Endoscopic Versus Open Surgical Intervention for Congenital Laryngeal Webs: A Systematic Review and Meta-Analysis.

OBJECTIVES: To examine and compare the outcomes of various surgical interventions for congenital laryngeal webs in terms of avoidance of tracheostomy, rate of decannulation, web recurrence, revision surgery, and mortality in children. DATA SOURCES: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted on December 10, 2021, using a comprehensive search in PubMed, Web of Science, Cochrane library, and Embase with no date restriction. REVIEW METHODS: Articles on surgical intervention for congenital laryngeal webs in pediatric (<18 years) patients were included in the analysis. Articles including acquired laryngeal webs, no surgical intervention, or exclusively adult population were excluded. RESULTS: 9027 articles were reviewed, 24 articles met the inclusion criteria and 126 patients were included. In patients with Grades I and II webs, there was no significant difference in rates of tracheostomy or decannulation, between endoscopic (100%) versus open approach (100%). For Grades III and IV webs, 96% of patients who received open surgery were decannulated or avoided tracheostomy compared to 84% of those managed endoscopically (p = 0.081). There were significantly lower rates of revision surgery in the open group compared to the endoscopic group (77.8% vs 30.9%, p = 0.008). CONCLUSION: This study showed no difference in rates of tracheostomy, decannulation, web recurrence, revision, or mortality between endoscopic and open approaches for the treatment of Grades I and II webs. For Grades III and IV, open surgical techniques achieved a lower revision rate. Results should be interpreted in light of associated increased morbidity with open procedures.

Molecular cytogenetic characterization of partial trisomy of the long arm of chromosome 11 in a patient with multiple congenital anomalies.

BACKGROUND: Partial trisomy of the long arm of chromosome 11 is a rare cytogenetic abnormality. It has been characterized by variable sized duplications that lead to a range of phenotypes including growth retardation, developmental delay/intellectual disability, and distinctive craniofacial abnormalities. Congenital heart defects, skeletal abnormalities, urogenital anomalies, and hypotonia are found in some affected individuals. METHODS: We describe a 16-year-old patient presented with most of the hallmark phenotypes of trisomy 11q syndrome as well as exhibiting symptoms of hearing loss, seizures, and abnormal endocrinological and ophthalmological findings. Routine chromosome analysis and subsequent chromosomal microarray analysis (CMA) were performed to detect genetic abnormalities in this patient. RESULTS: We identified an abnormal male karyotype with a derivative chromosome 4 due to an unbalanced translocation between chromosomes 4 and chromosome 11. The CMA results revealed a 56 Mb duplication of chromosome 11q14.1-qter and a 874 Kb terminal deletion of the short arm of chromosome 4. CONCLUSION: A genomic imbalance resulting in partial trisomy 11q was found in a patient with multiple congenital anomalies. We compared the phenotypes of all known "pure" trisomy 11q cases in the literature and find that trisomy 11q23-qter is both recurrent and the most common cytogenetic abnormality found in the reported cases. It is associated with the core features of trisomy 11q syndrome.

The impact of standardized huddle tools on case duration in pediatric microlaryngoscopy/bronchoscopy.

OBJECTIVE: Equipment necessary to perform pediatric microlaryngoscopy/bronchoscopy (MLB) varies considerably depending on the selected interventions. In procedures with equipment variability, surgical case length may be increased due to the need to procure items intraoperatively. We hypothesized that use of standardized huddle tools listing necessary equipment would be associated with a shortened case duration in MLB. METHODS: As part of a quality improvement initiative at our academic, tertiary care pediatric hospital, a standardized huddle sheet was created that listed options of equipment for MLB. Listed items included telescope/bronchoscope size, laryngoscope selection, interventional equipment, suspension, microscopes, and topical medications. The tool was completed by otolaryngology and shared with the circulating nurse at the beginning of the day so equipment needs could be anticipated. The tool was introduced to staff in November 2017 and to trainees in February 2018. To assess intervention impact, monthly median surgical case duration and room turnover time were retrospectively tracked using control chart analysis from March 2017 to June 2019. RESULTS: At baseline, the centerline case duration was 49 min. Two months following introduction of the huddle sheet to trainees, the centerline duration decreased to 43 min. This change was sustained throughout the period studied. No changes in room turnover time were observed during this period. CONCLUSIONS: Standardized huddle tool use prior to MLB was associated with a median decrease of 6 min of operating room time without a change in operating room turnover time. Use of similar tools in procedures with significant equipment variability may be beneficial.

Ultrasound-Guided Lateral Abdominal Wall Botulinum Toxin Injection Before Ventral Hernia Repair: A Review for Radiologists.

Preoperative ultrasound-guided lateral abdominal wall botulinum toxin injection is a promising method for improving patient outcomes and reducing recurrence rates after ventral hernia repair. A review of the literature demonstrates variability in the procedural technique, without current standardization of protocols. As radiologists may be increasingly asked to perform ultrasound-guided botulinum toxin injections of the lateral abdominal wall, familiarity with the procedure and current literature is necessary.

Roughened graphite biointerfaced with P450 liver microsomes: Surface and electrochemical characterizations.

Low-cost, voltage-driven biocatalytic designs for rapid drug metabolism assay, chemical toxicity screening, and pollutant biosensing represent considerable significance for pharmaceutical, biomedical, and environmental applications. In this study, we have designed biointerfaces of human liver microsomes with various roughened, high-purity graphite disk electrodes to study electrochemical and electrocatalytic properties. Successful spectral and microscopic characterizations, direct bioelectronic communication, direct electron-transfer rates from the electrode to liver microsomal enzymes, microsomal heme-enzyme specific oxygen reduction currents, and voltage-driven diclofenac hydroxylation (chosen as the probe reaction) are presented.

Analysis of novel domain-specific mutations in the zebrafish ndr2/cyclops gene generated using CRISPR-Cas9 RNPs.

Nodal-related protein (ndr2) is amember of the transforming growth factor type ß superfamily of factors and is required for ventral midline patterning of the embryonic central nervous system in zebrafish. In humans, mutations in the gene encoding nodal cause holoprosencephaly and heterotaxy. Mutations in the ndr2 gene in the zebrafish (Danio rerio) lead to similar phenotypes, including loss of the medial floor plate, severe deficits in ventral forebrain development and cyclopia. Alleles of the ndr2 gene have been useful in studying patterning of ventral structures of the central nervous system. Fifteen different ndr2 alleles have been reported in zebrafish, of which eight were generated using chemical mutagenesis, four were radiation-induced and the remaining alleles were obtained via random insertion, gene targeting (TALEN) or unknown methods. Therefore, most mutation sites were random and could not be predicted a priori. Using the CRISPR-Cas9 system from Streptococcus pyogenes, we targeted distinct regions in all three exons of zebrafish ndr2 and observed cyclopia in the injected (G0) embryos.We show that the use of sgRNA-Cas9 ribonucleoprotein (RNP) complexes can cause penetrant cyclopic phenotypes in injected (G0) embryos. Targeted polymerase chain reaction amplicon analysis using Sanger sequencing showed that most of the alleles had small indels resulting in frameshifts. The sequence information correlates with the loss of ndr2 activity. In this study, we validate multiple CRISPR targets using an in vitro nuclease assay and in vivo analysis using embryos. We describe one specific mutant allele resulting in the loss of conserved terminal cysteine-coding sequences. This study is another demonstration of the utility of the CRISPR-Cas9 system in generating domain-specific mutations and provides further insights into the structure-function of the ndr2 gene.

Self-reported Black race predicts significant prostate cancer independent of clinical setting and clinical and socioeconomic risk factors.

INTRODUCTION AND OBJECTIVE: Studies have linked Black race to prostate cancer (CaP) risk but most fail to account for established risk factors such as 5-ARI use, prostate volume, socioeconomic status, and hospital setting. We assess whether Black race remains associated with CaP and Gleason ≥3 + 4 CaP, after adjusting for clinical setting and socioeconomic and clinical factors at prostate biopsy, with a focus on men aged 40-54 years, who may be excluded from current screening guidelines. METHODS: We recruited 564 men age 40-79 undergoing initial prostate biopsy for abnormal PSA or digital rectal examination (DRE) from three publicly funded and two private hospitals from 2009-2014. Univariate and multivariate analyses examined the associations between hospital type, race, West African Ancestry (WAA), clinical, and sociodemographic risk factors with CaP diagnosis and Gleason ≥3 + 4 CaP. Given changes in CaP screening recommendations, we also assess the multivariate analyses for men aged 40-54. RESULTS: Black and White men had similar age, BMI, and prostate volume. Black men had higher PSA (8.10 ng/mL vs. 5.63 ng/mL) and PSA density (0.22 ng/mL/cm3 vs. 0.15 ng/mL/cm3, all p < 0.001). Blacks had higher frequency of CaP (63.1% vs. 41.5%, p<0.001) and Gleason ≥3+4 CaP relative to Whites in both public (27.7% vs 11.6%, p<0.001) and private (48.4% vs 21.6%, p = 0.002) settings. In models adjusted for age, first degree family history, prostate volume, 5-ARI use, hospital type, income, marital and educational status, Black race was independently associated with overall CaP diagnosis (OR = 2.13, p = 0.002). There was a significant multiplicative interaction with Black race and abnormal DRE for Gleason ≥3 + 4 CaP (OR = 2.93, p = 0.01). WAA was not predictive of overall or significant CaP among Black men. Black race (OR = 5.66, p = 0.02) and family history (OR = 4.98, p = 0.01) were independently positively associated with overall CaP diagnosis for men aged 40 to 54. CONCLUSIONS: Black race is independently associated with CaP and Gleason ≥3+4 CaP after accounting for clinical and socioeconomic risk factors including clinical setting and WAA, and has a higher odds ratio of CaP diagnosis in younger men. Further investigation into optimizing screening in Black men aged 40 to 54 is warranted.

Active cathepsins B, L, and S in murine and human pancreatitis.

Cathepsins regulate premature trypsinogen activation within acinar cells, a key initial step in pancreatitis. The identity, origin, and causative roles of activated cathepsins in pancreatic inflammation and pain are not defined. By using a near infrared-labeled activity-based probe (GB123) that covalently modifies active cathepsins, we localized and identified activated cathepsins in mice with cerulein-induced pancreatitis and in pancreatic juice from patients with chronic pancreatitis. We used inhibitors of activated cathepsins to define their causative role in pancreatic inflammation and pain. After GB123 administration to mice with pancreatitis, reflectance and confocal imaging showed significant accumulation of the probe in inflamed pancreas compared with controls, particularly in acinar cells and macrophages, and in spinal cord microglia and neurons. Biochemical analysis of pancreatic extracts identified them as cathepsins B, L, and S (Cat-B, Cat-L, and Cat-S, respectively). These active cathepsins were also identified in pancreatic juice from patients with chronic pancreatitis undergoing an endoscopic procedure for the treatment of pain, indicating cathepsin secretion. The cathepsin inhibitor K11777 suppressed cerulein-induced activation of Cat-B, Cat-L, and Cat-S in the pancreas and ameliorated pancreatic inflammation, nocifensive behavior, and activation of spinal nociceptive neurons. Thus pancreatitis is associated with an increase in the active forms of the proteases Cat-B, Cat-L, and Cat-S in pancreatic acinar cells and macrophages, and in spinal neurons and microglial cells. Inhibition of cathepsin activation ameliorated pancreatic inflammation and pain. Activity-based probes permit identification of proteases that are predictive biomarkers of disease progression and response to therapy and may be useful noninvasive tools for the detection of pancreatic inflammation.