Homogeneous Group Of Patients Research Articles

The Evolving Landscape: Exploring the Future of Myelodysplastic Syndrome Treatment with Dr. Rami Komrokji.

This perspective delves into the evolving landscape of Myelodysplastic Syndrome (MDS) treatment. MDS presents a significant clinical challenge, often progressing to acute myeloid leukemia. For low-risk MDS, the emphasis is on personalized care through comprehensive risk assessment, clinical monitoring, and tailored interventions, including promising agents like erythropoiesis-stimulating agents, lenalidomide, and luspatercept, with the anticipation of an expanding therapeutic arsenal and early intervention for improved outcomes. In contrast, high-risk MDS treatment is evolving towards upfront doublet or triplet therapies with a focus on minimal residual disease (MRD) monitoring. A holistic approach integrates various modalities, including stem cell transplant and post-transplant maintenance, all guided by individual patient circumstances. Risk-adapted strategies are crucial for enhancing patient outcomes. Precision medicine for MDS treatment is budding, largely driven by Next Generation Sequencing (NGS). NGS aids in early diagnosis, prognostication, and the targeting of specific mutations, with molecular data increasingly informing treatment responses and allowing for tailored interventions. Clinical trials within homogeneous patient groups with similar molecular profiles are becoming more common, enhancing treatment precision. In conclusion, the future of MDS treatment is moving towards personalized medicine, leveraging advanced technologies like NGS and molecular insights to improve outcomes in the realm of hematological malignancies.

New ACR/EULAR 2022 classification criteria for ANCA-associated vasculitis

The new 2022 classification criteria for antineutrophil cytoplasmic antibodies associated vasculitis (AAV), proposed by the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR), was an important stage in the development of the doctrine of systemic vasculitis. Based on the analysis of large international cohorts, the criteria for granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis were revised, and classification criteria for microscopic polyangiitis were proposed for the first time. The creation’s history of the AAV classification criteria is discussed over the past three decades, and their limitations are considered. It should be noted, the ACR/EULAR 2022 criteria were developed for creating homogeneous groups of patients for scientific studies and cannot be widely used in clinical practice for the various AAV nosological forms diagnosis, primarily at early stage of the disease or mono organ damage (for example, kidneys). As before, decisive importance in AVV diagnostic belong to a detailed clinical analysis and a complete examination of patients to identify pathognomonic symptoms, including asymptomatic ones.

The Effect of Neoadjuvant Therapy on Esophagectomy for cT2N0M0 Esophageal Adenocarcinoma.

For cT2N0M0 esophageal adenocarcinomas, the effects of neoadjuvant chemoradiotherapy (NT) on surgical outcomes and the oncological benefits to the patients are debatable. In this study, we investigated the optimal management for cT2N0M0 adenocarcinoma (1) assessing the perioperative impact of NT on esophagectomy and (2) evaluating the oncologic effect of NT in a homogeneous group of patients with clinical stage IIA. We hypothesized that NT does not negatively affect perioperative outcomes and provides an oncologic benefit to selected patients with cT2N0M0 disease. The National Cancer Database was queried (2010-2019) for patients with cT2N0M0 esophageal adenocarcinoma undergoing esophagectomy. After propensity-matching to adjust for differences in patient and tumor characteristics, we compared postoperative outcomes (logistic regression) and survival (Kaplan-Meier and Cox regression) among those who underwent NT vs upfront surgery (S). This study included 3413 patients, of whom 2359 (69%) received NT, and 1054 (31%) S. In contrast to those who underwent S, in the matched cohort, patients treated with NT had comparable conversion rates (8% vs11.1%, p = 0.06), length of stay (9 vs 10 days, p = 0.078), unplanned readmission (5.4% vs 8.8%, p = 0.109), and 30- (3.9% vs 3.7%, p = 0.90) and 90-day mortality (5.7% vs 4.7%, p = 0.599). In addition, NT associated with improved survival in patients with cT2N0M0 tumors > 5 cm (HR 0.30, 95% CI 0.17-0.36). NT does not appear to increase technical complexity or to adversely affect postoperative outcomes after esophagectomy. Furthermore, minimally invasive esophagectomy is feasible following NT, with comparable conversion rates to those who had upfront surgery. Lastly, NT was selectively associated with improved survival in patients with cT2N0M0 esophageal cancer.

Characterising diabetes in Kazakhstan: a cluster analysis

Abstract Background Diabetes is a global pandemic, affecting 537 million adults worldwide in 2021. Diabetes is much more complex than the classification into type 1 diabetes and type 2 diabetes suggests. We aimed to identify homogeneous groups of patients with diabetes based on routinely collected measurements using unsupervised, data-driven cluster analysis. Methods We analyzed the data from Electronic Medical Records of 558 patients with newly diagnosed diabetes from 4 outpatient clinics in Astana. We performed a k-means cluster analysis of 9 routinely measured variables using the KMeans function (iterations=3 million) from the Scikit-Learn Python library. Results Cluster 1, consisting of 176 (31,5%) patients, was defined by late-onset diabetes, relatively low blood pressure (BP) and body mass index (BMI), moderate metabolic derangements, and comparably low glomerular filtration rate (GFR). The 83 (14,9%) patients in cluster 2 were characterized by a late manifestation of diabetes, high BP and BMI, relatively poor glycemic control, moderate dyslipidemia, and comparably low GFR. Cluster 3, including 98 (17,6%) patients, was represented by a low age at onset, comparably low BP and BMI, moderately poor glycemic and lipid controls, and high GFR. The 110 (19,7%) patients in cluster 4 had late-onset diabetes, high BP and BMI, subcompensated diabetes, poor lipid control, and relatively low GFR. Cluster 5, which involved 91 (16,3%) patients, was characterized by comparably low BP and BMI, poor glycemic control, modest dyslipidemia, and high GFR. Conclusions We intend to continue the project for further conducting a prospective study with dynamic monitoring of study participants, tracking specific patterns in the development of diabetic complications in each cluster. The results of this work will contribute to the development of a model for identifying patients with an initially predictable course of diabetes and a high risk of its complications at the time of diagnosis. Key messages • We identified five clusters of patients with diabetes with clinically significant characteristics in each cluster. • Identification of subgroups of patients with an initially predictable course can be useful for recognizing those at highest risk of complications and applying personalized treatment strategies.

Identification of shared disease marker genes and underlying mechanisms between major depression and rheumatoid arthritis

Both depression and rheumatoid arthritis (RA) have a very high comorbidity rate. A bilateral association is estimated to increase the mutual risk and the common denominator is inflammation being observed in both diseases. Previous studies have mainly focused on assessing peripheral blood's inflammatory and pro-inflammatory cytokines levels.We aimed to extend insights into the molecular mechanisms of depression based on hub RA genes. To do so, we prioritized RA-related genes using in-silico tools. We then investigated whether RA-related genes undergo altered expression in patients with unipolar and bipolar depression without a concurrent RA diagnosis and any exponents of active inflammation. In addition, we selected a homogeneous group of patients treated with lithium (Li), which has immunomodulatory properties.The study was performed on patients with bipolar depression (BD, n = 45; Li, n = 20), unipolar depression (UD, n = 27), and healthy controls (HC, n = 22) of both sexes. To identify DEGs in peripheral blood mononuclear cells (PBMCs), we used the SurePrint G3 Microarray and GeneSpring software.We selected a list of 180 hub genes whose altered expression we analyzed using the expression microarray results. In the entire study group, we identified altered expression of 93 of the 180 genes, including 35 down-regulated (OPRM1 gene with highest FC > 3) and 58 up-regulated (TLR4 gene with highest FC > 3). In UD patients, we observed maximally up-regulated expression of the TEK gene (FC > 3), and in BD of the CXCL8 gene (FC > 5). On the other hand, in lithium-treated patients, the gene with the most reduced expression was the TRPV1 gene.The study proved that depression and RA are produced by a partially shared “inflammatory interactome” in which the opioid and angiogenesis pathways are important.

Relationship of End Expiratory Lung Volume, Compliance, and Plateau Pressure in Acute Respiratory Distress Syndrome.

COVID-19 ARDS (acute respiratory distress syndrome), caused by SARS-CoV-2,involves a decrease in the end expiratory lung volume (EELV), compliance, and hypoxemia. The authors retrospectively analysed the relationship between the EELV, Plateau pressure (Pplat), and compliance of the respiratory system in a group of 21 mechanically ventilated COVID ARDS patients with moderate to severe hypoxia who were subjected to a recruitment manoeuvre. Further, these parameters were studied after dividing them into two groups as Group 1 of clinically non-recruitable and Group 2 of clinically recruitable patients.There was relationship between EELV, compliance, and Pplat among those patients who were clinically recruited versus those who were not in a homogeneous group of COVID ARDS patients. In Group 1, the statistical value of EELV and compliance were r = 0.395, p>0.05, EELV and Pplat were r = 0.021, p>0.05, and compliance and Pplat were r = -0.848, p<0.001. In Group 2, the statistical values of EELV and compliance were (r = 0.605, p<0.001), EELV and Pplat were r = -0.391, p<0.05, compliance and Pplat were r = -0.848, p<0.001. The additional information gained after understanding this relationship can help to optimise ventilator settings. Key Words: COVID, ARDS, End expiratory lung volume, Plateau pressure, Compliance, Recruitment, Ventilation.

Metalloproteinase-2 in failed back surgery syndrome caused by epidural fibrosis: can it play a role in persistent pain?

Failed Back Surgery Syndrome (FBSS) occurs in 10-40% of patients treated surgically due to disk herniation (DH). There are several factors that can cause a predisposition to FBSS, but the exact pathomechanism has not been elucidated. The aim of this study was to investigate Metalloproteinase-2 (MMP-2) and Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) activities in a homogeneous group of FBSS patients with epidural fibrosis in comparison to its activity in patients with surgically treated DH. DH, FBSS, and control (CG) groups consisted of 30 subjects. The patients were assessed clinically by the Numerical Rating Scale (NRS), McGill Pain Questionnaire (SF -MPQ), Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI). Serum concentrations of MMP-2 and TIMP-2 were measured by using the immunoenzymatic method. There was a significantly higher MMP-2 expression (medians: 4797.49 vs. 2656.65; p < 0.0001) and TIMP-2 concentration (medians: 166.40 vs. 109.60; p < 0.0001) in the DH compared to the CG. Significantly higher MMP-2 expression (4219.95 vs. 2656.65; p < 0.0001) and TIMP-2 concentration (medians: 150.17 vs. 109.60; p = 0.0003) were also found in the FBSS compared to the CG. The activity of MMP-2, measured as MMP-2/TIMP-2, did not significantly change between the DH, FBSS, and CG. MMP2 expression (p < 0.0001) and TIMP-2 concentration (p < 0.0001) were significantly higher in the DH than FBSS. Results indicate the presence of a contribution of MMP-2 and TIMP-2 in DH and FBSS. Unchanged activity of MMP-2 can indicate an insufficiency in the MMP-2 repair system in both diseases. Lower MMP-2 expression and TIMP-2 concentration in the FBSS group can reflect the chronicity of the process.

P21.06.A TIME IN ONCOLOGY. GLIOBLASTOMA REAL-WORLD DATA

Abstract BACKGROUND Time is a crucial component in all diagnostic and therapeutic processes of cancer. Retard in the treatment can have adverse consequences on outcomes. Total treatment delays could be due to patient interval (from the first perceived symptom to the first medical consultation) and system interval (from the first medical consultation to end of treatment). To minimize delays, it is essential to know the time intervals elapsed between each of the steps in the diagnostic and the treatment phase.The purpose of this pilot study is to holistically analyze the total treatment interval of cancer patients as a part of process-oriented total quality management with the ultimate intention of having more useful information for benchmarking and making decisions to improve time in oncology. MATERIAL AND METHODS During 2019 in a context of public health-care system all relevant clinical pathway time data from the patient’s perceived first symptom until the end of oncological treatment were collected in a prospective cohort of newly diagnosed glioblastoma patients. Clinical pathway is defined as a description of the current practice in an homogeneous patient group treated by a multidisciplinary team and an inventory of actions defining a diagnostic and therapeutic sequence. This cohort was compared with a serie of glioblastoma patients treated in 2020 (COVID-19-year). We analyzed the mean, median and quartile data of 16-time intervals represented on a time scale RESULTS From January 1 to December 31, 2019, we collected data from 59 patients diagnosed and treated for a glioblastoma. There were 24 women and 35 men with a mean age of 60,9 years. We collected 1062 time-points. This group was compared with a COVID-19-year cohort of 49 patients (14 women and 35 men with a mean age of 61,7 years and 630 time-points). The median patient interval time and the system interval time were 6 days (0-210) vs 5 (0-150) and 240 days (81-363) vs 255 (120-482) respectively. Median time from surgery to the start of adjuvancy was 34 days (19-56) vs 34 (17-108). No differences were found in any of the intervals analyzed, in the overall treatment time of radiotherapy or in the dose intensity of chemotherapy. CONCLUSION The routine measurement of the intervals between the different diagnostic and therapeutic actions is essential to monitor the time of clinical processes in terms of quality and benchmarking. It is also essential to standardize in a holistic way the distressing temporality in oncology.

Cognitive effect of antiseizure medications in medial temporal lobe epilepsy.

The specific effects of antiseizure medications (ASMs) on cognition are a rich field of study, with many ongoing questions. The aim of this study was to evaluate these effects in a homogeneous group of patients with epilepsy to guide clinicians to choose the most appropriate medications. We retrospectively identified 287 refractory patients with medial temporal lobe epilepsy associated with hippocampal sclerosis. Scores measuring general cognition (global, verbal and performance IQ), working memory, episodic memory, executive functions, and language abilities were correlated with ASM type, number, dosage and generation (old vs. new). We also assessed non-modifiable factors affecting cognition, such as demographics and epilepsy-related factors. Key parameters were total number of ASMs and specific medications, especially topiramate (TPM) and sodium valproate (VPA). Four cognitive profiles of the ASMs were identified: (i) drugs with an overall detrimental effect on cognition (TPM, VPA); (ii) drugs with negative effects on specific areas: verbal memory and language skills (carbamazepine), and language functions (zonisamide); (iii) drugs affecting a single function in a specific and limited area: visual denomination (oxcarbazepine, lacosamide); and (iv) drugs without documented cognitive side effects. Non-modifiable factors such as age at testing, age at seizure onset, and history of febrile seizures also influenced cognition and were notably influenced by total number of ASMs. We conclude that ASMs significantly impact cognition. Key parameters were total number of ASMs and specific medications, especially TPM and VPA. These results should lead to a reduction in the number of drugs received and the avoidance of medications with unfavorable cognitive profiles.

AML with CEBPA mutations: A comparison of ICC and WHO-HAEM5 criteria in patients with 20% or more blasts

AML with CEBPA mutation and AML with in-frame bZIP CEBPA mutations define favorable-risk disease entities in the proposed 5th edition of the World Health Organization Classification (WHO-HAEM5) and the International Consensus Classification (ICC), respectively. However, the impact of these new classifications on clinical practice remains unclear. We sought to assess the differences between the ICC and WHO-HAEM5 for AML with CEBPA mutation. 741 AML patients were retrospectively analyzed. Cox proportional-hazard regression was used to identify factors predictive of outcome. A validation cohort from the UK-NCRI clinical trials was used to confirm our findings. 81 (11%) AML patients had CEBPA mutations. 39 (48%) patients met WHO-HAEM5 criteria for AML with CEBPA mutation, among which 30 (77%) had biallelic CEBPA mutations and 9 (23%) had a single bZIP mutation. Among the 39 patients who met WHO-HAEM5 criteria, 25 (64%) also met ICC criteria. Compared to patients only meeting WHO-HAEM5 criteria, patients with in-frame bZIP CEBPA mutations (ie. meeting both WHO-HAEM5 and ICC criteria) were younger, had higher bone marrow blast percentages and CEBPA mutation burden, infrequently harboured 2022 ELN high-risk genetic features and co-mutations in other genes, and had superior outcomes. The associations in clinicopathological features and outcomes between the CEBPA-mutated groups were validated in the UK-NCRI cohort. Our study indicates that in-frame bZIP CEBPA mutations are the critical molecular aberrations associated with favorable outcomes in AML patients treated with curative intent chemotherapy. Compared to WHO-HAEM5, the ICC identifies a more homogenous group of CEBPA-mutated AML patients with favorable outcomes.

Core protocol development for phase 2/3 clinical trials in the leukodystrophy vanishing white matter: a consensus statement by the VWM consortium and patient advocates

BackgroundThe leukodystrophy “Vanishing White Matter” (VWM) is an orphan disease with neurological decline and high mortality. Currently, VWM has no approved treatments, but advances in understanding pathophysiology have led to identification of promising therapies. Several investigational medicinal products are either in or about to enter clinical trial phase. Clinical trials in VWM pose serious challenges, as VWM has an episodic disease course; disease phenotype is highly heterogeneous and predictable only for early onset; and study power is limited by the small patient numbers. To address these challenges and accelerate therapy delivery, the VWM Consortium, a group of academic clinicians with expertise in VWM, decided to develop a core protocol to function as a template for trials, to improve trial design and facilitate sharing of control data, while permitting flexibility regarding other trial details. Overall aims of the core protocol are to collect safety, tolerability, and efficacy data for treatment assessment and marketing authorization.MethodsTo develop the core protocol, the VWM Consortium designated a committee, including clinician members of the VWM Consortium, family and patient group advocates, and experts in statistics, clinical trial design and alliancing with industries. We drafted three age-specific protocols, to stratify into more homogeneous patient groups, of ages ≥ 18 years, ≥ 6 to < 18 years and < 6 years. We chose double‐blind, randomized, placebo-controlled design for patients aged ≥ 6 years; and open-label non-randomized natural-history-controlled design for patients < 6 years. The protocol describes study populations, age-specific endpoints, inclusion and exclusion criteria, study schedules, sample size determinations, and statistical considerations.DiscussionThe core protocol provides a shared uniformity across trials, enables a pool of shared controls, and reduces the total number of patients necessary per trial, limiting the number of patients on placebo. All VWM clinical trials are suggested to adhere to the core protocol. Other trial components such as choice of primary outcome, pharmacokinetics, pharmacodynamics, and biomarkers are flexible and unconstrained by the core protocol. Each sponsor is responsible for their trial execution, while the control data are handled by a shared research organization. This core protocol benefits the efficiency of parallel and consecutive trials in VWM, and we hope accelerates time to availability of treatments for VWM.Trial registrationNA. From a scientific and ethical perspective, it is strongly recommended that all interventional trials using this core protocol are registered in a clinical trial register.

(016) The Effect of Phosphodiesterase-5-inhibitor on Female Sexual Function: A Systematic Review and Meta-analysis

Abstract Introduction The link between the attainment of healthy sexual function and a high quality of life in women is well established. However, while the management of male sexual dysfunction has been afforded huge research and development, far less time and effort has been lent in the achievement of successful remedies for females experiencing sexual dysfunction. The use of oral phosphodiesterase type 5 (PDE5) inhibitors, such as Sildenafil, has been the mainstay of treatment for male sexual dysfunction for the last two decades. PDE5 inhibitors have been shown to initiate penile erection, through smooth muscle relaxation and the subsequent increase in intracellular cGMP levels. PDE5-containing cells, similar to those found in the penis, have also been confirmed within the clitoris. No previous pooled analysis has been performed, looking at the possible effect of PDE5 inhibitors on female sexual function, in a population comprising of heterosexual cisgender population. Objectives We aimed to perform a systematic review and meta-analysis of the best possible available studies, to evaluate the efficacy and safety of PDE5 inhibitors versus placebo when used in an exclusively female population. Methods We conducted a comprehensive search of electronic databases (MEDLINE, PubMed, EMBASE, CINAHL, CENTRAL, SCOPUS, Google Scholar, Web of Science, EBSCO Host, TRIP and Epistemonikos), identifying studies comparing the PDE5 inhibitors versus placebo, and the resultant effect on female sexual function. The Cochrane risk-of-bias tool for RCTs and the Newcastle-Ottawa scale for observational studies were used to assess the included studies. Random effects modelling was used to calculate pooled outcome data. Results Searches of electronic databases resulted in 67 articles, from which 13 randomised control trials (RCTs) met the eligibility criteria, enrolling a total of 1605 patients. The use of PDE5 inhibitor was associated with a significantly improved orgasm satisfaction (P=0.01), increased sexual arousal (P=0.02), increase in sexual satisfaction (P=0.007) when compared to placebo. The use of PDE5i was also found to have a significant association with the incidence of headaches (P&amp;lt;0.0001) and flushing (P&amp;lt;0.00001). Conclusions Our meta-analysis demonstrated that the use PDE5 inhibitor was associated with a significantly higher attainment of orgasm satisfaction, sexual arousal, and sexual satisfaction when administered to a solely female population, when compared with placebo. However, the use of PDE5 inhibitors was also associated with a significantly increased risk of headache and flushing. Further large-scale high-quality RCTs are required in order to further evaluate the potential role of PDE5i’s in women, particularly in those suffering from significant sexual dysfunction. These future studies should focus on a more homogenous patient group, with stricter definitions of inclusion criteria. Disclosure

O-098 Improved pregnancy rates following day 5 eSET with early hatching/hatched blastocysts (116-118 hours) compared to expanded blastocysts in a strictly selected cohort: a prospective study

Abstract Study question To investigate whether blastocysts hatching early on day 5 following IVF are developmentally superior and lead to better clinical outcomes in non PGT-A eSET cycles. Summary answer Fresh eSET on day 5 with spontaneously early hatching blastocysts (116-118 hrs) results in significantly better pregnancy rates compared to top quality expanded blastocyst transfers. What is known already Most studies seem to indicate that transfer of blastocysts at more advanced stages of development result in higher pregnancy rates. However, most studies comparing results between full/expanded vs hatching/hatched blastocyst transfers are either retrospective, have relaxed inclusion criteria, or perform transfers following assisted hatching or extended culture. Moreover, there appears to be no data on proportion of blastocysts that spontaneously hatch early on day 5, or how well they perform comparatively. Yet it has been reported that earlier time-points of blastocyst development are associated with higher euploidy. We felt the need for a well-designed prospective study to address these questions. Study design, size, duration This prospective study to compare pregnancy rates between early hatching/hatched blastocysts and top quality expanded blastocysts (4 BB or higher) in fresh, non PGT-A eSET cycles took place between October 2021 and October 2022 following institutional ethical clearance. 115 patients&amp;lt;37 years with AMH&amp;gt;1.5 undergoing 1st IVF cycles for tubal, mild male factor, unexplained infertility consented for the study and 94 patients completed it to eSET. Patients with PCOS, endometriosis or previous pelvic surgery were excluded. Participants/materials, setting, methods The study was conducted at a tertiary IVF centre. All patients underwent antagonist cycles, egg retrievals and IVF as per standard protocol. Blastocyst culture decision was taken at 2-PN examination. Embryos were examined at 116-118 hours as per our practise and decisions made to exclude from data analysis patients without at least one blastocyst at 4BB or above. eSETs performed at 120-122 hours with hatching/hatched blastocysts where available, expanded blastocysts in others. Luteal support initiated. Main results and the role of chance Demographic parameters of the patient cohort such as age (30.79±4.06), BMI (25.53±3.11) and AMH (3.23±1.68) are presented as mean± SD. Data was analysed using IBM SPSS V.26 statistical package. Differences in pregnancy rates between early hatching/hatched vs expanded blastocyst eSET groups were tested using Z test for proportions at 5% level of significance. Data was analysed for 94 patients of whom 62 had single expanded blastocyst transfers (22 achieved pregnancies) and 32 had eSET with early hatching/hatched blastocysts (of whom 18 became pregnant). 55 out of a total 261 blastocysts in the whole cohort were found to have initiated spontaneous hatching (n = 39) or fully hatched (n = 16) at 116-118 hours post-fertilisation resulting in an early hatching rate of 21.1% per blastocyst. Clinical pregnancy rate (CPR) defined as fetal heartbeat on ultrasound at 6 weeks of gestation and ongoing pregnancy rate (OPR) defined as pregnancy continuing beyond 10 weeks were found to be significantly superior in early hatching/hatched group vs expanded blastocyst group (CPR: 56.3% vs 35.5%, p = 0.002; OPR: 50% vs 30.6%, p = 0.003). Difference between miscarriage rate in the hatching/hatched group (11.1%, n = 2) and expanded blastocyst group (13.6%, n = 3) was not statistically significant. Limitations, reasons for caution Our sample size was relatively small in order to rigorously select a homogeneous group of good prognosis patients and adhere to strict study criteria- only 1st cycle, autologous, fresh, non PGT-A, day 5 eSET cycles were included. Larger controlled prospective studies would be valuable to confirm these findings. Wider implications of the findings To our knowledge this is the first report of improved pregnancy rates with early hatching blastocyst eSETs compared with expanded blastocysts. Basic science studies may shed more light on the biological underpinnings of these findings. Such transfer strategy may also prove useful to select the best blastocysts in non-PGT-A cycles. Trial registration number not applicable

Automated measurements based on artificial intelligence software in pediatric echocardiography: a feasibility study

Abstract Funding Acknowledgements Type of funding sources: None. Background Transthoracic echocardiography is the first-line non-invasive investigation for assessing pediatric patients' cardiac anatomy, physiology, and hemodynamics, based on its accessibility and portability, but complete anatomic and hemodynamic assessment is time-consuming. The study aimed to determine the accuracy and reliability of a new automated artificial intelligence software initially developed for adults for analyzing the main echocardiographic parameters in pediatric patients. Materials and Methods The study was performed at the University Hospital of Bordeaux between August and September 2022 and included 45 patients who underwent a 2D transthoracic echocardiographic examination, mainly for murmur (n=8), post ASD closure evaluation(N=5), chest pain, or arrhythmia as we aimed to have a homogeneous group of patients with normal or near normal heart architecture. We compared AI automatic measurements with manual measurements performed by a senior and junior pediatric cardiologist. Pearson correlation and Bland and Altman analysis were used. As the AI software has been developed for adults, we decided to subclassify our patients into two subgroups: the first group (patients aged between 0–8 years) and the second group (patients over 8 years). The decision was made because pediatric anatomy differs from adults and to see if the dedicated artificial intelligence soft for adults has better reproducibility for pediatric patients older than 8 years. Results The median age was 8.9 years. Comparison between senior and junior pediatric cardiologists for all subgroups was significant (Pearson correlation &amp;gt;0,7 for most measurements performed). For younger patients (&amp;lt;8 years old), we found excellent correlations (Pearson correlation &amp;gt;0.8) for heart chambers measurements measured from A4CH and A2CH views (LV end-diastolic volume, LV end-systolic volume, RV end-diastolic area, and RV area) between AI software and both junior and senior pediatric cardiologist, but poor correlation for the measurements performed from parasternal long axis view (r=0.06 for STJ measurement). We achieved stronger correlations for the measurements evaluation of patients over 8 years old ( r&amp;gt;0.8 for aortic annulus, STJ, E, A, S waves, LV end-diastolic volume in A4CH, LV end-systolic volume in A4CH) for both junior and senior cardiologist in relation to AI measurements. Conclusion In this preliminary study, we found that automated artificial intelligence software provided promising results for measuring mainly volumes (LV end-diastolic volume, LV end-systolic volume) in A4CH and A2CH. The software requires improvements for automated measurements within the parasternal long-axis section to achieve better accuracy. Results obtained with the AI software for patients over 8 years old were significantly improved compared to those obtained for those under 8 years of age.

Non-Motor Symptoms and Quality of Life in Patients with PRRT2-Related Paroxysmal Kinesigenic Dyskinesia.

Monoallelic pathogenic variants of PRRT2 often result in paroxysmal kinesigenic dyskinesia (PKD). Little is known about health-related quality of life (HrQoL), non-motor manifestations, self-esteem, and stigma in patients with PKD. We investigated non-motor symptoms and how they related to HrQoL in a genetically homogeneous group of PRRT2-PKD patients. We paid special attention to perceived stigmatization and self-esteem. We prospectively enrolled 21 consecutive PKD patients with a pathogenic variant of PRRT2, and 21 healthy controls matched for age and sex. They were evaluated with dedicated standardized tests for non-motor symptoms, HrQoL, anxiety, depression, stigma, self-esteem, sleep, fatigue, pain, and psychological well-being. Patients reported an alteration of the physical aspects of HrQoL, regardless of the presence of residual paroxysmal episodes. Non-motor manifestations were frequent, and were an important determinant of the alteration of HrQoL. In addition, patients perceived a higher level of stigmatization which positively correlated with a delay in diagnosis (ρ = 0.615, P = 0.003) and the fear of being judged (ρ = 0.452, P = 0.04), but not with the presence of paroxysmal episodes (ρ = 0.203, P = 0.379). Our findings have important implications for care givers concerning patient management and medical education about paroxysmal dyskinesia. PRRT2-PKD patients should be screened for non-motor disorders in routine care. A long history of misdiagnosis may play a role in the high level of perceived stigmatization. Improving knowledge about diagnostic clues suggestive of PKD is mandatory.

Measuring Expiratory Diaphragm Activity: An Electrifying Tool to Guide Positive End-Expiratory Pressure Strategy in Critically Ill Children?

Measuring Expiratory Diaphragm Activity: An Electrifying Tool to Guide Positive End-Expiratory Pressure Strategy in Critically Ill Children?

Cortical mean diffusivity is reliable in measuring brain abnormalities in drug-naïve essential tremor patients

ObjectiveEssential tremor (ET) is a common movement disorder, but the pathogenesis is poorly understood. Several associated brain areas were reported with inconsistent results due to heterogeneous populations. It is necessary to analyze a more homogeneous patient group. MethodsWe recruited 25 drug-naïve ET patients and 36 age- and sex-matched controls. All participants were right-handed. ET. ET was defined according to diagnostic criteria of the Consensus Statement of the Movement Disorder Society on Tremor. ET patients were divided into sporadic (SET) and familial ET (FET). We assessed tremor severity in ET. The cortical microstructural changes were compared between ET patients and controls using mean diffusivity (MD) of diffusion tensor imaging, and cortical thickness. The correlation of tremor severity with the cortical MD and thickness were respectively analyzed. ResultsMD values were increased in the insular, precuneus, medial orbitofrontal, posterior, and isthmus cingulate and temporo-occipital areas in ET. In comparison between SET and FET, MD values were higher in the superior and caudal middle frontal, postcentral, and temporo-occipital regions in FET. The cortical thickness of ET patients was more increased in the left lingual gyrus and lower in the right bankssts gyrus. We could not find any correlation of tremor severity with the MD values in ET patients. Still, there was a positive correlation with the cortical thickness of the frontal and parietal areas. ConclusionsOur results support the idea that ET is a disorder that disrupts widespread brain regions and indicates that cortical MD may be more sensitive to measure brain abnormalities than cortical thickness.

The Effects of Two Kinds of Dietary Interventions on Serum Metabolic Profiles in Haemodialysis Patients.

The goal of this study was to evaluate the effects of two kinds of 24-week dietary interventions in haemodialysis patients, a traditional nutritional intervention without a meal before dialysis (HG1) and implementation of a nutritional intervention with a meal served just before dialysis (HG2), in terms of analysing the differences in the serum metabolic profiles and finding biomarkers of dietary efficacy. These studies were performed in two homogenous groups of patients (n = 35 in both groups). Among the metabolites with the highest statistical significance between HG1 and HG2 after the end of the study, 21 substances were putatively annotated, which had potential significance in both of the most relevant metabolic pathways and those related to diet. After the 24 weeks of the dietary intervention, the main differences between the metabolomic profiles in the HG2 vs. HG1 groups were related to the higher signal intensities from amino acid metabolites: indole-3-carboxaldehyde, 5-(hydroxymethyl-2-furoyl)glycine, homocitrulline, 4-(glutamylamino)butanoate, tryptophol, gamma-glutamylthreonine, and isovalerylglycine. These metabolites are intermediates in the metabolic pathways of the necessary amino acids (Trp, Tyr, Phe, Leu, Ile, Val, Liz, and amino acids of the urea cycle) and are also diet-related intermediates (4-guanidinobutanoic acid, indole-3-carboxyaldehyde, homocitrulline, and isovalerylglycine).

P43 MUSIC THERAPY IN HAEMODYNAMICS: PRELIMINARY STUDY OF THE CHANGE IN VITAL PARAMETERS IN PATIENTS UNDERGOING INTERVENTIONAL PROCEDURES

Abstract Introduction Patients undergoing invasive procedures may have abnormal emotional reactivity that can lead to impaired vital signs. Music has been shown to modify physiological responses, but there is insufficient data in the literature to demonstrate the relationship between the improvement in vital signs and listening to music during interventional procedures. The aim of this study is to investigate how listening to music modifies vital signs in patients undergoing coronary angiography. Methods Patients admitted to the Campus Bio–Medico University Hospital of Rome for diagnostic coronary angiography were included in the study. During the procedures, patients listened to music selected by an experienced music therapist. The songs belonged to 6 musical genres and were also evaluated for agogic, tempo, and tonality. 7 phases were defined for the collection of vital signs (from the arrival in the waiting room to the stay in the "recovery room"). The results were compared with a homogeneous group of patients undergoing the same procedures. Results During phase 3 (insertion of the introducer), the mean systolic blood pressure was lower in the music therapy group than in the control group (139.9+–23.9 vs 145+–25.5 mmHg; p=0.529). During phase 2 (entering the room), mean oxygen saturation was higher in the music therapy group than in the control group (96 1.5% vs 95.4 1.8%; p=0.212). In all phases, the mean heart rate was lower in the music therapy group than in the control group (70.7+–10.8 vs 75+–18.1 bpm; p=0.33). The lowest mean systolic blood pressure and heart rate were recorded while listening to the Adagio and with 2/4 tempo tracks (mean systolic blood pressure 143,3+–26,9 mmHg; mean heart rate 69,7+–9,3 bpm). Conclusions This study was the first one to focus on changes in vital signs during music therapy in patients undergoing interventional cardiology procedures. Patients receiving music therapy showed a reduction in heart rate in all phases, a reduction in systolic blood pressure in phase 3, and an improvement in oxygen saturation in phase 2 compared with the control group. This approach may reduce the need for drug sedation and its side effects. The results are preliminary and require further analysis with a larger sample size.

An integrative analysis of endometrial steroid metabolism and transcriptome in relation to endometrial receptivity in in vitro fertilization patients

To study the relation between the steroid concentration in endometrium, in serum and the gene expression level of steroid metabolizing enzymes in the context of endometrial receptivity in IVF patients. Case-control study of 40 IVF patients recruited in the SCRaTCH study (NTR5342), a randomized controlled trial investigating pregnancy outcome after 'endometrial scratching'. Endometrial biopsies and serum were obtained from patients with a first failed IVF cycle randomized to the endometrial scratch in the mid-luteal phase of the natural cycle prior to the next fresh embryo transfer during the second IVF cycle. Twenty women with clinical pregnancy were compared with 20 women that did not conceive after fresh embryo transfer. Cases and controls were matched for primary versus secondary infertility, embryo quality and age. Steroid concentrations in endometrial tissue homogenates and serum were measured with liquid chromatography-mass spectrometry. The endometrial transcriptome was profiled by RNA-sequencing followed by principal component analysis and differential expression analysis. False Discovery Rate-adjusted p<0.05 and log Fold Change >|0.5| were selected as threshold for differentially expressed genes. Estrogen levels were comparable in both serum (n=16) and endometrium (n=40). Androgens and 17-hydroxyprogesterone were higher in serum as compared to endometrium. Although steroid levels did not vary between pregnant and non-pregnant groups, subgroup analysis of primary infertile women showed a significantly lower estrone concentration and estrone:androstenedione ratio in serum of the pregnant group (n=5) compared to the non-pregnant group (n=2). Expression of 34 out of 46 genes encoding the enzymes controlling the local steroid metabolism was detected and estrogen receptor β gene was differentially expressed between pregnant and non-pregnant women. When only the primary infertile group was considered, 28 genes were differentially expressed between pregnant and non-pregnant women, including HSD11B2, that catalyses the conversion of cortisol into cortisone. Steroidomic and transcriptomic analyses show that steroid concentrations are regulated by the local metabolism in the endometrium. Although no differences were found in endometrial steroid concentration in the pregnant and non-pregnant IVF patients, primary infertile women showed deviations in steroid levels and gene expression, indicating that a more homogeneous patient group is required to uncover the exact role of steroid metabolism in endometrial receptivity.