Publications by authors named "K Koivisto"

80 Publications

RSV Specific Antibodies in Pregnant Women and Subsequent Risk of RSV Hospitalization in Young Infants.

J Infect Dis 2021 Jun 15. Epub 2021 Jun 15.

Helsinki University Hospital and University of Helsinki, Children's Hospital, Helsinki, Finland.

Background: The fusion (F) glycoprotein of respiratory syncytial virus (RSV) represents the major neutralizing antigen, and antibodies against the pre-F conformation have the most potent neutralizing activity. This study aimed to assess the correlation between maternal antibody (Ab) titers against the pre-F, post-F and G glycoproteins and the child's risk of developing severe RSV bronchiolitis early in infancy.

Methods: We identified previously healthy term infants less than 3 months of age hospitalized with RSV bronchiolitis from December 2015 to March 2016. We measured IgG Ab titers to pre-F, post-F, and G proteins in maternal sera obtained at 9-12 weeks of pregnancy of these hospitalized infants' mothers (n=94) and compared them with serum Ab titers of control pregnant mothers (n=130), whose children were not hospitalized.

Results: All maternal samples (n= 224) had detectable pre-F Abs. Pre-F Ab titers were significantly lower in mothers whose infants were hospitalized with RSV bronchiolitis compared with those mothers whose infants were not (23.9 [1.4-273.7] vs 30.6 [3.4-220.0] ug/l; p=0.0026). There were no significant differences in maternal post-F and G Ab titers between hospitalized versus non-hospitalized infants.

Conclusions: Our findings indicate that maternal pre-F antibodies are fundamental for providing immune protection to the infant.
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June 2021

Serum biomarkers for Modic changes in patients with chronic low back pain.

Eur Spine J 2021 04 9;30(4):1018-1027. Epub 2021 Jan 9.

AO Research Institute, Davos, Switzerland.

Purpose: Lumbar Modic change (MC) can serve as a diagnostic marker as well as an independent source of chronic low back pain (CLBP). This study aimed to test for the existence of serum biomarkers in CLBP patients with MC.

Methods: Age- and sex-matched CLBP patients with confirmed MC on lumbar MRI (n = 40) and pain-free controls (n = 40) were assessed. MC was classified into M1, predominating M1, predominating M2 and M2. MC volumes were calculated. Fasting blood samples were assessed for inflammatory mediators, signalling molecules, growth factors and bone turnover markers. Serum concentrations of 46 biomarkers were measured.

Results: Median concentrations of interleukin (IL)-15 (p < 0.001), IL-8 (p < 0.001), tumour necrosis factor (TNF)-alpha (p < 0.001), Eotaxin-1 (p < 0.05), Eotaxin-3 (p < 0.001), monocyte chemotactic protein (MCP)-1 (p < 0.05), macrophage inflammatory protein (MIP)-1alpha (p < 0.01), TEK receptor tyrosine kinase (Tie)-2 (p < 0.001), vascular cell adhesion molecule (VCAM)-1 (p < 0.001), RANTES (p < 0.001), C telopeptide of type I collagen (CTX)-1 (p < 0.001), vascular endothelial growth factor (VEGF)-C (p < 0.001), VEGF-D (p < 0.05), fms-related tyrosine kinase (Flt)-1 (p < 0.01) and intercellular adhesion molecule (ICAM)-1 (p < 0.01) were significantly higher among controls. IL-1sRII (23.2 vs. 15.5 ng/ml, p < 0.001) and hepatocyte growth factor (HGF)-1 (169 vs. 105 pg/ml, p < 0.01) concentrations were significantly higher among patients. Type or volume of MC was not associated with biomarker concentrations.

Conclusions: This is the first study to assess the blood serum biomarker profile in individuals with CLBP with MC. Several biomarkers were suppressed, while two markers (IL-1sRII and HGF) were elevated among MC patients, irrespective of MC type or size, with CLBP compared with asymptomatic controls.
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April 2021

Serotonin toxicity from isolated bupropion overdoses.

Clin Toxicol (Phila) 2020 12 14;58(12):1347-1349. Epub 2020 Apr 14.

Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Bupropion is a synthetic cathinone, which acts therapeutically through norepinephrine and dopamine reuptake inhibition. Recent evidence suggests that serotonin receptor activation occurs with high doses of bupropion and severe serotonin toxicity can occur after isolated bupropion overdoses. Prior observational studies may therefore underestimate the incidence of serotonin toxicity. A retrospective study of patients with bupropion toxicity at a toxicology referral center from 2015-2017 was performed. Patients who overdosed on other serotonergic medications were excluded. Serotonin toxicity was diagnosed retrospectively using Hunter Criteria. Overall, 96 patients were identified with bupropion toxicity. Of these, 18 patients ingested bupropion in the absence of other serotonergic drugs. The incidence of serotonin toxicity was 33% in this population. Serotonin toxicity was more likely after a suicide attempt than those with an accidental ingestion or after recreational drug use. The median dose of bupropion ingested was 2,250 mg in the cohort diagnosed with serotonin syndrome. The incidence of bupropion induced serotonin toxicity is higher than reported. Clinicians should monitor for serotonergic toxicity when evaluating patients after bupropion overdose.
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December 2020

The Effect of Zoledronic Acid on Serum Biomarkers among Patients with Chronic Low Back Pain and Modic Changes in Lumbar Magnetic Resonance Imaging.

Diagnostics (Basel) 2019 Dec 4;9(4). Epub 2019 Dec 4.

AO Research Institute Davos, 7270 Davos Platz, Switzerland.

The aim of the current study was to compare changes in serum biomarkers, including inflammatory mediators, signaling molecules, growth factors and markers of bone turnover after a single intravenous infusion of 5 mg zoledronic acid (ZA, a long-acting bisphosphonate; = 20) or placebo ( = 20) among patients with Modic changes (MC) and chronic low back pain in a randomized controlled design. The MCs were classified into M1, predominating M1, predominating M2, and M2. We measured the serum concentrations of 39 biomarkers at baseline, and one month and one year after treatment. After Benjamini-Hochberg (B-H) correction, we observed significant differences in three biomarkers over one year: Interferon-γ-inducible protein (IP10) had risen in the ZA group (p = 0.005), whereas alkaline phosphatase (AFOS) and intact procollagen I N-terminal propeptide (iPINP) had significantly decreased in the ZA group, but had not changed in the placebo group (p < 0.001 for both). Change in iPINP correlated with change in the volume of all MC and M1 lesions. ZA downregulated bone turnover markers as expected and, surprisingly, increased the chemokine IP-10 relative to placebo treatment. This adds to our knowledge of the effects of ZA on MC and the biomarkers that signal this process.
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December 2019

The effect of zoledronic acid on type and volume of Modic changes among patients with low back pain.

BMC Musculoskelet Disord 2017 Jun 23;18(1):274. Epub 2017 Jun 23.

Institute of Diagnostics, Department of Diagnostic Radiology, Oulu University Hospital, Oulu, Finland.

Background: Modic changes (MC) are associated with low back pain (LBP). In this study, we compared changes in size and type of MC, after a single intravenous infusion of 5 mg zoledronic acid (ZA) or placebo, among chronic LBP patients with MC on magnetic resonance imaging (MRI), and evaluated whether the MRI changes correlate with symptoms.

Methods: All patients (N = 19 in ZA, 20 in placebo) had MRI at baseline (0.23-1.5 T) and at one year (1.5-3 T). We evaluated the level, type and volume of all the MC. The MC were classified into M1 (M1 (100%)), predominating M1 (M1/2 (65:35%)) or predominating M2 (M1/2 (35:65%)), and M2 (M2 (100%)). The first two were considered M1-dominant, and the latter two M2-dominant. Volumes of M1 and M2 were calculated separately for the primary MC, which was assumed to cause the symptoms, and the other MC. We analysed the one-year treatment differences in M1 and M2 volumes using analysis of covariance with adjustments for age, sex, body mass index, and smoking. The correlations between the MRI changes and the changes in LBP symptoms were analysed using Pearson correlations.

Results: In the ZA group, 84.2% of patients had M1-dominant primary MC at baseline, compared to 50% in the placebo group (p = 0.041). The primary MC in the ZA group converted more likely to M2-dominant (42.1% ZA, 15% placebo; p = 0.0119). The other MC (15 ZA, 8 placebo) were on average 42% smaller and remained largely M2-dominant. The M1 volume of the primary MC decreased in the ZA group, but increased in the placebo group (-0.83 cm vs 0.91 cm; p = 0.21). The adjusted treatment difference for M1 volume was -1.9 cm (95% CI -5.0 to 1.2; p = 0.22) and for M2 volume 0.23 cm (p = 0.86). In the MC that remained M1-dominant, volume change correlated positively with increased symptoms in the placebo group, whereas the correlations were negative and weak in the ZA group.

Conclusions: Zoledronic acid tended to speed up the conversion of M1-dominant into M2-dominant MC and decrease the volume of M1-dominant MC, although statistical significance was not demonstrated.

Trial Registration: The registration number in is NCT01330238 and the date of registration February 11, 2011.
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June 2017