Low technology, mild controlled hypothermia for necrotizing enterocolitis treatment: an initiative to improve healthcare to preterm neonates.

Necrotizing enterocolitis (NEC) treatment remains unchanged for years. Data suggest that mild controlled hypothermia could potentially improve NEC outcomes. Our units presented unfavourable outcomes on NEC. The aim was to assess our experience with low technology, mild controlled hypothermia on NEC outcomes, and improve preterm infants' healthcare. This was a single-center quality improvement study with retrospective cohort design at the neonatal intensive care unit in the university hospital. Forty-three preterm infants with NEC (Modified Bell's Stage II/III) were included: 19 in the control group (2015-2018) and 24 in the hypothermia group (2018-2020). The control group received standard treatment (fasting, abdominal decompression, and broad-spectrum antibiotics). The hypothermia group underwent cooling to 35.5 °C for 48 h after NEC diagnosis, along with conventional treatment. The primary outcomes are intestinal perforation, need for surgery, duration of parenteral nutrition, death, and extensive resection of the small intestine. There was no statistical difference in the NEC score. The hypothermia group required less surgery (aRR 0.40; 95% CI 0.19-0.85), presented less bowel perforation (aRR 0.39; 95% CI 0.18; 0.83), had a shorter duration of parenteral nutrition (aHR 5.28; 95% CI 1.88-14.89), did not need extensive intestinal resection, (0 vs 15.7%), and did not experience any deaths (0 vs 31.6%).Conclusions: In our experience, low technology, mild controlled hypothermia was feasible, not related to adverse effects, and effective treatment for NEC Modified Bell's Stage II/III. It avoided surgery, bowel perforation, and extensive intestinal resection; reduced mortality; and shortened parenteral nutrition duration. What is Known: • New approaches have been proposed to avoid enterocolitis incidence; however, the treatment of enterocolitis stage 2 has been the same for decades, and unfavourable outcomes remain despite conventional management. • Studies suggest that hypothermia can be an alternative to enterocolitis treatment. What is New: • Mild controlled hypothermia can be an additional practice to treat enterocolitis stage 2, is feasible, and is not related to adverse effects to preterm infants. • It can decrease surgery needs, duration of parenteral nutrition, and death and avoids extensive intestinal resection in preterm infants.

Therapeutic efficacy and biodistribution of allogeneic mesenchymal stem cells delivered by intrasplenic and intrapancreatic routes in streptozotocin-induced diabetic mice.

INTRODUCTION: Mesenchymal stromal/stem cells (MSCs) are multipotent cells that have the ability to express and secrete a wide range of immunomodulatory molecules, cytokines, growth factors and antiapoptotic proteins. MSCs modulate both innate and adaptive immune responses making them potential candidates for the treatment of patients with type 1 diabetes mellitus (T1D). However, one problem frequently associated with the systemic MSCs administration is the entrapment of the cells mainly in the lungs. In this sense, trying to avoid the lung barrier, the purpose of this study was to evaluate the long-term therapeutic efficacy and biodistribution of allogeneic adipose tissue-derived MSCs (ADMSCs) injected via two different delivery routes (intrasplenic/I.Sp and intrapancreatic/I.Pc) in a murine model of diabetes induced by streptozotocin (STZ). METHODS: Experimental diabetes was induced in C57BL/6 male mice by multiple low-doses of STZ. MSCs were isolated from adipose tissue (ADMSCs) of Balb/c mice. A single dose of 1x10(6) ADMSCs was microinjected into the spleen or into the pancreas of diabetic mice. Control group received injection of PBS by I.Sp or I.Pc delivery routes. Glycemia, peripheral glucose response, insulin-producing ß cell mass, regulatory T cell population, cytokine profile and cell biodistribution were evaluated after ADMSCs/PBS administration. RESULTS: ADMSCs injected by both delivery routes were able to decrease blood glucose levels and improve glucose tolerance in diabetic mice. ADMSCs injected by I.Sp route reverted hyperglycemia in 70% of diabetic treated mice, stimulating insulin production by pancreatic ß cells. Using the I.Pc delivery route, 42% of ADMSCs-treated mice responded to the therapy. Regulatory T cell population remained unchanged after ADMSCs administration but pancreatic TGF-ß levels were increased in ADMSCs/I.Sp-treated mice. ADMSCs administrated by I.Sp route were retained in the spleen and in the liver and ADMSCs injected by I.Pc route remained in the pancreas. However, ADMSCs injected by these delivery routes remained only few days in the recipients. CONCLUSION: Considering the potential role of MSCs in the treatment of several disorders, this study reports alternative delivery routes that circumvent cell entrapment into the lungs promoting beneficial therapeutic responses in ADMSCs-treated diabetic mice.