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Epidemiological surveillance of nasopharyngeal pneumococcal carriage is important for monitoring serotype distribution and antibiotic resistance, particularly before and after the implementation of pneumococcal conjugate vaccines (PCVs). With a prospective surveillance study in France, we aimed to analyze the dynamics of pneumococcal carriage, antibiotic susceptibility and serotype distribution in children aged 6 to 24 months who had acute otitis media between 2001 and 2022 with a focus on the late PCV13 period from May 2014 to July 2022. Trends were analyzed with segmented linear regression with autoregressive error. For the 17,136 children enrolled, overall pneumococcal carriage was stable during the study. During the late PCV13 period, the five most frequent serotypes were all non-PCV13 serotypes: 15B/C (14.3%), 23B (11.0%), 11A (9.6%), 15A (7.4%) and 35B (6.5%). During the same period, we observed a rebound of penicillin non-susceptibility (+0.15% per month, 95% confidence interval, +0.08 to 0.22, p < 0.001). Five serotypes accounted for 64.4% of the penicillin non-susceptible strains: 11A (17.5%), 35B (14.9%), 15A (13.9%), 15B/C (9.9%) and 19F (8.2%); non-PCV13/PCV15 accounted for <1%, and non-PCV15/PCV20 accounted for 28%. The next generation PCVs, particularly PCV20, may disrupt nasopharyngeal carriage and contribute to decreasing the rate of antibiotic resistance among pneumococci.

Purpose To investigate whether liver enhancing tumor burden (LETB) assessed at contrast-enhanced CT indicates early response and helps predict survival outcomes in patients with multifocal neuroendocrine liver metastases (NELM) after intra-arterial treatment. Materials and Methods This retrospective study included patients with NELM who underwent intra-arterial treatment with transarterial embolization (TAE) or chemoembolization (TACE) between April 2006 and December 2018. Tumor response in treated NELM was evaluated by using the Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST). LETB was measured as attenuation 2 SDs greater than that of a region of interest in the nontumoral liver parenchyma. Overall survival (OS); time to unTA(C)Eable progression, defined as the time from the initial treatment until the time when intra-arterial treatments were considered technically unfeasible, either not recommended by the multidisciplinary tumor board or until death; and hepatic and whole-body progression-free survival (PFS) were evaluated using multivariable Cox proportional hazards analyses, the Kaplan-Meier method, and log-rank test. Results The study included 119 patients (mean age, 60 years ± 11 [SD]; 61 men) who underwent 161 treatments. A median LETB change of -25.8% best discriminated OS (83 months in responders vs 51 months in nonresponders; P = .02) and whole-body PFS (18 vs 8 months, respectively; P < .001). A -10% LETB change best discriminated time to unTA(C)Eable progression (32 months in responders vs 12 months in nonresponders; P < .001) and hepatic PFS (18 vs 8 months, respectively; P < .001). LETB change remained independently associated with improved OS (hazard ratio [HR], 0.56), time to unTA(C)Eable progression (HR, 0.44), hepatic PFS (HR, 0.42), and whole-body PFS (HR, 0.47) on multivariable analysis. Neither RECIST nor mRECIST helped predict patient outcome. Conclusion Response according to LETB change helped predict survival outcomes in patients with NELM after intra-arterial treatments, with better discrimination than RECIST and mRECIST. Keywords: CT, Chemoembolization, Embolization, Abdomen/GI, Liver Supplemental material is available for this article. © RSNA, 2023.

Background: to report the safety of outpatient prostatic artery embolization (PAE) after a significant learning curve., Methods: a retrospective bi-institutional study was conducted between June 2018 and April 2022 on 311 consecutive patients, with a mean age of 69 years ± 9.8 (47-102), treated by outpatient PAE. Indications included lower urinary tract symptoms, acute urinary retention, and hematuria. When needed, 3D-imaging and/or coil protection of extra-prostatic supplies were performed to avoid non-target embolization. Adverse events were monitored at 1-, 6-, and 12-month follow-ups., Results: bilateral PAE was achieved in 305/311 (98.1%). Mean dose area product/fluoroscopy times were 16,408.3 ± 12,078.9 (2959-81,608) μGy.m 2 /36.3 ± 1.7 (11-97) minutes. Coil protection was performed on 67/311 (21.5%) patients in 78 vesical, penile, or rectal supplies. Embolization-related adverse events varied between 0 and 2.6%, access-site adverse events between 0 and 18%, and were all minor. There was no major event., Conclusion: outpatient PAE performed after achieving a significant learning curve may lead to a decreased and low rate of adverse events. Experience in arterial anatomy and coil protection may play a role in safety, but the necessity of the latter in some patterns may need confirmation by additional studies in randomized designs.

Background: to evaluate the safety and feasibility of a shorter time to hemostasis applied to outpatient transradial (TR) Prostatic Artery Embolization (PAE)., Methods: a retrospective bi-institutional study was conducted between July 2018 and April 2022 on 300 patients treated by outpatient TR PAE. Indications included lower urinary tract symptoms, acute urinary retention, and hematuria. Mean patient height was 176 ± 6.3 (158-192) cm. The primary endpoint was safety of a 45 min deflation protocol for hemostasis. The secondary endpoint was the feasibility of PAE using TR access., Results: technical success was 98.7% (296/300). There was one failure due to patient height. Mean DAP/fluoroscopy times were 16,225 ± 12,126.3 (2959-81,608) μGy·m 2 /35 ± 14.7 (11-97) min, and mean time to discharge was 80 ± 6 (75-90) min. All access site and embolization-related adverse events were minor. Mild hematoma occurred in 10% (30/300), radial artery occlusion (RAO) in 10/300 (3.3%) cases, and history of smoking was a predictor for RAO. There was no major event., Conclusion: the safety of TR PAE using a 45 min time to hemostasis was confirmed, and TR PAE is feasible in most cases. Radial artery occlusion was still observed and may be favored by smoking.

In this study, we investigated the combination of extracellular (nano) vesicles (EVs) from pig adipose tissue-derived stromal cells (ADSCs) and a thermoresponsive gel, Pluronic® F-127 (PF-127), to prevent stricture formation after endoscopic resection in a porcine model. ADSC EVs were produced at a liter scale by a high-yielding turbulence approach from ADSCs 3D cultured in bioreactors and characterized in terms of size, morphology and membrane markers. The thermoresponsive property of the PF-127 gel was assessed by rheology. The pro-regenerative potency of ADSC EVs was investigated ex vivo in esophageal biopsies under starvation. In vivo tests were performed in a porcine model after extended esophageal endoscopic mucosal dissection (ESD). Pigs were randomized into 3 groups: control ( n = 6), gel ( n = 6) or a combination of 1.45 × 10 12 EVs + gel ( n = 6). Application of gel ± EVs was performed just after ESD with a follow-up finalized on day 21 post-ESD. There was a trend towards less feeding disorder in the EV + gel group in comparison with the gel and the control groups (16.67% vs. 66.7% vs. 83.33%, respectively) but without reaching a statistically significant difference. A significant decrease in the esophageal stricture rate was confirmed by endoscopic, radiological and histological examination for the EV + gel group. A decrease in the mean fibrosis area and larger regenerated muscularis mucosae were observed for the EV + gel group. In summary, the application of EVs + gel after extended esophageal endoscopic resection succeeded in preventing stricture formation with an anti-fibrotic effect. This nano-therapy may be of interest to tackle an unmet medical need considering that esophageal stricture is the most challenging delayed complication after extended superficial cancer resection by endoscopy.

Objectives: Curative treatment of oligometastatic pulmonary disease aims at eradication of all metastases. Radiofrequency ablation (RFA) has been shown to be an efficient method and the frequency of local tumor progression (LTP) should be minimized. The objective of this study was to determine the morphological and treatment-related risk factors for LTP after RFA of pulmonary metastases., Materials and Methods: All patients treated with RFA for pulmonary metastases from 2002 to 2014 were reviewed. All LTPs from 2011 to 2014 were individually matched on the basis of tumor size, number, and histology. In total, 48 LTPs and 112 controls were blindly analyzed for morphological factors including vicinity of bronchus and vessels as well as treatment-related factors such as the size of the ablation zone and ablation margins., Results: In the simple regression analysis, the significant predictive variables were ≤ 5-mm distance to a large bronchus (OR = 4.94; p = 0.0095) or large vessel (OR = 7.09; p < 0.001), minimal ablation margin (≤ 5 mm (OR = 42.67; p < 0.001), and a central-peripheral ablation offset/ablation zone size > 0.36 (OR = 13.83; p = 0.013). In the multiple regression model, only a minimal ablation margin ≤ 5 mm remained a significant risk factor for LTP., Conclusion: Only the minimal ablation margin remains significant in the multiple regression analysis; the other factors are presumably surrogates of an insufficient ablation margin. Improvement of lung RFA outcomes can probably be obtained by immediate post RFA evaluation of ablation margins to ensure a minimal ablation margin of at least 5 mm., Key Points: • A distance < 5 mm to a bronchus or vessel of over 3 mm diameter is associated with insufficient ablation margin and thus risk factors for local tumor progression after pulmonary radiofrequency ablation. • A minimal ablation margin of > 5 mm after pulmonary RFA is associated with significantly less local tumor progression and should be looked for at the end of treatment session before needle removal in order to decrease local tumor progression. • Tumor location, pleural contact, occurrence of intra-alveolar hemorrhage, pulmonary atelectasis, and pneumothorax are not associated with an increased risk of local tumor progression.

Purpose To evaluate the efficacy, durability, and safety of percutaneous fixation by internal cemented screw (FICS) for prophylactic consolidation of impending pathologic fractures of the pelvic ring. Materials and Methods In this single-institute retrospective study, patients with large, minimally symptomatic to asymptomatic osteolytic tumors of the pelvic ring that were treated with percutaneous cone-beam CT-guided FICS procedures were included (January 2014 to May 2019). Follow-up cross-section imaging and clinical reports were reviewed for procedural complications and assessment of the long-term consolidation efficacy on the basis of the development of pathologic fracture or need for additional surgical intervention. All continuous variables were expressed as a mean with standard deviation, and dichotomous variables were expressed as frequencies and percentages. Results Fifty consecutive patients (mean age, 60 years ± 12; 27 men) underwent prophylactic FICS for consolidation of 54 osteolytic tumors (mean size, 51 mm ± 21.5; range, 30-114 mm). Local tumor destruction was performed in association with FICS in 38 patients (76%) using percutaneous thermal and/or radiation therapy. Follow-up exceeded a year in 35 patients (70%), with mean follow-up of 22 months ± 18 (range, 1-67 months). Long-term consolidation efficacy was 98% (49 of 50), with the development of a pathologic fracture in only one patient 20 months after FICS. Procedural complications were limited to two patients with self-resolving hematoma, one patient with inflammatory sciatic pain, and one patient with focal pain at the ischial tuberosity. Conclusion Percutaneous FICS provides a safe and durable minimally invasive treatment for the prevention of pathologic fractures of the pelvic ring. Keywords: Interventional-MSK, Percutaneous, Skeletal-Axial, Metastases, Oncology Supplemental material is available for this article. © RSNA, 2020.

Background: Despite being one of the most common cancers, bladder cancer is largely inefficiently and inaccurately staged and monitored. Current imaging methods detect cancer only when it has reached "visible" size and has significantly disrupted the structure of the organ. By that time, thousands of cells will have proliferated and perhaps metastasized. Repeated biopsies and scans are necessary to determine the effect of therapy on cancer growth. In this report, we describe a novel approach based on multimodal nanoparticle contrast agent technology and its application to a preclinical animal model of bladder cancer. The innovation relies on the engineering core of mesoporous silica with specific scanning contrast properties and surface modification that include fluorescence and magnetic resonance imaging (MRI) contrast. The overall dimensions of the nano-device are preset at 80-180 nm, depending on composition with a pore size of 2 nm., Methods: To facilitate and expedite discoveries, we combined a well-known model of bladder cancer and our novel technology. We exposed nanoparticles to MB49 murine bladder cancer cells in vitro and found that 70 % of the cells were labeled by nanoparticles as measured by flow cytometry. The in vivo mouse model for bladder cancer is particularly well suited for T1- and T2-weighted MRI., Results: Under our experimental conditions, we demonstrate that the nanoparticles considerably improve tumor definition in terms of volumetric, intensity and structural characteristics. Important bladder tumor parameters can be ascertained, non-invasively, repetitively, and with great accuracy. Furthermore, since the particles are not biodegradable, repetitive injection is not required. This feature allows follow-up diagnostic evaluations during cancer treatment. Changes in MRI signals show that in situ uptake of free particles has predilection to tumor cells relative to normal bladder epithelium. The particle distribution within the tumors was corroborated by fluorescent microscopy of sections of excised bladders. In addition, MRI imaging revealed fibrous finger-like projections into the tumors where particles insinuated themselves deeply. This morphological characteristic was confirmed by fluorescence microscopy., Conclusions: These findings may present new options for therapeutic intervention. Ultimately, the combination of real-time and repeated MRI evaluation of the tumors enhanced by nanoparticle contrast may have the potential for translation into human clinical studies for tumor staging, therapeutic monitoring, and drug delivery.

Progressive Multifocal Leukoencephalopathy (PML) is a primary demyelinating disease of the central nervous system occurring almost exclusively in individuals with impaired cell-mediated immunity. The JC polyoma virus has been accepted as the etiologic agent ofPML. Using a two-step in-situ polymerase chain reaction procedure to amplify and detect genomic DNA of human herpesvirus-6 (HHV6) in formalin-fixed paraffin-embedded archival brain tissues, a high frequency of infected cells was consistently detected in PML white matter both within and surrounding demyelinative lesions and HHV6 genome was found mainly within oligodendrocytes. Lesser amounts of HHV6 genome were detected in most normal, AIDS, and other neurological disease control tissues. Immunocytochemistry for HHV6 antigens showed actively infected nuclei of swollen oligodendrocytic morphology only within the demyelinative lesions of PML but not in adjacent uninvolved tissue. In addition, no HHV6 antigens were detectable in control tissues including brains of individuals with HIV-1 encephalopathy but without PML. Double immunohistochemical staining for JC virus large T antigen and HHV6 antigens demonstrated co-labeling of many swollen intralesional oligodendrocytes in the PML cases. The evidence suggests that HHV6 activation in conjunction with JC virus infection is associated with the demyelinative lesions of PML.

The extrahepatic expression of UDP-glucuronosyltransferases (UGTs) is important in the detoxification of a number of endogenous and exogenous compounds, including 5-hydroxytryptamine and morphine. Studies were designed to investigate the extrahepatic expression of human UGTs using RT-PCR techniques and to determine the UGTs involved in the glucuronidation of 5-hydroxytryptamine. Human UGT2B7 expression was found in the human liver, kidney, pancreas, and brain, while UGT1A6 expression is found in the liver, kidney, and brain. This is the first observation of UGTs present in the human central nervous system. Using glucuronidation assays, a significant amount of 5-hydroxytryptamine glucuronide was found to be catalyzed by UGT1A6. These studies suggest that UGT2B7 may play an important role in the overall contribution of morphine analgesia by serving to generate the potent morphine-6-O-glucuronide in situ. UGT1A6 could play an important role in the glucuronidation of 5-hydroxytryptamine in vivo, therefore terminating the actions of the neurotransmitter., (Copyright 1999 Academic Press.)

A potential in vitro model of varicella-zoster virus (VZV) latency was developed. Dissociated human dorsal root ganglion cultures were infected with VZV and maintained for 1 wk in the presence of bromovinyl arabinosyl uracil, a potent inhibitor of VZV. Seven to 21 d after removing the inhibitor (> or = 14 d after infection), the cells were trypsinized, passed to monolayers of human embryonic lung fibroblasts, and observed for VZV reactivation as indicated by typical cytopathic effects and the appearance of VZV antigens. VZV reactivated from 56% of the cultures containing both neurons and satellite cells but not from cultures specifically enriched for either neurons, satellite cells, or ganglion-derived fibroblasts. The failure to isolate VZV from cell suspensions that were sonicated before cocultivation with fibroblasts indicated that infectious VZV was not present before reactivation. Moreover, immunohistochemical and immunoprecipitation studies revealed no VZV-specific antigens in any cultures before the reactivation stimulus. VZV antigens were detected after trypsinization and cocultivation. These findings suggest that cultures containing both neurons and satellite cells provide a model system for VZV persistence that possesses many properties of a latent infection.

The effect of Schwann cell-conditioned medium (SCM) on the development in vitro of spinal cord neurons was studied. Spinal cord neurons from 18-day-old rat embryos were cultured in serum-free conditioned medium obtained from confluent rat Schwann cells. In cultures fed SCM, the cells developed typical neuronal morphology and were identified by indirect immunofluorescence using a monoclonal antibody to neurofilament protein. SCM stimulated neurite outgrowth and supported survival of spinal cord neurons. Preliminary characterization suggests that the neurotrophic factor in SCM appears to be a protein with a molecular weight greater than 8000 daltons.

Previous studies have established that Schwann cells (SC) in culture express an NGF receptor. In this study, cultures of fetal human SC were established from fetal nerves and various light microscopic (LM) and electron microscopic (EM) techniques were used to localize the NGF receptor on the SC. Results indicate that NGF receptor is localized to the plasma membrane of the SC. Quantitative digital analysis determined that the distal portion of the SC process had high concentrations of NGF receptor. The possible functional significance of this latter observation is discussed in terms of SC migration and ensheathment of axons.

Glia maturation factor (GMF) is an acidic protein with a molecular weight of about 20,000 daltons, found in the adult brain of many species. Previously GMF was observed to stimulate the proliferation and subsequent maturation of rat astroblasts in culture. We investigated the effects of GMF on Schwann cells. Schwann cells were dissociated from rat sciatic nerve and purified by means of antimitotic agents and by selective immunoadsorption of contaminating fibroblasts. Cultured Schwann cells after 3 passages assumed a flat polygonal shape. Exposure of the cells to GMF converted the cells to the elongated, spindle morphology typical of Schwann cells. GMF also stimulated a 7-fold increase in DNA synthesis when compared with control cultures grown in F10 medium containing 5% fetal calf serum. The mitogenic activity of GMF was still detectable at 5 ng protein/ml medium. The maximal effect on DNA synthesis occurred 72 h after the initial exposure to GMF. Although the cells were positive for the Schwann cell marker Ran-1, GMF failed to induce the production of myelin-associated glycolipids (galactocerebroside) and proteins (Po) nor did it induce the astrocytic marker glial fibrillary acidic protein (GFAP). The effects of GMF on Schwann cells extend its biological role beyond the central nervous system.

Cultures of human Schwann cells and astrocytes were established from fetal nerves and brains respectively. The human Schwann cells in culture expressed a nerve growth factor (NGF) receptor as determined by indirect immunofluorescence, autoradiography, and immunoprecipitation. In contrast, the human astrocytes in culture did not have an NGF receptor. Cultures of rat Schwann cells and astrocytes were also established for comparison, with similar results. The rat Schwann cells had an NGF receptor whereas the astrocytes did not. The functional significance of this NGF receptor on Schwann cells, as well as the lack of the receptor on astrocytes, is discussed.

Neurite-promoting activity in feeding medium conditioned by rat astrocytes and Schwann cells in culture was examined. The conditioned medium (CM) from both types of glial cultures stimulated extensive neurite outgrowth from embryonic chick dorsal root ganglia (DRG) as well as pheochromocytoma (PC12) cells. Both the DRG and PC12 cells also produce neurite outgrowth in the presence of nerve growth factor (NGF). With the DRG, the neurite growth rates observed with the glial cell CM were identical to growth rates seen with NGF. Although anti-NGF antibody did not inhibit the neurite outgrowth produced by either of the glial CM, a nerve growth factor radioreceptor assay did detect an NGF-like molecule in both CM. Since the extensive neurite outgrowth stimulated by the glial CM was not mimicked by pure laminin alone, we conclude that the glial neurite promoting factors are distinct from laminin.

We report a method for deriving purified rat Schwann cells by immunoselective removal of fibroblasts. Contaminating fibroblasts labeled with antibody against specific surface marker Thy 1.1 are bound on plastic surfaces coated with a second antibody. The efficacy of the method is demonstrated by flow cytometry and by specific Schwann cell Ran-1 immunofluorescence.