Outcomes of Patients Hospitalized with Neutropenic Fever and COVID-19 Infection: A Nationwide Analysis (preprint)

Importance: Neutropenic fever (NF) is an oncological emergency associated with worse outcomes. Unfortunately, there is a paucity of existing literature describing the association between neutropenic fever and COVID-19 infection. Objective: This study investigates the effect of COVID-19 infection on outcomes of hospitalization with neutropenic fever, highlighting the patients’ characteristics. Design: Retrospective cohort analyses were conducted using the National Inpatient Sample database year 2020. Setting:  Population-basedinpatient database in the United States Participants: All neutropenic fever adult hospitalizations (16,790 patients) were identified from the database using ICD-10 codes and were stratified into with and without COVID-19 infection. Main Outcomes and Measures: The primary outcome of interest was inpatient mortality. Secondary outcomes include respiratory failure, hemorrhagic shock, septic shock, acute kidney injury (AKI), health economic burden defined as longer length of stay (LOS), higher hospital cost, and patient charge. Results: The database query generated 16,790 adult patients with a primary diagnosis of neutropenic fever. Of these, 145 patients had concurrent neutropenic fever and COVID-19 infection. Patients with neutropenic fever and COVID-19 infection had 14 times higher odds (adjusted odds ratio (AOR) = 13.6, 95% confidence interval (CI) = 3.6 – 51.8) of inpatient mortality when compared to those without COVID-19. Additionally, they had 21 times greater odds of septic shock [10.3% vs. 0.4%, aOR/aIRR = 20.8, 95% CI 4.5 – 96.5], and 11 times higher odds of respiratory failure [27.6% vs. 4.0%, aOR/aIRR = 10.6, 95% CI 4.1 – 27.5] when compared to their counterparts without COVID-19. Furthermore, these patients had longer hospital stay (9.1 vs. 5.1 days, aIRR 1.14, 95% CI 1.3–2.4), higher average hospital cost ($20,279 vs. $15,357, aIRR 1.3, 95% CI 1.1–1.7), and higher average patient charges ($96,300 vs. $57,338, aIRR 1.7, 95% CI 1.1 – 2.7) Conclusion and Relevance: Neutropenic fever with concurrent COVID-19 infection was associated with significantly higher in-hospital mortality, greater risk of septic shock, respiratory failure, longer average hospital stay, and higher average hospital cost. Further research is needed to explore interventions to improve outcomes in hospitalized neutropenic fever patients with COVID-19. Prevention of COVID-19 infection in this population is expedient.

Club cell protein (CC)16 as potential lung injury marker in a porcine 72 h polytrauma model.

BACKGROUND: Polytrauma and respiratory tract damage after thoracic trauma cause about 25% of mortality among severely injured patients. Thoracic trauma can lead to the development of severe lung complications such as acute respiratory distress syndrome, and is, therefore, of great interest for monitoring in intensive care units (ICU). In recent years, club cell protein (CC)16 with its antioxidant properties has proven to be a potential outcome-related marker. In this study, we evaluated whether CC16 constitutes as a marker of lung damage in a porcine polytrauma model. METHODS: In a 72 h ICU polytrauma pig model (thoracic trauma, tibial fracture, hemorrhagic shock, liver laceration), blood plasma samples (0, 3, 9, 24, 48, 72 h), BAL samples (72 h) and lung tissue (72 h) were collected. The trauma group (PT) was compared to a sham group. CC16 as a possible biomarker for lung injury in this model, and IL-8 concentrations as known indicator for ongoing inflammation during trauma were determined by ELISA. Histological analysis of ZO-1 and determination of total protein content were used to show barrier disruption and edema formation in lung tissue from the trauma group. RESULTS: Systemic CC16 levels were significantly increased early after polytrauma compared vs. sham. After 72 h, CC16 concentration was significantly increased in lung tissue as well as in BAL in PT vs. sham. Similarly, IL-8 and total protein content in BAL were significantly increased in PT vs. sham. Evaluation of ZO-1 staining showed significantly lower signal intensity for polytrauma. CONCLUSION: The data confirm for the first time in a larger animal polytrauma model that lung damage was indicated by systemic and/or local CC16 response. Thus, early plasma and late BAL CC16 levels might be suitable to be used as markers of lung injury in this polytrauma model.

Resuscitation with blood products in patients with trauma-related haemorrhagic shock receiving prehospital care (RePHILL): a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red blood cells (PRBC) and lyophilised plasma (LyoPlas) was superior to use of 0·9% sodium chloride for improving tissue perfusion and reducing mortality in trauma-related haemorrhagic shock. METHODS: Resuscitation with pre-hospital blood products (RePHILL) is a multicentre, allocation concealed, open-label, parallel group, randomised, controlled, phase 3 trial done in four civilian prehospital critical care services in the UK. Adults (age ≥16 years) with trauma-related haemorrhagic shock and hypotension (defined as systolic blood pressure <90 mm Hg or absence of palpable radial pulse) were assessed for eligibility by prehospital critial care teams. Eligible participants were randomly assigned to receive either up to two units each of PRBC and LyoPlas or up to 1 L of 0·9% sodium chloride administered through the intravenous or intraosseous route. Sealed treatment packs which were identical in external appearance, containing PRBC-LyoPlas or 0·9% sodium chloride were prepared by blood banks and issued to participating sites according to a randomisation schedule prepared by the co-ordinating centre (1:1 ratio, stratified by site). The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. This study is completed and registered with ISRCTN.com, ISRCTN62326938. FINDINGS: From Nov 29, 2016 to Jan 2, 2021, prehospital critical care teams randomly assigned 432 participants to PRBC-LyoPlas (n=209) or to 0·9% sodium chloride (n=223). Trial recruitment was stopped before it achieved the intended sample size of 490 participants due to disruption caused by the COVID-19 pandemic. The median follow-up was 9 days (IQR 1 to 34) for participants in the PRBC-LyoPlas group and 7 days (0 to 31) for people in the 0·9% sodium chloride group. Participants were mostly white (62%) and male (82%), had a median age of 38 years (IQR 26 to 58), and were mostly involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, IQR 25 to 50). Before randomisation, participants had received on average 430 mL crystalloid fluids and tranexamic acid (90%). The composite primary outcome occurred in 128 (64%) of 199 participants randomly assigned to PRBC-LyoPlas and 136 (65%) of 210 randomly assigned to 0·9% sodium chloride (adjusted risk difference -0·025% [95% CI -9·0 to 9·0], p=0·996). The rates of transfusion-related complications in the first 24 h after ED arrival were similar across treatment groups (PRBC-LyoPlas 11 [7%] of 148 compared with 0·9% sodium chloride nine [7%] of 137, adjusted relative risk 1·05 [95% CI 0·46-2·42]). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in 0·9% sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the 0·9% sodium chloride group (abnormal liver function test). There were no treatment-related deaths. INTERPRETATION: The trial did not show that prehospital PRBC-LyoPlas resuscitation was superior to 0·9% sodium chloride for adult patients with trauma related haemorrhagic shock. Further research is required to identify the characteristics of patients who might benefit from prehospital transfusion and to identify the optimal outcomes for transfusion trials in major trauma. The decision to commit to routine prehospital transfusion will require careful consideration by all stakeholders. FUNDING: National Institute for Health Research Efficacy and Mechanism Evaluation.

Emergency lower gastrointestinal endoscopy performed safely in a COVID-19 patient on extracorporeal membrane oxygenation (ECMO) with hemorrhagic shock.

Emergency endoscopy in coronavirus disease 2019 (COVID-19) patients should be avoided whenever possible to ensure the safety of medical staff; however, it may be unavoidable in some cases. We report a case of emergency lower gastrointestinal endoscopy performed with full personal protective equipment in a patient on extracorporeal membrane oxygenation with severe COVID-19 pneumonia admitted in a restricted area under negative pressure in the intensive care unit. To avoid the risk of fecal-oral transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the procedure, the patient's lower body was covered with a 2 m2 vinyl sheet with an aperture (diameter, approximately 2 cm). None of the medical staff involved exhibited any signs of SARS-CoV-2 infection after the procedure. Although patients with severe COVID-19 pneumonia on extracorporeal membrane oxygenation have a high risk of bleeding, we believe that emergency lower endoscopy can be safely performed in such patients by reducing exposure to dispersed feces and using full personal protective equipment.

Spontaneous hemopneumothorax in a patient with COVID-19.

Coronavirus disease 2019 (COVID-19) is primarily a febrile respiratory illness that was first documented in China in December 2019 and shortly after declared a pandemic on March 11, 2020. The pathophysiology of the virus is still not completely understood and remains under investigation. Consequently, new symptomatic manifestations and complications of the disease continue to be discovered. Here we present the case of a spontaneous hemopneumothorax resulting in hemorrhagic shock in an adult male with PCR confirmed COVID-19.

Fresh whole blood from walking blood banks for patients with traumatic hemorrhagic shock: A systematic review and meta-analysis.

BACKGROUND: Whole blood is optimal for resuscitation of traumatic hemorrhage. Walking Blood Banks provide fresh whole blood (FWB) where conventional blood components or stored, tested whole blood are not readily available. There is an increasing interest in this as an emergency resilience measure for isolated communities and during crises including the coronavirus disease 2019 pandemic. We conducted a systematic review and meta-analysis of the available evidence to inform practice. METHODS: Standard systematic review methodology was used to obtain studies that reported the delivery of FWB (PROSPERO registry CRD42019153849). Studies that only reported whole blood from conventional blood banking were excluded. For outcomes, odds ratios (ORs) and 95% confidence interval (CI) were calculated using random-effects modeling because of high risk of heterogeneity. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation system. RESULTS: Twenty-seven studies published from 2006 to 2020 reported >10,000 U of FWB for >3,000 patients (precise values not available for all studies). Evidence for studies was "low" or "very low" except for one study, which was "moderate" in quality. Fresh whole blood patients were more severely injured than non-FWB patients. Overall, survival was equivalent between FWB and non-FWB groups for eight studies that compared these (OR, 1.00 [95% CI, 0.65-1.55]; p = 0.61). However, the highest quality study (matched groups for physiological and injury characteristics) reported an adjusted OR of 0.27 (95% CI, 0.13-0.58) for mortality for the FWB group (p < 0.01). CONCLUSION: Thousands of units of FWB from Walking Blood Banks have been transfused in patients following life-threatening hemorrhage. Survival is equivalent for FWB resuscitation when compared with non-FWB, even when patients were more severely injured. Evidence is scarce and of relative low quality and may underestimate potential adverse events. Whereas Walking Blood Banks may be an attractive resilience measure, caution is still advised. Walking Blood Banks should be subject to prospective evaluation to optimize care and inform policy. LEVEL OF EVIDENCE: Systematic/therapeutic, level 3.