Syntax (Italy)

BackgroundPaclitaxel drug‐coated balloons (DCB) prevent recurrent claudication after angioplasty, yet data from randomized trials with incomplete follow‐up have raised uncertainty regarding long‐term mortality.ObjectivesTo evaluate the effect of paclitaxel exposure on the long‐term safety and efficacy of angioplasty of femoropopliteal artery lesions in the combined IN.PACT randomized trials.MethodsThe IN.PACT randomized trials (SFA, N = 331 and Japan, N = 100) each compared the DCB with standard percutaneous transluminal angioplasty (PTA) for claudication, and consented patients for 5 and 3 years, respectively. To address long‐term safety, sites were requested to obtain vital status follow‐up. In the pooled, updated data set, we examined the association between randomized treatment and mortality by cumulative incidence and hazard ratio (HR), and freedom from clinically driven target lesion revascularization (CD‐TLR). Multivariable Cox regression with adjustment for baseline characteristics was used to evaluate the dose effect. Causes of death were adjudicated by a blinded clinical events committee that included oncologists with paclitaxel expertise.ResultsThe rate of long‐term vital status ascertainment increased from 81% to 97% for DCB and from 85% to 97% for PTA in the IN.PACT SFA trial. The cumulative incidence of mortality was 14.7% DCB versus 12.0% PTA at 5 years, HR 1.39, log‐rank p = .286. Paclitaxel dose (mg) was not an independent predictor of mortality (HR 1.02, p = .381), but was an independent predictor of reduced risk of CD‐TLR (HR 0.79; p < .001). Causes of death did not differ by treatment arm.ConclusionsIn pooled randomized trial data with updated vital status ascertainment, paclitaxel was associated with improved efficacy but was not associated with increased mortality.

A recent summary-level meta-analysis comprising randomized, controlled trials (RCTs) of femoropopliteal paclitaxel-coated balloon and stent intervention identified excess late mortality in the paclitaxel-treated patients. We evaluated the safety of the Stellarex drug-coated balloon (DCB) for femoropopliteal artery disease with an independently performed meta-analysis of patient-level data from all patients in the Stellarex femoropopliteal clinical program. To compare mortality after DCB or uncoated percutaneous transluminal angioplasty (PTA), we aggregated data from 2 RCTs comprising 419 patients treated with DCB and 170 patients treated with PTA. In an additional analysis, data were aggregated from 6 poolable Stellarex DCB studies (2 RCTs, 3 single-arm studies, and 1 registry). All serious adverse events including deaths were adjudicated by a blinded, third-party, independent Clinical Events Committee. Kaplan-Meier estimates in the RCTs were compared with restricted mean survival time. Predictors of death were assessed with hazard ratios (HRs) and Cox proportional hazards modeling. Baseline characteristics were similar in the patients treated with DCB and PTA in the pooled RCT analysis, with the exception that the DCB cohort was younger (67.4±9.7 versus 69.4±9.4 years, P=0.02), smoked more frequently (86.6% versus 78.8%, P=0.02), and were less often treated for recurrent lesions (8.8% versus 14.7%, P=0.04). In the RCTs, patients treated with DCB had all-cause mortality rates that were not different from those of patients treated with PTA (Kaplan-Meier estimates 1.8±0.7% versus 1.3±0.9%, 6.5±1.2% versus 5.9±1.9%, and 9.3±1.5% versus 9.9±2.4% at 1, 2, and 3 years, respectively, P=0.86). All-cause mortality rates were similar in a 1906-patient pooled nonrandomized DCB data set (Kaplan-Meier estimates of 2.1%, 4.9%, and 7.0% at 1, 2, and 3 years, respectively). Clinical Events Committee-adjudicated causes of death were balanced between the DCB and PTA cohorts. Multivariable Cox modeling identified age (HR, 1.06; 95% CI, 1.04-1.08; P<0.001), diabetes mellitus (HR, 1.42; 95% CI, 1.01-2.00; P=0.04), congestive heart failure (HR, 1.88; 95% CI, 1.12-3.16; P=0.02), and renal insufficiency (HR, 2.00; 95% CI, 1.33-3.01; P<0.001) as predictors of mortality. Paclitaxel exposure was unrelated to mortality (HR, 1.04; 95% CI, 0.98-1.10; P=0.23). The mortality rates for patients treated with the DCB and uncoated PTA were indistinguishable over 3-year follow-up. Additional patient-level, adequately powered meta-analyses with larger RCT data sets will be needed to confirm the generalizability of these findings. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02110524, NCT01858363, NCT01858428, NCT03421561, NCT01912937, NCT01927068, and NCT02769273.

The study assessed the pragmatic skills of 19 well-compensated Italian-speaking young adults with dyslexia compared with controls. A comprehensive pragmatic assessment tool was employed, targeting production and comprehension (Assessment of Pragmatic Abilities and Cognitive Substrates [APACS]). Participants were also administered a series of standardized tests to assess verbal and non-verbal cognitive abilities, including executive functions and social cognition tests. Data were analysed with the aim of understanding whether pragmatic abilities are compromised in dyslexia and of exploring associations between pragmatic performance and other cognitive domains. The performance of the dyslexia group was poorer than that of the control group in both expressive and receptive modalities. Data showed diffuse problems across several domains, with the greatest challenge posed by inferring nonliteral meanings, which indicates that pragmatic inefficiency is an important aspect of the linguistic and communicative profile of dyslexia in adulthood. Explorative correlations highlighted a relation between pragmatic performance and reading and vocabulary abilities, as well as between pragmatics and working memory. This suggests that pragmatic difficulties are strongly tied to the most distinctive aspects of dyslexia, namely, phonological awareness, verbal short-term memory, pseudo-word repetition, whereas the link with high-level executive functions and Theory of Mind is negligible.

A wide range of studies on language assessment during awake brain surgery is nowadays available. Yet, a consensus on a standardized protocol for intraoperative language mapping is still lacking. More specifically, very limited information is offered about intraoperative assessment of a crucial component of language such as syntax. This review aims at critically analyzing the intraoperative studies investigating the cerebral basis of syntactic processing. A comprehensive query was performed on the literature, returning a total of 18 studies. These papers were analyzed according to two complementary criteria, based on the distinction between morphosyntax and syntax. The first criterion focused on the tasks and stimuli employed intraoperatively. Studies were divided into three different groups: group 1 included those studies that overtly aimed at investigating morphosyntactic processes; group 2 included studies that did not explicitly focus on syntax, yet employed stimuli requiring morphosyntactic processing; and group 3 included studies reporting some generic form of syntactic deficit, although not further investigated. The second criterion focused on the syntactic structures of the sentences assessed intraoperatively, analyzing the canonicity of sentence structure (i.e., canonical versus non-canonical word order). The global picture emerging from our analysis indicates that what was investigated in the intraoperative literature is morphosyntactic processing, rather than pure syntax. The study of the neurobiology of syntax during awake surgery seems thus to be still at an early stage, in need of systematic, linguistically grounded investigations.

Theories on the processing of compound words differ on the role attributed to access to individual constituents. These theories are mostly based on empirical evidence obtained in experimental settings that could induce artificial effects normally not occurring in natural processing. In this study we investigated the processing of compounds as compared to noncompound complex words in Italian through a reading task with eye movement recording. We included both head-initial and head-final compounds, in order to test whether the position of the head may influence the reading process. After ruling out the effects of length and frequency, we observed that pseudocompounds (i.e., words with a segment homograph to a real word in the leftmost part) elicited longer total reading times than all other types of complex words, including compounds. Furthermore, head-final compounds elicited longer total reading times than head-initial compounds. The results suggest that a word structure resembling a compound may induce longer processing, presumably related to unexpected morphological structures. The results also converge with previous evidence that in some cases there is a higher processing costs for head-final as opposed to head-initial compounds, possibly indexing a reanalysis of the stimulus in order to correctly assign the constituent properties. However, a deeper analysis restricted to compounds revealed a more complex scenario where several variables interact with headedness (namely, first and second constituent frequency, compound frequency, and compound length), and future studies are needed to discriminate among possible interpretations. Overall, our findings suggest that longer reading times are related to solving incongruities due to noncanonical structures, rather than to morphologically complexity per se.