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Παρασκευή 20 Ιανουαρίου 2023

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

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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.

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

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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.

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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

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.

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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

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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.

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

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

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

alexandrossfakianakis shared this article with you from Inoreader
image18F-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.
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Treatment Response to Lycopene in Recurrent Prostate Cancer Confirmed on 18F-Fluciclovine PET/CT

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image18F-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.
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Langerhans Cell Histiocytosis of Bilateral Parotid and Submandibular Glands: Findings on: 18: F-FDG PET/CT

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imageLangerhans cell histiocytosis is a disorder of the mononuclear phagocytic system. Virtually any organ can be involved, the bone, skin, lungs, and pituitary gland being the most common. We describe the case of a 30-year-old man who presented with painless neck swelling. 18F-FDG PET/CT showed bilateral bulky parotid and submandibular glands with increased metabolic activity. Histopathology confirmed the diagnosis of Langerhans cell histiocytosis. To our knowledge, there has been no description of 18F-FDG PET/CT findings in Langerhans cell histiocytosis of salivary glands in literature. We aim to aid in the diagnosis an d management of this rare presentation.
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A Case of Metastatic Thymoma Responsive to Treatment With 177Lu-DOTATATE

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imageWe 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.
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Malignant Transformation of Warthin Tumor in the Cervical Lymph Node

alexandrossfakianakis shared this article with you from Inoreader
imageWarthin tumor is the second most common benign tumor of salivary glands. Here we present an interesting case of squamous cell carcinoma arising from the Warthin tumor in the cervical lymph node. The patient had another Warthin tumor in the parotid gland as well. Both the malignant transformation of Warthin tumor and the heterotopic occurrence of Warthin tumor in the cervical lymph node are rare. This exceptionally rare case demonstrates that the 2 rare clinical entities can occur simultaneously and affect clinical decisions.
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