Discordance of the pediatric surgeon's intraoperative assessment of pediatric appendicitis with the pathologists report

Background/Purpose

The nature and duration of postoperative treatment in children with appendicitis is largely defined by the surgeon's intraoperative assessment of the degree of disease. Therefore, misclassification of patients could result in either inadequate or excessive duration of treatment.

Materials/Methods

During the execution of an institutional review board-approved multicenter, randomized, prospective, single-blinded trial of laparoscopic versus open appendectomy in children, we tracked the attending pediatric surgeon's determination of the degree of appendicitis and compared it to the pathologists report. Postoperative care was determined, per protocol, by the surgeon's intraoperative classification. “Interval” appendectomies were excluded from the analysis. Statistical significance was analyzed using χ² analyses.

Results

A total of 133 patients were randomized into the open group, whereas 122 randomized to laparoscopy during the first 2 years of the study. The attending pediatric surgeons and pathologists were concordant in the determination of acute appendicitis in 90% of open patients and 93% of laparoscopic patients (P = not significant). When children were classified by the attending surgeon as having complicated appendicitis (gangrenous or ruptured), the concordance rate dropped to 38% and 52%, respectively (P = not significant). When open and laparoscopic patients were combined, the length of postoperative stay (LOS) of concordantly classified acute appendicitis patients was 35 ± 16 hours. Concordantly classified complicated appendicitis LOS was 118 ± 61 hours, and discordantly classified complicated appendicitis (pathology = acute) LOS was 85 ± 41 hours (P = .01). Wound infection rates in the concordant and discordant “complicated” appendicitis groups were 23% and 7%, respectively (P = .05).When the surgeons are grouped as “junior”(n = 2) and “senior” (n = 3), there is a trend toward greater concordance in the latter group (P = .08).

Conclusions

In the 2 institutions studied, the 5 pediatric surgeon's intraoperative classification of appendicitis correlated with the pathologist's reading in a high percentage of those patients labeled “acute” but in only approximately one half of those defined as “complicated.” These phenomena are independent of the operative approach but may correlate with surgeon experience. Interventions to improve the timeliness of pathologic diagnosis may improve the accuracy and efficiency of care of pediatric appendicitis.     

C1B domain peptide of protein kinase Cγ significantly suppresses growth of human colon cancer cells in vitro and in an in vivo mouse xenograft model through induction of cell cycle arrest and apoptosis

Two peptides derived from the C1B domain of protein kinase Cγ (PKCγ) were shown to associate with classical PKC isozymes and modulate their activities. These C1B peptides are designated C1B1 (amino acid residues 101-112) and C1B5 (residues 141-151). Since PKC enzyme activity is shown to be involved in colon cancer development, the effect of C1B peptides on the growth of various human colon cancer cell lines was examined in vitro and in vivo. Sub-micromolar to micromolar levels of both C1B peptides induced approximately 60-70% growth attenuation in multiple colon cancer cell lines in a soft agar tumor colony assay; however, C1B5 peptide was not cytotoxic to normal colon epithelial cells in two dimensional culture. The effect of C1B5 peptide on colony growth of COLO205 cells was reversed by treatment with the PKCα/β inhibitor, Ro-32-0432. C1B peptide treatment attenuated COLO205 cells via two mechanisms: 1) cell cycle arrest and 2) stimulation of apoptosis. This is evident in G 2 arrest and increases in levels of cleaved caspase 3 and p53 phosphorylated at serine 20. Intratumoral injection of C1B5 peptide (20 mg/kg/day, every three days) markedly attenuated the growth of subcutaneous xenografts of COLO205 cells in SCID mice by 76% compared with the control. Taken together, these results strongly suggest that C1B peptides have negligible effects on normal tissues but are potentially effective chemotherapeutic agents for colon cancer.     

Polysaccharide-based tissue adhesives for sealing corneal incisions

PURPOSE: To investigate the ability of a novel polysaccharide-based tissue adhesive to seal corneal incisions, and to determine the effect of the tissue adhesive on corneal endothelial cells. METHODS: A polysaccharide-based tissue adhesive composed of dextran aldehyde and star PEG amines was applied to a 5-mm corneal incision on an enucleated rabbit eye, and the leak pressure of the eye was measured. The tissue adhesive was additionally incubated in direct contact with bovine corneal endothelial cells to evaluate cytotoxicity. RESULTS: The polysaccharide-based tissue adhesive was successful in sealing corneal incisions to pressures of > 10 psi (500 mmHg). The tissue adhesive was non-cytotoxic to bovine corneal endothelial cells. CONCLUSIONS: Polysaccharide-based tissue adhesives are efficacious in sealing corneal wounds and are non-cytotoxic to corneal endothelial cells. Such adhesives represent a promising new technology for ophthalmic surgery.     

An approach for evaluating the effects of dietary fiber polysaccharides on the human gut microbiome and plasma proteome

Increases in snack consumption associated with Westernized lifestyles provide an opportunity to introduce nutritious foods into poor diets. We describe two 10-wk-long open label, single group assignment human studies that measured the effects of two snack prototypes containing fiber preparations from two sustainable and scalable sources; the byproducts remaining after isolation of protein from the endosperm of peas and the vesicular pulp remaining after processing oranges for the manufacture of juices. The normal diets of study participants were supplemented with either a pea- or orange fiber-containing snack. We focused our analysis on quantifying the abundances of genes encoding carbohydrate-active enzymes (CAZymes) (glycoside hydrolases and polysaccharide lyases) in the fecal microbiome, mass spectrometric measurements of glycan structures (glycosidic linkages) in feces, plus aptamer-based assessment of levels of 1,300 plasma proteins reflecting a broad range of physiological functions. Computational methods for feature selection identified treatment-discriminatory changes in CAZyme genes that correlated with alterations in levels of fiber-associated glycosidic linkages; these changes in turn correlated with levels of plasma proteins representing diverse biological functions, including transforming growth factor type β/bone morphogenetic protein-mediated fibrosis, vascular endothelial growth factor-related angiogenesis, P38/MAPK-associated immune cell signaling, and obesity-associated hormonal regulators. The approach used represents a way to connect changes in consumer microbiomes produced by specific fiber types with host responses in the context of varying background diets.

Advances in our understanding of the role of the gut microbiome in regulating many aspects of human physiology hold the promise of evolving our view of human nutrition by establishing mechanistic connections between the foods we consume and how they affect health status. One manifestation of this effort is a series of studies, performed on well-phenotyped cohorts, that seek to relate features of gut microbial community composition (organisms, genes), dietary practices, and pre- and postprandial cardiometabolic responses to test meals (1–4). A key question raised by these initiatives relates to the nature of the “bioactive” components of foods. Specifically, what are the nutrients utilized by various gut community members or microbiome-encoded metabolic pathways? What products are produced by biotransformation of these nutrients? How are these products linked to specific host physiologic (or pathophysiologic) processes?Plant-derived dietary fibers represent a “poster child” for these efforts and illustrate the formidable challenges faced. The health benefits of dietary fibers are widely known, as is their inadequate representation in Western diets. However, natural fibers are structurally complex and highly diverse. They contain numerous, typically undefined polysaccharide structures and largely unspecified protein, lipid, and small molecule constituents. Their composition varies as a function of their origin (food staple and cultivar), the different methods employed to recover them from these sources, as well as the different techniques used to incorporate them into processed foods with acceptable organoleptic properties (5). Moreover, analyzing the host effects of metabolism of different fibers is confounded by the fact that there is substantial intra- and interpersonal variation in microbiome configuration (6, 7).Snacking is becoming an ever more dominant feature of daily life worldwide and thus provides an opportunity to introduce nutritious ingredients, such as fibers, into diets. However, obtaining structure-activity relationships for specific fiber types and their corresponding targets in the gut community is foundational for designing snack foods that evoke and/or reinforce microbiome responses that are beneficial to the host.Degradation of dietary polysaccharides is a function primarily performed by bacterial carbohydrate-active enzymes (CAZymes). The gut microbiome harbors tens of thousands of CAZyme genes belonging to at least 136 glycoside hydrolase (GH) and 29 polysaccharide lyase (PL) families [extrapolated and updated from El Kaoutari et al. (8)]. In contrast, the human genome only contains 98 GH and no PL genes (9), of which <20% contribute to the processing of dietary glycans.In the current study, we test the effects of dietary supplementation with two snack food prototypes, one containing pea fiber and the other orange fiber, in two pilot studies of overweight and obese individuals consuming their normal, unrestricted diets. Our strategy was to focus on fiber-associated changes in the abundances of microbial GH and PL genes to determine whether responses to the pea or orange fiber prototypes in the gut microbiome and host are decipherable against a background of varying dietary practices and starting microbiome configurations. Higher order singular value decomposition (10) was utilized as a feature selection tool to identify treatment-discriminating changes in GH and PL gene representation. Mass spectrometric assays of the levels of fecal glycan structures (glycosidic linkages) were subsequently performed and the results were correlated with changes in the abundances of treatment-discriminating GH and PL genes with known or predicted substrate specificities. Our analysis concluded by measuring changes in levels of 1,305 plasma proteins in each study participant as a function of fiber treatment and applying computational tools to identify links between these microbiome and plasma proteome changes in response to fiber consumption. Our results provide an approach, using pilot human studies, for selecting specific fiber preparations, plus informative microbiome and host biomarkers, that can be advanced to proof-of-concept clinical trials which assess their capacity for precise manipulation of microbiome and host features.     

Burnout and well‐being in otolaryngology trainees: A systematic review

ObjectiveTo comprehensively review the recent published literature to characterize current trends of burnout and well‐being among otolaryngology trainees.MethodsStudy design: systematic review and meta‐analysis. A comprehensive literature review from 2000 to 2021 of studies related to otolaryngology resident burnout and well‐being, as well as the general topic of well‐being among surgical residents was completed. All included studies were summarized qualitatively. For the quantitative analysis, only articles reporting a Maslach burnout inventory (MBI), modified MBI or Mini‐Z‐ Burnout assessment were included.ResultsTwenty‐five articles were included in the qualitative summary and nine articles in the quantitative analysis. In the qualitative summary, trainees were reported to have increased levels of distress and emotional hardening compared to attending otolaryngologists. Total hours worked per week and female gender were associated with worsened well‐being. Residency program strategies to improve trainee well‐being include program‐sponsored wellness activities, dedicated wellness champions, and assistance with clerical burden. Implementation of protected nonclinical time has been shown to decrease burnout and increase well‐being among trainees. Moreover, formal trainee mentorship programs have also been shown to reduce trainee burnout and stress. In the quantitative analysis, rates of trainee burnout ranged from 29.7% to 86% with an overall trend towards reduced rates of burnout from 2006 to 2021. Utilizing a weighted average, the overall burnout among otolaryngology residents was 58.6%.ConclusionsRates of burnout remain high among otolaryngology trainees. Implementing formal mentorship programs and providing protected time during regular work hours appear to be effective tools to improve resident well‐being.