Association of antenatal corticosteroids with mortality and morbidities in very preterm infants born to women with hypertensive disorders of pregnancy: a multicenter prospective cohort study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is the most common cause of indicated preterm delivery, but the impact of prenatal steroid exposure on the outcomes of preterm infants born to HDP mothers, who may be at risk for intrauterine hypoxia-ischemia, remains uncertain. The study objective is to evaluate the mortality and morbidities in HDP for very preterm infants (VPIs) exposed to different course of ANS. METHODS: This is a prospective cohort study comprising infants with < 32 weeks gestation born to women with HDP only from 1 Jan. 2019 to 31 Dec. 2021 within 40 participating neonatal intensive care units (NICUs) in Sino-northern network. ANS courses included completed, partial, repeated, and no ANS. Univariate and multivariable analyses were performed on administration of ANS and short-term outcomes before discharge. RESULTS: Among 1917 VPIs born to women with HDP only, 987(51.4%) received a complete course of ANS within 48 h to 7 days before birth, 560(29.2%) received partial ANS within 24 h before delivery, 100(5.2%) received repeat ANS and 270 (14.1%) did not receive any ANS. Compared to infants who received complete ANS, infants unexposed to ANS was associated with higher odds of death (AOR 1.85; 95%CI 1.10, 3.14), Severe Neurological Injury (SNI) or death (AOR 1.68; 95%CI 1.29,3.80) and NEC or death (AOR 1.78; 95%CI 1.55, 2.89), the repeated ANS group exhibits a significant negative correlation with the duration of oxygen therapy days (correlation coefficient - 18.3; 95%CI-39.2, -2.1). However, there were no significant differences observed between the full course and partial course groups in terms of outcomes. We can draw similar conclusions in the non-SGA group, while the differences are not significant in the SGA group. From KM curve, it showed that the repeated group had the highest survival rate, but the statistical analysis did not indicate a significant difference. CONCLUSIONS: Even partial courses of ANS administered within 24 h before delivery proved to be protective against death and other morbidities. The differences mentioned above are more pronounced in the non-SGA group. Repeat courses demonstrate a trend toward protection, but this still needs to be confirmed by larger samples.

Determining resuscitation threshold for extremely preterm infants based on the survival rates without severe neurological injury.

Background: Published guidelines on decision-making and resuscitation of extremely preterm infants primarily focus on high-income countries. For rapidly industrializing ones like China, there is a lack of population-based data for informing prenatal management and practice guidelines. Methods: The Sino-northern Neonatal Network conducted a prospective multi-centre cohort study between 1 January 2018 and 31 December 2021. Infants with a gestational age (GA) between 22 (postnatal age in days = 0) and 28 (postnatal age in days = 6) admitted to 40 tertiary NICUs in northern China were included and evaluated for death or severe neurological injury before discharge. Results: For all extremely preterm infants (n = 5838), the proportion of admission to the neonatal was 4.1% at 22-24 weeks, 27.2% at 25-26 weeks, and 75.2% at 27 and 28 weeks. Among 2228 infants admitted to the NICU, 216 (11.1%) were still elected for withdrawal of care (WIC) due to non-medical factors. Survival rates without severe neurological injury were 6.7% for infants at 22-23 weeks, 28.0% at 24 weeks, 56.7% at 24 weeks, 61.7% at 25 weeks, 79.9% at 26 weeks, and 84.5% at 27 and 28 weeks. Compared with traditional criterion at 28 weeks, the relative risk for death or severe neurological injury were 1.53 (95% confidence interval (CI) = 1.26-1.86) at 27 weeks, 2.32 (95% CI = 1.73-3.11) at 26 weeks, 3.62 (95% CI = 2.43-5.40) at 25 weeks, and 8.91 (95% CI = 4.69-16.96) at 24 weeks. The NICUs with higher proportion of WIC also had a higher rate of death or severe neurological injury after maximal intensive care (MIC). Conclusions: Compared to the traditional threshold of 28 weeks, more infants received MIC after 25 weeks, leading to significant increases in survival rates without severe neurological injury. Therefore, the resuscitation threshold should be gradually adjusted from 28 to 25 weeks based on reliable capacity. Registration: China Clinical Trials Registry. ID: ChiCTR1900025234.

Longer duration of initial invasive mechanical ventilation is still a crucial risk factor for moderate-to-severe bronchopulmonary dysplasia in very preterm infants: a multicentrer prospective study.

OBJECTIVES: We aimed to evaluate the risk factors for moderate-to-severe bronchopulmonary dysplasia (BPD) and focus on discussing its relationship with the duration of initial invasive mechanical ventilation (IMV) in very preterm neonates less than 32 weeks of gestational age (GA). METHODS: We performed a prospective cohort study involving infants born at 23-31 weeks of GA who were admitted to 47 different neonatal intensive care unit (NICU) hospitals in China from January 2018 to December 2021. Patient data were obtained from the Sina-northern Neonatal Network (SNN) Database. RESULTS: We identified 6538 very preterm infants, of whom 49.5% (3236/6538) received initial IMV support, and 12.6% (823/6538) were diagnosed with moderate-to-severe BPD symptoms. The median duration of initial IMV in the moderate-to-severe BPD group was 26 (17-41) days, while in the no or mild BPD group, it was 6 (3-10) days. The incidence rate of moderate-to-severe BPD and the median duration of initial IMV were quite different across different GAs. Multivariable logistic regression analysis showed that the onset of moderate-to-severe BPD was significantly associated with the duration of initial IMV [adjusted odds ratio (AOR): 1.97; 95% confidence interval (CI): 1.10-2.67], late-onset neonatal sepsis (LONS), and patent ductus arteriosus (PDA). CONCLUSION: In this multicenter cohort study, the duration of initial IMV was still relatively long in very premature infants, and the longer duration of initial IMV accounts for the increased risk of moderate-to-severe BPD.

[Roles of interleukin-21 and its receptor in autoimmune diseases].

Interleukin-21 (IL-21) is a new member of the interleukin-2 family. It is mainly synthesized and secreted by the activated of CD4(+) T cells and natural killer T cells. IL-21 receptor (IL-21R) is mainly expressed in T cells, B cells, and natural killer (NK) cells. After binding to its receptor, IL-21 can regulate the activation and proliferation of T cells, B cells, and NK cells through activating JAKs-STATs signaling pathways. As a new immunoregulatory factor, IL-21 and its receptor play important roles in the development and progression of various autoimmune diseases. Regulation of the expression levels of IL-21 and IL-21R and blocking of their signal transduction pathways with blockers may be new treatment options for autoimmune diseases.

Bilateral chylothorax following left supraclavicular lymph node dissection for breast cancer: one case report and literature review.

Chylothorax is a rare complication of neck dissection, and bilateral chylothorax is even rarer. However, both are potentially serious and sometimes life-threatening, especially those that are associated with left neck dissection for head and neck neoplasms. We report one case of bilateral chylothorax following left supraclavicular dissection for breast cancer. This case was treated successfully with a new conservative management approach.

Preparation and drug-delivery potential of metronidazole-loaded PELA tri-block co-polymeric electrospun membranes.

The aim of this study was to investigate the potential of poly(ethylene glycol-co-lactide) (PELA tri-block with a segmental sequence of PLA-PEG-PLA) electrospun membranes as drug-delivery vehicles using metronidazole as a model drug. PELA membranes with smooth surfaces and no bead defects were electrospun from polymer solutions containing 20% (w/v) PELA in 8:2 N,N-dimethyl formamide (DMF)/acetone. The morphology of the drug-loaded electrospun membranes was influenced by electrospinning parameters such as the flow rate and voltages during preparation. Metronidazole could be released from the electrospun membranes and was characterized by an initial burst effect. Higher voltages led to faster release rates, while an increase in the flow rate decreased the drug release. The incorporation of metronidazole into the electrospun membranes decreased their surface hydrophilicity. The amount of drug released from the electrospun membranes was effective in inhibiting microbial growth. Cell adhesion on the PELA membranes with or without drug was less than that on the homo-polymeric PDLLA membranes. Proliferation of L929 mouse fibroblasts on the PELA membranes was observed. This study confirms the potential of metronidazole-loaded PELA biodegradable electrospun membranes for optimizing the clinical therapy of post-surgical adhesions and infections.

Tissue anti-adhesion potential of biodegradable PELA electrospun membranes.

The most commonly used anti-adhesion device for separation and isolation of wounded tissues after surgery is the polymeric membrane. In this study, a new anti-adhesion membrane from polylactide-polyethylene glycol tri-block copolymer (PELA) has been synthesized. The synthesized copolymers were characterized by gel permeation chromatography and (1)H nuclear magnetic resonance spectroscopy. PELA membrane was prepared by electrospun. The prepared copolymer membranes were more flexible than the control poly-d-l-lactic acid (PDLLA) membrane, as investigated by the measurements of glass transition temperature. Its biocompatibility and anti-adhesion capabilities were also evaluated. In vitro cell adhesions on the PELA copolymer membrane and PDLLA membrane were compared by the culture of mouse fibroblasts L929 on the surfaces. For in vivo evaluation of tissue anti-adhesion potential, the PDLLA and PELA copolymer membranes were implanted between cecum and peritoneal wall defects of rats and their tissue adhesion extents were compared. It was observed that the PELA copolymer membrane was very effective in preventing cell or tissue adhesion on the membrane surface, probably owing to the effects of hydrophilic polyethylene glycol.

An ionically crosslinked hydrogel containing vancomycin coating on a porous scaffold for drug delivery and cell culture.

The aim of this study was to prepare and characterize a scaffold with an ionically crosslinked hydrogel coating layer containing a water-soluble drug, vancomycin, via a novel drug loading method for sustained drug delivery and surface modification. The poly(D,L-lactide acid) (PDLLA)/biphasic calcium phosphate (BCP) scaffold with a highly inter-connected porous structure was fabricated by a particle-leaching/thermally induced phase separation (TIPS) method. The pre-vacuumized scaffold was immersed into an alginate/vancomycin solution. Following impregnation by the solution, the scaffold was removed and immersed in a CaCl(2) solution for 30 min to allow gelation of the alginate solution. In this way, the drug was not exposed to organic solvents or detrimental temperature conditions and it could avoid loss of drug during the leaching process. The water contact angles of the scaffold surface decreased after being coated with the hydrogel. The in vitro drug release profile showed sustained release properties which were influenced by the alginate concentration and the dissolution medium. A standardized bacterial assay showed that the drug was still active after association with the scaffold by this gentle method of drug loading. The in vitro osteoblast culture experiments confirmed the biocompatibility of the scaffold for attachment and proliferation of osteoblasts.

Fabrication and characterization of hydrophilic electrospun membranes made from the block copolymer of poly(ethylene glycol-co-lactide).

To improve the hydrophilicity, pliability, and egradability of some biodegradable polymers such as polylactide (PLA), a triblock copolymer, and poly(ethylene glycol-co-lactide) (PELA) has been electrospun into fibrous membranes in the fiber sizes of 7.5 microm to 250 nm. The relationship between electrospinning parameters (such as voltage, concentration, and feeding rate) and the fiber diameters has been investigated. The characterizations for the structure and morphology of electrospun membranes were carried out using differential scanning calorimetry (DSC), (1)H NMR, and scanning electron microscopy (SEM). The hydrophilicity of the membrane was determined by contact angle measurements in bi-distilled water, and it was shown that the hydrophilicity of the copolymer could be adjusted by the content of the poly (ethylene glycol) (PEG) segment in the copolymer. The results of in vitro degradation study showed that the submicrostructure of the fibrous membrane and the incorporation of hydrophilic PEG into PLA block could accelerate the degradation of the membrane in regards to the changes of inherent viscosity, tensile strength, and weight loss.