Patient and Process Outcomes among Pediatric Patients Undergoing Appendectomy during the COVID-19 Pandemic: An International Retrospective Cohort Study.

BACKGROUND: COVID-19 forced healthcare systems to make unprecedented changes in clinical care processes. The authors hypothesized that the COVID-19 pandemic adversely impacted timely access to care, perioperative processes, and clinical outcomes for pediatric patients undergoing primary appendectomy. METHODS: A retrospective, international, multicenter study was conducted using matched cohorts within participating centers of the international PEdiatric Anesthesia COVID-19 Collaborative (PEACOC). Patients younger than 18 yr old were matched using age, American Society of Anesthesiologists Physical Status, and sex. The primary outcome was the difference in hospital length of stay of patients undergoing primary appendectomy during a 2-month period early in the COVID-19 pandemic (April to May 2020) compared with prepandemic (April to May 2019). Secondary outcomes included time to appendectomy and the incidence of complicated appendicitis. RESULTS: A total of 3,351 cases from 28 institutions were available with 1,684 cases in the prepandemic cohort matched to 1,618 in the pandemic cohort. Hospital length of stay was statistically significantly different between the two groups: 29 h (interquartile range: 18 to 79) in the pandemic cohort versus 28 h (interquartile range: 18 to 67) in the prepandemic cohort (adjusted coefficient, 1 [95% CI, 0.39 to 1.61]; P < 0.001), but this difference was small. Eight centers demonstrated a statistically significantly longer hospital length of stay in the pandemic period than in the prepandemic period, while 13 were shorter and 7 did not observe a statistically significant difference. During the pandemic period, there was a greater occurrence of complicated appendicitis, prepandemic 313 (18.6%) versus pandemic 389 (24.1%), an absolute difference of 5.5% (adjusted odds ratio, 1.32 [95% CI, 1.1 to 1.59]; P = 0.003). Preoperative SARS-CoV-2 testing was associated with significantly longer time-to-appendectomy, 720 min (interquartile range: 430 to 1,112) with testing versus 414 min (interquartile range: 231 to 770) without testing, adjusted coefficient, 306 min (95% CI, 241 to 371; P < 0.001), and longer hospital length of stay, 31 h (interquartile range: 20 to 83) with testing versus 24 h (interquartile range: 14 to 68) without testing, adjusted coefficient, 7.0 (95% CI, 2.7 to 11.3; P = 0.002). CONCLUSIONS: For children undergoing appendectomy, the COVID-19 pandemic did not significantly impact hospital length of stay.

Prevalence of COVID-19 and Risk Factors for Infection Among Pediatric Anesthesia Patients: A Report From the PEACOC Research Network.

BACKGROUND: The Pediatric Anesthesia COVID-19 Collaborative (PEACOC) is a research network to advance the care of children during the pandemic. Here we calculate the prevalence of coronavirus disease 2019 (COVID-19) among children undergoing anesthesia, look at prevalence in the population data from the Centers for Disease Control and Prevention (CDC), and assess independent risk factors for infection. METHODS: This was a multicenter, retrospective, observational study. Children aged 28 days to 18 years scheduled for anesthesia services at 12 centers requiring universal COVID-19 testing from March 29, 2020 to June 30, 2020 were included. COVID-19 positivity rates among those tested were plotted and trends were assessed using the Cochran Armitage test of trend. Independent risk factors were explored using multivariable logistic regression. RESULTS: Data were collected and analyzed on 33,320 anesthesia encounters including 265 children with COVID-19. Over the study period, the rates of infections in the pediatric anesthesia population did not demonstrate a significant trend. In the general population, there was a significant downward trend in infection rates ( P < .001). In exploratory analysis, multivariable risk factors for a COVID-19 positive test were Black/African American race, Hispanic ethnicity, American Society of Anesthesiologists (ASA) physical status III or above, overweight and obese body mass index (BMI), orthopedic cases, abdominal cases, emergency cases, absence of injury and trauma, and West region (all P < .05). CONCLUSIONS: Rates of COVID-19 in pediatric anesthesia patients were consistently lower than in the general population. Independent risk factors of a positive test for children were identified. This is the first time universal testing for a single infectious disease was undertaken on a wide scale. As such, the association of infection with surgical case type or emergency case status is unprecedented.

A retrospective analysis of severe intraoperative respiratory compliance changes during ophthalmic arterial chemosurgery for retinoblastoma.

BACKGROUND AND OBJECTIVES: Ophthalmic arterial chemosurgery for retinoblastoma has been associated with intraoperative decreases in respiratory compliance. Through the analysis of data from computerized records, we objectively defined severe respiratory compliance events and correlated them with demographic and clinical information in patients undergoing this procedure. METHODS: Data were collected from ophthalmic arterial chemosurgery cases from 2006 to 2013. Intraoperative PIP, PEEP, TV, SpO2 , and EtCO2 were analyzed. Compliance changes, desaturations, decreases in EtCO2 , and clinical outcomes were assessed. RESULTS: Respiratory compliance decreases with a bimodal distribution. Severe events were defined as exhibiting a minimum compliance decrease of 40%. Seventy-eight of 122 children (64%) experienced a severe compliance event during at least one treatment, and it occurred in 137/468 cases (29%). A subset of 94 children had complete or at least the first three records. The incidence of a severe respiratory compliance event in this subgroup was 17/94 (18%) on the first and 84/261 (32%) on subsequent procedures. The probability of developing a severe respiratory compliance event on a subsequent procedure was 0.40 if the child developed it on the first procedure, 0.30 if he did not; this difference was not significant. The incidence of desaturation below 90% with severe respiratory compliance events was 0.20; the incidence of a 30% drop in EtCO2 was 0.34. No morbidity, no extended recovery, and no admissions were associated with intraoperative severe respiratory compliance events. We found no correlation between history, age, sex, weight or allergies, and intraoperative severe respiratory compliance events. CONCLUSIONS: Here, most patients experienced a severe respiratory compliance event during at least one of their procedures. Overall incidence was 29% and was more likely on subsequent procedures. A severe respiratory compliance event at the initial procedure was poorly predictive of its occurrence on subsequent procedures. No morbidity was associated with intraoperative severe respiratory compliance events.

Predictive value of cytologic atypia in indeterminate thyroid fine-needle aspirate biopsies.

BACKGROUND: Fine-needle aspiration (FNA) biopsies are the most accurate method for diagnosis of thyroid nodules. Unfortunately, biopsies are indeterminate 15-30% of the time and surgery is thus required for a definitive diagnosis. We aimed to determine whether specific descriptors of cytologic atypia mentioned in indeterminate FNA reports were associated with malignancy on final histopathology. METHODS: Retrospective review of 1000 surgery patients identified 466 indeterminate FNA lesions that underwent either a hemi- or total thyroidectomy between 1998 and 2009. We screened FNA reports for specific descriptors of nuclear atypia. Univariate and multivariate analyses were performed to evaluate the independent effect of cytologic atypia descriptors on the risk of malignancy. RESULTS: Nuclear atypia on FNA conferred a risk of malignancy of 42% (P < 0.0001). Risk of malignancy increased from 17% for zero descriptors to 81.2% when four or more descriptors of atypia were described. Nuclear grooves and inclusions together conferred a risk of malignancy, specificity, and false positive rate of 79.3%, 98.2% and 1.8% respectively. CONCLUSIONS: The presence of four or more descriptors of cytologic atypia or the presence of both nuclear inclusions and grooves together confers a high risk of malignancy on final histopathology and a low false positive rate. These findings should be taken into consideration when interpreting FNA reports and total thyroidectomy should be considered for those patients at higher risk.

Selenium decreases thyroid cancer cell growth by increasing expression of GADD153 and GADD34.

Selenium (Se) supplementation is reported to decrease the incidence and total mortality of cancer. Whereas in vitro and in vivo studies have shown a decrease in prostate, lung, and liver cancers, this has not been shown in thyroid cancer. ARO (anaplastic), NPA (BRAF positive papillary), WRO (BRAF negative papillary), and FRO (follicular) cells treated with 150 microM seleno-l-methionine (SM) were assessed for viability at 24, 48, and 72 h. Treated FRO cells were examined for cell cycle using flow cytometry, for apoptosis using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, and for gene expression using microarray. Genes identified as upregulated were confirmed by real-time PCR (RT-PCR) and proteins by Western blot analysis. SM treatment significantly decreased the proliferation of all cell lines. TUNEL assay showed no evidence of apoptosis, and flow cytometry showed a significant cell-cycle arrest in S (271% increase, P = 0.006) and G2/M (61% increase, P = 0.002) compared to control. Microarray revealed 21 differentially expressed genes with greater than twofold change. A relative overexpression of growth arrest and DNA damage inducible (GADD)34 and GADD153 in treated cells was confirmed with RT-PCR and Western blot. SM inhibits thyroid cancer cell proliferation through a time dependent upregulation of the GADD family of genes and arrest in S and G2/M phases of the cell cycle. This is the first report of selenium induced inhibition of thyroid cancer cell growth.

Molecular markers in thyroid cancer diagnostics.

Although fine-needle aspiration biopsy (FNA) remains the mainstay of the preoperative workup of thyroid nodules, it does not provide a diagnosis in up to 20% of nodules. This group of indeterminate lesions, including lesions with cellular atypia, suspicious cytology, and demonstrating a follicular pattern, provides one of the greatest challenges to researchers in thyroid cancer today. Over the last 2 decades, considerable work has been done to find molecular markers to resolve this diagnostic dilemma. This article explores some of the markers including galectin-3, HBME-1, BRAF, RET/PTC, PAX8-PPARgamma, hTERT, telomerase, miRNA, and microarray and multigene assays. Although no one marker has proven to be a panacea, several combinations of markers have shown great promise as an adjunct to FNA.

Identification of borderline thyroid tumors by gene expression array analysis.

BACKGROUND: A subset of follicular lesions of the thyroid is encapsulated similar to follicular adenomas but with partial nuclear features suggestive of papillary thyroid carcinoma (PTC), raising the possibility of biologically borderline tumors. METHODS: Gene expression profiling and advanced significance analyses were performed on 50 histologically unequivocal benign and malignant tumors, and a list of 61 differentially expressed genes was generated. By using this 61-gene list, unsupervised hierarchical and K-means cluster analyses were performed on 40 additional tumors, including 15 histologically borderline tumors, 11 benign tumors, and 14 PTCs. RESULTS: Analysis revealed 3 distinct tumor groups-benign, malignant, and intermediate. Tumors in the intermediate group (n = 15) were mostly histologic borderline tumors and had an expression profile overlapping with the benign and malignant groups. Twenty-seven genes were expressed differentially between the benign and intermediate groups, including the cyclic AMP response element-binding protein/p300-interactivator with glutamic acid/aspartic acid-rich carboxy-terminal domain 1 or CITED1 gene and the fibroblast growth factor receptor 2 or FGFR2 gene. Fourteen genes were expressed differentially between the intermediate group and malignant tumors, notably overexpression of the met proto-oncogene and of the high-mobility group adenine/thymine-hook 2 or HMGA2 gene in malignancies. Mutations of the v-raf murine sarcoma viral oncogene homolog B1 or BRAF gene were identified in 4 of 14 malignant tumors but not in benign or intermediate tumors. Patients who had either histologically or molecularly borderline tumors did not have metastasis or recurrences. CONCLUSIONS: Gene expression profiling supported the finding that encapsulated thyroid follicular lesions with partial nuclear features of PTC are biologically borderline tumors that are distinct molecularly from benign and malignant tumors.

Papillary thyroid carcinoma and microcarcinoma: is there a need to distinguish the two?

BACKGROUND: The clinical significance of papillary thyroid microcarcinoma (PTMC) tumors < or =1 cm is widely debated. The objective of this study was to compare conventional papillary thyroid carcinoma (PTC) (tumors >1 cm) to PTMC and assess for differences in tumor characteristics and patient outcome. METHODS: A retrospective chart review of patients with PTC or PTMC who were followed for a minimum of 3 years postoperatively and managed at a single academic institute was performed. RESULTS: Of 202 patients in the study, 66 (32.7%) had PTMC and 136 (67.3%) had conventional PTC. Patient and tumor characteristics including tumor multifocality, extrathyroidal extension, angiolymphatic invasion, and lymph node metastasis were similar between both groups. Twenty-one percent of the PTMC tumors were discovered incidentally. Patients with conventional PTC were significantly more likely to undergo treatment with radioactive iodine therapy compared to PTMC patients (86.4% vs. 66.7%, respectively, p < 0.003). Disease recurrence was observed in 40 patients and was not statistically different between the two groups; 11 (16.7%) in PTMC and 29 (21.3%) in conventional PTC, p = 0.57. Within the PTMC group, tumors of patients that recurred were significantly larger than those who remained disease free (8.1 mm vs. 6.4 mm, p < 0.05). None of the patients with incidental PTMC had disease recurrence. Angiolymphatic invasion was the only significant prognostic indicator of recurrence on multivariate analysis (p < 0.02). CONCLUSIONS: Nonincidental PTMC can have aggressive tumor features and disease recurrence similar to conventional PTC. These tumors should be managed like any other papillary thyroid malignancy.