Prolonged use of pentoxifylline increases the life expectancy of patients with compensated cirrhosis: A 20­year retrospective study.

Liver cirrhosis is a pathology of varied etiology with a high prevalence and mortality, resulting in >1 million mortalities per year. Patients with liver cirrhosis typically have a survival time of 12 years following diagnosis. The treatment for this disease is directed at the complications of cirrhosis; however, to the best of our knowledge, the long-term management of patients with cirrhosis has been scarcely studied. Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor with rheological activity and antioxidant, anti-inflammatory and antifibrotic properties. PTX has been used in the treatment of peripheral arterial disease, inflammatory liver diseases and hepatocellular carcinoma with encouraging results. The aim of the present study was to evaluate the effect of PTX use on the survival of patients with compensated cirrhosis. For this purpose, a cross-sectional study was performed at the Gastroenterology and Hepatitis C Department of Dr. Valentín Gómez Farias Hospital (Institute for Security and Social Services for State Workers, Zapopan, Mexico) from June, 1996 to December, 2019. The follow-up time for these patients was 22.6 years (up to the end of the study period). In the present study, 326 patient files were analyzed and 118 patients with the disease were identified, 81 of whom (68.64%) died within 12 years after diagnosis. Of the included patients, 26 received PTX combined with PEG IFN-α-2a plus ribavirin, and 11 received PTX plus propranolol, with a median treatment duration of 20.6±0.8 years. Furthermore, 16 patients (43%) did not develop co-morbidities within this time, and the transition to decompensated cirrhosis was 16.6 years, with a survival time of 20 years. Therefore, the results of the present study suggest that PTX may improve the long-term survival of patients with compensated cirrhosis, rendering PTX a candidate for repurposing in the treatment of hepatic cirrhosis.

Mortality, Functional Status, and Quality of Life after 5 Years of Patients Admitted to Critical Care for Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The objective of this study was to assess long-term outcome in patients with spontaneous intracerebral hemorrhage admitted to the intensive care unit. METHODS: Mortality and Glasgow Outcome Scale, Barthel Index, and 5-level EQ-5D version (EQ-5D-5L) scores were analyzed in a multicenter cohort study of three Spanish hospitals (336 patients). Mortality was also analyzed in the Medical Information Mart for Intensive Care III (MIMIC-III) database. RESULTS: The median (25th percentile-75th percentile) age was 62 (50-70) years, the median Glasgow Coma Score was 7 (4-11) points, and the median Acute Physiology and Chronic Health disease Classification System II (APACHE-II) score was 21 (15-26) points. Hospital mortality was 54.17%, mortality at 90 days was 56%, mortality at 1 year was 59.2%, and mortality at 5 years was 66.4%. In the Glasgow Outcome Scale, a normal or disabled self-sufficient situation was recorded in 21.5% of patients at 6 months, in 25.5% of patients after 1 year, and in 22.1% of patients after 5 years of follow-up (4.5% missing). The Barthel Index score of survivors improved over time: 50 (25-80) points at 6 months, 70 (35-95) points at 1 year, and 90 (40-100) points at 5 years (p < 0.001). Quality of life evaluated with the EQ-5D-5L at 1 year and 5 years indicated that greater than 50% of patients had no problems or slight problems in all items (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). In the MIMIC-III study (N = 1354), hospital mortality was 31.83% and was 40.5% at 90 days and 56.2% after 5 years. CONCLUSIONS: In patients admitted to the intensive care unit with a diagnosis of nontraumatic intracerebral hemorrhage, hospital mortality up to 90 days after admission is very high. Between 90 days and 5 years after admission, mortality is not high. A large percentage of survivors presented a significant deficit in quality of life and functional status, although with progressive improvement over time. Five years after the hemorrhagic stroke, a survival of 30% was observed, with a good functional status seen in 20% of patients who had been admitted to the hospital.

STTRE: A Spatio-Temporal Transformer with Relative Embeddings for multivariate time series forecasting.

The prevalence of multivariate time series data across several disciplines fosters a demand and, subsequently, significant growth in the research and advancement of multivariate time series analysis. Drawing inspiration from a popular natural language processing model, the Transformer, we propose the Spatio-Temporal Transformer with Relative Embeddings (STTRE) to address multivariate time series forecasting. This work primarily focuses on developing a Transformer-based framework that can fully exploit the spatio-temporal nature of a multivariate time series by incorporating several of the Transformer's key components, but with augmentations that allow them to excel in multivariate time series forecasting. Current Transformer-based models for multivariate time series often neglect the data's spatial component(s) and utilize absolute position embeddings as their only means to detect the data's temporal component(s), which we show is flawed for time series applications. The lack of emphasis on fully exploiting the spatio-temporality of the data can incur subpar results in terms of accuracy. We redesign relative position representations, which we rename to relative embeddings, to unveil a new method for detecting latent spatial, temporal, and spatio-temporal dependencies more effectively than previous Transformer-based models. We couple these relative embeddings with a restructuring of the Transformer's primary sequence learning mechanism, multi-head attention, in a way that allows for full utilization of relative embeddings, thus achieving up to a 24% improvement in accuracy over other state-of-the-art multivariate time series models on a comprehensive selection of publicly available multivariate time series forecasting datasets.

Role of IP-10 to Predict Clinical Progression and Response to IL-6 Blockade With Sarilumab in Early COVID-19 Pneumonia. A Subanalysis of the SARICOR Clinical Trial.

Background: The Clinical Trial of Sarilumab in Adults With COVID-19 (SARICOR) showed that patients with coronavirus disease 2019 (COVID-19) pneumonia and increased levels of interleukin (IL)-6 might benefit from blockade of the IL-6 pathway. However, the benefit from this intervention might not be uniform. In this subanalysis, we sought to determine if other immunoactivation markers, besides IL-6, could identify which subgroup of patients benefit most from this intervention. Methods: The SARICOR trial was a phase II, open-label, multicenter, controlled trial (July 2020-March 2021) in which patients were randomized to receive usual care (UC; control group), UC plus a single dose of sarilumab 200 mg (sarilumab-200 group), or UC plus a single dose of sarilumab 400 mg (sarilumab-400 group). Patients who had baseline serum samples for cytokine determination (IL-8, IL-10, monocyte chemoattractant protein-1, interferon-inducible protein [IP]-10) were included in this secondary analysis. Progression to acute respiratory distress syndrome (ARDS) according to cytokine levels and treatment received was evaluated. Results: One hundred one (88%) of 115 patients enrolled in the SARICOR trial had serum samples (control group: n = 33; sarilumab-200: n = 33; sarilumab-400: n = 35). Among all evaluated biomarkers, IP-10 showed the strongest association with treatment outcome. Patients with IP-10 ≥2500 pg/mL treated with sarilumab-400 had a lower probability of progression (13%) compared with the control group (58%; hazard ratio, 0.19; 95% CI, 0.04-0.90; P = .04). Conversely, patients with IP-10 <2500 pg/mL did not show these differences. Conclusions: IP-10 may predict progression to ARDS in patients with COVID-19 pneumonia and IL-6 levels >40 pg/mL. Importantly, IP-10 value <2500 pg/mL might discriminate those individuals who might not benefit from sarilumab therapy among those with high IL-6 levels.

[Prevalence and pattern of alcohol consumption in patients with hepatocellular carcinoma]. / Prevalencia y patrón de consumo de alcohol en pacientes con carcinoma hepatocelular.

AIM: Prospective cross-sectional study conducted to determine the prevalence and pattern of alcohol consumption (AC) in patients with hepatocellular carcinoma (HCC) and to assess the utility of the AUDIT in HCC patients. METHODS: One hundred and two consecutive patients form our HCC monographic outpatient clinic visited between February and March 2022 were included. Patients with hepatic encephalopathy at the time of the interview, on the waiting list for liver transplantation and those undergoing post-transplant follow-up were excluded. RESULTS: The prevalence of AC in patients diagnosed with HCC is 35%, although less than 10% consume more than 100g per week. AC was more frequent in males, in an urban environment, with a diagnosis of HCC more than a year ago, and in patients in early/very early stages of BCLC. AUDIT score greater than or equal to 3 (AUROC 0.849) predicts any AC with a sensitivity of 75% (95% CI: 59.47-90.53%) and a specificity of 84% (95% CI: 74.70-94.05%). CONCLUSIONS: Despite the diagnosis of HCC, more than a third of the patients consume alcohol. An AUDIT score equal to or greater than 3 discriminates any AC with a sensitivity of 75% and a specificity of 84% in this population.

Evolution of Carbonate-Intercalated γ-NiOOH from a Molecularly Derived Nickel Sulfide (Pre)Catalyst for Efficient Water and Selective Organic Oxidation.

The development of a competent (pre)catalyst for the oxygen evolution reaction (OER) to produce green hydrogen is critical for a carbon-neutral economy. In this aspect, the low-temperature, single-source precursor (SSP) method allows the formation of highly efficient OER electrocatalysts, with better control over their structural and electronic properties. Herein, a transition metal (TM) based chalcogenide material, nickel sulfide (NiS), is prepared from a novel molecular complex [NiII (PyHS)4 ][OTf]2 (1) and utilized as a (pre)catalyst for OER. The NiS (pre)catalyst requires an overpotential of only 255 mV to reach the benchmark current density of 10 mA cm-2 and shows 63 h of chronopotentiometry (CP) stability along with over 95% Faradaic efficiency in 1 m KOH. Several ex situ measurements and quasi in situ Raman spectroscopy uncover that NiS irreversibly transformed to a carbonate-intercalated γ-NiOOH phase under the alkaline OER conditions, which serves as the actual active structure for the OER. Additionally, this in situ formed active phase successfully catalyzes the selective oxidation of alcohol, aldehyde, and amine-based organic substrates to value-added chemicals, with high efficiencies.

Local Stability and Convergence Analysis of Neural Network Controllers With Error Integral Inputs.

This article investigates the local stability and local convergence of a class of neural network (NN) controllers with error integrals as inputs for reference tracking. It is formally proved that if the input of the NN controller consists exclusively of error terms, the control system shows a non-zero steady-state error for any constant reference except for one specific point, for both single-layer and multi-layer NN controllers. It is further proved that adding error integrals to the input of the (single- and multi-layers) NN controller is one sufficient way to remove the steady-state error for any constant reference. Due to the nonlinearity of the NN controllers, the NN control systems are linearized at the equilibrium points. We provide proof that if all the eigenvalues of the linearized NN control system have negative real parts, local asymptotic stability and local exponential convergence are guaranteed. Two case studies were explored to verify the theoretical results: a single-layer NN controller in a 1-D system and a four-layer NN controller in a 2-D system applied to renewable energy integration. Simulations demonstrate that when NN controllers and the corresponding generalized proportional-integral (PI) controllers have the same eigenvalues, all control systems exhibit almost the same responses in a small neighborhood of their respective equilibrium points.

Upper gastrointestinal bleeding secondary to late gastric metastasis of renal cell carcinoma.

Clear cell renal cell carcinoma is the most common renal neoplasm in adults. It has a relatively slow growth pattern that delays diagnosis until the onset of local, paraneoplastic or metastasis-related manifestations, and an unpredictable behavior ranging from aggressive tumors with poor short-term prognosis to late recurrence cases where metastases are identified years after nephrectomy, the latter scenario being the subject of the case we herein report.

Visualization System for the Impact of Context Open Data in Clinical Settings.

The usage of context open data, such as environmental data, socio-economic resources, etc., in clinical settings has been limited till now. But in recent years the number of studies that consider these factors is increasing. However, for clinicians, researchers or other stakeholders to be able to use this information in clinical practice, appropriate visualizations tools must be developed. At the same time, the data are generally displayed in formats that are difficult to interpret. The use of geolocalized visualizing tools through maps provides a better understanding in most cases. The proposed tool aims to contribute to the development of systems that can help to the exploitation of clinical and context open data, making them more easily interpretable.

Hospital Readmission Prediction via Keyword Extraction and Sentiment Analysis on Clinical Notes.

Unplanned hospital readmission is a problem that affects hospitals worldwide and is due to different factors. The identification of those factors can help determine which patients are at greater risk of hospital readmission for early intervention. Our end goal is to predict and identify patterns to (i) feed a decision support system for efficient management of patients and resources and (ii) detect patients at high risk of 30-days readmission enabling preventive actions to improve management of hospital discharges. This study aims to analyze whether natural language processing and specifically keyword extractions tools and sentiment analysis can support 30-days readmission prediction. Features extracted from medical history notes and discharge reports were used to train a Logistic Regression model. The resulting model obtains an AUC of 0.63 indicating that the sentiment polarity score of the discharge report and several of the extracted keywords are representative features to consider.

Diagnosis of biliary papillomatosis with a Spyglass® cholangioscope.

We report the case of a 78-year-old woman with dyspepsia for several years and a history of cholecystectomy, informed by pathology as calculous cholecystopathy, where CT revealed a left-sided intrahepatic bile duct dilation. Cholangio-MRI confirmed a size increase in the distal intrahepatic bile duct on the left side, with T2-hyperintense contents with scarce contrast enhancement, which resulted in the observed dilation. . A Spybite® forceps was used to obtain a biopsy sample, which showed a benign papillary growth compatible with biliary papillomatosis. Biliary papillomatosis or intraductal papillary neoplasm of the biliary tract is a rare, uncommon condition characterized by intraductal papillary growth of the biliary epithelium. It has a tendency towards malignization, hence must be considered a premalignant condition . Major symptoms include jaundice, abdominal pain, and repeat cholangitis, with imaging studies being key for diagnostic suspicion . The development of cholangioscopy with biopsies allows an early diagnosis of malignant precursor lesions of the bile duct, thus allowing early treatment.

Ethmoidal metastasis as an uncommon presentation and diagnostic form of hepatocellular carcinoma.

Nasopharynx metastases are an extremely rare cause of hepatocarcinoma debut. We report the case of a 71 year old man who presented symptoms of nosebleed and diplopia event, diagnosed by imaging and biopsy of ethmoidal metastasis of hepatocarcinoma.

Endoscopic submucosal dissection of gastric plexiform fibromyxoma, an alternative to the traditional approach.

We report the case of a 62-year-old woman with no history of interest who presented with dyspepsia of 2 years' standing. Gastroscopy revealed a subepithelial lesion at the greater antral curvature with irregular surface and preserved mucosal and vascular pattern, 15 mm in diameter. Because of clinical persistence a radial endoscopic ultrasonogram (EUS) was performed, which showed a well-delimited hypoechoic lesion with heterogeneous areas that was dependent on the muscularis mucosae layer. A biopsy was obtained using the "bite-on-bite" technique, which provided no pathological findings. With these findings an endoscopic submucosal dissection (ESD) procedure was performed with wide margins and no complications. Pathology found low-grade mesenchymal fusicellular proliferation dependent on the muscularis mucosae with immunohistochemistry positive for smooth-muscle vimentin and actin, consistent with plexiform fibromyxoma.

Evaluation of procalcitonin elevation during ICU stay and its relationship with mortality in ICU patients for COVID-19 with respiratory involvement. A multicenter prospective cohort study.

Introduction: A multicenter prospective cohort study studied patients admitted to the intensive care unit (ICU) by coronavirus-19 (COVID-19) with respiratory involvement. We observed the number of occasions in which the value of procalcitonin (PCT) was higher than 0.5 ng/ml. Objective: Evaluation of PCT elevation and influence on mortality in patients admitted to the ICU for COVID-19 with respiratory involvement. Measurements and main results: We studied 201 patients. On the day of admission, acute physiology and chronic health evaluation (APACHE)-II was 13 (10-16) points. In-hospital mortality was 36.8%. During ICU stay, 104 patients presented 1 or more episodes of PCT elevation and 60 (57.7%) died and 97 patients did not present any episodes of PCT elevation and only 14 (14.4%) died (p < 0.001). Multivariable analysis showed that mortality was associated with APACHE-II: [odds ratio (OR): 1.13 (1.04-1.23)], acute kidney injury [OR: 2.21 (1.1-4.42)] and with the presentation of one or more episodes of escalating PCT: [OR: 5.07 (2.44-10.53)]. Of 71 patients who died, 59.2% had an elevated PCT value on the last day, and of the 124 patients who survived, only 3.2% had an elevated PCT value on the last day (p < 0.001). On the last day of the ICU stay, the sequential organ failure assessment (SOFA) score of those who died was 9 (6-11) and 1 (0-2) points in survivors (p < 0.001). Of the 42 patients who died and in whom PCT was elevated on the last day, 71.4% were considered to have a mainly non-respiratory cause of death. Conclusion: In patients admitted to the ICU by COVID-19 with respiratory involvement, numerous episodes of PCT elevation are observed, related to mortality. PCT was elevated on the last day in more than half of the patients who died. Serial assessment of procalcitonin in these patients is useful because it alerts to situations of high risk of death. This may be useful in the future to improve the treatment and prognosis of these patients.

Early Use of Sarilumab in Patients Hospitalized with COVID-19 Pneumonia and Features of Systemic Inflammation: the SARICOR Randomized Clinical Trial.

The objective of this study was to investigate the efficacy and safety of early treatment with sarilumab, added to standard of care (SOC), in hospitalized adults with COVID-19. Methods included phase II, open-label, randomized, controlled clinical trial of hospitalized patients with COVID-19 pneumonia and interleukin (IL)-6 levels ≥ 40 pg/mL and/or d-dimer > 1,500 ng/mL. Participants were randomized (1:1:1) to receive SOC (control group), SOC plus a single subcutaneous dose of sarilumab 200 mg (sarilumab-200 group), or SOC plus a single subcutaneous dose of sarilumab 400 mg (sarilumab-400 group). The primary outcome variable was the development of acute respiratory distress syndrome (ARDS) requiring high-flow nasal oxygenation (HFNO), non-invasive mechanical ventilation (NIMV) or invasive mechanical ventilation (IMV) at day 28. One-hundred and 15 participants (control group, n = 39; sarilumab-200, n = 37; sarilumab-400, n = 39) were included. At randomization, 104 (90%) patients had supplemental oxygen and 103 (90%) received corticosteroids. Eleven (28%) patients in the control group, 10 (27%) in sarilumab-200, and five (13%) in sarilumab-400 developed the primary outcome (hazard ratio [95% CI] of sarilumab-400 vs control group: 0.41 [0.14, 1.18]; P = 0.09). Seven (6%) patients died: three in the control group and four in sarilumab-200. There were no deaths in sarilumab-400 (P = 0.079, log-rank test for comparisons with the control group). In patients recently hospitalized with COVID-19 pneumonia and features of systemic inflammation, early IL-6 blockade with a single dose of sarilumab 400 mg was safe and associated with a trend for better outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT04357860.).

Capecitabine-induced hyperammonemic encephalopathy.

We report the case of a 79-year-old male who had undergone surgery for a mucus-secreting, stage-III pancreatic adenocarcinoma 2 years previously, who was recently started on capecitabine monotherapy for radiographic local progression. He developed disorientation, asterixis, nausea and elevated serum ammonia (221 µmol/L) 48-72 hours after treatment onset with preserved liver function. After ruling out potential causes of encephalopathy and tumor progression by abdominal and brain CT scans, his symptoms were related by exclusion to the recently initiated treatment with capecitabine. Capecitabine discontinuation, onset of standard anti-encephalopathy measures, and intravenous hydration led to a rapid, complete resolution of symptoms with serum ammonia normalization.

Classification and Visualisation of Normal and Abnormal Radiographs; A Comparison between Eleven Convolutional Neural Network Architectures.

This paper investigates the classification of radiographic images with eleven convolutional neural network (CNN) architectures (GoogleNet, VGG-19, AlexNet, SqueezeNet, ResNet-18, Inception-v3, ResNet-50, VGG-16, ResNet-101, DenseNet-201 and Inception-ResNet-v2). The CNNs were used to classify a series of wrist radiographs from the Stanford Musculoskeletal Radiographs (MURA) dataset into two classes-normal and abnormal. The architectures were compared for different hyper-parameters against accuracy and Cohen's kappa coefficient. The best two results were then explored with data augmentation. Without the use of augmentation, the best results were provided by Inception-ResNet-v2 (Mean accuracy = 0.723, Mean kappa = 0.506). These were significantly improved with augmentation to Inception-ResNet-v2 (Mean accuracy = 0.857, Mean kappa = 0.703). Finally, Class Activation Mapping was applied to interpret activation of the network against the location of an anomaly in the radiographs.

Prognostic Value of Variations in Serum Biomarkers and Prognostic Scores Values Between Admission and Second Day in Intensive Care Unit Septic Patients.

Objective To determinate the prognostic value of procalcitonin (PCT) and C-reactive protein (CRP) changes during the first two days of admission to the ICU with sepsis and/or septic shock, and to compare it with changes in Acute Physiology And Chronic Health Evaluation II (APACHE-II) and Sepsis-related Organ Failure Assessment (SOFA) prognostic scores. Methods A single-center prospective observational study was performed. Fifty consecutive patients admitted to the ICU, diagnosed of severe sepsis/septic shock were included. We considered risk factors for infection: diabetes mellitus, chronic obstructive pulmonary disease (COPD), previous antibiotic treatment, central intravascular catheter, bladder catheter, active neoplasia. Results Median aged 67(52-75) years with median APACHE-II 19(14-25) points and SOFA scores 7(5-11) points on admission, and 28-day mortality of 42%. When we studied the relationship between mortality and the changes between the day of admission and the second day of the variables studied, we found that APACHE-II (p = 0.001) and SOFA (p = 0.002) between admission and second day raised significantly in no survivors, with no significant changes in CRP and PCT. Multivariate analysis showed that mortality was significantly associated to changes in SOFA score (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.18-3.86) and to the presence of one or more risk factors for infection (OR, 6.01; 95% CI, 1.01-35.78) but not with PCT changes. Mortality was also related to the variations between the day of admission and the fifth day on APACHE-II (p = 0.002), SOFA (p < 0.001) and PCT (p = 0.012). Conclusions Changes in SOFA and APACHE-II scores between admission and second day in ICU septic patients are more sensitive mortality predictors than the observed changes in CRP and PCT values. Changes in PCT levels between the day of ICU admission and the fifth day are significantly related to mortality and may be useful as an additional marker in patient outcome.

Motor learning impairment in rats under a high sucrose diet.

Motor learning skills are reliable indicators of behavioral acquisition and cognitive disorders. The ease with which learning skills are measured disparities the complexity of the interpretation concerning neural plasticity. Conversely, a wealth of information regarding metabolic derangements has long been reported with direct connection to high sucrose diets. However, the impact of excessive sucrose consumption on undergoing cognitive processes has been only scarcely addressed up to now. Therefore, the goal of this work was to describe the associative relationship between high sucrose consumption and changes in motor learning skills acquisition. Motor learning impairments conditioned by central alterations are hypothesized. Rotarod, elevated plus-maze and open field trials, along with metabolic and pro-inflammatory biomarkers tests in Wistar rats under a high sucrose treatment, were performed. Motor learning impairment in high sucrose diet-treated rats was found while spontaneous locomotor activity remained unchanged. Even though, no anxiety-like behavior under high sucrose diet-treatment was observed. Consistently, the worst outcome in the glucose tolerance test was developed, the worst motor learning performance was observed. Furthermore, insulin resistance correlated positively with a pro-inflammatory state and a decreased latency to fall in the rotarod test. Indeed, C-reactive protein and tumor necrosis factor-α serum levels, along with the homeostasis model assessment of insulin resistance (HOMA-IR), significantly increased in motor learning impairment. Together, these results support behavioral, metabolic and pro-inflammatory changes associated with deleterious changes in central nervous system likely involving crucial motor learning structures. Underlying pro-inflammatory-triggered processes may explain cognitive disorders in advanced states of metabolic derangements.