Purpose:Cherry juice (CJ) and cold water immersion (CWI) are both effective recovery strategies following strenuous endurance exercise. However, athletes routinely combine recovery interventions and less is known about the impact of a combined CJ and CWI protocol. Therefore, this study investigated the effects of combining CWI and CJ (a "cocktail" (CT)) on inflammation and muscle damage following a marathon.Methods:A total 39 endurance trained males were randomly assigned to a placebo (PL), CWI, CJ, or CT group before completing a trail marathon run. Muscle damage (creatine kinase (CK)), muscle function (maximal voluntary isometric contraction (MVIC)), and inflammation (interleukin-6 (IL-6); C-reactive protein (CRP)) were measured at baseline, immediately after marathon (only IL-6), 24 h, and 48 h after marathon.Results:There were no statistically significant differences between groups and no group × time interaction effects for any of the dependent variables. Confidence intervals (CI) illustrated that CT had unclear effects on inflammation (IL-6; CRP) and MVIC, but may have increased CK to a greater extent than PL and CJ conditions.Conclusion:There is no evidence of an additive effect of CJ and CWI when the treatments are used in conjunction with each other. On the contrary, combining CJ and CWI may result in slightly increased circulating CK.

SESSION TITLE: Fellows Critical Care Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Community-acquired purulent ventriculitis is very rare. We present a case of community-acquired purulent nontypeable Haemophilus influenzae meningitis with ventriculitis requiring cerebrospinal fluid diversion. CASE PRESENTATION: 46-year-old female with sickle cell disease presented in late fall with two days of headache, fever, and confusion. On arrival, she was febrile to 103F. On exam, she was agitated and unable to follow commands. Laboratory studies showed a white blood cell count of 23,000 (94% neutrophils), and procalcitonin 36 mg/dL. Blood and urine cultures were collected. The patient was given dexamethasone, vancomycin, meropenem (anaphylactic to penicillin), acyclovir, and doxycycline for community-acquired meningoencephalitis. CT Brain was consistent with cerebral edema. The patient required intubation for airway protection. Lumbar puncture showed purulent cerebrospinal fluid with opening pressure 21. CSF protein was 900, glucose 1, and 24,000 neutrophils. Gram stain showed numerous gram negative coccobacilli. MRI Brain showed layering debris within the ventricles and hydrocephalus. Due to intracranial hypertension, mannitol was given and an external ventricular drain placed. Blood and CSF cultures grew non-type B Haemophilus influenzae. The patient completed 14 days of ceftriaxone and was eventually extubated and ventriculostomy removed. DISCUSSION: Anatomical and functional asplenia poses high risk for invasive infections with encapsulated organisms such as S. pneumoniae, N. meningitidis, and H. influenzae. However, we present a case of community-acquired nontypeable H influenza meningitis with associated ventriculitis requiring CSF diversion. Nontypeable Haemophilus species lack a polysaccharide capsule for which splenic function provides less immunity. Serotype B was a common invasive pathogen prior to the institution of Hib vaccination in 1987. Nontypeable H influenzae is a common pathogen in otitis media in children and exacerbations of COPD in adults. Invasive diseases such as bacteremia and pneumonia are mostly seen at the extremes of age. Our patient is also unique in that she developed purulent ventriculitis complicated by hydrocephalus. Hydrocephalus complicates community-acquired bacterial meningitis in about 5% of cases and is associated with high mortality. H influenza ventriculitis is a rare condition and is mostly described in children and patient’s after neurosurgical CNS manipulation. CONCLUSIONS: We present a case of community-acquired nontypeable Haemophilus influenzae meningitis with ventriculitis. This case is unique in that the patient had purulent ventriculitis required CSF diversion. Community-acquired purulent ventriculitis is very rare without neurosurgical manipulation or indwelling CSF drainage catheters. Also, nontypeable H flu is an uncommon pathogen in the central nervous system and usually affects the respiratory tract. Reference #1: Eldere, J.V., Slack, M, Ladhani,Shamez, Cripps, A. Non-typeable Haemophilus infl uenzae, an under-recognised pathogen.Lancet Infect Dis 2014; 14: 1281–92. Reference #2: Bakaletz, L, Novotny, L. NontypeableHaemophilusinfluenzae(NTHi). Trends in Microbiology, August 2018,Vol. 26,No.8. Reference #3: Langereis, J, Jonge, M. Invasive Disease Caused by Nontypeable Haemophilus influenzae. Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 10, October 2015. DISCLOSURES: No relevant relationships by Andrew Holt, source=Web Response No relevant relationships by Scott Sinclair, source=Web Response

Airway narrowing due to hyperresponsiveness severely limits gas exchange in patients with asthma. Imaging studies in humans and animals have shown that bronchoconstriction causes patchy patterns of ventilation defects throughout the lungs, and several computational models have predicted that these regions are due to constriction of smaller airways. However, these imaging approaches are often limited in their ability to capture dynamic changes in small airways, and the patterns of constriction are heterogeneous. To directly investigate regional variations in airway narrowing and the response to deep inspirations (DIs), we utilized tantalum dust and microfocal X-ray imaging of rat lungs to obtain dynamic images of airways in an intact animal model. Airway resistance was simultaneously measured using the flexiVent system. Custom-developed software was used to track changes in airway diameters up to generation 19 (~0.3-3 mm). Changes in diameter during bronchoconstriction were then measured in response to methacholine (MCh) challenge. In contrast with the model predictions, we observed significantly greater percent constriction in larger airways in response to MCh challenge. Although there was a dose-dependent increase in total respiratory resistance with MCh, the percent change in airway diameters was similar for increasing doses. A single DI following MCh caused a significant reduction in resistance but did not cause a significant increase in airway diameters. Multiple DIs did, however, cause significant increases in airway diameters. These measurements allowed us to directly quantify dynamic changes in airways during bronchoconstriction and demonstrated greater constriction in larger airways.

Cannabinoids, the bioactive components of marijuana, have adverse cardiovascular consequences, including symptomatic sinus bradycardia, sinus arrest and ventricular asystole. Physicians should be aware of these deleterious consequences which can appear in otherwise healthy persons who are chronic marijuana users.

Cryotherapy is an increasingly popular recovery strategy used in an attempt to attenuate the negative impact of strenuous physical activity on subsequent exercise. Therefore, this study aimed to assess the effects of whole body cryotherapy (WBC) and cold water immersion (CWI) on markers of recovery following a marathon.Thirty-one endurance trained males completed a marathon. Participants were randomly assigned to a CWI, WBC or placebo group. Perceptions of muscle soreness, training stress and markers of muscle function were recorded before the marathon and at 24 and 48 h post exercise. Blood samples were taken at baseline, post intervention and 24 and 48 h post intervention to assess inflammation and muscle damage.WBC had a harmful effect on muscle function compared to CWI post marathon. WBC positively influenced perceptions of training stress compared to CWI. With the exception of C-reactive protein (CRP) at 24 and 48 h, neither cryotherapy intervention positively influenced blood borne markers of inflammation or structural damage compared to placebo.The findings show WBC has a negative impact on muscle function, perceptions of soreness and a number of blood parameters compared to CWI, contradicting the suggestion that WBC may be a superior recovery strategy. Further, cryotherapy is no more effective than a placebo intervention at improving functional recovery or perceptions of training stress following a marathon. These findings lend further evidence to suggest that treatment belief and the placebo effect may be largely responsible for the beneficial effects of cryotherapy on recovery following a marathon.

Objective: Vancomycin empirical dosing studies in thermally injured patients have netted low successful target attainment and most excluded renal dysfunction, limiting applicability. In a previous study, the authors performed a retrospective analysis of 124 patients' measured pharmacokinetic parameters to calculate optimal dose and interval for intermittent infusion regimens and find predictors of clearance and total daily dose. The objective of this study was to improve the accuracy of attaining goal therapeutic targets with initial vancomycin regimens in patients with thermal injury through retrospective modeling. Methods: In this phase 2 study, variables collected and calculated regimens in phase 1 were utilized to try and create an improved empiric vancomycin dosing algorithm in patients with thermal injury. Logistic regression was utilized to determine best predictors of dosing vancomycin every 6 and 8h. The strongest models were built as individual algorithms and tested for accuracy of target attainment. Each algorithm produced a regimen for each patient that was then tested utilizing each patient's actual measured pharmacokinetic parameters. Results: Univariable logistic regression of 41 variables identified 27 and 23 to be predictive of dosing every 8 or 6h, respectively. The most predictive multivariable model for dosing every 8h consisted of creatinine clearance (CrCl) >= 80ml/min, Acute Kidney Injury Network classification <1, and total body surface area burned >= 10 percent. For dosing every 6h, CrCl >= 80ml/min, age <= 40years old, days since injury <= 6, and serum creatinine (SCr) <= 0.8 were most predictive. Based on the top 5 multivariable models for each dosing interval, 7 algorithms were built to produce recommended regimens. The highest performing algorithm resulted in trough concentrations of <10mg/L (23%), 10-20mg/L (65%), 15-20mg/L (26%), and >20mg/L (11%); area under the concentration curve (AUC)>400mghr/L (83%); and AUC >400mghr/L without having a trough >20mg/L (72%). Conclusions: The algorithm that resulted in the highest target attainment without overdosing recommended 15mg/kg dosed every 24h for CrCl >= 30, every 12h for CrCl 31-79, every 8h for patients with CrCl >= 80ml/min, and every 6h only if the patient with a CrCl >= 80ml/min is also <= 40 years old and has a SCr <= 0.8. Caution is warranted for groups underrepresented in this study, such as those with very low CrCl, a low BMI, or receiving renal replacement therapy. This algorithm should be validated in other centers for patients with thermal injuries. (C) 2018 Elsevier Ltd and ISBI. All rights reserved.

Sepsis is the largest cause of mortality in thermally injured patients. Traditional systemic inflammatory response syndrome (SIRS) criteria do not aid diagnosis of sepsis in burn centers. Studies have attempted identification of the best indicators of sepsis in the thermal injured patient, but predictive variables are inconsistent across the various studies. Currently, consensus guidelines lack evidential support as to which patients will benefit most from prompt antimicrobial therapy. The purpose of our study was to evaluate novel diagnostic parameters for thermal injured patients with known sepsis and compare these parameters with existing diagnostic criteria. This study was a retrospective, electronic medical record review. Baseline demographics were analyzed utilizing chi-square, Mann-Whitney U test, or t test. Each patient served as their own control. Generalized linear mixed modeling was utilized for univariable and multivariable analysis. Several models with ≤6 variables each were built with the top performing variables. Performance was analyzed using area under receiver operating curves, sensitivity, specificity, positive predictive value, and negative predictive value. Three hundred and ninety-nine patients were screened. Twenty-nine patients remained after exclusions, leaving 198 blood culture results (62 positive) for analysis. Forty variables were statistically significant during univariable analysis. From multivariable analysis, the best performing model was: Temperature > 39°C or < 36°C, heart rate > 130 beats/min, 10% decrease in mean arterial pressure, and gastric residual volumes twice the feeding rate. Meeting at least one variable of the presented model best identified incidence of sepsis with positive bloodstream infections and outperformed current models in our patients.

Caring for patients with burn injuries is challenging secondary to the acute disease process, chronic comorbidities, and underrepresentation in evidence-based literature. Much current practice relies on extrapolation of guidance from different patient populations and wide variations in universal practices. Identifying infections or sepsis in this hypermetabolic population is imperfect and often leads to overpre-scribing of antimicrobials, suboptimal dosing, and multidrug resistance. An understanding of pharmacokinetics and pharmacodynamics may aid optimization of dosing regimens to better attain treatment targets. This article provides an overview of the current status of burn infection and attempts recommendations for consideration to improve universally accepted care.

CASE PRESENTATION: An African American man in his late 30s was referred to the pulmonary clinic for evaluation of a persistent cough of several weeks' duration. Cough was productive of mucopurulent sputum mixed with blood. He also noted generalized weakness and dyspnea with minimal exertion.

CASE PRESENTATION:An African American man in his late 30s was referred to the pulmonary clinic for evaluation of a persistent cough of several weeks' duration. Cough was productive of mucopurulent sputum mixed with blood. He also noted generalized weakness and dyspnea with minimal exertion.

Alveolar type II epithelial cells (ATII) are instrumental in early wound healing in response to lung injury, restoring epithelial integrity through spreading and migration. We previously reported in separate studies that focal adhesion kinase-1 (FAK) and the chemokine receptor CXCR4 promote epithelial repair mechanisms. However, potential interactions between these two pathways were not previously considered. In the present study, we found that wounding of rat ATII cells promoted increased association between FAK and CXCR4. In addition, protein phosphatase-5 (PP5) increased its association with this heteromeric complex, while apoptosis signal regulating kinase-1 (ASK1) dissociated from the complex. Cell migration following wounding was decreased when PP5 expression was decreased using shRNA, but migration was increased in ATII cells isolated from ASK1 knockout mice. Interactions between FAK and CXCR4 were increased upon depletion of ASK1 using shRNA in MLE-12 cells, but unaffected when PP5 was depleted. Furthermore, we found that wounded rat ATII cells exhibited decreased ASK1 phosphorylation at Serine-966, decreased serine phosphorylation of FAK, and decreased association of phosphorylated ASK1 with FAK. These changes in phosphorylation were dependent upon expression of PP5. These results demonstrate a unique molecular complex comprising CXCR4, FAK, ASK1, and PP5 in ATII cells during wound healing.

Airway hyperresponsiveness severely limits gas exchange in patients with asthma. Imaging studies have shown that bronchoconstriction causes patchy patterns of ventilation defects throughout the lungs, and computational models have predicted that these regions are due to constriction of small airways. Since these imaging approaches are limited in their ability to capture dynamic changes in small airways, we utilized tantalum dust and microfocal X‐ray imaging of rat lungs to obtain dynamic images of airways in an intact animal model. The flexiVent system was used to simultaneously measure airway resistance. Custom software was used to track changes in airway diameters up to 13 generations (~0.3 mm to 3 mm in diameter). The objective of the study was to identify the size and location of airways with changes in diameter during bronchoconstriction in response to methacholine. In contrast with the model predictions, we observed significantly greater percent constriction in larger airways in response to methacholine challenge. Although there was a dose‐dependent increase in airway resistance, the percent change in airway diameters was similar for increasing doses. Paradoxically, a deep inspiration following methacholine caused greater percent constriction in smaller airways. These measurements allow us to directly quantify dynamic changes in airways during bronchoconstriction.Grant Funding Source: Supported by NIH HL094366 (CMW) and APS UGSRF (TNP)

Objectives: We previously reported the expression of the two-pore-domain K+ channel TREK-1 in lung epithelial cells and proposed a role for this channel in the regulation of alveolar epithelial cytokine secretion. In this study, we focused on investigating the role of TREK-1 in vivo in the development of hyperoxia-induced lung injury.Design: Laboratory animal experiments.Setting: University research laboratory.Subjects: Wild-type and TREK-1-deficient mice.Interventions: Mice were anesthetized and exposed to 1) room air, no mechanical ventilation, 2) 95% hyperoxia for 24 hours, and 3) 95% hyperoxia for 24 hours followed by mechanical ventilation for 4 hours.Measurements and Main Results: Hyperoxia exposure accentuated lung injury in TREK-1-deficient mice but not controls, resulting in increase in lung injury scores, bronchoalveolar lavage fluid cell numbers, and cellular apoptosis and a decrease in quasi-static lung compliance. Exposure to a combination of hyperoxia and injurious mechanical ventilation resulted in further morphological lung damage and increased lung injury scores and bronchoalveolar lavage fluid cell numbers in control but not TREK-1-deficient mice. At baseline and after hyperoxia exposure, bronchoalveolar lavage cytokine levels were unchanged in TREK-1-deficient mice compared with controls. Exposure to hyperoxia and mechanical ventilation resulted in an increase in bronchoalveolar lavage interleukin-6, monocyte chemotactic protein-1, and tumor necrosis factor- levels in both mouse types, but the increase in interleukin-6 and monocyte chemotactic protein-1 levels was less prominent in TREK-1-deficient mice than in controls. Lung tissue macrophage inflammatory protein-2, keratinocyte-derived cytokine, and interleukin-1 gene expression was not altered by hyperoxia in TREK-1-deficient mice compared with controls. Furthermore, we show for the first time TREK-1 expression on alveolar macrophages and unimpaired tumor necrosis factor- secretion from TREK-1-deficient macrophages.Conclusions: TREK-1 deficiency resulted in increased sensitivity of lungs to hyperoxia, but this effect is less prominent if overwhelming injury is induced by the combination of hyperoxia and injurious mechanical ventilation. TREK-1 may constitute a new potential target for the development of novel treatment strategies against hyperoxia-induced lung injury.

Alveolar type II (ATII) epithelial cells play a crucial role in the repair and remodeling of the lung following injury. ATII cells have the capability to proliferate and differentiate into alveolar type I (ATI) cells in vivo and into an ATI-like phenotype in vitro. While previous reports indicate that the differentiation of ATII cells into ATI cells is a complex biological process, the underlying mechanism responsible for differentiation is not fully understood. To investigate factors involved in this differentiation in culture, we used a PCR array and identified several genes that were either up- or downregulated in ATI-like cells (day 6 in culture) compared with day 2 ATII cells. Insulin-like growth factor-I (IGF-I) mRNA was increased nearly eightfold. We found that IGF-I was increased in the culture media of ATI-like cells and demonstrated a significant role in the differentiation process. Treatment of ATII cells with recombinant IGF-I accelerated the differentiation process, and this effect was abrogated by the IGF-I receptor blocker PQ401. We found that Wnt5a, a member of the Wnt-Frizzled pathway, was activated during IGF-I-mediated differentiation. Both protein kinase C and β-catenin were transiently activated during transdifferentiation. Knocking down Wnt5a using small-interfering RNA abrogated the differentiation process as indicated by changes in the expression of an ATII cell marker (prosurfactant protein-C). Treatment of wounded cells with either IGF-I or Wnt5a stimulated wound closure. These results suggest that IGF-I promotes differentiation of ATII to ATI cells through the activation of a noncanonical Wnt pathway.