Clinical implications of C6 complement component deficiency.

Background: Terminal complement component deficiencies are risk factors for neisserial infections. Objective: To review the clinical characteristics, the diagnosis and the management of patients with a terminal complement component deficiency. Methods: Pertinent articles were selected and reviewed in relation to a case presentation of C6 deficiency. Results: A case of a 56-year old patient with a history of meningitis, chronic rash, and C6 deficiency was presented, followed by discussion of clinical characteristics, diagnosis, and management of terminal complement component deficiencies. Clinical pearls and pitfalls were reviewed for the practicing allergist/immunologist and fellow-in-training. Conclusion: C6 deficiency is the most common terminal complement component deficiency and can present later in age with N. meningitidis infections. Patients can be screened for terminal complement component deficiency by checking CH50.

Improvement in Quality Metrics by the UPMC Enhanced Care Program: A Novel Super-Utilizer Program.

The aim was to evaluate pre-post quality of care measures among super-utilizer patients enrolled in the Enhanced Care Program (ECP), a primary care intensive care program. A pre-post analysis of metrics of quality of care for diabetes, hypertension, cancer screenings, and connection to mental health care for participants in the ECP was conducted for patients enrolled in ECP for 6 or more months. Patients enrolled in ECP showed statistically significant improvements in hemoglobin A1c, retinal exams, blood pressure measurements, and screenings for colon cancer, and trends toward improvement in diabetic foot exams and screenings for cervical and breast cancer. There was a significant increase in connecting patients to mental health care. This study shows that super-utilizer patients enrolled in the ECP had significant improvements in quality metrics from those prior to enrollment in ECP.

Forgetting heart break: a fascinating case of transient left ventricular apical ballooning syndrome associated with dissociative amnesia.

Transient left ventricular apical ballooning syndrome (TLVABS), also known as takotsubo cardiomyopathy, is characterized by transient left ventricular dysfunction, electrocardiographic changes, and release of myocardial enzymes that mimic acute myocardial infarction in patients without angiographic evidence of coronary artery disease. Most patients are post-menopausal women and an emotional or physiologic stressor frequently precedes the presentation. Psychogenic or dissociative amnesia is a memory disorder characterized by sudden retrograde memory loss with inability to recall personal information said to occur for a period of time ranging from hours to years after a stressful event. Interestingly, the mechanism of both disorders has been linked to plasma elevation in catecholamines. Here we present the case of a 66-year-old female diagnosed with both TLVABS and dissociative amnesia following the sudden unexpected death of her sister. To our knowledge, this is surprisingly the first report of the co-occurrence of TLVABS and dissociative amnesia, two processes with a potential shared underlying etiology.

Stat 6-dependent induction of myeloid derived suppressor cells after physical injury regulates nitric oxide response to endotoxin.

OBJECTIVE: To delineate the role of T-helper 2 (Th2) cytokines in the induction of trauma induced myeloid suppressor cells (TIMSC) and the regulation of nitric oxide production. BACKGROUND: Trauma induces myeloid cells that express CD11b+/Gr1+ and arginase 1 and exhibit an immune suppressing activity. This article explores the mechanisms that induce TIMSC and the effects on nitric oxide production in response to endotoxin. METHODS: TIMSC were studied in response to Th2 cytokines and a subsequent challenge to endotoxin. The role of Th2 cytokines was studied in STAT6-/- mice. Accumulation of TIMSC in spleens was studied using flow cytometry and immunhistochemistry. Plasma was recovered to measure accumulation of nitric oxide metabolites. RESULTS: TIMSC accumulated in the spleen of injured mice and were particularly sensitive to IL-4 and IL-13 with large inductions of arginase activity. Significant blunting in both the accumulation of TIMSC in the spleen and induction of arginase 1 was observed in STAT6-/- mice after physical injury. Accumulation of nitric oxide metabolites to endotoxin was observed in STAT6-/- mice. CONCLUSION: This study shows that induction of CD11b+/Gr1+ cells after physical injury play an essential role in the regulation of nitric oxide production after a septic challenge. The accumulation and induction of arginase 1 in TIMSC is Th2 cytokine dependent. To our knowledge, the role of TIMSC in the regulation of nitric oxide is a novel finding. This observation adds to the possibility that TIMSC could play an important role in immunosuppression observed after physical injury.

Nature of myeloid cells expressing arginase 1 in peripheral blood after trauma.

BACKGROUND: Myeloid cells that express arginase 1 are upregulated by different stimuli, including trauma, and are capable of depleting arginine from the surrounding environment. Through arginine depletion, myeloid cells are capable of regulating T-cell function. We have previously reported increased arginase 1 expression in the peripheral blood mononuclear cells (PBMCs) after injury. The nature of the cells expressing arginase in humans after trauma is unknown and is the focus of this article. METHODS: PBMCs were isolated using a Ficoll-Hypaque gradient. Arginase activity was measured by conversion of arginine to ornithine, and arginase 1 protein expression was measured by Western blot. The percent CD16 granulocytes and phenotypical analysis of the cells present in PBMCs were determined by flow cytometry. Magnetic microbeads were used for isolation and exclusion of specific cell subpopulations. RESULTS: Trauma patients exhibited a dramatic increase in arginase activity (p < 0.05) and an increased percentage of CD16 granulocytes in the PBMC layer (p < 0.05) compared with control volunteers. Increased arginase activity in the PBMC layer was due to the contamination of this layer by granulocytes, as their exclusion decreased arginase activity back to baseline (p < 0.05). Granulocytes isolated from the PBMC layer expressed increased CD11b (p < 0.05) and CD66b (p < 0.05), markers of granulocyte activation. Furthermore, these granulocytes were significantly more swollen and degranulated compared with noncontaminating granulocytes. CONCLUSION: In humans, increased arginase 1 expression after trauma observed in the PBMC layer seems to be exclusively the result of an increased number of activated granulocytes.

Use of a colorimetric carbon dioxide sensor for nasoenteric feeding tube placement in critical care patients compared with clinical methods and radiography.

BACKGROUND: Misplacement of nasoenteric feeding tubes (NFTs) into the airway instead of the esophagus leads to complications. Healthcare providers have relied on clinical methods, devices such as carbon dioxide (CO(2)) sensors, and radiography (the gold standard) to evaluate NFT placements. Most institutions include radiographs in their protocols for NFT insertions, making it expensive and cumbersome. A new commercial CO(2) sensor was developed to assist in these procedures, and the authors evaluated its use. METHODS: Nurses performing NFT placement completed questionnaires following each procedure. The nurses recorded the clinical methods used to determine proper insertion and, based on them, where the NFT was located. Nurses then evaluated NFT insertion with the CO(2) sensor; from the readings, they recorded where the tube was located. Confirmation of tube placement was performed radiographically. RESULTS: The authors evaluated 424 NFT insertions. Of these, 15 (3.5%) were incorrectly placed into the airway, and 409 were correctly placed into the esophagus. The CO(2) sensor correctly assessed NFT placement in 421 (99%) of the 424 cases. The authors found the device to have a sensitivity of 86.7% and a specificity of 99.8%. CONCLUSIONS: The CO(2) sensor is a helpful bedside tool to use in conjunction with clinical methods during NFT insertions. However, there is insufficient evidence to abandon the use of radiographs to confirm tube placement.

Effect of citrulline and glutamine on nitric oxide production in RAW 264.7 cells in an arginine-depleted environment.

BACKGROUND: Nitric oxide (NO) is a highly reactive free radical essential for antimicrobial and tumor immunity as well as endothelial function. Arginine is a limiting factor in NO synthesis. Citrulline can be converted to arginine and might restore NO production when arginine availability is limited, while glutamine may competitively inhibit citrulline availability. We aimed to assess how these amino acids interact to generate NO using an in vitro model. METHODS: RAW 264.7 cells were exposed to various amino acid concentrations before and after lipopolysaccharide (LPS) stimulation, and NO production was assessed. RESULTS: NO production directly correlated up to 200 microM with arginine available after LPS stimulation (R(2) = 0.99). Provided the same arginine concentrations following LPS stimulation, low arginine precultured cells produced significantly less NO than high arginine precultured cells (P < .01). Citrulline added to low arginine preculture significantly increased NO production compared to cells in low arginine alone (P < .01). When glutamine was withdrawn before and after LPS stimulation, cells precultured in low arginine and citrulline produced NO equivalent to that of high arginine precultured cells. Additional citrulline provided after LPS stimulation additionally improved NO production beyond that observed in cells precultured in high arginine (P < .01), and NO production became less dependent on arginine availability (R(2) = 0.78). CONCLUSION: Arginine availability is a limiting factor for NO production. Citrulline is a potential substitute to restore NO production when arginine availability is limited. Glutamine appears to be an important modulator that interferes with citrulline-mediated NO production.

Effect of calorically dense enteral nutrition formulas on outcome in critically ill trauma and surgical patients.

BACKGROUND: Surgical and trauma patients are traditionally provided with calorically dense dietary formulas to deliver high amounts of nutrients. The benefits of these formulas remain unproven and may be associated with significant side effects and even increased mortality. We studied outcomes on surgical and trauma patients receiving either a calorically dense dietary formula or a normocaloric dietary formula. METHODS: A retrospective analysis comparing outcomes in intensive care unit (ICU) surgical and trauma patients receiving either a calorically dense dietary formula or a normocaloric dietary formula was performed at the University of Pittsburgh Medical Center. RESULTS: One hundred seventeen patients met study criteria. Surgical and trauma patients were analyzed separately. Despite receiving different calorically dense diets, caloric intake was not significantly different in surgical patients receiving either diet. However, surgical patients receiving a normocaloric formula exhibited decreased length of stay (14.7 +/- 10.1 vs 25.0 +/- 11.3 days; p = .01), ventilator days (14.3 +/- 12.9 vs 21.3 +/- 10.5 days; p = .04), and average daily glucose levels (129.8 +/- 4.1 vs 157.9 +/- 13.6 mg/dL; p =.01), and were more likely to be directly discharged home compared with those receiving a calorically dense dietary formula. Trauma patients receiving a calorically dense dietary formula were on average 17 years younger (p = .01). However, trauma patients receiving a normocaloric formula exhibited decreased length of stay (15.3 +/- 1.6 vs 18.7 +/- 1.6 days; p = .02) and a greater likelihood of direct discharge home. CONCLUSIONS: The data generated suggest that what a patient is fed affects both short- and long-term outcomes. A prospective study should be designed to determine the ideal calories needed in surgical and trauma patients.