Circulating extracellular histones exacerbate acute lung injury by augmenting pulmonary endothelial dysfunction via TLR4-dependent mechanism.

Extracellular histones released into the circulation following trauma, sepsis, and ARDS may act as potent damage-associated molecular pattern signals leading to multiple organ failure. Endothelial cell (EC) dysfunction caused by extracellular histones has been demonstrated in vitro and in vivo; however, precise mechanistic details of histone-induced EC dysfunction and exacerbation of ongoing inflammation remain poorly understood. This study investigated the role of extracellular histones in exacerbating preexisting endothelial dysfunction and acute lung injury. Histone subunits H3 and H4, but not H1, H2A, or H2B, induced permeability in human pulmonary EC. H3 and H4 at concentrations above 30 µg/mL caused EC inflammation reflected by activation of the NF-κB pathway, transcriptional activation, and release of cytokines and chemokines including IL-6 and IL-8, and increased mRNA and protein expression of EC adhesion molecules VCAM-1 and ICAM-1. Pharmacological inhibitors targeting Toll-like receptor TLR4 but not TLR2/6, blocked histone-induced EC dysfunction. H3 and H4 also strongly augmented EC permeability and inflammation caused by Gram-negative and Gram-positive bacterial particles, endotoxin, and TNFα. Heparin blocked histone-induced augmentation of EC inflammation caused by endotoxin and TNFα. Injection of histone in mouse models of lung injury caused by bacterial wall lipopolysaccharide (LPS) and heat-killed Staphylococcus aureus (HKSA) augmented ALI parameters: increased protein content, cell count, and inflammatory cytokine secretion in bronchoalveolar lavage fluid. Important clinical significance of these findings is in the demonstration that even a modest increase in extracellular histone levels can act as a severe exacerbating factor in conjunction with other EC barrier disruptive or proinflammatory agents.

Outcomes associated with stroke volume variation versus central venous pressure guided fluid replacements during major abdominal surgery.

BACKGROUND AND AIMS: There is limited data on the impact of perioperative fluid therapy guided by dynamic preload variables like stroke volume variation (SVV) on outcomes after abdominal surgery. We studied the effect of SVV guided versus central venous pressure (CVP) guided perioperative fluid administration on outcomes after major abdominal surgery. MATERIAL AND METHODS: Sixty patients undergoing major abdominal surgeries were randomized into two equal groups in this prospective single blind randomized study. In the standard care group, the CVP was maintained at 10-12 mmHg while in the intervention group a SVV of 10% was achieved by the administration of fluids. The primary end-points were the length of Intensive Care Unit (ICU) and hospital stay. The secondary end points were intraoperative lactate, intravenous fluid use, requirement for inotropes, postoperative ventilation and return of bowel function. RESULTS: The ICU stay was significantly shorter in the intervention group as compared to the control group (2.9 ± 1.15 vs. 5.4 ± 2.71 days). The length of hospital stay was also shorter in the intervention group, (9.9 ± 2.68 vs. 11.96 ± 5.15 days) though not statistically significant. The use of intraoperative fluids was significantly lower in the intervention group than the control group (7721.5 ± 4138.9 vs. 9216.33 ± 2821.38 ml). Other secondary outcomes were comparable between the two groups. CONCLUSION: Implementation of fluid replacement guided by a dynamic preload variable (SVV) versus conventional static variables (CVP) is associated with lesser postoperative ICU stay and reduced fluid requirements in major abdominal surgery.

Impact of the Coronavirus Disease 2019 Pandemic on Physical and Mental Health of Patients With COPD: Results From a Longitudinal Cohort Study Conducted in the United States (2020-2021).

Background: Patients with chronic obstructive pulmonary disease (COPD) are at higher risk for severe coronavirus disease 2019 (COVID-19). From the pandemic's onset there has been concern regarding effects on health and well-being of high-risk patients. Methods: This was an ancillary study to the Losartan Effects on Emphysema Progression (LEEP) Trial and was designed to collect descriptive information longitudinally about the health and wellbeing of COPD patients who were enrolled in a clinical trial. Participants were interviewed by telephone about their health status every 2 weeks and their mental health, knowledge, and behaviors every 8 weeks from June 2020 to April 2021. There were no pre-specified hypotheses. Results: We enrolled 157 of the 220 participants from the parent LEEP trial. Their median age was 69 years, 55% were male, and 82% were White; median forced expiratory volume in 1 second (FEV1)% predicted was 48%. Nine confirmed COVID-19 infections were reported, 2 resulting in hospitalization. Rates of elevated anxiety or depressive symptoms were 8% and 19% respectively in June 2020 and remained relatively stable during follow-up. By April 2021, 85% of participants said they were "very likely" to receive a vaccine; 91% were vaccinated (≥1 dose) by the end of December 2021. Conclusion: Our select cohort of moderate to severe COPD patients who were well integrated into a health care network coped well with the COVID-19 pandemic. Few participants were diagnosed with COVID-19, levels of depression and anxiety were stable, most adopted accepted risk reduction behaviors, and did not become socially isolated; most were vaccinated by the end of 2021.

Are active warming measures required during paediatric cleft surgeries?

BACKGROUND: During paediatric cleft surgeries intraoperative heat loss is minimal and hence undertaking all possible precautions available to prevent hypothermia and use of active warming measures may result in development of hyperthermia. This study aims to determine whether there will be hyperthermia on active warming and hypothermia if no active warming measures are undertaken. The rate of intraoperative temperature changes with and without active warming was also noted. METHODS: This study was conducted on 120 paediatric patients undergoing cleft lip and palate surgeries. In Group A, forced air warming at 38°C was started after induction. In Group B, no active warming was done. Body temperature was recorded every 30 min starting after induction until 180 min or end of surgery. Intragroup comparison of variables was done using Paired sample test and intergroup comparison using independent sample t-test. RESULTS: In Group A, all intraoperative temperature readings were significantly higher than baseline. In Group B, there was a significant reduction in temperature at 30 and 60 min. Temperature at 90 min did not show any significant difference, but further readings were significantly higher. Maximum rise in temperature occurred in Group A between 120 and 150 min and maximum fall in temperature in Group B was seen during first 30 min. CONCLUSION: In pediatric cleft surgeries, we recommend active warming during the first 30 minutes if the surgery is expected to last for <2h, and no such measures are required if the expected duration is >2h.