Tissue Involvement Research Articles

Immunohistochemical expression of angiotensin-converting enzyme 2 in superficial and deep maxillofacial tissues: A cross-sectional study.

Background and AimsThe involvement of maxillofacial tissues in SARS‐CoV‐2 infections ranges from mild dysgeusia to life‐threatening tissue necrosis, as seen in SARS‐CoV‐2‐associated mucormycosis. Angiotensin‐converting enzyme 2 (ACE2) which functions as a receptor for SARS‐CoV‐2 was reported in the epithelial surfaces of the oral and nasal cavities; however, a complete understanding of the expression patterns in deep oral and maxillofacial tissues is still lacking.MethodsThe immunohistochemical expression of ACE2 was analyzed in 95 specimens from maxillofacial tissues and 10 specimens of pulmonary alveolar tissue using a semiquantitative immunohistochemical scoring procedure, taking into account all superficial and deep maxillofacial tissue cells. We also explored the associations of age, gender, and anatomical site with expression scores.ResultsACE2 was detected in keratinized epithelia (57.34%), non‐keratinized epithelia (46.51%), nasal respiratory epithelial cells (73.35%), pulmonary alveolar cells (82.54%), fibroblasts (63.69%), vascular endothelial cells (58.43%), mucous acinar cells (59.88%), serous acinar cells (79.49%), salivary duct cells (86.26%) skeletal muscle fibers (71.01%), neuron support cells (94.25%), and bone marrow cells (72.65%). Age and gender did not affect the expression levels significantly in epithelial cells (p = 0.76, and p = 0.7 respectively); however, identical cells expressed different protein levels depending on the site from which the specimens were obtained. For example, dorsal tongue epithelia expressed significantly lower ACE2 scores than alveolar epithelia (p < 0.001). A positive correlation was found between ACE2 expression in fibroblasts and epithelial cells (r = 0.378, p = 0.001), and between vascular endothelial and epithelial cells (r = 0.395, p = 0.001).ConclusionACE2 is expressed by epithelial cells and subepithelial tissues including fibroblasts, vascular endothelia, skeletal muscles, peripheral nerves, and bone marrow. No correlation was detected between ACE2 expression and patient age or sex while the epithelial expression scores were correlated with stromal scores.

Treatment of Epstein-Barr Virus-Related Post-Renal Transplantation Development of Diffuse Large B Cell Lymphoma of the Distal Ureter: A Case Report

Posttransplant lymphoproliferative disorder with involvement of the donor urogenital tissue is a rare and serious complication of solid organ transplant. We report an adult kidney transplant recipient who developed the diffuse large B cell lymphoma of the distal ureter in the setting of new allograft nephropathy. Early intervention, reduction of immunosuppression, surgical reconstruction and chemotherapy salvaged the allograft kidney and averted a fatal outcome. The renal function recovered to the baseline with creatinine ranging between 1.3 and 1.5. The patient did not require dialysis at any point after ureteral stent placement and reconstructive surgery. In addition, the case highlights the importance of multidisciplinary management involving transplant nephrology, oncology, transplant surgery, and urology in such a complicated disease process.

COVID-associated rhino-orbito-cerebral mucormycosis

INTRODUCTION: Rhino-orbito-cerebral mucormycosis (ROCM), a life-threatening, acute fungal infection of the nasal cavities and paranasal sinuses, once considered a rare and lethal complication in immunocompromised patients, is now having a massive increase in ROCM incidence in India associated with COVID-19, i.e., COVID-associated mucormycosis with more than 15,000 cases as of May 2021. Early imaging by computed tomography (CT) and magnetic resonance imaging (MRI) is not only helpful in assessing the extent of involvement of this lethal disease but also helps in early diagnosis leading to prompt and aggressive treatment. The present study is aimed at determining and comparing the imaging findings on CT and MRI in ROCM patients, for early diagnosis in suspected cases of ROCM. MATERIALS AND METHODS: The present study is a comparative study of CT and MRI done on 11 patients suspected of ROCM, for 2 months from May to June 2021. RESULTS: Among 11 patients in the study group, ranging from 29 to 65 years of age, 45.4% belonged in 41–60 years of age group, with female predominance. 90.90% cases (10 patients) had maxillary sinus involvement among which 7 cases were diagnosed with ROCM, followed by 63.60% cases (7 patients) had ethmoidal sinus involvement among which 6 cases were diagnosed with ROCM. The involvement of retromaxillary space, pterygopalatine fossa space and masticator space, and cellulitis in premaxillary and preseptal spaces were findings seen only in diagnosed cases of ROCM. Erosions of bones were seen in ROCM cases, 27.20% cases (3 patients) had erosions of walls of maxillary sinus and lamina papyracea each. Orbital involvement in the form of intraconal space and extraocular muscles involvement was seen in 27.20% cases (3 patients) each. Optic nerve involvement was seen in 18.10% cases (2 patients) followed by extraconal space involvement in 9.01% cases (1 patient). Taking KOH staining and/or histopathology (HPR) as standard of reference, CT has a Sensitivity (Sn) of 71.40%, Specificity (Sp) of 100%, Positive predictive value (PPV) of 100%, Negative Predictive Value (NPV) of 66%, and Diagnostic accuracy (DA) of 81% as compared to MRI which has a Sn of 85.7%, Sp of 100%, PPV of 100%, NPV of 80%, and DA of 90.9%. CONCLUSIOIN: CT and MRI play a complementary role in diagnosis of ROCM, as CT is better in detecting bone erosions, whereas MRI is better in detecting soft tissue, orbital and central nervous system involvement. In the acute state of emergency as in the current pandemic with rising cases of ROCM and acute shortage of amphotericin-B, MRI is the single best modality for accurate detection of ROC, helping clinicians in the judicious use of Amphotericin-B.

Overview of Orbital Inflammation/Unmet Needs

Diseases of the orbit and periorbital eye tissues manifest in a wide variety of clinical presentations. Space occupying lesions in the orbit include infections, inflammations, vascular malformations, and malignancies. The significant variation in presentations is due to the complex anatomy of the orbit and the heterogeneous nature of the multiple disease processes that present themselves as orbital inflammatory processes. Additionally, although specific disease entities often show similar patterns of orbital tissue involvement, there is still a spectrum of clinical presentations within disease processes, which furthermore overlap with other inflammatory etiologies. This heterogeneity creates a significant challenge in determining specific diagnoses and subsequently instituting timely medical and surgical management of patients with orbital inflammation. Despite advances in imaging, physical examination, and laboratory tests, a biopsy is often needed for diagnosis and to guide treatment. Unfortunately, the biopsy is too often read as non-specific or idiopathic inflammation, a term that gives minimal guidance to the patient or to the clinician. There is clearly a need for developing more specific and sensitive clinical diagnostic testing.

Magnetic Resonance Imaging Prognostic Findings for Visual and Mortality Outcomes in Acute Invasive Fungal Rhinosinusitis

To identify initial, preintervention magnetic resonance imaging (MRI) findings that are predictive of visual and mortality outcomes in acute invasive fungal rhinosinusitis (AIFRS). Retrospective cohort study. Patients with histopathologically or microbiologically confirmed AIFRS cared for at a single, tertiary academic institution between January 2000 and February2020. A retrospective review of MRI scans and clinical records of patients with confirmed diagnosis of AIFRS was performed. For each radiologic characteristic, a modified Poisson regression with robust standard errors was used to estimate the risk ratio for blindness. A multivariate Cox proportional hazards model was used to study AIFRS-specific risk factors associated with mortality. Identification of initial, preintervention MRI findings associated with visual and mortality outcomes. The study comprised 78 patients (93 orbits, 63 with unilateral disease and 15 with bilateral disease) with AIFRS. The leading causes of immunosuppression were hematologic malignancy (38%) and diabetes mellitus (36%). Mucormycota constituted 56% of infections, and Ascomycota constituted 37%. The overall death rate resulting from infection was 38%. Risk factors for poor visual acuity outcomes on initial MRI included involvement of the orbital apex (relative risk [RR], 2.0; 95% confidence interval [CI], 1.1-3.8; P= 0.026) and cerebral arteries (RR, 1.8; 95% CI, 1.3-2.5; P &lt; 0.001). Increased mortality was associated with involvement of the facial soft tissues (hazard ratio [HR], 4.9; 95% CI, 1.3-18.2; P= 0.017), nasolacrimal drainage apparatus (HR, 5.0; 95% CI, 1.5-16.1; P= 0.008), and intracranial space (HR, 3.5; 95% CI, 1.4-8.6; P= 0.006). Orbital soft tissue involvement was associated with decreased mortality (HR, 0.3; 95% CI, 0.1-0.6; P= 0.001). Extrasinonasal involvement in AIFRS typically signals advanced infection with the facial soft tissues most commonly affected. The initial, preintervention MRI is prognostic for a poor visual acuity outcome when orbital apex or cerebral arterial involvement, or both, are present. Facial soft tissues, nasolacrimal drainage apparatus, intracranial involvement, or a combination thereof is associated with increased mortality risk, whereas orbital soft tissue involvement is correlated with a reduced risk of mortality.

Brain-Derived Neurotrophic Factor And Coronary Artery Disease

Coronary artery disease (CAD) is defined as myocardial damage developing as a result of its organic and functional changes, and leading to impaired blood flow through the coronary arteries. An important pathogenetic component of CAD is atherosclerosis. Currently, key aspects of the molecular relationship between inflammation and atherosclerosis are being actively studied, the immunometabolic theory of atherosclerosis is being discussed, along with an involvement of perivascular adipose tissue in the pathogenesis of this pathology, due to its ability to respond to atherogenic stimuli via developing inflammatory reactions. Evidence has been accumulated that in patients with CAD, both in their blood and perivascular adipose tissue, the level of neurotrophic factors (in particular, brain-derived neurotrophic factor, BDNF) changes, which may be a promising area of research from the standpoint of studying this factor as a therapeutic target for atherosclerosis in CAD. Neurotrophic growth factors control the functioning of both immune and nervous systems, and the balance of energy metabolism and innervation of adipose tissue. They affect vascular homeostasis, and are also involved in causing and stopping inflammation. Currently, there are data on the role of BDNF in the pathogenesis of cardiovascular, neurodegenerative and metabolic diseases, and on the effect of polyunsaturated fatty acids and eicosanoids on the level of BDNF and, accordingly, the development and progression of coronary artery atherosclerosis. Our review summarizes published data (2019-2021) on the pathophysiological and pathogenetic mechanisms of the relationship between BDNF and CAD (atherosclerosis).

PB2107: CLINICAL MANIFESTATIONS AND EFFICACY ANALYSIS OF 71 CASES OF AIDS-RELATED LYMPHOMA

Background: Patients with AIDS-related lymphoma (ARL) is difficult to accept standard treatment for various reasons. Aims: To summarize the clinical characteristics of AIDS-related lymphoma (ARL) patients admitted to Chongqing Cancer Hospital and improve the understanding of the disease. Methods: The clinical data of 71 ARL patients admitted from January 2008 to January 2021 were retrospectively analyzed. Results: The ratio of male to female in 71 ARL patients was 6.1:1, and the median age was 50 years. Fifty-one percent of patients had no other HIV-related manifestations and were only found at the time of lymphoma diagnosis. 20% of patients were diagnosed with lymphoma within 1 year of AIDS diagnosis and antiviral therapy. At the time of diagnosis of lymphoma, 35 cases (49.3%) with CD4+ cell count>200×10^6/L, 22 cases (30.9%) with CD4+ cell count 100-200×10^6/L, and CD4+ cell count<100×10^6/L and 6 cases of <50×10^6/L (accounting for 8.5 ), and 2 other cases are unknown. The most common pathological type in the 71 patients was diffuse large B-cell lymphoma (38 cases, accounting for 53.5%), Burkitt lymphoma (13 cases, accounting for 18.3), and the types also include Hodgkin lymphoma, high-grade B-cell lymphoma, plasmablastic lymphoma, follicular lymphoma, marginal zone B-cell lymphoma tumor, CLL/SLL, T lymphoblastic lymphoma and Castleman disease. Thirty patients (42.3%) had extranodal involvement at the initial diagnosis, including lung, kidney, intestinal, pancreas, breast, testis, skin and soft tissue involvement. Ann-Arbor staging included 56 patients (78.8%) with stage III-IV, and 19 patients (26.8%) with B symptoms. Survival analysis showed that patients with central involvement, elevated LDH, and intermediate-high-risk IPI scores had shorter progression-free survival, and patients with large masses, intermediate-high-risk and high-risk IPI scores had shorter overall survival. Both CHOP and EPOCH-based chemotherapy regimens are used in AIDS-related non-Hodgkin lymphoma, but the efficacy varies greatly. ABVD treatment of AIDS-related Hodgkin lymphoma is effective, but extranodal involvement may be a poor prognostic factor. Summary/Conclusion: ARL has diverse clinical manifestations, frequent extranodal involvement, late clinical stage, high malignancy, and poor clinical efficacy.

Clinicopathological and molecular genetic characteristics of nodular fasciitis in unusual sites

Objective: To study the clinicopathological, immunophenotypic and molecular genetic characteristics of nodular fasciitis (NF) in unusual sites. Methods: A total of 50 cases of NF diagnosed between January 2015 and January 2021 were reviewed in the Department of Pathology, Henan Provincial People's Hospital, and the clinical and pathologic data were analyzed. Among them, 14 cases from unusual sites were included in this study. Immunohistochemical (IHC) staining was used to detect the expression of related proteins, and fluorescence in situ hybridization (FISH) was used to detect the breakage of the USP6 gene. Results: There were seven males and seven females in the 14 NF respectively. The lesions were located in the extremities, perineum, breast, wrist joints, the gap between lumbar vertebra 4/5, and in eight cases there was involvement of unusual tissues (six cases in skeletal muscle, one case in nerve root, and one case was intravascular). The tumor boundary was unclear with infiltrating growth. Spindle-shaped myofibroblasts were arranged in bundles or chaotically, with mild pleomorphic, small nucleoli and various mitotic figures. The tumor stroma showed collagenization to myxoid degeneration with erythrocyte extravasation and infiltration of inflammatory cells. IHC staining showed that the spindle cells expressed SMA focally or partially, and p16 diffusely and strongly. FISH showed that 12 of 14 cases had USP6 gene breakage, and two of them occurred in the intrathoracic skeletal muscle with the red signal amplification of USP6 gene. Conclusions: NF in unusual sites shows similar clinicopathological and genetic characteristics to classic NF, but the tumor mostly has infiltrating borders, non-specific and strong expression of p16, and USP6 red signal amplification. The pathological diagnosis of NF in rare sites should be highly vigilant.

P53 Regulates a miRNA-Fructose Transporter Axis in Brown Adipose Tissue Under Fasting.

Active thermogenic adipocytes avidly consume energy substrates like fatty acids and glucose to maintain body temperature upon cold exposure. Despite strong evidence for the involvement of brown adipose tissue (BAT) in controlling systemic energy homeostasis upon nutrient excess, it is unclear how the activity of brown adipocytes is regulated in times of nutrient scarcity. Therefore, this study aimed to scrutinize factors that modulate BAT activity to balance thermogenic and energetic needs upon simultaneous fasting and cold stress. For an unbiased view, we performed transcriptomic and miRNA sequencing analyses of BAT from acutely fasted (24 h) mice under mild cold exposure. Combining these data with in-depth bioinformatic analyses and in vitro gain-of-function experiments, we define a previously undescribed axis of p53 inducing miR-92a-1-5p transcription that is highly upregulated by fasting in thermogenic adipocytes. p53, a fasting-responsive transcription factor, was previously shown to control genes involved in the thermogenic program and miR-92a-1-5p was found to negatively correlate with human BAT activity. Here, we identify fructose transporter Slc2a5 as one direct downstream target of this axis and show that fructose can be taken up by and metabolized in brown adipocytes. In sum, this study delineates a fasting-induced pathway involving p53 that transactivates miR-92a-1-5p, which in turn decreases Slc2a5 expression, and suggests fructose as an energy substrate in thermogenic adipocytes.

Liver-Directed Adeno-Associated Virus–Mediated Gene Therapy for Mucopolysaccharidosis Type VI

BackgroundMucopolysaccharidosis type VI (MPS VI) is an inherited multisystem lysosomal disorder due to arylsulfatase B (ARSB) deficiency that leads to widespread accumulation of glycosaminoglycans (GAG), which are excreted in increased amounts in urine. MPS VI is characterized by progressive dysostosis multiplex, connective tissue and cardiac involvement, and hepatosplenomegaly. Enzyme replacement therapy (ERT) is available but requires life-long and costly intravenous infusions; moreover, it has limited efficacy on diseased skeleton and cardiac valves, compromised pulmonary function, and corneal opacities.MethodsWe enrolled nine patients with MPS VI 4 years of age or older in a phase 1/2 open-label gene therapy study. After ERT was interrupted, patients each received a single intravenous infusion of an adeno-associated viral vector serotype 8 expressing ARSB. Participants were sequentially enrolled in one of three dose cohorts: low (three patients), intermediate (two patients), or high (four patients). The primary outcome was safety; biochemical and clinical end points were secondary outcomes.ResultsThe infusions occurred without severe adverse events attributable to the vector, meeting the prespecified end point. Participants in the low and intermediate dose cohorts displayed stable serum ARSB of approximately 20% of the mean healthy value but returned to ERT by 14 months after gene therapy because of increased urinary GAG. Participants in the high-dose cohort had sustained serum ARSB of 30% to 100% of the mean healthy value and a modest urinary GAG increase that did not reach a concentration at which ERT reintroduction was needed. In the high-dose group, there was no clinical deterioration for up to 2 years after gene therapy.ConclusionsLiver-directed gene therapy for participants with MPS VI did not have a dose-limiting side-effect and adverse event profile; high-dose treatment resulted in ARSB expression over at least 24 months with preliminary evidence of disease stabilization. (Funded by the Telethon Foundation ETS, the European Commission Seventh Framework Programme, and the Isaac Foundation; ClinicalTrials.gov number, NCT03173521; EudraCT number, 2016-002328-10.)

Isolated echinococcal infection of the spleen: a rare case report

Echinococciasis is a zoonotic infection observed in almost every anatomic location in the body. The liver and lungs are the most frequent sites of infection. However, spleen involvement is rare, and isolated splenic hydatid disease is even less common. Herein, we report a case of isolated splenic hydatid cyst without any tissue involvement that was treated with the classical surgical approach.

P60: A decade on LVAD support

Objective: The use of left ventricular assist devices (LVADs) to support patients with end-stage heart failure (HF) has been progressively adopted over the past 2 decades, with long-term outcomes reporting 50% survival at 5 years, particularly related to development of complications on support. However, there is a paucity of information related to survival beyond 10 years. Herein, we report the case of an 85-year-old man with end stage ischemic cardiomyopathy with an 11-year continuous LVAD support as destination therapy (DT). Case Report: An 85-year-old man transferred from an outside hospital, presented to the emergency department due to concerns for a driveline infection. The patient has an 11-year-old history of HeartMate2-LVAD support as destination therapy (DT) due to an end-stage ischemic cardiomyopathy. Patient has undergone automatic implantable cardioverter defibrillator secondary to atrial fibrillation, as well as a primary coronary artery disease requiring multiple percutaneous coronary interventions, in addition to an aortic and mitral valve repair. He was last seen 2 years prior to this consultation for an external LVAD drive line replacement and a chronic infection which is under oral Cefalexin management (500mg/day). Additionally, the patient continues anticoagulation therapy (aspirin 81 mg/day; warfarin 10 mg/day) with a target INR of 2.5, and has not experienced any thromboembolic or hemorrhagic complications. On clinical evaluation, driveline insertion showed a non-tender, mild erythematous aspect, with no exudation. A CT scan of the thorax and abdomen was performed, demonstrating no involvement of deep tissues. Results: Initial echocardiographic evaluation showed a left ventricular ejection fraction of 20%, moderate-to-severely reduced right ventricular systolic function, a right atrial pressure of 15 mmHg, moderate tricuspid regurgitation, and a left ventricular end diastolic diameter of 6.5 cm. Upon physical examination the patient was warm and well-perfused with an euvolemic appearance. The LVAD settings remain steady at 9400 rpm and a 5.0 L/min flow. The driveline exit site elicited no pain at palpation, with mild erythema. Due to a sustained hemodynamic function in perspective to the patient’s end-stage heart failure, 500 mg of cefalexin/daily was continued and patient was discharged with no complications and continued monitorization. Conclusion: To the authors’ knowledge, this case represents one of longest reports of LVAD support as DT. The continuing improvement of LVAD management has led to the safe and feasible application of long-term cardiac function support as DT for patients deemed not transplant candidates. As our elderly population expands, and over 80% of patients with heart failure are older than 65 years, the role LVAD for long-term support will become more relevant, and this case reveals that safe LVAD support is possible beyond 10 years.

460-P: Cellular Communication of Schwann Cell Subtypes in Metabolically-Acquired Neuropathy

The prevalence of the metabolic syndrome (MetS) is increasing worldwide due in part to the increased consumption of a Western diet. MetS is associated with peripheral neuropathy (PN) . PN develops in a cell non-autonomous manner with involvement of axons, Schwann cells (SC) and nerve tissue- infiltrating macrophages (TIM) . SC are divided into subtypes with different roles in nerve injury. Our aim in the current study was to determine how gene expression of different types of SC and macrophages are affected in MetS and how these cells communicate with one another. C57BL6/j male mice (6-weeks old) were fed either a standard diet (SD, 10% fat) or high fat diet (HFD, 60%) for 17 weeks. Metabolic and PN phenotyping were performed for all mice and SC were extracted from sciatic nerves for single cell RNA sequencing (scRNA-seq) . Cellular communication was determined using the CellChat tool. Mice on HFD had higher fasting blood glucose (FBG) , glycated hemoglobin (HbA1c) and decreased nerve conduction velocities and intraepidermal nerve fiber densities consistent with PN compared to mice on SD. Analysis of SC scRNA-seq data revealed unique RNA expression signatures for TIM and 4 subpopulations of SC denoted as myelinating SC (mySC) , non-myelinating SC (nmSC) , SC precursors (SCP) and regenerating SC. Inflammatory genes such as Ptprc and Il1b were significantly more expressed in both TIM and mySC in HFD mice compared to SD mice. CellChat analysis of cellular communication revealed more crosstalk between TIM and various types of SC in HFD animals and identified multiple metabolic and inflammatory pathways that were activated in HFD compared to SD mice. In conclusion, our study shows that there are many subtypes of SC that behave differently in MetS. Their communication with each other and with TIM strongly implicates these two cell types in the pathogenesis of metabolically acquired PN. Disclosure S.Eid: None. M.H.Noureldein: None. F.Mendelson: None. E.L.Feldman: None. Funding Funding was provided by the National Institutes of Health (NIH) (1R24082841 to ELF) , Novo Nordisk Foundation (NNF14OC0011633 to ELF) , the Nathan and Rose Milstein Research Fund (to SAE) , NeuroNetwork for Emerging Therapies at the University of Michigan (to SAE, MHN, and ELF) , and the A. Alfred Taubman Medical Research Institute (to SAE, MHN, and ELF) .

Pathological involvement of placenta in COVID-19: a systematic review

The mammalian placenta, which is responsible for bonding between the mother and the fetus, is one of the first organs to develop. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has caused a great threat to public health and affected almost all the organs including the placenta. Owing to limited available data on vertical transmission and pathological changes in the placenta of SARS-CoV-2 positive patients, we aim to review and summarize histopathological and ultrastructural changes in the placental tissue following SARS-CoV-2 infection. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 guidelines were used for review writing. Multiple studies have reported significant pathological changes in the placental tissue of SARS-CoV-2 positive mothers. On the other hand, some studies have demonstrated either no or very little involvement of the placental tissue. The most common pathological changes reported are fetal and maternal vascular malformation, villitis of unknown etiology, thrombus formation in the intervillous space and sub-chorionic space, and chorangiosis. Reports on vertical transmission are less in number. The observations of this review present a strong base for the pathological involvement of the placenta in SARS-CoV-2 infected mothers. However, a smaller number of original studies have been done until now, and most of them have small sample sizes and lack matched control groups, which are the big limitations for drawing an effective conclusion at this stage. Antenatal care can be improved by a better understanding of the correlation between maternal SARS-CoV-2 infection and placental pathology in COVID-19.

Clinicopathologic characteristics and treatment outcomes of de novo myeloid sarcoma.

e19002 Background: Extramedullary disease in acute myeloid leukemia (AML), also known as myeloid sarcoma (MS), is an uncommon presentation of de novo AML. Clinicopathologic characteristics and optimal treatment strategies of de novo MS remain unclear in both isolated MS without bone marrow (BM) involvement and synchronous MS with BM involvement. Methods: In a single-site retrospective study, medical records of patients with de novo extramedullary AML who received oncological care at any Mayo Clinic site between 1996 and 2021 were analyzed. Using BlueSky Statistics software, survival outcomes were analyzed using Kaplan-Meier and Cox-proportional hazard models for univariate and multivariate analysis, respectively. Results: 83 patients with de novo MS were identified; 49 (59%) presented with synchronous MS and 34 (41%) exhibited isolated MS. Median age at diagnosis was 56 years (range, 17-89); 63% were male. Next-generation sequencing of the blood +/- BM revealed abnormalities in 24/27 (88%) analyzed patients; aberrations included mutations in RTK-RAS pathways (12/27), NPM1 (10/27), TET2 (6/27), and IDH2 (4/27). Median length of follow-up was 1.73 years (95% CI; 0.03-3.0); 53 patients (64%) had expired. Median event free survival was 0.64 years and 0.61 years in isolated and synchronous MS, respectively (p = 0.5). Median overall survival (mOS) in isolated and synchronous MS was 2.1 years and 1.5 years, respectively (p = 0.5). Induction treatment with intensive chemotherapy (IC) was administered in 70 patients (84%). IC regimens included 7+3, MEC, CLAG-M, and hyper-CVAD. Variables associated with improved survival in both groups included treatment with IC +/- allogenic stem cell transplant (alloSCT) (p &lt; 0.001), normal or favorable risk karyotype (p = 0.001), and age less than 60 (p = 0.001). Localized therapy (LT) did not provide an added survival benefit. Patients with synchronous MS were more likely to relapse in the BM and blood than isolated MS (p = 0.02). Conclusions: Enriched with RTK-RAS mutations, de novo MS remains an aggressive form of AML, particularly in patients with intermediate or high-risk genomics or those with skin, soft tissue, or lymphatic involvement. IC should be employed with consideration of alloSCT in eligible patients, particularly in synchronous MS due to a heightened risk for medullary and leukemic relapse.[Table: see text]

Role of 18F-FDG PET/CT in the diagnosis and management of patients with Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm that can involve multisystem organs. Positron emission tomography/computed tomography (PET/CT) has been widely used in tumor staging and efficacy evaluation. However, at present, there are few 18F-fluorodeoxyglucose (FDG) PET/CT studies on LCH. This study aimed to explore the possible role of 18F-FDG PET/CT in the diagnosis and management of patients with LCH. 18F-FDG PET/CT images of 22 Chinese patients diagnosed with LCH on biopsy or surgery histopathology between January 2011 and December 2020 were retrospectively analyzed. The incidence of LCH in each system was assessed by a PET/CT scan. The imaging characteristics were analyzed semiquantitatively and qualitatively. The discrepancies between PET/CT and conventional imaging modalities were recorded. Evaluations of curative effect according to RECIST1.1 and PERCIST1.0 were compared using Fisher's exact chi-squared test, and P values <0.05 were considered significant. Eight (36.4%) of the 22 patients presented with single system involvement (4 isolated site involvement, 4 multiple site involvement), and 14 (63.6%) presented with multiple system involvement. Twenty-one (95.5%) patients had hypermetabolic lesions. Musculoskeletal, lymphatic, respiratory, liver, skin-soft tissue and thyroid involvement were seen in 14 (63.6%), 13 (59.1%), 5 (22.7%), 4 (18.2%), 5 (22.7%) and 1 (4.5%) patient, respectively. Cranial and facial bones were the most common sites of musculoskeletal involvement. Ten patients underwent PET/CT follow-up, and there was no significant difference in curative effect evaluations according to RECIST1.1 and PERCIST1.0. However, among the complete remission cases assessed by RECIST1.1, three were partial metabolic responses assessed by PERCIST1.0, while among the partial response cases assessed by RECIST1.1, one was metabolic progressive disease assessed by PERCIST1.0. 18F-FDG PET/CT is an imaging modality option for the diagnosis and assessment of the curative effect of LCH.

Longitudinal association of thyroid-stimulating immunoglobulin levels with clinical characteristics in thyroid eye disease

ObjectivesThe clinical course of thyroid eye disease (TED) is heterogeneous and predicting patients who may develop the severe sequelae of the disease is difficult. In this study, we evaluated the...

Clinical and Imaging Features of Tumors in the Scapula.

The scapula is a small irregular-shaped flat bone, which may suffer from a variety of tumors or tumor-like lesions. As the imaging manifestations are complex and changeable, correct imaging diagnosis is difficult. At present, there are few related radiology literatures, and it is necessary to fully analyze the imaging signs of different types of benign and malignant tumors in scapula to guide clinical treatment. This study was to investigate clinical and imaging presentations of tumors and tumor- like lesions in the scapula so as to increase the diagnostic accuracy of diseases in the scapula. Patients with scapular tumors confirmed by pathology were enrolled. The imaging and clinical data were analyzed. Among 108 patients, benign tumors were in 53 (49.1%) cases, intermediate in seven (6.5%), and malignant in 48 (44.4%) involving 16 diseases. Osteochondroma was the first benign tumors in 45 cases accounting for 84.9% of all benign scapular tumors, followed by chondroma in four cases (7.5%). The intermediate tumors were mainly eosinophilic granuloma in four cases. Metastatic tumors were the commonest malignant tumor (27 cases or 56.2% of all malignant tumors), followed by chondrosarcoma (in 13 cases). Except for the one case of chondroblastoma in which the lesion involved the glenoid cavity, all the other cartilaginous tumors were located in the scapular body and processes. The type of lesions in the bony processes is the same as in the scapular body, the common lesions in the central area of the body were malignant tumors, and the commonest lesions in the glenoid area were metastasis. Common imaging features of malignant scapular tumors were ill-defined margins, cortical destruction and soft tissue involvement. The imaging features of chondrosarcoma lack specificity except for calcification. Benign lesions usually had a clear boundary and marginal sclerosis. A wide variety of benign and malignant tumors may occur in the scapula with mostly cartilaginous and metastatic tumors, and the location and distribution of lesions are similar in the scapula to those in the long bones.

Translated article] Metaphysary fractures of the distal tibia: Comparative analysis of the results obtained by means of a blocked plate and intramedular nail

IntroductionFractures of the distal third of the tibia are mostly the consequence of high-energy trauma with significant soft tissue involvement, being more frequent in men.These types of fractures differ from the tibial pilon joint fracture in their mechanism of injury, management and prognosis.The objective of the present study was to analyse and compare the results obtained in the treatment of fractures of the distal third of the tibia without joint extension using a locked plate and intramedullary nail. Material and methodsWe carried out a retrospective study with patients diagnosed of “distal third tibia fracture” segment 43A according to the classification proposed by the “Trauma Orthopedic Association” who were intervened between January 2015 and May 2019 were included. We obtained 24 patients intervened with a nail intramedullary and 29 using a blocked plate. ResultsThe study included 53 patients, 36 men and 17 women with a mean age of 51 years (range: 15–77 years). The mean follow-up time was 6 months (3–30 months). No significant differences were found in the time to fracture healing, although the beginning with load walking was earlier in the nail group. DiscussionCurrently there is no consensus on the therapeutic management of distal tibia fractures without joint extension. ConclusionsAfter analyzing the results, we consider that both intramedullary nail osteosynthesis and a locked plate are valid options in the treatment of fractures of the distal third of the tibia.

Circulating Th2 cell reduction and Th1/Th2 imbalance are correlated with primary Sjogren’s syndrome-associated interstitial lung disease

ObjectivePrimary Sjogren’s syndrome (pSS) is a heterogeneous chronic autoimmune disorder characterized by lymphocyte infiltration of the exocrine glands and the involvement and dysfunction of multiple organs and tissues. Interstitial lung disease (ILD) is the most common type of respiratory system damage. This study ascertained the factors related to ILD in patients with pSS (pSS-ILD), such as altered levels of circulating lymphocyte subtypes.MethodsEighty healthy controls and 142 patients diagnosed with pSS were included. The pSS patients were classified into groups with pSS-ILD or pSS without ILD (pSS-non-ILD). Baseline clinical and laboratory data were collected for all subjects, including the levels of lymphocytes measured by modified flow cytometry.ResultsThe pSS-ILD patients were older, had higher ESSDAI scores, had higher positivity rates for anti-SSB and anti-Ro52 antibodies, and had more frequent symptoms of respiratory system involvement than pSS-non-ILD patients. pSS-ILD patients had the lowest Th2 cell counts among the three groups. Although the absolute numbers of Treg and NK cells were lower in pSS patients with and without ILD than in the healthy controls, there was no significant difference between the two pSS groups. The Th1/Th2 ratio was significantly higher in patients with ILD than in patients without ILD. Further analysis showed that older age (OR=1.084), lower Th2 count (OR=0.947), higher Th1/Th2 ratio (OR=1.021), and positivity for anti-SSB (OR=3.620) and anti-Ro52 (OR=5.184) antibodies were associated with the occurrence of ILD in patients with pSS.ConclusionDecreased circulating Th2 cells and an elevated Th1/Th2 ratio may be the immunological mechanism underlying the development of ILD in pSS patients.