bluuebunny/crossref_metadata_2025 huggingface dataset:
On the persistence and related mechanisms for day–night compound humid heat extremes in the Northern Hemisphere
Authors: Guo Yixuan , Fu Zuntao
Published: May 2024

Hot extremes pose adverse impacts on human health and ecosystem, leading to aggravated damage when they combine high-humidity and occur in the both daytime and nighttime. Although considerable studies have focused on hot extremes, understandings about day–night Compound humid heat (quantified by Moist Enthalpy) Extremes (CMEEs) are still lacking. This work investigates their frequency, linear trends and temporal persistence in the Northern Hemisphere, and two typical vulnerable regions are selected as Central Europe (CE) and the Arabian Peninsula (AP), both exhibiting high frequency and positive trends, but with contrasting persistence, which is quantified by the bivariate Dynamical System method. Results reveal their regional dependence and physical processes: the dual importance of sensible and latent heat in CE is attributed to the combination of an anomalous anticyclone and evaporation, whereas the dominance of latent heat in AP is largely owing to the convective precipitation. CMEEs in AP can be further divided into two groups with distinct persistence, and this disparity actually depends on the preceding precipitation duration and its associated water vapor supply.
Analysis of application range of simplified models for field to thermo-field to thermionic emission processes from the cathode
Authors: SUN 孙 Li 丽 , DAI 代 Zhuo 卓 , XU 徐 Ming 鸣 , WANG 王 Wei 伟 , LI 李 Zengyao 增耀
Published: May 2024

Electron emission plays a dominant role in plasma–cathode interactions and is a key factor in many plasma phenomena and industrial applications. It is necessary to illustrate the various electron emission mechanisms and the corresponding applicable description models to evaluate their impacts on discharge properties. In this study, detailed expressions of the simplified formulas valid for field emission to thermo-field emission to thermionic emission typically used in the numerical simulation are proposed, and the corresponding application ranges are determined in the framework of the Murphy–Good theory, which is commonly regarded as the general model and to be accurate in the full range of conditions of the validity of the theory. Dimensionless parameterization was used to evaluate the emission current density of the Murphy–Good formula, and a deviation factor was defined to obtain the application ranges for different work functions (2.5‒5 eV), cathode temperatures (300‒6000 K), and emitted electric fields (105 to 1010 V·m−1). The deviation factor was shown to be a nonmonotonic function of the three parameters. A comparative study of particle number densities in atmospheric gas discharge with a tungsten cathode was performed based on the one-dimensional implicit particle-in-cell (PIC) with the Monte Carlo collision (MCC) method according to the aforementioned application ranges. It was found that small differences in emission current density can lead to variations in the distributions of particle number density due to changes in the collisional environment. This study provides a theoretical basis for selecting emission models for subsequent numerical simulations.
Regression calibration of self-reported mobile phone use to optimize quantitative risk estimation in the COSMOS study
Authors: Reedijk Marije , Portengen Lützen , Auvinen Anssi , Kojo Katja , Heinävaara Sirpa , Feychting Maria , Tettamanti Giorgio , Hillert Lena , Elliott Paul , Toledano Mireille B , Smith Rachel B , Heller Joël , Schüz Joachim , Deltour Isabelle , Poulsen Aslak Harbo , Johansen Christoffer , Verheij Robert , Peeters Petra , Rookus Matti , Traini Eugenio , Huss Anke , Kromhout Hans , Vermeulen Roel ,   The COSMOS Study Group
Published: May 2024

The Cohort Study of Mobile Phone Use and Health (COSMOS) has repeatedly collected self-reported and operator-recorded data on mobile phone use. Assessing health effects using self-reported information is prone to measurement error, but operator data were available prospectively for only part of the study population and did not cover past mobile phone use. To optimize the available data and reduce bias, we evaluated different statistical approaches for constructing mobile phone exposure histories within COSMOS. We evaluated and compared the performance of 4 regression calibration (RC) methods (simple, direct, inverse, and generalized additive model for location, shape, and scale), complete-case analysis, and multiple imputation in a simulation study with a binary health outcome. We used self-reported and operator-recorded mobile phone call data collected at baseline (2007-2012) from participants in Denmark, Finland, the Netherlands, Sweden, and the United Kingdom. Parameter estimates obtained using simple, direct, and inverse RC methods were associated with less bias and lower mean squared error than those obtained with complete-case analysis or multiple imputation. We showed that RC methods resulted in more accurate estimation of the relationship between mobile phone use and health outcomes by combining self-reported data with objective operator-recorded data available for a subset of participants.
Real-world data are not always big data: the case for primary data collection on medication use in pregnancy in the context of birth defects research
Authors: Ailes Elizabeth C , Werler Martha M , Howley Meredith M , Jenkins Mary M , Reefhuis Jennita
Published: May 2024

Many examples of the use of real-world data in the area of pharmacoepidemiology include “big data,” such as insurance claims, medical records, or hospital discharge databases. However, “big” is not always better, particularly when studying outcomes with narrow windows of etiologic relevance. Birth defects are such an outcome, for which specificity of exposure timing is critical. Studies with primary data collection can be designed to query details about the timing of medication use, as well as type, dose, frequency, duration, and indication, that can better characterize the “real world.” Because birth defects are rare, etiologic studies are typically case‑control in design, like the National Birth Defects Prevention Study, Birth Defects Study to Evaluate Pregnancy Exposures, and Slone Birth Defects Study. Recall bias can be a concern, but the ability to collect detailed information about both prescription and over-the-counter medication use and other exposures such as diet, family history, and sociodemographic factors is a distinct advantage over claims and medical record data sources. Case‑control studies with primary data collection are essential to advancing the pharmacoepidemiology of birth defects.

This article is part of a Special Collection on Pharmacoepidemiology.
Introducing the special issue: the lasting legacy of the 1996 Arbitration Act
Authors: Brekoulakis Stavros
Published: May 2024

This article introduces the special issue and sets the scene for the other contributors which address in more detail specific areas of the Bill. Specifically, this introductory article aims to do three things. First, to take a step back and place the New Act against England’s long history of arbitration law. Second, to identify and discuss the most important decisions of the English courts in the 25 years of the 1996 Act and examine whether they played any role in the constitution of the New Act. Finally, to offer a broad assessment of the Bill.
Optimal fusion of genotype and drug embeddings in predicting cancer drug response
Authors: Nguyen Trang , Campbell Anthony , Kumar Ankit , Amponsah Edwin , Fiterau Madalina , Shahriyari Leili
Published: May 2024

Predicting cancer drug response using both genomics and drug features has shown some success compared to using genomics features alone. However, there has been limited research done on how best to combine or fuse the two types of features. Using a visible neural network with two deep learning branches for genes and drug features as the base architecture, we experimented with different fusion functions and fusion points. Our experiments show that injecting multiplicative relationships between gene and drug latent features into the original concatenation-based architecture DrugCell significantly improved the overall predictive performance and outperformed other baseline models. We also show that different fusion methods respond differently to different fusion points, indicating that the relationship between drug features and different hierarchical biological level of gene features is optimally captured using different methods. Considering both predictive performance and runtime speed, tensor product partial is the best-performing fusion function to combine late-stage representations of drug and gene features to predict cancer drug response.
scMNMF: a novel method for single-cell multi-omics clustering based on matrix factorization
Authors: Qiu Yushan , Guo Dong , Zhao Pu , Zou Quan
Published: May 2024

Motivation

The technology for analyzing single-cell multi-omics data has advanced rapidly and has provided comprehensive and accurate cellular information by exploring cell heterogeneity in genomics, transcriptomics, epigenomics, metabolomics and proteomics data. However, because of the high-dimensional and sparse characteristics of single-cell multi-omics data, as well as the limitations of various analysis algorithms, the clustering performance is generally poor. Matrix factorization is an unsupervised, dimensionality reduction-based method that can cluster individuals and discover related omics variables from different blocks. Here, we present a novel algorithm that performs joint dimensionality reduction learning and cell clustering analysis on single-cell multi-omics data using non-negative matrix factorization that we named scMNMF. We formulate the objective function of joint learning as a constrained optimization problem and derive the corresponding iterative formulas through alternating iterative algorithms. The major advantage of the scMNMF algorithm remains its capability to explore hidden related features among omics data. Additionally, the feature selection for dimensionality reduction and cell clustering mutually influence each other iteratively, leading to a more effective discovery of cell types. We validated the performance of the scMNMF algorithm using two simulated and five real datasets. The results show that scMNMF outperformed seven other state-of-the-art algorithms in various measurements.

Availability and implementation

scMNMF code can be found at https://github.com/yushanqiu/scMNMF.
The potential effect of melatonin on in vitro oocyte maturation and embryo development in animals
Authors: Nadri Parisa , Zahmatkesh Azadeh , Bakhtari Azizollah
Published: May 2024

Melatonin is a hormone mainly secreted by the pineal gland during the circadian cycle, with low levels during the daytime and prominent levels during the night. It is involved in numerous physiological functions including the immune system, circadian rhythm, reproduction, fertilization, and embryo development. In addition, melatonin exerts anti-inflammatory and antioxidant effects inside the body by scavenging reactive oxygen and reactive nitrogen species, increasing antioxidant defenses, and blocking the transcription factors of pro-inflammatory cytokines. Its protective activity has been reported to be effective in various reproductive biotechnological processes, including in vitro maturation (IVM), embryo development, and survival rates. In this comprehensive review, our objective is to summarize and debate the potential mechanism and impact of melatonin on oocyte maturation and embryo development through various developmental routes in different mammalian species.
Colour-coded collateral and venous outflow patterns in estimating infarct progression and predicting functional independence for stroke patients in late time window
Authors: Lin Yu , Xing Zhen , Lv Shaomao , Yang Xiefeng , Kang Jianghe , Kang Nannan , Wang Jinan , Cao Dairong
Published: May 2024

Objectives

To investigate whether cerebral collateral and venous outflow (VO) patterns on colour-coded multi-phase computed tomography angiography (mCTA) can estimate ischaemic core growth rate (IGR) and predict 90-day functional independence for patients with late-presenting acute ischaemic stroke (AIS).

Methods

The retrospective analysis included 127 AIS patients with a late time window. All patients underwent baseline mCTA with colour-coded reconstruction and computed tomography perfusion. Both collateral score and VO score on colour-coded mCTA maps were analysed and recorded. The IGR was calculated as ischaemic core volume divided by the time from onset to imaging. A 90-day modified Rankin Scale score of 0-2 was defined as functional independence. Kendall’s Tau-b analysis was used for nonparametric correlation analysis. Propensity scores, logistic regressions, and receiver operator characteristic (ROC) curves were applied to construct the prediction model.

Results

Moderate correlations were found between collateral delay and IGR (Tau-b = -0.554) and between VO and IGR (Tau-b = -0.501). High collateral score (odds ratio = 3.01) and adequate VO (odds ratio = 4.89) remained independent predictors for 90-day functional independence after adjustment. The joint predictive model, which integrated the VO score and clinical features, demonstrated an area under the ROC curve (AUC) of 0.878. The AUCs of collateral score and VO score were 0.836 and 0.883 for outcome prediction after adjustment.

Conclusions

Cerebral collateral and VO patterns based on colour-coded mCTA can effectively predict infarct progression and 90-day clinical outcomes, even for AIS patients beyond the routine time window.

Advances in knowledge

Colour-coded mCTA is a readily understandable post-processing technique for the rapid assessment of collateral circulation and VO status in stroke imaging. A moderate correlation was observed between the characteristics of collateral delay/VO on colour-coded mCTA and IGR in patients with AIS. Both high-quality collateral circulation and “red superficial middle cerebral vein sign” can predict 90-day functional independence even for patients beyond the routine time window.
How Preoperative Investigations Affect the Management of Bariatric Patients - Results of a Cohort Study of 897 Patients
Authors: Poljo A , Schneider R , Süsstrunk J , Klasen J M , Billeter A T , Peterli R , Kraljević M
Published: May 2024

Background

Poorly defined preoperative diagnostic protocols worldwide vary in their emphasis on comprehensive investigations, with some prioritizing patient safety while others question routine procedures.

Aims

This study explores how diverse preoperative findings, from inflammatory processes to structural abnormalities, significantly influence patients’ management and the choice of bariatric procedures, underscoring the complexity in decision-making for individualized surgical interventions based on a cohort study's findings.

Methods

In a retrospective analysis of prospective data of over 1000 bariatric surgery patients from January 2017 to December 2022, we specifically included those who underwent primary laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG). In all patients, preoperative upper endoscopy was performed, with selected candidates also undergoing additional procedures like upper GI series and esophageal manometry, especially when LSG was planned. The study primarily analyzed the impact of preoperative examinations on therapeutic approaches.

Results

In this study, 897 patients were included, with 741 undergoing laparoscopic LRYGB and 156 LSG. All patients underwent upper endoscopy, revealing common findings such as type C gastritis, gastroesophageal reflux disease, and detection of Helicobacter pylori. Upper endoscopy prompted a therapeutic change in 216 patients (24.3%), resulting in a number needed to screen (NNS) of 4.1, with no significant differences based on the initially scheduled procedure. Preoperatively, upper GI series were more frequently conducted before planned LSG, uncovering hiatal hernias and motility disorders. However, no change in the surgical procedure resulted from upper GI series findings. Esophageal manometry, primarily performed for LSG, indicated normal findings in 84.6%, with a procedural change in 3 patients (2.0%). Overall, 14 (1.6%) patients experienced a change in the planned procedure, with 12 changes prompted by preoperative findings and two by technical difficulties.

Conclusion

We recommend routine upper endoscopy for all bariatric surgery patients, with additional manometry for planned LSG. Upper GI series should be reserved for selected cases and specific clinical indications.
Proficiency and Depth of Surgical Education in Switzerland is Heading in the Wrong Direction
Authors: Schöb T , Klein I
Published: May 2024

Background

In Switzerland, surgical resident training has become increasingly difficult over the past decades for numerous reasons. While the number of surgical residents has doubled over twenty years, the average workweek dropped from 70 to 50 hours. At the same time, the surgical caseload increased only marginally as opposed to the proportion of administrative responsibilities, resulting in a substantial decrease of intraoperative exposure in surgical residency training.

Aims

To assess the surgical exposure of our residents.

Methods

This study is a review of all performed surgical procedures in the field of general, abdominal, thoracic, vascular and trauma surgery at a category-A Cantonal hospital in Switzerland, performed from September 1st 2021 to August, 31st 2023. The primary outcome was surgical exposure of residents as primary, secondary, and assisting surgeons. Secondary outcomes were case-distribution during daytime workhours as opposed to on-call hours per resident.

Results

The surgical exposure of a surgical resident at our cantonal hospital as primary and secondary surgeon was 41.19 and 39.06 minutes respectively per week. This surgical exposure as was paired with a total of 127.46 minutes as assisting surgeons per week. On average this results in 1.34 operations per week and 60.3 cases per year per surgical resident. 73.51% of these cases are performed during daytime work hours and 26.49% during on-call hours.

Conclusion

To fulfill the minimal number of 510 cases in the mandatory FMH surgical catalogue of becoming a general surgeon, a total residency period of 8.46 years would become necessary to take the exam based on the average number of operative cases in this category-A teaching hospital which is considerably longer compared to residency training 20 years ago. While surgical procedures and techniques continue to become more complex, the need to exploit ways to maintain a sufficient level of surgical exposure inside and outside the OR is eminent.
Autonomous and Self-sustained Circadian Oscillators Displayed in Human Primary Parathyroid Cell Culture Drive Parathormone Secretion
Authors: Petrenko V , Dibner C , Golaz O , Triponez F , de Vito C , Demarchi M S
Published: May 2024

Background

Most cells in our body possess circadian oscillators controlling diurnal rhythmicity of body metabolism. The role of molecular clocks in regulating the function and disfunction of human parathyroid gland (PG), responsible for calcium homeostasis, has not been unraveled. Hyperparathyroidism is a common endocrine pathology, characterized by an unadapted PTH secretion to calcium levels.

Aims

Here we aimed at characterizing molecular makeup of circadian clocks in human primary parathyroid cell culture (HPPCC), and at establishing differential transcriptional patterns of normal and pathological PGs.

Methods

RNA extracted from normal, adenomatous, and hyperplastic PG tissues was subjected to RNA sequencing (RNAseq) analysis. The rim of normal PG tissue was dissected from parathyroid adenoma specimens based on the higher autofluorescence intensity assessed by the near infra-red imaging. HPPCCs were established from adenomatous and hyperplastic PG biopsies. Efficient circadian clock disruption was achieved in HPPCCs by small interfering RNA-mediated knockdown of CLOCK. The functionality of circadian clock machinery was assessed by continuous recording of circadian bioluminescence introduced via lentivectors and paralleled with around-the-clock measurement of PTH secretion using perfusion system.

Results

The RNAseq analyses revealed transcriptional signatures that distinguished between pathological and normal PGs, and among adenomatous and hyperplastic PGs. We report, for the first time, robust anti-phasic circadian rhythmicity of Per2-luciferase and Bmal1-luciferase reporters in HPPCCs synchronized in vitro. Strikingly, we observed circadian rhythmicity of PTH secretion by parathyroid adenoma cells. Moreover, clock disruption in PG adenoma cells has an impact on transcription of functional genes.

Conclusion

Our data indicate presence of cell-autonomous molecular clock in human PG cells paralleled with circadian rhythmic PTH secretion and provide large-scale transcriptional pattern of parathyroid adenoma and hyperplastic tissues.
Syndromic MEN1 Parathyroid Adenomas Consist of Both Subclonal Nodules and Clonally Independent Tumors
Authors: Nesti C , Bräutigam K , Niederle B , Perren A , Kaderli R M
Published: May 2024

Background

Primary hyperparathyroidism with parathyroid tumors is a characteristic presentation in Multiple Endocrine Neoplasia Type 1 (MEN1), historically referred to as "primary hyperplasia." The question of whether these tumors signify a multi-glandular clonal disorder or hyperplasia remains inconclusive. Loss of Menin protein expression serves as a reliable surrogate marker for biallelic inactivation and indicates a mutation in the MEN1 gene. The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene, associated with MEN4, encodes the p27 protein, whose expression is inadequately explored in the context of syndromic MEN1.

Aims

The aim was to explore the molecular basis of syndromic MEN1 parathyroid adenomas, identifying hyperplasia, multiple independent clones, and the extent of Menin loss. Additionally, p27 expression was assessed to evaluate its potential in indicating a germline mutation, especially in distinguishing MEN4 as a clinical alternative to MEN1.

Methods

In this investigation, we examined histomorphology and protein expression of Menin and p27 in parathyroid adenomas from 25 patients in two independent, well-characterized MEN1 cohorts. Loss of heterozygosity (LOH) patterns were evaluated using fluorescence in situ hybridization (FISH) in one MEN1-associated parathyroid adenoma. Furthermore, next-generation sequencing (NGS) was conducted on eleven nodules from four MEN1 patients.

Results

Morphologically, the majority of MEN1 adenomas displayed multiple distinct nodules, characterized by predominantly lost Menin expression and reduced p27 protein expression. FISH analysis indicated that most nodules exhibited MEN1 loss, with or without centromere 11 loss. NGS demonstrated both subclonal evolution and the existence of clonally unrelated tumors.

Conclusion

Syndromic MEN1 parathyroid adenomas, therefore, consist of multiple clones with subclones, aligning with the current framework of the novel WHO classification of parathyroid tumors (2022). The observed loss of p27 expression in a significant fraction of MEN1 parathyroids emphasizes the need for caution when inferring MEN4 solely based on p27 expression.
Our Experience with Primary Trapeziometacarpal Implant Arthroplasty in Severely Comminuted Rolando Fractures
Authors: Greminger M , Buechel R
Published: May 2024

Background

The concept of primary joint replacement in severely comminuted fractures in elderly patients has proven to be a suitable treatment option in the shoulder, elbow and knee joint. Comminuted intra-articular fractures of the first metacarpal base can pose significant technical challenges, and no established gold standard treatment currently exists. Conventional methods like open reduction and internal fixation or external fixation are commonly employed, emphasizing the importance of anatomical reduction for restoring the articular surface. However, achieving articular surface congruity is often unattainable in severely comminuted intra-articular fractures, leading to short-term joint stiffness and instability, as well as long-term complications like secondary osteoarthritis.

Aims

This case report aims to share our experience with the use of primary trapeziometacarpal implant arthroplasty in the treatment of two patients with severely comminuted Rolando fractures.

Methods

In two cases of comminuted Rolando fractures, a primary trapeziometacarpal prosthesis (MAÏA™) was implanted based on preoperative decision-making facilitated by 3D-CT analysis. Patient’s visual analogue score for pain, range of motion, pinch and grip strength compared to the contralateral side were asked and examined.

Results

Both patients exhibited successful adaptation to their daily routines within a three-month postoperative period. No complications, such as cup or stem loosening or dislocation, were identified. Both patients almost reached equal range of motion, pinch and grip strength compared to the contralateral side.

Conclusion

The use of primary trapeziometacarpal implant arthroplasty seems to be a viable alternative for managing severely comminuted Rolando fractures, particularly in elderly patients and those with pre-existing osteoarthritis. This approach offers promising outcomes. Studies with other implant arthroplasties have shown better outcomes in patients treated primarily, than after several failed surgeries. We suggest the same is true for the trapeziometacarpal joint. Further studies are necessary to validate the efficacy of this intervention in a larger cohort of patients.
Correlation of Self-Assessed Manual Dexterity and Actual Performance in Surgical Simulation – One Year Follow Up
Authors: Hillinger S , Brunn T , Opitz I , Held U , Hofer L , Zellweger N , Battilana B , Werner R
Published: May 2024

Background

Simulation training has proved to be beneficial in many fields of professions including medicine and might be included already during medical school.

Aims

We evaluated if medical students rate their manual dexterity as good or above average and if this self-assessment (SA) correlates with the actual performance in a surgical simulation.

Methods

Basic surgical tasks have been performed by medical students in the 3rd and 4th year for a total of 4 rounds on 2 identical Lap-Sim® surgical simulators. Three questionnaires, before and after the simulation as well as follow up after 1 year had to be answered.

Descriptive statistics stratified by career goal (surgical/ undecided/ nonsurgical) for outcomes of simulation parameters are reported. Associations between surgical career goal and SA of manual dexterity with three performance parameters (tissue damage, time and path length) are estimated in linear regression models.

Results

Out of 102 participating students 41 stated surgery as their career goal, 18 a nonsurgical field, and 43 were undecided. 87.8% of the surgical group rated their dexterity as good or above average (86.1% in the undecided group), 88.9% of the nonsurgical group as below average or good. A positive association of SA with tissue damage has been found statistically significant (p=0.033).

One year after the simulation (n=97) 13.4% changed their career goal from undecided to surgical, whereas 8.2% changed from undecided to non-surgical. 92.7% wanted to have simulation training integrated into the curriculum.

Conclusion

A correlation of self-assessed manual dexterity has been found in the surgical group for tissue damage, but not for time and path length. Simulation training might help students in decision making for a surgical field and therefore recruit future surgeons, which could be shown in the one-year follow-up.
Impact of Transjugular Intrahepatic Portosystemic Shunt on Hepatocellular Carcinoma: Prospective Cohort of Liver Transplant Candidates’ Analysis
Authors: El Hajji S , Toso C , Möckli B , Compagnon P , Lacotte S , Cauchy F
Published: May 2024

Background

Transjugular intrahepatic portosystemic shunt (TIPS) is used to mitigate the side effects of portal hypertension. However, its impact on hepatocellular carcinoma (HCC) remains unclear.

Aims

We aimed to evaluate its effect on HCC dynamics and patients’ survival.

Methods

We analysed 43’734 liver transplant candidates diagnosed with HCC from the prospective Scientific Registry of Transplant Recipients database (1985-2022). A total 7’404 patients with and without TIPS were propensity score matched 1:3. We assessed wait-list changes in total tumor volume, HCC count, and alpha-fetoprotein levels. We examined survival rates from time of listing and post-transplantation, as well as the incidence of HCC recurrence post-transplantation.

Results

Pre-matching, TIPS patients exhibited poorer liver function and less advanced HCCs. Post-matching, TIPS correlated with a decrease in HCC nodules count (-0.24 vs 0.11, p = 0.008) over a median waiting period of 225 days (IQR 94; 441) and better overall survival rate from listing (93.0% vs 89.1% at one year, p = 0.0003). TIPS was not associated with altered changes in waitlist tumor volume (0.26 vs -0.07 cm3/month, p = 0.26) and AFP (14.62 vs 12.67 ng/mL, p = 0.79) compared to the non-TIPS group. Post-transplant survival rates (91.8% vs 91.7% at one year, p = 0.25) and HCC recurrence (5.2% vs 5.4% at 5 years, p = 0.73) were similar, with a median follow-up of 5.6 years (IQR 2.7; 9.6)

Conclusion

TIPS improved waitlist survival and is associated with decreased HCC nodule count, potentially due to a better efficacy in HCC treatment. However, TIPS did not have a measurable impact on HCC growth or aggressiveness.
Long-Term Ex Situ Normothermic Kidney Perfusion
Authors: Sousa Da Silva R X , Binz J , Huwyler F , Helmchen B M , Mancina L , Wernlé K , Kalbas Y , Müller M , Hefti M , Becker D , Weisskopf M , Tibbitt M W , Dutkowski P , Clavien P A , Kron P
Published: May 2024

Background

Marginal grafts are increasingly considered for transplantation due to the widening gap of available donor grafts and waiting recipients. Graft assessment and repair prior to implantation are therefore essential to minimize the risk of failure. Normothermic perfusion has not been widely evaluated for kidney grafts, with existing perfusions limited to 2 days.

Aims

The aim of this study was to develop a long-term (>3 days) normothermic ex situ swine perfusion model in kidney grafts, while maintaining organ viability. We also wanted to investigate possible regenerative processes of the kidney during this period outside the donor animal.

Methods

Swine kidneys were retrieved with minimal injury. After cannulation, organs were perfused at 37°C for up to several days in a newly designed normothermic ex situ device with automated blood gas and glucose regulation, addition of nutrition, antibiotics, and vasodilators. Kidney biopsies, urine and perfusate samples were taken daily for analysis as well as markers of viability.

Results

In total 17 kidneys were perfused. Four kidneys were perfused for 3 or more days. Viability was maintained up to 4 days without histological evidence of glomerular and minimal to moderate tubular necrosis. We observed upregulation of ki67 and pH3 in tubular cells with mean values of up to 14.2% and 2.2% respectively. This expression of ki67, a proliferation associated protein, correlated with the duration of ex situ perfusion.

Conclusion

This is the first report of normothermic kidney perfusion for up to 4 days with unprecedented observation of upregulated ki67 and pH3 after multiple days of perfusion. These preclinical results open the door for development of long-term perfusion protocols for discarded human grafts while also hinting at limitations and challenges.
Assessment of Safe Early Fixation Strategies in a Cohort Polytraumatized Patients – How is the Surgical Treatment Influenced by the Injury Pattern?
Authors: Halva S , Pfeifer R , Klingebiel F K L , Kalbas Y , Berk T , Neuhaus V , Pape H C
Published: May 2024

Background

While the inital assessment and the intial treatment of potentially life-threatening injuries is well-described, the surgical treatment strategy following initial resuscitation remains controversial. Timepoint of surgery and type of surgery still reamin topic of discussions. Various, different strategies for optimal timing of fracture fixation in polytrauma patients exist.

Aims

This study tests the hypothesis that a concept of clearing patients for early definitive surgery that relies on anatomical and physiologic parameters is influenced by the injury distribution.

Methods

Polytrauma patients treated at a Level 1 trauma center (01.01.2016 - 31.12.2018). Inclusion: primary admission, injury severity score (ISS) ≥16points, requirement of surgical fixation of major extremity or a truncal injury. Exclusion: death <72h after admission, severe traumatic brain injury (TBI). Stratification according to surgical fixation concept: Early total care (ETC, all surgeries <24 h), safe definitive surgery (SDS, staged surgeries <72h), and damage control orthopaedics (DCO, definitive care after stabilization). Endpoints: mortality, complication rates. Parameters of interest: Injury severity and distribution (ISS/AIS), pathophysiologic parameters of hemorrhagic shock, coagulopathy, hypothermia, soft tissue trauma.

Results

527 patients, mean age 54.8 SD19.9 years, mean ISS 26.9 SD9.0 points, mortality 20.5%. Group ETC (n=21, 3.9%), Group SDS (n = 284, 53.9%), Group DCO (n = 222, 42.1%). Abdominal and spinal injuries associated with ETC (AIS Abdomen; OR 2.1, 95%CI 1.1 to 4.0, p = 0.026: AIS Spine OR 2.0, 95%CI 1.2 to 3.4, p = 0.007). Extremity and pelvic injuries associated with SDS (OR 1.8, 95%CI 1.1 to 2.8, p = 0.012 and OR 1.3, 95%CI 1.0 to 1.7, p = 0.036), head injuries associated with DCO (OR1.5, 95%CI 1.3 to 1.8, p <0.001). Head injuries were most relevant for mortality and were associated with patients undergoing DCO (29.7%) (ETC; 23.8%, SDS; 13.0%).

Conclusion

The concept of staged early fixation for major extremity and axial injuries (SDS) was successfully applied in the majority of patients. Predominant head and abdominal injuries were associated with ETC or DCO. The injury distribution influences decision making towards surgical management that is associated with a low complication rate.
Small Cuts, Big Difference? The Impact of a Minimally Invasive Thoracic Phase during Ivor Lewis Esophagectomy on Long-Term Quality of Life of Esophageal Cancer Patients
Authors: Neuschütz K , Fourie L , Germann N , Pieters A , Däster S , Angehrn F , Klasen J , Müller B , Steinemann D , Bolli M
Published: May 2024

Background

Due to improved survival of esophageal cancer patients, long-term quality of life (QoL) is increasingly gaining importance. We analyzed QoL of patients treated with open Ivor Lewis esophagectomy (Open-E) or a hybrid operation including laparotomy and a robot-assisted thoracic phase (hRob-E), as well as a standard group of healthy individuals.

Aims

The aim of this study is to evaluate the impact of a minimally invasive compared to an open approach during the thoracic phase of Ivor Lewis esophagectomies on quality of life.

Methods

With a median follow-up of 36 months after hRob-E (n=28) and 40 months after Open-E (n=43), patients' QoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire Core 30 (QLQ-C30) and the EORTC Esophagus specific QoL questionnaire 18 (QLQ-OES18).

Results

Patients showed similar clinical-histological characteristics, yet hRob-E patients had significantly higher ASA scores at surgery (p<0.001). Patients and healthy controls reported similar global health status, emotional and cognitive functions. All of the surgically treated cancer patients reported reduced role and social functioning, fatigue, nausea and vomiting, dyspnea and diarrhea. However, physical functioning of Open-E patients was significantly reduced compared to healthy controls (p=0.019). In addition, a trend towards a better pain score after hRob-E compared to Open-E emerged (p=0.063). Regarding QLQ-OES18, hRob-E and Open-E treated patients similarly reported eating problems, reflux, and troubles swallowing saliva.

Conclusion

The general health status is not impaired after esophagectomy. Despite higher ASA scores, QoL of hRob-E patients is similar to that of patients operated with Open-E. Moreover, patients after hRob-E appear to have a better score regarding physical functioning and a better pain profile than patients after Open-E, indicating a benefit of a minimally invasive approach during the thoracic phase.
De novo variants in ATXN7L3 lead to developmental delay, hypotonia and distinctive facial features
Authors: Harel Tamar , Spicher Camille , Scheer Elisabeth , Buchan Jillian G , Cech Jennifer , Folland Chiara , Frey Tanja , Holtz Alexander M , Innes A Micheil , Keren Boris , Macken William L , Marcelis Carlo , Otten Catherine E , Paolucci Sarah A , Petit Florence , Pfundt Rolph , Pitceathly Robert D S , Rauch Anita , Ravenscroft Gianina , Sanchev Rani , Steindl Katharina , Tammer Femke , Tyndall Amanda , Devys Didier , Vincent Stéphane D , Elpeleg Orly , Tora László
Published: May 2024

Deubiquitination is crucial for the proper functioning of numerous biological pathways, such as DNA repair, cell cycle progression, transcription, signal transduction and autophagy. Accordingly, pathogenic variants in deubiquitinating enzymes (DUBs) have been implicated in neurodevelopmental disorders and congenital abnormalities. ATXN7L3 is a component of the DUB module of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex and two other related DUB modules, and it serves as an obligate adaptor protein of three ubiquitin-specific proteases (USP22, USP27X or USP51).

Through exome sequencing and by using GeneMatcher, we identified nine individuals with heterozygous variants in ATXN7L3. The core phenotype included global motor and language developmental delay, hypotonia and distinctive facial characteristics, including hypertelorism, epicanthal folds, blepharoptosis, a small nose and mouth, and low-set, posteriorly rotated ears.

To assess pathogenicity, we investigated the effects of a recurrent nonsense variant [c.340C>T; p.(Arg114Ter)] in fibroblasts of an affected individual. ATXN7L3 protein levels were reduced, and deubiquitylation was impaired, as indicated by an increase in histone H2Bub1 levels.

This is consistent with the previous observation of increased H2Bub1 levels in Atxn7l3-null mouse embryos, which have developmental delay and embryonic lethality. In conclusion, we present clinical information and biochemical characterization supporting ATXN7L3 variants in the pathogenesis of a rare syndromic neurodevelopmental disorder.
1H-nuclear magnetic resonance analysis reveals dynamic changes in the metabolic profile of patients with severe burns
Authors: Su Sen , Zhang Yong , Wu Dan , Wang Chao , Hu Jianhong , Wei Yan , Peng Xi
Published: May 2024

Background

Severe burn injury causes a hypermetabolic response, resulting in muscle protein catabolism and multiple organ damage syndrome. However, this response has not yet been continuously characterized by metabolomics in patients. This study aims to quantify temporal changes in the metabolic processes of patients with severe burns.

Methods

We employed 1H-nuclear magnetic resonance (NMR) spectroscopy to scrutinize metabolic alterations during the initial 35 days following burn injury in a cohort of 17 adult patients with severe burns, with 10 healthy individuals included as controls. Plasma specimens were collected from patients on postburn days 1, 3, 7, 14, 21, 28 and 35. After performing multivariate statistical analysis, repeated-measures analysis of variance and time-series analysis, we quantified changes in metabolite concentrations.

Results

Among the 36 metabolites quantified across 119 samples from burn patients, branched-chain amino acids, glutamate, glycine, glucose, pyruvate, lactate, trimethylamine N-oxide and others exhibited obvious temporal variations in concentration. Notably, these metabolites could be categorized into three clusters based on their temporal characteristics. The initial response to injury was characterized by changes in lactate and amino acids, while later changes were driven by an increase in fatty acid catabolism and microbial metabolism, leading to the accumulation of ketone bodies and microbial metabolites.

Conclusions

Metabolomics techniques utilizing NMR have the potential to monitor the intricate processes of metabolism in patients with severe burns. This study confirmed that the third day after burn injury serves as the boundary between the ebb phase and the flow phase. Furthermore, identification of three distinct temporal patterns of metabolites revealed the intrinsic temporal relationships between these metabolites, providing clinical data for optimizing therapeutic strategies.
Multimodal neuroimaging network associated with executive function in adolescent major depressive disorder patients via cognition-guided magnetic resonance imaging fusion
Authors: Liao Qi-Meng , Liu Yi-Lin , Dou Yi-Kai , Du Yue , Wang Min , Wei Jin-Xue , Zhao Lian-Sheng , Yang Xiao , Ma Xiao-Hong
Published: May 2024

Adolescents are high-risk population for major depressive disorder. Executive dysfunction emerges as a common feature of depression and exerts a significant influence on the social functionality of adolescents. This study aimed to identify the multimodal co-varying brain network related to executive function in adolescent with major depressive disorder. A total of 24 adolescent major depressive disorder patients and 43 healthy controls were included and completed the Intra-Extra Dimensional Set Shift Task. Multimodal neuroimaging data, including the amplitude of low-frequency fluctuations from resting-state functional magnetic resonance imaging and gray matter volume from structural magnetic resonance imaging, were combined with executive function using a supervised fusion method named multimodal canonical correlation analysis with reference plus joint independent component analysis. The major depressive disorder showed more total errors than the healthy controls in the Intra-Extra Dimensional Set Shift task. Their performance on the Intra-Extra Dimensional Set Shift Task was negatively related to the 14-item Hamilton Rating Scale for Anxiety score. We discovered an executive function-related multimodal fronto-occipito-temporal network with lower amplitude of low-frequency fluctuation and gray matter volume loadings in major depressive disorder. The gray matter component of the identified network was negatively related to errors made in Intra-Extra Dimensional Set Shift while positively related to stages completed. These findings may help to deepen our understanding of the pathophysiological mechanisms of cognitive dysfunction in adolescent depression.
Cardio-oncology rehabilitation: are we ready?
Authors: Bisceglia Irma , Venturini Elio , Canale Maria Laura , Ambrosetti Marco , Riccio Carmine , Giallauria Francesco , Gallucci Giuseppina , Abrignani Maurizio G , Russo Giulia , Lestuzzi Chiara , Mistrulli Raffaella , De Luca Giovanni , Maria Turazza Fabio , Mureddu Gianfrancesco , Di Fusco Stefania Angela , Lucà Fabiana , De Luca Leonardo , Camerini Andrea , Halasz Geza , Camilli Massimiliano , Quagliariello Vincenzo , Maurea Nicola , Fattirolli Francesco , Gulizia Michele Massimo , Gabrielli Domenico , Grimaldi Massimo , Colivicchi Furio , Oliva Fabrizio
Published: May 2024

Cardio-oncology rehabilitation (CORE) is not only an essential component of cancer rehabilitation but also a pillar of preventive cardio-oncology. Cardio-oncology rehabilitation is a comprehensive model based on a multitargeted approach and its efficacy has been widely documented; when compared with an ‘exercise only’ programme, comprehensive CORE demonstrates a better outcome. It involves nutritional counselling, psychological support, and cardiovascular (CV) risk assessment, and it is directed to a very demanding population with a heavy burden of CV diseases driven by physical inactivity, cancer therapy-induced metabolic derangements, and cancer therapy-related CV toxicities. Despite its usefulness, CORE is still underused in cancer patients and we are still at the dawning of remote models of rehabilitation (tele-rehabilitation). Not all CORE is created equally: a careful screening procedure to identify patients who will benefit the most from CORE and a multidisciplinary customized approach are mandatory to achieve a better outcome for cancer survivors throughout their cancer journey. The aim of this paper is to provide an updated review of CORE not only for cardiologists dealing with this peculiar population of patients but also for oncologists, primary care providers, patients, and caregivers. This multidisciplinary team should help cancer patients to maintain a healthy and active life before, during, and after cancer treatment, in order to improve quality of life and to fight health inequities.
SURGERY OF TYPE A AORTIC DISSECTIONS: WHAT HAS CHANGED? SINGLE CENTER EXPERIENCE
Authors: Fiorentino M , Mikus E , Calvi S , Panzavolta M , Ceresa R , Sangiorgi D , Tripodi A , Savini C
Published: May 2024

Introduction

Our knowledge on type A aortic dissection (ATAAD) has evolved, and there are some differences in surgical approach. In this paper, we focused on what changed in the surgical treatment of ATAAD and on the impact of these changes on patients’ survival, analyzing our center experience and comparing it with literature latest evidences.

Materials and Methods

From 2010 to 2022, 342 consecutive patients underwent surgery for Acute Type A Aortic dissection at our institution. In order to identify changes in these patients’ management over time, we divided our population in two groups according to the year of surgery: Group A before 2016 (146 patients) and Group B after 2016 (196 patients).

Results

Patients from Group B (after 2016) showed more comorbidities and a worse clinical presentation than patients from Group A (chronic kidney disease 9.2% vs 2.1% p=0.006, neurological deficit on admission 8.7% vs 0% p < 0.001, cardiac tamponade 12.2% vs 0.7% p < 0.001, and pre–operative catecholamine support 4.1% vs 0% p=0.012). Also of pre–operative malperfusion was more frequent (coronary 6.6% vs 0% p < 0.001 and peripheral 6.6% vs 0% p < 0.001). In Group B in 70.4% of the population the circulatory arrest with antegrade selective cerebral perfusion was used vs 30.8% in Group A (p < 0.001) and we find a bigger percentage of emiarch replacement (43.4% vs 23.3% P=0.008) and total arch replacement (27% vs 13.7% p=0.017) than in Group A. In–hospital mortality resulted to be 10.2% with no differences between the groups. Neurological events (p<0.001) and post–operative dialysis (p=0.036) were more frequent in Group B. On the other hand, in Group A post–operative cardiac tamponade (9.65 vs 3.1% p=0.007) and red blood cells transfusions were higher.

Conclusions

Nowadays surgery is performed on more critical patients with higher surgical risk and the tendency is to perform more complex operations with replacement of a largest portion of the diseased aorta in order to reduce reintervention rate. Recently, clinical studies and guidelines highlighted the importance of creating a multidisciplinary aortic team to discuss and manage these patients in order to assure the best treatment options to each patient and to reduce mortality and morbidity.