Positive Staining For CD34 Research Articles

TMIC-45. CYTOMEGALOVIRUS PP65 ANTIGEN EXPRESSION FOLLOWING PP65-SPECIFIC DENDRITIC CELL VACCINATION IN MATCHED PRIMARY AND RECURRENT GLIOBLASTOMA SPECIMENS

Abstract BACKGROUND Human cytomegalovirus (HCMV) expression in glioblastoma (GBM) has been corroborated by multiple independent laboratories. HCMV genes have been directly linked to GBM cell proliferation, invasion, and angiogenesis. The HCMV tegument protein pp65 has served as a tumor-specific antigen in serial pp65 RNA-pulsed autologous dendritic cell (DC) vaccine trials. Here we report pp65 expression in matched primary and recurrent GBM samples from those trials following pp65-DC vaccination. METHODS Paired GBM specimens were collected from patients receiving pp65-DC vaccines according to ATTAC and ATTAC-GM clinical trials (NCT00639639). Of 23 treated patients, 9 cases were available for analysis. Formalin-fixed paraffin-embedded specimens were mounted on glass slides and stained for pp65 via immunohistochemistry (IHC). CD31 served as a control for tissue quality and to investigate the role of pp65 co-staining in the tumor perivascular niche. RESULTS Of 9 available cases, 5 were excluded due to poor tissue quality/absent CD31 staining on aged slides. Among the remaining four cases, three showed pp65 staining in non-vascular and perivascular areas within both primary and recurrent samples. However, recurrent specimens of these positive cases demonstrated a clear reduction in both intensity and distribution of pp65 staining within non-vascular regions but retained a strong positivity within the perivascular space. The fourth case showed absent pp65 staining and only weakly positive CD31 staining in both primary and recurrent specimens. Necrotic areas within pp65-positive slides showed minimal to no pp65 staining. CONCLUSIONS This study confirms HCMV pp65 expression in both primary and recurrent GBM following pp65-DC vaccination, with an interesting phenomenon of retained pp65 expression specifically in the perivascular niche. These findings support the role of HCMV in GBM angiogenesis and tumor progression as well as mechanisms of immune evasion following single antigen vaccine platforms. Our study reinforces the importance of tissue quality for proper HCMV detection in GBM.

Sporadic hypertrophic and nodular port-wine stain: a study of 27 cases with emphasis on histological features and novel mutation type

AimsTo investigate the clinicopathological features and molecular characteristics of sporadic hypertrophic and nodular port-wine stains (PWS).MethodsWe analysed the clinicopathological and molecular characteristics of 27 sporadic hypertrophic and nodular PWS retrieved...

The protective effects of apelin-13 in HIV-1 tat- induced macrophage infiltration and BBB impairment

ABSTRACT Impairment of the blood – brain barrier (BBB) and subsequent inflammatory responses contribute to the development of human immunodeficiency virus (HIV)-1-associated neurocognitive disorders (HAND). Apelin-13, the most abundant member of the apelin family, acts as the ligand of the angiotensin receptor-like 1 (APJ). However, its pharmacological function in HAND and its underlying mechanism are unknown. In the current study, we report that the presence of HIV-1 Tat reduced the levels of Apelin-13 and APJ in the cortex tissue of mice. Importantly, Apelin-13 preserved BBB integrity against HIV-1 Tat in mice by increasing the expression of the tight junction protein zonula occludens-1 (ZO-1) and occludin. Interestingly, increased macrophage infiltration, indicated by elevated CD68-positive staining was observed in the cortex after stimulation with HIV-1, which was mitigated by the administration of Apelin-13. Correspondingly, Apelin-13 reduced the expression of monocyte chemoattractant protein-1; (MCP-1). An in vitro two-chamber and two-cell trans-well assay demonstrated that HIV-1 Tat challenge significantly promoted macrophage migration, which was notably attenuated by the introduction of Apelin-13. Accordingly, treatment with Apelin-13 restored the HIV-1 Tat-induced reduction of occludin and ZO-1, while preventing the upregulation of MCP-1 in human brain microvascular endothelial cells (HBMVECs). Our results suggest that Apelin-13 may reduce macrophage infiltration into brain tissues and mitigate BBB dysfunction in patients with HAND.

Imlifidase in Highly Sensitized Kidney Transplant Recipients With a Positive Crossmatch Against a Deceased Donor

IntroductionImlifidase is authorized for desensitization of highly sensitized adult kidney transplant candidates with a positive crossmatch against a deceased donor. Here, we report on the results for the first 9 patients transplanted in this context who had at least 3 months of follow-up. MethodsThe eligibility criteria were: calculated panel reactive antibodies (cPRA) ≥ 98%, ≥ 3 years on the waiting list, immunodominant donor specific antibodies (iDSA) with mean fluorescence intensity (MFI) > 6,000 (and < 5,000 at 1:10 dilution) and a negative post-imlifidase complement-dependent cytotoxic crossmatch (CDCXM). ResultsAll 9 patients had been on dialysis for an average of 123±41 months, with cPRA at 99% (n=2) or 100% (n=7). At transplantation, the mean number of DSA was 4.3±1.4. The median iDSA MFI was 9,153 (6,430-16,980). Flow cytometry and CDC XMs before imlifidase were positive in 9 and 2 patients, respectively. After one injection of imlifidase all were negative. Patients received polyclonal antibodies, intravenous immunoglobulins, rituximab, tacrolimus, and mycophenolate. Five patients had a DSA rebound within the first 14 days: 2 had concomitant clinical antibody-mediated rejection (ABMR), 2 had subclinical ABMR, and 1 had isolated positive C4d staining. No ABMR was observed in patients without rebound. CKD-EPI eGFR was 56±22 mL/min/1.73m2 at the last follow-up (7±2.8 months). No graft loss or death were observed. Four patients developed at least one infection. ConclusionThese real-life data demonstrate that the use of imlifidase to desensitize highly sensitized patients can have an acceptable short-term efficacy and safety profile in selected patients.

Rosuvastatin attenuates airway inflammation and remodeling in a chronic allergic asthma model through modulation of the AMPKα signaling pathway.

The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-β, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5'-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis.

Giant Cell Tumor of Soft Tissue Masquerading as a Fibroma - A Rare Clinical Entity

Giant cell tumor of the soft tissue (GCT-ST) is a rare and distinctive entity, separate from its bony counterpart, giant cell tumor of bone. This primary soft tissue tumor is often encountered in middle-aged individuals but rarely in children, with common sites including superficial soft tissue of the extremities. GCT-ST typically presents as a painless, slowly growing mass, emphasizing the importance of complete excision to prevent recurrences and metastasis. We present a case of GCT-ST in a 7-year-old boy with a nodular swelling on the right hip, initially suspected to be a fibroma. Histopathological examination revealed characteristic features of GCT-ST, including spindle and stellate cells, multinucleated giant cells, and haemosiderin-laden macrophages with metaplastic osseous tissue. This case adds to the limited literature on GCT-ST, highlighting its diverse clinical presentations and challenging diagnostic nature. The discussion includes a review of reported cases of GCT-ST, which have shown varied clinical presentations and outcomes. Histologically, GCT-ST resembles a giant cell tumor of bone, with positive staining for CD68, SMA, Vimentin, and p63. Imaging studies typically reveal a solid hemorrhagic mass. Differential diagnoses include benign and malignant soft tissue tumors rich in giant cells. Keywords: Giant Cell Tumor of Soft Tissue (GCT-ST), Rare, Fibro-Histiocytic Tumor Of Intermediate Malignancy, Soft Tissue Tumor, Rare Tumors In Children.

ANXA1 Enhances the Proangiogenic Potential of Human Dental Pulp Stem Cells.

Dental trauma is highly prevalent in children and adolescents, alongside tooth decay. This condition mainly induces pulp contamination, pulp necrosis, and tooth avulsion in the clinical context. The disturbance to root growth is prone to occur in immature permanent teeth. However, conventional endodontic treatment may not achieve favorable outcomes in these cases, necessitating conducting relevant exploration. Therefore, this study was performed to examine the impact of Annexin A1 (ANXA1) on the vascular repair of dental pulp using human dental pulp stem cells (DPSCs). Specifically, RNA sequencing (RNA-Seq) and functional clustering analyses were employed to identify key genes involved in pulp regeneration. ANXA1 was detected in DPSCs and may correlate with pulp restoration. However, it remains undefined about the potential of ANXA1 to promote the angiogenetic differentiation of DPSCs. The results of this study revealed that the addition of ANXA1 significantly enhanced the secretion of vascular endothelial growth factor-A (VEGF-A) in DPSCs. Moreover, the incubation of DPSCs with ANXA1 resulted in a higher expression level of endothelial markers and promoted vessel formation through the upregulation of the phosphorylated p38 (p-p38) pathway. The in vivo results corroborated that the ANXA1 group exhibited more blood vessels and an increased ratio of positive staining for CD31. In conclusion, these findings indicate that ANXA1 enhances the in vivo and in vitro vascularization of DPSCs, and the activation of p-p38 may play a pivotal role in mediating the differentiation process.

Temporal correlation between postreperfusion complement deposition and severe primary graft dysfunction in lung allografts

Growing evidence implicates complement in the pathogenesis of primary graft dysfunction (PGD). We hypothesized that early complement activation postreperfusion could predispose to severe PGD grade 3 (PGD-3) at 72 hours, which is associated with worst posttransplant outcomes. Consecutive lung transplant patients (n = 253) from January 2018 through June 2023 underwent timed open allograft biopsies at the end of cold ischemia (internal control) and 30 minutes postreperfusion. PGD-3 at 72 hours occurred in 14% (35/253) of patients; 17% (44/253) revealed positive C4d staining on postreperfusion allograft biopsy, and no biopsy-related complications were encountered. Significantly more patients with PGD-3 at 72 hours had positive C4d staining at 30 minutes postreperfusion compared with those without (51% vs 12%, P < .001). Conversely, patients with positive C4d staining were significantly more likely to develop PGD-3 at 72 hours (41% vs 8%, P < .001) and experienced worse long-term outcomes. In multivariate logistic regression, positive C4d staining remained highly predictive of PGD-3 (odds ratio 7.92, 95% confidence interval 2.97-21.1, P < .001). Hence, early complement deposition in allografts is highly predictive of PGD-3 at 72 hours. Our data support future studies to evaluate the role of complement inhibition in patients with early postreperfusion complement activation to mitigate PGD and improve transplant outcomes.

Increased Activated Protein C Response Rates to Thrombin Formation in Asymptomatic Factor V Leiden Carriers Are Driven By the Endothelium

Background The thrombophilic factor V Leiden (FVL) mutation shows a highly variable clinical expressivity. We have shown in vivo that asymptomatic FVL carriers respond to extrinsic coagulation activation with higher activated protein C (APC) formation rates than those with a history of venous thromboembolism (VTE). Recently we have established an ex vivo model for personalized assessment of the protein C (PC) pathway combining endothelial colony forming cells (ECFCs) and autologous plasma. Aim of this study was to investigate potential modulating factors of the APC response in the endothelium unraveling the enigma of the variable expressivity of the FVL phenotype. Methods ECFCs were isolated from FVL carriers with (FVL VTE+) or without (FVL VTE-) a history of unprovoked VTE and healthy controls (non-FVL) (n=7 each). Quality control of cultured cells included cobblestone morphology as examined by light microscopy, positive staining for CD31, CD309, CD201, and CD141, CD34, and negative staining for CD45 analyzed by flow cytometry. We either added autologous or pooled normal defibrinated plasma to the confluent cell culture and inititated thrombin formation by addition of tissue factor (1 pmol/L) and CaCl 2 (16.6 mmol/L) ( Fig. 1A). Thrombin and APC formation were measured over time using oligonucleotide-based enzyme capture assays (OECAs) and the ratio between the area under the curve (AUC) of APC formation and the AUC of thrombin formation was calculated as measure for APC response to thrombin. Moreover, we quantified thrombomodulin (TM) and endothelial protein C receptor (EPCR) expression in cell-based enzyme-linked immunosorbent assays (cell-ELISAs) and measured activation of purified PC on ECFCs in the APC-OECA. Results ECFC morphology in light microscopy and characteristic surface marker expression in flow cytometry did not differ between non-FVL, FVL VTE-, and FVL VTE+ subgroups. In the ECFC-based ex vivo model, the APC response in plasma on autologous cells was significantly higher in asymptomatic FVL VTE- carriers compared to non-FVL carriers (P = .0072) and compared to the FVL VTE+ subgroup (P = .0292) whereas it did not differ significantly between non-FVL and FVL VTE+ carriers. EPCR expression on ECFCs measured by cell-ELISA was higher in non-FVL carriers compared to FVL VTE+ subjects (P = .0374) but did not differ significantly when comparing non-FVL versus FVL VTE-, and FVL VTE+ versus FVL VTE-. Similarly, we showed that TM expression as well as activation of purified PC on ECFCs did not differ between cohorts. However, when the APC response was assessed on FVL VTE- and FVL VTE+ ECFCs using non-FVL plasma, the difference in the APC response between asymptomatic FVL carriers and FVL carriers with a history of VTE persisted (P = .0111) ( Fig. 1B). Conclusion Consistent with previous in vivo experiments, APC response rates to thrombin formation were increased on ECFCs obtained from asymptomatic FVL carriers compared to those from FVL carriers with a history of VTE in autologous plasma. Although TM and EPCR expression did not differ between both groups, we showed that the endothelial APC response in asymptomatic FVL carriers remained increased when using plasma from healthy controls. Our observations suggest that the increased APC response to thrombin in asymptomatic FVL carriers is driven by the endothelium. Further studies are warranted to elucidate the underlying mechanism for a better understanding of endogenous protective factors in FVL carriers. These findings may pave the way towards personalized, precision medicine approaches for managing the thrombotic risk in FVL and other disorders related to the PC pathway.

Pseudoangiomatous Spindle Cell Lipoma: A Rare and Distinct Pattern of Lipomatous Tumors.

Pseudoangiomatous spindle cell lipoma is a rare pattern within the spindle cell lipoma spectrum that exhibits a remarkable histological pattern characterized by its resemblance to vascular lesions, creating a pseudoangiomatous appearance. Approximately 20 to 30 reports have been described in the literature. In this context, we present an intriguing report of pseudoangiomatous spindle cell lipoma showcasing a unique low-fat pseudo angiomatous pattern in a 61-year-old male patient presented with a 6-cm subcutaneous mass on his right arm, which was thoroughly investigated and subsequently excised. Microscopic examination revealed bland spindle cells infiltrates within a fibromyxoid stroma. Notably, the tumor exhibited distinctive branching and dilated vascular-like spaces that formed pseudopapillary (villiform) projections. Interestingly, the tumor displayed certain regions featuring mature adipose tissue components, alongside hyalinized blood vessels. No necrosis, atypical spindle cells, increased mitotic activity, or pleomorphic lipoblasts were observed. The immunohistochemical evaluation demonstrated diffuse positive staining for CD34 and negative staining for STAT6. This report of a low-fat pattern of pseudoangiomatous spindle cell lipoma underscores the importance of recognizing and characterizing rare entity subtype for accurate diagnosis and appropriate management. This report contributes to the expanding understanding of the diverse presentations of pseudo angiomatous spindle cell lipomas and underscores the significance of comprehensive histopathological assessment.

Anti-CD20 Antibody and Calcineurin Inhibitor Combination Therapy Effectively Suppresses Antibody-Mediated Rejection in Murine Orthotopic Lung Transplantation.

Antibody-mediated rejection (AMR) is a risk factor for chronic lung allograft dysfunction, which impedes long-term survival after lung transplantation. There are no reports evaluating the efficacy of the single use of anti-CD20 antibodies (aCD20s) in addition to calcineurin inhibitors in preventing AMR. Thus, this study aimed to evaluate the efficacy of aCD20 treatment in a murine orthotopic lung transplantation model. Murine left lung transplantation was performed using a major alloantigen strain mismatch model (BALBc (H-2d) → C57BL/6 (BL/6) (H-2b)). There were four groups: isograft (BL/6→BL/6) (Iso control), no-medication (Allo control), cyclosporine A (CyA) treated, and CyA plus murine aCD20 (CyA+aCD20) treated groups. Severe neutrophil capillaritis, arteritis, and positive lung C4d staining were observed in the allograft model and CyA-only-treated groups. These findings were significantly improved in the CyA+aCD20 group compared with those in the Allo control and CyA groups. The B cell population in the spleen, lymph node, and graft lung as well as the levels of serum donor-specific IgM and interferon γ were significantly lower in the CyA+aCD20 group than in the CyA group. Calcineurin inhibitor-mediated immunosuppression combined with aCD20 therapy effectively suppressed AMR in lung transplantation by reducing donor-specific antibodies and complement activation.

Renal C4d is a potential biomarker of disease activity and severity in pediatric lupus nephritis patients.

Systemic lupus erythematosus (SLE), a multisystemic autoimmune disease, is very aggressive in pediatric-onset patients as they are prone to develop lupus nephritis (LN). Although renal C4d positivity is correlated with the activity of renal disease and SLE in adult-onset LN patients, available information for pediatric-onset patients is limited. To evaluate the potential diagnostic significance of renal C4d staining in pediatric LN patients, we retrospectively detected C4d staining by immunohistochemistry on renal biopsy specimens from 58 pediatric LN patients. The clinical and laboratory data at the time of the kidney biopsy and the renal disease activity of histological injury were analyzed according to the C4d staining status. Glomerular C4d (G-C4d)-positive staining was detected in all 58 cases of LN. Patients with a G-C4d score of 2 displayed more severe proteinuria than those with a G-C4d score of 1 (24-h urinary protein: 3.40 ± 3.55 g vs. 1.36 ± 1.24 g, P < 0.05). Peritubular capillary C4d (PTC-C4d) positivity was found in 34 of 58 LN patients (58.62%). The PTC-C4d-positive patient groups (patients with a PTC-C4d score of 1 or 2) had higher serum creatinine and blood urea nitrogen levels as well as renal pathological activity index (AI) and SLE disease activity index (SLEDAI) scores; however, they had lower serum complement C3 and C4 levels compared to PTC-C4d-negative patients (P < 0.05). In addition, there was positive tubular basement membrane C4d (TBM-C4d) staining in 11 of 58 LN patients (18.96%), and a higher proportion of TBM-C4d-positive patients than TBM-C4d-negative patients (63.63% vs. 21.27%) had hypertension. Our study revealed that G-C4d, PTC-C4d, and TMB-C4d were positively correlated with proteinuria, disease activity and severity, and hypertension, respectively, in pediatric LN patients. These data suggest that renal C4d is a potential biomarker for disease activity and severity in pediatric LN patients, providing insights into the development of novel identification and therapeutic approaches for pediatric-onset SLE with LN.

Evaluation and management of abnormal liver enzymes in the liver transplant recipient: When, why, and what now?

Evaluation and management of abnormal liver enzymes in the liver transplant recipient: When, why, and what now?

C4d Staining Is Present in Normal Placentas From Pregnancies Prior to Pregnancy Loss Associated With Chronic Histiocytic Intervillositis and Is Reduced by Immunomodulatory Therapy in Subsequent Pregnancies.

Chronic histiocytic intervillositis (CHI) is associated with adverse pregnancy outcomes and high recurrence risk. Recent studies suggest that CHI may represent a host-vs-graft rejection, and that C4d immunostain can be used as a marker for complement activation and antibody-mediated rejection in the CHI. This retrospective cohort study focused on 5 fetal autopsy cases associated with CHI (5 index cases) from 5 women. We analyzed placentas from the index cases (fetal autopsy cases associated with CHI) and placentas from the women's previous and subsequent pregnancies. We assessed the presence and extent of CHI and C4d immunostaining in these placentas. We evaluated each available placenta and graded the severity of CHI as either <50% or ≥50%. Additionally, we conducted C4d immunostaining on one representative section from each placenta and graded the staining levels as follows: 0+ for staining <5%; 1+ for staining between 5% and <25%; 2+ for staining between 25% and <75%; and 3+ for staining ≥75%. Three of the 5 women had pregnancies prior to their index cases (fetal autopsy cases associated with CHI). Despite the absence of CHI in their initial pregnancies, the placentas displayed positive C4d staining with grades of 1+, 3+, and 3+, respectively. These results suggest the presence of complement activation and antibody-mediated rejection in placentas from their prior pregnancies without CHI. Three of the 5 women received immunomodulatory therapy after experiencing pregnancy losses associated with CHI. After treatment, 2 of these women had live births at 35 and 37 gestational weeks, respectively, while the third had a stillbirth at 25 gestational weeks. The severity of CHI and the degree of C4d staining in the placentas decreased in all 3 cases following immunomodulatory therapies. Specifically, the level of C4d staining decreased from 3+ to 2+, 2+ to 0+, and 3+ to 1+ in these 3 cases, respectively. In women with a history of recurrent pregnancy loss associated with CHI, C4d immunostaining was present in the placentas from their previous non-CHI pregnancies, suggesting activation of the classical complement pathway and antibody-mediated reaction in their prior non-CHI pregnancies before the development of CHI in subsequent pregnancies. Immunomodulatory therapy may improve pregnancy outcomes by reducing complement activation, as shown by the reduction of C4d immunopositivity in the placentas after immunomodulatory treatment. Although we believe that the study provides valuable insights, we acknowledge that there are limitations to the findings. Therefore, to further elucidate the pathogenesis of CHI, additional research efforts with a collaborative and multidisciplinary approach are necessary.

Abstract #1400148: Anterior Cervical Liposarcoma Masquerading as a Thyroid Nodule

Primary sarcomas of the head and neck account for < 1% of tumors in this anatomic region. We present a case of a large anterior neck mass initially thought to originate from the thyroid gland but diagnosed as a cervical liposarcoma closely adjacent to the thyroid. A 64-year-old woman was referred for a right anterior neck mass that she first noticed about 6 weeks prior to evaluation. The patient reported mild degrees of dysphagia and dyspnea. Examination was notable for a large, painless, right anterolateral neck mass that was mobile on deglutition. Serum TSH level was unremarkable. Neck ultrasound revealed a well circumscribed 6.0 x 3.7 x 5.4 cm isoechoic mass that appeared to largely replace the right thyroid lobe. Fine needle biopsy yielded a specimen composed only of peripheral blood elements. Computed tomography of the neck revealed a 9.1 x 6.2 x 6.0 cm hypodense (- 4 Hounsfield units) mass originating in the right carotid space and displacing the trachea, larynx, and esophagus to the left of midline, the right sternocleidomastoid muscle anteriorly, and the right carotid artery and jugular vein laterally. Cytology on a core biopsy was notable for a pleomorphic spindle cell neoplasm with lipoid differentiation and positive staining for CD34 and vimentin felt to be consistent with a liposarcoma. The mass was removed during a right modified radical neck dissection, and postsurgical histopathology revealed an encapsulated tumor with negative surgical margins and MDM2 amplification by fluorescent in situ hybridization (FISH), making the final diagnosis a well-differentiated liposarcoma. Neck masses adjacent to the thyroid may appear to arise from thyroid parenchyma. Several tumors, including paragangliomas, very large parathyroid tumors, lipomas, and a case of low-grade fibromyxoid sarcoma are reported as mimicking thyroid nodules on initial evaluation. There is limited literature on liposarcomas of the head and neck, with 30 patients seen at M.D. Anderson from 1945-2005 the largest published case series. Well-differentiated liposarcomas accounted for approximately 25% (7/30) of cases, and painless neck mass as in this case was the most common presenting symptom. No patients with well-differentiated extrathyroidal liposarcomas died of their tumors in the M.D. Anderson series, in contrast to a tumor-related mortality rate of approximately 30% in the rare (N=13) cases of liposarcoma arising from the thyroid. A PubMed search failed to reveal any cases of liposarcoma mimicking a thyroid nodule. This case illustrates that large anterior neck masses require careful imaging evaluation to confirm apparent origin from the thyroid gland.

Untargeted metabolomics identified kynurenine as a predictive prognostic biomarker in acute myocardial infarction.

The occurrence of cardiovascular adverse events in the first year after ST-acute myocardial infarction (STEMI) remains high; therefore, identification of patients with poor prognosis is essential for early intervention. This study aimed to evaluate the prognostic value of metabolomics-based biomarkers in STEMI patients and explore their functional mechanisms. Metabolite profiling was performed using nuclear magnetic resonance. The plasma concentration of Kynurenine (Kyn) was measured using ultraperformance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry. Major adverse cardiac and cerebral events were assessed for 1 year. A functional metabolomics strategy was proposed for investigating the role of Kyn in both vitro and vivo models. The adjusted hazard ratios in STEMI patients for Kyn in the 4th quartile 7.12(5.71-10.82) was significantly higher than that in the 3rd quartile 3.03(2.62-3.74), 2nd quartile 1.86(1.70-2.03), and 1st quartile 1.20(0.93-1.39).The incidence of MACCE was significantly different among Kyn quartiles and the highest incidence of MACCE was observed in the 4th quartile when compared with the 1st quartile (9.84% vs.2.85%, P<0.001).Immunofluorescence staining indicated that indoleamine-pyrrole 2,3-dioxygenase (IDO1) was located in the CD68 positive staining area of thrombi from STEMI patients and Kyn was induced in the early phase after myocardial infarction. Kyn could trigger inflammation and oxidative stress of macrophage cells by activation of the Sirt3-acSOD2/IL-1β signaling pathway in vitro. Plasma Kyn levels were positively associated with the occurrence of STEMI. Kyn could induce macrophage cells inflammation and oxidative stress by activating the Sirt3-acSOD2/IL-1β pathway following myocardial ischemia injury. Kyn could be a robust biomarker for STEMI prognosis and reduction of Kyn could be beneficial in STEMI patients.

Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging for Monitoring the Immune Response of Immunogenic Chemotherapy.

ObjectiveTo evaluate the predictive value of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in the quantitative assessment of conventional chemotherapy-activated immune responses in mouse tumor models and clinics.MethodsA total of 19 subcutaneous tumor-bearing mice were randomly divided into treated and control groups. Both groups had orderly IVIM DWI examinations before and on days 6 and 12 after the administration of cyclophosphamide (CPA) or saline. Pathologic examinations were performed, including HE staining and immunohistochemistry (IHC). The expressions of immune-related genes in the tumor were measured by qPCR. In addition, six patients with breast cancer requiring neoadjuvant chemotherapy (NACT) also underwent functional MRI examinations and IHC to determine potential antitumor immune response.ResultsAt the end of the study, the CPA treatment group showed the lowest tumor volume compared to the control group. For pathological examinations, the CPA treatment group showed a lower percentage of CD31 staining (P < 0.01) and Ki-67 staining (P<0.01), and a higher percentage of TUNEL staining (P < 0.01). The tumoral pseudodiffusion coefficient (D*) value showed a positive correlation with the CD31-positive staining rate (r = 0.729, P < 0.0001). The diffusion related parameters (D) value was positively correlated with TUNEL (r = 0.858, P < 0.0001) and negatively correlated with Ki-67 (r = -0.904, P < 0.0001). Moreover, a strong induction of the expression of the immune responses in the CPA treatment group was observed on day 12. D values showed a positive correlation with the Ifnb1-, CD8a-, Mx1-, Cxcl10- (r = 0.868, 0.864, 0.874, and 0.885, respectively, P < 0.0001 for all). Additionally, the functional MRI parameters and IHC results in patients with breast cancer after NACT also showed a close correlation between D value and CD8a (r = 0.631, P = 0.028).ConclusionsThe treatment response induced by immunogenic chemotherapy could be effectively evaluated using IVIM-DWI. The D values could be potential, sensitive imaging marker for identifying the antitumor immune response initiated by immunogenic chemotherapy.

Teaching NeuroImage: Intradural ALK-Positive Histiocytosis With Involvement of Nerve Roots and Spinal Dura.

A 3-year-old boy presented with progressive lower extremity weakness and difficulty walking for 2 months. Neurologic examination found the muscle strength of his left lower limb was grade 3 and tendon reflex was weakened. MRI demonstrated an intradural extramedullary mass between T10-11 with multiple and diffuse enhancement of thickened nerve roots and spinal dura (Figure). Juvenile xanthogranuloma was suspected as positive staining for CD68 and negative for S100 and CD1a, while immunoreactivity for ALK did not support it. The genetic test confirmed the diagnosis of ALK-positive histiocytosis with KIF5B-ALK fusion, which is a relatively new subtype of histiocytic disease.1,2

Potential Involvement of Complement Activation in Kidney Vascular Lesions of Arterionephrosclerosis.

BackgroundComplement dysregulation has been implicated in the pathogenesis of malignant nephrosclerosis with typical pathological manifestation as thrombotic microangiopathy (TMA) in recent studies. The aim of the present study was to evaluate the potential role of complement activation in arterionephrosclerosis, the major pathological change in benign hypertensive nephrosclerosis.MethodsPatients with biopsy-proven arterionephrosclerosis from 2010 to 2018 in our center were retrospectively enrolled in the present study. The clinical data were retrieved from the medical chart record. The pathological changes of renal biopsy were semiquantitatively evaluated. The ratio of inner-/outer-luminal diameter of the arterioles was calculated to evaluate the degree of arteriosclerosis. Immunohistochemical staining of CD34 and CD68 was adopted to evaluate peritubular capillary (PTC) density and macrophage infiltration, respectively. Complement components, including C3d, C4d, C1q, and C5b-9, were detected by immunohistochemical staining in paraffin-embedded sections. IgM and albumin were detected by immunofluorescence staining in frozen renal tissues.ResultsFifty-two patients were enrolled. The mean age was 45.0 ± 12.7 years, with 39 (75%) males. The median duration of hypertension was 66 months (IQR: 24–138 months). A total of 950 arterioles were evaluated, with a mean ratio of the inner/outer luminal diameter of 0.43 ± 0.05. The ratio of the inner-/outer-luminal diameter correlated with eGFR (r = 0.341, p = 0.013), sclerotic/ischemic glomerular lesions (r = –0.364, p = 0.008) and PTC density (r = 0.426, p = 0.002). Seventy-four percent (703/950) of the evaluated arterioles had C3d deposition with various patterns and intensities. The percentage of C3d-positive arterioles ranged from 63.6 to 100.0% in each specimen. The ratio of the inner/outer luminal diameter of arterioles correlated with the intensity of C3d deposition (r = –0.174, p = 0.001). Infiltration of macrophages was observed around C3d-positive arterioles. The percentage of C3d-positive arterioles was correlated with macrophage infiltration in each specimen (r = 0.330, p = 0.018). Occasional C4d-positive staining on arterioles was observed with no deposition of C1q or C5b-9 in arterionephrosclerosis specimens.ConclusionOur findings provide evidence for potential complement activation in the pathogenesis of vascular lesions in arterionephrosclerosis.

POS-373 THE LEVEL OF URINARY C4d IN PATIENTS WITH IgA NEPHROPATHY IS ASSOCIATED WITH DISEASE PROGRESSION: A COHORT STUDY

Positive glomerular C4d staining, representative of lectin pathway activation, has been proven to be associated with unfavorable outcomes in IgA nephropathy (IgAN). Our previous study suggested that urinary C4d correlated positively with an increase in crescents. While the relationship between urinary C4d and disease severity and progression remains unelucidated. In this study, we enrolled 168 patients diagnosed of IgAN with varying proportions of crescents formation at the time of biopsy. An independent cohort of 107 IgAN patients were enrolled for validation. Kidney biopsy specimens were stained using immunohistochemistry. Urinay C4d levels at renal biopsy were measured by enzyme-linked immunosorbent assay. The primary endpoint was end-stage kidney disease (ESKD). Levels of urinary C4d/Urine creatine(C4d/Ucr) demonstrated the same tendency as the stepwise increase in glomerular C4d positivity (p for trend <0.001). Higher urinary C4d/Ucr levels were associated with a lower estimated glomerular filtration rate (eGFR); massive proteinuria; hypertension; and severe Oxford-M, Oxford-E, Oxford-T and Oxford-C scores. After a median follow-up of 19 months (interquartile range, 9–27 months), 53 (31.5%) participants reached end-stage of kidney disease (ESKD). High urinary C4d/creatinine ratio levels were independently and significantly associated with a risk of developing ESKD (hazard ratio [HR], per standard deviation increment of log transformed C4d/creatinine of 7.623; 95% confidence interval [CI]: 4.117–14.113). Urinary C4d/creatinine ratio was a potential useful biomarker that was associated with disease severity and progression in patients with IgAN and crescents.