bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the potential impact of vitamin C in postoperative spinal pain
Authors: Ranjbari Fatemeh , Alimohammadi Ehsan
Published: June 2024

Background

Spinal surgery is a common procedure associated with significant postoperative pain, and identifying effective interventions to manage this pain is crucial for optimizing patient outcomes. This review assesses the existing literature to determine the overall impact of vitamin C supplementation on spinal postoperative pain.

Vitamin C, also known as ascorbic acid, is an essential nutrient that plays a vital role in numerous physiological processes. It functions as a potent antioxidant, neutralizing free radicals and reducing oxidative stress within the body. Furthermore, vitamin C is a cofactor in collagen synthesis, a crucial component of connective tissues, including those found in the spinal structures. Given its antioxidant and collagen-promoting properties, vitamin C has piqued interest as a potential therapeutic option for postoperative spinal pain.

Based on the available evidence, vitamin C may have a beneficial effect on postoperative spinal pain, including reducing pain scores, analgesic consumption, and the incidence of complications such as complex regional pain syndrome. However, more research is needed to fully understand the optimal dosage and duration of vitamin C supplementation for postoperative pain management.

Conclusion

Vitamin C could be considered a potentially beneficial adjunctive therapy for managing spinal postoperative pain, but its routine use requires further investigation.
Does using a higher dialysate sodium concentration result in lower sodium losses with dialysis treatments?
Authors: Chhabra Roohi , Davenport Andrew
Published: June 2024

Introduction

Many dialysis centres prescribe a uniform dialysate sodium (DialNa) concentration, but as there is no consensus on the choice of a universal DialNa, we wished to determine dialysate sodium balance comparing DialNa of 140 and < 140 mEq/L.

Methods

Waste dialysate was continuously collected during sessions and thoroughly mixed, and sodium was measured in both the waste and fresh dialysate. Sodium removal was calculated as the difference in concentrations, dialysate flow rate, session time and ultrafiltration.

Results

Dialysate sodium balance was measured during 139 dialysis treatments (34 DialNa 140 versus 105 DialNa < 140, median 136 mEq/L), in 111 patients, 63% male, mean age 64.0 ± 16.2 years and 33.3% diabetic. There was no difference using the higher DialNa [net loss median 482 (238–573) versus 312 (124–599) mEq], ultrafiltration losses [226 (131–280) versus 204 (125–290)mEq] and non-ultrafiltration losses [217 (0–384) versus 173 (−90 to 350)mEq]. We also compared haemodiafiltration and haemodialysis (118 versus 23 sessions), and there were no differences in net loss [311 (91–608) versus 381 (167–597)], ultrafiltration [212 (127–290) versus 169 (110–258)mEq] and non-ultrafiltration losses [180 (−51 to 386) versus 192 (−74 to 387)mEq].

Conclusions

Although most dialysis centres prescribe a universal dialysate sodium concentration, there is no consensus on the optimum universal concentration. We found no difference in net dialysate sodium balance when comparing patients dialysing with a dialysate sodium concentration of 140 or < 140 mEq/L. Similarly, we found no differences in dialysate sodium balance between haemodiafiltration and haemodialysis sessions.
The gut microbiota patterns of patients with COVID-19: protocol for a case-control study
Authors: Nejadghaderi Seyed Aria , Nazemalhosseini-Mojarad Ehsan , Fazlollahi Asra , Pirsadeghi Ali , Khalili Ainaz , Ebrahimi Rasoul , Rezaei Nima
Published: June 2024

Background

SARS-CoV-2 caused an outbreak in late December 2019. It has been suggested that gut microbiota dysbiosis influences the severity, mortality, and quality of life of patients with COVID-19. So, identifying the gut microbiota pattern could be helpful to determine the prognosis of the disease, and maybe determine some potential treatment approaches. Our aim will be to compare gut microbiota patterns between patients with severe or non-severe COVID-19, and healthy controls.

Methods

We will include 183 samples: 122 samples from COVID-19 patients, including 61 severe patients and 61 non-severe patients, and 61 samples from healthy controls. Total bacterial DNA will be extracted from samples and 16 S rRNA gene will be amplified through two polymerase chain reaction (PCR) stages. Fecal samples will be analyzed using a targeted metabolomics technique. The differences in each RNA or DNA expression between patients with severe COVID-19, patients with non-severe COVID-19, and controls will be compared. Also, we will assess the relationships between each DNA or RNA and the risk of COVID-19 severity, sort of clinical manifestations, and comorbidities. Concurrent medication data will be collected and patients will also be grouped based on their drug history.

Results

We hypothesize that the gut microbiota composition will be affected by the COVID-19 severity and there might be differences in terms of sex and age.

Conclusions

The results of our study could be the backbone for further trials which might lead to the development of prognostic factors and treatment options. Further studies can also consider the limitations of the study like potential confounders and selection and recall biases.
Fibrotic remodeling in joint diseases: induction and inhibition of fibrosis in fibroblast-like synoviocytes
Authors: Madsen Sofie Falkenløve , Madsen Sarah Spliid , Madrid Alexander Scheller , Andersen Mikkel Rathsach , Bay-Jensen Anne-Christine , Thudium Christian S.
Published: June 2024

Background

We aimed to investigate the development of synovial fibrosis in vitro and how the fibrosis can be halted. Synovial fibrosis causes joint stiffness in arthritic diseases. The pathway of the fibrotic growth factor, transforming growth factor-beta (TGF-β), has been associated with joint pain in osteoarthritis (OA) and with the fibroid phenotype of rheumatoid arthritis (RA). This suggests that synovial fibrosis, thus accumulation of extracellular matrix (ECM) proteins, plays a role in the clinical manifestations of the diseases. Improving our understanding of fibrotic development may aid in selecting appropriate treatments and development of drugs that can target synovial fibrosis.

Methods

We isolated primary fibroblast-like synoviocytes (FLS) from the synovial membrane of patients undergoing total knee replacement surgery. To investigate the development of synovial fibrosis, the FLS were cultured in a crowded in vitro model mimicking the ECM. TGF-β1 was used as the fibrotic initiator, the activin receptor-like kinase 5 inhibitor (ALK5i), the anti-fibrotic drug nintedanib, and the anti-inflammatory drug tofacitinib were used as fibrotic inhibitors. The ECM protein formation was quantified in the conditioned media using specific biomarkers of type I, III, and VI collagen formation and fibronectin turnover.

Results

The TGF-β stimulation inducted fibrogenesis by increasing the biomarkers of fibronectin turnover, type I, III, and VI collagen formation. ALK5i and nintedanib inhibited the TGF-β response across all biomarkers. Tofacitinib trended towards inhibiting TGF-β response with up to 78% inhibition. All the treatments preserved cell viability.

Conclusion

We have established an in vitro model for assessing fibrogenesis in primary FLS, which can be used to assess the anti-fibrotic effect of multiple drug types. Our study implies that synovial fibrosis can be induced by TGF-β, which additionally can be halted by both direct and indirect inhibition with anti-fibrotic substances. The anti-inflammatory drug tofacitinib also halted the fibrogenesis to some extent; thus, it may exert an anti-fibrotic effect.
Absolute quantitation of sympathetic nerve activity using [123I] metaiodobenzylguanidine SPECT-CT in neurology
Authors: Saito Shintaro , Nakajima Kenichi , Komatsu Junji , Shibutani Takayuki , Wakabayashi Hiroshi , Mori Hiroshi , Takata Aki , Ono Kenjiro , Kinuya Seigo
Published: June 2024

Background and purpose

The ability of [123I]metaiodobenzylguanidine (MIBG) sympathetic nerve imaging with three-dimensional (3D) quantitation to clinically diagnose neurological disorders has not been evaluated. This study compared absolute heart counts calculated as mean standardized uptake values (SUVmean) using conventional planar imaging and assessed the contribution of [123I]MIBG single-photon emission computed tomography (SPECT)-CT to the diagnosis of neurological diseases.

Methods

Seventy-two patients with neurological diseases were consecutively assessed using early and delayed [123I]MIBG SPECT-CT and planar imaging. Left ventricles were manually segmented in early and delayed SPECT-CT images, then the SUVmean and washout rates (WRs) were calculated. Heart-to-mediastinum ratios (HMRs) and WRs on planar images were conventionally computed. We investigated correlations between planar HMRs and SPECT-CT SUVmeans and between WRs obtained from planar and SPECT-CT images. The cutoff for SPECT-CT WRs defined by linear regression and that of normal planar WRs derived from a database were compared with neurological diagnoses of the patients. We assigned the patients to groups according to clinical diagnoses as controls (n = 6), multiple system atrophy (MSA, n = 7), progressive supranuclear palsy (PSP, n = 17), and Parkinson’s disease or dementia with Lewy bodies (PD/DLB, n = 19), then compared SPECT-CT and planar image parameters.

Results

We found significant correlations between SPECT-CT SUVmean and planar HMR on early and delayed images (R2 = 0.69 and 0.82, p < 0.0001) and between SPECT-CT and planar WRs (R2 = 0.79, p < 0.0001). A threshold of 31% for SPECT-CT WR based on linear regression resulted in agreement between planar and SPECT-CT WR in 67 (93.1%) of 72 patients. Compared with controls, early and delayed SUVmean in patients with PSP and MSA tended more towards significance than planar HMR. This trend was similar for SPECT-CT WRs in patients with PSP.

Conclusions

Absolute heart counts and SUVmean determined using [123I]MIBG SPECT-CT correlated with findings of conventional planar images in patients with neurological diseases. Three-dimensional quantitation with [123I]MIBG SPECT-CT imaging might differentiate patients with PSP and MSA from controls.
A comprehensive examination of camel (Camelus Dromedaries) otic prominence through morphological and CT imaging studies
Authors: El-Sherif Mohamed W. , Nazih Mohamed A.
Published: June 2024

Background

This study explored the morphological anatomy of otic prominences in camels using advanced computed tomography (CT). Nine adult cadaver camel heads underwent CT scanning to generate detailed images of the otic prominences, mastoid process, styloid process, stylomastoid foramen, external acoustic meatus, bulla tympanica, and muscular processes. The morphological anatomy of otic prominences was studied in nine skulls.

Results

The anatomical features were analyzed, revealing a compact and closely collected configuration of otic prominences. Unique characteristics of the mastoid process, bulla tympanica, and styloid process were observed, challenging the conventional descriptions.

Conclusions

This study underscores the value of CT scans in enhancing anatomical studies and provides insights into comparative veterinary anatomy, facilitating the evaluation of various conditions and disorders in camels.
HSS: enhancing IoT malicious traffic classification leveraging hybrid sampling strategy
Authors: Luo Yuantu , Tao Jun , Zhu Yuehao , Xu Yifan
Published: June 2024

Using deep learning models to deal with the classification tasks in network traffic offers a new approach to address the imbalanced Internet of Things malicious traffic classification problems. However, the employment difficulty of these models may be immense due to their high resource consumption and inadequate interpretability. Fortunately, the effectiveness of sampling methods based on the statistical principles in imbalance data distribution indicates the path. In this paper, we address these challenges by proposing a hybrid sampling method, termed HSS, which integrates undersampling and oversampling techniques. Our approach not only mitigates the imbalance in malicious traffic but also fine-tunes the sampling threshold to optimize performance, as substantiated through validation tests. Employed across three distinct classification tasks, this method furnishes simplified yet representative samples, enhancing the baseline models’ classification capabilities by a minimum of 6.02% and a maximum of 182.66%. Moreover, it notably reduces resource consumption, with sample numbers diminishing to a ratio of at least 83.53%. This investigation serves as a foundation, demonstrating the efficacy of HSS in bolstering security measures in IoT networks, potentially guiding the development of more adept and resource-efficient solutions.
The Bulgarian ethnic tradition of manufacturing rakia: a cultural heritage and a potential functional food resource
Authors: Nashar Milka , Ivanova Diana
Published: June 2024

Ethnic foods and beverages are cultural heritage. This review summarizes the available data about the manufacturing, flavouring, and colouring of the homemade Bulgarian ethnic alcoholic beverage rakia, including information from scientific and grey literature, published surveys, traditional old recipe books, and field observations and interviews with local producers of homemade rakia. Taking into consideration the scarce scientific evidence available on the subject, this study aims to contribute to the preservation of a valuable Bulgarian tradition and cultural heritage for future generations. A detailed description of the process of manufacturing homemade rakia is presented, and the role of this ancient technology in the extraction of bioactive compounds is discussed. Different aspects of the consumption of alcoholic beverages and their dual metabolic effects on human health are elucidated. The centuries-old knowledge about the preparation of the homemade beverage rakia, flavoured and coloured using arboreal species, is discussed as a basis for the development of low-alcohol or non-alcoholic functional beverages with high content of bioactive compounds with beneficial health effects.
Injectable hyaluronate/collagen hydrogel with enhanced safety and efficacy for facial rejuvenation
Authors: Song Lu , Qiu He , Chen Zhiru , Wang Jing , Xu Yang , Liu Zhanhong , Liu Shuo , Wang Zhiyuan , Zhu Xiangdong , Zhang Kai , Lin Hai , Zhang Xingdong
Published: June 2024

Collagen, known for its excellent biocompatibility and biological properties, has limited in vivo maintenance duration after implantation, while hyaluronic acid faces challenges such as various complications and insufficient support for cell proliferation. In this study, an injectable hyaluronic acid/collagen (HCol) hydrogel was developed to achieve enhanced cell-material interactions and accelerated skin regeneration. Physical and chemical characterizations demonstrated that the HCol hydrogel was injectable and stable after the implantation. In vitro cell culture results illustrated that the hydrogel promoted the proliferation of human dermal fibroblasts, extracellular matrix expression and angiogenesis. The subcutaneous implantation in rats showed the superior biocompatibility of HCol hydrogel and enhanced secretion and deposition of extracellular matrix, compared with commercial hyaluronic acid dermal filler. MRI analysis showed that the hydrogel stably remained in vivo for at least three months. The histological examination and SHG signals further demonstrated that the hydrogel modulated fibroblast phenotype and stimulated vascular ingrowth and collagen synthesis, without inducing significant inflammation, swelling or erythema in vivo.

Graphical Abstract
Effectiveness of albumin infusion for the management of hyponatremia in decompensated cirrhosis: a systematic review
Authors: Roy Akash , Giri Suprabhat , Sharma Sanchit , Singh Surender , De Arka , Jalal Prasun , Goenka Mahesh
Published: June 2024

Background

Hyponatremia portends a poor prognosis in decompensated cirrhosis and is an independent predictor of mortality. Multiple modalities have been evaluated in the management of hyponatremia, including albumin infusion. However, the effect of albumin infusion on the resolution of hyponatremia is unclear. We conducted a systematic review to explore the available literature on the use of albumin infusion in hyponatremia.

Methods

We performed a comprehensive search up to 31st December 2022 using MEDLINE, EMBASE, and Scopus for studies reporting the effectiveness of albumin infusion in the resolution of hyponatremia. The impact of albumin infusion of any dose, administration frequency, and duration of therapy was recorded. The study protocol was prospectively registered (CRD42021245914).

Results

The literature search yielded 1322 references after duplicate removal. Only seven studies (three randomized trials, three cohort studies, and one case series) satisfied the predefined selection criteria after a full-text review. While hyponatremia was clearly defined as serum sodium < 130 meEq/L in all studies, two studies explicitly defined hyponatremia resolution (serum sodium > 135 mEq/L). No differentiation was made between the types of hyponatremia. The strength of the albumin infusion used was 5% and 20%. All but one study reported significant improvement in hyponatremia with albumin infusion. A subgroup analysis showed albumin infusion improved 30-day survival (odds ratio 0.43, 95% CI 0.25–0.74, I2 = 0.) No studies reported adverse events or the impact of concomitant associations (diuretic withdrawal, lactulose use, sepsis).

Conclusion

Despite available literature on the use of albumin infusion for the resolution of hyponatremia, the level of evidence remains low. Large prospective studies with pre-defined selection criteria and endpoints are required to generate the evidence.
The analytical model of crimping springback for large-diameter longitudinal welded pipe
Authors: Zhang Ji , Sun Kai
Published: June 2024

The crimping technique is widely used in the manufacturing process of large-diameter longitudinal welded pipe. In the bending process, the springback is the critical problem affecting the shape, which is the key index of forming quality. So, crimping faces more challenges in accurate springback prediction for difficult-to-form metals such as pipeline steels and non-circular nature of the punch. This paper has established an analytical model of crimping springback for the longitudinal welded pipe. Firstly, the crimping process mathematical model which considered the impact of elastic modulus attenuation on springback calculation during plastic deformation is established, and the cross-section bending moment is calculated based on Hill’s bending theory. Secondly, a semi-analytical and semi-numerical method for calculating the crimping shape is presented. Finally, the comparison of the crimping shape of the real product shows that the calculation accuracy and efficiency of this method can meet the requirements of engineering applications. The relative error of the springback angle calculated by the analytical model is −5.84%, and the absolute error is 0.3°. This method can accurately predict the springback of longitudinal welded pipe after crimping and provide a reference for crimping process optimization.
Piloting “From the Inside Out” — a toolkit addressing tuberculosis-related self-stigma
Authors: Macdonald Stephen H.-F. , France Nadine Ferris , Hodgson Ian , Ali Fadhil , Dewi Christa , Abdurrakhman Iman , Runtu Yeremia Mozart , Juan Alva , Sugiharto Jhon , Byrne Elaine , Conroy Ronan M.
Published: June 2024

Background

Self-stigma among people who have tuberculosis (TB) can contribute to non-adherence to medication and disengagement from care. It can manifest in feelings of worthlessness, shame, and guilt, leading to social withdrawal and disengagement from life opportunities. Self-stigma may also affect families of those who have TB, or healthcare workers who treat them. However, few interventions addressing TB self-stigma exist to date.

Methods

We piloted the delivery of a toolkit of psychosocial interventions using a “training-of-trainers” approach with six staff members of a TB-focused NGO (Non-Governmental Organisation) and partner organisations in Jakarta, Indonesia. These trainers could then disseminate the toolkit among community partner organisations. Local staff involvement throughout the study supported translation and adaptation to enhance cultural and language appropriateness. Over a 2-day training-of-trainers workshop, the NGO staff were familiarised with the mode of delivery of the toolkit, which they then delivered via a four-day participatory workshop with 22 people who have TB/TB survivors, who were representatives of partner organisations working among communities affected by TB.

Results

The newly-trained local facilitators delivered the toolkit to the participants, who self-reported significant increases in knowledge and efficacy around TB self-stigma post-intervention compared to baseline (Z = 1.991, p = 0.047, Wilcoxon signed-rank test). The participants’ levels of self-compassion were also significantly higher post-workshop (Z = 2.096, p = 0.036, Wilcoxon signed-rank test); however, these effects were not maintained at 3-month timepoint. There was also a significant increase post-workshop in one of the participants’ Ryff dimensions of psychological wellbeing, that of positive relationships with others (Z = 2.509, p = 0.012, Wilcoxon signed-rank test) but this was also not maintained at the 3-month timepoint.

Conclusions

The observed changes in recipients’ self-reported levels of knowledge and efficacy, self-compassion, and psychological wellbeing may warrant further investigation into the best modalities for toolkit delivery (frequency, dose, duration) and support for individuals as they progress through the TB treatment journey.
Conflict of Interest Disclosure in Oncology: Preliminary Insights From the Global ONCOTRUST-1 Cross-Sectional Study
Authors: El Bairi Khalid , Najem Salma , Chowdhury Arman Reza , Omar Abeid , Abdihamid Omar , Teuwen Laure-Anne , Benhima Nada , Madariaga Ainhoa , Elkefi Safa , Diaz Fernando Cristobal , Hussain Sadaqat , Jenei Kristina , Hammad Nazik , Mutebi Miriam , Rubagumya Fidel , Trapani Dario , El Kadmiri Nadia , Laouali Nasser , Fourtassi Maryam
Published: June 2024

PURPOSE

Conflicts of interest (COIs) between oncologists and industry might considerably influence how the presentation of the research results is delivered, ultimately affecting clinical decisions and policy-making. Although there are many regulations on reporting COI in high-income countries (HICs), little is known about their reporting in low- and middle-income countries (LMICs). Oncology Transparency Under Scrutiny and Tracking (ONCOTRUST-1) is a pilot global survey to explore the knowledge and perceptions of oncologists regarding COI.

MATERIALS AND METHODS

We designed an online 27-question–based survey in the English language to explore the perceptions and knowledge of oncologists regarding COI, with an emphasis on LMICs. Descriptive statistics and the Consensus-Based Checklist for Reporting of Survey Studies guidelines were used to report the findings.

RESULTS

ONCOTRUST-1 surveyed 200 oncologists, 70.9% of them practicing in LMICs. Median age of the respondents was 36 (range, 26-84) years; 47.5% of them were women. Of the respondents, 40.5% reported weekly visits by pharmaceutical representatives to their institutions. Regarding oncologists' perceptions of COI that require disclosure, direct financial benefits, such as honoraria, ranked highest (58.5%), followed by gifts from pharmaceutical representatives (50%) and travel grants for attending conferences (44.5%). By contrast, personal or institutional research funding, sample drugs, consulting or advisory board, expert testimony, and food and beverage funded by pharmaceutical industry were less frequently considered as COI. Moreover, only 24% of surveyed oncologists could correctly categorize all situations representing a COI.

CONCLUSION

These findings underscore the importance of clear guidelines, education, and transparency in reporting COI in oncology. This hypothesis-generating pilot survey provided the rationale for ONCOTRUST-2 study, which will compare perceptions of COI among oncologists in LMICs and HICs.
AI/ML-derived mechanistically interpretable whole-genome biomarkers of patient survival in pre-treatment primary neuroblastoma tumors and whole blood.
Authors: Alter Orly , Newman Elizabeth , Ponnapalli Sri Priya , Tsai Jessica W.
Published: June 2024

10043

Background: Prediction, understanding, and management, of neuroblastoma (NBL) outcomes, from spontaneous regression to relapse and death, remain limited, and rely mostly on the International Neuroblastoma Staging System (INSS) stage, age, and the one-gene test for MYCN amplification. The entire multi-ome affects every aspect of the disease. But typical artificial intelligence and machine learning (AI/ML) cannot discover effective biomarkers from real-life, small-cohort, multi-omic, and noisy data. Methods: We use our AI/ML to identify two whole-genome biomarkers from open-source pre-treatment NBL patient-matched primary tumor and whole blood DNA copy numbers, and primary tumor mRNA expression. Our data-agnostic, unsupervised algorithms extend the mathematics that underlies quantum mechanics to overcome the limitations of typical AI/ML [1,2]. Our platform- and reference genome-agnostic biomarkers in astrocytoma, including glioblastoma, and lung, ovarian, and uterine adenocarcinomas, were mathematically discovered, and computationally and experimentally validated, repeatedly, in federated, imbalanced datasets from as few as 50–100 patients [3]. Results: We discover the biomarkers in “skinny” datasets of minimally preprocessed ≈3M-bin whole-genome sequences from tumors and blood of a set of 101 patients. Blindly, i.e., label-free, we separate both biomarkers from the normal X chromosome-number variation, demonstrating sex-agnostic learning. Combined, the biomarkers are statistically independent of all standard-of-care indicators, with the univariate Cox hazard ratio of 4.0 (log-rank P-value=2.3×10–5) within the 95% confidence intervals of the bivariate ratios. The risk that the tumor’s whole genome confers upon outcome, as is reflected by the bivariate ratios, is greater than that conferred by all standard-of-care indicators, including DNA ploidy, the Children’s Oncology Group (COG) risk, and the mitosis-karyorrhexis index (MKI), except for histopathology. We validate the biomarkers in ≈10K-bin target-capture sequences of a mutually-exclusive set of 419 patients, demonstrating generalizability as well as site-, platform-, and protocol-agnostic transfer learning. At 73–80% concordance, in both the tumor and blood profiles of both the discovery and validation sets, the biomarkers combined are more accurate than MYCN. We show that the biomarkers identify known and previously unrecognized disease mechanisms and druggable gene alterations, including co-amplification of MYCN with genes encoding for extra-embryonic transcripts, as well as the hijacking of embryonic development toward aneuploidy, which can spontaneously regress via embryonic self-correction. Conclusions: Our AI/ML is uniquely suited for personalized medicine. 1. doi: 10.1063/1.5099268 2. doi: 10.1073/pnas.0530258100 3. doi: 10.1063/1.5142559.
The effects of oral nutritional supplements on functional outcomes and body composition in patients with solid cancer undergoing systemic chemotherapy: A pilot study.
Authors: kang sora , Koh Jeong Suk , Lee Myungwon , Song Ik-Chan , Lee Hyo Jin , Yun Hwan-Jung , Jo Deog Yeon , Ryu Hyewon
Published: June 2024

10074

Background: Cancer cachexia is a complex syndrome characterized by significant weight loss and depletion of skeletal muscle mass. Despite its profound impact on the well-being of cancer patients, the effective management of cancer cachexia remains a challenging and underexplored aspect of oncology. This study aims to investigate the potential benefits of oral nutritional supplements (ONS) to cancer patients undergoing chemotherapy. Methods: This is single-arm, prospective pilot study. Patients with cancer cachexia undergoing chemotherapy were included. Patients received ONS twice a day for 8 weeks. The ONS contained 200 kcal, 22.5 gram of carbohydrates, 7.5 gram of fat, and 12.5 gram of protein per 200 mL. Primary endpoints were improvements of lean body mass and physical performance. The secondary endpoints were changes of health-care related quality-of-life (HRQoL), nutritional status, and gut microbiomes profiles. EORTC-QLQ-C30 questionnaire, body composition analysis, 4-meter-walk test, hand grip strength test, and fecal microbiome analysis were conducted at baseline and after 8 weeks. The bacterial 16S rRNA gene (V3 and V4 region) was amplified using PCR and sequenced on the Illumina MiSeq platform. The QIIME 2 pipelines were used to analyze the raw data. Results: From January 2023 to October 2023, total of 10 patients were included. There were no significant differences of the mean daily energy intake (p=0.62) and calf-circumferences (p=0.2) between baseline and after 8 weeks. However, participants exhibited a statistically significant improvement in hand-grip strength (p=0.002) and 4-meter walk test (p=0.021) after 8 weeks. In the body composition analysis using dual-energy X-ray absorptiometry, no differences were observed in body weight (p=0.43), fat mass (p=0.62), fat-free mass (p=0.27), and fat-free mass index (p=0.38). Also, no significant differences were detected in the results of HRQoL survey (p=0.85). In the microbiome analysis, no differences of microbiome composition at phylum and genus levels, α-diversity, and β-diversity were observed between baseline and after 8 weeks. Conclusions: While ONS have shown potential in enhancing physical functions of patients with cancer cachexia undergoing chemotherapy, this did not correlate with the anticipated microbiome changes or improvements in body composition. The absence of expected microbiome alterations, despite enriched protein and dietary fiber, underscores the complexity of cachexia and indicates that its management may extend beyond nutritional supplementation alone. Further research should explore the broader context of cachexia, including nutrition, metabolic processes, and the impact of chemotherapy.
Breast cancer polygenic risk score and patient survival outcomes in the Pathways study.
Authors: Roy Arya Mariam , Zeinomar Nur , Sheng Haiyang , Roh Janise M. , Laurent Cecile , Ergas Isaac J. , Delmerico Jennifer , Zhu Qianqian , Kwan Marilyn L. , Kushi Lawrence H. , Ambrosone Christine B. , Yao Song
Published: June 2024

10502

Background: Many common, low-penetrance variants have been identified for breast cancer risk through genome-wide association studies, leading to the development of polygenic scores (PGS) to aggregate the effects of individual variants for risk prediction. Much less is known about genetic determinants of breast cancer-related outcomes. We hypothesized that breast cancer patients with high breast cancer PGS are at risk of a second breast-related adverse event, such as recurrence, contralateral breast cancer, or death. Methods: The Pathways Study is a prospective cohort study of breast cancer survivors enrolled shortly after diagnosis in 2006-2013 at Kaiser Permanente Northern California, with ongoing follow-up. Genome-wide genotype data were available from 3,995 patients for calculation of 4 PGS, including PGS313, PGS4k, PGS5k, and PGS6m. Scores were categorized into tertiles to investigate their associations with 7 survival outcomes including recurrence, contralateral second primary breast cancer, other second primary cancer, and death. Hazard ratios (HR) and 95% confidence intervals (CI) were derived from multivariable Cox proportional hazards regression models. Results: The median age at diagnosis was 60 (23.6-94.8) years, and most (68%) self-identified as White. Many women had estrogen receptor (ER)+ (83.4%), stage I and II tumors (89%), with 13.3% HER2+ tumors. The majority (60%) received lumpectomy and some type of adjuvant therapy (44.3% radiotherapy, 47.0% chemotherapy, and 74.6% received hormonal therapy). By December 31, 2021, the median follow-up time was 10.5 (0.2-14.2) years, with 504 recurrences, 419 total second primary cancers, 146 contralateral second primary breast cancers, 237 non-breast second primary cancers, and 762 deaths (352 breast cancer-specific deaths) observed. In Table 1, patients with medium (T2) and high (T3) PGS313 had higher risk of recurrence, but not contralateral breast cancer or other second primary cancer. They also had higher risk of all-cause death, breast cancer-specific death, total breast cancer event, and invasive disease. The other 3 PGS were not associated with survival outcomes examined. Conclusions: Our study reveals that breast cancer patients with higher PGS313 had higher risk of recurrence, total breast cancer and invasive breast cancer events, and death. These findings highlight a potential role of breast cancer PGS for prognosis, warranting further exploration. [Table: see text]
Association between rare pathogenic variants in established cancer risk genes and the diagnosis of single and multiple common cancers: A UK Biobank study.
Authors: Shevach Jeffrey , Xu Jianfeng , Snyder Nathan , Wei Jun , Shi Zhuqing , Tran Huy , Zheng S. Lilly , Schwartz Ann G. , Beebe-Dimmer Jennifer Lynn , Cooney Kathleen A.
Published: June 2024

10505

Background: Much of our understanding of cancer risk attributable to rare pathogenic variants (RPV) is derived from family-based and case-only cohort studies, which may be limited by ascertainment bias. We sought to identify associations between RPVs and cancer diagnoses in a large population-based study. Methods: We conducted a case-control study using the UK Biobank. We performed gene-based aggregate testing to examine the relationship between RPVs (defined as pathogenic or likely pathogenic variants) in 96 genes implicated in cancer risk and the diagnosis of 11 common cancers using the combined optimal unified sequence kernel association test (SKAT-O). Odds ratios (OR) and 95% confidence intervals (CI) were then calculated using Firth logistic regression. Results were adjusted for age, sex and genetic ancestry. Bonferroni-adjusted p-values were used to determine statistical significance. Variant pathogenicity was determined by American College of Medical Genetics criteria. Results: We identified 24 genes in which RPVs were statistically significantly associated with at least one of 11 common cancers among 183,626 individuals. The presence of an RPV in one of these 24 genes was associated with increased odds of one cancer (OR 1.8; 95% CI: 1.7-2.0), and multiple cancers (OR 2.5; 95% CI: 2.2-2.9). Conclusions: This large population-based study identified 24 established cancer risk genes in which RPVs were associated with common cancers. We identified both known and novel associations between cancer and RPVs. Some associations—i.e. renal/pancreas and MEN1—may be due to ascertainment and/or misclassification bias. We also show that individuals with RPVs in cancer risk genes not only have higher odds of one cancer diagnosis, but also multiple cancers.[Table: see text]
Blood type as a risk factor for pancreatic ductal adenocarcinoma.
Authors: Rahimi Larki Navid , Skanderson Melissa , Tate Janet , Levinson Rachel , Hauser Ronald G , Brandt Cynthia , Yang Yu-Xiao , Justice Amy C. , Wang Louise
Published: June 2024

10559

Background: Non-O blood type has been associated with increased risk of pancreatic ductal adenocarcinoma (PDAC), the third leading cause of cancer death in the United States (US), in largely white populations. We aimed to explore PDAC risk across blood types in the racially diverse Veteran’s Health Administration (VA), the largest integrated healthcare system in the US. Methods: We included all individuals in the VA from 2002 - 2022 with at least one inpatient or outpatient encounter and a non-missing race. We defined the index date as 1.5 years after the initial VA encounter and excluded individuals with prior PDAC. We defined the exposure by non-O (A, B, AB) or type O blood type. We defined PDAC based on a previously validated algorithm of ≥2 sources (cancer registry, hospitalizations, or outpatient oncology encounters) with 95% positive predictive value. Using time to PDAC as the outcome in a multivariable Cox regression, we evaluated the association between blood type and PDAC risk, adjusting for age, sex, BMI, smoking, alcohol use, Hepatitis C (HCV) and diabetes. We censored at time of death, 1.5 years after the last VA encounter, or the end of the study period. We performed a subgroup analysis to evaluate the association of blood type by race. Results: Of the 2.5 million individuals with an available blood type, 1.35 million (52.6%) had a non-O blood type (Table) and over a quarter of our cohort (28.2%, 725,878) were over baseline age 50. Median time to PDAC diagnosis was 8.6 years. There were 877 PDAC cases (0.03%), with 530 (60.4%) of those having a non-O blood type. Compared to those with type O blood, risk of PDAC for individuals with non-O blood type was higher overall [adjusted HR = 1.37 (95% CI 1.20-1.57)], and higher among Whites (n=1,689,092, HR 1.52, 95% CI 1.27-1.82) than Black patients (n=525,666, HR 1.15, 95% CI 0.90-1.48), though this was limited by smaller sample size. Conclusions: Non-O blood type was associated with higher risk of PDAC in a diverse population. Given the potential differences between races, we will further explore the impact of neighborhood-level socioeconomic data on PDAC risk. [Table: see text]
Association between wildfire PM2.5 and genitourinary cancer survival in California.
Authors: Gulati Shuchi , Alaniz Mariela , Mitsiades Nicholas , Parikh Mamta , Raffuse Sean , Keegan Theresa , Hertz-Picciotto Irva , Lara Primo N , Hussain Shehnaz K
Published: June 2024

10567

Background: Aerosolized particulate matter (PM) 2.5 (i.e., particles ≤ 2.5 µm in diameter or fine particles), including those that emanate from wildfires, has been previously associated with cancer risk and survival. While prior studies have focused primarily on etiology, little is known about the effects of wildfire PM2.5 on cancer prognosis. We sought to explore the effects of wildfire PM2.5 on genitourinary (GU) cancer survival in the state of California where episodic wildfires are considered a component of its climate. Methods: Using the California Cancer Registry, we identified incident prostate (n=81,261), urothelial (n=26,689), and kidney (n=26,303) cancers diagnosed between 2017-2020. Daily PM2.5 was estimated over the same period. Random forests regression was used to fuse diverse datasets (official air quality monitoring, satellite observations, meteorological modeling, predictive smoke modeling, and low-cost sensor networks [PurpleAir]) and produce a consensus estimate of PM2.5 for each centroid of a 1-square kilometer grid across California. We used home address at the time of cancer diagnosis to map each cancer case to the nearest centroid, and averaged PM2.5 exposures over the 6 months preceding cancer diagnosis for each case. Cox-proportional hazards regression was used to quantify the hazard ratio (HR) for death from any cause following cancer diagnosis associated with PM2.5, adjusting for key covariates including age, sex, race/ethnicity, neighborhood socioeconomic status, comorbidity, smoking status, rural/urban residence, and stage at diagnosis. Results: In patients with prostate cancer, a 10 µg/m³ increase in PM2.5 concentration was associated with an 18% increased hazard of death (HR=1.18; 95% confidence interval (CI)= 1.02-1.36, p=0.023). When stratified by stage at diagnosis, the association of PM2.5 and survival was limited to stages I, II, and III (HR=1.39; CI= 1.11-1.74, p=0.005) versus stage IV (HR=1.06; CI= 0.87-1.27, p=0.566). For urothelial cancer, a 10 µg/m³ increase in PM2.5 concentration was associated with a non-statistically significant 11% increased hazard of death (HR=1.11; CI= 0.96-1.29, p=0.151), which did not differ by stage at diagnosis. Kidney cancer survival was not associated with PM2.5 (HR= 0.94; CI= 0.79-1.11, p= 0.44). Conclusions: These findings suggest that higher PM2.5 exposure could influence prostate and urothelial cancer prognosis, perhaps through alteration of physiological pathways relevant to cancer aggressiveness or impairing response to treatment, including cellular immune response, inflammation, angiogenesis, or cell-signaling pathways. Further studies should look into the mechanisms and design mitigating strategies in patients diagnosed with these high-risk cancers who have been exposed to wildfire PM2.5.
Clinical and economic benefit of genomic testing strategies to guide the treatment of patients with HR+/HER2- breast cancer in the US.
Authors: Gouldson Mark , Berdunov Vlad , Le Quang Anh , Millen Steve , Racz Jennifer M. , Arrick Bradley A. , Hartzfeld Deborah , Thakkar Snehal Govind , Heald Brandie , Russell Christy A , Eymere Sebastien , Moyon Camille , Simmons Harriet , Cuyun Carter Gebra
Published: June 2024

10584

Background: Multiple testing technologies are available to inform treatment decisions for hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer, including tumor profiling and germline genetic testing (GGT). The 21-gene assay provides an estimate of distant recurrence risk and potential clinical benefit of chemotherapy. GGT identifies pathogenic variants which inform lifetime cancer risk as well may inform therapy options. This study explored the potential synergy of utilizing both tests by assessing the cost-effectiveness of this strategy compared to no testing from a societal perspective. Methods: A health economic model was developed using best practices to assess a patient cohort with HR+/HER2-, node-negative (N0) or node-positive (N1) breast cancer that was guided to surgical and adjuvant treatment by GGT ( ATM, BRCA1/2, CDH1, CHEK2, PALB2, PTEN,and TP53) and the 21-gene assay. Treatment effectiveness was informed by clinical trials (TAILORx and RxPONDER); costs for treatment, monitoring, and health utilities were sourced from literature. Clinical expert opinion and guidelines informed current US clinical practice. The base case analysis evaluated lifetime total costs, life-years, and quality-adjusted life years (QALYs) versus no testing. Scenario and sensitivity analyses were performed to evaluate model robustness. Results: The testing strategy was dominant (lower cost and higher QALYs gained) compared to no testing leading to a QALY improvement of 0.286 and cost savings of $16,463 in the N0 population (Table) and a 0.099 QALY improvement and $299 cost savings in the N1 population. Scenario analyses indicated that while the 21-gene assay was the primary driver of results, there were synergistic effects when tests were combined. Sensitivity analysis supported cost-effectiveness at most willingness-to-pay thresholds and identified the probability of chemotherapy and rate of distant recurrence as the most impactful model inputs. Conclusions: Using a testing strategy including both the 21-gene assay and GGT enables optimization of treatment decisions in early HR+/HER2- breast cancer, improving patient outcomes at reduced costs. [Table: see text]
Impact of pathogenic germline variants in HRR genes on gastroesophageal cancer in a large real-world Chinese population: A comprehensive study.
Authors: Li Jian , Zhang Zhe , Zhu Liangjun , Shi Jun , Hou Ting , Su Lan , Lv Xinze , Zhang Zhou , Shen Lin
Published: June 2024

10588

Background: Genetic testing in gastroesophageal cancer has been limited to those with hereditary cancer syndromes, restricting understanding of the impact of germline variants in sporadic cancers. Our study expands this by exploring germline and somatic characteristics in a broad Chinese cohort, enhancing risk assessment and guiding treatment strategies in a wider population. Methods: From October 2017 to April 2023, we retrospectively analyzed 2596 Chinese gastroesophageal cancer (GEC) patients, including 2003 with gastric cancer (GC), 196 with gastroesophageal junction cancer (GEJC), and 397 with esophageal cancer (EC). A 520-gene panel including 62 genes associated with cancer predisposition, was employed for genomic profiling of paired tumor and white blood cell samples. The pathogenicity of germline variants was determined according to ACMG guidelines. Results: In this retrospective cohort, the proportion of patients carrying pathogenic/likely pathogenic (P/LP) germline variants was 5.3% in GC, 5.6% in GEJC, and 5.0% in EC, respectively. Notably, genes associated with HRR exhibited the highest rates of P/LP germline mutations in GEC (94, 3.7%), with the majority occurring in non-BRCA HRR genes (77, 3.0%). The top five genes with the highest mutation rates were ATM, PALB2, FANCA, CHEK2, and RAD54L. Compared to the East Asian population without cancer in the genomAD database, a higher proportion of P/LP germline mutations were found in the CDH1(Inf [6.46-Inf], p < 0.001), PALB2 (5.60 [1.61-13.09], p = 0.002), SDHA (8.99 [1.29-99.42], p = 0.012), ATM (2.15 [1.08-4.09], p = 0.02), and CHEK2 (3.83 [1.06-13.32], p = 0.02) genes in GC. Similarly, significant increases in PALB2 (10.36 [2.32-37.28], p = 0.002) and ATM (4.42 [0.86-14.33], p = 0.036) were also observed in EC and GEJC. The HRR P/LP variant group exhibited a higher incidence of biallelic inactivation (loss of wildtype allele) compared to the B/LB variant group (24.7% vs 6.6%, p<0.001). Moreover, the similar trend was observed for the moderately/uncertainly penetrant gene ATM and FANCA (38.5% vs 0.6%, p < 0.001; 42.9% vs 9.8%, p = 0.025), which suggests that ATM and FANCA may be associated with a high risk. The HRR genes ATM(56 vs 61, p = 0.052), CDH1(33 vs 61, p = 0.003), and FANCI(48 vs 61, p = 0.041) with P/LP variants were associated with a younger age of onset. Carriers of HRR P/LP variants had less prevalent somatic TP53 variants in GC and GEC and higher HRD score compared to non-carriers (p=0.005). Conclusions: Our research delineates the germline P/LP variant landscape in Chinese GEC, revealing the significant role of HRR P/LP variants. The presence of P/LP variants in HRR genes in GEC is linked to distinct disease characteristics and progression, underscoring their importance in guiding personalized treatment approaches and risk evaluation.