Min-max Range Research Articles

12342 Retrospective Multicenter Study Of Prolactinomas In Men

Abstract Disclosure: M.A. Guitelman: None. G. Cardenas: None. A. Rogozinski: None. C. Ballarino: None. M.F. Battistone: None. K. Danilowicz: None. S. Diez: None. P. Fainstein-Day: None. A. Furioso: None. V. Garcia Roel: None. M.S. Gonzalez Pernas: None. D.A. Katz: None. M.G. Loto: None. S. Mallea Gil: None. M.P. Manavela: None. M.S. Martinez: None. K.A. Miragaya: None. P. Slavinsky: None. S. Sosa: None. J. Tkatch: None. G. Tubert: None. M. Vitale: None. M. Glerean: None. Prolactinomas in men: a retrospective multicenter study Introduction and Objectives: prolactinomas in men have recently been included by the World Health Organization as a more aggressive tumor category due to their size, invasiveness and response to treatment. Our objective was to evaluate clinical, biochemical, and imaging characteristics, therapeutic response, and long-term evolution (outcome) of a cohort of men with prolactinoma. Patients and Methods: multicenter retrospective study including 311 men with prolactinoma. Initial clinical parameters, therapeutic modalities, PRL normalization rate and gonadal recovery, as well as tumor reduction were analyzed. The results were expressed as median (min-max range). Results: 35 micro (Mi) and 276 macroadenomas (Ma) were found (199 invasive, 71 Giant ≥4 cm). The median age at diagnosis was 41 (13-84) and 40 y-old (15-73) for micro and macro respectively. The most frequent reasons for consultation were symptoms of hypogonadism in patients with Mi, while visual disturbances, headache, and incidental findings were seen in patients with Ma. Apoplexy as presentation was observed in two patients with Ma. Hypogonadotrophic hypogonadism was present in 90 % of patients in whole cohort. Median basal PRL was 144 in Mi and 1633 ng/ml in Ma. Treatment with cabergoline (CAB) was indicated in all but one patient with Ma who remitted after surgery. Normalization of PRL was achieved in 85.7% and 65.7% of Mi and Ma respectively. The median follow-up time was 48 months (6-240). Sixty-three Ma and only one Mi were submitted to surgery, 2 patients achieved remission criteria (Mi/Ma); a patient with micro experienced recurrence after 3 years, the remaining patients continued or started CAB after surgery. Ki-67 ≥3% was reported in 17/46 available pathologies. The maximum dose of CAB was 4.5 and 12 mg/wk , with a median of 0.5 and 1.5 mg/wk for Mi and Ma, respectively. Resistance to CAB (dose ≥3mg/week) occurred in 5.7% Mi and 35.4% Ma. Gonadal function recovery without testosterone requirement was achieved in 80% of Mi and 63% of Ma. Tumor remnant was observed in 34% and 49% of Mi and Ma respectively Ten patients with Ma received radiotherapy. Five patients presented CSF fistula during treatment with CAB, and another 3 impulse control disorder. One patient with carcinomatous transformation was treated with temozolomide. Conclusions: In our series of 311 men with prolactinomas, majority Ma consulted for neuro-ophthalmological symptoms, while hypogonadism was the most frequent initial symptom in Mi, despite the fact that 90% of the total population showed it at presentation. Giant, invasive and proliferative tumor were highly prevalent in Ma. Pharmacological treatment continues to be the first line of choice, with a high rate of normalization of PRL and recovery of gonadal function, but a low rate of long-term remission. Presentation: 6/2/2024

Winter Season Outdoor Cultivation of an Autochthonous Chlorella-Strain in a Pilot-Scale Prototype for Urban Wastewater Treatment

The global population increase during the last century has significantly amplified freshwater demand, leading to higher wastewater (WW) production. European regulations necessitate treating WW before environmental. Microalgae have gained attention for wastewater treatment (WWT) due to their efficiency in remediating nutrients and pollutants, alongside producing valuable biomass. This study investigates the phycoremediation potential of a Chlorella-like strain isolated from urban WW in a 600L-scale system under winter conditions. Experiments in December 2021 and February 2022 tested the strain’s adaptability to varying environmental conditions, particularly temperatures (min-max temperature range: from −3.69 to 10.61 °C in December and −3.96 to 17.61 °C in February), and its ability to meet legal discharge limits. In December, low temperatures algal growth. Nitrates showed an RE of about 92%, while ammonia slightly decreased (RE, about 32%), and phosphorous remained unchanged. In February, mild temperatures increased algal density (33.3 × 106 cell mL−1) and, at the end of experiment, all nutrients were below legal limits with very high RE % (NH4+, 91.43; PO43− 97.32). Both trials showed an E. coli RE, % = 99%. The study highlights the potential of microalgae for WWT and the importance of considering seasonal variations when implementing these systems.

Performance Assessment for the Validation of Wireless Communication Engines in an Innovative Wearable Monitoring Platform.

In today's health-monitoring applications, there is a growing demand for wireless and wearable acquisition platforms capable of simultaneously gathering multiple bio-signals from multiple body areas. These systems require well-structured software architectures, both to keep different wireless sensing nodes synchronized each other and to flush collected data towards an external gateway. This paper presents a quantitative analysis aimed at validating both the wireless synchronization task (implemented with a custom protocol) and the data transmission task (implemented with the BLE protocol) in a prototype wearable monitoring platform. We evaluated seven frequencies for exchanging synchronization packets (10 Hz, 20 Hz, 30 Hz, 40 Hz, 50 Hz, 60 Hz, 70 Hz) as well as two different BLE configurations (with and without the implementation of a dynamic adaptation of the BLE Connection Interval parameter). Additionally, we tested BLE data transmission performance in five different use case scenarios. As a result, we achieved the optimal performance in the synchronization task (1.18 ticks as median synchronization delay with a Min-Max range of 1.60 ticks and an Interquartile range (IQR) of 0.42 ticks) when exploiting a synchronization frequency of 40 Hz and the dynamic adaptation of the Connection Interval. Moreover, BLE data transmission proved to be significantly more efficient with shorter distances between the communicating nodes, growing worse by 30.5% beyond 8 m. In summary, this study suggests the best-performing network configurations to enhance the synchronization task of the prototype platform under analysis, as well as quantitative details on the best placement of data collectors.

Identification of Distinct Brain MRI Phenotypes and Their Association With Long-Term Dementia Risk in Community-Dwelling Older Adults.

Individual brain MRI markers only show at best a modest association with long-term occurrence of dementia. Therefore, it is challenging to accurately identify individuals at increased risk for dementia. We aimed to identify different brain MRI phenotypes by hierarchical clustering analysis based on combined neurovascular and neurodegenerative brain MRI markers and to determine the long-term dementia risk within the brain MRI phenotype subgroups. Hierarchical clustering analysis based on 32 combined neurovascular and neurodegenerative brain MRI markers in community-dwelling individuals of the Age-Gene/Environment Susceptibility Reykjavik Study was applied to identify brain MRI phenotypes. A Cox proportional hazards regression model was used to determine the long-term risk for dementia per subgroup. We included 3,056 participants and identified 15 subgroups with distinct brain MRI phenotypes. The phenotypes ranged from limited burden, mostly irregular white matter hyperintensity (WMH) shape and cerebral atrophy, mostly irregularly WMHs and microbleeds, mostly cortical infarcts and atrophy, mostly irregularly shaped WMH and cerebral atrophy to multiburden subgroups. Each subgroup showed different long-term risks for dementia (min-max range hazard ratios [HRs] 1.01-6.18; mean time to follow-up 9.9 ± 2.6 years); especially the brain MRI phenotype with mainly WMHs and atrophy showed a large increased risk (HR 6.18, 95% CI 3.37-11.32). Distinct brain MRI phenotypes can be identified in community-dwelling older adults. Our results indicate that distinct brain MRI phenotypes are related to varying long-term risks of developing dementia. Brain MRI phenotypes may in the future assist in an improved understanding of the structural correlates of dementia predisposition.

Balancing the scales: achieving the optimal beta-lactam to beta-lactamase inhibitor ratio with continuous infusion piperacillin/tazobactam against extended spectrum beta-lactamase producing Enterobacterales.

Piperacillin/tazobactam (TZP) is administered intravenously in a fixed ratio (8:1) with the potential for inadequate tazobactam exposure to ensure piperacillin activity against Enterobacterales. Adult patients receiving continuous infusion (CI) of TZP and therapeutic drug monitoring (TDM) of both agents were evaluated. Demographic variables and other pertinent laboratory data were collected retrospectively. A population pharmacokinetic approach was used to select the best kidney function model predictive of TZP clearance (CL). The probability of target attainment (PTA), cumulative fraction of response (CFR) and the ratio between piperacillin and tazobactam were computed to identify optimal dosage regimens by continuous infusion across kidney function. This study included 257 critically ill patients (79.3% male) with intra-abdominal, bloodstream, and hospital-acquired pneumonia infections in 89.5% as the primary indication. The median (min-max range) age, body weight, and estimated glomerular filtration rate (eGFR) were 66 (23-93) years, 75 (39-310) kg, and 79.2 (6.4-234) mL/min, respectively. Doses of up to 22.5 g/day were used to optimize TZP based on TDM. The 2021 chronic kidney disease epidemiology equation in mL/min best modeled TZP CL. The ratio of piperacillin:tazobactam increased from 6:1 to 10:1 between an eGFR of <20 mL/min and >120 mL/min. At conventional doses, the PTA is below 90% when eGFR is ≥100 mL/min. Daily doses of 18 g/day and 22.5 g/day by CI are expected to achieve a >80% CFR when eGFR is 100-120 mL/min and >120-160 mL/min, respectively. Inadequate piperacillin and tazobactam exposure is likely in patients with eGFR ≥ 100 mL/min. Dose regimen adjustments informed by TDM should be evaluated in this specific population.

Relative aerobic load of walking in people with multiple sclerosis.

To examine the energy demand of walking relative to aerobic capacity in people with multiple sclerosis. Cross-sectional cohort study. A total of 45 people with multiple sclerosis (32 females), median disease duration 15 years (interquartile range (IQR) 9; 20), median Expanded Disability Status Scale 4 (min-max range: 2.0; 6.0). Aerobic capacity, derived from a cardiopulmonary exercise test and gas exchange measurements, assessed during a 6-min overground walk test at comfortable speed, were analysed. The relative aerobic load of walking was determined as the energy demand of walking relative to oxygen uptake at peak and at the first ventilatory threshold. Healthy reference data were used for clinical inference. People with multiple sclerosis walk at a mean relative aerobic load of 60.0% (standard deviation 12.8%) relative to peak aerobic capacity, and 89.1% (standard deviation 19.9%) relative to the first ventilatory threshold. Fourteen participants walked above the first ventilatory threshold (31%). Peak aerobic capacity was reduced in 45% of participants, and energy demands were increased in 52% of participants. People with multiple sclerosis walk at a relative aerobic load close to their first ventilatory threshold. A high relative aerobic load can guide clinicians to improve aerobic capacity or reduce the energy demands of walking.

A203 PERORAL ENDOSCOPIC MYOTOMY (POEM) FOR COMPLEX ACHALASIA AND THE POEM DIFFICULTY SCORE: AN UPDATE

Abstract Background POEM for achalasia can be challenging in patients with complex achalasia (CA) (i.e., type III achalasia, multiple prior treatments, prior myotomy, and sigmoid type). The POEM difficulty score (PDS) identifies factors that contribute to challenging POEM procedures. (Figure 1) Here, we present an update on the PDS in a series of patients with non-CA and CAs. Aims Our aim was to determine whether, with the introduction of the TT-J knife with waterjet functionality, the PDS still maintains a strong correlation with procedural efficiency and technical difficulty. Methods We retrospectively reviewed patients who underwent POEM for achalasia between May 2018 to July 2023 at the Kingston Health Sciences Center. 139 consecutive POEMs were performed, with 74 CAs. Primary outcomes include correlation of procedural efficiency with the PDS. Secondary outcomes include clinical success at the last followup and adverse events. Demographics and procedural variables were compared with descriptive statistics (mean ± SD; median, min-max range) and the Mann-Whitney U-test. Pre and post-POEM Echkhardt scores were compared using the Wilcoxon signed-rank test. Results 74 (56.7% male) complex and 65 (55.4% male) non-complex POEM procedures were carried out. The mean age is 56.7 ± 16.5 years and 47.3 ± 20.2 years in CA and non-CA respectively. PDS correlates moderately with procedural efficiency with a correlation coefficient of 0.595 (Spearman’s Pampersand:003C0.001). A subanalysis is available in Table 1. The mean efficiency for non-CA was 3.3min/cm±1.2. The median PDS for non-CA was 1 (0-5). In comparison, the mean efficiency for CA were 3.3min/cm ± 1.3 (type III), 5.3min/cm ± 2.3 (prior myotomy), 4.0min/cm ± 1.7 (≥4 prior procedures), and 5.2min/cm ± 2.4 (sigmoid type). The median PDS for CA was 3 (0-6) (type III), 4 (0-8) (prior myotomy), 3 (0-8) (≥4 prior procedures), and 3 (0-6) (sigmoid type). CA and non-CA POEM procedures were completed with 97% and 98% clinical success, respectively. Conclusions PDS continues to moderately correlate with procedural efficiency using the TT-J knife. However, the presence of spastic contractions correlated poorly with procedural efficiency. Thus, it may be omitted with the use of the TT-J knife. The order of increasing difficulty of POEM in CA appears to be type III, prior myotomy, sigmoid type, and ≥4 prior procedures. Multi-center prospective studies are needed to validate PDS in different clinical settings. Table 1: Sub-analysis of individual PDS factors and procedural velocity Figure 1: Peroral Endoscopic Myotomy (POEM) difficulty score (PDS): "FOODS" Funding Agencies None

Greenhouse gas emissions and their trends over the last 3 decades across Africa

Abstract. A key goal of the Paris Agreement (PA) is to reach net-zero greenhouse gas (GHG) emissions by 2050 globally, which requires mitigation efforts from all countries. Africa's rapidly growing population and gross domestic product (GDP) make this continent important for GHG emission trends. In this paper, we study the emissions of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) in Africa over 3 decades (1990–2018). We compare bottom-up (BU) approaches, including United Nations Convention Framework on Climate Change (UNFCCC) national inventories, FAO, PRIMAP-hist, process-based ecosystem models for CO2 fluxes in the land use, land use change and forestry (LULUCF) sector and global atmospheric inversions. For inversions, we applied different methods to separate anthropogenic CH4 emissions. The BU inventories show that, over the decade 2010–2018, fewer than 10 countries represented more than 75 % of African fossil CO2 emissions. With a mean of 1373 Mt CO2 yr−1, total African fossil CO2 emissions over 2010–2018 represent only 4 % of global fossil emissions. However, these emissions grew by +34 % from 1990–1999 to 2000–2009 and by +31 % from 2000–2009 to 2010–2018, which represents more than a doubling in 30 years. This growth rate is more than 2 times faster than the global growth rate of fossil CO2 emissions. The anthropogenic emissions of CH4 grew by 5 % from 1990–1999 to 2000–2009 and by 14.8 % from 2000–2009 to 2010–2018. The N2O emissions grew by 19.5 % from 1990–1999 to 2000–2009 and by 20.8 % from 2000–2009 to 2010–2018. When using the mean of the estimates from UNFCCC reports (including the land use sector) with corrections from outliers, Africa was a mean source of greenhouse gases of 262221863239 Mt CO2 eq. yr−1 from all BU estimates (the subscript and superscript indicate min–max range uncertainties) and of +263717615873 Mt CO2 eq. yr−1 from top-down (TD) methods during their overlap period from 2001 to 2017. Although the mean values are consistent, the range of TD estimates is larger than the one of the BU estimates, indicating that sparse atmospheric observations and transport model errors do not allow us to use inversions to reduce the uncertainty in BU estimates. The main source of uncertainty comes from CO2 fluxes in the LULUCF sector, for which the spread across inversions is larger than 50 %, especially in central Africa. Moreover, estimates from national UNFCCC communications differ widely depending on whether the large sinks in a few countries are corrected to more plausible values using more recent national sources following the methodology of Grassi et al. (2022). The medians of CH4 emissions from inversions based on satellite retrievals and surface station networks are consistent with each other within 2 % at the continental scale. The inversion ensemble also provides consistent estimates of anthropogenic CH4 emissions with BU inventories such as PRIMAP-hist. For N2O, inversions systematically show higher emissions than inventories, on average about 4.5 times more than PRIMAP-hist, either because natural N2O sources cannot be separated accurately from anthropogenic ones in inversions or because BU estimates ignore indirect emissions and underestimate emission factors. Future improvements can be expected thanks to a denser network of monitoring atmospheric concentrations. This study helps to introduce methods to enhance the scope of use of various published datasets and allows us to compute budgets thanks to recombinations of those data products. Our results allow us to understand uncertainty and trends in emissions and removals in a region of the world where few observations exist and where most inventories are based on default IPCC guideline values. The results can therefore serve as a support tool for the Global Stocktake (GST) of the Paris Agreement. The referenced datasets related to the figures are available at https://doi.org/10.5281/zenodo.7347077 (Mostefaoui et al., 2022).

Luspatercept in the Treatment of Beta Thalassemia in Italy: Lights and Shadows in Clinical Practice

Luspatercept has been demonstrated to reduce the need for blood transfusion with manageable side effects in clinical trials, thus receiving the approval for the treatment of anemia associated with transfusion dependent beta thalassemia in adults. However, very little data on its safety and efficacy in real life have been hitherto published. Special warnings and precautions for use refer to the possibility of occurrence of thromboembolic events, extramedullary hemopoiesis masses and increased blood pressure. Ten Italian Specialized Centres for the treatment of Hemoglobinopathies, with the patronage of the “Società Italiana Talassemie ed Emoglobinopatie” (SITE), evaluated the effects of luspatercept in terms of safety and blood transfusion reduction in 116 patients (Table 1) who received the first dose of the drug after its marketing. The median duration of treatment was 158 days (min-max: 15-442). β globin genotype was β 0/β 0 in 42 subjects (36.2%), β 0/ β + in 33 (28.4%), β +/ β + in 23 (19.8%), β 0/β wt plus α gene triplication in 4 (3.4%) and unknown in 14 (12%). Sixty-four patients (55.2%) were splenectomized. At the time of data collection, 32 patients (27.6%) had already discontinued the drug. Discontinuation had occurred after a median time of 132 days of treatment (min-max: 15-338) due to insufficient efficacy in the judgement of the physician (10) or patient (3), side effects attributed to luspatercept (16) that were detrimental to the continuation of therapy in the judgement of the physician (6) or patient (10), pregnancy (1) and other causes (2). There were 13 patients with a transfusion-free interval of at least 8 weeks during the treatment period (median 12 weeks, min-max range 9-48). Their median age at baseline was 37.6 years (min-max range 18.4 - 51.6) and age at first transfusion 24 years (min-max range 1 - 33). β globin genotype was β 0/ β 0 in 1 (7.7 %), β 0/ β + in 2 (15.4 %), β +/ β + in 7 (53.8 %), β 0/ β wt plus α gene triplication in 3 (23.1 %). Patients who decreased transfusion requirements by ≥ 33% and ≥ 50% in at least one of the follow-up periods of 12-weeks were 52 (44.8%) and 36 (31%), respectively. When considering the 13-24 week interval (considered as the primary endpoint of the Believe study), of the 66 patients who completed the second follow-up, 31 of 66 patients (47.0%) reduced their transfusion load by ≥33% and 20 of 66 patients (30%) by ≥50%. Focusing on the first two quarters of treatment, the pairwise t test showed a progressive and significant (p&amp;lt;0.05) reduction in the number of transfused units and pure red blood cell volumes (figure). There were no significant differences between the pre-treatment hemoglobin value and that during treatment. Serum ferritin also decreased progressively (p&amp;lt;0.05) during treatment (basal: median 576 ng/mL (Q1-Q3: 289-992); weeks 1-12: 479 ng/mL (232- 848); weeks 13-24: 385 ng/mL (212-644). The pregnancy that was initiated during the luspatercept treatment is still ongoing and no definitive information can be given. Sixty patients (51.7%) reported at least one side effect potentially related to luspatercept. The most frequent side effects were bone pain (40), asthenia-fatigue (11), hypertension requiring therapy or modification of therapy (11), joint pain (11), folic acid deficiency (6), heart palpitations (4) and edema (4). In two patients, an asymptomatic increased volume of masses of extramedullary erythropoiesis was reported. Another two patients presented with thromboembolic events: ischemic stroke in one case and superficial venous thrombosis in the other. Both were splenectomized with no other known risk factors. Despite the limitations of the short duration of follow-up, the analysis reports several significant results. The high percentage of patients who decided not to continue treatment underlines the need for a proper management of patient expectations and selection. The drug proves to be effective also in real life and those who respond best in the short and medium term seem to be who already have residual erythropoiesis, as seen from the age at the start of transfusions and the genotype of those who have had a long period of transfusion independence. Although the drug is generally well-tolerated, some adverse events appear more frequent than reported in Believe. Finally, the report of the two patients who developed a thromboembolic event including stroke, suggests the importance of continuing to be cautious in this regard.

Estimating the impact of COVID-19 vaccine inequities: a modeling study

Access to COVID-19 vaccines on the global scale has been drastically hindered by structural socio-economic disparities. Here, we develop a data-driven, age-stratified epidemic model to evaluate the effects of COVID-19 vaccine inequities in twenty lower middle and low income countries (LMIC) selected from all WHO regions. We investigate and quantify the potential effects of higher or earlier doses availability. In doing so, we focus on the crucial initial months of vaccine distribution and administration, exploring counterfactual scenarios where we assume the same per capita daily vaccination rate reported in selected high income countries. We estimate that more than 50% of deaths (min-max range: [54−94%]) that occurred in the analyzed countries could have been averted. We further consider scenarios where LMIC had similarly early access to vaccine doses as high income countries. Even without increasing the number of doses, we estimate an important fraction of deaths (min-max range: [6−50%]) could have been averted. In the absence of the availability of high-income countries, the model suggests that additional non-pharmaceutical interventions inducing a considerable relative decrease of transmissibility (min-max range: [15−70%]) would have been required to offset the lack of vaccines. Overall, our results quantify the negative impacts of vaccine inequities and underscore the need for intensified global efforts devoted to provide faster access to vaccine programs in low and lower-middle-income countries.

PO-04-227 CHARACTERISTICS AND OUTCOMES OF PREGNANT WOMEN WITHOUT STRUCTURAL HEART DISEASE PRESENTING WITH VENTRICULAR ARRHYTHMIAS

Ventricular arrhythmias (VA) are rare in pregnancy especially in women without a history of cardiac disease. We aimed to describe the characteristics of women without structural heart disease presenting with VA during pregnancy, and the maternal and fetal outcomes. Pregnant women without known structural heart disease referred to a specialized pregnancy program for VA during pregnancy were retrospectively reviewed. VA were defined as 1) high burden PVCs (PVC>500/24 hours), 2) non sustained VT (NSVT, 3 or more beats at a rate>100 bm lasting for less than 30 s) or 3) sustained VT (ventricular tachycardia at a rate>100 bm lasting for more than 30 minutes). Holter recordings, ECGs and telemetry strips were reviewed. Baseline characteristics and maternal and fetal outcomes were collected. Of 81 women referred for VA, 63 had documented VA during pregnancy and were included in the study. Mean age was 34±5 years and 28 (44%) were nulliparous. A total of 20 (32%) women presented for high PVC burden, 18 (28%) for NSVT, and 22 (35%) for both. Three patients (5%) presented with sustained VT requiring emergent intervention. The median Holter PVC burden was 12% (min-max range 1-66%); the median NSVT length was 10 beats± 8 and the median rate was 178±38 bpm. Most of the VA occurred during the second trimester (mean week 24 ±8). Nine (14%) women had an abnormal ECG at baseline. A total of 40 women had documentation of the VA morphology from the 12-lead-ECG and 18 (45%) of them had an origin from the right ventricular outflow tract (RVOT, Figure 1). A total of 41(66%) were treated with betablockers (29 with metoprolol, 3 bisoprolol, 2 nadolol, 5 with propranolol), 2 with verapamil, 2 with flecainide and 1 with amiodarone. Eleven (18%) women required hospital admission (Table 1) and initiation or adjustment of drug therapy. Three patients had thromboembolic events. Of the three patients who presented with sustained arrhythmias, one had symptomatic heart failure and one died during pregnancy. Eight babies and 6 twins (total 14) had a birthweight <2500 gr, four babies were born preterm and 4 required resuscitation at birth. No fetal deaths occurred. Ventricular arrhythmias from the RVOT are common in pregnant women without structural heart disease. Most of the women with non-sustained arrhythmias have favorable outcomes, however, careful fetal and maternal monitoring in a specialized pregnancy program is required.Tabled 1Table 1: Details of hospital admissions (PO-04-227)Patient numberAge at deliveryGA (weeks)SymptomsVA detailsRVOT morphologyTreatmentOutcomes1232329SyncopePre-syncopePVCs, NSVTYesMetoprolol 37.5 mg TIDTransition from verapamil 120 mg TID to flecainide 50 mg TIDDischarged home23512Pre-syncopePVCs, NSVTNo (polymorphic)Metoprolol titration from 50 mg bid to 75 mg BIDDischarged home33512Pre-syncope/palpitationsSustained VTNo (RBBB, QRS axis +60ˆ)IV procainamide+ IV metoprololFlecainide 150 BID+ nadolol 120 ODDischarged home44024Palpitations/shortness of breathPVCs, NSVTYesTransition from metoprolol 25 mg BID to verapamil 240 mg BIDDischarged home53835SyncopeNSVTYesMetoprolol 50 TIDDischarged home63529Pre-syncope/palpitationsSustained VTNo (LBBB, superior axis)Esmolol IV infusionMetoprolol 125 TIDAmiodarone 400 mg ODDischarged home73424Cardiac arrestSustained VTNo (LBBB, QRS axis -30ˆ)CPR + epinephrineDeath83929PalpitationsPVCs, NSVTNo (RBBB, inferior axis)None (patient refused)Discharged home93924PalpitationsNSVTUnknownPropranolol 20 TIDDischarged home103835PalpitationsPVCsYesNone (patient refused)Discharged home113113Pre-syncope/palpitationsNSVTNo (LBBB, superior axis)Metoprolol 37.5 mg TIDDischarged home Open table in a new tab

The Effect of Numerical Mapping Techniques on Performance in Genomic Research

In genomic signal processing applications, digitization of these signals is needed to process and analyze DNA signals. In the digitization process, the mapping technique to be chosen greatly affects the performance of the system for the genomic domain to be studied. The purpose of this review is to analyze how numerical mapping techniques used in digitizing DNA sequences affect performance in genomic studies. For this purpose, all digital coding techniques presented in the literature in the studies conducted in the last 10 years have been examined, and the numerical representations of these techniques are given in a sample DNA sequence. In addition, the frequency of use of these coding techniques in four popular genomic areas such as exon region identification, exon-intron classification, phylogenetic analysis, gene detection, and the min-max range of the performances obtained by using these techniques in that area are also given. This study is thought to be a guide for researchers who want to work in the field of bioinformatics.

Advanced EEG Signal Based Min to Mean Algorithm Approach For Human Emotion Taxonomy And Mental State Analysis

With electroencephalography (EEG) brain waves alone, it is full-scale phenomena in the field of computer-brain interface DNN, CNN, and SVM have improved detection and prediction accuracy in a number of researches during the last several years. But when it comes to recognizing global reliance, both deep learning and SVM have obvious limits. Pre-processing, extraction capabilities, and network design are the most common techniques used in deep learning models today, yet they are still unable to produce reliable results in noisy and sparse datasets. Any dataset, no matter how little or large, may suffer from poor SVM performance due to overlapping target instructions and boundaries. There are many different sorts of emotions that may be classified using the particular approach employed in this research. In order to get a whole picture of a person's mental state, it is best to use a "Min of mean” proposed technique. After comparison to the referential mean, a feeling is divided into one of four emotional quadrants. The MIN Max range is used to further split the emotion into 12 subcategories based on the amount of arousal. The proposed set of rules performed better than existing methods. Research on multi-class emotion reputation has shown that, compared to more recent studies, the proposed technique may be rather strong. It is possible to analyze a person's mental health by using the emotional spectrum, which has an accuracy rate of above 90%.

Assessing vascular complexity of PAOD patients by deep learning-based segmentation and fractal dimension

The assessment of vascular complexity in the lower limbs provides relevant information about peripheral artery occlusive diseases (PAOD), thus fostering improvements both in therapeutic decisions and prognostic estimation. The current clinical practice consists of visually inspecting and evaluating cine-angiograms of the interested region, which is largely operator-dependent. We present here an automatic method for segmenting the vessel tree and compute a quantitative measure, in terms of fractal dimension (FD), of the vascular complexity. The proposed workflow consists of three main steps: (i) conversion of the cine-angiographies to single static images with a broader field of view, (ii) automatic segmentation of the vascular trees, and (iii) calculation and assessment of FD as complexity index. In particular, this work defines (1) a method to reduce the inter-observer variability in judging vascular complexity in cine-angiography images from patients affected by peripheral artery occlusive disease (PAOD), and (2) the use of Fractal Dimension as a metric of shape complexity of vascular tree. The inter-class correlation coefficient (ICC) is computed as inter-observer agreement metric and to account for possible systematic error, that depends on the experience of the raters. The automatic segmentation of vascular tree achieved an Area Under the Curve mean value of 0.77~pm ~0.07, with a min-max range of 0.57-0.87. Absolute operator agreement was higher over the segmented image (ICC=0.96) compared to the video (ICC=0.76) and the a broader field of view image (ICC=0.92). Fractal Dimension computed on both manual segmented images (ground truths) and automatically showed a good correlation with the clinical score (0.85 and 0.75, respectively). Experimental analyses suggest that extracting the vascular tree from cine-angiography can substantially improve the reliability of visual assessment of vascular complexity in PAOD. Results also reveal the effectiveness of FD in evaluating complex vascular tree structures.

Pan-cancer proteomic map of 949 human cell lines.

SummaryThe proteome provides unique insights into disease biology beyond the genome and transcriptome. A lack of large proteomic datasets has restricted the identification of new cancer biomarkers. Here, proteomes of 949 cancer cell lines across 28 tissue types are analyzed by mass spectrometry. Deploying a workflow to quantify 8,498 proteins, these data capture evidence of cell-type and post-transcriptional modifications. Integrating multi-omics, drug response, and CRISPR-Cas9 gene essentiality screens with a deep learning-based pipeline reveals thousands of protein biomarkers of cancer vulnerabilities that are not significant at the transcript level. The power of the proteome to predict drug response is very similar to that of the transcriptome. Further, random downsampling to only 1,500 proteins has limited impact on predictive power, consistent with protein networks being highly connected and co-regulated. This pan-cancer proteomic map (ProCan-DepMapSanger) is a comprehensive resource available at https://cellmodelpassports.sanger.ac.uk.

Cerebral Ischemic Events: An Overlooked Complication of Transthyretin Cardiac Amyloidosis in Afro-Caribbean Patients

AimThe link between transthyretin cardiac amyloidosis (CATTR), and cerebral ischemic events (CIE) has only been hinted at till now, impeding progress in patient management. We seek to evaluate the frequency and characteristics of CIE in Afro-Caribbean patients followed for CATTR at our institution.MethodsIn this single-center retrospective observational study, Afro-Caribbean patients followed for CATTR between July 2005 and October 2019 were included. Occurrence of CIE was investigated, and their cardioembolic origin determined. Analysis of patient characteristics was conducted according to CIE and CATTR profiles.ResultsOverall, 120 CATTR patients were included: 17 wild-type ATTR (14.2%), 73 ATTR-V122I (60.8%), and 22 ATTR-I107V (18.3%). Thirty-six patients (30.0%) presented with CIE, including three transient ischemic attacks and 33 permanent ischemic strokes (75.8% with a cardioembolic pattern). CIE was concomitant with CATTR diagnosis in 16 (16/36: 44.4%) patients, while 14 patients (14/36: 38.9 %) experienced CIE over a median CATTR follow-up of 2.0 years (min-max range: 0.8–4.4 years). CATTR-CIE patients presented with atrial fibrillation (66.7%), left atrial enlargement (77.8%), a CHA2DS2-VASc ≥ 3 (97.2%) and a high anticoagulant intake (75.0%). Multivariate analysis retained only a high CHA2DS2-VASc score as an independent predictor of CIE risk (Hazard Ratio [95% CI]: 12.03 [1.62–89.24]).ConclusionConcomitant CIE, and CATTR diagnosis, potentially carries a worse prognosis. A CHA2DS2-VASc score ≥3 seems to be a strong and independent predictive factor of CIE in CATTR patients. Further studies are needed to assess the efficacy and timeliness of anticoagulation in CATTR patients, independently of atrial fibrillation.

MO015: The Interaction of Gender and Genotype in the Development of Polycystic Liver Disease in ADPKD

Abstract BACKGROUND AND AIMS Liver cysts are the most common extra-renal manifestation in autosomal dominant polycystic kidney disease (ADPKD) and polycystic liver disease (PLD) may result in significant morbidity in a proportion of patients. The major objective of this study was to investigate the relationship between the incidence of liver cysts and PLD with age, gender and genotype in a longitudinal ADPKD patient cohort (n = 625) followed up between 2010 and 2021. METHOD A retrospective analysis of PLD was performed on all patients with available abdominal US (US, n = 565) or abdominal MRI/CT (n = 321) imaging. Liver cyst counts were obtained from routine clinical reports (US) or quantified by a single-blinded observer (MR/CT). Patients were divided into subgroups of different severity based on cyst numbers detected on US (QIAN 0–4) or MRI/CT (CHEN 0–3): QIAN 0 (0), 1 (&amp;lt;10), 2 (10–20), 3/4 (&amp;gt;20); CHEN 0 (0), 1 (&amp;lt;20), 2 (21–40), 3 (&amp;gt;40). Patients who were genotyped (n = 390) were classified into those with PKD1 (T, truncating or NT, non-truncating), PKD2, other genes (non-PKD1 or PKD2) or NMD (no mutation detected). The potential influence of genotype and gender on the incidence of liver cysts and the time to the development of PLD (defined as QIAN 3/4 or CHEN 3) was investigated by survival analysis (Kaplan–Meier plots). Hazard ratios (HR) were calculated and statistical significance was determined via Log-rank (Mantel-Cox) or Chi-square tests. RESULTS Liver cysts were detected in 61% of patients by US and 72% by MRI/CT, increasing with age. Kaplan–Meier plots showed a significant effect of gender for the presence of liver cysts (M: F HR of 0.74 US, 0.69 MR/CT). Genotype had a major effect on the prevalence of liver cysts (US, n = 344) with a median age of 46, 53, 59, 75 and 77 years for PKD1-T, PKD1-NT, PKD2, other genes or NMD, respectively. A similar trend was noted for patients with MR/CT imaging. The percentage of patients with PLD (QIAN 3/4 or CHEN 3) ranged between 26% (US) and 36% (MR/CT) with a median age for developing PLD of 51 (US; min-max range 23–80 years) and 50 years (MR/CT; min-max range 27–81 years), respectively. The incidence of PLD was more strongly influenced by gender (M: F HR 0.53 US, 0.56 MR/CT) and was highly enriched in patients with PKD1 or PKD2 mutations. CONCLUSION Female patients with a PKD1-T genotype appear to be at the highest risk of developing PLD. Genotypes other than PKD1 or PKD2 are unlikely to develop PLD. Further work is needed to improve risk stratification and treatments for PLD by identifying additional pathogenic factors.

Levels of non-essential trace metals and their impact on placental health: a review.

According to recent research, even low levels of environmental chemicals, particularly heavy metals, can considerably disrupt placental homeostasis. This review aims to explore the profile of non-essential trace metals in placental tissues across the globe and to specify trace metal(s) that can be candidates for impaired placental health. Accordingly, we conducted an extensive survey on relevant databases of peer-reviewed papers published in the last two decades. Among a considerable number of non-essential trace metals, arsenic (As), lead (Pb), cadmium (Cd), and mercury (Hg) were identified as the most detrimental to placental health. Comparative analysis showed remarkable differences in placental levels of these trace metals worldwide. Based on current data reported across the globe, a median (min-max) range from 0.55 to 15ng/g for placental As levels could be deemed safe. The placental Cd and Pb levels were markedly higher in smokers than in non-smokers. Occupationally exposed pregnant women had several orders of magnitude higher Cd, Pb, and Hg levels in placental tissues than non-occupationally exposed women. Also, we concluded that even low-level exposure to As, Cd, Pb, and Hg could be deleterious to proper fetal development. This review implies the need to reduce exposure to non-essential trace metals to preserve placental health and prevent numerous poor pregnancy outcomes. Overall, the information presented is expected to help plan future fundamental and applied investigations on the placental toxicity of As, Cd, Pb, and Hg.

Age-related differences in the error-related negativity and error positivity in children and adolescents are moderated by sample and methodological characteristics: A meta-analysis.

The error‐related negativity (ERN) and the error positivity (Pe) are electrophysiological components associated with error processing that are thought to exhibit distinctive developmental trajectories from childhood to adulthood. To investigate the age and age moderation effects on the ERN and the Pe strength during development, we conducted a preregistered three‐level meta‐analysis synthesizing 120 and 41 effect sizes across 18 group comparison studies and 19 correlational studies, respectively. The meta‐analysis included studies with mean age between 3.6 and 28.7 (min‐max age range: 3.5 and 49.8) years for age‐group comparisons and 6.1 to 18.7 (min‐max age range: 4.0–35.7) years for age correlations. Results showed that age was associated with a more negative ERN (SMD = −.433, r = −.230). No statistically significant association between age and the Pe was found (SMD = .059, r = −.091), except for in a group comparison between younger and older adolescents. The age effects were not significantly moderated by whether a Flanker or a Go/No‐Go task was used, whereas a probabilistic learning task moderated the age effect on the Pe. Moreover, the Fz and Cz electrode sites yielded stronger negative associations between age and the ERN and the Pe, respectively. The results confirm that the ERN and the Pe show differential development courses and suggest that sample and methodological characteristics influence the age effects, and lay the foundation for investigations of developmental patterns of the ERN and the Pe in relation to psychopathology and early genetic and environmental risk factors.

The prolonged clinical benefit with metronomic chemotherapy (VEX regimen) in metastatic breast cancer patients.

Metronomic chemotherapy is a treatment option for metastatic breast cancer (MBC) patients who require prolonged disease control without cumulative toxicity. Data available on the efficacy and tolerability of prolonged usage of metronomic therapy are limited. We analyzed patients with MBC, enrolled in a clinical trial, who obtained a prolonged clinical benefit for a duration of at least 12 months with vinorelbine 30 or 40 mg orally three times a week, cyclophosphamide 50 mg daily and capecitabine 500 mg three times a day (VEX regimen). The patients were treated at the European Institute of Oncology, Milan. We identified 67 MBC patients. The median age before starting the VEX regimen was 53 years. There were 59 patients (88%) who had hormone-receptors positive and HER2 negative BC. We had 37 patients who received VEX as the first-line treatment for MBC, while 30 patients were pretreated. The objective response rate was 49% (95% CI, 37-62). The median duration of VEX treatment after the first year was 14 months (min-max range 0.3-81.3 months). The progression-free survival at 3 years was 25.4% (95% CI, 15.7-36.2) and at 4 years was 18.5% (95% CI, 10.1-28.8 time 0 corresponds to 1 year after starting VEX). A total of 25 patients required a dose reduction, 7% of patients experienced G3 hand and foot syndrome. Metronomic VEX regimen can induce prolonged clinical benefit in MBC. On the basis of this long-term safety evaluation, there is no evidence of specific cumulative or delayed toxicities with metronomic chemotherapy.