Combining multiple biomarkers differentiates between active SJIA, SJIA-MAS and EBV-HLH.

Cytokine storm syndromes are a clinically heterogeneous group of conditions resulting from a maladaptive host response to an inflammatory trigger. These syndromes lead to rapid progression of immune-mediated damage to healthy tissues resulting in life-threatening multi-system organ failure. Prompt recognition of disease and medical intervention to limit damage to healthy tissues is essential to prevent cytokine storm morbidity and mortality. However, the diagnosis of cytokine storm syndromes is challenging, given the clinical heterogeneity in disease presentations. Therefore, expeditious and readily available tests to diagnose disease and differentiate between the various types of cytokine storm syndromes are of clinical utility. The recently published work of Shimizu and colleagues brings us closer to making this a reality.

Glycosylated hemoglobin and hyperbaric oxygen coverage denials.

Some Medicaid and Medicare fiscal intermediaries are denying hyperbaric oxygen (HBO2) therapy for diabetic foot ulcer (DFU) patients if the glycosylated hemoglobin (HbA1c) > 7.0%. We performed multiple PubMed searches for any diabetic wound healing clinical trial that documented HbA1c and had a wound healing endpoint. We scrutinized 30 peer-reviewed clinical trials, representing more than 4,400 patients. The average HbA1c from the intervention side of the studies was 8.6% (7.2% - 9.9%) and the control/sham side was 8.3% (6.0% - 10.6%). Twelve studies made a direct attempt to link HbA1c and wound healing. Four retrospective studies and one prospective cohort study assert that lower HbA1c favors wound healing, but review of the studies reveal design flaws that invalidate these conclusions. In total, 25 studies showed no direct correlation between HbA1c levels and wound healing. There was no randomized controlled trial (RCT) data demonstrating that HbA1c < 7.0% improves diabetic wound healing. In every study reviewed, wounds healed with high HbA1c levels that would be considered poorly controlled by the American Diabetes Association (ADA). Frequently, patients lack optimal blood glucose control when they have a limb-threatening DFU. The evidence supports that denying hyperbaric oxygen to those with HbA1c > 7.0% is unfounded.

Structural and Volumetric Brain MRI Findings in Mild Traumatic Brain Injury.

BACKGROUND AND PURPOSE: Routine MR imaging findings are frequently normal following mild traumatic brain injury and have a limited role in diagnosis and management. Advanced MR imaging can assist in detecting pathology and prognostication but is not readily available outside research settings. However, 3D isotropic sequences with ∼1-mm3 voxel size are available on community MR imaging scanners. Using such sequences, we compared radiologists' findings and quantified regional brain volumes between a mild traumatic brain injury cohort and non-brain-injured controls to describe structural imaging findings associated with mild traumatic brain injury. MATERIALS AND METHODS: Seventy-one military personnel with persistent symptoms and 75 controls underwent 3T MR imaging. Three neuroradiologists interpreted the scans using common data elements. FreeSurfer was used to quantify regional gray and white matter volumes. RESULTS: WM hyperintensities were seen in 81% of the brain-injured group versus 60% of healthy controls. The odds of ≥1 WM hyperintensity in the brain-injured group was about 3.5 times the odds for healthy controls (95% CI, 1.58-7.72; P = .002) after adjustment for age. A frontal lobe-only distribution of WM hyperintensities was more commonly seen in the mild traumatic brain injury cohort. Furthermore, 7 gray matter, 1 white matter, and 2 subcortical gray matter regions demonstrated decreased volumes in the brain-injured group after multiple-comparison correction. The mild traumatic brain injury cohort showed regional parenchymal volume loss. CONCLUSIONS: White matter findings are nonspecific and therefore a clinical challenge. Our results suggest that prior trauma should be considered in the differential diagnosis of multifocal white matter abnormalities with a clinical history of mild traumatic brain injury, particularly when a frontal predilection is observed.

Carbon monoxide poisoning: a new incidence for an old disease.

PURPOSE: While carbon monoxide (CO) poisoning is common in the USA, its incidence is uncertain. Fatal poisonings are counted with relative accuracy from death certificate data, but estimates of the more common nonfatal poisonings are either old or limited. This study was performed to estimate the number of emergency department (ED) visits annually in the USA for carbon monoxide poisoning. BASIC PROCEDURES: ED visit rates in five states (Idaho, Maine, Montana, Utah, and Washington) from three prior studies, each using different methodology, were used to extrapolate independent estimates of national ED visits. MAIN FINDINGS: After correcting for regional differences in CO poisoning incidence, estimates of national ED visits per year ranging from 32,413 to 56,037 were obtained. Excluding the estimate derived from the Maine rate because it did not include intentional and fire-related poisonings, the national average is 50,558 +/- 4,843 visits per year. CONCLUSIONS: There are approximately 50,000 ED visits for CO poisoning in the USA annually, 3-5 times the numbers previously estimated. As this disease can result in significant long-term morbidity even when treated, enhanced prevention efforts are warranted.

Monoplace hyperbaric chamber use of U.S. Navy Table 6: a 20-year experience.

We report a 20-year experience at LDS Hospital, Salt Lake City, UT using the U.S. Navy Treatment Table 6 (TT6) in an oxygen-filled monoplace hyperbaric chamber (1985-2004). Air breathing was provided via a demand regulator fitted with a SCUBA mouthpiece while the patient wore a nose clip. Intubated patients were mechanically ventilated with a Sechrist 500A ventilator, with a modified circuit providing air, when specified. We treated 90 patients: 72 divers (decompression sickness [DCS] = 67, arterial gas embolism [AGE] = 5), 10 hospital-associated AGE, and 8 miscellaneous conditions. They received a total of 118 TT6 (9 TT6 in intubated patients). Ninety-four percent of the TT6 schedules were tolerated and completed. The intolerance rate from two surveyed multiplace chambers was zero and 3% of 100 TT6 schedules each. Failure to complete the TT6 was due to oxygen toxicity (4) and claustrophobia (3). The U.S. Navy TT6 was well tolerated by patients with DCS or AGE treated in monoplace hyperbaric chambers, but tolerance may not be as high as when treated in the multiplace chamber.

Hypoxemia with air breathing periods in U.S. NAVY Treatment Table 6.

Air breathing is used to lessen hyperbaric oxygen (HBO2) toxicity. Hypoxemia could occur during hyperbaric air breathing in patients with lung dysfunction, although this has not been previously reported. We report two cases of hypoxemia during air breathing with two patients treated with the US Navy Table 6. Patient 1 was an 11-year-old male with cerebral gas embolism (during cardiac transplantation), patient 2 was a 66-year-old female with cerebral gas embolism from a central venous catheter accident. Both were mechanically ventilated. We monitored arterial blood gas (ABG) during therapy. In both patients, ABG measurements showed hypoxia during the first air breathing period at 1.9 atm abs (192.5 kPa). If patients require > or = 40% inspired oxygen before HBO2 therapy, oxygenation monitoring is advisable during air breathing periods, especially at lower chamber pressures (< or = 2.0 atm abs).

Basal ganglia volumes following CO poisoning: A prospective longitudinal study.

Carbon monoxide (CO) poisoning may result in focal and diffuse neuropathological changes, including basal ganglia lesions. The effect of CO poisoning on basal ganglia volumes over time is unclear. We assessed basal ganglia volumes longitudinally following CO poisoning. We prospectively enrolled 73 CO poisoned patients who underwent brain MR imaging on day 1 (baseline), 2 weeks, and 6 months post-CO poisoning. Basal ganglia volumes were obtained. One patient had bilateral globus pallidus lesions at two weeks and 6 months. Of the CO-poisoned patients 28% had volume reduction in at least one basal ganglia structure by 6 months, of which 21% had putamen, 15% had caudate, 15% had globus pallidus, and 16% had total basal ganglia volume reduction. Putamen volumes were significantly smaller from baseline to six months (p = 0.02). Verbal memory and mental processing speed correlated with smaller putamen and globus pallidus volumes. Carbon monoxide poisoning results in basal ganglia volume reduction 6 months post CO poisoning. Slow mental processing speed and impaired memory correlated with smaller putamen and globus pallidus volumes. Clinicians need to be aware of basal ganglia neuropathologic changes in the absence of observable lesions following CO poisoning.

Comparison of three intravenous infusion pumps for monoplace hyperbaric chambers.

We compared the infusion accuracy of the Baxter Flo-Gard 6201, IVAC 530 and Abbott Lifecare 3HB pumps with saline and enteral formula at chamber pressures from 86.1 kPa (0.85 atm abs) to 304 kPa (3.0 atm abs). The Baxter pump infused +/- 10% saline at all tested pressures and rates (1-1,999 ml/hr). At 1 ml/hour, the IVAC infused 18% more saline than expected (86.1 kPa). The Abbott infused -15% and -23% than expected at 202.6 kPa (999 ml/hr) and 304 kPa (800 ml/hr), respectively. A 10-minute chamber compression and decompression (86.1-304-86.1 kPa) resulted in lower-than-expected measured volumes during compression (64-112%) and higher-than-expected measured volumes during decompression (62-114%) at rates of 1, 5, and 10 ml/hr for all pumps. Enteral infusions (100 ml/hour) resulted in -20% to +12% fluid volume discrepancies. In conclusion, the Baxter pump had the best overall performance. Changes observed during compression and decompression may be clinically important.

White matter hyperintensities and neuropsychological outcome following carbon monoxide poisoning.

BACKGROUND: Carbon monoxide (CO) poisoning may result in white matter hyperintensities (WMH) and neurocognitive impairments. OBJECTIVE: To assess in a prospective study WMH in CO-poisoned patients and their relationship to cognitive functioning. METHODS: Seventy-three consecutive CO-poisoned patients were studied. MR scans and neurocognitive tests were administered on day 1 (within 36 hours after CO poisoning), 2 weeks, and 6 months. Age- and sex-matched control subjects for white matter analyses only were obtained from the authors' normative imaging database. MR scans were rated for WMH in the periventricular and centrum semiovale regions, using a 4-point rating scale. Two independent raters rated the scans, and a consensus was reached. RESULTS: Thirty percent of CO-poisoned patients had cognitive sequelae. Twelve percent of the CO-poisoned patients had WMH, with significantly more periventricular, but not centrum semiovale, WMH than control subjects. The WMH in CO-poisoned patients did not change from day 1 to 6 months. Centrum semiovale hyperintensities were related to worse cognitive performance. Duration of loss of consciousness correlated with cognitive impairment at all three times. Initial carboxyhemoglobin levels correlated with loss of consciousness but not with WMH or cognitive sequelae. CONCLUSIONS: CO poisoning can result in brain injury manifested by WMH and cognitive sequelae. The WMH were not related to CO poisoning severity. The WMH occurred in both the periventricular and the centrum semiovale regions; however, only those in the centrum semiovale were significantly associated with cognitive impairments.

Normobaric measurement of arterial oxygen tension in subjects exposed to hyperbaric oxygen.

This study demonstrates the ability of an automated blood gas analyzer (Radiometer ABL 330) operated at atmospheric pressure to measure the arterial oxygen tension (PaO2) of ten healthy volunteers exposed to hyperbaric oxygen (HBO2) up to 3.0 atmospheres absolute. Arterial blood samples were aspirated from subjects compressed in a single-person hyperbaric chamber and were analyzed immediately in the blood gas analyzer. The subjects' values for PaO2 correlated with the calculated alveolar O2 tension (PAO2) (measured PaO2 = 0.827 x PAO2-15.1) (r2 = 0.97). Tonometric experiments indicated a difference between saline and blood PO2 measurements. We therefore derived a correction factor for blood measurements (corrected PaO2 = 0.908 x PAO2-52.4) (r2 = 0.98). These results compared favorably with PaO2 measurements made with blood gas analyzers calibrated inside walk-in hyperbaric chambers. We conclude that the PaO2 of normal subjects exposed to HBO2 can be measured accurately at atmospheric pressure with this automated blood gas analyzer. Prior to this study, hyperbaric PaO2 measurements could only be performed within walk-in chambers. Our observations generalize the normobaric measurement of hyperbaric PaO2 to patients treated in single-person and walk-in chambers.

Hypoxemia during hyperbaric oxygen therapy.

This report describes a patient with mucormycosis treated with hyperbaric oxygen therapy (HBO2). Arterial O2 tension (PaO2) during HBO2 was considerably lower (346 mm Hg) than expected (1,500 mm Hg) due to an inadvertent right main-stem intubation, which was not otherwise clinically evident. This case illustrates the influence of a large right-to-left shunt (Qs/Qt) on O2 loading during HBO2. We raise the question if routine hyperbaric treatment protocols are adequate to raise PaO2 in patients with large Qs/Qts.

Arterial oxygen tension of patients with abnormal lungs treated with hyperbaric oxygen is greater than predicted.

The arterial oxygen (O2) tension (PaO2) of patients with normal gas exchange treated with hyperbaric oxygen (HBO2) can be predicted from their pre-HBO2 arterial to alveolar O2 tension ratio (a/A) which remains constant up to a PaO2 of 2,000 mm Hg. We observed that the a/A could not be used to predict the PaO2 of patients with impaired gas exchange (reduced pre-HBO2 a/As) treated with HBO2. Our study provides information about the PaO2 of patients with abnormal lungs treated with HBO2. For clinical reasons, we measured the PaO2 of 24 patients treated with HBO2. We obtained arterial blood gas values from patients with lung dysfunction (a/A < 0.75) prior to, during, and after HBO2. The pre-HBO2 a/A = 0.45 +/- 0.17 (mean +/- 1 SD). During HBO2 the a/A ranged from 0.7 to 0.8 depending on chamber pressure and returned to the pre-HBO2 baseline after HBO2. We conclude the following: (1) The hyperbaric PaO2s of patients with a/A < 0.75 is greater than expected. (2) However, the PaO2 is lower than in patients with normal lung function (a/A > 0.75). Possible explanations include improvement in ventilation/perfusion matching, reduction of venous admixture, and/or extra-alveolar uptake of O2. (3) Exposures to HBO2 treatment pressures greater than recommended by existing protocols may be required in patients with impaired transfer of O2 across the lung to achieve PaO2s similar to patients with normal lung function treated with HBO2.

Venous and arterial gas embolism associated with positive pressure ventilation.

We report a 53-year-old woman with ARDS who required positive pressure ventilation with positive end-expiratory pressure. She sustained an acute right ventricular myocardial infarction associated with cardiovascular instability. The next day she sustained a fatal cerebral arterial gas embolism. Intravascular gas was documented within the cerebral, coronary, and pulmonary arterial circulations. Clinicians need to be aware of venous and arterial gas embolism as a complication of mechanical ventilation.

Pulmonary edema associated with hyperbaric oxygen therapy.

We report three cases of pulmonary edema associated with hyperbaric oxygen therapy, including one fatality. All three patients had cardiac disease and reduced left ventricular (LV) ejection fractions (EFs). Two patients had diabetes, and one patient had severe aortic stenosis. Hyperbaric oxygen therapy may contribute to pulmonary edema by increasing LV afterload, increasing LV filling pressures, increasing oxidative myocardial stress, decreasing LV compliance by oxygen radical-mediated reduction in nitric oxide, altering cardiac output between the right and left hearts, inducing bradycardia with concomitant LV dysfunction, increasing pulmonary capillary permeability, or by causing pulmonary oxygen toxicity. We advise caution in the use of hyperbaric oxygen therapy in patients with heart failure or in patients with reduced cardiac EFs.

Bilateral otorrhagia associated with continuous positive airway pressure.

A patient had bilateral tympanic membrane rupture and otorrhagia, an unusual complication of continuous positive airway pressure (CPAP). CPAP, applied by a bag/mask system using disposable spring valves, was used to treat acute pulmonary edema during volume resuscitation and vasopressin therapy for bleeding from esophageal varices.

Carboxyhemoglobin half-life in carbon monoxide-poisoned patients treated with 100% oxygen at atmospheric pressure.

STUDY OBJECTIVES: There are large reported differences for the carboxyhemoglobin (COHb) half-life (COHb t(1/2)) in humans breathing 100% atmospheric O(2) following CO inhalation in tightly controlled experiments compared to the COHb t(1/2) observed in clinical CO poisoning (range, 36 to 131 min, respectively). Other reports have suggested that the COHb t(1/2) may be affected by gender differences, age, and lung function. We wished to test the hypothesis that the COHb t(1/2) might also be influenced by CO poisoning vs experimental CO exposure, by a history of loss of consciousness (LOC), concurrent tobacco smoking, and by PaO(2). The purpose of the present study was to measure the COHb t(1/2) in a cohort of CO-poisoned patients and to determine if those listed factors influenced the COHb t(1/2). DESIGN: Retrospective chart review from 1985 to 1995. We calculated the COHb t(1/2) of CO-poisoned patients who were treated with high-flow supplemental atmospheric pressure O(2) delivered by nonrebreather face mask or endotracheal tube. SETTING: Hyperbaric medicine department of a tertiary-care teaching hospital. PATIENTS: Of 240 CO-poisoned patients, 93 had at least two COHb measurements > 2% (upper limit of normal) with recorded times of the measurements, permitting calculation of the COHb t(1/2). RESULTS: The COHb t(1/2) was 74 +/- 25 min (mean +/- 1 SD) with a range from 26 to 148 min. By stepwise multiple linear regression analysis, the PaO(2) influenced the COHb t(1/2) (R(2) = 0.19; p < 0.001), whereas the COHb t(1/2) was not influenced by gender, age, smoke inhalation, history of LOC, concurrent tobacco smoking, degree of initial metabolic acidosis (base excess), or initial COHb level. CONCLUSIONS: The COHb t(1/2) of 93 CO-poisoned patients treated with 100% O(2) at atmospheric pressure was 74 +/- 25 min, considerably shorter than the COHb t(1/2) reported in prior clinical reports (approximately 130 +/- 130 min) and was influenced only by the patient's PaO(2).

The adult respiratory distress syndrome. A report of survival and modifying factors.

The adult respiratory distress syndrome (ARDS) is a form of acute lung injury characterized by arterial hypoxemia, reduced thoracic compliance, normal pulmonary capillary wedge pressure, and diffuse infiltrates on chest roentgenograms. Mortality remains high and has been associated with sepsis, organ failure, age, and predisposing factors. We prospectively identified 215 ARDS patients over 34 months to examine how these factors influence outcome. One hundred two (47 percent) of 215 patients survived. Age 65 years or older was associated with a survival of 34 percent, which was statistically different from the 53 percent survival of those patients younger than 65 years (p = 0.02). Aspiration pneumonia as a predisposing factor of ARDS was associated with a better survival (p = 0.04). Survivors had statistically less organ failure and sepsis than did nonsurvivors (p less than 0.05). Cause of death was determined using the criteria of Montgomery et al for irreversible organ dysfunction. Forty-five (40 percent) of our patients died of respiratory failure (not sepsis). We conclude the following: (1) survival in our ARDS patients is different from previous reports; (2) the cause of death in our ARDS patients is different from that reported by Montgomery et al in 1985; and (3) multisystem organ failure, sepsis, age, and some predisposing factors of ARDS continue to be associated with decreased survival of ARDS patients.

A successful computerized protocol for clinical management of pressure control inverse ratio ventilation in ARDS patients.

We have developed a computerized protocol that provides a systematic approach for management of pressure control-inverse ratio ventilation (PCIRV). The protocols were used for 1,466 h in ten around-the-clock PCIRV evaluations on seven patients with severe adult respiratory distress syndrome (ARDS). Patient therapy was controlled by protocol 95 percent of the time (1,396 of 1,466 h) and 90 percent of the protocol instructions (1,937 of 2,158) were followed by the clinical staff. Of the 221 protocol instructions, 88 (39 percent) not followed were due to invalid PEEPi measurements. Compared with preceding values during CPPV, the expired minute ventilation was reduced by 27 percent during PCIRV while maintaining a pH that was not clinically different (mean difference in pH = 0.02). There was no difference in the PaO2, PEEPi, or the FIO2 between PCIRV and CPPV. The PEEP setting was reduced by 33 percent from 9 +/- 0.05 to 6 +/- 0.6 and the I:E ratio increased from 0.64 +/- 0.04 to 2.3 +/- 0.10. Peak airway pressure was reduced by 24 percent (from 59 +/- 1.5 to 45 +/- 0.6) and mean airway pressure increased by 27 percent (from 22 +/- 0.8 to 28 +/- 0.6) in PCIRV. Right atrial and pulmonary artery pressures were higher and cardiac output lower in PCIRV but blood pressure was unchanged. The success of this protocol has demonstrated the feasibility of using PEEPi as a primary control variable for oxygenation. This computerized PCIRV protocol should make the future use of PCIRV less mystifying, simpler, and more systematic.

Carbon monoxide poisoning.

Carbon monoxide (CO) poisoning is common and frequently unrecognized since the signs and symptoms are relatively nonspecific. CO poisoning causes tissue hypoxia. Additionally, various animal studies have demonstrated that CO interferes with myoglobin, P450, and other enzyme function; causes lipid peroxidation through neutrophil activation; produces oxidative stress manifested by peroxynitrate deposition in endothelium; binds to cytochrome aa3, disrupting intracellular oxygen utilization; can cause neuroexcitotoxicity; and contributes to hippocampal cellular death through apoptosis. Emergency treatment for CO poisoning is 100% oxygen. Hyperbaric oxygen therapy (HBO2) is accepted in CO poisoning, although data from randomized clinical trials regarding the efficacy of HBO2 in CO poisoning is conflicting. CO poisoning, even when treated with supplemental oxygen can leave the patient with permanent neurocognitive or affective problems. Unfortunately, there appears to be no marker or constellation of signs or symptoms at presentation that predicts long-term outcome following CO poisoning. Given the neurocognitive sequelae following CO poisoning, increased awareness and prevention of CO poisoning is imperative.

De novo cryptogenic hepatitis after sustained eradication of hepatitis C following liver transplantation.

Patients with recurrent hepatitis C (HCV) after liver transplantation (OLT) are often treated with interferon and ribavirin in an attempt to eradicate HCV and prevent cirrhosis. We report four patients who developed de novo cryptogenic hepatitis following sustained eradication of recurrent HCV, which led to decompensated liver disease in two patients, both of whom required listing for retransplantation. Between September 2000 and October 2001, 38 consecutive patients with recurrent HCV were treated with interferon alpha 2b and ribavirin, of whom eight patients (21%) developed a sustained response to HCV eradication. Four of these patients developed cryptogenic hepatitis, which led to decompensated cirrhosis in two patients. Both patients were listed for retransplantation but died on the waiting list. No etiology for liver disease was identified despite extensive investigations in all four patients including postmortem analysis in the two patients. We hypothesize that these individuals developed an aberrant immune response leading to allograft injury whose severity may be determined by underlying haplotype, degree of immunosuppression, presence/absence of HCV, and duration of treatment. We have not found any similar reports in the literature but anticipate more cases to be reported given the universal use of antiviral therapy for recurrent HCV.