From Hypertension to Beyond: Unraveling the Diverse Mechanisms of Olmesartan in Disease Modulation.

Olmesartan, originally known for its antihypertensive properties, exhibits promising potential in addressing inflammation-mediated diseases. As an angiotensin II receptor blocker (ARB), Olmesartan influences pivotal pathways, including reactive oxygen species, cytokines, NF-κB, TNF-α, and MAPK. This suggests a viable opportunity for repurposing the drug in conditions such as ulcerative colitis, neuropathy, nephropathy, and cancer, as supported by multiple preclinical studies. Ongoing clinical trials, particularly in cardiomyopathy and nephropathy, suggest a broader therapeutic scope for Olmesartan. Repurposing efforts would entail comprehensive investigations using disease-specific preclinical models and dedicated clinical studies. The drug's established safety profile, wide availability, and well-understood ARB mechanism of action offer distinct advantages that could facilitate a streamlined repurposing process. In summary, Olmesartan's versatile impact on inflammation-related pathways positions it as a promising candidate for repurposing across various diseases. Ongoing clinical trials and the drug's favorable attributes enhance its appeal for further exploration and potential application in diverse medical contexts.

MicroRNA-29b-3p degenerates terminally differentiated dopaminergic SH-SY5Y cells by perturbation of mitochondrial functions.

Mitochondrial dysfunction is the main cause of gradual deterioration of structure and function of neuronal cells, eventually resulting in neurodegeneration. Studies have revealed a complex interrelationship between neurotoxicant exposure, mitochondrial dysfunction, and neurodegenerative diseases. Alteration in the expression of microRNAs (miRNAs) has also been linked with disruption in mitochondrial homeostasis and bioenergetics. In our recent research (Cellular and Molecular Neurobiology (2023) https://doi.org/10.1007/s10571-023-01362-4), we have identified miR-29b-3p as one of the most significantly up-regulated miRNAs in the blood of Parkinson's patients. The findings of the present study revealed that neurotoxicants of two different natures, that is, arsenic or rotenone, dramatically increased miR-29b-3p expression (18.63-fold and 12.85-fold, respectively) in differentiated dopaminergic SH-SY5Y cells. This dysregulation of miR-29b-3p intricately modulated mitochondrial morphology, induced oxidative stress, and perturbed mitochondrial membrane potential, collectively contributing to the degeneration of dopaminergic cells. Additionally, using assays for mitochondrial bioenergetics in live and differentiated SH-SY5Y cells, a reduction in oxygen consumption rate (OCR), maximal respiration, basal respiration, and non-mitochondrial respiration was observed in cells transfected with mimics of miR-29b-3p. Inhibition of miR-29b-3p by transfecting inhibitor of miR-29b-3p prior to exposure to neurotoxicants significantly restored OCR and other respiration parameters. Furthermore, we observed that induction of miR-29b-3p activates neuronal apoptosis via sirtuin-1(SIRT-1)/YinYang-1(YY-1)/peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α)-regulated Bcl-2 interacting protein 3-like-dependent mechanism. Collectively, our studies have shown the role of miR-29b-3p in dysregulation of mitochondrial bioenergetics during degeneration of dopaminergic neurons via regulating SIRT-1/YY-1/PGC-1α axis.

Green, Solvent-Free Mechanochemical Synthesis of Nano Ag2O/MnO2/N-Doped Graphene Nanocomposites: An Efficient Catalyst for Additive-Base-Free Aerial Oxidation of Various Kinds of Alcohols.

Herein, we report a solvent-less, straightforward, and facile mechanochemical technique to synthesize nanocomposites of Ag2O nanoparticles-doped MnO2, which is further codoped with nitrogen-doped graphene (N-DG) [i.e., (X %)N-DG/MnO2-(1% Ag2O)] using physical milling of separately prepared N-DG and Ag2O NPs-MnO2 annealed at 400 °C over an eco-friendly ball-mill process. To assess the efficiency in terms of catalytic performance of the nanocomposites, selective oxidation of benzyl alcohol (BlOH) to benzaldehyde (BlCHO) is selected as a substrate model with an eco-friendly oxidizing agent (O2 molecule) and without any requirements for the addition of any harmful additives or bases. Various nanocomposites were prepared by varying the amount of N-DG in the composite, and the results obtained highlighted the function of N-DG in the catalyst system when they are compared with the catalyst MnO2-(1% Ag2O) [i.e., undoped catalyst] and MnO2-(1% Ag2O) codoped with different graphene dopants such as GRO and H-RG for alcohol oxidation transformation. The effects of various catalytic factors are systematically evaluated to optimize reaction conditions. The N-DG/MnO2-(1% Ag2O) catalyst exhibits premium specific activity (16.0 mmol/h/g) with 100% BlOH conversion and <99.9% BlCHO selectivity within a very short interval. The mechanochemically prepared N-DG-based nanocomposite displayed higher catalytic efficacy than that of the MnO2-(1% Ag2O) catalyst without the graphene dopant, which is N-DG in this study. A wide array of aromatic, heterocyclic, allylic, primary, secondary, and aliphatic alcohols have been selectively converted to respective ketones and aldehydes with full convertibility without further oxidation to acids over N-DG/MnO2-(1% Ag2O). Interestingly, it is also found that the N-DG/MnO2-(1% Ag2O) can be efficiently reused up to six times without a noteworthy decline in its effectiveness. The prepared nanocomposites were characterized using various analytical, microscopic, and spectroscopic techniques such as X-ray diffraction, thermogravimetric analysis, Fourier-transform infrared spectroscopy, Raman, field emission scanning electron microscopy, and Brunauer-Emmett-Teller.

Applications of some advanced sequencing, analytical, and computational approaches in medicinal plant research: a review.

The potential active chemicals found in medicinal plants, which have long been employed as natural medicines, are abundant. Exploring the genes responsible for producing these compounds has given new insights into medicinal plant research. Previously, the authentication of medicinal plants was done via DNA marker sequencing. With the advancement of sequencing technology, several new techniques like next-generation sequencing, single molecule sequencing, and fourth-generation sequencing have emerged. These techniques enshrined the role of molecular approaches for medicinal plants because all the genes involved in the biosynthesis of medicinal compound(s) could be identified through RNA-seq analysis. In several research insights, transcriptome data have also been used for the identification of biosynthesis pathways. miRNAs in several medicinal plants and their role in the biosynthesis pathway as well as regulation of the disease-causing genes were also identified. In several research articles, an in silico study was also found to be effective in identifying the inhibitory effect of medicinal plant-based compounds against virus' gene(s). The use of advanced analytical methods like spectroscopy and chromatography in metabolite proofing of secondary metabolites has also been reported in several recent research findings. Furthermore, advancement in molecular and analytic methods will give new insight into studying the traditionally important medicinal plants that are still unexplored.

γ-Aminobutyric acid is involved in overlapping pathways against chilling injury by modulating glutamate decarboxylase and defense responses in papaya fruit.

The effect of γ-aminobutyric acid (GABA) treatment at two concentrations (1 mM or 5 mM) on papaya fruit stored at 4°C and 80%-90% relative humidity for 5 weeks was investigated. The application of GABA at 5 mM apparently inhibited chilling injury, internal browning, electrolyte leakage, malondialdehyde (MDA), hydrogen peroxide (H2O2), polyphenol oxidase (PPO), phospholipase D (PLD), and lipoxygenase (LOX) activities of papaya fruit. Fruit treated with 5 mM GABA enhanced the activities of ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), glutamate decarboxylase (GAD), and phenylalanine ammonia-lyase (PAL). In addition, GABA treatment significantly displayed higher levels of proline, endogenous GABA accumulation, phenolic contents, and total antioxidant activity than the nontreated papaya. The results suggested that GABA treatment may be a useful approach to improving the chilling tolerance of papaya fruit by reducing oxidative stress and enhancing the defense system.

TIPS stent migration causing sinus of Valsalva rupture.

A man in his 40s presented with haematemesis and melaena and was found to have a massive variceal bleed. Endoscopic procedures were ineffective at controlling the bleed; thus, an emergent transjugular intrahepatic portosystemic shunt (TIPS) procedure was performed. There were no noted complications from the procedure and the patient was eventually discharged home. A month later, a murmur was auscultated on routine physical examination. This prompted an outpatient transthoracic echocardiogram which revealed a TIPS stent in the inferior vena cava (IVC) extending into the right atrium along with a ruptured sinus of Valsalva with left to right shunt.The patient declined surgical intervention. He is currently being followed in the outpatient setting with serial echocardiograms and medical management.

Surveillance and treatment of primary hepatocellular carcinoma (aka. STOP HCC): protocol for a prospective cohort study of high-risk patients for HCC using GALAD-score.

BACKGROUND: Vietnam and Saudi Arabia have high disease burden of primary hepatocellular carcinoma (HCC). Early detection in asymptomatic patients at risk for HCC is a strategy to improve survival outcomes in HCC management. GALAD score, a serum-based panel, has demonstrated promising clinical utility in HCC management. However, in order to ascertain its potential role in the surveillance of the early detection of HCC, GALAD needs to be validated prospectively for clinical surveillance of HCC (i.e., phase IV biomarker validation study). Thus, we propose to conduct a phase IV biomarker validation study to prospectively survey a cohort of patients with advanced fibrosis or compensated cirrhosis, irrespective of etiologies, using semi-annual abdominal ultrasound and GALAD score for five years. METHODS: We plan to recruit a cohort of 1,600 patients, male or female, with advanced fibrosis or cirrhosis (i.e., F3 or F4) and MELD ≤ 15, in Vietnam and Saudi Arabia (n = 800 each). Individuals with a liver mass ≥ 1 cm in diameter, elevated alpha-fetoprotein (AFP) (≥ 9 ng/mL), and/or elevated GALAD score (≥ -0.63) will be scanned with dynamic contrast-enhanced magnetic resonance imaging (MRI), and a diagnosis of HCC will be made by Liver Imaging Reporting and Data System (LiRADS) assessment (LiRADS-5). Additionally, those who do not exhibit abnormal imaging findings, elevated AFP titer, and/or elevated GALAD score will obtain a dynamic contrast-enhanced MRI annually for five years to assess for HCC. Only MRI nearest to the time of GALAD score measurement, ultrasound and/or AFP evaluation will be included in the diagnostic validation analysis. MRI will be replaced with an abdominal computed tomography scan when MRI results are poor due to patient conditions such as movement etc. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI will not be carried out in study sites in both countries. Bootstrap resampling technique will be used to account for repeated measures to estimate standard errors and confidence intervals. Additionally, we will use the Cox proportional hazards regression model with covariates tailored to the hypothesis under investigation for time-to-HCC data as predicted by time-varying biomarker data. DISCUSSION: The present work will evaluate the performance of GALAD score in early detection of liver cancer. Furthermore, by leveraging the prospective cohort, we will establish a biorepository of longitudinally collected biospecimens from patients with advanced fibrosis or cirrhosis to be used as a reference set for future research in early detection of HCC in the two countries. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov Registration date: 22 April 2022 Trial registration number: NCT05342350 URL of trial registry record.

Light-Driven Catalytic Activity of Green-Synthesized SnO2/WO3-x Hetero-nanostructures.

This work reports an environmentally friendly and economically feasible green synthesis of monometallic oxides (SnO2 and WO3) and their corresponding mixed metal oxide (SnO2/WO3-x) nanostructures from the aqueous Psidium guajava leaf extract for light-driven catalytic degradation of a major industrial contaminant, methylene blue (MB). P. guajava is a rich source of polyphenols that acts as a bio-reductant as well as a capping agent in the synthesis of nanostructures. The chemical composition and redox behavior of the green extract were investigated by liquid chromatography-mass spectrometry and cyclic voltammetry, respectively. Results acquired by X-ray diffraction and Fourier transform infrared spectroscopy confirm the successful formation of crystalline monometallic oxides (SnO2 and WO3) and bimetallic SnO2/WO3-x hetero-nanostructures capped with polyphenols. The structural and morphological aspects of the synthesized nanostructures were analyzed by transmission electron microscopy and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. Photocatalytic activity of the synthesized monometallic and hetero-nanostructures was investigated for the degradation of MB dye under UV light irradiation. Results indicate a higher photocatalytic degradation efficiency for mixed metal oxide nanostructures (93.5%) as compared to pristine monometallic oxides SnO2 (35.7%) and WO3 (74.5%). The hetero-metal oxide nanostructures prove to be better photocatalysts with reusability up to 3 cycles without any loss in degradation efficiency or stability. The enhanced photocatalytic efficiency is attributed to a synergistic effect in the hetero-nanostructures, efficient charge transportation, extended light absorption, and increased adsorption of dye due to the enlarged specific surface area.

The influence of non-thermal technologies on color pigments of food materials: An updated review.

The color of any food is influenced by several factors, such as food attributes (presence of pigments, maturity, and variety), processing methods, packaging, and storage conditions. Thus, measuring the color profile of food can be used to control the quality of food and examine the changes in chemical composition. With the advent of non-thermal processing techniques and their growing significance in the industry, there is a demand to understand the effects of these technologies on various quality attributes, including color. This paper reviews the effects of novel, non-thermal processing technologies on the color attributes of processed food and the implications on consumer acceptability. The recent developments in this context and a discussion on color systems and various color measurement techniques are also included. The novel non-thermal techniques, including high-pressure processing, pulsed electric field, ultrasonication, and irradiation which employ low processing temperatures for a short period, have been found effective. Since food products are processed at ambient temperature by subjecting them to non-thermal treatment for a very short time, there is no possibility of damage to heat-sensitive nutrient components in the food, any deterioration in the texture of the food, and any toxic compounds in the food due to heat. These techniques not only yield higher nutritional quality but are also observed to maintain better color attributes. However, suppose foods are exposed to prolonged exposure or processed at a higher intensity. In that case, these non-thermal technologies can cause undesirable changes in food, such as oxidation of lipids and loss of color and flavor. Developing equipment for batch food processing using non-thermal technology, understanding the appropriate mechanisms, developing processing standards using non-thermal processes, and clarifying consumer myths and misconceptions about these technologies will help promote non-thermal technologies in the food industry.

NMR spectroscopy-based analysis of gallstones of cancerous and benign gallbladders from different geographical regions of the Indian subcontinent.

Analysis of the chemical composition of gallstones is vital for the etiopathogenesis of gallstone diseases that can ultimately help in the prevention of its formation. In the present study, gallstones from seven different regions of India were analyzed to highlight the major difference in their composition. Also, gallstones of different pathological conditions i.e., benign (chronic cholecystitis, CC) and malignant gallbladder disease (gallbladder cancer GBC) were characterized. The type of polymorphs of cholesterol molecules was also studied to provide insight into the structure of gallstones. 1H solution state NMR spectroscopy 1D experiments were performed on a total of 94 gallstone (GS) samples collected from seven different geographical regions of India. Solid-State NMR spectroscopy 13C cross-polarization magic angle spinning (CPMAS) experiments were done on the 20 CC GS samples and 20 GBC GS samples of two regions. 1H NMR spectra from the solution state NMR of all the stones reveal that cholesterol was a major component of the maximum stones of the north India region while in south Indian regions, GS had very less cholesterol. 13C CPMAS experiments reveal that the quantity of cholesterol was significantly more in the GS of CC in the Lucknow region compared with GBC stones of Lucknow and Chandigarh. Our study also revealed that GS of the Lucknow region of both malignant and benign gallbladder diseases belong to the monohydrate crystalline form of cholesterol while GS of Chandigarh region of both malignant and benign gallbladder diseases exists in both monohydrate crystalline form with the amorphous type and anhydrous form. Gallstones have a complicated and poorly understood etiology. Therefore, it is important to understand the composition of gallstones, which can be found in various forms and clinical conditions. Variations in dietary practices, environmental conditions, and genetic factors may influence and contribute to the formation of GS. Prevention of gallstone formation may help in decreasing the cases of gallbladder cancer.

Sex differences in incident atherosclerotic cardiovascular disease events among women and men with HIV.

BACKGROUND: The protective advantage against atherosclerotic cardiovascular disease (ASCVD) experienced by women compared to men in the general population is diminished in some high- risk populations. People with HIV have a higher risk for ASCVD compared to the general population. OBJECTIVE: Compare the incidence of ASCVD among women versus men with HIV. METHODS: We analyzed data from women ( n  = 17 118) versus men ( n  = 88 840) with HIV, and women ( n  = 68 472) and men ( n  = 355 360) matched on age, sex, and calendar year of enrollment without HIV who had commercial health insurance in the MarketScan database between 2011 and 2019. ASCVD events during follow-up, including myocardial infarction, stroke, and lower-extremity artery disease, were identified using validated claims-based algorithms. RESULTS: Among those with and without HIV, the majority of women (81.7%) and men (83.6%) were <55 years old. Over a mean follow-up of 2.25-2.36 years depending on sex-HIV sub-group, the ASCVD incidence rate per 1000 person-years was 2.87 [95% confidence interval (CI) 2.35, 3.40] and 3.61 (3.35, 3.88) among women and men with HIV, respectively, and 1.24 (1.07, 1.42) and 2.57 (2.46, 2.67) among women and men without HIV, respectively. After multivariable adjustment, the hazard ratio for ASCVD comparing women to men was 0.70 (95% CI 0.58, 0.86) among those with HIV and 0.47 (0.40, 0.54) among those without HIV ( P -interaction = 0.001). CONCLUSION: The protective advantage of female sex against ASCVD observed in the general population is diminished among women with HIV. Earlier and more intensive treatment strategies are needed to reduce sex-based disparities.

The Efficacy and Safety of Imusil® Tablets in the Treatment of Adult Patients With Mild COVID-19: A Prospective, Randomized, Multicenter, Open-Label Study.

Introduction Coronavirus disease 2019 (COVID-19) is a serious concern of the new era. Along with antiviral synthetic medications, there is a need to discover efficacious herbal antiviral medicines with minimum side effects in patients against COVID-19. This study aimed to assess the efficacy and safety of Imusil® among patients with mild COVID-19. Methods A prospective, randomized, multicenter, open-label, interventional study was conducted in patients with mild COVID-19 infection. Patients received either Imusil one tablet four times a day (seven days) along with the standard of care (SoC) or only SoC. The study endpoints were reverse transcription-polymerase chain reaction (RT-PCR) negativity, changes in cycle threshold (CT), clinical improvement, change in blood inflammatory indexes, and safety assessment. Results A total of 100 patients were enrolled, and 98 received at least one dose of treatment. The median age of patients was 36.0 years, and 58 were males. By day 4, 85.4% of patients in the Imusil+SoC group tested negative for RT-PCR compared to 64% of patients exhibiting the same outcome in the SoC group (P=0.0156). After eight days, clinical improvement was observed in all patients from the Imusil+SoC group, while in the SoC group, clinical improvement was observed in 94.0% of patients (P=0.4947). During follow-up visits, the average C-reactive protein (CRP) levels decreased from baseline in both treatment groups. The decrease in the levels of CRP (-7.3 mg/dL versus -5.5 mg/dL), D-dimer (-231.0 ng/mL versus -151.6 ng/mL), and interleukin 6 (IL-6) (-2.3 pg/mL versus -2.0 pg/mL) at eight days was comparatively higher in the Imusil+SoC group versus the SoC group. There were no serious treatment-emergent adverse events in the drug arm. Conclusion Imusil provides effective antiviral activity and safety in mild COVID-19 patients. Imusil ensures faster RT-PCR negativity and clinical improvement and ensures effective reduction of inflammatory markers such as CRP, D-dimer and interleukin 6.

Recurrent solitary fibrous tumor of eyelid: A rare entity.

Orbital and adnexal solitary fibrous tumors (SFT) are rare entities. The clinico-radiological and histologic features overlap with those of other spindle cell variants, and hence the use of immunohistochemical stains helps in making an accurate diagnosis. Furthermore, a thorough surgical resection is imperative to prevent tumor recurrences. We report a rare case of SFT arising primarily from the eyelid with multiple recurrences.

Case Report: Culture-negative Prosthetic Valve Endocarditis.

BACKGROUND: Prosthetic valve endocarditis can be difficult to diagnose and cause significant morbidity and mortality, especially when no culture data are available to guide therapy. Transthoracic and transesophageal echocardiograms, the studies of choice for initial endocarditis evaluation, can be less reliable due to artifact and post-surgical changes. Some less common forms of endocarditis may be difficult to culture and, due to their fastidious nature, may delay the identification of causative organisms. Given the lack of directed antimicrobial treatment, culturenegative prosthetic valve endocarditis is specifically difficult. A wide differential diagnosis is critical to make a timely diagnosis and initiate treatment. CASE PRESENTATION: We present a case of a patient presenting with dyspnea which was found to have culture-negative endocarditis requiring mitral and aortic valve replacement that ultimately was complicated with culture-negative prosthetic valve endocarditis. Identifying a culprit organism made appropriate and timely antimicrobial treatment difficult, ultimately resulting in the patient dying from endocarditis complications. CONCLUSION: A high index of suspicion is needed when managing infective endocarditis, especially when prosthetic valves are involved. Diagnostic accuracy of cultures and echocardiography may be reduced when dealing with prosthetic valve endocarditis; thus, alternative methods of diagnosis may be required to make a timely diagnosis of causative organisms.

Clinical Manifestation of AGE-RAGE Axis in Neurodegenerative and Cognitive Impairment Disorders.

The receptor of Advanced Glycation Endproducts (RAGE) and Advanced Glycation Endproducts (AGE) have multiple functions in our body and their restraint are being observed in neurodegenerative and memory impairment disorders. The review of different pathways allows an understanding of the probable mechanism of neurodegeneration and memory impairment involving RAGE and AGE. Commonly we observe AGE accumulation in neural cells and tissues but the extent of accumulation increases with the presence of memory impairment disorder. The presence of AGEs can also be seen in morbid accumulation, pathological structures in the form of amyloid clots, and nervous fibrillary tangles in Alzheimer's Disease (AD) and memory impairment disease.Many neuropathological and biochemical aspects of AD are explained by AGEs, including widespread protein crosslinking, glial activation of oxidative stress, and neuronal cell death. Oxidative stress is due to different reasons and glycation end products set in motion and form or define various actions which are normally due to AGE changes in a pathogenic cascade. By regulating the transit of ß-amyloid in and out of the brain or altering inflammatory pathways, AGE and it's ensnare receptor such as soluble RAGE may function as blockage or shield AD development. RAGE activates the transcription-controlling factor Necrosis Factor (NF-κB) and increases the protraction of cytokines, like a higher number of Tumor Necrosis Factor (TNF-α) and Interleukin (IL-I) by inducing several signal transduction cascades. Furthermore, binding to RAGE can pro-activate reactive oxygen species (ROS), which is popularly known to cause neuronal death.

Adverse cardiac remodeling is absent in patients with true controlled resistant hypertension.

Resistant hypertension (RHTN), defined as blood pressure (BP) that is uncontrolled with ≥3 medications, including a long-acting thiazide diuretic, also includes a subset with BP that is controlled with ≥4 medications, so-called controlled RHTN. This resistance is attributed to intravascular volume excess. Patients with RHTN overall have a higher prevalence of left ventricular hypertrophy (LVH) and diastolic dysfunction compared to patients with non-RHTN. We tested the hypothesis that patients with controlled RHTN due to the intravascular volume excess have higher left ventricular mass index (LVMI), higher prevalence of LVH, larger intracardiac volumes, and more diastolic dysfunction compared to patients with controlled non-resistant hypertension (CHTN), defined as BP controlled with ≤3 anti-hypertensive medications. Patients with controlled RHTN (n = 69) or CHTN (n = 63) who were treated at the University of Alabama at Birmingham were offered enrollment and underwent cardiac magnetic resonance imaging. Diastolic function was assessed by peak filling rate, time needed in diastole to recover 80% of stroke volume, E:A ratios and left atrial volume. LVMI was higher in patients with controlled RHTN (64.4 ± 22.5 vs 56.9 ± 11.5; P = .017). Intracardiac volumes were similar in both groups. Diastolic function parameters were not significantly different between groups. There were no significant differences in age, gender, race, body mass index, dyslipidemia between the two groups. The findings show that patients with controlled RHTN have higher LVMI, but comparable diastolic function to those of patients with CHTN.

Detection of IDH1 Mutation in cfDNA and Tissue of Adult Diffuse Glioma with Allele-Specific qPCR.

BACKGROUND: The World Health Organization (WHO) classification of central nervous system (CNS) tumors necessitates testing of isocitrate dehydrogenase (IDH) 1/2 gene mutation in patients with adult-type diffuse glioma (ADG) for better disease management. In clinical practice, the testing of IDH1 is primarily achieved using immunohistochemistry (IHC) specific to IDH1-R132, which carries a sensitivity of 80% and specificity of 100%. However, in some cases, non-specific background staining or regional heterogeneity in the protein expression of IDH1 may necessitate confirmatory genetic analysis. Robust and reliable assays are needed for IDH1/2 mutation testing. The aim of the current study was to detect IDH1 mutation in cfDNA and tissue of adult-type diffuse glioma with allele-specific qPCR. MATERIALS AND METHODS: In the current study, IDH1-R132H mutation was analyzed in tumor tissue with paired cell-free DNA (cfDNA) in patients with ADG (n = 45) using IHC and competitive allele-specific Taqman PCR (CAST-PCR). Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue and matched serum for cfDNA using commercially available kits. CAST-PCR with IHC for the detection of IDH1-R132H mutation was also compared. RESULTS: The IDH1-R132H mutation was detected in 46.67% (21/45) cases and 57.78% (26/45) cases using IHC and allele-specific CAST-PCR. In cfDNA of matched IDH1-mutant FFPE tissue DNA, IDH1-R132H mutation was detected in 11.54% (3/26) using CAST-PCR. The concordance rate for IDH1-R132Hmutation between IHC and CAST-PCR was 80.77% (21/26). CONCLUSION: The CAST-PCR assay is more precise and sensitive for  IDH1-R132Hdetection than traditional IHC, and IDH1-R132H mutation detection using cfDNA may add to the current methods of glioma genomic characterization.

Impact of Frailty on Health Care Resource Utilization and Costs of Care in Myelodysplastic Syndromes.

PURPOSE: The role of frailty in affecting survival in myelodysplastic syndromes (MDS) is increasingly recognized. Despite this, a paucity of data exists on the association between frailty and other clinically meaningful outcomes including health care resource utilization and costs of care. METHODS: We linked the Ontario subset of the prospective Canadian MDS registry (including baseline patient/disease characteristics) to population-based health system administrative databases. Baseline frailty was calculated from the 15-item MDS-specific frailty scale (FS-15). Primary outcomes were public health care utilization and 30-day standardized costs of care (2019 Canadian dollars) determined for each phase of disease (initial, continuation, and terminal phases). Negative binomial regression was used to assess the association between frailty and health care costs with Poisson regression to explore predictors of hospitalization. RESULTS: Among 461 patients with complete FS-15 scores, 374 (81.1%) had a hospitalization with a mean length of stay of 10.6 days. Controlling for age, comorbidities, Revised International Prognostic Scoring System, and transfusion dependence, the FS-15 was independently associated with hospitalization during the initial (P = .02) and continuation (P = .01) phases but not the terminal disease phase (P = .09). The mean 30-day standardized cost per patient was $8,499 (median, $6,295; interquartile range, $2,798-$11,996), largely driven by cancer clinic visits and hospitalization. On multivariable analysis, the FS-15 was independently associated with costs of care during the initial disease phase (P = .02). CONCLUSION: We demonstrate an association between frailty and clinically meaningful outcomes including hospitalization and costs of care in patients with MDS. Our results suggest that baseline frailty may help to inform patients and physicians of expected outcomes.