Sanna Hoppu

Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study

IntroductionPositive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality.MethodsWe conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality.ResultsWe included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT.ConclusionsPatients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments.

Fate of Five Celiac Disease-Associated Antibodies During Normal Diet in Genetically At-Risk Children Observed from Birth in a Natural History Study

OBJECTIVES: To explore the natural history of antibodies against tissue transglutaminase (TGA), endomysium (EMA), reticulin (ARA), and gliadin (AGA-IgG and AGA-IgA) in children carrying HLA-conferred risk for celiac disease (CD) and observed frequently from birth.METHODS: TGA was measured in serum samples obtained between years 2000 and 2003 from 1,320 children carrying genetic CD risk. If a sample was TGA positive, all five antibodies were analyzed in all banked and forthcoming samples from that child, and a duodenal biopsy was recommended. At the end of this observation, in August 2004, the age of the children was from 1 to 9.5 yr (mean 4.1 yr).RESULTS: Forty-nine children (3.7%) were TGA positive. In these children, AGA-IgG had emerged at the mean age (± SD, range) of 2.0 ± 1.5, 0.5–6.6 yr, while TGA, EMA, and ARA all emerged concurrently somewhat later (TGA at 3.2 ± 1.5, 1.0–7.0 yr, P < 0.001 when compared to AGA-IgG). Despite continuing gluten exposure, positive TGA, EMA, ARA, AGA-IgA, and AGA-IgG values were spontaneously lost in 49%, 45%, 43%, 41%, and 32% of the children, respectively. CD was diagnosed by biopsy in 20 of the 26 TGA-positive children who consented to a biopsy.CONCLUSIONS: Potential CD trigger(s) other than only gluten probably function before AGA-IgG emerges, i.e., ≥3 months earlier than the transglutaminase-associated antibodies appear. In a remarkable proportion of the children, antibodies disappear spontaneously suggesting that regulatory immune phenomena under favorable circumstances are able to extinguish incipient CD in genetically at-risk children even without exclusion of gluten from the diet.

Deeper chest compression – More complications for cardiac arrest patients?

AIM OF THE STUDY Sternal and rib fractures are frequent complications caused by chest compressions during cardiopulmonary resuscitation (CPR). This study aimed to investigate the potential association of CPR-related thoracic and abdominal injuries and compression depth measured with an accelerometer. METHODS We analysed the autopsy records, CT scans or chest radiographs of 170 adult patients, suffering in-hospital cardiac arrest at the Tampere University Hospital during the period 2009-2011 to investigate possible association of chest compressions and iatrogenic injuries. The quality of manual compressions during CPR was recorded on a Philips, HeartStart MRx Q-CPR™-defibrillator. RESULTS Patients were 110 males and 60 females. Injuries were found in 36% of male and 23% of female patients. Among male patients CPR-related injuries were associated with deeper mean - and peak compression depths (p<0.05). No such association was observed in women. The frequency of injuries in mean compression depth categories <5, 5-6 and >6 cm, was 28%, 27% and 49% (p=0.06). Of all patients 27% sustained rib fractures, 11% sternal fracture and eight patients had haematomas/ruptures in the myocardium. In addition, we observed one laceration of the stomach without bleeding, one ruptured spleen, one mediastinal haemorrhage and two pneumothoraxes. CONCLUSION The number of iatrogenic injuries in male patients was associated with chest compressions during cardiopulmonary resuscitation increased as the measured compression depth exceeded 6 cm. While there is an increased risk of complications with deeper compressions it is important to realize that the injuries were by and large not fatal.

Natural history of transglutaminase autoantibodies and mucosal changes in children carrying HLA-conferred celiac disease susceptibility.

OBJECTIVE The natural history of the appearance and fate of transglutaminase autoantibodies (TGAs) and mucosal changes in children carrying HLA-conferred celiac disease (CD) risk remains obscure. The aim of this study was to investigate the sequence of events leading to overt CD by retrospective analysis of TGA values in serum samples collected frequently from genetically susceptible children since birth or early childhood. MATERIAL AND METHODS A total of 1101 at-risk children were recruited in the study. A duodenal biopsy was recommended to all TGA-positive children and performed if parental consent was obtained. RESULTS During up to 8 years of follow-up, 35 of the cohort children developed TGAs, the youngest at age 1.3 years. After age 1.3 years the annual TGA seroconversion rate was constantly around 1% at least until age 6 years. However, 18 of the 35 TGA-positive children (51%) lost TGAs, without any dietary manipulation. A further 7 children were IgA deficient; of these children, 2 developed IgG antigliadin antibodies (IgG-AGA). Only 13 of the 21 children (62%) who had duodenal biopsies had villous atrophy. The time that passed since emergence of TGAs failed to predict the biopsy findings. Only one of the children with TGAs and both of the IgA-deficient children with IgG-AGA had noticeable abdominal symptoms. CONCLUSIONS TGAs appear in children at a constant rate after 1 year of age until at least the age of 6 years. Over half of the children loose TGA without gluten exclusion, challenging TGA positivity-based CD prevalence estimates. In symptom-free children, a requirement of two consecutive TGA-positive samples taken >or=3 months apart before performing a duodenal biopsy might diminish the number of unnecessary intestinal biopsies.

GAD65 antibody isotypes and epitope recognition during the prediabetic process in siblings of children with type I diabetes.

We observed 42 initially non‐diabetic siblings of affected children to characterize the humoral immune response to the 65 kDa isoform of glutamic acid decarboxylase (GAD65) in preclinical type I diabetes. During the observation period with a mean duration of 9·6 years 21 siblings progressed to type I diabetes. The humoral immune response to GAD65 was observed initially as a simultaneous response to the middle (M) and carboxy (C)‐terminal regions of the GAD65 molecule in most cases, and if the response was restricted initially to the middle region, it spread rapidly to the C‐terminal domain and in a few cases later to the amino (N)‐terminal domain. There was some heterogeneity in the GAD65 isotype response, but it was composed mainly of antibodies of immunoglobulin (Ig) G1 subclass. Responses of IgG2‐, IgG4‐, IgM‐ and IgA‐GAD65Ab were observed frequently, whereas IgE‐ and IgG3‐GAD65Ab responses were seen more rarely. Initially, the non‐progressors tended more often to have IgG2‐ and IgG4‐GAD65Ab than the progressors. As a sign of a dynamic process a significant isotype spreading was seen for IgG2‐GAD65Ab (P < 0·05) and close to significant for IgM (P = 0·06) among progressors and for IgM‐GAD65Ab (P < 0·05) among non‐progressors during the observation period. This study failed to identify any GAD65 epitope‐ or isotype‐specific antibody reactivity that could be used as a marker for progression to disease, as such progression was not associated with any specific changes in reactivity over time. Our findings indicate that epitope‐ and isotype‐specific GAD65 antibodies are hardly capable of separating progressors from non‐progressors among GAD65Ab‐positive first‐degree relatives of children with type I diabetes.

Quality controlled manual chest compressions and cerebral oxygenation during in-hospital cardiac arrest

AIM The quality of cardiopulmonary resuscitation (CPR) is associated with the rate of return of spontaneous circulation (ROSC) during human cardiac arrest. Current advances in defibrillator technology enable measurement of CPR quality during resuscitation, but it is not known whether this is directly reflected in cerebral oxygenation. In this descriptive study we aimed to evaluate whether the quality of feedback-monitored CPR during in-hospital cardiac arrest is reflected in near infrared frontal cerebral spectroscopy (NIRS). METHODS Nine patients suffering an in-hospital cardiac arrest in a university hospital were included. All patients underwent quality-controlled CPR performed by a dedicated medical emergency team using a Philips HeartStart MRx defibrillator (Philips, Eindhoven, Netherlands) with a CPR quality (Q-CPR, Laerdal Medical, Stavanger, Norway) analysis feature. Simultaneously, bilateral frontal cerebral oximetry was measured using INVOS 5100c (Somanetics, Troy, MI, USA) NIRS. RESULTS During quality controlled resuscitation, regional cerebral oxygenation (rSO(2)) as measured with NIRS was low but it improved during CPR (p=0.043) and 8 min after ROSC (p=0.022). After the onset of NIRS recording, there were four episodes exceeding 30s, during which the quality of CPR was substandard. When CPR technique was corrected and maintained for 2 min, a minor non-significant increase in rSO(2) was observed in two cases. CONCLUSIONS High quality CPR was not significantly reflected in cerebral oxygenation as quantified using NIRS. Even after ROSC and subsequent significant increase in cerebral oxygenation, rSO(2) readings were below previously suggested threshold of cerebral ischaemia. Improving CPR technique after an episode of low quality CPR did not significantly increase rSO(2).

Insulin autoantibody isotypes during the prediabetic process in young children with increased genetic risk of type 1 diabetes.

This work aimed to assess the maturation of the humoral immune response to insulin in preclinical type 1 diabetes by observing the emergence of various isotypes of insulin autoantibodies (IAA) in children with HLA-DQB1-conferred disease susceptibility. The series was derived from the Finnish Type 1 Diabetes Prediction and Prevention Study and comprised 15 IAA-positive children who presented with type 1 diabetes during prospective observation (progressors) and 30 children who remained nondiabetic (nonprogressors). An isotype-specific radiobinding assay was used to determine isotype-specific IAA (IgG1-4 and IgA) from samples obtained with an interval of 3–12 mo. The progressors had IAA of subclass IgG3 in their first IAA-positive sample more often than did the nonprogressors (13 of 15 versus 12 of 30; p = 0.003). Nine progressors had a dominant IgG1-IAA response initially, and six had a dominant IgG3-IAA response. The corresponding distribution among the nonprogressors was that 20 had a dominant IgG1-IAA response, none had an IgG3-IAA response, and three had a dominant response other than IgG1- or IgG3-IAA (χ2df = 2 = 12.02; p = 0.002). The progressors had higher integrated levels (area under the curve) of IgG1-IAA (p = 0.05) and IgG3-IAA (p = 0.002). Nine progressors had a dominant integrated IgG1-IAA response and six had a dominant IgG3-IAA response over the observation period, whereas 22 nonprogressors had a dominant IgG1-IAA response, six had a dominant IgG2-IAA response, and one an IgG3-IAA response (χ2df = 2 = 11.23; p = 0.004). Genetically susceptible young children who progress rapidly to clinical type 1 diabetes are characterized by strong IgG1 and IgG3 responses to insulin, whereas a weak or absent IgG3 response is associated with relative protection from disease.

Age at Development of Type 1 Diabetes and Celiac Disease-Associated Antibodies and Clinical Disease in Genetically Susceptible Children Observed from Birth

OBJECTIVE To compare the ages and sequence in which antibodies associated with type 1 diabetes and celiac disease appear and overt diseases develop in children with an HLA-conferred susceptibility to both diseases. RESEARCH DESIGN AND METHODS We observed 2,052 children carrying genetic risks for both type 1 diabetes and celiac disease from birth until the median age of 5.7 years and analyzed diabetes- and celiac disease–associated antibodies in serum samples collected at 3- to 12-month intervals. Diabetes was confirmed by World Health Organization criteria and celiac disease by duodenal biopsies. RESULTS Altogether 342 children seroconverted to positivity for at least one diabetes-associated autoantibody and 88 to positivity for at least one celiac disease–associated antibody at the median ages of 3.0 and 1.5 years, respectively (P < 0.001). If only children with biochemically defined diabetes-associated autoantibodies against insulin, GAD, or IA-2A protein (n = 146) and children with tissue transglutaminase autoantibodies were compared (n = 86), the median seroconversion ages were 2.5 and 3.0 years (P = 0.011). Fifty-one children progressed to overt diabetes at 4.5 years and 44 children to celiac disease at 4.3 years (P = 0.257). Of the 19 children who developed both diabetes- and celiac disease–associated antibodies, 3 progressed to both diabetes and celiac disease. CONCLUSIONS Children with HLA-conferred susceptibility to type 1 diabetes and celiac disease develop celiac disease–associated antibodies mostly at a younger age or the same age at which they develop diabetes-associated autoantibodies. Clinical diabetes and celiac disease are commonly diagnosed at the same median age.

Medical emergency team activation : performance of conventional dichotomised criteria versus national early warning score

To activate the hospitals medical emergency team (MET), either conventional dichotomised activation criteria or an early warning scoring system may be used. The relative performance of these different activation patterns to discriminate high risk patients in a heterogenic general ward population after adjustment for multiple confounding factors has not been evaluated. We aimed to evaluate the dichotomised activation criteria used at our institution and the recently published national early warning score (NEWS, United Kingdom).

Viral interference induced by live attenuated virus vaccine (OPV) can prevent otitis media

Abstract Background The goal of this study was to evaluate whether a live attenuated poliovirus vaccine (OPV) has clinically relevant interfering effect with non-polio infections causing otitis media in young children. Methods Open trial in which the intervention group (64 children) received OPV at the age of 2, 3, 6 and 12months. The control group (250 children) received IPV (inactivated polio vaccine) at the age of 6 and 12months. Clinical symptoms were recorded by a questionnaire at the age of 3, 6, 12, 18 and 24months. Results Otitis media episodes were less frequent in the OPV than in the control group. A significant difference was seen at the age of 6–18months (IRR=0.76 [95% CI 0.59–0.94], P =0.011) and was particularly clear among children, who attended daycare (IRR 0.37 [95% CI 0.19–0.71], P =0.003). Conclusions OPV provides some protection against otitis media. This effect may be mediated by viral interference with non-polio viruses.