Citations

Abstract Objectives We investigated coronavirus disease 2019 (COVID-19) vaccine safety in pregnant and breastfeeding women with autoimmune diseases (AID) in the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. Methods Delayed-onset (>7 days) vaccine-related adverse events (AE), disease flares and AID-related treatment modifications were analysed upon diagnosis of AID vs healthy controls (HC) and the pregnancy/breastfeeding status at the time of at least one dose of vaccine. Results Among the 9201 participants to the self-administered online survey, 6787 (73.8%) were women. Forty pregnant and 52 breastfeeding patients with AID were identified, of whom the majority had received at least one dose of COVID-19 vaccine (100% and 96.2%, respectively). AE were reported significantly more frequently in pregnant than in non-pregnant patients (overall AE 45% vs 26%, P = 0.01; minor AE 40% vs 25.9%, P = 0.03; major AE 17.5% vs 4.6%, P < 0.01), but no difference was found in comparison with pregnant HC. No difference was observed between breastfeeding patients and HC with respect to AE. Post-vaccination disease flares were reported by 17.5% of pregnant and 20% of breastfeeding patients, and by 18.3% of age- and disease-matched non-pregnant and non-breastfeeding patients (n = 262). All pregnant/breastfeeding patients who experienced a disease flare were managed with glucocorticoids; 28.6% and 20% of them required initiation or change in immunosuppressants, respectively. Conclusion This study provides reassuring insights into the safety of COVID-19 vaccines administered to women with AID during the gestational and post-partum periods, helping overcome hesitant attitudes, as the benefits for the mother and for the fetus by passive immunization appear to outweigh potential risks.

Abstract Background Vitamin D supplementation is common practice for neonates and infants due to limited stores of vitamin D at birth. Although not commonly encountered, vitamin D toxicity can occur due to over-supplementation. However, toxic concentrations are often not included in method validation experiments, and assays often are not validated in the neonatal population. Methods We compared serial 25 hydroxy vitamin D [25(OH)D] measurements in pre-term neonates receiving 25(OH)D supplementation and identified 12 patients wherein concentrations of 25(OH)D were above 50 ng/mL (125 nM) that required additional investigations as the 25(OH)D results did not match the clinical picture. Available samples were compared across 4 immunoassay platforms (LIAISON XL, Roche Cobas e602, Abbott Alinity i, and Siemens Centaur XP) and LC–MS/MS. Results Concentrations of 25(OH)D observed on one individual immunoassay platform (LIAISON XL) fluctuated substantially between subsequent blood draws in select neonates with elevated concentrations. Serum samples from these patients showed variable agreement between LC–MS/MS and other immunoassay platforms. These fluctuations were not explained by the presence of 3-epimer-25(OH)D or 24,25(OH)2D. Conclusions Although we were unable to identify a cause for the variable elevated results, our findings suggest that neonatal 25(OH)D measurements alone should not be used for assessment of nutritional monitoring, and that clinical correlation and other laboratory parameters including ionized calcium should be considered.

Objectives: To report the results of a rigorous quality control (QC) process in the grading of total mesorectal excision (TME) specimens during a multicenter prospective phase 2 trial of transanal TME. Background: Grading of TME specimens is based on the macroscopic assessment of the mesorectum and standardized through synoptic pathology reporting. TME grade is a strong predictor of outcomes with incomplete (IC) TME associated with increased rates of local recurrence relative to complete or near complete (NC) TME. Although TME grade serves as an endpoint in most rectal cancer trials, in protocols incorporating centralized review of TME specimens for quality assurance, discordance in grading and the management thereof has not been previously described. Methods: A phase 2 prospective transanal TME trial was conducted from 2017 to 2022 across 11 North American centers with TME quality as the primary study endpoint. QC measures included (1) training of site pathologists in TME protocols, (2) blinded grading of de-identified TME specimen photographs by central pathologists, and (3) reconciliation of major discordance before trial reporting. Cohen Kappa statistic was used to assess agreement in grading. Results: Overall agreement in grading of 100 TME specimens between site and central reviewer was rated as fair, (κ = 0.35; 95% CI: 0.10–0.61; P < 0.0001). Concordance was noted in 54%, with minor and major discordance in 32% and 14% of cases, respectively. Upon reconciliation, 13/14 (93%) major discordances were resolved. Pre versus postreconciliation rates of complete or NC and IC TME are 77%/16% and 7% versus 69%/21% and 10%. Reconciliation resulted in a major upgrade (IC–NC; N = 1) or major downgrade (NC/C–IC, N = 4) in 5 cases overall (5%). Conclusions: A 14% rate of major discordance was observed in TME grading between the site and central reviewers. The resolution resulted in a major change in final TME grade in 5% of cases, which suggests that reported rates or TME completeness are likely overestimated in trials. QC through a central review of TME photographs and reconciliation of major discordances is strongly recommended.

AbstractBackgroundFractional carbon dioxide (CO2) laser resurfacing is used successfully for facial rejuvenation. Post procedure skincare is a variable that influences downtime caused by pain/tenderness, erythema, crusting, and bruising.AimsThe primary objective of this pilot study was to demonstrate the benefits of human platelet extract (HPE) (plated)™ CALM Serum, a new topical cosmetic product, following fractionated CO2 ablative laser resurfacing treatment to the entire face versus standard of care.MethodsIn a single‐center, randomized, evaluator‐blinded pilot study, a total of 18 subjects were randomized into two groups, CO2 facial resurfacing followed by post‐procedural standard of care (Stratacel silicone gel) or CO2 facial resurfacing with the addition of HPE renewosomes in the CALM Serum.ResultsCALM Serum demonstrated statistically significant less crusting at Day 10 compared to the control group (p = 0.0193) with less downtime in the first 14 days (p = 0.03). Subjects treated with CALM Serum had statistically significant brighter appearing skin at 14 days (p = 0.007) and more youthful looking skin on Days 14 and 30 (p = 0.003 and 0.04, respectively).ConclusionsThis study demonstrates that Renewosome™ technology provides statistically significant post‐laser clinical recovery over silicone gel for reducing crusting, and downtime. Subjects reported less diary days of symptoms of pain/tenderness, redness, crusting/flaking, bruising, and itching in the first 14 days compared to the control group. CALM also demonstrated statistically significant improvements in brighter and more youthful appearing skin. CALM is safe and well tolerated.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with a likely oligogenic etiology, but our understanding of the genetic complexities and pathogenic mechanisms leading to HLHS is limited. We performed whole genome sequencing (WGS) on 183 HLHS patient-parent trios to identify candidate genes, which were functionally tested in the Drosophila heart model. Bioinformatic analysis of WGS data from an index family of a HLHS proband born to consanguineous parents prioritized 9 candidate genes with rare, predicted damaging homozygous variants. Of them, cardiac-specific knockdown (KD) of mitochondrial MICOS complex subunit dCHCHD3/6 resulted in drastically compromised heart contractility, diminished levels of sarcomeric actin and myosin, reduced cardiac ATP levels, and mitochondrial fission-fusion defects. These defects were similar to those inflicted by cardiac KD of ATP synthase subunits of the electron transport chain (ETC), consistent with the MICOS complex’s role in maintaining cristae morphology and ETC assembly. Five additional HLHS probands harbored rare, predicted damaging variants in CHCHD3 or CHCHD6 . Hypothesizing an oligogenic basis for HLHS, we tested 60 additional prioritized candidate genes from these patients for genetic interactions with CHCHD3/6 in sensitized fly hearts. Moderate KD of CHCHD3/6 in combination with Cdk12 (activator of RNA polymerase II), RNF149 ( goliath , E3 ubiquitin ligase), or SPTBN1 ( β-Spectrin, scaffolding protein) caused synergistic heart defects, suggesting the likely involvement of diverse pathways in HLHS. Further elucidation of novel candidate genes and genetic interactions of potentially disease-contributing pathways is expected to lead to a better understanding of HLHS and other CHDs.

Background and Objectives: Social distancing and quarantine requirements imposed during the COVID-19 pandemic necessitated remote training in many learning situations that formerly focused on traditional in-person training. In this context, we developed an adaptive approach to teaching laceration repair remotely while allowing for synchronous instruction and feedback. Methods: In April 2020, 35 family medicine residents from 4 programs in the Midwest United States participated in a real-time, remotely-delivered, 2-hour virtual procedure workshop of instruction in suture techniques for laceration repair. Paired-sample t tests compared scores of learner self-confidence obtained during pre- and posttests. We interpreted short-answer responses with a mixed-methods analysis. Residents submitted photos and videos of suture techniques and received formative feedback based on a predefined rubric. Results: All residents completed the pre- and posttests. The posttest scores for self-confidence across the participants showed significant improvement for all suture techniques. Of the 67 short-answer responses, 38 responses (56.7%) were positive; 9 (13.4%) negative; 8 (11.9%) neutral; and 12 (17.9%) a combination of positive and negative. The workshop was rated by 34 residents (97.1%) as either “about the same as prior training experiences,” “better than prior training experiences,” or “much better than prior training experiences.” Conclusion: Learners reported that a remotely-delivered, real-time, synchronous suture technique workshop was a valuable experience. Further research is needed to establish the efficacy of this platform to promote procedural competence.