Helse Nord-Trøndelag HF

Patients with cancer who had sepsis experience a higher mortality risk than noncancer patients. However, it remains unclear how this risk varies with cancer type and metastasis status, sex, age, and infecting microbe.

This nationwide cohort study included all noncancer patients and those with cancer ≥18 years hospitalized with sepsis in Norway from 2008 to 2021. Cancer status, sepsis, and hospital mortality were identified from the Norwegian Patient Registry (International Classification of Diseases 10th revision codes). Multivariable regression analyses estimated absolute and relative risks (RR) of hospital mortality across subgroups.

Of 222,832 hospitalized patients with sepsis, 37,692 (16.9%) had cancer. Hospital mortality was higher in patients with cancer, at 16.9% (males) and 16.2% (females) with nonmetastatic disease, and at 27.1% (males) and 26.2% (females) with metastatic disease. Compared with noncancer patients, adjusted RRs (95% confidence interval) of hospital death were 1.39 (1.34–1.44, males) and 1.63 (1.55–1.71, females) for nonmetastatic cancer and 2.27 (2.18–2.37, males) and 2.75 (2.62–2.89, females) for metastatic cancer. The type of cancer was a key prognostic factor. The association between cancer and mortality was strongest in metastatic patients below 50 years [males 40–49 years: RR, 5.94 (4.43–7.97); females 18–39 years: RR, 8.28 (5.12–13.37)] and in those with gram-negative sepsis.

The increased hospital mortality in patients with cancer varied with cancer type and the presence of metastasis. The association between cancer and mortality was strongest in females and young adults, as well as in gram-negative sepsis.

Knowledge of the specific aspects of sepsis in patients with cancer may improve cancer care and guide future research on targeted sepsis therapies.

Helicobacter pylori infection seems to increase the risk of developing pancreatic cancer, but it is unknown whether eradication treatment of this bacterium changes this risk. We hypothesized that the increased risk of pancreatic cancer among individuals infected with Helicobacter pylori decreases over time after eradication treatment.

This multinational and population-based cohort study, using prospectively collected nationwide register data from 1995 to 2019, included all adults who received eradication treatment for Helicobacter pylori in Denmark, Finland, Iceland, Norway, or Sweden. Standardized incidence ratios (SIR) with 95 % confidence intervals (95 %CI) were calculated by dividing the incidence rates of pancreatic cancer in the eradication treatment cohort by that of the entire populations of the corresponding age, sex, calendar year, and country. The main outcome was changes in SIR over time after eradication treatment.

During up to 24 years of follow-up of 661,827 participants and 5494,255 person-years in the eradication treatment cohort, 2331 participants developed pancreatic cancer. The risk of pancreatic cancer was increased during the first 1-5 years after eradication treatment (SIR 1.14, 95 % CI 1.07-1.21), after which it decreased and became similar to the level of the background population 6-10 years (SIR 0.99, 95 % CI 0.92-1.07) and 11-24 years (SIR 1.00, 95 % CI 0.92-1.08) after eradication treatment.

The elevated risk of developing pancreatic cancer among individuals with Helicobacter pylori infection seems to decrease after eradication treatment, reaching the risk estimates of the background population.

Chronic hyperglycemia impairs mitochondrial function of beta cells. Changes in mitochondrial function preceding a negative glucose effect have not been fully characterized, nor interactions with ketones. To compare effects on beta cell mitochondrial function by short and longer exposures to elevated glucose and interactions with ketones oxygen consumption rate (OCR) was measured in intact clonal beta cells by an OROBOROS and in rat islets by a Seahorse instrument. Proteins (subunits) of mitochondrial complexes (C) were measured by immunoblotting. ATP and ROS were measured in islets. In INS-1 832/13 cells, overnight exposure to 27 vs. 11 mm glucose increased OCR and uncoupled mitochondrial respiration. These effects vanished when prolonging the exposure time of elevated glucose. C1 was decreased after two days of culture with high glucose. Interactions with racemic 5 and 20 mm beta-hydroxybutyrate (BHB) were not detected. In islets, culture overnight at 27 vs.11 mm glucose enhanced basal OCR. No decrease in glucose-induced OCR was seen after prolonging 27 mm glucose for two days. Interactions with 5 mm BHB were not detected. Prolonged exposure to 27 mm glucose enhanced basal ECAR (extracellular acidification rate) and an ECAR response to acute elevation of glucose. C1 and 3 and 4 were decreased after two days of 27 vs. 11 mm glucose. ATP levels were decreased at this time-point and extracellular ROS increased. High glucose time-dependently affects mitochondrial function in clonal beta cells and islets. C1 was uniformly decreased. Interactions with BHB were not detected.