Exosomes: Mediators in Microenvironment of Colorectal Cancer

AlexandrosSfakianakis shared this article with you from Inoreader Exosomes: Mediators in Microenvironment of Colorectal Cancer via International Journal of Cancer Abstract Tumor microenvironment, the soil where tumor thrives, plays a critical role in the development and progression of colorectal cancer (CRC). Various cell signaling molecules in the environment promote tumor angiogenesis, immune tolerance and facilitate immune escape. Exosomes, as messengers between tumor and host cells, are considered key mediators involved in the tumor-accelerating environment. However, the exosome-mediated communication networks in the CRC microenvironment are still largely unclear. In this review, we summarized the relationship between TME and CRC based on recent literature. Then, we revealed the unique impacts and signal molecules of exosomes on account of their regulatory role in the flora, hypoxia, inflammatory, and immunological microenvironment of CRC. Finally, we summarized the therapeutically effective of exosomes in CRC microenvironment and discussed their current status and prospects, aiming to provide new molecular targets and a theoretical basis for th e CRC treatment. View on Web

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Effectiveness and Accuracy of MRI‐Ultrasound Fusion Targeted Biopsy Based on PI‐RADS v2.1 Category in Transition/Peripheral Zone of the Prostate

AlexandrosSfakianakis shared this article with you from Inoreader Effectiveness and Accuracy of MRI‐Ultrasound Fusion Targeted Biopsy Based on PI‐RADS v2.1 Category in Transition/Peripheral Zone of the Prostate via Journal of Magnetic Resonance Imaging Background MRI-ultrasound fusion targeted biopsy (MRI-TBx) improves the clinically significant prostate cancer (csPCa) detection with fewer cores. However, whether systematic biopsy-guided by transrectal ultrasound (TRUS-SBx) can be omitted when undergoing MRI-TBx in transition zone (TZ) and peripheral zone (PZ) remains unclear. Purpose To assess the performance and effectiveness of MRI-TBx based on PI-RADS v2.1 for csPCa diagnosis in TZ and PZ, respectively. Study Type Retrospective. Subjects A total of 309 selected cases (median age 70 years) with 356 lesions who underwent both MRI-TBx and TRUS-SBx were enrolled. Field Strength/Sequence A 3.0 T, multiparametric MRI (mp-MRI) including T2-weighted turbo-spin echo imaging (T2WI), diffusion-weighted spin-echo echo planar imaging (DWI), dynamic contrast-enhanced MRI with time-resolved T1-weighted imaging (DCE). Assessment Mp-MRI was assessed by two radiologists using PI-RADS v2.1. The csPCa detection rates provided by MRI-TBx, TRUS-SBx and combined biopsy in TZ and PZ were calculated, respectively. Statistical Tests McNemar test was used to compare the csPCa detection rates in TZ and PZ, respectively. The frequencies and distribution of all detected prostate cancers by different biopsy methods were also compared. P < 0.05 was considered statistically significant. Results Among 356 lesions in 309 patients, 208 (68 in TZ, 140 in PZ) were pathologically confirmed as csPCa. In TZ, there were significant differences for csPCa detection with PI-RADS 3 between combined biopsy and TRUS-SBx (23.5% vs. 15.3%), MRI-TBx (23.5% vs. 16.3%), respectively. MRI-TBx detected 23% (19/83) cases missed by TRUS-SBx in which 68% (13/19) were csPCa. In PZ, there were no statistical differences between MRI-TBx and combined biopsy with PI-RADS 3–5 (P = 0.21, 0.25, 0.07, respectively). In 9% (14/152) cases only detected by MRI-TBx, 86% (12/14) were clinically significant. Five percent (7/152) of cases only detected by TRUS-SBx were completely nonclinically significant. Data Conclusion MRI-TBx played a positive role on csPCa diagnosis in TZ, but combined biopsy might be the best choice especially in the subgroup PI-RADS 3. In PZ, MRI-TBx had an advantage over TRUS-SBx for csPCa detection. Evidence Level 2. Technical Efficacy Stage 2. View on Web

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WHOLE‐GENOME SINGLE MOLECULE REAL‐TIME SEQUENCING OF SARS‐CoV‐2 OMICRON

AlexandrosSfakianakis shared this article with you from Inoreader WHOLE‐GENOME SINGLE MOLECULE REAL‐TIME SEQUENCING OF SARS‐CoV‐2 OMICRON via Journal of Medical Virology ABSTRACT New variants and genetic mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome can only be identified using accurate sequencing methods. Single molecule real-time (SMRT) sequencing has been used to characterize Alpha and Delta variants, but not Omicron variants harbouring numerous mutations in the SARS-CoV-2 genome. This study assesses the performance of a target capture SMRT sequencing protocol for whole genome sequencing (WGS) of SARS-CoV-2 Omicron variants and compared it to that of an amplicon SMRT sequencing protocol optimized for Omicron variants. The failure rate of the target capture protocol (6%) was lower than that of the amplicon protocol (34%, p<0.001) on our dataset, and the median genome coverage with the target capture protocol (98.6% [IQR: 86-99.4]) was greater than that with the amplicon protocol (76.6% [IQR: 66-89.6], (p<0.001)). The percentages of samples with >95% whole genome coverage were 64% with the target capture pro tocol and 19% with the amplicon protocol (p<0.05). The clades of 96 samples determined with both protocols were 93% concordant and the lineages of 59 samples were 100% concordant. Thus, target capture SMRT sequencing appears to be an efficient method for WGS, genotyping and detecting mutations of SARS-CoV-2 Omicron variants. This article is protected by copyright. All rights reserved. View on Web

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Characteristics and outcomes of gallbladder cancer patients at the Tata Medical Center, Kolkata 2017–2019

AlexandrosSfakianakis shared this article with you from Inoreader Characteristics and outcomes of gallbladder cancer patients at the Tata Medical Center, Kolkata 2017–2019 via Cancer Medicine The curative approach for gallbladder cancer (GBC) is radical cholecystectomy with adjuvant chemotherapy. GBC has non-specific symptoms, so screening/early detection is not possible. We report that 90% of GBC patients presented with late-stage inoperable disease. Patients with late-stage disease who received chemotherapy had significantly better survival over those who did not (p < 0.0001). Our real-world data suggests that GBC is a chemosensitive disease. Clinical trials in low-middle income countries to reposition available therapies are urgently required. Abstract Background The north and north-eastern regions of India have among the highest incidence of gallbladder cancer (GBC) in the world. We report the clinicopathological charateristics and outcome of GBC patients in India. Methods Electronic medical records of patients diagnosed with GBC at Tata Medical Center, Kolkata between 2017 and 2019 were analyzed. Results There were 698 cases of confirmed GBC with a median age of 58 (IQR: 50–65) years and female:male ratio of 1.96. At presentation, 91% (496/544) had stage III/IV disease and 30% (189/640) had incidental GBC. The 2-year overall survival (OS) was 100% (95% CI: 100–100); 61% (95% CI: 45–83); 30% (95% CI: 21–43); and 9% (95% CI: 6–13) for stages I–IV, respectively (p = <0.0001).   For all patients, the 2-year OS in patients who had a radical cholecystectomy followed by adjuvant therapy (N = 36) was 50% (95% CI: 39–64), compared to 29% (95% CI: 22–38) for those who had a simple cholecystectomy and/or chemotherapy (N = 265) and 9% (95% CI: 6–14) in patients who were palliated (N = 107) (p = <0.0001). Conclusion The combined surgical/chemotherapy approach for patients with stage II GBC showed the best outcomes. Early detection of GBC remains problematic with the majority of patients presenting with stage III–IV and who have a median survival of 9.1 months. Our data suggests that the tumor is chemoresponsive and multi-center collaborative clinical trials to identify alternative therapies are urgently required. View on Web

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Gastrointestinal and Hepatic Manifestations in Patients with Generalised Pustular Psoriasis

AlexandrosSfakianakis shared this article with you from Inoreader Gastrointestinal and Hepatic Manifestations in Patients with Generalised Pustular Psoriasis via Wiley: Experimental Dermatology: Table of Contents Abstract Generalised pustular psoriasis (GPP) is a rare and severe form of pustular psoriasis. It is defined by persisting or relapsing macroscopically visible sterile primary pustules occurring on non-acral skin and not within psoriasis plaques. Due to its rarity, there is a lack of randomised controlled trials on GPP and its associated gastrointestinal (GI) and liver disorders. In this article, we present a review of the GI and hepatic disorders associated with GPP. GPP is known to be associated with extracutaneous manifestations such as neutrophilic cholangitis. Abnormal liver function tests are reported in up to 90% of patients with GPP upon diagnosis. Less commonly, pancreatitis and gastrointestinal bleeding have been attributed to GPP. While a psoriasis registry with 7.5% prevalence of pustular psoriasis reported an association with viral hepatitis B and C, the true relationship remains to be elucidated as hepatitis B is endemic in Asia where GPP prevalence is higher. Common genetic mutations between GPP and conditions such as hepatocellular carcinoma and inflammatory bowel disease have been identified, explaining their possible associations and providing answers to potential therapeutic options for these conditions. A lack of recognition of these association may result in unnecessary withdrawal of efficacious and definitive drugs for the treatment of GPP. Understanding the characteristics of the associated GI and hepatic disorders will h ave important implications for targeting the appropriate therapeutics. View on Web

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Combined proliferation and apoptosis index provides better risk stratification in breast cancer

AlexandrosSfakianakis shared this article with you from Inoreader Combined proliferation and apoptosis index provides better risk stratification in breast cancer via Histopathology Introduction Breast cancer (BC) risk stratification is critical for predicting behaviour and guiding management decision-making. Despite the well-established prognostic value of cellular proliferation in BC, the interplay between proliferation and apoptosis remains to be defined. In this study, we hypothesised that the combined proliferation and apoptosis indices can provide a more accurate in vivo growth rate measure and a precise prognostic predictor. Methods and Results Apoptotic and mitotic figures were counted in whole slide images (WSI) generated from haematoxylin and eosin-stained sections of 1545 BC cases derived from two well-defined BC cohorts. Counts were carried out visually within defined areas. There was a significant correlation between mitosis and apoptosis scores. High apoptotic counts were associated with features of aggressive behaviour including high grade, high pleomorphism score, and hormonal receptor negativity. Although the mitotic index (MI) and apoptotic index (AI) were independent prognostic indicators, the prognostic value was synergistically higher when combined. BC patients with a high combined AI and MI had the shortest survival. Replacing the mitosis score with the mitosis-apoptosis index, in the Nottingham grading system, revealed that the modified grade with the new score had a higher significant association with BC-specific survival with a higher hazard ratio. Conclusion Apoptotic figures count provides additional prognostic value in BC when combined with MI, such a combination can be implemented to assess the behaviour of BC and provides an accurate prognostic indicator. This can be considered when using artificial intelligence algorithms to assess proliferation in BC. View on Web

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Key Modifiable Factors in Community Participation among Adults with Lower-Limb Amputation

AlexandrosSfakianakis shared this article with you from Inoreader Key Modifiable Factors in Community Participation among Adults with Lower-Limb Amputation via American Journal of Physical Medicine & Rehabilitation - Published Ahead-of-Print Objective To identify factors that may predict community participation among adults with lower-limb amputation (LLA). Design This study is a secondary analysis of a cross-sectional dataset, including 126 community-dwelling adults, ≥1 year after unilateral transfemoral- (n = 44; mean age = 59 ± 14 years) or transtibial-level amputation (n = 82; mean age = 59 ± 14 years) seen in an outpatient limb loss clinic. Participation was assessed with the Community Integration Questionnaire (CIQ). Factors, i.e., demographics, comorbidities, prosthesis-use per the Houghton Scale, Socket Comfort Score, assistive device use, falls history, and activity level per General Practice Physical Activity Questionnaire were evaluated. Moreover, balance-confidence per the Activities-Specific Balance Confidence Scale, mobility per the Locomotor Capabilities Index, fast and self-selected gait speed per 10-meter Walk Tests, and functional mobility via Timed Up and Go, were also included. Results Community participation was correlated with several factors (p ≤ 0.050). Stepwise regression of correlated factors found absence of peripheral neuropathy and greater self-reported physical activity, balance-confidence, and prosthesis use, as the strongest correlates, collectively explaining 50.1% of the variance in community participation post-LLA. Conclusions Findings identify key modifiable factors for consideration in future prospective research seeking to enhance community reintegration and participation among adults living with a unilateral transfemoral- or transtibial-level amputation. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved. View on Web

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Plasma Biomarkers and Positron Emission Tomography Tau Pathology in Progressive Supranuclear Palsy

AlexandrosSfakianakis shared this article with you from Inoreader Plasma Biomarkers and Positron Emission Tomography Tau Pathology in Progressive Supranuclear Palsy via Movement Disorders Plasma neurofilament light chain (NfL) is a promising biomarker of progressive supranuclear palsy (PSP) to assist in PSP diagnosis and differential diagnosis from Parkinson's disease (PD) and to monitor disease severity. Pending replication in independent cohorts, plasma glial fibrillary acidic protein (GFAP) holds promise for a PSP diagnosis and a differential diagnosis with multiple system atrophy with predominant parkinsonism (MSA-P) and for detecting brainstem atrophy and tau deposition in PSP. ABSTRACT Background Development of disease-modifying therapeutic trials of progressive supranuclear palsy (PSP) urges the need for sensitive fluid biomarkers. Objectives The objectives of this study were to explore the utility of plasma biomarkers in the diagnosis, differential diagnosis, and assessment of disease severity, brain atrophy, and tau deposition in PSP. Methods Plasma biomarkers were measured using a single-molecule array in a cohort composed of patients with PSP, Parkinson's disease (PD), multiple system atrophy with predominant parkinsonism (MSA-P), and healthy controls (HCs). Results Plasma neurofilament light chain (NfL) outperformed other plasma makers (ie, glial fibrillary acidic protein [GFAP], phosphorylated-tau 181 [p-tau181], amyloid-β 1–40, amyloid-β 1–42) in identifying PSP from HC (area under the curve [AUC] = 0.904) and from MSA-P (AUC = 0.711). Plasma GFAP aided in distinguishing PSP from HC (AUC = 0.774) and from MSA-P (AUC = 0.832). It correlated with brainstem atrophy and higher regional tau accumulation. However, plasma p-tau181 neither helped in diagnosis nor was it associated with clinical or neuroimaging measures. Conclusions Plasma NfL and GFAP showed different values in differentiating PSP from HC or controls with other forms of neurodegenerative parkinsonism and detecting disease severity, brain atrophy, or tau deposition in PSP. © 2023 International Parkinson and Movement Disorder Society. View on Web

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