| 1. |
- Svedman, F. C., et al.
(författare)
-
Plasma Thymidine Kinase Activity as a Novel Biomarker in Metastatic Melanoma Patients Treated with Immune Checkpoint Inhibitors
- 2022
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:3
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Immune checkpoint inhibitors (ICI) are effective in fractions of patients with disseminated melanoma. This study is the first to analyze the plasma activity of thymidine kinase (TK), an enzyme involved in DNA synthesis and repair, as a biomarker in melanoma patients. Meth-ods. Plasma samples were collected prior to treatment start in patients with unresectable metastatic cutaneous melanoma, treated with ICI (anti-CTLA-4 and/or anti-PD-1). Plasma TK activity (TKa) levels were determined using the DiviTum TKa ELISA assay. TKa levels were correlated with patients’ baseline characteristics, response rate (RR), progression-free survival (PFS), and overall survival (OS). Results. In the 90 study patients, the median TKa level was 42 Du/L (range <20–1787 Du/L). A significantly higher plasma TKa was found in patients with ECOG performance status ≥1 (p = 0.003), M1c-d disease (p = 0.015), and elevated lactate dehydrogenase levels (p < 0.001). The RR was 63.2% and 30.3% in those with low or high TKa, respectively (p = 0.022). The median PFS was 19.9 and 12.6 months in patients with low or high TKa, respectively (hazard ratio (HR) 1.83 (95% CI, 1.08–3.08), p = 0.024). The median OS was >60 months and 18.5 months in patients with low or high TKa, respectively (HR: 2.25 (95% CI, 1.25–4.05), p = 0.011. Conclusions. High pretreatment plasma TKa levels were significantly associated with worse baseline characteristics and poor response and survival in ICI-treated melanoma patients. TKa is hence a novel and interesting plasma biomarker in melanoma and should be further studied to define its role as a prognostic and predictive marker in this disease. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
|
|
| 2. |
- Marschall, Hanns-Ulrich, et al.
(författare)
-
Incidence, prevalence, and outcome of primary biliary cholangitis in a nationwide Swedish population-based cohort
- 2019
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Available epidemiological data on primary biliary cholangitis (PBC) in Sweden originate from regional studies in the 1980s and may not reflect modern day PBC. We aimed to estimate incidence and prevalence, survival and death causes, and gender differences in PBC. We used international classification of disease (ICD) codes to identify patients with PBC in inpatient and outpatient registries 1987-2014 who were then linked to the Swedish cause of death, cancer and prescribed drug registries. Each PBC patient was matched with 10 reference individuals from the general population. In sensitivity analyses, we examined PBC patients identified through clinical patient records from Karolinska, Sahlgrenska and Orebro University Hospitals. We identified 5,350 adults with PBC. Prevalence of PBC increased steadily from 5.0 (1987) to 34.6 (2014) per 100,000 inhabitants whereas the yearly incidence rate was relatively constant with a median of 2.6 per 100,000 person-years, with a female: male gender ratio of 4:1. Compared to reference individuals, PBC individuals aged 15-39 years at diagnosis had a substantially higher risk of death (Hazard Ratio [HR] 12.7, 95% Confidence Interval [CI] 8.3-19.5) than those diagnosed between 40-59 (HR 4.1, 95% CI 3.7-4.5) and > 60 (HR 3.7, 95% CI 3.5-3.9) years of age. Relative risks of mortality were highest in men. In conclusion, we found that recorded prevalence of PBC in Sweden has increased substantially during the last 30 years although incidence has been stable. Patients diagnosed in young adulthood were at a 12.7-fold increased risk of death, and male PBC patients had worse prognosis.
|
|
| 3. |
- Söderdahl, G, et al.
(författare)
-
Ursodeoxycholic acid increased bile flow and affects bile composition in the early postoperative phase following liver transplantation
- 1998
-
Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 11:Suppl 1, s. S231-S238
-
Tidskriftsartikel (refereegranskat)abstract
- Orally given ursodeoxycholic acid (UDCA) has beneficial effects on laboratory parameters in different cholestatic conditions. In order to investigate the effect on early graft function after liver transplantation, 33 patients were randomized to receive either UDCA 15 mg/kg per day or placebo from the 1st postoperative day until 3 months after transplantation. All liver grafts produced bile within 24 h after revascularization. In both groups there was an increasing bile flow each day until day 5 after transplantation. This increase was more pronounced in the UDCA group where the flow on day 2 reached a mean value of 183 +/- 28 ml/day compared to 106 +/- 17 ml/day in the placebo group (P < 0.05). The average daily volume of bile produced during the first 10 days was also found to be higher in the UDCA group compared to the placebo group (242 +/- 20 ml vs 176 +/- 18 ml, P < 0.02). In the UDCA group a significant decrease in total bile acid output between the 5th and 10th postoperative days was found, while in the placebo group the amount of bile acids excreted remained stable over time. The composition of bile differed between the two groups with an increase in the portion of UDCA in the UDCA group from the 2nd postoperative day (25% vs 4.6%, P < 0.0003). The fraction of UDCA then remained high during the whole study period with a peak at day 3 when 38.1 +/- 6.6% of the bile acids consisted of UDCA. In the placebo group, the fraction of UDCA was low from the beginning and diminished further over time. Prophylactic UDCA treatment was found to have a significant positive impact on the ALT level during the 4th and 5th postoperative days, but had no effect on bilirubin or GGT in the early postoperative phase (days 1-10). No differences in cyclosporine requirement were found between the two groups.
|
|
