Prevalence of spinocellulart ataxia type 2 mutation among ittalian Parkinsonian patients

We evaluated the prevalence of the SCA2 mutation among 224 Italian patients affected by typical Parkinsonism, including 145 sporadic and 79 familial forms. Pink1, Parkin, and LRRK2 gene mutations had been excluded previously. Molecular testing for the CAG expansion at the SCA 2 locus was performed on leukocyte DNA. Cloning and sequencing of the expanded allele was performed in patients positive for the SCA2 expansion. A 38 CAG expansion was detected in 1 of 79 families studied. The proband, a male age 67, and his sister, age 69, were both affected by a benign form of L-dopa–responsive Parkinsonism not associated with cerebellar signs. The inheritance was autosomal dominant. The CAG expansion was stable through meiotic transmission: sequence analysis showed that the CAG stretch was interrupted by 3 CAA. Our study shows that CAG expansion at the SCA 2 locus may represent a genetic cause of familial L-dopa–responsive Parkinsonism among Italian patients. The stability of the pathological CAG expansion detected in this family was related to the presence of CAA interruptions. These findings, together with literature data, suggest that the molecular intrinsic structure of the expanded allele may modulate the phenotypic expression of the SCA2 mutatio

Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): A randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX

Background: Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression. Patients and methods: We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progressionfree survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis. Results: Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7-8.0] versus 4.5 months (95% CI 3.3-5.7); [hazard ratio (HR), 0.81; 95% CI 0.58-1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5-8.2) versus 5.3 months (95% CI 3.7-6.9); HR, 0.56 (95% CI 0.33-0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4-28.0) versus 19.8 months (95% CI 14.9-24.7); HR, 0.57 (95% CI 0.32-1.02); P = 0.056]. Conclusions: Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials

"I know that you know that I know": neural substrates associated with social cognition deficits in DM1 patients

Myotonic dystrophy type-1 (DM1) is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients' dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM). We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the "Reading the Mind in the Eyes" and the ToM-story tests. These patients, together with 18 healthy controls, also underwent resting-state functional MRI. A composite Theory of Mind score was computed for all recruited patients and correlated with their brain functional connectivity. This analysis provided the patients' "Theory of Mind-network", which was compared, for its topological properties, with that of healthy controls. We found that DM1 patients showed deficits in both tests assessing ToM. These deficits were associated with specific patterns of abnormal connectivity between the left inferior temporal and fronto-cerebellar nodes in DM1 brains. The results confirm the previous suggestions of ToM dysfunctions in patients with DM1 and support the hypothesis that difficulties in social interactions and personal relationships are a direct consequence of brain abnormalities, and not a reaction symptom. This is relevant not only for a better pathophysiological comprehension of DM1, but also for non-pharmacological interventions to improve clinical aspects and impact on patients' success in life

COVID-19 atypical Parsonage-Turner syndrome: a case report

Background Neurological manifestations of Sars-CoV-2 infection have been described since March 2020 and include both central and peripheral nervous system manifestations. Neurological symptoms, such as headache or persistent loss of smell and taste, have also been documented in COVID-19 long-haulers. Moreover, long lasting fatigue, mild cognitive impairment and sleep disorders appear to be frequent long term neurological manifestations after hospitalization due to COVID-19. Less is known in relation to peripheral nerve injury related to Sars-CoV-2 infection. Case presentation We report the case of a 47-year-old female presenting with a unilateral chest pain radiating to the left arm lasting for more than two months after recovery from Sars-CoV-2 infection. After referral to our post-acute outpatient service for COVID-19 long haulers, she was diagnosed with a unilateral, atypical, pure sensory brachial plexus neuritis potentially related to COVID-19, which occurred during the acute phase of a mild Sars-CoV-2 infection and persisted for months after resolution of the infection. Conclusions We presented a case of atypical Parsonage-Turner syndrome potentially triggered by Sars-CoV-2 infection, with symptoms and repercussion lasting after viral clearance. A direct involvement of the virus remains uncertain, and the physiopathology is unclear. The treatment of COVID-19 and its long-term consequences represents a relatively new challenge for clinicians and health care providers. A multidisciplinary approach to following-up COVID-19 survivors is strongly advised

Design of jet-grouting for tunnel waterproofing

A case history in Barcelona is described where a tunnel was excavated by traditional methods below an active railway line through a formation with lenses of water-bearing granular material. To avoid the possibility of sudden collapses a massive jet-grout treatment was applied. The treatment took several forms. Subvertical double and triple-fluid injection was applied whenever possible. Sub-horizontal monofluid canopies and slabs executed from within the tunnel were however required in zones where no vertical access was possible. This communication focuses on the later type of treatments and gives an overview of the design tools that were applied. These comprised the execution of several large trial fields and the systematic application of a probabilistic framework for design.Postprint (published version

Design of jet-grouting for tunnel waterproofing

A case history in Barcelona is described where a tunnel was excavated by traditional methods below an active railway line through a formation with lenses of water-bearing granular material. To avoid the possibility of sudden collapses a massive jet-grout treatment was applied. The treatment took several forms. Subvertical double and triple-fluid injection was applied whenever possible. Sub-horizontal monofluid canopies and slabs executed from within the tunnel were however required in zones where no vertical access was possible. This communication focuses on the later type of treatments and gives an overview of the design tools that were applied. These comprised the execution of several large trial fields and the systematic application of a probabilistic framework for design

Design of jet-grouting for tunnel waterproofing

A case history in Barcelona is described where a tunnel was excavated by traditional methods below an active railway line through a formation with lenses of water-bearing granular material. To avoid the possibility of sudden collapses a massive jet-grout treatment was applied. The treatment took several forms. Subvertical double and triple-fluid injection was applied whenever possible. Sub-horizontal monofluid canopies and slabs executed from within the tunnel were however required in zones where no vertical access was possible. This communication focuses on the later type of treatments and gives an overview of the design tools that were applied. These comprised the execution of several large trial fields and the systematic application of a probabilistic framework for design

Persistence of abnormal electrophysiological findings after carpal tunnel release

Practitioners may refer to experienced hand surgeons to differentiate a recurrence in carpal tunnel syndrome (CTS) from a failed carpal tunnel release. The patient may complain about the reappearance of symptoms, whatever is the cause. Nerve conduction studies (NCS) are often required by the practitioner to assist the final diagnosis. We observed abnormal values in NCS in patients who were clinically healed from CTS. We evaluated the changes preoperatively and, then, at 1, 3, 6, 9, and 12 month postoperatively. At the same time, we performed a retrospective study on a group of 37 clinically healed patients. Follow-up ranged from 2 to 20 years. Surgical treatment let the electrophysiological parameters to improve toward physiological values; however, normality is hardly ever reached. This sort of ''electrophysiological scar'' is true for all the parameters measured. In presence of CTS, the latency difference between the radial and median sensory nerve action potentials, recorded following thumb stimulation, produces a double peak shift. The ''double peak shift'' best described this ''electrophysiological scar,'' being a parameter that should measure about zero in the normal population. In conclusion, abnormal postoperative electrophysiological findings cannot substantiate the diagnosis of a poor outcome of a carpal tunnel release nor a recurrence of CTS