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Gastrointestinal Toxicity Prediction Not Influenced By Rectal Contour or Dose-Volume Histogram Definition: Toxicity Prediction with Different Rectal Definitions

Int J Radiat Oncol Biol Phys. 2023 Jul 9:S0360-3016(23)07628-9. doi: 10.1016/j.ijrobp.2023.07.002. Online ahead of print.

ABSTRACT

BACKGROUND: Rectal dose delivered during prostate radiotherapy is associated with gastrointestinal toxicity. Treatment plans are commonly optimised using rectal dose-volume constraints, often whole-rectum relative-volumes (%). We investigate whether improved rectal contouring, use of absolute-volumes (cc) or rectal truncation might improve toxicity prediction.

MATERIALS/METHODS: Patients from the XXXXXX trial (receiving 74Gy/37 fractions (Fr) vs 60Gy/20Fr vs 57Gy/19Fr) were included if radiotherapy plans were available (2350/3216 patients), plus toxicity data for relevant analyses (2170/3216 patients). Whole solid rectum relative-volumes (%) dose-volume-histogram (DVH), as submitted by treating centre (original contour), was assumed standard-of-care. Three investigational rectal DVHs were generated: i) reviewed contour per XXXXXX protocol; ii) original contour absolute volumes (cc); iii) truncated original contour (two versions; ±0 and ±2cm from planning target volume (PTV)). Dose levels of interest (V30,40,50,60,70,74Gy) in 74Gy arm were converted by equivalent-dose-in-2Gy-fractions (EQD2α/β=3Gy) for 60Gy/57Gy arms. Bootstrapped logistic models predicting late toxicities (frequency G1+/G2+, bleeding G1+/G2+, proctitis G1+/G2+, sphincter control G1+, stricture/ulcer G1+) were compared by area-under-curve (AUC) between standard-of-care and the three investigational rectal definitions.

RESULTS: The alternative dose/volume parameters were compared with the original relative-volume (%) DVH of the whole rectal contour, itself fitted as a weak predictor of toxicity (AUC range 0.57-0.65, across the 8 toxicity measures). There were no significant differences in toxicity prediction for: i) original vs reviewed rectal contours (AUCs 0.57-0.66, p-values 0.21-0.98); ii) relative- vs absolute-volumes (AUCs 0.56-0.63, p-values 0.07-0.91) iii) whole-rectum vs truncation at PTV±2cm (AUCs 0.57-0.65, p-values 0.05-0.99), nor PTV±0cm (AUCs 0.57-0.66, p-values 0.27-0.98).

CONCLUSIONS: We used whole-rectum relative-volume DVH, submitted by the treating centre, as the standard-of-care dosimetric predictor for rectal toxicity. There were no statistically significant differences in prediction performance when using central rectal contour review, use of absolute-volume dosimetry, nor rectal truncation relative to PTV. Whole-rectum relative-volumes were not improved upon for toxicity prediction and should remain standard-of-care.

PMID:37433374 | DOI:10.1016/j.ijrobp.2023.07.002

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Effects of High-Speed Training on Messenger RNA Expression in Two-Year-Old Thoroughbred Racehorses

J Equine Vet Sci. 2023 Jul 9:104892. doi: 10.1016/j.jevs.2023.104892. Online ahead of print.

ABSTRACT

Accumulating high-speed exercise has been identified as a significant risk factor for catastrophic injuries in racing Thoroughbreds. Injuries, regardless of severity, are a main cause of withdrawal from the racing industry, raising animal welfare concerns and resulting in significant economic losses. While most of the current literature focuses on injuries incurred during racing rather than training, the present study aims to help fill this gap. As such, peripheral blood was collected weekly, prior to exercise or administration of medication, from eighteen, two-year-old Thoroughbreds throughout their first season of race training. Messenger RNA (mRNA) was isolated and used to analyze the expression of 34 genes via RT-qPCR. Statistical analysis of the non-injured horses (n=6) showed that 13 genes were significantly correlated with increasing average weekly furlong performance. Additionally, there was a negative correlation for CXCL1, IGFBP3, and MPO with both cumulative high-speed furlongs and week of training for all horses. Comparison of both groups showed opposing correlations between the anti-inflammation index (IL1RN, IL-10, and PTGS1) and average weekly furlong performance. Furthermore, evaluation of training effects on mRNA expression during the weeks surrounding injury, showed differences between groups in IL-13 and MMP9 at -3 and -2 weeks prior to injury. While some previously reported relationships between exercise adaptation and mRNA expression were not noted in this study, this may have been due to the small sample size. Several novel correlations, however, were identified and warrant further investigation as markers of exercise adaptation or potential risk for injury.

PMID:37433342 | DOI:10.1016/j.jevs.2023.104892

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Challenges detecting SARS-CoV-2 inCosta Rican domestic wastewater and river water

Sci Total Environ. 2023 Jul 9:165393. doi: 10.1016/j.scitotenv.2023.165393. Online ahead of print.

ABSTRACT

This study presents the development of a SARS-CoV-2 detection method for domestic wastewater and river water in Costa Rica, a middle-income country in Central America. Over a three-year period (November to December 2020, July to November 2022, and June to October 2022), 80 composite wastewater samples (43 influent and 37 effluent) were collected from a Wastewater Treatment Plant (SJ-WWTP) located in San José, Costa Rica. Additionally, 36 river water samples were collected from the Torres River near the SJ-WWTP discharge site. A total of three protocols for SARS-CoV-2 viral concentration and RNA detection and quantification were analyzed. Two protocols using adsorption-elution with PEG precipitation (Protocol A and B, differing in the RNA extraction kit; n = 82) were used on wastewater samples frozen prior to concentration, while wastewater (n = 34) collected in 2022 were immediately concentrated using PEG precipitation. The percent recovery of Bovine coronavirus (BCoV) was highest using the Zymo Environ Water RNA (ZEW) kit with PEG precipitation executed on the same day as collection (mean 6.06 % ± 1.37 %). It was lowest when samples were frozen and thawed, and viruses were concentrated using adsorption-elution and PEG concentration methods using the PureLink™ Viral RNA/DNA Mini (PLV) kit (protocol A; mean 0.48 % ± 0.23 %). Pepper mild mottle virus and Bovine coronavirus were used as process controls to understand the suitability and potential impact of viral recovery on the detection/quantification of SARS-CoV-2 RNA. Overall, SARS-CoV-2 RNA was detected in influent and effluent wastewater samples collected in 2022 but not in earlier years when the method was not optimized. The burden of SARS-CoV-2 at the SJ-WWTP decreased from week 36 to week 43 of 2022, coinciding with a decline in the national COVID-19 prevalence rate. Developing comprehensive nationwide surveillance programs for wastewater-based epidemiology in low-middle-income countries involves significant technical and logistical challenges.

PMID:37433341 | DOI:10.1016/j.scitotenv.2023.165393

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Effect of bio-based microplastics on earthworms Eisenia andrei

Sci Total Environ. 2023 Jul 9:165423. doi: 10.1016/j.scitotenv.2023.165423. Online ahead of print.

ABSTRACT

The contribution of bio-based plastics in the global market is gradually growing and diversifying. Therefore, it is necessary to assess their environmental impact including the biotic parts of ecosystems. Earthworms are regarded as functionally essential and useful bioindicators of ecological disturbances in the terrestrial ecosystems. The purpose of this study was to evaluate the impact of three innovative bio-based plastics on earthworms Eisenia andrei in the long-term experiments. It comprised the mortality, body mass and reproduction ability of earthworms as well as the oxidative stress response. Regarding the latter the activities of catalase (CAT) and superoxide dismutase (SOD) involved in the antioxidant system of earthworms were determined. Two out of three bio-based materials tested were polylactic acid-based (PLA-based) plastics, while one was poly(hydroxybutyrate-co-valerate)-based (PHBV-based) plastic. Neither mortality nor weight of adult earthworms was affected even at high concentration of the bio-based plastics up to 12.5 % w/w in the soil. Reproduction ability occurred to be more sensitive endpoint than mortality or body mass. At the concentration of 12.5 % w/w each of the studied bio-based plastics contributed to the decrease of the earthworm reproduction at statistically significant level. PLA-based plastics exerted stronger effect on earthworm reproduction ability than PHBV-based plastic did. CAT activity turned out to be a good indicator of the cellular response against oxidative stress induced by bio-based plastics in earthworms. The activity of this enzyme increased in the response to the exposure to the bio-based plastics compared to the level achieved in the control tests. It was from 16 % to about 84 % dependent on the material tested and its concentration in the soil. Finally, the reproduction ability and catalase activity are recommended to be used in the evaluation of the potential impacts of bio-based plastics on earthworms.

PMID:37433336 | DOI:10.1016/j.scitotenv.2023.165423

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Effectiveness of Medical Music Therapy Practice: Integrative Research Using the Electronic Health Record: Rationale, Design, and Population Characteristics

J Integr Complement Med. 2023 Jul 11. doi: 10.1089/jicm.2022.0701. Online ahead of print.

ABSTRACT

Background: Several clinical trials support the efficacy of music therapy (MT) for improving outcomes in hospitalized patients, but few studies have evaluated the real-world delivery and integration of MT across multiple medical centers. This article describes the rationale, design, and population characteristics of a retrospective study examining the delivery and integration of MT within a large health system. Methods: A retrospective electronic health record (EHR) review was conducted of hospitalized patients seen by and/or referred to MT between January 2017 and July 2020. MT was provided across ten medical centers, including an academic medical center, a freestanding cancer center, and eight community hospitals. Discrete demographic, clinical, and MT treatment and referral characteristics were extracted from the EHR, cleaned, and organized using regular expressions functions, and they were summarized using descriptive statistics. Results: The MT team (average 11.6 clinical fulltime equivalent staff/year) provided 14,261 sessions to 7378 patients across 9091 hospitalizations. Patients were predominantly female (63.7%), White (54.3%) or Black/African American (44.0%), 63.7 ± 18.5 years of age at admission, and insured under Medicare (51.1%), Medicaid (18.1%), or private insurance (14.2%). Patients’ hospitalizations (median length of stay: 5 days) were primarily for cardiovascular (11.8%), respiratory (9.9%), or musculoskeletal (8.9%) conditions. Overall, 39.4% of patients’ hospital admissions included a mental health diagnosis, and 15.4% were referred to palliative care. Patients were referred by physicians (34.7%), nurses (29.4%), or advanced practice providers (24.7%) for coping (32.0%), anxiety reduction (20.4%), or pain management (10.1%). Therapists provided sessions to patients discharged from medical/surgical (74.5%), oncology (18.4%), or intensive care (5.8%) units. Conclusions: This retrospective study indicates that MT can be integrated across a large health system for addressing the needs of socioeconomically diverse patients. However, future research is needed to assess MT’s impact on health care utilization (i.e., length of stay and rates of readmission) and immediate patient-reported outcomes.

PMID:37433198 | DOI:10.1089/jicm.2022.0701

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Assessing the Response of Biomarkers to Anti-Inflammatory Medications in PIMS-TS by Longitudinal Multilevel Modeling: Real-World Data from a UK Tertiary Center

Pediatr Allergy Immunol Pulmonol. 2023 Jul 11. doi: 10.1089/ped.2023.0024. Online ahead of print.

ABSTRACT

Background: Pediatric inflammatory multisystem syndrome temporarily associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PIMS-TS) is an acute complication of previous SARS-CoV-2 exposure. The relationship between inflammatory markers and anti-inflammatory medication in PIMS-TS is unknown. We retrospectively investigated the relationship between demographics, biomarkers, treatment, and length of stay (LOS) in this novel disease. Methods: We reviewed the case notes and blood tests of all patients who met the Royal College of Paediatrics and Child Health diagnostic criteria for PIMS-TS at a large tertiary center in the United Kingdom. Biomarker trajectories were modeled using log linear mixed effects, and factors affecting LOS in hospital were evaluated using multiple regression. Results: Between March 2020 and May 2022, a total of 56 patients attended Sheffield Children’s Hospital with PIMS-TS, 70% male. Mean age was 7.4 ± 3.7 years and mean LOS 8.7 ± 4.5 days with 50% requiring intensive care and 20% requiring inotropes. Older males had shorter LOS than younger males (P = 0.04), not seen in females. Treatment included intravenous glucocorticoids in 93%, intravenous immunoglobulins (IVIG) in 77%, Anakinra in 11%, and infliximab in 1.8%. Biomarkers correlated poorly with trajectories that peaked at different times. C-reactive protein peaked first after median 1.3 days postadmission; while LFT’s and neutrophils peaked after 3 days. Age had a large effect on some biomarkers, with older children having larger troponin and ferritin, and lower lymphocytes and platelets. Cumulative dose of glucocorticoids and IVIG had a statistically significant effect on some biomarkers, but effect size was small. Conclusions: The heterogenous nature of PIMS-TS highlights the importance of a multidisciplinary approach. Worse inflammatory markers in older children within our cohort may be an indication of a different disease process occurring at different ages. Future work to investigate the association between age and troponin and ferritin in hyperinflammatory states is warranted.

PMID:37433192 | DOI:10.1089/ped.2023.0024

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Association Between Indication for Descemet Stripping Automated Endothelial Keratoplasty and Rural Residency

Cornea. 2023 Jul 11. doi: 10.1097/ICO.0000000000003347. Online ahead of print.

ABSTRACT

PURPOSE: Residing in rural locations can be a barrier to health care access. This study investigated the impact of residing in rural and small town (RST) areas on Descemet stripping automated endothelial keratoplasty (DSAEK) indications and outcomes in Atlantic Canada.

METHODS: A retrospective cohort analysis examined consecutive DSAEKs performed in Nova Scotia between 2017 and 2020. Patient rurality was determined by the Statistical Area Classification system developed by Statistics Canada. Univariate and multivariate logistic regression models were used to assess for factors associated with DSAEK indication, including repeat keratoplasty, RST residence status, and travel time.

RESULTS: Of 271 DSAEKs during the study period, 87 (32.1%) were performed on the eyes of RST residents. The median postoperative follow-up time was 1.6 years. Undergoing DSAEK for a previous failed keratoplasty was not associated with a higher odds of RST residency (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.19-1.16; P = 0.13) but was associated with travel time (OR, 0.78 for each increasing hour of travel; 95% CI, 0.61-0.99; P = 0.044). RST residency was not associated with the occurrence of graft failure (OR, 0.48; 95% CI, 0.17-1.17; P = 0.13).

CONCLUSIONS: Residing in a rural area in Atlantic Canada was not associated with DSAEK graft failure. Repeat endothelial keratoplasty was associated with shorter travel time for corneal surgery but not rural residency status. Further research in this field could inform regional health strategies aimed at improving equity and accessibility to ophthalmology subspecialist care.

PMID:37433174 | DOI:10.1097/ICO.0000000000003347

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Apendicitis aguda dentro de una hernia de Spiegel: un caso infrecuente de una patología infrecuente

Cir Cir. 2023;91(3):432-436. doi: 10.24875/CIRU.21000783.

ABSTRACT

INTRODUCTION: Spigelian hernia is a rare entity, with higher improbability of acute appendicitis within it.

CASE REPORT: A 75-year-old female with a 30-year evolution hernia, abdominal pain, and fever of 1 week of onset, in whom was found an acute appendicitis within a Spigelian hernia.

DISCUSSION: Spigelian hernia comprises 0.12-2% of all abdominal hernias. Presurgical diagnosis is stablished only in 50% of cases, with an hernial ring less than 2 cm and hidden localization. There isn’t statistics of this complication because of the lack of case reports.

PMID:37433145 | DOI:10.24875/CIRU.21000783

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An approach for prioritizing candidate genes from RNA-seq using preclinical cocaine self-administration datasets as a test case

G3 (Bethesda). 2023 Jul 12:jkad143. doi: 10.1093/g3journal/jkad143. Online ahead of print.

ABSTRACT

RNA-sequencing (RNA-seq) technology has led to a surge of neuroscience research using animal models to probe the complex molecular mechanisms underlying brain function and behavior, including substance use disorders (SUDs). However, findings from rodent studies often fail to be translated into clinical treatments. Here, we developed a novel pipeline for narrowing candidate genes from preclinical studies by translational potential and demonstrated its utility in two RNA-seq studies of rodent self-administration. This pipeline uses evolutionary conservation and preferential expression of genes across brain tissues to prioritize candidate genes, increasing the translational utility of RNA-seq in model organisms. Initially, we demonstrate the utility of our prioritization pipeline using an uncorrected p-value. However, we found no differentially-expressed genes (DEGs) in either dataset after correcting for multiple testing (FDR < 0.05 or < 0.1). This is likely due to low statistical power that is common across rodent behavioral studies, and therefore we additionally illustrate use of our pipeline on a third dataset with DEGs corrected for multiple testing (FDR < 0.05). We also advocate for improved RNA-seq data collection, statistical testing, and metadata reporting that will bolster the field’s ability to identify reliable candidate genes and improve the translational value of bioinformatics in rodent research.

PMID:37433118 | DOI:10.1093/g3journal/jkad143

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Counts, incidence rates, and trends of pediatric cancer in the United States, 2003-2019

J Natl Cancer Inst. 2023 Jul 11:djad115. doi: 10.1093/jnci/djad115. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer is a leading cause of death by disease among children and adolescents in the United States. This study updates cancer incidence rates and trends using the most recent and comprehensive US cancer registry data available.

METHODS: We used data from US Cancer Statistics to evaluate counts, age-adjusted incidence rates, and trends among children and adolescents aged <20 years diagnosed with malignant tumors during 2003-2019. We calculated average annual percent change and annual percent change (APC) using joinpoint regression. Rates and trends were stratified by demographic and geographic characteristics and by cancer type.

RESULTS: With 248,749 cases reported during 2003-2019, the overall cancer incidence rate was 178.3 per 1 million; incidence rates were highest for leukemia (46.6), central nervous system (CNS) neoplasms (30.8), and lymphoma (27.3). Rates were highest for males, children aged 0-4 years, Non-Hispanic White children and adolescents, those in the Northeast census region, top 25% of counties by economic status, and metropolitan counties with population ≥1 million. While the overall incidence rate of pediatric cancer increased 0.5% per year on average during 2003-2019, the rate increased during 2003-2016 (APC = 1.1%) and then decreased during 2016-2019 (APC = -2.1%). During 2003-2019, rates of leukemia, lymphoma, hepatic tumors, bone tumors, and thyroid carcinomas increased, while melanoma rates decreased. CNS neoplasms rates increased until 2017 and then decreased. Other cancer types remained stable.

CONCLUSIONS: Incidence of pediatric cancer increased overall, although increases were limited to certain cancer types. These findings may guide future public health and research priorities.

PMID:37433078 | DOI:10.1093/jnci/djad115