Background
To date, there are no data available on the safety of COVID-19 vaccines in Latin American patients with Multiple Sclerosis (MS).
Objective
Characterize safety of COVID-19 vaccines in Latin ...American (LATAM) patients with Multiple Sclerosis (pwMS).
Methods
A cross-sectional study between February 1, 2021, and April 30, 2021. Individuals with MS from LATAM countries were invited to participate in a self-administered web-based survey, through MS patient organizations from the region.
Results
393 vaccinated pwMS from 10 different Latin American countries were included. The vaccines administered were: inactivated virus vaccines (IVV) in 38.2% of patients, adenovirus vector vaccines (AdV) in 48.8% and mRNA vaccines 13%. All patients received at least one dose of any of the COVID-19 vaccines and 123 (31.3%) declared receiving a second dose. Mean (SD) age 41.5 (11.8) years, 82.4% female, MS disease duration: 8.4 (8.2) years. No serious adverse events were reported with any of the COVID-19 vaccines after either the first or second dose. A lower frequency of adverse events was found with IVV (22%) in comparison with AdV (46.4%) and mRNA (35.3%) (p < 0.01). Five participants reported having an MS relapse after IVV first dose.
Conclusion
COVID-19 vaccines applied in LATAM proved safe for MS patients.
•Anxiety is prevalent in MS and has been associated with decreased quality of life.•Information from Latin America regarding psychiatric comorbidities in MS is scarce.•Our results show a high ...prevalence of anxiety in Argentinian MS outpatients.•Anxiety was strongly associated with depression and reduced quality of life .
There is scarce information in Latin America regarding the prevalence of anxiety in patients with multiple sclerosis (MS) and its association with different clinical-demographic factors.
We aimed to determine the prevalence of anxiety in Argentinian MS patients and to analyze associated factors.
A cross-sectional analysis was performed with consecutive MS outpatients from two centers in Buenos Aires, Argentina. Anxiety was evaluated according to the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A).
Eighty-three patients were included. Fifty-three (63%) were females, mean age: 46 (SD=13.9) years. Forty-five percent (n = 38) had anxiety according to the HADS-A. Patients with anxiety were significantly younger (42.2 vs 49.1 years, p = 0.02), had a shorter time since diagnosis (8.3 vs 12.3 years, p = 0.02), had a history of psychiatric disorders (36.8% vs 8.8%, p = 0.002), were depressed (57.8% vs 2.2%, p<0.001) and had worse health-related quality of life according to the COOP/Wonca questionnaire (mean score: 21.5 vs 15.2, p<0.001). Depression (OR: 15.2, 95% CI 1.4–157.3, p = 0.02) and worse health-related quality of life (OR: 1.2,95% CI 1–1.4, p = 0.008) remained significantly associated with anxiety after adjusting for all other significant variables. No differences were observed regarding sex, marital and occupational status, education, family history of psychiatric disorders, disease course and disability according to the EDSS.
The prevalence of anxiety in Argentinian MS outpatients was higher than previously reported in other populations. Anxiety was strongly associated with negative outcomes such as depression and reduced health-related quality of life. These results emphasize the burden of psychiatric morbidity in Argentinian MS patients.
•The COVID-19 pandemic resulted in uncertain access to medical treatments for people with MS.•We investigated changes in health care delivery to MS patients from Latin America.•We found that all ...aspects of the routine care of MS patients were disrupted, including laboratory and MRI monitoring, DMT use, and access to rehabilitation services.
The COVID-19 pandemic has resulted in uncertain access to medical treatment for people with multiple sclerosis (pwMS) all over the world. However, there is no data regarding its impact on access to health care of pwMS from Latin America.
We investigated and described changes in health care delivery for pwMS from Latin America during the COVID-19 pandemic.
PwMS from 18 patient organizations of the region completed a web-based survey hosted from May to October 2020.
A total of 602 pwMS completed the questionnaire. Changes in disease-modifying therapies (DMTs) use: 6.7% of pwMS on continuous DMTs claimed to stopped them; 14.1% of those on infusion therapies declared to postpone their dosing; 68.8% declared delaying the initiation of a DMT. Disruptions in accessing rehabilitation services were reported by 65.7%. Changes in laboratory and MRI monitoring were reported by 30% and 33%, respectively. In a multivariable-adjusted logistic regression model, changes in laboratory monitoring were significantly associated with increased odds of postponing MRI monitoring (OR 4.09 CI95% 2.79–6.00, p < 0.001).
The COVID-19 pandemic has disrupted all aspects of the routine care for pwMS from Latin America. Consequences are yet to be determined.
The vast majority of women with advanced ovarian cancer will ultimately relapse and develop a drug-resistant disease with
an overall 5-year survival of <50%. Unfortunately, the mechanisms of drug ...resistance actually operating in patients are still
unknown. To address this issue, in 41 patients affected by advanced ovarian cancer the three main mechanisms of paclitaxel
resistance were investigated: overexpression of MDR-1 gene, point mutations at prominently expressed α-tubulin and β-tubulin genes and selective alterations in the expression of β-tubulin isotypes. MDR-1 and the β-tubulin isotypes expression were
evaluated by semiquantitative and real-time PCR. On the same specimens, quantitative immunohistochemistry was also done in
the tumor area. No statistically significant changes of MDR-1 expression were noticed between the sensitive and resistant
patients either at the mRNA or protein level. The tubulin mutations for the ubiquitous α-tubulin and β-tubulin genes were evaluated by automated DNA sequencing, and in all patients, no mutations were detected in both resistant and sensitive
cases. With regard to the expression of tubulin isoforms, a statistically significant up-regulation of class III β-tubulin
was found in the resistant subset. It is worth noting that this statistically significant increase of the expression of class
III β-tubulin was detectable at the mRNA and protein level. By a direct comparison of the three main known mechanisms of paclitaxel
resistance, this study indicates that overexpression of class III β-tubulin is the most prominent mechanism of paclitaxel
resistance in ovarian cancer.
Abstract Objective Low-grade serous ovarian carcinomas (LGSOCs) are a histological subtype of epithelial ovarian tumors, accounting for fewer than 5% of all cases of ovarian carcinoma. Due to the ...chemoresistant nature of this subtype a search for more effective systemic therapies is actively ongoing, hormonal therapy showing some degree of activity in this clinical setting. The present study ought to investigate the hormone receptor status of LGSOCs, as a strategy to provide molecular support for patient-tailored hormonal treatments. Methods Estrogen receptor α (ERα), ERβ isoforms (i.e. ERβ1, ERβ2 and ERβ5), progesterone and androgen receptor (PR, AR) expression was evaluated by immunohistochemistry in 25 untreated LGSOC primary tumors, 6 matched metastases and 6 micropapillary variant of serous borderline tumors (micropapillary SBOTs). In vitro cellular models were used to provide insights into clinical observations. Results Our results showed prominent expression of nuclear ERα, ERβ2, ERβ5 and PR in LGSOC primary tissues, while metastatic lesions also exhibit considerable cytoplasmic ERβ2 levels. Notably, a higher expression of ERβ1 protein was determined in micropapillary SBOTs compared to LGSOCs. In vitro experiments on LGSOC cell lines (i.e. HOC-7 and VOA-1056) revealed low/absent ERα, PR and AR protein expression, whereas the three ERβ isoforms were all present. Proliferation of HOC-7 and VOA-1056 was not modulated by either the endogenous or the selective synthetic ligands. Conclusions These novel findings highlight the need of assessing relative levels of ERα and ERβ isoforms in the total receptor pool in future clinical studies investigating molecular predictors of response to hormonal therapy in LGSOC.
Dissemination of high-grade serous ovarian cancer (HG-SOC) in the omentum and intercalation into a mesothelial cell (MC) monolayer depends on functional α5β1 integrin (Intα5β1) activity. Although the ...binding of Intα5β1 to fibronectin drives these processes, other molecular mechanisms linked to integrin inside-out signaling might support metastatic dissemination. Here, we report a novel interactive signaling that contributes to Intα5β1 activation and accelerates tumor cells toward invasive disease, involving the protein β-arrestin1 (β-arr1) and the activation of the endothelin A receptor (ET
R) by endothelin-1 (ET-1). As demonstrated in primary HG-SOC cells and SOC cell lines, ET-1 increased Intβ1 and downstream FAK/paxillin activation. Mechanistically, β-arr1 directly interacts with talin1 and Intβ1, promoting talin1 phosphorylation and its recruitment to Intβ1, thus fueling integrin inside-out activation. In 3D spheroids and organotypic models mimicking the omentum, ET
R/β-arr1-driven Intα5β1 signaling promotes the survival of cell clusters, with mesothelium-intercalation capacity and invasive behavior. The treatment with the antagonist of ET
R, Ambrisentan (AMB), and of Intα5β1, ATN161, inhibits ET-1-driven Intα5β1 activity in vitro, and tumor cell adhesion and spreading to intraperitoneal organs and Intβ1 activity in vivo. As a prognostic factor, high EDNRA/ITGB1 expression correlates with poor HG-SOC clinical outcomes. These findings highlight a new role of ET
R/β-arr1 operating an inside-out integrin activation to modulate the metastatic process and suggest that in the new integrin-targeting programs might be considered that ET
R/β-arr1 regulates Intα5β1 functional pathway.
Adult granulosa cell tumor (AGCT) is a rare form of sex-cord stromal ovarian tumors. Due to their origin, AGCTs secrete estrogens, and thus, estrogen receptor (ER)-mediated signaling has been ...considered as a possible target for therapy. The aim of the present study was to get insights into estrogen receptor status and activity in AGCTs, as a strategy to provide molecular support for personalized hormonal treatments.
We evaluated by immunohistochemistry the expression of ERα, ERβ isoforms (i.e. ERβ1, ERβ2 and ERβ5), progesterone and androgen receptor (PR, AR) in 20 untreated AGCTs and 12 unmatched recurrent lesions. Thereafter, we visualized by immunofluorescence, the subcellular distribution of cytoplasmic receptors, and by the proximity ligation assays (PLA) we characterized in situ their ability to interact with other proteins involved in the apoptotic cascade.
Primary AGCTs predominantly expressed ERβ isoforms, along with PR and AR, while only 30% of patients showed ERα expression. Recurrent tumors were associated with a decrease in AR levels. From mechanistic studies it emerges that ERβ2, and to a lesser extent ERβ1 and AR, are mitochondrial components in cancer cells and that ERβ2 can act as a binding partner of proteins involved in the apoptotic cascade, in turn potentially inhibiting apoptosis.
As in other endocrine tumors, ERβ may play a role in the pathogenesis of AGCT; it is crucial to understand estrogen receptor-mediated pathways before planning hormonal treatment strategies in AGCT.
•We describe the hormone receptor profile of adult granulosa cell tumors (AGCTs).•We show that AGCTs express low ERα, and high ERβ1, ERβ2, ERβ5, PR and AR levels.•We show that ERβ2 is a mitochondrial component in granulosa cancer cells driving anti-apoptotic pathways.•It is critical to understand hormone receptor-mediated pathways before planning hormonal treatment strategies in AGCT.
A better understanding of locally advanced cervical cancer (LACC) is mandatory for further improving the rates of disease control, since a significant proportion of patients still fail to respond or ...undergo relapse after concurrent chemoradiation treatment (CRT), and survival for these patients has generally remained poor.
To identify specific markers of CRT response, we compared pretreatment biopsies from LACC patients with pathological complete response (sensitive) with those from patients showing macroscopic residual tumor (resistant) after neoadjuvant CRT, using a proteomic approach integrated with gene expression profiling. The study of the underpinning mechanisms of chemoradiation response was carried out through in vitro models of cervical cancer.
We identified annexin A2 (ANXA2), N-myc downstream regulated gene 1 (NDRG1) and signal transducer and activator of transcription 1 (STAT1) as biomarkers of LACC patients' responsiveness to CRT. The dataset collected through qPCR on these genes was used as training dataset to implement a Random Forest algorithm able to predict the response of new patients to this treatment. Mechanistic investigations demonstrated the key role of the identified genes in the balance between death and survival of tumor cells.
Our results define a predictive gene signature that can help in cervical cancer patient stratification, thus providing a useful tool towards more personalized treatment modalities.
PDF
