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The effect of Mitomycin-C in neoadjuvant concurrent chemoradiotherapy for rectal cancer

J Chin Med Assoc. 2022 Oct 4. doi: 10.1097/JCMA.0000000000000819. Online ahead of print.

ABSTRACT

BACKGROUND: Neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by total mesorectal excision has become the standard of care for advanced rectal cancer, but the most effective regimen of chemotherapeutic agents has not yet been determined. The purpose of this study is to determine the effect of Mitomycin-C (MMC) in nCCRT for rectal cancer.

METHODS: From 2000 to 2017, patients with rectal adenocarcinoma who received nCCRT followed by radical surgery were enrolled in our study. The patients were retrospectively separated into two groups according to nCCRT regimens (with or without MMC). Other factors related to cancer downstaging after nCCRT, disease-free survival (DFS) and overall survival (OS)were analyzed.

RESULTS: One hundred ninety-five patients received radiotherapy (RT) + MMC + oral tegafur-uracil (UFUR), and 191 patients received RT + UFUR without MMC as neoadjuvant CCRT. Adding MMC might increase the downstaging rate (odds ratio (OR) = 1.520, p = 0.058), and downstaging had significant effect to improve overall survival (OR = 1.726, p = 0.002) and disease-free survival (OR = 2.185, p < 0.001). The overall survival and disease-free survival were improved in patients who received MMC, although this result did not reach a statistically significant difference. There was a higher incidence of low-grade toxicities in the MMC group, especially neutropenia, genitourinary side effects, and dermatological side effects (p < 0.001).

CONCLUSION: Adding MMC to the regimen of nCCRT for rectal adenocarcinoma is shown to increase tumor downstaging rate and improve disease-free and overall survival, although these benefits come at the cost of increased low-grade toxicities. Prospective randomized studies are needed to explore the role of MMC in nCCRT for rectal cancer.

PMID:36194168 | DOI:10.1097/JCMA.0000000000000819

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Effect of ultramarathon running on iron metabolism

J Chin Med Assoc. 2022 Oct 4. doi: 10.1097/JCMA.0000000000000818. Online ahead of print.

ABSTRACT

BACKGROUND: Iron is a vital trace element for energy production and oxygen transportation; importantly, it is essential to athletic performance. Maintaining iron balance is tightly controlled at systemic and cellular levels. This study aimed to determine serum iron tests, hepcidin levels, and cellular iron import and export activities in peripheral blood mononuclear cells (PBMCs) in ultramarathon runners to elucidate the association of systemic inflammation response and iron metabolism.

METHODS: Sixteen amateur runners were enrolled. Blood samples were taken one week before, immediate, and 24 h after the run. Plasma hepcidin levels were measured by enzyme-linked immunosorbent assay. The expression levels of divalent metal iron transporter 1 (DMT1), ZRT/IRT-like protein 14 (ZIP14), transferrin receptor 1 (TfR1), and ferroportin (FPN) in PBMCs were measured using real-time quantitative reverse-transcription polymerase chain reaction.

RESULTS: Serum iron concentrations and transferrin saturation significantly decreased immediately after the race and dramatically recovered 24 h post-race. Serum ferritin levels had a statistically significant rise immediately after the race and remained high 24 h after the completion of the race. Ultramarathons were associated with increased plasma interleukin (IL)-6 concentrations corresponding to the state of severe systemic inflammation and therefore boosted plasma hepcidin levels. The expression levels of DMT1 and FPN mRNA were markedly decreased immediately and 24 h after the race. The ZIP14 and TfR1 mRNA expression in PBMCs significantly decreased immediately after the race and returned to the baseline level at 24 h post-race. Positive significant correlations were observed between plasma hepcidin and ferritin levels.

CONCLUSION: Iron homeostasis and systemic inflammatory response are closely interconnected. Cellular iron import and export mRNA activities in PBMCs were acutely inhibited during an ultramarathon.

PMID:36194166 | DOI:10.1097/JCMA.0000000000000818

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Multicenter Reproducibility of Liver Iron Quantification with 1.5-T and 3.0-T MRI

Radiology. 2022 Oct 4:213256. doi: 10.1148/radiol.213256. Online ahead of print.

ABSTRACT

Background MRI is a standard of care tool to measure liver iron concentration (LIC). Compared with regulatory-approved R2 MRI, R2* MRI has superior speed and is available in most MRI scanners; however, the cross-vendor reproducibility of R2*-based LIC estimation remains unknown. Purpose To evaluate the reproducibility of LIC via single-breath-hold R2* MRI at both 1.5 T and 3.0 T with use of a multicenter, multivendor study. Materials and Methods Four academic medical centers using MRI scanners from three different vendors (three 1.5-T scanners, one 2.89-T scanner, and two 3.0-T scanners) participated in this prospective cross-sectional study. Participants with known or suspected liver iron overload were recruited to undergo multiecho gradient-echo MRI for R2* mapping at 1.5 T and 3.0 T (2.89 T or 3.0 T) on the same day. R2* maps were reconstructed from the multiecho images and analyzed at a single center. Reference LIC measurements were obtained with a commercial R2 MRI method performed using standardized 1.5-T spin-echo imaging. R2*-versus-LIC calibrations were generated across centers and field strengths using linear regression and compared using F tests. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic performance of R2* MRI in the detection of clinically relevant LIC thresholds. Results A total of 207 participants (mean age, 38 years ± 20 [SD]; 117 male participants) were evaluated between March 2015 and September 2019. A linear relationship was confirmed between R2* and LIC. All calibrations within the same field strength were highly reproducible, showing no evidence of statistically significant center-specific differences (P > .43 across all comparisons). Calibrations for 1.5 T and 3.0 T were generated, as follows: for 1.5 T, LIC (in milligrams per gram [dry weight]) = -0.16 + 2.603 × 10-2 R2* (in seconds-1); for 2.89 T, LIC (in milligrams per gram) = -0.03 + 1.400 × 10-2 R2* (in seconds-1); for 3.0 T, LIC (in milligrams per gram) = -0.03 + 1.349 × 10-2 R2* (in seconds-1). Liver R2* had high diagnostic performance in the detection of clinically relevant LIC thresholds (area under the ROC curve, >0.98). Conclusion R2* MRI enabled accurate and reproducible quantification of liver iron overload over clinically relevant ranges of liver iron concentration (LIC). The data generated in this study provide the necessary calibrations for broad clinical dissemination of R2*-based LIC quantification. ClinicalTrials.gov registration no.: NCT02025543 © RSNA, 2022 Online supplemental material is available for this article.

PMID:36194113 | DOI:10.1148/radiol.213256

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Safety and Efficacy of Propofol and Ketamine Based Procedural Sedation Regimen in Pediatric During Burn Repetitive Dressing Change: 10 Years Single Center Experience

J Burn Care Res. 2022 Oct 4:irac144. doi: 10.1093/jbcr/irac144. Online ahead of print.

ABSTRACT

It is crucial to provide an adequate level of sedation and analgesia during burn dressing changes in the pediatric population due to the amount of pain and anxiety patients experience during the procedure. To evaluate the safety and efficacy of an intensivist-based deep sedation regimen using a combination of propofol and ketamine to provide procedural sedation to pediatric burn patients. This is a retrospective chart review of pediatric patients who underwent inpatient burn wound dressing changes from 2011 through 2021. Demographic and clinical data, including age, length of the procedure, recovery time, medications doses, and adverse events, were collected. A total of 104 patients aged between 45 and 135 months with a median total burn body surface area (TBSA) of 11.5 % (IQR 4.0, 25.0) underwent 378 procedural sedation encounters with propofol and ketamine-based sedation. The median total dose of propofol was 7 mg/kg (IRQ 5.3, 9.2). Of these sedations, 64 (17%) had minor adverse events, of which 50 (13%) were transient hypoxemia, 12 (3%) were upper airway obstruction, and 2 (0.5%) were hypotension. There were no serious adverse events. Hypoxemia was not related to age, weight, gender, burn TBSA, or total dose of propofol. There were 35 (33.6%) patients who had repetitive sedation encounters with no statistically significant changes in propofol dose or adverse events with the repeated encounters. Children can be effectively sedated for repetitive inpatient burn dressing changes. Given the high-risk patient populations, this procedure should be performed under the vigilance of highly trained providers.

PMID:36194090 | DOI:10.1093/jbcr/irac144

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New indexes for myofibril linearity in muscle image analysis

Eur J Transl Myol. 2022 Oct 4. doi: 10.4081/ejtm.2022.10736. Online ahead of print.

ABSTRACT

The endeavor to evaluate the linearity of myofibrillar structures and their potential deviation from a straight line is a fascinating problem in muscle tissue image analysis. In this Letter, we suggest two different strategies for solving the same challenge. The first strategy is based on an alignment index, which could be derived by comparing the sum of the lengths of the individual sarcomeres with the distance between the “head” of the first and the “tail” of the last sarcomere. The second strategy relies on circular statistics, which takes a cue from an already suggested method. Our proposed methods are alternatives: the former has the advantage of simplicity; the latter is certainly more elegant and gives greater substance to statistical analysis, but in contrast, it also has greater computational complexity.

PMID:36193819 | DOI:10.4081/ejtm.2022.10736

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Presentations to emergency departments in Melbourne, Australia diagnosed as allergic contact dermatitis

Contact Dermatitis. 2022 Oct 4. doi: 10.1111/cod.14230. Online ahead of print.

ABSTRACT

BACKGROUND: This study investigated cases diagnosed as allergic contact dermatitis (ACD) in emergency departments (EDs) and management.

METHODS: A multi-site retrospective study of patients attending EDs in metropolitan Melbourne between July 2017 and June 2018 was performed. Using International Statistical Classification of Disease-10 (ICD-10) codes, the Victorian Agency for Health Information generated a list of cases of contact dermatitis (CD). Demographic and clinical data were analysed.

RESULTS: 228 patients from 14 different sites were diagnosed with ACD. Hair dyes caused the most cases, and one such case was admitted to hospital. It was apparent from the specified causes that cases of irritant CD were misdiagnosed as ACD. There were significant differences in management with dermatology input, with dermatologists more often advising oral corticosteroids (33.3% vs 14.5%, p= 0.004) topical corticosteroids (92.9% vs 38.7% p <0.01), emollients (38.1% vs 20.4%, p = 0.01) and less often advising antihistamines (16.7% vs 44.6%, p <0.001). With dermatology input, potent or very potent steroids were more likely to be prescribed (69.3% vs 11.1%, p < 0.001); without, a mild potency steroid was more likely to be prescribed (63.9% vs 4%, p=0.01).

CONCLUSION: Improved understanding, diagnosis and management of CD is needed in EDs. This article is protected by copyright. All rights reserved.

PMID:36193797 | DOI:10.1111/cod.14230

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Family styles and Quality of life in adolescents with bronchial asthma: The important role of self-esteem and perceived threat of the disease

Pediatr Pulmonol. 2022 Oct 4. doi: 10.1002/ppul.26178. Online ahead of print.

ABSTRACT

OBJECTIVES: Analyze the relationship between family styles and quality of life in adolescents with bronchial asthma and study the influence of self-esteem as a protective factor and threat perception as a risk factor.

METHODS: Family styles, quality of life (QoL), perceived threat of the disease, and self-esteem were assessed in a total of 150 adolescents diagnosed with bronchial asthma with ages ranging from 12 to 16 years (M=13.28; SD=1.29), 60.7% being male. Descriptive statistics and mean comparisons were conducted according to the level of self-esteem. Relationships between variables were also studied using Pearson correlations, and finally, the mediating role of self-esteem and the perceived threat of the disease was assessed using PROCESS.

RESULTS: Adolescents shown healthy family characteristics (high scores on affect and parental mood and low scores on psychological control) and high scores on quality of life. 35% of adolescents showed low self-esteem and a tendency to underestimate the disease. There are existing relationships between family styles and quality of life; thus, healthy family characteristics (affection, parental mood, autonomy promotion) were positively associated with quality of life, while psychological control was negatively associated with QoL. Disease threat and self-esteem mediated the relationship between family styles and adolescent QoL. Disease threat was negatively, and self-esteem was positively associated with QoL.

CONCLUSIONS: Self-esteem and family support are protective factors for the well-being of adolescents with bronchial asthma; however, the high perceived threat of the disease can have negative consequences for the adolescent’s health and negatively impact their quality of life. This article is protected by copyright. All rights reserved.

PMID:36193795 | DOI:10.1002/ppul.26178

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Eye enucleation and exenteration in -cattle: a retrospective study of 38 cases (2013-2020)

Schweiz Arch Tierheilkd. 2022 Oct;164(10):687-693. doi: 10.17236/sat00368.

ABSTRACT

The study aimed to describe clinical indications for eye enucleation and exenteration, the occurrence of complications and long-term outcome in cattle, and examine owners’ attitude towards enucleation and exenteration and their satisfaction with the surgical outcome. Medical records from the two veterinary teaching hospitals in Switzerland were reviewed to identify cattle that underwent unilateral enucleation or exenteration between January 2013 and December 2020. Data extracted included medical history, ocular examination, clinical diagnosis, surgical procedure including anesthesia, suture material and pattern used, complications, and treatment thereof. Long-term follow-up was evaluated via national animal database inquiries to determine survival time and via owners’ interviews with the use of a standardized questionnaire that included questions regarding the occurrence of complications and reason for culling, production performances and perceived quality of life after surgery, concerns, factors affecting the decision to proceed with surgery, and general satisfaction with the outcome. Descriptive statistics, Fisher’s exact tests and unpaired t-test were used to summarize the data and assess association between variables. Association was considered significant if p < 0,05. Thirty-eight cases were identified, with a median age of 5 years. More than half of the cases (55,3 %) were diagnosed with non-neoplastic ocular lesions represented by severe trauma with loss of globe content, globe rupture with history of infectious keratoconjunctivitis or hypopyon, or congenital malformations. The remaining cases were diagnosed with neoplastic lesions, including ocular squamous cell carcinoma (OSCC), melanoma, or sarcoma. Complications following surgery were reported in 29 % of cases and included postoperative infection and recurrence of OSCC. There was no significant association between ocular diagnosis and the occurrence of postoperative complications or survival time. Surgery did not seem to influence the animals’ postoperative production performance or the perceived quality of life. Most owners (92 %) were satisfied with the surgical outcome. The occurrence of postoperative complications leading to increased overall costs and culling was the main reason for lower owner satisfaction.

PMID:36193779 | DOI:10.17236/sat00368

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Blood flow analyses by intraoperative transit-time flow measurements of free flaps for head and neck reconstructions: A prospective single-center study

Microsurgery. 2022 Oct 4. doi: 10.1002/micr.30967. Online ahead of print.

ABSTRACT

BACKGROUND: The behavior of blood flow changes within free flaps following microvascular anastomosis is not well described in the literature. The aim of this study was to determine the immediate blood flow behavior of different free flaps as reference values for various clinical applications.

METHODS: Intraoperative transit-time flow measurements were performed on patients receiving free flap transfer in the head and neck area comprising radial forearm flaps (RFF), peroneal artery perforator flaps (PAP), anterolateral thigh flaps (ALT), vastus lateralis flaps (VLF), parascapular flaps (PSF), latissimus dorsi flaps (LDF), fibula free flaps (FFF), deep circumflex iliac artery flaps (DCIA), and scapular flaps (SF). In accordance with a structured protocol, measurements took place at the pedicle directly before flap harvesting and at the recipient vessels 1 h after flap transfer. Heart rate, transplant weight, and other patient characteristics were recorded and analyzed.

RESULTS: A total of 129 were enrolled, comprising 66 RFF, 8 ALT, 6 PAP, 11 VLF, 3 PSF, 2 LDF, 24 FFF, 7 DCIA, and 2 SF. In most of the transplant groups, arterial perfusion increased after anastomosis at the recipient site. The arterial pulsatility index developed indirectly proportionally to arterial blood flow, whereas venous blood drainage did not show any statistically significant changes. Muscle flaps had the highest arterial perfusion before flap transfer. Composite transplants with hard and soft tissue presented the greatest increase in arterial perfusion. The lowest arterial blood flow after anastomosis was measured in PAP and RFF. In contrast, RFF and PAP presented the highest arterial perfusion per 100 g transplant weight.

CONCLUSIONS: Arterial perfusion changed, whereas venous blood flow did not show any statistically significant variations in any transplant group. Perfusion of free flaps does not only depend on the recipient vessel and the recipient bed, but also on flap-specific anatomy and physiology.

PMID:36193758 | DOI:10.1002/micr.30967

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Assessing Adverse Health Effects of Long-Term Exposure to Low Levels of Ambient Air Pollution: Implementation of Causal Inference Methods

Res Rep Health Eff Inst. 2022 Jan;(211):1-56.

ABSTRACT

This report provides a final summary of the principal findings and key conclusions of a study supported by an HEI grant aimed at “Assessing Adverse Health Effects of Long-Term Exposure to Low Levels of Ambient Air Pollution.” It is the second and final report on this topic. The study was designed to advance four critical areas of inquiry and methods development. First, it focused on predicting short- and long-term exposures to ambient fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) at high spatial resolution (1 km × 1 km) for the continental United States over the period 2000-2016 and linking these predictions to health data. Second, it developed new causal inference methods for estimating exposure-response (ER) curves (ERCs) and adjusting for measured confounders. Third, it applied these methods to claims data from Medicare and Medicaid beneficiaries to estimate health effects associated with short- and long-term exposure to low levels of ambient air pollution. Finally, it developed pipelines for reproducible research, including approaches for data sharing, record linkage, and statistical software. Our HEI-funded work has supported an extensive portfolio of analyses and the development of statistical methods that can be used to robustly understand the health effects of short- and long-term exposure to low levels of ambient air pollution. Our Phase 1 report (Dominici et al. 2019) provided a high-level overview of our statistical methods, data analysis, and key findings, grouped into the following five areas: (1) exposure prediction, (2) epidemiological studies of ambient exposures to air pollution at low levels, (3) sensitivity analysis, (4) methodological contributions in causal inference, and (5) an open access research data platform. The current, final report includes a comprehensive overview of the entire research project.

Considering our (1) massive study population, (2) numerous sensitivity analyses, and (3) transparent assessment of covariate balance indicating the quality of causal inference for simulating randomized experiments, we conclude that conditionally on the required assumptions for causal inference, our results collectively indicate that long-term PM2.5 exposure is likely to be causally related to mortality. This conclusion assumes that the causal inference assumptions hold and, more specifically, that we accounted adequately for confounding bias. We explored various modeling approaches, conducted extensive sensitivity analyses, and found that our results were robust across approaches and models. This work relied on publicly available data, and we have provided code that allows for reproducibility of our analyses.

Our work provides comprehensive evidence of associations between exposures to PM2.5, NO2, and O3 and various health outcomes. In the current report, we report more specific results on the causal link between long-term exposure to PM2.5 and mortality, even at PM2.5 levels below or equal to 12 μg/m3, and mortality among Medicare beneficiaries (ages 65 and older). This work relies on newly developed causal inference methods for continuous exposure.

For the period 2000-2016, we found that all statistical approaches led to consistent results: a 10-μg/m3 decrease in PM2.5 led to a statistically significant decrease in mortality rate ranging between 6% and 7% (= 1 – 1/hazard ratio [HR]) (HR estimates 1.06 [95% CI, 1.05 to 1.08] to 1.08 [95% CI, 1.07 to 1.09]). The estimated HRs were larger when studying the cohort of Medicare beneficiaries that were always exposed to PM2.5 levels lower than 12 μg/m3 (1.23 [95% CI, 1.18 to 1.28] to 1.37 [95% CI, 1.34 to 1.40]).

Comparing the results from multiple and single pollutant models, we found that adjusting for the other two pollutants slightly attenuated the causal effects of PM2.5 and slightly elevated the causal effects of NO2 exposure on all-cause mortality. The results for O3 remained almost unchanged.

We found evidence of a harmful causal relationship between mortality and long-term PM2.5 exposures adjusted for NO2 and O3 across the range of annual averages between 2.77 and 17.16 μg/m3 (included >98% of observations) in the entire cohort of Medicare beneficiaries across the continental United States from 2000 to 2016. Our results are consistent with recent epidemiological studies reporting a strong association between long-term exposure to PM2.5 and adverse health outcomes at low exposure levels. Importantly, the curve was almost linear at exposure levels lower than the current national standards, indicating aggravated harmful effects at exposure levels even below these standards.

There is, in general, a harmful causal impact of long-term NO2 exposures to mortality adjusted for PM2.5 and O3 across the range of annual averages between 3.4 and 80 ppb (included >98% of observations). Yet within low levels (annual mean ≤53 ppb) below the current national standards, the causal impacts of NO2 exposures on all-cause mortality are nonlinear with statistical uncertainty.

The ERCs of long-term O3 exposures on all-cause mortality adjusted for PM2.5 and NO2 are almost flat below 45 ppb, which shows no statistically significant effect. Yet we observed an increased hazard when the O3 exposures were higher than 45 ppb, and the HR was approximately 1.10 when comparing Medicare beneficiaries with annual mean O3 exposures of 50 ppb versus those with 30 ppb.

institutions, including those that support the Health Effects Institute; therefore, it may not reflect the views or policies of these parties, and no endorsement by them should be inferred.

A list of abbreviations and other terms appears at the end of this volume.

PMID:36193708