bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethiopian Consumer’s Behavior towards Purchasing Locally Produced Apparel Products: An Extended Model of the Theory of Planned Behavior
Authors: Minbale Eyob , Bizuneh Berihun , Seife Wendosen , Eyasu Alene , Asfaw Tinsaye , Sharew Shalemu
Published: March 2024

Consumers in developing countries, particularly Africans, are strongly criticized for their unfavorable feeling about locally produced apparel products. With this concern, this paper explores the determinants of Ethiopian consumers’ purchasing behavior towards locally produced apparel products by using the extended theory of planned behavior (TPB) model. A self-administered questionnaire which consists of open and closed-ended questions was developed based on the literature. Cross-sectional data were collected from 478 Ethiopian consumers by following the convenience sampling technique and were analyzed by structural equation modeling with AMOS V.26.0. The ethnocentric tendency of Ethiopian consumers was found at a moderate level. The consumers had a very high purchasing intention towards locally produced apparel products but had a low actual purchasing behavior. The result also showed that Ethiopian consumers use price, garment fitness, comfort, and color as the most important attributes, while the country of origin and notions were found to be the moderate important attributes. Moreover, consumers’ attitude towards locally produced apparel products was found as the most influential factor, while perceived behavioral control and subjective norms were the least influential factors in affecting consumers’ purchasing intention. The study’s findings provide insight into domestic apparel consumption as well as the factors affecting consumer purchasing intentions and behavior in the Ethiopian context. The study incorporates product attributes and ethnocentrism into the TPB model to investigate their impact on consumer purchasing intentions which are rarely investigated together.
Guidelines for Treatment of Hyperemesis Gravidarum and Implementation in Clinical Practice in Norway: A Descriptive Study
Authors: Erdal Hilde , Holst Lone , Heitmann Kristine , Volløyhaug Ingrid , Torkildsen Erik Andreas , Andreasen Stine , Kjelstad Katja Barlinn , Bakkebø Judit Bolette , Trovik Jone
Published: March 2024

Background. The severe pregnancy complication hyperemesis gravidarum (HG) requires intravenous fluids, antiemetics, and nutrition to prevent maternal and fetal complications. Several guidelines exist for the treatment of HG within and across countries. The aim of this study was to investigate whether the guideline issued by the Norwegian Society for Obstetrics and Gynecology (NGF) was implemented in clinical practice by comparing department treatment protocols and assessing provided treatment. Methods. Department protocols for the treatment of HG were requested from all Norwegian gynecology departments and compared to the NGF guideline regarding the use of Pregnancy Unique Quantification of Emesis (PUQE-24) score, antiemetics, thiamine, and fluid and nutritional therapy. Additionally, we performed a retrospective chart review of provided treatment during 2017–2019 at four hospitals. Results. In all, 28 of 39 (72%) departments replied, of which 11 reported using the NGF guidelines unaltered. Of the 17 local department protocols in use, 16 closely resembled the NGF guidelines regarding the use of PUQE score, fluid therapy, nutritional treatment, and thiamine. Eight department protocols differed slightly from the NGF guidelines regarding the antiemetic medication treatment pathway, and two recommended antiemetic medication not supported by national or international guidelines. The retrospective chart review of 343 patients at four hospitals showed that the provided care aligned with the guidelines regarding intravenous fluids and the use of PUQE score, and the use of antiemetics mostly aligned with the treatment pathway provided in the NGF guideline. However, the proportion of patients receiving ondansetron varied between 32% and 79% and thiamine from 38 to 86% between hospitals. Overall, few patients were provided with nutritional treatment by partial peripheral nutrition (14%), enteral tube feeding (8%), or total parenteral nutrition (1.5%). Conclusion. The NGF guideline was used unaltered or largely integrated in department protocols. Treatment data suggest that the guideline was implemented in clinical practice, but differences in the provision of ondansetron and thiamine suggest geographical inequality of care. Infrequent use of nutritional treatment by parenteral nutrition or enteral feeding tube could suggest improvements in pharmacological symptom management or undertreatment of malnutrition.
New Insights on Biosynthesis of Nanoparticles Using Plants Emphasizing the Use of Alfalfa (Medicago sativa L.)
Authors: Kokina Inese , Plaksenkova Ilona , Jankovskis Lauris , Jermaļonoka Marija , Galek Renata
Published: March 2024

Biological synthesis of nanoparticles (NPs) using alfalfa (Medicago sativa L.) and other plants has several advantages such as lower costs, reduction of pollution, and improvement of the environment and human health. Often, biosynthesis is used to synthesize Ag, Au, and ZnO NPs. Less often are also synthesized Cu and Fe NPs. Synthesis with plant extracts from their parts or callus cultures is a widely used method since extracts contain the most significant number of biomolecules. Synthesis with living plants (in vivo) provides NPs with improved properties for better interactions with plants but is used less often due to the long realization time, the need to control the plants’ growing conditions, and difficulty in controlling the size and shape of the synthesized NPs. Here, we performed a systematic review of various methods for the biological synthesis of different metal NPs with different plants, to highlight advantages and disadvantages of mentioned methods. For discussion, results showed that biosynthesis of NPs allows obtaining NPs with reduced toxicity, and their size and shape depend on the type and number of biomolecules present in plants. Plant biomolecules determine the antibacterial and anticancer properties of NPs, as well as increasing the use of NPs in biomedicine, for better drug transport, therefore medicinal plants or sea plants are mostly used for biosynthesis. NPs which were synthesized in marine plants could be a very effective agent against water bacteria; therefore, if NP biosynthesis takes place in water, biological water purification is possible. Limitations of the study included a great methodological diversity of the synthesis, it is still difficult to systematize the synthesis methods, and it seems that each described study uses a different synthesis protocol; therefore, in future studies, it is necessary to clarify which method can provide the most efficient biosynthesis and develop a unified approach.
Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy
Authors: Dias Matheus Henrique , Friskes Anoek , Wang Siying , Fernandes Neto Joao M. , van Gemert Frank , Mourragui Soufiane , Papagianni Chrysa , Kuiken Hendrik J. , Mainardi Sara , Alvarez-Villanueva Daniel , Lieftink Cor , Morris Ben , Dekker Anna , van Dijk Emma , Wilms Lieke H.S. , da Silva Marcelo S. , Jansen Robin A. , Mulero-Sánchez Antonio , Malzer Elke , Vidal August , Santos Cristina , Salazar Ramón , Wailemann Rosangela A.M. , Torres Thompson E.P. , De Conti Giulia , Raaijmakers Jonne A. , Snaebjornsson Petur , Yuan Shengxian , Qin Wenxin , Kovach John S. , Armelin Hugo A. , te Riele Hein , van Oudenaarden Alexander , Jin Haojie , Beijersbergen Roderick L. , Villanueva Alberto , Medema Rene H. , Bernards Rene
Published: March 2024

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity of such aberrant signaling. Although inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of protein phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor-suppressive resistance.

Significance: A therapy consisting of deliberate hyperactivation of oncogenic signaling combined with perturbation of the stress responses that result from this is very effective in animal models of colon cancer. Resistance to this therapy is associated with loss of oncogenic signaling and reduced oncogenic capacity, indicative of tumor-suppressive drug resistance.
Pancreatic Ductal Adenocarcinoma Encapsulated by a Tumor-Forming Type 1 Autoimmune Pancreatitis Located at the Pancreatic Tail: A Case Report
Authors: Ando Taro , Nitta Hiroyuki , Umemura Akira , Katagiri Hirokatsu , Kanno Shoji , Takeda Daiki , Nishiya Masao , Uesugi Noriyuki , Sugai Tamotsu , Sasaki Akira
Published: March 2024

Introduction: Autoimmune pancreatitis (AIP) is recognized as a disease with a good prognosis that responds well to steroids, but the complication of pancreatic ductal adenocarcinoma (PDAC) in AIP is a rare condition. We report a case of PDAC encapsulated by tumor-forming type 1 AIP. Case Presentation: The patient, a 65-year-old female, was found to have high CA19-9 levels and a pancreatic mass with a diameter of 30 mm on abdominal ultrasonography. Contrast-enhanced computed tomography revealed a 40-mm mass in the tail of the pancreas that had a 27-mm oligemic mass inside it. From these work-up examinations, this tumor was diagnosed as PDAC, with evidence of colonic invasion. As curative resection for PDAC, a distal pancreatectomy with splenectomy and combined colon resection were performed. Histopathological examination showed invasive PDAC surrounded by IgG4-positive plasma cell infiltration. Based on these findings, a diagnosis was made of PDAC located in the pancreatic tail capsulized by type 1 AIP. The postoperative course was uneventful, and the patient was discharged on postoperative day 15. She underwent postoperative adjuvant chemotherapy with S-1 for 6 months, and no recurrence was noted for 2 years after operation. Conclusion: Currently, there are two hypothetical mechanisms of PDAC induction by AIP: (1) carcinogenic stimulation due to chronic inflammation and (2) paraneoplastic syndrome caused by AIP. Further study of the relationship between AIP and pancreatic cancer is needed, and follow-up should be conducted while keeping in mind the possibility of complications.
Pitfalls in Urinary Tract Cytopathology
Authors: Hashim Mahmoud A. , Arshia Asma , Rehman Shafi , Chandra Ashish
Published: March 2024

Background: Urine cytopathology is a cost-effective method to diagnose and follow patients with high-grade urothelial carcinoma (UC). However, some benign, reactive, and metaplastic changes may mimic UC and pose a diagnostic challenge for cytopathologists. Summary: Our comprehensive review focuses on summarizing common pitfalls encountered in urine cytopathology, based on the 2nd edition of The Paris System (TPS) for reporting urinary tract cytopathology and other recent published literature. These pitfalls include urothelial tissue fragments, degenerative changes, treatment effects, viral cytopathic changes, iatrogenic and metaplastic changes. Our aim was to provide a clear understanding of these mimics in order to avoid diagnostic errors. Key Message: It is crucial for cytopathologists to recognize benign, reactive, or metaplastic lesions that sometimes resemble UC. An awareness of these cytological changes is essential to make an accurate diagnosis.
Coexisting Primary Sclerosing Cholangitis and Autoimmune Hepatitis: Overlapping Challenges in Diagnosis and Treatment
Authors: Fiske Hannah W. , Saeed Firrah , Ward Christopher , Sinayuk Boris , Ulici Veronica , Curry Michael , Feller Edward , Shah Samir A.
Published: March 2024

Introduction: Hepatobiliary overlap syndromes describe the coinciding presentation of more than one immune-mediated biliary and liver disease in a single patient and present complex challenges in diagnosis and treatment. We report a case of ulcerative colitis with primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome responsive to vancomycin. Case Presentation: The patient is a 30-year-old female with known ulcerative pancolitis and autoimmune hepatitis. She presented to the emergency department with a constellation of gastrointestinal symptoms, including diffuse lower abdominal pain, bloody diarrhea, and nausea with bilious vomiting. Subsequent imaging revealed the additional diagnosis of primary sclerosing cholangitis, and she was diagnosed with overlap syndrome. Multiple treatment regimens were trialed with minimal improvement. She eventually achieved normalization of both clinical status and biochemical markers after the addition of vancomycin. Conclusion: Vancomycin is an underutilized therapy; its potential role in primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome has not been previously reported.
Internal Limiting Membrane Peeling and Inverted Flap Technique in Macular Hole: Postoperative Metamorphopsia and Optical Coherence Tomography
Authors: Murakami Tomoya , Okamoto Fumiki , Sugiura Yoshimi , Izumi Iori , Iioka Aoi , Morikawa Shohei , Hiraoka Takahiro , Oshika Tetsuro
Published: March 2024

Introduction: We compared postoperative metamorphopsia and optical coherence tomography (OCT) findings between eyes that underwent internal limiting membrane (ILM) peeling and the inverted flap (IF) technique for macular hole (MH). Methods: This retrospective analysis included 64 eyes of 64 patients with idiopathic MH whose MH was closed after initial surgery. Thirty-nine patients were treated with pars plana vitrectomy (PPV) with ILM peeling, and 25 patients were treated with PPV with the IF technique. Best corrected visual acuity (BCVA), severity of metamorphopsia, and OCT images were collected before and 3, 6, and 12 months postoperatively. Based on the OCT images, the status of the external limiting membrane (ELM) and ellipsoid zone and the presence of hyperreflective plugs were assessed. Results: At baseline and 3, 6, and 12 months postoperatively, BCVA and severity of metamorphopsia were not significantly different between groups. The status of the ELM was significantly worse in the IF group than in the ILM peeling group at 3 and 6 months postoperatively. Significantly more hyperreflective plugs were observed in the IF group than in the ILM peeling group at 3 and 6 months postoperatively. Stepwise multiregression analysis revealed that hyperreflective plugs were significantly associated with the severity of metamorphopsia at 12 months postoperatively. Discussion/Conclusion: The alterations on the OCT were fewer in the ILM peeling group than in the IF group, while no significant differences were observed in postoperative severity of metamorphopsia between groups. Metamorphopsia was worse in eyes with hyperreflective plugs.
A Novel Missense Variant in the CHST3 Underlies Spondyloepiphyseal Dysplasia with Congenital Joint Dislocations
Authors: Mughal Tufail Akbar , Asim Muhammad , Gillani Syed Haseeb ul Hassan , Chughtai Nimra Obaid , Batool Syeda Afifa , Hussain Amir , Shujaat Kulsoom , Gilani Syed Zohaib Tayyab
Published: March 2024

Background: Spondyloepiphyseal dysplasia (SED) is characterized by skeletal dysplasia and multiple joint dislocations. SEDs encompass various types, such as SED congenita, SED tarda (SED-T), SED with congenital joint dislocations (SED-CJD), SED stanescu, and SED-T with progressive arthropathy. Methods and Results: In the present study, we clinically and genetically characterized a consanguineous Pakistani family with SED-CJD. The affected member showed large joint dislocation, spinal deformities, and previously unreported facial features. Exome sequencing followed by Sanger sequencing revealed a missense variant, [c.601T>A; p.(Tyr201Asn)], in the CHST3. Conclusion: This study has not only expended the mutation spectrum in the gene CHST3 but also will facilitate diagnosis and genetic counseling of related features in the Pakistani population.
Diagnostic Yield and Safety of the 19-Gauge versus 22-Gauge Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Needle in Subjects with Sarcoidosis (GUESS)
Authors: Dhooria Sahajal , Sehgal Inderpaul Singh , Prasad Kuruswamy Thurai , Muthu Valliappan , Dogra Pooja , Saini Mandeep , Gupta Nalini , Bal Amanjit , Aggarwal Ashutosh Nath , Agarwal Ritesh
Published: March 2024

Introduction: Observational data suggest that the 19-gauge (G) needle for endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) offers a higher diagnostic yield than the 22-G needle in sarcoidosis. No randomized trial has compared the yield of the two needles. Methods: We randomized consecutive subjects with suspected sarcoidosis and enlarged thoracic lymph nodes to undergo EBUS-TBNA with either the 19-G or the 22-G needle. We compared the study groups for diagnostic sensitivity (primary outcome) assessed by the yield of granulomas in subjects finally diagnosed with sarcoidosis. We also compared the sample adequacy, difficulty performing the needle puncture assessed on a visual analog scale (VAS), the subject’s cough intensity on an operator-rated VAS, and procedure-related complications (secondary outcomes). Results: We randomized 150 (mean age, 43.0 years; 55% women) subjects and diagnosed sarcoidosis in 116 subjects. The diagnostic sensitivity of the 19-G needle (45/60, 75.0%) was not higher (p = 0.52) than the 22-G needle (39/56, 69.6%). We obtained adequate aspirates in 90.0% and 85.7% of subjects in the respective groups (p = 0.48). The operators had greater difficulty puncturing lymph nodes with the 19-G needle (p = 0.03), while the operator-assessed cough intensity was similar in the groups (p = 0.41). Transient hypoxemia was the only complication encountered during EBUS-TBNA (two subjects in either group). Conclusion: We did not find the 19-G needle superior to the 22-G in diagnostic sensitivity, specimen adequacy, or safety of EBUS-TBNA in sarcoidosis. Puncturing the lymph nodes was more difficult with the 19-G needle.
Treatment and Long-Term Safety Outcomes of Peptide Receptor Radionuclide Therapy for Metastatic Neuroendocrine Tumours: An Asian Experience
Authors: Tham Wei Ying , Huang Hian Liang , Tai David Wai Meng , Allen Jr. John C. , Hwang Jacqueline S.G. , Loh Lih Ming , Goh Brian K.P. , Ong Simon Y.K. , Kek Peng Chin , Tan Damien M.Y. , Ng David C.E. , Loke Kelvin S.H.
Published: March 2024

Purpose: Peptide receptor radionuclide therapy (PRRT) is a targeted molecular therapy used to treat neuroendocrine tumours (NETs). It has been shown to be effective and well tolerated in patients with metastatic NETs in several centres in the USA, Europe, and Australia. Tolerability and efficacy data emerging from Asian centres remain few. Epidemiological evidence suggests that there are differences in neuroendocrine neoplasms between the population groups. We aim to describe the treatment and safety outcomes of PRRT in the Asian population. Methods: One hundred and seven (107) patients with metastatic NETs who had undergone PRRT treatment from January 2012 to March 2019 were included in this retrospective study. The response rates using RECIST 1.1 and qualitative analysis were examined. The overall and progression-free survival curves were also evaluated. Results: The median progression-free survival was 49 months. Response assessment after completion of treatment showed that 33 (37.9%) of 87 patients had partial or complete response. Subgroup analysis comparing high- and low-grade NET showed that there was a significant difference in the time to progression curves. Comparison of the number of cycles and progression-free and overall survival also showed a significant difference. Ten patients (9%) had grade 3 or more haematological toxicities. Four patients (4%) had grade 3/4 hepatobiliary toxicities, although the presence of extensive liver metastases was a confounding factor. None of the patients had grade 3/4 acute kidney injury. Conclusion: Our results show that PRRT is safe and effective in the treatment of metastatic NET in the Asian population. There was a significant difference in the progression-free survival curves between low-grade and high-grade NET and in the progression-free and overall survival comparing the number of cycles received.
Supply Chain Resilience During the Covid-19 Pandemic: Understanding the Role of Collaboration, Visibility, Velocity, and Flexibility in Supply Chain Resilience Using Structural Equation Modeling Approach
Authors: Moraga Melvin V. , Go Brandon Patrick , Go Chabeli Eunice , Tan Hannah , Ledesma Julia
Published: March 2024

The Covid-19 has wrought havoc on the supply chain across the world. During the global pandemic, supply chain managers were forced to rely on short-term solutions with little to no impact on their operations. This paper aims to assess the effect of collaboration, visibility, velocity, and flexibility on supply chain resilience. A total of 66 respondents constitutes the sample of the study, consisting of middle management employees across all depots nationwide. Eight research questions and eight hypotheses were generated and tested at 0.05 significance level using descriptive statistics and path analysis to quantify the relationships among multiple variables. Data were then analyzed through partial least squares - structural equation modeling. Results showed that collaboration, visibility, and flexibility have a significant impact on supply chain resilience. However, velocity did not have a significant impact on supply chain resilience. The research concludes that the supply chain capabilities play a crucial role in the supply chain resilience of the company and its supply chain partners. The key recommendations of the paper help enhance these capabilities to improve the resilience of its supply chain.
Transformational Leadership and Crisis Management Practices of Cebu Technological University-Tuburan
Authors: Maruhom Acmad P. , Minoza Joemar T. , Zosa Leo T.
Published: March 2024

In making important decisions, especially during times of crisis, it is likely that leadership style cannot be disregarded (Faeq & Ismael, 2022). This study aimed at determining the transformational leadership style of school administrators and its influence to the crisis management practices of CTU as a higher education institution utilizing quantitative research focusing on descriptive survey where it used a survey questionnaire in order to describe the demographic profile to the respondents, transformational leadership style of the school administrators and the effective implementation of crisis management. Respondents were chosen using the sample determination on Slovin formula. Data were collected using the adopted questionnaire from Donmez and Toker’s (2017) and Crises Management Practices adopted from The change leader, Inc. (2007). It was revealed that age and gender are diverse, probationary employees are greater in number, new and rank and file employees dominates the workforce. Furthermore, transformational leadership styles are evident among administrators, and crisis management practices are well-implemented. Gender and civil status have no direct influence to the perceived transformational leadership styles, but age, employment status, length of service and current position does.  Transformational leadership significantly influence crisis management practices in CTU-Tuburan. It can be concluded that sound decision can be made when leaders possess transformational leadership style. Hence, this calls for sustainability and consistency from the top management.
“Ignorance of the law excuses no one:” Fundamental Laws Every Filipino Teachers in Educational Institutions Should Know
Authors: Cada, Jr. Leonardo F.
Published: March 2024

In the Philippines, everyone is presumed to know the law. Laws in the Philippines take effect after fifteen days following the completion of their publication either in the Official Gazette or in a newspaper of general circulation in the Philippines. Respondents in this mini research were local teachers and professors from secondary and tertiary levels within the National Capital Region (NCR) with some of them from outside the NCR. Survey questionnaires were administered in this study through convenient and snowball sampling techniques. The initial pulse from the respondents indicated that they have a good percentage of the knowledge of the six identified laws. Most of their knowledge were acquired in attending seminars and conference.
Hiring Practices of Human Resource Practitioners in Selected Mabuhay Accommodations in Top Tourist Destinations in the Philippines
Authors: Escarilla Cherry C. , Canoy Orbel M. , Maming Jimmy B.
Published: March 2024

This research paper explores the complex field of modern HRM, with particular attention to the following topics: hiring process components, diversity and inclusion tactics, training and development programs, obstacles and advancements, legal and moral compliance, the critical function of HR, applicant competency evaluation, and technological integration. To give a thorough grasp of how these components come together inside a company's procedures, the research uses Yin's single-case study.  Six (6) human resource practitioners from the municipality of the Mabuhay Lodging took part in this study. The study revealed several themes, including 1) the hiring process; 2) the influence of inclusion as well as diversity on organizational dynamics; 3) assessing the efficacy of development and training initiatives; 4) resolving issues; 5) guaranteeing legal and ethical compliance; 6) realizing the critical role of human resources; 7) improving the evaluation of applicant competence; and 8) investigating the consequences of integrating technology in the hiring process. The study reveals a dynamic interaction between these components, highlighting their combined importance in creating an inclusive, diverse, and growth-oriented workplace culture. The results reveal the complicated coordination human resource practitioners need to uphold morality, overcome barriers, and grow their firms using technology.
Assessment on the User Interface of a Select Consumer Mobile Application and its Effect to Purchasing Behaviour of Generation Z
Authors: Agapay Arnel B. , Gutierrez Ernell Bautista , Cajayon Menrado V. , Cristobal Charito S.
Published: March 2024

The research assessed the User Interface of a Select Consumer Mobile Application and its effect to the buying behaviour of Generation Z. The Visual Appeal, Navigational Content and Application’s Data Modelling are used as factors for the Mobile App User Interface while Frequency, Quantity and Timing of Purchase are used for Purchase Behaviour. The research is quantitative in nature and utilized 250 respondents selected by way of purposive and random sampling. Results revealed that, in terms of the User’s Interface, respondents expressed a Strong Agreement on the aspect of usability in terms of features and functionalities of the select Consumer Mobile Application. Similarly, a Strong Agreement is also expressed by the respondents towards influence of the user interface in their Purchasing Behaviour. Also, result revealed that the User’s Interface of the Select Mobile Application Strongly Influenced the Purchasing Behaviour of the respondents.
Cardiovascular Effects of Oral Ketone Ester Treatment in Patients With Heart Failure With Reduced Ejection Fraction: A Randomized, Controlled, Double-Blind Trial
Authors: Berg-Hansen Kristoffer , Gopalasingam Nigopan , Christensen Kristian Hylleberg , Ladefoged Bertil , Andersen Mads Jønsson , Poulsen Steen Hvitfeldt , Borlaug Barry A. , Nielsen Roni , Møller Niels , Wiggers Henrik
Published: March 2024

BACKGROUND:

Heart failure triggers a shift in myocardial metabolic substrate utilization, favoring the ketone body 3-hydroxybutyrate as energy source. We hypothesized that 14-day treatment with ketone ester (KE) would improve resting and exercise hemodynamics and exercise capacity in patients with heart failure with reduced ejection fraction.

METHODS:

In a randomized, double-blind cross-over study, nondiabetic patients with heart failure with reduced ejection fraction received 14-day KE and 14-day isocaloric non-KE comparator regimens of 4 daily doses separated by a 14-day washout period. After each treatment period, participants underwent right heart catheterization, echocardiography, and blood sampling at plasma trough levels and after dosing. Participants underwent an exercise hemodynamic assessment after a second dosing. The primary end point was resting cardiac output (CO). Secondary end points included resting and exercise pulmonary capillary wedge pressure and peak exercise CO and metabolic equivalents.

RESULTS:

We included 24 patients with heart failure with reduced ejection fraction (17 men; 65±9 years of age; all White). Resting CO at trough levels was higher after KE compared with isocaloric comparator (5.2±1.1 L/min versus 5.0±1.1 L/min; difference, 0.3 L/min [95% CI, 0.1–0.5), and pulmonary capillary wedge pressure was lower (8±3 mm Hg versus 11±3 mm Hg; difference, −2 mm Hg [95% CI, −4 to −1]). These changes were amplified after KE dosing. Across all exercise intensities, KE treatment was associated with lower mean exercise pulmonary capillary wedge pressure (−3 mm Hg [95% CI, −5 to −1] ) and higher mean CO (0.5 L/min [95% CI, 0.1–0.8]), significantly different at low to moderate steady-state exercise but not at peak. Metabolic equivalents remained similar between treatments. In exploratory analyses, KE treatment was associated with 18% lower NT-proBNP (N-terminal pro-B-type natriuretic peptide; difference, −98 ng/L [95% CI, −185 to −23]), higher left ventricular ejection fraction (37±5 versus 34±5%;
P
=0.01), and lower left atrial and ventricular volumes.

CONCLUSIONS:

KE treatment for 14 days was associated with higher CO at rest and lower filling pressures, cardiac volumes, and NT-proBNP levels compared with isocaloric comparator. These changes persisted during exercise and were achieved on top of optimal medical therapy. Sustained modulation of circulating ketone bodies is a potential treatment principle in patients with heart failure with reduced ejection fraction.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT05161650.
Impact of a Medical Fitness Model on Incident Major Adverse Cardiovascular Events: A Prospective Cohort Study of 11 000 Members
Authors: Brar Ranveer , Whitlock Reid H. , Katz Alan , Di Nella Michelle , Komenda Paul , Bohm Clara , Rigatto Claudio , Tangri Navdeep , Solmundson Carrie , Collister David
Published: March 2024

Background

Cardiovascular disease remains the leading cause of disease burden and death in the world. The medical fitness model may be an alternative public health strategy to address cardiovascular risk factors with medical integrated programming.

Methods and Results

We performed a retrospective cohort study between January 1, 2005, and December 31, 2015. Adults (aged ≥18 years) who did not have a prior major adverse cardiovascular event were included. Controls were assigned a pseudo‐index date at random on the basis of the frequency distribution of start dates in the medical fitness facility group. Multivariate Cox proportional hazards regression models were adjusted for age, sex, socioeconomic status, comorbidities, and year of index date. We stratified the medical fitness facility group into low‐frequency attenders (≤1 weekly visit) and regular‐frequency attenders (>1 weekly visit). Our primary outcome was a hospitalization for nonfatal myocardial infarction and stroke, heart failure, or cardiovascular death. We included 11 319 medical fitness facility members and 507 400 controls in our study. Compared with controls, members had a lower hazard risk of a major adverse cardiovascular event‐plus (hazard ratio [HR], 0.88 [95% CI, 0.81–0.96]). Higher weekly attendance was associated with a lower hazard risk of a major adverse cardiovascular event‐plus compared with controls, but the effect was not significant for lower weekly attendance (low‐frequency attenders: HR, 0.94 [95% CI, 0.85–1.04]; regular‐frequency attenders: HR, 0.77 [95% CI, 0.67–0.89]).

Conclusions

Medical fitness facility membership and attendance at least once per week may lower the risk of a major adverse cardiovascular event‐plus. The medical fitness model should be considered as a public health intervention, especially for individuals at risk for cardiovascular disease.
Frailty and Metabolic Vulnerability in Heart Failure: A Community Cohort Study
Authors: Kumar Sant , Conners Katherine M. , Shearer Joseph J. , Joo Jungnam , Turecamo Sarah , Sampson Maureen , Wolska Anna , Remaley Alan T. , Connelly Margery A. , Otvos James D. , Larson Nicholas B. , Bielinski Suzette J. , Roger Véronique L.
Published: March 2024

Background

Frailty is common in heart failure (HF) and is associated with death but not routinely captured clinically. Frailty is linked with inflammation and malnutrition, which can be assessed by a novel plasma multimarker score: the metabolic vulnerability index (MVX). We sought to evaluate the associations between frailty and MVX and their prognostic impact.

Methods and Results

In an HF community cohort (2003–2012), we measured frailty as a proportion of deficits present out of 32 physical limitations and comorbidities, MVX by nuclear magnetic resonance spectroscopy, and collected extensive longitudinal clinical data. Patients were categorized by frailty score (≤0.14, >0.14 and ≤0.27, >0.27) and MVX score (≤50, >50 and ≤60, >60 and ≤70, >70). Cox models estimated associations of frailty and MVX with death, adjusted for Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) score and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide). Uno's C‐statistic measured the incremental value of MVX beyond frailty and clinical factors. Weibull's accelerated failure time regression assessed whether MVX mediated the association between frailty and death. We studied 985 patients (median age, 77; 48% women). Frailty and MVX were weakly correlated (Spearman's ρ=0.21). The highest frailty group experienced an increased rate of death, independent of MVX, MAGGIC score, and NT‐proBNP (hazard ratio, 3.3 [95% CI, 2.5–4.2]). Frailty improved Uno's c‐statistic beyond MAGGIC score and NT‐proBNP (0.69–0.73). MVX only mediated 3.3% and 4.5% of the association between high and medium frailty groups and death, respectively.

Conclusions

In this HF cohort, frailty and MVX are weakly correlated. Both independently contribute to stratifying the risk of death, suggesting that they capture distinct domains of vulnerability in HF.
Lower Recurrence Rates of Atrial Fibrillation and MACE Events After Early Compared to Late Ablation: A Danish Nationwide Register Study
Authors: Tønnesen Jacob , Ruwald Martin H. , Pallisgaard Jannik , Rasmussen Peter Vibe , Johannessen Arne , Hansen Jim , Worck Rene H. , Zörner Christopher R. , Riis‐Vestergaard Lise , Middelfart Charlotte , Sørensen Samuel K. , Sattler Stefan , Gislason Gunnar , Hansen Morten Lock
Published: March 2024

Background

Guidelines recommend prioritizing treatment with antiarrhythmic drugs before referral of patients with atrial fibrillation to ablation, delaying a potential subsequent ablation. However, delaying ablation may affect ablation outcomes. We sought to investigate the impact of duration from diagnosis to ablation on the risk of atrial fibrillation recurrence and adverse events.

Methods and Results

Using Danish nationwide registries, all patients with first‐time ablation for atrial fibrillation were identified and included from 2010 to 2018. Patients were divided into 4 groups by diagnosis‐to‐ablation time: <1.0 year (early ablation), 1.0 to 1.9 years, 2.0 to 2.9 years, and >2.9 years (late ablation). The primary end point was atrial fibrillation recurrence after the 90‐day blanking period, defined by admission for atrial fibrillation, cardioversions, use of antiarrhythmic drugs, or repeat atrial fibrillation ablations. The secondary end point was a composite end point of heart failure, ischemic stroke, or death, and each event individually. The study cohort consisted of 7705 patients. The 5‐year cumulative incidence of atrial fibrillation recurrence in the 4 groups was 42.9%, 54.8%, 55.9%, and 58.4%, respectively. Hazard ratios were 1.20 (95% CI, 1.07–1.35), 1.29 (95% CI, 1.13–1.47), and 1.40 (95% CI, 1.28–1.53), respectively, with the early ablation group as reference. The hazard ratio for the combined secondary end point was 1.22 (95% CI, 1.04–1.44) in the late ablation group compared with the early ablation group.

Conclusions

In patients undergoing ablation for atrial fibrillation, early ablation was associated with a significantly lower risk of atrial fibrillation recurrence. Furthermore, the associated risk of heart failure, ischemic stroke, or death was significantly lower in early‐compared with late‐ablation patients.
Cost‐Effectiveness of Increased Use of Dual Antiplatelet Therapy After High‐Risk Transient Ischemic Attack or Minor Stroke
Authors: Wechsler Paul M. , Pandya Ankur , Parikh Neal S. , Razzak Junaid A. , White Halina , Navi Babak B. , Kamel Hooman , Liberman Ava L.
Published: March 2024

Background

Rates of dual antiplatelet therapy (DAPT) after high‐risk transient ischemic attack or minor ischemic stroke (TIAMIS) are suboptimal. We performed a cost‐effectiveness analysis to characterize the parameters of a quality improvement (QI) intervention designed to increase DAPT use after TIAMIS.

Methods and Results

We constructed a decision tree model that compared current national rates of DAPT use after TIAMIS with rates after implementing a theoretical QI intervention designed to increase appropriate DAPT use. The base case assumed that a QI intervention increased the rate of DAPT use to 65% from 45%. Costs (payer and societal) and outcomes (stroke, myocardial infarction, major bleed, or death) were modeled using a lifetime horizon. An incremental cost‐effectiveness ratio <$100 000 per quality‐adjusted life year was considered cost‐effective. Deterministic and probabilistic sensitivity analyses were performed. From the payer perspective, a QI intervention was associated with $9657 in lifetime cost savings and 0.18 more quality‐adjusted life years compared with current national treatment rates. A QI intervention was cost‐effective in 73% of probabilistic sensitivity analysis iterations. Results were similar from the societal perspective. The maximum acceptable, initial, 1‐time payer cost of a QI intervention was $28 032 per patient. A QI intervention that increased DAPT use to at least 51% was cost‐effective in the base case.

Conclusions

Increasing DAPT use after TIAMIS with a QI intervention is cost‐effective over a wide range of costs and proportion of patients with TIAMIS treated with DAPT after implementation of a QI intervention. Our results support the development of future interventions focused on increasing DAPT use after TIAMIS.
Polygenic Scores and Preclinical Cardiovascular Disease in Individuals With HIV: Insights From the REPRIEVE Trial
Authors: Zou Roger S. , Ruan Yunfeng , Truong Buu , Bhattacharya Romit , Lu Michael T. , Karády Júlia , Bernardo Rachel , Finneran Phoebe , Hornsby Whitney , Fitch Kathleen V. , Ribaudo Heather J. , Zanni Markella V. , Douglas Pamela S. , Grinspoon Steven K. , Patel Aniruddh P. , Natarajan Pradeep
Published: March 2024

Background

Coronary artery disease (CAD) is a leading cause of death among the 38.4 million people with HIV globally. The extent to which cardiovascular polygenic risk scores (PRSs) derived in non‐HIV populations generalize to people with HIV is not well understood.

Methods and Results

PRSs for CAD (GPS
Mult
) and lipid traits were calculated in a global cohort of people with HIV treated with antiretroviral therapy with low‐to‐moderate atherosclerotic cardiovascular disease risk enrolled in REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV). The PRSs were associated with baseline lipid traits in 4495 genotyped participants, and with subclinical CAD in a subset of 662 who underwent coronary computed tomography angiography. Among participants who underwent coronary computed tomography angiography (mean age, 50.9 [SD, 5.8] years; 16.1% women; 41.8% African, 57.3% European, 1.1% Asian), GPS
Mult
was associated with plaque presence with odds ratio (OR) per SD in GPS
Mult
of 1.42 (95% CI, 1.20–1.68;
P
=3.8×10
−5
), stenosis >50% (OR, 2.39 [95% CI, 1.48–3.85];
P
=3.4×10
−4
), and noncalcified/vulnerable plaque (OR, 1.45 [95% CI, 1.23–1.72];
P
=9.6×10
−6
). Effects were consistent in subgroups of age, sex, 10‐year atherosclerotic cardiovascular disease risk, ancestry, and CD4 count. Adding GPS
Mult
to established risk factors increased the C‐statistic for predicting plaque presence from 0.718 to 0.734 (
P
=0.02). Furthermore, a PRS for low‐density lipoprotein cholesterol was associated with plaque presence with OR of 1.21 (95% CI, 1.01–1.44;
P
=0.04), and partially calcified plaque with OR of 1.21 (95% CI, 1.01–1.45;
P
=0.04) per SD.

Conclusions

Among people with HIV treated with antiretroviral therapy without documented atherosclerotic cardiovascular disease and at low‐to‐moderate calculated risk in REPRIEVE, an externally developed CAD PRS was predictive of subclinical atherosclerosis. PRS for low‐density lipoprotein cholesterol was also associated with subclinical atherosclerosis, supporting a role for low‐density lipoprotein cholesterol in HIV‐associated CAD.

Registration

URL:
https://www.reprievetrial.org
; Unique identifier: NCT02344290.
Duration of Remote Ischemic Conditioning and Outcome in Acute Ischemic Stroke
Authors: Cui Yu , Chen Yi‐Ning , Nguyen Thanh N. , Chen Hui‐Sheng
Published: March 2024

Background

Remote ischemic conditioning has been found to be effective in improving functional outcomes in acute ischemic stroke. We conducted a post hoc analysis of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial to determine whether long‐term remote ischemic conditioning duration after stroke onset is associated with better clinical outcomes in ischemic stroke.

Methods and Results

Patients from the full analysis set were included in this secondary analysis. The primary outcome was the proportion of patients with an excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. Among the 1776 patients, there were 55 patients in the 1 to 7 days remote ischemic conditioning group, 345 in the 8 to 10 days group, 412 in the 11 to 13 days group, 51 in the 14 to 16 days group, and 913 in the control group. Compared with the control group, a significantly higher proportion of excellent functional outcomes at 90 days was found in the 11 to 13 days remote ischemic conditioning group (adjusted absolute difference, 9.1% [95% CI, 3.7%–14.5%];
P
 =0.001), which was attenuated in the other groups (adjusted absolute difference in the 8–10 days group, 2.0% [95% CI, −4.0% to 8.0%];
P
=0.51; adjusted absolute difference in the 14–16 days group, 7.4% [95% CI, −5.8% to 20.5%];
P
=0.27), but compared to the control group, there was lower proportion of excellent functional outcomes in the 1 to 7 days group (adjusted absolute difference, −14.4% [95% CI, −27.8% to 0.0%];
P
=0.05).

Conclusions

Among patients with acute moderate ischemic stroke, a higher likelihood of excellent clinical outcome was found in patients with longer duration of remote ischemic conditioning.
Health Factors Associated With Development and Severity of Poststroke Dysphagia: An Epidemiological Investigation
Authors: Krekeler Brittany N. , Schieve Heidi J. P. , Khoury Jane , Ding Lili , Haverbusch Mary , Alwell Kathleen , Adeoye Opeolu , Ferioloi Simona , Mackey Jason , Woo Daniel , Flaherty Matthew , La Rosa Felipe De Los Rios , Demel Stacie , Star Michael , Coleman Elisheva , Walsh Kyle , Slavin Sabreena , Jasne Adam , Mistry Eva , Kleindorfer Dawn , Kissela Brett
Published: March 2024

Background

Dysphagia after stroke is common and can impact morbidity and death. The purpose of this population‐based study was to determine specific epidemiological and health risk factors that impact development of dysphagia after acute stroke.

Methods and Results

Ischemic and hemorrhagic stroke cases from 2010 and 2015 were identified via chart review from the GCNKSS (Greater Cincinnati Northern Kentucky Stroke Study), a representative sample of ≈1.3 million adults from southwestern Ohio and northern Kentucky. Dysphagia status was determined on the basis of clinical assessments and necessity for alternative access to nutrition via nasogastric or percutaneous endoscopic gastrostomy tube placement. Comparisons between patients with and without dysphagia were made to determine differences in baseline characteristics and premorbid conditions. Multivariable logistic regression determined factors associated with increased risk of dysphagia. Dysphagia status was ascertained from 4139 cases (1709 with dysphagia). Logistic regression showed that increased age, Black race, higher National Institutes of Health Stroke Scale score at admission, having a hemorrhagic stroke (versus infarct), and right hemispheric stroke increased the risk of developing dysphagia after stroke. Factors associated with reduced risk included history of high cholesterol, lower prestroke modified Rankin Scale score, and white matter disease.

Conclusions

This study replicated previous findings of variables associated with dysphagia (older age, worse stroke, right‐sided hemorrhagic lesions), whereas other variables identified were without clear biological rationale (eg, Black race, history of high cholesterol, and presence of white matter disease) and should be investigated in future studies to determine biological relevance and potential influence in stroke recovery.