Advocating Intraluminal Radiation Therapy in Cerebral Arteriovenous Malformation Treatment

In 2014, ARUBA (a randomized trial on cerebral Arteriovenous Malformation – AVM) found patients treated using prevalent interventional strategies are three times more likely to suffer a stroke/die compared with those treated conservatively (blood pressure reduction). Subsequent controversy led the European societies dealing with AVM to organize a consensus conference. Among the statements made was: “There may be indications for treating patients with higher Spetzler-Martin (SM) grades, based on a case-to-case consensus decision of the experienced team”. Thus, a clear accord emerges. There is a lacuna/weakness of interventional modalities when addressing high SM grade AVMs. This lack of a clear treatment choice originated our review. We attempt to identify the advantages and challenges of each present treatment/evaluation modality and highlight core requirements for future strategies. We conclude that existing modalities provide substantial recent improvements, yet the core challenge persists. Finally, we advocate testing a novel modality – intraluminal radiotherapy (active implants) by exploiting the “candy wrapper” or edge effect. If proven effective, this approach could offer gradual vessel occlusion with minimal abrupt hemodynamic changes known to induce hemorrhage, the lowest recurring session number (reduced costs), minimally invasive attributes and very low radiation (dose/dose rate) kinetics minimizing potential Adverse Radiation Effects (AREs)

Am I on Track? Evaluating Patient-Specific Weight Loss After Bariatric Surgery Using an Outcomes Calculator

PURPOSE: Individual weight loss outcomes after bariatric surgery can vary considerably. As a result, identifying and assisting patients who are not on track to reach their weight loss goals can be challenging. MATERIALS AND METHODS: Using a bariatric surgery outcomes calculator, which was formulated using a state-wide bariatric-specific data registry, predicted weight loss at 1 year after surgery was calculated on 658 patients who underwent bariatric surgery at 35 different bariatric surgery programs between 2015 and 2017. Patient characteristics, postoperative complications, and weight loss trajectories were compared between patients who met or exceeded their predicted weight loss calculation to those who did not based on observed to expected weight loss ratio (O:E) at 1 year after surgery. RESULTS: Patients who did not meet their predicted weight loss at 1 year (n = 237, 36%) had a mean O:E of 0.71, while patients who met or exceeded their prediction (n = 421, 63%) had a mean O:E = 1.14. At 6 months, there was a significant difference in the percent of the total amount of predicted weight loss between the groups (88% of total predicted weight loss for those that met their 1-year prediction vs 66% for those who did not, p \u3c 0.0001). Age, gender, procedure type, and risk-adjusted complication rates were similar between groups. CONCLUSION: Using a bariatric outcomes calculator can help set appropriate weight-loss expectations after surgery and also identify patients who may benefit from additional therapy prior to reaching their weight loss nadir

Factors associated with completion of patient surveys 1 year after bariatric surgery

BACKGROUND: Patient-reported outcomes (PRO) obtained from follow-up survey data are essential to understanding the longitudinal effects of bariatric surgery. However, capturing data among patients who are well beyond the recovery period of surgery remains a challenge, and little is known about what factors may influence follow-up rates for PRO. OBJECTIVES: To assess the effect of hospital practices and surgical outcomes on patient survey completion rates at 1 year after bariatric surgery. SETTING: Prospective, statewide, bariatric-specific clinical registry. METHODS: Patients at hospitals participating in the Michigan Bariatric Surgery Collaborative are surveyed annually to obtain information on weight loss, medication use, satisfaction, body image, and quality of life following bariatric surgery. Hospital program coordinators were surveyed in June 2017 about their practices for ensuring survey completion among their patients. Hospitals were ranked based on 1-year patient survey completion rates between 2011 and 2015. Multivariable regression analyses were used to identify associations between hospital practices, as well as 30-day outcomes, on hospital survey completion rankings. RESULTS: Overall, patient survey completion rates at 1 year improved from 2011 (33.9% ± 14.5%) to 2015 (51.0% ± 13.0%), although there was wide variability between hospitals (21.1% versus 77.3% in 2015). Hospitals in the bottom quartile for survey completion rates had higher adjusted rates of 30-day severe complications (2.6% versus 1.7%, respectively; P = .0481), readmissions (5.0% versus 3.9%, respectively; P = .0157), and reoperations (1.5% versus .7%, respectively; P = .0216) than those in the top quartile. While most hospital practices did not significantly impact survey completion at 1 year, physically handing out surveys during clinic visits was independently associated with higher completion rates (odds ratio, 13.60; 95% confidence interval, 1.99-93.03; P =.0078). CONCLUSIONS: Hospitals vary considerably in completion rates of patient surveys at 1 year after bariatric surgery, and lower rates were associated with hospitals that had higher complication rates. Hospitals with the highest completion rates were more likely to physically hand surveys to patients during clinic visits. Given the value of PRO on longitudinal outcomes of bariatric surgery, improving data collection across multiple hospital systems is imperative

CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus

Chronic hepatitis B virus (HBV) infection is prevalent, deadly, and seldom cured due to the persistence of viral episomal DNA (cccDNA) in infected cells. Newly developed genome engineering tools may offer the ability to directly cleave viral DNA, thereby promoting viral clearance. Here, we show that the CRISPR/Cas9 system can specifically target and cleave conserved regions in the HBV genome, resulting in robust suppression of viral gene expression and replication. Upon sustained expression of Cas9 and appropriately chosen guide RNAs, we demonstrate cleavage of cccDNA by Cas9 and a dramatic reduction in both cccDNA and other parameters of viral gene expression and replication. Thus, we show that directly targeting viral episomal DNA is a novel therapeutic approach to control the virus and possibly cure patients.United States. National Institutes of Health (DK085713)National Cancer Institute (U.S.) (P30-CA14051)National Institute of Environmental Health Sciences (P30-ES002109)United States. National Institutes of Health (1K08DK101754

Precision Epoch of Reionization studies with next-generation CMB experiments

Future arcminute resolution polarization data from ground-based Cosmic Microwave Background (CMB) observations can be used to estimate the contribution to the temperature power spectrum from the primary anisotropies and to uncover the signature of reionization near $\ell=1500$ in the small angular-scale temperature measurements. Our projections are based on combining expected small-scale E-mode polarization measurements from Advanced ACTPol in the range $300<\ell<3000$ with simulated temperature data from the full Planck mission in the low and intermediate $\ell$ region, $2<\ell<2000$. We show that the six basic cosmological parameters determined from this combination of data will predict the underlying primordial temperature spectrum at high multipoles to better than $1\%$ accuracy. Assuming an efficient cleaning from multi-frequency channels of most foregrounds in the temperature data, we investigate the sensitivity to the only residual secondary component, the kinematic Sunyaev-Zel'dovich (kSZ) term. The CMB polarization is used to break degeneracies between primordial and secondary terms present in temperature and, in effect, to remove from the temperature data all but the residual kSZ term. We estimate a $15 \sigma$ detection of the diffuse homogeneous kSZ signal from expected AdvACT temperature data at $\ell>1500$, leading to a measurement of the amplitude of matter density fluctuations, $\sigma_8$, at $1\%$ precision. Alternatively, by exploring the reionization signal encoded in the patchy kSZ measurements, we bound the time and duration of the reionization with $\sigma(z_{\rm re})=1.1$ and $\sigma(\Delta z_{\rm re})=0.2$. We find that these constraints degrade rapidly with large beam sizes, which highlights the importance of arcminute-scale resolution for future CMB surveys.Comment: 10 pages, 10 figure

Racial variation in baseline characteristics and wait times among patients undergoing bariatric surgery

BACKGROUND: Although bariatric surgery is the most effective treatment for obesity and weight-related comorbid diseases, utilization rates are disproportionately low among non-white patients. We sought to understand if variation in baseline characteristics or access to care exists between white and non-white patients. METHODS: Using a statewide bariatric-specific data registry, we evaluated all patients who underwent bariatric surgery between 2006 and 2020 and completed a preoperative baseline questionnaire, which included a question about self-identification of race. Patient characteristics, co-morbidities, and time from initial preoperative clinic evaluation to date of surgery were compared among racial groups. RESULTS: A total of 73,141 patients met inclusion criteria with 18,741 (25.5%) self-identified as non-white. These included Black/African American (n = 11,904), Hispanic (n = 3448), Asian (n = 121), Native Hawaiian/Pacific Islander (n = 41), Middle Eastern (n = 164), Multiple (n = 2047) and other (n = 608). Non-white males were the least represented group, accounting for only 4% of all bariatric cases performed. Non-white patients were more likely to be younger (43.0 years vs. 46.6 years, p \u3c 0.0001), disabled (16% vs. 11.4%, p \u3c 0.0001) and have Medicaid (8.4% vs. 3.8%, p \u3c 0.0001) when compared to white patients, despite having higher rates of college education (78.0% vs. 76.6, p \u3c 0.0001). In addition, median time from initial evaluation to surgery was also longer among non-white patients (157 days vs. 127 days, p \u3c 0.0001), despite having higher rates of patients with a body mass index above 50 kg/m(2) (39.0% vs. 33.2%, p \u3c 0.0001). CONCLUSIONS: Non-white patients undergoing bariatric surgery represent an extremely diverse group of patients with more socioeconomic disadvantages and longer wait times when compared to white patients despite presenting with higher rates of severe obesity. Current guidelines and referral patterns for bariatric surgery may not be equitable and need further examination when considering the management of obesity within diverse populations to reduce disparities in care-of which non-white males are particularly at risk

Surgical and functional outcome after resection of 64 petroclival meningiomas

Objective: The management of petroclival meningiomas (PCMs) remains notoriously difficult due to their close association with neurovascular structures and their complex anatomy, hence the surgical paradigm change from radical to functional resection in the past. With this study, we aimed to analyze surgical and functional outcomes of a modern consecutive series of patients with PCMs. Methods: We reviewed patient charts and imaging data of 64 consecutive patients from 2006 to 2018 with a PCM resected at our institution and compared surgical and functional outcomes between subgroups stratified by surgical approach. Results: Females comprised 67.2% of patients (n = 43), with a mean age of 55 years (median 56; range 21–84). Follow-up data were available for 68.8% and reached a mean of 42.3 months (range 1–129) with a median of 28.5 months. The mean tumor diameter was 37.3 mm (standard deviation (SD) 15.4; median 37.0). Infiltration of the cavernous sinus was observed in 34 cases (53.1%), and the lesions affected the brain stem in 28 cases (43.8%). Preoperative cranial nerve palsy was observed in 73.4% of cases; trigeminal neuropathy (42.2%), hearing loss (32.8%), and impairment of vision (18.8%) were the most common. A retrosigmoid approach was employed in 47 cases (78.1%), pterional in 10 (15.6%), combined petrosal in 2 (3.1%), and transnasal and subtemporal in 1 (1.6%). Fifteen cases (23.4%) were resected in a two-staged fashion. Gross total resection (GTR) was attempted in 30 (46.9%) cases without cavernous sinus infiltration and was achieved in 21 (70.0%) of these cases. Surgical complications occurred in 13 cases (20.3%), most commonly meningitis (n = 4; 6.3%). Postoperatively, 56 patients (87.5%) developed new cranial nerve palsy, of which 36 (63.6%) had improved or resolved on last follow up. Achieving GTR was not significantly associated with higher rates of surgical complications (chi-square; p = 0.288) or postoperative cranial nerve palsy (chi-square; p = 0.842). Of all cases, 20 (31.3%) underwent postoperative radiation. Tumor progression was observed in 10 patients (15.9%) after a mean 102 months (median 124). Conclusions: Surgical resection remains the mainstay of treatment for PCMs, with perioperative cranial neuropathies exhibiting favorable recovery rates. Most essentially, the preselection of patients with hallmarks of brain stem affection and cavernous sinus infiltration should dictate whether to strive for a functionally oriented strategy in favor of radical resection

The Atacama Cosmology Telescope: Dusty Star-Forming Galaxies and Active Galactic Nuclei in the Southern Survey

We present a catalog of 191 extragalactic sources detected by the Atacama Cosmology Telescope (ACT) at 148 GHz and/or 218 GHz in the 2008 Southern survey. Flux densities span 14-1700 mJy, and we use source spectral indices derived using ACT-only data to divide our sources into two sub-populations: 167 radio galaxies powered by central active galactic nuclei (AGN), and 24 dusty star-forming galaxies (DSFGs). We cross-identify 97% of our sources (166 of the AGN and 19 of the DSFGs) with those in currently available catalogs. When combined with flux densities from the Australian Telescope 20 GHz survey and follow-up observations with the Australia Telescope Compact Array, the synchrotron-dominated population is seen to exhibit a steepening of the slope of the spectral energy distribution from 20 to 148 GHz, with the trend continuing to 218 GHz. The ACT dust-dominated source population has a median spectral index of 3.7+0.62-0.86, and includes both local galaxies and sources with redshifts as great as 5.6. Dusty sources with no counterpart in existing catalogs likely belong to a recently discovered subpopulation of DSFGs lensed by foreground galaxies or galaxy groups.Comment: 13 pages, 8 figures, 4 table