Immune‐dysregulation in subacute sclerosing panencephalitis: an exploratory case‐control study

alexandrossfakianakis shared this article with you from Inoreader Immune‐dysregulation in subacute sclerosing panencephalitis: an exploratory case‐control study via Journal of Medical Virology ABSTRACT Subacute sclerosing panencephalitis (SSPE) is a chronic progressive neurological condition caused by a defective measles virus. It is postulated that immune-dysregulation might result in persistent infection (immune evasion) as well as initiation of autoimmune phenomenon (via natural killer cells) leading to panencephalitis. The primary objective was to study the pattern of immune dysregulation in cases with SSPE. The secondary objective was to assess the correlation between the measured immunological variables and disability/death at 6 months. This was an exploratory case-control study conducted at a tertiary-care referral-facility from January 2020 to September 2021. Thirty consecutive patients fulfilling the Dyken's criteria for SSPE and 30 age-and-sex-matched healthy controls were enrolled. Immunological profile constituted by lymphocyte subset analysis, immunoglobulin levels and complement levels were done in all cases and controls. Cases were staged as per Jabbour's system; disability was assessed using the modified Rankin Scale (mRS). Patients with SSPE had a mean age of 14.76 years (± 6.9 years). There were 25 males and 5 females; 6.7% cases belonged to Jabbour's first stage, 40% to second stage and 53.3% to third stage. At least 1/4th had evidence of measles vaccination. Levels of absolute lymphocyte count, B-cells, T cells, helper T-cells and cytotoxic T-cells were significantly higher in cases. IgG, IgM and IgE levels were significantly higher while IgD levels were significantly lower in cases. At baseline, 13.3% of cases had a mRS score of 0-2 and 86.7% had a score of 3-6; at 6 months 10% had a mRS score 0-2 (favourable outcome) while 90% had a mRS score 3-6 (poor outcome). Higher IgE levels were found to significantly correlate with favourable outcome. Immune-dysregulation may play a significant role in shaping one's response to measles infection as well as in determining vaccine-efficacy. This article is protected by copyright. All rights reserved. View on Web

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Covid Associated Immune Dysfunction (CAID) Leading to Increased Pediatric Hospitalizations

alexandrossfakianakis shared this article with you from Inoreader Covid Associated Immune Dysfunction (CAID) Leading to Increased Pediatric Hospitalizations via Journal of Medical Virology Summary Immunity debt is an increasingly popular hypothesis to explain the current pediatric respiratory disease epidemic. The theory is unproven and potentially harmful. A more reasoned explanation of the present pediatric hospitalization crisis and a broader increase in respiratory illness levels, in general, may be attributable to SARS-CoV-2 infection-associated immune dysfunction. The matter requires urgent investigation. This article is protected by copyright. All rights reserved. View on Web

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IFNL3/4 polymorphisms as a two‐edged sword: an association with COVID‐19 outcome

alexandrossfakianakis shared this article with you from Inoreader IFNL3/4 polymorphisms as a two‐edged sword: an association with COVID‐19 outcome via Journal of Medical Virology ABSTRACT Background COVID-19 has been ranked among the most fatal infectious diseases worldwide, with host's immune response significantly affecting the prognosis. Aim of the study With an aim to timely predict the most likely outcome of SARS-CoV-2 infection, we investigated the association of IFNL3 and IFNL4 polymorphisms, as well as other potentially relevant factors, with the COVID-19 mortality. Methods This prospective observational case-control study involved 178 COVID-19 patients, hospitalized at Corona Center or Clinic for Infectious Diseases of University Clinical Centre Kragujevac, Serbia, followed up until hospital discharge or in-hospital death. Demographic and clinical data on all participants were retrieved from the electronic medical records, and TaqMan assays were employed in genotyping for IFNL3 and IFNL4 SNPs, namely rs12980275, rs8099917, rs12979860 and rs368234815. Results 21.9% and 65.0% of ho spitalized and critically ill COVID-19 patients, respectively, died in-hospital. Multivariable logistic regression analysis revealed increased CCI, N/L, and LDH level to be associated with an increased likelihood of a lethal outcome. Similarly, females and the carriers of at least one variant allele of IFNL3 rs8099917 were almost 36-fold more likely not to survive SARS-CoV-2 infection. On the other hand, the presence of at least one ancestral allele of IFNL4 rs368234815 decreased more than 15-fold the likelihood of mortality from COVID-19. Conclusion Our results suggest that, in addition to LDH level, N/L ratio, and CCI, IFNL4 rs368234815 and IFNL3 rs8099917 polymorphisms, but also patients' gender, significantly affect the outcome of COVID-19. This article is protected by copyright. All rights reserved. View on Web

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A hepatitis B virus core antigen‐based virus‐like particle vaccine expressing SARS‐CoV‐2 B and T cell epitopes induces epitope‐specific humoral and cell‐mediated immune responses but confers limited protection against SARS‐CoV‐2 infection

alexandrossfakianakis shared this article with you from Inoreader A hepatitis B virus core antigen‐based virus‐like particle vaccine expressing SARS‐CoV‐2 B and T cell epitopes induces epitope‐specific humoral and cell‐mediated immune responses but confers limited protection against SARS‐CoV‐2 infection via Journal of Medical Virology Abstract The hepatitis B virus core antigen (HBcAg) tolerates insertion of foreign epitopes and maintains its ability to self-assemble into virus-like particles (VLPs). We constructed a ∆HBcAg-based VLP vaccine expressing three predicted SARS-CoV-2 B and T cell epitopes and determined its immunogenicity and protective efficacy. The recombinant ∆HBcAg-SARS-CoV-2 protein was expressed in E. coli, purified, and shown to form VLPs. K18-hACE2 transgenic C57BL/6 mice were immunized intramuscularly with ∆HBcAg VLP control (n=15) or ∆HBcAg-SARS-CoV-2 VLP vaccine (n=15). One week after the 2nd booster and prior to virus challenge, five ∆HBcAg-SARS-CoV-2 vaccinated mice were euthanized to evaluate epitope-specific immune responses. There is a statistically significant increase in epitope-specific IgG response, and statistically higher IL-6 and MCP-1 expression levels in ∆HBcAg-SARS-CoV-2 VLP-vaccinated mice compared to ∆HBcAg VLP controls. While not statistically sign ificant, the ∆HBcAg-SARS-CoV-2 VLP mice had numerically more memory CD8+ T-cells, and 3/5 mice also had numerically higher levels of IFN-γ and TNF. After challenge with SARS-CoV-2, ∆HBcAg-SARS-CoV-2 immunized mice had numerically lower viral RNA loads in the lung, and slightly higher survival, but the differences are not statistically significant. These results indicate that the ∆HBcAg-SARS-CoV-2 VLP vaccine elicits epitope-specific humoral and cell-mediated immune responses but they were insufficient against SARS-CoV-2 infection. This article is protected by copyright. All rights reserved. View on Web

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Extranodal Extension Improves AJCC‐8 Accuracy in HPV+ Oropharyngeal Cancer in a High‐Risk Population

alexandrossfakianakis shared this article with you from Inoreader Extranodal Extension Improves AJCC‐8 Accuracy in HPV+ Oropharyngeal Cancer in a High‐Risk Population via The Laryngoscope Although American Joint Committee on Cancer's 8th edition (AJCC-8) has demonstrated an improved ability to stratify OPSCCs into stages that predict overall survival, high-risk populations may be predisposed to worse outcomes. The goal of this manuscript is to validate the AJCC-8 as a better metric of survivability over AJCC-7 in a historically under-served rural population with confounding variables such as tobacco use, alcohol consumption, and poor healthcare access, and to analyze the role of extranodal extension in this population. Objectives The American Joint Committee on Cancer's 8th edition (AJCC-8) separates oropharyngeal squamous cell carcinomas (OPSCCs) into human papillomavirus-positive (HPV+) tumors and HPV-negative tumors. Although AJCC-8 improves prognostic prediction for survival for the majority of HPV+ OPSCC, outliers are still encountered. The goal of this manuscript is to validate the AJCC-8 as a better metric of survivability than the AJCC-7 in an historically under-served rural population with confounding variables, such as tobacco use, alcohol consumption, and poor health care access and to analyze the role of extranodal extension (ENE) in this population. Design Retrospective cohort study. Results Compared to AJCC-7, AJCC-8 had a higher odds ratio (OR) for predicting mortality of stage IV HPV+ OPSCCs versus stages I–III. On multivariate analysis, HPV+ OPSCCs with ENE had a higher OR of mortality compared to ENE- OPSCCs. In addition, HPV+ OPSCC patients with a Charlson Comorbidity Index (CCI) > 3 had a higher OR of mortality compared to those with a CCI ≤ 3. Patients with Medicaid/self-pay status had a higher OR of mortality compared to those with private insurance/Medicare. Finally, patients from rural populations had a higher OR of presenting with stage IV disease, a CCI > 3, and Medicaid/self-pay status. Conclusions Despite not being a discrete part of the AJCC-8 staging rubric, ENE was found to have a significant impact on mortality among this population, whereas tobacco use had no effect. Rural patients were more likely to present with stage IV disease, CCI > 3, and Medicaid/self-pay status. Stage IV disease was also associated with a higher OR of mortality. Level of Evidence 4 Laryngoscope, 2023 View on Web

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FDG PET/CT in a Case of Lung Adenocarcinoma With Diffuse Cavitary Intrapulmonary Metastases

alexandrossfakianakis shared this article with you from Inoreader FDG PET/CT in a Case of Lung Adenocarcinoma With Diffuse Cavitary Intrapulmonary Metastases via Clinical Nuclear Medicine - Published Ahead-of-Print We describe FDG PET/CT findings in a case of lung adenocarcinoma with diffuse cavitary intrapulmonary metastases at initial diagnosis. High-resolution CT of the chest showed the primary solid tumor in the right upper lobe and numerous cavitating metastases ranging from a few millimeters to 1 cm in the bilateral lungs. FDG PET/CT showed intense activity of the primary tumor, diffuse activity of the lung metastases, and hypermetabolic metastases in the mediastinal lymph nodes and bones. Familiarity with this atypical intrapulmonary metastatic pattern of lung cancer may be helpful for the diagnosis and differential diagno sis. View on Web

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Asymptomatic Prostate Cancer Metastasis in Rectal Mucosa Revealed by 18F-PSMA-1007 PET/CT

alexandrossfakianakis shared this article with you from Inoreader Asymptomatic Prostate Cancer Metastasis in Rectal Mucosa Revealed by 18F-PSMA-1007 PET/CT via Clinical Nuclear Medicine - Published Ahead-of-Print Prostate cancer metastasis to the rectal mucosa, a relatively rare metastatic site, leads to a higher clinical stage and poorer prognosis. A 65-year-old man with prostate cancer underwent 18F–prostate-specific membrane antigen (PSMA) PET/CT for staging. Intense 18F-PSMA uptake occurred at the primary lesion, bladder, adjacent seminal vesicle, and rectum. PET/CT imaging revealed increased homogeneous round activity of the rectal wall. The final diagnosis was prostate cancer metastasis to the rectal mucosa. This case suggested that 18F-PSMA PET/CT may assist in locating rare metastases of prostate cancer, with potenti al value for early staging. View on Web

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Extrastriatal 99mTc-TRODAT-1 Uptake in the Previous Hemorrhage With Hemosiderin Deposition

alexandrossfakianakis shared this article with you from Inoreader Extrastriatal 99mTc-TRODAT-1 Uptake in the Previous Hemorrhage With Hemosiderin Deposition via Clinical Nuclear Medicine - Published Ahead-of-Print We reported a 91-year-old man who was suspected of having parkinsonism, and brain 99mTc-TRODAT-1 scan revealed an extrastriatal uptake in the left side of brainstem, which was correlated to a previously hemorrhagic lesion with hemosiderin deposition. Macrophage or microglia might accumulate in the previous hemorrhagic lesion to phagocytize hemosiderin. We assumed that the 99mTc-TRODAT-1 uptake in the hemosiderin deposition might be partially mediated by macrophage expressing dopamine transporter. View on Web

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Hepatic Small Vessel Neoplasm Mimics Prostate Cancer on 18F-DCFPyl PET/CT

alexandrossfakianakis shared this article with you from Inoreader Hepatic Small Vessel Neoplasm Mimics Prostate Cancer on 18F-DCFPyl PET/CT via Clinical Nuclear Medicine - Published Ahead-of-Print 18F-DCFPyl is a Food and Drug Administration–approved radiotracer that targets prostate-specific membrane antigen and is used in the detection of recurrent or metastatic prostate cancer. As its use has increased, a growing number of nonprostatic disease entities have been identified that express prostate-specific membrane antigen and can mimic prostate cancer. Thus, the interpreting physician must also consider other variables such as serum prostate-specific antigen levels and the distribution of uptake to avoid an inappropriate diagnosis of metastatic prostate cancer. We describe 18F-DCFPyl uptake associated with a hep atic small vessel neoplasm, an association previously undescribed in the literature. View on Web

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Treatment Response to Lycopene in Recurrent Prostate Cancer Confirmed on 18F-Fluciclovine PET/CT

alexandrossfakianakis shared this article with you from Inoreader Treatment Response to Lycopene in Recurrent Prostate Cancer Confirmed on 18F-Fluciclovine PET/CT via Clinical Nuclear Medicine - Published Ahead-of-Print 18F-fluciclovine (Axumin; Blue Earth Diagnostics, Ltd, Oxford, United Kingdom) PET has shown value in detecting biochemical recurrent prostatic cancer. Lycopene, a plant-based carotenoid, is reported to have potential inhibitory effect on prostate cancer, as a complementary treatment. We report a case of biochemically recurrent prostate cancer showing treatment response to lycopene as seen on an 18F-fluciclovine PET/CT correlating with serum prostate-specific antigen response. View on Web

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A Case of Metastatic Thymoma Responsive to Treatment With 177Lu-DOTATATE

alexandrossfakianakis shared this article with you from Inoreader A Case of Metastatic Thymoma Responsive to Treatment With 177Lu-DOTATATE via Clinical Nuclear Medicine - Published Ahead-of-Print We describe a case of a 74-year-old woman with germline BRCA2 mutation, with an incidental diagnosis of metastatic thymoma presenting as a mediastinal mass with cardiac muscle and lymph node involvement. Despite surgical and radiotherapy treatment, there was marked advancement with new lung and liver metastases. All lesions demonstrated 68Ga-DOTATATE PET/CT uptake, and the patient received 4 peptide receptor radionuclide therapy cycles with 177Lu-DOTATATE, with pronounced reduction in the size of the liver, cardiac, and pleural lesions. This is the first case to demonstrate partial response to peptide receptor radionuclide t herapy in metastatic thymoma, thus suggesting possible treatment option to refractory and advancing metastatic thymoma. View on Web

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