Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Παρασκευή 20 Ιανουαρίου 2023

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

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

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

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

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imageProstate 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.
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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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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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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

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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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18FDG PET/CT Tumoral and Neurologic Therapeutic Response in a Case of Anti-GABABR Paraneoplastic Limbic Encephalitis

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imageA 70-year-old man with a history of small cell lung carcinoma 2 years earlier was addressed for the suspicion of a paraneoplastic limbic encephalitis. Brain 18FDG PET/CT revealed a bilateral amygdalian and hippocampal hypermetabolism, confirming a limbic encephalitis, and concurrent whole-body 18FDG PET/CT showed a small cell lung carcinoma plurifocal metastatic recurrence, consistent with a paraneoplastic limbic encephalitis. 18FDG PET/CT follow-up under chemotherapy revealed an almost complete normalization of brain metabolism and a partial metabolic response of the metastatic recurrence, consistent with the good clin ical neurological evolution of the patient. This case highlights the clinical-metabolic imaging correlation in paraneoplastic limbic encephalitis.
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Cervical Lymph Node Metastasis From Recurrent Glioblastoma Detected by MRI and 2-[18F]FDG PET/CT

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imageA 53-year-old man diagnosed with recurrent glioblastoma after multimodal treatment on a follow-up brain MRI. Because of a palpable mass in the neck, the patient underwent a whole-body 2-[18F]FDG PET/CT, which revealed hypermetabolic laterocervical confluent lymphadenopathies. A nodal cervical biopsy indicated distant metastases from glioblastoma. Recent studies have confirmed dural meningeal lymphatics, as part of the glymphatic system, which provide clearance of interstitial solutes from the brain parenchyma into cervical lymphatics. Nodal cervical metastases from glioblastoma, using this pathway, are extremely rare and have been almost unthinkable some years ago.
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High 18F-FDG Uptake in a Papillary Craniopharyngioma of the Third Ventricle

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imageCraniopharyngioma is a benign tumor classified as grade 1 by the World Health Organization Classification of Tumors of the Central Nervous System. We present a rare case of a high-18F-FDG-avidity papillary craniopharyngioma of the third ventricle. A 65-year-old man underwent CT and MRI examinations for gait disturbance, lower-limb weakness, and urinary incontinence, and an oval solid tumor that extended from the suprasellar region to the third ventricle was identified. 18F-FDG PET/CT showed high accumulation (SUVmax, 22.3) in the tumor. A transventricular endoscopic tumor biopsy led to the diagnosis of papillary craniopharyngioma.
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