Computational Simulator Models and Invasive Hemodynamic Monitoring as Tools for Precision Medicine in Pulmonary Arterial Hypertension

Precision medicine, providing the right therapeutic strategy for the right patient, could revolutionize management and prognosis of patients affected by cardiovascular diseases. Big data and artificial intelligence are pivotal for the realization of this ambitious design. In the setting of pulmonary arterial hypertension (PAH), the use of computational models and data derived from ambulatory implantable hemodynamic monitors could provide useful information for tailored treatment, as requested by precision medicine.

Neurogenic Inflammation in the Context of Endometriosis—What Do We Know?

Endometriosis (EM) is an estrogen-dependent disease characterized by the presence of epithelial, stromal, and smooth muscle cells outside the uterine cavity. It is a chronic and debilitating condition affecting ~10% of women. EM is characterized by infertility and pain, such as dysmenorrhea, chronic pelvic pain, dyspareunia, dysuria, and dyschezia. Although EM was first described in 1860, its aetiology and pathogenesis remain uncertain. Recent evidence demonstrates that the peripheral nervous system plays an important role in the pathophysiology of this disease. Sensory nerves, which surround and innervate endometriotic lesions, not only drive the chronic and debilitating pain associated with EM but also contribute to a growth phenotype by secreting neurotrophic factors and interacting with surrounding immune cells. Here we review the role that peripheral nerves play in driving and maintaining endometriotic lesions. A better understanding of the role of this system, as well as its interactions with immune cells, will unearth novel disease-relevant pathways and targets, providing new therapeutics and better-tailored treatment options.

127 SARS-CoV-2 pandemic: post-lockdown subclinic cardiovascular events detected by 12-leads electrocardiogram at Emergency Department

Aims Few data are available regarding changes in mitral regurgitation (MR) severity with guideline-directed medical therapy (GDMT) in heart failure (HF). We evaluated the evolution and impact of MR after GDMT in the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF). Methods and results A retrospective post hoc analysis was performed on HF patients from BIOSTAT-CHF with available data on MR status at baseline and at 9-month follow-up after GRMT optimization. The primary endpoint was a composite of all-cause death or HF hospitalization. Among 1022 patients with data at both time-points, 462 (45.2%) had moderate-severe MR at baseline and 360 (35.2%) had it at 9-month follow-up. Regression of moderate–severe MR from baseline to 9 months occurred in 192/462 patients (41.6%) and worsening from baseline to moderate–severe MR at 9 months occurred in 90/560 patients (16.1%). The presence of moderate–severe MR at 9 months, independent from baseline severity, was associated with an increased risk of the primary endpoint [unadjusted hazard ratio (HR), 2.03; 95% confidence interval (CI), 1.57–2.63; P < 0.001], also after adjusting for the BIOSTAT-CHF risk-prediction model (adjusted HR, 1.85; 95% CI, 1.43–2.39; P < 0.001). Younger age, LVEF ≥50% and treatment with higher ACEi/ARB doses were associated with a lower likelihood of moderate–severe MR at 9 months, whereas older age was the only predictor of worsening MR. Conclusions Among patients with HF undergoing GDMT optimization, ACEi/ARB up-titration and HFpEF were associated with MR improvement, and the presence of moderate–severe MR after GRMT was associated with worse outcome.

Molar Incisor Hypomineralization from Inception to Intervention–Evidence Based Review

Background: Molar Incisor Hypomineralization (MIH) is considered a highly prevalent clinical problem worldwide. The etiology of MIH involves a complex interaction between systemic and environmental insults with possible genetic contribution. Early diagnosis is facilitated by collaboration between clinicians responsible for oral health management of the patient and is the key for enhancing the long-term prognosis and quality of life of affected children. MIH management is a formidable oral health challenge due to the wide spectrum of clinical presentation with the need for tailored treatment for the child affected by MIH condition. Objective: To provide dental practitioners with an updated and evidence-based overview of MIH etiology, diagnosis, and treatments modalities available for its management. Conclusion: In this review, recent clinical evidence on MIH etiology, diagnosis and treatment is presented. Given recent availability of sophisticated technologies there is an increasing number of treatment modalities now at the fingertips of all oral health clinicians alike, ranging from preventive measures, management of hypersensitivity to advanced restorative techniques. The tailored treatment plan should encompass a short and long-term approach requiring more frequent dental check-ups in order to achieve better outcomes and prognosis. Future translational clinical research to best practice that will enhance our understanding of the exact causes of MIH and allow development of standardized diagnostic criteria as well as optimal treatment strategies are warranted.

Comparison of Effectiveness of Phonological and Whole-Word Treatment Programmes within Two Dyslexia Subtypes

<p>This thesis compares the effectiveness of two reading treatment programmes, each developed to address the key difficulties of two subtypes of developmental dyslexia - phonological and surface dyslexia, respectively. Previous cognitive neuropsychological research has commonly administered a single tailored treatment programme to each individual. However, this research administers both programmes to individuals from each subtype, and compares their effectiveness. In Experiment 1, a large group of reading-delayed children was screened, and, using Coltheart and Leahy's (1996) criteria, three children were identified as surface dyslexic and seven as phonological dyslexic. All were aged between 9 and 13 years. Following completion of a range of background tests to assess cognitive abilities potentially correlated with dyslexia, each child received two treatment programmes: 1) a phonologically-based programme training grapheme-to-phoneme correspondences (based on Broom and Doctor, 1995b) and 2) a whole-word programme (specifically designed for the current research), with pre- and post-tests throughout. Results indicated that all children significantly improved their reading of the trained words following both training programmes, regardless of subtype. For both subtypes, generalisation to untrained words was observed following the Phonological Programme, but not the Whole-word Programme. In Experiment 2, a second, more case-based investigation was conducted, focussing on one phonological dyslexic and one surface dyslexic, who were selected following extensive screening. Both were aged 10 years 11 months. Experiment 2 also examined the effectiveness of specific whole-word techniques. Results indicated a clear distinction between the responsiveness of the two participants, with each favouring their target treatment programme: the Phonological Programme was more effective for the phonological dyslexic than the Whole-word Programme, and vice versa for the surface dyslexic. The implications are discussed, with particular reference to suggestions for remediating reading disorders.</p>

Comparison of Effectiveness of Phonological and Whole-Word Treatment Programmes within Two Dyslexia Subtypes

<p>This thesis compares the effectiveness of two reading treatment programmes, each developed to address the key difficulties of two subtypes of developmental dyslexia - phonological and surface dyslexia, respectively. Previous cognitive neuropsychological research has commonly administered a single tailored treatment programme to each individual. However, this research administers both programmes to individuals from each subtype, and compares their effectiveness. In Experiment 1, a large group of reading-delayed children was screened, and, using Coltheart and Leahy's (1996) criteria, three children were identified as surface dyslexic and seven as phonological dyslexic. All were aged between 9 and 13 years. Following completion of a range of background tests to assess cognitive abilities potentially correlated with dyslexia, each child received two treatment programmes: 1) a phonologically-based programme training grapheme-to-phoneme correspondences (based on Broom and Doctor, 1995b) and 2) a whole-word programme (specifically designed for the current research), with pre- and post-tests throughout. Results indicated that all children significantly improved their reading of the trained words following both training programmes, regardless of subtype. For both subtypes, generalisation to untrained words was observed following the Phonological Programme, but not the Whole-word Programme. In Experiment 2, a second, more case-based investigation was conducted, focussing on one phonological dyslexic and one surface dyslexic, who were selected following extensive screening. Both were aged 10 years 11 months. Experiment 2 also examined the effectiveness of specific whole-word techniques. Results indicated a clear distinction between the responsiveness of the two participants, with each favouring their target treatment programme: the Phonological Programme was more effective for the phonological dyslexic than the Whole-word Programme, and vice versa for the surface dyslexic. The implications are discussed, with particular reference to suggestions for remediating reading disorders.</p>

EP.FRI.181 Beyond the adenoma- carcinoma sequence. A review of the morphogenetic basis of colorectal cancer

Introduction Looking beyond the adenoma carcinoma sequence researchers have discovered alternate morpho-genetic routes, and tumour biomarkers in colorectal cancer. This has caused a paradigm shift in the management, resulting in improved diagnosis, prevention, and delivery of tailored treatment aiming at specific molecular pathways. Aims, Methods This review summarises Methods PubMed, Google Scholar, NLM searches based on aims and key words were conducted. Further, academically and clinically relevant searches were made if more information was required. When required, references of articles were also retrieved. Results The two main theories regarding the morphological origins of colorectal cancer are the adenoma carcinoma sequence and the De-novo origins. The underlying genetic models are the (i) chromosomal instability pathway (CIN), (ii) the microsatellite instability pathway (MSI) and (iii) the CpG Island methylator phenotype (CIMP) pathways. Though unique, the pathways communicate with each other. The genetic fingerprinting of colorectal cancers has an impact on their tailored management and consequently a through grounding in the basics are essential for those in gastrointestinal subspecialties. Conclusions Two morphologically distinct pathways and three unique genetic mechanisms have been described. There are significant interactions between them. Behaviours of sporadic and inherited colorectal cancer, their treatment and prognosis depend on our understanding of these mechanisms and the availability of targeted therapies to assist surgical resection.

Patient positioning and immobilization procedures for hybrid MR-Linac systems

Hybrid magnetic resonance (MR)-guided linear accelerators represent a new horizon in the field of radiation oncology. By harnessing the favorable combination of on-board MR-imaging with the possibility to daily recalculate the treatment plan based on real-time anatomy, the accuracy in target and organs-at-risk identification is expected to be improved, with the aim to provide the best tailored treatment. To date, two main MR-linac hybrid machines are available, Elekta Unity and Viewray MRIdian. Of note, compared to conventional linacs, these devices raise practical issues due to the positioning phase for the need to include the coil in the immobilization procedure and in order to perform the best reproducible positioning, also in light of the potentially longer treatment time. Given the relative novelty of this technology, there are few literature data regarding the procedures and the workflows for patient positioning and immobilization for MR-guided daily adaptive radiotherapy. In the present narrative review, we resume the currently available literature and provide an overview of the positioning and setup procedures for all the anatomical districts for hybrid MR-linac systems.

943 Beyond the Adenoma Carcinoma Sequence

Introduction Looking beyond the adenoma carcinoma sequence researchers have discovered alternate morpho-genetic routes, and tumour biomarkers in colorectal cancer. This has caused a paradigm shift in the management, resulting in improved diagnosis, prevention, and delivery of tailored treatment aiming at specific molecular pathways. Aim This review summarises Method PubMed, Google Scholar, NLM searches based on aims and key words were conducted. Further, academically, and clinically relevant searches were made if more information was required. When required, references of articles were also retrieved. Results The two main theories regarding the morphological origins of colorectal cancer are the adenoma carcinoma sequence and the De-novo origins. The underlying genetic models are the (i) chromosomal instability pathway (CIN), (ii) the microsatellite instability pathway (MSI) and (iii) the CpG Island methylator phenotype (CIMP) pathways. Though unique, the pathways communicate with each other. The genetic fingerprinting of colorectal cancers has an impact on their tailored management and consequently a through grounding in the basics are essential for those in gastrointestinal subspecialties. Conclusions Two morphologically distinct pathways and three unique genetic mechanisms have been described. There are significant interactions between them. Behaviours of sporadic and inherited colorectal cancer, their treatment and prognosis depend on our understanding of these mechanisms and the availability of targeted therapies to assist surgical resection.