Responses to Hypoxia: How Fructose Metabolism and Hypoxia-Inducible Factor-1a Pathways Converge in Health and Disease.

PURPOSE OF REVIEW: Oxygen is critical for the high output of energy (adenosine triphosphate) generated by oxidative phosphorylation in the mitochondria, and when oxygen delivery is impaired due to systemic hypoxia, impaired or reduced delivery of red blood cells, or from local ischemia, survival processes are activated. RECENT FINDINGS: One major mechanism is the activation of hypoxia-inducible factors (HIFs) that act to reduce oxygen needs by blocking mitochondrial function and stimulating glucose uptake and glycolysis while also stimulating red blood cell production and local angiogenesis. Recently, endogenous fructose production with uric acid generation has also been shown to occur in hypoxic and ischemic tissues where it also appears to drive the same functions, and indeed, there is evidence that many of hypoxia-inducible factors effects may be mediated by the stimulation of fructose production and metabolism. Unfortunately, while being acutely protective, these same systems in overdrive lead to chronic inflammation and disease and may also be involved in the development of metabolic syndrome and related disease. The benefit of SGLT2 inhibitors may act in part by reducing the delivery of glucose with the stimulation of fructose formation, thereby allowing a conversion from the glycolytic metabolism to one involving mitochondrial metabolism. The use of hypoxia-inducible factor stabilizers is expected to aid the treatment of anemia but, in the long-term, could potentially lead to worsening cardiovascular and metabolic outcomes. We suggest more studies are needed on the use of these agents.

Maternal Stress and Neonatal Nutrition during the COVID-19 Era.

Objective: COVID-19 pandemic has put a tremendous amount of stress on people, which can negatively affect nursing. Previous studies showed that perceived stress and cortisol levels in the postpartum period correlate with the LATCH scores, which is a simple tool to assess the pattern of nursing. Likewise, greater prenatal anxiety was associated with a shorter breastfeeding duration. We aimed to evaluate whether pregnant women were under extra stress due to the COVID-19 pandemic and if this stress affected their breastfeeding patterns and anthropometric measures of the neonates. Methods: Pregnant women giving birth to healthy neonates were included. Coronavirus Anxiety Scale (CAS) and Beck Anxiety Inventory (BAI) were used to assess the anxiety levels of the mothers, and LATCH breastfeeding assessment tool was used to assess the nursing. The results of these scales and anthropometric measures of the neonates were recorded. Results: Only one mother showed coronavirus-specific anxiety. Therefore, further analysis was done based on the Beck Anxiety (BA) levels of the mothers. CAS and BA scores were positively correlated (p<0.001, r=0.444), indicating that coronavirus-specific anxiety increased with increasing general anxiety. None of the variables changed depending on the anxiety levels of the mothers, except for the % weight gain at day five (p=0.020, r=-0.248). Even though anxiety seemed to show a small effect on weight loss during the first neonatal days, percent weight gain results did not seem to correlate with the anxiety levels in later stages (first month of life). Furthermore, LATCH scores of the infants on day one were positively correlated with BA scores of the mothers (p=0.045, r=0.175). Conclusion: COVID-19 seemed to have no additional effect on the stress levels of the mothers. The more the mothers have anxiety, the more they may stress about the well-being of their infants, which can improve their nursing pattern.

Hypofractionated frameless gamma knife radiosurgery for large metastatic brain tumors.

Hypofractionated stereotactic radiosurgery has become an alternative for metastatic brain tumors (METs). We aimed to analyze the efficacy and safety of frameless hypofractionated Gamma Knife radiosurgery (hfGKRS) in the management of unresected, large METs. All patients who were managed with hfGKRS for unresected, large METs (> 4 cm3) between June 2017 and June 2020 at a single center were reviewed in this retrospective study. Local control (LC), progression-free survival (PFS), overall survival (OS), and toxicities were investigated. A total of 58 patients and 76 METs with regular follow-up were analyzed. LC rate was 98.5% at six months, 96.0% at one year, and 90.6% at 2 years during a median follow-up of 12 months (range, 2-37). The log-rank test indicated no difference in the distribution of LC for any clinical or treatment variable. PFS was 86.7% at 6 months, 66.6% at 1 year, and 58.5% at 2 years. OS was 81% at 6 months, 63.6% at one year, and 50.7% at 2 years. On the log-rank test, clinical parameters such as control status of primary cancer, presence of extracranial metastases, RTOG-RPA class, GPA group, and ds-GPA group were significantly associated with PFS and OS. Patients presented with grade 1 (19.0%), grade 2 (3.5%) and grade 3 (5.2%) side effects. Radiation necrosis was not observed in any patients. Our current results suggest that frameless hfGKRS for unresected, large METs is a rational alternative in selected patients with promising results.