Johanna Hästbacka

Prevalence and predictive value of ionized hypocalcemia among critically ill patients

Background:  Ionized hypocalcemia is common among critically ill patients, and it has been shown to correlate with increased mortality. The purpose of this study was to examine the performance and independence of ionized calcium (Ca2+) in prediction of all‐cause day‐30 mortality among critically ill adult patients.

Serum MMP-8, -9 and TIMP-1 in sepsis: high serum levels of MMP-8 and TIMP-1 are associated with fatal outcome in a multicentre, prospective cohort study. Hypothetical impact of tetracyclines.

Recent evidence suggests that matrix metalloproteinases (MMPs) and their endogenous inhibitors are involved in the pathogenesis of sepsis. We studied serum levels of MMP-8, MMP-9 and TIMP-1 (tissue inhibitor of matrix metalloproteinase-1) in a multicentre, prospective cohort study of patients with sepsis treated in Intensive Care Units (ICUs). We analyzed serum samples taken on ICU admission from 248 critically ill sepsis patients. MMP-8, -9 and TIMP-1 serum levels were analyzed by enzyme-linked immunosorbent assays. Serum MMP-8, MMP-9 and TIMP-1 levels were significantly higher in patients with severe sepsis than in healthy controls. Serum MMP-8 levels among non-survivors (n=33) were significantly (p=0.006) higher than among survivors (n=215). Serum TIMP-1 but not MMP-9 levels were significantly higher among non-survivors than survivors (p<0.0001, p=0.079, respectively). Systemic MMP-8 is upregulated in sepsis suggesting that MMP-8 may contribute to the host response during sepsis. High serum MMP-8 and TIMP-1 levels at ICU admission were seen among patients with fatal outcome. With this background, clinical studies examining the ability of MMP-inhibitors (such as the non-antimicrobial properties of tetracyclines) to diminish the MMP-mediated inflammatory response are needed to develop novel therapies in order to improve the outcome of sepsis.

G protein‐coupled receptor for asthma susceptibility associates with respiratory distress syndrome

Background. Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) have some common features with asthma. Aim. To study whether G protein‐coupled receptor for asthma susceptibility (GPRA) contributes to RDS or BPD. Methods. A haplotype association study was performed in a case‐control setting of 521 Finnish infants (including 176 preterm neonates with RDS and 37 with BPD). Immunoreactivity of GPRA isoforms A and B was determined in pulmonary samples of fetuses, term infants and preterm infants with RDS or BPD. GPRA mRNA expression was determined by quantitative real‐time polymerase chain reaction (PCR) in samples from nasal respiratory epithelium of adults, term infants and preterm infants. Results. In infants with RDS born at 32–35 weeks of gestation, GPRA haplotype H1 was significantly underrepresented in RDS, whereas haplotype H4/H5 was associated with an increased risk. As in asthma, GPRA B isoform was induced in bronchial smooth muscle cells in RDS and BPD. In nasal respiratory epithelium, relative GPRA mRNA expression was strong in adults, weak in preterm and slightly higher in term samples. Conclusions. The results suggest that near‐term RDS and asthma share the same susceptibility and protective GPRA haplotypes. Altered GPRA expression may play a role in the pathogenesis of RDS and BPD in preterm infants.

Serum matrix metalloproteinases in patients resuscitated from cardiac arrest. The association with therapeutic hypothermia

AIM To study the systemic levels of matrix metalloproteinases (MMP) -7, -8 and -9 and their inhibitor TIMP-1 in cardiac arrest patients and the association with mild therapeutic hypothermia treatment on the serum concentration of these enzymes. METHODS MMP-7, -8 and -9 and tissue inhibitor of metalloproteinases-1 (TIMP-1) were analysed in blood samples obtained from 51 patients resuscitated from cardiac arrest. The samples were taken at 24 and 48 h from restoration of spontaneous circulation (ROSC). The biomarker levels were compared between patients (N=51) and healthy controls (N=10) and between patients who did (N=30) and patients who did not (N=21) receive mild therapeutic hypothermia. RESULTS MMP-7 (median 0.47 ng/ml), MMP-8 (median 31.16 ng/ml) and MMP-9 (median 253.00 ng/ml) levels were elevated and TIMP-1 levels suppressed (median 78.50 ng/ml) in cardiac arrest patients as compared with healthy controls at 24h from ROSC. Hypothermia treatment associated with attenuated elevation of MMP-9 (p=0.001) but not MMP-8 (p=0.02) or MMP-7 (p=0.69). Concentrations of MMPs -7, -8 and -9 correlated with the leukocyte count but not with C-reactive protein (CRP) or neurone-specific enolase (NSE) levels. CONCLUSION We demonstrated that the systemic levels of MMP-7, -8 and -9 but not TIMP-1 are elevated in cardiac arrest patients in the 48 h post-resuscitation period relative to the healthy controls. Patients who received therapeutic hypothermia had lower MMP-9 levels compared to non-hypothermia treated patients, which generates hypothesis about attenuation of inflammatory response by hypothermia treatment.

The effect of buprenorphine and oxycodone on the intracholedochal passage pressure.

The effects of i.v, buprenorphine (0.3 mg) and oxycodone (10 mg) on intracholedochal passage pressure were studied in 20 patients who had undergone surgery of the common biliary tract, prior to the extraction of an indwelling T tube. Informed consent was obtained from all patients, each of whom was given buprenorphine or oxycodone in random order. The intracholedochal passage pressure was measured from the T tube perfused with continuous saline infusion (55 ml/h). Both analgesics significantly (P<0.01) increased the intracholedochal passage pressure after 5 min, with an equal peak increase of about 1.5 kPa at about 7 min. The pressure decline was rapid and similar in both groups: 20 min after administration of the test drug only about 40% of the maximum elevation caused by either drug remained. Thereafter, a slower fall towards the baseline was recorded after both drugs during the remaining 45 min of the study period. The results indicate that buprenorphine can be used with the same indications and precautions as other narcotics for postoperative pain relief in patients who have undergone surgery of the biliary tract.

Systemic matrix metalloproteinase-8 and tissue inhibitor of metalloproteinases-1 levels in severe sepsis-associated coagulopathy.

Matrix metalloproteinase‐8 (MMP‐8) and tissue inhibitor of metalloproteinases‐1 (TIMP‐1) have recently been suggested to be involved in coagulation process. Our objectives were to observe systemic MMP‐8 and TIMP‐1 levels in patients with severe sepsis with or without disseminated intravascular coagulation (DIC) and to study their relationship with coagulation markers over time.

Glucocorticoid receptor expression and binding capacity in patients with burn injury

Burn injuries are associated with strong inflammation and risk of secondary sepsis which both may affect the function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in leucocytes from patients admitted to a tertiary burn center.