Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study

Journal of Neurology - To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment. This was an...     

Autonomic cardiovascular alterations as therapeutic targets in chronic kidney disease

Clinical Autonomic Research - The present paper will review the impact of different therapeutic interventions on the autonomic dysfunction characterizing chronic renal failure. We reviewed the...     

Surgery for drug‐resistant tuberous sclerosis complex‐associated epilepsy: who,when, and what

Objective: Tuberous sclerosis complex (TSC) is a multisystem genetic disorder associated with refractory early‐onset epilepsy. Current evidence supports surgery as the intervention most likely to achieve long‐term seizure freedom, but no specific guidelines are available on TSC pre‐surgical workup. This critical review assesses which TSC patients are suitable for surgical treatment, when pre‐surgical evaluation should start, and what degree of surgical resection is optimal for postsurgical outcome. Methods: We searched for publications from 2000 to 2020 in Pubmed and Embase using the terms “tuberous sclerosis,” “epilepsy,” and “epilepsy surgery”. To evaluate postsurgical seizure outcome, we selected only studies with at least one year of follow‐up. Results: Overall, we collected data on 1,026 patients from 34 studies. Age at surgery ranged from one month to 54 years. Mean age at surgery was 8.41 years. Of the diagnostic non‐invasive pre‐surgical tools, MRI and video‐EEG were considered most appropriate. Promising data for epileptogenic tuber detection is provided from invasive SEEG studies. Data on surgery and related outcome were available for 769 patients. Seizure freedom was seen in 64.4% of patients who underwent tuberectomy, 68.9% treated with lobectomy and 65.1% with multilobar resection. The most effective surgical approach was lobectomy, even though more recently tuberectomy associated with the resection of the perituberal area seems to be the best approach to reach seizure freedom. Published postsurgical seizure freedom rates in patients with TSC were between 65% and 75%, but reduced to 48%‐57% over longer follow‐up periods. Early surgery might positively affect neurodevelopmental trajectory in some patients, even though data on cognitive outcome are still to be confirmed with longitudinal studies. Significance: Considering the strong correlation between epilepsy duration and neurocognitive outcome, all patients with TSC ought to be referred early to a dedicated epilepsy centre for individually tailored pre‐surgical evaluation by a multi‐disciplinary epilepsy surgery team.     

Anxiety,depression, and quality of life in Parkinson’s disease: the implications of multidisciplinary treatment

Anxiety and depression in Parkinson’s disease (PD) reduce well-being of the patients. Emotional alterations influence motor skills and cognitive performance; moreover, they contribute significantly and independently to worsen rehabilitative treatment response. We investigated anxiety, depression, and quality of life in PD patients subjected to multidisciplinary rehabilitative training. The self-controlled study included 100 PD patients (49 males and 51 females with the mean age of 64.66 years) admitted to 60 days hospitalization rehabilitative program, between January 2017 and December 2018. Motor, cognitive, linguistic abilities, and functional independence were evaluated at admission (T0 baseline visit) and 60 days after (T1) the multidisciplinary rehabilitation including motor exercises, speech therapies, and cognitive intervention. The multidisciplinary rehabilitation improved functional status in PD patients and exerted its positive effects on mood, motor abilities, autonomy in the activities of daily life, perception of quality of life, cognitive performance and speech skills. Non-motor symptoms may worsen severe disability and reduce quality of life. They are often poorly recognized and inadequately treated. Nonetheless, multidisciplinary rehabilitative training represents an optimal strategy to improve disease management. The study was approved by Istituito di Ricovero e Cura a Carattere Scientifico (IRCCS) Centro Neurolesi “Bonino-Pulejo” Ethical Committee (approval No. 6/2016) in June 2016.     

Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR-engineered T cells

The phenotype of infused cells is a major determinant of Adoptive T-cell therapy (ACT) efficacy. Yet, the difficulty in deciphering multiparametric cytometry data limited the fine characterization of cellular products. To allow the analysis of dynamic and complex flow cytometry samples, we developed cytoChain, a novel dataset mining tool and a new analytical workflow. CytoChain was challenged to compare state-of-the-art and innovative culture conditions to generate stem-like memory cells (T_SCM) suitable for ACT. Noticeably, the combination of IL-7/15 and superoxides scavenging sustained the emergence of a previously unidentified nonexhausted Fit-T_SCM signature, overlooked by manual gating and endowed with superior expansion potential. CytoChain proficiently traced back this population in independent datasets, and in T-cell receptor engineered lymphocytes. CytoChain flexibility and function were then further validated on a published dataset from circulating T cells in COVID-19 patients. Collectively, our results support the use of cytoChain to identify novel, functionally critical immunophenotypes for ACT and patients immunomonitoring.     

Evaluation of the commercial AD fosfomycin test for susceptibility testing of multidrug-resistant Enterobacterales and Pseudomonas aeruginosa

ObjectivesTo compare fosfomycin susceptibility testing with the commercial agar dilution (AD) test, AD Fosfomycin (Liofilchem, Roseto degli Abruzzi, Italy) and the reference AD method, using a collection of multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa clinical isolates.MethodsThe collection included 119 carbapenemase-producing Enterobacterales, 53 Enterobacterales producing acquired AmpC-type and/or extended-spectrum β-lactamases and 38 carbapenemase-producing P. aeruginosa, including representatives of different high-risk clones. AD Fosfomycin and AD reference method (ISO 20776-1:2019) were performed starting from the same microbial suspension. Results were interpreted according to EUCAST clinical breakpoints (10.0). Essential agreement (EA), category agreement (CA) and error rates were calculated as described by the International Organization for Standardization.ResultsOf 172 Enterobacterales, 143 (83.1%, including 92.9% (52 of 56) of the NDM-producers and 84.2% (48 of 57) of the KPC-producers) were susceptible to fosfomycin using reference AD. A CA of 91.9% (158 of 172; 95% CI 87.1%–95.3%) and an EA of 92.5% (136 of 147; 95% CI 87.4%–96.0%), respectively, were calculated for the commercial AD Fosfomycin test, with 9.8% (14 of 143) of major errors and no very major errors (0 of 29). Overall, 86.8% (33 of 38) of P. aeruginosa showed a fosfomycin MIC ≤128 mg/L using reference AD. An EA of 84.8% (95% CI 66.3%–92.0%) was calculated for the commercial AD Fosfomycin test, with a CA of 100% (95% CI 93.6%–100%) when considering a tentative breakpoint at 128 mg/L.ConclusionsAD Fosfomycin showed an overall good concordance compared with reference AD.     

Plasma PCSK9 levels and sepsis severity: an early assessment in the emergency department

Clinical and Experimental Medicine - The aim of the study is to evaluate the prognostic value of early PCSK9 levels in non-intubated septic patients admitted to the emergency department. This...     

Incidental findings detected with panoramic radiography: prevalence calculated on a sample of 2017 cases treated at a major Italian trauma and cancer centre

Objectives

This study aimed to assess the prevalence of incidental findings, not strictly related to dentistry, viewed with panoramic radiography.

Methods

Panoramic radiographs performed between December 2013 and June 2016 were retrospectively collected. These images were analyzed, searching for incidental findings. All the information collected was statistically analysed

Results

A total of 2307 Panoramic Radiograph were analyzed and 2017 of them were included in the study. 529 incidental findings were seen: 255 (48.2%) were ESP (Elongation of Styloid Process), 167 were CAC (Carotid Artery Calcification) (31.57%), 36 were maxillary sinus pathologies (6.8%) and 71 were other incidental findings (13.42%). The total prevalence of IF was 26, 23%., CAC was 8.28% in the total population, and it was higher in women (9.82%) than men (6.54%). 48.5% of CAC were bilateral. When unilateral, the right side showed a higher right side prevalence. The prevalence of ESP was 12.64% in total population (men: 13.82%; women: 11.60%). 84.71% of ESP were bilateral and, when present unilaterally, no side difference was seen. 13.33% of the ESP appeared segmented. The prevalence of maxillary sinus pathologies was 1.78% (men: 2.32%; women: 1.31%). Only 8.33% of these pathologies were bilateral, and, when unilateral, they were mostly present on the right side. Between the 71 other IF (prevalence: 3.52%), sialoliths and tonsilloliths were assessed most frequently.

Conclusion

Due to the high prevalence of incidental findings detected with panoramic radiography, dental practitioners should be aware of the various pathologic conditions seen on the panoramic radiographs.

     

Doubly heterozygous LMNA and TTN mutations revealed by exome sequencing in a severe form of dilated cardiomyopathy

Familial dilated cardiomyopathy (DCM) is a heterogeneous disease; although 30 disease genes have been discovered, they explain only no more than half of all cases; in addition, the causes of intra-familial variability in DCM have remained largely unknown. In this study, we exploited the use of whole-exome sequencing (WES) to investigate the causes of clinical variability in an extended family with 14 affected subjects, four of whom showed particular severe manifestations of cardiomyopathy requiring heart transplantation in early adulthood. This analysis, followed by confirmative conventional sequencing, identified the mutation p.K219T in the lamin A/C gene in all 14 affected patients. An additional variant in the gene for titin, p.L4855F, was identified in the severely affected patients. The age for heart transplantation was substantially less for LMNA:p.K219T/TTN:p.L4855F double heterozygotes than that for LMNA:p.K219T single heterozygotes. Myocardial specimens of doubly heterozygote individuals showed increased nuclear length, sarcomeric disorganization, and myonuclear clustering compared with samples from single heterozygotes. In conclusion, our results show that WES can be used for the identification of causal and modifier variants in families with variable manifestations of DCM. In addition, they not only indicate that LMNA and TTN mutational status may be useful in this family for risk stratification in individuals at risk for DCM but also suggest titin as a modifier for DCM.