative configuration and the versatility shown by the dual cell linear ion trap MS used, the most intense and reliable peptide markers were first identified by untargeted survey experiment, and subsequently employed to design an ad hoc multi-target SRM method, based on the most intense transitions recorded for each selected precursor peptide. A sample extraction and purification protocol was optimized also including an additional step based on sonication, which resulted in a considerable improvement in the detection of milk allergen peptides. Data Dependent™ Acquisition scheme allowed to fill out a tentative list of potential peptide markers, which were further filtered upon fulfilling specific requirements. A total of eleven peptides were monitored simultaneously for confirmation purposes of each allergenic contaminant and the two most sensitive peptide markers/protein were selected in order to retrieve quantitative information. Relevant LODs were found to range from 0.1μg/g for milk to 0.3μg/g for egg and 2μg/g for soy.
- MeSH
- Allergens isolation & purification MeSH
- Food Analysis methods MeSH
- Humans MeSH
- Limit of Detection MeSH
- Milk Proteins isolation & purification MeSH
- Milk chemistry MeSH
- Flour analysis MeSH
- Peptides analysis MeSH
- Soybean Proteins isolation & purification MeSH
- Soy Foods analysis MeSH
- Tandem Mass Spectrometry methods MeSH
- Egg Proteins isolation & purification MeSH
- Eggs analysis MeSH
- Sonication MeSH
- Chromatography, High Pressure Liquid methods MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
INTRODUCTION: The objective of this study was to evaluate the performance of different tumor diameters for identifying ≥ pT2 upper tract urothelial carcinoma (UTUC) at radical nephroureterectomy. PATIENTS AND METHODS: This was a multi-institutional retrospective study that included 932 patients who underwent radical nephroureterectomy for nonmetastatic UTUC between 2000 and 2016. Tumor sizes were pathologically assessed and categorized into 4 groups: ≤ 1 cm, 1.1 to 2 cm, 2.1 to 3 cm, and > 3 cm. We performed logistic regression and decision-curve analyses. RESULTS: Overall, 45 (4.8%) patients had a tumor size ≤ 1 cm, 141 (15.1%) between 1.1 and 2 cm, 247 (26.5%) between 2.1 and 3 cm, and 499 (53.5%) > 3 cm. In preoperative predictive models that were adjusted for the effects of standard clinicopathologic features, tumor diameters > 2 cm (odds ratio, 2.38; 95% confidence interval, 1.70-3.32; P < .001) and > 3 cm (odds ratio, 1.81; 95% confidence interval, 1.38-2.38; P < .001) were independently associated with ≥ pT2 pathologic staging. The addition of the > 2-cm diameter cutoff improved the area under the curve of the model from 58.8% to 63.0%. Decision-curve analyses demonstrated a clinical net benefit of 0.09 and a net reduction of 8 per 100 patients. CONCLUSION: The 2-cm cutoff appears to be most useful in identifying patients at risk of harboring ≥ pT2 UTUC. This confirms the current European Association of Urology guideline's risk stratification. Tumor size alone is not sufficient for optimal risk stratification, rather a constellation of features is needed to select the best candidate for kidney-sparing surgery.
OBJECTIVE: Myocardial perfusion imaging (MPI) can be challenging in some cases of multi vessel involvement. Our aim was to examine specific group of patients with diabetes mellitus (DM), who did not have significant reversible ischaemia diagnosed on perfusion study itself, and asses additional value of functional parameters obtained from gated acquisition and added information from coronary artery calcium score (CACS). SUBJECTS AND METHODS: One hundred and seventy eight patients with a history of DM, with summed difference score (SDS)≤1, were included in the study. All patients underwent gated acquisition with recording of functional parameters and CACS evaluation. During the follow-up, cardiac events (CE) were recorded. RESULTS: During the median follow-up of 20.3 months there were 23 CE encountered. Optimal cut-off value for CACS to predict CE was found at 1427, higher values were significantly related to CE (P<0.001). Low stress left ventricular ejection fraction (LVEF) <45% and induced stress LVEF drop for 5% were also more frequent in CE group (P=0.001, P=0.008). Multivariable Cox analysis revealed low stress LVEF (P=0.001, HR=4.48, 95%CI 1.79-11.22), stress induced LVEF drop (P=0.017, HR 3.13, 95%CI 1.22-8.01) and high CACS (P<0.001, HR 10.52, 95%CI 4.32-25.63) as significant predictors of CE. CONCLUSION: Low stress LVEF under 45%, post-stress LVEF drop for more than 5% and CACS more than or equal to 1427 are significant predictors of CE in patients with DM, who did not have reversible ischemia detected on MPI single photon emission computed tomography (SPECT).
- MeSH
- Diabetes Mellitus * diagnostic imaging MeSH
- Ventricular Function, Left MeSH
- Tomography, Emission-Computed, Single-Photon methods MeSH
- Coronary Vessels MeSH
- Humans MeSH
- Coronary Artery Disease * diagnostic imaging MeSH
- Heart Ventricles MeSH
- Stroke Volume MeSH
- Calcium MeSH
- Myocardial Perfusion Imaging * methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Adverse neurological events during extracorporeal membrane oxygenation (ECMO) are common and may be associated with devastating consequences. Close monitoring, early identification and prompt intervention can mitigate early and late neurological morbidity. Neuromonitoring and neurocognitive/neurodevelopmental follow-up are critically important to optimize outcomes in both adults and children. OBJECTIVE: To assess current practice of neuromonitoring during ECMO and neurocognitive/neurodevelopmental follow-up after ECMO across Europe and to inform the development of neuromonitoring and follow-up guidelines. METHODS: The EuroELSO Neurological Monitoring and Outcome Working Group conducted an electronic, web-based, multi-institutional, multinational survey in Europe. RESULTS: Of the 211 European ECMO centres (including non-ELSO centres) identified and approached in 23 countries, 133 (63%) responded. Of these, 43% reported routine neuromonitoring during ECMO for all patients, 35% indicated selective use, and 22% practiced bedside clinical examination alone. The reported neuromonitoring modalities were NIRS (n = 88, 66.2%), electroencephalography (n = 52, 39.1%), transcranial Doppler (n = 38, 28.5%) and brain injury biomarkers (n = 33, 24.8%). Paediatric centres (67%) reported using cranial ultrasound, though the frequency of monitoring varied widely. Before hospital discharge following ECMO, 50 (37.6%) reported routine neurological assessment and 22 (16.5%) routinely performed neuroimaging with more paediatric centres offering neurological assessment (65%) as compared to adult centres (20%). Only 15 (11.2%) had a structured longitudinal follow-up pathway (defined followup at regular intervals), while 99 (74.4%) had no follow-up programme. The majority (n = 96, 72.2%) agreed that there should be a longitudinal structured follow-up for ECMO survivors. CONCLUSIONS: This survey demonstrated significant variability in the use of different neuromonitoring modalities during and after ECMO. The perceived importance of neuromonitoring and follow-up was noted to be very high with agreement for a longitudinal structured follow-up programme, particularly in paediatric patients. Scientific society endorsed guidelines and minimum standards should be developed to inform local protocols.
