ABSTRACT
Takayasu arteritis (TA) primarily causes ischaemic nephrosclerosis but can occasionally be associated with glomerulopathy. We report a case of a female in her twenties with PLA2-negative, THSD7A-positive membranous nephropathy (MN) refractory to rituximab, who presented with neck pain and new-onset hypertension. Blood work showed elevated inflammatory markers. Imaging of the head and neck revealed focal dilation and irregularity of the vertebral arteries, consistent with TA. The patient was started on treatment with steroids, followed by mycophenolate mofetil, which led to the resolution of symptoms and nephrotic syndrome. This case highlights an uncommon sequence of events, with MN presenting before TA, underscoring the need to consider TA in differentials for patients with MN. Notably, this is the first reported case in a young female, emphasising the need for further understanding of TA-associated glomerular diseases. Additionally, the presence of THSD7A in MN, despite negative malignancy workup, is also noteworthy. LEARNING POINTS: Membranous nephropathy (MN) and Takayasu arteritis (TA) have distinct clinical presentations; therefore, diagnosing coexisting MN and TA is challenging, which may lead to delayed diagnoses.A multidisciplinary approach with tailored treatments is essential for prompt diagnosis and optimal management.Comprehensive follow-up studies are vital to understand the pathogenesis of this rare amalgamation, refine targeted treatment strategies and potentially improve overall prognosis.
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Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype. India has the highest dengue burden worldwide, but little is known about disease severity and its association with primary and secondary dengue infections. To address this issue, we examined 619 children with febrile dengue-confirmed infection from three hospitals in different regions of India. We classified primary and secondary infections based on IgM:IgG ratios using a dengue-specific enzyme-linked immunosorbent assay according to the World Health Organization guidelines. We found that primary dengue infections accounted for more than half of total clinical cases (344 of 619), severe dengue cases (112 of 202) and fatalities (5 of 7). Consistent with the classification based on binding antibody data, dengue neutralizing antibody titers were also significantly lower in primary infections compared to secondary infections (P ≤ 0.0001). Our findings question the currently widely held belief that severe dengue is associated predominantly with secondary infections and emphasizes the importance of developing vaccines or treatments to protect dengue-naive populations.
Subject(s)
Coinfection , Dengue Virus , Dengue , Severe Dengue , Humans , Child , Dengue/epidemiology , Severe Dengue/epidemiology , Antibodies, Viral , Coinfection/epidemiology , FeverABSTRACT
Importance: Economic policies have the potential to impact management and control of hypertension. Objectives: To review the evidence on the association between economic policies and hypertension management and control among adults with hypertension in the US. Evidence Review: A search was carried out of PubMed/MEDLINE, Cochrane Library, Embase, PsycINFO, CINAHL, EconLit, Sociological Abstracts, and Scopus from January 1, 2000, through November 1, 2023. Included were randomized clinical trials, difference-in-differences, and interrupted time series studies that evaluated the association of economic policies with hypertension management. Economic policies were grouped into 3 categories: insurance coverage expansion such as Medicaid expansion, cost sharing in health care such as increased drug copayments, and financial incentives for quality such as pay-for-performance. Antihypertensive treatment was measured as taking antihypertensive medications or medication adherence among those who have a hypertension diagnosis; and hypertension control, measured as blood pressure (BP) lower than â140/90 mm Hg or a reduction in BP. Evidence was extracted and synthesized through dual review of titles, abstracts, full-text articles, study quality, and policy effects. Findings: In total, 31 articles were included. None of the studies examined economic policies outside of the health care system. Of these, 16 (52%) assessed policies for insurance coverage expansion, 8 (26%) evaluated policies related to patient cost sharing for prescription drugs, and 7 (22%) evaluated financial incentive programs for improving health care quality. Of the 16 studies that evaluated coverage expansion policies, all but 1 found that policies such as Medicare Part D and Medicaid expansion were associated with significant improvement in antihypertensive treatment and BP control. Among the 8 studies that examined patient cost sharing, 4 found that measures such as prior authorization and increased copayments were associated with decreased adherence to antihypertensive medication. Finally, all 7 studies evaluating financial incentives aimed at improving quality found that they were associated with improved antihypertensive treatment and BP control. Overall, most studies had a moderate or low risk of bias in their policy evaluation. Conclusions and Relevance: The findings of this systematic review suggest that economic policies aimed at expanding insurance coverage or improving health care quality successfully improved medication use and BP control among US adults with hypertension. Future research is needed to investigate the potential effects of non-health care economic policies on hypertension control.
Subject(s)
Hypertension , Medicare Part D , Aged , Adult , Humans , United States/epidemiology , Antihypertensive Agents/therapeutic use , Reimbursement, Incentive , Hypertension/drug therapy , Delivery of Health CareABSTRACT
Pesticide is an inevitable substance used worldwide to kill pests, but their indiscriminate use has posed serious complications to health and the environment. Various physical, chemical, and biological methods are employed for pesticide treatment, but this paper deals with microbial fuel cell (MFC) as a futuristic technology for pesticide degradation with electricity production. In MFC, organic compounds are utilized as the carbon source for electricity production and the generation of electrons which can be replaced with pollutants such as dyes, antibiotics, and pesticides as carbon sources. However, MFC is been widely studied for a decade for electricity production, but its implementation in pesticide degradation is less known. We fill this void by depicting a real picture of the global pesticide scenario with an eagle eye view of the bioremediation techniques implemented for pesticide treatment with phytoremediation and rhizoremediation as effective techniques for efficient pesticide removal. The enormous literature survey has revealed that not many researchers have ventured into this new arena of MFC employed for pesticide degradation. Based on the Scopus database, an increase in annual trend from 2014 to 2023 is observed for MFC-implemented pesticide remediation. However, a novel MFC to date for effective remediation of pesticides with simultaneous electricity generation is discussed for the first time. Furthermore, the limitation of MFC technology and the implementation of MFC and rhizoremediation as a clubbed system which is the least applied can be seen as promising and futuristic approaches to enhance pesticide degradation by bacteria and electricity as a by-product.
Subject(s)
Bioelectric Energy Sources , Pesticides , Electricity , Organic Chemicals , Carbon , ElectrodesABSTRACT
BACKGROUND: Unexpected hypermetabolic activity is often encountered in the gastrointestinal tract when PET/CT is performed for various indications, prompting endoscopic evaluation. Our aim was to characterize the types of lesions seen in segments of the gastrointestinal tract with unexpected PET/CT abnormalities as well as clinically significant lesions seen on endoscopy which did not produce a PET/CT abnormality to guide the endoscopist tasked with evaluating these imaging findings. METHODS: We retrospectively reviewed a database of endoscopies performed at City of Hope Comprehensive Cancer Center between January 1, 2016 and September 30, 2021 for an indication of "abnormal PET." We divided the gastrointestinal tract into segments and defined categories of endoscopic/histologic findings for each segment. We counted the number of segments with an abnormal PET/CT finding and corresponding endoscopic/histologic abnormality as well as the number of segments with an endoscopic/histologic abnormality but normal PET/CT. RESULTS: PET/CT identified 209 segments with hypermetabolic activity, 109 of which had corresponding endoscopic/histologic abnormalities. In the jejunum and ileum, all corresponding lesions were malignant. Seventy-three percent of corresponding lesions in the stomach were H. pylori positive. PET/CT failed to detect 34.7% of clinically significant lesions diagnosed endoscopically, including 1 malignancy in the transverse colon and many inflammatory or low-risk premalignant lesions. CONCLUSION: PET/CT abnormalities seen in the small bowel should be evaluated urgently as nearly all correlates were malignant, while abnormalities in the stomach should prompt workup for H. pylori. Most lesions missed by PET/CT were inflammatory or low-risk premalignant yet clinically significant, confirming the need to inspect the entirety of the upper or lower gastrointestinal tract during endoscopy.
Subject(s)
Positron Emission Tomography Computed Tomography , Precancerous Conditions , Humans , Retrospective Studies , Fluorodeoxyglucose F18 , Gastrointestinal Tract/diagnostic imaging , Endoscopy, Gastrointestinal , Positron-Emission TomographyABSTRACT
The Siglecs (sialic acid-binding immunoglobulin-like lectins) are glycoimmune checkpoint receptors that suppress immune cell activation upon engagement of cognate sialoglycan ligands. The cellular drivers underlying Siglec ligand production on cancer cells are poorly understood. We find the MYC oncogene causally regulates Siglec ligand production to enable tumor immune evasion. A combination of glycomics and RNA-sequencing of mouse tumors revealed the MYC oncogene controls expression of the sialyltransferase St6galnac4 and induces a glycan known as disialyl-T. Using in vivo models and primary human leukemias, we find that disialyl-T functions as a "don't eat me" signal by engaging macrophage Siglec-E in mice or the human ortholog Siglec-7, thereby preventing cancer cell clearance. Combined high expression of MYC and ST6GALNAC4 identifies patients with high-risk cancers and reduced tumor myeloid infiltration. MYC therefore regulates glycosylation to enable tumor immune evasion. We conclude that disialyl-T is a glycoimmune checkpoint ligand. Thus, disialyl-T is a candidate for antibody-based checkpoint blockade, and the disialyl-T synthase ST6GALNAC4 is a potential enzyme target for small molecule-mediated immune therapy.
Subject(s)
Neoplasms , Proto-Oncogene Proteins c-myc , Sialic Acid Binding Immunoglobulin-like Lectins , Animals , Humans , Mice , Antigens, CD/metabolism , Ligands , Macrophages/metabolism , Neoplasms/metabolism , Sialic Acid Binding Immunoglobulin-like Lectins/metabolism , Proto-Oncogene Proteins c-myc/metabolismABSTRACT
Aquaculture is a fast-growing food sector but is plagued by a plethora of bacterial pathogens that infect fish. The rearing of fish at high population densities in aquaculture facilities makes them highly susceptible to disease outbreaks, which can cause significant economic loss. Thus, immunity development in fish through vaccination against various pathogens of economically important aquaculture species has been extensively studied and has been largely accepted as a reliable method for preventing infections. Vaccination studies in aquaculture systems are strategically associated with the economically and environmentally sustainable management of aquaculture production worldwide. Historically, most licensed fish vaccines have been developed as inactivated pathogens combined with adjuvants and provided via immersion or injection. In comparison, live vaccines can simulate a whole pathogenic illness and elicit a strong immune response, making them better suited for oral or immersion-based therapy methods to control diseases. Advanced approaches in vaccine development involve targeting specific pathogenic components, including the use of recombinant genes and proteins. Vaccines produced using these techniques, some of which are currently commercially available, appear to elicit and promote higher levels of immunity than conventional fish vaccines. These technological advancements are promising for developing sustainable production processes for commercially important aquatic species. In this review, we explore the multitude of studies on fish bacterial pathogens undertaken in the last decade as well as the recent advances in vaccine development for aquaculture.
ABSTRACT
Gastrostomy tube placement is a procedure that achieves enteral access for nutrition, decompression, and medication administration. Preprocedural evaluation and selection of patients is necessary to provide optimal benefit and reduce the risk of adverse events (AEs). Appropriate indications, contraindications, ethical considerations, and comorbidities of patients referred for gastrostomy placement should be weighed and balanced. Additionally, endoscopist should consider either a transoral or transabdominal approach is appropriate, and radiologic or surgical gastrostomy tube placement is needed. However, medical history, physical examination, and imaging prior to the procedure should be considered to tailor the appropriate approach and reduce the risk of AEs.
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Background: Extensive evidence of elevated chromium (Cr) in the surface and groundwater exists. However, the importance of exposure toward Cr-associated health risks in areas with tanneries is still often neglected. These situations prompted an independent research study to investigate the views of those close-knit communities who are being directly affected by this tannery village. Objectives: To establish an understanding of the local demographics and; exploratory data analysis (EDA) to discover patterns in the occurrence of diseases; measure the awareness of residents of the presence of Cr and its harmful health effects. Methods: The EDA technique was used to conduct survey studies on data to uncover patterns, identify anomalies, test hypotheses, and validate assumptions using summary statistics and graphical representations. Results: Out of 14 diseases directly linked to high Cr toxicity, the study reported high levels of diarrhea, epigastric pain, and moderate-to-severe cases of vertigo among those aged more than 22 years. With over 90 active tanneries and toxic Cr released to the environment in a town of <78 km2 area (1.2 tannery/km), there are only 15 hospitals (0.2 hospitals/km) for the population currently accommodating more than a quarter-million people daily (3205 people/km). Conclusion: New mitigation strategies must be put forth to alleviate the negative impacts of the tanneries on the residents and nature most affected as well as the population as a whole.
Subject(s)
Chromium , Public Health , Adult , Chromium/analysis , Chromium/toxicity , Humans , India/epidemiology , Tanning , Wastewater , Young AdultABSTRACT
BACKGROUND: The fecal immunochemical test (FIT) is the primary modality used by the Los Angeles County Department of Health Services (LADHS) for colorectal cancer (CRC) screening in average-risk patients. Some patients referred for FIT-positive diagnostic colonoscopy have neither adenomas nor more advanced pathology. We aimed to identify predictors of false-positive FIT (FP-FIT) results in our largely disenfranchised, low socioeconomic status population. METHODS: We conducted a retrospective study of 596 patients who underwent diagnostic colonoscopy following a positive screening FIT. Colonoscopies showing adenomas (or more advanced pathology) were considered positive. We employed multiple logistic and linear regression as well as machine learning models (MLMs) to identify clinical predictors of FP-FIT (primary outcome) and the presence of advanced adenomas (secondary outcome). RESULTS: Overall, 268 patients (45.0%) had a FP-FIT. Female sex and hemorrhoids (odds ratios [ORs] 1.59 and 1.89, respectively) were associated with increased odds of FP-FIT and fewer advanced adenomas (ß = - 0.658 and - 0.516, respectively). Conversely, increasing age and BMI (ORs 0.94 and 0.96, respectively) were associated with decreased odds of FP-FIT and a greater number of advanced adenomas (ß = 0.073 and 0.041, respectively). MLMs predicted FP-FIT with high specificity (93.8%) and presence of advanced adenoma with high sensitivity (94.4%). CONCLUSION: Increasing age and BMI are associated with lower odds of FP-FIT and greater number of advanced adenomas, while female sex and hemorrhoids are associated with higher odds of FP-FIT and fewer advanced adenomas. The presence of the aforementioned predictors may inform the decision to proceed with diagnostic colonoscopy in FIT-positive patients.
Subject(s)
Adenoma , Colorectal Neoplasms , Hemorrhoids , Adenoma/diagnosis , Adenoma/epidemiology , Adenoma/pathology , Colonoscopy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/pathology , Early Detection of Cancer/methods , Feces , Female , Humans , Mass Screening/methods , Occult Blood , Retrospective StudiesABSTRACT
BACKGROUND AND AIM: Immune checkpoint inhibitors (ICIs) have shown promise in treating a variety of cancers. Their increased use coincides with increased incidence of immunotherapy-mediated colitis (IMC), a common adverse effect. Optimal strategy for endoscopic evaluation of IMC (full colonoscopy or flexible sigmoidoscopy) is not well-defined. METHODS: Retrospective review of all patients at City of Hope referred to gastroenterology for evaluation of IMC due to gastrointestinal symptoms was performed. Patients with an existing histologic diagnosis of IMC established at an outside hospital or a diagnosis of infectious or chronic colitis were excluded. RESULTS: We identified 51 symptomatic patients on ICIs prompting evaluation for IMC with colonoscopy (47/51) or flexible sigmoidoscopy (4/51). All distal rectosigmoid biopsies during flexible sigmoidoscopy demonstrated histologic evidence of IMC. In full colonoscopy, IMC was either present in all segments of colon simultaneously (35/47) or absent from all segments (12/47). No isolated proximal colonic biopsies demonstrated IMC. Endoscopically normal mucosa demonstrated histologic evidence of IMC up to 68.6% of the time. Endoscopically abnormal right, transverse, and left colon had low sensitivity (35.3%, 34.3%, and 41.7%, respectively) and high specificity (100.0%, 100.0%, and 91.7%, respectively) for histological presence of IMC. CONCLUSIONS: Distal colon biopsies in patients on ICI therapy with diarrhea and suspected IMC were sufficient for diagnosing IMC in our cohort. Further, we found histologic evidence of IMC in biopsies taken from normal-appearing mucosa in a number of patients, suggesting that a normal endoscopic appearance does not preclude the presence of IMC and biopsies should be taken from both normal and abnormal-appearing mucosa.
Subject(s)
Colitis , Immunotherapy , Sigmoidoscopy , Colitis/diagnosis , Cross-Sectional Studies , Humans , Immunotherapy/adverse effects , Retrospective Studies , Sensitivity and SpecificityABSTRACT
BACKGROUND: Tall cell variant of papillary thyroid carcinoma is an aggressive subtype of papillary thyroid carcinoma. We examined expression of cancer stem cell markers in tall cell variant compared with other well-differentiated thyroid cancers. METHODS: Expression of cancer stem cell markers was examined in 572 thyroid tumors from The Cancer Genome Atlas Thyroid Cancer database and tall cell variant and papillary thyroid carcinoma tumors by immunohistochemistry. RESULTS: Expression of the PROM1 gene, encoding the cancer stem cell marker CD133, was elevated in tall cell variant compared to classic papillary thyroid carcinoma in a large cohort of unmatched samples from The Cancer Genome Atlas Thyroid Cancer database (P < .001). By immunohistochemistry in age and stage matched samples, CD133 protein was confirmed to be significantly increased in tall cell variant versus classic papillary thyroid carcinoma (P = .006). Analyzing all thyroid cancers, high PROM1 expression was associated with worse disease-specific survival. Optimal cutoffs were determined to define a tall cell variant-like cancer stem cell signature characterized by high PROM1, high ALDH1A3, and low CD24 expression. Classic papillary thyroid carcinoma with a tall cell variant-like gene signature had worse recurrence disease-free survival compared to classic papillary thyroid carcinoma with a non-tall cell variant signature (P = .02). CONCLUSION: Tall cell variant of papillary thyroid carcinoma has increased expression of cancer stem cell markers compared to classic papillary thyroid carcinoma. The tall cell variant-like cancer stem cell gene signature identified a molecular subtype of classic papillary thyroid carcinoma that has a worse recurrence-free survival.
Subject(s)
Biomarkers, Tumor/metabolism , Neoplasm Recurrence, Local/epidemiology , Neoplastic Stem Cells/metabolism , Thyroid Cancer, Papillary/mortality , Thyroid Gland/pathology , Biomarkers, Tumor/analysis , Disease-Free Survival , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Neoplastic Stem Cells/pathology , Retrospective Studies , Risk Assessment/methods , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/therapy , Thyroid Gland/cytology , Thyroid Neoplasms/pathologyABSTRACT
Bioremediation is an essential feature of microorganisms concerning contaminations in soil and water. The use of microorganisms has been proved to be an effective treatment of industrially released effluents comprising of heavy metals, such as chromium (VI). In the current study, seasonal variations were observed in the concentrations of chromium(VI) as the samples from selected locations showed an increase in mean concentration during the summer compared to the low mean during winter, suggesting excessive evaporation in the summer leading to the heavy metal accumulation. Among the 35 isolates obtained from tannery effluent contaminated wastewater sources the 3 unique strains identified as Streptococcus pyogenes strain APRRJVITS10, Pseudomonas putida strain APRRJVITS11, and Bacillus thuringiensis strain APRRJVITS15, showed tolerance toward chromium(VI) and the maximum tolerance for each strain was 1250 ppm. The media optimization through shake flask methods showed chromium(VI) (in 100 ml LB broth) removal of 47.82%, 48.11%, and 49.93% by S. pyogenes, P. putida, and B. thuringiensis respectively. Further, Pseudomonas putida showed chromium(VI) (in 1500 ml LB broth) removal of 50.48% in optimized conditions, proving to be highly potential for treating effluent wastewater for chromium(VI) removal.
Subject(s)
Chromium/isolation & purification , Pseudomonas putida/metabolism , Wastewater/chemistry , Water Pollutants, Chemical/isolation & purification , Bacillus thuringiensis/metabolismABSTRACT
PURPOSE: This surgical window of opportunity (window) study assessed the short-term effect of medroxyprogesterone acetate (MPA) alone versus MPA plus the histone deacetylase (HDAC) inhibitor entinostat on regulation of progesterone receptor (PR) in women with newly diagnosed endometrioid endometrial adenocarcinoma. PATIENTS AND METHODS: This multisite, randomized, open-label surgical window study treated women intramuscularly on day 1 with 400 mg MPA. Entinostat given 5 mg by mouth on days 1, 8, and 15 was randomly assigned with equal probability. Surgery followed on days 21-24. Pretreatment and posttreatment tissue was assessed for PR H-scores, Ki-67 levels, and histologic response. RESULTS: Fifty patients were accrued in 4 months; 22 and 20 participants had PR evaluable pretreatment and posttreatment slides in the MPA and MPA/entinostat arms, respectively. Median posttreatment PR H-scores were significantly lower than pretreatment H-scores in both arms but did not differ significantly (MPA: 247 vs. 27, MPA/entinostat 260 vs. 23, respectively, P = 0.87). Decreased Ki-67 was shown in 90% treated with MPA/entinostat compared with 68% treated with MPA alone (P = 0.13). Median PR H-score decreases were larger when Ki-67 was decreased (208) versus not decreased (45). The decrease in PR pretreatment versus posttreatment was associated with loss of Ki-67 nuclear staining, consistent with reduced cellular proliferation (P < 0.008). CONCLUSIONS: This surgical window trial rapidly accrued in a multisite setting and evaluated PR as its primary endpoint and Ki-67 as secondary endpoint. Despite no immediate effect of entinostat on PR in this short-term study, lessons learned can inform future window and treatment trials.
Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Endometrial Neoplasms/therapy , Hysterectomy , Medroxyprogesterone Acetate/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Benzamides/administration & dosage , Clinical Decision-Making , Disease Management , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/etiology , Female , Humans , Hysterectomy/methods , Medroxyprogesterone Acetate/administration & dosage , Medroxyprogesterone Acetate/adverse effects , Middle Aged , Pyridines/administration & dosage , Time-to-Treatment , Treatment OutcomeABSTRACT
The Toll-like receptor 8 (TLR8) agonist VTX-2337 (motolimod) is an anti-cancer immunotherapeutic agent that is believed to augment natural killer (NK) and dendritic cell (DC) activity. The goal of this work is to examine the role of TLR8 expression/activity in head and neck squamous cell carcinoma (HNSCC) to facilitate the prediction of responders to VTX-2337-based therapy. The prognostic role of TLR8 expression in HNSCC patients was assessed by TCGA and tissue microarray analyses. The anti-tumor effect of VTX-2337 was determined in SCCVII/C3H, mEERL/C57Bl/6 and TUBO-human EGFR/BALB/c syngeneic mouse models. The effect of combined VTX-2337 and cetuximab treatment on tumor growth, survival and immune cell recruitment was assessed. TLR8 expression was associated with CD8+ T cell infiltration and favorable survival outcomes. VTX-2337 delayed tumor growth in all 3 syngeneic mouse models and significantly increased the survival of cetuximab-treated mice. The anti-tumor effects of VTX-2337+ cetuximab were accompanied by increased splenic lymphoid DCs and IFNγ+ CD4+ and tumor-specific CD8+ T cells. Depletion of CD4+ T cells, CD8+ T cells and NK cells were all able to abolish the anti-tumor effect of VTX-2337+ cetuximab. Altogether, VTX-2337 remains promising as an adjuvant for cetuximab-based therapy however patients with high TLR8 expression may be more likely to derive benefit from this drug combination compared to patients with low TLR8 expression.
Subject(s)
Benzazepines/pharmacology , Cetuximab/pharmacology , T-Lymphocytes/metabolism , Animals , Antibody-Dependent Cell Cytotoxicity/immunology , Antineoplastic Agents/pharmacology , Benzazepines/metabolism , Biomarkers, Pharmacological , CD8-Positive T-Lymphocytes/immunology , Cell Line, Tumor , Cetuximab/metabolism , Cytokines/metabolism , Databases, Genetic , Female , Gene Expression/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Killer Cells, Natural/immunology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , Neoplasms/drug therapy , Neoplasms/immunology , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/immunology , T-Lymphocytes/immunology , Toll-Like Receptor 8/drug effects , Toll-Like Receptor 8/genetics , Toll-Like Receptor 8/metabolismABSTRACT
BACKGROUND AND AIMS: Noninvasive predictors of choledocholithiasis have generally exhibited marginal performance characteristics. We aimed to identify noninvasive independent predictors of endoscopic retrograde cholangiopancreatography (ERCP)-confirmed choledocholithiasis and accordingly developed predictive machine learning models (MLMs). METHODS: Clinical data of consecutive patients undergoing first-ever ERCP for suspected choledocholithiasis from 2015-2019 were abstracted from a prospectively-maintained database. Multiple logistic regression was used to identify predictors of ERCP-confirmed choledocholithiasis. MLMs were then trained to predict ERCP-confirmed choledocholithiasis using pre-ERCP ultrasound (US) imaging only and separately using all available noninvasive imaging (US/CT/magnetic resonance cholangiopancreatography). The diagnostic performance of American Society for Gastrointestinal Endoscopy (ASGE) "high-likelihood" criteria was compared to MLMs. RESULTS: We identified 270 patients (mean age 46 years, 62.2% female, 73.7% Hispanic/Latino, 59% with noninvasive imaging positive for choledocholithiasis) with native papilla who underwent ERCP for suspected choledocholithiasis, of whom 230 (85.2%) were found to have ERCP-confirmed choledocholithiasis. Logistic regression identified choledocholithiasis on noninvasive imaging (odds ratio (OR) = 3.045, P = 0.004) and common bile duct (CBD) diameter on noninvasive imaging (OR=1.157, P = 0.011) as predictors of ERCP-confirmed choledocholithiasis. Among the various MLMs trained, the random forest-based MLM performed best; sensitivity was 61.4% and 77.3% and specificity was 100% and 75.0%, using US-only and using all available imaging, respectively. ASGE high-likelihood criteria demonstrated sensitivity of 90.9% and specificity of 25.0%; using cut-points achieving this specificity, MLMs achieved sensitivity up to 97.7%. CONCLUSIONS: MLMs using age, sex, race, presence of diabetes, fever, body mass index (BMI), total bilirubin, maximum CBD diameter, and choledocholithiasis on pre-ERCP noninvasive imaging predict ERCP-confirmed choledocholithiasis with good sensitivity and specificity and outperform the ASGE criteria for patients with suspected choledocholithiasis.
ABSTRACT
Numerical simulation is growing in its importance toward the design, testing and evaluation of medical devices. Computational fluid dynamics and finite element analysis allow improved calculation of stress, heat transfer, and flow to better understand the medical device environment. Current research focuses not only on improving medical devices, but also on improving the computational tools themselves. As methods and computer technology allow for faster simulation times, iterations and trials can be performed faster to collect more data. Given the adverse events associated with long-term inferior vena cava (IVC) filter placement, IVC filter design and device evaluation are of paramount importance. This work reviews computational methods used to develop, test, and improve IVC filters to ultimately serve the needs of the patient.
Subject(s)
Vena Cava Filters , Computer Simulation , Device Removal , Humans , Hydrodynamics , Vena Cava, InferiorABSTRACT
Bioremediation is an important function of microorganisms in relation to contaminated soils, wastewater and effluent. Microbes have always been demonstrated to be cost-efficient in the treatment of industrial effluents containing heavy metals like chromium(VI). As more and more new and novel isolates are being discovered with having the ability to acclimatize to varying environments. The application of microorganisms, especially that of bacteria, proves to be showing a greater potential as a low costing biotechnological application. The procedure can be adjusted according to the needs and conditional requirements where the bio-absorbents utilized might be either dead or living. Microbial bioabsorption of chromium(VI) stands out to be an alternative for the removal of the toxic contaminant. This review is focused on the different biosorbent features appropriate in the removal of chromium; different types of bioreactors; and the evolution of research with an overview of bioabsorption.