Autoimmune encephalitis associated with an ovarian teratoma in a 29-year old woman
Published on: 15th May, 2019
OCLC Number/Unique Identifier: 8165450551
NMDA receptor encephalitis is a rare disease first described in 2007. Anti-NMDA receptor encephalitis affects mostly young women as neoplasms, mostly ovarian teratomas, are the underlying cause. The disease is caused by antibodies binding to extracellular epitopes of neuronal cell-surface, which leads to an internalization of NMDA-receptors. The characteristic syndrome of patients with anti-NMDAR as well as its recovery follows a certain pattern. Treatment includes immunotherapy and removal of the immunologic trigger. This case report describes a young woman with anti-NMDA receptor encephalitis caused by an ovarian teratoma.
Triple negative breast cancer: Early stages management and evolution, a two years experience at the department of breast cancer of CHSF
Published on: 30th June, 2020
OCLC Number/Unique Identifier: 8625623678
Breast cancer is the most common cancer in women and is a major public health problem. It is divided into several subtypes, including triple negatives. The general objective of our study is to establish the profile and the management of patients with triple negative breast cancer over a period of 2 years, operated in our department.
During our study period, triple-negative breast cancers accounted for 10% of our population. The most affected age group ranges from 50 to 60. The majority of patients in our sample are pauciparous. In the group of patients who received hormone therapy, it was mainly HRT for 4 to 6 years. 96.77% of patients consulted a health worker within 3 months of the discovery of the signs. Adenopathies are frequently present at the time of diagnosis. 93.54% of the cases have an invasive ductal carcinoma. Triple negative cancers are essentially poorly differentiated. Triple-negative cancer has a high rate of cell renewal. In our study, neoadjuvant chemotherapy is mostly indicated for triple-negative breast cancers ≥ 30 mm at diagnosis and a delayed lumpectomy is then performed in 23.52% of the patients. For tumors of < 30 mm size, a lumpectomy is performed immediately in 76.47% of the patients, followed by adjuvant chemotherapy.
Mastectomy was performed in 45.16% of patients; it was mainly indicated in front of a large tumor size associated with a small breast volume, then multifocal breast tumors. Breast reconstruction was performed in 21.42%. Radiation therapy is indicated in the majority of patients, postoperatively. In our population, 11 patients were proposed to have an oncogenetic survey; it was mainly indicated based on the Manchester criteria in front of a young age and a family history of cancer. There are two BRCA 1 mutations, one BRCA 2 mutation, and one case of absence of mutation. The therapeutic intake in case of a mutation is directed towards a prophylactic bilateral mastectomy and adnexectomy, proposed at the age of 40. Two patients had presented triple negative recurrences of their already treated breast cancer; first case PDL1 positive PD-L1 ≥ 1% treated with immunotherapy combined with chemotherapy (atezolizumab/abraxane) while the second and second PDL1 negative treated with chemotherapy alone.
Despite their low frequency, triple negative breast cancers represent a subgroup marked by pejorative characteristics, a reserved prognosis, with limited treatment options.
The beneficial effects of varicella zoster virus
Published on: 15th July, 2019
OCLC Number/Unique Identifier: 8186245399
Varicella zoster virus behaves differently from other herpes viruses as it differs from them in many aspects. Recently, there has been growing evidence on the beneficial effects of the virus in immune compromised hosts and these effects are translated into prolongation of survival. The reported beneficial effects of the virus include: (1) stimulation of bone marrow activity in patients with hematologic malignancies and bone marrow failure syndromes, (2) antitumor effects in various hematologic malignancies and solid tumors, and (3) association with graft versus host disease which has anticancer effects. Additionally, there are several reports on the safety of the live-attenuated even in severely immune suppressed individuals and on the emerging role of the virus in cancer immunotherapy. In this review, the following aspects of the virus will be thoroughly discussed: (1) new data on the genetic background, pathogenesis, vaccination, and new therapeutic modalities; (2) bone marrow microenvironment and hematopoiesis; (3) cells involved in the pathogenesis of the virus such as: mesenchymal stem cells, dendritic cells, natural killer cells, T-cells and mononuclear cells; (4) cellular proteins such as open reading frames, glycoproteins, promyelocytic leukemia protein, chaperons, and SUMOs; (5) extracellular vesicles, exosomes, and micro-RNAs; and (6) signaling pathways, cytokines, and interferons.
The use of Allergoids and Adjuvants in Allergen Immunotherapy
Published on: 20th September, 2017
OCLC Number/Unique Identifier: 7317597241
Allergen immunotherapy (AIT) is the unique curative treatment to help allergic patients to get over their allergies. With a personalized approach, AIT is the best example of precision medicine. After a century of intensive studies and innovative discoveries, allergists have in their hands many tools to orchestrate the best strategy to re-educate the hypersensitive immune systems that decrease the quality of life of their patients. This review describes both the historical and the promising acquisitions in this field, focusing the biochemical and Bioengineering tools that render an allergen more suitable for a secure, convenient and effective immunotherapy.
Cyn d 1 airborne allergen in a Southern Brazilian city
Published on: 26th February, 2021
OCLC Number/Unique Identifier: 8971180635
By researching the factors related to exposure to indoor and outdoor allergens, such seasons, climate changes and particulate matter, allergists can screen the sensitization profile of individuals according to their exposures and conduct preventive treatment and individualized immunotherapy. Molecular allergology has improved aerobiological screening of allergenic components toward more specific results on allergic exposure, sensitization, and symptoms [1,2]. The Enzyme-Linked Immunosorbent Assay (ELISA) is a colorimetric enzyme immunoassay technique used to quantify soluble substances such as proteins, peptides, antibodies, and hormones. Due to its high sensitivity and specificity, ELISA can quantify substances at low concentrations, such as allergens [3].
Herpes simplex virus (HSV)-1 encephalitis can induce chronic anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis
Published on: 27th July, 2018
OCLC Number/Unique Identifier: 7814922521
Herpes simplex virus (HSV)-1 encephalitis is the most common infectious cause of sporadic encephalitis. Despite treatment with acyclovir, HSV encephalitis is still associated with severe morbidity characterized by persistent neurological deficits. HSV encephalitis usually follows a monophasic course, however, some patients might develop relapsing symptoms caused by the formation of auto-antibodies directed against the N-methyl-D-aspartate receptor (NMDAR). Here we present an 82-year-old male patient with HSV encephalitis who developed shortly after his hospital discharge a Post-HSV NMDAR encephalitis, characterized by recurrent epileptic seizures and deterioration of his residual aphasia. First-line immunotherapy with intravenous immunoglobulins (IgIV) was administered and the patient returned almost to his baseline residual deficits of HSV encephalitis. Subsequently, he presented with recurrent relapses of NMDAR encephalitis. Since periodic treatment with IgIV has been started the patient is seizure-free and his neuropsychiatric condition is stable. In conclusion, the recognition of Post-HSV NMDAR encephalitis is very important because neurological manifestations can markedly improve with immunotherapy. Interestingly, in some patients cerebral HSV infection seems to trigger a chronic inflammatory disorder with persistent autoimmune activation which requires chronic treatment.
Flow cytometry potential applications in characterizing solid tumors main phenotype, heterogeneity and circulating cells
Published on: 24th August, 2021
OCLC Number/Unique Identifier: 9213084224
Flow cytometry (FCM) is a unique technique that allows rapid quantitative measurement of multiple parameters on a large number of cells at the individual level. FCM is based on immunolabelling with fluorochrome-conjugated antibodies, leading to high sensitivity and precision while time effective sample preparation. FCM can be performed on tissue following enzymatic or mechanical dissociation. The expression of epithelial antigens and cytokeratin isoforms help in distinguishing tumor cells from adjacent epithelial cells and from tumor infiltrating leukocytes. Tumor phenotypes can be characterized on expression intensity, aberrancies and presence of tumor-associated antigens as well as their cell proliferation rate and eventual heteroploidy. FCM can measure quantitative expression of hormone or growth factor receptors, immunoregulatory proteins to guide adjuvant therapy. Expression of adhesion molecules tells on tumor’s capacity for tissue invasion and metastasis seeding. Tumor heterogeneity can be explored quantitatively and rare, potentially emerging, clones with poor prognosis can be detected. FCM is easily applicable on fine needle aspiration and in any tumor related biological fluids. FCM can also be used to detect circulating tumor cells (CTC) to assess metastatic potential at diagnosis or during treatment. Detecting CTC could allow early detection of tumors before they are clinically expressed although some difficulties still need to be solved. It thus appears that FCM should be in the pathologist tool box to improve cancer diagnosis, classification and prognosis evaluation as well as in orientating personalized adjuvant therapy and immunotherapy. More developments are still required to better known tumor phenotypes and their potential invasiveness
Evaluation of long antigen exposition dendritic cell therapy (LANEX-DC®) in the adjuvant treatment of pancreatic cancer – results of a single center analysis
Published on: 25th July, 2022
OCLC Number/Unique Identifier: 9575035340
Introduction: Even after surgical resection and adjuvant chemotherapy in pancreatic cancer the 5-year disease-free survival times (DFS), as well as overall survival rates (OS), are still low and median survival times are below 2 years. Here we retrospectively analyzed the outcome of immunotherapy in the additional adjuvant treatment of pancreatic cancer with long antigen exposition dendritic cell therapy (LANEX-DC®) in 28 patients who were treated at our institution. Patients: Data were available from 28 patients. Dendritic cells (LAEX-DC®) were produced according to a recently published protocol.Results: Therapy was well tolerated and no serious side effects were observed. The median disease-free survival times and the median survival times were 16,9 months and 29,4 months respectively. Five-year DFS and OS were 14,3% and 17,9%. Conclusion: We were able to show in a small cohort of patients that additional treatment with dendritic cells (LANEX-DC®) is highly effective and extends the median disease-free survival times as well as the median survival in the adjuvant treatment of pancreatic cancer, whereas the five-year overall survival still remains unsatisfactory.
Impact of coronavirus pandemic on safety and time of administration of subcutaneous immunotherapy among pediatric patients
Published on: 2nd September, 2022
OCLC Number/Unique Identifier: 9617323801
Introduction: Allergen immunotherapy is the only targeted therapy that can modify the natural course of allergic diseases. In pediatric patients, SCIT with aeroallergens is an effective treatment and should be considered as a preventive strategy in the treatment of allergic diseases, even though one of the major concerns about it is its safety. The main purposes of this study were to assess the safety of SCIT ultra-rush schedules with polymerized extracts in a pediatric population and to determine the impact of the COVID-19 pandemic on the safety and time of administration of subcutaneous immunotherapy among pediatric patients.Methods: A retrospective medical records review of patients under 18 years of age undergoing SCIT was made and re-scheduling due to restrictions imposed by the COVID-19 pandemic was recorded. Results: A total of 192 pediatric patients were included. Fifty-nine (31%) had local reactions and systemic reactions were not reported. In March 2020, the first case of COVID-19 was diagnosed in Portugal and all non-urgent appointments and procedures were postponed. In our group of pediatric patients, 43 (22%) were referred to primary care, 38 (20%) stopped AIT definitively and 111 (58%) maintained administrations in the hospital. Only 2 (2%) of them had reactions upon reinitiation. Conclusion: In this study, the ultra-rush protocol using polymerized extracts was safe in pediatric patients. Although the effectiveness of AIT may be compromised due to prolonged suspension of the treatment, it is important to note that despite longer interruptions, administrations may continue without compromising safety, maintaining shorter visits and a lower number of injections.
Design and optimization of mRNAs encoding an Anti-TIGIT antibody with therapeutic potential for cancer in TIGIT-humanized BALB/c Mice
Published on: 7th April, 2023
mRNA drugs are synthesized using cell-free systems without complex and stringent manufacturing processes, which makes their preparation simple, efficient, and economical. Over the past few years, mRNAs encoding antibodies have been one of the research frontiers of antibody drug development. In cancer immunotherapy, mRNAs encoding immune checkpoint antibodies may be advantageous regarding antibody persistence and durability of the anti-tumor immune response of patients. In our previous study, a candidate antibody—AET2010—targeting the novel immune checkpoint TIGIT was reported. Its anti-tumor activity was also investigated using adoptive transfer of NK-92MI cells in a xenograft mouse model, but the limitations of the model did not facilitate precise evaluation. In the present study, we further investigated the therapeutic potential of AET2010 for cancer in TIGIT-humanized BALB/c mice. Next, we explored the design, synthesis, and optimization of mRNAs encoding AET2010 and ultimately obtained a candidate mRNA (mRNA-BU) with favorable in vitro and in vivo expression levels of active AET2010. Particularly, lipid-nanoparticle-encapsulated mRNA-BU delivered to mice produced AET2010 with significantly higher peak concentration and expression duration than an equivalent dose of original AET2010. This study provides a sound basis for developing novel drugs targeting TIGIT.
Clinical Approach to Immunotherapy-induced Type 1 Diabetes Mellitus: A Case of Pembrolizumab Associated Insulin-dependent Diabetes in a Patient with NSCLC
Published on: 25th September, 2023
As the introduction of immune checkpoint inhibitors in the treatment of various cancers is now proven to be already acquired knowledge, so does a new challenge arise for clinicians; the understanding, diagnosis, and management of the rarest adverse effects of immunotherapy. We present a case of type-1 diabetes Mellitus (T1DM) in a patient with non-small cell lung carcinoma (NSCLC) treated with pembrolizumab. Following ten cycles of treatment, our patient was diagnosed with T1DM after being admitted for diabetic ketoacidosis and stayed hospitalized in the ICU. Later, they continued treatment with insulin, having shown disease response to pembrolizumab, and resumed immunotherapy while on insulin. Immunotherapy-induced T1DM can sometimes occur with PD1/PD-L1 blockage therapies. It has a rapid onset, is characterized by insulin deficiency due to the autoimmune destruction of beta-cells, and usually presents itself with diabetic ketoacidosis. Unlike most of the other adverse effects of immunotherapy, glucocorticoids don’t seem to be of therapeutic value, and insulin substitution is required. Regular glucose monitoring can be key to early diagnosis and prevention of hospitalization.
Navigating Neurodegenerative Disorders: A Comprehensive Review of Current and Emerging Therapies for Neurodegenerative Disorders
Published on: 4th April, 2024
Neurodegenerative disorders (NDDs) pose a significant global health challenge, impacting millions with a gradual decline in neurons and cognitive abilities. Presently, available NDD therapies focus on symptom management rather than altering the disease trajectory. This underscores the critical necessity for groundbreaking treatments capable of addressing the root causes of neurodegeneration, offering both neuroprotection and neuro-restoration. This in-depth review delves into the forefront of emerging NDD therapies, encompassing gene therapy, stem cell therapy, immunotherapy, and neurotrophic factors. It sheds light on their potential advantages, hurdles, and recent advancements gleaned from both preclinical and clinical studies. Additionally, the document outlines existing NDD treatments, spanning pharmacological and non-pharmacological interventions, along with their inherent limitations. The overarching conclusion emphasizes the immense potential of emerging therapies in NDD treatment, yet underscores the imperative for continued research and optimization to ensure their safety, efficacy, and specificity.
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