Tolerance to apoptotic cells is regulated by indoleamine 2,3-dioxygenase

Tolerance to self-antigens present in apoptotic cells is critical to maintain immune-homeostasis and prevent systemic autoimmunity. However, mechanisms that sustain self-tolerance are poorly understood. Here we show that systemic administration of apoptotic cells to mice induced splenic expression of the tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO). IDO expression was confined to the splenic marginal zone and was abrogated by depletion of CD169(+) cells. Pharmacologic inhibition of IDO skewed the immune response to apoptotic cells, resulting in increased proinflammatory cytokine production and increased effector T-cell responses toward apoptotic cell-associated antigens. Presymptomatic lupus-prone MRL(lpr/lpr) mice exhibited abnormal elevated IDO expression in the marginal zone and red pulp and inhibition of IDO markedly accelerated disease progression. Moreover, chronic exposure of IDO-deficient mice to apoptotic cells induced a lupus-like disease with serum autoreactivity to double-stranded DNA associated with renal pathology and increased mortality. Thus, IDO limits innate and adaptive immunity to apoptotic self-antigens and IDO-mediated regulation inhibits inflammatory pathology caused by systemic autoimmune disease.     

Diagnostic Yield of Electroencephalography in the Medical and Surgical Intensive Care Unit

Background

To determine the incidence of electrographic seizures during continuous electroencephalography (cEEG) in the medical and surgical ICU.

Methods

We retrospectively reviewed the records of all adults who underwent cEEG in our medical and surgical ICU over a 4.5 year period. Patients with acute brain injury were excluded. Our primary outcome was cEEG documentation of an electrographic seizure, defined as a rhythmic discharge or spike and wave pattern demonstrating definite evolution and lasting at least 10 s. To assess inter-rater variability in cEEG interpretation, two electrophysiologists independently reviewed all available cEEGs of subjects with electrographic seizures documented on their clinical cEEG report and those of an equal number of randomly selected subjects from the remaining cohort.

Results

Kappa analysis showed a value of 0.88, indicating excellent inter-rater agreement. Electrographic seizures were identified in 12 of 105 patients (11 %, 95 % CI 5–18 %). This rate did not change after excluding patients with a history of seizure, remote brain injury, or seizure-like events before cEEG. In an ordinal logistic regression model controlling for age, sex, and SOFA score, electrographic seizures were associated with lower odds of good outcomes on the Glasgow Outcome Scale at discharge (OR 0.3, 95 % CI 0.1–0.8).

Conclusion

In a tertiary care medical and surgical ICU, electrographic seizures were seen on 11 % of cEEGs ordered for the evaluation of encephalopathy, and were associated with worse functional outcomes at discharge. Our findings confirm the results of a prior study suggesting a substantial burden of electrographic seizures in critically ill encephalopathic patients.     

SLC34A3 intronic deletion in a new kindred with hereditary hypophosphatemic rickets with hypercalciuria

Objective: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is an autosomal recessive form of hypophosphatemia with hyperphosphaturia, hypercalciuria, and hypercalcemia. In two reports on six affected kindreds with HHRH, the disease was mapped to chromosome 9q34, which contains the SLC34A3 gene that encodes the renal type 2c sodium-phosphate cotransporter. Our objective was to define the clinical course of these cases in a family with HHRH and to screen for SLC34A3 gene in order to determine whether these mutations are responsible for HHRH.Methods: After clinical and biochemical evaluations, the entire SLC34A3 gene was screened using PCR amplification followed by direct sequencing technique. In this paper, we describe a new kindred with HHRH and a case of progressive and complicated HHRH presenting at age 27 years.Results: We found 101-bp deletion in intron 9 of the SLC34A3 gene. The index patient was homozygous for this mutation which has been previously reported in a Caucasian population. This is the first report for presence of SLC34A3 intron 9 deletion in an Iranian population.Conclusions: These data showed that HHRH can be easily missed or underdiagnosed. Genetic evaluation of patients with familial hypercalciuria, hypophosphatemia and nephrolithiasis is needed for further information on the prevalence and management of this rare disorder. Conflict of interest:None declared.     

Prevalence, clinical features, and CPAP adherence in REM-related sleep-disordered breathing: a cross-sectional analysis of a large clinical population

Purpose  

Due to inconsistent definitions used in the literature, the prevalence of rapid eye movement (REM)-related sleep-disordered breathing (SDB) has been quite variable and its clinical significance remains unclear. This study aimed to compare the prevalence of and clinical characteristics between various criteria for defining REM-related SDB. We also investigated how frequently CPAP therapy was recommended in patients with REM-related SDB and if they had lower CPAP adherence compared to non-stage-specific SDB.     

Molecularly engineered electroplex emission for an efficient near-infrared light-emitting electrochemical cell (NIR-LEC)

Electroplex emission is rarely seen in ruthenium polypyridyl complexes, and there have been no reports from light-emitting electrochemical cells (LECs) to date. Here, for the first time, near-infrared (NIR) emission via the electroplex mechanism in a LEC based on a new blend of ruthenium polypyridyl complexes is described. The key factor in the design of the new complexes is the 0.4 V decrease in the oxidation half-potential of Ru(ii)/Ru(iii) in [Ru(DPCO)(bpy)₂]ClO₄ (DPCO = diphenylcarbazone, bpy = 2,2 bipyridine), which is about one-third of the value for benchmark [Ru(bpy)₃](ClO₄)₂, as well as the long lifetime of excited states of 350–450 ns. The LEC based on the new blend with a narrow band gap (≈1.0 eV) of a Ru(DPCO) complex and Ru(bpy)₃²⁺ can produce an electroluminescence spectrum centred at about 700 nm, which extends to the NIR region with a high external quantum efficiency (EQE) of 0.93% at a very low turn-on voltage of 2.6 V. In particular, the very simple LEC structure was constructed from indium tin oxide (anode)/Ru(DPCO):Ru(bpy)₃²⁺/Ga:In (cathode), avoiding any polymer or transporting materials, as well as replacing Al or Au by a molten alloy cathode. This system has promising applications in the production of LECs via microcontact or inkjet printing.

Electroplex emission is rarely seen in ruthenium polypyridyl complexes, and there have been no reports from light-emitting electrochemical cells (LECs) to date. Here, near-infrared (NIR) emission via the electroplex mechanism in a LEC was reported.     

Sleep-Disordered Breathing and Postoperative Outcomes After Bariatric Surgery: Analysis of the Nationwide Inpatient Sample

Background

Sleep-disordered breathing (SDB), also known as obstructive sleep apnea (OSA), has been increasingly recognized as a possible risk factor for adverse perioperative outcomes in non-bariatric surgeries. However, the impact of SDB on postoperative outcomes in patients undergoing bariatric surgery remains less clearly defined. We hypothesized that SDB would be independently associated with worse postoperative outcomes.

Methods

Data were obtained from the Nationwide Inpatient Sample database and included a total of 91,028 adult patients undergoing bariatric surgeries from 2004 to 2008. The primary outcomes were in-hospital death, total charges, and length of stay. There were two secondary outcomes of interest: respiratory and cardiac complications. Regression models were fitted to assess the independent association between SDB and the outcomes of interest.

Results

SDB was independently associated with decreased mortality (OR?=?0.34, 95% CI?=?0.23–0.50, p?<?0.001), total charges (?$869, p?<?0.001), and length of stay (?0.25 days, p?<?0.001). SDB was independently associated with significantly increased odds ratio of emergent endotracheal intubation (OR?=?4.35, 95% CI?=?3.97–4.77, p?<?0.001), noninvasive ventilation (OR?=?14.12, 95% CI?=?12.09–16.51, p?<?0.001), and atrial fibrillation (OR?=?1.25, 95% CI?=?1.11–1.41, p?<?0.001). Emergent intubation occurred significantly earlier in the postoperative course in patients with SDB. Although non-SDB patients had an overall lower risk of emergent intubation compared to SDB patients, their outcomes were significantly worse when they did get emergently intubated.

Conclusions

In this large nationally representative sample, despite the increased association of SDB/OSA with postoperative cardiopulmonary complications, the diagnosis of SDB/OSA was negatively, rather than positively, associated with in-hospital mortality and resource use.     

Fractures of the C1 and C2 Vertebrae

Upper cervical fractures of the axis and atlas (C1 and C2, respectively) typically occur in children and in the elderly population. The anatomic characteristics of the craniocervical junction allows for unique fracture patterns. Jefferson fractures of the atlas are the classic fracture presentation of the C1 vertebrae. Odontoid fractures and traumatic spondylolisthesis of the axis are the most commonly reported fractures of the C2 vertebrae. This chapter will review the anatomy, injury mechanisms, and fracture types seen in the C1 and C2 vertebrae. In addition, several nonoperative and operative treatment options, supported by the literature, will be discussed.     

Prospective Study Examining Clinical Outcomes Associated with a Negative Pressure Wound Therapy System and Barker’s Vacuum Packing Technique

Background

The open abdomen has become a common procedure in the management of complex abdominal problems and has improved patient survival. The method of temporary abdominal closure (TAC) may play a role in patient outcome.

Methods

A prospective, observational, open-label study was performed to evaluate two TAC techniques in surgical and trauma patients requiring open abdomen management: Barker’s vacuum-packing technique (BVPT) and the ABThera^TM open abdomen negative pressure therapy system (NPWT). Study endpoints were days to and rate of 30-day primary fascial closure (PFC) and 30-day all-cause mortality.

Results

Altogether, 280 patients were enrolled from 20 study sites. Among them, 168 patients underwent at least 48 hours of consistent TAC therapy (111 NPWT, 57 BVPT). The two study groups were well matched demographically. Median days to PFC were 9 days for NPWT versus 12 days for BVPT (p = 0.12). The 30-day PFC rate was 69 % for NPWT and 51 % for BVPT (p = 0.03). The 30-day all-cause mortality was 14 % for NPWT and 30 % for BVPT (p = 0.01). Multivariate logistic regression analysis identified that patients treated with NPWT were significantly more likely to survive than the BVPT patients [odds ratio 3.17 (95 % confidence interval 1.22–8.26); p = 0.02] after controlling for age, severity of illness, and cumulative fluid administration.

Conclusions

Active NPWT is associated with significantly higher 30-day PFC rates and lower 30-day all-cause mortality among patients who require an open abdomen for at least 48 h during treatment for critical illness.