A20 promoted the phagocytosis of lymphoma cells by dendritic cells from activated B-cell-like non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) is a lymphoproliferative disorder derived from either B or T lymphocytes. Among NHL, activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) and T cell non-Hodgkin lymphomas (T-NHL) are poor prognosis and aggressive subtypes. Macrophages are professional phagocytic cells and dendritic cells (DCs) are professional antigen-presenting cells in immune system. Doxorubicin (Dox) and Etoposide (ET) are the most effective anti-cancer drugs. A20 and CYLD are negative regulators of NF-κB-dependent functions in many cell types. Little is known about the roles of A20 and CYLD in regulating functions of DCs and macrophages from NHL. The present study, therefore, explored whether A20/CYLD expression contributes to functions of DCs and macrophages from NHL. To this end, blood samples of seventy-nine patients with ABC DLBCL and T-NHL were examined. Gene expression profile was determined by quantitative RT-PCR and immunophenotype, cell apoptosis and phagocytosis by flow cytometry. As a result, immunophenotypic analysis showed that the numbers of CD13+CD117-, CD56+CD40+ and CD23+CD40+ expressing cells were significantly elevated in ABC DLBCL cases compared to healthy individuals and T-NHL patients. Interestingly, upon treatment of Dox and ET, the phagocytosis of lymphoma cells was significantly reduced by CD11c+CD123- DCs and the percentage of CD56+ mature DCs was significantly enhanced in ABC DLBCL patients only in the presence of A20 siRNA, but not CYLD siRNA. In conclusion, ABC DLBCL patients with low A20 expression were defective in elimination of lymphoma cells by DCs and linked to killer DC expansion in circulation.

[Laparoscopic ultrasound-guided radiofrequency ablation of uterine fibroid: A retrospective study]. / Myolyse des fibromes utérins par radiofréquence cœlioscopique sous contrôle échographique : à propos d'une série rétrospective.

OBJECTIVE: To assess clinical and radiological efficacy and safety of laparoscopic ultrasound-guided radiofrequency ablation of uterine leiomyomas. MATERIAL AND METHODS: Thirty-three patients with symptomatic uterine leiomyomas FIGO type 2 to 7, have undergone a laparoscopic ultrasound-guided radiofrequency ablation at Croix Rousse University Hospital Center (Hospices civils de Lyon) and at Saint-Vincent de Paul Hospital in Lille, between June 2020 and December 2022. The characteristics of each myoma and the symptoms were assessed with pelvic MRI and with Higham score, SSS and HRQL scores preoperatively and at 6 months. RESULTS: A total of 54 fibroids have been treated in 33 patients. We observed a significant decrease of the volume 6 months after the surgery, on average 21mL (55.97 vs. 74.37mL, 95% CI [7.13-34.88], P=0.001). The maximum diameter of each fibroid was also significantly reduced on average 11.78mm (41.89 vs. 52.06, 95% CI [8.83-14.73], P<0.05). We noticed a significant decrease of the NRS for dysmenorrhea on average 2.79 points (2.1 vs. 4.89, 95% CI [1.14-4.42], P<0.05). There was also a trend to improvement of menorrhagia, assess by Higham score. Indeed, 70.8% of the patients had menorrhagia. Menorrhagia was improved of 108,3 points with an average Higham score before surgery of 197.3 versus 87.9 after surgery (95% CI [47.9-168.8], P=0.001). Concerning UFS-QOL score: the symptom severity score (SSS) decreased on average 33 points, testifying of symptom improvement (27.04 vs. 60.89, 95% CI [22.92-43.39], P<0.001) and the HRQL score increased on average 20 points testifying quality of life improvement (65.57 vs. 42.7, 95% CI [15.83-37.85]. P<0.001). No severe adverse event has been reported. CONCLUSION: In this first French study about radiofrequency ablation. We confirm its efficiency for improvement of symptoms and quality of life but other study is mandatory to confirm the safety of this procedure in particular in patients with a wish to conceive.

Multi-Modality Imaging in Vasculitis.

Systemic vasculitides are a rare and complex group of diseases that can affect multiple organ systems. Clinically, presentation may be vague and non-specific and as such, diagnosis and subsequent management are challenging. These entities are typically classified by the size of vessel involved, including large-vessel vasculitis (giant cell arteritis, Takayasu's arteritis, and clinically isolated aortitis), medium-vessel vasculitis (including polyarteritis nodosa and Kawasaki disease), and small-vessel vasculitis (granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis). There are also other systemic vasculitides that do not fit in to these categories, such as Behcet's disease, Cogan syndrome, and IgG4-related disease. Advances in medical imaging modalities have revolutionized the approach to diagnosis of these diseases. Specifically, color Doppler ultrasound, computed tomography and angiography, magnetic resonance imaging, positron emission tomography, or invasive catheterization as indicated have become fundamental in the work up of any patient with suspected systemic or localized vasculitis. This review presents the key diagnostic imaging modalities and their clinical utility in the evaluation of systemic vasculitis.

Dynamic Visualization of DNA Methylation in Cell Cycle Genes during iPSC Cardiac Differentiation.

Background: Epigenetic DNA methylation is an essential mechanism controlling gene expression and cellular function. Existing analyses with conventional assays have generated significant insights into static states of DNA methylation, but were unable to visualize the dynamics of epigenetic regulation. Aim: We utilized a genomic DNA methylation reporter (GMR) system to track changes in DNA methylation during cardiac differentiation. Methods and Results: The promoter region of Cdk1 (Cyclin-dependent kinase 1) or Sox2 (SRY-Box Transcription Factor 2) gene was cloned upstream of the small nuclear ribonucleoprotein polypeptide N (Snrpn) minimal promoter followed by a fluorescent reporter gene. Mouse induced pluripotent stem cells (iPSCs) carrying Sox2 GMR rapidly lost fluorescent reporter signal upon the induction of differentiation. Cdk1 GMR reporter signal was strong in undifferentiated iPSCs, and gradually decreased during directed cardiomyocyte (CM) differentiation. RT-qPCR and pyrosequencing demonstrated that the reduction of Sox2 and Cdk1 was regulated by hypermethylation of their CpG regions during cardiac differentiation. The present study demonstrated the dynamic DNA methylation along the course of cell cycle withdrawal during CM differentiation. Conclusion: The GMR reporter system can be a useful tool to monitor real-time epigenetic DNA modification at single-cell resolution.

An Unusual Presentation: High-Grade Serous Carcinoma of the Fallopian Tube Manifesting With Altered Mental Status Secondary to a Single Brain Metastasis-A Case Report and Review of the Literature.

Epithelial ovarian and fallopian cancers are aggressive lesions that rarely metastasize to the central nervous system. Brain metastases usually occur in the setting of known primary disease or widespread metastatic disease. However, in extremely rare cases, an isolated intracranial neoplasm may be the first presentation of fallopian cancer. To the best of our knowledge, only one such case has been reported previously. We present an illustrative case with multimodality imaging and histopathologic correlation of a fallopian tube carcinoma first presenting with altered mental status secondary to an isolated brain metastasis. A 64-year-old female with no pertinent medical history presented with altered mentation. Initial workup identified a 1.6 cm avidly enhancing, solitary brain lesion at the gray-white junction with associated vasogenic edema concerning for either central nervous system lymphoma or metastatic disease. Additional imaging identified a 7.5 × 3 cm left adnexal lesion, initially thought to be a hydrosalpinx with hemorrhage, but magnetic resonance imaging suggested gynecologic malignancy. No lesions elsewhere in the body were identified. Given the lack of locoregional or systemic disease, the intracranial and pelvic lesions were assumed to represent synchronous but distinct processes. The intracranial lesion was biopsied. Preliminary results were suggestive of lymphoma, but further analysis was consistent with high-grade serous carcinoma of müllerian origin. Positron emission tomography/computed tomography was performed to evaluate for other neoplastic lesions, only highlighting the intracranial and pelvic lesions. At this point, a diagnosis of metastatic fallopian cancer was made. The patient was taken for robot-assisted laparoscopy with surgical debulking of the pelvic neoplasm, pathology demonstrating high-grade serous carcinoma of the fallopian tube, matching that of the intracranial lesion. Even though rare, metastatic fallopian cancer should be considered in patients with isolated brain lesions and adnexal lesions, even in the absence of locoregional or systemic disease.

Relationships of BRAF V600E Gene Mutation With Some Immunohistochemical Markers and Recurrence Rate in Patients With Thyroid Carcinoma.

Background: The B-type rafkinase (BRAF) V600E gene mutation plays an important role in the pathogenesis, diagnosis, and prognosis of thyroid carcinoma. This study was conducted to investigate the rate of the BRAF V600E mutation, the relationships between the BRAF V600E gene mutation and some immunohistochemical markers, and recurrence rate in patients with differentiated thyroid cancer. Method: The study was conducted by a descriptive and longitudinal follow-up method on 102 thyroid carcinoma patients at 103 Military Hospital, Hanoi, Vietnam. All patients were identified with the BRAF V600E gene mutation by real-time polymerase chain reaction. Results: The rate of BRAF V600E gene mutation in patients with thyroid cancer was 60.8%. Patients with BRAF V600E gene mutation had a significantly higher rate of positive cyclooxygenase 2 (COX-2) and Ki67 markers than those without the mutation (COX-2: odds ratio [OR] = 2.93; 95% confidence interval [CI] = 1.27-6.74, P = .011; Ki67: OR = 3.41; 95% CI = 1.31-8.88, P = .01). A statistically significant relationship was identified between the rate of BRAF V600E mutation and the rate of positive Hector Battifora mesothelial 1 (HBME-1) (B = -1.040; P = .037) and COX-2 (B = -1.123; P = .023) markers. The recurrence rate in patients with BRAF V600E gene mutation was significantly higher than that in those without the mutation (P = .007). The mean of the recurrence time of patients with BRAF V600E mutation was significantly lower than that in those without the mutation (P = .011). Conclusions: A high prevalence of BRAF V600E gene mutation was found in thyroid carcinoma patients. The rates of positive HBME-1, COX-2, and Ki67 markers were significantly correlated to BRAF V600E gene mutation. Patients with BRAF V600E gene mutation showed a significantly higher relapse rate and earlier relapse time than those without the mutation.

Dopamine Receptor D1 Is Exempt from Transforming Growth Factor ß-Mediated Antifibrotic G Protein-Coupled Receptor Landscape Tampering in Lung Fibroblasts.

Pulmonary fibroblasts are the primary producers of extracellular matrix (ECM) in the lungs, and their pathogenic activation drives scarring and loss of lung function in idiopathic pulmonary fibrosis (IPF). This uncontrolled production of ECM is stimulated by mechanosignaling and transforming growth factor beta 1 (TGF-ß1) signaling that together promote transcriptional programs including Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). G protein-coupled receptors (GPCRs) that couple to G α s have emerged as pharmacological targets to inactivate YAP/TAZ signaling and promote lung fibrosis resolution. Previous studies have shown a loss of expression of "antifibrotic GPCRs"-receptors that couple to G α s, in IPF patient-derived fibroblasts compared with non-IPF samples. Of the 14 G α s GPCRs we found to be expressed in lung fibroblasts, the dopamine receptor D1 (DRD1) was one of only two not repressed by TGF-ß1 signaling, with the ß2-adrenergic receptor being the most repressed. We compared the potency and efficacy of multiple D1 and ß2 receptor agonists +/- TGF-ß1 treatment in vitro for their ability to elevate cAMP, inhibit nuclear localization of YAP/TAZ, regulate expression of profibrotic and antifibrotic genes, and inhibit cellular proliferation and collagen deposition. Consistently, the activity of ß2 receptor agonists was lost, whereas D1 receptor agonists was maintained, after stimulating cultured lung fibroblasts with TGF-ß1. These data further support the therapeutic potential of the dopamine receptor D1 and highlight an orchestrated and pervasive loss of antifibrotic GPCRs mediated by TGF-ß1 signaling. SIGNIFICANCE STATEMENT: Idiopathic pulmonary fibrosis (IPF) is a deadly lung disease with limited therapies. GPCRs have emerged as a primary target for the development of novel antifibrotic drugs; however, a challenge to this approach is the dramatic changes in GPCR expression in response to profibrotic stimuli. Here, we investigate the impact of TGF-ß1 on the expression of antifibrotic GPCRs and show the D1 dopamine receptor expression is uniquely maintained in response to TGF-ß1, further implicating it as a compelling target to treat IPF.

Chest Wall Keloids Depicted by 18 F-Piflufolastat PET/CT Imaging.

ABSTRACT: Keloids are pathological scars from exuberant fibroproliferative collagen response and excessive extracellular matrix production usually extending beyond the original wound margins. Although keloids are mostly of dermatological concern, they could be incidentally depicted on scintigraphic planar and PET/CT imaging and could mimic other types of skin diseases. The authors present a case of chest wall keloids documented on 18 F-piflufolastat PET/CT during the evaluation of prostate cancer recurrence.

Anatomic and Functional Imaging of Immunoglobulin G4-related Disease and Its Mimics.

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated fibrosclerosing disease with tumefactive lesions infiltrated by IgG4-positive plasma cells. Initially described as autoimmune pancreatitis, IgG4-RD is now recognized as a discrete entity and is found to affect virtually any organ in the body. Common extrapancreatic sites include the biliary tree, salivary glands, periorbital tissue, lungs, kidneys, lymph nodes, aorta, retroperitoneum, and thyroid gland. Diagnosis-which relies on histopathologic, serologic, and radiologic features-can be challenging with the disease underdiagnosed, as IgG4-RD often mimics malignancy, infectious processes, or other immune-mediated conditions. Patients may present with signs of compression of nearby structures due to mass effect or with organ failure when the disease is left untreated. The clinical course is complex, with single- or multiorgan involvement and metachronous or synchronous occurrence of lesions. IgG4-RD responds well to glucocorticoid therapy, disease-modifying antirheumatic drugs, and B-cell-depleting biologic agents; prompt diagnosis is important to avoid delay in treatment and unnecessary pharmacologic or surgical intervention. While imaging features may not be specific for IgG4-RD, functional whole-body imaging with fluorine 18-fluorodeoxyglucose PET/CT is a useful adjunct for localizing extrapancreatic sites for biopsy, monitoring therapeutic response, and demonstrating disease relapse. The authors describe the pancreatic and extrapancreatic sites of involvement in IgG4-RD, with imaging features and patterns to aid in distinguishing IgG4-RD from its mimics through a multimodality approach with emphasis on functional imaging evaluation. ©RSNA, 2023 Quiz questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Hemophagocytic lymphohistiocytosis secondary to diffuse large B-cell lymphoma presenting with recurrent multi-territory infarcts: A case report.

Lymphoma-associated hemophagocytic syndrome is a life-threatening disease with poor prognosis and may present as ischemic stroke. We report a case of a 56-year-old female with recurrent multi-territory infarcts caused by diffuse large B-cell lymphoma with secondary hemophagocytic lymphohistiocytosis. She had been diagnosed with ischemic stroke and hemophagocytic syndrome probably secondary to Epstein-Barr virus infection 3 months previously and treated with Dexamethasone and Aspirin. High resolution vessel wall magnetic resonance imaging showed vessel wall thickening at some intracranial vessels suggesting vasculitis. Abdominal computed tomography scan revealed splenomegaly, multiple bilateral small nodules of the lung, multiple liver lesions, multiple bilateral renal masses, gastric wall thickening and multiple nodules in the omentum. Cerebrospinal fluid cytology showed increased cerebrospinal-fluid protein level. Hemophagocytosis was showed on bone marrow aspirate cytology. Gastric tissue biopsy revealed large B cell lymphoma. Chemotherapy was not given because the patient had severe pneumonia and sepsis. The patient died 28 days after the definitive diagnosis was confirmed. Ischemic stroke in our patient with diffuse large B-cell lymphoma may be due to vasculitis or intravascular large B-cell lymphoma.

Treatment Outcome and Safety of the TCX Regimen for Advanced Gastric Cancer: A Prospective Cohort Study.

Objective: To evaluate the outcome and safety of the paclitaxel, carboplatin, and capecitabine (TCX) regimen in patients with advanced gastric cancer. Methods: Advanced gastric cancer patients received the TCX regimen for up to six cycles, which were 3 weeks apart. Paclitaxel (175 mg/m2) was given over a 3-hour infusion, followed by carboplatin in a 1-hour infusion on day 1. Capecitabine (850 mg/m2) was given orally twice daily from day 1 to day 14. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: Among 83 patients at stage IVa and IVb, the median PFS was 9.3 months; 6-month, 1-year, and 2-year PFS were 74.6%, 32.5%, and 14.4%, respectively. The median OS was 17.0 months; 6-month, 1-year, and 2-year OS were 97.5%, 68.7%, and 21.7%, respectively. In the multivariable Cox regression model, higher CEA was associated with poor OS. Common adverse events included hand-food syndrome (77.9%), peripheral neuropathy (63.2%), fatigue (68.7%), and nausea (54.2%). Conclusion: The TCX regimen provided good survival and a better safety profile. More clinical trials are needed to confirm its treatment efficacy and safety, especially in comparison with other triplet regimens.

JAK2 rs10974944 is associated with both V617F-positive and negative myeloproliferative neoplasms in a Vietnamese population: A potential genetic marker.

The JAK2 gene encodes for a non-receptor tyrosine kinase that plays a key role in the JAK/STAT signaling transfer pathway. Genetic polymorphisms of this gene have been indicated to be associated with myeloproliferative neoplasm-associated thrombosis in recent studies. This research aimed to evaluate the association between the variant rs10974944 and different types of Myeloproliferative neoplasms disorders in the Vietnamese population. DNA samples were obtained from 172 essential thrombocythemia patients, 14 primary myelofibrosis patients, 76 polycythemia vera patients, and 192 healthy controls. The JAK2 rs10974944 and V617F genotypes were identified by the polymerase chain reaction-restriction fragment length polymorphism genotyping and Sanger sequencing methods. Results showed that there was a strong association between rs10974944 and Myeloproliferative neoplasms phenotype (p < .0001) and the most significant association was observed in the recessive model of the mutant allele (G). The G allele carriers had a 1.74, 2.86, and 3.03 higher risk of getting essential thrombocythemia, primary myelofibrosis, and polycythemia vera, respectively. Interestingly, this effect of rs10974944 seemed to be independent of the JAK2 V617F genotype. The distribution of rs10974944 genotypes were significantly different between V617F-positive and negative groups (p = .008). Moreover, the GG genotype of rs10974944 was observed to be associated with the risk of getting Myeloproliferative neoplasms both in JAK2 V617F-positive group, and for the first time in JAK2 V617F-negative patients. A systematic meta-analysis in different populations strengthened the evidence regarding the correlation between rs10974944 and myeloproliferative neoplasm disorders. To sum up, our results suggested that rs10974944 can be used as a predisposition screening marker for predicting Myeloproliferative neoplasms susceptibility.

PET/CT of delayed uterine leiomyoma metastasizing to lung and femur.

Benign metastasizing leiomyomas are benign disseminated extra-uterine tumors in patients with prior history of uterine leiomyomas and may occur years after hysterectomy. The lung is mostly affected, with less common occurrence in the brain, heart, spine, retroperitoneum, and bone. The authors present the role of 18F-FDG PET/CT in the metabolic staging and post-surgical monitoring of a patient with lung and femoral involvement.

Highly sensitive detection of EGFR L858R mutation at the mRNA level.

The missense mutation EGFR L858R implies increased sensitivity to EGFR tyrosine kinase inhibitor (TKIs) therapy, despite a significant non-response rate. Currently, detection of EGFR L858R mutation is mostly DNA based, therefore, the allele-specific expression level of the mutated gene and its clinical relevance is hidden. Based on the extendable blocking probes and hot-start protocol for reverse transcription, we have developed and validated a novel one-step realtime RT-PCR assay that enables detection of EGFR L858R mutation at the mRNA level. This RNA-based assay was able to detect the EGFR L858R mutation in a 10,000-fold excess of its wildtype counterpart, indicating an analytical sensitivity of 0.01%. In comparison to the reference DNA-based assay, the RNA-based assay further detected the EGFR L858R mutation in significantly additional formalin-fixed paraffin-embedded (FFPE) samples (19.2% vs 15.0%). Interestingly, our data showed that the relative mRNA levels of EGFR L858R mutation varied greatly in tumor tissues (∼4 logs); and the circulating mRNA of EGFR L858R mutation was detectable in plasma of NSCLC patients. This novel RNA-based PCR assay provides a simple and ultrasensitive tool for detection of EGFR L858R mutation at the mRNA level as a new class of biomarkers.

Allele and Haplotype Frequencies of HLA-A, -B, -C, and -DRB1 Genes in 3,750 Cord Blood Units From a Kinh Vietnamese Population.

The frequencies and diversities of human leukocyte antigen (HLA) alleles and haplotypes are representative of ethnicities. Matching HLA alleles is essential for many clinical applications, including blood transfusion, stem cell transplantation, and tissue/organ transplantation. To date, the information about the frequencies and distributions of HLA alleles and haplotypes among the Kinh Vietnamese population is limited because of the small sample size. In this study, more than 3,750 cord blood units from individuals belonging to the Kinh Vietnamese population were genotyped using PCR sequence-specific oligonucleotide (PCR-SSO) for HLA testing. The results of the study demonstrated that the most frequently occurring HLA-A, -B, -C, and -DRB1 alleles were A*11:01 (25%), A*24:02 (12.3%), A*02:01 (11.2); A*03:03 (8.95%), A*02:03 (7.81%), A*29:01 (7.03%); B*15:02 (15.1%), B*46:01 (10.7%), B*58:01 (7.65%), B*38:02 (7.29%); C*08:01 (17.2), C*07:02 (16.2%), C*01:02 (15.2), C*03:02 (8.3%), C*15:05 (6.13); DRB1*12:02 (31.0%), DRB1*09:01 (10.47%), DRB1*15:02 (7.54%); DRB1*07:01 (6.68%), DRB1*10:01 (6.63%), respectively, with the highest allele diversity level observed in locus B (93 alleles). The most frequent haplotypes of two-locus combinations of HLA-A-B, HLA-A-C, HLA-A-DRB1, HLA-B-C, HLA-B-DRB1, and HLA-C-DRB1 haplotypes were A*11:01-B*15:02 (7.63%), A*11:01-C*08:01 (7.98%), A*11:01-DRB1*12:02 (10.56%), B*15:02-C*08:01 (14.0%), B*15:02-DRB1*12:02 (10.47%), and C*08:01-DRB1*12:02 (11.38%), respectively. In addition, the most frequent haplotypes of three- and four-locus sets of HLA-A-B-C, HLA-A-B-DRB1, HLA-A-C-DRB1, HLA-B-C-DRB1, and HLA-A-B-C-DRB1 were A*11:01-B*15:02-C*08:01 (7.57%), A*11:01-B*15:02-DRB1*12:02 (5.39%), A*11:01-C*08:01-DRB1*12:02 (5.54%), B*15:02-C*08:01-DRB1*12:02 (10.21%), and A*11:01-B*15:02-C*08:01-DRB1*12:02 (5.45%), respectively. This study provides critical information on the frequencies and distributions of HLA alleles and haplotypes in the Kinh Vietnamese population, accounting for more than 85% of Vietnamese citizens. It paves the way to establish an umbilical cord blood bank for cord blood transplantation programs in Vietnam.

Cardiac hemangioma mimicking a neuroendocrine tumor on 68 Ga Dotatate PET/CT.

Cardiac hemangioma is a rare, benign primary tumor characterized by endothelial proliferation. While reports of cardiac hemangiomas demonstrating 18 F FDG avidity and other forms of hemangiomas showing 68 Ga Dotatate avidity have been published, we present a rare case of primary cardiac hemangioma demonstrating 68 Ga Dotatate avidity, mimicking a primary neuroendocrine tumor.

PET/CT Imaging of Hemorrhagic Pseudotumor Arising From Treated Plasmacytoma.

ABSTRACT: Hemorrhagic pseudotumor occurs in approximately 1% to 2% of patients with hemophilia. This lesion is exceptionally rare in nonhemophiliac individuals. The authors present a case of treated right ischial plasmacytoma with a progressively enlarging expansile hemorrhagic pseudotumor, documented on 18 F-FDG PET/CT and MRI and confirmed by histology.