Central venous catheter use in severe malaria: time to reconsider the World Health Organization guidelines?

<p>Abstract</p> <p>Background</p> <p>To optimize the fluid status of adult patients with severe malaria, World Health Organization (WHO) guidelines recommend the insertion of a central venous catheter (CVC) and a target central venous pressure (CVP) of 0-5 cmH₂O. However there are few data from clinical trials to support this recommendation.</p> <p>Methods</p> <p>Twenty-eight adult Indian and Bangladeshi patients admitted to the intensive care unit with severe <it>falciparum </it>malaria were enrolled in the study. All patients had a CVC inserted and had regular CVP measurements recorded. The CVP measurements were compared with markers of disease severity, clinical endpoints and volumetric measures derived from transpulmonary thermodilution.</p> <p>Results</p> <p>There was no correlation between the admission CVP and patient outcome (p = 0.67) or disease severity (p = 0.33). There was no correlation between the baseline CVP and the concomitant extravascular lung water (p = 0.62), global end diastolic volume (p = 0.88) or cardiac index (p = 0.44). There was no correlation between the baseline CVP and the likelihood of a patient being fluid responsive (p = 0.37). On the occasions when the CVP was in the WHO target range patients were usually hypovolaemic and often had pulmonary oedema by volumetric measures. Seven of 28 patients suffered a complication of the CVC insertion, although none were fatal.</p> <p>Conclusion</p> <p>The WHO recommendation for the routine insertion of a CVC, and the maintenance of a CVP of 0-5 cmH₂O in adults with severe malaria, should be reconsidered.</p

Guanosine stimulates neurite outgrowth in PC12 cells via activation of heme oxygenase and cyclic GMP

Undifferentiated rat pheochromocytoma (PC12) cells extend neurites when cultured in the presence of nerve growth factor (NGF). Extracellular guanosine synergistically enhances NGF-dependent neurite outgrowth. We investigated the mechanism by which guanosine enhances NGF-dependent neurite outgrowth. Guanosine administration to PC12 cells significantly increased guanosine 3-5-cyclic monophosphate (cGMP) within the first 24 h whereas addition of soluble guanylate cyclase (sGC) inhibitors abolished guanosine-induced enhancement of NGF-dependent neurite outgrowth. sGC may be activated either by nitric oxide (NO) or by carbon monoxide (CO). \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} $$N^{\omega }$$ \end{document}-Nitro-l-arginine methyl ester (l-NAME), a non-isozyme selective inhibitor of nitric oxide synthase (NOS), had no effect on neurite outgrowth induced by guanosine. Neither nNOS (the constitutive isoform), nor iNOS (the inducible isoform) were expressed in undifferentiated PC12 cells, or under these treatment conditions. These data imply that NO does not mediate the neuritogenic effect of guanosine. Zinc protoporphyrin-IX, an inhibitor of heme oxygenase (HO), reduced guanosine-dependent neurite outgrowth but did not attenuate the effect of NGF. The addition of guanosine plus NGF significantly increased the expression of HO-1, the inducible isozyme of HO, after 12 h. These data demonstrate that guanosine enhances NGF-dependent neurite outgrowth by first activating the constitutive isozyme HO-2, and then by inducing the expression of HO-1, the enzymes responsible for CO synthesis, thus stimulating sGC and increasing intracellular cGMP

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Orthopedic Trauma and Aging

The elderly (age 70+) patient with orthopedic trauma is a rapidly growing subset of patients in the United States. Due to increased medical comorbidities and decreased physiological reserve, morbidity and mortality after trauma may significantly differ from those patients younger than 70 years old. A retrospective review was performed to investigate the effect of age on orthopedic trauma. A total of 870 records of patients with orthopedic trauma from 2006 to 2009 at our Level One trauma center were reviewed. A database was created to include demographics, type and number of comorbid conditions at presentation, injuries, intensive care unit (ICU) and hospital length of stay, and description of the fracture. Patients aged 70 years and older had an increased number of comorbidities per person (3.3214— P < .0001). Length of stay in patients aged 70 years and older was not significantly greater than that of the younger patients. They spent an average of 14.76 days in the hospital compared to 13.42 days for the combined younger patients ( P = .45), but they spent significantly ( P < .0001) more of their stay in the ICU (52.74% vs 34.9% for the younger cohorts). The number of fractures per patient was lower (1.66) in the 70 and older age-group when compared to younger populations ( P < .0001). The 70 and older group was more likely to have their injury due to a fall and less likely to have solid organ injuries. As the number of elderly patients increase, continued research in the management of elderly patients with trauma can lead to protocols and practice guidelines to improve outcomes

Experimental posterolateral spinal fusion with porous ceramics and mesenchymal stem cells

lternatives to autogenous bone graft for spinal fusion have been investigated for many years. It has been shown that osteoconductive materials alone do not give a rate of fusion which is comparable to that of autogenous bone graft. We analysed the effectiveness of porous ceramic loaded with cultured mesenchymal stem cells as a new graft material for spinal fusion in an animal model. Posterolateral fusion was carried out at the L4/L5 level in 40 White New Zealand rabbits using one of the following graft materials: porous ceramic granules plus cultured mesenchymal stem cells (group I); ceramic granules plus fresh autogenous bone marrow (group II); ceramic granules alone (group III); and autogenous bone graft (group IV). The animals were killed eight weeks after surgery and the spines were evaluated radiographically, by a manual palpation test and by histological analysis. The rate of fusion was significantly higher in group I compared with group III and higher, but not significantly, in group I compared with groups II and IV. In group I histological analysis showed newly formed bone in contact with the implanted granules and highly cellular bone marrow between the newly formed trabecular bone. In group II, thin trabeculae of newly formed bone were present in the peripheral portion of the fusion mass. In group III, there was a reduced amount of newly formed bone and abundant fibrous tissue. In group IV, there were thin trabeculae of newly formed bone close to the decorticated transverse processes and dead trabecular bone in the central portion of the fusion mass. In vitro cultured mesenchymal stem cells may be loaded into porous ceramic to make a graft material for spinal fusion which appears to be more effective than porous ceramic alone. Further studies are needed to investigate the medium-to long-term results of this procedure, its feasibility in the clinical setting and the most appropriate carrier for mesenchymal stem cells

Geriatric Patients With Fractures Below the Hip are Medically Similar to Geriatric Patients With Hip Fracture

The objective of this study was to compare a cohort of geriatric patients with operatively managed isolated fractures below the hip to a cohort of geriatric patients with operatively managed isolated hip fractures. All patients greater than 59 years of age admitted to our institution for surgical care of an isolated lower extremity fracture during a 3-year period were included. Patients were divided into 2 cohorts: BTH (fracture below the subtrochanteric region of the femur) and HIP (proximal femoral fracture at subtrochanteric region or proximal). We identified 141 patients included in cohort BTH and 205 patients included in cohort HIP. HIP patients were older ( P < .01) and less obese ( P < .01) but were otherwise very similar. An extensive comorbidity review revealed that the 2 cohorts were similar, with the exception of an increased incidence of dementia ( P = .012) or glaucoma ( P = .04) in HIP patients and of peripheral neuropathy ( P = .014) in BTH patients. HIP patients were more likely to be under active antiosteoporotic medication management and were more likely to be receiving pharmacological anticoagulation at the time of admission. HIP patients and BTH patients were similar with regard to necessity of assistance with ambulation preinjury, but HIP patients were less likely to reside independently at home than were BTH patients ( P < .001). HIP patients were also less likely to be discharged directly home from the hospital ( P < .001). Geriatric patients with fractures below the hip are medically similar to geriatric patients with hip fracture. Medical comanagement protocols have been extensively published that improve care of geriatric patients with hip fracture; consideration should be given to similar protocol-driven medical comanagement programs for geriatric patients with fractures below the hip