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Cases of concurrent duodenal adenocarcinoma and gastrointestinal stromal tumors (GISTs) are rare, and only a few have been reported. While some cases of other synchronous primary tumors with GIST have been reported, no shared mutations have been consistently found, creating challenges in selecting chemotherapy in cases of inoperable tumors. Here, we presented a case of a stage IIIA locally advanced/unresectable duodenal adenocarcinoma with concurrent metastatic small bowel GIST successfully being treated with combined imatinib and modified folinic acid, 5-fluorouracil, and irinotecan (mFOLFIRI) regimen.
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Gastrointestinal cancers represent one of the more challenging cancers to treat. Current strategies to cure and control gastrointestinal (GI) cancers like surgery, radiation, chemotherapy, and immunotherapy have met with limited success, and research has turned towards further characterizing the tumor microenvironment to develop novel therapeutics. Myeloid-derived suppressor cells (MDSCs) have emerged as crucial drivers of pathogenesis and progression within the tumor microenvironment in GI malignancies. Many MDSCs clinical targets have been defined in preclinical models, that potentially play an integral role in blocking recruitment and expansion, promoting MDSC differentiation into mature myeloid cells, depleting existing MDSCs, altering MDSC metabolic pathways, and directly inhibiting MDSC function. This review article analyzes the role of MDSCs in GI cancers as viable therapeutic targets for gastrointestinal malignancies and reviews the existing clinical trial landscape of recently completed and ongoing clinical studies testing novel therapeutics in GI cancers.
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Neoplasias Gastrointestinais , Células Supressoras Mieloides , Humanos , Células Supressoras Mieloides/metabolismo , Neoplasias Gastrointestinais/metabolismo , Células Mieloides , Imunoterapia , Microambiente TumoralRESUMO
PURPOSE: To develop recommendations for systemic therapy for well-differentiated grade 1 (G1) to grade 3 (G3) metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS: Eight randomized controlled trials met the inclusion criteria for the systematic review. RECOMMENDATIONS: Somatostatin analogs (SSAs) are recommended as first-line systemic therapy for most patients with G1-grade 2 (G2) metastatic well-differentiated GI-NETs. Observation is an option for patients with low-volume or slow-growing disease without symptoms. After progression on SSAs, peptide receptor radionuclide therapy (PRRT) is recommended as systematic therapy for patients with somatostatin receptor (SSTR)-positive tumors. Everolimus is an alternative second-line therapy, particularly in nonfunctioning NETs and patients with SSTR-negative tumors. SSAs are standard first-line therapy for SSTR-positive pancreatic (pan)NETs. Rarely, observation may be appropriate for asymptomatic patients until progression. Second-line systemic options for panNETs include PRRT (for SSTR-positive tumors), cytotoxic chemotherapy, everolimus, or sunitinib. For SSTR-negative tumors, first-line therapy options are chemotherapy, everolimus, or sunitinib. There are insufficient data to recommend particular sequencing of therapies. Patients with G1-G2 high-volume disease, relatively high Ki-67 index, and/or symptoms related to tumor growth may benefit from early cytotoxic chemotherapy. For G3 GEP-NETs, systemic options for G1-G2 may be considered, although cytotoxic chemotherapy is likely the most effective option for patients with tumor-related symptoms, and SSAs are relatively ineffective. Qualifying statements are provided to assist with treatment choice. Multidisciplinary team management is recommended, along with shared decision making with patients, incorporating their values and preferences, potential benefits and harms, and other characteristics and circumstances, such as comorbidities, performance status, geographic location, and access to care.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.
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Neoplasias Intestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Guias de Prática Clínica como Assunto , Neoplasias Gástricas , Humanos , Everolimo/uso terapêutico , Neoplasias Intestinais/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Somatostatina , Neoplasias Gástricas/tratamento farmacológico , SunitinibeRESUMO
Over the last several decades, a number of new treatment options for patients with hepatocellular carcinoma (HCC) have been developed. While treatment decisions for some patients remain clear cut, a large numbers of patients have multiple treatment options, and it can be hard for multidisciplinary teams to come to unanimous decisions on which treatment strategy or sequence of treatments is best. This article reviews the available data with regard to two treatment strategies, immunotherapies and locoregional therapies, with a focus on the potential of locoregional therapies to be combined with checkpoint inhibitors to improve outcomes in patients with locally advanced HCC. In this review, the available data on the immunomodulatory effects of locoregional therapies is discussed along with available clinical data on outcomes when the two strategies are combined.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Imunoterapia , ImunomodulaçãoRESUMO
In the past several decades, major advances in both systemic and locoregional therapies have been made for many cancer patients. This has led to modern cancer treatment algorithms frequently calling for active interventions by multiple subspecialists at the same time. One of the areas where this can be clearly seen is the concomitant use of locoregional and systemic therapies in patients with primary or secondary cancers of the liver. These combined algorithms have gained favor over the last decade and are largely focused on the allure of the combined ability to control systemic disease while at the same time addressing refractory/resistant clonal populations. While the general concept has gained favor and is likely to only increase in popularity with the continued establishment of viable immunotherapy treatments, for many patients questions remain. Lingering concerns over the increase in toxicity when combining treatment methods, patient selection, and sequencing remain for multiple cancer patient populations. While further work remains, some of these questions have been addressed in the literature. This article reviews the available data on three commonly treated primary and secondary cancers of the liver, namely, hepatocellular carcinoma, cholangiocarcinoma, and metastatic colorectal cancer. Furthermore, strengths and weaknesses are reviewed and future directions are discussed.
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Background: Heart failure (HF) is a complex clinical syndrome with symptoms and signs that result from any structural or functional impairment of ventricular filling or ejection of blood. Limited data is available regarding the in-hospital outcomes of TAVR compared to SAVR in the octogenarian population with HF. Methods: The National Inpatient Sample (NIS) database was used to compare TAVR versus SAVR among octogenarians with HF. The primary outcome was in-hospital mortality. The secondary outcome included acute kidney injury (AKI), cerebrovascular accident (CVA), post-procedural stroke, major bleeding, blood transfusions, sudden cardiac arrest (SCA), cardiogenic shock (CS), and mechanical circulatory support (MCS). Results: A total of 74,995 octogenarian patients with HF (TAVR-HF n = 64,890 (86.5%); SAVR n = 10,105 (13.5%)) were included. The median age of patients in TAVR-HF and SAVR-HF was 86 (83-89) and 82 (81-84) respectively. TAVR-HF had lower percentage in-hospital mortality (1.8% vs. 6.9%;p < 0.001), CVA (2.5% vs. 3.6%; p = 0.009), SCA (9.9% vs. 20.2%; p < 0.001), AKI (17.4% vs. 40.8%); p < 0.001), major transfusion (26.4% vs 67.3%; p < 0.001), CS (1.8% vs 9.8%; p < 0.001), and MCS (0.8% vs 7.3%; p < 0.001) when compared to SAVR-HF. Additionally, post-procedural stroke and major bleeding showed no significant difference. The median unmatched total charges for TAVR-HF and SAVR-HF were 194,561$ and 246,100$ respectively. Conclusion: In this nationwide observational analysis, TAVR is associated with an improved safety profile for octogenarians with heart failure (both preserved and reduced ejection fraction) compared to SAVR.
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BACKGROUND: Intravascular lithotripsy (IVL) can be used to assist stent deployment in severe coronary artery calcifications (CAC). METHODS: Studies employing IVL for CAC lesions were included. The primary outcomes included clinical and angiographic success. The secondary outcomes, including lumen gain, maximum calcium thickness, and calcium angle at the final angiography site, minimal lumen area site, and minimal stent area site, were analyzed by the random-effects model to calculate the pooled standardized mean difference. Tertiary outcomes included safety event ratios. RESULTS: Seven studies (760 patients) were included. The primary outcomes: pooled clinical and angiographic success event ratio parentage of IVL was 94.4% and 94.8%, respectively. On a random effect model for standard inverse variance for secondary outcomes showed: minimal lumen diameter increase with IVL was 4.68 mm (p-value < 0.0001, 95% CI 1.69-5.32); diameter decrease in the stenotic area after IVL session was -5.23 mm (95 CI -22.6-12.8). At the minimal lumen area (MLA) and final minimal stent area (MSA) sites, mean lumen area gain was 1.42 mm2 (95% CI 1.06-1.63; p < 0.00001) and 1.34 mm2 (95% CI 0.71-1.43; p < 0.00001), respectively. IVL reduced calcium thickness at the MLA site (SMD -0.22; 95% CI -0.40-0.04; P = 0.02); calcium angle was not affected at the MLA site. The tertiary outcomes: most common complication was major adverse cardiovascular events (n = 48/669), and least common complication was abrupt closure of the vessel (n = 1/669). CONCLUSIONS: Evidence suggests that IVL safely and effectively facilitates stent deployment with high angiographic and clinical success rates in treating severely calcified coronary lesions.
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The COVID-19 pandemic has severely impacted many industries, in particular the healthcare sector exposing systemic vulnerabilities in emergency preparedness, risk mitigation, and supply chain management. A major challenge during the pandemic was related to the increased demand for Personal Protective Equipment (PPE), resulting in critical shortages for healthcare and frontline workers. This is due to the lack of information visibility combined with the inability to precisely track product movement within the supply chain, requiring a robust traceability solution. Blockchain technology is a distributed ledger that ensures a transparent, safe, and secure exchange of data among supply chain stakeholders. The advantages of adopting blockchain technology to manage and track PPE products in the supply chain include decentralized control, security, traceability, and auditable time-stamped transactions. In this paper, we present a blockchain-based approach using smart contracts to transform PPE supply chain operations. We propose a generic framework using Ethereum smart contracts and decentralized storage systems to automate the processes and information exchange and present detailed algorithms that capture the interactions among supply chain stakeholders. The smart contract code was developed and tested in Remix environment, and the code is made publicly available on Github. We present detailed cost and security analysis incurred by the stakeholders in the supply chain. Adopting a blockchain-based solution for PPE supply chains is economically viable and provides a streamlined, secure, trusted, and transparent mode of communication among various stakeholders.
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Transradial (TR) access for percutaneous coronary intervention (PCI) improves outcomes and reduces the risk of major bleeding compared with transfemoral (TF) access. However, data on gender-stratified outcomes based on vascular access are limited. Databases were queried to find relevant articles. Primary outcomes, including major bleeding complications, mortality, and secondary outcome including major adverse cardiovascular events (MACEs), myocardial infarction, and cerebrovascular accidents, were analyzed using a random-effect model to calculate unadjusted odds ratio (OR) of TR-PCI and TF-PCI between the genders. A total of 9 studies comprising 3,889,257 patients (389,580 in the TR arm and 3,499,677 in the TF arm) were included. Males comprised 73% and 67% of the TR and TF arms, respectively. TR-PCI was associated with lower major bleeding (pooled OR 0.51, 95% CI 0.40 to 0.64, p = 0.00; female OR 0.49, 95% CI 0.34 to 0.71, p = 0.00; male OR 0.54, 95% CI 0.40 to 0.73, p = 0.00) and mortality (pooled OR 0.54, 95% CI 0.45 to 0.66, p = 0.00; female OR 0.56, 95% CI 0.44 to 0.71, p = 0.27; male OR 0.54, 95% CI 0.39 to 0.75, p = 0.00) regardless of gender as compared with TF-PCI. Furthermore, TR-PCI also showed lower MACE (pooled OR 0.74, 95% CI 0.66 to 0.84, p = 0.00; female OR 0.64, 95% CI 0.59 to 0.70, p = 0.00; male OR 0.81, 95% CI 0.66 to 0.98, p = 0.00) as compared with TF-PCI in both genders. On analysis of interaction magnitude of the difference of favor of female and male for TR-PCI showed no statistically significant measurable difference. Periprocedural myocardial infarction and cerebrovascular accidents were not statistically different in TR and TF-PCI and were not different based on gender. In conclusion, TR-PCI was associated with a lower risk of major bleeding, mortality, and MACE irrespective of gender. In conclusion, TR-PCI should be the default access.
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Artéria Femoral , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Artéria Radial , Feminino , Humanos , Masculino , Fatores SexuaisRESUMO
BACKGROUND: The relative accuracy of pulsatile photoplethysmography applications (PPG) or handheld (HH) devices compared with the gold standard 12-lead electrocardiogram (ECG) for the diagnosis of atrial fibrillation is unknown. METHODS: Digital databases were searched to identify relevant articles. Raw data were pooled using a bivariate model to calculate diagnostic accuracy measures and estimate Hierarchical Summary Receiver Operating Characteristic (HSROC). RESULTS: A total of 10 articles comprising 4296 patients (mean age 68.9 years, with 56% males) were included in the analysis. Compared with EKG, the pooled sensitivity of PPG and HH devices in AF detection was 0.93 (95% CI 0.87-0.96; p < 0.05) and 0.87 (95% CI. 0.74-0.94; p < 0.05), respectively. The pooled specificity of PPG and HH devices in AF detection was 0.91 (95% CI 0.88-0.94; p < 0.05) and 0.96 (95% CI 0.90-0.98; p < 0.05), respectively. The diagnostic odds ratio was 129 and 144 for PPG and HH devices, respectively. Fagan's nomogram showed the probability of a patient having AF and normal rhythm on PPG or HH devices was 2-3%, while the post-test probability of having AF with an irregular R-R interval on PPG or HH devices was 73% and 82%, respectively. The scatter plot of positive and negative likelihood ratio showed high confirmation of AF and reliability of exclusion of absence of irregular R-R intervals (positive likelihood ratio > 10, and negative likelihood ratio < 0.1) on HH devices while PPG was used as confirmation only. CONCLUSIONS: The PPG or HH devices can serve as a reliable alternative for the detection of AF.
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Fibrilação Atrial , Fotopletismografia , Idoso , Fibrilação Atrial/diagnóstico , Eletrocardiografia , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Studies comparing clinical outcomes with intravascular ultrasound (IVUS) versus optical coherence tomography (OCT) guidance for percutaneous coronary intervention (PCI) in patients presenting with coronary artery disease, including stable angina or acute coronary syndrome, are limited. METHODS: We performed a detailed search of electronic databases (PubMed, Embase, and Cochrane) for randomized controlled trials and observational studies that compared cardiovascular outcomes of IVUS versus OCT. Data were aggregated for the primary outcome measure using the random-effects model as pooled risk ratio (RR). The primary outcome of interest was major adverse cardiac events (MACE), cardiac mortality, and all-cause mortality. Secondary outcomes included myocardial infarction (MI), stent thrombosis (ST), target lesion revascularization (TLR), and stroke. RESULTS: A total of seven studies met the inclusion criteria, comprising 5917 patients (OCT n = 2075; IVUS n = 3842). OCT-PCI versus IVUS-guided PCI comparison yielded no statistically significant results for all the outcomes; MACE (RR 0.78; 95% confidence interval [CI], 0.57-1.09; p = 0.14), cardiac mortality (RR 0.97; 95% CI, 0.27-3.46; p = 0.96), all-cause mortality (RR 0.74; 95% CI, 0.39-1.39; p = 0.35), MI (RR 1.27; 95% CI, 0.52-3.07; p = 0.60), ST (RR 0.70; 95% CI, 0.13-3.61; p = 0.67), TLR (RR 1.09; 95% CI, 0.53-2.25; p = 0.81), and stroke (RR 2.32; 95% CI, 0.42-12.90; p = 0.34). Furthermore, there was no effect modification on meta-regression including demographics, comorbidities, lesion location, lesion length, and stent type. CONCLUSIONS: In this meta-analysis, OCT-guided PCI was associated with no difference in clinical outcomes compared with IVUS-guided PCI.
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Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Tomografia de Coerência Óptica , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
Background: We aim to conduct a comprehensive meta-analysis encompassing all studies to assess the efficacy of Vascepa in patients with diabetes mellitus (DM) in preventing or treating existing coronary artery disease (CAD). Methods: Digital databases were queried. Odds ratios (OR) were calculated for the following outcomes: composite outcome, all-cause mortality, and cardiovascular mortality. Results: A total of 4 randomized control trials (33,092 patients; Vascepa n = 16586; Placebo n = 16506) were included in our analysis. The overall mean age was 64.3 years old (Vascepa = 64.3 years; Placebo = 64.3 years). The sample was 61.5% male (Vascepa = 60.8%; Placebo = 62.1%). In patients with DM, Vascepa was found to have no significant effect on the primary composite outcome (OR 0.97, 95%CI 0.91-1.04, p > 0.05), all-cause mortality (OR 0.96, 95%CI 0.90-1.03, p > 0.05), and cardiovascular mortality (OR 0.90, 95%CI 0.74-1.10, p > 0.05). Subgroup analysis by Vascepa type and treatment type was similarly non-significant. Conclusion: Our study concluded that Vascepa did not affect cardiovascular outcomes in patients with DM.
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We performed a retrospective analysis of angiosarcoma (AS) genomic biomarkers and their associations with the site of origin in a cohort of 143 cases. Primary sites were head and neck (31%), breast (22%), extremity (11%), viscera (20%), skin at other locations (8%), and unknown (9%). All cases had Next Generation Sequencing (NGS) data with a 592 gene panel, and 53 cases had Whole Exome Sequencing (WES) data, which we used to study the microenvironment phenotype. The immunotherapy (IO) response biomarkers Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), and PD-L1 status were the most frequently encountered alteration, present in 36.4% of the cohort and 65% of head and neck AS (H/N-AS) (p < 0.0001). In H/N-AS, TMB-High was seen in 63.4% of cases (p < 0.0001) and PDL-1 positivity in 33% of cases. The most common genetic alterations were TP53 (29%), MYC amplification (23%), ARID1A (17%), POT1 (16%), and ATRX (13%). H/N-AS cases had predominantly mutations in TP53 (50.0%, p = 0.0004), POT1 (40.5%, p < 0.0001), and ARID1A (33.3%, p = 0.5875). In breast AS, leading alterations were MYC amplification (63.3%, p < 0.0001), HRAS (16.1%, p = 0.0377), and PIK3CA (16.1%, p = 0.2352). At other sites, conclusions are difficult to generate due to the small number of cases. A microenvironment with a high immune signature, previously associated with IO response, was evenly distributed in 13% of the cases at different primary sites. Our findings can facilitate the design and optimization of therapeutic strategies for AS.
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The clinical efficacy of remote dielectric sensing (ReDS) monitoring is not well known. Digital databases were searched to identify relevant articles. Pooled unadjusted odds ratio (OR) for dichotomous outcomes were calculated using a random-effects model. Findings were reported as a point estimate with its 95% confidence interval (CI). A total of 985 patients across seven studies were included in the meta-analysis. Patients with heart failure monitored with ReDS had significantly lower odds of hospital readmission compared with non-ReDS patients (OR = 0.40; 95% CI 0.29-0.56; z = 5.43 p = 0.000, I2 = 0%). Subgroup analysis based on the duration of follow-up showed a lower odd of readmission within 30 days (OR = 0.36; 95% CI 0.18-0.71; z = 2.93; p = 0.003; I2 5.7%), as well as between 1 and 3 months (OR = 0.42; 95% CI 0.29-0.61; z = 4.54; p = 0.000; I2 = 0.0%). ReDS effect of lower readmissions of HF was observed irrespective of the duration of follow-up (<1-month vs 1-3 months). ReDS monitoring significantly lowers the odds of HF readmission within 3 months compared to participants not using ReDS.
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Gastrointestinal stromal tumors (GIST) are the most common mesenchymal soft tissue sarcoma of the gastrointestinal tract. The management of locally advanced or metastatic unresectable GIST involves detecting KIT, PDGFR, or other molecular alterations targeted by imatinib and other tyrosine kinase inhibitors. The role of immunotherapy in soft tissue sarcomas is growing fast due to multiple clinical and pre-clinical studies with no current standard of care. The potential therapies include cytokine-based therapy, immune checkpoint inhibitors, anti-KIT monoclonal antibodies, bi-specific monoclonal antibodies, and cell-based therapies. Here we provide a comprehensive review of the immunotherapeutic strategies for GIST.
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DNA technology is rapidly moving towards digitization. Scientists use software tools and applications for sequencing, synthesizing, analyzing and sharing of DNA and genomic data, operate lab equipment and store genetic information in shared datastores. Using cutting-edge computing methods and techniques, researchers have decoded human genome, created organisms with new capabilities, automated drug development and transformed food safety. Such software applications are typically developed to progress scientific understanding and as such cyber security is never a concern for these applications. However, with the increasing commercialisation of DNA technologies, coupled with the sensitivity of DNA data, there is a need to adopt a security-by-design approach. In this paper we investigate bio-cyber security threats to genomic-DNA data and software applications making use of such data to advance scientific research. Specifically, we adopt an empirical approach to analyse and identify vulnerabilities within genomic-DNA databases and bioinformatics software applications that can lead to cyber-attacks affecting the confidentiality, integrity and availability of such sensitive data. We present a detailed analysis of these threats and highlight potential protection mechanisms to help researchers pursue these research directions.
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Segurança Computacional , Privacidade , Confidencialidade , DNA , Genômica , HumanosRESUMO
Objective This trial aimed to evaluate the safety and efficacy of pre-exposure prophylaxis (PrEP) with various hydroxychloroquine (HCQ) doses against a placebo among healthcare personnel (HCP) with high-risk exposure to coronavirus disease 2019 (COVID 19). Methods A phase II, randomized, placebo-controlled trial was conducted including 200 subjects with no active or past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (antibody testing and reverse transcription-polymerase chain reaction (RT-PCR) were taken at the time of enrollment). Subjects of experimental groups one to three received HCQ in various doses and the control group received a placebo. The study outcomes in terms of safety and efficacy were monitored. Participants exhibiting COVID-19 symptoms were tested for SARS-CoV-2 during the study and by the end of week 12 with RT-PCR or serology testing (COVID-19 IgM/IgG antibody testing). Results Out of the total participants, 146 reported exposure to a confirmed COVID-19 case in the first month, and 192 were exposed by week 12 of the study. Moreover, the precautionary use of personal protective equipment (PPE) significantly varied; initially more than 80% of the exposed HCPs were not ensuring PPE being used by the patients treated by them, which gradually developed over time. Mild treatment-related side effects were observed among the interventional and placebo arm patients. There was no significant clinical benefit of PrEP with HCQ as compared to placebo (p>0.05). Conclusion It is concluded that the PrEP HCQ does not significantly prevent COVID-19 among high-risk HCPs.
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Today's smartphones are equipped with a large number of powerful value-added sensors and features, such as a low-power Bluetooth sensor, powerful embedded sensors, such as the digital compass, accelerometer, GPS sensors, Wi-Fi capabilities, microphone, humidity sensors, health tracking sensors, and a camera, etc. These value-added sensors have revolutionized the lives of the human being in many ways, such as tracking the health of the patients and the movement of doctors, tracking employees movement in large manufacturing units, monitoring the environment, etc. These embedded sensors could also be used for large-scale personal, group, and community sensing applications especially tracing the spread of certain diseases. Governments and regulators are turning to use these features to trace the people's thoughts to have symptoms of certain diseases or viruses, e.g., COVID-19. The outbreak of COVID-19 in December 2019, has seen a surge of the mobile applications for tracing, tracking, and isolating the persons showing COVID-19 symptoms to limit the spread of the disease to the larger community. The use of embedded sensors could disclose private information of the users, thus potentially bring a threat to the privacy and security of users. In this article, we analyzed a large set of smartphone applications that have been designed to contain the spread of the COVID-19 virus and bring the people back to normal life. Specifically, we have analyzed what type of permission these smartphone apps require, whether these permissions are necessary for the track and trace, how data from the user devices are transported to the analytic center, and analyzing the security measures these apps have deployed to ensure the privacy and security of users.
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Introduction: Gastrointestinal stromal tumor (GIST) is the most common malignant mesenchymal tumor of the gastrointestinal system. Multiple advances in the management of GIST from the discovery of KIT/PDGRA and other genetic alterations have led to the development of multiple tyrosine kinase inhibitors. Response assessment in GIST is determined with iRECIST (Response Evaluation Criteria in Solid Tumors), PERCIST (PET response criteria in solid tumors), or Choi criteria. Molecular genotyping of the tissue samples is the recent standard for diagnosis, treatment, and response to treatment.Areas covered: In this study, we provide a brief overview of the history of the GIST, molecular sequencing, available treatment options and clinical trials, radiologic response assessment, and the role of ctDNA in response evaluation.Expert opinion: Future GIST management is related to the development of sensitive assays to detect genetic alterations for initial diagnosis, treatment selection, monitoring the response to treatment, resistant mutations, and predicting survival.
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Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Desenvolvimento de Medicamentos , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Background: Leiomyosarcoma is a malignant mesenchymal tumor of cells of smooth muscle lineage arising commonly in retroperitoneum, uterus, large veins, and the limbs. The genetics of leiomyosarcomas are complex and there is very limited understanding of common driver mutations. Circulating tumor DNA (ctDNA) offers a rapid and noninvasive method of next-generation sequencing (NGS) that could be used for diagnosis, therapy, and detection of recurrence. Methods: ctDNA testing was performed using Guardant360, which detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion mutations in 73 genes using NGS. Results: Of 73 patients, 59 were found to have one or more cancer-associated genomic alteration. Forty-five (76%) were female with a median age of 63 (range, 38-87) years. All samples were designated metastatic. The most common alterations were detected in Tp53 (65%), BRAF (13%), CCNE (13%), EGFR (12%), PIK3CA (12%), FGFR1 (10%), RB1(10%), KIT (8%), and PDGFRA (8%). Some of the other alterations included RAF1, ERBB2, MET, PTEN TERT, APC, and NOTCH1. Potentially targetable mutations, by Food and Drug Administration-approved or clinical trials, were found in 24 (40%) of the 73 patients. Four patients (5%) were found to have incidental germline TP53 mutations. Conclusion: NGS of ctDNA allows identification of genomic alterations in plasma from patients with leiomyosarcoma. Unfortunately, there is limited activity of current targeted agents in leiomyosarcomas. These results suggest opportunities to develop therapy against TP53, cell cycle, and kinase signaling pathways. Further validation and prospective evaluation is warranted to investigate the clinical utility of ctDNA for patients with leiomyosarcoma.