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Medicine Jun 2024This study aimed to assess hematological diseases next-generation sequencing (NGS) panel enhances the diagnosis and classification of myeloid neoplasms (MN) using the... (Observational Study)
Observational Study
This study aimed to assess hematological diseases next-generation sequencing (NGS) panel enhances the diagnosis and classification of myeloid neoplasms (MN) using the 5th edition of the WHO Classification of Hematolymphoid Tumors (WHO-HAEM5) and the International Consensus Classification (ICC) of Myeloid Tumors. A cohort of 112 patients diagnosed with MN according to the revised fourth edition of the WHO classification (WHO-HAEM4R) underwent testing with a 141-gene NGS panel for hematological diseases. Ancillary studies were also conducted, including bone marrow cytomorphology and routine cytogenetics. The cases were then reclassified according to WHO-HAEM5 and ICC to assess the practical impact of these 2 classifications. The mutation detection rates were 93% for acute myeloid leukemia (AML), 89% for myelodysplastic syndrome (MDS), 94% for myeloproliferative neoplasm (MPN), and 100% for myelodysplasia/myeloproliferative neoplasm (MDS/MPN) (WHO-HAEM4R). NGS provided subclassified information for 26 and 29 patients with WHO-HAEM5 and ICC, respectively. In MPN, NGS confirmed diagnoses in 16 cases by detecting JAK2, MPL, or CALR mutations, whereas 13 "triple-negative" MPN cases revealed at least 1 mutation. NGS panel testing for hematological diseases improves the diagnosis and classification of MN. When diagnosed with ICC, NGS produces more classification subtype information than WHO-HAEM5.
Topics: Humans; High-Throughput Nucleotide Sequencing; Female; Male; Middle Aged; Aged; Myeloproliferative Disorders; Adult; Myelodysplastic Syndromes; Mutation; Aged, 80 and over; Janus Kinase 2; World Health Organization; Leukemia, Myeloid, Acute; Receptors, Thrombopoietin; Calreticulin; Young Adult
PubMed: 38875377
DOI: 10.1097/MD.0000000000038556 -
Frontiers in Neurology 2024Exergaming has the potential to increase adherence to exercise through play, individually tailored training, and (online) remote monitoring. Reality Digital Therapeutics...
Remotely prescribed, monitored, and tailored home-based gait-and-balance exergaming using augmented reality glasses: a clinical feasibility study in people with Parkinson's disease.
BACKGROUND
Exergaming has the potential to increase adherence to exercise through play, individually tailored training, and (online) remote monitoring. Reality Digital Therapeutics (Reality DTx) is a digital therapeutic software platform for augmented reality (AR) glasses that enables a home-based gait-and-balance exergaming intervention specifically designed for people with Parkinson's disease (pwPD).
OBJECTIVE
The primary objective was to evaluate the feasibility and potential efficacy of Reality DTx AR exergaming intervention for improving gait, balance, and walking-adaptability fall-risk indicators. The secondary objective was to evaluate the potential superiority of AR glasses [Magic Leap 2 (ML2) vs. HoloLens 2 (HL2)].
METHODS
This waitlist-controlled clinical feasibility study comprised three laboratory visits (baseline; pre-intervention; and post-intervention), a home visit, and a 6-week AR exergaming intervention. Five complementary gait-and-balance exergames were remotely prescribed (default five sessions/week of 30 active minutes/session), monitored, and tailored. Feasibility was assessed in terms of safety, adherence, and user experience. During laboratory visits, gait-and-balance capacity was assessed using standard clinical gait-and-balance tests and advanced walking-adaptability fall-risk assessments.
RESULTS
In total, 24 pwPD participated. No falls and four near falls were reported. Session adherence was 104%. The User Experience Questionnaire scores for Reality DTx ranged from above average to excellent, with superior scores for HL2 over ML2 for Perspicuity and Dependability. Intervention effects were observed for the Timed Up and Go test (albeit small), the Five Times Sit to Stand test, and walking speed. Walking-adaptability fall-risk indicators all improved post-intervention.
CONCLUSION
Reality DTx is a safe, adherable, usable, well-accepted, and potentially effective intervention in pwPD. These promising results warrant future randomized controlled trials on the (cost-)effectiveness of home-based AR exergaming interventions for improving gait, balance, and fall risk.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT05605249.
PubMed: 38872812
DOI: 10.3389/fneur.2024.1373740 -
European Stroke Journal Jun 2024Cirrhosis is associated with an increased risk of hemorrhagic stroke. Liver fibrosis, typically a silent condition, is antecedent to cirrhosis. The objective of this...
BACKGROUND
Cirrhosis is associated with an increased risk of hemorrhagic stroke. Liver fibrosis, typically a silent condition, is antecedent to cirrhosis. The objective of this study was to test the hypothesis that elevated Fibrosis-4 (FIB-4) index, indicating a high probability of liver fibrosis, is associated with an increased risk of hemorrhagic stroke.
METHODS
We performed a cohort analysis of the prospective United Kingdom Biobank cohort study. Participants 40-69 years old were enrolled between 2007 and 2010 and had available follow-up data until March 1, 2018. We excluded participants with prevalent hemorrhagic stroke or thrombocytopenia. High probability of liver fibrosis was defined as having a value >2.67 of the validated FIB-4 index. The primary outcome was hemorrhagic stroke (intracerebral or subarachnoid hemorrhage), defined based on hospitalization and death registry data. Secondary outcomes were intracerebral and subarachnoid hemorrhage, separately. We used Cox proportional hazards models to evaluate the association of FIB-4 index >2.67 with hemorrhagic stroke while adjusting for potential confounders including hypertension, alcohol use, and antithrombotic use.
RESULTS
Among 452,994 participants (mean age, 57 years; 54% women), approximately 2% had FIB-4 index >2.67, and 1241 developed hemorrhagic stroke. In adjusted models, FIB-4 index >2.67 was associated with an increased risk of hemorrhagic stroke (HR, 2.0; 95% CI, 1.6-2.6). Results were similar for intracerebral hemorrhage (HR, 2.0; 95% CI, 1.5-2.7) and subarachnoid hemorrhage (HR, 2.2; 95% CI, 1.5-3.5) individually.
CONCLUSIONS
Elevated FIB-4 index was associated with an increased risk of hemorrhagic stroke.
PubMed: 38872255
DOI: 10.1177/23969873241259561 -
Parasites & Vectors Jun 2024Dirofilaria immitis, commonly known as heartworm (HW), is a parasitic nematode transmitted by various mosquito species, leading to heartworm disease (HWD) in dogs....
Evaluation of diagnostic techniques for early detection of heartworm in experimentally infected dogs: identification of Dirofilaria immitis-derived microRNA in the initial 28 weeks post-inoculation.
BACKGROUND
Dirofilaria immitis, commonly known as heartworm (HW), is a parasitic nematode transmitted by various mosquito species, leading to heartworm disease (HWD) in dogs. Diagnosis of HW typically involves antigen or microfilariae detection, or visualization of adult worms through imaging or post mortem examination. Polymerase chain reaction (PCR) and micro RNA (miRNA) detection have been explored for HW diagnosis.
METHODS
Three dogs, previously experimentally infected with HW, underwent blood sampling every 4 weeks for 7 months. Samples were assessed for antigen presence after heat treatment, PCR amplification, and microfilaria examination using Giemsa-stained thick smears. Additionally, whole blood aliquots underwent miRNA deep sequencing and bioinformatic analysis.
RESULTS
Heartworm antigen was detectable after heat treatment at 20 weeks post-inoculation and via PCR at 24 weeks, with microfilariae observed in peripheral blood smears at 28 weeks. However, deep miRNA sequencing revealed that the miRNA candidate sequences are not consistently expressed before 28 weeks of infection.
CONCLUSIONS
While ancillary molecular methods such as PCR and miRNA sequencing may be less effective than antigen detection for detecting immature larval stages in an early stage of infection, our experimental findings demonstrate that circulating miRNAs can still be detected in 28 weeks post-infection.
Topics: Animals; Dirofilaria immitis; Dogs; Dirofilariasis; MicroRNAs; Dog Diseases; Antigens, Helminth; Early Diagnosis; Polymerase Chain Reaction; Microfilariae; High-Throughput Nucleotide Sequencing
PubMed: 38872227
DOI: 10.1186/s13071-024-06337-y -
BMJ Global Health Jun 2024Clear guidelines to implement ancillary care (AC) in clinical trials conducted in resource-constrained settings are lacking. Here, we evaluate an AC policy developed for... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Clear guidelines to implement ancillary care (AC) in clinical trials conducted in resource-constrained settings are lacking. Here, we evaluate an AC policy developed for a vaccine trial in the Democratic Republic of the Congo and formulate policy recommendations.
METHODS
To evaluate the AC policy, we performed a longitudinal cohort study, nested in an open-label, single-centre, randomised Ebola vaccine trial conducted among healthcare personnel. Participants' demographic information, residence distance to the study site and details on the financial and/or medical support provided for any (serious) adverse events ((S)AE) were combined and analysed. To assess the feasibility of the AC policy, an expenditure analysis of the costs related to AC support outcomes was performed.
RESULTS
Enrolment in this evaluation study started on 29 November 2021. The study lasted 11 months and included 655 participants from the Ebola vaccine trial. In total, 393 participants used the AC policy, mostly for AE management (703 AE and 94 SAE) via medication provided by the study pharmacy (75.3%). Men had a 35.2% (95% CI 4.0% to 56.6%) lower likelihood of reporting AE compared with women. Likewise, this was 32.3% lower (95% CI 5.8% to 51.4%) for facility-based compared with community-based healthcare providers. The daily AE reporting was 78.8% lower during the passive vs the active trial stage, and 97.4% lower during unscheduled vs scheduled visits (p<0.001). Participants living further than 10 km from the trial site more frequently reported the travel distance as a reason for not using the policy (p<0.04). In practice, only 1.1% of the operational trial budget was used for AC policy support.
CONCLUSION
The trial design, study population and local health system impacted the use of the AC policy. Nonetheless, the AC policy implementation in this remote and resource-constrained setting was feasible, had negligible budgetary implications and contributed to participants' healthcare options and well-being.
Topics: Humans; Male; Female; Ebola Vaccines; Adult; Democratic Republic of the Congo; Longitudinal Studies; Hemorrhagic Fever, Ebola; Health Policy; Middle Aged; Health Personnel
PubMed: 38857947
DOI: 10.1136/bmjgh-2024-015259 -
Juntendo Iji Zasshi = Juntendo Medical... 2023Septal myectomy confers survival benefits on patients with hypertrophic cardiomyopathy. However, its role in the treatment of severe aortic stenosis (sAS) with left...
OBJECTIVES
Septal myectomy confers survival benefits on patients with hypertrophic cardiomyopathy. However, its role in the treatment of severe aortic stenosis (sAS) with left ventricular outflow tract obstruction (LVOTO) remains under investigation. Another challenging question in the era of transcatheter aortic valve replacement is who would benefit more from traditional surgical aortic valve replacement (SAVR) with myectomy. Therefore, this study aimed to investigate myectomy cases at our hospital in Japan.
METHODS
A total of 740 patients who underwent SAVR for sAS between 2012 and 2019 were identified. The demographics and baseline echocardiographic findings were retrospectively compared between patients who underwent concomitant myectomy and those who did not. The myectomy group was further assessed for factors predisposing to LVOTO, operative details, echocardiographic changes, and prognosis. The resected septa were histopathologically analyzed.
RESULTS
The myectomy group mostly comprised elderly females with a small hypercontractile heart. Myectomy with SAVR led to statistically significant improvements in concentric left ventricular hypertrophy and LVOTO parameters. Survival was comparable with that reported in previous reports, even in the elderly subset (≥ 75 years). The septa showed mild fibrosis.
CONCLUSIONS
Myectomy can be safely performed with SAVR for sAS with LVOTO, even in the elderly, and it effectively improves LVOTO. Special attention should be paid to elderly females with relatively more severe AS and a small yet extra-hypertrophic and extra-hypercontractile heart. Such patients warrant comprehensive assessment of LVOTO, and despite its invasiveness, SAVR may be potentially more beneficial by allowing direct observation of LVOTO and ancillary myectomy.
PubMed: 38855434
DOI: 10.14789/jmj.JMJ22-0036-OA -
Medical Research Archives Oct 2023Stress and stressful events are widely accepted risk factors for cardiometabolic diseases, including coronary heart disease and diabetes. As language plays a seminal...
Stress and stressful events are widely accepted risk factors for cardiometabolic diseases, including coronary heart disease and diabetes. As language plays a seminal role in development and regulation of emotions and appraisals of stressful situations, it may contribute to documented differences in the stress-cardiometabolic disease association across ethnic groups. We investigated associations between language preferences (Spanish vs English) and downstream health consequences of stress. Using data from the Sociocultural Ancillary Study of the Hispanic Community Health Study/Study of Latinos, we assessed the relationship between reported stress and risk factors (alcohol use, smoking, body mass index, depressive symptoms) and prevalence of self-reported (coronary heart disease, stroke, chronic obstructive pulmonary disease [COPD]) and clinically assessed chronic conditions (diabetes, hypertension) among 5154 Hispanic/Latino adults living in the US. Factor analysis was used to calculate a composite stress variable from participants' self-reported chronic stress, perceived stress, and adverse childhood experiences. Sampling weights and survey methodology were integrated in all analyses to account for this study's complex survey design. After controlling for sociodemographic factors (Hispanic/Latino background, study site, years in the US, social acculturation, education, income, age, sex), higher composite stress scores were associated with elevated risk factors and greater prevalence of coronary heart disease, diabetes, and COPD. Furthermore, the relationship between stress and COPD was significantly stronger among Hispanic/Latino adults who preferred to be interviewed in Spanish (compared to English). Stronger connections between stress and likelihood of drinking alcohol among English-preferring persons also emerged. These results are interpreted in light of the Hispanic health paradox and the role of cultural processes in the development of health risk factors and chronic conditions. Our findings can be integrated into relevant approaches to address health disparities within and across Hispanic/Latino populations in the US.
PubMed: 38846550
DOI: 10.18103/mra.v11i10.4625 -
Cureus May 2024Urinary bladder cancer (UBC) is amongst the most common urological malignancies.
BACKGROUND
Urinary bladder cancer (UBC) is amongst the most common urological malignancies.
AIM
To study different types of urinary bladder lesions in the north Indian population and to correlate various clinical and pathological findings.
MATERIALS AND METHODS
The present prospective study was conducted on 100 cases undergoing transurethral resection of bladder tumor (TURBT) and/or radical cystectomy over a period of 2.5 years followed by histopathological examination. Liquid-based cytology for malignant cells in urine was also performed. Immunohistochemistry was employed for tumor typing wherever needed.
RESULTS
A total of 100 cases were studied. Male to female ratio was 15.7:1 and most of the patients were in the sixth decade (40%). Painless hematuria was the commonest clinical presentation (60%) and smoking was the commonest risk factor (80%). The most common lesion was infiltrating urothelial carcinoma seen in 72 cases followed by papillary urothelial neoplasm of low malignant potential (PUNLMP) seen in eight cases. Grade and depth of invasion were assessed and correlated. Several variants of infiltrating urothelial carcinoma such as squamous differentiation, glandular differentiation, microcystic, clear cell, nested, and micropapillary were also identified. Clinical, cystoscopic and histopathological findings were correlated in all the cases.
CONCLUSION
Infiltrating urothelial carcinoma high grade was the most common bladder lesion identified and muscle invasion was more common with higher-grade lesions. A decade-younger age group was found to be more affected in the present series. Urine cytology for malignant cells is useful for early diagnosis of cancer. Immunohistochemistry is an important ancillary adjunct.
PubMed: 38846211
DOI: 10.7759/cureus.59792 -
Microbiology Spectrum Jun 2024Quantitation of cytomegalovirus (CMV) DNA load in specimens other than blood such as bronchoalveolar lavages, intestinal biopsies, or urine has become a common practice...
Quantitation of cytomegalovirus (CMV) DNA load in specimens other than blood such as bronchoalveolar lavages, intestinal biopsies, or urine has become a common practice as an ancillary tool for the diagnosis of CMV pneumonitis, intestinal disease, or congenital infection, respectively. Nevertheless, most commercially available CMV PCR platforms have not been validated for CMV DNA detection in these specimen types. In this study, a laboratory-developed test based on Alinity m CMV ("Alinity LDT") was evaluated. Reproducibility assessment using spiked bronchial aspirate (BAS) or urine samples showed low standard deviations of 0.08 and 0.27 Log IU/mL, respectively. Evaluating the clinical performance of Alinity LDT in comparison to a laboratory-developed test based on RealTie CMV ("RealTie LDT") showed good concordance across 200 clinical specimens including respiratory specimens, intestinal biopsies, urine, and stool. A high Pearson's correlation coefficient of r = 0.92, a low mean bias of -0.12 Log IU/mL, a good qualitative agreement of 90%, and a Cohen's kappa value of 0.76 (substantial agreement) were observed. In separate analyses of the sample types BAS, tracheal aspirates, bronchoalveolar lavage, biopsies, and urine, the assay results correlated well between the two platforms with r values between 0.88 and 0.99 and a bias <0.5 Log IU/mL. Overall, the fully automated, continuous, random access Alinity LDT yielded good reproducibility, high concordance, and good correlation to RealTie LDT in respiratory, gastrointestinal, and urine samples and may enhance patient management with rapid result reporting.IMPORTANCEIn transplant recipients, a major cause for morbidity and mortality is end-organ disease by primary or secondary CMV infection of the respiratory or gastrointestinal tract. In addition, sensorineural hearing loss and neurodevelopmental abnormalities are frequent sequelae of congenital CMV infections in newborns. Standard of care for highly sensitive detection and quantitation of the CMV DNA load in plasma and whole blood specimens is real-time PCR testing. Beyond that, there is a need for quantitative determination of CMV DNA levels in respiratory, gastrointestinal, and urinary tract specimens using a highly automated, random access CMV PCR assay with a short turnaround time to enable early diagnosis and treatment. In the present study, clinical performance of the fully automated Alinity m analyzer in comparison to the current RealTie LDT assay was evaluated in eight different off-label sample types.
PubMed: 38842363
DOI: 10.1128/spectrum.04201-23 -
Frontiers in Veterinary Science 2024This study aimed to determine the sensitivity (Se) and specificity (Sp) of a circulating pathogen-specific biomarker (polyketide synthetase 5, Pks5)-based enzyme-linked...
This study aimed to determine the sensitivity (Se) and specificity (Sp) of a circulating pathogen-specific biomarker (polyketide synthetase 5, Pks5)-based enzyme-linked immunosorbent assay (ELISA) independently or in conjunction with a caudal fold tuberculin (CFT) test for bovine tuberculosis (bTB) screening in dairy cattle. We enrolled 987 dairy cows from 34 herds in Chiang Mai province, Thailand. A conditionally independent Bayesian model with a single population was inferred from the test results. The percentage of positive results for the Pks5-ELISA using 0.4 OD cutoff test and CFT test were 9.0% (89/987) and 10.5% (104/987), respectively. The median of posterior estimates of Se for the Pks5-ELISA test was 90.2% (95% posterior probability interval [PPI] = 76.6-97.4%), while the estimated Sp was slightly higher (median = 92.9, 95% PPI = 91.0-94.5%). The median estimated Se of the CFT test was 85.9% (95% PPI = 72.4-94.6%), while the estimated Sp was higher, with a median of 90.7% (95% PPI = 88.7-92.5%). The posterior estimate for true disease prevalence was 2.4% (95% PPI = 1.2-3.9%). The Pks5-ELISA test yielded characteristics at or above the acceptable standards for bTB detection. Therefore, the pathogen-specific biomarker, Pks5, is a potential detection system for bTB screening and may be applied as an ancillary test together with the currently applied standard method (CFT test) to reinforce the bTB control and eradication programs.
PubMed: 38840633
DOI: 10.3389/fvets.2024.1384537