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Racial and Ethnic Residential Segregation and Monocyte DNA Methylation Age Acceleration

JAMA Netw Open. 2023 Nov 1;6(11):e2344722. doi: 10.1001/jamanetworkopen.2023.44722.

ABSTRACT

IMPORTANCE: Neighborhood segregation and poverty may be important drivers of health inequities. Epigenomic factors, including DNA methylation clocks that may mark underlying biological aging, have been implicated in the link between social factors and health.

OBJECTIVE: To examine the associations of neighborhood segregation and poverty with 4 DNA methylation clocks trained to capture either chronological age or physiological dysregulation.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study uses data from the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal study that started in 2000 to 2002, with follow-up in 2002 to 2004, 2004 to 2005, 2005 to 2007, and 2010 to 2012. In 2000 to 2002, adults who identified as White or Black race or Hispanic or Chinese ethnicity in 6 US sites (Baltimore, Maryland; Chicago, Illinois; Forsyth County, North Carolina; Los Angeles County, California; Northern Manhattan, New York; and St. Paul, Minnesota) were sampled for recruitment. A random subsample of 4 sites (Maryland, North Carolina, New York, and Minnesota) were selected for inclusion in the MESA epigenomics ancillary study at examination 5 (2010-2012). Participants who identified as White or Black race or Hispanic ethnicity, were aged 45 to 84 years, and did not have clinical cardiovascular disease were included in this analysis. Data were analyzed from May 2021 to October 2023.

EXPOSURE: Information on 2000 census tract poverty and Getis-Ord G statistic segregation of Hispanic residents, non-Hispanic Black residents, or non-Hispanic White residents were linked to participant addresses at examination 1 (2000-2002).

MAIN OUTCOMES AND MEASURES: At examination 5, DNA methylation was measured in purified monocytes. DNA methylation age acceleration was calculated using 4 clocks trained on either chronological age or physiological dysregulation. Linear regressions were used to test associations.

RESULTS: A total of 1102 participants (mean [SD] age, 69.7 [9.4] years; 562 [51%] women) were included, with 348 Hispanic participants, 222 non-Hispanic Black participants, and 533 non-Hispanic White participants. For non-Hispanic Black participants, living in tracts with greater segregation of Black residents was associated with GrimAge DNA methylation age acceleration, a clock designed to capture physiological dysregulation. A 1-SD increase in segregation was associated with 0.42 (95% CI, 0.20-0.64) years age acceleration (P < .001); this association was not observed with other clocks. This association was particularly pronounced for participants living in high poverty tracts (interaction term, 0.24; 95% CI, 0.07-0.42; P = .006). In the overall sample, census tract poverty level was associated with GrimAge DNA methylation age acceleration (β = 0.45; 95% CI, 0.20-0.71; adjusted P = .005).

CONCLUSIONS AND RELEVANCE: These findings suggest that epigenomic mechanisms may play a role in the associations of segregated and poor neighborhoods with chronic conditions.

PMID:38019517 | DOI:10.1001/jamanetworkopen.2023.44722

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Emergency Medical Responses at US Immigration and Customs Enforcement Detention Centers in California

JAMA Netw Open. 2023 Nov 1;6(11):e2345540. doi: 10.1001/jamanetworkopen.2023.45540.

ABSTRACT

IMPORTANCE: Knowledge of medical care in US Immigration and Customs Enforcement (ICE) detention centers is limited. Reviews show high rates of preventable deaths while in detention due to substandard medical care within detention centers.

OBJECTIVE: To describe characteristics of medical emergencies at ICE detention centers in California.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed emergency medical services (EMS)-reported medical emergencies activated through 911 from January 1, 2018, to December 31, 2022, at 3 of the 5 ICE detention centers in California: Adelanto ICE Processing Center, Imperial Regional Detention Facility, and Otay Mesa Detention Center.

EXPOSURE: Medical services requiring 911 activation.

MAIN OUTCOMES AND MEASURES: Data included the number of EMS-reported medical emergencies; ICE-reported medical emergencies; patient age and sex; and medical data in the EMS report, including primary symptom, EMS provider (emergency medical technician or paramedic) impression, vital signs, and interventions performed, using descriptive statistics.

RESULTS: In this analysis of 3 detention centers with a mean daily census of 775 (range, 504-1001) individuals per center, there was a median of 68 (IQR, 10-88) EMS-reported emergencies per center per year for a total of 1224 emergencies. The EMS-reported emergencies involved 881 males (72%) and 338 females (28%) with a median age of 39.0 (IQR 30.0-49.0) years. The ratios of female-to-male EMS-reported emergencies were 0.51 (95% CI, 0.31-0.87) at Adelanto, 0.86 (95% CI, 0.31-2.43) at Imperial, and 1.60 (95% CI, 1.40-1.83) at Otay Mesa. Pregnancy-related emergencies accounted for 12.4% (42 of 338) of emergencies in females. A total of 357 individuals (29.2%) had at least 1 abnormal vital sign during their EMS encounter. Psychiatric emergencies comprised 48 EMS responses (3.9%), despite higher rates of ICE-reported psychiatric-related complaints. The median number of monthly EMS-reported emergencies across all 3 centers was 3 (IQR, 0-9) vs 4 ICE-reported emergencies (IQR, 1-15).

CONCLUSIONS AND RELEVANCE: In this study of medical emergencies at 3 of 5 ICE detention facilities in California, there were discrepancies in EMS vs ICE reported emergencies. The data suggested that vulnerable populations, such as pregnant women, had an increased number of medical emergencies, while individuals with psychiatric emergencies accounted for fewer reported emergencies. Based on these findings, emergency medical care provision in ICE detention centers requires increased transparency to ensure appropriate delivery of care.

PMID:38019513 | DOI:10.1001/jamanetworkopen.2023.45540

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Aneurysm and Artery Dissection After Oral VEGFR-TKI Use in Adults With Cancer

JAMA Netw Open. 2023 Nov 1;6(11):e2345977. doi: 10.1001/jamanetworkopen.2023.45977.

ABSTRACT

IMPORTANCE: The association of tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR-TKIs) with aneurysm and artery dissection (AAD) has been frequently reported in spontaneous reporting databases.

OBJECTIVE: To investigate the risk and incidence of AAD occurrence in patients with cancer treated with oral VEGFR-TKIs, with capecitabine as an active comparator.

DESIGN, SETTING, AND PARTICIPANTS: This national, historical cohort study was conducted using national claims data from the National Health Insurance Service in Korea from 2007 to 2020, with a 1-year follow-up. Patients with cancer aged 40 years or older prescribed oral VEGFR-TKIs or capecitabine were enrolled. Data were analyzed from September 2022 through April 2023.

EXPOSURE: Oral VEGFR-TKIs (sorafenib, regorafenib, vandetanib, sunitinib, lenvatinib, axitinib, and pazopanib) or capecitabine as a comparator.

MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) were used to investigate the association between VEGFR-TKI use and AAD after propensity score matching. The primary outcome was AAD, and secondary outcomes were aortic aneurysm and dissection and AAD with rupture. Outcomes were defined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes.

RESULTS: Among 127 710 patients with cancer eligible for the study (80 386 males [62.9%]; mean [SD] age, 62.6 [10.9] years), 37 308 patients received VEGFR-TKIs and 90 402 patients received capecitabine. Among 27 535 matched patients receiving VEGFR-TKIs, the incidence of AAD within 1 year of treatment initiation was 6.0 per 1000 person-years. The median (IQR) time to AAD onset in the matched AAD group was 114 (67-257) days after treatment initiation, with the highest incidence observed during the first 3 months (45 incidents vs 31, 17, and 16 incidents during 3- to 6-month, 6- to 9-month, and 9- to 12-month periods, respectively). Cox regression modeling showed that the risk of AAD occurrence was significantly higher among patients prescribed VEGFR-TKIs than those receiving capecitabine (HR, 1.48; 95% CI, 1.08-2.02); similar results were obtained among females (HR, 2.08; 95% CI, 1.26-3.42), older adults (aged ≥65 years; HR, 1.42; 95% CI, 1.01-1.99), and patients with dyslipidemia (HR, 1.58; 95% CI, 1.11-2.24).

CONCLUSIONS AND RELEVANCE: In this study, the use of oral VEGFR-TKIs was associated with an increased risk of AAD occurrence. These findings elucidate vascular toxic effects and may provide a substantial reference for reducing the socioeconomic burden of adverse events associated with VEGFR-TKI use.

PMID:38019511 | DOI:10.1001/jamanetworkopen.2023.45977

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An Evaluation of the Repeatability of Visual Function Following Surgical Repair of Macula-Off Rhegmatogenous Retinal Detachment

Transl Vis Sci Technol. 2023 Nov 1;12(11):35. doi: 10.1167/tvst.12.11.35.

ABSTRACT

PURPOSE: To evaluate the reliability and reproducibility of visual function assessments for patients with macula-off rhegmatogenous retinal detachment (RRD).

METHODS: This prospective study included patients with unilateral macula-off RRD of <10-day duration successfully treated with a single, uncomplicated surgery at least 1 year following repair. Visual function assessments were performed at time of enrollment and 1 month later. Testing included Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), low-contrast visual acuity (VA) 2.5% and 5%, contrast sensitivity assessment with Mars and Gabor patches, reading speed (acuity, speed, and critical print size), color vision testing (protan, deutan, and tritan), and microperimetry. Spectral-domain ocular coherence tomography (SD-OCT) was performed. Paired t-statistics were used to compare values between visits and between the study and fellow eyes.

RESULTS: Fourteen patients (9 male, 5 female) with a mean age of 69 years at time of surgery were evaluated. Correlation coefficients across the two visits were highest for ETDRS BCVA (0.97), tritan color vision testing (0.96), and low-contrast VA 5% (0.96), while the average t-statistic was largest for low-luminance deficit (4.2), ETDRS BCVA (4.1), and reading speed critical print size (3.7). ETDRS BCVA did not correlate with SD-OCT findings.

CONCLUSIONS: ETDRS BCVA can be considered a highly reliable and reproducible outcome measure. LLVA, protan color discrimination, contrast sensitivity, and reading speed may be useful secondary outcome measures.

TRANSLATIONAL RELEVANCE: This study provides guidance on the selection of visual function outcome measures for clinical trials of patients with macula-off RRD.

PMID:38019499 | DOI:10.1167/tvst.12.11.35

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Predictive modeling of submarining risk in car occupants based on pelvis angle and lap belt positioning

Traffic Inj Prev. 2023 Nov 29:1-9. doi: 10.1080/15389588.2023.2278419. Online ahead of print.

ABSTRACT

OBJECTIVE: The engagement of the lap belt with the pelvis is critical for occupant safety during vehicle frontal crashes to prevent occupant submarining. This study aims to develop a predictive model for submarining risk based on anthropometric parameters and lap belt positioning using finite element (FE) analyses.

METHODS: FE analyses were conducted using human body models representing various body shapes (a 50th percentile male, low and high BMI males, and a 5th percentile female) in three seated postures (standard, reclined, and slouched). The lap belt-ASIS overlap and the belt-pelvis angle were used as key parameters for predicting submarining risk. A logistic regression analysis was utilized to correlate submarining occurrence with the initial values of these two parameters at the beginning of impact. Subsequently, this submarining prediction model was applied to computer tomography (CT) measurements of human subjects in different seated postures (upright, reclined, and slouched), and submarining risks were calculated based on the developed model.

RESULTS: FE simulations indicated that submarining was more likely to occur as the initial belt-pelvis angle approached zero and there was a smaller initial belt-ASIS overlap. The logistic regression analysis demonstrated that the initial belt-pelvis angle and belt-ASIS overlap were statistically significant for predicting submarining risk. The derived model effectively distinguished submarining occurrence based on the initial values of these two parameters. The application of the submarining model to CT measurements of human subjects showed that submarining risk was lower in the order of upright, slouched, and reclined postures. In the reclined posture, the high submarining risk was attributed to a small belt-ASIS overlap and a rearward-tilted pelvis angle; whereas in the slouched posture, the risk was mostly associated with a rearward-tilted pelvis angle.

CONCLUSIONS: The submarining prediction model was developed based on the belt-pelvis angle and the belt-ASIS overlap. This predictive model may help to design restraint systems for various body types and seated postures of occupants.

PMID:38019483 | DOI:10.1080/15389588.2023.2278419

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Data-Based Opioid Risk Review in Patients with Chronic Pain: A Retrospective Chart Review

J Pain Palliat Care Pharmacother. 2023 Nov 29:1-10. doi: 10.1080/15360288.2023.2288109. Online ahead of print.

ABSTRACT

A retrospective, cohort, single center, chart review was conducted to compare rates of opioid-associated serious adverse events (SAEs) in a patient cohort 6 months before and 6 months after data-based opioid risk review. The primary objective was the composite reduction in opioid-related SAEs including suicide-related events and opioid overdoses. The impact of the reviews was assessed via multivariate logistic regression and a McNemar’s test to analyze difference in rates of opioid-associated SAEs. This study demonstrates that data-based opioid risk review can reduce opioid-related SAEs, opioid overdoses, and suicide-related events in the 6 months post-review. The primary outcome was not statistically significant with a p-value of 0.080. In the population that underwent opioid tapers, the hazard ratios (HR) for suicide-related events and opioid-related SAEs were 6.64 (1.09-40.53, p = 0.05) and 10.43 (0.48-226.80, p = 0.02) respectively when compared to non-tapered patients. The HR for suicide-related events and opioid-related SAEs when opioid therapy was discontinued were 9.95 (2.16-45.94, p = 0.009) and 15.64 (1.09-225.19, p = 0.001) respectively when compared to continuation of opioids. This study showed that data-based opioid risk review may reduce incidence of opioid-related SAEs in patients with chronic pain. Additionally, opioid tapers and discontinuations are significant risk factors for suicide-related events and opioid-related SAEs.

PMID:38019479 | DOI:10.1080/15360288.2023.2288109

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A prospective comparative study on bladder volume measurement with portable ultrasound scanner and CT simulator in pelvic tumor radiotherapy

Phys Eng Sci Med. 2023 Nov 29. doi: 10.1007/s13246-023-01344-2. Online ahead of print.

ABSTRACT

OBJECTIVE: The consistency of bladder volume is very important in pelvic tumor radiotherapy, and portable bladder scanner is a promising device to measure bladder volume. The purpose of this study was to investigate whether the bladder volume of patients with pelvic tumor treated with radiotherapy can be accurately measured using the Meike Palm Bladder Scanner PBSV3.2 manufactured in China and the accuracy of its measurement under different influencing factors.

METHODS: A total of 165 patients with pelvic tumor undergoing radiotherapy were prospectively collected. The bladder volume was measured with PBSV3.2 before simulated localization. CT simulated localization was performed when the bladder volume was 200-400ml. The bladder volume was measured with PBSV3.2 immediately after localization and recorded. The bladder volume was then delineated on CT simulation images and recorded. To compare the consistency of CT simulation bladder volume and bladder volume measured by PBSV3.2. To investigate the accuracy of PBSV3.2 in different sex, age, treatment purpose, and bladder volume.

RESULTS: There was a significant positive correlation with bladder volume on CT and PBSV3.2 (r = 0.874; p < 0.001). The mean difference between CT measured values and PBSV3.2 was (-0.14 ± 50.17) ml. The results of the different variables showed that the overall mean of PBSV3.2 and CT measurements were statistically different in the age ≥ 65 years, bladder volumes > 400ml and ≤ 400ml groups (p = 0.028, 0.002, 0.001). There was no statistical significance between the remaining variables. The volume difference between PBSV3.2 measurement and CT was 12.87ml in male patients, which was larger than that in female patients 3.27ml. Pearson correlation analysis showed that the correlation coefficient was 0.473 for bladder volume greater than 400ml and 0.868 for bladder volume less than 400ml; the correlation coefficient of the other variables ranged from 0.802 to 0.893.

CONCLUSION: This is the first large-sample study to evaluate the accuracy of PBSV3.2 in a pelvic tumor radiotherapy population using the convenient bladder scanner PBSV3.2 made in China. PBSV3.2 provides an acceptable indicator for monitoring bladder volume in patients with pelvic radiotherapy. It is recommended to monitor bladder volume with PBSV3.2 when the planned bladder volume is 200-400ml. For male and patients ≥ 65 years old, at least two repeat measurements are required when using a bladder scanner and the volume should be corrected by using a modified feature to improve bladder volume consistency.

PMID:38019446 | DOI:10.1007/s13246-023-01344-2

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Effects of Non-invasive Brain Stimulation on Hereditary Ataxia: a Systematic Review and Meta-analysis

Cerebellum. 2023 Nov 29. doi: 10.1007/s12311-023-01638-x. Online ahead of print.

ABSTRACT

Numerous studies have demonstrated the potential of non-invasive brain stimulation (NIBS) techniques as a viable treatment option for cerebellar ataxia. However, there is a notable dearth of research investigating the efficacy of NIBS specifically for hereditary ataxia (HA), a distinct subgroup within the broader category of cerebellar ataxia. This study aims to conduct a comprehensive systematic review and meta-analysis in order to assess the efficacy of various NIBS methods for the treatment of HA. A thorough review of the literature was conducted, encompassing both English and Chinese articles, across eight electrical databases. The focus was on original articles investigating the therapeutic effectiveness of non-invasive brain stimulation for hereditary ataxia, with a publication date prior to March 2023. Subsequently, a meta-analysis was performed specifically on randomized controlled trials (RCTs) that fulfilled the eligibility criteria, taking into account the various modalities of non-invasive brain stimulation. A meta-analysis was conducted, comprising five RCTs, which utilized the Scale for the Assessment and Rating of Ataxia (SARA) as the outcome measure to evaluate the effects of transcranial magnetic stimulation (TMS). The findings revealed a statistically significant mean decrease of 1.77 in the total SARA score following repetitive TMS (rTMS) (p=0.006). Subgroup analysis based on frequency demonstrated a mean decrease of 1.61 in the total SARA score after high-frequency rTMS (p=0.05), while no improvement effects were observed after low-frequency rTMS (p=0.48). Another meta-analysis was performed on three studies, utilizing ICARS scores, to assess the impact of rTMS. The results indicated that there were no statistically significant differences in pooled ICARS scores between the rTMS group and the sham group (MD=0.51, 95%CI: -5.38 to 6.39; p=0.87). These findings align with the pooled results of two studies that evaluated alterations in post-intervention BBS scores (MD=0.74, 95%CI: -5.48 to 6.95; p=0.82). Despite the limited number of studies available, this systematic review and meta-analysis have revealed promising potential benefits of rTMS for hereditary ataxia. However, it is strongly recommended that further high-quality investigations be conducted in this area. Furthermore, the significance of standardized protocols for NIBS in future studies was also emphasized.

PMID:38019418 | DOI:10.1007/s12311-023-01638-x

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Effect of BI 1358894 on Cholecystokinin-Tetrapeptide (CCK-4)-Induced Anxiety, Panic Symptoms, and Stress Biomarkers: A Phase I Randomized Trial in Healthy Males

CNS Drugs. 2023 Nov 29. doi: 10.1007/s40263-023-01042-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Depression, anxiety, and/or panic disorder are often comorbid and have a complex etiology mediated through the same neuronal network. Cholecystokinin-tetrapeptide (CCK-4), a synthetic analog of the endogenous neuropeptide cholecystokinin (CCK), is thought to be implicated in this network. The CCK-4 challenge model is an accepted method of investigating the pathophysiology of panic and has been shown to mediate neuronal activation via the transient receptor potential canonical (TRPC) ion channels.

OBJECTIVES: This study aimed to assess the pharmacodynamic effects of BI 1358894, a small-molecule inhibitor of TRPC ion channel members 4 and 5 (TRPC4/5), on CCK-4-induced anxiety/panic-like symptoms and evaluate circuit engagement.

METHODS: Twenty healthy male CCK-4-sensitive volunteers entered a Phase I, double blind, randomized, two-way cross-over, single dose, placebo-controlled trial. Randomization was to oral BI 1358894 100 mg in the fed state followed by oral placebo in the fed state, or vice versa. Treatments were administered 5 h prior to intravenous CCK-4 50 µg. The primary endpoint was maximum change from baseline of the Panic Symptom Scale (PSS) sum intensity score after CCK-4 injection. Further endpoints included the emotional faces visual analog score (EVAS), the Spielberger State-Trait Anxiety Inventory (STAI), plasma adrenocorticotropic hormone (ACTH), and serum cortisol values. The safety and tolerability of BI 1358894 was assessed based on a number of parameters including occurrence of adverse events (AEs). All pharmacodynamic, pharmacokinetic, and safety endpoints were analyzed using descriptive statistics.

RESULTS: Single oral doses of BI 1358894 were generally well tolerated by the healthy male volunteers included in this study. Adjusted mean maximum change from baseline in PSS sum intensity score was 24.4 % lower in volunteers treated with BI 1358894 versus placebo, while adjusted mean maximum change from baseline of EVAS was reduced by 19.2 % (BI 1358894 vs placebo). The STAI total score before CCK-4 injection was similar in both groups (placebo: 25.1; BI 1358894: 24.3). Relative to placebo, BI 1358894 reduced CCK-4-induced mean maximum plasma ACTH and serum cortisol values by 58.6 % and 27.3 %, respectively. Investigator-assessed drug-related AEs were reported for 13/20 participants (65.0 %). There were no serious or severe AEs, AEs of special interest, AEs leading to discontinuation of trial medication, or deaths.

CONCLUSIONS: Overall, BI 1358894 reduced psychological and physiological responses to CCK-4 compared with placebo, as measured by PSS, subjective EVAS and objectively measured stress biomarkers. BI 1358894 had a positive safety profile, and single oral doses were well tolerated by the healthy volunteers. This trial (NCT03904576/1402-0005) was registered on Clinicaltrials.gov on 05.04.19.

PMID:38019356 | DOI:10.1007/s40263-023-01042-3

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Radiofrequency ablation induces tumor cell dissemination in a mouse model of hepatocellular carcinoma

Eur Radiol Exp. 2023 Nov 29;7(1):74. doi: 10.1186/s41747-023-00382-5.

ABSTRACT

BACKGROUND: We tested the hypothesis that radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) promotes tumor cell release and explored a method for reducing these effects.

METHODS: A green fluorescent protein-transfected orthotopic HCC model was established in 99 nude mice. In vivo flow cytometry was used to monitor circulating tumor cell (CTC) dynamics. Pulmonary fluorescence imaging and pathology were performed to investigate lung metastases. First, the kinetics of CTCs during the periablation period and the survival rate of CTCs released during RFA were investigated. Next, mice were allocated to controls, sham ablation, or RFA with/without hepatic vessel blocking (ligation of the portal triads) for evaluating the postablation CTC level, lung metastases, and survival over time. Moreover, the kinetics of CTCs, lung metastases, and mice survival were evaluated for RFA with/without ethanol injection. Pathological changes in tumors and surrounding parenchyma after ethanol injection were noted. Statistical analysis included t-test, ANOVA, and Kaplan-Meier survival curves.

RESULTS: CTC counts were 12.3-fold increased during RFA, and 73.7% of RFA-induced CTCs were viable. Pre-RFA hepatic vessel blocking prevented the increase of peripheral CTCs, reduced the number of lung metastases, and prolonged survival (all p ≤ 0.05). Similarly, pre-RFA ethanol injection remarkably decreased CTC release during RFA and further decreased lung metastases with extended survival (all p ≤ 0.05). Histopathology revealed thrombus formation in blood vessels after ethanol injection, which may clog tumor cell dissemination during RFA.

CONCLUSION: RFA induces viable tumor cell dissemination, and pre-RFA ethanol injection may provide a prophylactic strategy to reduce this underestimated effect.

RELEVANCE STATEMENT: RFA for HCC promotes viable tumor cell release during ablation, while ethanol injection can prevent RFA induced tumor cell release.

KEY POINTS: • RFA induced the release of viable tumor cells during the ablation procedure in an animal model. • Hepatic vessel blocking can suppress tumor cells dissemination during RFA. • Ethanol injection can prevent RFA-induced tumor cell release, presumably because of the formation of thrombosis.

PMID:38019353 | DOI:10.1186/s41747-023-00382-5