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Abstract Background Platinum-containing anti-cancer drugs such as cisplatin are widely used for patients with various types of cancers, however, resistance to cisplatin is observed in some cases. Whereas we have recently reported that high dose UV-C (200 J/m²) induces colorectal cancer cell proliferation by desensitization of EGFR, which leads oncogenic signaling in these cells, in this study we investigated the combination effect of low dose cisplatin (10 μM) and low dose UV-C (10 J/m²) on cell growth and apoptosis in several human colorectal cancer cells, SW480, DLD-1, HT29 and HCT116. Results The combination inhibited cell cycle and colony formation, while either cisplatin or UV-C alone had little effect. The combination also induced apoptosis in these cells. In addition, the combination caused the downregulation of EGFR and HER2. Moreover, UV-C alone caused the transient internalization of the EGFR, but with time EGFR recycled back to the cell surface, while cisplatin did not affect its localization. Surprisingly, the combination caused persistent internalization of the EGFR, which results in the lasting downregulation of the EGFR. Conclusions The combination of low dose cisplatin and low dose UV-C synergistically exerted anti-cancer effect by down-regulating RTK, such as EGFR and HER2. These findings may provide a novel strategy for the treatment of patients with colorectal cancer.

Abstract Background Alternating ibuprofen and acetaminophen for the treatment of febrile children is a prevalent practice among physicians and parents, despite the lack of evidence on effectiveness or safety. This randomized, double-blind and placebo-controlled clinical trial aims at comparing the antipyretic effectiveness and safety of a single administration of alternating ibuprofen and acetaminophen doses to that of ibuprofen mono-therapy in febrile children. Methods Seventy febrile children were randomly allocated to receive either a single oral dose of 10 mg/kg ibuprofen and 15 mg/kg oral acetaminophen after 4 hours, or a similar dose of ibuprofen and placebo at 4 hours. Rectal temperature was measured at baseline, 4, 5, 6, 7 and 8 hours later. Endpoints included proportions of afebrile children at 6, 7 and 8 hours, maximum decline in temperature, time to recurrence of fever, and change in temperature from baseline at each time point. Intent-to-treat analysis was planned with statistical significance set at P < 0.05. Results A higher proportion of subjects in the intervention group (83.3%) became afebrile at 6 hours than in the control group (57.6%); P = 0.018. This difference was accentuated at 7 and 8 hours (P < 0.001) with a significantly longer time to recurrence of fever in the intervention group (mean ± SD of 7.4 ± 1.3 versus 5.7 ± 2.2 hours), P < 0.001. Odds ratios (95%CI) for defervescence were 5.6 (1.3; 23.8), 19.5 (3.5; 108.9) and 15.3 (3.4; 68.3) at 6, 7 and 8 hours respectively. Two-way ANOVA with repeated measures over time revealed a significantly larger decline in temperature in the intervention group at times 7 (P = 0.026) and 8 (P = 0.002) hours. Conclusion A single dose of alternating ibuprofen and acetaminophen appears to be a superior antipyretic regimen than ibuprofen mono-therapy. Further studies are needed to confirm these findings.

This paper is a multi-institutional review of image-guided renal parenchymal biopsies. Among the topics covered are indications, preprocedural considerations, biopsy technique, complications, and postprocedural management. Both native kidney and transplant kidney biopsies are considered in this review., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intracranial aneurysms (IAs) affect 1%-5% of the public and are a major cause of subarachnoid hemorrhage. Currently, there is no medical treatment to prevent the progression or rupture of IAs. Recent studies have defined IA as a chronic inflammatory disease in which macrophages infiltrate intracranial arteries via the CCL2-CCR2 axis. The chemokine signal regulator FROUNT mediates this axis, and it can be inhibited by the anti-alcoholism drug disulfiram. Therefore, inhibition of macrophage infiltration by interfering with FROUNT using disulfiram may represent a strategy to prevent exacerbation of IAs. Here, effects of disulfiram were investigated in vitro and in an animal model of IAs. FROUNT expression was observed on infiltrated macrophages both in human IAs and in the rat IA model by immunohistochemistry. In vitro treatment with disulfiram suppressed CCL2-mediated migration of cultured rat macrophages in a transwell system. Disulfiram administered in a rat model of IAs inhibited both the initiation and the enlargement of IAs in a dose-dependent manner; this was accompanied by suppression of macrophage infiltration. These results suggest that pharmacological inhibition of the CCL2-CCR2-FROUNT signaling cascade could be a treatment of patients with IAs., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The inferior mesenteric artery (IMA) and inferior mesenteric vein (IMV) supply and drain blood from the distal colon and rectum, respectively. Routinely imaged at cross-sectional imaging of the abdomen and pelvis, these vessels play a vital role in gastrointestinal tract health but may be neglected due to their diminutive caliber relative to other mesenteric vessels and potential lack of inclusion in routine search patterns. The authors describe and illustrate normal and abnormal appearances of the IMA and IMV and findings that are diagnostic of primary vascular abnormalities or can offer diagnostic clues. After the embryologic features, normal anatomy, and anatomic variants of the IMA and IMV are reviewed, various manifestations of IMA and IMV abnormalities, such as aneurysm and pseudoaneurysm, stenosis, occlusion, dissection, hemorrhage, arteriovenous malformations and fistulas, tumoral invasion, vasculitis, and perivascular lymphatic dilatation, are explored with use of case examples. The role of the IMA and IMV as collateral vasculature, including the clinical scenarios of superior mesenteric arterial occlusion, aortic endoleak, and portosystemic venous shunt, are discussed. Finally, diagnostic clues that the inferior mesenteric vessels and adjacent soft tissues can provide, including mesenteric venous gas, compression or displacement from bowel volvulus or internal hernias, lymphadenopathy, and venous flow artifacts, are highlighted. The authors provide a comprehensive reference for radiologists who evaluate the IMA and IMV on cross-sectional images and shine a spotlight on these neglected but important vessels. © RSNA, 2024 Supplemental material is available for this article.

As the use of cross-sectional abdominal and pelvic imaging has increased exponentially in the past several decades, incidental musculoskeletal findings have become commonplace. These are often unrelated to the indication for the examination and are frequently referred to as the "radiologist's blind spot" on these studies. The differential diagnosis for abnormalities of the paraspinal and pelvic musculature is, in many cases, quite different from the anterior abdominal wall muscles. Furthermore, due to their relatively deep location, pathology involving the former muscle groups is more likely to be clinically occult, often presenting only incidentally when the patient undergoes cross-sectional imaging. Effective treatment of diseases of these muscles is dependent on adherence to a diverse set of diagnostic and treatment algorithms. The purpose of this review article is to familiarize the radiologist with the unique pathology of these often-overlooked muscles of the abdomen and pelvis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Study Aims: There is an increasing trend to inappropriately prescribe proton pump inhibitors (PPIs) in different clinical settings despite the reported adverse outcomes. This study aimed to assess (1) the prevalence of potentially inappropriate use of PPIs and its associated risk factors among hospitalized patients, at pre-admission and discharge and (2) the prevalence of valid indications of PPIs use without prescription., Patients and Methods: A retrospective observational study was performed at a single center, examining the records of patients aged ≥18 years who were admitted to the Family Medicine inpatient service over a one-year period. The appropriateness of PPIs use was assessed against a set of pre-approved indications., Results: A total of 289 patients were included in the analysis. Of these, 34.67 % were taking PPIs upon admission, increasing to 43.67 % at discharge (p < 0.001). Inappropriate PPI use was identified in 51.92 % at pre-admission and 57.25 % at discharge. Multivariate analysis identified significant factors contributing to inappropriate PPI use: polypharmacy at both admission and discharge (OR = 4.587, p = 0.031), and the presence of two or more comorbidities at discharge (OR = 5.421, p = 0.011; OR = 13.005, p = 0.037). Age ≤65 was associated with increased inappropriate use only at discharge (p < 0.003). Conversely, appropriate prescribing was noted in patients over 65 and those on antiplatelet therapy, aligning with clinical guidelines., Conclusions: This study reveals a high prevalence of inappropriate PPI use among hospitalized patients, notably increasing from admission to discharge. Key contributors to inappropriate PPI usage included polypharmacy and high comorbidity scores at discharge, particularly in patients under 65. This emphasizes the need for targeted interventions to optimize PPI prescribing practices in clinical settings., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Subarachnoid hemorrhage due to rupture of intracranial aneurysms has a poor outcome, making this disease being the social problem. Inflammation evoked by the increase in intracranial pressure and the clot in the subarachnoid space after the onset of SAH exacerbates neuronal death and vasospasm, resulting in the poor outcome and severe aftereffects. Here, FROUNT mediates CCR2 and CCR5 signaling as an intracellular molecule binding to these chemoattractant receptors which facilitate the migration of inflammatory cells, such as macrophages, in situ to trigger inflammation there. Animal model of subarachnoid hemorrhage was established in rats through intrathecal injection of autologous blood. The effect of the FROUNT inhibitor, disulfiram, on survival rate, neuronal death in hippocampus or vasospasm was then examined. The intrathecal administration of disulfiram significantly suppressed the infiltration of CD68-positive macrophages and myeloperoxidase-positive neutrophils toward the clot in the cistern in situ. In this condition, disulfiram ameliorated the death of animals after the onset of subarachnoid hemorrhage in rats. In addition, disulfiram suppressed both the two major events after subarachnoid hemorrhage, the neuronal death in hippocampus and vasospasm. The pharmacological inhibition of CCR2 and CCR5 signaling by disulfiram could thus be the therapeutic strategy to improve the outcome of subarachnoid hemorrhage., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: Perianal fistulas on 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) can be an incidental site of FDG uptake in patients undergoing PET for other indications. There are no longitudinal studies describing FDG uptake patterns in perianal fistulas. Therefore, we aimed to analyze changes in FDG uptake over time in patients with incidental perianal fistulas., Patients and Methods: Patients who underwent at least two FDG-PET/CTs between January 2011 and May 2023, with incidental perianal fistula, were retrospectively identified. We analyzed all sequential PET/CTs to determine the presence of a perianal fistula and recorded the fistula's maximum standardized uptake value (SUV max ). Statistical analysis compared fistula FDG-avidity in the initial versus final PET/CT examinations and assessed the correlation between initial fistula SUV max and percent change over time., Results: The study included 15 fistulas in 14 patients, with an average of 5 PET/CT examinations per patient. The average interval between the first and last PET/CT was 24 months (range: 6-64). The average initial fistula SUV max (11.28 ± 3.81) was significantly higher than the final fistula SUV max (7.22 ± 3.99) (p = 0.0067). The fistula SUV max declined by an average of 32.01 ± 35.33% with no significant correlation between initial fistula SUV max and percent change over time (r = -0.213, p = 0.443, 95% CI -0.66-0.35)., Conclusion: FDG uptake in perianal fistulas shows temporal fluctuations but follows a decreasing SUV max trend, possibly indicating a relationship with inflammatory activity. Further studies with larger cohorts paired with perianal fistula pelvic MR imaging are needed to validate these observations and their utility in guiding further management., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. David H. Ballard reports a relationship with Takeda Pharmaceutical Company Limited that includes: funding grants. Dr. Parakkal Deepak reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory and funding grants. Dr. Parakkal Deepak reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory and funding grants. Dr. Parakkal Deepak reports a relationship with Boehringer Ingelheim Pharmaceuticals Inc that includes: consulting or advisory and funding grants. Dr. Parakkal Deepak reports a relationship with AbbVie Inc that includes: consulting or advisory and funding grants. Dr. Parakkal Deepak reports a relationship with CorEvitas LLC that includes: consulting or advisory. Dr. Parakkal Deepak reports a relationship with Takeda Pharmaceuticals USA Inc that includes: consulting or advisory and funding grants. Dr. Parakkal Deepak reports a relationship with Sandoz Inc that includes: consulting or advisory. Dr. Parakkal Deepak reports a relationship with Landos Biopharma that includes: funding grants. Dr. Parakkal Deepak reports a relationship with Pfizer Inc that includes: consulting or advisory and funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Ultrasound (US) is the imaging modality of choice for evaluation of superficial palpable lesions. A large proportion of these lesions have characteristic sonographic appearance and can be confidently diagnosed with US without the need for biopsy or other intervention. The Society of Radiologists in Ultrasound (SRU) recently published a Consensus Conference Statement on superficial soft tissue masses. The goal of this manuscript is (a) to serve as a sonographic pictorial review for palpable lesions based on the SRU statement, (b) present the typical sonographic features of palpable lesions that can be confidently diagnosed with US, and (c) provide an overview of other palpable lesions with a framework to interpret the US studies and advise on appropriate further management., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intracranial aneurysms (IA) affect 1-5 % of the population and are a major cause of subarachnoid hemorrhage. Thus, preventing IA development and progression is crucial for public health. IA has been considered a non-physiological, high shear stress-induced chronic inflammatory disease affecting the bifurcation site of the intracranial arteries. Therefore, factors that sense high shear stress and induce IAs by triggering inflammation could potentially act as therapeutic targets. P2RX4 is a member of the purinoreceptor family that converts the strength of shear stress into intracellular signals. To verify its therapeutic potential, we investigated the effects of P2RX4 and a selective antagonist on the formation of IAs. Results showed that P2RX4 deficiency significantly suppressed the formation of IAs. Consistently, the selective P2RX4 antagonist NC-2600, which potently inhibited Ca 2+ influx in response to shear-stress loading in endothelial cells in vitro, significantly suppressed the formation of IAs. The results of the present study contribute to our understanding of the pathogenesis of IAs and may provide benefits to society through the future development of medical therapies targeting P2RX4., Competing Interests: Declaration of competing interest Authors declare that there are no potential conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The radiologic diagnosis of biliary disease can be challenging due to atypical or delayed presentation, rare or less common entities, and imaging overlap of benign and malignant processes. Establishing a specific diagnosis, when possible, is important to avoid progression of infections to sepsis and multiorgan failure, and for appropriate staging and management in cases of malignancy. Gallstones are the most common biliary disease, and along with stone-related complications, including cholecystitis and choledocholithiasis, constitute the majority of acute biliary pathology. Late and atypical manifestations of acute cholecystitis demonstrate imaging overlap with primary gallbladder cholangiocarcinoma, especially with cases of exuberant inflammatory reaction such as xanthogranulomatous cholecystitis. Additional challenging scenarios related to gallbladder disease, that may be benign or malignant, include adjacent fistulas and lymphadenopathy. Dropped gallstones, especially in atypical locations, may be misdiagnosed as neoplastic. Recurrent cholecystitis after cholecystectomy, whether related to subtotal cholecystectomy or to stumpitis, is another entity that can be confusing to the radiologist with a documented history of cholecystectomy. Inflammatory and autoimmune conditions, such as pseudotumors and IgG4 disease, are a less common but not infrequent cause of diagnostic dilemma. Furthermore, biliary strictures and hepatobiliary cystic lesions can be benign or malignant and could constitute a diagnostic and management challenge. The goal of this manuscript is to present the lessons learned from multidisciplinary conferences on the above entities and suggest tips and pearls to maximize the value of radiologists' contribution to patient management., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

PET and MRI both play valuable roles in the management of hepatobiliary and pancreatic (HBP) malignancies. Simultaneous PET/MRI combines the excellent soft-tissue resolution and anatomic details from MRI with functional information from PET in a single comprehensive examination. MRI is the main imaging modality in evaluating HCC, playing important roles in screening, characterization, local extent, and evaluating tumor response, whereas 18 F-fluorodeoxyglucose (FDG) PET can help evaluate for lymph node involvement and metastatic disease. In cholangiocarcinoma and pancreatic malignancies, both PET and MRI have excellent utility in initial staging as well as assessing treatment response. In all HBP malignancies, FDG-PET/MRI is a unique problem-solving tool in complex cases and diagnostic challenges, especially after locoregional therapy and when differentiating residual or recurrent viable disease from inflammatory and other benign processes. In this manuscript, we review the role of PET/MRI in the diagnosis, staging, assessing treatment response, and characterizing post-treatment processes. With the introduction of multiple new tracers, the value of PET/MRI has not yet been fully realized, and more studies are needed to demonstrate the utility and efficacy of PET/MRI in improving patient care in hepatobiliary and pancreatic oncology., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In oncologic PET, the SUV and standardized uptake ratio (SUR) of a viable tumor generally increase during the postinjection period. In contrast, the net influx rate ( K i ), which is derived from dynamic PET data, should remain relatively constant. Uptake-time-corrected SUV (cSUV) and SUR (cSUR) have been proposed as uptake-time-independent, static alternatives to K i Our primary aim was to quantify the intrascan repeatability of K i , SUV, cSUV, SUR, and cSUR among malignant lesions on PET/CT. An exploratory aim was to assess the ability of cSUR to estimate K i Methods: This prospective, single-center study enrolled adults undergoing standard-of-care oncologic PET/CT. SUV and K i images were reconstructed from dynamic PET data obtained before (∼35-50 min after injection) and after (∼75-90 min after injection) standard-of-care imaging. Tumors were manually segmented. Quantitative metrics were extracted. cSUVs and cSURs were calculated for a 60-min postinjection reference uptake time. The magnitude of the intrascan test-retest percent change (test-retest |%Δ|) was calculated. Coefficients of determination ( R 2 ) and intraclass correlation coefficients (ICC) were also computed. Differences between metrics were assessed via the Wilcoxon signed-rank test (α, 0.05). Results: This study enrolled 78 subjects; 41 subjects (mean age, 63.8 y; 24 men) with 116 lesions were analyzed. For both tracers, SUV max and maximum SUR (SUR max ) had large early-to-late increases (i.e., poor intrascan repeatability). Among [ 18 F]FDG-avid lesions ( n = 93), there were no differences in intrascan repeatability (median test-retest |%Δ|; ICC) between the maximum K i ( K i ,max ) (13%; 0.97) and either the maximum cSUV (cSUV max ) (12%, P = 0.90; 0.96) or the maximum cSUR (cSUR max ) (13%, P = 0.67; 0.94). For DOTATATE-avid lesions ( n = 23), there were no differences in intrascan repeatability between the K i ,max (11%; 0.98) and either the cSUV max (13%, P = 0.41; 0.98) or the cSUR max (11%, P = 0.08; 0.94). The SUV max , cSUV max , SUR max , and cSUR max were all strongly correlated with the K i ,max for both [ 18 F]FDG ( R 2 , 0.81-0.92) and DOTATATE ( R 2 , 0.88-0.96), but the cSUR max provided the best agreement with the K i ,max across early-to-late time points for [ 18 F]FDG (ICC, 0.69-0.75) and DOTATATE (ICC, 0.90-0.91). Conclusion: K i ,max , cSUV max , and cSUR max had low uptake time dependence compared with SUV max and SUR max The K i ,max can be predicted from cSUR max ., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Intracranial aneurysms, a major cause of subarachnoid hemorrhage(SAH), pose a significant social burden due to their poor patient outcomes. Recent studies, including those using animal models, have shed light on a new disease concept: intracranial aneurysms as a chronic inflammatory disease. This process is triggered by abnormal hemodynamic forces and mediated by immune cells like macrophages and neutrophils. The initiation of intracranial aneurysms is a two-step process. First, high wall shear stress and mechanical stretch work together to promote macrophage infiltration into the arterial walls. This infiltration is facilitated by endothelial cells and fibroblasts, which are activated to produce chemoattractants. Once the lesions enlarge, low wall shear stress and turbulent flow take over, maintaining macrophage infiltration. As the disease progresses towards rupture, infiltration creates hypoxic conditions that exacerbate the situation. These conditions, in turn, induce the formation of neovessels at the weakest point of the aneurysm and promote specific inflammatory microenvironments rich in neutrophils. The excessive tissue destruction caused by neutrophil-mediated inflammation ultimately leads to lesion rupture. Therefore, intracranial aneurysm rupture requires not only structural changes but also qualitative alterations within the chronic inflammatory environment. This suggests that factors mediating chronic inflammation could be potential targets for predicting or preventing aneurysm rupture.

Abstract: The risk of malignancy in nonvisualized ovaries on pelvic ultrasound is presumed to be close to zero per imaging correlation; the goal of this manuscript is to define the risk of malignancy in nonvisualized ovaries on pelvic ultrasound as defined by surgical pathology. Records for patients with pelvic ultrasound and surgical pathology containing the word "ovary" or "ovaries" performed at our institution between 10/1/2015 and 9/30/2021 were reviewed. Data for ovarian visualization were extracted from the radiology report and correlated with surgical pathology results within each ovary. Eighty-seven ovaries in 71 patients out of 422 ovaries (20.6%) in 215 eligible patients were not visualized on ultrasound. Twenty ovaries were excluded because imaging showed large pelvic mass, and 19 ovaries were excluded because surgical pathology for the ovary of interest was not available. A total of 48 ovaries in 37 patients were nonvisualized and had available surgical pathology. Out of 48 nonvisualized ovaries, 31 were normal on surgical pathology and 17 had abnormalities, with 15 benign lesions (12 of which were ≤1 cm in size). Two ovaries in 1 patient contained malignant lesions; although the ovaries were not visualized on ultrasound, the scan demonstrated peritoneal carcinomatosis. In conclusion, a high proportion of ovaries (20.6%, 87/422) are not visualized on pelvic ultrasound, and surgical pathology reveals ovarian lesions in 35.4% (17/48) of nonvisualized ovaries on pelvic ultrasound, with the majority being subcentimeter benign lesions. In the absence of peritoneal carcinomatosis, nonvisualized ovaries had no malignant lesions., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Intracranial aneurysm (IA) can cause subarachnoid hemorrhage or some other hemorrhagic stroke after rupture. Because of the poor outcome in spite of the intensive medical care after the onset of hemorrhage, the development of a novel therapeutic strategy like medical therapy to prevent the progression of the disease becomes a social need. As the reduction of arterial stiffness due to the degeneration of the extracellular matrix via Matrix Metalloproteinases (MMPs) becomes one of the central machineries leading to the progression of IAs through a series of studies, factors regulating the expression or the activity of MMPs could be a therapeutic target. In the present study, specimens from human IA lesions and the animal model of IAs were used to examine the expression of c-Jun N-terminal kinase (JNK) which might exacerbate expressions of MMPs in the lesions to weaken arterial walls resulting in the progression of the disease. In some human IA lesions examined, the expression of p-JNK, the activated form of JNK, could be detected mostly in the medial smooth muscle cells. In IA lesions induced in rats, the activation of JNK was induced during the progression of the disease and accompanied with the activation of downstream transcriptional factor c-Jun and importantly with the expression of MMP-2 or -9. The genetic deletion of Jnk2, not Jnk1, in mice significantly prevented the incidence of IAs with the suppression of the expression of MMP-2 or MMP-9. These results combined together have suggested the crucial role of JNK in the progression of IAs through regulating the expression of MMPs. The results from the present study provides the novel insights about the pathogenesis of IA progression and also about the therapeutic target., (© 2024. The Author(s).)

Background and Objectives: There is a need for knowledge regarding the natural course of diabetic polyneuropathy (DPN), a complication in type 2 diabetes (T2D). The aim of this study was to examine the development of DPN over time., Methods: Patients with newly diagnosed T2D, recruited from a national cohort, and controls without diabetes of similar age and sex, underwent sensory phenotyping in 2016-2018. The Toronto consensus criteria were used to classify patients into possible, probable, and confirmed DPN. For this 5-year, observational, follow-up, cohort study, all participants were invited to a reexamination combining bedside sensory examination, quantitative sensory testing (QST), nerve conduction studies (NCSs), and skin biopsies measuring intraepidermal nerve fiber density (IENFD) in order to compare phenotypic and diagnostic changes over time., Results: Of the baseline 389 patients and 97 controls, 184 patients (median [interquartile range] diabetes duration 5.9 [4.1-7.4] years, mean hemoglobin A1c [HbA1c] 51 ± 11 mmol/mol at baseline) and 43 controls completed follow-up (46.9%). Confirmed DPN was present in 35.8% and 50.3%, probable DPN in 27.2% and 14.6%, possible DPN in 17.2% and 16.6%, and no DPN in 15.2% and 17.9% at baseline and follow-up, respectively. The estimated prevalence (95% CI) of confirmed DPN was 33.5% (24.9-42.1) compared with 22.7% (17.5-28.0) at baseline. During the follow-up period, 43.9% of patients with probable DPN developed confirmed DPN. Progression of neuropathy occurred in 16.5% and 24.7% and regression in 5.9% and 18.6% of patients based on NCS and IENFD, respectively. Progression based on NCS and/or IENFD was associated with higher baseline waist circumference and triglycerides, and regression with lower baseline HbA1c. Patients with at least probable DPN at baseline but neither patients without DPN nor controls developed increased spread of hyposensitivity, more hyposensitivity on QST and lower NCS z -scores at follow-up, and worsening of nerve parameters at follow-up correlated with higher baseline triglycerides., Discussion: In patients with well-regulated T2D, the proportion of patients with confirmed DPN increased over 5 years driven by progression from probable DPN. A large proportion of patients progressed, and a smaller proportion regressed on nerve parameters. Higher triglycerides correlated with this progression and may constitute a risk factor.

Rationale and Objectives: The use of 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) in assessing inflammatory diseases has shown significant promise. Uptake patterns in perianal fistulas, which may be an incidental finding on PET/CT, have not been purposefully studied. Our aim was to compare FDG uptake of perianal fistulas to that of the liver and anal canal in patients who underwent PET/CT for hematologic/oncologic diagnosis or staging., Materials and Methods: We retrospectively identified patients who underwent FDG-PET/CT imaging between January 2011 and May 2023, where the report described a perianal fistula or abscess. PET/CTs of patients included in the study were retrospectively analyzed to record the maximum standardized uptake value (SUV max ) of the fistula, abscess, anal canal, rectum, and liver. Fistula-to-liver and Fistula-to-anus SUV max ratios were calculated. We statistically compared FDG activity among the fistula, liver, and anal canal. We also assessed FDG activity in patients with vs. without anorectal cancer, as well as across different St. James fistula grades., Results: The study included 24 patients with identifiable fistulas. Fistula SUV max (mean=10.8 ± 5.28) was significantly higher than both the liver (mean=3.09 ± 0.584, p < 0.0001) and the anal canal (mean=5.98 ± 2.63, p = 0.0005). Abscess fistula SUV max was 15.8 ± 4.91. St. James grade 1 fistulas had significantly lower SUV max compared to grades 2 and 4 (p = 0.0224 and p = 0.0295, respectively). No significant differences existed in SUV max ratios between anorectal and non-anorectal cancer groups., Conclusion: Perianal fistulas have increased FDG avidity with fistula SUV max values that are significantly higher than the anal canal., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. David H. Ballard reports a relationship with Takeda Pharmaceutical Company Limited that includes: funding grants. Dr. Parakkal Deepak reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory and funding grants. Dr. Parakkal Deepak reports a relationship with Pfizer Inc that includes: consulting or advisory and funding grants. Dr. Parakkal Deepak reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory and funding grants. Dr. Parakkal Deepak reports a relationship with Boehringer Ingelheim Pharmaceuticals Inc that includes: consulting or advisory and funding grants. Dr. Parakkal Deepak reports a relationship with AbbVie Inc that includes: consulting or advisory and funding grants. Dr. Parakkal Deepak reports a relationship with CorEvitas LLC that includes: consulting or advisory. Dr. Parakkal Deepak reports a relationship with Takeda Pharmaceuticals USA Inc that includes: consulting or advisory and funding grants. Dr. Parakkal Deepak reports a relationship with Sandoz Inc that includes: consulting or advisory. Dr. Parakkal Deepak reports a relationship with Landos Biopharma that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Importance: Among patients with metastatic colorectal cancer (mCRC), data are limited on disparate biomarker testing and its association with clinical outcomes on a national scale., Objective: To evaluate the socioeconomic and demographic inequities in microsatellite instability (MSI) and KRAS biomarker testing among patients with mCRC and to explore the association of testing with overall survival (OS)., Design, Setting, and Participants: This cohort study, conducted between November 2022 and March 2024, included patients who were diagnosed with mCRC between January 1, 2010, and December 31, 2017. The study obtained data from the National Cancer Database, a hospital-based cancer registry in the US. Patients with mCRC and available information on biomarker testing were included. Patients were classified based on whether they completed or did not complete MSI or KRAS tests., Exposure: Demographic and socioeconomic factors, such as age, race, ethnicity, educational level in area of residence, median household income, insurance type, area of residence, facility type, and facility location were evaluated., Main Outcomes and Measures: The main outcomes were MSI and KRAS testing between the date of diagnosis and the date of first-course therapy. Univariable and multivariable logistic regressions were used to identify the relevant factors in MSI and KRAS testing. The OS outcomes were also evaluated., Results: Among the 41 061 patients included (22 362 males [54.5%]; mean [SD] age, 62.3 [10.1] years; 17.3% identified as Black individuals, 78.0% as White individuals, 4.7% as individuals of other race, with 6.5% Hispanic or 93.5% non-Hispanic ethnicity), 28.8% underwent KRAS testing and 43.7% received MSI testing. A significant proportion of patients had Medicare insurance (43.6%), received treatment at a comprehensive community cancer program (40.5%), and lived in an area with lower educational level (51.3%). Factors associated with a lower likelihood of MSI testing included age of 70 to 79 years (relative risk [RR], 0.70; 95% CI, 0.66-0.74; P < .001), treatment at a community cancer program (RR, 0.74; 95% CI, 0.70-0.79; P < .001), rural residency (RR, 0.80; 95% CI, 0.69-0.92; P < .001), lower educational level in area of residence (RR, 0.84; 95% CI, 0.79-0.89; P < .001), and treatment at East South Central facilities (RR, 0.67; 95% CI, 0.61-0.73; P < .001). Similar patterns were observed for KRAS testing. Survival analysis showed modest OS improvement in patients with MSI testing (hazard ratio, 0.93; 95% CI, 0.91-0.96; P < .001). The median (IQR) follow-up time for the survival analysis was 13.96 (3.71-29.34) months., Conclusions and Relevance: This cohort study of patients with mCRC found that older age, community-setting treatment, lower educational level in area of residence, and treatment at East South Central facilities were associated with a reduced likelihood of MSI and KRAS testing. Highlighting the sociodemographic-based disparities in biomarker testing can inform the development of strategies that promote equity in cancer care and improve outcomes for underserved populations.

Abstract: Inflammatory increased metabolic activity was discovered in the left anal canal on an 18 F-FDG PET/CT scan performed for initial staging of anal squamous cell carcinoma in a patient with history of perianal Crohn disease. This increased uptake was due to a complex intersphincteric perianal fistula with supralevator extension, with a secondary, contiguous, superficial focus of squamous cell carcinoma at the anal verge that was identified on an MRI performed on the same day., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Patlak slope (PS) images have the potential to improve lesion conspicuity compared with standardized uptake value (SUV) images but may be more artifact-prone. This study compared PS versus SUV image quality and hepatic tumor-to-background ratios (TBRs) at matched time points. Early and late SUV and PS images were reconstructed from dynamic positron emission tomography (PET) data. Two independent, blinded readers scored image quality metrics (a four-point Likert scale) and counted tracer-avid lesions. Hepatic lesions and parenchyma were segmented and quantitatively analyzed. Differences were assessed via the Wilcoxon signed-rank test (alpha, 0.05). Forty-three subjects were included. For overall quality and lesion detection, early PS images were significantly inferior to other reconstructions. For overall quality, late PS images (reader 1 [R1]: 3.95, reader 2 [R2]: 3.95) were similar ( p > 0.05) to early SUV images (R1: 3.88, R2: 3.84) but slightly superior ( p ≤ 0.002) to late SUV images (R1: 2.97, R2: 3.44). For lesion detection, late PS images were slightly inferior to late SUV images (R1 only) but slightly superior to early SUV images (both readers). PS-based TBRs were significantly higher than SUV-based TBRs at the early time point, with opposite findings at the late time point. In conclusion, late PS images are similar to early/late SUV images in image quality and lesion detection; the superiority of SUV versus PS hepatic TBRs is time-dependent.

Sodium chloride (NaCl) activates Th17 and dendritic cells in hypertension by stimulating serum/glucocorticoid kinase 1 (SGK1), a sodium sensor. Memory T cells also play a role in hypertension by infiltrating target organs and releasing proinflammatory cytokines. We tested the hypothesis that the role of T cell SGK1 extends to memory T cells. We employed mice with a T cell deletion of SGK1, SGK1 fl/fl × tgCD4 cre mice, and used SGK1 fl/fl mice as controls. We treated the mice with L-NAME (0.5 mg/mL) for 2 weeks and allowed a 2-week washout interval, followed by a 3-week high-salt (HS) diet (4% NaCl). L-NAME/HS significantly increased blood pressure and memory T cell accumulation in the kidneys and bone marrow of SGK1 fl/fl mice compared to knockout mice on L-NAME/HS or groups on a normal diet (ND). SGK1 fl/fl mice exhibited increased albuminuria, renal fibrosis, and interferon-γ levels after L-NAME/HS treatment. Myography demonstrated endothelial dysfunction in the mesenteric arterioles of SGK1 fl/fl mice. Bone marrow memory T cells were adoptively transferred from either mouse strain after L-NAME/HS administration to recipient CD45.1 mice fed the HS diet for 3 weeks. Only the mice that received cells from SGK1 fl/fl donors exhibited increased blood pressure and renal memory T cell infiltration. Our data suggest a new therapeutic target for decreasing hypertension-specific memory T cells and protecting against hypertension., Competing Interests: None of the authors have any commercial or financial relationships that can be perceived as conflicts of interest.

Biliary duct dilatation is a common incidental finding in practice, but it is unlikely to indicate biliary obstruction in the absence of clinical symptoms or elevated levels on liver function tests (LFTs). However, the clinical presentation may be nonspecific, and LFTs may either be unavailable or difficult to interpret. The goal of this AJR Expert Panel Narrative Review is to highlight a series of topics fundamental to the management of biliary duct dilatation, providing consensus recommendations in a question-and-answer format. We start by covering a basic approach to interpreting LFT results, the strengths and weaknesses of the biliary imaging modalities, and how and where to measure the extrahepatic bile duct. Next, we define the criteria for biliary duct dilatation, including patients with prior cholecystectomy and advanced age, and discuss when and whether biliary duct dilatation can be attributed to papillary stenosis or sphincter of Oddi dysfunction. Subsequently, we discuss two conditions in which the duct is pathologically dilated but not obstructed: congenital cystic dilatation (i.e., choledochal cyst) and intraductal papillary neoplasm of the bile duct. Finally, we provide guidance regarding when to recommend obtaining additional imaging or testing, such as endoscopic ultrasound or ERCP, and include a discussion of future directions in biliary imaging.

Purpose: Disparities in cancer care have been exacerbated by the COVID-19 pandemic. The aim of this study is to establish how telehealth mitigated the effect of COVID-19 on the healthcare sector and to identify potential disparities in perception and experience with telehealth in cancer care during and after the pandemic., Methods: We identified individuals with an established cancer diagnosis who received treatment at a comprehensive academic cancer center with a diverse patient population between 2019 and 2021, during the COVID-19 pandemic. Participants were asked to complete a self-administrated survey intended to collect patient-reported outcomes on socioeconomic and mental health challenges incurred during the pandemic as well as participants' experience with telehealth. The assessment was adapted from a 21-question-based survey applied for mental health. Descriptive statistics were used to summarize participant characteristics and the response to the survey items. Multivariable logistic regression was performed to assess and analyze the contributing factors to the survey responses., Results: A total of N = 136 participants were included in this analysis. The majority of participants (60.6%) reported increased anxiety, stress, or experience of distress as a direct result of COVID-19. However, among 54.1% of survey responders participated in a telehealth appointment and 84.4% agreed it was an easy and effective experience., Conclusion: Elderly, male, and black participants reported the worst impact related to the pandemic. The majority of patients had a positive experience with telehealth. The results of the study suggest that telehealth services can serve as a tool for patients with cancer during and beyond active treatment to access supportive services., (© 2024. The Author(s).)

Abstract: Percutaneous core-needle biopsy (PCNB) plays a growing and essential role in many medical specialties. Proper and effective use of various PCNB devices requires basic understanding of how they function. Current literature lacks a detailed overview and illustration of needle function and design differences, a potentially valuable reference for users ranging from early trainees to experts who are less familiar with certain devices. This pictorial aims to provide such an overview, using diagrams and magnified photographs to illustrate the intricate components of these devices. Following a brief historical review of biopsy needle technology for context, we emphasize distinctions in design between 2 major classes of PCNB devices (side- and end-cutting devices), focusing on practical implications for how each device is most effectively used. We believe a nuanced understanding of biopsy device function sheds light on certain lingering ambiguities in biopsy practice, such as the optimal needle gauge in organ biopsy, the benefits and risks associated with coaxial technique, the impact of needle selection and technique on bleeding, and the risk of unsuccessful sampling. In a subsequent pictorial, we will draw on the concepts presented here to illustrate examples of biopsy needle failure and how unrecognized needle failure can be an important and often preventable cause of increased biopsy risk and lower tissue yield., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Metabolic syndrome comprises a set of risk factors that include abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, low high-density lipoprotein levels, and high blood pressure, at least three of which must be fulfilled for diagnosis. Metabolic syndrome has been linked to an increased risk of cardiovascular disease and type 2 diabetes mellitus. Multimodality imaging plays an important role in metabolic syndrome, including diagnosis, risk stratification, and assessment of complications. CT and MRI are the primary tools for quantification of excess fat, including subcutaneous and visceral adipose tissue, as well as fat around organs, which are associated with increased cardiovascular risk. PET has been shown to detect signs of insulin resistance and may detect ectopic sites of brown fat. Cardiovascular disease is an important complication of metabolic syndrome, resulting in subclinical or symptomatic coronary artery disease, alterations in cardiac structure and function with potential progression to heart failure, and systemic vascular disease. CT angiography provides comprehensive evaluation of the coronary and systemic arteries, while cardiac MRI assesses cardiac structure, function, myocardial ischemia, and infarction. Liver damage results from a spectrum of nonalcoholic fatty liver disease ranging from steatosis to fibrosis and possible cirrhosis. US, CT, and MRI are useful in assessing steatosis and can be performed to detect and grade hepatic fibrosis, particularly using elastography techniques. Metabolic syndrome also has deleterious effects on the pancreas, kidney, gastrointestinal tract, and ovaries, including increased risk for several malignancies. Metabolic syndrome is associated with cerebral infarcts, best evaluated with MRI, and has been linked with cognitive decline. © RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Pickhardt in this issue.

Recent studies have indicated the involvement of neutrophil-mediated inflammatory responses in the process leading to intracranial aneurysm (IA) rupture. Receptors mediating neutrophil recruitment could thus be therapeutic targets of unruptured IAs. In this study, complement C5a receptor 1 (C5AR1) was picked up as a candidate that may cause neutrophil-dependent inflammation in IA lesions from comprehensive gene expression profile data acquired from rat and human samples. The induction of C5AR1 in IA lesions was confirmed by immunohistochemistry; the up-regulations of C5AR1/C5ar1 stemmed from infiltrated neutrophils, which physiologically express C5AR1/C5ar1, and adventitial fibroblasts that induce C5AR1/C5ar1 in human/rat IA lesions. In in vitro experiments using NIH/3T3, a mouse fibroblast-like cell line, induction of C5ar1 was demonstrated by starvation or pharmacological inhibition of mTOR signaling by Torin1. Immunohistochemistry and an experiment in a cell-free system using recombinant C5 protein and recombinant Plasmin indicated that the ligand of C5AR1, C5a, could be produced through the enzymatic digestion by Plasmin in IA lesions. In conclusion, we have identified a potential contribution of the C5a-C5AR1 axis to neutrophil infiltration as well as inflammatory responses in inflammatory cells and fibroblasts of IA lesions. This cascade may become a therapeutic target to prevent the rupture of IAs., (© 2024. The Author(s).)

Background: The COVID-19 pandemic strained healthcare systems around the world. This study aims to understand the preparedness of private remote hospitals in Lebanon to respond to the pandemic and evaluate the impact of inter-hospital collaborations on the hospitals' readiness., Methods: A multi-centered study was conducted between August 2020 and June 2021 in ten Lebanese private remote hospitals based on a mixed-methods embedded approach where the quantitative supported the qualitative. Through the AUB-USAID (American University of Beirut-United States Agency for International Development) COVID-19 project, these hospitals received personal protective equipment and medical equipment in addition to COVID-19-related training using the Train-the-Trainer model. The quantitative part used knowledge and evaluation questionnaires and a pre-post-intervention hospital preparedness checklist. The qualitative approach adopted semi-structured interviews with a purposive sample from key hospital personnel. Quantitative data were analyzed using SPSS version 27, and a p -value of <0.05 was considered to be statistically significant. For the qualitative data, a thematic analysis was performed by adopting the six-phase process described by Braun and Clarke., Results: Of the 393 healthcare workers who attended the training and completed the evaluation questionnaire, 326 completed the pre- and post-training knowledge questionnaire. A significant improvement was observed in mean knowledge scores following training for infection control, nursing, and polymerase chain reaction sampling staff ( p -value < 0.001, p -value < 0.001, and p -value = 0.006, respectively), but not for housekeeping staff. More than 93% of the participants showed high trainer and content evaluation scores. As for the hospitals' preparedness assessments, there was a clear improvement in the pre- and post-assessment scores for each hospital, and there was a significant difference in the mean of the total scores of partner hospitals pre- and post-USAID-AUB project ( p -value = 0.005). These findings were supported by the qualitative analysis, where nine hospitals expressed the positive impact of the USAID-AUB intervention in improving their preparedness to respond to the COVID-19 pandemic at a critical time when it was highly needed. Despite the intervention, persistent challenges remained., Conclusions: A timely and proactive collaborative program between academic/tertiary care centers and remote community hospitals that includes sharing supplies and expertise is feasible and highly effective during public health emergencies.

Background Splenic biopsy is rarely performed because of the perceived risk of hemorrhagic complications. Purpose To evaluate the safety of large bore (≥18 gauge) image-guided splenic biopsy. Materials and Methods This retrospective study included consecutive adult patients who underwent US- or CT-guided splenic biopsy between March 2001 and March 2022 at eight academic institutions in the United States. Biopsies were performed with needles that were 18 gauge or larger, with a comparison group of biopsies with needles smaller than 18 gauge. The primary outcome was significant bleeding after the procedure, defined by the presence of bleeding at CT performed within 30 days or angiography and/or surgery performed to manage the bleeding. Categorical variables were compared using the χ 2 test and medians were compared using the Mann-Whitney test. Results A total of 239 patients (median age, 63 years; IQR, 50-71 years; 116 of 239 [48.5%] female patients) underwent splenic biopsy with an 18-gauge or smaller needle and 139 patients (median age, 58 years [IQR, 49-69 years]; 66 of 139 [47.5%] female patients) underwent biopsy with a needle larger than 18 gauge. Bleeding was detected in 20 of 239 (8.4%) patients in the 18-gauge or smaller group and 11 of 139 (7.9%) in the larger than 18-gauge group. Bleeding was treated in five of 239 (2.1%) patients in the 18-gauge or smaller group and one of 139 (1%) in the larger than 18-gauge group. No deaths related to the biopsy procedure were recorded during the study period. Patients with bleeding after biopsy had smaller lesions compared with patients without bleeding (median, 2.1 cm [IQR, 1.6-5.4 cm] vs 3.5 cm [IQR, 2-6.8 cm], respectively; P = .03). Patients with a history of lymphoma or leukemia showed a lower incidence of bleeding than patients without this history (three of 90 [3%] vs 28 of 288 [9.7%], respectively; P = .05). Conclusion Bleeding after splenic biopsy with a needle 18 gauge or larger was similar to biopsy with a needle smaller than 18 gauge and seen in 8% of procedures overall, with 2% overall requiring treatment. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Grant in this issue.

Molecular imaging plays a vital role in the management of neuroendocrine neoplasms (NENs). Somatostatin receptor (SSTR) PET is critical for evaluating NENs, ascertaining peptide receptor radionuclide therapy (PRRT) eligibility, and treatment response. SSTR-PET/MRI can provide a one-stop-shop multiparametric evaluation of NENs. The acquisition of complementary imaging information in PET/MRI has distinct advantages over PET/CT and MR imaging acquisitions. The purpose of this manuscript is to provide a comprehensive overview of PET/MRI and a current review of recent PET/MRI advances in the diagnosis, staging, treatment, and surveillance of NENs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: Thyroglossal duct cyst is the most common congenital neck mass, but the incidence of malignancy within a thyroglossal duct cyst is rare, estimated at 1%. Most cancers arising within thyroglossal duct cysts are incidentally detected after surgical excision. We present the preoperative radiologic findings of 8 patients with papillary thyroid cancer arising within a thyroglossal duct cyst, as evaluated on ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography scan., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Imagine being in a crowded room with a cacophony of speakers and having the ability to focus on or remove speech from a specific 2D region. This would require understanding and manipulating an acoustic scene, isolating each speaker, and associating a 2D spatial context with each constituent speech. However, separating speech from a large number of concurrent speakers in a room into individual streams and identifying their precise 2D locations is challenging, even for the human brain. Here, we present the first acoustic swarm that demonstrates cooperative navigation with centimeter-resolution using sound, eliminating the need for cameras or external infrastructure. Our acoustic swarm forms a self-distributing wireless microphone array, which, along with our attention-based neural network framework, lets us separate and localize concurrent human speakers in the 2D space, enabling speech zones. Our evaluations showed that the acoustic swarm could localize and separate 3-5 concurrent speech sources in real-world unseen reverberant environments with median and 90-percentile 2D errors of 15 cm and 50 cm, respectively. Our system enables applications like mute zones (parts of the room where sounds are muted), active zones (regions where sounds are captured), multi-conversation separation and location-aware interaction., (© 2023. Springer Nature Limited.)

Contrast-enhanced ultrasound (CEUS) uses intravenously injected gas microbubbles as a pure blood pool contrast agent to demonstrate blood flow and tissue perfusion at a much higher sensitivity than color Doppler and power Doppler ultrasound. CEUS has gained traction in abdominal diagnostic imaging for improved lesion detection and characterization and a complementary problem-solving tool to CT and MRI. In addition to its diagnostic applications, CEUS has also proven useful for pre-procedure planning, procedure guidance, and post-procedure evaluation. This review provides a practical overview and guides to the application of CEUS in percutaneous, ultrasound-guided, needle-driven procedures, focusing on 2 common procedures, which illustrate the many benefits of CEUS- core needle biopsy (CNB) and percutaneous hepatic lesion ablation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Inflammation is triggered by various intrinsic and extrinsic stimuli as a protective machinery to maintain homeostasis in the human body. Usually, it is magnified in intensity initially and regresses rapidly afterwards; this phenomenon is called acute inflammation. However, it occasionally lasts a long time; this phenomenon is called chronic inflammation. Induction of some specific machineries, i.e., formation of a positive feedback loop, inflammatory cell infiltration, and changes in tissue architecture, is required for the transition to chronic inflammation; this differentiates chronic and acute inflammation in nature. Chronic inflammation is a common pathogenesis of various diseases, including cancer, vascular disease, and stroke. Recent experimental studies have clarified the crucial role of inflammatory responses in the development and progression of hemorrhagic stroke mediated by tissue destruction or some other aspects of diseases. In this review, we summarize the research findings of the role of inflammation in hemorrhagic stroke.

Background: Social determinants of health thoroughly explored in the literature include insurance status, race, and ethnicity. There are over 50 million self-identifying Hispanics in the United States. This, however, represents a heterogeneous population. We used a national registry to investigate for significant differences in outcomes of Hispanic patients with non-small cell lung cancer (NSCLC) in the Unites states, by geographic region of origin., Materials and Methods: We identified a cohort of Hispanic patients in the Unites states with NSCLC for which region of origin was documented within the 2004 to 2016 National Cancer Database (NCDB) registry. This included patients from Cuba, Puerto Rico, Mexico, South and Central America, and the Dominican Republic. We performed multivariate logistic regression modeling to determine whether origin was a significant predictor of cancer staging at diagnosis, adjusting for age, sex, histology, grade, insurance status, and facility type. Race was not included due to a nonsignificant association with stage at diagnosis at the bivariate level in this cohort. Subsequently, we used Kaplan-Meier modeling to identify whether overall survival (OS) of Hispanic patients differed by origin., Results: A total of 12,557 Hispanic patients with NSCLC were included in this analysis. The breakdown by origin was as follows: n = 2071 (16.5%) Cuban, n = 2360 (18.8%) Puerto Rican, n = 4950 (39.4%) Mexican, n = 2329 (18.5%) from South or Central America, and n = 847 (6.7%) from the Dominican Republic. After controlling for age, sex, histology, grade, insurance status and treating facility type, we found that geographic origin was a significant predictor of advanced stage at diagnosis (P = .015). Compared to Cubans, patients of Puerto Rican origin were less likely to present with advanced disease (68.4% vs. 71.9%; OR: 0.82; 95%CI: 0.69-0.98; P = .026). We also identified a significant (log-rank P-value<.001) difference in OS by geographic origin, even at early-stages of diagnosis. Dominican patients with NSCLC exhibited the highest 5-year OS rate (63.3%), followed by patients from South/Central America (59.7%), Puerto Rico (52.3%), Mexico (45.9%), and Cuba (43.8%)., Conclusion: This study showed that for Hispanic individuals living in the Unites states, region/country of origin is significantly associated with outcomes, even after accounting for other known determinants of health. We suggest that region of origin should be studied further as a potential determinant of outcomes in patients with cancer., (Copyright © 2023. Published by Elsevier Inc.)

Pancreatic neuroendocrine tumors (PanNETs) in familial tuberous sclerosis (TSC1 and TSC2 mutations) have been known and studied. However, little is known about PanNET patients harboring the very rare (less than 2%) sporadic TSC mutations. Some renal tumors have been shown to harbor sporadic TSC mutations, with a distinctive morphological correlate. We hereby describe this rather unusual molecular alteration in well-differentiated pancreatic neuroendocrine tumors (WD PanNETs) with a focus on their morphology and treatment outcomes. Six cases of WD PanNETs harboring sporadic TSC mutations were identified retrospectively. H&E slides and corresponding immunostains were reviewed for all cases. Clinical, molecular, and radiological information was obtained using the electronic medical records. Cohort consisted of 4 males and 2 females. Median age at diagnosis was 50 years (range 33-74 years). Origin of neoplasm was the pancreas and, in all but one, patient had liver metastasis by the time of presentation. Six out of six cases demonstrated a unique tumor morphology, with ample eosinophilic cytoplasm. Tumors were arranged in sheets and nests; prominent cystic change was noted in one case. Two cases were additionally biopsied post-treatment with capecitabine and temozolomide, and showed even more abundant oncocytic cytoplasm, eccentric nuclei, and a prominent cherry red nucleolus, and were arranged in a cluster of 3-4 cells, separated by stromal cells. Every patient had a different TSC2 variant with no cases of TSC1 mutations. Other common variants included MEN1 (4/6), DAXX (2/6), and TP53 (2/6). Per the WH0 2019 classification, tumors were graded as NET-G3 (n = 3) and NET-G2 (n = 3). Ki-67 s ranged from 7.2 to 60. All cases had retained MMR protein expression. The majority of patients (4/6) have expired. Although they received multiple treatments, a consistent pattern observed in patients was marked radiologic response to chemotherapy with capecitabine and temozolomide (offered in 5/6 patients) with duration of responses reaching 11 months in the majority of cases, with one patient showing near complete pathologic response of localized disease. TSC2 mutations may confer distinctive appearance in WD PanNETs, reminiscent of their effects in renal tumors. Although not entirely specific, this distinct morphological pattern with abundant eosinophilic cytoplasm in WD PanNETs could be reflective of an associated TSC mutation, with suggestions of significant therapeutic response to a specific cytotoxic chemotherapy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)