Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT)

Background: Immune-checkpoint inhibitors (ICI) can lead to immune-related adverse events (irAEs) in a significant proportion of patients. The mechanisms underlying irAEs development are mostly unknown and might involve multiple immune effectors, such as T cells, B cells and autoantibodies (AutoAb). Methods: We used custom autoantigen (AutoAg) microarrays to profile AutoAb related to irAEs in patients receiving ICI. Plasma was collected before and after ICI from cancer patients participating in two clinical trials (NCT03686202, NCT02644369). A one-time collection was obtained from healthy controls for comparison. Custom arrays with 162 autoAg were used to detect IgG and IgM reactivities. Differences of median fluorescent intensity (MFI) were analyzed with Wilcoxon sign rank test and Kruskal–Wallis test. MFI 500 was used as threshold to define autoAb reactivity. Results: A total of 114 patients and 14 healthy controls were included in this study. irAEs of grade (G) ≥ 2 occurred in 37/114 patients (32%). We observed a greater number of IgG and IgM reactivities in pre-ICI collections from patients versus healthy controls (62 vs 32 p < 0.001). Patients experiencing irAEs G ≥ 2 demonstrated pre-ICI IgG reactivity to a greater number of AutoAg than patients who did not develop irAEs (39 vs 33 p = 0.040). We observed post-treatment increase of IgM reactivities in subjects experiencing irAEs G ≥ 2 (29 vs 35, p = 0.021) and a decrease of IgG levels after steroids (38 vs 28, p = 0.009). Conclusions: Overall, these results support the potential role of autoAb in irAEs etiology and evolution. A prospective study is ongoing to validate our findings (NCT04107311)

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Adding to the story, did penetrating trauma really increase? changes in trauma patterns during the COVID-19 pandemic: A multi-institutional, multi-region investigation

•Blunt traumatic injury volumes decreased secondary to decreased MVCs during the initial four months of the COVID-19 pandemic.•Penetrating injury increased during the first four months of the COVID-19 pandemic, along with a significant increase in GSW volume.•Stay at home orders (SAHOs) were associated with the observed decrease in blunt injuries, specifically decreased MVCs.•4. Stay at home orders did not account for observed volume changes in non-MVC related blunt injuries or penetrating injuries. Results from single-region studies suggest that stay at home orders (SAHOs) had unforeseen consequences on the volume and patterns of traumatic injury during the initial months of the Coronavirus disease 2019 (COVID-19). The aim of this study was to describe, using a multi-regional approach, the effects of COVID-19 SAHOs on trauma volume and patterns of traumatic injury in the US. A retrospective cohort study was performed at four verified Level I trauma centers spanning three geographical regions across the United States (US). The study period spanned from April 1, 2020 – July 31, 2020 including a month-matched 2019 cohort. Patients were categorized into pre-COVID-19 (PCOV19) and first COVID-19 surge (FCOV19S) cohorts. Patient demographic, injury, and outcome data were collected via Trauma Registry queries. Univariate and multivariate analyses were performed. A total 5,616 patients presented to participating study centers during the PCOV19 (2,916) and FCOV19S (2,700) study periods.  Blunt injury volume decreased (p = 0.006) due to a significant reduction in the number of motor vehicle collisions (MVCs) (p = 0.003). Penetrating trauma experienced a significant increase, 8% (246/2916) in 2019 to 11% (285/2,700) in 2020 (p = 0.007), which was associated with study site (p = 0.002), not SAHOs. Finally, study site was significantly associated with changes in nearly all injury mechanisms, whereas SAHOs accounted for observed decreases in calculated weekly averages of blunt injuries (p < 0.02) and MVCs (p = 0.003). Results of this study suggest that COVID-19 and initial SAHOs had variable consequences on patterns of traumatic injury, and that region-specific shifts in traumatic injury ensued during initial SAHOs. These results suggest that other factors, potentially socioeconomic or cultural, confound trauma volumes and types arising from SAHOs. Future analyses must consider how regional changes may be obscured with pooled cohorts, and focus on characterizing community-level changes to aid municipal preparation for future similar events

Planning for the Next Pandemic: Trauma Injuries Require Pre-COVID-19 Levels of High-Intensity Resources

As hospital systems plan for health care utilization surges and stress, understanding the necessary resources of a trauma system is essential for planning capacity. We aimed to describe trends in high-intensity resource utilization (operating room [OR] usage and intensive care unit [ICU] admissions) for trauma care during the initial months of the COVID-19 pandemic. Trauma registry data (2019 pre-COVID-19 and 2020 COVID-19) were collected retrospectively from 4 level I trauma centers. Direct emergency department (ED) disposition to the OR or ICU was used as a proxy for high-intensity resource utilization. No change in the incidence of direct ED to ICU or ED to OR utilization was observed (2019: 24%, 2020 23%; P = .62 and 2019: 11%, 2020 10%; P = .71, respectively). These results suggest the need for continued access to ICU space and OR theaters for traumatic injury during national health emergencies, even when levels of trauma appear to be decreasing

Management of coronary disease in patients with advanced kidney disease

BACKGROUND Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P=0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P=0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P=0.03). CONCLUSIONS Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction

Health status after invasive or conservative care in coronary and advanced kidney disease

BACKGROUND In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of &lt;30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, 120.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, 122.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, 121.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, 122.2 to 3.4). CONCLUSIONS Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy