Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential role in the disease pathogenesis, and are an essential target for therapy. Three generations of mTOR inhibitors have been developed and are clinically used for immunosuppression and chemotherapy for multiple cancers. Only a few mTOR inhibitors have been investigated for the treatment of medulloblastoma and other pediatric tumors. The first-generation mTOR, sirolimus, temsirolimus, and everolimus, went through phase I clinical trials. The second-generation mTOR, AZD8055 and sapanisertib, suppressed medulloblastoma cell growth; however, limited studies have investigated possible resistance pathways. No clinical trials have been found to treat medulloblastoma using third-generation mTOR inhibitors. This systematic review highlights the mechanisms of resistance of mTOR inhibitors in medulloblastoma and includes IDO1, T cells, Mnk2, and eIF4E, as they prolong malignant cell survival. The findings promote the importance of combination therapy in medulloblastoma due to its highly resistant nature.
Background Multiple sclerosis (MS) is associated with a physical disability and disturbed psychosocial functioning in young people. Many psychological and psychiatric comorbidities have been reported in MS. Objective To determine the frequency of social anxiety disorder (SAD) and obsessive-compulsive disorder (OCD) among MS patients and their relation to MS severity. Methods A cross-sectional survey was conducted in an adult MS cohort. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Social Phobia Inventory (SPIN) were used to determine the presence and severity of OCD and SAD. The Statistical Package for the Social Sciences (SPSS) version 22 (IBM Corp., Armonk, NY) was used for statistical analysis. The Mann-Whitney U test and logistic regression were used to assess the association of the two diseases with the severity of MS. Results A total of 145 persons with MS (pwMS) were studied. The mean age was 33.5 (±8.5) years; the mean duration of MS was 7.2 (± 5.1) years. The majority (74.1%) were women; 57.3% were married; 63% had a college education; 50% belonged to the higher middle-class socioeconomic strata. Relapsing-remitting multiple sclerosis was the most common type of MS (92.2%). The mean Expanded Disability Status Scale (EDSS) score was 2.24 (±2.19). SAD was reported by 26.9%, and OCD was reported by 31% of the cohort. PwMS with walking difficulty but not wheelchair-bound had a statistically significant increased risk of SAD (p = 0.036). There was no direct association between MS-related disability and OCD. However, pwMS with SAD were more likely to have concomitant OCD (t=4.68, p-value <0.001, 95% CI: 0.47-1.16). Increasing disability was associated with higher chances of developing social anxiety and, in turn, OCD (t=3.39, p-value <0.001, 95% CI: 0.66-2.52). Conclusions Social anxiety and obsessive-compulsive disorders were present in nearly one-third of pwMS. Impaired walking but not wheelchair dependence was associated with social anxiety. PwMS with SAD were more likely to have obsessive-compulsive disorder.
Background and Objective: Cisplatin is a chemotherapy drug used to treat several types of malignancies. It is a platinum-based compound that interferes with cell division and DNA replication. Cisplatin has been associated with renal damage. This study evaluates the early detection of nephrotoxicity through routine laboratory tests. Materials and Methods: This is a retrospective chart review based on the Saudi Ministry of National Guard Hospital (MNGHA). We evaluated deferential laboratory tests for cancer patients treated with cisplatin between April 2015 and July 2019. The evaluation included age, sex, WBC, platelets, electrolytes, co-morbidities and interaction with radiology. Results: The review qualified 254 patients for evaluation. Around 29 patients (11.5%) had developed kidney function abnormality. These patients presented with abnormally low magnesium 9 (31%), potassium 6 (20.7%), sodium 19 (65.5%) and calcium 20 (69%). Interestingly, the whole sample size had abnormal electrolytes presenting magnesium 78 (30.8%), potassium 30 (11.9%), sodium 147 (58.1%) and calcium 106 (41.9%). Some pathological features were detected, such as hypomagnesemia, hypocalcemia and hypokalemia. In addition, infections that needed antibiotics were dominant in patients treated with cisplatin alone, representing 50% of this group. Conclusions: We report that an average of 15% of patients with electrolyte abnormalities develop renal toxicity and reduced function. Moreover, electrolytes may serve as an early indicator for renal damage as part of chemotherapy complication. This indication represents 15% of renal toxicity cases. Changes in electrolyte levels have been reported with cisplatin. Specifically, it has been linked to hypomagnesemia, hypocalcemia and hypokalemia. This study will help reduce the risk of dialysis or the need for kidney transplant. It is also important to manage any underlying conditions and control patients’ intake of electrolytes.
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