Comparative analysis of glymphatic system alterations in multiple sclerosis and neuromyelitis optica spectrum disorder using MRI indices from diffusion tensor imaging.

OBJECTIVE: The glymphatic system is a glial-based perivascular network that promotes brain metabolic waste clearance. Glymphatic system dysfunction has been observed in both multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), indicating the role of neuroinflammation in the glymphatic system. However, little is known about how the two diseases differently affect the human glymphatic system. The present study aims to evaluate the diffusion MRI-based measures of the glymphatic system by contrasting MS and NMOSD. METHODS: This prospective study included 63 patients with NMOSD (n = 21) and MS (n = 42) who underwent DTI. The fractional volume of extracellular-free water (FW) and an index of diffusion tensor imaging (DTI) along the perivascular space (DTI-ALPS) were used as indirect indicators of water diffusivity in the interstitial extracellular and perivenous spaces of white matter, respectively. Age and EDSS scores were adjusted. RESULTS: Using Bayesian hypothesis testing, we show that the present data substantially favor the null model of no differences between MS and NMOSD for the diffusion MRI-based measures of the glymphatic system. The inclusion Bayes factor (BF10) of model-averaged probabilities of the group (MS, NMOSD) was 0.280 for FW and 0.236 for the ALPS index. CONCLUSION: Together, these findings suggest that glymphatic alteration associated with MS and NMOSD might be similar and common as an eventual result, albeit the disease etiologies differ. PRACTITIONER POINTS: Previous literature indicates important glymphatic system alteration in MS and NMOSD. We explore the difference between MS and NMOSD using diffusion MRI-based measures of the glymphatic system. We show support for the null hypothesis of no difference between MS and NMOSD. This suggests that glymphatic alteration associated with MS and NMOSD might be similar and common etiology.

An exploratory clinical trial of preoperative non-invasive localization before breast-conserving surgery using augmented reality technology.

PURPOSE: This single-center, randomized, prospective, exploratory clinical trial was conducted to assess the clinical efficacy of an augmented reality (AR)-based breast cancer localization imaging solution for patients with breast cancer. METHODS: This clinical trial enrolled 20 women who were diagnosed with invasive breast cancer between the ages of 19 and 80, had a single lesion with a diameter ≥ 5 mm but ≤ 30 mm, had no metastases to other organs, and had not received prior chemotherapy. All patients underwent mammography, ultrasound, computed tomography, and magnetic resonance imaging for preoperative assessment. Patients were randomly assigned to ultrasound-guided skin marking localization (USL) and AR-based localization (ARL) groups (n = 10 in each group). Statistical comparisons between USL and ARL groups were made based on demographics, radiologic features, pathological outcomes, and surgical outcomes using chi-square and Student t-tests. RESULTS: Two surgeons performed breast-conserving surgery on 20 patients. Histopathologic evaluation of all patients confirmed negative margins. Two independent pathologists evaluated the marginal distances, and there were no intergroup differences in the readers' estimates (R1, 6.20 ± 4.37 vs. 5.04 ± 3.47, P = 0.519; R2, 5.10 ± 4.31 vs. 4.10 ± 2.38, P = 0.970) or the readers' average values (5.65 ± 4.19 vs. 4.57 ± 2.84, P = 0.509). In comparing the tumor plane area ratio, there was no statistically significant difference between the two groups in terms of either reader's mean values (R1, 15.90 ± 9.52 vs. 19.38 ± 14.05, P = 0.525; R2, 15.32 ± 9.48 vs. 20.83 ± 12.85, P = 0.290) or the overall mean values of two readers combined (15.56 ± 9.11 vs. 20.09 ± 13.38, P = 0.388). Convenience, safety, satisfaction, and reusability were all superior in the AR localization group (P < 0.001) based on the two surgeons' responses. CONCLUSION: AR localization is an acceptable alternative to ultrasound-guided skin marking with no significant differences in surgical outcomes.

Development of opioid-induced hyperalgesia depends on reactive astrocytes controlled by Wnt5a signaling.

Opioids are the frontline analgesics for managing various types of pain. Paradoxically, repeated use of opioid analgesics may cause an exacerbated pain state known as opioid-induced hyperalgesia (OIH), which significantly contributes to dose escalation and consequently opioid overdose. Neuronal malplasticity in pain circuits has been the predominant proposed mechanism of OIH expression. Although glial cells are known to become reactive in OIH animal models, their biological contribution to OIH remains to be defined and their activation mechanism remains to be elucidated. Here, we show that reactive astrocytes (a.k.a. astrogliosis) are critical for OIH development in both male and female mice. Genetic reduction of astrogliosis inhibited the expression of OIH and morphine-induced neural circuit polarization (NCP) in the spinal dorsal horn (SDH). We found that Wnt5a is a neuron-to-astrocyte signal that is required for morphine-induced astrogliosis. Conditional knock-out of Wnt5a in neurons or its co-receptor ROR2 in astrocytes blocked not only morphine-induced astrogliosis but also OIH and NCP. Furthermore, we showed that the Wnt5a-ROR2 signaling-dependent astrogliosis contributes to OIH via inflammasome-regulated IL-1ß. Our results reveal an important role of morphine-induced astrogliosis in OIH pathogenesis and elucidate a neuron-to-astrocyte intercellular Wnt signaling pathway that controls the astrogliosis.

Diagnostic performance and prognostic value of CT-defined visceral pleural invasion in early-stage lung adenocarcinomas.

OBJECTIVES: To analyze the diagnostic performance and prognostic value of CT-defined visceral pleural invasion (CT-VPI) in early-stage lung adenocarcinomas. METHODS: Among patients with clinical stage I lung adenocarcinomas, half of patients were randomly selected for a diagnostic study, in which five thoracic radiologists determined the presence of CT-VPI. Probabilities for CT-VPI were obtained using deep learning (DL). Areas under the receiver operating characteristic curve (AUCs) and binary diagnostic measures were calculated and compared. Inter-rater agreement was assessed. For all patients, the prognostic value of CT-VPI by two radiologists and DL (using high-sensitivity and high-specificity cutoffs) was investigated using Cox regression. RESULTS: In 681 patients (median age, 65 years [interquartile range, 58-71]; 382 women), pathologic VPI was positive in 130 patients. For the diagnostic study (n = 339), the pooled AUC of five radiologists was similar to that of DL (0.78 vs. 0.79; p = 0.76). The binary diagnostic performance of radiologists was variable (sensitivity, 45.3-71.9%; specificity, 71.6-88.7%). Inter-rater agreement was moderate (weighted Fleiss κ, 0.51; 95%CI: 0.43-0.55). For overall survival (n = 680), CT-VPI by radiologists (adjusted hazard ratio [HR], 1.27 and 0.99; 95%CI: 0.84-1.92 and 0.63-1.56; p = 0.26 and 0.97) or DL (HR, 1.44 and 1.06; 95%CI: 0.86-2.42 and 0.67-1.68; p = 0.17 and 0.80) was not prognostic. CT-VPI by an attending radiologist was prognostic only in radiologically solid tumors (HR, 1.82; 95%CI: 1.07-3.07; p = 0.03). CONCLUSION: The diagnostic performance and prognostic value of CT-VPI are limited in clinical stage I lung adenocarcinomas. This feature may be applied for radiologically solid tumors, but substantial reader variability should be overcome. CLINICAL RELEVANCE STATEMENT: Although the diagnostic performance and prognostic value of CT-VPI are limited in clinical stage I lung adenocarcinomas, this parameter may be applied for radiologically solid tumors with appropriate caution regarding inter-reader variability. KEY POINTS: • Use of CT-defined visceral pleural invasion in clinical staging should be cautious, because prognostic value of CT-defined visceral pleural invasion remains unexplored. • Diagnostic performance and prognostic value of CT-defined visceral pleural invasion varied among radiologists and deep learning. • Role of CT-defined visceral pleural invasion in clinical staging may be limited to radiologically solid tumors.

Tomato and lemon extracts synergistically improve cognitive function by increasing brain-derived neurotrophic factor levels in aged mice.

Brain ageing, the primary risk factor for cognitive impairment, occurs because of the accumulation of age-related neuropathologies. Identifying effective nutrients that increase cognitive function may help maintain brain health. Tomatoes and lemons have various bioactive functions and exert protective effects against oxidative stress, ageing and cancer. Moreover, they have been shown to enhance cognitive function. In the present study, we aimed to investigate the effects of tomato and lemon ethanolic extracts (TEE and LEE, respectively) and their possible synergistic effects on the enhancement of cognitive function and neurogenesis in aged mice. The molecular mechanisms underlying the synergistic effect of TEE and LEE were investigated. For the in vivo experiment, TEE, LEE or their mixture was orally administered to 12-month-old mice for 9 weeks. A single administration of either TEE or LEE improved cognitive function and neurogenesis in aged mice to some extent, as determined using the novel object recognition test and doublecortin immunohistochemical staining, respectively. However, a significant enhancement of cognitive function and neurogenesis in aged mice was observed after the administration of the TEE + LEE mixture, which had a synergistic effect. N-methyl-d-aspartate receptor 2B, postsynaptic density protein 95, and brain-derived neurotrophic factor (BDNF) levels and tropomyosin receptor kinase B (TrkB)/extracellular signal-regulated kinase (ERK) phosphorylation also synergistically increased after the administration of the mixture compared with those in the individual treatments. In conclusion, compared with their separate treatments, treatment with the TEE + LEE mixture synergistically improved the cognitive function, neurogenesis and synaptic plasticity in aged mice via the BDNF/TrkB/ERK signalling pathway.

Interventional Radiology for Bleeding Ectopic Varices: Individualized Approach Based on Vascular Anatomy.

Ectopic varices are rare but potentially life-threatening conditions usually resulting from a combination of global portal hypertension and local occlusive components. As imaging, innovative devices, and interventional radiologic techniques evolve and are more widely adopted, interventional radiology is becoming essential in the management of ectopic varices. The interventional radiologist starts by diagnosing the underlying causes of portal hypertension and evaluating the afferent and efferent veins of ectopic varices with CT. If decompensated portal hypertension is causing ectopic varices, placement of a transjugular intrahepatic portosystemic shunt is considered the first-line treatment, although this treatment alone may not be effective in managing ectopic variceal bleeding because it may not sufficiently resolve focal mesenteric venous obstruction causing ectopic varices. Therefore, additional variceal embolization should be considered after placement of a transjugular intrahepatic portosystemic shunt. Retrograde transvenous obliteration can serve as a definitive treatment when the efferent vein connected to the systemic vein is accessible. Antegrade transvenous obliteration is a vital component of interventional radiologic management of ectopic varices because ectopic varices often exhibit complex anatomy and commonly lack catheterizable portosystemic shunts. Superficial veins of the portal venous system such as recanalized umbilical veins may provide safe access for antegrade transvenous obliteration. Given the absence of consensus and guidelines, a multidisciplinary team approach is essential for the individualized management of ectopic varices. Interventional radiologists must be knowledgeable about the anatomy and hemodynamic characteristics of ectopic varices based on CT images and be prepared to consider appropriate options for each specific situation. ©RSNA, 2024 Supplemental material is available for this article.

Predicting hematoma expansion in acute spontaneous intracerebral hemorrhage: integrating clinical factors with a multitask deep learning model for non-contrast head CT.

PURPOSE: To predict hematoma growth in intracerebral hemorrhage patients by combining clinical findings with non-contrast CT imaging features analyzed through deep learning. METHODS: Three models were developed to predict hematoma expansion (HE) in 572 patients. We utilized multi-task learning for both hematoma segmentation and prediction of expansion: the Image-to-HE model processed hematoma slices, extracting features and computing a normalized DL score for HE prediction. The Clinical-to-HE model utilized multivariate logistic regression on clinical variables. The Integrated-to-HE model combined image-derived and clinical data. Significant clinical variables were selected using forward selection in logistic regression. The two models incorporating clinical variables were statistically validated. RESULTS: For hematoma detection, the diagnostic performance of the developed multi-task model was excellent (AUC, 0.99). For expansion prediction, three models were evaluated for predicting HE. The Image-to-HE model achieved an accuracy of 67.3%, sensitivity of 81.0%, specificity of 64.0%, and an AUC of 0.76. The Clinical-to-HE model registered an accuracy of 74.8%, sensitivity of 81.0%, specificity of 73.3%, and an AUC of 0.81. The Integrated-to-HE model, merging both image and clinical data, excelled with an accuracy of 81.3%, sensitivity of 76.2%, specificity of 82.6%, and an AUC of 0.83. The Integrated-to-HE model, aligning closest to the diagonal line and indicating the highest level of calibration, showcases superior performance in predicting HE outcomes among the three models. CONCLUSION: The integration of clinical findings with non-contrast CT imaging features analyzed through deep learning showed the potential for improving the prediction of HE in acute spontaneous intracerebral hemorrhage patients.

A distinctive subgingival microbiome in patients with periodontitis and Alzheimer's disease compared with cognitively unimpaired periodontitis patients.

AIM: Periodontitis is caused by dysbiosis of oral microbes and is associated with increased cognitive decline in Alzheimer's disease (AD), and recently, a potential functional link was proposed between oral microbes and AD. We compared the oral microbiomes of patients with or without AD to evaluate the association between oral microbes and AD in periodontitis. MATERIALS AND METHODS: Periodontitis patients with AD (n = 15) and cognitively unimpaired periodontitis patients (CU) (n = 14) were recruited for this study. Each patient underwent an oral examination and neuropsychological evaluation. Buccal, supragingival and subgingival plaque samples were collected, and microbiomes were analysed by next-generation sequencing. Alpha diversity, beta diversity, linear discriminant analysis effect size, analysis of variance-like differential expression analysis and network analysis were used to compare group oral microbiomes. RESULTS: All 29 participants had moderate to severe periodontitis. Group buccal and supragingival samples were indistinguishable, but subgingival samples demonstrated significant alpha and beta diversity differences. Differential analysis showed subgingival samples of the AD group had higher prevalence of Atopobium rimae, Dialister pneumosintes, Olsenella sp. HMT 807, Saccharibacteria (TM7) sp. HMT 348 and several species of Prevotella than the CU group. Furthermore, subgingival microbiome network analysis revealed a distinct, closely connected network in the AD group comprised of various Prevotella spp. and several anaerobic bacteria. CONCLUSIONS: A unique microbial composition was discovered in the subgingival region in the AD group. Specifically, potential periodontal pathogens were found to be more prevalent in the subgingival plaque samples of the AD group. These bacteria may possess a potential to worsen periodontitis and other systemic diseases. We recommend that AD patients receive regular, careful dental check-ups to ensure proper oral hygiene management.

Higher Expression of Lympho-epithelial Kazal-type-Related Inhibitor-1 Fragments and Decreased Desquamation in the Lesional Skin of Nummular Eczema.

Nummular eczema, a chronic dermatitis characterized by coin-shaped lesions, was first documented in 1857. However, its pathophysiological characteristics are still not well known. To investigate differences in the regulation of the desquamation process in the stratum corneum of lesional and nonlesional skin of patients with nummular eczema and healthy control subjects, tape-stripped stratum corneum samples from patients with nummular eczema and healthy volunteers were analysed using immunofluorescence staining and western blot analysis. In the nummular eczema lesional skin, expression of desmoglein-1, desmocollin-1, and corneodesmosin exhibited a disorganized, dense or partially diffuse non-peripheral pattern with increased intensity, compared with the peripheral patterns observed in healthy or nonlesional skin, suggesting the impaired desquamation process in nummular eczema. Furthermore, although the expression of the desquamation-related serine proteases, kallikrein-related peptidase 7 and 5, was increased in nummular eczema lesional skin, the immunofluorescence staining of lympho-epithelial Kazal-type-related inhibitor-1, an endogenous inhibitor of various kallikrein-related peptidases, and its fragments were significantly increased in the nummular eczema lesional skin, suggesting its contribution to the inhibition of corneodesmosomal degradation. Therefore, the increased detection of corneodesmosomal proteins in nummular eczema lesions may be due to the increased amount of the fragments of lympho-epithelial Kazal-type-related inhibitor-1, which could contribute to delayed desquamation.

Risk Factors of Postpartum Depression Among Korean Women: An Analysis Based on the Korean Pregnancy Outcome Study (KPOS).

BACKGROUND: Postpartum depression (PPD) can negatively affect infant well-being and child development. Although the frequency and risk factors of PPD symptoms might vary depending on the country and culture, there is limited research on these risk factors among Korean women. This study aimed to elucidate the potential risk factors of PPD throughout pregnancy to help improve PPD screening and prevention in Korean women. METHODS: The pregnant women at 12 gestational weeks (GW) were enrolled from two obstetric specialized hospitals from March 2013 to November 2017. A questionnaire survey was administered at 12 GW, 24 GW, 36 GW, and 4 weeks postpartum. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale, and PPD was defined as a score of ≥ 10. RESULTS: PPD was prevalent in 16.3% (410/2,512) of the participants. Depressive feeling at 12 GW and postpartum factors of stress, relationship with children, depressive feeling, fear, sadness, and neonatal intensive care unit admission of baby were significantly associated with a higher risk of PPD. Meanwhile, high postpartum quality of life and marital satisfaction at postpartum period were significantly associated with a lower risk of PPD. We developed a model for predicting PPD using factors as mentioned above and it had an area under the curve of 0.871. CONCLUSION: Depressive feeling at 12 GW and postpartum stress, fear, sadness, relationship with children, low quality of life, and low marital satisfaction increased the risk of PPD. A risk model that comprises significant factors can effectively predict PPD and can be helpful for its prevention and appropriate treatment.

Plasma-Activated Media Produced by a Microwave-Excited Atmospheric Pressure Plasma Jet Is Effective against Cisplatin-Resistant Human Bladder Cancer Cells In Vitro.

Media exposed to atmospheric pressure plasma (APP) produce reactive oxygen and nitrogen species (RONS), with hydrogen peroxide (H2O2), nitrite (NO2-), and nitrate (NO3-) being among the most detected species due to their relatively long lifetime. In this study, a standardized microwave-excited (ME) APP jet (APPJ) source was employed to produce gaseous RONS to treat liquid samples. The source was a commercially available plasma jet, which generated argon plasma utilizing a coaxial transmission line resonator at the operating frequency of 2.45 GHz. An ultraviolet-visible spectrophotometer was used to measure the concentrations of H2O2 and NO3- in plasma-activated media (PAM). Three different types of media (deionized water, Hank's balanced salt solution, and cell culture solution Dulbecco's modified eagles medium [DMEM]) were utilized as liquid samples. Among these media, the plasma-treated DMEM was observed to have the highest levels of H2O2 and NO3-. Subsequently, the feasibility of using argon ME-APPJ-activated DMEM (PAM) as an adjuvant to enhance the therapeutic effects of cisplatin on human bladder cancer cells (T-24) was investigated. Various cancer cell lines, including T-24 cells, treated with PAM were observed in vitro for changes in cell viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. A viability reduction was detected in the various cancer cells after incubation in PAM. Furthermore, the study's results revealed that PAM was effective against cisplatin-resistant T-24 cells in vitro. In addition, a possible connection between HER expression and cell viability was sketched.

Deciphering the Role of ERBB3 Isoforms in Renal Cell Carcinoma: A Comprehensive Genomic and Transcriptomic Analysis.

ERBB3, a key member of the receptor tyrosine kinase family, is implicated in the progression and development of various human cancers, affecting cellular proliferation and survival. This study investigated the expression of ERBB3 isoforms in renal clear cell carcinoma (RCC), utilizing data from 538 patients from The Cancer Genome Atlas (TCGA) Firehose Legacy dataset. Employing the SUPPA2 tool, the activity of 10 ERBB3 isoforms was examined, revealing distinct expression patterns in RCC. Isoforms uc001sjg.3 and uc001sjh.3 were found to have reduced activity in tumor tissues, while uc010sqb.2 and uc001sjl.3 demonstrated increased activity. These variations in isoform expression correlate with patient survival and tumor aggressiveness, indicating their complex role in RCC. The study, further, utilizes CIBERSORTx to analyze the association between ERBB3 isoforms and immune cell profiles in the tumor microenvironment. Concurrently, Gene Set Enrichment Analysis (GSEA) was applied, establishing a strong link between elevated levels of ERBB3 isoforms and critical oncogenic pathways, including DNA repair and androgen response. RT-PCR analysis targeting the exon 21-23 and exon 23 regions of ERBB3 confirmed its heightened expression in tumor tissues, underscoring the significance of alternative splicing and exon utilization in cancer development. These findings elucidate the diverse impacts of ERBB3 isoforms on RCC, suggesting their potential as diagnostic markers and therapeutic targets. This study emphasizes the need for further exploration into the specific roles of these isoforms, which could inform more personalized and effective treatment modalities for renal clear cell carcinoma.

Aging Aggravates Periodontal Inflammatory Responses and Alveolar Bone Resorption by Porphyromonas gingivalis Infection.

Periodontitis is a chronic inflammatory disease driven by periodontal pathogens such as Porphyromonas gingivalis (P. gingivalis), and its prevalence increases with age. However, little is known about the effect of immunosenescence on inflammatory response to P. gingivalis infection. In the present study, 16S rDNA sequencing analysis showed the relative abundance of P. gingivalis was significantly higher in periodontitis patients than healthy group, but there was no difference between the young (20 to 40 years old) and old (65 to 86 years old) periodontitis groups. Furthermore, the cytotoxic effect of P. gingivalis was greater on old THP-1 macrophages and on bone mar-row-derived cells (BMDMs) from old mice, and levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-12 were higher in old than in young THP-1 macrophages. Furthermore, the activations of inflammasome components for IL-1ß production by P. gingivalis infection were greater in old THP-1 macrophages. Finally, bone loss was significantly greater in P. gingivalis-infected aged mice than in young mice. These findings indicate that aging aggravates P. gingivalis-induced inflammatory cytokine secretion and inflammasome activation. The study enhances understanding of the relationship between periodontal immunosenescence and inflammatory response in the elderly.

Spinal GABAergic disinhibition allows microglial activation mediating the development of nociplastic pain in male mice.

Previously we developed a murine model in which postinjury stimulation of an injured area triggers a transition to a nociplastic pain state manifesting as persistent mechanical hypersensitivity outside of the previously injured area. This hypersensitivity was maintained by sex-specific mechanisms; specifically, activated spinal microglia maintained the hypersensitivity only in males. Here we investigated whether spinal microglia drive the transition from acute injury-induced pain to nociplastic pain in males, and if so, how they are activated by normally innocuous stimulation after peripheral injury. Using intraplantar capsaicin injection as an acute peripheral injury and vibration of the injured paw as postinjury stimulation, we found that inhibition of spinal microglia prevents the vibration-induced transition to a nociplastic pain state. The transition was mediated by the ATP-P2X4 pathway, but not BDNF-TrkB signaling. Intrathecally injected GABA receptor agonists after intraplantar capsaicin injection prevented the vibration-induced transition to a nociplastic pain state. Conversely, in the absence of intraplantar capsaicin injection, intrathecally injected GABA receptor antagonists allowed the vibration stimulation of a normal paw to trigger the transition to a spinal microglia-mediated nociplastic pain state only in males. At the spinal level, TNF-α, IL-1ß, and IL-6, but not prostaglandins, contributed to the maintenance of the nociplastic pain state in males. These results demonstrate that in males, the transition from acute injury-induced pain to nociplastic pain is driven by spinal microglia causing neuroinflammation and that peripheral injury-induced spinal GABAergic disinhibition is pivotal for normally innocuous stimulation to activate spinal microglia.

Ideal Size Range for Embolic Agents in Interventional Oncology Experiments Involving Rat Models of Hepatocellular Carcinoma.

PURPOSE: To optimize future translational research, this study aimed to determine the ideal range of sizes for embolic agents in interventional oncology experiments utilizing rat models of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty-five male Sprague-Dawley rats were divided into 2 groups to evaluate the distribution of microparticles and tumor response rates. After implanting hepatoma cells into the rodent liver, fluorescent microparticles of sizes ranging from 5 to 35 µm were administered via the hepatic artery. In the first group, the distribution of microparticles was evaluated in hepatoma-free rats, and the tumor necrosis rates following administration of a predetermined aliquot of microparticles (0.4 mL) were measured in tumor-bearing rats. Thereafter, the 3 microparticle sizes associated with the best tumor response rates were chosen for analysis of the tumor necrosis rates following hepatic artery embolization until angiographic stasis is achieved in the second group. RESULTS: The tendency for microparticles to distribute in nontarget organs increased as the microparticle size decreased below 15 µm. Tumor necrosis rates tended to be higher in rats treated with 15-19-µm microparticles than in those treated with 19-24-µm or 19-24-µm microparticles. The in-group deviation of the tumor necrosis rates was highest for microparticle sizes of 19-24 and 25-35 µm, which implies the proximal embolization of the hepatic artery for larger microparticle sizes. However, there was no statistical significance among the 3 groups (P = .095). CONCLUSIONS: The 15-19-µm embolic agents were the most favorable for causing tumor necrosis without nontarget toxicity in the transarterial treatments of rat HCC models.

Radiologic Extranodal Extension of Metastatic Lymph Nodes in Patients With Non-Small Cell Lung Cancer: Prognostic Utility and Diagnostic Performance.

BACKGROUND. Pathologic extranodal extension (ENE) in metastatic lymph nodes (LNs) has been associated with unfavorable prognosis in patients with non-small cell lung cancer (NSCLC). OBJECTIVE. The purpose of this article was to evaluate the prognostic utility of radiologic ENE and its diagnostic performance in predicting pathologic ENE in patients with NSCLC. METHODS. This retrospective study included 382 patients (mean age, 67 ± 10 [SD] years; 297 men, 85 women) diagnosed with NSCLC and clinical N1 or N2 disease between January 2010 and December 2016. Two thoracic radiologists reviewed staging chest CT examinations to record subjective overall impression for radiologic ENE (no ENE, possible/probable ENE, or unambiguous ENE), reviewing 30 examinations in consensus and the remaining examinations independently. Kaplan-Meier survival analysis and multivariable Cox proportional hazards model were used to evaluate the utility of radiologic ENE in predicting overall survival (OS). Prognostic utility of radiologic ENE was also assessed in patients with clinical N2a disease. In patients who underwent surgery, sensitivity and specificity were determined of radiologic unambiguous ENE in predicting pathologic ENE. RESULTS. The 5-year OS rates for no ENE, possible/probable ENE, and unambiguous ENE were 44.4%, 39.1%, and 20.9% for reader 1 and 45.7%, 36.6%, and 25.6% for reader 2, respectively. Unambiguous ENE was an independent prognostic factor for worse OS (reader 1: adjusted HR, 1.72, p = .008; reader 2: adjusted HR, 1.56, p = .03), whereas possible/probable ENE was not (reader 1: adjusted HR, 1.18, p = .33; reader 2: adjusted HR, 1.21, p = .25). In patients with clinical N2a disease, 5-year OS rate in patients with versus without unambiguous ENE for reader 1 was 22.2% versus 40.6% (p = .59) and for reader 2 was 27.6% versus 41.0% (p = .49). In 203 patients who underwent surgery (66 with pathologic ENE), sensitivity and specificity of radiologic unambiguous ENE for predicting pathologic ENE were 11% and 93% for reader 1 and 23% and 87% for reader 2. CONCLUSION. Radiologic unambiguous ENE was an independent predictor of worse OS in patients with NSCLC. The finding had low sensitivity but high specificity for pathologic ENE. CLINICAL IMPACT. Radiologic ENE may have a role in NSCLC staging workup and treatment selection.

Hepatocellular Carcinoma Supplied by the Inferior Phrenic Artery or Cystic Artery: Anatomic and Technical Considerations.

Intra-arterial treatment has been identified as one of the mainstays in the management of unresectable hepatocellular carcinoma. A thorough knowledge of tumor arterial supply enables selective therapy, which improves both safety and efficacy. The inferior phrenic artery (IPA) is the most common extrahepatic collateral artery that feeds hepatocellular carcinoma. The bilateral IPAs are known to have a specific vascular anatomy. A systemic-to-pulmonary shunt and a gastric branch from the IPAs may be present and should not be confused with tumor blush. The supraceliac aorta and celiac trunk are the common origin sites of the IPAs, and their orifice may be compressed by the diaphragm. Various techniques and catheters are used for catheterization of the IPAs, depending on their origin sites. Because the IPA is normally connected with the intercostal, internal mammary, retroperitoneal, and hepatic arteries, its hemodynamics may be altered when its orifice is occluded. In general, superselective chemoembolization via the target branch of the IPA is safe and effective. When a systemic-to-pulmonary shunt from the IPA is adequately embolized with coils or particles, radioembolization through the IPA can be performed safely in most cases. The cystic artery branches into deep and superficial cystic arteries; deep cystic arteries often supply tumors near the gallbladder. Chemoembolization through the cystic artery is relatively safe, with transient embolic materials. Radioembolization through the cystic artery has been recently tried, with acceptable efficacy and toxicity results, but it requires further investigation. ©RSNA, 2022.

A neuron-to-astrocyte Wnt5a signal governs astrogliosis during HIV-associated pain pathogenesis.

Chronic pain is the most common neurological disorder of HIV patients. Multiple neuropathologies were identified in the pain pathway. Among them is the prominent astrocytic reaction (also know an astrogliosis). However, the pathogenic role and mechanism of the astrogliosis are unclear. Here, we show that the astrogliosis is crucial for the pain development induced by a key neurotoxic HIV protein gp120 and that a neuron-to-astrocyte Wnt5a signal controls the astrogliosis. Ablation of astrogliosis blocked the development of gp120-induced mechanical hyperalgesia, and concomitantly the expression of neural circuit polarization in the spinal dorsal horn. We demonstrated that conditional knockout of either Wnt5a in neurons or its receptor ROR2 in astrocytes abolished not only gp120-induced astrogliosis but also hyperalgesia and neural circuit polarization. Furthermore, we found that the astrogliosis promoted expression of hyperalgesia and NCP via IL-1ß regulated by a Wnt5a-ROR2-MMP2 axis. Our results shed light on the role and mechanism of astrogliosis in the pathogenesis of HIV-associated pain.

Dasatinib Attenuates Fibrosis in Keloids by Decreasing Senescent Cell Burden.

Keloids are skin tumours caused by aberrant growth of dermal fibroblasts. Cellular senescence contributes to aging and various pathological conditions, including cancer, atherosclerosis, and fibrotic diseases. However, the effects of cellular senescence and senolytic drugs on keloids remain largely unknown. This study investigated senescent fibroblasts in keloids and assessed the effects of dasatinib on these cells. Tissues acquired from keloid removal surgery were analysed for senescence-associated ß-galactosidase-positive cells, p16 expression, and the effects of dasatinib treatment on keloids. Keloid tissue was xenotransplanted into mice, and the effect of intralesional dasatinib injection on keloid growth was observed. The results showed that the numbers of ß-galactosidase-positive and p16-expressing cells were higher in the keloids compared with in the controls. Dasatinib induced selective clearance of senescent cells and decreased procollagen expression in cultured keloid fibroblasts. In this xenotransplant keloid mouse model, intralesional injection of dasatinib reduced gross keloid tissue weight and the expression of both procollagen and p16. In addition, dasatinib-treated keloid fibroblasts conditioned medium reduced procollagen and p16 expression in cultured keloid fibroblasts. In conclusion, these results suggest that an increased number of senescent fibroblasts may play an important role in the pathogenesis of keloids. Therefore, dasatinib could be an alternative treatment for patients with keloids.

C-Arm Computed Tomographic Image Fusion for Repetitive Transarterial Chemoembolization of Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to evaluate the potential implications of fusion imaging with C-arm computed tomography (CACT) scans for repetitive conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma. MATERIALS AND METHODS: Fifty-six cTACE sessions were performed using fusion CACT images from September 2020 to June 2021 in a tertiary referral center, and the data were retrospectively analyzed. Fusion of unenhanced and enhanced CACT images was considered when previously accumulated iodized oil hampered the identification of local tumor progression or intrahepatic distant metastasis (indication A), when a tumor was supplied by multiple arteries with different origins from the aorta and missing tumor enhancement was suspected (indication B), or when iodized oil distribution on immediate post-cTACE CACT images needed to be precisely compared with the pre-cTACE images (indication C). Fusion image quality, initial tumor response, time to local progression (TTLP) of index tumors, and time to progression (TTP) were evaluated. RESULTS: The fusion quality was satisfactory with a mean misregistration distance of 1.4 mm. For the 40 patients with indication A, the initial tumor responses at 3 months were nonviable, equivocal, and viable in 27 (67.5%), 4 (10.0%), and 9 (22.5%) index tumors, respectively. The median TTLP and TTP were 14.8 months and 4.5 months, respectively. For 10 patients with indication B, the median TTLP and TTP were 8.3 months and 2.6 months, respectively. Among the 6 patients with indication C, 2 patients were additionally treated at the same cTACE session after confirming incomplete iodized oil uptake on fusion imaging. CONCLUSIONS: Fusion CACT images are useful in patients with hepatocellular carcinoma undergoing repetitive cTACE.