Gene Therapy for ALS-A Perspective.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease (MND) with no cure. Recent advances in gene therapy open a new perspective to treat this disorder-particularly for the characterized genetic forms. Gene therapy approaches, involving the delivery of antisense oligonucleotides into the central nervous system (CNS) are being tested in clinical trials for patients with mutations in SOD1 or C9orf72 genes. Viral vectors can be used to deliver therapeutic sequences to stably transduce motor neurons in the CNS. Vectors derived from adeno-associated virus (AAV), can efficiently target genes and have been tested in several pre-clinical settings with promising outcomes. Recently, the Food and Drug Administration (FDA) approved Zolgensma, an AAV-mediated treatment for another MND-the infant form of spinal muscular atrophy. Given the accelerated progress in gene therapy, it is potentially a promising avenue to develop an efficient and safe cure for ALS.

Systemic immune-inflammation index: a prognostic tiebreaker among all in advanced pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) detains a dismal prognosis and has a limited number of prognostic factors. Inflammation has been demonstrated to play a key role both in PDAC initiation and progression and several inflammation-based prognostic scores have been investigated in a wide range of malignancies. We compared the most analyzed inflammation-based prognostic scores in order to establish their potential impact on prediction of the outcome in advanced PDAC patients. METHODS: A total of 234 advanced PDAC patients undergoing first-line chemotherapy in our institute were retrospectively analyzed. Baseline clinicopathological and pre-treatment laboratory data were collected. Survival was estimated using Kaplan-Meier method and survival differences were evaluated using the log-rank test. Level of statistical significance P was set at 0.05. Only those variables that proved to be associated with statistically significant differences in outcome were compared in multivariate analysis using multiple Cox regression, as to identify their independent role and their relative power against each other. RESULTS: In the whole cohort, median overall survival (OS) was 8.7 months (95% CI: 7.8-9.4 months), median progression-free survival (PFS) was 3.8 months (95% CI: 3.1-4.2 months). At univariate analysis high systemic immune-inflammation index (SII) was related to shorter OS [hazard ratio (HR) =2.04, 95% CI: 1.59-4.19, P=0.0001] and PFS (HR =1.52, 95% CI: 1.11-2.20, P=0.01). This was maintained at multivariate analysis both for OS (HR =2.11, 95% CI: 1.29-3.46, P=0.003) and PFS (HR =1.64, 95% CI: 1.14-2.37, P=0.008), whereas other inflammation-based scores lost their independent role. Elevated SII (≥1,200) was associated with low albumin levels (P=0.03) and with elevated lactate dehydrogenase (LDH) (P=0.01). CONCLUSIONS: Elevated SII represents an independent negative prognostic factor above all others for both OS and PFS in advanced PDAC patients treated with first-line chemotherapy, thus confirming a pivotal role of systemic inflammation on PDAC progression and on patient outcome.