Valganciclovir as Add-on to Second-Line Therapy in Patients with Recurrent Glioblastoma

Simple Summary Patients with glioblastoma have a dismal prognosis. The major challenge with this disease is that it recurs despite aggressive first-line therapy and rapidly becomes therapy resistant. Cytomegalovirus has been found in most glioblastoma tumors and may contribute to tumor aggressiveness. Antiviral therapy may thus represent a novel therapeutic strategy and has shown promising results in patients with newly diagnosed glioblastoma. We performed a retrospective analysis of survival data of 29 patients with recurrent glioblastoma receiving the antiviral drug valganciclovir as an add-on to second-line therapy and of 109 contemporary controls treated at our institution. Valganciclovir was well tolerated and seemed to improve survival after tumor recurrence in patients with recurrent disease both in re-operated and non-re-operated patients and in patients with unmethylated and methylated MGMT promoter status. Prospective controlled clinical studies on patients with recurrent glioblastoma are warranted to evaluate if valganciclovir treatment offers a novel therapeutic option. Glioblastoma invariably recurs despite aggressive and multimodal first-line treatment and no standardized second-line therapy exists. We previously reported that treatment with the antiviral drug valganciclovir as an add-on to standard therapy significantly prolonged overall survival in 102 patients with newly diagnosed glioblastoma compared to contemporary controls. Here we present the results of retrospective survival analyses including patients with glioblastoma that initiated valganciclovir therapy after recurrence. Twenty-nine patients with recurrent glioblastoma received valganciclovir as an add-on to second-line therapy at Karolinska University Hospital. Contemporary controls were 109 patients with glioblastoma who received similar second-line therapy at our institution. We retrospectively analyzed survival data of these patients. Patients with recurrent glioblastoma who received valganciclovir had longer median overall survival after recurrence than controls (12.1 vs. 7.4 months, respectively, p = 0.0028). The drug was well tolerated. Both patients who underwent re-operation and patients that were not re-operated after recurrence benefitted significantly from valganciclovir therapy. Valganciclovir prolonged survival after recurrence both in patients with an unmethylated and methylated MGMT promoter gene. Valganciclovir was safe to use and prolonged median survival after recurrence for patients with recurrent glioblastoma, re-operated or not after recurrence, and with methylated or unmethylated MGMT promoter gene.</p

Carotid Body and Vagal Paragangliomas: Epidemiology, Genetics, Clinicopathological Features, Imaging, and Surgical Management

ABSTRACT Carotid body and vagal paragangliomas, although considered indolent tumors, represent a challenge for the treating physician. This is mainly because of their peculiar localization, in close proximity with important anatomical structures. In addition, there is no chemotherapy available for these tumors, the role of radiation therapy is debated, and the only successful therapy is surgery. However, to achieve the best treatment goals, it is fundamental for the professional caregiver to master not only the clinical and surgical procedures but also the genetic backgrounds and the histopathological features of these tumors. We provide in this chapter a comprehensive review of the above mentioned aspects, with the aim to address the complexity of these tumors with a multidisciplinary approach

Reendothelization of porcine heart valve scaffolds with WJ-MSC: a new approach in the heart valve tissue engineering.

Heart valve substitution, based on biosynthetic or mechanical prosthesis replacement, is one of the most frequent surgical approach to treat heart valve diseases. Even if the prosthesis implantation gives a good life quality for patients, there are many long-term disadvantages related to the substitution, such as structural deterioration, non-structural dysfunction and re-intervention. The heart valve tissue engineering (HVTE), a novel branch of regenerative medicine, is developing innovative models and testing new methods to overcome the above reported limitations. In the present study, we investigated the possibility to reendothelize a porcine heart valve scaffold, previously decellularized, by using two cell types: Wharton’s Jelly mesenchymal stem cells (WJ-MSC) and human umbilical vein endothelial cells (HUVEC), the last used as control cells for the reendothelialization process. Both cell types showed, by fluorescence microscopy, that they were able to reconstitute a valid and functional monolayer of neo-endothelium, characterized by the surface expression of typical endothelial markers (i.e. CD144 and CD146). All together, these data suggest that both HUVEC and WJ-MSC are suitable for in vitro autologous endothelium regeneration, opening new perspectives in the field of HVTE

Valganciclovir as Add-on to Second-Line Therapy in Patients with Recurrent Glioblastoma

Glioblastoma invariably recurs despite aggressive and multimodal first-line treatment and no standardized second-line therapy exists. We previously reported that treatment with the antiviral drug valganciclovir as an add-on to standard therapy significantly prolonged overall survival in 102 patients with newly diagnosed glioblastoma compared to contemporary controls. Here we present the results of retrospective survival analyses including patients with glioblastoma that initiated valganciclovir therapy after recurrence. Twenty-nine patients with recurrent glioblastoma received valganciclovir as an add-on to second-line therapy at Karolinska University Hospital. Contemporary controls were 109 patients with glioblastoma who received similar second-line therapy at our institution. We retrospectively analyzed survival data of these patients. Patients with recurrent glioblastoma who received valganciclovir had longer median overall survival after recurrence than controls (12.1 vs. 7.4 months, respectively, p = 0.0028). The drug was well tolerated. Both patients who underwent re-operation and patients that were not re-operated after recurrence benefitted significantly from valganciclovir therapy. Valganciclovir prolonged survival after recurrence both in patients with an unmethylated and methylated MGMT promoter gene. Valganciclovir was safe to use and prolonged median survival after recurrence for patients with recurrent glioblastoma, re-operated or not after recurrence, and with methylated or unmethylated MGMT promoter gene

Fatal Acute Hemorrhagic Encephalomyelitis and Antiphospholipid Antibodies following SARS-CoV-2 Vaccination: A Case Report

Acute hemorrhagic encephalomyelitis (AHEM) is a rare hyperacute form of acute disseminated encephalomyelitis (ADEM). The disease is characterized by fulminant inflammation and demyelination in the brain and spinal cord and is often preceded by an infection or vaccination. This case report presents a 53-year-old male with rheumatoid arthritis and ongoing treatment with methotrexate and etanercept who developed fatal AHEM following the second dose of the COVID-19 vaccine. The disease course was complicated by multiorgan thromboembolic disease and the presence of high/moderate levels of cardiolipin IgG antibodies and anti-beta-2 glycoprotein 1 IgG antibodies suggesting a possible antiphospholipid syndrome. Treatment with immunosuppressive therapies failed to improve the course. The report comprises comprehensive clinical, neuroimaging, and neuropathological findings. The case highlights diagnostic challenges in a patient with several preceding risk factors, including autoimmune disease, immunotherapy, and vaccination, with possible pathophysiological implications. The temporal association with the COVID-19 vaccination may suggest possible causality although evidence cannot be ascertained. Reporting possible adverse events following COVID-19 vaccination is important to identify at-risk populations and to accomplish control of the current pandemic

Fatal Acute Hemorrhagic Encephalomyelitis and Antiphospholipid Antibodies following SARS-CoV-2 Vaccination: A Case Report

Acute hemorrhagic encephalomyelitis (AHEM) is a rare hyperacute form of acute disseminated encephalomyelitis (ADEM). The disease is characterized by fulminant inflammation and demyelination in the brain and spinal cord and is often preceded by an infection or vaccination. This case report presents a 53-year-old male with rheumatoid arthritis and ongoing treatment with methotrexate and etanercept who developed fatal AHEM following the second dose of the COVID-19 vaccine. The disease course was complicated by multiorgan thromboembolic disease and the presence of high/moderate levels of cardiolipin IgG antibodies and anti-beta-2 glycoprotein 1 IgG antibodies suggesting a possible antiphospholipid syndrome. Treatment with immunosuppressive therapies failed to improve the course. The report comprises comprehensive clinical, neuroimaging, and neuropathological findings. The case highlights diagnostic challenges in a patient with several preceding risk factors, including autoimmune disease, immunotherapy, and vaccination, with possible pathophysiological implications. The temporal association with the COVID-19 vaccination may suggest possible causality although evidence cannot be ascertained. Reporting possible adverse events following COVID-19 vaccination is important to identify at-risk populations and to accomplish control of the current pandemic

Detection of human cytomegalovirus proteins in paraffin‐embedded breast cancer tissue specimens—a novel, automated immunohistochemical staining protocol

Emerging evidence supports a significant association between human cytomegalovirus (HCMV) and human malignancies, suggesting HCMV as a human oncomodulatory virus. HCMV gene products are found in &gt;90% of breast cancer tumors and seem to be correlated with more aggressive disease. The definitive diagnosis of HCMV relies on identification of virus inclusions and/or viral proteins by different techniques including immunohistochemical staining. In order to reduce biases and improve clinical value of HCMV diagnostics in oncological pathology, automation of the procedure is needed and this was the purpose of this study. Tumor specimens from 115 patients treated for primary breast cancer at Akershus University Hospital in Norway were available for the validation of the staining method in this retrospective study. We demonstrate that our method is highly sensitive and delivers excellent reproducibility for staining of HCMV late antigen (LA), which makes this method useful for future routine diagnostics and scientific applications

Human Cytomegalovirus Infection Induces High Expression of Prolactin and Prolactin Receptors in Ovarian Cancer

One of the potential biomarkers for ovarian cancer patients is high serum level of prolactin (PRL), which is a growth factor that may promote tumor cell growth. The prolactin receptor (PRLR) and human cytomegalovirus (HCMV) proteins are frequently detected in ovarian tumor tissue specimens, but the potential impact of HCMV infection on the PRL system have so far not been investigated. In this study, HCMV&rsquo;s effects on PRL and PRLR expression were assessed in infected ovarian cancer cells (SKOV3) by PCR and Western blot techniques. The levels of both PRL and PRLR transcripts as well as the corresponding proteins were highly increased in HCMV-infected SKOV3 cells. Tissue specimens obtained from 10 patients with ovarian cancer demonstrated high expression of PRLR, HCMV-IE, and pp65 proteins. Extensive expression of PRLR was detected in all examined ovarian tumor tissue specimens except for one from a patient who had focal expression of PRLR and this patient was HCMV-negative in her tumor. In conclusion, PRL and PRLR were induced to high levels in HCMV-infected ovarian cancer cells and PRLR expression was extensively detected in HCMV-infected ovarian tissue specimens. Highly induced PRL and PRLR by HCMV infection may be of relevance for the oncomodulatory role of this virus in ovarian cancer