Non-selected Population Research Articles

From evidence to practice: real-world insights into outpatient management of acute uncomplicated diverticulitis.

Diverticulitis is experiencing a significant increase in prevalence and its widespread in-hospital management results in a high burden on healthcare systems worldwide. This study compared inpatient and outpatient approach of acute non-complicated diverticulitis using a non-selected population in a real-world setting. This observational retrospective study included all consecutive patients from two Portuguese institutions diagnosed between January 2017 and December 2021 with non-complicated diverticulitis according to the modified Hinchey Classification. The primary endpoints were to identify criteria for inpatient treatment and compare the outcomes on the basis of the treatment regimen. The secondary endpoints were to determine the predictive factors for clinical outcomes, focusing on treatment failure, pain recurrence, and the need for elective surgery following the initial episode. A total of 688 patients were included in this study, 437 treated as outpatients and 251 hospitalized. Inpatient management was significantly associated with higher preadmission American society of anesthesiologists (ASA) score (p = 0.004), fever (p = 0.030), leukocytosis (p < 0.001), and elevated C-reactive protein (CRP) (p < 0.001). No significant association was found between failure of conservative treatment and patient's age, ASA score, baseline CRP, presence of systemic inflammatory response syndrome (SIRS), and inpatient or outpatient treatment regimen. Pain recurrence was significantly associated with higher CRP levels (p = 0.049), inpatient treatment regime (p = 0.009) and post index episode mesalazine prescription (p = 0.006). Moreover, the need for elective surgery was significantly associated with the presence of previous episodes (p = 0.004) and pain recurrence (p < 0.001). The majority of patients with uncomplicated diverticulitis of the left colon experience successful conservative approach and can be safely managed in an ambulatory setting. Neither treatment failure, recurrence of pain, or need for posterior elective surgery are associated with outpatient treatment regimen.

Surgical patterns of care of pancreatic cancer. A French population-based study

IntroductionSurgical resection is the standard recommended treatment in localized pancreatic cancer. The benefit of neoadjuvant chemotherapy is still debated. The aim of this population-based study was to describe the pancreatic cancer surgical management. Material and methodsAn observational real-world study from the French Network of Cancer Registries sampled 638 pancreatic adenocarcinomas diagnosed in 2019. Characteristics of patients, tumours and recommended and administered treatments were collected. Operability of the patients and resectability of the tumours were described. A multivariate logistic regression was used to identify factors associated with the probability of having surgical resection. ResultsAmong the 263 (41 %) patients with M0 pancreatic adenocarcinomas, 202 patients (77 %) were considered operable and 157 (60 %) also had a tumour considered resectable. Upfront resection was recommended for 68 % and resection after neoadjuvant chemotherapy for 32 % of these patients. Among operable patients with resectable tumour, 36 % underwent upfront R0 resection, and 15 % achieved R0 resection following neoadjuvant chemotherapy. Eventually, among M0 pancreatic adenocarcinomas, age over 80 years (OR≥80 years vs < 65 years: 0.16 [0.06–0.39], p < 0.001) and WHO performance status over 0 (OR1-2 vs 0: 0.43 [0.24–0.79], p = 0.013) decreased the odds of having resection. R0 surgical resection was achieved in 61 % of patients selected for upfront surgical recommendation, and 29 % of those selected for a prior neoadjuvant chemotherapy. ConclusionIn a non-selected population, one-third of patients with localized pancreatic cancer had a complete R0 surgical resection. Neoadjuvant chemotherapy did not achieve a resection rate similar to that of patients selected for upfront surgical indication.

The incidence of atypical fibroxanthoma and pleomorphic dermal sarcoma in Denmark from 2002 to 2022

BackgroundThe purpose of this study was to assess trends in the incidence rates and overall survival of atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) in the Danish population from 2002 to 2022. MethodsWe included all patients diagnosed with AFX or PDS in the Danish National Pathology Register (DNPR) during the study period. We computed the age-adjusted incidence rate (AAIR) per 100,000 and the average annual percent change (AAPC) and developed an age-period-cohort (APC) model of incidence. ResultsWe included a total of 1118 patients, 78.3 % of whom were men. The median age upon diagnosis for AFX and PDS was 77.6 and 78.4 years, respectively. 84.5 % of the 1118 patients received an AFX diagnosis, while 15.5 % received a PDS diagnosis. The AAIR rose from 0.2 per 100,000 individuals in 2002 to 0.5 per 100,000 by 2022, with a peak increase of 0.75 per 100,000 in 2014. The AAPC for both tumors was 5.3 (95 % CI 2.9 %–7.7 %). We found a significant difference in overall survival between AFX and PDS, with PDS having worse overall survival than AFX. ConclusionThis study, which included the largest non-selected national population to date, found a significant increase in the incidence of AFX and PDS between 2002 and 2015, followed by a decrease.

Prediction of Upper Limb Motor Recovery by the PREP2 Algorithm in a Nonselected Population: External Validation and Influence of Cognitive Syndromes

Background Early prediction of poststroke motor recovery is challenging in clinical settings. The Prediction recovery potential (PREP2) algorithm is the most accurate approach for prediction of Upper Limb function available to date but lacks external validation. Objectives (i) To externally validate the PREP2 algorithm in a prospective cohort, (ii) to study the characteristics of patients misclassified by the algorithm, and (iii) to compare the performance according to the presence of cognitive syndromes (aphasia, neglect, cognitive disorders). Methods We enrolled 143 patients with stroke and upper extremity weakness persistent at Day 3. Evaluation to predict the recovery status according to the PREP2 algorithm included age, SAFE and NIHSS scores at Day 3 and transcranial magnetic stimulation to determine the presence of the motor-evoked potential before day seven. Actual recovery (excellent, good, limited, or poor) was defined based on the Action Research Arm test score at 3 months. Accuracy was computed by comparing the predictions of the PREP2 and the actual category of the patient. Additionally, to investigate misclassifications and the impact of cognitive syndromes, we recorded SAFE and NIHSS scores at Day 7, the Montreal Cognitive Assessment (MoCA) score, the presence of aphasia and neglect and Magnetic Resonance Imaging was used to evaluate the corticospinal tract lesion load. Results The PREP2 algorithm showed a very good predictive value with 78% accuracy [95% CI: 71.2%-86.1%], especially for the extreme categories of recovery (EXCELLENT 87.5% [95% CI: 78.9%-96.2%] and POOR 94.9% [95% CI: 87.9%-100%]), and only 46.5% [95% CI: 19.05%-73.25%] for the GOOD category and even worse than chance for the LIMITED category 0%. Pessimistic predictions (false-negative cases) had a drastic improvement in the SAFE score acutely compared to that of well-predicted patients with unfavorable recovery (P < 001). The predictive value of PREP2 decreased significantly when patients had cognitive disorders (MoCA score <24) versus not (69.4% [95% CI: 52.8%-86.1%] vs 93.1% [95% CI: 83.9%-100%], P = .01). Conclusion Our study provides an external validation of the PREP2 algorithm in a prospective population and underlines the importance of taking into account cognitive syndromes in motor recovery prediction.

Ultrasonographic threshold of ovarian structure in premenopausal women of different ethnicity

The polycystic ovarian morphology (PCOM) is a generally accepted ultrasound marker for ovulatory dysfunction, is one of the criteria for polycystic ovary syndrome (PCOS) and is established based on the assessment of ovarian volume (OV) and the follicle number per ovary (FNPO), taking into account the upper normal values determined in healthy premenopausal women. However, there is a necessity for regular revision of the PCOM characteristics depending on ethnic and age characteristics.The aim. To develop differentiated standards for assessing the ultrasonographic ovary structure in premenopausal women of various ethnicity.Materials and methods. From March 2016 to December 2019, a multicenter cross-sectional prospective study was conducted in Eastern Siberia (Irkutsk region) and in the neighboring Republic of Buryatia. The study included 1134 participants: 715 women of Caucasian origin, 312 Asian women, 107 women of mixed ethnic subpopulation.Results. It has been established that for Caucasians, it is advisable to diagnose PCOM when the ovarian volume is 9 cm3 and/or FNPO ≥ 12; for women of the Asian population – when the ovarian volume is 7 cm3 and/or FNPO ≥ 11; for women of mixed ethnicity – when the ovarian volume is 8 cm3 and/or FNPO ≥ 9. An important advantage of our study is that all participants were recruited from a non-selective multi-ethnic population of women with comparable socio-demographic characteristics living in the same geographical conditions.Conclusion. Differentiated approach for identifying the polycystic ovarian morphology in premenopausal women of different ethnic groups requires using ethnically differentiated normative readings

Lung and Liver Stereotactic Body Radiation Therapy During Mechanically Assisted Deep Inspiration Breath-Holds: A Prospective Feasibility Trial

PurposeRadiation therapy of tumours subject to breathing-related motion during breath-holds (BH) has the potential to substantially reduce the irradiated volume. Mechanically-assisted and non-invasive ventilation (MANIV) could ensure the target repositioning accuracy during each BH while facilitating treatment feasibility through oxygen supplementation and a perfectly replicated mechanical support. However, there is currently no clinical evidence substantiating the use of MANIV-induced BH for moving tumours. The aim of this work was therefore to evaluate the technique performances under real treatment conditions. Methods and MaterialsPatients eligible for lung or liver stereotactic body radiotherapy were prospectively included in a single-arm trial. The primary endpoint corresponded to the treatment feasibility with MANIV. Secondary outcomes comprised intrafraction geometrical uncertainties extracted from real-time imaging, tolerance to BH and treatment time. ResultsTreatment was successfully delivered in 92.9% (13/14) of patients: one patient with a liver tumour was excluded due to a mechanically-induced gastric insufflation displacing the liver cranially by more than 1 cm. In the Left-right/Anteroposterior/Craniocaudal directions, the recalculated safety margins based on intrafraction positional data were 4.6 mm / 5.1 mm / 5.6 mm and 4.7 mm / 7.3 mm / 5.9 mm for lung and liver lesions, respectively. Compared to the free-breathing internal target volume and mid-position approaches, the average reduction in the planning target volume with MANIV reached -47.2±15.3 %, p<0.001 and -29.4±19.2 %, p=0.007 for intra-thoracic tumours and -23.3±12.4 %, p<0.001 and -9.3±15.3 %, p=0.073 for upper abdominal tumours, respectively. For one liver lesion, large caudal drifts of occasionally more than one centimetre were measured. The total slot time was 53.1 ± 10.6 minutes with a BH comfort level of 80.1±10.6%. ConclusionsMANIV enables high treatment feasibility within a non-selected population. Accurate intrafraction tumour repositioning is achieved for lung tumours. Due to occasional intra-BH caudal drifts, pre-treatment assessment of BH stability for liver lesions is however recommended.

P-221 The efficiency of a PGT-A program is negatively impacted by the utilization of frozen-thawed oocytes in patients of all ages

Abstract Study question Are there any differences in the use of fresh or frozen-thawed oocytes in a PGT-A program? Summary answer While euploidy rates are comparable, the efficiency of a PGT program is adversely impacted when utilizing frozen-thawed oocytes. What is known already Oocyte vitrification has become one of the key assisted reproduction procedures. Some studies have reported rates of embryonic development, clinical pregnancy, and embryo implantation comparable between fresh and cryopreserved oocytes in egg donor patients. Vitrified oocyte accumulation before the blastocyst biopsy is a commonly used strategy in PGT programs to enhance the chances of obtaining a euploid blastocyst with the patient’s own oocytes. Further research is needed to assess the impact of frozen-thawed oocytes on aneuploidy and the efficiency of PGT programs. Study design, size, duration We conducted a retrospective comparison of 777 PGT-A cycles, using either fresh or frozen-thawed oocytes, regarding embryo development (fertilization rates, blastocyst formation, and rates of good-quality blastocysts), PGT outcomes (euploidy and mosaicism rates), and the overall efficiency of the PGT cycle, measured as the number of euploid blastocyst per available mature oocytes, between April 2018 and November 2023. The study groups were stratified based on the age of the patients (≤35 and &amp;gt;35 years old). Participants/materials, setting, methods PGT-A cycles were categorized into two groups: patients who utilized fresh oocytes (n = 641) and those who utilized frozen-thawed oocytes (n = 136). A total of 6,370 fresh oocytes and surviving oocytes from the initially vitrified ones (972 out of 1,153) were fertilized and cultured to the blastocyst stage, at which point biopsies were performed. The biopsied cells were subjected to NGS screening, and statistical data analysis was conducted using the Chi-square test, with significance set at P &amp;lt; 0.05. Main results and the role of chance In the group of patients aged ≤35 years old, significant differences were observed when comparing PGT cycles using fresh or frozen-thawed oocytes in terms of the fertilization rate (78.4% vs. 72.0%), blastocyst formation rate (47.4% vs. 37.7%), and the efficiency of the PGT cycle (24.0% vs. 16.0%), corresponding to a 33.3% reduction in efficiency. No differences were observed between fresh and frozen-thawed oocytes regarding euploidy rate (64.6% vs. 68.4%), mosaicism rate (4.9% vs. 5.1%), and the percentage of good-quality embryos (60.0% vs. 56.1%). Similarly, in patients aged &amp;gt;35 years old, fertilization (81.5% vs. 73.5%), blastocyst formation (40.5% vs. 33.4%), and the efficiency of the PGT cycle (11.7% vs. 7.2%), which correspond to a 38.5% reduction in efficiency, were improved when using fresh oocytes. No differences were observed regarding euploidy (35.6% vs. 35.3%) or mosaicism rate (3.8% vs. 5.3%), and the percentage of good-quality embryos (55.2% vs. 54.7%). The oocyte survival rate was 84.3%. Limitations, reasons for caution Our study is limited by its sample size and retrospective design, as well as the inclusion of a non-selected and general infertile population, which could amplify the impact of confounding variables. Wider implications of the findings We found that the utilization of frozen-thawed oocytes reduces the PGT program efficiency by decreasing fertilization and blastocyst formation rates. This suggests that the oocyte accumulation strategy should be approached with caution. However, vitrification did not lead to an increase in the rates of aneuploidy, mosaicism, or poor-quality blastocysts. Trial registration number NOT APPLICABLE

Prognostic Value and Limits of Heart Rate and QT—Corrected in A Large Population

Background: The study aimed to compare the prognostic importance of the heart rate (HR) and QT—corrected (QTc) according to Fridericia, Framingham, and Bazett with respect to all-cause mortality in a large non-selected population. Methods: The analysis of digital electrocardiograms archived from 2008 to 2022 in the metropolitan area of Modena, Italy, was carried out. The population under study was divided into three groups based on age, and survival analysis was performed. Results: 131,627 patients were enrolled and, during the follow-up (mean 1641.4 days), all-cause mortality was 8.9%. Both HR and QTc were associated with mortality. All-cause mortality significantly increased with HR values greater than 81 BPM and QTc values greater than 440 msec in young subjects and 455 msec in old subjects (values of the 75th percentiles/optimal operating point). A Cox analysis confirmed the better prognostic value of Bazett’s QTc and HR in the whole population and in the three age-groups. Conclusion: Bazett’s method performed better than the others, but, unexpectedly, the HR had the same or an even better correlation with all-cause mortality. Since the HR is simple and readily available, its evaluation should be improved. However, QTC and HR values are difficult to define, causing many confounding factors, and further population studies are required.

Gut bacteriome and mood disorders in women with PCOS.

How does the gut bacteriome differ based on mood disorders (MDs) in women with polycystic ovary syndrome (PCOS), and how can the gut bacteriome contribute to the associations between these two conditions? Women with PCOS who also have MDs exhibited a distinct gut bacteriome with reduced alpha diversity and a significantly lower abundance of Butyricicoccus compared to women with PCOS but without MDs. Women with PCOS have a 4- to 5-fold higher risk of having MDs compared to women without PCOS. The gut bacteriome has been suggested to influence the pathophysiology of both PCOS and MDs. This population-based cohort study was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), which includes all women born in Northern Finland in 1966. Women with PCOS who donated a stool sample at age 46years (n = 102) and two BMI-matched controls for each case (n = 205), who also responded properly to the MD criteria scales, were included. A total of 102 women with PCOS and 205 age- and BMI-matched women without PCOS were included. Based on the validated MD criteria, the subjects were categorized into MD or no-MD groups, resulting in the following subgroups: PCOS no-MD (n = 84), PCOS MD (n = 18), control no-MD (n = 180), and control MD (n = 25). Clinical characteristics were assessed at age 31years and age 46years, and stool samples were collected from the women at age 46years, followed by the gut bacteriome analysis using 16 s rRNA sequencing. Alpha diversity was assessed using observed features and Shannon's index, with a focus on genera, and beta diversity was characterized using principal components analysis (PCA) with Bray-Curtis Dissimilarity at the genus level. Associations between the gut bacteriome and PCOS-related clinical features were explored by Spearman's correlation coefficient. A P-value for multiple testing was adjusted with the Benjamini-Hochberg false discovery rate (FDR) method. We observed changes in the gut bacteriome associated with MDs, irrespective of whether the women also had PCOS. Similarly, PCOS MD cases showed a lower alpha diversity (Observed feature, PCOS no-MD, median 272; PCOS MD, median 208, FDR = 0.01; Shannon, PCOS no-MD, median 5.95; PCOS MD, median 5.57, FDR = 0.01) but also a lower abundance of Butyricicoccus (log-fold changeAnalysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC)=-0.90, FDRANCOM-BC=0.04) compared to PCOS no-MD cases. In contrast, in the controls, the gut bacteriome did not differ based on MDs. Furthermore, in the PCOS group, Sutterella showed positive correlations with PCOS-related clinical parameters linked to obesity (BMI, r2=0.31, FDR = 0.01; waist circumference, r2=0.29, FDR = 0.02), glucose metabolism (fasting glucose, r2=0.46, FDR < 0.001; fasting insulin, r2=0.24, FDR = 0.05), and gut barrier integrity (zonulin, r2=0.25, FDR = 0.03). Although this was the first study to assess the link between the gut bacteriome and MDs in PCOS and included the largest PCOS dataset for the gut microbiome analysis, the number of subjects stratified by the presence of MDs was limited when contrasted with previous studies that focused on MDs in a non-selected population. The main finding is that gut bacteriome is associated with MDs irrespective of the PCOS status, but PCOS may also modulate further the connection between the gut bacteriome and MDs. This research was funded by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement (MATER, No. 813707), the Academy of Finland (project grants 315921, 321763, 336449), the Sigrid Jusélius Foundation, Novo Nordisk Foundation (NNF21OC0070372), grant numbers PID2021-12728OB-100 (Endo-Map) and CNS2022-135999 (ROSY) funded by MCIN/AEI/10.13039/501100011033 and ERFD A Way of Making Europe. The study was also supported by EU QLG1-CT-2000-01643 (EUROBLCS) (E51560), NorFA (731, 20056, 30167), USA/NIH 2000 G DF682 (50945), the Estonian Research Council (PRG1076, PRG1414), EMBO Installation (3573), and Horizon 2020 Innovation Grant (ERIN, No. EU952516). The funders did not participate in any process of the study. We have no conflicts of interest to declare. N/A.

Prenatal diagnosis, pregnancy determination and follow up of sex chromosome aneuploidy screened by non-invasive prenatal testing from 122 453 unselected singleton pregnancies: A retrospective analysis of 7-year experience.

The phenotype of SCA patients are diversities, make prenatal counseling and parental decision-making following the prenatal diagnosis of SCA more complicated and challenging. NIPT has higher sensitivity and specificity in screening trisomy 21 syndrome, but the effectiveness of NIPT in detecting SCA is still controversial. This study is a large-scale retrospective cohort of positive SCA screened from unselected singleton pregnancies by non-invasive prenatal testing (NIPT) from a single prenatal center of a tertiary hospital. Clinical information, indications, diagnostic results, ultrasound findings, pregnancy determinations, and follow-up were reviewed and analyzed. 596 cases of SCA positive were screened out of 122 453, giving a positive detection rate of 0.49%. 510 cases (85.6%) conducted with amniocentesis to detect fetal chromosome, of which 236 were confirmed as true positive of SCA with PPV of 46.3% (236/510). Of the 236 cases confirmed as true positive SCA, 114 cases (48.3%)chose to terminate the pregnancy (93.0%, 65.3%, 15.4% and 10.9% for 45,X, 47,XXY, 47,XXX and 47,XYY, respectively), 122 cases (51.7%) elected to continue the pregnancy. In conclusions, NIPT as a first-tier routine method for screening autosomal aneuploidies, also could play an important role in screening SCA. Low-risk pregnant women are the main indication for the detection of SCA as NIPT test provides to non-selective population. For 47,XXX and 47,XYY with mild phenotype, couples would like to continue the pregnancy. But for 45,X and 47,XXY, parents apt to terminate pregnancy no matter ultrasound abnormalities were found or not.

Blood-Based Biomarkers for Early Alzheimer's Disease Diagnosis in Real-World Settings.

As our knowledge about the biology of Alzheimer's disease (AD) expands and we recognize the significance of early intervention for effective treatment, there is a shift in focus toward detecting the disease at an early stage. AD is characterized by the accumulation of misfolded amyloid-β (Aβ) and phosphorylated tau proteins in the brain, leading to the formation of senile plaques and neurofibrillary tangles. While a definitive diagnosis of AD can only be confirmed through autopsy by examining these pathological features, there are now reliable methods available for diagnosing the disease in living individuals. These methods involve analyzing cerebrospinal fluid and using positron emission tomography to accurately assess the presence of Aβ and tau proteins. While these diagnostic markers have shown high accuracy in memory-clinic populations, they do have limitations such as the requirement for invasive lumbar puncture or exposure to ionizing radiation. Additionally, they are not easily accessible outside of specialized healthcare settings. Blood-based biomarkers of the core pathological features of AD are being developed, showing promise for less invasive, scalable identification of AD cases in the community. The advantages for the healthcare systems of this development are obvious, but the diagnostic performance of blood-based biomarkers in broader, non-selected populations outside of retrospective analyses and research cohorts still requires further investigation, including the combination with more effective neuropsychological assessments such as digital cognitive test solutions.

Prevalence of corpus callosum pathology in an unselected population. Should assessment of the corpus callosum be included in the routine 20weeks scan?

To determine the prevalence of abnormalities of the corpus callosum (AbnCC) in a non-selected population, to propose a systematic screening protocol for AbnCC in all populations through direct assessment, and to describe the follow-up and prognosis of all AbnCC cases diagnosed in our clinical setting. This was a retrospective review of the prevalence of AbnCC over 11years. We included a sagittal assessment of the corpus callosum (CC) in the second-trimester scan. AbnCC was classified into complete agenesis of CC (ACC) and dysgenesis of CC (DCC; including small, partial agenesis, thick and with lipoma). Of the 38,586 second-trimester scans performed during our screening, 43 cases of AbnCC were detected (prevalence of 0.8/1000). Of the AbnCC cases, 10 cases were identified as ACC (29.40%) and 24 as DCC (70.59%). Follow-up investigations showed that in the 43 cases with AbnCC, 76.5% had other associated ultrasound abnormalities, 26.5% had genetic abnormalities, 11.8% had other MRI abnormalities, and 25% of the children had neurodevelopmental delays (8.8% of the total), which were severe in only one case. AbnCC is found in approximately 0.8/1000 of cases in an unselected population. The findings suggest that systematic and direct assessment of the CC as part of screening ultrasound in the second trimester of gestation should be recommended as a routine practice.

Imaging for prevalence assessment of cardiac transthyretin amyloidosis in patients &amp;gt; 60 years hospitalized in cardiology : the IMPACT study

Abstract Introduction Transthyretin cardiac amyloidosis (ATTR-CA) is a severe condition with poor prognosis if left untreated (1). Its true prevalence remains unknown because of frequent underdiagnosis, and most published series have focused on highly selected populations (2-3). The objectives of this prospective study were 1) to determine the prevalence of ATTR-CA in consecutive patients &amp;gt; 60 years hospitalized in cardiology wards and presenting with left ventricular hypertrophy (LVH) ≥ 12 mm on transthoracic echocardiography (TTE), using a systematic 99mTc-HMDP bone scintigraphy for diagnosis screening 2) to analyze the characteristics associated with the final diagnosis of ATTR-CA. Population &amp; methods: Between october 2021 and june 2022, 251 patients with echocardiographic LVH (from any cause, including high blood pressure or aortic stenosis) and without any previous diagnosis of CA, were prospectively included and underwent 99mTc-HMDP bone scintigraphy. A monoclonal gammapathy was systematically sought-after to exclude light-chain cardiac amyloidosis (AL-CA) (4). Genetic analysis of the TTR gene was systematically performed in case of definite diagnosis of ATTR-CA. The design of the trial is provided in Figure 1. This is an interim analysis of a private funded study currently being finalized, with a target of 400 patients to be included. Results Among the 251 patients, definite ATTR-CA was diagnosed in 17 patients (6.8%), all of them being wild-type. No AL-CA was identified. The 2 subgroups of patients with the highest prevalence of ATTR-CA (&amp;gt;10%) were patients ≥ 65 years with either heart failure or bilateral carpal tunnel syndrom. The majority of diagnosed patients had symptoms or signs suggestive of ATTR-CA, even though CA was never looked-after during their medical pathway, while 30% had no or only one red flag of ATTR-CA. Using multivariable analysis, we found four parameters independently associated with the diagnosis of ATTR-CA as presented in Table 1, one clinical and three echocardiographic, including the alteration of left atrial strain. Conclusion We report a high prevalence (6.8%) of ATTRwt-CA in a non-selected cardiological population with LVH from any cause. Most patients were underdiagnosed since they had at least 2 red-flags for ATTR-CA, thus emphasizing the need for continuous and strengthened education on CA. On the other hand, 30% of patients had no obvious sign for CA and the diagnosis was only established by our systematic screening strategy. We report 4 factors significantly associated with ATTR-CA in our population, including the alteration of left atrial reservoir strain. These new data confirm the interest of a complete echocardiographic analysis in case of LVH, to refine the selection of patients who could benefit from 99mTc-HMDP bone scan screening.Study designPredictive factors of ATTR-CA

Genetic selection for high growth improves the efficiency of gilthead sea bream (Sparus aurata) in using novel diets with insect meal, single-cell protein and a DHA rich-microalgal oil

Genetic selection and novel raw materials for aquafeeds are current key tools in the ongoing effort to increase the productivity, efficiency, and sustainability of the aquaculture sector. Selective breeding could also improve the utilization of novel dietary formulations with emergent ingredients. Gilthead sea bream juveniles, either coming from a selective breeding program based on growth traits, or a non-selected population, were nutritionally challenged with two novel dietary formulations that were compared with a Control diet based on 15% FM and 6% FO dietary commercial levels for this species. The novel formulations included an insect meal diet (INS) at 5% of the diet to replace 33.3% of the dietary FM, or a single-cell protein diet (SCP) at 10% of the diet and to replace 66.7% of the dietary FM. Fish oil was also totally replaced in these diets by a blend of poultry oil and Veramaris algal oil. Better growth and feed utilization of the selected genotype compared to non-selected fish was observed, at any of the diets assayed. INS and SCP novel diets reduced general performance of fish by reducing feed intake. However, selected fish fed novel diets showed very similar growth and lower feed conversion ratio compared with non-selected fish fed a control diet. The novel formulations increased n-3 LC-PUFA in fish tissues, particularly DHA, irrespective of the genotype, as a result of the dietary inclusion of the DHA-rich microalgal oil. Neither genetic selection nor the use of novel raw materials affected fillet proximate composition and consequently, sea bream fillet quality in terms of texture and sensorial perception of consumers. Overall, the results reaffirm the positive effects of selective breeding programs in improving sea bream key productive indicators, as well as support the use of novel dietary formulations, using insect meal from H. illucens, single-cell protein from M. capsulatus as partial replacers of FM in diets for gilthead sea bream (33 and 66% of replacement, respectively), and a blend of DHA-rich microalgal and poultry oils as total replacer of FO.

Standardized First-Trimester Ultrasound Screening for Fetal Structural Abnormalities in A Non-Selective Population: A Single-Center Experience

Standardized First-Trimester Ultrasound Screening for Fetal Structural Abnormalities in A Non-Selective Population: A Single-Center Experience

Left Ventricular Abnormal Substrate in Brugada Syndrome

BackgroundSlow-conductive structural abnormalities located in the epicardium of the right ventricle (RV) underlie Brugada syndrome (BrS). The extent of such substrate in the left ventricle (LV) has not been investigated. ObjectivesThis study sought to characterize the extent of epicardial substrate abnormalities in BrS. MethodsWe evaluated 22 consecutive patients (mean age 46 ± 11 years, 21 male) referred for recurrent ventricular arrhythmias (mean 10 ± 13 episodes) in the setting of BrS. The patients underwent clinical investigations and wide genetic screening to identify SCN5A mutations and common risk variants. High-density biventricular epicardial mapping was performed to detect prolonged (>70 ms) fragmented electrograms, indicating abnormal substrate area. ResultsAll patients presented with abnormal substrate in the epicardial anterior RV (27 ± 11 cm2). Abnormal substrate was also identified on the LV epicardium in 10 patients (45%), 9 at baseline and 1 after ajmaline infusion, covering 15 ± 11 cm2. Of these, 4 had severe LV fascicular blocks. Patients with LV substrate had a longer history of arrhythmia (11.4 ± 6.7 years vs 4.3 ± 4.3 years; P = 0.003), longer PR (217 ± 24 ms vs 171 ± 14 ms; P < 0.001) and HV (60 ± 12 ms vs 46 ± 5 ms; P = 0.005) intervals, and abnormal substrate also extending into the inferior RV (100% vs 33%; P = 0.001). SCN5A mutation was present in 70% of patients with LV substrate (vs 25%; P = 0.035). SCN5A BrS patients with recurrent ventricular arrhythmias present a higher polygenic risk score compared with a nonselected BrS population (median of differences: −0.86; 95% CI: −1.48 to −0.27; P = 0.02). ConclusionsA subset of patients with BrS present an abnormal substrate extending onto the LV epicardium and inferior RV that is associated with SCN5A mutations and multigenic variants.

P-784 First trimester screening for preterm preeclampsia after ART: high risk, high gain?

Abstract Study question What is the preterm preeclampsia (pPE) incidence in selected high-risk ART patient populations when applying a first trimester screening approach to recommend prevention via aspirin? Summary answer One in five high-risk ART patients had a calculated risk &amp;gt;1/100 and despite aspirin prophylaxis still 22.2% of them developed pPE. What is known already Preeclampsia (PE) is an obstetrical complication defined by new-onset hypertension after 20 weeks’ gestation with proteinuria, end-organ (including placental) dysfunction or both. First trimester pPE screening is gaining ground in prenatal care since a study on approximately 60.000 singleton pregnancies reported an algorithm able to detect 76% of pPE and 38% of term PE (tPE). A RCT showed that aspirin, prescribed upon positive screening, led to an effective (62%) reduction of pPE incidence. This screening/prevention strategy has not been validated in the context of ART pregnancies, while some ART patient groups are known to be at higher risk for PE. Study design, size, duration This is a retrospective, single-center, observational cohort study, including 242 patients between 18 and 48 years old, pregnant after ART and considered at higher risk of PE because of one of the following characteristics: diagnosed with polycystic ovary syndrome (PCOS), being an oocyte recipient (OR) or pregnant from a frozen embryo transfer in an artificially prepared cycle (HRT-FET). Patients were included from May 2021 until July 2022. Participants/materials, setting, methods Screening was systematically offered between 11-14 weeks’ gestation, according to the Fetal Medicine Foundation (FMF) algorithm including maternal factors, mean arterial pressure, uterine arteries pulsatility index and serum placental growth factor. If the risk of developing PE was &amp;gt;1/100, administration of 160mg aspirin was started until 36 weeks’ gestation. Primary outcome was the incidence of pPE(&amp;lt;37 weeks). Secondary outcomes were the incidence of tPE(≥37 weeks) and the incidence of positive first trimester screening (risk &amp;gt;1/100). Main results and the role of chance A total of 242 unique patients were screened: 58 oocyte recipients (ORs), 89 PCOS and 95 HRT-FET patients (the latter having no PCOS and using autologous oocytes). The overall positive screening incidence was 21.9%(53/242), with the highest positive screening rate in ORs (27.6%, 16/58). In PCOS and HRT-FET patients, we observed a positive screening test in 20.2%(18/89) and 20.0%(19/95), respectively. For comparison, the positive screening rate reported for the general population was 10.5%. Despite the prophylactic aspirin regimen started upon positive screening, in the current study an overall pPE incidence of 22.6%(12/53) was observed while the reported pPE incidence in the general population in this setting was only 1.6%. More specifically, 31.2%(5/16) ORs with positive screening developed pPE although they used aspirin. For PCOS and HRT-FET patients, this was 11.1%(2/18) and 21.1% (4/19), respectively. tPE occurred in 7.5%(4/53) of women with positive screening and aspirin intake (1/16 in ORs, 1/18 in PCOS patients and 2/19 following HRT-FET). For comparison, in the general population this was 6.7%. Following a negative first trimester screening test, 2.1%(4/189) of patients developed pPE and 3.7%(7/189) tPE. In a non-selected population, these incidences have been reported to be 0.2% and 1.1%, respectively. Limitations, reasons for caution This study is limited by its retrospective study design, small sample size and observational nature. Nevertheless, it is of major importance to communicate the strikingly high pPE incidences in specific subtypes of ART patients despite first trimester screening and aspirin prophylaxis. Wider implications of the findings Our findings suggest that current screening algorithms are not optimized for women pregnant following ART. In pregnancies from oocyte donation, aspirin might be less effective. Future research should aim at finetuning PE screening methods specifically for ART patients and differential mechanisms of PE origin need to be further investigated. Trial registration number Not applicable

P-733 A non-selection study to evaluate non-invasive preimplantation genetic testing for aneuploidy

Abstract Study question How does non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) perform to predict sustained implantation or live birth (SI/LB)? Summary answer Though not comparable to conventional PGT-A, niPGT-A can still be considered an appealing tool for clinical embryo prioritizing given its high negative predictive value (NPV). What is known already To omit the need for the invasive trophectoderm biopsy, niPGT-A which screens embryonic ploidy using embryonic cell free DNA released into the spent embryo culture medium (SEM) or blastocoel fluid (BF) was developed. Although the feasibility of niPGT-A has been shown and healthy live births have been reported from embryos screened by niPGT-A, the predictive value of niPGT-A for embryo transfer outcome has not been established yet and evidence is still lacking as to whether embryo selection by niPGT-A is associated with improved pregnancy outcomes. The answers to these are of vital importance to justify niPGT-A for clinical care. Study design, size, duration This is a single center, blinded, non-selection study consisting of single frozen embryo transfer cycles with a duration of two years, of which 117 cycles (Arm-1) were completed for 83 patients by transferring an embryo that was only morphologically assessed, and 90 cycles (Arm-2) were completed for 67 patients by transferring an euploid embryo that was screened by conventional biopsy-based PGT-A. Participants/materials, setting, methods Embryos were cultured in 25 μL continuous culture medium until blastocyst stage. The “SEM+BF” samples were ongoingly collected and archived at the end of culture. In Arm-1, after pregnancy outcomes were determined, the corresponding “SEM+BF” samples were pulled out for niPGT-A. In Arm-2, niPGT-A was also performed for some cases that did not end up in an SI/LB. NiPGT-A was completed by NICS and the incorporated ChromGo platform (Yikon Genomics). Main results and the role of chance Out of the 117 “SEM+BF” samples in Arm-1, 110 (94%) yielded an informative niPGT-A result. Among these, 46 transferred embryos were determined as “euploid” by niPGT-A and 15 resulted in SI/LB; 32 were determined as “aneuploid” and 27 did not resulted in SI/LB. Therefore, the positive and negative predictive values (PPV and NPV) of niPGT-A were 32.6% (15/46) and 84.4% (27/32), respectively. Another 32 transferred embryos in Arm-1 were determined as “suspected mosaic” and they showed a similar rate of SI/LB per embryo transfer to those “euploid” ones (37.5% vs. 32.6%, P = 0. 8092). Compared to Arm-1 overall, the “transferrable” embryos (“euploid” + “suspected mosaic”) determined by niPGT-A resulted in a much higher rate of SI/LB (34.6% vs. 27.6%, P = 0.3399). In Arm-2, 39 out of the 90 transferred euploid embryos resulted in SI/LB. “Euploid” embryos determined by PGT-A resulted in significantly better rate of SI/LB than “euploid” embryos determined by niPGT-A in Arm-1 (43.3% vs. 32.6%, P = 0.0243). Out of the 51 PGT-A “euploid” embryos that did not end up in SI/LB, 25 were also tested by niPGT-A with 6 being “suspected mosaic” and 3 being “abnormal/aneuploid”, raising the concern of possible false negative of conventional PGT-A. Limitations, reasons for caution The study enrolled a non-selected patient population which resulted in the inclusion of a few patients with a history of repeated implantation failure. Therefore, the PPV of niPGT-A might be underestimated as implantation failure could be attributed to defects in endometrial receptivity rather than in embryo quality. Wider implications of the findings This is the first non-selection study to validate niPGT-A in the setting of continuous culture medium. The high informative rate indicates its feasibility for clinics using a similar culture system. It also forms the foundation of a prospective, randomized controlled trial to further assess the benefit of niPGT-A. Trial registration number Not applicable

CAR-T Cells and the Kidney: Insights from the WHO Safety Database.

Chimeric antigen receptor T (CAR-T) cells have proven to be a game changer for treating several hematologic malignancies. Randomized controlled trials have highlighted potential life-threatening adverse drug reactions (ADRs), including cytokine release syndrome (CRS). Acute renal failure (ARF) has also been reported in 20% of the patients treated. However, an analysis of renal safety supported by large-scale real-life data seems warranted. We queried VigiBase® for all reports of the Standardised MedDRA Query "acute renal failure" (ARF) involving a CAR-T cell, registered until 24 July 2022. Disproportionality for this ADR was analyzed through calculation of the Information Component [IC (95% confidence interval)]. A positive lower end of the 95% confidence interval of the IC is the threshold used in statistical signal detection in VigiBase®. The same analysis was carried out for various hydroelectrolytic disorders. We gathered 224 reports of ARF, and 125 reports of hydroelectrolytic disorders involving CAR-T cells. CAR-T cells were disproportionately reported with ARF [IC 1.5 (1.3-1.7)], even after excluding reports mentioning CRS. A significant disproportionate reporting was also found for hypernatremia [IC 3.1 (2.2-3.8)], hyperphosphatemia [IC 3.1 (1.8-3.9)], hypophosphatemia [IC 2.0 (0.6-2.9)], metabolic acidosis [IC 1.8 (1.2-2.2)], hyponatremia [IC 1.6 (1.1-2.0)], and hypercalcemia [IC 1.4 (0.5-2.1)]. There was no disproportionate reporting of dyskalemia. This study is limited by the inherent flaws of pharmacovigilance approaches. Nonetheless, our findings suggest that ARF and an array of hydroelectrolytic disorders are potential ADRs of CAR-T cell therapy, in real-life settings and in a nonselected population.

Association between sex and survival after out-of-hospital cardiac arrest: A systematic review and meta-analysis.

The current literature on sex differences in 30-day survival following out-of-hospital cardiac arrest (OHCA) is conflicting, with 3 recent systematic reviews reporting opposing results. To address these contradictions, this systematic literature review and meta-analysis aimed to synthesize the literature on sex differences in survival after OHCA by including only population-based studies and through separate meta-analyses of crude and adjusted effect estimates. MEDLINE and Embase databases were systematically searched from inception to March 23, 2022 to identify observational studies reporting sex-specific 30-day survival or survival until hospital discharge after OHCA. Two meta-analyses were conducted. The first included unadjusted effect estimates of the association between sex and survival (comparing males vs females), whereas the second included effect estimates adjusted for possible mediating and/or confounding variables. The PROSPERO registration number was CRD42021237887, and the search identified 6712 articles. After the screening, 164 potentially relevant articles were identified, of which 26 were included. The pooled estimate for crude effect estimates (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.22-1.66) indicated that males have a higher chance of survival after OHCA than females. However, the pooled estimate for adjusted effect estimates shows no difference in survival after OHCA between males and females (OR, 0.93; 95% CI, 0.84-1.03). Both meta-analyses involved high statistical heterogeneity between studies: crude pooled estimate I2=95.7%, adjusted pooled estimate I2=91.3%. There does not appear to be a difference in survival between males and females when effect estimates are adjusted for possible confounding and/or mediating variables in non-selected populations.