Architectural Distortion Research Articles

Cytokine signaling converging on IL11 in ILD fibroblasts provokes aberrant epithelial differentiation signatures.

Interstitial lung disease (ILD) is a heterogenous group of lung disorders where destruction and incomplete regeneration of the lung parenchyma often results in persistent architectural distortion of the pulmonary scaffold. Continuous mesenchyme-centered, disease-relevant signaling likely initiates and perpetuates the fibrotic remodeling process, specifically targeting the epithelial cell compartment, thereby destroying the gas exchange area. With the aim of identifying functional mediators of the lung mesenchymal-epithelial crosstalk with potential as new targets for therapeutic strategies, we developed a 3D organoid co-culture model based on human induced pluripotent stem cell-derived alveolar epithelial type 2 cells that form alveolar organoids in presence of lung fibroblasts from fibrotic-ILD patients, in our study referring to cases of pulmonary fibrosis, as well as control cell line (IMR-90). While organoid formation capacity and size was comparable in the presence of fibrotic-ILD or control lung fibroblasts, metabolic activity was significantly increased in fibrotic-ILD co-cultures. Alveolar organoids cultured with fibrotic-ILD fibroblasts further demonstrated reduced stem cell function as reflected by reduced Surfactant Protein C gene expression together with an aberrant basaloid-prone differentiation program indicated by elevated Cadherin 2, Bone Morphogenic Protein 4 and Vimentin transcription. To screen for key mediators of the misguided mesenchymal-to-epithelial crosstalk with a focus on disease-relevant inflammatory processes, we used mass spectrometry and characterized the secretome of end stage fibrotic-ILD lung fibroblasts in comparison to non-chronic lung disease (CLD) patient fibroblasts. Out of the over 2000 proteins detected by this experimental approach, 47 proteins were differentially abundant comparing fibrotic-ILD and non-CLD fibroblast secretome. The fibrotic-ILD secretome profile was dominated by chemokines, including CXCL1, CXCL3, and CXCL8, interfering with growth factor signaling orchestrated by Interleukin 11 (IL11), steering fibrogenic cell-cell communication, and proteins regulating extracellular matrix remodeling including epithelial-to-mesenchymal transition. When in turn treating alveolar organoids with IL11, we recapitulated the co-culture results obtained with primary fibrotic-ILD fibroblasts including changes in metabolic activity. We identified mediators likely contributing to the disease-perpetuating mesenchymal-to-epithelial crosstalk in ILD. In our alveolar organoid co-cultures, we were able to highlight the importance of fibroblast-initiated aberrant epithelial differentiation and confirmed IL11 as a key player in fibrotic-ILD pathogenesis by unbiased fibroblast secretome analysis.

Management of Mammographic Architectural Distortion Based on Contrast-enhanced MRI and US Correlation.

The objective was to evaluate outcomes of mammographic architectural distortion (AD) with and without MRI and US correlates. A retrospective review of unexplained mammographic AD with subsequent MRI from January 1, 2007 to September 30, 2017 was performed using a reader-based study design. Mammographic, MRI, and US features and outcomes were documented. Truth was based on biopsy results or minimum two-year imaging follow-up. Measures of diagnostic accuracy were calculated. Fifty-six cases of AD were included: 29 (51.8%) detected on 2D mammogram and 27 (48.2%) detected on digital breast tomosynthesis. Of 35.7% (20/56) with MRI correlate, 40.0% (8/20) were enhancing masses, 55.0% (11/20) were non-mass enhancement (NME), and 5.0% (1/20) were nonenhancing AD. Of eight enhancing masses, 75.0% (6/8) were invasive cancers, and 25.0% (2/8) were high-risk lesions. Of 11 NME, 18.2% (2/11) were ductal carcinoma in situ, 36.4% (4/11) were high-risk lesions, and 45.4% (5/11) were benign. Of 64.3% (36/56) without MRI correlate, 94.4% (34/36) were benign by pathology or follow-up, one (2.8%, 1/36) was a 4-mm focus of invasive cancer with US correlate, and one (1/36, 2.8%) was a high-risk lesion. Of cases without MRI and US correlates, one (3.0%, 1/33) was a high-risk lesion and 97.0% (32/33) were benign. The negative predictive value of mammographic AD without MRI correlate was 97.2% (35/36) and without both MRI and US correlates was 100.0% (33/33). Mammographic AD without MRI or US correlate was not cancer in our small cohort and follow-up could be considered, reducing interventions.

Myeloid Sarcoma of the Breast: A Diagnostic Dilemma With Pathologic Correlation.

Myeloid sarcoma (MS) is a rare extramedullary solid tumor arising most often in patients with current or subsequent acute myeloid leukemia (AML). Patients of all ages may present with involvement of the skin, lymph nodes, intestinal tract, bone, and/or central nervous system. Isolated involvement of the breast is rare, and only a small number of cases have been described in the literature. Breast MS may present as a palpable mass on clinical evaluation. In this broad literature review from 2010 to 2022, the most common findings on mammography are either solitary or multiple masses, followed by architectural distortion and, less commonly, no discrete findings. Sonography may demonstrate hypoechoic or mixed echogenicity mass(es) with circumscribed or indistinct, not discrete margins. Myeloid sarcoma may present as an enhancing mass or nonmass enhancement on breast MRI and is typically moderately radiotracer avid on 18F-fluorodeoxyglucose-PET. At histopathology, MS is characterized by myeloid blasts in varying stages of granulocytic or neutrophilic maturation; diagnosis typically requires immunophenotyping. There is no consensus for treatment of MS, although systemic chemotherapy for AML is often used as MS is considered the tissue equivalent of AML. This article will discuss and illustrate imaging and pathology findings when the breast is involved by MS.

Single-nucleus chromatin accessibility identifies a critical role for TWIST1 in idiopathic pulmonary fibrosis myofibroblast activity.

In idiopathic pulmonary fibrosis (IPF), myofibroblasts are key effectors of fibrosis and architectural distortion by excessive deposition of extracellular matrix and their acquired contractile capacity. Single-cell RNA-sequencing (scRNA-seq) has precisely defined the IPF myofibroblast transcriptome, but identifying critical transcription factor activity by this approach is imprecise. We performed single-nucleus assay for transposase-accessible chromatin sequencing on explanted lungs from patients with IPF (n=3) and donor controls (n=2) and integrated this with a larger scRNA-seq dataset (10 IPF, eight controls) to identify differentially accessible chromatin regions and enriched transcription factor motifs within lung cell populations. We performed RNA-sequencing on pulmonary fibroblasts of bleomycin-injured Twist1-overexpressing COL1A2 Cre-ER mice to examine alterations in fibrosis-relevant pathways following Twist1 overexpression in collagen-producing cells. TWIST1, and other E-box transcription factor motifs, were significantly enriched in open chromatin of IPF myofibroblasts compared to both IPF nonmyogenic (log2 fold change (FC) 8.909, adjusted p-value 1.82×10-35) and control fibroblasts (log2FC 8.975, adjusted p-value 3.72×10-28). TWIST1 expression was selectively upregulated in IPF myofibroblasts (log2FC 3.136, adjusted p-value 1.41×10- 24), with two regions of TWIST1 having significantly increased accessibility in IPF myofibroblasts. Overexpression of Twist1 in COL1A2-expressing fibroblasts of bleomycin-injured mice resulted in increased collagen synthesis and upregulation of genes with enriched chromatin accessibility in IPF myofibroblasts. Our studies utilising human multiomic single-cell analyses combined with in vivo murine disease models confirm a critical regulatory function for TWIST1 in IPF myofibroblast activity in the fibrotic lung. Understanding the global process of opening TWIST1 and other E-box transcription factor motifs that govern myofibroblast differentiation may identify new therapeutic interventions for fibrotic pulmonary diseases.

CORRELATION OF MAMMOGRAPHIC AND HISTOPATHOLOGICAL CHARACTERISTICS OF BREAST LESIONS

Introduction: Breast Imaging Reporting and Data System (BI-RADS) is the universal standard developed bythe American College of Radiology to characterize breast lesions on mammography.Histopathological assessment is usually doneaftersurgery,helpstocorrelatetheBI-RADSscoringsystem.).Molecular markers including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2(Her2) have prognostic and predictive values and hence can be used to recommend treatmentguidelines. Methodology: A 2-year prospective cross-sectional observational study was conductedin the Departments of Pathology and Radiodiagnosis, Christian Medical College, Ludhiana. Atotalof62caseswhichhadundergonemammographyfollowedbyabreastbiopsywereincludedinthe study. Mammograms and Histopathology slides of all cases were reviewed independently by tworadiologists and pathologists respectively. Results: Lesions with smaller diameters on mammography and biopsy showed a stroke positive correlation (r =0.5461,p=0.0007). Significant associations of biomarkers with mammography characteristics were observed(ER with architectural distortion, p=0.005 ER with margins, p=0.005 PR with architecturaldistortion,p=0.009PRwithmargins,p=0.005Her2witharchitecturaldistortion,p=0.007Her2with margins, p=0.006). Conclusion: Significant associations between histopathological biomarkers and mammography characteristics could provide additional information at the first contact of a patient with a breast lesion.

Morphological, biochemical, and histopathological effects of levetiracetam on pregnant albino rats and their offspring

ABSTRACT One of the most widely used medications for epilepsy is the broad-spectrum antiseizure levetiracetam. The study aimed to evaluate the impact of levetiracetam on the bodyweight and liver of pregnant rats and their offspring. The study involved treating the rats during pregnancy and lactation and then examining the pregnant rats and their offspring. Two groups of 40 pregnant rats were created (I, II). Each group was split up into two smaller groups (A, B). About 1.5 mL/day of distilled water was gavaged to the rats in group I, either continuously throughout pregnancy (IA) or continuously throughout pregnancy and 15 days after delivery (IB). Group II rats received 1.5 ml/day of distilled water (containing levetiracetam) either during pregnancy (IIA) or during pregnancy plus 15 days postpartum (IIB). At the end of the work, blood samples were taken from the adult rats, body weight of different groups were recorded, and then, their liver was subjected for histological and morphometric analysis. Levetiracetam treatment showed reduction in the body weight of adult rats and their offspring and pathological changes in their liver. These changes were in the form of distortion of the hepatic architecture, cytoplasmic vacuolation, nuclear changes, and swollen mitochondria with loss of their cristae. Such changes were proved by alteration in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme levels of the liver. It is advised to monitor the liver functions continuously when using levetiracetam.

Idiopathic Granulomatous Mastitis or Breast Cancer? A Comparative MRI Study in Patients Presenting with Non-Mass Enhancement.

To compare and determine discriminative magnetic resonance imaging (MRI) findings of idiopathic granulomatous mastitis (IGM) and breast cancer (BC) that present as non-mass enhancement. This retrospective study includes 68 IGM and 75 BC cases that presented with non-mass enhancement on breast MRI. All patients with a previous history of breast surgery, radiotherapy, or chemotherapy due to BC or a previous history of mastitis were excluded. On MRI images, presence of architectural distortion skin thickening, edema, hyperintense ducts containing protein, dilated fat-containing ducts and axillary adenopathies were noted. Cysts with enhancing walls, lesion size, lesion location, fistulas, distribution, internal enhancement pattern and kinetic features of non-mass enhancement were recorded. Apparent diffusion coefficient (ADC) values were calculated. Pearson chi-square test, Fisher's exact test, independent t test and Mann-Whitney U test were used as needed for statistical analysis and comparison. Multivariate logistic regression model was used to determine the independent predictors. IGM patients were significantly younger than BC patients (p < 0.001). Cysts with thin (p < 0.05) or thick walls (p = 0.001), multiple cystic lesions, (p < 0.001), cystic lesions draining to the skin (p < 0.001), and skin fistulas (p < 0.05) were detected more often in IGM. Central (p < 0.05) and periareolar (p < 0.001) location and focal skin thickening (p < 0.05) were significantly more common in IGM. Architectural distortion (p = 0.001) and diffuse skin thickening (p < 0.05) were associated with BC. Multiple regional distribution was more common in IGM, whereas diffuse distribution and clumped enhancement were more common in BC (p < 0.05). In kinetic analysis, persistent enhancement was more common in IGM, whereas plateau and wash-out types were more common in BC (p < 0.001). Independent predictors for BC were age, diffuse skin thickening and kinetic curve types. There was no significant difference in the diffusion characteristics. Based on these findings, MRI had a sensitivity, specificity and accuracy of 88%, 67.65%, and 78.32%, respectively, in differentiating IGM from BC. In conclusion, for non-mass enhancement, MRI can rule out malignancy with a considerably high sensitivity; however, specificity is still low, as many IGM patients have overlapping findings. Final diagnosis should be complemented with histopathology whenever necessary.

Comparison of prone and upright, stereotactic, and tomosynthesis-guided biopsies with secondary analysis of ultrasound-occult architectural distortions.

Compare prone and upright, stereotactic, and tomosynthesis-guided vacuum-assisted breast biopsies (prone DM-VABB, prone DBT-VABB, upright DM-VABB, and upright DBT-VABB) in a community-practice setting and review outcomes of ultrasound-occult architectural distortions (AD). Consecutive biopsies performed at two community-based breast centers from 2016 to 2019 were retrospectively reviewed. Technical details of each procedure and patient outcomes were recorded. Separate analyses were performed for ultrasound-occult ADs. Two sample t-tests and Fisher's exact test facilitated comparisons. A total of 1133 patients underwent 369 prone DM-VABB, 324 prone DBT-VABB, 437 upright DM-VABB, and 123 upright DBT-VABB with 99.2%, 100%, 99.3%, and 99.2% success, respectively (p-values > 0.25). Mean lesion targeting times were greater for prone biopsy (minutes: 6.94 prone DM-VABB, 8.54 prone DBT-VABB, 5.52 upright DM-VABB, and 5.51 upright DBT-VABB; p-values < 0.001), yielding longer total prone procedure times for prone biopsy (p < 0.001). Compared to DM-VABB, DBT-VABB used fewer exposures (p < 0.001) and more commonly targeted AD, asymmetries, or masses (p < 0.001). Malignancy rates were similar between procedures: prone DM-VABB 22.4%, prone DBT-VABB 21.9%, upright DM-VABB 22.8%, and upright DBT-VABB 17.2% (p-values > 0.19). One hundred forty of the 1133 patients underwent 145 biopsies for ultrasound-occult AD (143 DBT-VABB and 2 DM-VABB). Biopsy yielded 27 malignancies and 47 high-risk lesions (74 of 145, 51%). Malignancy rate was 20.7% after surgical upgrade of one benign-discordant and two high-risk lesions. All biopsy procedure types were extremely successful. The 20.7% malignancy rate for ultrasound-occult AD confirms a management recommendation for tissue diagnosis. Upright biopsy was faster than prone biopsy, and DBT-VABB used fewer exposures than DM-VABB. Our results highlight important differences between prone DM-VABB, prone DBT-VABB, upright DM-VABB, and upright DBT-VABB. Moreover, the high likelihood of malignancy for ultrasound-occult AD will provide confidence in recommending tissue diagnosis in lieu of observation or clinical follow-up. • Upright and prone stereotactic and tomosynthesis-guided breast biopsies were safe and effective in the community-practice setting. • The malignancy rate for ultrasound-occult architectural distortion of 20.7% confirms the management recommendation for biopsy. • Upright procedures were faster than prone procedures, and tomosynthesis-guided biopsy used fewer exposures than stereotactic biopsy.

Diagnostic value of multimodal ultrasound strategies in the differentiation of non-mass-like breast lesions.

The study aims to assess the diagnostic performance of convention ultrasound (US), Angio PLUS microvascular US imaging (AP), and shear-wave elastography (SWE) in differentiating malignant and benign non-mass-like (NML) breast lesions. Sixty patients aged 21-70 years with 60 NML lesions were recruited. All patients were examined by conventional US, AP, and SWE. According to the pathological results, the performances of the multimodal US strategies were analyzed, while the diagnostic efficiency of AP and SWE in serial and parallel was also explored. Age, together with posterior features, microcalcification, and architectural distortion were considered significant in evaluating NML lesions. The sensitivity, specificity, PPV, NPV, and accuracy of AP combined SWE in serial were 72.7, 96.3, 96.0, 74.3, and 83.3%, while those in parallel were 90.9, 63.0, 75.0, 85.0, and 78.3%, respectively. The two in serial indicated the highest specificity, PPV, accuracy, and AUC value, which could increase the true positive rate and reduce the chance of misdiagnosis, while the two in parallel exhibited the best sensitivity and NPV, which might serve as an effective tool to avoid excessive or nonessential biopsy. The multimodal US strategies could provide precise and reliable diagnostic results for NML breast lesions.

Artificial Intelligence for Neuroimaging and Musculoskeletal Radiology: Overview of Current Commercial Algorithms

To assess differences in the mammographic and sonographic appearance of breast cancer in African American (AA) and Non-Latina White (NLW) women.We identified AA and NLW women with biopsy proven ductal carcinoma in situ or invasive breast cancer between June 1, 2015 and May 31, 2018. Racial differences in Breast Imaging and Reporting Data System (BI-RADS) imaging features were analyzed by imaging cohorts, i.e. screen detected vs. clinical presentation, using logistic regression adjusted for histology and molecular subtypes.We analyzed 270 AA women with 278 cancers (166 screen detected, 112 clinical) and 586 NLW women with 599 cancers (397 screen detected, 202 clinical). Compared with NLW women, AA women had higher rates of non-dense breast composition (almost entirely fatty 12.0% vs. 4.6%, scattered fibroglandular 50.9% vs. 45.2%; overall P < 0001) in both cohorts and were less likely to have screen detected architectural distortion, (odds ratio (OR) = 0.38, 95% CI 0.18–0.80). AA women were less likely than NLW women to have screen detected irregular than oval/round masses (mammography: OR = 0.36, 95% CI 0.19–0.68; sonography: OR = 0.48, 95% CI 0.24–0.94), and more likely to present clinically with high density masses (OR = 3.03, 95% CI 1.12–8.20) demonstrating posterior enhancement (OR = 3.02, 95% CI 1.11–8.27).There are racial differences in the mammographic and sonographic appearance of breast cancer even after accounting for higher rates of triple negative breast cancer in AA women. Understanding these differences may provide breast imagers with a framework to approach breast cancer diagnosis in the AA population in clinical practice.

PRIMARY EOSINOPHILIC COLITIS WITH CONCOMITANT NEWLY DIAGNOSED INFLAMMATORY BOWEL DISEASE – A DIAGNOSITIC CONUNDRUM

Eosinophilic colitis (EC) is a rare primary condition characterized by eosinophilic infiltration of the colon in the absence of secondary causes. Affecting only 0.003% of people in the United States, clinical manifestations of the disease can range from abdominal pain, bloody stools, and diarrhea to colonic obstruction, intussusception, volvulus, and perforation. The diagnosis is made upon histopathological analysis of colonic biopsies with the inflammatory infiltrate consisting predominantly or exclusively of eosinophils with focal collections greater than 100 per high-power field (hpf). Unlike inflammatory bowel disease (IBD), granulomas, crypt architectural distortion, pseudopyloric metaplasia, and fibrosis are not usually present with EC, but differentiating between the two conditions has proven to be difficult over the decades.

Trends of Chronic Liver Disease in a Tertiary Care Centre in the Eastern Part of India: A Retrospective Study.

To assess the relationship between the severity of liver cirrhosis and its outcomesbased on laboratory parameters, Child-Turcotte-Pugh (CTP) score, and upper gastrointestinal (UGI) endoscopy findings. Cirrhosis is the end stage of chronic liver disease (CLD)and is characterised by progressive liver fibrosis and distortion of the liver architecture. It is a major cause of morbidity and mortality all over the world. Cirrhosis is compensated in the initial stages and later progresses to the decompensated stage with various complications. The CTP scoring system predicts mortality inpatients with cirrhosis. This retrospective study was done in the Department ofMedicine and Gastroenterology of Tata Main Hospital (TMH), Jamshedpur, Jharkhand, India. It wasconducted over a period of two years between 1 January2019 and31 December 2020, on 150 confirmed cases ofcirrhosis. The most common age group was 41-60 years (86, 57.33%) and the mean age ± standard deviation (SD) for all patients was 49.82 ± 11.63 years. In a total of 150 CLD cases, males were 96 (64%). The most common cause of CLD was alcohol (76, 50.67%). Based on presenting symptoms, most CLD patients presented with generalized weakness (144, 96.00%). The most common signs were icterus (68, 45.33%) and ascites (44, 29.33%). Most patients belonged to CTP class A (77, 51.33%), followed by CTP class B (44, 29.33%) and class C (29, 19.34%). The most common UGI endoscopy findingwas portal hypertensive gastropathy (mild or severe) (135, 75%). Total deaths were 24 (16.00%), with 17 deaths (70.83%) in patients belonging to CTP class C. CLD is a common entity in eastern India with male preponderance and affects mostly people of the middle age group.Alcohol intake is a major cause of CLD,followed by non-alcoholic fatty liver disease and chronic hepatitis B and C. A significant rise inmorbidity and mortality due toalcoholic liver disease (ALD)was observed in the study and needs urgent social and medical intervention. The incidence of ALD in our study was 50.67%.

Longitudinal Lung Function Assessment of Patients Hospitalized With COVID-19 Using 1H and 129Xe Lung MRI

Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pulmonary changes in these patients remains unclear. Do patients hospitalized with COVID-19 without evidence of architectural distortion on structural imaging exhibit longitudinal improvements in lung function measured by using 1H and 129Xe MRI between 6 and 52weeks following hospitalization? Patients who were hospitalized with COVID-19 pneumonia underwent a pulmonary 1H and 129Xe MRI protocol at 6, 12, 25, and 51weeks following hospital admission in a prospective cohort study between November 2020 and February 2022. The imaging protocol was as follows: 1H ultra-short echo time, contrast-enhanced lung perfusion, 129Xe ventilation, 129Xe diffusion-weighted, and 129Xe spectroscopic imaging of gas exchange. Nine patients were recruited (age 57 ± 14 [median ± interquartile range] years; six of nine patients were male). Patients underwent MRI at 6 (n= 9), 12 (n= 9), 25 (n= 6), and 51 (n= 8) weeks following hospital admission. Patients with signs of interstitial lung damage were excluded. At 6weeks, patients exhibited impaired 129Xe gas transfer (RBC to membrane fraction), but lung microstructure was not increased (apparent diffusion coefficient and mean acinar airway dimensions). Minor ventilation abnormalities present in four patients were largely resolved in the 6- to 25-week period. At 12weeks, all patients with lung perfusion data (n= 6) showed an increase in both pulmonary blood volume and flow compared with 6weeks, although this was not statistically significant. At 12weeks, significant improvements in 129Xe gas transfer were observed compared with 6-week examinations; however, 129Xe gas transfer remained abnormally low at weeks 12, 25, and51. 129Xe gas transfer was impaired up to 1 year following hospitalization in patients who were hospitalized with COVID-19 pneumonia, without evidence of architectural distortion on structural imaging, whereas lung ventilation was normal at 52weeks.

Identification and diagnosis of mammographic malignant architectural distortion using a deep learning based mask regional convolutional neural network.

Architectural distortion (AD) is a common imaging manifestation of breast cancer, but is also seen in benign lesions. This study aimed to construct deep learning models using mask regional convolutional neural network (Mask-RCNN) for AD identification in full-field digital mammography (FFDM) and evaluate the performance of models for malignant AD diagnosis. This retrospective diagnostic study was conducted at the Second Affiliated Hospital of Guangzhou University of Chinese Medicine between January 2011 and December 2020. Patients with AD in the breast in FFDM were included. Machine learning models for AD identification were developed using the Mask RCNN method. Receiver operating characteristics (ROC) curves, their areas under the curve (AUCs), and recall/sensitivity were used to evaluate the models. Models with the highest AUCs were selected for malignant AD diagnosis. A total of 349 AD patients (190 with malignant AD) were enrolled. EfficientNetV2, EfficientNetV1, ResNext, and ResNet were developed for AD identification, with AUCs of 0.89, 0.87, 0.81 and 0.79. The AUC of EfficientNetV2 was significantly higher than EfficientNetV1 (0.89 vs. 0.78, P=0.001) for malignant AD diagnosis, and the recall/sensitivity of the EfficientNetV2 model was 0.93. The Mask-RCNN-based EfficientNetV2 model has a good diagnostic value for malignant AD.

Characterizing morphologic subtypes of high-grade serous ovarian cancer by CT: a retrospective cohort study

ObjectiveA novel classification system of high-grade serous ovarian carcinoma based on gross morphology observed at pre-treatment laparoscopy was recently defined. The purpose of this study was to identify radiographic features...

Effects of piperlonguminine on lung injury in severe acute pancreatitis &lt;em&gt;via&lt;/em&gt; the TLR4 /NF-κB pathway

Acute pancreatitis is an inflammatory response in the pancreas, involving activation of pancreatic enzymes. Severe acute pancreatitis (SAP) often causes systemic complications that affect distant organs, including the lungs. The aim of this study was to explore the therapeutic potential of piperlonguminine on SAP-induced lung injury in rat models. Acute pancreatitis was induced in rats by repetitive injections with 4% sodium taurocholate. Histological examination and biochemical assays were used to assess the severity of lung injury, including tissue damage, and levels of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), reactive oxygen species (ROS), and inflammatory cytokines. We found that piperlonguminine significantly ameliorated pulmonary architectural distortion, hemorrhage, interstitial edema, and alveolar thickening in rats with SAP. In addition, NOX2, NOX4, ROS, and inflammatory cytokine levels in pulmonary tissues were notably decreased in piperlonguminine-treated rats. Piperlonguminine also attenuated the expression levels of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB). Together, our findings demonstrate for the first time that piperlonguminine can ameliorate acute pancreatitis-induced lung injury via inhibitory modulation of inflammatory responses by suppression of the TLR4/NF-κB signaling pathway.

Renal Ultrasonography Findings in Cats with Feline Infectious Peritonitis

Feline infectious peritonitis (FIP) is a fatal disease caused by a mutated feline enteric coronavirus (FECV) that causes a wide diversity of clinical findings. Antemortem diagnosis may be challenging as the non-effusive form causes pyogranulomatous inflammation in various organs including the eye, brain, omentum, liver and kidney compared to the effusive form. Since it has been discussed that the kidney is the organ most susceptible to FIP-related lesion development, this study aimed to evaluate the renal ultrasonography findings in cats with naturally developed non-effusive FIP. Clinical and renal ultrasonographic examinations of 17 cats with compatible clinical findings that would suggest the presence of non-effusive FIP were performed with the appropriate protocol. Both cats’ kidneys were evaluated for echogenicity, size (longitudinal length), shape, presence of free fluid, if any, and echogenicity of this fluid. As a result of renal ultrasonography, it was observed that the most prominent abnormal ultrasonographic findings were cortical hyperechogenicity (11 out of 17 cats), medullary rim sign (11 out of 17 cats), renomegaly (10 out of 17 cats), pyelectasis (5 out of 17 cats), loss of corticomedullary differentiation (4 out of 17 cats) and distortion of internal architecture (4 out of 17 cats). In conclusion, it was observed that morphological and parenchymal alterations occur in the renal ultrasonographic evaluation in cats with non-effusive FIP, and renal ultrasonography could provide useful clinical information in evaluating the clinical reflection of vasculitis due to FIP. Although these abnormal renal ultrasonography findings were not specific for FIP, it was concluded that the combination of the observed ultrasonographic findings and other compatible clinical findings and their evaluation together can be used to increase the index of suspicion for antemortem FIP infection.

The Role of Pyrazolo[3,4-d]pyrimidine-Based Kinase Inhibitors in The Attenuation of CCl4-Induced Liver Fibrosis in Rats

Liver Fibrosis can be life-threatening if left untreated as it may lead to serious, incurable complications. The common therapeutic approach is to reverse the fibrosis while the intervention is still applicable. Celecoxib was shown to exhibit some antifibrotic properties in the induced fibrotic liver in rats. The present study aimed to investigate the possible antifibrotic properties in CCl4-induced liver fibrosis in male Sprague-Dawley rats compared to celecoxib of three novel methoxylated pyrazolo[3,4-d]pyrimidines. The three newly synthesized compounds were proved to be safe candidates. They showed a therapeutic effect against severe CCl4-induced fibrosis but at different degrees. The three compounds were able to partially reverse hepatic architectural distortion and reduce the fibrotic severity by showing antioxidant properties reducing MDA with increasing GSH and SOD levels, remodeling the extracellular matrix proteins and liver enzymes balance, and reducing the level of proinflammatory (TNF-α and IL-6) and profibrogenic (TGF-β) cytokines. The results revealed that the dimethoxy-analog exhibited the greatest activity in all the previously mentioned parameters compared to celecoxib and the other two analogs which could be attributed to the different methoxylation patterns of the derivatives. Collectively, the dimethoxy-derivative could be considered a safe promising antifibrotic candidate.

Are Interstitial Lung Abnormalities a Prognostic Factor of Worse Outcome in COVID-19 Pneumonia?

To assess the association between interstitial lung abnormalities (ILAs) and worse outcome in patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19)-related pneumonia. The study included patients older than 18 years, who were admitted at the emergency department between February 29 and April 30, 2020 with findings of COVID-19 pneumonia at chest computed tomography (CT), with positive reverse-transcription polymerase chain reaction nasal-pharyngeal swab for SARS-CoV-2, and with the availability of prepandemic chest CT. Prepandemic CTs were reviewed for the presence of ILAs, categorized as fibrotic in cases with associated architectural distortion, bronchiectasis, or honeycombing. Worse outcome was defined as intensive care unit (ICU) admission or death. Cox proportional hazards regression analysis was used to test the association between ICU admission/death and preexisting ILAs. The study included 147 patients (median age 73y old; 95% CIs: 71-76-y old; 29% females). On prepandemic CTs, ILA were identified in 33/147 (22%) of the patients, 63% of which were fibrotic ILAs. Fibrotic ILAs were associated with higher risk of ICU admission or death in patients with COVID-19 pneumonia (hazard ratios: 2.73, 95% CIs: 1.50-4.97, P =0.001). In patients affected by COVID-19 pneumonia, preexisting fibrotic ILAs were an independent predictor of worse prognosis, with a 2.7 times increased risk of ICU admission or death. Chest CT scans obtained before the diagnosis of COVID-19 pneumonia should be carefully reviewed for the presence and characterization of ILAs.

The challenging imaging and histopathologic features of diffusely infiltrating breast cancer

PurposeClinical, imaging and outcome observations indicate that diffusely infiltrating breast cancer, presenting as a large region of architectural distortion on the mammogram and conventionally termed classic infiltrating lobular carcinoma of diffuse type, represents a very unusual breast malignancy. This article aims to draw attention to the complex clinical, imaging, and large format thin and thick section histopathologic features of this malignancy, which challenges our current diagnostic and therapeutic management practices. MethodsProspectively collected data from the randomized controlled trial (1977–85) and from the subsequent, ongoing population-based mammography service screening (1985–2019) with more than four decades of follow up in Dalarna County, Sweden provided the database for investigating this breast cancer subtype. Large format thick (subgross) and thin section histopathologic images of breast cancers diagnosed as “diffusely infiltrating lobular carcinoma of the breast” were correlated with their mammographic tumour features (imaging biomarkers) and the long-term patient outcome. ResultsThis malignancy does not have a distinct tumour mass or focal skin retraction at clinical breast examination; instead, it causes an indistinct “thickening” and eventually shrinks the entire breast. A dominant feature is extensive architectural distortion on the mammograms caused by an excessive amount of cancer-associated connective tissue. Unlike other invasive breast malignancies, this subtype forms concave contours with the surrounding adipose connective tissue, a feature that makes it difficult to detect on mammograms. Women with this diffusely infiltrating breast malignancy have a 60% long-term survival. Its long-term patient outcome is surprisingly poor compared to that expected from its relatively favourable immunohistochemical biomarkers, including a low proliferation index and remains unaffected by adjuvant therapy. ConclusionsThe unusual clinical, histopathologic and imaging features of this diffusely infiltrating breast cancer subtype are consistent with a site of origin quite different from that of other breast cancers. Additionally, the immunohistochemical biomarkers are deceptive and unreliable because they indicate a cancer with favourable prognostic features predictive of a good long-term outcome. The low proliferation index is usually indicative of a breast cancer with a good prognosis, but in this subtype the prognosis is poor. If we are to improve the dismal outcome of this malignancy, it will be necessary to clarify its true site of origin, which will be a prerequisite for gaining a better understanding why current management efforts often fail and why the fatality rate is so unfortunately high. Breast radiologists should be watchful for the development of subtle signs of architectural distortion at mammography. Large format histopathologic technique enables adequate correlation of the imaging and histopathologic findings.