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Tumor infiltrating lymphocytes associated competitive endogenous RNA networks as predictors of outcome in hepatic carcinoma based on WGCNA analysis.

PLoS One 2021 29;16(7):e0254829. Epub 2021 Jul 29.

Department of Infectious Disease, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.

Background: The important regulatory role of competitive endogenous RNAs (ceRNAs) in hepatocellular carcinoma (HCC) has been confirmed. Tumor infiltrating lymphocytes (TILs) are of great significance to tumor outcome and prognosis. This study will systematically analyze the key factors affecting the prognosis of HCC from the perspective of ceRNA and TILs. Read More

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Safety of direct oral provocation testing using the Amoxicillin-2-step-challenge in children with history of non-immediate reactions to amoxicillin.

World Allergy Organ J 2021 Jul 9;14(7):100560. Epub 2021 Jul 9.

Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand.

Background: Previous studies have shown that direct oral provocation tests, without prior skin testing, in children having delayed onset, benign rashes to beta-lactam antibiotic is safe and effective. Although, this test is useful in confirming drug hypersensitivity reactions, there is no standard protocol recommendation of drug provocation tests. This study aimed to evaluate the safety of the direct oral provocation test, using the Amoxicillin-2-step-challenge without prior skin testing, in children with history of non-immediate reactions to amoxicillin. Read More

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Peripheral blood transcriptome heterogeneity and prognostic potential in lung cancer revealed by RNA-Seq.

J Cell Mol Med 2021 Jul 21. Epub 2021 Jul 21.

State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Understanding of the complex interaction between the peripheral immune system and lung cancer (LC) remains incomplete, limiting patient benefit. Here, we aimed to characterize the host peripheral immune response to LC and investigate its potential prognostic value. Bulk RNA-sequencing data of peripheral blood leucocytes (PBLs) from healthy volunteers and LC patients (n = 142) were analysed for characterization of host systemic immunity in LC. Read More

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Anti-CD52 Therapy for Multiple Sclerosis: An Update in the COVID Era.

Immunotargets Ther 2021 7;10:237-246. Epub 2021 Jul 7.

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.

CD52 is a small surface glycoprotein composed of 12 amino acids. CD52 is found mostly on the surface of mature immune cells, such as lymphocytes, monocytes, eosinophils, and dendritic cells, as well as the male genital tract: within the epididymis and on the surface of mature sperm. Low CD52 expression is also found in neutrophils. Read More

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Possible spontaneous regression of hepatocellular carcinoma with unique histopathological features confirmed by surgical resection: a case report.

Surg Case Rep 2021 Jul 13;7(1):162. Epub 2021 Jul 13.

Department of Human Pathology, Kanazawa University Graduate School of Medicine, 13-1, Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan.

Background: Spontaneous regression of hepatocellular carcinoma (HCC) is a rare event, and its clinicopathological features and underlying mechanism are not fully understood.

Case Presentation: An 84-year-old female with hepatitis C virus infection and diabetes mellitus was referred to our hospital for further examination. Abdominal ultrasonography showed a 3. Read More

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Actin Dynamics at the T Cell Synapse as Revealed by Immune-Related Actinopathies.

Front Cell Dev Biol 2021 24;9:665519. Epub 2021 Jun 24.

Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), Vienna, Austria.

The actin cytoskeleton is composed of dynamic filament networks that build adaptable local architectures to sustain nearly all cellular activities in response to a myriad of stimuli. Although the function of numerous players that tune actin remodeling is known, the coordinated molecular orchestration of the actin cytoskeleton to guide cellular decisions is still ill defined. T lymphocytes provide a prototypical example of how a complex program of actin cytoskeleton remodeling sustains the spatio-temporal control of key cellular activities, namely antigen scanning and sensing, as well as polarized delivery of effector molecules, via the immunological synapse. Read More

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or Knockdown in Mature, but Not Immature, T Lymphocytes Similarly Cripples the Human TCRαβ Complex.

Front Cell Dev Biol 2021 25;9:608490. Epub 2021 Jun 25.

Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine and 12 de Octubre Health Research Institute (imas12), Madrid, Spain.

The human αβ T-cell receptor (TCR) is composed of a variable heterodimer (TCRαβ) and three invariant dimers (CD3γε, CD3δε, and ζζ/CD247). The role of each invariant chain in the stepwise interactions among TCR chains along the assembly is still not fully understood. Despite the high sequence homology between CD3γ and CD3δ, the clinical consequences of the corresponding immunodeficiencies (ID) in humans are very different (mild and severe, respectively), and mouse models do not recapitulate findings in human ID. Read More

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Single-cell analysis reveals cell communication triggered by macrophages associated with the reduction and exhaustion of CD8 T cells in COVID-19.

Cell Commun Signal 2021 07 8;19(1):73. Epub 2021 Jul 8.

Department of Respiration, Hubei Provincial Hospital of Integrated Chinese & Western Medicine, No. 11, Linjiao Lake Road, Jianghan District, Wuhan, 430015, China.

Background: The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has become an ongoing pandemic. Understanding the respiratory immune microenvironment which is composed of multiple cell types, together with cell communication based on ligand-receptor interactions is important for developing vaccines, probing COVID-19 pathogenesis, and improving pandemic control measures.

Methods: A total of 102 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study. Read More

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Tumor microenvironment of human breast cancer, and feline mammary carcinoma as a potential study model.

Biochim Biophys Acta Rev Cancer 2021 Jul 5;1876(1):188587. Epub 2021 Jul 5.

CIISA - Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Departamento de Morfologia e Função, Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal. Electronic address:

In recent years, the tumor microenvironment (TME) has been a research hotspot, as it is composed of distinct cellular and non-cellular elements that may influence the diagnosis, prognosis, and treatment of breast cancer patients. Cancer cells are able to escape immune control through an immunoediting process which depends on complex communication networks between immune and cancer cells. Thus, a better understanding of the immune cell infiltrate in the breast cancer microenvironment is crucial for the development of more effective therapeutic approaches. Read More

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Cutaneous Lymphadenoma Is a Distinct Trichoblastoma-like Lymphoepithelial Tumor With Diffuse Androgen Receptor Immunoreactivity, Notch1 Ligand in Reed-Sternberg-like Cells, and Common EGFR Somatic Mutations.

Am J Surg Pathol 2021 May 12. Epub 2021 May 12.

*Department of Pathology, University Clinic Hospital, INCLIVA Biomedical Research Institute Departments of †Pathology §Biochemistry and Molecular Biology, University of Valencia, Valencia ‡Department of Pathology, Costa del Sol Health Agency, Málaga, Spain ∥Barr Dermatopathology, Laguna Beach, CA.

The term "cutaneous lymphadenoma" was coined in this journal for an unusual lymphoepithelial cutaneous adnexal neoplasm, possibly with immature pilosebaceous differentiation. Some authors further proposed that cutaneous lymphadenoma was an adamantinoid trichoblastoma. However, although a hair follicle differentiation is widely accepted, the fact that this is a lymphoepithelial tumor is not appropriately explained by the trichoblastoma hypothesis. Read More

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A new glaucoma drainage implant with the use of Polytetrafluoroethylene (PTFE). A pilot study.

Rom J Ophthalmol 2021 Apr-Jun;65(2):150-156

Department of Ophthalmology, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

To investigate the implantation of Polytetrafluoroethylene (PTFE) as a glaucoma drainage device. This study has been done in two steps. First, the constructed implants have been used in 4 rabbits and the histopathologic response was evaluated. Read More

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The cellular architecture of the antimicrobial response network in human leprosy granulomas.

Nat Immunol 2021 Jul 24;22(7):839-850. Epub 2021 Jun 24.

Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Granulomas are complex cellular structures composed predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated the single-cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single-cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RRs), a dynamic process whereby some patients with disseminated lepromatous leprosy (L-lep) transition toward self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. Read More

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C4b-binding protein α-chain enhances antitumor immunity by facilitating the accumulation of tumor-infiltrating lymphocytes in the tumor microenvironment in pancreatic cancer.

J Exp Clin Cancer Res 2021 Jun 24;40(1):212. Epub 2021 Jun 24.

Department of General Surgery, Chiba University, Graduate School of Medicine, 1-8-1, Inohana, Chuo-ku, Chiba City, Chiba, 260-8677, Japan.

Background: Recent studies indicate that complement plays pivotal roles in promoting or suppressing cancer progression. We have previously identified C4b-binding protein α-chain (C4BPA) as a serum biomarker for the early detection of pancreatic ductal adenocarcinoma (PDAC). However, its mechanism of action remains unclear. Read More

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B Cell Orchestration of Anti-tumor Immune Responses: A Matter of Cell Localization and Communication.

Front Cell Dev Biol 2021 7;9:678127. Epub 2021 Jun 7.

Translational Immuno-oncology Group, International Research Center, A.C. Camargo Cancer Center, São Paulo, Brazil.

The immune system plays a crucial role in cancer development either by fostering tumor growth or destroying tumor cells, which has open new avenues for cancer immunotherapy. It was only over the last decade that the role of B cells in controlling anti-tumor immune responses in the tumor milieu has begun to be appreciated. B and plasma cells can exert anti-tumor effects through antibody-dependent cell cytotoxicity (ADCC) and activation of the complement cascade, even though their effector functions extend beyond the classical humoral immunity. Read More

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The Prognostic Value of New Index (LANR) Composed of Pre-operative Lymphocytes, Albumin, and Neutrophils in Patients With Resectable Colorectal Cancer.

Front Oncol 2021 25;11:610264. Epub 2021 May 25.

Colorectal Cancer Clinical Research Center of Hubei Province, Wuhan, China.

Inflammatory factors and nutritional status are critical to the prognosis of colorectal cancer patients. This study aimed to investigate the prognostic value of the combination of preoperative lymphocytes, albumin, and neutrophils (LANR) in patients with resectable colorectal cancer. A total of 753 patients with pathologically diagnosed primary colorectal cancer were included in the study. Read More

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Predictive Value of IL-6 Combined with NLR in Inflammation and Cancer.

Cancer Invest 2021 Jul-Aug;39(6-7):489-504. Epub 2021 Jun 18.

School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, China.

The strong association between inflammation and cancer is reflected by the high interleukin-6 (IL-6) levels in the tumor microenvironment, where it promotes carcinogenesis by regulating all hallmarks of cancer and multiple signaling pathways. In this study, we investigated the prognostic value of IL-6 and other clinical indexes in inflammatory and cancer patients. All the patients were divided into the inflammation group ( = 400) and the cancer group ( = 672) composed of hematological malignancies group ( = 338) and solid tumors group ( = 334). Read More

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Nanostructured Non-Newtonian Drug Delivery Barrier Prevents Postoperative Intrapericardial Adhesions.

ACS Appl Mater Interfaces 2021 Jun 17;13(25):29231-29246. Epub 2021 Jun 17.

Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.

With the increasing volume of cardiovascular surgeries and the rising adoption rate of new methodologies that serve as a bridge to cardiac transplantation and that require multiple surgical interventions, the formation of postoperative intrapericardial adhesions has become a challenging problem that limits future surgical procedures, causes serious complications, and increases medical costs. To prevent this pathology, we developed a nanotechnology-based self-healing drug delivery hydrogel barrier composed of silicate nanodisks and polyethylene glycol with the ability to coat the epicardial surface of the heart without friction and locally deliver dexamethasone, an anti-inflammatory drug. After the fabrication of the hydrogel, mechanical characterization and responses to shear, strain, and recovery were analyzed, confirming its shear-thinning and self-healing properties. Read More

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The ocular pyogranulomatous lesion in a Gentoo penguin (Pygoscelis papua) from the Antarctic Peninsula: evaluation of microbiological and histopathological analysis outcomes.

Vet Res Commun 2021 Jun 15. Epub 2021 Jun 15.

Department of Microbiology, Faculty of Veterinary Medicine, Erciyes University, Kayseri, Turkey.

In this study, it was aimed to present the results of microbiological, cytological, histopathological, and immunohistochemical analyses of ocular samples from an Antarctic (Ardley Island, King George Island) Gentoo penguin chick (Pygoscelis papua) with a pyogranulomatous lesion in the right eye. Samples were taken from both the healthy left eye and the lesion in the right eye. Conventional culture methods and phenotypic and molecular tests were used for bacterial isolation and identification, respectively. Read More

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Design of a multi-epitope vaccine against cervical cancer using immunoinformatics approaches.

Sci Rep 2021 Jun 11;11(1):12397. Epub 2021 Jun 11.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Cervical cancer, caused by human papillomavirus (HPV), is the fourth most common type of cancer among women worldwide. While HPV prophylactic vaccines are available, they have no therapeutic effects and do not clear up existing infections. This study aims to design a therapeutic vaccine against cervical cancer using reverse vaccinology. Read More

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A Virus-Specific Immune Rheostat in the Immunome of Patients Recovering From Mild COVID-19.

Front Immunol 2021 25;12:674279. Epub 2021 May 25.

Duke-NUS Medical School, Singapore, Singapore.

An accurate depiction of the convalescent COVID-19 immunome will help delineate the immunological milieu crucial for disease resolution and protection. Using mass cytometry, we characterized the immune architecture in patients recovering from mild COVID-19. We identified a virus-specific immune rheostat composed of an effector T (T) cell recall response that is balanced by the enrichment of a highly specialized regulatory T (T) cell subset. Read More

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Complete spontaneous regression of primary Merkel cell carcinoma with tumoural infiltration: a systematic review.

Eur J Dermatol 2021 Jun;31(3):381-391

Service de Dermatologie, Université de Nantes, CHU Nantes, CIC 1413, CRCINA, F-44000 Nantes, France, CIC 1413, CRCINA INSERM 1232, Nantes, France.

Merkel cell carcinoma (MCC) is an aggressive tumour that rapidly evolves to metastasis, however, paradoxically, complete spontaneous regression (CSR) of MCC has been reported. CSR may be linked to the presence of Merkel cell polyomavirus (MCPyV) combined with immune response tumour-infiltrating lymphocytes (TILs). To elucidate the mechanism of CSR by studying the profile of TIL infiltration and the role of MCPyV. Read More

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Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma.

Cancers (Basel) 2021 May 24;13(11). Epub 2021 May 24.

Department of Oncology, University of Turin, 10043 Orbassano, Italy.

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease that arises from pleural mesothelial cells, characterized by a median survival of approximately 13-15 months after diagnosis. The primary cause of this disease is asbestos exposure and the main issues associated with it are late diagnosis and lack of effective therapies. Asbestos-induced cellular damage is associated with the generation of an inflammatory microenvironment that influences and supports tumor growth, possibly in association with patients' genetic predisposition and tumor genomic profile. Read More

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Tumor Extracellular Matrix Stiffness Promptly Modulates the Phenotype and Gene Expression of Infiltrating T Lymphocytes.

Int J Mol Sci 2021 May 30;22(11). Epub 2021 May 30.

Fondazione Istituto Nazionale di Genetica Molecolare, 20122 Milan, Italy.

The immune system is a fine modulator of the tumor biology supporting or inhibiting its progression, growth, invasion and conveys the pharmacological treatment effect. Tumors, on their side, have developed escaping mechanisms from the immune system action ranging from the direct secretion of biochemical signals to an indirect reaction, in which the cellular actors of the tumor microenvironment (TME) collaborate to mechanically condition the extracellular matrix (ECM) making it inhospitable to immune cells. TME is composed of several cell lines besides cancer cells, including tumor-associated macrophages, cancer-associated fibroblasts, CD4 and CD8 lymphocytes, and innate immunity cells. Read More

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Pediatric Tumors-Mediated Inhibitory Effect on NK Cells: The Case of Neuroblastoma and Wilms' Tumors.

Cancers (Basel) 2021 May 14;13(10). Epub 2021 May 14.

Immunology Research Area, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.

Natural killer (NK) cells play a key role in the control of cancer development, progression and metastatic dissemination. However, tumor cells develop an array of strategies capable of impairing the activation and function of the immune system, including NK cells. In this context, a major event is represented by the establishment of an immunosuppressive tumor microenvironment (TME) composed of stromal cells, myeloid-derived suppressor cells, tumor-associated macrophages, regulatory T cells and cancer cells themselves. Read More

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Multi-Omics Perspective Reveals the Different Patterns of Tumor Immune Microenvironment Based on Programmed Death Ligand 1 (PD-L1) Expression and Predictor of Responses to Immune Checkpoint Blockade across Pan-Cancer.

Int J Mol Sci 2021 May 13;22(10). Epub 2021 May 13.

School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.

Immune checkpoint inhibitor (ICI) therapies have shown great promise in cancer treatment. However, the intra-heterogeneity is a major barrier to reasonably classifying the potential benefited patients. Comprehensive heterogeneity analysis is needed to solve these clinical issues. Read More

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A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity.

Signal Transduct Target Ther 2021 05 31;6(1):213. Epub 2021 May 31.

NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Although inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core-shell structured lipopolyplex (LPP) nanoparticles. SW0123 is easy to produce using a large-scale microfluidics-based apparatus. Read More

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Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study).

Ther Adv Med Oncol 2021 18;13:17588359211019642. Epub 2021 May 18.

Department of oncology and advanced technologies AUSL - IRCCS Reggio Emilia, Reggio Emilia, Italy.

Background: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need.

Methods: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. Read More

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Clinical and Histopathological Features of Congenital Fibrovascular Pupillary Membranes in a Chinese Case Series.

J Pediatr Ophthalmol Strabismus 2021 Mar-Apr;58(2):105-111. Epub 2021 Mar 1.

Purpose: To investigate the clinical and histopathological features of congenital fibrovascular pupillary membrane (CFPM) in Chinese patients.

Methods: This retrospective study reviewed CFPM cases treated at Beijing Children's Hospital. The clinical manifestations, approaches of treatment, outcomes, and histopathological findings were collected and analyzed. Read More

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Autoimmune Global Amnesia as Manifestation of AMPAR Encephalitis and Neuropathologic Findings.

Neurol Neuroimmunol Neuroinflamm 2021 07 20;8(4). Epub 2021 May 20.

From the Division of Neuropathology and Neurochemistry (G.R., A.F., R.H.), Department of Neurology, Medical University of Vienna, Austria; Department of Neurology (T.Z., S.M., P.A., P.R., T. Berger), Medical University of Vienna, Austria; Department of Neurology (J.T., J.W.), Klinikum Klagenfurt, Austria; Institute of Clinical Chemistry (K.K.F., K.-P.W., F.L.), University Hospital Schleswig-Holstein, Kiel/Lübeck, Germany; Institute of Pathology (A.K.), Klinikum Klagenfurt, Austria; Clinical Department of Laboratory Medicine (A.F., G.M.), Proteomics Core Facility, Medical University Vienna, Austria; Center of Physiology and Pharmacology (H.K.), Department of Neurophysiology and Neuropharmacology, Medical University of Vienna, Austria; and Department of Neurology (T. Bartsch, F.L.), University Hospital Schleswig-Holstein, Kiel, Germany.

Objective: To report an unusual clinical phenotype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis and describe associated neuropathologic findings.

Methods: We retrospectively investigated 3 AMPAR encephalitis patients with autoimmune global hippocampal amnesia using comprehensive cognitive and neuropsychologic assessment, antibody testing by in-house tissue-based and cell-based assays, and neuropathologic analysis of brain autopsy tissue including histology and immunohistochemistry.

Results: Three patients presented with acute-to-subacute global amnesia without affection of cognitive performance, attention, concentration, or verbal function. Read More

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