High-temporal resolution profiling reveals distinct immune trajectories following the first and second doses of COVID-19 mRNA vaccines.

Knowledge of the mechanisms underpinning the development of protective immunity conferred by mRNA vaccines is fragmentary. Here, we investigated responses to coronavirus disease 2019 (COVID-19) mRNA vaccination via high-temporal resolution blood transcriptome profiling. The first vaccine dose elicited modest interferon and adaptive immune responses, which peaked on days 2 and 5, respectively. The second vaccine dose, in contrast, elicited sharp day 1 interferon, inflammation, and erythroid cell responses, followed by a day 5 plasmablast response. Both post-first and post-second dose interferon signatures were associated with the subsequent development of antibody responses. Yet, we observed distinct interferon response patterns after each of the doses that may reflect quantitative or qualitative differences in interferon induction. Distinct interferon response phenotypes were also observed in patients with COVID-19 and were associated with severity and differences in duration of intensive care. Together, this study also highlights the benefits of adopting high-frequency sampling protocols in profiling vaccine-elicited immune responses.

Recent Major Transcriptomics and Epitranscriptomics Contributions toward Personalized and Precision Medicine.

With the advent of genome-wide screening methods-beginning with microarray technologies and moving onto next generation sequencing methods-the era of precision and personalized medicine was born. Genomics led the way, and its contributions are well recognized. However, "other-omics" fields have rapidly emerged and are becoming as important toward defining disease causes and exploring therapeutic benefits. In this review, we focus on the impacts of transcriptomics, and its extension-epitranscriptomics-on personalized and precision medicine efforts. There has been an explosion of transcriptomic studies particularly in the last decade, along with a growing number of recent epitranscriptomic studies in several disease areas. Here, we summarize and overview major efforts for cancer, cardiovascular disease, and neurodevelopmental disorders (including autism spectrum disorder and intellectual disability) for transcriptomics/epitranscriptomics in precision and personalized medicine. We show that leading advances are being made in both diagnostics, and in investigative and landscaping disease pathophysiological studies. As transcriptomics/epitranscriptomics screens become more widespread, it is certain that they will yield vital and transformative precision and personalized medicine contributions in ways that will significantly further genomics gains.

Surgical and Anesthetic Management of a Mediastinal Fatty Tumor: Lipoblastoma.

Lipoblastoma is a rare fatty tumor that is diagnosed almost exclusively in children. Presentation often consists of respiratory symptoms; chest computed tomography shows a hypodense, low, attenuated mediastinal mass. Surgical approach and anesthetic management are dependent on the location of the tumor and the degree of airway compression; in most cases, a thoracotomy is performed, although a sternotomy is used in selected cases. Final diagnosis can be confirmed using molecular genetic analysis; a genetic hallmark of lipoblastoma is the rearrangement of chromosomal region 8q12 and the PLAG1 gene. Tumor recurrence is rare when a complete resection is performed.

A modified triple test for palpable breast masses: the value of ultrasound and core needle biopsy.

BACKGROUND: The original triple test score (TTS)--clinical examination, mammogram, and fine-needle aspiration (FNA) biopsy--has long been used to evaluate palpable breast masses. We modified the original TTS to include ultrasound (US) and core biopsy to determine their role in evaluating palpable breast masses. METHODS: A retrospective chart review of 320 female patients was performed. We developed a modified triple test score (mTTS) that included physical examination, mammogram and/or US, and FNA and/or core biopsy. For the examination and imaging score, 1-3 points were given for low, moderate, or high suspicion. Biopsy scores were characterized as benign, atypical, or malignant. Final outcome was determined by open biopsy or follow-up greater than 1 year. RESULTS: Physical examination was 92% accurate (95% confidence interval [CI] 0.89-0.96, p < 0.0001) at predicting whether a mass was benign or malignant. Imaging was 88% accurate (95% CI 0.84-0.92, p < 0.0001) and needle biopsy was 95% accurate (95% CI 0.92-0.98, p < 0.0001). The modified triple test was 99% accurate (95% CI 0.98-1.00, p < 0.0001). Each 1-point increment in the mTTS was associated with an increased risk of cancer, with an odds ratio of 9.73 (CI 5.16-18.4, p < 0.0001). For 150 patients, we compared the original TTS with the mTTS. US and core biopsy changed the scores of 24 patients; only three changed clinical management. CONCLUSIONS: For patients with a palpable breast mass and a mTTS score of 3-4, no further assessment is necessary. Those with a mTTS of 8-9 can proceed to definitive therapy. Patients with a mTTS of 5-7 require further assessment. US and/or core biopsy added little to the accuracy or predictive value of the original TTS.

Testing of modified zeolite hemostatic dressings in a large animal model of lethal groin injury.

BACKGROUND: We have previously identified a granular zeolite hemostat (ZH) as an effective agent for control of severe bleeding, and it is currently being used by the US troops in the battlefield. ZH causes an exothermic reaction on application, which theoretically can be decreased by altering its chemical composition or changing its physical properties. However, the effect of these alterations on the hemostatic efficacy is unknown. We tested modified zeolites and a chitosan based dressing against controls in a swine model of battlefield injury. METHODS: A complex groin injury was created in 60 swine (40-55 kg). This included semi-transection of the proximal thigh (level of inguinal ligament), and complete division of the femoral artery and vein. After 3 minutes, the animals were assigned to (1) no dressing (ND), (2) standard dressing (SD), (3-5) SD + chemically modified ZHs, where calcium was substituted with sodium (Na), barium (Ba), or silver (Ag), respectively, (6) SD + physically modified ZH, where "beads" were packaged in a fabric bag, (7) SD + chitosan based dressing (CD). Resuscitation was started 15 minutes after application of dressing (500 mL of 6% hetastarch over 30 minutes). Survival for 180 minutes was the primary endpoint for this study. In addition, blood loss, wound temperatures, and histologic tissue damage were recorded. RESULTS: Mortality in the group that was treated with the application of bagged ZH was 10% versus 100% in the no dressing group and 50% in the SD group (p < 0.05 vs. ND and SD groups). The Na ZH group had a mortality rate of 43%, whereas application of Ba and Ag substituted zeolites, and CD were associated with a mortality rate of 25%. Ionic substitution of zeolite decreased the in vivo temperature peak by 5 to 10 degrees C. No histologic evidence of tissue necrosis was noted in this experiment. CONCLUSIONS: The use of zeolite hemostat can control hemorrhage and dramatically reduce mortality from a lethal groin wound. Modifications of zeolite hemostat can decrease the exothermic reaction and attenuate tissue damage.