Effectiveness of 1-year treatment with long-acting formulation of aripiprazole, haloperidol, or paliperidone in patients with schizophrenia: retrospective study in a real-world clinical setting

Background: Schizophrenia is a chronic mental illness that requires lifelong antipsychotic treatment. Therapy discontinuation, often due to poor adherence, increases the risk of relapses after both first and subsequent psychotic episodes. Long-acting injectable (LAI) antipsychotic drugs (APDs) have been introduced to increase therapeutic adherence, reducing blood-level variability compared to corresponding oral preparations. Purpose: To compare the effectiveness of three LAI-APDs: aripiprazole (Apr) prolonged release once monthly (OM) haloperidol decanoate (Hal-D) and paliperidone palmitate (PP-OM). Methods: We retrospectively collected data for all patients with schizophrenia or other psychoses (n=217) treated with the three LAI-APDs for the first time from January 1, 2012 to October 31, 2016: n=48 with Apr-OM, n=55 with Hal-D, and n=114 with PP-OM. After 6 and 12 months of LAI treatments, we assessed clinical and functioning improvement, urgent consultations, psychiatric hospitalizations, adverse effects, and dropout. We compared urgent consultations and psychiatric hospitalizations required by the same patient 6 and 12 months before and after LAI implementation. Data were statistically analyzed. Results: The three LAI groups differed significantly only for “need for economic support from social service” (more frequent in the Hal-D group) and “schizoaffective disorder” (prevalent in the Apr-OM group). Apr-OM was prescribed at the maximum dose required by the official guidelines, whereas the other two LAIs were prescribed at lower doses. After 6 and 12 months’ treatment with the three LAI-APDs, we registered similar and significant reductions in both urgent consultations and psychiatric hospitalizations (P,0.001) and overlapping clinical and functioning improvement-scale scores (P,0.001), and 14.28% of patients dropped out, with no difference among the three LAI-APDs. Different kinds of adverse effects, though similar for number and severity, were reported in the three LAI groups. Conclusion: Our results suggest that both first- and second-generation LAI-APDs represent important therapeutic options, useful for improving schizophrenia’s clinical course and its economic burden. Our study, which offers a wide and comprehensive observation of real-world clinical settings, combined an effectiveness evaluation through mirror analysis performed for each individual patient to a subsequent comparison among the three LAI-APDs, allowing us a more complete evaluation of clinical efficacy

Endovascular aortic graft infection resulting in retroperitoneal abscess: report of a case

Infection is a rare complication of aortoiliac endovascular procedures, with an incidence inferior to 0.5%, and it may result in a retroperitoneal abscess potentially evolving to sepsis and gastrointestinal bleeding. In more than 50% of cases endovascular aortoiliac prosthetic grafts infection occur months or years after the procedure. The growing number of endovascular procedures, and as the actually midterm follow up in most cases, septic sequelae will no doubt continue to occur with increased frequency and may represent an emerging problem in the ED for the emergency physician. Endovascular graft infection begins with unspecific clinical manifestations. An high index of suspicion in any patient with an aortic stent graft presenting prolonged or recurrent fever and or abdominal or back pain and a low threshold for obtaining CT scan should increase the clinician's ability to make a timely diagnosis in the ED setting

Stroke Gait Rehabilitation: A Comparison of End-Effector, Overground Exoskeleton, and Conventional Gait Training

Gait recovery is one of the main goals of post-stroke rehabilitation and Robot-Assisted Gait Training (RAGT) has shown positive outcomes. However, there is a lack of studies in the literature comparing the effects of different devices. This paper aims to study the effects, in terms of clinical and gait outcomes, of treadmill-based and overground RAGT, compared to conventional gait training in stroke subjects. The results showed a significant improvement of clinical outcomes in both robotic treatments and in conventional therapy. The performance of locomotor tasks was clinically significant in the robotic groups only. The spatio-temporal gait parameters did not reveal any significant difference. Results suggest future multicentre studies on a larger number of subjects

Association between proton-pump inhibitors (PPI) and metronomic capecitabine (MCAP) as salvage treatment for patients with advanced gastro-intestinal tumoursa. A randomized phase II study

Background: Several researches have shown that acidification of tumor microenvironment is the basis for tumor invasiveness, ability to metastasize S382 Abstracts and cytotoxic agents resistance; therefore proton pump inhibitors (PPI) could significantly increase the chemosensitivity. In our retrospective work we have investigated the role of capecitabine (mCAP) at metronomic dosage of 1500 mg/die as salvage chemotherapy in patients with metastatic colorectal cancer, showing a moderately activity and well tolerability. In this prospective study we evaluated safety and activity of mCAP in the advanced gastro-intestinal patients and the putative chemosensitizing activity of a specific PPI (Rabeprazole) in association to this therap

Diagnostic accuracy and applicability of intestinal auto-antibodies in the wide clinical spectrum of coeliac disease

BACKGROUND: Intestinal coeliac auto-antibodies are the marker of coeliac disease (CD). Since the determination of these antibodies is still not widely available, we used immunoassays to identify the most suitable technology for revealing intestinal auto-antibodies in the wide clinical spectrum of CD. METHODS: Intestinal auto-antibodies have been prospectively investigated in CD suspected children using two immunoassays: intestinal-deposits of IgA anti-tissue transglutaminase antibodies (anti-tTG) and biopsy-culture IgA anti-endomysium (AEA). Intestinal IgM antibodies have been determined in IgA-deficient subjects. FINDINGS: Two-hundred and twenty-one suspected CD patients were enrolled. Intestinal antibodies were tested positive for both assays in classical CD patients (n\u202f=\u202f178) with villous atrophy and positive serum-CD antibodies, potential CD patients (n\u202f=\u202f16) with normal intestinal mucosa and positive serum-CD antibodies, and pre-potential CD patients (n\u202f=\u202f14) with normal intestinal mucosa and negative serum-CD antibodies. In 13/221 with normal intestinal mucosa, negative CD-serum antibodies and negative intestinal antibodies CD has been excluded. All classical, 14/16 potential and 11/14 pre-potential CD patients on gluten-free diet (GFD) improved their symptoms. In 9/11 pre-potential patients intestinal antibodies disappeared on GFD. Both assays were negative in 69/71 control subjects. The two assays showed high diagnostic sensitivity (100%) and specificity (99%). INTERPRETATION: Intestinal CD-antibodies make prompt diagnosis in the wide clinical spectrum of CD reducing the delay in diagnosis and treatment, especially in pre-potential CD patients. The easy handling biopsy culture assay is an effective diagnostic tool which should be carried out by any gastroenterology unit to recognize all CD clinical manifestations

QTL analysis on a lemon population provides novel insights on the genetic regulation of the tolerance to the two-spotted spider mite attack

Background: Among the Citrus species, lemon (Citrus limon Burm f.) is one of the most affected by the two-spotted spider mite (Tetranychus urticae Koch). Moreover, chemical control is hampered by the mite's ability to develop genetic resistance against acaricides. In this context, the identification of the genetic basis of the host resistance could represent a sustainable strategy for spider mite control. In the present study, a marker-trait association analysis was performed on a lemon population employing an association mapping approach. An inter-specific full-sib population composed of 109 accessions was phenotyped through a detached-leaf assays performed in modified Huffaker cells. Those individuals, complemented with two inter-specific segregating populations, were genotyped using a target-sequencing approach called SPET (Single Primer Enrichment Technology), the resulting SNPs were employed for the generation of an integrated genetic map. Results: The percentage of damaged area in the full-sib population showed a quantitative distribution with values ranging from 0.36 to 9.67%. A total of 47,298 SNPs were selected for an association mapping study and a significant marker linked with resistance to spider mite was detected on linkage group 5. In silico gene annotation of the QTL interval enabled the detection of 13 genes involved in immune response to biotic and abiotic stress. Gene expression analysis showed an over expression of the gene encoding for the ethylene-responsive transcription factor ERF098-like, already characterized in Arabidopsis and in rice for its involvement in defense response. Conclusion: The identification of a molecular marker linked to the resistance to spider mite attack can pave the way for the development of marker-assisted breeding plan for the development of novel selection coupling favorable agronomical traits (e.g. fruit quality, yield) with a higher resistance toward the mit

Ask Doctor Smartphone! An App to Help Physicians Manage Foreign Body Ingestions in Children

Abstract: Background: Foreign body ingestion (FBI) represents the most common cause of emergent gastrointestinal endoscopy in children. FBI’s management can be quite challenging for physicians because of the variability of the clinical presentation, and the decision tree becomes even more intricate because of patient-specific variables that must be considered in the pediatric age range (e.g., age of patients and neuropsychiatric disorders) in addition to the mere characteristics of the foreign body. We present an application for smartphones designed for pediatricians and pediatric surgeons based on the latest guidelines from the official pediatric societies. The app aims to help physicians manage FBI quickly and properly in children. Materials and methods: The latest pediatric FBI management guidelines were reviewed and summarized. The flow chart we obtained guided the development of a smartphone application. A questionnaire was administered to all pediatric surgeon trainees at our institute to test the feasibility and helpfulness of the application. Results: An app for smartphones was obtained and shared for free on the Google Play Store and Apple Store. The app guides the physician step by step in the diagnostic process, analyzing all patient- and foreign body-specific characteristics. The app consultation ends with a suggestion of the most proper decision to make in terms of further radiological investigations and the indication and timing of endoscopy. A questionnaire administered to trainees proved the app to be useful and easy to use. Conclusion: We developed an app able to help pediatricians and pediatric surgeons manage FBI in children, providing standardized and updated recommendations in a smart and easily available way

Histologic analysis of idiopathic pulmonary fibrosis by morphometric and fractal analysis

: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disorder, ultimately leading to respiratory failure and death. Despite great research advances in understanding the mechanisms underlying the disease, its diagnosis, and its treatment, IPF still remains idiopathic without known biological or histological markers able to predict disease progression or response to treatment. The histologic hallmark of IPF is usual interstitial pneumonia (UIP), with its intricate architectural distortion and temporal inhomogeneity. We hypothesize that normal lung alveolar architecture can be compared to fractals, such as the Pythagoras tree with its fractal dimension (Df), and every pathological insult, distorting the normal lung structure, could result in Df variations. In this study, we aimed to assess the UIP histologic fractal dimension in relationship to other morphometric parameters in newly diagnosed IPF patients and its possible role in the prognostic stratification of the disease. Clinical data and lung tissue specimens were obtained from twelve patients with IPF, twelve patients with non-specific interstitial pneumonia (NSIP), and age-matched "healthy" control lung tissue from patients undergoing lung surgery for other causes. Histology and histomorphometry were performed to evaluate Df and lacunarity measures, using the box counting method on the FracLac ImageJ plugin. The results showed that Df was significantly higher in IPF patients compared to controls and fibrotic NSIP patients, indicating greater architectural distortion in IPF. Additionally, high Df values were associated with higher fibroblastic foci density and worse prognostic outcomes in IPF, suggesting that Df may serve as a potential novel prognostic marker for IPF. The scalability of Df measurements was demonstrated through repeated measurements on smaller portions from the same surgical biopsies, which were selected to mimic a cryobiopsy. Our study provides further evidence to support the use of fractal morphometry as a tool for quantifying and determining lung tissue remodeling in IPF, and we demonstrated a significant correlation between histological and radiological Df in UIP pattern, as well as a significant association between Df and FF density. Furthermore, our study demonstrates the scalability and self-similarity of Df measurements across different biopsy types, including surgical and smaller specimens

Genomic landscape and survival analysis of ctDNA “neo-RAS wild-type” patients with originally RAS mutant metastatic colorectal cancer

Background: The term “neo-RAS wild-type” refers to the switch to RAS wild-type disease in plasma circulating tumor DNA (ctDNA) from originally RAS mutant colorectal cancers. Consistently, the hypothesis to re-determine RAS mutational status in ctDNA at disease progression in RAS mutant mCRC opened to a new perspective for clinically-based selection of patients to be treated with EGFR inhibitors. Currently, the genomic landscape of “neo-RAS wild-type” is unknown. This is a prospective study aimed to investigate clinical and genomic features associated with RAS mutation clearance in a large cohort of RAS mutant mCRC patients who converted to RAS wild- type in liquid biopsy at failure of first-line treatments. Secondary aim was to investigate the long term prognostic significance of “true neo-RAS wild- type”. Patients and methods: 70 patients with stage IV RAS mutant colorectal cancer were prospectively enrolled. Plasma samples were collected at progression from first-line treatment. RAS/BRAF mutations in plasma were assessed by RT-PCR. In RAS/BRAF wild-type samples, ctDNA was used to generate libraries using a 17 genes panel whose alteration has clinical relevance. To investigate the prognostic significance of RAS mutation clearance, test curves for PFS and OS were represented by Kaplan-Meier estimator plot and Log-rank test. Results: The most commonly detected actionable mutations in “neo-RAS wild-type” were: PIK3CA (35.7%); RET (11.9%); IDH1 (9.5%); KIT (7%); EGFR (7%); MET (4.7%); ERBB2 (4.7%); FGFR3 (4.7%). Both OS and post-progression survival were longer in patients with “neo-RAS wild-type” compared to those who remained RAS mutant (p<0.001 for both). Conclusions: De-novo-targetable mutations occured in a large percentage of “neo-RAS wild-type”, being PIK3CA the most commonly detected. RAS mutation clearance in ctDNA is associated with long- term improvement of overall survival