Assessing long-term locoregional control of spinal osseous metastases after microwave ablation.

Osseous metastases to the spine result in significant pain and decreased quality of life. The purpose of this study was to evaluate the long-term efficacy of microwave ablation (MWA) for the treatment of spinal metastases regarding pain reduction and local control of disease progression. In this single center retrospective study, patients with osseous metastases to the spine undergoing MWA with vertebroplasty from 2013 to 2020 were included. Locoregional control of metabolic activity at the treated level was assessed using PET/CT scan both pre- and post-procedure. Pain reduction was measured using change in visual analog scale (VAS) pain score. Forty-eight spinal levels were treated with MWA in 28 patients (57 % male, mean age 68 ± 9 years). Median ablation time, energy, and temperature were 4 min and 13 s, 3.6 kJ, and 80 °C, respectively. Median pre-procedure maximum standard uptake value (SUVmax) was significantly reduced following ablation, from 4.55 (IQR 3.65-6.1) to 0 (IQR 0-1.8; p < 0.001), over an average of 29 ± 14.1 month follow up period. Pre-procedure VAS pain score was reduced from median (IQR) of 8 (6.5-9) to 1(1-2), 2(1-3) and 1(0.5-3) at 24 h, four weeks, and six months post-procedure, respectively (all p < 0.001 with respect to pre-procedure scores). In conclusion, this study supports microwave ablation as an effective technique for pain palliation and long-term locoregional tumor control of oligometastatic spinal disease as assessed by metabolic response.

Optimization and Mechanistic Investigations of Novel Allosteric Activators of PKG1α.

Activation of PKG1α is a compelling strategy for the treatment of cardiovascular diseases. As the main effector of cyclic guanosine monophosphate (cGMP), activation of PKG1α induces smooth muscle relaxation in blood vessels, lowers pulmonary blood pressure, prevents platelet aggregation, and protects against cardiac stress. The development of activators has been mostly limited to cGMP mimetics and synthetic peptides. Described herein is the optimization of a piperidine series of small molecules to yield activators that demonstrate in vitro phosphorylation of vasodilator-stimulated phosphoprotein as well as antiproliferative effects in human pulmonary arterial smooth muscle cells. Hydrogen/deuterium exchange mass spectrometry experiments with the small molecule activators revealed a mechanism of action consistent with cGMP-induced activation, and an X-ray co-crystal structure with a construct encompassing the regulatory domains illustrated a binding mode in an allosteric pocket proximal to the low-affinity cyclic nucleotide-binding domain.

CT for detection of malignant posterior intercostal lymph nodes in patients undergoing pre-operative staging for malignant pleural mesothelioma.

INTRODUCTION: Recent evidence suggests that patients with malignant pleural mesothelioma (MPM) undergoing extended pleurectomy/decortication (eP/D) with metastasis to the posterior intercostal lymph nodes (PILN) have a worse prognosis. In this study, we determine if MPM PILN metastasis can be reliably detected on computed tomography (CT). MATERIALS AND METHODS: Preoperative staging CT exams were reviewed for the presence of PILN in MPM patients undergoing eP/D between 2007-2013 with surgical sampling of their PILN. CT images were reviewed by two thoracic radiologists blinded to clinical records, including operative pathology reports. The number and short axis size of PILN were recorded and correlated with surgical pathology. Statistical analysis examined the value of preoperative CT to detect metastatic PILN. RESULTS: Of 36 patients that underwent eP/D with PILN sampling had preoperative CT images for review. At surgery, 22 of these patients had metastatic PILN and 14 had benign PILN. The positive and negative predictive values for one or more nodes seen on preoperative CT were 60 % and 38 % respectively. The number of PILN on preoperative CT did not predict metastasis (p = 0.40) with an average of 2 PILN seen, regardless of PILN pathology. The average nodal short axis size was 4.6 mm and 4.8 mm for benign and malignant PILN, respectively, and PILN short axis size did not predict metastasis (p = 0.39). There was little inter-observer variability between the size and number of nodes detected by each radiologist. CONCLUSIONS: CT does not reliably identify metastatic PILN on preoperative CT for patients with MPM undergoing extended pleurectomy/decortication.

Small molecule agonists of toll-like receptors 7 and 8: a patent review 2014 - 2020.

INTRODUCTION: Toll-like receptors 7 and 8 (TLR7 and TLR8) are endosomal immune receptors that initiate an innate immune response and can facilitate activation of the adaptive immune system. Both preclinical and clinical studies have shown the downstream inflammatory response from TLR7 and TLR8 agonism results in preliminary efficacy for the treatment of cancer, viral infections, and for use as a vaccine adjuvant. AREAS COVERED: This patent review covers recent developments in small molecule TLR7 and TLR8 agonists published between January 2014 - February 2020. We summarize relevant chemical scaffolds, observed structure-activity relationships, and where available, preliminary animal models, and clinical data. EXPERT OPINION: In the last 6 years, there has been significant progress in the optimization of novel TLR7 and TLR8 small molecule agonists. These novel compounds are currently being evaluated in the clinic for multiple antiviral and oncology indications. Clinical data from these trials will provide a clearer outlook on 1) the TLR7/8 engagement necessary to obtain the desired immune response, 2) safety margin improvement using directed delivery, and 3) potential synergistic effects with checkpoint inhibitor combination therapies.

Lymphangitic carcinomatosis: A common radiographic manifestation of local failure following extended pleurectomy/decortication in patients with malignant pleural mesothelioma.

INTRODUCTION: The lymphangitic carcinomatosis (LC) pattern of metastatic malignancy is associated with a poor prognosis but is currently not well defined in malignant pleural mesothelioma (MPM). Here, we report the incidence and prognostic significance of the radiographic development of LC in MPM following extended pleurectomy/decortication (EPD). METHODS: Consecutive patients with biopsy-proven MPM undergoing EPD with intraoperative photodynamic therapy (PDT) at our institution from 2008 to 2014 were included in this retrospective study. Patients without available post-surgical clinical or imaging data for direct review were excluded. CT images were reviewed by an experienced, board-certified thoracic radiologist and confirmed by consensus review. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan Meier methodology. Hazard ratios were compared with a cox proportional hazard model. RESULTS: 44 patients underwent EPD with PDT during the study period and had available clinical and imaging data. During the follow-up period (median 34 months), 17 patients (39%) developed LC at a median of 10 months after surgery (IQR 5-21 months). 16 of the 17 patients who developed LC (94%) died during the follow-up period, compared to 17 of the 27 who did not develop LC (63%). OS for the LC versus non-LC group was 53% versus 93% at 1 year and 18% versus 67% at 3 years. LC was significantly associated with a lower OS (HR 4.07; 95% confidence interval 1.44-11.48; p = 0.008). PFS for the LC group versus non-LC group was 8 months (IQR 5-9 months) compared to 17 months (IQR 11-24 months) (p < 0.001). CONCLUSION: LC is a common form of failure in MPM following EPD and is associated with a poor prognosis. Thus, further studies are warranted to determine if any evidence of preoperative LC should be an absolute contraindication to EPD and may warrant an EPP or no surgery at all.

The value of delayed phase enhanced imaging in malignant pleural mesothelioma.

BACKGROUND: Cross-sectional imaging of malignant pleural mesothelioma (MPM) can underestimate the presence of local tumor invasion. Since accurate staging is vital optimal choice of therapy, techniques that optimize pleural imaging are needed. Here we estimate the optimal timing of MPM enhancement on magnetic resonance imaging (MRI). METHODS: All MPM patients with intravenous (IV) contrast enhanced staging MRI between 2000-2016 at our institution were retrospectively selected for image analysis. Patients with incomplete imaging protocol and maximum pleural tumor thickness <1 cm were excluded. Quantitative measurements of tumor signal intensity were obtained on pre-contrast and post-contrast phases where MRI acquisition parameters were fixed. Using best-fit model curves, predicted maximum time points of enhancement were determined using a simulation of predicted values. Additionally, a qualitative assessment of tumor conspicuity was performed at all IV contrast time delays imaged. A statistical analysis assessed for correlation between qualitative lesion conspicuity and quantitative tumor enhancement. RESULTS: Of the 42 MPM patients who had undergone staging MRI during the study period, 12 patients met the study criteria. Peak tumor enhancement was between 150 and 300 sec following IV contrast administration. Within this time window, 80% of patients are projected to have reached >80%, >85%, and >90% peak tumor enhancement. There was a statistically significant correlation between increasing tumor enhancement and subjective lesion conspicuity. CONCLUSIONS: Optimal MPM enhancement on MRI likely occurs at a time delay between 2.5-5 min following IV contrast administration. Further study of delayed phase enhancement of MPM with dynamic contrast enhanced MRI is warranted.

Use of warm carbon dioxide insufflators does not affect intra-colonic gas temperature and has no effect on polyp detection rate during colonoscopy - a randomized controlled trial.

BACKGROUND AND STUDY AIMS: Methods to improve polyp detection during colonoscopy have been investigated, with conflicting results for warm water irrigation. Carbon Dioxide (CO 2) warmed to 37 °C may have similar or more pronounced effects on bowel motility. This study aimed to assess whether warmed CO 2 would improve polyp detection compared to room temperature air insufflation. PATIENTS AND METHODS: This was a double-blind, randomized controlled trial that enrolled 204 patients undergoing screening or surveillance outpatient colonoscopy. The primary outcome was polyp per patient detection rate. Secondary outcomes included adenoma per patient detection rates, bowel spasm, and patient comfort. RESULTS: The trial was terminated after an interim analysis determined futility. Between the warmed CO 2 and room air groups, no significant differences were found in the per-colonoscopy polyp detection rate ( P  = 0.57); overall polyp detection rate ( P  = 0.69); or adenoma detection rates ( P  = 0.74). More patients in the room temperature group had lower spasm scores (p = 0.02); however, there was a trend towards greater patient comfort in the warmed CO 2 group ( P  = 0.054). An ex-vivo study showed a significant difference between exiting CO 2 temperature at the insufflator end vs. delivered CO 2 temperature at the colonoscope tip end. The temperature of insufflation at the tip of the colonoscope was not different when using warmed vs. unwarmed insufflation ( P  = 0.62). CONCLUSION: When compared with room air insufflation, warmed CO 2 insufflation did not affect polyp detection rates.

Complementary roles of interventional radiology and therapeutic endoscopy in gastroenterology.

Acute upper and lower gastrointestinal bleeding, enteral feeding, cecostomy tubes and luminal strictures are some of the common reasons for gastroenterology service. While surgery was initially considered the main treatment modality, the advent of both therapeutic endoscopy and interventional radiology have resulted in the paradigm shift in the management of these conditions. In this paper, we discuss the patient's work up, indications, and complementary roles of endoscopic and angiographic management in the settings of gastrointestinal bleeding, enteral feeding, cecostomy tube placement and luminal strictures. These conditions often require multidisciplinary approaches involving a team of interventional radiologists, gastroenterologists and surgeons. Further, the authors also aim to describe how the fields of interventional radiology and gastrointestinal endoscopy are overlapping and complementary in the management of these complex conditions.

Beware of positive pressure: coronary artery air embolism following percutaneous lung biopsy.

Patients undergoing percutaneous lung biopsy are at risk of developing a systemic air embolism. Air embolism may manifest as a catastrophic iatrogenic event with ischemic insult to the end organs, with sites of least resistance such as coronary and cerebral circulation the most susceptible. We review the available literature and present a case of iatrogenic air embolism during computed tomography guided percutaenous lung biopsy under general anesthesia. Management, outcome, and periprocedural factors that may have contributed to the complication are discussed.

Racial disparities in mortality in patients undergoing bariatric surgery in the U.S.A.

BACKGROUND: Non-Hispanic blacks bear a disproportionate burden of the growing obesity epidemic. Bariatric surgery is an effective treatment for morbid obesity. We sought to assess for racial disparities in short-term outcomes following bariatric surgery. METHODS: Patients undergoing bariatric surgery were extracted from the Nationwide Inpatient Sample between 1999 and 2007. In-hospital mortality and length of stay were compared between different racial groups undergoing bariatric surgery after stratification by gender, and multivariate analysis was conducted to adjust for demographic, surgery year, and clinical and hospital characteristics. RESULTS: There were 115,507 bariatric surgeries. Overall mortality rate was 2.5 deaths per 1,000 and was higher among non-Hispanic blacks compared to non-Hispanic whites (3.7 vs. 2.3 per 1,000; P = 0.007). Racial mortality disparities were most pronounced among males and at hospitals with lowest surgical volumes. In multivariate analysis, predictors of mortality were non-Hispanic black race (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.22-2.45), increasing age, increasing Charlson index (OR, 1.26; 95% CI, 1.16-1.37), Medicare (OR, 2.13; 95% CI, 1.57-2.91), and Medicaid (OR, 3.35; 95% CI, 2.29-4.91) insurance. Incremental calendar year had reduced odds of mortality (OR, 0.80; 95% CI, 0.76-0.83). Above national median neighborhood income (OR, 0.59; 95% CI, 0.42-0.83) was protective in males, while teaching hospital status conveyed greater mortality (OR, 2.12; 95% CI, 1.40-3.22). CONCLUSIONS: Non-Hispanic blacks undergoing bariatric surgery demonstrate higher in-hospital mortality than their racial counterparts. It is unclear if this disparity is due to susceptibility to obesity-related mortality or suboptimal delivery of healthcare in the perioperative setting.