胎儿头面部异常的临床咨询

胎儿头面部异常，是较为常见的结构异常。文章就常见的胎儿头面异常，包括唇腭裂、小颌畸形、耳郭畸形、巨舌症、眼畸形、颈项透明层增厚和颈部淋巴水囊瘤的分型与发生率、影像学诊断、病因、临床处理及预后分别进行论述，为临床决策和咨询提供参考。       

High-flow via a tracheostomy tube and speaking valve during weaning from mechanical ventilation and tracheostomy

Background

Weaning from mechanical ventilation and tracheostomy after prolonged intensive care consume enormous resources with optimal management not currently well described. Restoration of respiratory flow via the upper airway is essential and early cuff-deflation using a one-way valve (OWV) is recommended. However, extended OWV use may cause dry airways and thickened secretions which challenge the weaning process. High-flow therapy via the tracheostomy tube (HFT-T) humidifies inspired air and may be connected via an in-line OWV (HFT-T-OWV) alleviating these problems. We aim to provide clinical and experimental data on the safety of HFT-T-OWV along with a practical guide to facilitate clinical use during weaning from mechanical ventilation and tracheostomy.

Methods

Data on adverse events of HFT-T-OWV were retrieved from a quality register for patients treated at an intensive care rehabilitation center between 2019 and 2022. Benchtop experiments were performed to measure maximum pressures and pressure support generated by HFT-T-OWV at 25–60 L/min flow using two different HFT-T adapters (interfaces). In simulated airway obstruction using a standard OWV (not in-line) maximum pressures were measured with oxygen delivered via the side port at 1–3 L/min.

Results

Of 128 tracheostomized patients who underwent weaning attempts, 124 were treated with HFT-T-OWV. The therapy was well tolerated, and no adverse events related to the practice were detected. The main reason for not using HFT-T-OWV was partial upper airway obstruction using a OWV. Benchtop experiments demonstrated HFT-T-OWV maximum pressures <4 cmH₂O and pressure support 0–0.6 cmH₂O. In contrast, 1–3 L/min supplemental oxygen via a standard OWV caused pressures between 84 and 148 cmH₂O during simulated airway obstruction.

Conclusions

Current study clinical data and benchtop experiments indicate that HFT-T-OWV was well tolerated and appeared safe. Pressure support was low, but humidification may enable extended use of a OWV without dry airway mucosa and thickened secretions. Results suggest the treatment could offer advantages to standard OWV use, with or without supplementary oxygen, as well as to HFT-T without a OWV, for weaning from mechanical ventilation and tracheostomy. However, for definitive treatment recommendations, randomized clinical trials are needed.     

Rociletinib (CO-1686) enhanced the efficacy of chemotherapeutic agents in ABCG2-overexpressing cancer cells in vitro and in vivo

Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells in vitro and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in ABCG2-overexpressing cancer cells, rociletinib inhibited ABCG2-mediated drug efflux and increased intracellular accumulation of ABCG2 probe substrates. Moreover, rociletinib, inhibited the ATPase activity, and competed with [¹²⁵I] iodoarylazidoprazosin (IAAP) photolabeling of ABCG2. However, ABCG2 expression at mRNA and protein levels was not altered in the ABCG2-overexpressing cells after treatment with rociletinib. In addition, rociletinib did not inhibit EGFR downstream signaling and phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Our results collectively showed that rociletinib reversed ABCG2-mediated MDR by inhibiting ABCG2 efflux function, thus increasing the cellular accumulation of the transporter substrate anticancer drugs. The findings advocated the combination use of rociletinib and other chemotherapeutic drugs in cancer patients with ABCG2-overexpressing MDR tumors.     

The key role of macrophage depolarization in the treatment of COPD with ergosterol both in vitro and in vivo

Macrophages are the most abundant immune cells in the lung, which play an important role in COPD. The anti-inflammatory and anti-oxidation of ergosterol are well documented. However, the effect of ergosterol on macrophage polarization has not been studied. The objective of this work was to investigate the effect of ergosterol on macrophage polarization in CSE-induced RAW264.7 cells and Sprague-Dawley (SD) rats COPD model. Our results demonstrate that CSE-induced macrophages tend to the M1 polarization via increasing ROS, IL-6 and TNF-α, as well as increasing MMP-9 to destroy the lung construction in both RAW264.7 cells and SD rats. However, treatment of RAW264.7 cells and SD rats with ergosterol inhibited CSE-induced inflammatory by decreasing ROS, IL-6 and TNF-α, and increasing IL-10 and TGF-β, shuffling the dynamic polarization of macrophages from M1 to M2 both in vitro and in vivo. Ergosterol also decreased the expression of M1 marker CD40, while increased that of M2 marker CD163. Moreover, ergosterol improved the lung characters in rats by decreasing MMP-9. Furthermore, ergosterol elevated HDAC3 activation and suppressed P300/CBP and PCAF activation as well as acetyl NF-κB/p65 and IKKβ, demonstrating that HDAC3 deacetylation was involved in the effect of ergosterol on macrophage polarization. These results also provide a proof in immunoregulation of ergosterol for therapeutic effects of cultured C. sinensis on COPD patients.     

Re-engineering the interpretation of electronic fetal monitoring to identify reversible risk for cerebral palsy: a case control series

Background: Even key opinion leaders now concede that electronic fetal monitoring (EFM) cannot reliably identify fetal acidemia which many vouch as the only labor mediated pathophysiologic precursor for cerebral palsy (CP). We have developed the “Fetal Reserve Index” – an algorithm combining five dynamic components of EFM (1. Rate, 2. Variability, 3. Accelerations, 4. Decelerations, and 5. Excessive uterine activity) considered individually that are combined with the presence of: 6. maternal, 7. obstetrical, and 8. fetal risk factors.

Objective: Here, we compare this 8-point fetal reserve index (FRI) against the performance of ACOG monograph criteria and ACOG Category systems for predicting risk for both CP and the need for emergency operative delivery (EOD). We then studied how varied management for screen positives (Red zone-defined below) impacts the outcome of such cases.

Study design: Four hundred twenty term patients were studied: all entered labor with normal EFMs and no apparent cause of harm except events of labor and delivery. Sixty subsequently developed CP, and 360 were apparently normal controls. An FRI, normal on all eight parameters scored 100%, 4 of the 8 was 50%, etc. We divided cases into Green zone >50%, Yellow 50–26%, and Red ≤25%. An FRI in the Red zone was considered a positive screen. We then compared performance metrics for the three evaluation schemes and differences between controls that reached Red against those controls whose worst scores were Green/Yellow.

Results: For detection of injury during labor, the FRI performed much better than the ACOG Category criteria (sensitivity 28%), and Category III (45%) (p?Conclusions: FRI shows better discrimination for adverse fetal outcome and EOD than traditional EFM interpretation. The Category system is a very poor, subjective screening method as the vast majority of CP babies never reach the “action point” result of Category III. While reaching the Red zone does not ordain a bad outcome, how it is managed, does. Compared to CP cases, Red controls were delivered faster, had higher FRIs, and often had prompt management including IR maneuvers, which improved the FRI and lowered the risk of EODs even for cases with normal outcomes. With further study and validation, the quantitative FRI approach may replace the current, very subjective interpretation with a quantitative “lab test” approach.     

Intracardiac echogenic focus and its location: association with congenital heart defects

Purpose: Significance of intracardiac echogenic focus (ICEF) in the fetal heart remains controversial. We aimed to investigate whether the location of ICEF is associated with fetal cardiac structure defects (CSDs) in low-risk pregnant women.

Materials and Methods: A retrospective cohort study was conducted. Singleton pregnancies with normal values of triple fetal serum markers were included. 758 of 9782 fetuses with ICEF were reviewed for involvement of three ICEF locations (left, right, and bilateral ventricles (BVs)) in CSDs. χ² or Fisher’s exact test was performed for statistical analysis.

Results: ICEF prevalence was 7.7% and its location was most frequently in the left ventricle (LV) (84.8%), followed by the BV (11.6%) and the right ventricle (RV) (3.6%). No statistically significant difference was found between the ICEF location and maternal age (χ²?=?3.92, p-value?=?.1409). There were cardiac defects with an isolated echogenic focus in 24 of 758 fetuses (3.2%). Significant difference for CSDs was observed among groups of RV, LV, and BV (p-fisher?=?.0146).

Conclusions: Significantly more CSDs cases were identified in fetuses with ICEF in RV. Further investigation is warranted to examine the histological characteristics of fetal echogenic focus in the RV.     

Prenatal Diagnosis of Aortopulmonary Window by 2‐Dimensional Echocardiography: Summary of 8 Cases

Aortopulmonary window (APW) is a rare congenital heart anomaly. A total of 8 cases with APW confirmed by echocardiography and surgery were retrospectively reviewed and the echocardiographic features analyzed. Among the 8 APW cases, 5 were type II and 3 were type III, the latter of which includes 2 cases complicated with Berry syndrome. Prenatal echocardiography can provide accurate information for the diagnosis of fetal APW. The prognosis depends on the timing of surgery and the nature of the associated cardiac anomalies.