Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Multicenter Study
OUTCOMES FOLLOWING ZONE 3 AND ZONE 1 AORTIC OCCLUSION FOR THE TREATMENT OF BLUNT PELVIC INJURIES.
Background: A 2021 report of the Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery multicenter registry described the outcomes of patients treated with Zone 3 resuscitative endovascular balloon occlusion of the aorta (REBOA zone 3). Our study builds upon that report, testing the hypothesis that REBOA zone 3 is associated with better outcomes than REBOA Zone 1 in the immediate treatment of severe, blunt pelvic injuries. Methods: We included adults who underwent aortic occlusion (AO) via REBOA zone 1 or REBOA Zone 3 in the emergency department for severe, blunt pelvic injuries [Abbreviated Injury Score ≥ 3 or pelvic packing/embolization/first 24 hours] in institutions with >10 REBOAs. ⋯ These patients did not differ in systolic blood pressure (SBP), cardiopulmonary resuscitation in the prehospital/hospital settings, SBP at the start of AO, time to AO start, likelihood of achieving hemodynamic stability or requirement of a second AO. After controlling for confounders, compared with REBOA Zone 3, REBOA Zone 1 was associated with a significantly higher mortality (adjusted hazard ratio, 1.51; 95% confidence interval [CI], 1.04-2.19), but there were no differences in VFD > 0 (adjusted relative risk, 0.66; 95% CI, 0.33-1.31), IFD > 0 (adjusted relative risk, 0.78; 95% CI, 0.39-1.57), discharge GCS (adjusted difference, -1.16; 95% CI, -4.2 to 1.90) or discharge GOS (adjusted difference, -0.67; 95% CI -1.9 to 0.63). Conclusions: This study suggests that compared with REBOA Zone 1, REBOA Zone 3 provides superior survival and is not inferior regarding other adverse outcomes in patients with severe blunt pelvic injuries.
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Introduction: Sepsis is a dysregulated host response to infection that can lead to life-threatening organ dysfunction. Clinical and animal studies consistently demonstrate that female subjects are less susceptible to the adverse effects of sepsis, demonstrating the importance of understanding how sex influences sepsis outcomes. The signal transducer and activator of transcription 3 (STAT3) pathway are a major signaling pathway that facilitates inflammation during sepsis. ⋯ Conclusions: Our study demonstrates that sex influences white adipose tissue STAT3 activation and morphology during sepsis, which is not dependent on the presence of functional STAT3 in mature adipocytes. Furthermore, genetic inhibition of adipocyte STAT3 activation in male, but not female mice, results in reduced lung neutrophil infiltration and lung injury during sepsis. The results from our study demonstrate the importance of considering biological sex and the white adipose tissue as potential sources and targets of inflammation during sepsis.
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While fluid resuscitation is fundamental in the treatment of sepsis-induced tissue hypoperfusion, a sustained positive fluid balance is associated with excess mortality. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water, has not been tested previously as adjuvant to fluid resuscitation in sepsis. In a prospective, parallel-grouped, blinded model of porcine peritonitis sepsis, we randomized animals to intervention with adjuvant hyaluronan (add-on to standard therapy, n = 8) or 0.9% saline (n = 8). ⋯ Plasma IL-6 increased to 2,450 (1,420-6,890) pg/mL and 3,690 (1,410-11,960) pg/mL (18 hours of resuscitation) in the intervention and control groups (nonsignificant). The intervention counteracted the increase in proportion of fragmented hyaluronan associated with peritonitis sepsis (mean peak elution fraction [18 hours of resuscitation] intervention group: 16.8 ± 0.9 versus control group: 17.9 ± 0.6 [ P = 0.031]). In conclusion, hyaluronan did not reduce the volume needed for fluid resuscitation or decrease the inflammatory reaction, even though it counterbalanced the peritonitis-induced shift toward increased proportion of fragmented hyaluronan.
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Purpose: This study is designed to explore the role and mechanism of circ_0099188 in LPS-engendered HPAEpiC cells. Methods: Circ_0099188, microRNA-1236-3p (miR-1236-3p), and high mobility group box 3 (HMGB3) levels were measured using real-time quantitative polymerase chain reaction. Cell viability and apoptosis were assessed using cell counting kit-8 (CCK-8) and flow cytometry assays. ⋯ Also, the downregulation of circ_0099188 might overturn LPS-triggered HPAEpiC cell proliferation, apoptosis, and inflammatory response. Mechanically, circ_0099188 is able to affect HMGB3 expression by sponging miR-1236-3p. Conclusion: Circ_0099188 knockdown might mitigate LPS-induced HPAEpiC cell injury by targeting the miR-1236-3p/HMGB3 axis, providing an underlying therapeutic strategy for pneumonia treatment.
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Randomized Controlled Trial Multicenter Study
Evaluation of Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Septic Shock: A Randomized Controlled Trial (The HYVITS Trial).
Purpose: The aim of the study is to evaluate the effect of combined hydrocortisone, vitamin C, and thiamine (triple therapy) on the mortality of patients with septic shock. Methods : This multicenter, open-label, two-arm parallel-group, randomized controlled trial was conducted in four intensive care units in Qatar. Adult patients diagnosed with septic shock requiring norepinephrine at a rate of ≥0.1 μg/kg/min for ≥6 h were randomized to a triple therapy group or a control group. ⋯ Conclusion: Triple therapy did not improve in-hospital mortality at 60 days in critically ill patients with septic shock or reduce the vasopressor duration or SOFA score at 72 h. Trial Registration:ClinicalTrials.gov identifier: NCT03380507. Registered on December 21, 2017.