Gold Nanoprobes for Detection of a Crucial EGFR Deletion for Early Diagnosis of Non-Small-Cell Lung Cancer.

Gold nanoparticles (AuNPs) exhibit improved optical and spectral properties compared to bulk materials, making them suitable for the detection of DNA, RNA, antigens, and antibodies. Here, we describe a simple, selective, and rapid non-cross linking detection assay, using approx. 35 nm spherical Au nanoprobes, for a common mutation occurring in exon 19 of the epidermal growth factor receptor (EGFR), associated with non-small-cell lung cancer cells. AuNPs were synthesized based on the seed-mediated growth method and functionalized with a specific 16 bp thiolated oligonucleotide using a pH-assisted method. Both AuNPs and Au nanoprobes proved to be highly stable and monodisperse through ultraviolet-visible spectrophotometry, dynamic light scattering (DLS), and electrophoretic light scattering (ELS). Our results indicate a detection limit of 1.5 µg mL-1 using a 0.15 nmol dm-3 Au nanoprobe concentration. In conclusion, this work presents an effective possibility for a straightforward, fast, and inexpensive alternative for the detection of DNA sequences related to lung cancer, leading to a potential platform for early diagnosis of lung cancer patients.

Leveraging opportunities for treatment/user simplicity (LOTUS): Navigating the current treatment landscape for achieving hepatitis C virus elimination among persons who inject drugs.

All-oral, direct-acting antivirals can cure hepatitis C virus (HCV) in almost all infected individuals; yet, many individuals with chronic HCV are not treated, and the incidence of acute HCV is increasing in some countries, including the United States. Strains on healthcare resources during the COVID-19 pandemic negatively impacted the progress toward the World Health Organization goal to eliminate HCV by 2030, especially among persons who inject drugs (PWID). Here, we present a holistic conceptual framework termed LOTUS (Leveraging Opportunities for Treatment/User Simplicity), designed to integrate the current HCV practice landscape and invigorate HCV treatment programs in the setting of endemic COVID-19: (A) treatment as prevention (especially among PWID), (B) recognition that HCV cure may be achieved with variable adherence with evidence supporting some forgiveness for missed doses, (C) treatment of all persons with active HCV infection (viremic), regardless of acuity, (D) minimal monitoring (MinMon) during treatment, and (E) rapid test and treat (TnT). The objective of this article is to review the current literature supporting each LOTUS petal; identify remaining gaps in knowledge or data; define the remaining barriers facing healthcare providers; and review evidence-based strategies for overcoming key barriers.

Birth cohort-specific consideration in an Emergency Department Hepatitis C Testing Programme: A description of age-related characteristics and outcomes.

The emergency department (ED) has increasingly become an important public health partner in non-targeted hepatitis C virus (HCV) testing and referral to care efforts. HCV has traditionally been an infection associated with the Baby Boomer generation; however, recent exacerbation of the opioid epidemic has resulted in a growing number of younger cohorts, namely Millennials, also impacted by HCV. Examination of this age-related demographic shift, including subsequent linkage success and linkage barriers, from the perspective of an ED-based testing and linkage programme may have implications for future population and health systems interventions. A retrospective descriptive chart review was performed, inclusive of data from August 2015 through December 2020. We compared the quantity of positive HCV screening antibody (Ab) and confirmatory (RNA) tests and further considered linkage rates and correlative demographics (e.g. gender, race). Patient barriers to HCV care linkage (e.g. substance misuse, lack of health insurance, homelessness) were also evaluated. The data set was disaggregated by birth cohort to include Silent Generation (SG) (1928-45), Baby Boomer (BB) (1946-64), Generation X (Gen X) (1965-80), Millennial (1981-96) and Generation Z (1997-2012). Descriptive statistics and chi-square analysis were performed. Overall, 83,817 patients were tested for HCV (50.6% of eligible); 6187 (7.4%) were HCV Ab positive, and 2665 were HCV RNA positive (3.2%). RNA-positive individuals were more likely to be white (70.4%) and male (67.7%); generational distribution was similar (BB 33.3%, Gen X 32.0% and Millennials 32.7%). Amongst Ab-positive patients, white (45.5%), male (47.2%) and Millennial (49.7%) individuals were most likely to be RNA-positive. Overall, 28.1% of the RNA-positive cohort successfully linked to care; linkage to care rates were significantly higher in older generations (38.1% in BB vs. 17.8% in Millennials) (p < .00001). Over 90% were identified as having at least one linkage to care barrier. Younger generations (Gen X and Millennials) were disproportionately impacted by linkage barriers, including incarceration, lack of health insurance, history of mental health and substance use disorders, as well as history of or active injection drug use (IDU) (p < .00001). Older generations (SG and BB) were more likely to be impacted by competing medical comorbidities (p < .00001). The ED population represents a particularly vulnerable, at-risk cohort with a high prevalence of HCV and linkage to care barriers. While past HCV-specific recommendations and interventions have focused on Baby Boomers, this data suggests that younger generations, including Gen X and Millennials, are increasingly affected by HCV and face disparate social risk and social need factors which impede definitive care linkage and treatment.

Hepatitis C Virus Elimination Programs in Louisiana and Washington: Importance of Screening and Surveillance Systems.

The US government has established a national goal of hepatitis C virus (HCV) elimination by 2030. To date, most HCV elimination planning and activity have been at the state level. Fifteen states presently have publicly available HCV elimination plans. In 2019, Louisiana and Washington were the first states to initiate 5-year funded HCV elimination programs. These states differ on motivation for pursuing HCV elimination and ranking on several indicators. Simultaneously, however, they have emphasized several similar elimination components including HCV screening promotion through public awareness, screening expansion, surveillance enhancement (including electronic reporting and task force development), and harm reduction. The 13 other states with published elimination plans have proposed the majority of the elements identified by Louisiana and Washington, but several have notable gaps. Louisiana's and Washington's comprehensive plans, funding approaches, and programs provide a useful framework that can move states and the nation toward HCV elimination.

Sustained virologic response from hepatitis C from an emergency department screening & linkage program: A retrospective review.

INTRODUCTION: The role of the Emergency Department (ED) as a vital constituent in Hepatitis C (HCV) screening has become increasingly evident. A key component of the ED's role in HCV screening is the ability to effectively link HCV-RNA positive patients to definitive, HCV-specific care, to include direct-acting antiviral (DAA) medication with resultant sustained virologic response (SVR). We sought to consider the rate of HCV-specific linkage, DAA initiation, and SVR obtained in HCV patients identified from an ED screening program. METHODS: A retrospective chart review was conducted in February of 2022 of all individuals who participated in an opt-out ED-based HCV screening program between January 2018 and December 2019. Data was disaggregated by race, gender, age/birth cohort, insurance status, and achievement of sustained virologic response (SVR). Bivariate analysis using Pearson's chi-square was utilized to compare outcomes based on insurance status, race, sex, and birth cohort. RESULTS: Of 66,634 individuals screened for HCV during the study period, 885 (1.33%) patients were RNA-positive. Of those individuals, 121 (13.67%) were linked to HCV-specific care. Of those linked, the majority (66.9%) were male, white (66.1%; 33.1% Black), baby boomers or older (53.7%) and publicly insured (57.9%; private insurance 23.1%, self-pay 19%). Among linked patients, 88 (72.7%) started DAA medication. Mirroring linked demographics, majority were male (64.8%), white (64.8%), baby boomers or older (52.3%), and publicly insured (57.6%). White patients initiated on DAA were more likely to obtain SVR (64.9% versus 41.9% Black; p = .04) and uninsured patients were more likely to obtain SVR (82.4% versus 50.7% insured; p = .02). Bivariate consideration of SVR-patients specifically demonstrates that Black patients tended to be older, with significant overrepresentation of Baby boomers (77.5%) as compared to whites (37.5%; p < .0001). Black patients were also more likely to be publicly insured (82.5%) while white patients were more likely to have private insurance (28.8%) or be uninsured (26.3%) than their Black counterparts (12.5% and 5% respectively; p < .05). CONCLUSION: An ED-based HCV screening program can result in successful HCV-specific linkage and care, to include DAA initiation and ultimately, SVR. Among linked patients, specific cohort considerations may demonstrate differences in age and insurance status which may have implications on DAA application and adherence, and therefore, individual ability to achieve SVR.

A simple polystyrene microfluidic device for sensitive and accurate SERS-based detection of infection by malaria parasites.

Early and accurate detection of infection by pathogenic microorganisms, such as Plasmodium, the causative agent of malaria, is critical for clinical diagnosis and ultimately determines the patient's outcome. We have combined a polystyrene-based microfluidic device with an immunoassay which utilises Surface-Enhanced Raman Spectroscopy (SERS) to detect malaria. The method can be easily translated to a point-of-care testing format and shows excellent sensitivity and specificity, when compared to the gold standard for laboratorial detection of Plasmodium infections. The device can be fabricated in less than 30 min by direct patterning on shrinkable polystyrene sheets of adaptable three-dimensional microfluidic chips. To validate the microfluidic system, samples of P. falciparum-infected red blood cell cultures were used. The SERS-based immunoassay enabled the detection of 0.0012 ± 0.0001% parasitaemia in a P. falciparum-infected red blood cell culture supernatant, an ∼7-fold higher sensitivity than that attained by most rapid diagnostic tests. Our approach successfully overcomes the main challenges of the current Plasmodium detection methods, including increased reproducibility, sensitivity, and specificity. Furthermore, our system can be easily adapted for detection of other pathogens and has excellent properties for early diagnosis of infectious diseases, a decisive step towards lowering their high burden on healthcare systems worldwide.

Hepatitis C Treatment Initiation Among US Medicaid Enrollees.

Importance: Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection is highly effective but remains underused. Understanding disparities in the delivery of DAAs is important for HCV elimination planning and designing interventions to promote equitable treatment. Objective: To examine variations in the receipt of DAA in the 6 months following a new HCV diagnosis. Design, Setting, and Participants: This retrospective cohort study used national Medicaid claims from 2017 to 2019 from 50 states, Washington DC, and Puerto Rico. Individuals aged 18 to 64 years with a new diagnosis of HCV in 2018 were included. A new diagnosis was defined as a claim for an HCV RNA test followed by an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis code, after a 1-year lookback period. Main Outcomes and Measures: Outcome was receipt of a DAA prescription within 6 months of diagnosis. Logistic regression was used to examine demographic factors and ICD-10-identified comorbidities associated with treatment initiation. Results: Among 87 652 individuals, 43 078 (49%) were females, 12 355 (14%) were age 18 to 29 years, 35 181 (40%) age 30 to 49, 51 282 (46%) were non-Hispanic White, and 48 840 (49%) had an injection drug use diagnosis. Of these individuals, 17 927 (20%) received DAAs within 6 months of their first HCV diagnosis. In the regression analyses, male sex was associated with increased treatment initiation (OR, 1.24; 95% CI, 1.16-1.33). Being age 18 to 29 years (OR, 0.65; 95% CI, 0.50-0.85) and injection drug use (OR, 0.84; 95% CI, 0.75-0.94) were associated with decreased treatment initiation. After adjustment for state fixed effects, Asian race (OR, 0.50; 95% CI, 0.40-0.64), American Indian or Alaska Native race (OR, 0.68; 95% CI, 0.55-0.84), and Hispanic ethnicity (OR, 0.81; 95% CI, 0.71-0.93) were associated with decreased treatment initiation. Adjustment for state Medicaid policy did not attenuate the racial or ethnic disparities. Conclusions: In this retrospective cohort study, HCV treatment initiation was low among Medicaid beneficiaries and varied by demographic characteristics and comorbidities. Interventions are needed to increase HCV treatment uptake among Medicaid beneficiaries and to address disparities in treatment among key populations, including younger individuals, females, individuals from minoritized racial and ethnic groups, and people who inject drugs.

Impact of hepatitis C cure on risk of mortality and morbidity in people with HIV after antiretroviral therapy initiation.

OBJECTIVE: Hepatitis C virus (HCV) co-infection is associated with increased morbidity and mortality in people with HIV (PWH). Sustained virological response (SVR) decreases the risk of HCV-associated morbidity. We compared mortality, risk of AIDS-defining events, and non-AIDS nonliver (NANL) cancers between HCV-co-infected PWH who reached SVR and mono-infected PWH. DESIGN: Adult PWH from 21 cohorts in Europe and North America that collected HCV treatment data were eligible if they were HCV-free at the time of ART initiation. METHODS: Up to 10 mono-infected PWH were matched (on age, sex, date of ART start, HIV acquisition route, and being followed at the time of SVR) to each HCV-co-infected PWH who reached SVR. Cox models were used to estimate relative hazards (hazard ratio) of all-cause mortality, AIDS-defining events, and NANL cancers after adjustment. RESULTS: Among 62 495 PWH, 2756 acquired HCV, of whom 649 reached SVR. For 582 of these, at least one mono-infected PWH could be matched, producing a total of 5062 mono-infected PWH. The estimated hazard ratios comparing HCV-co-infected PWH who reached SVR with mono-infected PWH were 0.29 [95% confidence interval (CI) 0.12-0.73] for mortality, 0.85 [0.42-1.74] for AIDS-defining events, and 1.21 [0.86-1.72] for NANL cancer. CONCLUSION: PWH who reached SVR a short time after HCV acquisition were not at higher risk of overall mortality compared with mono-infected PWH. However, the apparent higher risk of NANL cancers in HCV-co-infected PWH who reached SVR after a DAA-based treatment compared with mono-infected PWH, though compatible with a null association, suggests a need for monitoring of those events following SVR.

Sexual Transmission of Viral Hepatitis.

Ongoing sexual transmission presents a significant barrier to viral hepatitis control. Endemic transmission of hepatitis A virus continues through communities of men with male sex partners, despite vaccine availability. Increased incidence of hepatitis B virus from 2014-2018 prompted expanded vaccination guidelines, but uptake and physician awareness remain poor. Hepatitis C virus while strongly associated with injection drug use, is also transmitted by high-risk sexual contact. Despite universal screening recommendations and curative treatment, incidence continues to increase. Even with safe and highly effective vaccinations or treatments, sexual transmission of viral hepatitides must be addressed to achieve disease elimination.

Silver Nanostar-Based SERS for the Discrimination of Clinically Relevant Acinetobacter baumannii and Klebsiella pneumoniae Species and Clones.

The development of rapid, reliable, and low-cost methods that enable discrimination among clinically relevant bacteria is crucial, with emphasis on those listed as WHO Global Priority 1 Critical Pathogens, such as carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant or ESBL-producing Klebsiella pneumoniae. To address this problem, we developed and validated a protocol of surface-enhanced Raman spectroscopy (SERS) with silver nanostars for the discrimination of A. baumannii and K. pneumoniae species, and their globally disseminated and clinically relevant antibiotic resistant clones. Isolates were characterized by mixing bacterial colonies with silver nanostars, followed by deposition on filter paper for SERS spectrum acquisition. Spectral data were processed with unsupervised and supervised multivariate data analysis methods, including principal component analysis (PCA) and partial least-squares discriminant analysis (PLSDA), respectively. Our proposed SERS procedure using silver nanostars adsorbed to the bacteria, followed by multivariate data analysis, enabled differentiation between and within species. This pilot study demonstrates the potential of SERS for the rapid discrimination of clinically relevant A. baumannii and K. pneumoniae species and clones, displaying several advantages such as the ease of silver nanostars synthesis and the possible use of a handheld spectrometer, which makes this approach ideal for point-of-care applications.

Microfluidic SERS devices: brightening the future of bioanalysis.

A new avenue has opened up for applications of surface-enhanced Raman spectroscopy (SERS) in the biomedical field, mainly due to the striking advantages offered by SERS tags. SERS tags provide indirect identification of analytes with rich and highly specific spectral fingerprint information, high sensitivity, and outstanding multiplexing potential, making them very useful in in vitro and in vivo assays. The recent and innovative advances in nanomaterial science, novel Raman reporters, and emerging bioconjugation protocols have helped develop ultra-bright SERS tags as powerful tools for multiplex SERS-based detection and diagnosis applications. Nevertheless, to translate SERS platforms to real-world problems, some challenges, especially for clinical applications, must be addressed. This review presents the current understanding of the factors influencing the quality of SERS tags and the strategies commonly employed to improve not only spectral quality but the specificity and reproducibility of the interaction of the analyte with the target ligand. It further explores some of the most common approaches which have emerged for coupling SERS with microfluidic technologies, for biomedical applications. The importance of understanding microfluidic production and characterisation to yield excellent device quality while ensuring high throughput production are emphasised and explored, after which, the challenges and approaches developed to fulfil the potential that SERS-based microfluidics have to offer are described.

Minimally invasive peritoneal access: A new approach of catheter placement for peritoneal dialysis.

BACKGROUND: Catheter implantation techniques for peritoneal dialysis (PD) have advanced significantly in recent years. We aimed to analyze the survival and associated complications of catheters inserted using a new technique that is guided by ultrasound and fluoroscopy and requires minimal tissue dissection. The procedure was performed by nephrologists in the outpatient basis, we compared these results of the minimally invasive insertion with traditional implantation using trocars. METHODS: A total of 152 PD catheters were placed in 152 patients with stage 5 chronic kidney disease; 62.5% of the patients were men, with a mean age of 56.6 ± 18.5 years. The following two methods were used: minimally invasive insertion (MI group, n = 73) and trocar insertion (T group, n = 79). Patients in both the groups were followed prospectively for 26 months from the date of the first implantation. RESULTS: Gender, age, and prevalence of diabetes mellitus were not significantly different between the groups, while the body mass index, presence of obesity, and abdominal scars from previous surgeries were higher in the MI group (p = 0.021). The incidence of catheter dysfunction was lower in the MI group compared to group T (6.8% vs 20.3%; p = 0.019). Exit site infection was also lower with the new technique (4.1% vs. 18.9%; p = 0.005). Further, the cumulative incidence of peritonitis also reduced with MI (p = 0.034). Finally, the overall catheter survival at 1 year was 89%, which has been shown as higher in group MI (95% vs 82% in group T; p = 0.025). CONCLUSION: The MI technique for catheter insertion showed low complication rates and excellent catheter survival as compared to traditional implantation methods; thus, it may be an alternative method for PD catheter placement.

Hepatitis C active viremia over time in an ED-based testing programme: Impact, disparities and surveillance tool.

Hepatitis C virus (HCV) surveillance is a critical component of a comprehensive strategy to prevent and control HCV infection and HCV-related chronic liver disease. The emergency department (ED) has been increasingly recognized as a vital partner in HCV testing and linkage. We sought to consider active RNA HCV viremia over time in patients participating in an ED-based testing programme as a measure of local HCV surveillance and as a barometer of ED-testing programme impact. We performed a retrospective analysis of individuals participating in our ED-based HCV testing programme between 2015 and 2021. Chi-square tests were used to compare the demographic characteristics of HCV antibody positive tests with active viremia to those without active viremia. Cox proportional hazard models were used to estimate the trend in active viremia risk over time in the overall study population as well as in key subpopulations of interest. Of 5456 HCV antibody positive individuals, 3102 (56.8%) had active viremia. In the overall study population, we found that the risk of active viremia decreased by 4.8% per year during the study period (RR: 0.95, 95% CI: 0.93-0.97|p < .0001). Baby boomers experienced a 9% decrease in active viremia risk per year over the study period while non-baby boomers only had a 2% decrease in risk per year (p = .0009). Compared with insured patients, uninsured patients had a smaller decrease in risk of active HCV viremia per year (p = .003). No significant differences in the risk of active viremia over time were observed for gender (p = .4694) or by primary care provider status (p = .2208). In conclusion, this ED-based testing and linkage programme demonstrates significantly decreased active HCV viremia over time. It also highlights subpopulations, specifically non-baby boomers and uninsured patients, who may benefit from focused interventions to improve access to and adoption of definitive HCV care.

Safety and efficacy of arteriovenous fistula angioplasties performed by nephrologists: report from a Brazilian interventional nephrology center / Segurança e eficácia de angioplastias de fístulas arteriovenosas realizadas por nefrologistas: relato de um centro de nefrologia intervencionista brasileiro

ABSTRACT Introduction: Arteriovenous fistulas (AVF) are the first choice vascular access for hemodialysis. However, they present a high incidence of venous stenosis leading to thrombosis. Although training in interventional nephrology may improve accessibility for treatment of venous stenosis, there is limited data on the safety and efficacy of this approach performed by trained nephrologists in low-income and developing countries. Methods: This study presents the retrospective results of AVF angioplasties performed by trained nephrologists in a Brazilian outpatient interventional nephrology center. The primary outcome was technical success rate (completion of the procedure with angioplasty of all stenoses) and secondary outcomes were complication rates and overall AVF patency. Findings: Two hundred fifty-six angioplasties were performed in 160 AVF. The technical success rate was 88.77% and the main cause of technical failure was venous occlusion (10%). The incidence of complications was 13.67%, with only one patient needing hospitalization and four accesses lost due to the presence of hematomas and/or thrombosis. Grade 1 hematomas were the most frequent complication (8.2%). The overall patency found was 88.2 and 80.9% at 180 and 360 days after the procedure, respectively. Conclusion: Our findings suggest that AVF angioplasty performed by trained nephrologists has acceptable success rates and patency, with a low incidence of major complications as well as a low need for hospitalization.

RESUMO Introdução: As fístulas arteriovenosas (FAV) são a primeira escolha de acesso vascular para hemodiálise. No entanto, elas apresentam uma alta incidência de estenoses venosas levando à trombose. Embora o treinamento em nefrologia intervencionista possa melhorar a acessibilidade para o tratamento das estenoses venosas, há dados limitados sobre a segurança e a eficácia desta abordagem realizada por nefrologistas treinados em países em desenvolvimento e de baixa renda. Métodos: Este estudo apresenta os resultados retrospectivos de angioplastias de FAV realizadas por nefrologistas treinados em um centro ambulatorial brasileiro de nefrologia intervencionista. O desfecho primário foi a taxa de sucesso técnico (conclusão do procedimento com angioplastia de todas as estenoses) e os desfechos secundários foram taxas de complicação e a patência geral das FAV. Achados: Duzentas e cinquenta e seis angioplastias foram realizadas em 160 FAV. A taxa de sucesso técnico foi de 88,77% e a principal causa de falha técnica foi a oclusão venosa (10%). A incidência de complicações foi de 13,67%, com apenas um paciente necessitando de internação e quatro acessos perdidos devido à presença de hematomas e/ou trombose. Hematomas de grau 1 foram a complicação mais frequente (8,2%). A patência geral encontrada foi de 88,2 e 80,9% a 180 e 360 dias após o procedimento, respectivamente. Conclusão: Nossos achados sugerem que a angioplastia de FAV realizada por nefrologistas treinados tem taxas de sucesso e patência aceitáveis, com uma baixa incidência de complicações maiores, bem como uma baixa necessidade de hospitalização.

Development and Validation of a Model for Prediction of End-Stage Liver Disease in People With HIV.

BACKGROUND: End-stage liver disease (ESLD) is a leading cause of non-AIDS-related death among people with HIV (PWH). Factors that increase the progression of liver disease include comorbidities and HIV-specific factors, but we currently lack a tool to apply this evidence into clinical practice. METHODS: We developed and validated a risk prediction model for ESLD among PWH who received care in 12 cohorts of the North American AIDS Cohort Collaboration on Research and Design between 2000 and 2016 and had fibrosis-4 index > 1.45. The first occurrence of ascites, variceal bleed, spontaneous bacterial peritonitis, or hepatic encephalopathy was verified by standardized medical record review. The Bayesian model averaging was used to select predictors among biomarkers and diagnoses and the Harrell C statistic to assess model discrimination. RESULTS: Among 13,787 PWH in the training set, 82% were men and 54% were Black with a mean age of 48 years. Three hundred ninety ESLD events occurred over a mean 5.4 years. Among the ESLD cases, 52% had hepatitis C virus, 15% hepatitis B virus, and 31% alcohol use disorder. Twelve factors together predicted ESLD risk moderately well (C statistic 0.79, 95% confidence interval: 0.76 to 0.81): age, sex, race/ethnicity, chronic hepatitis B or C, and routinely collected laboratory values reflecting hepatic impairment (serum albumin, aspartate aminotransferase, total bilirubin, and platelets) and lipid metabolism (triglycerides, high-density lipoprotein, and total cholesterol). Our model performed well in the test set (C statistic 0.81, 95% confidence interval: 0.76 to 0.86). CONCLUSION: This model of readily accessible clinical parameters predicted ESLD in a large diverse population of PWH.