Ketogenic Diet in the Treatment of Gliomas and Glioblastomas

In recent years, scientific interest in the use of the ketogenic diet (KD) as a complementary approach to the standard cancer therapy has grown, in particular against those of the central nervous system (CNS). In metabolic terms, there are the following differences between healthy and neoplastic cells: neoplastic cells divert their metabolism to anaerobic glycolysis (Warburg effect), they alter the normal mitochondrial functioning, and they use mainly certain amino acids for their own metabolic needs, to gain an advantage over healthy cells and to lead to a pro-oncogenetic effect. Several works in literature speculate which are the molecular targets of KD used against cancer. The following different mechanisms of action will be explored in this review: metabolic, inflammatory, oncogenic and oncosuppressive, ROS, and epigenetic modulation. Preclinical and clinical studies on the use of KD in CNS tumors have also increased in recent years. An interesting hypothesis emerged from the studies about the possible use of a ketogenic diet as a combination therapy along with chemotherapy (CT) and radiotherapy (RT) for the treatment of cancer. Currently, however, clinical data are still very limited but encouraging, so we need further studies to definitively validate or disprove the role of KD in fighting against cancer

Botulinum toxin type A for genitofemoral neuralgia: A case report

Genitofemoral neuralgia is an uncommon pain disorder that could be resistant to conventional treatment. A 78-year-old woman with refractory right genitofemoral neuralgia was treated with BoNT/A subcutaneous injections; the treatment was performed three times with significant pain improvement, although temporary, and without adverse events. BoNT/A may be a promising alternative intervention in the setting of genitofemoral neuralgia refractory to oral and/or topical treatment

NK Cell Levels Correlate with Disease Activity in Patients with Multiple Sclerosis on Ocrelizumab/Rituximab Therapy

Background: Recently, research on the pathogenesis of multiple sclerosis (MS) has focused on the role of B lymphocytes and the possibility of using specific drugs, such as Ocrelizumab and Rituximab, directed toward these cells to reduce inflammation and to slow disease progression. Objective: We aimed to evaluate the effect of Ocrelizumab/Rituximab on laboratory immune parameters and identify the predictors of treatment responses. Methods: A retrospective single-center study was conducted among patients who received infusion therapy with an anti-CD20 drug to treat MS. Results: A total of 64 patients met the inclusion criteria, with 277 total cycles of therapy studied. Compared with the baseline values, anti-CD20 infusions resulted in absolute-value and percentage decreases in B lymphocyte levels and increased the absolute and percentage levels of NK cells 3 and 5 months after therapy (p < 0.001). After multivariate logistic regression analysis, a reduced percentage level of NK cells 3 months after infusion could predict disease activity 6 months after Ocrelizumab/Rituximab administration (p = 0.041). Conclusions: Lower percentage levels of NK cells 3 months after anti-CD20 infusion correlate with the presence of disease activity 6 months after therapy, confirming a possible protective role of NK cells in MS

Drug resistance in B and non-B subtypes amongst subjects recently diagnosed as primary/recent or chronic HIV-infected over the period 2013–2016: Impact on susceptibility to first-line strategies including integrase strand-transfer inhibitors

Objectives To characterize the prevalence of transmitted drug resistance mutations (TDRMs) by plasma analysis of 750 patients at the time of HIV diagnosis from January 1, 2013 to November 16, 2016 in the Veneto region (Italy), where all drugs included in the recommended first line therapies were prescribed, included integrase strand transfer inhibitors (InNSTI). Methods TDRMs were defined according to the Stanford HIV database algorithm. Results Subtype B was the most prevalent HIV clade (67.3%). A total of 92 patients (12.3%) were expected to be resistant to one drug at least, most with a single class mutation (60/68–88.2% in subtype B infected subjectsand 23/24–95.8% in non-B subjects) and affecting mainly NNRTIs. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. The diagnosis of primary/recent infection was made in 73 patients (9.7%): they had almost only TDRMs involving a single class. Resistance to InSTI was studied in 484 subjects (53 with primary-recent infection), one patient had 143C in 2016, a total of thirteen 157Q mutations were detected (only one in primary/recent infection). Conclusions Only one major InSTI-TDRM was identified but monitoring of TDRMs should continue in the light of continuing presence of NNRTI-related mutation amongst newly diagnosed subjects, sometime impacting also to modern NNRTI drugs recommended in first-line therapy

The Present and Future of Optic Pathway Glioma Therapy

Optic pathway gliomas (OPGs) encompass two distinct categories: benign pediatric gliomas, which are characterized by favorable prognosis, and malignant adult gliomas, which are aggressive cancers associated with a poor outcome. Our review aims to explore the established standards of care for both types of tumors, highlight the emerging therapeutic strategies for OPG treatment, and propose potential alternative therapies that, while originally studied in a broader glioma context, may hold promise for OPGs pending further investigation. These potential therapies encompass immunotherapy approaches, molecular-targeted therapy, modulation of the tumor microenvironment, nanotechnologies, magnetic hyperthermia therapy, cyberKnife, cannabinoids, and the ketogenic diet. Restoring visual function is a significant challenge in cases where optic nerve damage has occurred due to the tumor or its therapeutic interventions. Numerous approaches, particularly those involving stem cells, are currently being investigated as potential facilitators of visual recovery in these patients

The Effect of Three Different Ketogenic Diet Protocols on Migraine and Fatigue in Chronic and High-Frequency Episodic Migraine: A Pilot Study

Aims: We aimed to evaluate the efficacy of three different ketogenic diets on migraine and fatigue in chronic and high-frequency episodic migraineurs. Methods: 76 patients with migraine were treated with the KD for at least three months. Three different KD protocols were used (2:1 KD, LGID, and VLCKD). We evaluated the fatigue severity scale (FSS), migraine frequency, migraine intensity, MIDAS, and HIT-6 at the baseline and 3-month follow-up, and we compared the results. We also correlated the mean FSS reduction with the mean migraine frequency, migraine intensity, BMI, fat mass, free-fat mass, MIDAS, and HIT-6 reduction. Results: FSS improved from 4.977 ± 1.779 to 3.911 ± 1.779 at the 3-month follow-up (p < 0.001). This improvement was significant in both high-frequency and chronic migraineurs. Moreover, the three KD protocols effectively improved migraine intensity, frequency, MIDAS, and HIT-6. There was a mild correlation between mean FSS reduction (p < 0.001), mean MIDAS (p = 0.001), and HIT-6 (p = 0.002) reduction. Conclusions: The VLCKD, LGID, and 2:1 KD may improve migraine intensity, frequency, and fatigue in chronic and high-frequency episodic migraineurs

Subclinical finding in the perception of tactile sensation involvement after SARS-CoV2 infection: comparison with healthy controls using Semmes–Weinstein monofilament testing

Background: Post-acute COVID-19 syndrome patients complain of sensory alterations, mainly positive symptoms such as paresthesia or neuropathic pain but also decreased tactile sensation. Using the Semmes–Weinstein monofilament test (SWMT), our study aims to confront recently infected SARS-CoV2 subjects with a control group. Methods: This is a cross-sectional, single-centric study. We performed the SWMT (North Coast Medical Inc.) on 30 patients with previous SARS-CoV2 infection (COVID group) and 46 controls (control group). These patients did not present comorbidities or sensory impairment and did not take any medications. The control group tested negative for SARS-CoV2 infection since the COVID-19 pandemic; the COVID group was examined for this study after the resolution of the infection. We tested the threshold of tactile sensation of the tips of the thumb, index, and little finger of each hand, one hand at a time; the dorsum and the hypothenar regions were also tested. Results: Both groups presented the perception of tactile sensation within the reference value. Despite this result, subclinical changes suggestive of the involvement in peripheral sensory nerve function have been identified in the tested sites in the COVID group compared to the control group. The overall mean target force (grams) was higher in the COVID group than in the control group: 27 (7) vs. 19 (10) mg, p < 0.001. Conclusion: Controls and the COVID group infection had normal tactile sensation thresholds. However, the COVID group presented a higher threshold than the control group, suggesting a possible subclinical perception of tactile sensation involvement of A-beta nerve fibers

Serum proteomic test in advanced non-squamous non-small cell lung cancer treated in first line with standard chemotherapy

Background:VeriStrat is a blood-based proteomic test with predictive and prognostic significance in second-line treatments for non-small cell lung cancer (NSCLC). This trial was designed to investigate the role of VeriStrat in first-line treatment of advanced NSCLC with standard chemotherapy. Here we present the results for 76 non-squamous patients treated with a combination of carboplatin or cisplatin with pemetrexed.Methods:The test-assigned classifications of VeriStrat Good or VeriStrat Poor to samples collected at baseline. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and objective response. Exploratory analyses of end points separately in carboplatin/pemetrexed and cisplatin/pemetrexed subgroups were also conducted.Results:Patients classified as VeriStrat Good had longer PFS and OS than VeriStrat Poor: 6.5 vs 1.6 months and 10.8 vs 3.4 months, respectively; the corresponding hazard ratios (HRs) were 0.36 (P&lt;0.0001) and 0.26 (P&lt;0.0001); they were also more likely to achieve objective response. Prognostic significance of VeriStrat was confirmed in multivariate analysis. Significant differences in OS and PFS between Veristrat classifications were also found when treatment subgroups were analysed separately.Conclusions:The trial demonstrated clinical utility of VeriStrat as a prognostic test for standard first-line chemotherapy of non-squamous advanced NSCLC