Case Series of Thrombosis With Thrombocytopenia Syndrome After COVID-19 Vaccination-United States, December 2020 to August 2021.

BACKGROUND: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. It presents similarly to spontaneous heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis after vaccination with the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson) have previously been described. OBJECTIVE: To describe surveillance data and reporting rates of all reported TTS cases after COVID-19 vaccination in the United States. DESIGN: Case series. SETTING: United States. PATIENTS: Case patients receiving a COVID-19 vaccine from 14 December 2020 through 31 August 2021 with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction) reported to the Vaccine Adverse Event Reporting System. If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for antiplatelet factor 4 antibodies or functional heparin-induced thrombocytopenia platelet test result was required. MEASUREMENTS: Reporting rates (cases per million vaccine doses) and descriptive epidemiology. RESULTS: A total of 57 TTS cases were confirmed after vaccination with Ad26.COV2.S (n = 54) or a messenger RNA (mRNA)-based COVID-19 vaccine (n = 3). Reporting rates for TTS were 3.83 per million vaccine doses (Ad26.COV2.S) and 0.00855 per million vaccine doses (mRNA-based COVID-19 vaccines). The median age of patients with TTS after Ad26.COV2.S vaccination was 44.5 years (range, 18 to 70 years), and 69% of patients were women. Of the TTS cases after mRNA-based COVID-19 vaccination, 2 occurred in men older than 50 years and 1 in a woman aged 50 to 59 years. All cases after Ad26.COV2.S vaccination involved hospitalization, including 36 (67%) with intensive care unit admission. Outcomes of hospitalizations after Ad26.COV2.S vaccination included death (15%), discharge to postacute care (17%), and discharge home (68%). LIMITATIONS: Underreporting and incomplete case follow-up. CONCLUSION: Thrombosis with thrombocytopenia syndrome is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the 3 cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine: Updated Interim Recommendations from the Advisory Committee on Immunization Practices - United States, December 2021.

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the adenovirus-vectored COVID-19 vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson), and on February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for its use as a single-dose primary vaccination in persons aged ≥18 years (1,2). On April 13, 2021, CDC and FDA recommended a pause in the use of Janssen COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome (TTS), a rare condition characterized by low platelets and thrombosis, including at unusual sites such as the cerebral venous sinus (cerebral venous sinus thrombosis [CVST]), after receipt of the vaccine.* ACIP rapidly convened two emergency meetings to review reported cases of TTS, and 10 days after the pause commenced, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in persons aged ≥18 years, but included a warning regarding rare clotting events after vaccination, primarily among women aged 18-49 years (3). In July, after review of an updated benefit-risk assessment accounting for risks of Guillain-Barré syndrome (GBS) and TTS, ACIP concluded that benefits of vaccination with Janssen COVID-19 vaccine outweighed risks. Through ongoing safety surveillance and review of reports from the Vaccine Adverse Event Reporting System (VAERS), additional cases of TTS after receipt of Janssen COVID-19 vaccine, including deaths, were identified. On December 16, 2021, ACIP held an emergency meeting to review updated data on TTS and an updated benefit-risk assessment. At that meeting, ACIP made a recommendation for preferential use of mRNA COVID-19 vaccines over the Janssen COVID-19 vaccine, including both primary and booster doses administered to prevent COVID-19, for all persons aged ≥18 years. The Janssen COVID-19 vaccine may be considered in some situations, including for persons with a contraindication to receipt of mRNA COVID-19 vaccines.

US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021.

Importance: Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021. Objective: To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt. Design, Setting, and Participants: Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021). Exposures: Receipt of Ad26.COV2.S vaccine. Main Outcomes and Measures: Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians. Results: Patients' ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 ×103/µL to 127 ×103/µL. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4). Conclusions and Relevance: The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia.

Clinical predictors of port infections within the first 30 days of placement.

PURPOSE: To identify risk factors for port infections within 30 days of placement. MATERIAL AND METHODS: A retrospective chart review of port placements from 2002-2009 was conducted. Patients who had port removals secondary to infection within the first 30 days of placement were included. This group of patients was compared with a control group of patients with ports with no evidence of infection. For every one patient with a port infection, two control subjects were chosen of the same gender and new port placement during the same month as the corresponding patient with an infected port. RESULTS: From 2002-2009, 4,404 ports were placed. Of the 4,404 patients, 33 (0.7%) were found to have a port infection within 30 days of placement. Compared with the control group, the early infection group had a higher prevalence of leukopenia (21.2% vs 6.1%, P = .039) and thrombocytopenia (33% vs 12%, P = .0158). There was also a higher prevalence of an inpatient hospital stay during port placement and high international normalized ratio in the early infection group. CONCLUSIONS: Low preoperative white blood cell and platelet counts were risk factors for early infection. Abnormal coagulation profiles and inpatient access of ports after placement could be additional risk factors.

Academic medical centers and underserved communities: modern complexities of an enduring relationship.

BACKGROUND: Most private academic medical centers are located in underserved areas, yet fiscal pressures have led many to struggle with balancing their commitment to surrounding communities with other missions. OBJECTIVE: To explore stakeholders' views regarding the ethical, legal, and financial obligations of private academic medical centers to their surrounding neighborhoods. DESIGN, PARTICIPANTS, AND MEASURES: QualitatiVe analysis of key informant interviews during 2008 with medical students, faculty and community physicians, administrators, and community health leaders at a large urban academic medical center. Grounded theory was used to iteratively review, code, and revise a taxonomy of themes, with abstraction of illustrative quotes. RESULTS: Nineteen in-depth interviews were conducted. All respondents believed academic medical centers have an obligation to their surrounding communities but characterized the extent of this obigation in a variety of ways. Respondents disagreed about how the core mission of an academic center should be defined, although many recognized the tripartite mission, conflict centered on the balance that should be sought between research and clinical care. A majority of interviewees expressed frustration with the nation's current health care system. Many provided unprompted recommendations regarding how academic medical centers might engage their underserved communities, including conducting formal needs analyses, promoting ongoing dialogue, and using information technology to bridge the provision of clinical care in community and academic settings. CONCLUSIONS: These data provide enriching perspectives from stakeholders regarding this enduring yet evolving relationship. The diversity of views illustrates one of the challenges that will accompany health care reform impacting academic medical centers and their surrounding, often underserved, communities.

Adaptive differentiation of quantitative traits in the globally distributed weed, wild radish (Raphanus raphanistrum).

Weedy species with wide geographical distributions may face strong selection to adapt to new environments, which can lead to adaptive genetic differentiation among populations. However, genetic drift, particularly due to founder effects, will also commonly result in differentiation in colonizing species. To test whether selection has contributed to trait divergence, we compared differentiation at eight microsatellite loci (measured as F(ST)) to differentiation of quantitative floral and phenological traits (measured as Q(ST)) of wild radish (Raphanus raphanistrum) across populations from three continents. We sampled eight populations: seven naturalized populations and one from its native range. By comparing estimates of Q(ST) and F(ST), we found that petal size was the only floral trait that may have diverged more than expected due to drift alone, but inflorescence height, flowering time, and rosette formation have greatly diverged between the native and nonnative populations. Our results suggest the loss of a rosette and the evolution of early flowering time may have been the key adaptations enabling wild radish to become a major agricultural weed. Floral adaptation to different pollinators does not seem to have been as necessary for the success of wild radish in new environments.

Weed evolution: Genetic differentiation among wild, weedy, and crop radish.

Approximately 200 weed species are responsible for more than 90% of crop losses and these comprise less than one percent of all named plant species, suggesting that there are only a few evolutionary routes that lead to weediness. Agricultural weeds can evolve along three main paths: they can be escaped crops, wild species, or crop-wild hybrids. We tested these three hypotheses in weedy radish, a weed of small grains and an emerging model for investigating the evolution of agricultural weeds, using 21 CAPS and SSR markers scored on 338 individuals from 34 populations representing all major species and sub-species in the radish genus Raphanus. To test for adaptation of the weeds to the agricultural environment, we estimated genetic differentiation in flowering time in a series of common garden experiments with over 2,400 individuals from 43 populations (all but one of the genotyped populations plus 10 additional populations). Our findings suggest that the agricultural weed radish R. r. raphanistrum is most genetically similar to native populations of R. r. raphanistrum and is likely not a feral crop or crop hybrid. We also show that weedy radish flowers more rapidly than any other Raphanus population or cultivar, which is consistent with rapid adaptation to the frequent and severe disturbance that characterizes agricultural fields.

Undertriage of Firearm-Related Injuries in a Major Metropolitan Area.

Importance: National anatomic triage criteria prescribe specific transport rules for injured patients. However, there is limited information about patients with firearm-related injuries undertriaged to nondesignated facilities (ie, hospitals without specialized trauma teams or units), including what clinical outcomes are achieved and how many are transferred to a higher level of care. Without these data, it is difficult to make informed regional or national policy decisions about triage practices. Undertriage of firearm-related injuries is a good model for evaluating the undertriage of patients with trauma because the anatomic triage criteria for patients with firearm-related injuries are simple. Objective: To evaluate the prevalence, spatial distribution, and clinical outcomes of undertriage of firearm-related injuries. Design, Setting, and Participants: This study is a retrospective analysis of firearm-related injuries in residents of Cook County, Illinois, from January 1, 2009, to December 31, 2013. Outpatient and inpatient hospital databases were used. Participants included patients with International Classification of Diseases, Ninth Revision, Clinical Modification firearm-related cause-of-injury codes. Data were collected all at once in August 2014. Data analysis took place from March 12, 2015, to February 1, 2016. Main Outcomes and Measures: Undertriaged cases were defined as patients who met the national anatomic triage criteria for transfer to higher-level trauma center care. Spatial distribution, injury severity, and clinical outcomes, including death, were analyzed. Results: Of the 9886 patients included in this analysis, 8955 (90.6%) were male, 7474 (75.6%) were African American, and 5376 (54.4%) were aged 15 to 24 years.In Cook County, Illinois, where there are 19 trauma centers, 2842 of 9886 (28.7%) firearm-related injuries were initially treated in nondesignated facilities. Among the 4934 cases with firearm-related injury who met the anatomic triage criteria, 884 (17.9%) received initial treatment at a nondesignated facility and only 92 (10.4%) were transferred to a designated trauma center. Significant spatial clustering was identified on the west side of Chicago and in the southern parts of Chicago and Cook County. In the multivariable models, patients treated in nondesignated facilities were less likely to die than were patients treated in designated trauma centers. Conclusions and Relevance: Undertriage of firearm-related injuries was much more prevalent than expected. Although the likelihood of dying during hospitalization was greater among patients treated in designated trauma centers, these patients were substantially in worse condition across all measures of injury severity. A smaller proportion of patients treated in designated trauma centers died during the first 24 hours of hospitalization. This study highlights the need for better regional coordination, especially with interhospital transfers, as well as the importance of assessing the distribution of emergency medical services resources to make the trauma care system more effective and equitable.