Outcomes of patients with acute respiratory failure after abdominal surgery treated with noninvasive positive pressure ventilation

OBJECTIVES: Little is known about the physiologic and clinical effects of noninvasive positive pressure ventilation (NPPV) in patients who have acute respiratory failure (ARF) after abdominal surgery. We evaluated our clinical experience with the use of NPPV in the treatment of ARF after abdominal surgery. METHODS: We prospectively evaluated NPPV use during a 2-year period in a medical-surgical ICU of a university hospital. We documented demographic and diagnostic data, gas exchange, and clinical outcomes. We compared patients who were not intubated to those who were intubated after a trial of NPPV. RESULTS: Of 72 patients with ARF after abdominal surgery who were treated with NPPV, 48 patients avoided intubation (67%). Patients in the intubated and nonintubated groups had similar demographic characteristics, and similar American Society of Anesthesiologists physical status and simplified acute physiology score II scores at admission. The intubated group had a significantly lower Pa(O2)/fraction of inspired oxygen (Fi(O2)) ratio (123 +/- 62 mm Hg vs 194 +/- 76 mm Hg, p < 0.01) and more extended bilateral alveolar infiltrates (67% vs 31%, p < 0.01) than the non-intubated group. Within the first NPPV observation period, the Pa(O2)/Fi(O2) increased (+ 36 +/- 29% [+/- SD], p = 0.04) and the respiratory rate decreased (28.2 +/- 3.4 breaths/min vs 23.1 +/- 3.8 breaths/min, p < 0.01) significantly only in the non-intubated group. The non-intubated group had significantly lower length of ICU stay (17.3 +/- 10.9 days vs 34.1 +/- 28.5 days, p < 0.01) and mortality rate (6% vs 29%, p < 0.01). CONCLUSION: NPPV may be an alternative to conventional ventilation in selected patients with ARF after abdominal surgery who require ventilatory support.     

A prospective study of agitation in a medical-surgical ICU: incidence, risk factors, and outcomes

STUDY OBJECTIVES: Although agitation is thought to be common in the ICU, it has been poorly studied. We evaluated the incidence, risks factors, and outcomes of agitation in ICU. DESIGN: Prospective observational study. INTERVENTIONS: None. METHOD: All consecutive ICU admissions over an 8-month period were analyzed. MEASUREMENTS AND RESULTS: Two hundred eleven patients were admitted a total of 216 times during the period of the study. Twenty-nine patients were excluded from the study because their pathology findings did not allow an evaluation of their level of consciousness; 182 patients were actually enrolled. Agitation developed in 95 of 182 patients (52%). Agitation began 4.4 +/- 5.6 days (+/- SD) after admission to the ICU and lasted 3.9 +/- 4.1 days. Patients with agitation had a higher Simplified Acute Physiology Score II on ICU admission than those who did not have agitation (40 +/- 16 vs 33 +/- 13, p < 0.01). By stepwise logistic regression, the independent risks factors for development of agitation included psychoactive drug use at the time of ICU admission (odds ratio, 5.63; 95% confidence interval [CI], 1.32 to 23.70), history of alcohol abuse (odds ratio, 3.32; 95% CI, 1.12 to 10.00), dysnatremia (odds ratio, 4.95; 95% CI, 1.95 to 12.54), fever (odds ratio, 4.52; 95% CI, 1.80 to 11.49), use of sedatives in the ICU (odds ratio, 4.03; 95% CI, 1.62 to 10.40), and sepsis (odds ratio, 2.61; 95% CI, 1.03 to 6.58). Agitation was associated with a prolonged ICU stay (16 +/- 19 days vs 6 +/- 6 days, p = 0.0001), nosocomial infections (34% vs 7%, p < 0.0001), unplanned extubations (17% vs 2%, p = 0.003), and unplanned central venous catheter removal (16% vs 1%, p = 0.001), but not with mortality (12% in the agitation group vs 8% in patients without agitation). CONCLUSIONS: Agitation is a common event in a mixed medical-surgical ICU. It is associated with adverse outcomes including prolonged stay, nosocomial infections, and unplanned extubations. A better knowledge of incidence and risk factors should facilitate identification of patients at risk and decrease the incidence of agitation.     

Human liver stem/progenitor cells decrease serum bilirubin in hyperbilirubinemic Gunn rat

AIM:To test the ability of adult-derived human liver stem/progenitor cells(ADHLSC)from large scale cultures to conjugate bilirubin in vitro and in bilirubin conjugation deficient rat.METHODS:ADHLSC from large scale cultures were tested for their phenotype and for their capacity to conjugate bilirubin in vitro after hepatogenic differentiation.In vivo,Gunn rats[uridine diphosphate-glucuronosyltransferase 1A1(UGT1A1)deficient animal]were injected with ADHLSC and cryopreserved hepatocytes(positive control).Two,4,13 and 27 wk posttransplantation,transplanted Gunn rat bilirubin serum levels were determined by high performance liquid chromatography.Human cell engraftment of trans-planted cells was assessed 27 wk post-transplantation using immunohistochemistry and RTqPCR.RESULTS:Large scale culture conditions do not modified ADHLSC phenotype,ADHLSC were able to specifically conjugate bilirubin.ADHLSC were intraportally injected into Gunn rats and blood UCB was measured at different times post-transplantation,infused-Gunn rats exhibited a metabolic effect 3 mo post-transplantation and maintained over a 6 mo period.ADHLSC engraftment into Gunn rat’s liver was demonstrated by RTqPCR and immunohistochemistry against albumin and UGT1A1.CONCLUSION:ADHLSC from large scale cultures are efficient in conjugating bilirubin in vitro and in restoring a deficient metabolic function(reducing bilirubin level)in hyperbilirubinemic rats.     

Chemokines and Antimicrobial Peptides Have a cag-Dependent Early Response to Helicobacter pylori Infection in Primary Human Gastric Epithelial Cells

Helicobacter pylori infection systematically causes chronic gastric inflammation that can persist asymptomatically or evolve toward more severe gastroduodenal pathologies, such as ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. The cag pathogenicity island (cag PAI) of H. pylori allows translocation of the virulence protein CagA and fragments of peptidoglycan into host cells, thereby inducing production of chemokines, cytokines, and antimicrobial peptides. In order to characterize the inflammatory response to H. pylori, a new experimental protocol for isolating and culturing primary human gastric epithelial cells was established using pieces of stomach from patients who had undergone sleeve gastrectomy. Isolated cells expressed markers indicating that they were mucin-secreting epithelial cells. Challenge of primary epithelial cells with H. pylori B128 underscored early dose-dependent induction of expression of mRNAs of the inflammatory mediators CXCL1 to -3, CXCL5, CXCL8, CCL20, BD2, and tumor necrosis factor alpha (TNF-α). In AGS cells, significant expression of only CXCL5 and CXCL8 was observed following infection, suggesting that these cells were less reactive than primary epithelial cells. Infection of both cellular models with H. pylori B128ΔcagM, a cag PAI mutant, resulted in weak inflammatory-mediator mRNA induction. At 24 h after infection of primary epithelial cells with H. pylori, inflammatory-mediator production was largely due to cag PAI substrate-independent virulence factors. Thus, H. pylori cag PAI substrate appears to be involved in eliciting an epithelial response during the early phases of infection. Afterwards, other virulence factors of the bacterium take over in development of the inflammatory response. Using a relevant cellular model, this study provides new information on the modulation of inflammation during H. pylori infection.     

Human herpesvirus 6 is associated with status epilepticus and hyponatremia after umbilical cord blood transplantation

Status epilepticus after allogeneic hematopoietic cell transplantation (alloHCT) is rare. The authors report a case involving a 65-year-old man with nonconvulsive status epilepticus 34 days after umbilical cord blood transplantion for chronic lymphocytic leukemia. Cerebrospinal fluid and serum were positive for human herpesvirus 6 (HHV6). Magnetic resonance imaging of the brain showed symmetric T2 hyper-intensity bilaterally in the mesial temporal lobes, and T2 hyperintensi-ties and restricted diffusion of bilateral putamina. Despite aggressive anticonvulsive therapy, his seizures only abated with initiation of ganciclovir therapy. The patient completed six weeks of combination antiviral therapy (ganciclovir and foscarnet). His cognitive function gradually improved and, after prolonged rehabilitation, the patient was discharged home with residual intermittent memory loss but otherwise functional. HHV6 should be considered in the differential diagnosis of nonconvulsive status epilepticus after alloHCT, especially in patients with hyponatremia. Empirical antiviral therapy targeting HHV6 should be administered to these patients.     

Mutations in NSCLC and their link with lung cancer-associated thrombosis: A case-control study

Introduction

The association of venous thromboembolic events (VTE) and lung cancer is highly prevalent. Additionally, the occurrence of a VTE with cancer has been associated with a worse prognosis and a poor quality of life. Underlying cancer biological features such as tumour mutations may contribute to VTE risk and cancer prognosis. Since preclinical data suggest a link between thrombosis and KRAS mutations in tumours, we aimed to validate this association in a patient registry cohort. Methods: A retrospective case control study was performed using the CHUM NSCLC registry. Cases had VTE occurring 6 months previous to or after a diagnosis of NSCLC. Diagnosis of VTE (venous thrombosis, pulmonary embolism, and migratory superficial thrombophlebitis) was confirmed by a review of the imaging reports. Controls were patients with NSCLC without thrombosis matched for age and stage (I-IIIA/IIIB-IV). Exclusion criteria included insufficient tissue for KRAS/EGFR mutation analysis or insufficient clinical information.

Results

Between Jan 2000 and Dec 2009 a total of 57 cases with VTE and 102 controls without VTE were included. The OR for thrombosis in KRAS and EGFR mutated NSCLC patients are respectively 2.67 (1.12-6.42; p = 0.014) and 0.99 (0.27-3.48; p = 0.99).

Conclusions

KRAS mutation is associated with an increased risk of VTE in this NSCLC cohort. These findings are consistent with preclinical studies. Prospective data on VTE rates from clinical trials with molecularly defined NSCLC are needed to confirm these findings.     

INSL5-Deficient Mice Display an Alteration in Glucose Homeostasis and an Impaired Fertility

Insulin-like factor 5 (INSL5), a member of the insulin superfamily, is expressed in the colorectum and hypothalamus. To facilitate studies into the role of INSL5, we generated Insl5(-/-) mice by gene targeting. Insl5(-/-) mice were born in the expected Mendelian ratio, reached normal body weight, but displayed impaired male and female fertility that are due to marked reduction in sperm motility and irregular length of the estrous cycle. Furthermore, Insl5(-/-) mice showed impairment in glucose homeostasis with characteristic elevation of serum glucose levels at an advanced age. Glucose and insulin tolerance tests revealed that the increased blood glucose in Insl5(-/-) mice was due to glucose intolerance resulting from reduced insulin secretion. Morphometric and immunohistological analyses revealed that the Insl5(-/-) mice had markedly reduced average islets area and β-cell numbers. Furthermore, immunohistochemistry showed the expression of INSL5 in enteroendocrine cells in the colorectal epithelium and the presence of its putative receptor relaxin family peptide receptor 4 in pancreatic islet cells. These results suggest the potential role of INSL5 signaling in the regulation of insulin secretion and β-cell homeostasis.     

Relation of plasma total homocysteine, folate and vitamin B12 levels to bone mineral density in Moroccan healthy postmenopausal women

To test whether in Moroccan healthy postmenopausal women, levels of plasma total homocysteine (tHcy), folate, and vitamin B12 are related to BMD. A total of 188 volunteer postmenopausal women were recruited from our blood taking center between April 2008 and December 2008. Each subject completed a standardized questionnaire designed to document putative risk factors of osteoporosis. Bone mineral density was determined by a Lunar Prodigy Vision DXA system, and blood samples for plasma tHcy, folate, vitamin B12, and serum parathyroid hormone (PTH) were taken. Comparison between women with osteoporosis, osteopenia and normal BMD showed that the osteoporotic women were significantly older, had lower weight and height than the women of the other groups. Plasma tHcy was significantly higher in the osteoporotic group. Levels of tHcy were inversely related to BMD at the lumbar spine, at the total hip and plasma vitamin B12 and positively related to age and creatinine. Multiple regression analysis showed that age and BMI were the main predictors of BMD at the lumbar spine, whereas the main predictors of BMD at the total hip were age, BMI, plasma tHcy, and plasma vitamin B₁₂. tHcy and vitamin B12 are independent risk factors for osteoporosis in Moroccan healthy postmenopausal women.