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CytoJournal 2024Cell blocks (CBs) are paraffin-embedded versions of cytology specimens. These versions are contrasted with tissues made from surgical pathology specimens of... (Review)
Review
Cell blocks (CBs) are paraffin-embedded versions of cytology specimens. These versions are contrasted with tissues made from surgical pathology specimens of formalin-fixed paraffin-embedded (FFPE) tissue. CBs enable various elective ancillary studies of a range of specimens. These studies include the potential to perform molecular tests with the enhanced cytopathological interpretation. CBs are increasingly reported in cytology specimens. The enhanced role of CBs incorporates additives with new markers for immunohistochemistry (IHC), including the multicolored approach to IHC, and the subtractive coordinate immunoreactivity pattern. Even when archived material is retrospectively retrieved, CBs are a major tissue source for many supplementary studies. The CBs have been qualitatively and quantitatively improved. CBs are significant since they have increased molecular markers standardized on FFPE tissue. High-quality CBs can serve as useful additions to cytological smear preparations and touch imprint cytology. Most cytological specimens, such as fine-needle aspirations, cavitary effusion, washings, brushings, and gynecological and non-gynecological liquid specimens, may be used to produce CBs. This review deals with the CB-making process and discusses various historical limitations with an emphasis on recent advances.
PubMed: 38343761
DOI: 10.25259/Cytojournal_56_2023 -
Thorax Dec 2023Traditional electromagnetic navigation bronchoscopy (ENB) is a real-time image-guided system and used with thick bronchoscopes for the diagnosis of peripheral pulmonary...
BACKGROUND
Traditional electromagnetic navigation bronchoscopy (ENB) is a real-time image-guided system and used with thick bronchoscopes for the diagnosis of peripheral pulmonary nodules (PPNs). A novel ENB that could be used with thin bronchoscopes was developed. This study aimed to evaluate the diagnostic yield and the experience of using this ENB system in a real clinical scenario.
METHODS
This multicentre study enrolled consecutive patients with PPNs adopting ENB from March 2019 to August 2021. ENB was performed with different bronchoscopes, ancillary techniques and sampling instruments according to the characteristics of the nodule and the judgement of the operator. The primary endpoint was the diagnostic yield. The secondary endpoints included the diagnostic yield of subgroups, procedural details and complication rate.
RESULTS
In total, 479 patients with 479 nodules were enrolled in this study. The median lesion size was 20.9 (IQR, 15.9-25.9) mm. The overall diagnostic yield was 74.9% (359/479). A thin bronchoscope was used in 96.2% (461/479) nodules. ENB in combination with radial endobronchial ultrasound (rEBUS), a guide sheath (GS) and a thin bronchoscope was the most widely used guided method, producing a diagnostic yield of 74.1% (254/343). The median total procedural time was 1325.0 (IQR, 1014.0-1676.0) s. No severe complications occurred.
CONCLUSION
This novel ENB system can be used in combination with different bronchoscopes, ancillary techniques and sampling instruments with a high diagnostic yield and safety profile for the diagnosis of PPNs, of which the combination of thin bronchoscope, rEBUS and GS was the most common method in clinical practice.
TRIAL REGISTRATION NUMBER
NCT03716284.
Topics: Humans; Bronchoscopy; Solitary Pulmonary Nodule; Prospective Studies; Electromagnetic Phenomena; Lung Neoplasms
PubMed: 37734951
DOI: 10.1136/thorax-2022-219664 -
Journal of Cardiovascular Development... Jul 2023In dilated cardiomyopathy (DCM), where the heart muscle becomes stretched and thin, heart failure (HF) occurs, and the cardiomyocytes suffer from an energetic... (Review)
Review
In dilated cardiomyopathy (DCM), where the heart muscle becomes stretched and thin, heart failure (HF) occurs, and the cardiomyocytes suffer from an energetic inefficiency caused by an abnormal cardiac metabolism. Although underappreciated as a potential therapeutic target, the optimal metabolic milieu of a failing heart is still largely unknown and subject to debate. Because glucose naturally has a lower P/O ratio (the ATP yield per oxygen atom), the previous studies using this strategy to increase glucose oxidation have produced some intriguing findings. In reality, the vast majority of small-scale pilot trials using trimetazidine, ranolazine, perhexiline, and etomoxir have demonstrated enhanced left ventricular (LV) function and, in some circumstances, myocardial energetics in chronic ischemic and non-ischemic HF with a reduced ejection fraction (EF). However, for unidentified reasons, none of these drugs has ever been tested in a clinical trial of sufficient size. Other pilot studies came to the conclusion that because the heart in severe dilated cardiomyopathy appears to be metabolically flexible and not limited by oxygen, the current rationale for increasing glucose oxidation as a therapeutic target is contradicted and increasing fatty acid oxidation is supported. As a result, treating metabolic dysfunction in HF may benefit from raising ketone body levels. Interestingly, treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) improves cardiac function and outcomes in HF patients with or without type 2 diabetes mellitus (T2DM) through a variety of pleiotropic effects, such as elevated ketone body levels. The improvement in overall cardiac function seen in patients receiving SGLT2i could be explained by this increase, which appears to be a reflection of an adaptive process that optimizes cardiac energy metabolism. This review aims to identify the best metabolic therapeutic approach for DCM patients, to examine the drugs that directly affect cardiac metabolism, and to outline all the potential ancillary metabolic effects of the guideline-directed medical therapy. In addition, a special focus is placed on SGLT2i, which were first studied and prescribed to diabetic patients before being successfully incorporated into the pharmacological arsenal for HF patients.
PubMed: 37504543
DOI: 10.3390/jcdd10070287 -
Current Opinion in Microbiology Aug 2023The approval of the first-in-class antibacterial bedaquiline for tuberculosis marks a breakthrough in antituberculosis drug development. The drug inhibits mycobacterial... (Review)
Review
The approval of the first-in-class antibacterial bedaquiline for tuberculosis marks a breakthrough in antituberculosis drug development. The drug inhibits mycobacterial respiration and represents the validation of a wholly different metabolic process as a druggable target space. In this review, we discuss the advances in the development of mycobacterial respiratory inhibitors, as well as the potential of applying this strategy to other pathogens. The non-fermentative nature of mycobacteria explains their vulnerability to respiration inhibition, and we caution that this strategy may not be equally effective in other organisms. Conversely, we also showcase fundamental studies that reveal ancillary functions of the respiratory pathway, which are crucial to some pathogens' virulence, drug susceptibility and fitness, introducing another perspective of targeting bacterial respiration as an antibiotic strategy.
Topics: Humans; Antitubercular Agents; Tuberculosis; Respiration; Mycobacterium tuberculosis
PubMed: 37235914
DOI: 10.1016/j.mib.2023.102327 -
The EMBO Journal May 2024The transition of mouse embryonic stem cells (ESCs) between serum/LIF and 2i(MEK and GSK3 kinase inhibitor)/LIF culture conditions serves as a valuable model for...
The transition of mouse embryonic stem cells (ESCs) between serum/LIF and 2i(MEK and GSK3 kinase inhibitor)/LIF culture conditions serves as a valuable model for exploring the mechanisms underlying ground and confused pluripotent states. Regulatory networks comprising core and ancillary pluripotency factors drive the gene expression programs defining stable naïve pluripotency. In our study, we systematically screened factors essential for ESC pluripotency, identifying TEAD2 as an ancillary factor maintaining ground-state pluripotency in 2i/LIF ESCs and facilitating the transition from serum/LIF to 2i/LIF ESCs. TEAD2 exhibits increased binding to chromatin in 2i/LIF ESCs, targeting active chromatin regions to regulate the expression of 2i-specific genes. In addition, TEAD2 facilitates the expression of 2i-specific genes by mediating enhancer-promoter interactions during the serum/LIF to 2i/LIF transition. Notably, deletion of Tead2 results in reduction of a specific set of enhancer-promoter interactions without significantly affecting binding of chromatin architecture proteins, CCCTC-binding factor (CTCF), and Yin Yang 1 (YY1). In summary, our findings highlight a novel prominent role of TEAD2 in orchestrating higher-order chromatin structures of 2i-specific genes to sustain ground-state pluripotency.
Topics: Animals; Mice; TEA Domain Transcription Factors; Chromatin; Transcription Factors; DNA-Binding Proteins; Mouse Embryonic Stem Cells; Pluripotent Stem Cells; Promoter Regions, Genetic; Enhancer Elements, Genetic
PubMed: 38605224
DOI: 10.1038/s44318-024-00086-5 -
Seminars in Diagnostic Pathology Mar 2024Autoimmune pancreatitis (AIP) is classified into type 1 (IgG4-related) and type 2 (IgG4-unrelated) and the interpretation of pancreatic biopsy findings plays a crucial... (Review)
Review
Autoimmune pancreatitis (AIP) is classified into type 1 (IgG4-related) and type 2 (IgG4-unrelated) and the interpretation of pancreatic biopsy findings plays a crucial role in their diagnosis. Needle biopsy of type 1 AIP in the acute or subacute phase shows a diffuse lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis, and the infiltration of many IgG4-positive plasma cells. In a later phase, changes become less inflammatory and more fibrotic, making interpretations more challenging. Confirmation of the lack of 'negative' findings that are unlikely to occur in type 1 AIP (e.g., neutrophilic infiltration, abscess) is important to avoid an overdiagnosis. The number of IgG4-positive plasma cells increases to >10 cells/high-power field (hpf), and the IgG4/IgG-positive plasma cell ratio exceeds 40 %. However, these are minimal criteria and typical cases show >30 positive cells/hpf and a ratio >70 % even in biopsy specimens. Therefore, cases with a borderline increase in this number or ratio need to be diagnosed with caution. In cases of ductal adenocarcinoma, the upstream pancreas rarely shows type 1 AIP-like changes; however, the ratio of IgG4/IgG-positive plasma cells is typically <40 %. Although the identification of a granulocytic epithelial lesion (GEL) is crucial for type 2 AIP, this finding needs to be interpreted in conjunction with a background dense lymphoplasmacytic infiltrate. An isolated neutrophilic duct injury can occur in peritumoral or obstructive pancreatitis. Drug-induced pancreatitis in patients with inflammatory bowel disease often mimics type 2 AIP clinically and pathologically. IL-8 and PD-L1 are potential ancillary immunohistochemical markers for type 2 AIP, requiring validation studies.
Topics: Humans; Autoimmune Pancreatitis; Diagnosis, Differential; Autoimmune Diseases; Pancreatitis; Biopsy, Needle; Immunoglobulin G
PubMed: 38184420
DOI: 10.1053/j.semdp.2024.01.001 -
Pain Mar 2024A diet supplemented with vitamin D and marine omega-3 fatty acids may prevent and treat painful disorders by promoting the resolution of inflammation. However, large,... (Randomized Controlled Trial)
Randomized Controlled Trial
The effect of vitamin D and omega-3 fatty acid supplementation on pain prevalence and severity in older adults: a large-scale ancillary study of the VITamin D and OmegA-3 triaL (VITAL).
A diet supplemented with vitamin D and marine omega-3 fatty acids may prevent and treat painful disorders by promoting the resolution of inflammation. However, large, randomized placebo-controlled trials evaluating the effects of supplementation with omega-3 fatty acids and vitamin D on the presence and severity of pain are lacking. VITamin D and OmegA-3 triaL-Pain (VITAL-Pain) is an ancillary study to the VITAL trial, a large randomized, double-blind, placebo-controlled trial of vitamin D (2000 IU/day) and omega-3 supplementation (1 g/day) over 5.3 years of median follow-up, among 25,871 older men and women. We assessed pain among those reaching the end of the VITAL intervention phase using questions from the 2012 National Health Interview Survey. We used ordinal logistic regression to test the effect of vitamin D and omega-3 fatty acids on the odds ratio (OR) and 95% confidence interval [CI] of reporting higher pain prevalence or severity. Overall, 19,611 participants provided complete pain information at the end of the VITAL trial. The ORs for higher pain prevalence or severity for vitamin D and omega-3 supplementation vs placebo were 0.99 ([CI] 0.94-1.05) and 0.99 ([CI] 0.94-1.04), respectively. There was no interaction between the 2 active treatments. Dietary supplementation with commonly used moderate doses of vitamin D or omega-3 fatty acids over a median of 5.3 years did not result in a lower prevalence or severity of pain in middle-aged and older U.S. adults.
Topics: Male; Middle Aged; Humans; Female; Aged; Vitamin D; Fatty Acids, Omega-3; Prevalence; Vitamins; Cholecalciferol; Dietary Supplements; Double-Blind Method; Pain
PubMed: 37878483
DOI: 10.1097/j.pain.0000000000003044 -
Behavior Analysis in Practice Dec 2023Individuals with developmental disabilities sometimes display avoidance responses such as a lack of cooperation, aggression, and vocal refusal when completing...
UNLABELLED
Individuals with developmental disabilities sometimes display avoidance responses such as a lack of cooperation, aggression, and vocal refusal when completing health-care routines such as dental cleanings, physicals, and haircuts. This study evaluated the effects of both graduated exposure and a differential reinforcement procedure on the acquisition, maintenance, and generalization of cooperation with dental routines. In addition, autonomic responses were used as an ancillary measure of distress or comfort and were included in the decision tree of practitioner actions. Procedures were completed in a simulated context of a dental examination. The results of this study may lead to more comprehensive treatment plans that include the use of physiological responses in addition to cooperation with procedures as an indicator that an avoidance response has been extinguished. Assessing autonomic arousal may be a useful addition to the procedures of exposing participants to dental visit routines, to improve adaptation, cooperation, and generalization.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40617-023-00808-x.
PubMed: 38076753
DOI: 10.1007/s40617-023-00808-x -
International Journal of Surgical... Aug 2023rearranged Renal cell carcinoma (RCC) is not very common, and demonstrates unique heterogenous morphological features overlapping other recognized entities and distinct... (Review)
Review
rearranged Renal cell carcinoma (RCC) is not very common, and demonstrates unique heterogenous morphological features overlapping other recognized entities and distinct immunoprofile. It can be seen in any age group, therefore practicing pathologists should be aware of the distinctive clinical settings and histologic findings associated with these tumors and subsequently employ an adequate panel of ancillary studies in order to confirm the diagnosis. Recognizing these entities remains crucial for future clinical trials and development of novel therapies.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; In Situ Hybridization, Fluorescence; Immunohistochemistry; Translocation, Genetic
PubMed: 35912477
DOI: 10.1177/10668969221108517 -
Radiology Feb 2024Background The independent contribution of each Liver Imaging Reporting and Data System (LI-RADS) CT or MRI ancillary feature (AF) has not been established. Purpose To... (Meta-Analysis)
Meta-Analysis
Background The independent contribution of each Liver Imaging Reporting and Data System (LI-RADS) CT or MRI ancillary feature (AF) has not been established. Purpose To evaluate the association of LI-RADS AFs with hepatocellular carcinoma (HCC) and malignancy while adjusting for LI-RADS major features through an individual participant data (IPD) meta-analysis. Materials and Methods Medline, Embase, Cochrane Central Register of Controlled Trials, and Scopus were searched from January 2014 to January 2022 for studies evaluating the diagnostic accuracy of CT and MRI for HCC using LI-RADS version 2014, 2017, or 2018. Using a one-step approach, IPD across studies were pooled. Adjusted odds ratios (ORs) and 95% CIs were derived from multivariable logistic regression models of each AF combined with major features except threshold growth (excluded because of infrequent reporting). Liver observation clustering was addressed at the study and participant levels through random intercepts. Risk of bias was assessed using a composite reference standard and Quality Assessment of Diagnostic Accuracy Studies 2. Results Twenty studies comprising 3091 observations (2456 adult participants; mean age, 59 years ± 11 [SD]; 1849 [75.3%] men) were included. In total, 89% (eight of nine) of AFs favoring malignancy were associated with malignancy and/or HCC, 80% (four of five) of AFs favoring HCC were associated with HCC, and 57% (four of seven) of AFs favoring benignity were negatively associated with HCC and/or malignancy. Nonenhancing capsule (OR = 3.50 [95% CI: 1.53, 8.01]) had the strongest association with HCC. Diffusion restriction (OR = 14.45 [95% CI: 9.82, 21.27]) and mild-moderate T2 hyperintensity (OR = 10.18 [95% CI: 7.17, 14.44]) had the strongest association with malignancy. The strongest negative associations with HCC were parallels blood pool enhancement (OR = 0.07 [95% CI: 0.01, 0.49]) and marked T2 hyperintensity (OR = 0.18 [95% CI: 0.07, 0.45]). Seventeen studies (85%) had a high risk of bias. Conclusion Most LI-RADS AFs were independently associated with HCC, malignancy, or benignity as intended when adjusting for major features. © RSNA, 2024 See also the editorial by Crivellaro in this issue.
Topics: Adult; Male; Humans; Middle Aged; Female; Carcinoma, Hepatocellular; Liver Neoplasms; Radionuclide Imaging; Magnetic Resonance Imaging
PubMed: 38376399
DOI: 10.1148/radiol.231501