Survival Impact of Combined Biguanide and Temozolomide in Glioblastoma Preclinical Models: A Systematic Review and Meta-Analysis.

BACKGROUND: Glioblastoma (GBM) is an aggressive tumor known for its poor prognosis. Despite extensive research into its molecular and clinical aspects, the current management strategies have shown limited efficacy in improving survival rate. Despite some preclinical studies exploring the combination of temozolomide (TMZ) with biguanides such as metformin (MET) and others, the potential benefits of this combination remain uncertain. The aim of this study is to evaluate the overall survival (OS) in GBM murine-models treated with a combination of TMZ + biguanide compared to those treated with TMZ alone. METHODS: We systematically searched Medline, Embase, and Lilacs databases for studies comparing TMZ + biguanide versus TMZ alone in GBM models and reporting OS data. The mean difference (MD) with 95% confidence interval and random-effects model was adopted. RESULTS: Nine studies were included in this systematic review. The meta-analysis comprised 6 studies involving 85 rat-models, with 45 subjects undergoing combined-treatment. GBM-murine models treated with TMZ + biguanide exhibited notably superior OS rates compared to those who received TMZ alone, showing an MD of 21.0 days (6.9-35.0). Within the subgroup of orthotopic models, the OS was also significantly better in combination-therapy with an MD of 23.7 days (6.5-40.9). Similarly, in the subgroup where MET was used as biguanide therapy, TMZ + MET demonstrated a significant increase in OS, with an MD of 27.4 days (6.0-48.8). In immunocompromised models, the combination-therapy also exhibited higher survival rates, with an MD of 13 days (9.4-16.6). CONCLUSIONS: This systematic review and meta-analysis provide compelling evidence regarding the beneficial effects of TMZ + biguanide in GBM models compared with TMZ alone, resulting in a significant improvement in OS.

Unraveling Muscle Impairment Associated With COVID-19 and the Role of 3D Culture in Its Investigation.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been considered a public health emergency, extensively investigated by researchers. Accordingly, the respiratory tract has been the main research focus, with some other studies outlining the effects on the neurological, cardiovascular, and renal systems. However, concerning SARS-CoV-2 outcomes on skeletal muscle, scientific evidence is still not sufficiently strong to trace, treat and prevent possible muscle impairment due to the COVID-19. Simultaneously, there has been a considerable amount of studies reporting skeletal muscle damage in the context of COVID-19. Among the detrimental musculoskeletal conditions associated with the viral infection, the most commonly described are sarcopenia, cachexia, myalgia, myositis, rhabdomyolysis, atrophy, peripheral neuropathy, and Guillain-Barré Syndrome. Of note, the risk of developing sarcopenia during or after COVID-19 is relatively high, which poses special importance to the condition amid the SARS-CoV-2 infection. The yet uncovered mechanisms by which musculoskeletal injury takes place in COVID-19 and the lack of published methods tailored to study the correlation between COVID-19 and skeletal muscle hinder the ability of healthcare professionals to provide SARS-CoV-2 infected patients with an adequate treatment plan. The present review aims to minimize this burden by both thoroughly exploring the interaction between COVID-19 and the musculoskeletal system and examining the cutting-edge 3D cell culture techniques capable of revolutionizing the study of muscle dynamics.

Prevalence and Predictors of Fatigue and Neuropsychiatric Symptoms in Patients with Minor Ischemic Stroke.

OBJECTIVES: Patients who are victims of a mild stroke are vulnerable to several invisible and neglected neurological sequelae. In parallel, it is known that fatigue and neuropsychiatric symptoms are common complications after a stroke in general. Our aim was to describe the prevalence and the factors associated with these two outcomes after a minor stroke. MATERIALS AND METHODS: We conducted a prospective observational cohort study that included consecutive patients diagnosed with minor ischemic stroke between 2015 and 2019. Minor stroke was defined as NIHSS < 4 and modified Rankin Scale (mRS) < 2. Patients were followed for 12 months after the index stroke. The primary endpoints included fatigue and neuropsychiatric impairment, which were evaluated with the Fatigue Severity Scale (FSS) and the Hospital Anxiety Depression Scale (HADS), respectively. RESULTS: A total of sixty patients were followed in our cohort. The mean age was 53.0 (SD 15.0) and 51.7% were male. There were 32 (53.3%) and 25 (41.7%) patients who developed PSF and post-stroke neuropsychiatric symptoms, respectively. The use of antidepressants and statins were associated with post-stroke fatigue, while women and younger patients were more likely to develop neuropsychiatric symptoms after the stroke (p < 0.05). Eighteen (30.0%) patients were diagnosed with both post-stroke fatigue and psychiatric disorders. CONCLUSIONS: Post-stroke fatigue and neuropsychiatric symptoms are prevalent in minor stroke and should be independently addressed as a part of the recovery goal.

Social, professional and neuropsychiatric outcomes in patients with myasthenia gravis.

BACKGROUND: Recent medical advances have enabled the control of neurological symptoms and increased survival of patients with myasthenia gravis (MG). However, MG has many veiled consequences that may be underestimated by neurologists. Our aim was to clarify the social, professional, and neuropsychiatric issues of MG patients. METHODS: We carried out a cross-sectional cohort study with MG patients from a university-affiliated referral hospital. We registered clinical and sociodemographic data, and patients were classified according the MGFA classification. Clinical severity was assessed with Myasthenia Gravis Composite (MGC) scale. Trained and blind investigators analyzed social and professional outcomes. Neuropsychiatric symptoms were evaluated with the Hospital Anxiety and Depression Scale (HADS) and the social support with the Multidimensional Scale of Perceived Social Support (MSPSS). RESULTS: We enrolled 49 patients with MG. The mean age was 45.3 ± 18.1 years and 39 (79.6%) were women. There were 19 (38.8%) patients who become unemployed, 23 (46.9%) who had to retire prematurely, 31 (63.3%) that reported a significant reduction in work performance, and 23 (46.9%) who had a reduction in monthly income after the diagnosis of MG. Only 16 (32.6%) received any financial support and 24 (48.9%) patients had the perception of receiving a satisfactory social support. The practice of physical activity is a habit in only 10 patients (20.4%). Neuropsychiatric symptoms were present in 26 (53.1%) patients. CONCLUSION: Patients with MG are vulnerable to social, professional, and mental disadvantages. Therapeutic success in MG goes beyond symptom relief and inevitably depends on a personalized approach to the patient.