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Objective: Pain and quality of death are important considerations in treatment choices for children. Our objective is to assess the intensive care-associated experiences of 22-25 weeks gestational age (GA) infants who die despite intensive care treatment. Study Design: In a 1:1 case-control study, medical records were screened for all inborn 22-25 weeks GA infants who received intensive care treatments between 2014 and 2020. Cases were all infants who died. Each case was matched by GA and birth weight to an infant who survived to discharge (control). Data was collected on cases and controls for a matched timeframe based on the case's duration of intensive care treatment. Information collected included intensive care-associated negative experiences (invasive procedures, surgeries, use of pain medication) and positive experiences (enteral feedings, being held by family). Results: The cases (n=20) survived for 0 to 93 days, with median (IQR) survival 8 (5, 24) days. The mean (SD) number of invasive procedures was higher for cases than controls, 34 (30) vs. 24 (22), p=0.004. Cases underwent 8 surgeries compared to 4 in the controls. Additionally, compared to controls, cases spent more time receiving pain medications (64% vs. 27%, p<0.001) and without being fed (54% vs. 39%, p<0.001). Half of cases were never held by parents until the day they died. Conclusion: Extremely premature infants who die despite intensive care face more treatment burdens than the survivors. Larger studies are needed to confirm these findings and gather information necessary for informed decisions about intensive care treatment of these infants.
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The authors wish to make the following corrections to this paper [...].
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Cancer has been conceptualized as a chronic wound with a predominance of tumor promoting inflammation. Given the accumulating evidence that the microenvironment supports tumor growth, we investigated hyaluronan (HA)-CD44 interactions within breast cancer cells, to determine whether this axis directly impacts the formation of an inflammatory microenvironment. Our results demonstrate that breast cancer cells synthesize and fragment HA and express CD44 on the cell surface. Using RNA sequencing approaches, we found that loss of CD44 in breast cancer cells altered the expression of cytokine-related genes. Specifically, we found that production of the chemokine CCL2 by breast cancer cells was significantly decreased after depletion of either CD44 or HA. In vivo, we found that CD44 deletion in breast cancer cells resulted in a delay in tumor formation and localized progression. This finding was accompanied by a decrease in infiltrating CD206+ macrophages, which are typically associated with tumor promoting functions. Importantly, our laboratory results were supported by human breast cancer patient data, where increased HAS2 expression was significantly associated with a tumor promoting inflammatory gene signature. Because high levels of HA deposition within many tumor types yields a poorer prognosis, our results emphasize that HA-CD44 interactions potentially have broad implications across multiple cancers.
