Constructional Impairments and Their Neural Correlates in Nondemented Adults With Cerebral Autosomal-dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.

BACKGROUND: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic small-vessel disease that is characterized by a wide range of neurologic and neuropsychological impairments. Constructional impairments have been reported in some cases but have never been assessed systematically. OBJECTIVE: To evaluate constructional abilities and their cognitive and neural correlates in nondemented individuals with CADASIL. METHOD: Thirty individuals with CADASIL who were not affected by clinically relevant cognitive deterioration and 30 healthy controls (HC) underwent an extensive cognitive assessment and paper-and-pencil visuoconstructional tasks in order to detect constructional impairments. Performance on the visuoconstructional tasks was correlated with the cognitive assessment scores and with quantitative indices of regional gray matter atrophy (obtained via FreeSurfer image analysis) and white matter involvement. RESULTS: The individuals with CADASIL achieved significantly lower scores on the cognitive assessment compared with the HC. Poor visuoconstructional abilities were observed in seven (23.3%) of the individuals with CADASIL when performing the copy drawing task and in nine (30%) when performing the Rey Complex Figure Test. Logistic regression revealed that visuoconstructional impairments were significantly associated with scores on the Frontal Assessment Battery and the Attentional Matrices Test. Morphometric results revealed that scores on the visuoconstructional tasks were related to gray matter atrophy of the left frontal lobe and right parietal lobe. CONCLUSION: Impairments on visuoconstructional tasks are quite common in individuals with CADASIL, even in the lack of clinically relevant cognitive deterioration, and are critically related to frontal and parietal atrophy.

Analgesic effects of breast- and formula feeding during routine childhood immunizations up to 1 year of age.

BACKGROUND: Data on analgesic effects of breast/formula milk sucking while receiving routine childhood immunizations are available only in early infancy, have rarely been compared in the same study, and are not accompanied by information on mothers' satisfaction/acceptance. Here we aimed to compare the analgesic effect of both methods vs. held-only controls up to 1 year of age, and verify mothers' satisfaction. METHODS: Two to 12 months children subjected to vaccine were allocated into three groups: breastfed, formula-fed, and held-only controls. A video recording was performed to analyze pain parameters: crying latency/duration and specific scales [FLACC (Face, Legs, Activity, Cry, and Consolability), NIPS (Neonatal Infant Pain Scale)]. After the procedure, mothers filled in a satisfaction questionnaire. RESULTS: One-hundred and sixty-two children were recruited: 54 breastfed, 35 formula fed, and 73 controls. Breastfed showed the longest crying latency, and together with formula fed, had the shortest duration and lowest pain scores. Most mothers appreciated not only the respective feeding-mediated pain mitigation method used, but also the simply-holding procedure. In all cases, they felt reassured, with an unexpected frequent underestimation of their child's pain during the shot. CONCLUSIONS: The analgesic effect of breastfeeding during vaccination extends also to children >6 months old, and is obtained by formula too. Embracing the child may help to reassure mothers. IMPACT: We confirmed the analgesic effect of breastfeeding during the vaccination procedures in early infancy. We show for the first time that this effect is extended also to children up to 1 year of age, and it may be obtained by formula feeding as well. Most mothers appreciated pain mitigation not only through feeding, but also the simply-holding procedure. In all cases, mothers felt reassured, with an unexpected frequent underestimation of their child' pain during the shot. The promotion of these easily feasible and well-accepted strategies should be further encouraged within health professionals during vaccination procedures.

Incidence trends of vulvar squamous cell carcinoma in Italy from 1990 to 2015.

OBJECTIVE: The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged <50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy. METHOD: Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analysed using joinpoint regression models, with calculation of the estimated annual percent change (EAPC), and age-period-cohort models. RESULTS: Total incidence showed a regular and significant decreasing trend (EAPC, -0.96; 95% confidence interval (CI), -1.43 to -0.48). This was entirely accounted for by women aged ≥60 years (EAPC, -1.34; 95% CI, -1.86 to -0.81). For younger women, the EAPC between 1990 and 2012 was 1.20 (95% CI, 0.34 to 2.06) with a non-significant acceleration thereafter. This pattern did not vary substantially in a sensitivity analysis for the effect of geographic area and duration of the registry. The age-period-cohort analysis revealed a risk decrease in cohorts born between 1905 and 1940 and a new increase in cohorts born since 1945. CONCLUSIONS: The decreasing trend observed among older women and the resulting decrease in total rate are at variance with reports from most Western countries. Age-period-cohort analysis confirmed a decreasing trend for earliest birth cohorts and an opposite one for recent ones.

Transanal total mesorectal excision (TaTME): are we doing it for the right indication? An assessment of the external validity of published online video resources.

BACKGROUND: The steep learning curve for safe introduction of transanal total mesorectal excision (TaTME) highlights the need for mentored training reserved for surgeons with expertise in minimally invasive colorectal surgery and transanal surgery. Video-based education in minimally invasive surgery is considered by surgical trainers as a useful teaching aid to maximize learning. This study aims to systematically assess the availability and quality of online TaTME videos. METHODS: TaTME videos were systematically searched on YouTube.com , Colorectal diseases video channel, WebSurg.com , and AIS channel. Data collected included video characteristics, presence of supplementary educational content, patient details, indication for surgery, different steps of TaTME presented, and surgical outcomes. RESULTS: Forty-six videos were included with a median of 92 views per month. Nineteen videos (41.3%) reported the age of the participants and 29 patients were male (63%). Body mass index (BMI) was reported in 20 videos (43.5%) with a median of 27 and it indicated obesity (BMI ≥ 30) in 2 cases only. The use of neoadjuvant treatment was reported in 8 cases (17.4%). Eighteen videos (39.1%) reported the distance of the tumor from the anal verge, with a median of 6.4 cm and in 9 out of 18 cases, the tumor distance from the anal verge was 7 cm or higher. Pathological staging was reported in 17 videos (37.0%), with 1 T1, 3 T2, 10 T3, and 3 T4 tumors. CONCLUSIONS: There is considerable interest in TaTME videos. Lack of consensus on reporting of these videos limits the educational value of these resources, which are missing important patient details and postoperative outcomes.

Characteristics of people living in Italy after a cancer diagnosis in 2010 and projections to 2020.

BACKGROUND: Estimates of cancer prevalence are widely based on limited duration, often including patients living after a cancer diagnosis made in the previous 5 years and less frequently on complete prevalence (i.e., including all patients regardless of the time elapsed since diagnosis). This study aims to provide estimates of complete cancer prevalence in Italy by sex, age, and time since diagnosis for all cancers combined, and for selected cancer types. Projections were made up to 2020, overall and by time since diagnosis. METHODS: Data were from 27 Italian population-based cancer registries, covering 32% of the Italian population, able to provide at least 7 years of registration as of December 2009 and follow-up of vital status as of December 2013. The data were used to compute the limited-duration prevalence, in order to estimate the complete prevalence by means of the COMPREV software. RESULTS: In 2010, 2,637,975 persons were estimated to live in Italy after a cancer diagnosis, 1.2 million men and 1.4 million women, or 4.6% of the Italian population. A quarter of male prevalent cases had prostate cancer (n = 305,044), while 42% of prevalent women had breast cancer (n = 604,841). More than 1.5 million people (2.7% of Italians) were alive since 5 or more years after diagnosis and 20% since ≥15 years. It is projected that, in 2020 in Italy, there will be 3.6 million prevalent cancer cases (+ 37% vs 2010). The largest 10-year increases are foreseen for prostate (+ 85%) and for thyroid cancers (+ 79%), and for long-term survivors diagnosed since 20 or more years (+ 45%). Among the population aged ≥75 years, 22% will have had a previous cancer diagnosis. CONCLUSIONS: The number of persons living after a cancer diagnosis is estimated to rise of approximately 3% per year in Italy. The availability of detailed estimates and projections of the complete prevalence are intended to help the implementation of guidelines aimed to enhance the long-term follow-up of cancer survivors and to contribute their rehabilitation needs.

Time to grow up: readiness associated with improved clinical outcomes in pediatric inflammatory bowel disease patients undergoing transition.

Background: The transition from pediatric to adult healthcare in individuals with inflammatory bowel disease (IBD) poses significant challenges mainly due to the high burden of IBD during adolescence, a critical period of psychosocial development. So far, there are few longitudinal data linking transition readiness to long-term disease outcomes. Objective: We aimed to assess patients' readiness to transition and its impact on clinical outcomes, quality of life, and adherence to therapy. Design: An observational, prospective study was conducted in a tertiary adult and pediatric center, including adolescents aged ⩾17 years with a diagnosis of IBD, who underwent a 'structured transition' program including two joint adult-pediatric visits. Methods: Transition readiness skills were assessed with the Transition Readiness Assessment Questionnaire (TRAQ). All patients completed the TRAQ at the time of recruitment, which occurred during the initial joint adult-pediatric visit, to determine those deemed ready for transition versus those not ready. The Morisky Medication Adherence Scale and the 36-Item Short Form Health Survey Questionnaire (SF-36) were also completed at baseline and after 12 months. Clinical outcomes were collected at the 12-month follow-up. Results: In all, 80 patients were enrolled who had transitioned through a structured transition clinic and completed 12 months of follow-up. In total, 54 patients were ready for the transition, with a mean TRAQ = 3.2 ± 0.5. The number of clinical relapses and hospitalizations at 12 months was lower in ready compared to not-ready patients (p = 0.004 and p = 0.04, respectively). SF-36 did not differ between ready and not-ready patients and pre- and post-transition clinics (p > 0.05). Based on the receiver operating characteristic curve, a TRAQ cutoff ⩾3.16 could predict medication adherence with a sensibility of 77%, a specificity of 82%, and an AUC of 0.81 (0.71-0.91; p < 0.001). Conclusion: Patients ready for transition had better outcomes at 12 months compared to those who were not ready. Therefore, readiness assessment tools should be integrated into transition management to ensure that interventions are targeted, patient-centered, and responsive to individuals' changing needs.

Transition readiness associated with improved clinical outcomes The transition for individuals with inflammatory bowel disease (IBD) is a dynamic and complex process that must be planned and cannot simply be performed once the patient is 18 years old. Since it does not depend solely on the patient's age but also on developmental readiness, it requires preparation and education starting from early adolescence. In the current study, a 'joint-visit' including both pediatric and adult providers yields positive clinical outcomes over 12 months. Patients ready for transition reported fewer relapses, hospitalizations, and improved therapy adherence compared to those not ready. Readiness assessment tools should be integrated into transition clinics to facilitate targeted interventions for IBD patients based on the changing needs of individuals.

Switching from VEDOlizumab intravenous to subcutaneous formulation in ulcerative colitis patients in clinical remission: The SVEDO Study, an IG-IBD study.

BACKGROUND: The administration of biological drugs in inflammatory bowel diseases (IBD) is increasingly moving from intravenous to subcutaneous formulations. AIMS: To evaluate the efficacy and safety of vedolizumab subcutaneous administration after switching from intravenous administration in ulcerative colitis (UC) patients in corticosteroid-free clinical remission. METHODS: An observational, multicentre, prospective study was conducted by the Italian Group for the study of IBD (IG-IBD). UC patients in clinical remission (pMAYO < 2) not receiving steroids for > 8 months before the switch, and with at least 6 months of follow-up were included. Switch from intravenous to subcutaneous vedolizumab was defined as successful in patients not experiencing a disease flare (pMAYO ≥ 2) or needing oral steroids or stopping subcutaneous vedolizumab during the 6 months of follow-up after the switch. RESULTS: Overall, 168 patients were included. The switch was a success in 134 patients (79.8%). Vedolizumab retention rate was 88.7% at month six. C-reactive protein and faecal calprotectin values did not change after the switch (p = 0.07 and p = 0.28, respectively). Ten of the 19 patients who stopped subcutaneous formulation switched back to intravenous formulation recapturing clinical remission in 80%. Side effects were observed in 22 patients (13.1%). CONCLUSION: Effectiveness of switching from intravenous to subcutaneous vedolizumab formulation in UC patients in steroid-free clinical remission is confirmed in a real-world setting.

The Use of JAK/STAT Inhibitors in Chronic Inflammatory Disorders.

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays a critical role in orchestrating immune and inflammatory responses, and it is essential for a wide range of cellular processes, including differentiation, cell growth, and apoptosis. Over the years, this pathway has been heavily investigated due to its key role in the pathogeneses of several chronic inflammatory conditions, e.g., psoriasis, atopic dermatitis (AD), and inflammatory bowel diseases (IBDs). Nevertheless, the impact of this pathway on the pathogenesis of inflammatory conditions remains unclear. This review describes the role of the JAK/STAT signaling pathway in the pathogenesis of inflammatory diseases such as psoriasis (Pso), psoriatic arthritis (PsA), AD, and IBD with a focus on ulcerative colitis (UC) and briefly resumes the use of JAK inhibitors in their clinical management.

The Impact of Intestinal Ultrasound on the Management of Inflammatory Bowel Disease: From Established Facts Toward New Horizons.

Intestinal ultrasound (IUS) plays a crucial role as a non-invasive and accurate tool to diagnose and assess inflammatory bowel disease (IBD). The rationale for using IUS in Crohn's disease (CD), a transmural disease, is widely acknowledged. While the use of IUS in ulcerative colitis (UC), a mucosal disease, is often underestimated, but, recently, it is increasingly expanding. In the context of a treat-to-target approach, the role of IUS is shifting toward a monitoring tool for predicting response to therapy. Hence, adjusting therapeutic strategies based on IUS response could reduce the burden related to endoscopy and speed the decision process with the ultimate goal to alter the natural course of IBD. Assessment of bowel wall thickness (BWT) is the most reliable IUS measure. However, the development of validated and reproducible sonographic scores to measure disease activity and the identification of parameters of therapeutic response remain relevant issues to implement the daily adoption of IUS in clinical practice. Accordingly, this review focuses on the current literature investigating the impact of IUS on CD with emphasis on the concept of transmural healing (TH) and the main related advantages. We further explore new insights on the role of IUS in UC and its clinical implications.

Exclusive Enteral Nutrition in Adult Crohn's Disease: an Overview of Clinical Practice and Perceived Barriers.

Recently, the role of nutrition in the management of Crohn's disease (CD) is of increasing interest and the exploration of novel nutritional interventions to improve long-term management of the disease is challenging. So far, the majority of the studies on the role of exclusive enteral nutrition (EEN) in CD are conducted in the pediatric population and have highlighted the efficacy of EEN for achieving mucosal healing. This implicates that a similar approach would be beneficial in adult patients. However, the evidence for EEN in adults is heterogeneous, with meta-analyses reporting it as inferior to steroids while growing data demonstrate improvement in complicated CD. Currently, EEN is less used in adult patients with IBD. Indeed, the lack of palatability of enteral formula leads to difficulties in acceptance and compliance. The search for more tolerable and still effective diets has become an intense area of research aiming to explore the potential role of diet to control inflammation in patients with CD. Thus, this narrative review provides the state-of-the-art on the use of EEN treatment in CD and highlights the perceived barriers to its implementation in adult CD patients.

Increased Postoperative Use of Computed Tomography Following Emergency Surgery for Ileocaecal Crohn Disease.

INTRODUCTION: Multiple imaging modalities are often required for the relapsing nature of Crohn disease (CD). Computed tomography (CT) offers a rapid acquisition of images and shows high specificity and sensitivity. However, CT imaging exposes to a higher dose of ionizing radiation than other abdominal imaging modalities. The aim of this study was to compare the use of preoperative and postoperative CT scan in patients undergoing emergency and elective surgery for CD. METHODS: All patients undergoing emergency and elective surgery for ileocaecal CD January 2014 to December 2018 were included in this prospective observational study. The study objective was to evaluate the frequency of use of CT scan perioperatively with the number and findings of preoperative and postoperative CT being the primary outcomes. The secondary outcomes were operating time, length of hospital stay, reoperations, and rehospitalization. RESULTS: A total of 75 patients were included, 33 in the emergency group (43%) and 44 in the elective group (57%). There was a higher use of preoperative CT scan in the emergency surgery group, with 14 patients (42%) having a CT scan before surgery compared with 2 (5%) in the elective group (P=0.14). Thirteen patients (39.4%) had a postoperative CT scan in the emergency surgery group, compared with 10 patients (23.8%) in the elective surgery group. CONCLUSION: Patients undergoing emergency surgery for CD are at increased risk of exposure to ionizing radiations due to high perioperative use of CT scan.

Changes in life expectancy for cancer patients over time since diagnosis.

The aims of this study were to provide life expectancy (LE) estimates of cancer patients at diagnosis and LE changes over time since diagnosis to describe the impact of cancer during patients' entire lives. Cancer patients' LE was calculated by standard period life table methodology using the relative survival of Italian patients diagnosed in population-based cancer registries in 1985-2011 with follow-up to 2013. Data were smoothed using a polynomial model and years of life lost (YLL) were calculated as the difference between patients' LE and that of the age- and sex-matched general population. The YLL at diagnosis was highest at the youngest age at diagnosis, steadily decreasing thereafter. For patients diagnosed at age 45 years, the YLL was above 20 for lung and ovarian cancers and below 6 for thyroid cancer in women and melanoma in men. LE progressively increased in patients surviving the first years, decreasing thereafter, to approach that of the general population. YLL in the long run mainly depends on attained age. Providing quantitative data is essential to better define clinical follow-up and plan health care resource allocation. These results help assess when the excess risk of death from tumour becomes negligible in cancer survivors.

The impact of overdiagnosis on thyroid cancer epidemic in Italy,1998-2012.

AIMS: In Italy, incidence rates of thyroid cancer (TC) are among the highest worldwide with substantial intracountry heterogeneity. The aim of the study was to examine time trends of TC incidence in Italy and to estimate the proportion of TC cases potentially attributable to overdiagnosis. METHODS: Data on TC cases reported to Italian cancer registries during 1998-2012 aged <85 years were included. Age-standardised incidence rates (ASR) were computed by sex, period, and histology. TC overdiagnosis was estimated by sex, period, age, and Italian region. RESULTS: In Italy between 1998-2002 and 2008-2012, TC ASR increased of 74% in women (from 16.2 to 28.2/100,000) and of 90% in men (from 5.3 to 10.1/100,000). ASR increases were nearly exclusively due to papillary TC (+91% in women, +120% in men). In both sexes, more than three-fold differences emerged between regions with highest and lowest ASR. Among TC cases diagnosed in 1998-2012 in Italy, we estimated that overdiagnosis accounted for 75% of cases in women and 63% in men and increased over the study period leading to overdiagnosis of 79% in women and 67% in men in 2008-2012. Notably, overdiagnosis was over 80% among women aged <55 years, and substantial variations were documented across Italian regions, in both genders. CONCLUSION(S): Incidence rates of TC are steadily increasing in Italy and largely due to overdiagnosis. These findings call for an update of thyroid gland examination practices in the asymptomatic general population, at national and regional levels.

Multi-organ investigation in 16 CADASIL families from central Italy sharing the same R1006C mutation.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) may involve many target organs with relevant variability among affected individuals. We performed a multi-organ assessment tapping nervous system, skeletal muscle and cardiovascular system in thirty-nine individuals belonging to 16 families from Central Italy sharing the same R1006C CADASIL mutation. Stroke prevalence was larger in female patients (66.7%) than in males (23.8%); high levels of CKemia were quite frequent (21.6%) and were related to a myopathy without mitochondrial alterations; several individuals had atrial septal aneurysm (10.3%). No specific relationships between common cardiovascular risk factors and clinical manifestations were found. The present systematic study thus identified several gender-related, myopathic and cardiovascular peculiarities of R1006C mutation. This kind of comprehensive approach is necessary to define clinical course, prognosis and treatment options for a multi-organ disease such as CADASIL.

Acceptance and safety of the intradermal influenza vaccine among the elderly in Italy: an on-field national study.

INTRODUCTION: An observational multicenter study was carried out in Italy, to evaluate the acceptability and safety of the new intradermal (ID) influenza vaccine (Intanza Sanofi Pasteur SA, Lyon, France) among subjects aged≥60 years, compared with that of other intramuscular (IM) influenza vaccines. Compliance with the use of the ID vaccine by healthcare professionals was also assessed. METHODS: A previously validated and self-administered questionnaire, Vaccinees' Perception of Injection (VAPI®), consisting of 21 questions, mainly focused on four dimensions (bother, arm movements, sleep, and acceptability), was administered to >1,600 individuals with spontaneous access to outpatient clinics, located in Northern, Central, and Southern Italy, to evaluate the acceptance of the vaccines. Occurrence of solicited and unsolicited side effects and of serious adverse events was assessed in a subset of subjects (n=500), using a clinical diary filled in by vaccinees following immunization. Compliance with the new ID vaccine by healthcare professionals was investigated using an ad-hoc questionnaire. RESULTS: A very favorable opinion concerning the acceptability of both the vaccines under survey, with the most positive answers ranging between 75.5% and 94.9%, was registered within the study population. Also the compliance by healthcare professionals (n=130) with the novel ID vaccine was favorable. No serious adverse event occurred during the 6-month follow-up period. The frequency of solicited systemic reactions was comparable between the two study groups, while solicited local reactions were significantly higher in the ID-vaccine group than in the IM-vaccine group, even if at values lower than those reported in phase 3 clinical trials (ranges=18.5-32.6% vs. 29.5-70.9%). These local events were mild and transient, thus without any clinical relevance. CONCLUSION: The novel ID influenza vaccine can be widely recommended in clinical practice, representing a useful tool to improve immunization coverage rates, and thus the control of influenza.