Chinese Bioethicists Speak Out on Covid-19, and Others Follow

Shortly after Wuhan, the city where the novel coronavirus was first identified, was placed on lockdown in January, I received an email from two Hastings Center fellows in China: Renzong Qiu, of Renmin University of China in Beijing, and Ruipeng Lei, of Huazhong University of Science and Technology in Wuhan. Attached was a post for our blog, Hastings Bioethics Forum, that raised ethical and legal questions about China's response. “Hegel says, ‘We learn from history that we do not learn from history,’” their piece began. “The recurrence of the coronavirus epidemic in China proves his insight to be right.” This bold report from bioethicists in China was courageous and eye-opening. It was among the first discussions in bioethics of what has since become a global crisis, and it turned out to be the first in a string of commentaries in Hastings Bioethics Forum with insights about the crisis, the issues it raises, and how the world should respond to it.     

Albumin-to-Globulin Ratio at 1 Year after Anti-Tumor Necrosis Factor α Therapy Can Serve as a Prognostic Biomarker in Pediatric Crohn’s Disease Patients

Background/AimsThe efficacy of biologics for the treatment of Crohn’s disease (CD) is affected by the drug concentrations. We aimed to evaluate the importance of albumin and globulin which are known to be associated with drug concentrations as prognostic biomarkers in CD.MethodsIn total, 121 pediatric patients with CD who had received anti-tumor necrosis factor (TNF)-α therapy were retrospectively examined between January 2010 and February 2019.ResultsRelapse was observed in 48.8% of patients (59/121). The level of calprotectin (odds ratio, 2.13; p=0.03) and the albumin-to-globulin ratio (AGR) at 1 year after anti-TNF-α therapy (odds ratio, 0.0002; p=0.003) were associated with relapse. The AGR at 1 year after anti-TNF-α therapy was the only factor associated with the time-to-relapse (hazard ratio, 0.02; p<0.001). The optimal AGR cutoff value for the prediction of relapse was 1.47 (area under the curve, 0.916; p<0.001). The median infliximab trough level (TL) was lower in patients with AGRs <1.47 than in those with AGRs ≥1.47. Anti-drug antibody (ADA) concentrations were negatively correlated with the AGR at 1 year of anti-TNF-α therapy (r=–0.413, p=0.032).ConclusionsAGR can be used to predict relapse. Patients with AGRs <1.47 at 1 year after anti-TNF-α therapy are more likely to have low drug TLs and develop ADAs, which increase the possibility of relapse than those with AGRs ≥1.47. Therefore, if the AGR at 1 year after anti-TNF-α therapy is less than 1.47, clinicians should monitor disease activity, assess the TLs of the anti-TNF-α agents, test for ADAs and determine the appropriate therapeutic strategies.     

A Novel One-Step Knife Approach Can Reduce the Submucosal Injection Time of Endoscopic Submucosal Dissection: A Single-Blinded Randomized Multicenter Clinical Trials

Background/AimsEndoscopic submucosal dissection (ESD) is a curative treatment modality for early gastric neoplasms; however, ESD can be a time-consuming process. To overcome this pitfall, we developed the one-step knife (OSK) approach, which combines an endoscopic knife and injection needle on a single sheath. We aimed to evaluate whether this approach could reduce the ESD procedure time.MethodsThis single-blinded randomized multicenter trial at four tertiary hospitals from June 2019 to June 2020 included patients aged 19 to 85 years undergoing ESD. Patients were randomly assigned to two groups (OSK or conventional knife [CK]). The injection time, total procedure time, resected specimen size, submucosal fluid amount, degree of device satisfaction, and adverse events were evaluated and compared between groups.ResultsFifty-one patients were analyzed (OSK 25 patients and CK 26 patients). No baseline differences were observed between groups, with the exception of a higher portion of males in the OSK group. The mean injection time was significantly reduced in the OSK group (39.0 seconds) compared to that in the CK group (87.5 seconds, p<0.001). A decrease of more than 10 minutes in the total procedure time (18.0 minutes vs 28.1 minutes, p=0.055) in the OSK group compared to the CK group was observed. Second-look esophagogastroduodenoscopy revealed two delayed bleeding cases in the OSK group that were easily controlled by endoscopic hemostasis.ConclusionsOSK reduced the injection time and showed a decrease in total procedure time compared with the CK approach. OSK can be a feasible tool for ESD, especially in difficult cases.     

Difference between bone age at the hand and elbow at the onset of puberty

In the pubertal period, bone age advances rapidly in conjunction with growth spurts. Precise bone-age assessments in this period are important, but results from the hand and elbow can be different. We aimed to compare the bone age between the hand and elbow around puberty onset and to elucidate the chronological age confirming puberty onset according to elbow-based bone age.A total of 211 peripubertal subjects (127 boys and 84 girls) who underwent hand and elbow radiographs within 2 months was enrolled. Two radiologists and a pediatric orthopedic surgeon assessed bone age. Hand bone age was graded using the Greulich–Pyle (GP) method, and elbow bone age was determined using the Sauvegrain method. The correlation of 2 methods was evaluated by Demining regression analysis, and the mean absolute difference (MAD) with chronological age was compared between pre-pubertal and pubertal subjects. Receiver-operating characteristic curve analysis was performed to determine the chronological age confirming puberty onset.There was a statistically significant difference in bone age revealed by the GP and Sauvegrain methods in the pubertal group. In the pubertal group, the MAD was 1.26 ± 0.90 years with the GP method and 0.61 ± 0.47 years with the Sauvegrain method in boys (P < .001), while in girls, the MAD was 0.84 ± 0.60 years and 0.53 ± 0.36 years with the same 2 methods (P = .033). The chronological age for confirming puberty onset using the elbow was 12.2 years in boys and 10.3 years in girls.The bone ages of hand and elbow were different at puberty, and the elbow was a more reliable location for bone-age assessment at puberty. Puberty onset according to elbow occurred slightly earlier than expected.     

Tracking SARS-CoV-2 Spike Protein Mutations in the United States (January 2020—March 2021) Using a Statistical Learning Strategy

The emergence and establishment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of interest (VOIs) and variants of concern (VOCs) highlight the importance of genomic surveillance. We propose a statistical learning strategy (SLS) for identifying and spatiotemporally tracking potentially relevant Spike protein mutations. We analyzed 167,893 Spike protein sequences from coronavirus disease 2019 (COVID-19) cases in the United States (excluding 21,391 sequences from VOI/VOC strains) deposited at GISAID from 19 January 2020 to 15 March 2021. Alignment against the reference Spike protein sequence led to the identification of viral residue variants (VRVs), i.e., residues harboring a substitution compared to the reference strain. Next, generalized additive models were applied to model VRV temporal dynamics and to identify VRVs with significant and substantial dynamics (false discovery rate q-value < 0.01; maximum VRV proportion >10% on at least one day). Unsupervised learning was then applied to hierarchically organize VRVs by spatiotemporal patterns and identify VRV-haplotypes. Finally, homology modeling was performed to gain insight into the potential impact of VRVs on Spike protein structure. We identified 90 VRVs, 71 of which had not previously been observed in a VOI/VOC, and 35 of which have emerged recently and are durably present. Our analysis identified 17 VRVs ~91 days earlier than their first corresponding VOI/VOC publication. Unsupervised learning revealed eight VRV-haplotypes of four VRVs or more, suggesting two emerging strains (B1.1.222 and B.1.234). Structural modeling supported a potential functional impact of the D1118H and L452R mutations. The SLS approach equally monitors all Spike residues over time, independently of existing phylogenic classifications, and is complementary to existing genomic surveillance methods.     

Prognostic factors of facial nerve function after vestibular schwannoma removal via translabyrinthine approach

Background: Prediction of facial function is a major concern when proposing surgery for patients with vestibular schwannoma (VS).

Aims/objectives: To evaluate postoperative facial function of patients who underwent operation of VS via a translabyrinthine approach (TL), and to analyze factors that influence facial functions.

Material and methods: A total of 91 VS patients, who were operated via a TL approach, between March 1997 and December 2016, were analyzed. Demographics, tumor-related factors, and operative findings were collected. Facial function was assessed according to the House-Brackmann (HB) grading system before surgery, immediately after surgery, and 1-, 3-, 6-months, and 1 year after surgery.

Results: In cases of patients that had a tumor that extended to the CPA, an unsatisfactory facial outcome was noted in 12 (30.0%) patients. FN outcomes after tumor removal depend on tumor size (p?=?.040). Among FN-related factors, only the FN recovery timing was correlated with facial outcomes (p?=?.030). Univariable and multivariable analysis revealed that tumor size and the timing of FN recovery were significant as favorable prognostic factors for good facial outcomes.

Conclusions and significance: Tumor size and the FN recovery timing are significant prognostic factors of facial outcome in VS patients who underwent operations via a TL approach.     

Deep Ethical Learning: Taking the Interplay of Human and Artificial Intelligence Seriously

From predicting medical conditions to administering health behavior interventions, artificial intelligence technologies are being developed to enhance patient care and outcomes. However, as Mélanie Terrasse and coauthors caution in an article in this issue of the Hastings Center Report, an overreliance on virtual technologies may depersonalize medical interactions and erode therapeutic relationships. The increasing expectation that patients will be actively engaged in their own care, regardless of the patients’ desire, technological literacy, and economic means, may also violate patients’ autonomy and exacerbate access. Moreover, since AI design is both a technical and social process, algorithms may mirror human biases, calling into question the vision of AI technologies surpassing human judgment and avoiding prejudices in decision‐making. The best answer to these problems is to develop AI health technologies as part of a culture of health care quality improvement, responding to existing needs while being proactive about potential technical and ethical problems that can arise from the technologies’ design and implementation.