Efficacy and tolerability of therapies set under pharmacogenetic tools suggestions: A systematic review with meta-analysis about mood disorders

Background: Bipolar Disorder (BD) and Major Depressive Disorder (MDD) have a huge impact on functioning and quality of life; moreover, they are linked to extensive direct and indirect costs. This systematic review with metaanalysis aims to evaluate the utility of pharmacogenetic tests (PGT) in terms of efficacy and tolerability into the routine clinical treatment of mood disorders. Materials and methods: The first part of the review is a qualitative overview of the PGTs used in the included studies. The second part aims to compare, in terms of efficacy and tolerability, patients affected by BD and MDD treated as usual (TAU), according to the clinicians\u2019 prescribing attitude, versus patients whose psychopharmacological treatments were set up following the PGT suggestions. Results: 6 studies on MDD and 2 studies on BD were included. Regarding MDD, the meta-analysis shows a significantly higher number of patients achieving better outcome in terms of efficacy, through the evaluation of response rate and remission rate at the HDRS (Hamilton Depression Rating Scale) in the group of patients treated under the PGT suggestions; regarding BD the meta-analysis does not show any significant difference in terms of efficacy. In terms of adverse events, the available data suggest promising results about the utility of PGT to set more tolerated therapies. Conclusions: Although the limited number of studies, results confirm the importance of PGT in setting up psychopharmacological therapies as a support to clinicians\u2019 choices

The Crotone Megalandslide, southern Italy: Architecture, timing and tectonic control

Large-scale submarine gravitational land movements involving even more than 1,000 m thick sedimentary successions are known as megalandslides. We prove the existence of large-scale gravitational phenomena off the Crotone Basin, a forearc basin located on the Ionian side of Calabria (southern Italy), by seismic, morpho-bathymetric and well data. Our study reveals that the Crotone Megalandslide started moving between Late Zanclean and Early Piacenzian and was triggered by a contractiona I tectonic event leading to the basin inversion. Seaward gliding of the megalandslide continued until roughly Late Gelasian, and then resumed since Middle Pleistocene with a modest rate. Interestingly, the onshore part of the basin does not show a gravity-driven deformation comparable to that observed in the marine area, and this peculiar evidence allows some speculations on the origin of the megalandslide

The "Combo" radiotherapy treatment for high-risk grade 2 meningiomas: dose escalation and initial safety and efficacy analysis

Purpose The subgroup "high-risk" WHO grade 2 (hRG2) meningiomas may benefit from adjuvant radiation therapy (RT), but results are still suboptimal with high rates of local progression. A dose escalation using high-conformal RT techniques needs to be evaluated in terms of efficacy and safety. We report the results of a dose-escalation study, named "Combo-RT", combining Intensity Modulated Radiotherapy (IMRT) or Volumetric Arc Therapy (VMAT) with Hypofractionated Stereotactic Radiotherapy (hSRT) boost. Patients and methods From November 2015 to January 2019, we prospectively enrolled 16 patients with hRG2. Seven patients had subtotal resection (STR) and 9 patients had a recurrent tumor. All patients received Combo-RT: LINAC-IMRT/ VMAT on the surgical bed and CyberKnife-hSRT boost on residual/recurrent meningioma Toxicity and initial efficacy were evaluated. Results The median age was 62 years (range, 31-80 years). The median cumulative dose delivered was 46 Gy For IMRT or VMAT and 15 Gy in 3 fractions at a median isodose line of 77% for hSRT. The median cumulative BED and EQD2 were 108.75 Gy and 72.5 Gy respectively. 3-year-PFS was 75% for the whole cohort,100% for patients with STR, and 55.5% for recurrent patients. Negligible toxicities, and stable or improved symptoms during long-term follow-up were observed. Salvage treatment for recurrence was an independent predictor of treatment failure (P = 0.025). Conclusions With the limitation of a small series of patients, our results suggest that a dose escalation for hRG2 meningiomas, using a Combo-RT approach, is safe and particularly effective in the subgroup of patients with STR. Further studies are warranted