bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the role of the Rab network in epithelial-to-mesenchymal transition
Authors: Jaygude Unmani , Hughes Graham M , Simpson Jeremy C
Published: December 2024

Motivation

Rab GTPases (Rabs) are crucial for membrane trafficking within mammalian cells, and their dysfunction is implicated in many diseases. This gene family plays a role in several crucial cellular processes. Network analyses can uncover the complete repertoire of interaction patterns across the Rab network, informing disease research, opening new opportunities for therapeutic interventions.

Results

We examined Rabs and their interactors in the context of epithelial-to-mesenchymal transition (EMT), an indicator of cancer metastasizing to distant organs. A Rab network was first established from analysis of literature and was gradually expanded. Our Python module, resnet, assessed its network resilience and selected an optimally sized, resilient Rab network for further analyses. Pathway enrichment confirmed its role in EMT. We then identified 73 candidate genes showing a strong up-/down-regulation, across 10 cancer types, in patients with metastasized tumours compared to only primary-site tumours. We suggest that their encoded proteins might play a critical role in EMT, and further in vitro studies are needed to confirm their role as predictive markers of cancer metastasis. The use of resnet within the systematic analysis approach described here can be easily applied to assess other gene families and their role in biological events of interest.

Availability and implementation

Source code for resnet is freely available at https://github.com/Unmani199/resnet
Multitask knowledge-primed neural network for predicting missing metadata and host phenotype based on human microbiome
Authors: Monshizadeh Mahsa , Hong Yuhui , Ye Yuzhen
Published: December 2024

Motivation

Microbial signatures in the human microbiome are closely associated with various human diseases, driving the development of machine learning models for microbiome-based disease prediction. Despite progress, challenges remain in enhancing prediction accuracy, generalizability, and interpretability. Confounding factors, such as host’s gender, age, and body mass index, significantly influence the human microbiome, complicating microbiome-based predictions.

Results

To address these challenges, we developed MicroKPNN-MT, a unified model for predicting human phenotype based on microbiome data, as well as additional metadata like age and gender. This model builds on our earlier MicroKPNN framework, which incorporates prior knowledge of microbial species into neural networks to enhance prediction accuracy and interpretability. In MicroKPNN-MT, metadata, when available, serves as additional input features for prediction. Otherwise, the model predicts metadata from microbiome data using additional decoders. We applied MicroKPNN-MT to microbiome data collected in mBodyMap, covering healthy individuals and 25 different diseases, and demonstrated its potential as a predictive tool for multiple diseases, which at the same time provided predictions for the missing metadata. Our results showed that incorporating real or predicted metadata helped improve the accuracy of disease predictions, and more importantly, helped improve the generalizability of the predictive models.

Availability and implementation

https://github.com/mgtools/MicroKPNN-MT.
MOLGENIS Armadillo: a lightweight server for federated analysis using DataSHIELD
Authors: Cadman Tim , Slofstra Mariska K , van der Geest Marije A , Avraam Demetris , Bishop Tom R P , de Boer Tommy , Duijts Liesbeth , Haakma Sido , Hyde Eleanor , Jaddoe Vincent , Karramass Tarik , Kelpin Fleur , Marcon Yannick , Pinot de Moira Angela , Postma Dick , Tolboom Clemens , Veenstra Ruben L , Wheater Stuart , Welten Marieke , Wilson Rebecca C , Zwart Erik , Swertz Morris
Published: December 2024

Extensive human health data from cohort studies, national registries, and biobanks can reveal lifecourse risk factors impacting health. Combining these sources offers increased statistical power, rare outcome detection, replication of findings, and extended study periods. Traditionally, this required data transfer to a central location or separate partner analyses with pooled summary statistics, posing ethical, legal, and time constraints. Federated analysis—which involves remote data analysis without sharing individual-level data—is a promising alternative. One promising solution is DataSHIELD (https://datashield.org/), an open-source R based implementation. To enable federated analysis, data owners need a user-friendly way to install the federated infrastructure and manage users and data. Here, we present MOLGENIS Armadillo: a lightweight server for federated analysis solutions such as DataSHIELD.

Availability and implementation

Armadillo is implemented as a collection of three packages freely available under the open source licence LGPLv3: two R packages downloadable from the Comprehensive R Archive Network (CRAN) (“MolgenisArmadillo” and “DSMolgenisArmdillo”) and one Java application (“ArmadilloService”) as jar and docker images via Github (https://github.com/molgenis/molgenis-service-armadillo).
Protocol for obtaining doubled haploids in isolated microspore culture in vitro for poorly responsive genotypes of brassicaceae family
Authors: Kozar Elena V , Domblides Elena A
Published: December 2024

In this protocol for obtaining doubled haploids plants (DH), we propose a new method for microspore isolation. This method is useful for genotypes of the Brassicaceae family with low responsiveness to DH technology. For such crops, it allows increasing the embryo yield several times and sometimes obtaining embryos for the first time. This method of microspore isolation reduces the mechanical impact on the bud tissue, which minimizes somatic cell destruction and reduces to get it into the preparation through the filter, thus increasing its purity. The new isolation method also increases the relative concentration of embryogenic microspores in the preparation. This is possible because the anther tissues are not destroyed during the isolation process. Therefore, the anther retains its structure and microspores of early and late stages are trapped by the anther tissue, thus the anther acts as a sieve. Late stages are trapped because of their larger size, while early stages are trapped because they are even more tightly bound to the anther tissue. Together, these factors increase the efficiency of the technology for DH production in vitro microspore culture. This protocol article provides a detailed experimental protocol to the method presented in the experimental article (E.V. Kozar, E.G. Kozar, E.A. Domblides. Effect of the Method of Microspore Isolation on the Efficiency of Isolated Microspore Culture In Vitro for Brassicaceae Family. Horticulturae. 2022. Vol. 8, No. 10. P. 864. DOI 10.3390/horticulturae8100864) but does not repeat all the results documenting the efficacy of the actual method.
BAMITA: Bayesian multiple imputation for tensor arrays
Authors: Jiang Ziren , Li Gen , Lock Eric F
Published: December 2024

Data increasingly take the form of a multi-way array, or tensor, in several biomedical domains. Such tensors are often incompletely observed. For example, we are motivated by longitudinal microbiome studies in which several timepoints are missing for several subjects. There is a growing literature on missing data imputation for tensors. However, existing methods give a point estimate for missing values without capturing uncertainty. We propose a multiple imputation approach for tensors in a flexible Bayesian framework, that yields realistic simulated values for missing entries and can propagate uncertainty through subsequent analyses. Our model uses efficient and widely applicable conjugate priors for a CANDECOMP/PARAFAC (CP) factorization, with a separable residual covariance structure. This approach is shown to perform well with respect to both imputation accuracy and uncertainty calibration, for scenarios in which either single entries or entire fibers of the tensor are missing. For two microbiome applications, it is shown to accurately capture uncertainty in the full microbiome profile at missing timepoints and used to infer trends in species diversity for the population. Documented R code to perform our multiple imputation approach is available at https://github.com/lockEF/MultiwayImputation.
Diagnostic performance of axial T2-weighted MRI sequence for exclusion of brain tumour in paediatric patients with non-localizing symptoms
Authors: Gerrish Amy C , Malik Luqman , Swain Charlotte , Thomas Adam G , Jaspan Timothy , Dineen Rob A
Published: December 2024

Objective

To establish diagnostic performance of a single axial T2-weighted sequence for detection of brain tumours in children with non-localizing symptoms, compared to a standard MRI protocol.

Methods

Retrospective analysis of children undergoing MRI brain imaging for suspected brain tumours with non-localizing symptoms over a 3-year period. Axial T2-weighted images were blindly reviewed by 2 experienced paediatric neuroradiologists. Primary analysis was calculation of diagnostic performance metrics for tumour identification using axial T2-weighted image only compared to the standard MRI protocol.

Results

For 312 children undergoing MRI brain during the study period, sensitivity and specificity for brain tumour detection based on axial T2-weighted images in children with non-localizing symptoms were 1.000 (95% CIs 0.598, 1.000) and 0.998 (95% CI 0.990, 0.999), respectively. Based on T2-weighted images alone, 50 patients (16%) were flagged as needing recall for further imaging compared to 14 (4.5%) recalled after the standard protocol.

Conclusions

Axial T2-weighted images have high sensitivity and specificity for detection of brain tumours in children with non-localizing symptoms but are associated with increased imaging recall rates. Prospective evaluation of this approach to identify patients requiring more comprehensive imaging is warranted.

Advances in knowledge

A truncated MRI protocol with single axial T2-weighted sequence has high diagnostic performance for brain tumour detection in children with non-localizing features. Radiologists can be reassured that a child with this presentation who is unable to complete the full MRI scan protocol is very unlikely to have a brain tumour missed provided an axial T2-weighted sequence is obtained.
Clearance of beta-amyloid and tau aggregates is size dependent and altered by an inflammatory challenge
Authors: Fertan Emre , Hung Christy , Danial John S H , Lam Jeff Y L , Preman Pranav , Albertini Giulia , English Elizabeth A , Böken Dorothea , Livesey Frederick J , De Strooper Bart , Patani Rickie , Klenerman David
Published: December 2024

Extracellular beta-amyloid aggregation and inflammation are in a complex and not fully understood interplay during hyperphosphorylated tau aggregation and pathogenesis of Alzheimer’s disease. Our group has previously shown that an immune challenge with tumour necrosis factor alpha can alter extracellular beta-sheet containing aggregates in human-induced pluripotent stem cell-derived cortical neurons carrying familial Alzheimer’s disease-related presenilin 1 mutations. Here, using single-molecule detection and super-resolution imaging techniques, we quantified and characterized the intra- and extracellular beta-amyloid and AT8-positive tau aggregates. Our results indicate a pre-existing Alzheimer’s disease-like pathology caused by the presenilin 1 mutation, with increased beta-amyloid aggregates in both the cell lysate and conditioned media compared to isogenic controls and also increased intracellular tau aggregates. The main effect of tumour necrosis factor alpha treatment on presenilin 1 neurons was the formation of larger intracellular beta-amyloid aggregates. In contrast, isogenic controls showed more significant changes with tumour necrosis factor alpha treatment with an increase in beta-amyloid aggregates in the media but not intracellularly and an increase in tau aggregates in both the media and cell lysate, suggesting a chronic inflammation-driven mechanism for the development of sporadic Alzheimer’s disease. Remarkably, we also found significant morphological differences between intra- and extracellular beta-amyloid and tau aggregates in human-induced pluripotent stem cell-derived cortical neurons, suggesting these neurons can only clear aggregates when small, and that larger aggregates stay inside the neurons. While majority of the beta-amyloid aggregates were cleared into the media, a greater portion of the tau aggregates remained intracellular. This size-dependent aggregate clearance was also shown to be conserved in vivo, using soaked and homogenized mouse and human post-mortem Alzheimer’s disease brain samples. As such, our results are proposing a previously unknown, size-dependent aggregate clearance mechanism, which can possibly explain the intracellular aggregation of tau and extracellular aggregation of beta-amyloid.
Characteristics of spontaneous regression of Merkel cell carcinoma: a retrospective analysis of patient and tumour features
Authors: Gamissans Marta , Muntaner-Virgili Clara , Penín Rosa-Maria , Marcoval Joaquim
Published: December 2024

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine neoplasia. Complete spontaneous regression (CSR) of MCC has been linked to good prognosis. We conducted a retrospective review of a single-centre cohort of patients with MCC to analyse the characteristics of patients and tumours that exhibited regression. The calculated incidence of CSR was 4.5% (n = 5/112). The median age at diagnosis was 69 years (interquartile range 31), tumours were primarily located on the head and neck, and the cohort exhibited a low rate of immunosuppression. After a median follow-up period of 4 years, none of the patients who underwent CSR showed recurrence or distant metastases. Merkel cell polyomavirus (MCPyV) positivity was associated with CSR (P = 0.045). There is limited understanding of the mechanisms underlying regression in MCC. However, biopsy-induced immune responses linked with host and tumour factors, such as age, immunosuppression and MCPyV positivity, may play an important role. More research in this field is crucial to improve our understanding of this rare phenomenon.
Comparative efficacy of leniolisib (CDZ173) versus standard of care on rates of respiratory tract infection and serum immunoglobulin M (IgM) levels among individuals with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): an externally controlled study
Authors: Whalen John , Chandra Anita , Kracker Sven , Ehl Stephan , Seidel Markus G , Gulas Ioana , Dron Louis , Velummailum Russanthy , Nagamuthu Chenthila , Liu Sichen , Tutein Nolthenius Joanne , Maccari Maria Elena
Published: December 2024

Leniolisib, an oral, targeted phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, was well-tolerated and efficacious versus placebo in treating individuals with activated PI3Kδ syndrome (APDS), an ultra-rare inborn error of immunity (IEI), in a 12-week randomised controlled trial. However, longer-term comparative data versus standard of care are lacking. This externally controlled study compared the long-term effects of leniolisib on annual rate of respiratory tract infections and change in serum immunoglobulin M (IgM) levels versus current standard of care, using data from the leniolisib single-arm open-label extension study 2201E1 (NCT02859727) and the European Society for Immunodeficiencies (ESID) registry. The endpoints were chosen following feasibility assessment considering comparability and availability of data from both sources. Baseline characteristics between groups were balanced through inverse probability of treatment weighting. The leniolisib-treated group included 37 participants, with 62 and 49 participants in the control group for the respiratory tract infections and serum IgM analyses, respectively. Significant reductions in the annual rate of respiratory tract infections (rate ratio: 0.34; 95% confidence interval [CI]: 0.19, 0.59) and serum IgM levels (treatment effect: –1.09 g/L; 95% CI: –1.78, –0.39, P = 0.002) were observed in leniolisib-treated individuals versus standard of care. The results were consistent across all sensitivity analyses, regardless of censoring, baseline infection rate definition, missing data handling, or covariate selection. These novel data provide an extended comparison of leniolisib treatment versus standard of care, highlighting the potential for leniolisib to deliver long-term benefits by restoring immune system function and reducing infection rate, potentially reducing complications and treatment burden.
Paramagnetic monomer and diamagnetic polymer of 5-(1-adamantyl)-1,3-phenylene bis(tert-butyl nitroxide)
Authors: Ueno Shunya , Takeshi Shin-ichiro , Suzuki Shuichi , Ishida Takayuki
Published: December 2024

In the crystalline state of the title biradical each nitroxide group is located close to each other, to form a covalently bonded diamagnetic polymer having a head-to-tail (N-O)2 motif. The solid irreversibly turned paramagnetic above 365 K. ESR spectra on a PVC solid solution displayed a zero-field splitting pattern together with a half-field signal at room temperature. Density functional theory calculations support the interpretation of the magnetic ground states and a four-center two-electron bonding character. Coordination ability was also explored.
Stannylation of alkyl chlorides with stannylpotassium
Authors: Hiraoka Yuta , Nakamoto Masaaki , Tsushima Takumi , Yoshida Hiroto
Published: December 2024

A stannylpotassium reagent, generated in situ from a readily available silylstannane and t-BuOK, is demonstrated to react smoothly with an alkyl bromide to give an alkylstannane in high yield. The superior nucleophilicity of the stannylpotassium reagent is illustrated in the efficient stannylative substitution of less reactive alkyl chlorides. Mechanistic studies reveal that the reaction proceeds through an ionic, SN2-type pathway.
The risk of sodium overcorrections in severe hyponatremia and the utility of desmopressin: a large retrospective study
Authors: Lamarche Florence , Ammann Hélène , Dallaire Gabriel , Deslauriers Louis , Troyanov Stéphan
Published: December 2024

Background

The suggested narrow rate of serum sodium (sNa) correction in hyponatremia can be difficult to respect, leading to overcorrections. Our ability to anticipate the rapidity of correction according to the mechanism of hyponatremia is uncertain. While desmopressin is often used to pause a rapid rise in sNa, its dose-related effect is also not well described. We studied the rate of hyponatremia overcorrections, its prediction and the utility of desmopressin in its management.

Methods

We retrospectively reviewed all cases of severe hyponatremia (sNa <120 mmol/L) in a large university hospital that occurred over 10 years. We assessed investigations, causes and treatments. We compared all sNa separated by at least 8 h and calculated correction rates. Significant overcorrection rates were defined by any rise of sNa >9 mmol/L per day sustained over at least 24 h.

Results

After exclusions, we found 355 episodes of severe hyponatremia. Low, appropriate and inappropriate antidiuretic hormone (ADH)-defined mechanisms accounted for 17%, 24% and 29% of etiologies, respectively, with the remaining 25% secondary to diuretics and 5% of uncertain causes. First urinary sodium and osmolality were consistent with the final diagnosis in 73%. Significant overcorrections were seen in 45% and were frequent in the setting of low ADH. Desmopressin was given in 82 episodes, more often as a rescue than a preventive measure, with the subsequent sNa dropping by ≥5 mmol/L by 12 h in eight instances. The dose of desmopressin (≥2 µg versus 1 µg) and a higher volume of intravenous free-water coadministration resulted in a clinically meaningful greater reduction in sNa in the following 12 h.

Conclusions

Overcorrections in severe hyponatremia are common, mainly when ADH is low. Initial urinary measurements anticipate this risk. Desmopressin effectively halted the rate of correction in a dose-dependent manner. Caution should be given when coadministrating water, which can significantly lower the sNa.
Impact of heart rate on eGFR decline in ischemic stroke patients
Authors: Lee Jiann-Der , Kuo Ya-Wen , Lee Chuan-Pin , Huang Yen-Chu , Lee Meng , Lee Tsong-Hai
Published: December 2024

Background

Resting heart rate is a potent predictor of various renal outcomes. However, the decline rate of renal function in ischemic stroke patients is not well defined. We tested the association of heart rate with estimated eGFR decline and the composite renal outcomes in patients with recent ischemic stroke.

Methods

The data of 9366 patients with ischemic stroke with an eGFR of ≥30 mL/min/1.73 m2 were retrieved from the Chang Gung Research Database. Mean initial in-hospital heart rates were averaged and categorized into 10-beats-per-minute (bpm) increments. The outcomes were the annualized change in eGFR across the heart rate subgroups and composite renal outcomes, namely a ≥40% sustained decline in eGFR, end-stage renal disease, or renal death. Generalized estimating equation models were used to determine the annualized change in eGFR and Cox proportional hazards regression models were used to estimate the relative hazard of composite renal outcomes by referencing the subgroup with a heart rate of <60 bpm.

Results

The annual eGFR decline in the patients with a mean heart rate of <60, 60–69, 70–79, 80–89, and ≥90 bpm was 2.12, 2.49, 2.83, 3.35, and 3.90 mL/min/1.73 m2, respectively. Compared with the reference group, the adjusted hazard ratios for composite renal outcomes were 1.17 [95% confidence interval (CI), 0.89–1.53), 1.54 (95% CI, 1.19–2.00), 1.72 (95% CI, 1.30–2.28), and 1.84 (95% CI, 1.29–2.54] for the patients with a heart rate of 60–69, 70–79, 80–89, and ≥90 bpm, respectively. In the subgroup analysis, the associations between higher heart rate and both eGFR decline and composite renal outcomes were more evident and statistically significant in patients without atrial fibrillation.

Conclusions

A higher heart rate is associated with a faster rate of eGFR decline and an increased risk of composite renal outcomes after ischemic stroke, particularly in patients without atrial fibrillation. These results underscore the importance of heart rate monitoring and management in ischemic stroke patients in sinus rhythm to potentially mitigate renal function decline. Further studies are needed to explore this relationship in patients with atrial fibrillation and across different ethnic groups.
Top ten tips in managing ANCA vasculitis
Authors: Tan Min Hui , Jayne David
Published: December 2024

Diagnosing and managing antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remain a challenge for many clinicians, due to the complexity of the disease manifestations and its treatment. There has been a paradigm shift in ANCA vasculitis management, where treatment incorporates both emergency life- and organ-saving procedures and longer-term care to manage relapse and co-morbidity risk and the complications of organ damage. Here, we highlight 10 key tips for the management of ANCA-associated vasculitis based on current evidence and clinical experience. First, we advise making the diagnosis as early as possible, emphasizing the importance of using high-quality ANCA assays. Second, we recommend the use of glucocorticoids in combination with rituximab and/or cyclophosphamide as induction therapy. Third, plasma exchange should be considered in patients with severe renal impairment and diffuse alveolar haemorrhage. We advise the use of rapidly reducing glucocorticoid regimens and advocate consideration of avacopan early in the disease course. We recommend the use of rituximab as maintenance therapy and routine monitoring of kidney function, proteinuria, ANCA and immunoglobulin levels at baseline and during follow-up. The use of prophylactic antibiotics in susceptible patients and timely vaccination schedules is discussed. Rituximab is the preferred immune suppressive for treatment of relapse. Finally, we recommend switching treatment modalities in patients whose vasculitis is refractory to induction therapy and to consider plasma exchange in selected patients. These key tips aim to provide the necessary guidance to improve patient outcomes and reduce adverse events.
Upper normal serum magnesium is associated with a reduction in incident death from fatal heart failure, coronary heart disease and stroke in non-dialysis patients with CKD stages 4 and 5
Authors: Moyano-Peregrin Cayetana , Rodelo-Haad Cristian , Martín-Malo Alejandro , Muñoz-Castañeda Juan Rafael , Ojeda Raquel , Lopez-Lopez Isabel , Rodríguez Mariano , Pendon-Ruiz de Mier Mª Victoria , Santamaría Rafael , Soriano Sagrario
Published: December 2024

Background

Serum magnesium disturbances are common in patients with cardiovascular disease (CVD). However, the well-established link between low serum magnesium and nutritional or inflammatory disorders has limited its consideration as a non-traditional risk factor for mortality. This study aims to elucidate the relationship between serum magnesium concentrations and mortality due to fatal heart failure (HF), coronary heart disease (CHD) and stroke in non-dialysis patients with chronic kidney disease (CKD) stages 4 and 5.

Methods

A cohort of 1271 non-dialysis patients with CKD stages 4 and 5 was followed from 2008 to 2018. Patients with prior major adverse cardiovascular events (MACE) were excluded. Serum magnesium levels were stratified into tertiles and the primary outcomes were incidence rates of fatal HF, CHD and stroke. Secondary outcomes included composite MACE and all-cause mortality. Hazard ratios (HRs) were calculated using multivariate Cox regression, adjusting for demographics, comorbidities and biochemical parameters. E-values were used to assess the robustness of the results.

Results

Over the 10-year follow-up, 186 patients died. Higher serum magnesium levels were significantly associated with reduced mortality risk from HF [HR 0.49 (95% CI 0.27–0.89) for T2; HR 0.31 (95% CI 0.16–0.60) for T3] compared with the lowest tertile. Similar trends were observed for CHD and stroke mortality. The incidence rate of MACE per 1000 person-years was reduced from 68.2 in tertile 1 to 26.2 in tertile 2 and 16.8 in tertile 3. Secondary endpoints, including all-cause mortality and composite MACE, followed trends similar to the primary outcomes.

Conclusions

Higher serum magnesium concentrations were associated with lower risks of death from fatal HF, CHD and stroke in non-dialysis patients with CKD stages 4 and 5.
A path forward: improving Internet routing security by enabling zones of trust
Authors: Clark David , Testart Cecilia , Luckie Matthew , claffy kc
Published: December 2024

Although Internet routing security best practices have recently seen auspicious increases in uptake, Internet Service Providers (ISPs) have limited incentives to deploy them. They are operationally complex and expensive to implement and provide little competitive advantage. The practices with significant uptake protect only against origin hijacks, leaving unresolved the more general threat of path hijacks. We propose a new approach to improved routing security that achieves four design goals: improved incentive alignment to implement best practices; protection against path hijacks; expanded scope of such protection to customers of those engaged in the practices; and reliance on existing capabilities rather than needing complex new software in every participating router. Our proposal leverages an existing coherent core of interconnected ISPs to create a zone of trust, a topological region that protects not only all networks in the region, but all directly attached customers of those networks. Customers benefit from choosing ISPs committed to the practices, and ISPs thus benefit from committing to the practices. We discuss the concept of a zone of trust as a new, more pragmatic approach to security that improves security in a region of the Internet, as opposed to striving for global deployment. We argue that the aspiration for global deployment is unrealistic, since the global Internet includes malicious actors. We compare our approach to other schemes and discuss how a related proposal, ASPA, could be used to increase the scope of protection our scheme achieves. We hope this proposal inspires discussion of how the industry can make practical, measurable progress against the threat of route hijacks in the short term by leveraging institutionalized cooperation rooted in transparency and accountability.
Chylothorax as an unusual manifestation of transthyretin cardiac amyloidosis: a case report
Authors: Pöschl Christina , Kratzer Theresa , Martinek Martin , Steringer-Mascherbauer Regina
Published: December 2024

Background

Amyloidosis is a multi-organ disease of emerging significance in the field of cardiology. Chylothorax, a specific form of pleural effusion characterized by lymphatic fluid accumulation in the pleural cavity, is an extremely rare manifestation of amyloidosis. Notably, only five cases of chylothorax related to cardiac amyloidosis have been reported worldwide, all in amyloid light chain (AL) amyloidosis. No cases have been documented in amyloid transthyretin (ATTR) amyloidosis. Furthermore, elevated levels of serum carbohydrate antigen (CA) 125 have been associated with a poor prognosis in patients with AL cardiac amyloidosis.

Case summary

We report the case of an 85-year-old Austrian man with pronounced left ventricular hypertrophy, monoclonal gammopathy, and a history of atrial fibrillation. Further examinations, including myocardial biopsy, confirmed the diagnosis of ATTR cardiac amyloidosis. A significant right-sided pleural effusion was also observed. Thoracocentesis diagnosed chylothorax, confirmed by lymphangiography. Elevated CA 125 levels were found in both serum and pleural fluid, with no other findings suspicious for malignancy. The patient underwent a short break in oral anticoagulation and received prophylactic low-molecular-weight heparin for myocardial biopsy, thoracocentesis, and lymphangiography. However, they died a few days later due to an embolic stroke.

Discussion

At this time, we can only speculate about the pathomechanism of chylothorax development in the context of amyloidosis. We recommend further investigation of similar cases to deepen understanding of the underlying causes and identify potential treatment strategies. Additionally, the utility of CA 125 as a prognostic marker in ATTR amyloidosis needs further investigation.
Brugada phenocopy in fulminant eosinophilic myocarditis: a case series
Authors: Kawauchi Dai , Yunoki Kei , Yoshino Tomohiro , Oka Takefumi
Published: December 2024

Background

Brugada phenocopy (BrP) is a condition that induces reversible Brugada-like electrocardiographic (ECG) changes in patients without true Brugada syndrome. We present two cases of fulminant eosinophilic myocarditis that showed Type 1 Brugada ECG changes in the early phase of the clinical course.

Case summary

Case 1 was a 76-year-old man who developed fulminant eosinophilic myocarditis with ventricular tachycardia while hospitalized for heart failure. Case 2 was a 60-year-old man who presented with cardiogenic shock and was diagnosed with fulminant eosinophilic myocarditis. Both patients showed a Type 1 Brugada ECG at onset, and their ventricular function was greatly reduced. Regarding mechanical circulatory support, Case 1 was treated with venous-arterial extracorporeal membrane oxygenation and intra-aortic balloon pumping. Case 2 had venous-arterial extracorporeal membrane oxygenation and Impella CP insertion. Steroid therapy was introduced in both cases. In Case 1, the Type 1 Brugada ECG took 7 days to improve. Left ventricular function improved with time but right heart function was poor and right heart enlargement remained. In Case 2, the Type 1 Brugada ECG improved on the second day, and left and right heart function improved over time.

Discussion

We report two cases of fulminant eosinophilic myocarditis with Brugada-like ECG and severe right heart dysfunction. BrP in acute myocarditis may be an indicator of right heart failure and an important ECG marker in determining the indication for mechanical circulatory support and improvement of right heart function.
Optimal site of pacemaker lead implantation for persistent atrial standstill guided by electroanatomical mapping following a cox-maze procedure: a case report
Authors: Ujiro Sae , Yamashita Soichiro , Takemoto Makoto , Okuda Masanori
Published: December 2024

Background

Atrial standstill is characterized by the absence of atrial activity. We report a case of a patient with extensive atrial fibrosis who underwent electrophysiologic study (EPS) and electroanatomical mapping (EAM) to identify surviving atrial sites amenable for pacemaker lead implantation.

Case summary

A 72-year-old man with persistent atrial fibrillation (AF) and atrial functional mitral regurgitation/tricuspid regurgitation (MR/TR) underwent a Cox-Maze surgery, mitral and tricuspid valve repair, and biatrial plication. He was referred because of post-operative presyncope symptoms. Electrocardiography revealed atrial standstill and junctional rhythm (JR); however, EAM revealed that both atria were almost entirely scarred and isolated fibrillation in left pulmonary veins and coronary sinus. Junctional rhythm retrogradely conducted around an atrioventricular (AV) node and pacing at this area could conduct to the ventricle through the AV node. An atrial pacing lead was implanted at this area, which yielded a QRS wave similar to the own beat. However, the atrial lead voltage was quite low; hence, ventricular pacing lead was implanted to avoid a future occurrence of pacing failure.

Discussion

This report demonstrates the benefits of EPS and EAM in informing optimal pacemaker implantation for patients with extensive scar in atrium.
Effect of SGLT2i on kidney outcomes of individuals with type 2 diabetes according to body mass index: nationwide cohort study
Authors: Jimba Takahiro , Kaneko Hidehiro , Suzuki Yuta , Okada Akira , Azegami Tatsuhiko , Ko Toshiyuki , Fujiu Katsuhito , Morita Hiroyuki , Takeda Norifumi , Hayashi Kaori , Yokoo Takashi , Node Koichi , Komuro Issei , Yasunaga Hideo , Nangaku Masaomi , Takeda Norihiko
Published: December 2024

Aims

To investigate the clinical significance of the modification of the kidney protective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors by baseline body mass index (BMI).

Methods and results

We included individuals with SGLT2 inhibitors or dipeptidyl peptidase-4 (DPP4) inhibitors newly prescribed for type 2 diabetes using a nationwide epidemiological cohort and performed propensity score matching (1:2). The primary outcome was the annual eGFR decline, assessed using a linear mixed-effects model, compared between individuals with SGLT2 inhibitors and DPP4 inhibitors. We investigated the interaction effect of BMI at the time of prescription using a three-knot restricted cubic spline model. We analysed 2165 individuals with SGLT2 inhibitor prescriptions and 4330 individuals with DPP4 inhibitor prescriptions. Overall, the annual decline in eGFR was less pronounced in the group treated with SGLT2 inhibitors than in those treated with DPP4 inhibitors (−1.34 mL/min/1.73 m2 vs. −1.49 mL/min/1.73 m2). The advantage of SGLT2 inhibitors in mitigating eGFR decline was augmented in the individuals with higher BMI (P-value for interaction 0.0017). Furthermore, even upon adjusting the definition of outcomes to encompass a 30 or 40% reduction in eGFR, the potential advantages of SGLT2 inhibitors over DPP4 inhibitors persisted, with a trend of augmented effects with higher BMI. This interaction effect was evident in the individuals with preserved kidney function.

Conclusion

Our nationwide epidemiological study substantiated the improved kidney outcomes in the SGLT2 inhibitor users compared with the DPP4 inhibitor users across a wide range of BMI, which was pronounced for individuals with higher BMI.
Causes of death in patients with atrial fibrillation in the UK: a nationwide electronic health record study
Authors: Lai Yongtong , Yoshimura Hiroyuki , Zakkak Nadine , Marijon Eloi , Chahal Anwar , Lip Gregory Y H , Schmidt Floriaan , Providencia Rui
Published: December 2024

Aims

Causes of death remain largely unexplored in the atrial fibrillation (AF) population. We aimed to (i) thoroughly assess causes of death in patients with AF, especially those associated with sudden cardiac death (SCD) and (ii) evaluate the potential association between AF and SCD.

Methods and results

Linked primary and secondary care United Kingdom Clinical Practice Research Datalink dataset comprising 6 529 382 individuals aged ≥18. We identified 214 222 patients with newly diagnosed AF, and an equivalent number of non-AF patients matched for age, sex and primary care practice. The underlying primary cause of death for each patient was assessed in the form of International Classification of Diseases Tenth Revision (ICD-10) codes and also as part of broader disease categories (i.e. ICD-10 chapters).

Findings

Over a median follow-up of 2.7 (interquartile range: 0.7–6.0) years, 124 781 (58.25%) patients with AF died. Sudden cardiac death occurred in 13 923 patients with AF [6.50% patients with AF vs. 2.01% non-AF patients; odds ratio (OR) = 3.38, 95% confidence interval (CI): 3.27–3.50, P < 0.0001], contributing to 11.05% of all AF mortality. Diseases of the circulatory system, neoplasms and respiratory diseases explained 45% of AF mortality. Sudden cardiac death occurred more frequently in males (OR = 1.87, 95% CI: 1.80–1.93, P < 0.0001), and females with AF died more often of diseases of the circulatory, respiratory, digestive, and genitourinary system and less often of neoplastic disorders.

Interpretation

Conditions of the circulatory system are the main driver of mortality in the AF population. Females with AF experience higher cardiovascular and respiratory mortality but die less frequently of neoplasms. The risk of SCD is higher in the AF population, occurring more frequently in males.
Supraventricular ectopic activity predicts postoperative atrial fibrillation, new onset atrial fibrillation and worse survival in obstructive hypertrophic cardiomyopathy
Authors: Nie Changrong , Zhu Changsheng , Xiao Minghu , Wu Zining , Yang Qiulan , Lu Zhengyang , Lu Tao , Meng Yanhai , Wang Shuiyun
Published: December 2024

Background

Supraventricular ectopic activity (SVEA) is a marker of foci that may initiate atrial fibrillation (AF) and is associated with worse survival. The types and frequencies of SVEA for predicting postoperative AF (POAF), new-onset AF, and clinical outcomes in obstructive hypertrophic cardiomyopathy(oHCM) remain unknown.

Method

Our study consecutively recruited 961 patients with oHCM. All patients underwent a 24-hour Holter monitor before surgery.

Results

POAF incidence was 20.7% and increased with the burden of premature atrial contractions (PACs). Multivariable analysis showed that supraventricular tachycardia (SVT) was independently associated with POAF, with the model including SVT yielding the largest area under the curve (AUC) [0.710, 95%CI 0.670-0.750] for predicting POAF. During a median follow-up of 2.9 years, 12 deaths, 60 new-onset AF, and 139 composite endpoints were observed. A Spearman correlation indicated a linear relationship between the incidence of new-onset AF and composite endpoints with PAC frequency. The Kaplan-Meier survival curves demonstrated that patients with PACs >200 beats/day had significantly higher cumulative rates of new-onset AF[HR 3.13, (95%CI 1.74-5.62), p<0.001] and composite endpoints [HR 2.00, (95%CI 1.30-3.06), p=0.002] than their counterparts. Adding PACs >200 beats/day to the multivariable model significantly improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI) for predicting new-onset AF (NRI=0.264, IDI=0.033) and composite endpoints (NRI=0.233, IDI=0.014).

Conclusion

The incidence of POAF was 20.7%, increasing with PACs severity. Furthermore, PACs burden was positively associated with a higher incidence of adverse events. Specially, PACs>200 beats/day may best predict a higher incidence of new-onset AF and worse survival.
Relationship between hospital mortality and readmission rates after transcatheter aortic valve replacement
Authors: Kolte Dhaval , Tale Archana , Song Yang , Yeh Robert W
Published: December 2024

Background

There is substantial hospital-level variation in 30-day risk-standardized mortality rate (RSMR) and risk-standardized readmission rate (RSRR) after transcatheter aortic valve replacement (TAVR). However, the relationship between hospital RSMRs and RSRRs has not been well characterized.

Methods and results

We analysed data on 141 905 Medicare fee-for-service beneficiaries who underwent TAVR across 512 hospitals between 1 October 2015 and 31 December 2020. The primary and secondary outcomes of interest were 30-day all-cause mortality and 30-day all-cause readmissions, respectively. Hierarchical logistic regression models with random hospital-level intercepts were used to estimate RSMRs and RSRRs for each hospital. We used Pearson correlation coefficient (r) and restricted cubic spline regression to determine the relationship between RSMR and RSRR in the overall cohort and within subgroups based on hospital characteristics. The median [interquartile range (IQR)] hospital-level 30-day RSMR was 2.2% (2.1–2.4%), ranging from 1.3 to 3.5%. Similarly, the median (IQR) hospital-level 30-day RSRR was 13.2% (12.7–13.8%), ranging from 10.6 to 16.8%. In the overall cohort, there was weak correlation between 30-day RSMR and RSRR after TAVR (r = 0.25, 95% CI 0.17–0.33, P < 0.001). Subgroup analyses by hospital characteristics demonstrated the weakest correlation between RSMR and RSRR for non-JCAHO accredited hospitals (r = 0.07), hospitals in the Midwest (r = 0.12), and West (r = 0.14), and hospitals with low TAVR volume (r = 0.15).

Conclusion

Risk-standardized mortality and readmission rates after TAVR are weakly correlated, suggesting that hospital practices and processes of care influencing mortality are likely different from those influencing readmissions after TAVR, thereby necessitating measurement of both outcomes and developing specific interventions to decrease mortality and readmissions.
Performance of the ARC-HBR criteria in ST-elevation myocardial infarction. Significance of smoking as an additional bleeding risk factor
Authors: Kesti Henri , Mattila Kalle , Jaakkola Samuli , Lehto Joonas , Söderblom Nea , Kalliovalkama Kalle , Porela Pekka
Published: December 2024

Background and aims

The Academic Research Consortium for High Bleeding Risk criteria (ARC-HBR) are recommended by guidelines for bleeding risk assessment in ST-elevation myocardial infarction (STEMI). The aim of this study was to identify possible other risk factors and adjust the original ARC-HBR criteria for confounders.

Methods and results

All consecutive STEMI patients managed in a Finnish tertiary hospital between 2016 and 2022 were identified using a database search. Data collection was done by reviewing electronic patient records. Bleeding risk was assessed according to the ARC-HBR criteria. The primary endpoint was non-access site bleeding academic research consortium (BARC) type 3 or 5 bleeding during 1-year follow-up. A total of 1548 STEMI patients were analysed. HBR criteria was fulfilled in 661 (42.7%). Multivariable competing risk analysis identified only 4 individual ARC-HBR criteria as independent risk factors for bleeding. Smoking status was identified as a novel bleeding risk factor. Current and former smokers had increased bleeding risk compared with never smokers [hazard ratio (HR) 3.01, 95% confidence interval (CI) 1.62–5.61 and HR 1.99, CI 1.19–3.34]. In those not meeting any ARC-HBR criteria, cumulative BARC 3 or 5 incidence of current smoking was 3.40% and intracranial haemorrhage (ICH) 1.36%. Thus, exceeding ARC-HBR definition for a major criterion. In the non-HBR group the prevalence of current smoking was 40.4% (n = 358).

Conclusion

Current and former smoking predicts major bleeding complications after STEMI. Current smoking is highly prevalent among those classified as non-HBR according to the ARC-HBR criteria.
Enhanced recovery after minimally invasive cardiac surgery following a zero ICU concept—a propensity score-matched analysis
Authors: Pitts Leonard , Dini Martina , Goecke Simon , Kofler Markus , Ott Sascha , Stoppe Christian , O’Brien Benjamin , Jacobs Stephan , Falk Volkmar , Hommel Matthias , Kempfert Jörg
Published: December 2024

OBJECTIVES

This study investigates our enhanced recovery after minimally invasive cardiac surgery program “enhanced recovery after minimally invasive cardiac surgery” (ERMICS) following a ‘Zero ICU’ concept compared to standard-of-care treatment in terms of safety and clinical efficacy.

METHODS

All patients who underwent minimally invasive mitral valve surgery for primary severe mitral valve regurgitation between 2021 and 2023 were included. Propensity score matching (2:1) was performed between patients who received standard-of-care treatment and those who underwent ERMICS. Patients treated with the ERMICS approach were transferred to the peripheral ward instead of the intensive care unit on the day of surgery (Zero ICU). Separate primary end-points were safety (mortality, stroke), postoperative ventilation time and hospital length of stay.

RESULTS

A total of 611 patients (566 standard of care vs 45 ERMICS) were included in the study. After 2:1 matching, the cohort comprised 135 patients (90 standard of care vs 45 ERMICS) and were well balanced in terms of pre- and intraoperative variables. Thirty-day mortality was 0% in both groups. Postoperative ventilation time [P = 0.018, odds ratio (OR) < 0.01, confidence interval (CI) < 0.001], postoperative pain (P = 0.005, OR = 0.36, CI 0.18–0.74) and hospital length of stay (P = 0.049, OR = 0.28, CI 0.08–0.98) was significantly lower in ERMICS patients, while postoperative complications did not differ.

CONCLUSIONS

Our ERMICS ‘Zero ICU’ concept is safe and leads to significantly shorter postoperative ventilation time and hospital length of stay for patients undergoing minimally invasive mitral valve surgery for primary severe mitral valve regurgitation.