New-onset or flare-up of bullous pemphigoid associated with COVID-19 vaccines: a systematic review of case report and case series studies.

Background: Numerous cutaneous manifestations have been associated with the Coronavirus Disease 2019 (COVID-19) outbreak and vaccination, but new-onset bullous pemphigoid (BP) or flaring up of pre-existing BP is a rare side effect of COVID-19 vaccines that has been mentioned to a lesser extent in the literature. Therefore, we aimed to conduct a systematic review focused on the association between the new- onset or flare-up of BP and the COVID-19 vaccination. Method: A comprehensive literature search was conducted using PubMed (MEDLINE), Scopus, and the Web of Science databases up to 11 March 2023. The search aimed to identify English-language studies reporting new-onset or flare-ups of BP as a potential side effect of the COVID-19 vaccination. The search terms included bullous pemphigoid and COVID-19 vaccination-related MeSH terms. Results: The systematic review of 40 articles investigating the incidence of BP in individuals who received various COVID-19 vaccines revealed pertinent findings. Among the 54 patients with new-onset BP, the median age was 72.42 years, and most were men (64%). Conversely, the median age of the 17 patients experiencing a flare-up of BP was 73.35 years, with a higher proportion of women (53%). Regarding vaccination types, a significant number of patients (56%) developed new-onset BP after receiving the BNT162b2 vaccine (Pfizer-BioNTech). Conclusion: This study indicates a potential association between COVID-19 vaccinations, particularly mRNA vaccines, and the occurrence of BP. It suggests that this rare autoimmune disorder may be triggered as an adverse event following the COVID-19 vaccination. However, it is important to note that the majority of BP patients in our study were unaffected by the COVID-19 vaccine, and even those who experienced worsening of their conditions were managed without significant consequences. These findings provide additional evidence supporting the safety of COVID-19 vaccines. Physicians should be mindful of this uncommon adverse event and encourage patients to complete their planned vaccination schedules.

The Potential Therapeutic Impact of Metformin in Glioblastoma Multiforme.

In terms of frequency and aggressiveness, glioblastoma multiforme (GBM) is undoubtedly the most frequent and fatal primary brain tumor. Despite advances in clinical management, the response to current treatments is dismal, with a 2-year survival rate varying between 6 and 12 percent. Metformin, a derivative of biguanide widely used in treating type 2 diabetes, has been shown to extend the lifespan of patients with various malignancies. There is limited evidence available on the long-term survival of GBM patients who have taken metformin. This research examined the literature to assess the connection between metformin's anticancer properties and GBM development. Clinical findings, together with the preclinical data from animal models and cell lines, are included in the present review. This comprehensive review covers not only the association of hyperactivation of the AMPK pathway with the anticancer activity of metformin but also other mechanisms underpinning its role in apoptosis, cell proliferation, metastasis, as well as its chemo-radio-sensitizing behavior against GBM. Current challenges and future directions for developments and applications of metformin-based therapeutics are also discussed.

JAK inhibitors in lichen planus: a review of pathogenesis and treatments.

Lichen planus (LP) is an auto-inflammatory skin disorder identified by a presence of T-cell lymphocytes at the dermal-epidermal junction. It is hypothesized that the INF-γ/CXCL10 axis fulfills a major role in the onset and persistence of chronic inflammation in LP. Since Janus kinases (JAKs) are involved in the transduction of INF-γ signals, they may be good targets for LP treatment. Several case reports and case series described the safety and efficacy of upadacitinib (2 articles), tofacitinib (6 articles), baricitinib (4 articles), and Ruxolitinib (1 Article) in the treatment of LP variants. The predominant variants that JAK inhibitors improved were lichen planopilaris, nail LP, and erosive LP. Considering the role of the JAK pathway in LP pathogenesis and the evidence provided by these reports, it seems JAK inhibitors would be effective therapeutic agents for LP treatment. Hence, these agents should be trialed and evaluated further.

Using Ozone Therapy as an Option for Treatment of COVID-19 Patients: A Scoping Review.

Recent investigations are seeking a novel treatment to control the new pandemic of coronavirus 19 (COVID-19). The aim of this systematic review was to study the effect of ozone therapy on COVID-19 patients and the available supporting evidence. Electronic databases including MEDLINE (via PubMed), EMBASE, Cochrane Library (CENTRAL), and TRIP, clinical trial registries, and preprint sources were searched for published evidence-based articles. In addition, manual searching was conducted for articles published up to April 6, 2020, using MeSH and free text keywords with no language limitation. Articles were screened, categorized, and extracted for relative data. Data were reported in a descriptive manner. Among 234 articles, 9 were selected for review of the inclusion criteria. No published original articles were found regarding the efficacy of ozone therapy on COVID-19. Five review studies were found in which the potential role of systemic ozone therapy was concluded to be effective in controlling COVID-19 because of its antiviral, oxygenation, anti-inflammatory, oxidation balancing, and immunomodulation effects. Three ongoing clinical trials were registered in China. A preliminary report of an ongoing study in Italy on 46 patients (11 intubated and 35 non-intubated) showed that in 39 (84%) of the patients, an improvement was seen. In spite of the promising background data, as well as the expert opinions and a preliminary report indicating the effectiveness of ozone, there is still not enough evidence to confirm this as a viable treatment option for COVID-19.

Effects of hypothermia and pentoxifylline on the adnexal torsion/detorsion injuries in a rat testis model.

This study was designed to investigate the effects of separate and combined administration of hypothermia and pentoxifylline to preserve the effects on the testicles in an experimental model of testicular torsion/ detorsion injuries in rats. Forty male adult Wistar rats were randomly divided into five groups, control, torsion/detorsion (TD), torsion/detorsion/hypothermia (TD+ICE), torsion/detorsion received of pentoxifylline (40mg/kg, ip) (TD+PTX) and torsion/detorsion/hypothermia/PTX (TD+ICE+PTX). Left testicular torsion (TT) was performed for 4 and half hours, and ice fragments have been used at the beginning of torsion. After the reperfusion period (a week), oxidative maker's serum levels, testosterone hormone, sperm parameters, and histopathological and gene expression evaluations have been performed. Significant adverse changes were observed in the TD group for histological variables, sperm count, oxidative marker, testosterone hormone, Bax, BCL2 and caspase-3 expression. The parameters studied in the group receiving PTX improved in comparison with the TD group, while macroscopical parameters of both the hypothermia and PTX+ICE groups were not different compared with the TD group. The results revealed that PTX, as an antioxidant component, was protective against testicular torsion, while hypothermia and hypothermia plus PTX did not exhibit this property, which may have been due to the duration of hypothermia (4 hr) or reperfusion period.

Neurokinin-1 Receptor (NK-1R) Antagonists: Potential Targets in the Treatment of Glioblastoma Multiforme.

The current standard of care in glioblastoma multiforme (GBM), as the most morbid brain tumor, is not adequate, despite substantial progress in cancer therapy. Among patients receiving current standard treatments, including surgery, irradiation, and chemotherapy, the overall survival (OS) period with GBM is less than one year. The high mortality frequency of GBM is due to its aggressive nature, including accelerated growth, deregulated apoptosis, and invasion into surrounding tissues. The understanding of the molecular pathogenesis of GBM is, therefore, crucial for identifying, designing, and repurposing potential agents in future therapeutic approaches. In recent decades, it has been apparent that several neurotransmitters, specifically substance P (SP), an undecapeptide in the family of neuropeptides tachykinins, are found in astrocytes. After binding to the neurokinin-1 receptor (NK-1R), the SP controls cancer cell growth, exerts antiapoptotic impacts, stimulates cell invasion/metastasis, and activates vascularization. Since SP/NK-1R signaling pathway is a growth driver in many cancers, this potential mechanism is proposed as an additional target for treating GBM. Following an evaluation of the function of both SP and its NK-1R inhibitors in neoplastic cells, we recommend a unique and promising approach for the treatment of patients with GBM.