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Gut Jul 2023IBD therapies and treatments are evolving to deeper levels of remission. Molecular measures of disease may augment current endpoints including the potential for less...
OBJECTIVE
IBD therapies and treatments are evolving to deeper levels of remission. Molecular measures of disease may augment current endpoints including the potential for less invasive assessments.
DESIGN
Transcriptome analysis on 712 endoscopically defined inflamed (Inf) and 1778 non-inflamed (Non-Inf) intestinal biopsies (n=498 Crohn's disease, n=421 UC and 243 controls) in the Mount Sinai Crohn's and Colitis Registry were used to identify genes differentially expressed between Inf and Non-Inf biopsies and to generate a molecular inflammation score (bMIS) via gene set variance analysis. A circulating MIS (cirMIS) score, reflecting intestinal molecular inflammation, was generated using blood transcriptome data. bMIS/cirMIS was validated as indicators of intestinal inflammation in four independent IBD cohorts.
RESULTS
bMIS/cirMIS was strongly associated with clinical, endoscopic and histological disease activity indices. Patients with the same histologic score of inflammation had variable bMIS scores, indicating that bMIS describes a deeper range of inflammation. In available clinical trial data sets, both scores were responsive to IBD treatment. Despite similar baseline endoscopic and histologic activity, UC patients with lower baseline bMIS levels were more likely treatment responders compared with those with higher levels. Finally, among patients with UC in endoscopic and histologic remission, those with lower bMIS levels were less likely to have a disease flare over time.
CONCLUSION
Transcriptionally based scores provide an alternative objective and deeper quantification of intestinal inflammation, which could augment current clinical assessments used for disease monitoring and have potential for predicting therapeutic response and patients at higher risk of disease flares.
Topics: Humans; Colitis, Ulcerative; Inflammation; Crohn Disease; Biopsy; Biomarkers; Intestinal Mucosa
PubMed: 36109152
DOI: 10.1136/gutjnl-2021-326451 -
Cell Reports. Medicine Oct 2023The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive... (Review)
Review
The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National Cancer Institute. The Liquid Biopsy Consortium has developed new methods/assays and validated existing methods/technologies to capture and characterize tumor-derived circulating cargo, as well as addressed existing challenges and provided recommendations for advancing biomarker assays.
Topics: Humans; Liquid Biopsy; Cell-Free Nucleic Acids; Biomarkers; Neoplastic Cells, Circulating; Extracellular Vesicles
PubMed: 37716353
DOI: 10.1016/j.xcrm.2023.101198 -
Journal of Gynecology Obstetrics and... Jun 2023This practice guideline provides updated evidence for the gynecologist who performs endometrial biopsy (EB) in gynecologic clinical practice. An international committee... (Review)
Review
This practice guideline provides updated evidence for the gynecologist who performs endometrial biopsy (EB) in gynecologic clinical practice. An international committee of gynecology experts developed the recommendations according to AGREE Reporting Guideline. An adequate tissue sampling is mandatory when performing an EB. Blind methods should not be first choice in patients with suspected endometrial malignancy. Hysteroscopy is the targeted-biopsy method with highest diagnostic accuracy and cost-effectiveness. Blind suction techniques are not reliable for the diagnosis of endometrial polyps. In low resources settings, and in absence of the capacity to perform office hysteroscopy, blind techniques could be used for EB. Hysteroscopic punch biopsy allows to collect only limited amount of endometrial tissue. grasp biopsy technique should be considered first choice in reproductive aged women, bipolar electrode chip biopsy should be preferred with hypotrophic or atrophic endometrium. EB is required for the final diagnosis of chronic endometritis. There is no consensus regarding which endometrial thickness cut-off should be used for recommending EB in asymptomatic postmenopausal women. EB should be offered to young women with abnormal uterine bleeding and risk factors for endometrial carcinoma. Endometrial pathology should be excluded with EB in nonobese women with unopposed hyperestrogenism. Hysteroscopy with EB is useful in patients with abnormal bleeding even without sonographic evidence of pathology. EB has high sensitivity for detecting intrauterine pathologies. In postmenopausal women with uterine bleeding, EB is recommended. Women with sonographic endometrial thickness > 4 mm using tamoxifen should undergo hysteroscopic EB.
Topics: Female; Humans; Adult; Endometrium; Uterine Diseases; Endometrial Neoplasms; Uterine Hemorrhage; Uterine Neoplasms; Biopsy
PubMed: 37061093
DOI: 10.1016/j.jogoh.2023.102588 -
Molecular Aspects of Medicine Jun 2023Extracellular vesicles (EVs) are released from all cells in the body, forming an important intercellular communication network that contributes to health and disease.... (Review)
Review
Extracellular vesicles (EVs) are released from all cells in the body, forming an important intercellular communication network that contributes to health and disease. The contents of EVs are cell source-specific, inducing distinct signaling responses in recipient cells. The specificity of EVs and their accumulation in fluid spaces that are accessible for liquid biopsies make them highly attractive as potential biomarkers and therapies for disease. The duality of EVs as favorable (therapeutic) or unfavorable (pathological) messengers is context dependent and remains to be fully determined in homeostasis and various disease states. This review describes the use of EVs as biomarkers, drug delivery vehicles, and regenerative therapeutics, highlighting examples involving viral infections, cancer, and neurological diseases. There is growing interest to provide personalized therapy based on individual patient and disease characteristics. Increasing evidence suggests that EV biomarkers and therapeutic approaches are ideal for personalized medicine due to the diversity and multifunctionality of EVs.
Topics: Humans; Precision Medicine; Extracellular Vesicles; Drug Delivery Systems; Biomarkers; Liquid Biopsy
PubMed: 36456416
DOI: 10.1016/j.mam.2022.101155 -
Nature Medicine Oct 2023There are no approved diagnostic biomarkers for at-risk non-alcoholic steatohepatitis (NASH), defined by the presence of NASH, high histological activity and fibrosis...
There are no approved diagnostic biomarkers for at-risk non-alcoholic steatohepatitis (NASH), defined by the presence of NASH, high histological activity and fibrosis stage ≥2, which is associated with higher incidence of liver-related events and mortality. FNIH-NIMBLE is a multi-stakeholder project to support regulatory approval of NASH-related biomarkers. The diagnostic performance of five blood-based panels was evaluated in an observational (NASH CRN DB2) cohort (n = 1,073) with full spectrum of non-alcoholic fatty liver disease (NAFLD). The panels were intended to diagnose at-risk NASH (NIS4), presence of NASH (OWLiver) or fibrosis stages >2, >3 or 4 (enhanced liver fibrosis (ELF) test, PROC3 and FibroMeter VCTE). The prespecified performance metric was an area under the receiver operating characteristic curve (AUROC) ≥0.7 and superiority over alanine aminotransferase for disease activity and the FIB-4 test for fibrosis severity. Multiple biomarkers met these metrics. NIS4 had an AUROC of 0.81 (95% confidence interval: 0.78-0.84) for at-risk NASH. The AUROCs of the ELF test, PROC3 and FibroMeterVCTE for clinically significant fibrosis (≥stage 2), advanced fibrosis (≥stage 3) or cirrhosis (stage 4), respectively, were all ≥0.8. ELF and FibroMeter VCTE outperformed FIB-4 for all fibrosis endpoints. These data represent a milestone toward qualification of several biomarker panels for at-risk NASH and also fibrosis severity in individuals with NAFLD.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Liver; Liver Cirrhosis; Fibrosis; Biomarkers; Biopsy
PubMed: 37679433
DOI: 10.1038/s41591-023-02539-6 -
Journal of Experimental & Clinical... Aug 2023Tissue-based biopsy is the present main tool to explore the molecular landscape of cancer, but it also has many limits to be frequently executed, being too invasive with... (Review)
Review
Tissue-based biopsy is the present main tool to explore the molecular landscape of cancer, but it also has many limits to be frequently executed, being too invasive with the risk of side effects. These limits and the ability of cancer to constantly evolve its genomic profile, have recently led to the need of a less invasive and more accurate alternative, such as liquid biopsy. By searching Circulating Tumor Cells and residues of their nucleic acids or other tumor products in body fluids, especially in blood, but also in urine, stools and saliva, liquid biopsy is becoming the future of clinical oncology. Despite the current lack of a standardization for its workflows, that makes it hard to be reproduced, liquid biopsy has already obtained promising results for cancer screening, diagnosis, prognosis, and risk of recurrence.Through a more accessible molecular profiling of tumors, it could become easier to identify biomarkers predictive of response to treatment, such as EGFR mutations in non-small cell lung cancer and KRAS mutations in colorectal cancer, or Microsatellite Instability and Mismatch Repair as predictive markers of pembrolizumab response.By monitoring circulating tumor DNA in longitudinal repeated sampling of blood we could also predict Minimal Residual Disease and the risk of recurrence in already radically resected patients.In this review we will discuss about the current knowledge of limitations and strengths of the different forms of liquid biopsies for its inclusion in normal cancer management, with a brief nod to their newest biomarkers and its future implications.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Biomarkers, Tumor; Lung Neoplasms; Circulating Tumor DNA; Liquid Biopsy
PubMed: 37542343
DOI: 10.1186/s13046-023-02743-9 -
Hepatology (Baltimore, Md.) Jan 2024Early identification of those with NAFLD activity score ≥ 4 and significant fibrosis (≥F2) or at-risk metabolic dysfunction-associated steatohepatitis (MASH) is a...
BACKGROUND
Early identification of those with NAFLD activity score ≥ 4 and significant fibrosis (≥F2) or at-risk metabolic dysfunction-associated steatohepatitis (MASH) is a priority as these patients are at increased risk for disease progression and may benefit from therapies. We developed and validated a highly specific metabolomics-driven score to identify at-risk MASH.
METHODS
We included derivation (n = 790) and validation (n = 565) cohorts from international tertiary centers. Patients underwent laboratory assessment and liver biopsy for metabolic dysfunction-associated steatotic liver disease. Based on 12 lipids, body mass index, aspartate aminotransferase, and alanine aminotransferase, the MASEF score was developed to identify at-risk MASH and compared to the FibroScan-AST (FAST) score. We further compared the performance of a FIB-4 + MASEF algorithm to that of FIB-4 + liver stiffness measurements (LSM) by vibration-controlled transient elastography (VCTE).
RESULTS
The diagnostic performance of the MASEF score showed an area under the receiver-operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of 0.76 (95% CI 0.72-0.79), 0.69, 0.74, 0.53, and 0.85 in the derivation cohort, and 0.79 (95% CI 0.75-0.83), 0.78, 0.65, 0.48, and 0.88 in the validation cohort, while FibroScan-AST performance in the validation cohort was 0.74 (95% CI 0.68-0.79; p = 0.064), 0.58, 0.79, 0.67, and 0.73, respectively. FIB-4+MASEF showed similar overall performance compared with FIB-4 + LSM by VCTE ( p = 0.69) to identify at-risk MASH.
CONCLUSION
MASEF is a promising diagnostic tool for the assessment of at-risk MASH. It could be used alternatively to LSM by VCTE in the algorithm that is currently recommended by several guidance publications.
Topics: Humans; Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Fibrosis; Predictive Value of Tests; Elasticity Imaging Techniques; Biopsy
PubMed: 37505221
DOI: 10.1097/HEP.0000000000000542 -
Sultan Qaboos University Medical Journal Feb 2024Trichodysplasia spinulosa (TS) is a unique, rare clinical and histological dermatologic entity described mainly in a setting of immunosuppression. It is caused by a...
Trichodysplasia spinulosa (TS) is a unique, rare clinical and histological dermatologic entity described mainly in a setting of immunosuppression. It is caused by a novel human polymoavirus, TS-associated polyomavirus. Reduction of immunosuppression and/or anti-viral therapy is the main therapeutic strategies used to treat such cases. We report a biopsy-proven case of TS in a male renal transplant patient who presented to a dermatology outpatient clinic in Montreal, Canada, in 2015. He was managed with valgancyclovir with no obvious response. Subsequently, a trial of topical imiquimod was commenced. Awareness of TS can prompt early diagnosis and management to prevent possible complications.
Topics: Humans; Male; Biopsy; Canada; Skin Diseases
PubMed: 38434466
DOI: 10.18295/squmj.5.2023.035 -
Neurotherapeutics : the Journal of the... Jul 2023Several advances in fluid and tissue-based biomarkers for use in Parkinson's disease (PD) and other synucleinopathies have been made in the last several years. While... (Review)
Review
Several advances in fluid and tissue-based biomarkers for use in Parkinson's disease (PD) and other synucleinopathies have been made in the last several years. While work continues on species of alpha-synuclein (aSyn) and other proteins which can be measured from spinal fluid and plasma samples, immunohistochemistry and immunofluorescence from peripheral tissue biopsies and alpha-synuclein seeding amplification assays (aSyn-SAA: including real-time quaking induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA)) now offer a crucial advancement in their ability to identify aSyn species in PD patients in a categorical fashion (i.e., of aSyn + vs aSyn -); to augment clinical diagnosis however, aSyn-specific assays that have quantitative relevance to pathological burden remain an unmet need. Alzheimer's disease (AD) co-pathology is commonly found postmortem in PD, especially in those who develop dementia, and dementia with Lewy bodies (DLB). Biofluid biomarkers for tau and amyloid beta species can detect AD co-pathology in PD and DLB, which does have relevance for prognosis, but further work is needed to understand the interplay of aSyn tau, amyloid beta, and other pathological changes to generate comprehensive biomarker profiles for patients in a manner translatable to clinical trial design and individualized therapies.
Topics: Humans; Parkinson Disease; alpha-Synuclein; Amyloid beta-Peptides; Alzheimer Disease; Biopsy; Biomarkers
PubMed: 37138160
DOI: 10.1007/s13311-023-01379-z -
Ugeskrift For Laeger Dec 2023In this case report, a 61-year-old male presented with odynophagia and ulceration in palatum durum after inhalating dust from machinery containing a weak acid. It was at...
In this case report, a 61-year-old male presented with odynophagia and ulceration in palatum durum after inhalating dust from machinery containing a weak acid. It was at first diagnosed as an acidic ulcer due to two biopsies verifying this. Because of progressing ulceration a third biopsy was taken - this time with the diagnosis extranodal NK/T-cell lymphoma, nasal type. This illustrates the diagnostic challenges of the illness, typically requiring multiple biopsies, and one should have this differential diagnosis in mind in case of progressing ulceration.
Topics: Male; Humans; Middle Aged; Lymphoma, Extranodal NK-T-Cell; Nose Neoplasms; Nose; Biopsy; Diagnosis, Differential
PubMed: 38078472
DOI: No ID Found