Dendritic cells (DCs) are first responders of the innate immune system that integrate signals from external stimuli to direct context-specific immune responses. Current models suggest that an active switch from mitochondrial metabolism to glycolysis accompanies DC activation to support the anabolic requirements of DC function. We show that early glycolytic activation is a common program for both strong and weak stimuli, but that weakly activated DCs lack long-term HIF-1α-dependent glycolytic reprogramming and retain mitochondrial oxidative metabolism. Early induction of glycolysis is associated with activation of AKT, TBK, and mTOR, and sustained activation of these pathways is associated with long-term glycolytic reprogramming. We show that inhibition of glycolysis impaired maintenance of elongated cell shape, DC motility, CCR7 oligomerization, and DC migration to draining lymph nodes. Together, our results indicate that early induction of glycolysis occurs independent of pro-inflammatory phenotype, and that glycolysis supports DC migratory ability regardless of mitochondrial bioenergetics.
Background
Radical cystectomy for urinary bladder cancer is a procedure associated with a high risk of complications, and poor overall survival (OS) due to both patient and tumour factors. Sarcopenia is one such patient factor. We have developed a fully automated artificial intelligence (AI)-based image analysis tool for segmenting skeletal muscle of the torso and calculating the muscle volume.
Methods
All patients who have undergone radical cystectomy for urinary bladder cancer 2011–2019 at Sahlgrenska University Hospital, and who had a pre-operative computed tomography of the abdomen within 90 days of surgery were included in the study. All patients CT studies were analysed with the automated AI-based image analysis tool. Clinical data for the patients were retrieved from the Swedish National Register for Urinary Bladder Cancer. Muscle volumes dichotomised by the median for each sex were analysed with Cox regression for OS and logistic regression for 90-day high-grade complications. The study was approved by the Swedish Ethical Review Authority (2020-03985).
Results
Out of 445 patients who underwent surgery, 299 (67%) had CT studies available for analysis. The automated AI-based tool failed to segment the muscle volume in seven (2%) patients. Cox regression analysis showed an independent significant association with OS (HR 1.62; 95% CI 1.07–2.44; p = 0.022). Logistic regression did not show any association with high-grade complications.
Conclusion
The fully automated AI-based CT image analysis provides a low-cost and meaningful clinical measure that is an independent biomarker for OS following radical cystectomy.
A 26-year-old woman presented with a 5-day history of fever and 3-day history of left upper quadrant abdominal pain and cough associated with left shoulder tip pain. Initial blood cultures did not display growth. On CT imaging, there was a cyst measuring 7.2×8 cm originally interpreted to be haemorrhagic in nature. Repeat cultures during admission revealed Salmonella Thompson. Percutaneous drainage and antibiotic treatment, rather than splenectomy, was successfully pursued with the patient afebrile and in no pain at 6 weeks follow-up.
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