Perinatal Caffeine Administration Improves Outcomes in an Ovine Model of Neonatal Hypoxia-Ischemia

Stroke, Ahead of Print. BACKGROUND:Neonatal hypoxic-ischemic encephalopathy disproportionately affects low- and middle-income countries, where ≈96% of affected infants reside. The current standard of care, therapeutic hypothermia, is frequently ineffective in this setting, likely because injury may be occurring earlier during labor. Here, we studied the pharmacokinetics, safety, and efficacy of perinatal caffeine administration in near-term lambs following global ischemic injury to support the development of earlier treatment strategies targeting the fetus in utero as well as the infant postnatally.METHODS:Ewes were randomly assigned to receive either 1 g IV caffeine citrate or placebo before delivery and placental transport assessed. Near-term lambs (141–143 days) of both sexes were subjected to severe global hypoxia-ischemia utilizing an acute umbilical cord occlusion model. Lambs that received caffeine in utero also received 20 mg/kg IV caffeine citrate following resuscitation and 10 mg/(kg·d) IV for 2 days. An additional cohort received 60 mg/kg followed by 30 mg/(kg·d) (low dose versus high dose) postnatally. Biochemical, histological, and neurological outcome measures in lambs were assessed over a 6-day period.RESULTS:Perinatal caffeine administration demonstrated excellent placental transport kinetics and was well tolerated with lamb plasma levels comparable to those targeted in neonates with apnea of prematurity. Caffeine administration resulted in a systemic immunomodulatory effect, evidenced by significant reductions in proinflammatory IP-10 levels. Treated lambs demonstrated improved neurodevelopmental outcomes, while histological analysis revealed that caffeine reduced gray matter injury and attenuated inflammation in the cingulate and parasagittal cortex. This neuroprotective effect was greater and via a different mode of action than we previously reported for azithromycin. A higher caffeine dosing regimen demonstrated significant toxicity.CONCLUSIONS:Perinatal caffeine administration is well tolerated, attenuates systemic and brain inflammation, and contributes to improvements in histological and neurological outcomes in an ovine model of neonatal hypoxic-ischemic encephalopathy.

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Metabolic and bariatric surgery for obstructive sleep apnoea syndrome: bibliometric analysis and visualisation from 1999 to 2023

Objectives
Metabolic and bariatric surgery (MBS) for obstructive sleep apnoea syndrome (OSAS) has garnered significant research interest. The main aim of this study was to analyse the unique characteristics of publications centred around MBS for OSAS. We aimed to provide valuable insights into the present status of the field and offer predictions regarding future trends.

Design
Bibliometric analysis through science mapping and performance analysis methods.

Data sources
Scientific articles.

Data extraction and synthesis
A comprehensive search was conducted in the Web of Science database to retrieve publications on MBS for OSAS within the time frame of 1999–2023. The search was performed using keywords such as “Obstructive Sleep Apnea syndrome”, “OSAS”, “metabolic surgery” and “bariatric surgery” to identify relevant papers. To analyse the bibliometric characteristics of these publications, VOSviewer and R software were used. This analysis encompassed various aspects, including the number of publications, contributions by different countries and institutions, the most cited author, journal publications, citation frequency and the identification of keywords related to popular scientific fields.

Results
1264 papers on MBS for OSAS were identified and are currently in a stage of rapid growth. The relevant study involved 1230 institutions from 53 different countries, with the USA topping the field with 465 publications contributed. Assistance Publique Hopitaux Paris proved to be the most productive institution, with De Vries N posting the highest number of papers (n=24). The most prolific journal was Obesity Surgery, with 241 publications. Keywords “Bariatric surgery”, “Obstructive sleep apnea”, “Obesity”, “Weight loss” and “Morbid obesity” have the highest frequency of occurrence.

Conclusions
The relationship between obesity and OSAS, various metabolic surgical techniques, and the mechanism of MBS for OSAS will continue to be related areas of frontiers. Furthermore, while there has been a gradual increase in basic research, the mechanisms involved and the long-term efficacy of bariatric MBS for OSAS still require further investigation. It is anticipated that these research areas may emerge as potential hot topics in the future.

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