bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness of single-pill and separate-pill administration of antihypertensive triple combination therapy: a population-based microsimulation study
Authors: Morabito Gabriella , Gregorio Caterina , Ieva Francesca , Barbati Giulia , Mancia Giuseppe , Corrao Giovanni , Rea Federico
Published: July 2024

Background

Single-pill combination (SPC) of three antihypertensive drugs has been shown to improve adherence to therapy compared with free combinations, but little is known about its long-term costs and health consequences. This study aimed to evaluate the lifetime cost-effectiveness profile of a three-drug SPC of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic vs the corresponding two-pill administration (a two-drug SPC plus a third drug separately) from the Italian payer perspective.

Methods

A cost-effectiveness analysis was conducted using multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged ≥ 40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug dispensation until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies, assigning each of them to each cohort member. Costs and life-years gained were discounted by 3%. Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty.

Results

Compared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61–1.14), with a mean cost differential of -€12 (95% CI -9,719–8,131), making it the dominant strategy (ICER = -14, 95% CI -€15,871–€7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17–7,813) and €2,027 (95% CI 19–8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574–10,640 vs. €3,710, 95% CI 263–11,955). The cost-effectiveness profile did not significantly change according to age, sex, and clinical status.

Conclusions

The SPC was projected to be cost-effective compared with the two-pill combination at almost all reasonable willingness-to-pay thresholds. As it is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system.
Relationship between oral hypofunction and salivary biomarkers in older adults: a cross-sectional study
Authors: Masutomi Kenji , Bando Mika , Inagaki Yuji , Kido Rie , Uemura Yuta , Hatada Yukari , Kido Jun-ichi , Fukui Makoto , Hinode Daisuke , Yumoto Hiromichi
Published: July 2024

Background

Oral health problems have increased among older adults. Oral hypofunction is characterized by seven signs and symptoms: oral uncleanness, oral dryness, decline in occlusal force, decline in the movement function of the tongue and lips, decline in tongue pressure, decline in masticatory function, and decline in swallowing function, the latter being a significant risk factors for oral frailty. Recent research has suggested that salivary biomarkers can be used to assess not only oral diseases, including dental caries and periodontitis, but also systemic diseases, such as cancer and diabetes mellitus. This cross-sectional study investigated the relationship between oral hypofunction and the levels of salivary biomarkers.

Methods

In total, 116 patients, aged 65 years or older, were included in this cross-sectional study. If three or more signs or symptoms in seven kinds of tests met the criteria of each test, oral hypofunction was diagnosed. The levels of biomarkers in the saliva collected from the patients were analyzed using an enzyme-linked immunosorbent assay.

Results

In total, 63.8% of patients were diagnosed with oral hypofunction. Multivariable linear regression analysis showed that calprotectin levels in the saliva were significantly related to oral moisture and masticatory function. Furthermore, 8-OHdG levels in saliva were associated with the movement function of the tongue and lips and oral hygiene level, and salivary AGE correlated only with the movement function of the tongue and lips. Multiple logistic regression analysis revealed that calprotectin levels in the saliva were significantly correlated with the prevalence of oral hypofunction, even after adjusting for age, sex, and periodontal status. However, none of the biomarker levels in the saliva had a significant relationship with the number of examinations outside the reference range.

Conclusions

Calprotectin, 8-OHdG, and AGE levels are associated with oral hypofunction in older adults.
Strengthening a culture of research dissemination: A narrative report of research day at King Faisal Hospital Rwanda, a tertiary-level teaching hospital in Rwanda
Authors: Neil Kara L. , Nduwayezu Richard , Uwurukundo Belise S. , Dukundane Damas , Mbabazi Ruth , Nyirigira Gaston
Published: July 2024

Background

There are significant gaps in research output and authorship in low- and middle-income countries. Research dissemination events have the potential to help bridge this gap through knowledge transfer, institutional collaboration, and stakeholder engagement. These events may also have an impact on both clinical service delivery and policy development. King Faisal Hospital Rwanda (KFH) is a tertiary-level teaching hospital located in Kigali, Rwanda. To strengthen its research dissemination, KFH conducted an inaugural Research Day (RD) to disseminate its research activities, recognize staff and student researchers at KFH, define a research agenda for the hospital, and promote a culture of research both at KFH and in Rwanda.

Methods

RD was coordinated by an interdisciplinary committee of clinical and non-clinical staff at KFH. Researchers were encouraged to disseminate their research across all disciplines. Abstracts were blind reviewed using a weighted rubric and ranked by overall score. Top researchers were also awarded and recognized for their work, and equity and inclusion was at the forefront of RD programming.

Results

RD had over 100 attendees from KFH and other public, private, and academic institutions. Forty-seven abstracts were submitted from the call for abstracts, with the highest proportion studying cancer (17.02%) and sexual and reproductive health (10.64%). Thirty-seven researchers submitted abstracts, and most of the principal investigators were medical doctors (35.14%), allied health professionals (27.03%), and nurses and midwives (16.22%). Furthermore, 30% of principal investigators were female, with the highest proportion of them being nurses and midwives (36.36%).

Conclusion

RD is an effective way to disseminate research in a hospital setting. RD has the potential to strengthen the institution’s research agenda, engage the community in ongoing projects, and provide content-area support to researchers. Equity and inclusion should be at the forefront of research dissemination, including gender equity, authorship representation, and the inclusion of interdisciplinary health professionals. Stakeholder engagement can also be utilized to strengthen institutional research collaboration for greater impact.
Serum macroelements and microelements levels in periparturient dairy cows in relation to fatty liver diseases
Authors: Zhang Ke-Xin , Li Ke , Li Zhe-Hao , Liu Xiao-Chen , Li Meng-Meng , Jiang Shan , Fan Rui-Feng , Yan Zhen-Gui
Published: July 2024

Background

Fatty liver in dairy cows is a common metabolic disease defined by triglyceride (TG) buildup in the hepatocyte. Clinical diagnosis of fatty liver is usually done by liver biopsy, causing considerable economic losses in the dairy industry owing to the lack of more effective diagnostic methods. Therefore, this study aimed to investigate the potential utility of blood biomarkers for the diagnosis and early warning of fatty liver in dairy cows.

Results

A total of twenty-four lactating cows within 28 days after parturition were randomly selected as experimental animals and divided into healthy cows (liver biopsy tested, n = 12) and cows with fatty liver (liver biopsy tested, n = 12). Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the macroelements and microelements in the serum of two groups of cows. Compared to healthy cows (C), concentrations of calcium (Ca), potassium (K), magnesium (Mg), strontium (Sr), selenium (Se), manganese (Mn), boron (B) and molybdenum (Mo) were lower and copper (Cu) was higher in fatty liver cows (F). Meanwhile, the observed differences in macroelements and microelements were related to delivery time, with the greatest major disparity between C and F occurring 7 days after delivery. Multivariable analysis was used to test the correlation between nine serum macroelements, microelements and fatty liver. Based on variable importance projection and receiver operating characteristic (ROC) curve analysis, minerals Ca, Se, K, B and Mo were screened as the best diagnostic indicators of fatty liver in postpartum cows.

Conclusions

Our data suggested that serum levels of Ca, K, Mg, Se, B, Mo, Mn, and Sr were lower in F than in C. The most suitable period for an early-warning identification of fatty liver in cows was 7 days after delivery, and Ca, Se, K, B and Mo were the best diagnostic indicators of fatty liver in postpartum cows.
Prevalence, antibiogram and molecular characterization of Listeria monocytogenes from ruminants and humans in New Valley and Beheira Governorates, Egypt
Authors: Sotohy Sotohy A. , Elnaker Yasser F. , Omar Aya M. , Alm Eldin Nehal K. , Diab Mohamed Said
Published: July 2024

Background

Listeriosis is a global health threat to both animals and humans, especially in developing countries. This study was designed to isolate Listeria monocytogenes from faeces; environmental samples; and cow, sheep and goat milk, as well as human stool, to study its molecular characteristics and antibiotic sensitivity in the New Valley and Beheira Governorates, Egypt. The isolation and identification of L. monocytogenes were carried out using traditional culture and biochemical methods, followed by antibiography, genus confirmation of some isolates and detection and sequencing of InlB genes via PCR.

Results

Out of 2097 examined samples, the prevalence of L. monocytogenes was 13.4% in animals; the prevalence was 9.2%, 2.4%, 25.4%, 4%, 42.4%, and 6.4% in cattle faeces, cattle milk, sheep faeces, sheep milk, goat faeces, and goat milk, respectively. However, the prevalence of L. monocytogenes was 8.3% in human samples. Both animal and human isolates showed 100% resistance to trimethoprim-sulfamethoxazole, and the isolates showed the highest sensitivity to flumequine (100%), amikacin (99.2%), gentamicin (97.6%), and levofloxacin (94.6%). Multidrug resistance (MDR) was detected in 86.9% of the tested isolates. The 16 S rRNA and inlB genes were detected in 100% of the randomly selected L. monocytogenes isolates. Phylogenetic analysis of three isolates based on the inlB gene showed 100% identity between faecal, milk and human stool isolates.

Conclusions

Faeces and milk are major sources of listeriosis, and the high degree of genetic similarity between animal and human isolates suggests the possibility of zoonotic circulation. The high prevalence of MDR L. monocytogenes in both animal and human samples could negatively impact the success of prevention and treatments for animal and human diseases, thereby imposing serious risks to public health.
A ferritin-based nanoparticle displaying a neutralizing epitope for foot-and-mouth disease virus (FMDV) confers partial protection in guinea pigs
Authors: Lu Bingzhou , Ru Yi , Hao Rongzeng , Yang Yang , Liu Huanan , Li Yajun , Zhang Yue , Mao Yuhan , Yang Rui , Pan Yangyang , Yu Sijiu , Zheng Haixue , Cui Yan
Published: July 2024

Background

Foot-and-mouth disease (FMD) is a devastating disease affecting cloven-hoofed animals, that leads to significant economic losses in affected countries and regions. Currently, there is an evident inclination towards the utilization of nanoparticles as powerful platforms for innovative vaccine development. Therefore, this study developed a ferritin-based nanoparticle (FNP) vaccine that displays a neutralizing epitope of foot-and-mouth disease virus (FMDV) VP1 (aa 140–158) on the surface of FNP, and evaluated the immunogenicity and protective efficacy of these FNPs in mouse and guinea pig models to provide a strategy for developing potential FMD vaccines.

Results

This study expressed the recombinant proteins Hpf, HPF-NE and HPF-T34E via an E. coli expression system. The results showed that the recombinant proteins Hpf, Hpf-NE and Hpf-T34E could be effectively assembled into nanoparticles. Subsequently, we evaluated the immunogenicity of the Hpf, Hpf-NE and Hpf-T34E proteins in mice, as well as the immunogenicity and protectiveness of the Hpf-T34E protein in guinea pigs. The results of the mouse experiment showed that the immune efficacy in the Hpf-T34E group was greater than the Hpf-NE group. The results from guinea pigs immunized with Hpf-T34E showed that the immune efficacy was largely consistent with the immunogenicity of the FMD inactivated vaccine (IV) and could confer partial protection against FMDV challenge in guinea pigs.

Conclusions

The Hpf-T34E nanoparticles stand out as a superior choice for a subunit vaccine candidate against FMD, offering effective protection in FMDV-infected model animals. FNP-based vaccines exhibit excellent safety and immunogenicity, thus representing a promising strategy for the continued development of highly efficient and safe FMD vaccines.
Unusual sex chromosomal DSD in a domestic Shorthair cat with a 37,X/38,XY mosaic karyotype
Authors: Montenegro L. , Costa I. , Maltez L. , Evaristo V. , Dias I. R. , Martins C. , Borges I. , Morinha F. , Pereira R. , Neto N. , Oliveira C. , Martins-Bessa A.
Published: July 2024

Background

Sex chromosome abnormalities associated with disorders of sexual development (DSD) are rarely described in cats, mainly due to the lack of chromossome studies that precisely reveal the condition. Genetic approaches are therefore required in order to detect sex chromossomes abnormalities as variations in the number and structure of chromosomes, or the presence of a second cell line as mosaicim or chimerism.

Case presentation

A male Shorthair cryptorchid cat was presented with clinical signs of anorexia, tenesmus and hyperthermia. Ultrasonography revealed a fluid-filled structure, with approximately 1 cm in diameter, adjacent to the descending colon. Computed tomography evidenced a tubular structure, ventral to the descending colon and caudal to the bladder, which extended cranially, through two branches. Histopathological evaluation confirmed the presence of two atrophic uterine horns and one hypoplastic testicle with epididymis at the end of one of the uterine horns. The end of the other uterine horn was attached to a structure composed by a mass of adipocytes. Cytogenetic analysis revealed a mosaic 37,X/38,XY karyotype. The two cell lines were found in 15% and 85% of the lymphocytes, respectively. Genetic analysis confirmed the presence of SRY and ZFY genes in blood and hair bulbs, and revealed a marked reduction in SRY expression in the testicle. Additionally, this case presented exceptionally rare features, such as a Leydig’ cell tumour and a chronic endometritis in both uterine horns.

Conclusions

Complete imaging workup, cytogenetic analysis and SRY gene expression should be systematically realized, in order to properly classify disorders of sexual development (DSD) in cats.
An investigation of inequalities in exposure to PM2.5 air pollution across small areas in Ireland
Authors: Hoy Aislinn , Mohan Gretta , Nolan Anne
Published: July 2024

The link between exposure to air pollution and adverse effects on human health is well documented. Yet, in a European context, research on the spatial distribution of air pollution and the characteristics of areas is relatively scarce, and there is a need for research using different spatial scales, a wider variety of socioeconomic indicators (such as ethnicity) and new methodologies to assess these relationships. This study uses comprehensive data on a wide range of demographic and socioeconomic indicators, matched to data on PM2.5 concentrations for small areas in Ireland, to assess the relationship between social vulnerability and PM2.5 air pollution. Examining a wide range of socioeconomic indicators revealed some differentials in PM2.5 concentration levels by measure and by rural and urban classification. However, statistical modelling using concentration curves and concentration indices did not present substantial evidence of inequalities in PM2.5 concentrations across small areas. In common with other western European countries, an overall decline in the levels of PM2.5 between 2011 and 2016 was observed in Ireland, though the data indicates that almost all small areas in Ireland were found to have exceeded the World Health Organization (WHO)’s PM2.5 annual guideline (of 5 µg/m3), calling for greater policy efforts to reduce air pollution in Ireland. The recent Clean Air Strategy contains a commitment to achieve the WHO guideline limits for PM2.5 by 2040, with interim targets at various points over the next two decades. Achieving these targets will require policy measures to decarbonise home heating, promote active travel and the transition to electric vehicles, and further regulations on burning fossil fuels and enforcing environmental regulations more tightly. From a research and information-gathering perspective, installing more monitoring stations at key points could improve the quality and spatial dimension of the data collected and facilitate the assessment of the implementation of the measures in the Clean Air Strategy.
Cost analysis of establishing and operating the first human milk bank at Da Nang Hospital for Women and Children in Vietnam: an activity-based costing ingredients study
Authors: Hoang Minh V. , Nguyen Tuan T. , Tran Anh T. , Luu Toan Q. , Vu Mai Q. , Tran Hoang T. , Nguyen Oanh T. X. , Mathisen Roger
Published: July 2024

Background

Breastfeeding is the biological norm for feeding infants and young children. When mothers’ breastmilk is unavailable, donor human milk (DHM) from a human milk bank (HMB) becomes the next option for small vulnerable newborns. A comprehensive cost analysis is essential for understanding the investments needed to establish, operate, and scale up HMBs. This study aims to estimate and analyze such costs at the first facility established in Vietnam.

Methods

An activity-based costing ingredients (ABC-I) approach was employed, with the cost perspective from service provision agencies (specifically, the project conducted at Da Nang Hospital for Women and Children and Development Partners). Estimated financial costs, based on actual expenditures, were measured in 2023 local currency and then converted to 2023 US dollars (USD). We examined three scenarios: 1) direct start-up costs + indirect start-up costs + implementation costs, 2) direct start-up costs + implementation costs, and 3) capital costs + implementation costs over the 6.5 years of operation.

Results

The total start-up cost was USD 616,263, with total expenditure on direct activities at USD 228,131 and indirect activities at USD 388,132. Investment in equipment accounted for the largest proportion (USD 84,213). The monthly costs of Da Nang HMB were USD 25,217, 14,565, and 9,326, corresponding to scenarios 1, 2, and 3, respectively. Over HMB's 6.5 years of operation, on average, the unit costs were USD 166, USD 96, and USD 62 for DHM received and USD 201, USD 116, and USD 74 for pasteurized DHM meeting specified criteria in the corresponding scenarios. Unit costs were highest in the initial six months, decreased, and reached their lowest levels after a year. Then, the unit costs experienced an increase in late 2020 and early 2021.

Conclusion

Although the unit cost of DHM in Da Nang HMB is comparable to that in certain neighboring countries, intentional measures to reduce disposal rates, improve HMB efficiency, motivate more community-based donors, and establish an HMB service network should be implemented to lower costs.
Comprehensive insights into health services accessibility and quality of life of families with individuals with 22q11.2 deletion syndrome in Brazil
Authors: Silva Isabela Mayá Wayhs , Gil-da-Silva-Lopes Vera Lúcia
Published: July 2024

Background

The 22q11.2 Deletion Syndrome (22q11.2 DS) presents unique healthcare challenges for affected individuals, families, and healthcare systems. Despite its rarity, 22q11.2 DS is the most common microdeletion syndrome in humans, emphasizing the need to understand and address the distinctive healthcare requirements of those affected. This paper examines the multifaceted issue of health service access and caregivers’ quality of life in the context of 22q11.2 DS in Brazil, a condition with diverse signs and symptoms requiring multidisciplinary care. This study employs a comprehensive approach to evaluate health service accessibility and the quality of life of caregivers of individuals with 22q11.2 DS. It utilizes a structured Survey and the WHOQOL-bref questionnaire for data collection.

Results

Individuals with 22q11.2 DS continue to receive incomplete clinical management after obtaining the diagnosis, even in the face of socioeconomic status that enabled an average age of diagnosis that precedes that found in sample groups that are more representative of the Brazilian population (mean of 3.2 years versus 10 years, respectively). In turn, caring for individuals with 22q11.2 DS who face difficulty accessing health services impacts the quality of life associated with the caregivers' environment of residence.

Conclusions

Results obtained help bridge the research gap in understanding how caring for individuals with multisystem clinical conditions such as 22q11.2 DS and difficulties in accessing health are intertwined with aspects of quality of life in Brazil. This research paves the way for more inclusive healthcare policies and interventions to enhance the quality of life for families affected by this syndrome.
Parallel activation of helicopter and ground transportation after dispatcher identification of suspected anterior large vessel occlusion stroke in rural areas: a proof-of-concept case with modeling from the LESTOR trial
Authors: Henningsen Max , Herrmann Matthias L. , Meier Simone , Bergmann Ulrike , Busch Hans-Jörg , Taschner Christian A. , Brich Jochen
Published: July 2024

Background

When stroke patients with suspected anterior large vessel occlusion (aLVO) happen to live in rural areas, two main options exist for prehospital transport: (i) the drip-and-ship (DnS) strategy, which ensures rapid access to intravenous thrombolysis (IVT) at the nearest primary stroke center but requires time-consuming interhospital transfer for endovascular thrombectomy (EVT) because the latter is only available at comprehensive stroke centers (CSC); and (ii) the mothership (MS) strategy, which entails direct transport to a CSC and allows for faster access to EVT but carries the risk of IVT being delayed or even the time window being missed completely. The use of a helicopter might shorten the transport time to the CSC in rural areas. However, if the aLVO stroke is only recognized by the emergency service on site, the helicopter must be requested in addition, which extends the prehospital time and partially negates the time advantage. We hypothesized that parallel activation of ground and helicopter transportation in case of aLVO suspicion by the dispatcher (aLVO-guided dispatch strategy) could shorten the prehospital time in rural areas and enable faster treatment with IVT and EVT.

Methods

As a proof-of-concept, we report a case from the LESTOR trial where the dispatcher suspected an aLVO stroke during the emergency call and dispatched EMS and HEMS in parallel. Based on this case, we compare the provided aLVO-guided dispatch strategy to the DnS and MS strategies regarding the times to IVT and EVT using a highly realistic modeling approach.

Results

With the aLVO-guided dispatch strategy, the patient received IVT and EVT faster than with the DnS or MS strategies. IVT was administered 6 min faster than in the DnS strategy and 22 min faster than in the MS strategy, and EVT was started 47 min earlier than in the DnS strategy and 22 min earlier than in the MS strategy.

Conclusion

In rural areas, parallel activation of ground and helicopter emergency services following dispatcher identification of stroke patients with suspected aLVO could provide rapid access to both IVT and EVT, thereby overcoming the limitations of the DnS and MS strategies.
Study protocol for an adaptive, multi-arm, multi-stage (MAMS) randomised controlled trial of brief remotely delivered psychosocial interventions for people with serious mental health problems who have experienced a recent suicidal crisis: Remote Approaches to Psychosocial Intervention Delivery (RAPID)
Authors: Pyle Melissa , Loftus Lucy , Emsley Richard , Freeman Daniel , Gillard Steven , Gumley Andrew , Sierpatowska Justyna , Wood Lisa , O’Connor Rory C. , Pfeiffer Paul , Simpson Sharon Anne , Cockayne Nicole , Shields Gemma , Beckley Ariane , Beckwith Helen , Filippidou Maria , Glen Callum , Allan Stephanie , Hazzard Raj , Longden Eleanor , Peel Heather , Larsen Mark , Bucci Sandra , Morrison Anthony P.
Published: July 2024

Background

People with serious mental health problems (SMHP) are more likely to be admitted to psychiatric hospital following contact with crisis services. Admissions can have significant personal costs, be traumatic and are the most expensive form of mental health care. There is an urgent need for treatments to reduce suicidal thoughts and behaviours and reduce avoidable psychiatric admissions.

Methods

A multi-stage, multi-arm (MAMS) randomised controlled trial (RCT) with four arms conducted over two stages to determine the clinical and cost effectiveness of three psychosocial treatments, compared to treatment as usual (TAU), for people with SMHP who have had recent suicidal crisis. Primary outcome is any psychiatric hospital admissions over a 6-month period. We will assess the impact on suicidal thoughts and behaviour, hope, recovery, anxiety and depression. The remote treatments delivered over 3 months are structured peer support (PREVAIL); a safety planning approach (SAFETEL) delivered by assistant psychologists; and a CBT-based suicide prevention app accessed via a smartphone (BrighterSide). Recruitment is at five UK sites. Stage 1 includes an internal pilot with a priori progression criteria. In stage 1, the randomisation ratio was 1:1:1:2 in favour of TAU. This has been amended to 2:2:3 in favour of TAU following an unplanned change to remove the BrighterSide arm following the release of efficacy data from an independent RCT. Randomisation is via an independent remote web-based randomisation system using randomly permuted blocks, stratified by site. An interim analysis will be performed using data from the first 385 participants from PREVAIL, SAFETEL and TAU with outcome data at 6 months. If one arm is dropped for lack of benefit in stage 2, the allocation ratio of future participants will be 1:1. The expected total sample size is 1064 participants (1118 inclusive of BrighterSide participants).

Discussion

There is a need for evidence-based interventions to reduce psychiatric admissions, via reduction of suicidality. Our focus on remote delivery of established brief psychosocial interventions, utilisation of different modalities of delivery that can provide sustainable and scalable solutions, which are also suitable for a pandemic or national crisis context, will significantly advance treatment options.

Trial registration

ISRCTN33079589. Registered on June 20, 2022.
Nicotinamide mitigates visceral leishmaniasis by regulating inflammatory response and enhancing lipid metabolism
Authors: Zhou Qi , Zheng Zhiwan , Yin Shuangshuang , Duan Dengbinpei , Liao Xuechun , Xiao Yuying , He Jinlei , Zhong Junchao , Zeng Zheng , Su Liang , Luo Lu , Dong Chunxia , Chen Jianping , Li Jiao
Published: July 2024

Background

Currently, treatment regimens for visceral leishmaniasis (VL) are limited because of the presence of numerous adverse effects. Nicotinamide, a readily available and cost-effective vitamin, has been widely acknowledged for its safety profile. Several studies have demonstrated the anti-leishmanial effects of nicotinamide in vitro. However, the potential role of nicotinamide in Leishmania infection in vivo remains elusive.

Methods

In this study, we assessed the efficacy of nicotinamide as a therapeutic intervention for VL caused by Leishmania infantum in an experimental mouse model and investigated its underlying molecular mechanisms. The potential molecular mechanism was explored through cytokine analysis, examination of spleen lymphocyte subsets, liver RNA-seq analysis, and pathway validation.

Results

Compared to the infection group, the group treated with nicotinamide demonstrated significant amelioration of hepatosplenomegaly and recovery from liver pathological damage. The NAM group exhibited parasite reduction rates of 79.7% in the liver and 86.7% in the spleen, respectively. Nicotinamide treatment significantly reduced the activation of excessive immune response in infected mice, thereby mitigating hepatosplenomegaly and injury. Furthermore, nicotinamide treatment enhanced fatty acid β-oxidation by upregulating key enzymes to maintain lipid homeostasis.

Conclusions

Our findings provide initial evidence supporting the safety and therapeutic efficacy of nicotinamide in the treatment of Leishmania infection in BALB/c mice, suggesting its potential as a viable drug for VL.

Graphical Abstract
DNA methylation profile of inflammatory breast cancer and its impact on prognosis and outcome
Authors: Faldoni Flavia Lima Costa , Bizinelli Daniela , Souza Cristiano Pádua , Santana Iara Viana Vidigal , Marques Márcia Maria Chiquitelli , Rainho Claudia Aparecida , Marchi Fabio Albuquerque , Rogatto Silvia Regina
Published: July 2024

Background

Inflammatory breast cancer (IBC) is a rare disease characterized by rapid progression, early metastasis, and a high mortality rate.

Methods

Genome-wide DNA methylation analysis (EPIC BeadChip platform, Illumina) and somatic gene variants (105 cancer-related genes) were performed in 24 IBCs selected from a cohort of 140 cases.

Results

We identified 46,908 DMPs (differentially methylated positions) (66% hypomethylated); CpG islands were predominantly hypermethylated (39.9%). Unsupervised clustering analysis revealed three clusters of DMPs characterized by an enrichment of specific gene mutations and hormone receptor status. The comparison among DNA methylation findings and external datasets (TCGA-BRCA stages III-IV) resulted in 385 shared DMPs mapped in 333 genes (264 hypermethylated). 151 DMPs were associated with 110 genes previously detected as differentially expressed in IBC (GSE45581), and 68 DMPs were negatively correlated with gene expression. We also identified 4369 DMRs (differentially methylated regions) mapped on known genes (2392 hypomethylated). BCAT1, CXCL12, and TBX15 loci were selected and evaluated by bisulfite pyrosequencing in 31 IBC samples. BCAT1 and TBX15 had higher methylation levels in triple-negative compared to non-triple-negative, while CXCL12 had lower methylation levels in triple-negative than non-triple-negative IBC cases. TBX15 methylation level was associated with obesity.

Conclusions

Our findings revealed a heterogeneous DNA methylation profile with potentially functional DMPs and DMRs. The DNA methylation data provided valuable insights for prognostic stratification and therapy selection to improve patient outcomes.

Graphical Abstract
Clinical application of plasma P-tau217 to assess eligibility for amyloid-lowering immunotherapy in memory clinic patients with early Alzheimer’s disease
Authors: Howe Matthew D. , Britton Karysa J. , Joyce Hannah E. , Menard William , Emrani Sheina , Kunicki Zachary J. , Faust Melanie A. , Dawson Brittany C. , Riddle Meghan C. , Huey Edward D. , Janelidze Shorena , Hansson Oskar , Salloway Stephen P.
Published: July 2024

Background

With the approval of disease-modifying treatments (DMTs) for early Alzheimer’s disease (AD), there is an increased need for efficient and non-invasive detection methods for cerebral amyloid-β (Aβ) pathology. Current methods, including positron emission tomography (PET) and cerebrospinal fluid (CSF) analysis, are costly and invasive methods that may limit access to new treatments. Plasma tau phosphorylated at threonine-217 (P-tau217) presents a promising alternative, yet optimal cutoffs for treatment eligibility with DMTs like aducanumab require further investigation. This study evaluates the efficacy of one- and two-cutoff strategies for determining DMT eligibility at the Butler Hospital Memory & Aging Program (MAP).

Methods

In this retrospective, cross-sectional diagnostic cohort study, we first developed P-tau217 cutoffs using site-specific and BioFINDER-2 training data, which were then tested in potential DMT candidates from Butler MAP (total n = 150). ROC analysis was used to calculate the area under the curve (AUC) and accuracy of P-tau217 interpretation strategies, using Aβ-PET/CSF testing as the standard of truth.

Results

Potential DMT candidates at Butler MAP (n = 50), primarily diagnosed with mild cognitive impairment (n = 29 [58%]) or mild dementia (21 [42%]), were predominantly Aβ-positive (38 [76%]), and half (25 [50%]) were subsequently treated with aducanumab. Elevated P-tau217 predicted cerebral Aβ positivity in potential DMT candidates (AUC = 0.97 [0.92–1]), with diagnostic accuracy ranging from 0.88 (0.76–0.95, p = 0.028) to 0.96 (0.86–1, p < .001). When using site-specific cutoffs, a subset of DMT candidates (10%) exhibited borderline P-tau217 (between 0.273 and 0.399 pg/mL) that would have potentially required confirmatory testing.

Conclusions

This study, which included participants treated with aducanumab, confirms the utility of one- and two-cutoff strategies for interpreting plasma P-tau217 in assessing DMT eligibility. Using P-tau217 could potentially replace more invasive diagnostic methods, and all aducanumab-treated participants would have been deemed eligible based on P-tau217. However, false positives remain a concern, particularly when applying externally derived cutoffs that exhibited lower specificity which could have led to inappropriate treatment of Aβ-negative participants. Future research should focus on prospective validation of P-tau217 cutoffs to enhance their generalizability and inform standardized treatment decision-making across diverse populations.
Stage IA papillary and chromophobe renal cell carcinoma: effectiveness of cryoablation and partial nephrectomy
Authors: Uhlig Annemarie , Uhlig Johannes , Shuch Brian , Kim Hyun S.
Published: July 2024

Objectives

To evaluate the effectiveness of cryoablation compared to partial nephrectomy in patients with stage IA papillary and chromophobe renal cell carcinoma (pRCC; chRCC).

Material and methods

The 2004–2016 National Cancer Database was queried for adult patients with stage IA pRCC or chRCC treated with cryoablation or partial nephrectomy. Patients receiving systemic therapy or radiotherapy, as well as those with bilateral RCC or prior malignant disease were excluded. Overall survival (OS) was assessed using Kaplan–Meier plots and Cox proportional hazard regression models. Nearest neighbor propensity matching (1:1 cryoablation:partial nephrectomy, stratified for pRCC and chRCC) was used to account for potential confounders.

Results

A total of 11122 stage IA renal cell carcinoma patients were included (pRCC 8030; chRCC 3092). Cryoablation was performed in 607 (5.5%) patients, and partial nephrectomy in 10515 (94.5%) patients. A higher likelihood of cryoablation treatment was observed in older patients with non-private healthcare insurance, as well as in those with smaller diameter low-grade pRCC treated at non-academic centers in specific US geographic regions. After propensity score matching to account for confounders, there was no statistically significant difference in OS comparing cryoablation vs partial nephrectomy in patients with pRCC (HR = 1.3, 95% CI: 0.96–1.75, p = 0.09) and those with chRCC (HR = 1.38, 95% CI: 0.67–2.82, p = 0.38).

Conclusion

After accounting for confounders, cryoablation, and partial nephrectomy demonstrated comparable OS in patients with stage IA papillary and chromophobe RCC. Cryoablation is a reasonable treatment alternative to partial nephrectomy for these histological RCC subtypes when radiologically suspected or diagnosed after biopsy.

Critical relevance statement

Cryoablation might be considered as an upfront treatment alternative to partial nephrectomy in patients with papillary and chromophobe stage IA renal cell carcinoma, as both treatment approaches yield comparable oncological outcomes.

Key Points

The utilization of cryoablation for stage IA papillary and chromophobe RCC increases.

In the National Cancer Database, we found specific patterns of use of cryoablation.

Cryoablation and partial nephrectomy demonstrate comparable outcomes after accounting for confounders.

Graphical Abstract
Deep learning CT reconstruction improves liver metastases detection
Authors: Kanan Achraf , Pereira Bruno , Hordonneau Constance , Cassagnes Lucie , Pouget Eléonore , Tianhoun Léon Appolinaire , Chauveau Benoît , Magnin Benoît
Published: July 2024

Objectives

Detection of liver metastases is crucial for guiding oncological management. Computed tomography through iterative reconstructions is widely used in this indication but has certain limitations. Deep learning image reconstructions (DLIR) use deep neural networks to achieve a significant noise reduction compared to iterative reconstructions. While reports have demonstrated improvements in image quality, their impact on liver metastases detection remains unclear. Our main objective was to determine whether DLIR affects the number of detected liver metastasis. Our secondary objective was to compare metastases conspicuity between the two reconstruction methods.

Methods

CT images of 121 patients with liver metastases were reconstructed using a 50% adaptive statistical iterative reconstruction (50%-ASiR-V), and three levels of DLIR (DLIR-low, DLIR-medium, and DLIR-high). For each reconstruction, two double-blinded radiologists counted up to a maximum of ten metastases. Visibility and contour definitions were also assessed. Comparisons between methods for continuous parameters were performed using mixed models.

Results

A higher number of metastases was detected by one reader with DLIR-high: 7 (2–10) (median (Q₁–Q₃); total 733) versus 5 (2–10), respectively for DLIR-medium, DLIR-low, and ASiR-V (p < 0.001). Ten patents were detected with more metastases with DLIR-high simultaneously by both readers and a third reader for confirmation. Metastases visibility and contour definition were better with DLIR than ASiR-V.

Conclusion

DLIR-high enhanced the detection and visibility of liver metastases compared to ASiR-V, and also increased the number of liver metastases detected.

Critical relevance statement

Deep learning-based reconstruction at high strength allowed an increase in liver metastases detection compared to hybrid iterative reconstruction and can be used in clinical oncology imaging to help overcome the limitations of CT.

Key Points

Detection of liver metastases is crucial but limited with standard CT reconstructions.

More liver metastases were detected with deep-learning CT reconstruction compared to iterative reconstruction.

Deep learning reconstructions are suitable for hepatic metastases staging and follow-up.

Graphical Abstract
How to update esophageal masses imaging using literature review (MRI and CT features)
Authors: Qu Jinrong , Wang Zhaoqi , Zhang Hongkai , Lu Yanan , Jia Zhengyan , Lu Shuang , Zhao Keke , Chu Funing , Bai Bingmei , Zheng Yan , Xia Qingxin , Li Xu , Wang Shaoyu , Kamel Ihab R.
Published: July 2024

MRI offers new opportunities for detailed visualization of the different layers of the esophageal wall, as well as early detection and accurate characterization of esophageal lesions. Staging of esophageal tumors including extramural extent of disease, and status of the adjacent organ can also be performed by MRI with higher accuracy compared to other imaging modalities including CT and esophageal endoscopy. Although MDCT appears to be the primary imaging modality that is indicated for preoperative staging of esophageal cancer to assess tumor resectability, MDCT is considered less accurate in T staging. This review aims to update radiologists about emerging imaging techniques and the imaging features of various esophageal masses, emphasizing the imaging features that differentiate between esophageal masses, demonstrating the critical role of MRI in esophageal masses.

Critical relevance statement

MRI features may help differentiate mucosal high-grade neoplasia from early invasive squamous cell cancer of the esophagus, also esophageal GISTs from leiomyomas, and esophageal malignant melanoma has typical MR features.

Key Points

MRI can accurately visualize different layers of the esophagus potentially has a role in T staging.

MR may accurately delineate esophageal fistulae, especially small mediastinal fistulae.

MRI features of various esophageal masses are helpful in the differentiation.

Graphical Abstract
Predictors of lung cancer subtypes and lymph node status in non-small-cell lung cancer: intravoxel incoherent motion parameters and extracellular volume fraction
Authors: Han Huizhi , Guo Wenxiu , Ren Hong , Hao Huiting , Lin Xiangtao , Tian Mimi , Xin Jiaxiang , Zhao Peng
Published: July 2024

Objective

To determine the performance of intravoxel incoherent motion (IVIM) parameters and the extracellular volume fraction (ECV) in distinguishing between different subtypes of lung cancer and predicting lymph node metastasis (LNM) status in patients with non-small-cell lung cancer (NSCLC).

Methods

One hundred sixteen patients with lung cancer were prospectively recruited. IVIM, native, and postcontrast T1 mapping examinations were performed, and the T1 values were measured to calculate the ECV. The differences in IVIM parameters and ECV were compared between NSCLC and small-cell lung cancer (SCLC), adenocarcinoma (Adeno-Ca) and squamous cell carcinoma (SCC), and NSCLC without and with LNM. The assessment of each parameter’s diagnostic performance was based on the area under the receiver operating characteristic curve (AUC).

Results

The apparent diffusion coefficient (ADC), true diffusion coefficient (D), and ECV values in SCLC were considerably lower compared with NSCLC (all p < 0.001, AUC > 0.887). The D value in SCC was substantially lower compared with Adeno-Ca (p < 0.001, AUC = 0.735). The perfusion fraction (f) and ECV values in LNM patients were markedly higher compared with those without LNM patients (p < 0.01, < 0.001, AUC > 0.708).

Conclusion

IVIM parameters and ECV can serve as non-invasive biomarkers for assisting in the pathological classification and LNM status assessment of lung cancer patients.

Critical relevance statement

IVIM parameters and ECV demonstrated remarkable potential in distinguishing pulmonary carcinoma subtypes and predicting LNM status in NSCLC.

Key Points

Lung cancer is prevalent and differentiating subtype and invasiveness determine the treatment course.

True diffusion coefficient and ECV showed promise for subtyping and determining lymph node status.

These parameters could serve as non-invasive biomarkers to help determine personalized treatment strategies.

Graphical Abstract
Cervical cystic hygroma in adults: a case report
Authors: Askarpour Shahnam , Arabi Milad , Ghaedamini Hossein , Salmanpour Fardis
Published: July 2024

Backgrounds

Manifestation of cystic hygroma in adulthood is very rare. The rarity of cystic hygroma in adults has caused problems in its diagnosis and management and few studies have reported cystic hygroma in adults.

Case presentation

In this study, we reported a rare case with cervical cystic hygroma in adults. We report a 20-year-old Iranian male (Iranian ethnicity) with a diagnosis of right-side neck cystic hygroma and discuss the presentation, diagnosis, and clinical, radiological, and operative aspects of it.

Conclusion

Cystic hygromas are a rare occurrence in adults. They are typically asymptomatic, rarely complicated, and can be mistaken for a cystic neck mass. This study showed that in our case, surgical resection may be a safe and effective treatment for cystic hygroma, with minimal risk of complications during the procedure.
Rankl genetic deficiency and functional blockade undermine skeletal stem and progenitor cell differentiation
Authors: Schiavone M. L. , Crisafulli L. , Camisaschi C. , De Simone G. , Liberati F. R. , Palagano E. , Rucci N. , Ficara F. , Sobacchi Cristina
Published: July 2024

Background

Skeletal Stem Cells (SSCs) are required for skeletal development, homeostasis, and repair. The perspective of their wide application in regenerative medicine approaches has supported research in this field, even though so far results in the clinic have not reached expectations, possibly due also to partial knowledge of intrinsic, potentially actionable SSC regulatory factors. Among them, the pleiotropic cytokine RANKL, with essential roles also in bone biology, is a candidate deserving deep investigation.

Methods

To dissect the role of the RANKL cytokine in SSC biology, we performed ex vivo characterization of SSCs and downstream progenitors (SSPCs) in mice lacking Rankl (Rankl−/−) by means of cytofluorimetric sorting and analysis of SSC populations from different skeletal compartments, gene expression analysis, and in vitro osteogenic differentiation. In addition, we assessed the effect of the pharmacological treatment with the anti-RANKL blocking antibody Denosumab (approved for therapy in patients with pathological bone loss) on the osteogenic potential of bone marrow-derived stromal cells from human healthy subjects (hBMSCs).

Results

We found that, regardless of the ossification type of bone, osteochondral SSCs had a higher frequency and impaired differentiation along the osteochondrogenic lineage in Rankl−/− mice as compared to wild-type. Rankl−/− mice also had increased frequency of committed osteochondrogenic and adipogenic progenitor cells deriving from perivascular SSCs. These changes were not due to the peculiar bone phenotype of increased density caused by lack of osteoclast resorption (defined osteopetrosis); indeed, they were not found in another osteopetrotic mouse model, i.e., the oc/oc mouse, and were therefore not due to osteopetrosis per se. In addition, Rankl−/− SSCs and primary osteoblasts showed reduced mineralization capacity. Of note, hBMSCs treated in vitro with Denosumab had reduced osteogenic capacity compared to control cultures.

Conclusions

We provide for the first time the characterization of SSPCs from mouse models of severe recessive osteopetrosis. We demonstrate that Rankl genetic deficiency in murine SSCs and functional blockade in hBMSCs reduce their osteogenic potential. Therefore, we propose that RANKL is an important regulatory factor of SSC features with translational relevance.