T-cell activation profiles distinguish hemophagocytic lymphohistiocytosis and early sepsis.

Hemophagocytic lymphohistiocytosis (HLH) is a fatal disorder of immune hyperactivation that has been described as a cytokine storm. Sepsis due to known or suspected infection has also been viewed as a cytokine storm. Although clinical similarities between these syndromes suggest similar immunopathology and may create diagnostic uncertainty, distinguishing them is critical as treatments are widely divergent. We examined T-cell profiles from children with either HLH or sepsis and found that HLH is characterized by acute T-cell activation, in clear contrast to sepsis. Activated T cells in patients with HLH were characterized as CD38high/HLA-DR+ effector cells, with activation of CD8+ T cells being most pronounced. Activated T cells were type 1 polarized, proliferative, and displayed evidence of recent and persistent activation. Circulating activated T cells appeared to be broadly characteristic of HLH, as they were seen in children with and without genetic lesions or identifiable infections and resolved with conventional treatment of HLH. Furthermore, we observed even greater activation and type 1 polarization in tissue-infiltrating T cells, described here for the first time in a series of patients with HLH. Finally, we observed that a threshold of >7% CD38high/HLA-DR+ cells among CD8+ T cells had strong positive and negative predictive value for distinguishing HLH from early sepsis or healthy controls. We conclude that the cytokine storm of HLH is marked by distinctive T-cell activation whereas early sepsis is not, and that these 2 syndromes can be readily distinguished by T-cell phenotypes.

Virtual Communication Embedded Bedside ICU Rounds: A Hybrid Rounds Practice Adapted to the Coronavirus Pandemic.

OBJECTIVES: Coronavirus disease 2019 containment strategies created challenges with patient-centered ICU rounds. We examined how hybrid rounds with virtual communication added to in-person rounds could facilitate social distancing while maintaining patient-centered care. DESIGN: Continuous quality improvement. SETTING: Quaternary care referral pediatric hospital. PATIENTS: Daytime rounds conducted on PICU patients. INTERVENTIONS: Following a needs assessment survey and pilot trials, multiple technological solutions were implemented in a series of plan-do-study-act cycles. Hybrid rounds model was deployed where a videoconference platform was used to establish communication between the bedside personnel (nurse, patient/family, and partial ICU team) with remotely located remaining ICU team, ancillary, and consultant providers. Floor labels marking 6-feet distance were placed for rounders. MEASUREMENTS AND MAIN RESULTS: Outcome metrics included compliance with social distancing, mixed methods analysis of surveys, direct interviews of providers and families, and reports of safety concerns. The clinicians adopted hybrid rounds readily. Compliance with social distancing and use of floor labels needed reminders. One-hundred fourteen providers completed the feedback survey. Twenty-five providers and 11 families were interviewed. Feedback about hybrid rounds included inability to teach effectively, suboptimal audio-video quality, loss of situational awareness of patient/unit acuity, alarm interference, and inability to socially distance during other ICU interactions. Benefits noted were improved ancillary input, fewer interruptions, improved efficiency, opportunity to integrate with data platforms, and engage remote consultants and families. Nurses and families appreciated the efforts to ensure safety but wanted the ICU attending/fellow supervising the team to participate at bedside, during rounds. Clinicians appreciated the multidisciplinary input but felt that teaching was difficult. CONCLUSIONS: Hybrid rounds employed during pandemic facilitated social distancing while retaining patient-centered multidisciplinary ICU rounds but compromised teaching during rounds. A change to ingrained rounding habits needs team commitment and ongoing optimization. The hybrid rounds model has potential for generalizability to other settings.

Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis.

The HLH-2004 criteria are used to diagnose hemophagocytic lymphohistiocytosis (HLH), yet concern exists for their misapplication, resulting in suboptimal treatment of some patients. We sought to define the genomic spectrum and associated outcomes of a diverse cohort of children who met the HLH-2004 criteria. Genetic testing was performed clinically or through research-based whole-exome sequencing. Clinical metrics were analyzed with respect to genomic results. Of 122 subjects enrolled over the course of 17 years, 101 subjects received genetic testing. Biallelic familial HLH (fHLH) gene defects were identified in only 19 (19%) and correlated with presentation at younger than 1 year of age (P < .0001). Digenic fHLH variants were observed but lacked statistical support for disease association. In 28 (58%) of 48 subjects, research whole-exome sequencing analyses successfully identified likely molecular explanations, including underlying primary immunodeficiency diseases, dysregulated immune activation and proliferation disorders, and potentially novel genetic conditions. Two-thirds of patients identified by the HLH-2004 criteria had underlying etiologies for HLH, including genetic defects, autoimmunity, and malignancy. Overall survival was 45%, and increased mortality correlated with HLH triggered by infection or malignancy (P < .05). Differences in survival did not correlate with genetic profile or extent of therapy. HLH should be conceptualized as a phenotype of critical illness characterized by toxic activation of immune cells from different underlying mechanisms. In most patients with HLH, targeted sequencing of fHLH genes remains insufficient for identifying pathogenic mechanisms. Whole-exome sequencing, however, may identify specific therapeutic opportunities and affect hematopoietic stem cell transplantation options for these patients.

Comprehensive Improvement of Cardiology Inpatient Transfers: A Bed-availability Triggered Approach.

Introduction: Patient transfers pose a potential risk during hospitalizations. Structured communication practices are necessary to ensure effective handoffs, but occur amidst competing priorities and constraints. We sought to design and implement a multidisciplinary process to enhance communication between pediatric cardiovascular intensive care unit and cardiology floor teams with a comprehensive approach evaluating efficiency, safety, and culture. Methods: We conducted a prospective quality improvement study to enact a bed-availability triggered bedside handoff process. The primary aim was to reduce the time between handoff and unit transfer. Secondary metrics captured the impact on safety (reported safety events, overnight transfers, bounce backs, and I-PASS utilization), efficiency (transfer latency, unnecessary patient handoffs, and cumulative time providers were engaged in handoffs), and culture (team members perceptions of satisfaction, collaboration, and handoff efficiency via survey data). Results: Eighty-two preimplementation surveys, 26 stakeholder interviews, and 95 transfers were completed during the preintervention period. During the postintervention period, 145 handoffs were audited. We observed significant reductions in transfer latency, unnecessary handoffs, and cumulative provider handoff time. Overnight transfers decreased, and no negative impact was observed in reported safety events or bouncebacks. Survey results showed a positive impact on collaboration, efficiency, and satisfaction among team members. Conclusions: Developing safer handoff practices require a collaborative, structured, and stepwise approach. Advances are attainable in high-volume centers, and comprehensive measurement of change is necessary to ensure a positive impact on the overall patient and provider environment.

The role of plasmapheresis in critical illness.

In this article, the authors review the current recommendations from the American Society for Apheresis regarding the use of plasmapheresis in many of the diseases that intensivists commonly encounter in critically ill patients. Recent experience indicates that therapeutic plasma exchange may be useful in a wide spectrum of illnesses characterized by microvascular thrombosis, the presence of autoantibodies, immune activation with dysregulation of immune response, and some infections.