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Clinical relevance of polymerase chain reaction (PCR) assays and antigen-driven immunoblots for the diagnosis of neurological infectious diseases.

Polymerase chain reaction assays are a powerful tool for detecting the presence of infectious genomes in the cerebrospinal fluid. Positive results always mean a current or pending infection of the central nervous system. Subacute (>7 days) or chronic infections induce an intrathecal humoral immune response and the appearance of oligoclonal IgG antibodies directed against the causal infectious agent. This local synthesis may be observed even in cases of severe systemic immunodeficiency. The use of polymerase chain reactions in combination with the detection of a specific intrathecal immune resp

Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients.

BACKGROUND: Comprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far. OBJECTIVE: To analyze systematically the CSF profile in COVID-19. METHODS: Retrospective analysis of 150 lumbar punctures in 127 patients with PCR-proven COVID-19 and neurological symptoms seen at 17 European university centers RESULTS: The most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72-50.8]), which was present in 58/116 (50%) samples from patients without pr

Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 3 treatment practicalities and recommendations. MS Neurology Group of the Australian and New Zealand Association of Neurologists.

In this third and final part of our review of multiple sclerosis (MS) treatment we look at the practical day-to-day management issues that are likely to influence individual treatment decisions. Whilst efficacy is clearly of considerable importance, tolerability and the potential for adverse effects often play a significant role in informing individual patient decisions. Here we review the issues surrounding switching between therapies, and the evidence to assist guiding the choice of therapy to change to and when to change. We review the current level of evidence with regards to the managemen

Antigen-Specific T Cell Receptor Discovery for Treating Progressive Multifocal Leukoencephalopathy.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a frequently fatal disease of the central nervous system caused by JC virus (JCV). Survival is dependent on early diagnosis and ability to re-establish anti-viral T cell immunity. Adoptive transfer of polyomavirus-specific T cells has shown promise; however, there are no readily available HLA-matched anti-viral T cells to facilitate rapid treatment. OBJECTIVE: Identify epitopes of the JCV major capsid protein VP1 that elicit an immune response in the context of human leukocyte antigen allele A*02:01 (HLA-A2) and isolate cognate T…

Detection of JC polyomavirus DNA sequences and cellular localization of T-antigen and agnoprotein in oligodendrogliomas.

PURPOSE: Productive infection of the human neurotropic polyomavirus JCPyV in oligodendrocytes leads to the development of progressive multifocal leukoencephalopathy, a fatal demyelinating disorder of the central nervous system. In addition to its role in viral infection, JCPyV T-antigen can transform cells in vitro and induce tumors in experimental animals in the absence of viral DNA replication and late gene expression. The goal of this study is to examine the presence of JCPyV DNA sequences and viral antigens in a series of human oligodendrogliomas. EXPERIMENTAL DESIGN: A total of 20 well-c

Mechanism of Shuangyang Houbitong granules against acute erythroleukemia through PI3K/AKT and JAK/STAT signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) posits that the onset of leukemia is often attributed to internal deficiencies and imbalances between yin and yang. Shuangyang Houbitong granules (SY) have been used in folk medicine to treat leukemia by balancing the yin-yang. However, the molecular mechanisms in which SY exerts anti-leukemia effects remain largely unexplored. AIM OF THE STUDY: To investigate the molecular mechanisms and bioactive ingredients of SY for the treatment of acute erythroleukemia (AEL). MATERIALS AND METHODS: A mouse model of erythroleukemia was e

Ferroptosis and Dysfunction of CD3+CD4-CD8- T Cells are Associated with Poor Immune Reconstitution in HIV Patients.

INTRODUCTION: Some HIV patients stay in an immune unresponsive state after antiretroviral therapy (ART), with a notably higher risk of AIDS-related and non-AIDS-related complications. Double-negative T cells (DNT) can compensate for immunity and prevent immune overactivation in HIV patients. Also, immune non-responders (INRs) have fewer DNT cells than immune responders (IRs). HIV infection and ART can change the dynamic function of cell mitochondria, which are crucial in ferroptosis. Ferroptosis is a form of cell death marked by the accumulation of reactive oxygen species (ROS) and iron-depend

[Mechanisms of Piezo1-mediated microglial ferroptosis in inhibiting spinal cord injury repair].

OBJECTIVE: To investigate the mechanism of the mechanosensitive ion channel Piezo1 in microglial ferroptosis following spinal cord injury (SCI), and to assess the effects of Piezo1 inhibition on ameliorating the injury microenvironment and promoting neurological functional recovery. METHODS: Primary microglia cells were extracted from neonatal 1-2 days C57BL/6 mice and divided into control group, Yoda1 (Piezo1 agonist) group, and Yoda1+GsMTx4 (Piezo1 inhibitor) group. Live/dead cell staining, reactive oxygen species (ROS) fluorescence staining, 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethyl

Natalizumab for induction of remission in Crohn's disease.

BACKGROUND: The pathogenesis of Crohn's disease involves migration of leukocytes into gut tissue and subsequent inflammation. Natalizumab (T … ggest that it may be possible to identify patients at risk for PML by testing for the appearance of JC virus in plasma.

Natalizumab for induction of remission in Crohn's disease.

BACKGROUND: The pathogenesis of Crohn's disease involves migration of leukocytes into gut tissue and subsequent inflammation. Natalizumab (T … ggest that it may be possible to identify patients at risk for PML by testing for the appearance of JC virus in plasma.

Innovative therapeutic concepts of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral disease of the brain-caused by human polyomavirus 2. It affects patients whose immune system is compromised by a corresponding underlying disease or by drugs. Patients with an underlying lymphoproliferative disease have the worst prognosis with a mortality rate of up to 90%. Several therapeutic strategies have been proposed but failed to show any benefit so far. Therefore, the primary therapeutic strategy aims to reconstitute the impaired immune system to generate an effective endogenous antiviral response. Recently, an

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… Cortese I Reich DS Nath A Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease Nat Rev Neurol 2021 17 37 51 33219338 10.1038/s41582-020-00427-y PMC7678594 12. … Beck ES Cortese I Checkpoint inhibitors for the treatment of JC virus-related progressive multifocal leukoencephalopathy Curr Opin Virol 2020 40 19 27 32279025 10.1016/j.coviro.2020.02.005 52. …

BK and JC polyomavirus co-infection resulting in polyomavirus nephropathy and progressive multifocal leukoencephalopathy at the same time, a case report.

John Cunningham Virus (JCV) and BK Virus (BKV) are the most extensively studied Human Polyomaviruses (HPyVs), primarily associated with Progressive Multifocal Leukoencephalopathy (PML) and BKV Nephropathy (BKVN), respectively. While co-infection with these viruses has been documented in the same disease, simultaneous manifestation in distinct pathologies has not been previously reported. We present the first documented case of concurrent PML and Polyomavirus Nephropathy (PVN) due to reactivation of two different HPyVs, offering new insights into the clinical spectrum of HPyV-related diseases.

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… Cerebrospinal Fluid (CSF) analysis showed no pleocytosis, normal glucose, protein, and lactate levels, a negative bacterial culture, and a JC virus PCR result of 150,236 copies/mL. … A case of ureteral lesions in a renal transplant recipient with a co-infection of BK virus and JC virus. Nephrol Dial Transplant. 2007;22:1275. doi: 10.1093/ndt/gfl725. 14. Kastrup O., Göricke S., Kretzschmar H., Wauschkuhn B., Diener H.C. …

Mixed cryoglobulinemia.

Mixed cryoglobulinemia (MC), type II and type III, refers to the presence of circulating cryoprecipitable immune complexes in the serum and manifests clinically by a classical triad of purpura, weakness and arthralgias. It is considered to be a rare disorder, but its true prevalence remains unknown. The disease is more common in Southern Europe than in Northern Europe or Northern America. The prevalence of 'essential' MC is reported as approximately 1:100,000 (with a female-to-male ratio 3:1), but this term is now used to refer to a minority of MC patients only. MC is characterized by variable

Review: Oncolytic virotherapy, updates and future directions.

Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or no

Efficacy and safety of ruxolitinib in the treatment of chronic graft-versus-host disease: a retrospective analysis.

Steroid-refractory chronic graft-versus-host disease (cGvHD) is associated with significant morbidity and mortality, with ruxolitinib being the first drug approved for its treatment. We retrospectively analyzed the safety and efficacy of ruxolitinib for treatment of cGvHD at our center between 07/2015 and 12/2022 and identified 48 patients receiving ruxolitinib as second (18/48) or advanced (30/48) treatment line. Ruxolitinib was started on median day 340 (range 119-595) after cGvHD onset; median duration of administration was 176 (range, 79-294) days with 16/48 patients continuing treatment a

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… One more patient received additional ISM due to progressive cGvHD and discontinued ruxolitinib therapy later due to severe BK- and John Cunningham (JC)- virus nephropathy. … virus 25 5 6 4 4 1 1 3 1 7 3 - 1 1 - - 1 1 Abbreviations: AE = adverse event; BK virus, human polyomavirus 1; COVID-19, coronavirus disease 2019; CTCAE = Common Terminology Criteria for Adverse Events; HBV, hepatitis B virus; JC virus, John Cunningham; no. of pts. …

Infectious complications after hematopoietic stem cell transplantation: current status and future perspectives in Korea.

Hematopoietic stem cell transplantation (HSCT) is a treatment for hematologic malignancies, immune deficiencies, or genetic diseases, ect. Recently, the number of HSCTs performed in Korea has increased and the outcomes have improved. However, infectious complications account for most of the morbidity and mortality after HSCT. Post-HSCT infectious complications are usually classified according to the time after HSCT: pre-engraftment, immediate post-engraftment, and late post-engraftment period. In addition, the types and risk factors of infectious complications differ according to the stem cell

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… virus) | Respiratory viruses with seasonal variations | Respiratory viruses with seasonal variations | Tuberculosis, NTM BACTERIA Epidemiology As shown in Table 1 , the infectious diseases that occur before the engraftment are similar to those that develop during the neutropenic phase after chemotherapy … Viral hemorrhagic cystitis can be caused by polyomaviruses (BK and JC viruses), adenovirus, CMV, HSV, and HHV6 [ 107 , 108 ]. Of these viruses, BK virus (BKV) is the most common; 80% to 90% of adults are BKV seropositive [ 109 - 111 ]. …

Анализ иммунологической памяти Джона Каннингема о мексиканском населении пациентов с множественным склерозом под лечением.

Фон/цели: Множественный склероз (MS) - это болезнь, характеризующаяся демиелинацией и аксонным повреждением центральной нервной системы. Несмотря на наблюдаемые преимущества, высокоэффективная терапия на основе ВИЧ-инфекции имеет негативные последствия, включая повышенный риск развития прогрессивной многофукальной лейкоэнцефалопатии (ПМП). Кроме того, риск возрастает, если пациент имеет антитела для вируса Джона Каннингема (JCV). Появляется ПМЛ редко, и в Мексике имеется лишь один доклад. Цель этого исследования состояла в том, чтобы определить и проанализировать иммунологическую память ОЖЦ у

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… Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort. Neurology. 2012;78:1736–1742. doi: 10.1212/WNL.0b013e3182583022. 30. Brew B.J., Davies N.W.S., Cinque P., Clifford D.B., Nath A. Progressive multifocal leukoencephalopathy and other forms of JC virus disease. … Anti-JC Virus Antibody Prevalence in Canadian MS Patients. Can. J. Neurol. Sci. 2014;41:748–752. doi: 10.1017/cjn.2014.32. 40. …

Management of herpesvirus reactivations in patients with solid tumours and hematologic malignancies: update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) on herpes simplex virus type 1, herpes simplex virus type 2, and varicella zoster virus.

Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on reactivation rates and clinical manifestations has increased for conventional chemotherapeutics as well as for many new antineoplastic agents. This guideline summarizes current evidence on herpesvirus reactivation in patients with solid tumours and hemato

Septic shock in the immunocompromised cancer patient: a narrative review.

Immunosuppressed patients, particularly those with cancer, represent a momentous and increasing portion of the population, especially as cancer incidence rises with population growth and aging. These patients are at a heightened risk of developing severe infections, including sepsis and septic shock, due to multiple immunologic defects such as neutropenia, lymphopenia, and T and B-cell impairment. The diverse and complex nature of these immunologic profiles, compounded by the concomitant use of immunosuppressive therapies (e.g., corticosteroids, cytotoxic drugs, and immunotherapy), superimpose

Particularities of Neurological Manifestations in Adult T-Cell Leukemia/Lymphoma: Need for a Multidisciplinary Approach-A Narrative Review.

ATL is a rare but a highly aggressive T-cell neoplasm associated with human T-cell leukemia virus-1 (HTLV-1) infection. Human T-cell lymphotropic virus type-1 (HTLV-1) is a oncogenic retrovirus responsible for the development of adult T-cell leukemia (ATL), but also for other non-malignant diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 has a higher prevalence in Japan, the Caribbean, South America, intertropical Africa, Romania, and northern Iran. ATL patients can have an extensive spectrum of neurological manifestations. Numerous factors can be i

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… Aspergillus , Toxoplasma , mucoromycetes, and John Cunningham (JC) virus are prevalent in these patients, while bacterial CNS infections are uncommon [ 98 ]. … Transcriptional Activation of JC Virus by Human T-Lymphotropic Virus Type I Tax Protein in Human Neuronal Cell Lines J. Biol. Chem. 2000 275 17016 17023 10.1074/jbc.275.22.17016 10828075 …