Adverse Events Reported by Patients With Cancer After Administration of a 2-Dose mRNA COVID-19 Vaccine.

BACKGROUND: Most safety and efficacy trials of the SARS-CoV-2 vaccines excluded patients with cancer, yet these patients are more likely than healthy individuals to contract SARS-CoV-2 and more likely to become seriously ill after infection. Our objective was to record short-term adverse reactions to the COVID-19 vaccine in patients with cancer, to compare the magnitude and duration of these reactions with those of patients without cancer, and to determine whether adverse reactions are related to active cancer therapy. PATIENTS AND METHODS: A prospective, single-institution observational study was performed at an NCI-designated Comprehensive Cancer Center. All study participants received 2 doses of the Pfizer BNT162b2 vaccine separated by approximately 3 weeks. A report of adverse reactions to dose 1 of the vaccine was completed upon return to the clinic for dose 2. Participants completed an identical survey either online or by telephone 2 weeks after the second vaccine dose. RESULTS: The cohort of 1,753 patients included 67.5% who had a history of cancer and 12.0% who were receiving active cancer treatment. Local pain at the injection site was the most frequently reported symptom for all respondents and did not distinguish patients with cancer from those without cancer after either dose 1 (39.3% vs 43.9%; P=.07) or dose 2 (42.5% vs 40.3%; P=.45). Among patients with cancer, those receiving active treatment were less likely to report pain at the injection site after dose 1 compared with those not receiving active treatment (30.0% vs 41.4%; P=.002). The onset and duration of adverse events was otherwise unrelated to active cancer treatment. CONCLUSIONS: When patients with cancer were compared with those without cancer, few differences in reported adverse events were noted. Active cancer treatment had little impact on adverse event profiles.

Enclathration and Confinement of Small Gases by the Intrinsically 0D Porous Molecular Solid, Me,H,SiMe2.

The stable, guest-free crystal form of the simple molecular cavitand, Me,H,SiMe2, is shown to be intrinsically porous, possessing discrete, zero-dimensional (0D) pores/microcavities of about 28 Å(3). The incollapsible 0D pores of Me,H,SiMe2 have been exploited for the enclathration and room temperature (and higher) confinement of a wide range of small gases. Over 20 isostructural x(gas/guest)@Me,H,SiMe2 (x ≤ 1) clathrates (guest = H2O, N2, Ar, CH4, Kr, Xe, C2H4, C2H6, CH3F, CO2, H2S, CH3Cl, CH3OCH3, CH3Br, CH3SH, CH3CH2Cl, CH2Cl2, CH3I, CH3OH, BrCH2Cl, CH3CH2OH, CH3CN, CH3NO2, I2), and a propyne clathrate (CH3CCH@Me,H,SiMe2·2CHCl3), have been prepared and characterized, and their single crystal structures determined. Gas enclathration is found to be highly selective for gases that can be accommodated by the predefined, though slightly flexible 0D pore. The structure determinations provide valuable insight, at subangstrom resolution, into the factors that govern inclusion selectivity, gas accommodation, and the kinetic stability of the clathrates, which has been probed by thermal gravimetric analysis. The activation (emptying) of several clathrates (guest = H2O, N2, CO2, Kr, CH3F) is shown to occur in a single-crystal-to-single-crystal (SC → SC) fashion, often requiring elevated temperatures. Akin to open pore materials, water vapor and CO2 gas are shown to be taken up by single crystals of empty Me,H,SiMe2 at room temperature, but sorption rates are slow, occurring over weeks to months. Thus, Me,H,SiMe2 exhibits very low, but measurable, gas permeability, despite there being no obvious dynamic mechanism to facilitate gas uptake. The unusually slow exchange kinetics has allowed the rates of gas (water vapor and CO2) sorption to be quantified by single crystal X-ray diffraction. The data are well fit to a simple three-dimensional diffusion model.

Critical Factors Driving the High Volumetric Uptake of Methane in Cu3(btc)2.

A thorough experimental and computational study has been carried out to elucidate the mechanistic reasons for the high volumetric uptake of methane in the metal-organic framework Cu3(btc)2 (btc(3-) = 1,3,5-benzenetricarboxylate; HKUST-1). Methane adsorption data measured at several temperatures for Cu3(btc)2, and its isostructural analogue Cr3(btc)2, show that there is little difference in volumetric adsorption capacity when the metal center is changed. In situ neutron powder diffraction data obtained for both materials were used to locate four CD4 adsorption sites that fill sequentially. This data unequivocally shows that primary adsorption sites around, and within, the small octahedral cage in the structure are favored over the exposed Cu(2+) or Cr(2+) cations. These results are supported by an exhaustive parallel computational study, and contradict results recently reported using a time-resolved diffraction structure envelope (TRDSE) method. Moreover, the computational study reveals that strong methane binding at the open metal sites is largely due to methane-methane interactions with adjacent molecules adsorbed at the primary sites instead of an electronic interaction with the metal center. Simulated methane adsorption isotherms for Cu3(btc)2 are shown to exhibit excellent agreement with experimental isotherms, allowing for additional simulations that show that modifications to the metal center, ligand, or even tuning the overall binding enthalpy would not improve the working capacity for methane storage over that measured for Cu3(btc)2 itself.

Vessel and Airway Characteristics in One-Year Computed Tomography-defined Rapid Emphysema Progression: SPIROMICS.

Rationale: Rates of emphysema progression vary in chronic obstructive pulmonary disease (COPD), and the relationships with vascular and airway pathophysiology remain unclear. Objectives: We sought to determine if indices of peripheral (segmental and beyond) pulmonary arterial dilation measured on computed tomography (CT) are associated with a 1-year index of emphysema (EI; percentage of voxels <-950 Hounsfield units) progression. Methods: Five hundred ninety-nine former and never-smokers (Global Initiative for Chronic Obstructive Lung Disease stages 0-3) were evaluated from the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort: rapid emphysema progressors (RPs; n = 188, 1-year ΔEI > 1%), nonprogressors (n = 301, 1-year ΔEI ± 0.5%), and never-smokers (n = 110). Segmental pulmonary arterial cross-sectional areas were standardized to associated airway luminal areas (segmental pulmonary artery-to-airway ratio [PAARseg]). Full-inspiratory CT scan-derived total (arteries and veins) pulmonary vascular volume (TPVV) was compared with small vessel volume (radius smaller than 0.75 mm). Ratios of airway to lung volume (an index of dysanapsis and COPD risk) were compared with ratios of TPVV to lung volume. Results: Compared with nonprogressors, RPs exhibited significantly larger PAARseg (0.73 ± 0.29 vs. 0.67 ± 0.23; P = 0.001), lower ratios of TPVV to lung volume (3.21 ± 0.42% vs. 3.48 ± 0.38%; P = 5.0 × 10-12), lower ratios of airway to lung volume (0.031 ± 0.003 vs. 0.034 ± 0.004; P = 6.1 × 10-13), and larger ratios of small vessel volume to TPVV (37.91 ± 4.26% vs. 35.53 ± 4.89%; P = 1.9 × 10-7). In adjusted analyses, an increment of 1 standard deviation in PAARseg was associated with a 98.4% higher rate of severe exacerbations (95% confidence interval, 29-206%; P = 0.002) and 79.3% higher odds of being in the RP group (95% confidence interval, 24-157%; P = 0.001). At 2-year follow-up, the CT-defined RP group demonstrated a significant decline in postbronchodilator percentage predicted forced expiratory volume in 1 second. Conclusions: Rapid one-year progression of emphysema was associated with indices indicative of higher peripheral pulmonary vascular resistance and a possible role played by pulmonary vascular-airway dysanapsis.

Comparing Lifestyle Modifications and the Magnitude of Their Associated Benefit on Cancer Mortality.

Many cancers are associated with poor diet, lack of physical activity, and excess weight. Improving any of these three lifestyle factors would likely reduce cancer deaths. However, modifications to each of these-better nutrition, enhanced activity and fitness, and loss of extra body fat-have different effect sizes on cancer mortality. This review will highlight the relative benefit that each lifestyle change, enacted prior to a diagnosis of cancer, might impart on cancer-related deaths, as well as attempt to quantify the changes required to derive such a benefit. The review relies primarily on epidemiological data, with meta-analyses serving as the backbone for comparisons across interventions and individual studies within the larger meta-analyses providing the data necessary to form more quantitative conclusions. The reader can then use this information to better understand, recommend, and implement behaviors that might ultimately reduce cancer mortality. Of all the interventions, it seems clear that exercise, specifically improving cardiorespiratory fitness, is the best way to decrease the risk of dying from cancer.

Use of Lean Six Sigma to Improve Access to Care in a Surgical Subspecialty Clinic.

INTRODUCTION: At the Naval Medical Center San Diego urology clinic, patients reported waiting for greater than 1 month for an initial consult. A Lean Six Sigma approach was used to improve access to care (ATC) and decrease variation in access by improving scheduling. METHODS: A Define-Measure-Analyze-Improve-Control approach was used. Delay to new patient visits was identified as the focus of intervention. The scheduling template was changed from a fixed stream to a modified wave based on simulation software analysis of appointment cycle times. Appointment length was adjusted based on cycle time analysis, and two rooms per clinician were used instead of one. The ratio of initial consults relative to established follow-ups and procedures was adjusted upward to better balance with the historic demand. RESULTS: Statistically significant improvement was seen in ATC and compliance with the Defense Health Agency (DHA) standard that new consults be seen within 28 days. Average days for a new consult to be seen were reduced by 7.2 days in the pediatric urology clinic (P < 0.0001) and 6.4 days in the adult urology clinic (P < 0.0001). Compliance with the Defense Health Agency 28-day ATC standard increased from a baseline of 69.2% to 88.9% and 61.7% to 84.4%, respectively, in the pediatric and adult clinics (P < 0.001 for both). Patient satisfaction was maintained at or above the goal threshold throughout the project. CONCLUSIONS: An Lean Six Sigma model was used to improve timeliness of care for our patients, improving the overall quality of their healthcare experience. Simulation software can be used to model the clinic throughput and test alternative scheduling templates. ATC was significantly improved and patient satisfaction was maintained at or above goal thresholds.

The Most Difficult Lesson From Cancer Just Might Be Its Most Valuable.

In this essay, the author reflects on his experience treating patients with cancer.

A semi-automatic framework of measuring pulmonary arterial metrics at anatomic airway locations using CT imaging.

Pulmonary vascular dysfunction has been implicated in smoking-related susceptibility to emphysema. With the growing interest in characterizing arterial morphology for early evaluation of the vascular role in pulmonary diseases, there is an increasing need for the standardization of a framework for arterial morphological assessment at airway segmental levels. In this paper, we present an effective and robust semi-automatic framework to segment pulmonary arteries at different anatomic airway branches and measure their cross-sectional area (CSA). The method starts with user-specified endpoints of a target arterial segment through a custom-built graphical user interface. It then automatically detect the centerline joining the endpoints, determines the local structure orientation and computes the CSA along the centerline after filtering out the adjacent pulmonary structures, such as veins or airway walls. Several new techniques are presented, including collision-impact based cost function for centerline detection, radial sample-line based CSA computation, and outlier analysis of radial distance to subtract adjacent neighboring structures in the CSA measurement. The method was applied to repeat-scan pulmonary multirow detector CT (MDCT) images from ten healthy subjects (age: 21-48 Yrs, mean: 28.5 Yrs; 7 female) at functional residual capacity (FRC). The reproducibility of computed arterial CSA from four airway segmental regions in middle and lower lobes was analyzed. The overall repeat-scan intra-class correlation (ICC) of the computed CSA from all four airway regions in ten subjects was 96% with maximum ICC found at LB10 and RB4 regions.

Emerging therapeutic options for eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus that often occurs in atopic persons. Management strategies include pharmacotherapy, dietary modification, and endoscopic therapy, although patients will often have a relapsing and remitting course. Currently, the primary pharmacotherapy for EoE consists of corticosteroids. Immuno-modulators, leukotriene antagonists, biologies, and monoclonal antibodies are currently under study for treatment of EoE. The role of immunoglobulin E-mediated allergic reactions has been well documented and may provide insight into the etiology and effective therapy of EoE.

An investigation of flumazenil to antagonize gamma-hydroxybutyrate intoxication in a murine model.

OBJECTIVE: Prior animal studies have suggested that flumazenil may blunt GHB's sedative-hypnotic affects. We hypothesized that flumazenil would decrease the affects of GHB in a murine model of intoxication. METHODS: We performed a controlled, pilot experiment using 32 mice divided into 3 groups. All mice received intraperitoneal injections of GHB (1.5 g/kg). Group I received sham injections at time 0, and then GHB at 5 minutes. Group II received flumazenil (0.3 mg/kg) at time 0, and then GHB at 5 minutes. Group III received sham injection at time 0, then GHB at 5 minutes, and then 4 escalating flumazenil doses administered at 3-minute intervals (0.003 to 1 mg/kg). We measured certain functions: time to loss/recovery of righting reflexes (RR), time to sprawl/recovery of sprawl (postural tone [PT]), and death. RESULTS: There were statistically significant delays in the loss of PT and shortened recovery time to RR in pre-treated mice (group II) versus controls (group I). There were no differences in group III versus group I for any outcome parameters. CONCLUSIONS: In this model, pre-dosing flumazenil prior to GHB administration delayed clinical intoxication.