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In vivo multiplexed imaging aims for noninvasive monitoring of tumors with multiple channels without excision of the tissue. While most of the preclinical imaging has provided a number of multiplexing channels up to three, Raman imaging with surface-enhanced Raman scattering (SERS) nanoparticles was suggested to offer higher multiplexing capability originating from their narrow spectral width. However, in vivo multiplexed SERS imaging is still in its infancy for multichannel visualization of tumors, which require both sufficient multiplicity and high sensitivity concurrently. Here we create multispectral palettes of gold multicore-near-infrared (NIR) resonant Raman dyes-silica shell SERS (NIR-SERRS) nanoparticle oligomers and demonstrate noninvasive and five-plex SERS imaging of the nanoparticle accumulation in tumors of living mice. We perform the five-plex ratiometric imaging of tumors by varying the administered ratio of the nanoparticles, which simulates the detection of multiple biomarkers with different expression levels in the tumor environment. Furthermore, since this method does not require the excision of tumor tissues at the imaging condition, we perform noninvasive and longitudinal imaging of the five-color nanoparticles in the tumors, which is not feasible with current ex vivo multiplexed tissue analysis platforms. Our work surpasses the multiplicity limit of previous preclinical tumor imaging methods while keeping enough sensitivity for tumor-targeted in vivo imaging and could enable the noninvasive assessment of multiple biological targets within the tumor microenvironment in living subjects.

Pain is a complex syndrome that is difficult to treat. The increasing numbers of patients living with chronic diseases has led to increasing pain management needs and the rise of opioid use disorder (OUD) as a major and potentially lethal public health concern. Treatment of chronic pain with prescription opioids alone is not always successful, and a multidisciplinary approach is paramount to address the needs of patients at risk of developing or suffering from OUD. Interventional radiologists trained to perform minimally invasive procedures with negligible downtime and postprocedure pain can help stem the tide of opioid-related deaths and disability. This article reviews a wide range of minimally invasive procedures, including vertebral augmentation, sacroplasty, thermal ablation of osseous metastasis, nerve blocks, and gonadal vein embolization, that interventional radiologists are now using successfully to treat chronic pain. The evidence to support use of such procedures is highlighted. This article also briefly discusses emerging techniques such as arterial embolization and ablation for knee and shoulder osteoarthritis that have not yet been fully tested but exhibit strong potential in chronic pain management. By reducing opioid use in patients suffering from chronic pain, these minimally invasive procedures can potentially prevent escalation to OUD.

Recurrent or metastatic peri-urethral pelvic malignancies are a difficult-to-treat entity. Re-resection is recommended when possible but is frequently unfavorable due to scar tissue, fibrosis, and obliteration of tissue planes following previous interventions such as surgical resection and/or radiation therapy. Curative options for patients that have unresectable cancer are limited. Cryo-ablation has been extensively studied in the treatment of unresectable renal, liver and lung malignancies and has the potential to provide definitive treatment for recurrent pelvic malignancy. There is a paucity of reports of salvage cryo-ablation in patients with recurrent pelvic malignancies, as most of these tumors are located close to critical structures that could be irreversibly injured by thermal ablation and are hence treated with some form of radiation therapy. But, for patients who fail surgical and radiation treatments, options are limited. Here, we describe two cases of regional tumor recurrence in the pelvis treated with percutaneous cryoablation using protective techniques to avoid thermal injury to adjacent structures. In each case, cryo-ablation was performed successfully despite extensive previous surgical and radiation interventions. Salvage cryo-ablation resulted in a positive clinical and imaging response with an improvement in quality of life and absence of recurrence on follow-up imaging which continues to persist at the writing of this manuscript about 8 and 12-months following treatment.

Purpose The role of computed tomography (CT)-guided gastrostomy tube placement is still evolving. It is a valuable alternative to guide gastrostomy tube placement in a few selected patients, who are not candidates for the established endoscopy- or fluoroscopy-guided gastrostomy tube placement. Our objective was to describe our institutional experience placing gastrostomy tubes using CT guidance and to conduct a review of literature for similar studies to provide the best current evidence on success rates and complications. Methods We identified gastrostomy tubes placed under CT guidance at our institution using a comprehensive case log. We also identified studies in the literature, through a systematic search of PubMed. In both the local and literature analyses, we recorded success and complication rates. Results A total of 31 patients underwent 33 attempted CT-guided gastrostomy tube placements at our institution, with 32 successful procedures yielding a success rate of 97%. The overall rate of successful gastrostomy tube placement using CT-guidance was 94.9% (634/668), as reported in the existing literature. Conclusion CT-guidance is an effective method for gastrostomy tube placement and may play an important role in patients for whom endoscopic or fluoroscopic gastrostomy tube placement is not feasible.

Bladder cancer (BC) is a relatively common tumor, with a male preponderance. High-grade muscle invasive bladder cancer (MIBC) has a very high incidence of pelvic lymph node metastasis at presentation. Involvement of the retro-crural lymph nodes, although has been described in other pelvic tumors, is very uncommon for BC. Cryoablation in the retro-crural region is extremely challenging due to the proximity to the critical structures like inferior venacava and aorta and has not been extensively reported. We describe a 56-year old male patient with MIBC who underwent extensive treatments including radical cystoprostatectomy, chemoradiation and immunotherapy, ultimately with localized disease in the retro-crural region. Single session cryoablation of these lymph nodes was performed with a curative intent yielding a positive response that has persisted for more than 2 years.

Persistent eating of non-nutritive, nonfood substances (Pica) is seen in children and adult patients with psychiatric problems. Ingestion of multiple metallic FBs with resultant bezoar formation is rare. While many FBs are passed without complication, mucosal injury, bleeding, obstruction or perforation can occur in some cases. Endoscopic FB removal is performed in 20% of patients following FB ingestion. Generally, these are safe procedures, and very effective in extracting ingested FBs. We report, a 25-year-old male patient with a metal ingestion predominant Pica, requiring multiple prior extraction procedures (including open gastrostomy). He developed a splenic artery pseudoaneurysm following his latest endoscopic FB removal, that was successfully treated with transarterial coil embolization. The unique circumstances leading to this rare complication and its successful endovascular management make this case worthy of report.

Kaposi’s sarcoma-associated herpesvirus (KSHV) establishes a latent infection in the cell nucleus, but where KSHV episomal genomes are tethered and the mechanisms underlying KSHV lytic reactivation are unclear. Here, we study the nuclear microenvironment of KSHV episomes and show that the KSHV latency-lytic replication switch is regulated via viral long non-coding (lnc)RNA-CHD4 (chromodomain helicase DNA binding protein 4) interaction. KSHV episomes localize with a CHD4 complex, ChAHP, at epigenetically active genomic regions and tethers frequently near centromeric regions of host chromosomes. The ChAHP complex also occupies the 5’-region of a highly-inducible lncRNAs and terminal repeats of KSHV genome with latency-associated nuclear antigen (LANA). Viral lncRNA binding competes with CHD4 DNA binding, and KSHV reactivation is accompanied by the detachment of KSHV episomes from host chromosome docking sites We propose a model in which elevated lncRNA expression determines the KSHV latency-lytic decision by regulating LANA/ChAHP DNA binding at inducible viral enhancers.

BACKGROUND Primary appendiceal cancers are rare, and they generally present with liver and/or peritoneal metastases. Currently there are no guidelines to treat metastatic appendiceal cancer, and hence they are treated as metastatic colorectal cancer. Combining Yttrium 90 (Y-90) radioembolization (RE) with systemic chemotherapy early in the treatment of right sided colon cancers has been shown to improve survival. Based on this data, a combination of systemic chemotherapy and Y-90 RE was used to treat a case of metastatic appendiceal cancer. CASE SUMMARY A 76-year-old male presented to the emergency room with progressive right lower quadrant pain. A Computed Tomography of the abdomen and pelvis was performed which showed acute appendicitis and contained perforation. Urgent laparoscopic appendectomy was then followed by histological analysis, which was significant for appendiceal adenocarcinoma. After complete workup he underwent right hemicolectomy and lymph node dissection. He received adjuvant chemotherapy as the local lymph nodes were positive. Follow-up imaging was significant for liver metastasis. Due to rapid growth of the liver lesions and new peritoneal nodules, the patient was treated with a combination of Y-90 RE and folinic acid, fluorouracil, and irinotecan with bevacizumab and not microwave ablation as previously planned. Follow up imaging demonstrated complete response of the liver lesions. At 12-mo follow-up, the patient continued to enjoy good quality of life with no recurrent disease. CONCLUSION Utilization of Y-90 RE concomitantly with systemic chemotherapy early in the treatment of appendiceal cancer may provide improved control of this otherwise aggressive cancer.

Aryl carbonates, a common protecting group in synthetic organic chemistry, are potentially valuable electrophiles in cross-coupling reactions. Here, after performing a thorough evaluation of different precatalysts, we demonstrate that (dcypf)Ni(2-ethylphenyl)(Br) (dcypf = 1,1-bis-(dicyclohexylphosphino)ferrocene) is an efficient precatalyst for Suzuki-Miyaura reactions using a variety of aryl carbonates as substrates. Mechanistic studies indicate that (dcypf)Ni(2-ethylphenyl)(Br), which contains a bidentate phosphine that binds in a trans geometry, is an effective precatalyst for these reactions for two reasons: (i) it rapidly forms the Ni(O) active species and (ii) it minimizes comproportionation reactions between the Ni(O) active species and both the unactivated Ni(II) precatalyst and on-cycle Ni(II) complexes to form catalytically inactive Ni(I) species. In contrast, the state of the art precatalyst (dppf)Ni(o-tolyl)(Cl) (dppf = 1,1-bis(diphenylphosphino)ferrocene), which contains a bidentate phosphine that binds in a cis geometry, forms Ni(I) species during activation and is essentially inactive for aryl carbonate couplings. Although the exact reasons on a molecular level why the dcypf system is more active than the dppf system are unclear, our results indicate that in general Ni catalysts supported by the dcypf ligand will give better performance for catalytic reactions involving substrates which undergo relatively slow oxidative addition, such as aryl carbonates.

Ectopic varices are complex and highly variable entities that are not fully understood. Duodenal varices from pancreatitis have rarely been reported. Ectopic varices have much higher bleeding rates than the more common gastro-esophageal varices, and are associated with higher mortality. The ideal management of this difficult problem is not only to ensure prompt hemostasis, but also address the etiology or hemodynamics of the ectopic varices. We discuss the endovascular management of bleeding duodenal varices, which developed from superior mesenteric vein occlusion, following repeated attacks of pancreatitis. This unusual case was managed by a multidisciplinary collaborative approach between the gastrointestinal service and Interventional radiology. The classification system for ectopic varices and management options has been discussed in some detail. Medium term follow-up (8 months), at the time of this writing, showed that the patient is doing well, without interval hematemesis, imaging findings of recurrent/new varices or stent occlusion.

Sepsis is a leading cause of morbidity and mortality in patients that have sustained a severe burn injury. Early detection and treatment of infections improves outcomes and understanding changes in the host microbiome following injury and during treatment may aid in burn care. The loss of functional barriers, systemic inflammation, and commensal community dysbiosis all contribute to a burn patient’s increased risk of infection. We sampled 10 burn patients to evaluate cutaneous microbial populations on the burn wound and corresponding spared skin on days 0, 3, 7, 14, 21, and 28 post-intensive care unit admission. In addition, skin samples were paired with perianal and rectal locations to evaluate changes in the burn patient gut microbiome following injury and treatment. We found significant (P = 0.011) reduction in alpha diversity on the burn wound compared to spared skin throughout the sampling period as well as reduction in common skin commensal bacteria such as Propionibacterium acnes and Staphylococcus epidermitis. Compared to healthy volunteers (n = 18), the burn patient spared skin also exhibited a significant reduction in diversity (P = 0.001). Treatments such as systemic or topical antibiotic administration, skin grafting, and nutritional formulations also impact diversity and community composition at the sampling locations. When evaluating each subject individually, an increase in relative abundance of a clinically isolated bacteria could be seen in 5/9 infections detected among the burn patient cohort.

Objectives: The objective of the study was to retrospectively investigate the safety and efficacy of computerized tomography-guided microwave ablation (MWA) in the treatment of Stage I non-small cell lung cancers (NSCLCs). Material and Methods: This retrospective, single-center study evaluated 21 patients (10 males and 11 females; mean age 73.8 ± 8.2 years) with Stage I peripheral NSCLCs treated with MWA between 2010 and 2020. All patients were surveyed for metastatic disease. Clinical success was defined as absence of FDG avidity on follow-up imaging. Tumor growth within 5 mm of the original ablated territory was defined as local recurrence. Welch t-test and Fisher’s exact test were used for univariate analysis. Hazard ratio (HR) and odds ratio (OR) were determined using Cox regression and Firth logistic regression. Significance was P < 0.05. Data are expressed as mean ± standard deviation. Results: Ablated tumors had longest dimension 17.4 ± 5.4 mm and depth 19.7 ± 15.1 mm from the pleural surface. Median follow-up was 20 months (range, 0.6–56 months). Mean overall survival (OS) following lung cancer diagnosis or MWA was 26.2 ± 15.4 months (range, 5–56 months) and 23.7 ± 15.1 months (range, 3–55 months). OS at 1, 2, and 5 years was 67.6%, 61.8%, and 45.7%, respectively. Progression-free survival (PFS) was 19.1 ± 16.2 months (range, 1–55 months). PFS at 1, 2, and 5 years was 44.5%, 32.9%, and 32.9%, respectively. Technical success was 100%, while clinical success was observed in 95.2% (20/21) of patients. One patient had local residual disease following MWA and was treated with chemotherapy. Local control was 90% with recurrence in two patients following ablation. Six patients (28.6%) experienced post-ablation complications, with pneumothorax being the most common event (23.8% of patients). Female gender was associated with 90% reduction in risk of death (HR 0.1, P = 0.014). Tumor longest dimension was associated with a 10% increase in risk of death (P = 0.197). Several comorbidities were associated with increased hazard. Univariate analysis revealed pre-ablation forced vital capacity trended higher among survivors (84.7 ± 15.2% vs. 73 ± 21.6%, P = 0.093). Adjusted for age and sex, adenocarcinoma, and neuroendocrine histology trended toward improved OS (OR: 0.13, 0.13) and PFS (OR: 0.88, 0.37) compared to squamous cell carcinoma. Conclusion: MWA provides a safe and effective alternative to stereotactic brachytherapy resulting in promising OS and PFS in patients with Stage I peripheral NSCLC. Larger sample sizes are needed to further define the effects of underlying comorbidities and tumor biology.

Objectives: Percutaneous renal biopsy (PRB) plays a critical role in the work-up of renal parenchymal disease. Although it is considered a low-risk procedure, additional interventions may be required in about 7% of the cases following biopsy. The purpose of this study was to identify risk factors for major hemorrhage by microscopic analysis of the cores obtained following PRB, with an intent to enhance the sensitivity and specificity of the risk stratification process, especially in patients undergoing this procedure in an outpatient setting. Material and Methods: A retrospective review identified 17 of 179 patients (9.50%) with major hemorrhage following PRB between July 2014 and June 2019. Using propensity score matching, 26 controls (without major hemorrhage) were matched to 17 cases (with major hemorrhage). The biopsy cores obtained from the cases and controls were analyzed by a single pathologist for medullary, cortical, total (medullary + cortical) lengths, and the number of arcuate arteries (AAs). Medullary:cortical (M:C), cortical:total (C:T), and medullary:total (M:T) length ratios were then calculated. Results: A stratified version of logistic regression was used to test for an association between each of the variables identified on the cores and the probability of a major hemorrhage. The analysis revealed that there was a statistically significant association between the number of AAs per specimen with the risk of major hemorrhage (P = 0.0006). When 0, 1, or >2 AAs were identified, the frequency of major hemorrhage was 13.04%, 66.67%, and 75.00%, respectively. The odds of major hemorrhage were 6 times higher with one AA and (95% CI, 1.28–32.30) and 15 times higher with >2 AAs (95% CI, 1.41–169.57). No significant association was found between medullary length (P = 0.228), medulla:cortex (M:C) (P = 0.089), medulla:total (M:T) (P = 0.108), or cortex:total (C:T) (P = 0.112) length ratios and major hemorrhage. Conclusion: There was a strong and incremental correlation between major renal hemorrhage following PRB and the number of AAs per core specimen. Identification of AAs by the pathologist, while assessing for sample adequacy, in the US suite can help predict major hemorrhage in patients undergoing PRBs.

Inferior vena cava (IVC) filter in venous thromboembolism (VTE) is an alternative to anticoagulation when the latter is contraindicated. The use of IVC filter in pediatrics continues to be rare and has not increased despite the ever-increasing rates of childhood VTE. Historically, septic VTE was regarded as a contraindication to IVC filter. Safety and efficacy of IVC filters in septic VTE have been reported in adult patients but not in pediatric patients. In this study, we reported a safe use of IVC filter in a critically ill 12-year-old patient with a large IVC thrombus and multiple pulmonary embolisms with favorable outcome.

PURPOSE: Post-thoracotomy pain syndrome is a common condition affecting up to 50% of post-thoracotomy patients. However, percutaneous computed tomography (CT)-guided intercostal nerve cryoablation may provide symptomatic benefit in chronic and/or refractory cases. METHODS: A retrospective review of our institution’s comprehensive case log from October 2017 to September 2018 for patients who underwent cryoablation was analyzed. Thirteen patients with post-thoracotomy pain syndrome, refractory to medical management, were treated with CT-guided intercostal nerve cryoablation. Most patients had treatment of the intercostal nerve at the level of their thoracotomy scar, two levels above and below. The safety and technical success of this technique and the clinical outcomes of the study population were then retrospectively reviewed. RESULTS: Of the patients, 69% experienced significant improvement in their pain symptoms with a median pain improvement score of 3 points (range, −1 to 8 points) over a median follow-up of 11 months (range, 2–18.6 months). Complications included pneumothorax in 8% and pseudohernia in 23% of patients. CONCLUSION: CT-guided intercostal nerve cryoablation may be an effective technique in the treatment of post-thoracotomy pain syndrome and requires further study.

Solitary fibrous tumors are primary mesenchymal tumors, which may occur in any part of the body. Overall, these tumors are considered to have intermediate malignant potential with 5- and 10-year metastasis-free and overall disease-specific survival rates of 74% and 55%, and 89% and 73%, respectively (Demicco et al, 2012). Herein we present an unusual case of solitary fibrous tumors involving the ischioanal fossa in a 19-year-old woman with radiologic-pathologic correlation. This case was complicated by extensive tumor vascularity and was thus managed with preoperative embolization followed by en bloc surgical resection. Keywords: Solitary fibrous tumor, Embolization, Ischioanal, Hemangiopericytoma

Background: Inferior vena cava (IVC) filter placement still plays an essential role in preventing pulmonary embolism (PE) in patients with contraindications to anticoagulant therapy. However, IVC filter placement does have long-term risks which may be mitigated by retrieving them as soon as clinically acceptable. A dedicated IVC filter clinic provides a potential means of assuring adequate follow-up and retrieval. Aim: To assess the efficacy of our Inferior vena cava (IVC) filter retrieval clinic at improving the rate of patient follow-up, effective filter management, and retrieval rates. Materials and Methods: During the period of August 2017 through July 2018, 70 IVC filters were placed at our institution, and these patients were automatically enrolled into our IVC filter retrieval clinic for quarterly follow-up. We retrospectively reviewed data including appropriateness for removal at 3 months, overall retrieval rates, removal technique(s) employed, and technical success. Results: 62.9% of the potentially retrievable filters were removed during the study period. The technical success of extraction, using a combination of standard and advanced techniques, was 91.7%. Overall, 15% of the patients were lost to follow-up. Conclusion: Our findings add to the growing body of literature to support the need for a robust IVC filter retrieval clinic to ensure adequate follow-up and timely retrieval of IVC filters.

Cancers of the gastrointestinal (GI) tract are among the most frequent and most lethal cancers worldwide. An important reason for this high mortality is that early disease is typically asymptomatic, and patients often present with advanced, incurable disease. Even in high-risk patients who routinely undergo endoscopic screening, lesions can be missed due to their small size or subtle appearance. Thus, current imaging approaches lack the sensitivity and specificity to accurately detect incipient GI tract cancers. Here we report our finding that a single dose of a high-sensitivity surface-enhanced resonance Raman scattering nanoparticle (SERRS-NP) enables reliable detection of precancerous GI lesions in animal models that closely mimic disease development in humans. Some of these animal models have not been used previously to evaluate imaging probes for early cancer detection. The studies were performed using a commercial Raman imaging system, a newly developed mouse Raman endoscope, and finally a clinically applicable Raman endoscope for larger animal studies. We show that this SERRS-NP-based approach enables robust detection of small, premalignant lesions in animal models that faithfully recapitulate human esophageal, gastric, and colorectal tumorigenesis. This method holds promise for much earlier detection of GI cancers than currently possible and could lead therefore to marked reduction of morbidity and mortality of these tumor types.

Raman spectroscopic imaging has shown great promise for improved cancer detection and localization with the use of tumor targeting surface enhanced Raman scattering (SERS) nanoparticles. With the ultrasensitive detection and multiplexing capabilities that SERS imaging has to offer, scientists have been investigating several clinical applications that could benefit from this unique imaging strategy. Recently, there has been a push to develop new image-guidance tools for surgical resection to help surgeons sensitively and specifically identify tumor margins in real time. We hypothesized that SERS nanoparticles (NPs) topically applied to breast cancer resection margins have the potential to provide real-time feedback on the presence of residual cancer in the resection margins during lumpectomy. Here, we explore the ability of SERS nanoparticles conjugated with a cluster of differentiation-47 (CD47) antibody to target breast cancer. CD47 is a cell surface receptor that has recently been shown to be overexpressed on several solid tumor types. The binding potential of our CD47-labeled SERS nanoparticles was assessed using fluorescence assisted cell sorting (FACS) on seven different human breast cancer cell lines, some of which were triple negative (negative expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2)). Xenograft mouse models were also used to assess the ability of our Raman imaging system to identify tumor from normal tissue. A ratiometric imaging strategy was used to quantify specific vs. nonspecific probe binding, resulting in improved tumor-to-background ratios. FACS analysis showed that CD47-labeled SERS nanoparticles bound to seven different breast cancer cell lines at levels 12-fold to 70-fold higher than isotype control-labeled nanoparticles (p &lt, 0.01), suggesting that our CD47-targeted nanoparticles actively bind to CD47 on breast cancer cells. In a mouse xenograft model of human breast cancer, topical application of CD47-targeted nanoparticles to excised normal and cancer tissue revealed increased binding of CD47-targeted nanoparticles on tumor relative to normal adjacent tissue. The findings of this study support further investigation and suggest that SERS nanoparticles topically applied to breast cancer could guide more complete surgical resection during lumpectomy.

Manganese oxides are often highly reactive and easily reduced, both abiotically, by a variety of inorganic chemical species, and biologically during anaerobic respiration by microbes. To evaluate the reaction mechanisms of these different reduction routes and their potential lasting products, we measured the sequence progression of microbial manganese(IV) oxide reduction mediated by chemical species (sulfide and ferrous iron) and the common metal-reducing microbe Shewanella oneidensis MR-1 under several endmember conditions, using synchrotron X-ray spectroscopic measurements complemented by X-ray diffraction and Raman spectroscopy on precipitates collected throughout the reaction. Crystalline or potentially long-lived phases produced in these experiments included manganese(II)-phosphate, manganese(II)-carbonate, and manganese(III)-oxyhydroxides. Major controls on the formation of these discrete phases were alkalinity production and solution conditions such as inorganic carbon and phosphate availability. The formation of a long-lived Mn(III) oxide appears to depend on aqueous Mn(2+) production and the relative proportion of electron donors and electron acceptors in the system. These real-time measurements identify mineralogical products during Mn(IV) oxide reduction, contribute to understanding the mechanism of various Mn(IV) oxide reduction pathways, and assist in interpreting the processes occurring actively in manganese-rich environments and recorded in the geologic record of manganese-rich strata.

Objectives: Over 25% of the high-risk population screened for lung cancer have an abnormal computed tomography (CT) scan. Conventionally, these lesions have been biopsied with CT guidance with a high diagnostic yield. Electromagnetic navigational bronchoscopy (ENB) with transbronchial biopsy has emerged as a technology that improves the diagnostic sensitivity of conventional bronchoscopic biopsy. It has been used to biopsy lung lesions, due to the low risk of pneumothorax. It is, however, a new technology that is expensive and its role in the diagnosis of the solitary pulmonary nodule (SPN) is yet to be determined. The purpose of this study was to evaluate the diagnostic yield of CT-guided biopsy (CTB) following non-diagnostic ENB biopsy and identify characteristics of the lesion that predicts a low diagnostic yield with ENB, to ensure appropriate use of ENB in the evaluation of SPN. Materials and Methods: One hundred and thirty-five lung lesions were biopsied with ENB from January 2017 to August 2019. Biopsies were considered diagnostic if pathology confirmed malignancy or inflammation in the appropriate clinical and imaging setting. We evaluated lesions for several characteristics including size, lobe, and central/peripheral distribution. The diagnostic yield of CTB in patients who failed ENB biopsies was also evaluated. Logistic regression was used to identify factors likely to predict a non-diagnostic ENB biopsy. Result: Overall, ENB biopsies were performed in 135 patients with solitary lung lesions. ENB biopsies were diagnostic in 52% (70/135) of the patients. In 23 patients with solitary lung lesions, CTBs were performed following a non-diagnostic ENB biopsy. The CTBs were diagnostic in 87% of the patients (20/23). ENB biopsies of lesions Conclusion: CTBs have a high diagnostic yield even following non-diagnostic ENB biopsies. Lesions

Background: Mechanical thrombectomy plays an important role in the management of acute pulmonary embolism (PE), either when rapid clot dissolution is needed or when thrombolytics are contraindicated. We describe our clinical and technical experience with the FlowTriever mechanical thrombectomy device in patients with acute PE. Materials and Methods: A retrospective analysis was performed on all cases of acute PE treated with the FlowTriever device at a single tertiary care hospital system during the trial period (November 2019–January 2020). Technical and clinical results, including complications, are reported. Results: Technical success was achieved in all eight successive cases (seven cases of submassive and 1 case of massive PE). Mean pulmonary artery pressure (MPAP) improved significantly after mechanical thrombectomy (27.8 ± 6.4 mmHg preprocedure; 20.5 ± 3.8 mmHg postprocedure; 7.3 ± 5.2 mmHg decrease after the procedure; P = 0.016). Hemoglobin levels did not change significantly after mechanical thrombectomy (11.8 g/dl ± 3.4 preprocedure; 9.9 g/dl ± 2.1 postprocedure; P = 0.20). Reduction in MPAP was achieved in 88% of cases (7/8) and hypoxia improved in all the nonintubated patients (7/7). Mortality observed in one patient with a massive central PE, was not related to the procedure. No mortality or procedural complications were observed in patients with submassive PE. Conclusions: The positive initial clinical experience and safety profile using the FlowTriever in the treatment of acute PE suggests, it has the potential to fill the unmet needs of a good mechanical thrombectomy device to treat massive and submassive high-risk PE especially when thrombolytics are contraindicated.

Bladder cancer has the highest recurrence rate of all cancers due in part to inadequate transurethral resection. Inadequate resection is caused by the inability of cystoscopes to detect invisible lesions during the resection procedure. To improve detection and resection of nonmuscle invasive bladder cancer, we quantified the ability of a surface-enhanced Raman nanoparticle and endoscope system to classify bladder tissue as normal or cancerous. Both antibody-based (active) and tissue permeability-based (passive) targeting mechanisms were evaluated by topically applying nanoparticles to ex vivo human bladder tissue samples. Multiplexed molecular imaging of CD47 and Carbonic Anhydrase 9 tumor proteins gave a receiver operating characteristic area under the curve (ROC AUC of 0.93 (0.75, 1.00). Furthermore, passively targeted nanoparticles enabled tissue classification with an ROC AUC of 0.93 (0.73, 1.00). Passively targeted nanoparticles penetrated 5-fold deeper and bound to tumor tissue at 3.3-fold higher concentrations in cancer compared to normal bladder urothelium, suggesting the existence of an enhanced surface permeability and retention effect in human bladder cancer.

Esters are valuable electrophiles for cross-coupling due to their ubiquity and ease of synthesis. However, harsh conditions are traditionally required for the effective cross-coupling of ester substrates. Utilizing a recently discovered precatalyst, Pd-catalyzed Suzuki–Miyaura and Buchwald–Hartwig reactions involving cleavage of the C(acyl)–O bond of aryl esters that proceed under mild conditions are reported. The Pd(II) precatalyst is highly active because it is reduced to the Pd(0) active species more rapidly than previous precatalysts.

Purpose Intermolecular multiple quantum coherences (iMQCs) are a source of MR contrast with applications including temperature imaging, anisotropy mapping, and brown fat imaging. Because all applications are limited by signal-to-noise ratio (SNR), we developed a pulse sequence that detects intermolecular zero quantum coherences with improved SNR. Methods A previously developed pulse sequence that detects iMQCs, HOMOGENIZED with off resonance transfer (HOT), was modified with a multi-spin echo spatial encoding scheme (MSE-HOT). MSE-HOT uses a series of refocusing pulses to generate a stack of images that are averaged in postprocessing for higher SNR. MSE-HOT performance was quantified by measuring its temperature accuracy and precision during hyperthermia of ex vivo red bone marrow samples. Results MSE-HOT yielded a three-fold improvement in temperature precision relative to previous pulse sequences. Sources of improved precision were 1) echo averaging and 2) suppression of J-coupling in the methylene protons of fat. MSE-HOT measured temperature change with an accuracy of 0.6°C. Conclusion MSE-HOT improved the temperature accuracy and precision of HOT to a level that is sufficient for hyperthermia of bone marrow. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

This profile traces the creative trajectory of the queer choreographer and performance maker Miguel Gutierrez. Drawing on José Esteban Muñoz’s theories of queer futurity and resistance, it analyzes the ways in which Gutierrez and his dancers defy reductive constraints on sexual, artistic, and political expression. It explores the politics of personality, style, and the male body as a site of desire.

During hyperthermia (HT), the therapeutic response of tumours varies substantially within the target temperature range (39-43 °C). Current thermometry methods are either invasive or measure only temperature change, which limits the ability to study tissue responses to HT. This study combines manganese-containing low temperature sensitive liposomes (Mn-LTSL) with proton resonance frequency shift (PRFS) thermometry to measure absolute temperature in tumours with high spatial and temporal resolution using MRI.Liposomes were loaded with 300 mM MnSO(4). The phase transition temperature (T(m)) of Mn-LTSL samples was measured by differential scanning calorimetry (DSC). The release of manganese from Mn-LTSL in saline was characterised with inductively coupled plasma atomic emission spectroscopy. A 2T GE small animal scanner was used to acquire dynamic T1-weighted images and temperature change images of Mn-LTSL in saline phantoms and fibrosarcoma-bearing Fisher-344 rats receiving hyperthermia after Mn-LTSL injection.The T(m) of Mn-LTSL in rat blood was 42.9 ± 0.2 °C (DSC). For Mn-LTSL samples (0.06 mM-0.5 mM Mn(2+) in saline) heated monotonically from 30 °C to 50 °C, a peak in the rate of MRI signal enhancement occurred at 43.1° ± 0.3 °C. The same peak in signal enhancement rate was observed during heating of fibrosarcoma tumours (N = 3) after injection of Mn-LTSL, and the peak was used to convert temperature change images into absolute temperature. Accuracies of calibrated temperature measurements were in the range 0.9-1.8 °C.The release of Mn(2+) from Mn-LTSL affects the rate of MR signal enhancement which enables conversion of MRI-based temperature change images to absolute temperature.

Long-lived nuclear spin states could greatly enhance the applicability of hyperpolarized nuclear magnetic resonance. Using singlet states between inequivalent spin pairs has been shown to extend the signal lifetime by more than an order of magnitude compared to the spin lattice relaxation time (T1), but they have to be prevented from evolving into other states. In the most interesting case the singlet is between chemically equivalent spins, as it can then be inherently an eigenstate. However this presents major challenges in the conversion from bulk magnetization to singlet. In the only case demonstrated so far, a reversible chemical reaction to break symmetry was required. Here we present a pulse sequence technique that interconverts between singlet spin order and bulk magnetization without breaking the symmetry of the spin system. This technique is independent of field strength and is applicable to a broad range of molecules.

The Kaposi sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) is a multifunctional protein with roles in gene regulation and maintenance of viral latency. Post-translational modification of LANA is important for functional diversification. Here, we report that LANA is subject to arginine methylation by protein arginine methyltransferase 1 in vitro and in vivo. The major arginine methylation site in LANA was mapped to arginine 20. This site was mutated to either phenylalanine (bulky hydrophobic, constitutive methylated mimetic) or lysine (positively charged, non-arginine methylatable) residues. The significance of the methylation in LANA function was examined in both the isolated form and in the context of the viral genome through the generation of recombinant KSHV. In addition, authentic LANA binding sites on the KSHV episome in naturally infected cells were identified using a whole genome KSHV tiling array. Although mutation of the methylation site resulted in no significant difference in KSHV LANA subcellular localization, we found that the methylation mimetic mutation resulted in augmented histone binding in vitro and increased LANA occupancy at identified LANA target promoters in vivo. Moreover, a cell line carrying the methylation mimetic mutant KSHV showed reduced viral gene expression relative to controls both in latency and in the course of reactivation. These results suggest that residue 20 is important for modulation of a subset of LANA functions and properties of this residue, including the hydrophobic character induced by arginine methylation, may contribute to the observed effects.

Glioblastoma multiforme (GBM) is the most aggressive and common form of brain cancer in adults and is currently incurable. To identify new therapeutic targets for GBM, we performed genome-wide CRISPR-Cas9 "knockout" (KO) screens in patient-derived GBM stem-like cells (GSCs) and human neural stem cells (NSCs), non-neoplastic tissue of origin controls. These screens revealed thousands of gene candidates acting to promote or limit expansion of GSCs and NSCs. In vitro and in vivo validation studies revealed several novel therapeutic targets, including the wee1-like kinase, PKMYT1/Myt1. Mechanistic studies revealed that PKMYT1 acts redundantly with WEE1 to facilitate mitosis in NSCs, but that this redundancy is lost in most GBM isolates and in NSCs harboring activated alleles of EGFR and AKT1. In addition to lethal genes, KOs promoting in vitro expansion of NSCs were also examined. For this category, we validated multiple genes, including: ARID1A, ARID1B, CREBBP, EP300, NF2, PDCD10, PTPN14, TAOK1, TGFBR2, and TP53, whose inhibition shortens NSC cell cycle transit times, causing dramatic growth advantages, and, in the case of CREBBP KO, dramatic deregulation of cell cycle gene expression and precocious S-phase entry. Taken together, these results demonstrate the use of CRISPR-Cas9 gene editing to identify novel cancer therapeutic targets and growth suppressor genes in human GBM isolates and NSCs. The results also inform precision medicine approaches for GBM, since most, if not all, candidate therapeutic targets could not be predicted from mutation, CNV, or gene expression analysis of the patient isolates alone.

Red bone marrow metastases are common in breast and prostate cancer patients, but those metastases are currently incurable. Recent developments show that hyperthermia could be a successful treatment for bone metastasis, but thermometry remains difficult or inaccurate in red marrow.The technique evaluated in this study measures the evolution frequency of intermolecular zero quantum coherences (iZQCs) between fat and water. The iZQC evolution frequency was mapped linearly to temperature. The temperature accuracy and coherence lifetime of the iZQC method were evaluated against other thermometry methods that are based on localized spectroscopy and multiple gradient echo imaging.The temperature coefficient (α) was 9.8 ± 0.7 ppb/°C with the iZQC method and 2 ± 7 ppb/°C with traditional localized spectroscopy.Because the accuracy of thermometry is limited by the reproducibility of α between samples, iZQCs provide nearly a 10-fold accuracy improvement in red marrow (0.7 ppb/°C for iZQCs versus 7 ppb/°C for localized spectroscopy.) The iZQC technique in this study will for the first time allow accurate and quantitative thermal imaging of red marrow. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc. Magn Reson Med 74:63-70, 2015. © 2014 Wiley Periodicals, Inc.

The recent development of a bi-modality magnetic resonance imaging/electron paramagnetic resonance imaging (MRI/EPRI) platform has enabled longitudinal monitoring of both tumor oxygenation and redox status in murine cancer models. The current study used this imaging platform to test the hypothesis that a more reducing tumor microenvironment accompanies the development of tumor hypoxia. To test this, the redox status of the tumor was measured using Tempol as a redox‑sensitive MRI contrast agent, and tumor hypoxia was measured with Oxo63, which is an oxygen-sensitive EPRI spin probe. Images were acquired every 1-2 days in mice bearing SCCVII tumors. The median pO(2) decreased from 14 mmHg at 7 days after tumor implantation to 7 mmHg at 15 days after implantation. Additionally, the hypoxic fraction, defined as the percentage of the tumor that exhibited a pO(2)10 mmHg, increased with tumor size (from 10% at 500 mm(3) to 60% at 3,500 mm(3)). The rate of Tempol reduction increased as a function of tumor volume (0.4 min(-1) at 500 mm(3) to 1.7 min(-1) at 3,500 mm(3)), suggesting that the tumor microenvironment became more reduced as the tumor grew. The results show that rapid Tempol reduction correlates with decreased tumor oxygenation, and that the Tempol decay rate constant may be a surrogate marker for tumor hypoxia.

Individuals are exposed to ionizing radiation during medical procedures and nuclear disasters, and this exposure can be carcinogenic, toxic, and sometimes fatal. Drugs that protect individuals from the adverse effects of radiation may therefore be valuable countermeasures against the health risks of exposure. In the current study, the LD(50/30) (the dose resulting in 50% of exposed mice surviving 30 days after exposure) was determined in control C3H mice and mice treated with the nitroxide radioprotectors Tempol, 3-CP, 16c, 22c, and 23c. The pharmacokinetics of 22c and 23c were measured with magnetic resonance imaging (MRI) in the brain, blood, submandibular salivary gland, liver, muscle, tongue, and myocardium. It was found that 23c was the most effective radioprotector of the five studied: 23c increased the LD(50/30) in mice from 7.9±0.15Gy (treated with saline) to 11.47±0.13Gy (an increase of 45%). Additionally, MRI-based pharmacokinetic studies revealed that 23c is an effective redox imaging agent in the mouse brain, and that 23c may allow functional imaging of the myocardium. The data in this report suggest that 23c is currently the most potent known nitroxide radioprotector, and that it may also be useful as a contrast agent for functional imaging.