Significant Higher Mortality Research Articles

Different Functions of the Insect Soluble and Membrane-Bound Trehalase Genes in Chitin Biosynthesis Revealed by RNA Interference

BackgroundTrehalase, an enzyme that hydrolyzes trehalose to yield two glucose molecules, plays a pivotal role in various physiological processes. In recent years, trehalase proteins have been purified from several insect species and are divided into soluble (Tre-1) and membrane-bound (Tre-2) trehalases. However, no functions of the two trehalases in chitin biosynthesis in insects have yet been reported.Principal FindingsThe membrane-bound trehalase of Spodoptera exigua (SeTre-2) was characterized in our laboratory previously. In this study, we cloned the soluble trehalase gene (SeTre-1) and investigated the tissue distribution and developmental expression pattern of the two trehalase genes. SeTre-1 was expressed highly in cuticle and Malpighian tubules, while SeTre-2 was expressed in tracheae and fat body. In the midgut, the two trehalase genes were expressed in different locations. Additionally, the expression profiles of both trehalase mRNAs and their enzyme activities suggest that they may play different roles in chitin biosynthesis. The RNA interference (RNAi) of either SeTre-1 or SeTre-2 was gene-specific and effective, with efficiency rates up to 83% at 72 h post injection. After RNAi of SeTre-1 and SeTre-2, significant higher mortality rates were observed during the larva-pupa stage and pupa-adult stage, and the lethal phenotypes were classified and analyzed. Additionally, the change trends of concentration of trehalose and glucose appeared reciprocally in RNAi-mutants. Moreover, knockdown of SeTre-1 gene largely inhibited the expression of chitin synthase gene A (CHSA) and reduced the chitin content in the cuticle to two-thirds relative to the control insects. The chitin synthase gene B (CHSB) expression, however, was inhibited more by the injection of dsRNA for SeTre-2, and the chitin content in the midgut decreased by about 25%.Conclusions SeTre-1 plays a major role in CHSA expression and chitin synthesis in the cuticle, and SeTre-2 has an important role in CHSB expression and chitin synthesis in the midgut.

Challenges of T cell therapies for virus-associated diseases after hematopoietic stem cell transplantation

Importance of the field: Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many hematological malignancies and genetic disorders. The majority of patients do not have a human leukocyte antigen (HLA) identical sibling donor, and alternative stem cell sources include HLA-matched or mismatched unrelated donors and haploidentical related donors. However, alternative donor HSCT are associated with three major complications i) graft rejection; ii) graft-versus-host disease (GvHD); and iii) delayed immune reconstitution leading to viral infections and relapse.Areas covered in this review: Graft rejection and the risk of GvHD can be significantly reduced by using intensive conditioning regimens, including in vivo T cell depletion as well as ex vivo T cell depletion of the graft. However, the benefits of removing alloreactive T cells from the graft are offset by the concomitant removal of T cells with anti-viral or anti-tumor activity as well as the profound delay in endogenous T cell recovery post-transplant. Thus, opportunistic infections, many of which are not amenable to conventional small-molecule therapeutics, are frequent in these patients and are associated with significant morbidity and high mortality rates. This review discusses current cell therapies to prevent or treat viral infections/reactivations post-transplant.What the reader will gain: The reader will gain an understanding of the current state of cell therapy to prevent and treat viral infections post-HSCT, and will be introduced to preclinical studies designed to develop and validate new manufacturing procedures intended to improve therapeutic efficacy and reduce associated toxicities.Take home message: Reconstitution of HSCT recipients with antigen-specific T cells, produced either by allodepletion or in vitro reactivation, can offer an effective strategy to provide both immediate and long-term protection without harmful alloreactivity.

Pflegerische Ansätze der nicht-medikamentösen Therapie des Deliriums

The prevalence of deliria is increasing exponentially with cumulative age. At the University Hospital of Basel 16 % of patients in the 70-79 year age-group, 27 % in the 80-89 year age-group and 39 % of the over 90 year old are rated as confused and disoriented. Delirious patients suffer from functional decline and show a significant higher mortality and institutionalization rate after hospital discharge. Nurses have an important role in the multi-component delirium-management. In addition to the assessment of medication, laboratory parameters, oxygenation or urinary excretion, patient-oriented evaluations, pain and stress management, assessment of patient perception and communication are of particular importance. To meet these goals, nurses need knowledge, education and proof of clinical evidence.

Severe Bivalvular Pneumococcal Endocarditis and Suppurative Pericarditis in an Immunocompetent Patient

Pneumococcal endocarditis is a very serious and rare clinical entity that results in significant morbidity and high mortality rates. It causes severe disease and is typically seen in alcoholics and immunocompromised patients. Antimicrobial therapy and timely surgery are warranted for optimal management and improving outcomes. We present a case of a previously healthy 31-year-old Hispanic man with bicuspid aortic valve who developed severe bivalvular pneumococcal endocarditis complicated by suppurative pericarditis that was promptly treated with antimicrobial therapy and subsequent aortic valve replacement with initial favorable clinical and hemodynamic improvement.

Prueba de extractos vegetales para el control de Dasiops spp., en granadilla (Passiflora ligularis Juss.) en el Huila, Colombia

Las moscas negras de la fruta (Dasiops spp.) son responsables de la caída de los botones florales y del daño en frutos en el cultivo de granadilla (Passiflora ligularis Juss.), causando pérdidas económicas a los cultivadores. El objetivo de este estudio fue determinar qué especies atacan botones florales y frutos de granadilla en el sur del Huila, evaluar y caracterizar el daño, conocer los enemigos naturales de Dasiops inedulis y evaluar el efecto insecticida de nueve extractos vegetales acuosos sobre adultos. Se muestrearon 30 fincas de granadilla en los municipios de Pitalito, Palestina, Isnos y Gigante (Huila, Colombia). Se encontraron las especies Dasiops inedulis infestando botones florales y D. yepezi, frutos. Los porcentajes de infestación de D. inedulis en botones florales oscilaron entre 3,87 ± 2,78 en Isnos y 24,60 ± 5,36 en Pitalito. Se encontró que el ataque fue más frecuente en botones de tamaño medio (2-4 cm). La relación de sexos fue de 1:1. Los enemigos naturales de D. inedulis encontrados fueron: Aspilota sp., Pentapria sp., Basalys sp., Pachycrepoideus vindemmiae y una especie de la subfamilia Eucoilinae. Los extractos vegetales que provocaron la mortalidad más cercana al testigo comercial en condiciones de casa de malla fueron los de Hura crepitans (Euphorbiaceae) al 5% (72,5% mortalidad) y Ricinus communis (Euphorbiaceae) al 25% (40% mortalidad); en las condiciones anteriores y en campo, el testigo comercial fue siempre más efectivo que los extractos vegetales. En condiciones de campo, el extracto que se diferenció del testigo absoluto fue el de R. communis al 25% con 40% de mortalidad.

Impact of insecticide-treated nets on wild pyrethroid resistant Anopheles epiroticus population from southern Vietnam tested in experimental huts

BackgroundIn this study, the efficacy of insecticide-treated nets was evaluated in terms of deterrence, blood-feeding inhibition, induced exophily and mortality on a wild resistant population of Anopheles epiroticus in southern Vietnam, in order to gain insight into the operational consequences of the insecticide resistance observed in this malaria vector in the Mekong delta.MethodAn experimental station, based on the model of West Africa and adapted to the behaviour of the target species, was built in southern Vietnam. The study design was adapted from the WHO phase 2 guidelines. The study arms included a conventionally treated polyester net (CTN) with deltamethrin washed just before exhaustion, the WHO recommended long-lasting insecticidal net (LLIN) PermaNet 2.0® unwashed and 20 times washed and PermaNet 3.0®, designed for the control of pyrethroid resistant vectors, unwashed and 20 times washed.ResultsThe nets still provided personal protection against the resistant An. epiroticus population. The personal protection ranged from 67% for deltamethrin CTN to 85% for unwashed PermaNet 3.0. Insecticide resistance in the An. epiroticus mosquitoes did not seem to alter the deterrent effect of pyrethroids. A significant higher mortality was still observed among the treatment arms despite the fact that the An. epiroticus population is resistant against the tested insecticides.ConclusionThis study shows that CTN and LLINs still protect individuals against a pyrethroid resistant malaria vector from the Mekong region, where insecticide resistance is caused by a metabolic mechanism. In the light of a possible elimination of malaria from the Mekong region these insights in operational consequences of the insecticide resistance on control tools is of upmost importance.

In ovo nanoinjection of nonylphenol affects embryonic development of a transgenic see-through medaka ( Oryzias latipes), olvas-GFP/STII-YI strain

We performed in ovo nanoinjection of 4-nonylphenol (NP) into embryos of a transgenic see-through medaka ( Oryzias latipes), olvas-GFP/STII-YI strain, which has two genotypic sex markers, and examined the effects on development and sexual differentiation. The transgene consisted of a green fluorescent protein (GFP) gene fused to the regulatory region of the medaka vasa gene. Germ cell-specific GFP expression was visualized in the gonad through the transparent body wall of the living fish. The development of each embryo was observed after nanoinjection of 2.0, 10, 50, 125, or 250 ng of NP. NP administration caused significant higher mortality at ⩾50 ng egg −1 and inhibited embryonic development, including abnormal hatch and swim-up failure in all treatment groups except 10 ng egg −1 group. However, it did not cause adverse effects on germ cell proliferation by 10 d posthatch (dph) or sex differentiation of survivors by 100 dph. We concluded that single-dose in ovo exposure to nonylphenol affected embryonic development in the medaka but not gonadal development by 10 dph or sexual differentiation in adult fish by 100 dph. Although further investigations might be needed to elucidate the usefulness of nanoinjection of embryos of this strain, present study indicated that the nanoinjection model using olvas-GFP/STII-YI strain medaka has potential for use in evaluating the effects of chemicals on early development and sexual differentiation.

Risk factors for prosthetic valve endocarditis—A case control study

Objective Prosthetic valve endocarditis is a catastrophic complication of cardiac valve replacement associated with significant morbidity and high mortality. The aim of this study was to assess the risk factors leading to the development of prosthetic valve endocarditis.

Intraoperative therapy with liposomal drug delivery: Retention and distribution in human head and neck squamous cell carcinoma xenograft model

The focus of this study is to investigate the retention and biodistribution of technetium-99m ( 99mTc) labeled liposomes in a human head and neck squamous cell carcinoma (HNSCC) positive surgical margin animal xenograft model. Positive surgical margin (with margin < 1 mm) in HNSCC is associated with significant higher mortality and recurrence rate when compared to clear margin. An immediate intraoperative application of liposome-carried therapeutic agents may treat the residual disease intraoperatively and improve long term survival in these patients. To understand the feasibility of this intraoperative therapy in HNSCC, the in vivo behavior of liposomes after intraoperative administration of 99mTc-labeled liposomes using non-invasive nuclear imaging was investigated in an animal xenograft model. Neutral and cationic 99mTc-labeled liposomes of 100 nm, 1 μm and 2 μm in diameter (6 study groups with 4 rats per study group) were injected into a nude rat HNSCC positive surgical margin xenograft model. Intratumoral, locoregional, and systemic retention and distribution of the 99mTc-liposomes were determined using non-invasive nuclear imaging and post-mortem organ distribution. The 99mTc-liposomes demonstrated high locoregional retention rate of 55.9 ± 3.7% to 72.9 ± 2.4% at 44 h after intraoperative injection to allow significant radiation to the surgical cavity if therapeutic radionuclides were used. Overall, the cationic liposomes demonstrated higher intratumoral retention rate, and the neutral liposomes showed greater retention in the paratumoral cavity ( p < 0.05 respectively). In conclusion, intraoperative therapy with liposome carried radionuclide drug delivery system carries great potential in treating unresectable HNSCC, and further study using therapeutic radionuclide should be explored.

Role of beta‐blockers in patients admitted for worsening heart failure in a real world setting: data from the Italian Survey on Acute Heart Failure†

Randomized trials have shown that beta-blockers (BBs) reduce mortality in chronic heart failure (HF). Less data are available on the role of BBs in patients with acute HF, specifically if BBs should be continued or temporarily withdrawn. The aim of this study was to evaluate the role of BBs on in-hospital outcomes of patients admitted for worsening HF in a Cardiology setting. One thousand five hundred and seventy-two patients enrolled in the Italian Survey on Acute HF were evaluated. According to the BB therapy before and during hospitalization, four groups were defined: group A, no/no (51.6%); group B, no/yes (16.4%); group C, yes/no (9.0%); and group D, yes/yes (23.0%). Groups B and D had a significantly lower in-hospital mortality rate (group B 1.2%, group D 2.8%, group A 10.1%, and group C 12.1%; P < 0.0001). The association between non-use or withdrawal of BBs and higher mortality rate was confirmed by the multivariable analysis [group D, reference group; odds ratio (OR) 3.28, 95% confidence interval (CI) 1.47-7.32 and OR 4.20, 95% CI 1.59-11.10 for groups A and C, respectively], whereas no difference was found between groups B and D (OR 0.34, 95% CI 0.07-1.78). In patients hospitalized for worsening HF, non-use or discontinuation of BBs was associated with a significant higher mortality.

An overview of hepatitis A at Tygerberg Children s Hospital.

Introduction: Hepatitis A is a vaccine-preventable infection, often seen in children in the Western Cape. Objectives: To describe childhood Hepatitis A morbidity and mortality at Tygerberg Children’s Hospital (TCH), a level two and three referral hospital in the Western Cape, South Africa Methods: A retrospective chart review was conducted in children younger than 13 at TCH. Patients with positive Hepatitis A IgM were identified from the Tygerberg Hospital virology laboratory database. The cases were cross-referenced with the paediatric gastroenterology database. Data collected included demographics, clinical and laboratory information, outcome, notification and primary prophylaxis. Results. 184 subjects were identified, comprising 117 males and 67 females with a median age of 69 (5 to 152) months. Two had hepatic failure and both died. Ten (5%) had known Hepatitis A contacts but received no post-exposure prophylaxis and only thirty-one (17%) were notified. A small percentage of patients were Hepatitis B, Hepatitis C and HIV positive, i.e. 2%, 0.5% and 0.5% respectively. The median population incidence was 45.4 per 100 000, higher than the 20 per 100 000 advocated as a threshold for introducing vaccination into the immunization schedule. Conclusions. This study emphasises that Hepatitis A is a serious public health issue and a risk to young children. It is not a benign disease, but has significant high morbidity and mortality. In addition, a sizeable number of cases were preventable, and only a small number were notified. These results suggest that Hepatitis A vaccination should be introduced for children in the Western Cape attending public health facilities.

350: Macrophage Migration Inhibitory Factor as a New Target in Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation

Acute graft versus host disease (GVHD) is the major complication after allogeneic (allo) stem cell transplantation (SCT) involving injury to host tissues by both inflammatory cytokines and donor-derived cellular effectors. Macrophage migration inhibitory factor (MIF) is produced by various cell types and has a broad range of proinflammatory properties. We tested, whether MIF contributes to GVHD by using a well established murine model. Lethally (1300 cGy) irradiated B6D2F1 (H-2bxd) mice received SCT either from syngeneic (syn) (B6D2F1) or allo (B6; H-2b) donors. One half of animals after either syn or allo SCT were treated with polyclonal antibodies against mouse MIF from day 0 until day 14, whereas the other halves of syn and allo recipients received control IgG. GVHD severity was assessed after SCT by survival and a clinical scoring system assessing weight changes, fur texture, skin integrity, mobility and posture. Syn recipients stayed clinically well and all animals survived regardless their treatment with control or anti-MIF. Animals receiving allo-SCT plus control IgG developed significant aGVHD and high mortality. By contrast, in allo anti-MIF treated recipients, GVHD scores (day 21: 4.4 ± 0.4 vs. 5.7 ± 0.5) and weight loss (24.6% vs. 45.4%) were reduced, and survival significantly improved (p < 0.05). In addition, target organ injury to the gut (histopathology score: 4.3 ± 0.7 vs. 8.0 ± 2.6) as well as serum IFNγ (4397 ± 995 vs. 6070 ± 525 pg/ml) and TNFα (113.9 ± 12.7 vs. 159.2 ± 22.5 pg/ml) levels of anti-MIF treated allo recipients were decreased by day 7 when compared to controls. Alloantigen-specific T cell activation in vitro was significantly suppressed in the presence of anti-MIF, as determined by a reduction in T cell proliferation, IFNγ and TNFα secretion.We next challenged syn and allo recipients with P815 lymphoblast-like mastocytoma cells (H-2d) at the time of transplantation to asses the effect of anti-MIF on graft versus leukemia (GVL) responses. Significant P815 cell infiltration was seen after syn SCT as demonstrated by FACS analysis of the spleens (67.2% infiltration) and by histopathology of the liver between day 14 and day 21 after SCT. In contrast, P815 cells were significantly cleared in allo recipients treated with either control or anti-MIF (0.81% and 12.1% infiltration).In summary, our data show an important role for MIF in GVHD pathophysiology and suggest MIF as a promising target in reducing GVHD without the loss of GVL. Acute graft versus host disease (GVHD) is the major complication after allogeneic (allo) stem cell transplantation (SCT) involving injury to host tissues by both inflammatory cytokines and donor-derived cellular effectors. Macrophage migration inhibitory factor (MIF) is produced by various cell types and has a broad range of proinflammatory properties. We tested, whether MIF contributes to GVHD by using a well established murine model. Lethally (1300 cGy) irradiated B6D2F1 (H-2bxd) mice received SCT either from syngeneic (syn) (B6D2F1) or allo (B6; H-2b) donors. One half of animals after either syn or allo SCT were treated with polyclonal antibodies against mouse MIF from day 0 until day 14, whereas the other halves of syn and allo recipients received control IgG. GVHD severity was assessed after SCT by survival and a clinical scoring system assessing weight changes, fur texture, skin integrity, mobility and posture. Syn recipients stayed clinically well and all animals survived regardless their treatment with control or anti-MIF. Animals receiving allo-SCT plus control IgG developed significant aGVHD and high mortality. By contrast, in allo anti-MIF treated recipients, GVHD scores (day 21: 4.4 ± 0.4 vs. 5.7 ± 0.5) and weight loss (24.6% vs. 45.4%) were reduced, and survival significantly improved (p < 0.05). In addition, target organ injury to the gut (histopathology score: 4.3 ± 0.7 vs. 8.0 ± 2.6) as well as serum IFNγ (4397 ± 995 vs. 6070 ± 525 pg/ml) and TNFα (113.9 ± 12.7 vs. 159.2 ± 22.5 pg/ml) levels of anti-MIF treated allo recipients were decreased by day 7 when compared to controls. Alloantigen-specific T cell activation in vitro was significantly suppressed in the presence of anti-MIF, as determined by a reduction in T cell proliferation, IFNγ and TNFα secretion. We next challenged syn and allo recipients with P815 lymphoblast-like mastocytoma cells (H-2d) at the time of transplantation to asses the effect of anti-MIF on graft versus leukemia (GVL) responses. Significant P815 cell infiltration was seen after syn SCT as demonstrated by FACS analysis of the spleens (67.2% infiltration) and by histopathology of the liver between day 14 and day 21 after SCT. In contrast, P815 cells were significantly cleared in allo recipients treated with either control or anti-MIF (0.81% and 12.1% infiltration). In summary, our data show an important role for MIF in GVHD pathophysiology and suggest MIF as a promising target in reducing GVHD without the loss of GVL.

Abstract 3358: Resistance to Endogenous Erythropoietin Predicts Survival in Anemic Heart Failure Patients

Background In response to hypoxia the kidney produces erythropoietin (EPO). Elevated levels of EPO are observed in patients with chronic heart failure (CHF) and are related to an impaired outcome. However it is unknown whether these EPO-levels are adequate for the degree of anemia and how the adequacy of EPO levels relates to prognosis. Methods Therefore, we studied 240 CHF patients (96% were in NYHA functional class III). The adequacy of EPO levels was assessed by an observed-predicted ratio. A value &lt;0.9 indicates inadequate low EPO levels (=blunted EPO-response), whereas &gt;1.1 indicates inappropriate high EPO levels (=EPO resistance). Group comparisons were therefore made between low EPO responders n = 30 normal EPO responders n = 25 EPO-resistance n = 22. Anemia was defined according to the WHO definition (males and postmenopausal females Hemoglobin (Hb) &lt; 3.0 g/dL and premenopausal females Hb &lt; 12.0 g/dL). The primary endpoint was mortality. Results During a median follow up of 3.8 years, 98 patients died (41.4% mortality rate). EPO levels were an independent predictor of mortality, also adjusted for hemoglobin levels (HR 1.013, 95%CI [1.007–1.018], p=0.001). Anemia was present in 77 (32%) patients. Inadequate low EPO levels were observed in 30 anemic patients (39%) and related to renal failure (glomerular filtration rate &lt; 30 ml/min/1.73m2 (p&lt;0.009). EPO resistance was present in 22 anemic patients (29%) and was associated with a significant higher mortality rate compared to patients with a normal EPO response and a low EPO response, 72.7% vs 34.8% and 40.0% respectively (p=0.012 and p=0.021, respectively). EPO resistance was an independent predictor of an increased mortality risk in Cox regression analyses adjusted for variables with p&lt;0.10 in the univariate analysis including age, sex and high sensitive CRP; HR 2.63 95%CI [1.12– 6.17], p=0.026, whereas a low EPO response was not associated with an impaired outcome; HR 1.12 95% CI [0.45–2.79], p=0.81, compared to normal EPO responders. Conclusion EPO resistance is common in CHF patients and is associated with a high mortality.

CHOLINESTERASE INHIBITORS AND ALZHEIMER'S DISEASE OUTCOMES

To the Editor: In their article, ‘‘Outcome of Alzheimer’s Disease: Potential Impact of Cholinesterase Inhibitors,’’ Gillette-Guyonnet and colleagues investigated the impact of cholinesterase inhibitors (CEIs) on the natural history of Alzheimer’s disease (AD) using rapid deterioration of cognitive function, institutionalization, and weight loss as outcomes (1). They found that the risk of all three outcomes was significantly decreased after one year’s use of CEIs. These results support the role of CEIs in improving AD outcomes. The authors excluded patients whose follow-up was discontinued for any reason, including death, and no information is provided about whether mortality rates varied significantly between treated and untreated groups. Previous studies of mortality in dementia have found that it is reduced (2) or unchanged (3) by CEI use. Trials investigating the use of galantamine in mild cognitive impairment were terminated due to a nonstatistically significant higher mortality rate in the treated arm (4). Given these varied findings, mortality is an important outcome to consider in the postmarket analysis of CEIs. We have conducted a retrospective mortality review of all patients seen at our Memory Clinics since their commencement in October 1999 to May 2005. Charts were systematically reviewed to obtain the cognitive diagnosis, the treatment given and its duration, past medical history, medication use including over-the-counter supplements, physical examination findings, and imaging results. Patient status (dead or alive) was assessed by direct contact with the patients, their families, their family doctors, and by searches of local obituary columns. Of the 440 patients seen, 248 were eligible for treatment with CEIs, based on a diagnosis of Alzheimer’s disease, Lewy body dementia, or mixed dementia. Of these, 22 patients were lost to follow-up. The remaining 226 were divided into two groups based on whether they had been treated with any CEI for a period longer than 3 months, with 26 who had declined treatment (group 1) and 200 who had received it (group 2). Group 1 (untreated) patients were significantly older at referral than those in group 2 (81.4 6 4.7 vs 75.9 6 8.0, t 5 3.049, p , .05), and group 1 contained a higher proportion of female participants than group 2 (p , .05). There were no differences in MiniMental State Exam score or comorbidities at baseline. There were 8/26 (30.8%) deaths in group 1, and 35/200 (17.6%) in group 2, a difference that was not significant. Within group 1, only high blood pressure was significantly more frequent among dead patients (p , .05). Group 2 was further subdivided based on the last medication taken: donepezil (n 5 97), rivastigmine (n 5 43), or galantamine (n 5 60). The mortality rates between the three subgroups were not significantly different. The size of our sample does not allow us to analyze the extent to which the age or sex difference between groups 1 and 2 accounted for our results. Schaufele (5) cites previous estimates of survival time in dementia from 5 to 10 years. The average time of follow-up in our population (from diagnosis to last in-clinic contact) was 25.7 months in group 1 and 26.9 in group 2. Our analysis shows no increased mortality in patients treated with CEIs compared with those who were not, or between patients receiving different CEIs. However, the number of untreated patients was small and prevents us from drawing firm conclusions. It is important to continue the postmarket evaluation of these drugs. Similar research in a larger population would be desirable to clarify the possible impact of CEIs on mortality in patients with dementia.

Effective Treatment of Prevalent Pneumonia Reduces in-Hospital Mortality in Patients Undergoing Percutaneous Endoscopic Gastrostomy (PEG)

Background: Percutaneous endoscopic gastrostomy (PEG) is a widely used method for long-term enteral nutrition. Though considered as safe and technically simple, high early mortality rates up to 54% among hospitalized patients have been reported. The aim of this study was, to evaluate retrospectively the outcome after PEG in hospitalized patients at our institution. After identifying active pneumonia as a predictive factor for early mortalitiy, we investigated in a second period prospectively, if effective treatment of preexisting pneumonia could reduce the early mortality rates after PEG. Patients and methods: We compared the outcome after PEG insertion of different strategies in two periods: In a first period between February 03 and March 04 patients were scheduled for PEG as soon as requested by their attending physician. Indications, comorbidity and mortality of these hospitalized patients were evaluated. There was a high mortality rate in patients with a preexisting pneumonia, that was not cured before the time of PEG insertion (i.e. clinical and radiological diagnosed pneumonia and an elevated c-reactive proteine > 5 mg/dl). In a second period from May 05 to July 06 we investigated, if mortality could be reduced by postponing PEG in patients with active pneumonia, while pneumonia was treated. Statistical analysis was performed using the Mann- Whitney test and the chi-square test. Results: In the first and second period, PEG tubes were inserted in 77 and 86 hospitalized patients, respectively. There was no difference between patients of the two periods in regard to age (74/75 years), sex (53/59% male), mental status (dementia in 56/52%), underlying disease, rate of prevalent pneumonia (30/31%). In the first period the overall in-hospital mortalitiy was 18% (14 pat.), with a significant higher mortality (50%) in a subgroup of patients, who had an active pneumonia at the time of PEG insertion (P = 0,007). In the second period, preexisting active pneumonia was treated before PEG. Thereby the rate of active pneumonia at the time of PEG insertion could be reduced from 21% (16 pat.) in the first period to 6% (5 pat.) in the second period (P = 0,005). The in-hospital mortality rate dropped form 18% (14 pat.) in the first period to 7% (6 pat.) (P = 0,03). Conclusion: Active pneumonia at the time of PEG insertion is a risk factor for early mortalitiy after PEG. By prior treatment of preexisting pneumonia mortality after PEG insertion is significantly reduced.

Rheumatoid Arthritis-Associated Necrotizing Scleritis and Peripheral Ulcerative Keratitis Treated Successfully With Infliximab

In patients with rheumatoid arthritis (RA), necrotizing scleritis, an ocular manifestation of a systemic vasculitic process, is associated with significant ocular morbidity and high mortality. We present a 60-year-old man with RA who developed necrotizing scleritis and peripheral ulcerative keratitis. The scleritis was refractory to local measures, systemic corticosteroids, and cyclophosphamide but responded rapidly to infliximab. Our case illustrates that biologic agents may be considered in refractory cases of sight- and life-threatening scleritis.

Effects of 3-thia fatty acids on expression of some lipid related genes in Atlantic salmon ( Salmo salar L.)

In this study, the effects of in vivo administration of 3-thia fatty acids (FAs) on lipid metabolism in muscle and liver of Atlantic salmon were investigated. Prior to analysis, the fish were kept in tanks supplied with 5 °C seawater for 20 weeks. The fish were fed fish meal and fish oil (FO)-based diets supplemented with either nothing (FO), or 0.3% and 0.6% of the 3-thia FAs dodecylthioacetic acid (DTA) and tetradecylthioacetic acid (TTA) respectively. The fish grew from an initial weight of 110 g to 220 g in the FO group and to approximately 160 g in the 3-thia FA groups. There was a significant higher mortality (66%) in fish fed 0.6% TTA than in fish fed the 0.3% DTA (15%) and FO diets (15%). None of the 3-thia FA diets affected the lipid content of the salmon muscle. The liver index, however, was significantly higher and the total liver fat content lower in the TTA group than in the FO group. Both DTA and TTA were incorporated into the lipid fraction of muscle and liver (0.4% to 0.9%). There were no major differences in the total FA composition of liver and muscle between the dietary groups; except for a small increase of n-3 polyunsaturated FAs (PUFAs) in liver of the DTA group. The mRNA expression of peroxisome proliferator-activated receptor (PPAR) α, apolipoprotein AI (ApoAI), apolipoprotein CII (ApoCII) and low-density lipoprotein receptor (LDL-R) was down-regulated in liver of the salmon fed 0.3% DTA. PPARα and ApoAI transcripts were also reduced in liver of salmon fed 0.6% TTA. Additionally, the hepatic lipoprotein lipase (LPL) mRNA level was 3.8 fold increased in TTA fish relative to the FO group. In muscle there were no significant changes in gene expression pattern of any of the genes investigated. This is the first report on the effects of 3-thia FAs on gene expression in Atlantic salmon.

Outcome of Older Critically lIl Patients: A Matched Cohort Study

Background: Admission of older patients to intensive care units is a controversial issue. Objective: To estimate age-associated mortality of critically ill patients. Methods: A prospective matched cohort study in the Medical-Surgical Intensive Care Unit of a tertiary hospital was conducted. We included 100 consecutive patients older than 70 years admitted to the intensive care unit (cases) and 100 patients younger than 70 years (controls). The matching criterion was the severity of illness at admission to the intensive care unit as estimated by the simplified acute physiological score (SAPS II) without including age in its calculation. Results: Mortality in the intensive care unit was higher, but not statistically significant, in the older group: 26% vs. 19% (p = 0.23). Patients older than 70 years had a longer duration of mechanical ventilation (median 7 vs. 3 days) and longer stay in the intensive care unit (median 8 vs. 5 days). There were no differences in organ dysfunctions, except for a higher incidence of respiratory failure in the older group (p < 0.001). The use of invasive procedures was similar in both groups. There were more orders for the withholding/withdrawal of treatment in patients older than 70 years (9 vs. 3%, p = 0.07). Conclusion: In our study, age was not related with a significant higher mortality. In the older patients included in our study the survival was greater than 70% with a similar resource utilization except for a longer stay in the intensive care unit.

Crosslinking of decellularized porcine heart valve matrix by procyanidins

Heart valve diseases have a significant high mortality, and the valve replacement using glutaraldehyde crosslinked porcine heart valves is one of the main curing techniques. But its application is limited due to poor durability, calcification of the valves and immunogenic reactions. The aim of this study was to evaluate the crosslinking effect of procyanidins on porcine heart valve matrix. After crosslinking of the decellularized porcine aortic heart valves by procyanidins, the tensile strength, the in vitro enzymatic degradation resistance, procyanidins release from the crosslinked materials and the cytotoxicity of procyanidins to heart valvular interstitial cells were examined. The results showed that the tensile strength of procyanidins crosslinked valve matrix was higher than that of glutaraldehyde crosslinked valve matrix. Valve matrix crosslinked by 10 mg/ml procyanidins could be stored in D-Hanks solution for at least 45 days without any decline in ultimate tensile strength and maintained the elasticity as the fresh valves. Furthermore, procyanidins was found to release when the crosslinked tissue stored in D-Hanks solution. The release rate was high during the first 4 days and then dramatically decreased thereafter. During releasing phase, the concentration of procyanidins was no toxicity to heart valve interstitial cells. In vitro enzymatic degradation revealed that crosslinked matrix could resist the enzymatic hydrolysis, and the resistant capacity was approximately the same as glutaraldehyde crosslinked valve matrix. This study shows that procyanidins can crosslink porcine heart valves effectively without toxicity. Our results suggested that this method might be a useful approach for preparation of bioprosthetic heart valve.

Neonatal mortality in intensive care units of Central Brazil

To identify potential prognostic factors for neonatal mortality among newborns referred to intensive care units. A live-birth cohort study was carried out in Goiânia, Central Brazil, from November 1999 to October 2000. Linked birth and infant death certificates were used to ascertain the cohort of live born infants. An additional active surveillance system of neonatal-based mortality was implemented. Exposure variables were collected from birth and death certificates. The outcome was survivors (n=713) and deaths (n=162) in all intensive care units in the study period. Cox's proportional hazards model was applied and a Receiver Operating Characteristic curve was used to compare the performance of statistically significant variables in the multivariable model. Adjusted mortality rates by birth weight and 5-min Apgar score were calculated for each intensive care unit. Low birth weight and 5-min Apgar score remained independently associated to death. Birth weight equal to 2,500 g had 0.71 accuracy (95% CI: 0.65-0.77) for predicting neonatal death (sensitivity =72.2%). A wide variation in the mortality rates was found among intensive care units (9.5-48.1%) and two of them remained with significant high mortality rates even after adjusting for birth weight and 5-min Apgar score. This study corroborates birth weight as a sensitive screening variable in surveillance programs for neonatal death and also to target intensive care units with high mortality rates for implementing preventive actions and interventions during the delivery period.