Stabilized Palladium Nanoparticles from Bis-(N-benzoylthiourea) Derived-PdII Complexes as Efficient Catalysts for Sustainable Cross-Coupling Reactions in Water.

Stable palladium (II) complexes, incorporating a double (N-benzoylthiourea) arrangement bonded to a complex heterocyclic scaffold, are used as precursors of catalytic species able to promote Suzuki-Miyaura, Mizoroki-Heck, Hiyama, Buchwald-Hartwig, Hirao and Sonogashira-Hagihara cross-coupling transformations in water. These sustainable processes are chemoselective and very versatile. The nanoparticles responsible for these catalytic reactions were analyzed and studied. Their usefulness is demonstrated after several tests and analyses. The heterogeneous character of this species in water was also confirmed.

Endoscopy-Related Bleeding and Thromboembolic Events in Patients on Direct Oral Anticoagulants or Vitamin K Antagonists.

BACKGROUND & AIMS: Few prospective studies have assessed the safety of direct oral anticoagulants (DOACs) in elective endoscopy. Our primary aim was to compare the risks of endoscopy-related gastrointestinal bleeding and thromboembolic events in patients on DOACs or vitamin K antagonists (VKAs) in this setting. Secondarily, we examined the impact of the timing of anticoagulant resumption on the risk of delayed bleeding in high-risk therapeutic procedures. METHODS: We conducted a multicenter, prospective, observational study from January 2018 to March 2020 of 1602 patients on oral anticoagulants (1004 on VKAs and 598 on DOACs) undergoing 1874 elective endoscopic procedures. Our primary outcomes were 90-day thromboembolic events and 30-day endoscopy-related gastrointestinal bleeding. The inverse probability of treatment weighting propensity score method was used for baseline covariate adjustment. RESULTS: The 2 groups had similar risks of endoscopy-related gastrointestinal bleeding (VKAs vs DOACs, 6.2% vs 6.7%; adjusted odds ratio [OR], 1.05; 95% CI, 0.67-1.65) and thromboembolic events (VKAs vs DOACs, 1.3% vs 1.5%; adjusted OR, 0.90; 95% CI, 0.34-2.38). In high bleeding risk procedures (n = 747), delayed anticoagulant resumption (> 48 hours or 24-48 hours vs < 24 hours) did not reduce the risk of postprocedural bleeding (10.3%, 9%, and 5.8%, respectively; adjusted P = .43). Hot and cold snare polypectomy were the most frequent high-risk interventions (41.8% and 39.8%, respectively). CONCLUSION: In a prospective study of patients on DOACs or VKAs undergoing elective endoscopy, endoscopy-related bleeding and thromboembolic events showed similar risk. Our study suggests that early anticoagulant resumption is safe in most patients, but more data are needed for advanced high-risk therapeutic procedures.

Deep Convolutional Generative Adversarial Networks to Enhance Artificial Intelligence in Healthcare: A Skin Cancer Application.

In recent years, researchers designed several artificial intelligence solutions for healthcare applications, which usually evolved into functional solutions for clinical practice. Furthermore, deep learning (DL) methods are well-suited to process the broad amounts of data acquired by wearable devices, smartphones, and other sensors employed in different medical domains. Conceived to serve the role of diagnostic tool and surgical guidance, hyperspectral images emerged as a non-contact, non-ionizing, and label-free technology. However, the lack of large datasets to efficiently train the models limits DL applications in the medical field. Hence, its usage with hyperspectral images is still at an early stage. We propose a deep convolutional generative adversarial network to generate synthetic hyperspectral images of epidermal lesions, targeting skin cancer diagnosis, and overcome small-sized datasets challenges to train DL architectures. Experimental results show the effectiveness of the proposed framework, capable of generating synthetic data to train DL classifiers.

Laboratory Hyperspectral Image Acquisition System Setup and Validation.

Hyperspectral Imaging (HSI) techniques have demonstrated potential to provide useful information in a broad set of applications in different domains, from precision agriculture to environmental science. A first step in the preparation of the algorithms to be employed outdoors starts at a laboratory level, capturing a high amount of samples to be analysed and processed in order to extract the necessary information about the spectral characteristics of the studied samples in the most precise way. In this article, a custom-made scanning system for hyperspectral image acquisition is described. Commercially available components have been carefully selected in order to be integrated into a flexible infrastructure able to obtain data from any Generic Interface for Cameras (GenICam) compliant devices using the gigabyte Ethernet interface. The entire setup has been tested using the Specim FX hyperspectral series (FX10 and FX17) and a Graphical User Interface (GUI) has been developed in order to control the individual components and visualise data. Morphological analysis, spectral response and optical aberration of these pushbroom-type hyperspectral cameras have been evaluated prior to the validation of the whole system with different plastic samples for which spectral signatures are extracted and compared with well-known spectral libraries.

Neural Networks-Based On-Site Dermatologic Diagnosis through Hyperspectral Epidermal Images.

Cancer originates from the uncontrolled growth of healthy cells into a mass. Chromophores, such as hemoglobin and melanin, characterize skin spectral properties, allowing the classification of lesions into different etiologies. Hyperspectral imaging systems gather skin-reflected and transmitted light into several wavelength ranges of the electromagnetic spectrum, enabling potential skin-lesion differentiation through machine learning algorithms. Challenged by data availability and tiny inter and intra-tumoral variability, here we introduce a pipeline based on deep neural networks to diagnose hyperspectral skin cancer images, targeting a handheld device equipped with a low-power graphical processing unit for routine clinical testing. Enhanced by data augmentation, transfer learning, and hyperparameter tuning, the proposed architectures aim to meet and improve the well-known dermatologist-level detection performances concerning both benign-malignant and multiclass classification tasks, being able to diagnose hyperspectral data considering real-time constraints. Experiments show 87% sensitivity and 88% specificity for benign-malignant classification and specificity above 80% for the multiclass scenario. AUC measurements suggest classification performance improvement above 90% with adequate thresholding. Concerning binary segmentation, we measured skin DICE and IOU higher than 90%. We estimated 1.21 s, at most, consuming 5 Watts to segment the epidermal lesions with the U-Net++ architecture, meeting the imposed time limit. Hence, we can diagnose hyperspectral epidermal data assuming real-time constraints.

Characteristics and outcome of incidental hepatocellular carcinoma after liver transplantation: a cohort study.

INTRODUCTION: despite advances in imaging diagnostic modalities, hepatocellular carcinoma is sometimes incidentally diagnosed on histological examination of the liver explant. The objectives of the study were: a) to compare the characteristics between incidental and known hepatocellular carcinoma; and b) to estimate survival and tumor recurrence after liver transplantation. MATERIAL AND METHODS: a retrospective, single-center study was performed. The inclusion criteria were: a) cirrhotic patients, age ≥ 18 years; b) liver transplantation between 1998 and 2018; and c) hepatocellular carcinoma diagnosed via histopathologic examination of the explanted liver. Cholangiocarcinoma and patients with early retransplantation were excluded. Multivariate analysis was performed using binomial logistic regression to assess the factors associated with incidental hepatocellular carcinoma. Kaplan-Meier curves were plotted to explore the impact on overall survival and recurrence free survival. RESULTS: two hundred and sixty-nine patients were enrolled. The prevalence of incidental hepatocellular carcinoma was 4.18 % (95 % CI: 2.89-6.01 %) of all liver transplants performed in cirrhotic patients. The median diameter of the main nodule was smaller in incidental hepatocellular carcinoma (20 vs 27 mm, p = 0.004), although they were more likely to be beyond the Up-to-Seven criteria on explant examination (22.2 % vs 7.5 %, p = 0.001), with no differences in any other histological features. No differences were found in overall survival rates (incidental 70.2 % vs 70.4 %, p = 0.87) or recurrence-free survival (incidental 100 % vs 83.8 %, p = 0.07) at five years. CONCLUSION: incidental hepatocellular carcinoma are smaller in size and are more frequently found to be beyond the Up-to-Seven criteria. However, no differences were found in overall survival rates or recurrence-free survival, although there was no tumor recurrence in the incidental hepatocellular carcinoma group.

The Intracellular Intensity of CD3 on Aberrant Intraepithelial Lymphocytes Is a Prognostic Factor of the Progression to Overt Lymphoma in Refractory Celiac Disease Type II (Pre-Enteropathy-Associated T Cell Lymphoma).

BACKGROUND: Refractory celiac disease type II (RCD-II) is a very rare yet severe complication of celiac disease (CD) with a 50% rate of progression to Enteropathy-associated T-cell lymphoma (EATL). Timely diagnosis and treatment of RCD-II is of the essence and requires the identification of a population of frequently clonal, phenotypically aberrant intraepithelial lymphocytes (IELs). Flow Cytometry of intestinal IELs is the recommended method to identify the aberrant surface CD3-negative (sCD3-) intracytoplasmic CD3-positive (icCD3ε+) IELs, and a proportion of >20% is diagnostic of RCD-II. There is substantial heterogeneity in the clinical course of RCD-II, and insufficient information on prognostic factors. AIM: To establish flow cytometric predictors of the clinical evolution of RCD-II, to help guide treatment approaches. PATIENTS AND METHODS: Retrospective single-center study of clinical and immunological features of 6 RCD-II patients and a control group, both identified from a 2,000-patient cohort over 16 years. IEL subset frequencies and the intensity of staining for surface (s) and intracytoplasmic (ic) CD3ε+ on IEL subsets were quantified and correlated with the clinical outcome. RESULTS: Unexpectedly, the frequency of aberrant sCD3- icCD3ε+ cells at diagnosis did not correlate with histological or clinical affection. However, a higher intensity of icCD3ε+ staining in the aberrant IELs relative to expression on normal IELs correlated with monoclonality and with worse clinical outcomes. CONCLUSION: The ratio of icCD3ε+ on aberrant IELs vs. normal IELs appears to be a useful indicator of prognosis at the time of diagnosis, and may represent a novel tool in the follow-up of RCD-II patients after therapy.

Clinical validation of Endofaster® for a rapid diagnosis of Helicobacter pylori infection.

BACKGROUND: this study aimed to evaluate the diagnostic accuracy of the Endofaster® for the detection of Helicobacter pylori. METHODS: during upper gastrointestinal endoscopy, gastric juice was aspirated to perform an analysis using the Endofaster®. This test was considered as positive when the ammonium concentration was > 67 ppm, negative when < 57 ppm and weakly positive between 57 and 67. Biopsy specimens were also taken as the gold standard. RESULTS: among the 86 patients enrolled in the study, the Endofaster® result was positive in 23.7%, negative in 54.7% and weakly positive in 11.6%, whereas infection was detected via histology in 38.4% of patients. The accuracy was 81.4%, with a Kappa value of 0.57. CONCLUSIONS: the Endofaster® could be useful to perform a rapid diagnosis of Helicobacter pylori infection (area under the curve = 0.81).

Genetic and flow cytometry analysis of seronegative celiac disease: a cohort study.

Background: Seronegative celiac disease (CD) poses a diagnostic challenge. Aims: Characterize and identify differences between seronegative and seropositive CD. Patients and methods: Retrospective cohort study examining adult patients diagnosed with CD (1980-2017). Clinical, analytical, histological, genetic and immunophenotypic data were compiled. Seronegative CD was defined as a anti-tissue transglutaminase type 2 IgA and endomysial antibodies (EMA) negative and HLA-DQ2 and/or DQ8 positive, showing clinical signs of CD plus an abnormal duodenal biopsy, and responding to a gluten-free diet (GFD). Factors associated with seronegative CD were identified through binomial logistic regression. Results: Of 315 CD patients, 289 were seropositive (91.7%) and 26 seronegative (8.3%). Among the seronegative patients, higher prevalence was observed for autoimmune thyroiditis (26.9% vs. 9.7%, p = .016), HLA-DQ8 heterozygosity (23.1% vs. 2.5%, p ˂ .001) and Marsh I lesion (34.6% vs. 3.7%, p ˂ .001). The two groups showed similar flow cytometry-determined duodenal immunophenotypes and rates of refractory CD. Conclusions: Seronegative CD differs mostly in genetic (more HLA-DQ8) and histologic (milder atrophy) features as compared with seropositive. Intestinal intraepithelial immunophenotype by flow cytometry, similar in both modalities, is a useful tool to diagnose seronegative CD.

Most Relevant Spectral Bands Identification for Brain Cancer Detection Using Hyperspectral Imaging.

Hyperspectral imaging (HSI) is a non-ionizing and non-contact imaging technique capable of obtaining more information than conventional RGB (red green blue) imaging. In the medical field, HSI has commonly been investigated due to its great potential for diagnostic and surgical guidance purposes. However, the large amount of information provided by HSI normally contains redundant or non-relevant information, and it is extremely important to identify the most relevant wavelengths for a certain application in order to improve the accuracy of the predictions and reduce the execution time of the classification algorithm. Additionally, some wavelengths can contain noise and removing such bands can improve the classification stage. The work presented in this paper aims to identify such relevant spectral ranges in the visual-and-near-infrared (VNIR) region for an accurate detection of brain cancer using in vivo hyperspectral images. A methodology based on optimization algorithms has been proposed for this task, identifying the relevant wavelengths to achieve the best accuracy in the classification results obtained by a supervised classifier (support vector machines), and employing the lowest possible number of spectral bands. The results demonstrate that the proposed methodology based on the genetic algorithm optimization slightly improves the accuracy of the tumor identification in ~5%, using only 48 bands, with respect to the reference results obtained with 128 bands, offering the possibility of developing customized acquisition sensors that could provide real-time HS imaging. The most relevant spectral ranges found comprise between 440.5-465.96 nm, 498.71-509.62 nm, 556.91-575.1 nm, 593.29-615.12 nm, 636.94-666.05 nm, 698.79-731.53 nm and 884.32-902.51 nm.

A multicentric Spanish study on the characteristics and survival of gastric adenocarcinoma under the age of 60.

INTRODUCTION: In Europe, gastric adenocarcinoma (GADC) is commonly regarded as a disease of the elderly. This study aims to assess the proportion, characteristics, and survival of patients diagnosed with GADC under the age of 60. MATERIALS AND METHODS: This is a retrospective, multicentric, and analytical study conducted at four tertiary Spanish hospitals. All patients diagnosed with GADC between 2008 and 2015 were included. Demographic, clinical, endoscopic, histologic, and survival data were retrieved. A multivariate analysis was performed to compare GADC in young (age≤60 years) and elderly patients. RESULTS: A total of 1374 patients with GADC were included. The mean age was 74 years (SD:11.1); 62.2% were males. There were 177 patients under the age of 60 (12.9%, 95% CI: 11.2-14.8%). GADC was frequently encountered as a metastatic disease in both young and elderly patients (Stage IV: 45.7% and 41%, respectively). In the multivariate analysis, alcohol abuse, ASA functional status I-II, diffuse subtype, neoadjuvant, and palliative therapy were independently associated (P<0.05) with age ≤60 years. No differences were found in 2-year survival (GADC ≤60: 39% vs. 35%, P=0.45). Curative-intent surgery, TNM stage I-II, body mass index<30kg/m2, and better functional status at diagnosis were independent predictors of survival in GADC under the age of 60. CONCLUSIONS: One out of eight cases of GADC were diagnosed under the age of 60. Metastatic disease was frequent at diagnosis and overall survival was poor regardless of age. Factors associated with localized disease correlated with improved survival in younger patients. Our results underline the need for early diagnosis strategies in our country.

Clinical experience of optimising thiopurine use through metabolite measurement in inflammatory bowel disease. / Experiencia en práctica clínica de optimización de tiopurinas mediante determinación de sus metabolitos en la enfermedad inflamatoria intestinal.

INTRODUCTION: Thiopurine therapy can be optimised by determining the concentration of the drug's metabolites. PATIENTS AND METHODS: Retrospective analysis on a prospective database of 31 patients with inflammatory bowel disease who failed therapy with thiopurines. Thiopurine metabolites (6-thioguanine, 6-TGN and 6-methylmercaptopurine, 6-MMP) were measured by high-performance liquid chromatography (Laboratorios Cerba, Barcelona) and treatment was duly adjusted in accordance with the results. Clinical response was reassessed after six months. RESULT: Despite the appropriate theoretical dose of thiopurines being administered, the dose was insufficient in 45.6% of patients (nonadherence to treatment suspected in 6.45%) and 16.2% received an excessive dose or the drug was metabolised by other metabolic pathways. After treatment was optimised based on metabolite levels, only 25.8% (8/31) were prescribed a biological agent, while 74.2% of cases (23/31) were managed through dose optimisation alone. DISCUSSION: Monitoring thiopurine metabolite levels may help clinicians to assess non-responsive patients before adding or switching to another drug (generally a biological agent), thereby avoiding any additional costs or potential toxicity. This strategy may also help to identify patients receiving an insufficient dose and those with an alternative metabolic pathway, who could be candidates for low-dose AZA with allopurinol, as well as patients who are suspected of being non-adherent. In three out of four patients, switching to a biological agent can be avoided.

Effects of exercise-based interventions on postpartum depression: A meta-analysis of randomized controlled trials.

BACKGROUND: There is inconsistent evidence about the effect of physical activity on the prevention and treatment of depression during the postnatal period. The aim of this meta-analysis was to determine the effect of physical activity interventions during pregnancy and the postpartum period for controlling postpartum depressive symptoms. METHODS: We systematically searched Cochrane Library Plus, Science Direct, EMBASE, CINAHL, PubMed, Web of Science, and Scopus, from January 1990 to May 2016, for randomized or nonrandomized controlled trials addressing the effect of physical activity on postpartum depression. The inverse variance-weighted method was used to compute pooled estimates of effect size and respective 95% confidence intervals (95% CI) for physical activity intervention on postpartum depression. Subgroup analyses were performed comparing women with and without postpartum depressive symptoms according to specific scales measuring this construct. Meta-regression and sensitivity analysis were computed to evaluate heterogeneity. RESULTS: Twelve studies were included in the meta-analysis. Effect size for the relationship between physical activity interventions during pregnancy and the postpartum period on postpartum depressive symptoms was 0.41 (95% CI 0.28-0.54). Heterogeneity was I2  = 33.1% (P = .117). When subgroup analyses were done, pooled effect sizes were 0.67 (95% CI 0.44-0.90) for mothers who met postpartum depressive symptoms criteria at baseline based on specific scales, and 0.29 (95% CI 0.14-0.45) for mothers who did not meet those depressive symptoms criteria at baseline. CONCLUSION: Physical exercise during pregnancy and the postpartum period is a safe strategy to achieve better psychological well-being and to reduce postpartum depressive symptoms.

A follow-up study to assess the determinants and consequences of physical activity in pregnant women of Cuenca, Spain.

BACKGROUND: In recent years, the influence of physical exercise on pregnancy outcomes has been widely debated. Despite the numerous studies addressing the relationship between maternal physical activity and pregnancy outcomes, the evidence for consistent and significant impact of regular exercise during pregnancy on fetal growth remains lacking. The aims of this study were, first, to assess the level of physical activity performed throughout the pregnancy by objective (accelerometer) and self-reported (questionnaire) measurements, and, second, to ascertain pre-pregnancy physical activity levels, to estimate the relationship between levels of physical activity and some pregnancy and neonatal outcomes. METHODS/DESIGN: This was a prospective cohort study. Participants were pregnant women (n = 194) aged 18 to 40 years who attended for three quarterly appointments for pregnancy ultrasound scans at the Virgen de la Luz Hospital in Cuenca, Spain. All participants provided written informed consents to participate in the study. Physical activity during the pregnancy follow-up was assessed by a self-reported Pregnancy Physical Activity Questionnaire and sleep log; also objectively by a GT3X accelerometer (ActiGraph). Furthermore, pregnancy symptoms inventory, nutritional behavioural assessment, socio-demographic characteristics, and anthropometry and body composition were measured. At the end of the follow up, the following main outcomes were determined: pregnancy outcomes (incidence of gestational diabetes mellitus, pre-eclampsia, pregnancy-induced hypertension, weight gain during pregnancy, type of delivery, and neonatal outcomes (gestational age, birth weight, gender, Apgar score 1 min/5 min, type of resuscitation (I/II/III/IV), and pH of umbilical cord blood). Descriptive statistics for cross-sectional data, linear mixed regression models for absolute differences in changes baseline-final measurements were used as statistical analyses. DISCUSSION: Although the effectiveness of physical activity programmes on improving maternal and neonatal outcomes has heretofore been studied, the impact of free time physical activity during pregnancy has not been assessed using objective measures. This paper reports the design of a prospective cohort study that aims to assess the physical activity levels of pregnant women, and to estimate the relationship between those physical activity levels with maternal and neonatal outcomes. This study could contribute to providing evidence for the formulation of recommendations for physical activity for pregnant women.

Effects of exercise during pregnancy on mode of delivery: a meta-analysis.

INTRODUCTION: We conducted a systematic review and meta-analysis to examine the influence of physical exercise interventions on the mode of delivery of healthy pregnant women with low to moderate levels of physical activity. MATERIAL AND METHODS: Key words were used to conduct a computerized search for articles on the topic in six databases: Cochrane Library Plus, Science Direct, EMBASE, PubMed, Web of Science and ClinicalTrials.gov. Ten randomized controlled trials were identified and included in the meta-analysis. Main outcome measures were mode of delivery (normal, instrumental vaginal, or cesarean delivery) and physical activity. RESULTS: Relative risk reductions and their 95% confidence interval were calculated for each study, and the heterogeneity of the studies was estimated using Cochran's Q statistic. The evidence suggests that physical exercise during pregnancy may increase the likelihood of normal delivery (relative risk = 1.12, 95% confidence interval 1.01-1.24; p = 0.041), in particular when exercise takes place during the second and third trimesters (relative risk = 1.14, 95% confidence interval 1.01-1.32; p = 0.048), even reducing the risk of cesarean delivery (relative risk = 0.66, 95% confidence interval 0.46-0.96; p = 0.028). CONCLUSIONS: Regular exercise during pregnancy appears to modestly increase the chance for normal delivery among healthy pregnant women. This applies to women with low to moderate levels of physical activity, but studies are needed to understand better the effect of physical exercise of moderate to vigorous intensity in the different trimesters.

Treatment of D alloimmunization in pregnancy with plasmapheresis and intravenous immune globulin: case report.

The prevalence of D alloimmunization occurs between 0.15% and 0.4%. The anti-D can cross the placenta and cause hemolysis and fetal anemia. At present, a Doppler study of the middle cerebral artery allows the monitoring of the degree of fetal anemia. The treatment in cases of moderate to severe anemia in fetuses of less than 34-35 weeks of gestation is intrauterine transfusion via cordocentesis. However, with high titers of anti-D, in the absence of fetal anemia it is possible to modulate the maternal immune response by plasmapheresis and intravenous immunoglobulin administration. We present a case report of an Rh(D) alloimmunized pregnancy treated with plasmapheresis followed by intravenous immunoglobulin administration. We performed a caesarean section at 31 weeks, 5 days of gestation. The hemoglobin at birth was 13.8 g/dl and hematocrit 40.8%. Intrauterine transfusion was not necessary.