Dysregulated naive B cells and de novo autoreactivity in severe COVID-19.

Severe SARS-CoV-2 infection1 has been associated with highly inflammatory immune activation since the earliest days of the COVID-19 pandemic2-5. More recently, these responses have been associated with the emergence of self-reactive antibodies with pathologic potential6-10, although their origins and resolution have remained unclear11. Previously, we and others have identified extrafollicular B cell activation, a pathway associated with the formation of new autoreactive antibodies in chronic autoimmunity12,13, as a dominant feature of severe and critical COVID-19 (refs. 14-18). Here, using single-cell B cell repertoire analysis of patients with mild and severe disease, we identify the expansion of a naive-derived, low-mutation IgG1 population of antibody-secreting cells (ASCs) reflecting features of low selective pressure. These features correlate with progressive, broad, clinically relevant autoreactivity, particularly directed against nuclear antigens and carbamylated proteins, emerging 10-15 days after the onset of symptoms. Detailed analysis of the low-selection compartment shows a high frequency of clonotypes specific for both SARS-CoV-2 and autoantigens, including pathogenic autoantibodies against the glomerular basement membrane. We further identify the contraction of this pathway on recovery, re-establishment of tolerance standards and concomitant loss of acute-derived ASCs irrespective of antigen specificity. However, serological autoreactivity persists in a subset of patients with postacute sequelae, raising important questions as to the contribution of emerging autoreactivity to continuing symptomology on recovery. In summary, this study demonstrates the origins, breadth and resolution of autoreactivity in severe COVID-19, with implications for early intervention and the treatment of patients with post-COVID sequelae.

Special Considerations for Secondary Surgery After Upper Extremity Transplantation.

BACKGROUND: Upper extremity (UE) transplantation is a complex undertaking that may require emergent or elective secondary surgery (SS) days to years following transplant. Various patient and transplantation may help determine what SS is needed. In this study, we characterize the SS needed by our UE transplant patients. METHODS: We retrospectively reviewed 6 patients who underwent hand and UE transplantation by one of the authors. Transplantation and SS details were obtained from medical records. Hand and arm function was quantified both subjectively (patient-reports) and objectively (Disabilities of the Arm, Shoulder, and Hand Score; Carroll test; Action Research Arm Tests; Box and Block test). RESULTS: Six patients underwent transplantation for a total of 10 transplanted limbs. Five transplants were performed below and 5 above the elbow. Mean time post-transplantation at last follow-up was 5 years (range: 1-9 years). In all, 66.7% of the patients required SS: total 7 surgeries comprising 13 procedures. The most common procedures were to improve hand function-nerve decompressions and tendon transfer, both in above-elbow transplant. Both patients showed a mean improvement of 15 points on Carroll scores. One above-elbow transplant had a brachioplasty for excess skin and another had a hematoma evacuation immediately after transplantation. Procedures in the below-elbow transplants included multiple incision and drainages for a septic wrist and an open reduction and internal fixation for a forearm fracture. CONCLUSION: Patients receiving UE transplantation often require one or more secondary procedures which may vary with level of transplantation. Secondary surgery should be an important aspect of pretransplant planning and cost-effectiveness determinations. LEVEL OF EVIDENCE: Level IV.

Using Pressure Mapping to Optimize Hospital-Acquired Pressure Injury Prevention Strategies in the Burn Intensive Care Unit.

Although prior studies have demonstrated the utility of real-time pressure mapping devices in preventing pressure ulcers, there has been little investigation of their efficacy in burn intensive care unit (BICU) patients, who are at especially high risk for these hospital-acquired injuries. This study retrospectively reviewed clinical records of BICU patients to investigate the utility of pressure mapping data in determining the incidence, predictors, and associated costs of hospital-acquired pressure injuries (HAPIs). Of 122 patients, 57 (47%) were studied prior to implementation of pressure mapping and 65 (53%) were studied after implementation. The HAPI rate was 18% prior to implementation of pressure monitoring, which declined to 8% postimplementation (chi square: P = .10). HAPIs were less likely to be stage 3 or worse in the postimplementation cohort (P < .0001). On multivariable-adjusted regression accounting for known predictors of HAPIs in burn patients, having had at least 12 hours of sustained pressure loading in one area significantly increased odds of developing a pressure injury in that area (odds ratio 1.3, 95% CI 1.0-1.5, P = .04). Patients who developed HAPIs were significantly more likely to have had unsuccessful repositioning efforts in comparison to those who did not (P = .02). Finally, implementation of pressure mapping resulted in significant cost savings-$6750 (standard deviation: $1008) for HAPI-related care prior to implementation, vs $3800 (standard deviation: $923) after implementation, P = .008. In conclusion, the use of real-time pressure mapping decreased the morbidity and costs associated with HAPIs in BICU patients.

Inappropriate Transfer of Burn Patients: A 5-Year Retrospective at a Single Center.

OBJECTIVE: Burn injuries have an annual incidence exceeding 40,000. The Burn Center Referral Criteria published by the American Burn Association (ABA) serve to guide health centers in determining appropriateness of patient transfer to a specialized center. With inappropriate transfer rates reaching up to 77%, reliance on the ABA criteria is critical as the decision to transfer a patient can impose significant costs to both the patient and healthcare system. The aim of this study is to evaluate the appropriateness of all burn patient transfers to a single burn center over a 5-year period and assess the potential role of telemedicine to optimize the assessment and care of this patient population. METHODS: A 5-year retrospective review was conducted to all burn patients transferred or consulted for transfer to our burn center between January 2013 and January 2017. After application of inclusion and exclusion criteria, 767 cases were analyzed, with 612 ultimately being transferred. Outcome measures included basic clinical and demographic information, as well as logistical burn and transfer data such as percent total body surface area and transfer distance. After data collection, 5-year descriptive trends were analyzed, and the ABA criteria were applied to each patient case to evaluate appropriateness of transfer. Patients transferred despite not meeting at least one of the ABA criteria were classified as inappropriately transferred. RESULTS: A total of 25 patients (3.2%) were found to be inappropriate transfers. Statistical analysis compared appropriately transferred patients (n = 587) with those inappropriately transferred. Overall, inappropriately transferred patients were more likely to have superficial partial thickness burns (76% vs 46%, P = 0.05), were less likely to need surgery (4% vs 22%, P < 0.05), and had a higher incidence of upper extremity burns (32% vs 4%, P < 0.01). CONCLUSIONS: Our study increases awareness of the most commonly seen presentation of inappropriately transferred burn patients over a 5-year period at our center. Given the advent of telemedicine, the ability of institutions to pinpoint a subset of patients most vulnerable to inappropriate transfer will allow for a streamlining of resources that will serve to benefit both patients and the health system.