Switching from twice-daily raltegravir plus tenofovir disoproxil fumarate/emtricitabine to once-daily elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate in virologically suppressed, HIV-1-infected subjects: 48 weeks data.

BACKGROUND: Pill burden, dosing frequency, and concerns about safety and tolerability are important obstacles to maintaining adequate medication adherence. Raltegravir (RAL) is indicated for twice-daily dosing and when taken with emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF), it becomes a twice-daily multiple-tablet regimen. Elvitegravir (EVG)/cobicistat (COBI)/FTC/TDF, STB, is the first approved once-a-day integrase strand transfer inhibitor (INSTI) containing single-tablet regimen that combines EVG, an INSTI, and COBI, a novel pharmacoenhancer, with the preferred nucleos(t)ide backbone of FTC/TDF. METHODS: This was a 48-week prospective, single-arm open-label study of the switch to STB in virologically sup-pressed HIV-1-infected adult patients on FTC/TDF and twice-daily RAL for at least 6 months. Objectives were to evaluate the tolerability and safety of a regimen simplification to once-a-day STB, while maintaining viral suppression through 48 weeks. RESULTS: Forty-eight individuals in the United States were enrolled. The median age was 44 years, 96% were male, and 83% were White. The median time on RAL + FTC/TDF treatment prior to enrollment was 34 months. Ninety-six percent of participants cited regimen simplification as the reason to enroll in the switch study. At base-line, the median CD4 count was 714 cell/µL and estimated glomerular filtration rate (eGFR) was 105 mL/min. At week 48, all assessed study participants remained viro-logically suppressed to the lower limit of quantification (HIV-1 RNA<50 copies/mL) and maintained high CD4 cell count (median, 751 cells/mL) and stable eGFR (median, 100.5 mL/min). STB was well tolerated with no discontinuations, no study drug-related serious adverse events, and no study drug-related grade 3/4 adverse events. CONCLUSIONS: All participants switching to 1 tablet once-a-day STB from a twice-daily RAL + FTC/TDF regimen remained virologically suppressed. STB was well tolerated. Switching to STB may be a viable option for virologically suppressed patients wanting to simplify from a twice-daily RAL-containing regimen.

Rilpivirine versus efavirenz in HIV-1-infected subjects receiving emtricitabine/tenofovir DF: pooled 96-week data from ECHO and THRIVE Studies.

OBJECTIVES: Week 96 efficacy and safety of the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) was compared to efavirenz (EFV) in subset of 1,096 subjects who received emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in pooled data from 2 phase 3 studies. METHODS: ECHO and THRIVE are double-blind, double-dummy, randomized, active-controlled, non-inferiority phase 3 studies of RPV versus EFV plus 2 NRTIs in antiretroviral-naïve adult subjects. The primary and secondary endpoints were the proportion of subjects with HIV-1 RNA <50 copies/ mL using an intent-to-treat, time to loss of virologic response (ITT-TLOVR) analysis at weeks 48 and 96, respectively. Safety, tolerability, immunologic response, adherence level, and other measures were also evaluated. RESULTS: At week 48, noninferior efficacy of RPV+FTC/TDF over EFV+FTC/TDF was established, and at week 96 RPV+FTC/TDF remained noninferior (77% overall response rate in both groups). Through week 96, rates of virologic failure were higher in the RPV+FTC/ TDF group, with low and similar rates of virologic failure and resistance mutations occurring during the second year of follow-up. Treatment with RPV+FTC/TDF was associated with a lower rate of discontinuation due to adverse events and grade 2-4 adverse events including dizziness, abnormal dreams/nightmares, rash, and lipid abnormalities. CONCLUSIONS: The pooled ECHO and THRIVE studies demonstrated noninferiority of RPV+FTC/TDF in achieving virologic response with safety and tolerability advantages over EFV+FTC/TDF through 96 weeks. Higher rates of virologic failure in the RPV+FTC/TDF group were balanced with higher rates of discontinuations due to adverse events in the EFV+FTC/TDF group.

An evidence-based definition of anemia for singleton, uncomplicated pregnancies.

BACKGROUND: The definition for anemia in pregnancy is outdated, derived from Scandinavian studies in the 1970's to 1980's. To identity women at risk of blood transfusion, a common cause of Severe Maternal Morbidity, a standard definition of anemia in pregnancy in a modern, healthy United States cohort is needed. OBJECTIVE: To define anemia in pregnancy in a United States population including a large county vs. private hospital population using uncomplicated patients. MATERIALS AND METHODS: Inclusion criteria were healthy women with the first prenatal visit before 20 weeks. Exclusion criteria included preterm birth, preeclampsia, hypertension, diabetes, short interval pregnancy (<18 months), multiple gestation, abruption, and fetal demise. All women had iron fortification (Ferrous sulfate 325 mg daily) recommended. The presentation to care and pre-delivery hematocrits were obtained, and the percentiles determined. A total of 2000 patients were included, 1000 from the public county hospital and 1000 from the private hospital. Each cohort had 250 patients in each 2011, 2013, 2015, and 2018. The cohorts were compared for differences in the fifth percentile for each antepartum epoch. Student's t-test and chi-squared statistical tests were used for analysis, p-value of ≤0.05 was considered significant. RESULTS: In the public and private populations, 777 and 785 women presented in the first trimester while 223 and 215 presented in the second. The women at the private hospital were more likely to be older, Caucasian race, nulliparous, and present earlier to care. The fifth percentile was compared between the women in the private and public hospitals and were clinically indistinguishable. When combining the cohorts, the fifth percentile for hemoglobin/hematocrit was 11 g/dL/32.8% in the first trimester, 10.3 g/dL/30.6% in the second trimester, and 10.0 g/dL/30.2% pre-delivery. CONCLUSIONS: Fifth percentile determinations were made from a combined cohort of normal, uncomplicated pregnancies to define anemia in pregnancy. Comparison of two different cohorts confirms that the same definition for anemia is appropriate regardless of demographics or patient mix.

Examining the impact of trimester of diagnosis on COVID-19 disease progression in pregnancy.

BACKGROUND: COVID-19 infection is associated with increased morbidity in pregnancy and adverse maternal and neonatal outcomes. Little is currently known about how the timing of infection during pregnancy affects these outcomes. OBJECTIVE: This study aimed to evaluate the effect of trimester of COVID-19 infection on disease progression and severity in pregnant patients. STUDY DESIGN: This was a prospective cohort study of pregnant patients diagnosed with COVID-19 infection who delivered at a single urban hospital. Universal testing for SARS-CoV-2 was performed at hospital admission and for symptomatic patients in inpatient, emergency department, and outpatient settings. Disease severity was defined as asymptomatic, mild, moderate, severe, or critical on the basis of National Institutes of Health criteria. We evaluated disease progression from asymptomatic to symptomatic infection and from asymptomatic or mild infection to moderate, severe, or critical illness, and stratified by trimester of COVID-19 diagnosis. Primary outcomes included progression of COVID-19 disease severity and a composite obstetrical outcome, which included delivery at <37 weeks, preeclampsia with severe features, abruption, excess blood loss at delivery (>500 mL for vaginal or >1000 mL for cesarean delivery), and stillbirth. RESULTS: From March 18, 2020 to September 30, 2021, 1326 pregnant patients were diagnosed with COVID-19 and delivered at our institution, including 103 (8%) first-, 355 (27%) second-, and 868 (65%) third-trimester patients. First-trimester patients were older and had more medical comorbidities; 86% of patients in all trimesters were Hispanic. Among patients admitted within 14 days of a positive test, 3 of 18 (17%) first-trimester, 20 of 47 (43%) second-trimester, and 34 of 574 (6%) third-trimester patients were admitted for the indication of COVID-19 illness. Across all trimesters, 1195 (90%) of 1326 COVID-19 infections were asymptomatic or mild, and 45 (10%) of 436 initially asymptomatic patients developed symptoms. Of patients with asymptomatic or mild symptoms at diagnosis, 4 (4%) of 93 first-, 18 (5%) of 337 second-, and 49 (6%) of 836 third-trimester patients developed moderate, severe, or critical illness (P=.80). There was no significant difference in composite obstetrical outcome with respect to trimester of COVID-19 diagnosis (24% first-trimester, 28% second-trimester, 28% third-trimester patients; P=.69). CONCLUSION: Moderate, severe, or critical illness develops in almost 10% of pregnant patients. The frequency of COVID-19 disease progression in pregnancy does not differ by trimester of diagnosis.

An extrinsic membrane polypeptide associated with high-molecular-weight protein aggregates in human cataract.

A 43,000-dalton polypeptide has been isolated from the high-molecular-weight disulfide-rich fraction of the water-insoluble protein of human cataractous lenses. On the basis of immunochemical reactivity and fluorescent antibody binding, this polypeptide is localized in the membrane region of the lens cell. This observation suggests an interaction between the soluble lens proteins and membrane-associated polypeptides in the formation of large protein aggregates which may cause cataract.

Measuring gastric residual volumes in critically ill burn patients - A systematic review.

PURPOSE: Measuring gastric residual volumes (GRV) is common in intensive care units (ICU) in patients receiving enteral nutrition (EN) and are a common source of feeding interruptions. Interruptions in EN yield adverse outcomes and are an area of improvement in burn care. The objectives of this study are to summarize the literature's ICU GRV practices and offer practical suggestions to GRV management in the burn patient. METHODS: PubMed, SCOPUS, and OvidSP Medline were systematically reviewed using the keywords: burns; thermal injury; gastric residual volume; enteral feeding; tube feeding; enteral nutrition; gastric intolerance; ICU; critical illness. Reviews, case reports, and consensus and opinion papers were excluded. RESULTS: 26 articles were identified. Six burn-specific studies were identified. GRV practices vary widely and are a common cause of EN interruption. Elevated GRVs do not equate to gastrointestinal intolerance and do not always reflect aspiration risk. CONCLUSIONS: We advocate a GRV threshold of 500mL should be used to optimize the benefits of EN in burn ICUs. A single incident of elevated GRVs should not mandate immediate EN rate reduction or cessation but should prompt a thoughtful examination of secondary causes of gastrointestinal intolerance. Randomized controlled trials are needed to define the ideal GRV threshold and re-evaluate its role in burn care.

How long are burn patients really NPO in the perioperative period and can we effectively correct the caloric deficit using an enteral feeding "Catch-up" protocol?

OBJECTIVE: "NPO at midnight" is a standard preoperative practice intended to reduce aspiration risk but can result in prolonged feeding interruptions in critically ill burn patients. Postoperative hyperalimentation in the form of a "catch-up" tube feeding protocol is routine. A retrospective review of our perioperative fasting practices and "catch-up" enteral feeding protocols was performed. METHODS: Patients admitted to the Burn ICU from July 1st, 2015 to August 31st, 2016 were reviewed. Patients who had a protected airway in place, prescribed enteral nutrition, and underwent surgery were included. The time from NPO to surgical start (NPO-SS), NPO to feeding restart (NPO-FR), and calories received/prescribed were quantified. The efficacy of a postoperative catch-up feeding protocol was analyzed. RESULTS: There were 41 patients that fit inclusion criteria with some undergoing multiple surgeries, yielding 109 surgeries/discrete perioperative events. The average total body surface area burn (38.1±23.6%), age (38.8±20.1years), ICU days (45.0±37.3 days), and ventilator days (35.1±33.8 days) were calculated. Average fasting durations of NPO-SS and NPO-FR were 9.3±3.1 and 14.2±4.1h, respectively. The average caloric deficit to prescribed calories ratio during the NPO-SS and NPO-FR periods were 1154±629/3534±851kcal and 1765±928/3534±851kcal, respectively. A post-operative catch-up protocol completely compensated for perioperative caloric deficits 68.8% (22/32) of the time. CONCLUSIONS: In critically ill burn patients, a preoperative fast resulted in an average loss of greater than 50% of prescribed calories on the day of surgery. Clinicians should re-evaluate the standard practice of making preoperative patients "NPO at midnight". An effective catch-up protocol can adequately reduce caloric deficits.

Heparin-binding ligands mediate autocrine epidermal growth factor receptor activation In skin organ culture.

Exogenous EGF and TGF-alpha accelerate wound healing, but treatment effects are often modest. Using short-term human skin organ culture, we found that autocrine EGF receptor activation could account for this observation. Amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) transcripts were rapidly and markedly induced, whereas EGF and TGF-alpha mRNAs were undetectable or only slightly increased. Vascular permeability factor and keratin 6 transcripts were also strongly induced, albeit with a >/= 3 h delay relative to HB-EGF and amphiregulin. All four transcripts were upregulated in actual healing skin wounds, HB-EGF and keratin 6 being the most prominent. The highly EGF receptor-specific tyrosine kinase inhibitor PD153035 strongly inhibited induction of all four transcripts in organ culture, as well as release of immunoreactive HB-EGF into the medium. These effects were confirmed using the anti-EGF receptor mAb 225 IgG. Neither PD153035 nor 225 IgG was toxic to keratinocytes, as judged by calcein-AM uptake. PD153035 completely abrogated the proliferative phase of keratinocyte outgrowth in skin explant cultures, whereas it had no effect on the antecedent migratory phase. Based on these results, we conclude that EGF receptor activation by highly inducible, keratinocyte-derived heparin-binding ligands is an important mechanism for amplification and transmission of the cutaneous wound healing signal.

Steven Johnson Syndrome and Toxic Epidermal Necrolysis in a burn unit: A 15-year experience.

INTRODUCTION: The diffuse epidermal exfoliation seen in Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) is similar to skin loss in second degree burns, and many of these patients are referred for treatment at burn centers. Treatment can differ markedly from center to center, and mortality can range from 25% to 70%, including a considerable morbidity. However, our experience over a 15-year period from 2000 to 2015 with 40 patients found a mortality rate of only 10% (4/40). The purpose of this paper is to discuss our treatment algorithm as a model for other centers treating SJS/TENs patients. METHODS: Records were reviewed for all patients admitted to the LAC+USC burn unit between 2000 and 2015 and 40 patients were identified with biopsy-proven SJS or TENS. These cases were reviewed for age, gender, initial and greatest TBSA, causative drug, pre-existing medical conditions, and morbidity and mortality. All data were entered into the SPSS statistical software package and all statistical analyses were performed using this program. RESULTS: Our treatment algorithm focused on early referral to a specialty burn unit, immediate discontinuation of the offending drug, fluid resuscitation, nutritional supplementation, and meticulous wound care. Average time to transfer to a burn unit was 3.36 days. Silver-releasing antimicrobial dressings were applied to the affected skin surface and changed every 3 days. Mupirocin coated petroleum gauze was used for facial involvement. Steroids were tapered and discontinued if initiated at an outside facility (58% of patients), and starting after 2001, all patients received a course of IVIG. All patients received fluid resuscitation and the majority received supplemental tube feedings (69%). Average length of total stay was 17.1 days and length of ICU stay 15.9 days. While 44% were transferred to another facility for further rehabilitative care, 37% of patients discharge to home. In patients discharged home with complete resolution of skin lesions, time to healing was an average of 14 days. DISCUSSION: With our 10% mortality rate in 40 patients, our study represents a relatively large study population while maintaining a relatively low mortality rate. The demographic data from our study largely aligns with the existing literature, and we therefore feel that our low mortality rate is due to our treatment algorithm, rather than to a less severe pathology in our patient population. This claim is supported by a standard mortality ratio of 1.68. This ratio proves a significantly improved mortality than would be expected based on disease severity on admission.

Increased types I and III collagen and transforming growth factor-beta 1 mRNA and protein in hypertrophic burn scar.

Hypertrophic scar is the result of abnormal healing that often follows thermal injury. Hypertrophic scar is characterized by excessive dermal fibrosis and scarring. Five cases of human hypertrophic scar were compared with normal skin using in situ hybridization to localize mRNAs for procollagen types I and III and transforming growth factor-beta 1. Expression of type I procollagen and TGF-beta 1 were also examined with immunohistochemistry. The results demonstrated a significant increase in the expression of mRNA for types I and III procollagen and type I procollagen protein by fibroblasts in hypertrophic scar compared with normal skin. In all cases of hypertrophic scar, significant numbers of cells expressed TGF-beta 1 mRNA or peptide. Neither TGF-beta 1 mRNA nor protein was detected in control tissues. These results suggest a profound increase in production and expression of types I and III collagen mRNA by the fibroblasts in hypertrophic scar. This may result from increased TGF-beta 1 production, through paracrine and autocrine pathways, as have been described for this fibrogenic cytokine.

Phenotypic differences in cytokine responsiveness of hypertrophic scar versus normal dermal fibroblasts.

The alteration of normal dermal fibroblast function that leads to the development of hypertrophic scar after thermal injury is unknown. To determine functional differences that might explain this process, fibroblasts were cultured from biopsies of post-thermal injury mature hypertrophic scars and patient-matched normal skin. The mitogenic responses of scar cells to fetal bovine serum, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and tumor necrosis factor alpha (TNF alpha) were determined and compared to normal skin cells. Collagen synthetic rate was also compared in the presence and absence of transforming growth factor beta 1 (TGF beta 1). Whereas both scar and normal cells responded with increased thymidine uptake to serum and cytokines, the stimulation to EGF and serum was significantly lower in scar cells. In contrast, synthesis of collagen, but not of non-collagenous proteins, was increased in scar relative to normal cells, both basally and when stimulated with low doses of TGF beta 1. Additionally, the fraction of protein synthesized as collagen was significantly higher in scar fibroblasts. These results suggest that fibroblasts from hypertrophic scars demonstrate stable phenotypic differences in cytokine responsiveness in comparison to cells from unaffected skin. The increased rate of collagen synthesis and decreased responsiveness to mitogens are consistent with the increased extracellular matrix content and decreased cellularity of hypertrophic scars.

Neuronal thread protein gene modulation with cerebral infarction.

Neuronal thread proteins (NTP) are a family of phosphoproteins expressed during neuritic sprouting. The 15 to 18 kD NTP cluster is associated with development and neuronal differentiation, whereas the 21 kD and 39 to 42 kD species are overexpressed in Alzheimer's disease, correlating with neurodegenerative sprouting and synaptic disconnection. Empirical observations suggested that NTP might also be modulated with central nervous system injury and stroke. In this study of both human and experimental (rat) focal cerebral infarcts, in situ hybridization and immunocytochemical staining revealed NTP gene expression up-regulated in perifocal neurons. These findings were confirmed by quantitative Northern and Western blot analyses. Moreover, Western blot analysis demonstrated selectively increased expression of the 15 to 18 kD NTP species during the acute, subacute, and healing phases of cerebral infarction in both humans and experimental animals, corresponding with the expected period of neuronal repair. These results suggest an additional role for the 15 to 18 kD NTP species in neuritic sprouting required for neuronal regeneration after injury in the mature central nervous system.

Spectral characterization of lipid peroxidation in rabbit lens membranes induced by hydrogen peroxide in the presence of Fe2+/Fe3+ cations: a site-specific catalyzed oxidation.

The role of free-radical-induced lipid peroxidation (LPO) in relation to lens opacity is investigated using Fourier transform infrared spectroscopy. Phospholipids extracted from nuclear and cortical regions of the rabbit lens membranes are subjected to oxidative-damage induced by hydrogen peroxide and Fe2+/Fe3+ cations. Vibrational data suggest a homolytic decomposition of the unsaturated membrane hydrocarbon chains at cis-double bonds, as well as structural modifications at the carbonyl and phosphate-oxygen sites of the fiber cell membranes upon metal oxidation. This is also evident from a substantial induction of the carbonyl groups and a significant dephosphorylation of the phosphate groups in lens phospholipids. These covalent modifications and/or alterations of the carbonyl and phosphate groups, and specificity of certain vibrational modes only to iron oxidation, may serve as a diagnostic probe of the metal-catalyzed LPO in lens membranes. Despite covalent modifications of the hydrophilic part of the lens membranes, hydrocarbon chain region remains largely intact at physiological concentrations of hydrogen peroxide. However, at elevated concentrations of hydrogen peroxide, a substantial breakdown of the acyl chains occurs. Striking similarities observed between the spectral features of the oxidized rabbit lens phospholipids and those of the cataractous human lenses suggest that the mechanism and pathways of lipid oxidation in model animal membranes and in human lenses are similar. Differences in the nuclear or cortical regions are also evident upon metal oxidation. Nuclear lipids experience increased effects of the metal oxidation compared to cortical lipids. Both the nuclear or the cortical lipids indicate effective penetration of the bilayer water creating segregated membrane domains, possibly through breakdown of headgroup-specific lipid-water interactions. This could effectively alter the lens membrane permeability and fluidity, rendering it susceptible to a host of toxic oxidants present in the eye. These findings also demonstrate that LPO can lead to acyl chain degradation that may effectively derange the lens membrane function, which could be a contributing factor in cataractogenesis.

H2O2-modification of Na,K-ATPase. Alterations in external Na+ and K+ stimulation of K+ influx.

Studies, at steady state, of the Na,K-ATPase dependent influx of K+ into bovine lenses in organ culture are used to characterize further the H2O2-modification of the Na+ pump. Control lenses display constants for interaction with external Na+ and K+ similar to those obtained for the erythrocyte. H2O2 treatment of the bovine lens leads to total loss of external Na+ stimulation and alteration of external K+ stimulation.

Nuclear magnetic resonance microscopic ocular imaging for the detection of early-stage cataract.

A nuclear magnetic resonance (NMR) microscopic ocular imaging was performed at 7.0 Tesla to investigate its usefulness in the detection of early-stage cataracts. For this study, galactose cataracts were generated in experimental rabbits through diet (35% galactose), and enucleated eyes were imaged at various times after initiation of the diet. In previous studies using a 0.6 Tesla conventional magnetic resonance imager (MRI), the contrast between normal and cataractous tissues in the lens was not well defined, mainly due to the partial volume effect coming from the limitation of resolution and signal-to-noise ratio (SNR). With resolution of 60 X 60 X 80 microns, early localized precataractous tissue changes were clearly observed after 5 days diet. Precataractous tissue changes were seen histologically but no visible evidence of lens change was detected by the conventional slit lamp biomicroscope at this time. Substantially elongated spin-spin relaxation times (T2) in localized cataractous tissues (72.4 +/- 8.8 msec) were consistently observed compared with those in normal lens region (16.1 +/- 3.2 msec); however, the changes of the spin-lattice relaxation time (T1) were not significant. Some ocular NMR microscopic images with corresponding histological photographs are demonstrated to show the potential of NMR microscopy.

Airway pressure release ventilation (APRV). A human trial.

After operative coronary revascularization, 14 consenting adults received conventional positive pressure ventilation (PPV). When they were hemodynamically stable, data were collected during PPV and then during airway pressure release ventilation (APRV). During APRV, airway pressure (Paw) was reduced periodically at the lowest frequency which produced normal PaCO2. As anesthesia resolved, the rate of APRV breaths was decreased until patients breathed only with CPAP. During PPV and APRV, pHa, PaO2/FIO2, and hemodynamic variables were similar. All patients were weaned from APRV without complication. Optimal ventilator design for patients with acute lung injury would provide CPAP as a primary intervention and secondarily would augment alveolar ventilation. The APRV supported oxygenation and ventilation in patients with mild acute lung injury, yet with much lower peak airway pressure than produced by PPV.

Portable chest roentgenography and computed tomography in critically ill patients.

Computed tomography (CT) of the chest offers improved resolution and sensitivity for evaluating chest pathologic conditions compared with other imaging techniques. Intensive care unit patients with portable chest findings that diverge from the clinical course may actually have severe intrathoracic disease that can be detected with CT. Our three patients demonstrate chest CT can aid in the diagnosis of significant intrathoracic pathologic conditions which have been significantly underestimated by portable chest roentgenography. We discuss the reasons for this improved detectability by CT, as well as suggest alternative techniques that can be performed at the bedside in patients whose initial portable chest roentgenogram and clinical course do not correlate.

Recurrent hypersplenism caused by alcoholic cardiomyopathy after distal splenorenal shunt.

The hypersplenism associated with portal hypertension usually resolves with a successful shunting procedure. Recurrent hypersplenism has been associated with shunt thrombosis. We describe a patient with pancytopenia, jaundice, and diffuse edema after a distal splenorenal shunt. His shunt was angiographically proved patent. Extensive evaluation revealed severe alcoholic cardiomyopathy with passive splenic congestion. He died of cardiac failure. Alcohol is a systemic toxin that affects other organs, as well as the liver.

The effects of hyperoxia during fulminant sepsis.

Although adequate tissue oxygenation is essential to maintain cellular metabolism, the use of hyperoxia to improve oxygen delivery or to improve metabolic performance is controversial. For example, supplemental inspired oxygen is reportedly beneficial in the treatment of some experimental infections; however, oxygen therapy also has well-documented adverse side effects. To evaluate the effect of increased inspired oxygen concentration (FIO2) in animals with fulminant sepsis, 117 Sprague-Dawley rats underwent cecal ligation and puncture. Animals were then exposed to an FIO2 of either 0.21, 0.4, or 0.8. Twenty sham-operated controls had no mortality with any FIO2. Increasing the FIO2 increased mortality from 70% to 85% in animals receiving 40% O2, and to 100% in those receiving 80% O2. Autopsies revealed mild pulmonary oxygen toxicity with 80% O2 exposure in both control and septic animals, but normal lung histologic appearance in animals receiving lower levels of oxygen. Arterial blood gases documented maintenance of oxygenation and ventilation. Thus, pulmonary oxygen toxicity does not appear to be the mechanism for increased mortality. Supplemental oxygen may worsen, rather than improve, survival after fulminant infection.