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Chronic hepatitis B virus (HBV) infection affects about 262 million people worldwide, leading to over 820,000 deaths each year primarily due to cirrhosis and hepatocellular carcinoma. The World Health Organization has pledged to eliminate HBV as a health threat by 2030, but currently, no countries are on track to achieve this goal. One of the barriers to HBV elimination is stigma, causing shame, denial, self-isolation, self-rejection, and depression leading to those with chronic HBV less likely to get tested or seek treatment and more likely to conceal their infection. Other barriers include limited access to care and complicated and restrictive clinical practice guidelines. Increasing public and political efforts are necessary to raise awareness, increase access to care, and change screening and treatment guidelines. The current guidance of the American Association for the Study of Liver Diseases (AASLD) recommends testing only if patients are considered at risk, but this has proven to be ineffective. We propose a simplified "test all and treat all" approach with a 5-line guideline for HBV infection. Universal screening and treatment of adults is cost-effective and can prevent transmission by effectively managing chronic HBV. All patients who are hepatitis B surface antigen (HBsAg) positive with detectable HBV-DNA should receive treatment until HBsAg is undetectable for 12 months, as HBV-DNA transmission via blood transfusion can occur even at low viral loads of 16 copies/mL, and mother-to-child transmission is still a risk even with passive-active immunoprophylaxis. Furthermore, clinical outcomes after HBsAg clearance are significantly better than the clinical outcomes of those who remain HBsAg positive.
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The rotor or impeller is a rotational and key part of a pump and compressor. This article presents the detailed development process of a rotor of small size constructed from an EN8 steel cylindrical blank using a novel technique based on a computer numerical control engraving milling machine (CNC-EMM) equipped with a 4 mm tungsten carbide end mill cutter. We fabricated a total of twenty-eight stepped rotors following the Box-Behnken Design (BBD) DoE technique at fourteen distinct combinations of CNC-EMM variable parameters, namely rotational speed, feed, and plunge feed. Average roughness 'Ra', an important surface quality indicator, has been considered and presented in this article, as a quality measure for the fabricated rotors. Feed and plunge feed have been identified as the most influencing variable parameters as per an analysis of variance (ANOVA) test. The lowest average roughness value obtained by this process for the rotor blade was 0.11 µm. A micrograph obtained from a field-emission scanning electron microscope (FE-SEM) showed a uniform and accurate tooth profile along with burr formation at corner edges. This study claims to establish engraving milling as a viable alternative to other manufacturing processes used for rotor blades. The findings of this study are useful to scholars, engineers, and researchers who are exploring new ways to fabricate mechanical parts and components.
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Adenovirus-derived nanoparticles (ADDomer) comprise 60 copies of adenovirus penton base protein (PBP). ADDomer is thermostable, rendering the storage, transport, and deployment of ADDomer-based therapeutics independent of a cold chain. To expand the scope of ADDomers for new applications, we engineered ADDobodies, representing PBP crown domain, genetically separated from PBP multimerization domain. We inserted heterologous sequences into hyper-variable loops, resulting in monomeric, thermostable ADDobodies expressed at high yields in Escherichia coli. The X-ray structure of an ADDobody prototype validated our design. ADDobodies can be used in ribosome display experiments to select a specific binder against a target, with an enrichment factor of â¼104-fold per round. ADDobodies can be re-converted into ADDomers by genetically reconnecting the selected ADDobody with the PBP multimerization domain from a different species, giving rise to a multivalent nanoparticle, called Chimera, confirmed by a 2.2 Å electron cryo-microscopy structure. Chimera comprises 60 binding sites, resulting in ultra-high, picomolar avidity to the target.
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Engenharia de Proteínas , Sítios de LigaçãoRESUMO
Background: Due to COVID-19, pandemic preparedness emerges as a key imperative, necessitating new approaches to accelerate development of reagents against infectious pathogens. Methods: Here, we developed an integrated approach combining synthetic, computational and structural methods with in vitro antibody selection and in vivo immunization to design, produce and validate nature-inspired nanoparticle-based reagents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: Our approach resulted in two innovations: (i) a thermostable nasal vaccine called ADDoCoV, displaying multiple copies of a SARS-CoV-2 receptor binding motif derived epitope and (ii) a multivalent nanoparticle superbinder, called Gigabody, against SARS-CoV-2 including immune-evasive variants of concern (VOCs). In vitro generated neutralizing nanobodies and electron cryo-microscopy established authenticity and accessibility of epitopes displayed by ADDoCoV. Gigabody comprising multimerized nanobodies prevented SARS-CoV-2 virion attachment with picomolar EC50. Vaccinating mice resulted in antibodies cross-reacting with VOCs including Delta and Omicron. Conclusion: Our study elucidates Adenovirus-derived dodecamer (ADDomer)-based nanoparticles for use in active and passive immunization and provides a blueprint for crafting reagents to combat respiratory viral infections.
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Background and Aims: The interscalene brachial plexus block (ISB) affects the phrenic nerve, resulting in hemi-diaphragmatic paresis (HDP) and, possibly, respiratory distress. Suprascapular nerve block via an anterior approach (SSB-A) is performed more distally at the level of the trunk of the brachial plexus and, thus, may spare the phrenic nerve. This study compares the analgesic efficacy and decline of hemi-diaphragmatic excursion (HDE) following ultrasound (US)-guided SSB-A versus ISB for arthroscopic shoulder surgery. Methods: This study was conducted on 60 adult participants undergoing arthroscopic shoulder surgery under general anaesthesia. Both US-guided SSB-A (n = 30) and ISB (n = 30) were performed with a combination of 10 ml bupivacaine (0.5%) and 4 mg dexamethasone. The primary objective was to compare the duration of analgesia (time to first rescue analgesia), and secondary objectives were to compare 24-h postoperative numerical rating scale (NRS) scores, 24-h morphine consumption and post block change in HDE, and pulmonary function tests (PFTs) between the two groups. For analysing intergroup differences of NRS, HDE and PFT; Pearson's Chi-squared test or Fisher's exact test, unpaired t test, and Mann-Whitney U test were used. For intragroup differences, paired t test was used. A P value <0.05 was considered significant. Results: The duration of analgesia (mean ± Standard Deviation) was similar in two groups (SSB-A = 1,345 ± 182 min, ISB = 1,375 ± 156 min; P = 0.8). The reduction in HDE was significantly greater in the ISB group (44%) than in the SSB-A group (10%). Pulmonary function was better preserved in the SSB-A group. Conclusion: Compared to ISB, SSB-A has a similar analgesic efficacy for arthroscopic shoulder surgeries, but it is superior in preserving diaphragmatic function and pulmonary function.
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This paper presents a research investigation conducted on the turning of stainless steel 316 material under a dry environment using microwave-treated cutting tool inserts. Plain tungsten carbide WC tool inserts were exposed to microwave treatment for enhancement of their performance characteristics. It was found that a 20-min microwave treatment resulted in the best tool hardness and metallurgical characteristics. These tool inserts have been used to machine SS 316 material following the Taguchi L9 design of experimental techniques. A total of eighteen experiments have been conducted by varying three main machining parameters, i.e., cutting speed, feed rate, and depth of cut, at three levels per parameter. It has been found that tool flank wear increased with all three parameters and surface roughness decreased. At the longest dept of cut, surface roughness increased. An abrasion wear mechanism was found on the tool flank face at a high machining speed and adhesion at low speed. Chips with a helical shape and low serrations have been investigated. Turning SS 316 at optimum machining parameters of 170 m/min cutting speed, 0.2 mm/rev feed rate, and 1 mm depth of cut, as obtained by the multiperformance optimization technique grey relational analysis, resulted in the best values of all machinability indicators: 242.21 µm tool flank wear, 3.81 µm mean roughness depth, and 34,000 mm3/min material removal rate, at a single parameter setting. In terms of research achievements, the percentage reduction in surface roughness is approximately 30% and represents an almost ten-fold improvement in the material removal rate. The combination of machining parameters of 70 m/min cutting speed, 0.1 mm/rev feed rate, and 0.5 mm depth of cut is optimum for the lowest value of tool flank wear when considered for single parameter optimization.
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Low-volume antibody assays can be used to track SARS-CoV-2 infection rates in settings where active testing for virus is limited and remote sampling is optimal. We developed 12 ELISAs detecting total or antibody isotypes to SARS-CoV-2 nucleocapsid, spike protein or its receptor binding domain (RBD), 3 anti-RBD isotype specific luciferase immunoprecipitation system (LIPS) assays and a novel Spike-RBD bridging LIPS total-antibody assay. We utilized pre-pandemic (n=984) and confirmed/suspected recent COVID-19 sera taken pre-vaccination rollout in 2020 (n=269). Assays measuring total antibody discriminated best between pre-pandemic and COVID-19 sera and were selected for diagnostic evaluation. In the blind evaluation, two of these assays (Spike Pan ELISA and Spike-RBD Bridging LIPS assay) demonstrated >97% specificity and >92% sensitivity for samples from COVID-19 patients taken >21 days post symptom onset or PCR test. These assays offered better sensitivity for the detection of COVID-19 cases than a commercial assay which requires 100-fold larger serum volumes. This study demonstrates that low-volume in-house antibody assays can provide good diagnostic performance, and highlights the importance of using well-characterized samples and controls for all stages of assay development and evaluation. These cost-effective assays may be particularly useful for seroprevalence studies in low and middle-income countries.
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COVID-19 , SARS-CoV-2 , Humanos , Glicoproteína da Espícula de Coronavírus , Anticorpos Antivirais , Proteínas do Envelope Viral , Estudos Soroepidemiológicos , COVID-19/diagnóstico , Glicoproteínas de MembranaRESUMO
BACKGROUND AND AIMS: Endoscopic suturing and over-the-scope clips (OTSCs) are used to prevent migration of fully covered self-expandable metal stents (FCSEMSs). Recently, a dedicated OTSC was developed for securing FCSEMSs. Our primary aim was to compare the frequency of stent migration without stent fixation versus fixation with suturing or OTSCs, and out secondary aims were to compare clinical success, procedure duration, and adverse events. METHODS: A retrospective cohort study evaluated the outcome of stent placement throughout the entire GI tract from 2013 to 2021. Stent migration was determined as stent displacement ≥2 cm endoscopically or radiographically. Clinical success was defined as resolution of indication at follow-up. RESULTS: Four hundred thirty-three procedures were performed, 239 (55%) without fixation, 140 (32%) with suturing, and 54 (12%) with OTSCs. Stent migration rates were 62% without fixation, 57% with suturing, and 35% with OTSCs (P = .013). The median time to stent migration was 3 weeks without fixation, 5 weeks with suturing, and 6 weeks with OTSCs (P = .023). The clinical success rate was 43%. The median procedure time for OTSCs was shorter compared with suturing (42 vs 68 minutes, P = .002). Adverse event rates trended toward being lowest with OTSCs at 9% compared with 21% without fixation and 18% with suturing (P > .05). CONCLUSIONS: OTSCs for stent fixation were found to have significantly lower migration rates compared with no fixation and suturing. Moreover, OTSCs were associated with decreased overall procedure time and total costs per procedure while trending to be associated with fewer adverse events.
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Stents Metálicos Autoexpansíveis , Técnicas de Sutura , Humanos , Estudos Retrospectivos , Suturas , Stents Metálicos Autoexpansíveis/efeitos adversos , Stents , Esofagoscopia/métodos , Resultado do TratamentoRESUMO
Although pectoralis (PECS) blocks are commonly used for breast surgery, recommendations regarding the efficacy of these blocks have thus far not been developed by any professional anesthesia society. Given the potential impact of PECS blocks on analgesia after outpatient breast surgery, The Society for Ambulatory Anesthesia (SAMBA) convened a task force to develop a practice advisory on the use of this analgesic technique. In this practice advisory, we compare the efficacy of PECS blocks with systemic analgesia, local infiltration anesthesia, and paravertebral blockade. Our objectives were to advise on two clinical questions. (1) Does PECS-1 and/or -2 blockade provide more effective analgesia for breast-conserving surgery than either systemic analgesics or surgeon-provided local infiltration anesthesia? (2) Does PECS-1 and/or -2 blockade provide equivalent analgesia for mastectomy compared with a paravertebral block (PVB)? Among patients undergoing breast-conserving surgery, PECS blocks moderately reduce postoperative opioid use, prolong time to analgesic rescue, and decrease postoperative pain scores when compared with systemic analgesics. SAMBA recommends the use of a PECS-1 or -2 blockade in the absence of systemic analgesia (Strength of Recommendation A). No evidence currently exists that strongly favors the use of PECS blocks over surgeon-performed local infiltration in this surgical population. SAMBA cannot recommend PECS blocks over surgical infiltration (Strength of Recommendation C). For patients undergoing a mastectomy, a PECS block may provide an opioid-sparing effect similar to that achieved with PVB; SAMBA recommends the use of a PECS block if a patient is unable to receive a PVB (Strength of Recommendation A).
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Neoplasias da Mama , Bloqueio Nervoso , Nervos Torácicos , Analgésicos , Analgésicos Opioides , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia/efeitos adversos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controleAssuntos
Carcinoma Hepatocelular , Neoplasias Cardíacas , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Cardíacas/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Tomografia Computadorizada por Raios XRESUMO
SARS-CoV-2 infection is a major global public health concern with incompletely understood pathogenesis. The SARS-CoV-2 spike (S) glycoprotein comprises a highly conserved free fatty acid binding pocket (FABP) with unknown function and evolutionary selection advantage1,2. Deciphering FABP impact on COVID-19 progression is challenged by the heterogenous nature and large molecular variability of live virus. Here we create synthetic minimal virions (MiniVs) of wild-type and mutant SARS-CoV-2 with precise molecular composition and programmable complexity by bottom-up assembly. MiniV-based systematic assessment of S free fatty acid (FFA) binding reveals that FABP functions as an allosteric regulatory site enabling adaptation of SARS-CoV-2 immunogenicity to inflammation states via binding of pro-inflammatory FFAs. This is achieved by regulation of the S open-to-close equilibrium and the exposure of both, the receptor binding domain (RBD) and the SARS-CoV-2 RGD motif that is responsible for integrin co-receptor engagement. We find that the FDA-approved drugs vitamin K and dexamethasone modulate S-based cell binding in an FABP-like manner. In inflammatory FFA environments, neutralizing immunoglobulins from human convalescent COVID-19 donors lose neutralization activity. Empowered by our MiniV technology, we suggest a conserved mechanism by which SARS-CoV-2 dynamically couples its immunogenicity to the host immune response.
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COVID-19/imunologia , Ácidos Graxos/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vírion/imunologia , Células A549 , Sítio Alostérico/genética , Sequência de Aminoácidos , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Sítios de Ligação/genética , COVID-19/metabolismo , COVID-19/virologia , Células Cultivadas , Microscopia Crioeletrônica/métodos , Tomografia com Microscopia Eletrônica/métodos , Proteínas de Ligação a Ácido Graxo/imunologia , Proteínas de Ligação a Ácido Graxo/metabolismo , Ácidos Graxos/metabolismo , Humanos , Células MCF-7 , Microscopia Confocal/métodos , Ligação Proteica , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Homologia de Sequência de Aminoácidos , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Vírion/metabolismo , Vírion/ultraestruturaRESUMO
GOALS: Our aim was to compare the diagnostic yield of endoscopic ultrasound guided fine needle aspiration (EUS-FNA) versus combined fine needle aspiration and fine needle biopsy (EUS-FNA + FNB) in the evaluation of solid pancreatic masses (SPMs). BACKGROUND: EUS-FNA and EUS-FNB are established methods to diagnose SPMs. No studies have evaluated the efficacy of combination of both (EUS-FNA + FNB). Our senior author (MRS) hypothesized that combining the two techniques by using a single FNB needle improves diagnostic yield and started combination technique in October 2016. STUDY: Patients who underwent EUS for SPMs by MRS during January 2014-September 2019 were included. They were divided into the EUS-FNA group and EUS-FNA + FNB group. EUS-FNA was performed using a 22 or 25 gauge Expect Slimline needle (Boston Scientific, Marlborough, MA) and EUS-FNA + FNB was performed using a single 22 or 25 gauge Shark-core needle (Medtronics, Minneapolis, MN, USA). Our primary outcome was to compare the diagnostic yield in the two groups. RESULTS: Among 105 patients included, 58 were in the EUS-FNA group and 47 were in the EUS-FNA + FNB group. EUS-FNA + FNB group had significantly higher diagnostic yield and required fewer needle passes compared to EUS-FNA group, 95.7% vs. 77.6%, p = .01: and 4 vs. 5, p = .002; respectively. Procedural duration was similar in both groups but the combined technique required less number of needles per procedure. There was no difference in adverse events in the two groups. CONCLUSION: Our study showed that combined EUS-FNA + FNB had higher diagnostic yield compared to EUS-FNA in SPMs along with less number of needle passes and needles required. Further prospective studies are needed to validate these findings and cost-effectiveness of this strategy.
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Neoplasias Pancreáticas , Boston , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Endossonografia , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Estudos ProspectivosRESUMO
BACKGROUND: The incidence of non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), has been increasing for decades. Since the mainstay is lifestyle modification in this mainly asymptomatic condition, there is a need for accurate diagnostic methods. OBJECTIVES: This study proposes a method with a computer-aided diagnosis (CAD) system to predict NAFLD Activity score (NAS scores-steatosis, lobular inflammation, and ballooning) and fibrosis stage from histopathology slides. METHODS: A total of 87 pathology slides pairs (H&E and Trichrome-stained) were used for the study. Ground-truth NAS scores and fibrosis stages were previously identified by a pathologist. Each slide was split into 224 × 224 patches and fed into a feature extraction network to generate local features. These local features were processed and aggregated to obtain a global feature to predict the slide's scores. The effects of different training strategies, as well as training data with different staining and magnifications were explored. Four-fold cross validation was performed due to the small data size. Area Under the Receiver Operating Curve (AUROC) was utilized to evaluate the prediction performance of the machine-learning algorithm. RESULTS: Predictive accuracy for all subscores was high in comparison with pathologist assessment. There was no difference among the 3 magnifications (5x, 10x, 20x) for NAS-steatosis and fibrosis stage tasks. A larger magnification (20x) achieved better performance for NAS-lobular scores. Middle-level magnification was best for NAS-ballooning task. Trichrome slides are better for fibrosis stage prediction and NAS-ballooning score prediction task. NAS-steatosis prediction had the best performance (AUC 90.48%) in the model. A good performance was observed with fibrosis stage prediction (AUC 83.85%) as well as NAS-ballooning prediction (AUC 81.06%). CONCLUSIONS: These results were robust. The method proposed proved to be effective in predicting NAFLD Activity score and fibrosis stage from histopathology slides. The algorithms are an aid in having an accurate and systematic diagnosis in a condition that affects hundreds of millions of patients globally.
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Hepatopatia Gordurosa não Alcoólica , Algoritmos , Área Sob a Curva , Biópsia , Humanos , Fígado/patologia , Cirrose Hepática/diagnóstico , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologiaRESUMO
Virus-like particles (VLPs) play a prominent role in vaccination as safe and highly versatile alternatives to attenuated or inactivated viruses or subunit vaccines. We present here two innovations, VLP-factory™ and ADDomer© , for creating VLPs displaying entire proteins or peptide epitopes as antigens, respectively, to enable efficient vaccination. For producing these VLPs, we use MultiBac, a baculovirus expression vector system (BEVS) that we developed for producing complex protein biologics in insect cells transfected with an engineered baculovirus. VLPs are protein assemblies that share features with viruses but are devoid of genetic material, and thus considered safe. VLP-factory™ represents a customized MultiBac baculovirus tailored to produce enveloped VLPs based on the M1 capsid protein of influenza virus. We apply VLP-factory™ to create an array of influenza-derived VLPs presenting functional mutant influenza hemagglutinin (HA) glycoprotein variants. Moreover, we describe MultiBac-based production of ADDomer© , a synthetic self-assembling adenovirus-derived protein-based VLP platform designed to display multiple copies of pathogenic epitopes at the same time on one particle for highly efficient vaccination. © 2021 The Authors. Basic Protocol 1: VLP-factory™ baculoviral genome generation Basic Protocol 2: Influenza VLP array generation using VLP-factory™ Basic Protocol 3: Influenza VLP purification Basic Protocol 4: ADDomer© BioBrick design, expression, and purification Basic Protocol 5: ADDomer© candidate vaccines against infectious diseases.
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Vacinas contra Influenza , Orthomyxoviridae , Epitopos/genética , Hemaglutininas , Orthomyxoviridae/genética , Peptídeos/genéticaRESUMO
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and increased risk of cancer. The impacts of bariatric surgery on cancer risk in NAFLD patients are unknown. We investigated the effect of bariatric surgery on cancer risk in patients with NAFLD and severe obesity using the MarketScan database. METHODS: We conducted a retrospective cohort study of 18 to 64 years old newly diagnosed NAFLD patients with severe obesity between 2007 and 2017. We used Cox proportional hazard models to examine the association between bariatric surgery, modeled as a time-varying covariate, and the risks of any cancer and obesity-related cancer, while accounting for confounding using inverse probability of treatment weighting (IPTW). RESULTS: A total of 98,090 patients were included in the study, 33,435 (34.1%) received bariatric surgery. In those without surgery, 1898 incident cases of cancer occurred over 115,890.11 person-years of follow-up, compared with 925 cancer cases over 67,389.82 person-years among surgery patients (crude rate ratio, 0.84; 95% CI, 0.77- 0.91). The IPTW-adjusted risk of any cancer and obesity-related cancer was reduced by 18% (hazard ratio, 0.82; 95% CI, 0.76-0.89) and 25% (hazard ratio, 0.65; 95% CI, 0.56-0.75), respectively, in patients with versus without bariatric surgery. The adjusted risks of any cancer and obesity-related cancer were significantly lower in cirrhotic versus non-cirrhotic patients who underwent surgery. In cancer-specific models, bariatric surgery was associated with significant risk reductions for colorectal, pancreatic, endometrial, thyroid cancers, hepatocellular carcinoma, and multiple myeloma. CONCLUSION: Bariatric surgery was associated with significant reductions in the risks of any cancer and obesity-related cancer in NAFLD patients with severe obesity.
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Cirurgia Bariátrica , Neoplasias/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/cirurgia , Bases de Dados Factuais , Humanos , Incidência , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Obesidade/diagnóstico , Obesidade/epidemiologia , Fatores de Proteção , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
Schistosomiasis is a trematode infection rarely diagnosed in the United States. Intestinal involvement is common with chronic infection and causes abdominal pain, changes in bowel habits, hematochezia, and polyp formation. Chronic, disseminated infection can affect the intestines causing the aforementioned symptoms, but reports of intestinal polyps are rare. Most cases are inflammatory fibrous polyps in the colon. There are very few cases reported in the literature of hamartomatous polyps arising in the small intestine. We present the rare case of a U.S.-born, 35-year-old woman diagnosed with a large duodenal hamartomatous polyp in the setting of intestinal schistosomiasis.
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INTRODUCTION AND OBJECTIVES: Decompensated cirrhosis carries high inpatient morbidity and mortality. Consequently, advance care planning is an integral aspect of medical care in this patient population. Our study aims to identify do-not-resuscitate (DNR) order utilization and demographic disparities in decompensated cirrhosis patients. PATIENTS OR MATERIALS AND METHODS: Nationwide Inpatient Sample was used to extract the cohort of patients from January 1st, 2016 to December 31st, 2017, based on the most comprehensive and recent data. The first cohort included hospitalized patients with decompensated cirrhosis. The second cohort included patients with decompensated cirrhosis with at least one contraindication for liver transplantation. RESULTS: A cohort of 585,859 decompensated cirrhosis patients was utilized. DNR orders were present in 14.2% of hospitalized patients. DNR utilization rate among patients with relative contraindication for liver transplantation was 15.0%. After adjusting for co-morbid conditions, disease severity, and inpatient mortality, African-American and Hispanic patient populations had significantly lower DNR utilization rates. There were regional, and hospital-level differences noted. Moreover, advanced age, advanced stage of decompensated cirrhosis, inpatient mortality, and relative contraindications for liver transplantation (metastatic neoplasms, dementia, alcohol misuse, severe cardiopulmonary disease, medical non-adherence) were independently associated with increased DNR utilization rates. CONCLUSIONS: The rate of DNR utilization in patients with relative contraindications for liver transplantation was similar to patients without any relative contraindications. Moreover, there were significant demographic and hospital-level predictors of DNR utilization. This information can guide resource allocation in educating patients and their families regarding prognosis and outcome expectations.
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Hospitalização , Cirrose Hepática/mortalidade , Cirrose Hepática/terapia , Ordens quanto à Conduta (Ética Médica) , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Mortalidade Hospitalar , Humanos , Cirrose Hepática/complicações , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto JovemRESUMO
Background and study aims Early studies have shown that artificial intelligence (AI) has the potential to augment the performance of gastroenterologists during endoscopy. Our aim was to determine how gastroenterologists view the potential role of AI in gastrointestinal endoscopy. Methods In this cross-sectional study, an online survey was sent to US gastroenterologists. The survey included questions about physician level of training, experience, and practice characteristics and physician perception of AI. Descriptive statistics were used to summarize sentiment about AI. Univariate and multivariate analyses were used to assess whether background information about physicians correlated to their sentiment. Results Surveys were emailed to 330 gastroenterologists nationwide. Between December 2018 and January 2019, 124 physicians (38â%) completed the survey. Eighty-six percent of physicians reported interest in AI-assisted colonoscopy; 84.7â% agreed that computer-assisted polyp detection (CADe) would improve their endoscopic performance. Of the respondents, 57.2â% felt comfortable using computer-aided diagnosis (CADx) to support a "diagnose and leave" strategy for hyperplastic polyps. Multivariate analysis showed that post-fellowship experience of fewer than 15 years was the most important factor in determining whether physicians were likely to believe that CADe would lead to more removed polyps (odds ratioâ=â5.09; P â=â.01). The most common concerns about implementation of AI were cost (75.2â%), operator dependence (62.8â%), and increased procedural time (60.3â%). Conclusions Gastroenterologists have strong interest in the application of AI to colonoscopy, particularly with regard to CADe for polyp detection. The primary concerns were its cost, potential to increase procedural time, and potential to develop operator dependence. Future developments in AI should prioritize mitigation of these concerns.
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AIM OF THE STUDY: Combined magnetic resonance imaging and magnetic resonance cholangiopancreatography (MRI/MRCP) can identify biliary strictures and diagnose primary sclerosing cholangitis (PSC). Diagnosis of cholangiocarcinoma in patients with PSC remains challenging, and the accuracy of MRI/MRCP has not been completely established. We aimed to determine the sensitivity and specificity of MRI/MRCP in the diagnosis of cholangiocarcinoma among patients with PSC from the published literature. MATERIAL AND METHODS: We searched Embase, PubMed, Cochrane, Scopus, ClinicalTrials.gov, and abstracts from relevant scientific meetings and performed a systematic review and meta-analysis to estimate the diagnostic yield of MRI/MRCP in patients with PSC. Sensitivity and specificity were calculated from pooled estimates of cholangiocarcinoma cases identified and lesions missed. Modifying variables were included in a meta-regression model. RESULTS: Our literature search yielded 302 articles and 9 conference abstracts; 8 studies involving 846 liver patients from 5 countries were included in the final analysis. Of those, 531 had PSC and received MRI/MRCP. Thirty-six (6.8%) patients were diagnosed with cholangiocarcinoma (33 true positive, 3 false negative and 1 false positive). Pooled sensitivity was 98.9% (95% CI: 98.6-99.3%). Cholangiocarcinoma cases missed by MRI/MRCP were diagnosed as beading irregularities of the central hepatic ducts, or PSC-related diffuse stricture. Metaregression revealed that neither publication year, study design, nor sample size had a significant effect on observed cancer rates (p = 0.9, 0.3, and 0.3, respectively). CONCLUSIONS: MRI/MRCP followed by endoscopic retrograde cholangiopancreatography (ERCP) is a sensitive and specific tool to diagnose cholangiocarcinoma among patients with PSC. Further research should estimate MRI/MRCP diagnostic accuracy for cholangiocarcinoma using prospective methodology and longer term outcomes.