Neonatal asphyxia as an inflammatory disease: Reactive oxygen species and cytokines

Neonatologists resuscitate asphyxiated neonates by every available means, including positive ventilation, oxygen therapy, and drugs. Asphyxiated neonates sometimes present symptoms that mimic those of inflammation, such as fever and edema. The main pathophysiology of the asphyxia is inflammation caused by hypoxic-ischemic reperfusion. At birth or in the perinatal period, neonates may suffer several, hypoxic insults, which can activate inflammatory cells and inflammatory mediator production leading to the release of larger quantities of reactive oxygen species (ROS). This in turn triggers the production of oxygen stress-induced high mobility group box-1 (HMGB-1), an endogenous damage-associated molecular patterns (DAMPs) protein bound to toll-like receptor (TLR) -4, which activates nuclear factor-kappa B (NF-κB), resulting in the production of excess inflammatory mediators. ROS and inflammatory mediators are produced not only in activated inflammatory cells but also in non-immune cells, such as endothelial cells. Hypothermia inhibits pro-inflammatory mediators. A combination therapy of hypothermia and medications, such as erythropoietin and melatonin, is attracting attention now. These medications have both anti-oxidant and anti-inflammatory effects. As the inflammatory response and oxidative stress play a critical role in the pathophysiology of neonatal asphyxia, these drugs may contribute to improving patient outcomes

Developmental changes in neonatal hemodynamics during tactile stimulation using whole-head functional near-infrared spectroscopy

Neural-activity-associated hemodynamic changes have been used to noninvasively measure brain function in the early developmental stages. However, the temporal changes in their hemodynamics are not always consistent with adults. Studies have not evaluated developmental changes for a long period using the same stimuli; therefore, this study examined the normalized relative changes in oxygenated hemoglobin (Δ[oxy-Hb]) in full-term infants and compared them with neonates up to 10 months of age during the administration of tactile vibration stimuli to their limbs using whole-head functional near-infrared spectroscopy. The time to peak of normalized Δ[oxy-Hb] was not affected by age. The amplitude of normalized Δ[oxy-Hb] showed an effect of age in broader areas, including sensorimotor-related but excluding supplementary motor area; the amplitude of normalized Δ[oxy-Hb] decreased the most in the 1–2-month-old group and later increased with development. We hypothesized that these results may reflect developmental changes in neural activity, vasculature, and blood oxygenation

Changes in the Incidence of Infantile Spinal Muscular Atrophy in Shikoku, Japan between 2011 and 2020

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder. Al-though there was no cure for SMA, newly developed therapeutic drugs (nusinersen, onasemnogene abeparvovec, and risdiplam) have been proven effective for the improvement of motor function and prevention of respiratory insufficiency of infants with SMA. Nusinersen was introduced in Japan in 2017 and onasemnogene abeparvovec in 2020. We hypothesized that the introduction of these drugs might influence the incidence of SMA (more precisely, increase the diagnosis rate of SMA) in Japan. To test this hypothesis, we conducted a second epidemiological study of infantile SMA using questionnaires in Shikoku, Japan between October 2021 and February 2022. The incidence of infantile SMA during the period 2016–2020 was 7.08 (95% confidence interval [CI] 2.45–11.71) per 100,000 live births. According to our previous epidemiological study, the incidence of infantile SMA during 2011–2015 was 2.70 (95% CI 0.05–5.35) per 100,000 live births. The increased incidence of infantile SMA suggests that the widespread news in Japan regarding the introduction of therapeutic agents, nusinersen and onasemnogene abeparvovec, raised clinicians’ awareness about SMA, leading to increased and earlier diagnosis of SMA in Shikoku

Measurement of the Absolute Value of Cerebral Blood Volume and Optical Properties in Term Neonates Immediately after Birth Using Near-Infrared Time-Resolved Spectroscopy: A Preliminary Observation Study

The aim of this study was to use near-infrared time-resolved spectroscopy (TRS) to determine the absolute values of cerebral blood volume (CBV) and cerebral hemoglobin oxygen saturation (ScO2) during the immediate transition period in term neonates and the changes in optical properties such as the differential pathlength factor (DPF) and reduced scattering coefficient (μs’). CBV and ScO2 were measured using TRS during the first 15 min after birth by vaginal delivery in term neonates who did not need resuscitation. Within 2−3 min after birth, CBV showed various changes such as increases or decreases, followed by a gradual decrease until 15 min and then stability (mean (SD) mL/100 g brain: 2 min, 3.09 (0.74); 3 min, 3.01 (0.77); 5 min, 2.69 (0.77); 10 min, 2.40 (0.61), 15 min, 2.08 (0.47)). ScO2 showed a gradual increase, then kept increasing or became a stable reading. The DPF and μs’ values (mean (SD) at 762, 800, and 836 nm) were stable during the first 15 min after birth (DPF: 4.47 (0.38), 4.41 (0.32), and 4.06 (0.28)/cm; μs’: 6.54 (0.67), 5.82 (0.84), and 5.43 (0.95)/cm). Accordingly, we proved that TRS can stably measure cerebral hemodynamics, despite the dramatic physiological changes occurring at this time in the labor room

Predictive factors for hyperglycaemic progression in patients with schizophrenia or bipolar disorder

Background: Patients with schizophrenia or bipolar disorder have a high risk of developing type 2 diabetes. Aims: To identify predictive factors for hyperglycaemic progression in individuals with schizophrenia or bipolar disorder and to determine whether hyperglycaemic progression rates differ among antipsychotics in regular clinical practice. Method: We recruited 1166 patients who initially had normal or prediabetic glucose levels for a nationwide, multisite, l-year prospective cohort study to determine predictive factors for hyperglycaemic progression. We also examined whether hyperglycaemic progression varied among patients receiving monotherapy with the six most frequently used antipsychotics. Results: High baseline serum triglycerides and coexisting hypertension significantly predicted hyperglycaemic progression. The six most frequently used antipsychotics did not significantly differ in their associated hyperglycaemic progression rates over the 1-year observation period. Conclusions: Clinicians should carefully evaluate baseline serum triglycerides and coexisting hypertension and perform strict longitudinal monitoring irrespective of the antipsychotic used