A djuvant treatment in patients at high risk of recurrence of thymoma: Efficacy and safety of a three-dimensional conformal radiation therapy regimen

The clinical benefits of postoperative radiation therapy (PORT) for patients with thymoma are still controversial. In the absence of defined guidelines, prognostic factors such as stage, status of surgical margins, and histology are often considered to guide the choice of adjuvant treatment (radiotherapy and/or chemotherapy). In this study, we describe our single-institution experience of three-dimensional conformal PORT administered as adjuvant treatment to patients with thymoma. METHODS: Twenty-two consecutive thymoma patients (eleven male and eleven female) with a median age of 52 years and treated at our institution by PORT were analyzed. The patients were considered at high risk of recurrence, having at least one of the following features: stage IIB or III, involved resection margins, or thymic carcinoma histology. Three-dimensional conformal PORT with a median total dose on clinical target volume of 50 (range 44-60) Gy was delivered to the tumor bed by 6-20 MV X-ray of the linear accelerator. Follow-up after radiotherapy was done by computed tomography scan every 6 months for 2 years and yearly thereafter. RESULTS: Two of the 22 patients developed local recurrence and four developed distant metastases. Median overall survival was 100 months, and the 3-year and 5-year survival rates were 83% and 74%, respectively. Median disease-free survival was 90 months, and the 5-year recurrence rate was 32%. On univariate analysis, pathologic stage III and presence of positive surgical margins had a significant impact on patient prognosis. Radiation toxicity was mild in most patients and no severe toxicity was registered. CONCLUSION: Adjuvant radiotherapy achieved good local control and showed an acceptable toxicity profile in patients with high-risk thymoma

Comment on Kopańska et al. Disorders of the Cholinergic System in COVID-19 Era—A Review of the Latest Research. Int. J. Mol. Sci. 2022, 23, 672

We read the recent review article by Marta Kopańska et al. [...

Re-irradiation of brain metastases and metastatic spinal cord compression: clinical practice suggestions

The recent improvements of therapeutic approaches in oncology have allowed a certain number of patients with advanced disease to survive much longer than in the past. So, the number of cases with brain metastases and metastatic spinal cord compression has increased, as has the possibility of developing a recurrence in areas of the central nervous system already treated with radiotherapy.Clinicians are reluctant to perform re-irradiation of the brain, because of the risk of severe side effects. The tolerance dose for the brain to a single course of radiotherapy is 50-60 Gy in 2 Gy daily fractions. New metastases appear in 22-73% of the cases after whole brain radiotherapy, but the percentage of re-irradiated patients is 3-10%. An accurate selection must be made before giving an indication to re-irradiation. Patients with Karnofsky performance status >70, age <65 years, controlled primary and no extracranial metastases are those with the best prognosis. The absence of extracranial disease was the most significant factor in conditioning survival, and maximum tumor diameter was the only variable associated with an increased risk of unacceptable acute and/or chronic neurotoxicity. Re-treatment of brain metastases can be done with whole brain radiotherapy, stereotactic radiosurgery or fractionated stereotactic radiotherapy. Most patients had no relevant radiation-induced toxicity after a second course of whole brain radiotherapy or stereotactic radiosurgery. There are few data on fractionated stereotactic radiotherapy in the re-irradiation of brain metastases.In general, the incidence of an "in-field" recurrence of spinal metastasis varies from 2.5-11% of cases and can occur 2-40 months after the first radiotherapy cycle. Radiation-induced myelopathy can occur months or years (6 months-7 years) after radiotherapy, and the pathogenesis remains obscure. Higher radiotherapy doses, larger doses per fraction, and previous exposure to radiation could be associated with a higher probability of developing radiation-induced myelopathy. Experimental data indicate that also the total dose of the first and second radiotherapy, interval to re-treatment length of the irradiated spinal cord, and age of the treated animals influence the risk of radiation-induced myelopathy. An alpha/beta ratio of 1.9-3 Gy could be generally the reference value for fractionated radiotherapy. However, when fraction sizes are up to 5 Gy, the linear-quadratic equation become a less valid model. The early diagnosis of relapse is crucial in conditioning response to re-treatment

SARS-CoV-2-Related Olfactory Dysfunction: Autopsy Findings, Histopathology, and Evaluation of Viral RNA and ACE2 Expression in Olfactory Bulbs

Background: The COVID-19 pandemic has been a health emergency with a significant impact on the world due to its high infectiousness. The disease, primarily identified in the lower respiratory tract, develops with numerous clinical symptoms affecting multiple organs and displays a clinical finding of anosmia. Several authors have investigated the pathogenetic mechanisms of the olfactory disturbances caused by SARS-CoV-2 infection, proposing different hypotheses and showing contradictory results. Since uncertainties remain about possible virus neurotropism and direct damage to the olfactory bulb, we investigated the expression of SARS-CoV-2 as well as ACE2 receptor transcripts in autoptic lung and olfactory bulb tissues, with respect to the histopathological features. Methods: Twenty-five COVID-19 olfactory bulbs and lung tissues were randomly collected from 200 initial autopsies performed during the COVID-19 pandemic. Routine diagnosis was based on clinical and radiological findings and were confirmed with post-mortem swabs. Real-time RT-PCR for SARS-CoV-2 and ACE2 receptor RNA was carried out on autoptic FFPE lung and olfactory bulb tissues. Histological staining was performed on tissue specimens and compared with the molecular data. Results: While real-time RT-PCR for SARS-CoV-2 was positive in 23 out of 25 lung samples, the viral RNA expression was absent in olfactory bulbs. ACE2-receptor RNA was present in all tissues examined, being highly expressed in lung samples than olfactory bulbs. Conclusions: Our finding suggests that COVID-19 anosmia is not only due to neurotropism and the direct action of SARS-CoV-2 entering the olfactory bulb. The mechanism of SARS-CoV-2 neuropathogenesis in the olfactory bulb requires a better elucidation and further research studies to mitigate the olfactory bulb damage associated with virus action

Influence of Hermetia illucens meal dietary inclusion on the histological traits, gut mucin composition and the oxidative stress biomarkers in rainbow trout (Oncorhynchus mykiss)

Insect protein meals are considered as a promising alternative feedstuff in aquafeeds, but until now the effects induced by its dietary inclusion on histological features, gut mucin composition and oxidative stress in fish are still not assessed. In the present study, we describe these effects after inclusion of a partially defatted Hermetia illucens (HI) larvae meal in Oncorhynchus mykiss diets. Three isoproteic, isolipidic and isoenergetics diets were formulated containing HI larvae meal in partial substitution of fish meal: 0% (HI0, control diet), 25% (HI25) and 50% (HI50), corresponding to dietary inclusion levels of 0, 20% and 40% of HI. Fish were fed for 78\u202fdays with the experimental diets and at the end of the growing trial, histological and histochemical evaluations were performed on spleen, liver and gut samples of control and treatment groups. Oxidative stress biomarkers, such as superoxide dismutase, catalase, glutathione peroxidases, ethoxyresorufin O-deethylase, glutathione S-transferase, glutathione reductase, total glutathione and malondialdehyde were investigated in liver and kidney of experimental groups. Histopathological examination of liver, spleen and gut revealed no adverse effects following increasing levels of insect meal inclusions. Hermetia illucens consumption stimulated higher production of neutral than acidic mucins. Altered values of several antioxidant biomarkers indicated an unbalance of oxidative homeostasis in liver and mainly in kidney, linked to the feeding conditions. While lowering of glutathione peroxidase activity may reflect slight adverse effect of HI meals in both tissues, strengthening in levels of ethoxyresorufin O-deethylase, glutathione S-transferase and total glutathione may indicate the shielding of HI meals-mediated oxidative process. Although the administration of both inclusion levels of insect meal did not negatively affect the histological features in fish, the changes of oxidative stress biomarkers advise for an HI dietary inclusion lower than 20%

Design and Characterization of a Peptide Mimotope of the HIV-1 gp120 Bridging Sheet

The Bridging Sheet domain of HIV-1 gp120 is highly conserved among the HIV-1 strains and allows HIV-1 binding to host cells via the HIV-1 coreceptors. Further, the bridging sheet domain is a major target to neutralize HIV-1 infection. We rationally designed four linear peptide epitopes that mimic the three-dimensional structure of bridging sheet by using molecular modeling. Chemically synthesized peptides BS3 and BS4 showed a fair degree of antigenicity when tested in ELISA with IgG purified from HIV+ broadly neutralizing sera while the production of synthetic peptides BS1 and BS2 failed due to their high degree of hydrophobicity. To overcome this limitation, we linked all four BS peptides to the COOH-terminus of GST protein to test both their antigenicity and immunogenicity. Only the BS1 peptide showed good antigenicity; however, no envelope specific antibodies were elicited upon mice immunization. Therefore we performed further analyses by linking BS1 peptide to the NH2-terminus of the E2 scaffold from the Geobacillus Stearothermophylus PDH complex. The E2-BS1 fusion peptide showed good antigenic results, however only one immunized rabbit elicited good antibody titers towards both the monomeric and oligomeric viral envelope glycoprotein (Env). In addition, moderate neutralizing antibodies response was elicited against two HIV-1 clade B and one clade C primary isolates. These preliminary data validate the peptide mimotope approach as a promising tool to obtain an effective HIV-1 vaccine