Management and Outcomes of Wilms Tumor With Suprarenal Intravascular Extension: A Pediatric Surgical Oncology Research Collaborative Study.

OBJECTIVE: The purpose of this study was to describe management and outcomes from a contemporary cohort of children with Wilms tumor complicated by inferior vena caval thrombus. BACKGROUND: The largest series of these patients was published almost 2 decades ago. Since then, neoadjuvant chemotherapy has been commonly used to manage these patients, and outcomes have not been reported. METHODS: Retrospective review of 19 North American centers between 2009 and 2019. Patient and disease characteristics, management, and outcomes were investigated and analyzed. RESULTS: Of 124 patients, 81% had favorable histology (FH), and 52% were stage IV. IVC thrombus level was infrahepatic in 53 (43%), intrahepatic in 32 (26%), suprahepatic in 14 (11%), and cardiac in 24 (19%). Neoadjuvant chemotherapy using a 3-drug regimen was administered in 82% and postresection radiation in 90%. Thrombus level regression was 45% overall, with suprahepatic level showing the best response (62%). Cardiopulmonary bypass (CPB) was potentially avoided in 67%. The perioperative complication rate was significantly lower after neoadjuvant chemotherapy [(25%) vs upfront surgery (55%); P =0.005]. CPB was not associated with higher complications [CPB (50%) vs no CPB (27%); P =0.08]. Two-year event-free survival was 93% and overall survival was 96%, higher in FH cases (FH 98% vs unfavorable histology/anaplastic 82%; P =0.73). Neither incomplete resection nor viable thrombus cells affected event-free survival or overall survival. CONCLUSIONS: Multimodal therapy resulted in excellent outcomes, even with advanced-stage disease and cardiac extension. Neoadjuvant chemotherapy decreased the need for CPB to facilitate resection. Complete thrombectomy may not always be necessary.

Intraoperative Identification of Thyroid and Parathyroid Tissues During Human Endocrine Surgery Using the MasSpec Pen.

Importance: Intraoperative identification of tissues through gross inspection during thyroid and parathyroid surgery is challenging yet essential for preserving healthy tissue and improving outcomes for patients. Objective: To evaluate the performance and clinical applicability of the MasSpec Pen (MSPen) technology for discriminating thyroid, parathyroid, and lymph node tissues intraoperatively. Design, Setting, and Participants: In this diagnostic/prognostic study, the MSPen was used to analyze 184 fresh-frozen thyroid, parathyroid, and lymph node tissues in the laboratory and translated to the operating room to enable in vivo and ex vivo tissue analysis by endocrine surgeons in 102 patients undergoing thyroidectomy and parathyroidectomy procedures. This diagnostic study was conducted between August 2017 and March 2020. Fresh-frozen tissues were analyzed in a laboratory. Clinical analyses occurred in an operating room at an academic medical center. Of the analyses performed on 184 fresh-frozen tissues, 131 were included based on sufficient signal and postanalysis pathologic diagnosis. From clinical tests, 102 patients undergoing surgery were included. A total of 1015 intraoperative analyses were performed, with 269 analyses subject to statistical classification. Statistical classifiers for discriminating thyroid, parathyroid, and lymph node tissues were generated using training sets comprising both laboratory and intraoperative data and evaluated on an independent test set of intraoperative data. Data were analyzed from July to December 2022. Main Outcomes and Measures: Accuracy for each tissue type was measured for classification models discriminating thyroid, parathyroid, and lymph node tissues using MSPen data compared to gross analysis and final pathology results. Results: Of the 102 patients in the intraoperative study, 80 were female (78%) and the median (IQR) age was 52 (42-66) years. For discriminating thyroid and parathyroid tissues, an overall accuracy, defined as agreement with pathology, of 92.4% (95% CI, 87.7-95.4) was achieved using MSPen data, with 82.6% (95% CI, 76.5-87.4) accuracy achieved for the independent test set. For distinguishing thyroid from lymph node and parathyroid from lymph node, overall training set accuracies of 97.5% (95% CI, 92.8-99.1) and 96.1% (95% CI, 91.2-98.3), respectively, were achieved. Conclusions and Relevance: In this study, the MSPen showed high performance for discriminating thyroid, parathyroid, and lymph node tissues intraoperatively, suggesting this technology may be useful for providing near real-time feedback on tissue type to aid in surgical decision-making.

Defining the Full Spectrum of Pediatric Firearm Injury and Death in the United States: It is Even Worse Than We Think.

OBJECTIVE: To characterize the full spectrum of pediatric firearm injury in the United States by describing fatal and nonfatal injury data epidemiology, vulnerable populations, and temporal trends. BACKGROUND: Firearm injury is the leading cause of death in children and adolescents in the United States. Nonfatal injury is critical to fully define the problem, yet accurate data at the national level are lacking. METHODS: A cross-sectional study combining national firearm injury data from the Centers for Disease Control (fatal) and the National Trauma Data Bank (nonfatal) between 2008 and 2019 for ages 0 to 17 years. Data were analyzed using descriptive and χ 2 comparisons and linear regression. RESULTS: Approximately 5000 children and adolescents are injured or killed by firearms each year. Nonfatal injuries are twice as common as fatal injuries. Assault accounts for the majority of injuries and deaths (67%), unintentional 15%, and self-harm 14%. Black youth suffer disproportionally higher injuries overall (crude rate: 49.43/million vs White, non-Hispanic: 15.76/million), but self-harm is highest in White youth. Children <12 years are most affected by nonfatal unintentional injuries, 12 to 14 years by suicide, and 15 to 17 years by assault. Nonfatal unintentional and assault injuries, homicides, and suicides have all increased significantly ( P < 0.05). CONCLUSIONS: This study adds critical and contemporary data regarding the full spectrum and recent trends of pediatric firearm injury in the United States and identifies vulnerable populations to inform injury prevention intervention and policy. Reliable national surveillance for nonfatal pediatric firearm injury is vital to accurately define and tackle this growing public health crisis.

Outcomes After Extracorporeal Life Support Cannulation in Pediatric Patients With Trisomy 13 and Trisomy 18.

BACKGROUND: Indications for extracorporeal life support (ECLS) have evolved and expanded, yet its use in trisomy 13 (T13) and trisomy 18 (T18) patients remains controversial. We reviewed the experience of the Extracorporeal Life Support Organization with ECLS in these patients to inform practice at our institution. METHODS: The Extracorporeal Life Support Organization registry was queried for all patients younger than 18 y with an International Classification of Diseases, Ninth Edition/Tenth Edition code for T13 or T18 from 2000 to 2018. Basic demographics, ECLS details, and clinical outcomes were recorded. Descriptive statistics were performed. RESULTS: Twenty-eight patients were identified (15 with T13; 13 with T18), representing 0.06% (28 of 46,901) of pediatric ECLS cannulations. The median weight was 3.5 kg (range, 1.4-13), and age at cannulation was 52 d (range, 0 d-6.8 y). Time on ECLS ranged from 13 to 478 h (median, 114). Cardiac defects were diagnosed in 19 (68%) patients, of which 13 (46%) underwent surgical repair. Median oxygenation index pre-ECLS was 45. Venoarterial cannulations accounted for 82% of patients, whereas 14% underwent venovenous cannulation. Overall survival to hospital discharge was 46% with 86% of patients experiencing one or more complications. There were no survivors when cannulation continued past 12 d. CONCLUSIONS: Although complications are frequent, the mortality rate in patients with T13 and T18 remains within the reported range for the general pediatric population. T13 and T18 alone should not be viewed as absolute contraindications to ECLS within the pediatric population but rather considered during the evaluation of a patient's potential candidacy.

Variation in surgical management of primary hyperparathyroidism in the US Department of Veterans Affairs healthcare system: A 15-year observational study.

BACKGROUND: Primary hyperparathyroidism is underdiagnosed and undertreated nationally despite the benefits of parathyroidectomy. However, the degree of hospital-level variation in the management of primary hyperparathyroidism is unknown. METHODS: We performed a national, retrospective study of Veterans with primary hyperparathyroidism using the Veterans Affairs Corporate Data Warehouse from January 2000 to September 2015. The objective was to characterize the extent of hospital-level variation in the use of parathyroidectomy for the management of primary hyperparathyroidism within a national, integrated healthcare system. Rate of parathyroidectomy in patients with primary hyperparathyroidism was stratified by (1) geographic region, (2) facility complexity level, (3) volume of parathyroidectomies per facility, and (4) frequency of parathyroid hormone testing in hypercalcemic patients. RESULTS: Among 47,158 Veterans with primary hyperparathyroidism, 6,048 (12.8%) underwent parathyroidectomy. Rates of parathyroidectomy were significantly higher in the Continental (17.0%) and Pacific (16.0%) regions than in other areas (11.4%, P < .01). The highest complexity referral centers had the highest rate of parathyroidectomy (13.6%) compared with all other facilities (12.1%, P < .01). Centers that performed the highest volume of parathyroidectomies were more likely to offer surgery (13.3%) than low volume centers (8.9%, P < .01). Facilities with higher frequency of parathyroid hormone testing among hypercalcemic patients were more likely to offer parathyroidectomy (15.2%) than those with the lowest parathyroid hormone testing frequency (12.6%, P < .01). CONCLUSION: Although there is notable variation in parathyroidectomy use for definitive treatment of primary hyperparathyroidism between Veterans Affairs facilities, parathyroidectomy rates are low across the entire system. Further research is needed to understand additional local contextual and other patient and clinician-level factors for the undertreatment of primary hyperparathyroidism to subsequently guide corrective interventions.

Preoperative metabolic classification of thyroid nodules using mass spectrometry imaging of fine-needle aspiration biopsies.

Thyroid neoplasia is common and requires appropriate clinical workup with imaging and fine-needle aspiration (FNA) biopsy to evaluate for cancer. Yet, up to 20% of thyroid nodule FNA biopsies will be indeterminate in diagnosis based on cytological evaluation. Genomic approaches to characterize the malignant potential of nodules showed initial promise but have provided only modest improvement in diagnosis. Here, we describe a method using metabolic analysis by desorption electrospray ionization mass spectrometry (DESI-MS) imaging for direct analysis and diagnosis of follicular cell-derived neoplasia tissues and FNA biopsies. DESI-MS was used to analyze 178 tissue samples to determine the molecular signatures of normal, benign follicular adenoma (FTA), and malignant follicular carcinoma (FTC) and papillary carcinoma (PTC) thyroid tissues. Statistical classifiers, including benign thyroid versus PTC and benign thyroid versus FTC, were built and validated with 114,125 mass spectra, with accuracy assessed in correlation with clinical pathology. Clinical FNA smears were prospectively collected and analyzed using DESI-MS imaging, and the performance of the statistical classifiers was tested with 69 prospectively collected clinical FNA smears. High performance was achieved for both models when predicting on the FNA test set, which included 24 nodules with indeterminate preoperative cytology, with accuracies of 93% and 89%. Our results strongly suggest that DESI-MS imaging is a valuable technology for identification of malignant potential of thyroid nodules.

Ideal timing of early cholecystectomy for acute cholecystitis: An ACS-NSQIP review.

BACKGROUND: Current guidelines fail to specify optimal timing of early cholecystectomy for acute cholecystitis. We hypothesized delaying operation past hospital day (HD) 2 would result in increased 30-day morbidity and mortality. METHODS: The ACS-NSQIP database was queried from 2012 to 2015 for all cholecystectomies for acute cholecystitis from HD 1-7. RESULTS: Delay in cholecystectomy to HD 3-7 was observed in 30% of patients with acute cholecystitis. Patients undergoing operation on HD 3-7 were older with higher rates of comorbidities (median 58yrs; 66%) than HD 1 (48yrs; 51%) or HD 2 (51yrs, p < 0.001; 55%, p < 0.001). Operations on HD 3-7 had increased 30-day mortality (1.0%) and morbidity (12%) in comparison to HD 1 (0.3%, 7%) or HD 2 (0.5%, p < 0.001; 8%, p < 0.001). On multivariable analysis, HD was an independent predictor of mortality (OR 1.15, 95% CI [1.04-1.26]). CONCLUSIONS: Acute cholecystitis should be treated with an urgent operation within 2 days of admission due to increased morbidity and mortality when delayed past HD 2.

Diagnosis and Management of Primary Hyperparathyroidism Across the Veterans Affairs Health Care System.

IMPORTANCE: Untreated primary hyperparathyroidism impairs quality of life and incurs substantial costs. Parathyroidectomy is a low-risk, high-success, definitive intervention. OBJECTIVES: To determine the appropriateness of diagnostic evaluation for primary hyperparathyroidism in patients with hypercalcemia and the use of parathyroidectomy for the treatment of primary hyperparathyroidism across the Veterans Affairs (VA) health care system. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of veterans with hypercalcemia and primary hyperparathyroidism was conducted from January 1, 2000, through September 30, 2015, using the VA Corporate Data Warehouse, a national electronic health record-based repository. The study included 371 370 veterans with chronic hypercalcemia and 47 158 veterans with biochemical evidence of primary hyperparathyroidism diagnosed by hypercalcemia, elevated serum parathyroid hormone levels, and near-normal serum creatinine levels. Statistical analysis was performed from April 21, 2017, to April 10, 2019. MAIN OUTCOMES AND MEASURES: The proportion of veterans with hypercalcemia who have parathyroid hormone levels evaluated, the proportion of veterans with hyperparathyroidism who are treated surgically, and the factors associated with parathyroidectomy using generalized linear latent and mixed model regression. RESULTS: Of 371 370 patients with chronic hypercalcemia, 86 887 (23.4%) received further testing with parathyroid hormone level. Of 47 158 patients meeting diagnostic criteria for primary hyperparathyroidism (42 737 men [90.6%] and 4421 women [9.4%]; mean [SD] age, 67.3 [11.8] years), 6048 (12.8%) underwent parathyroidectomy. Of 5793 patients with primary hyperparathyroidism presenting with a serum calcium level more than 1 mg/dL above the upper limit of normal, 1501 (25.9%) underwent parathyroidectomy. There was a decreasing trend in the use of parathyroidectomy over time. Factors positively associated with parathyroidectomy were nephrolithiasis (odds ratio [OR], 2.23; 95% CI, 1.90-2.61) and non-Hispanic white race/ethnicity (OR, 1.31; 95% CI, 1.17-1.46), while age (OR, 0.95; 95% CI, 0.95-0.96), Elixhauser Comorbidity Index score (OR, 0.76; 95% CI, 0.72-0.80), decreased estimated glomerular filtration rate (OR, 0.52; 95% CI, 0.45-0.60), and diagnosis of osteoporosis (OR, 0.65; 95% CI, 0.52-0.80) were inversely related to surgery. CONCLUSIONS AND RELEVANCE: From this study's findings, parathyroid hormone level is infrequently tested in patients with hypercalcemia, suggesting underdiagnosis of primary hyperparathyroidism. Patients meeting diagnostic criteria for primary hyperparathyroidism are undertreated with recommended parathyroidectomy. Similar gaps have previously been observed in non-VA care of primary hyperparathyroidism, suggesting the need for a systematic evaluation of barriers to diagnosis and treatment that informs intervention design.

Population-level outcomes of early versus delayed appendectomy for acute appendicitis using the American College of Surgeons National Surgical Quality Improvement Program.

BACKGROUND: The optimal timing of appendectomy for acute appendicitis has been analyzed with mixed results. We hypothesized that delayed appendectomy would be associated with increased 30-d morbidity and mortality. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients undergoing nonelective appendectomy from 2012 to 2015 with a postoperative diagnosis of appendicitis. Patients were grouped based on hospital day (HD) of operation. Primary outcomes included 30-d mortality and major complications. Logistic regression was performed to determine predictors of major morbidity and mortality. RESULTS: From 2012 to 2015, 112,122 patients underwent appendectomy for acute appendicitis. Appendectomies performed on HD 3 had significantly worse outcomes as demonstrated by increased 30-d mortality (0.6%) and all major postoperative complications (8%) in comparison with operations taking place on HD 1 (0.1%; 3.4%) or HD 2 (0.1%, P < 0.001; 3.6%, P < 0.001). In subgroup analysis, open operations had significantly higher mortality and major postoperative complications, including organ/space surgical site infections (4.6% open versus 2.1% laparoscopic; P < 0.001). Patients with decreased baseline physical status by the American Society of Anesthesiologists Physical Status class had the worst outcomes (1.5% mortality; 14% major complications) when operation was delayed to HD 3. Logistic regression revealed higher American Society of Anesthesiologists Physical Status class and open operations as predictors of major complications; however, HD was not (P = 0.2). CONCLUSIONS: Data from the American College of Surgeons National Surgical Quality Improvement Program demonstrate similar outcomes of appendectomy for acute appendicitis when the operation is performed on HD 1 or 2; however, outcomes are significantly worse for appendectomies delayed until HD 3. Increased complications in this group are likely not attributable to HD of operation, but rather decreased baseline health status and procedure type.

Constructing post-surgical discharge instructions through a Delphi consensus methodology.

OBJECTIVE: Patient education materials are a crucial part of physician-patient communication. We hypothesize that available discharge instructions are difficult to read and fail to address necessary topics. Our objective is to evaluate readability and content of surgical discharge instructions using thyroidectomy to develop standardized discharge materials. METHODS: Thyroidectomy discharge materials were analyzed for readability and assessed for content. Fifteen endocrine surgeons participated in a modified Delphi consensus panel to select necessary topics. Using readability best practices, we created standardized discharge instructions which included all selected topics. RESULTS: The panel evaluated 40 topics, selected 23, deemed 4 inappropriate, consolidated 5, and did not reach consensus on 8 topics after 4 rounds. The evaluated instructions' reading levels ranged from grade 6.5 to 13.2; none contained all consensus topics. CONCLUSION: Current post surgical thyroidectomy discharge instructions are more difficult to read than recommended by literacy standards and omit consensus warning signs of major complications. Our easy-to-read discharge instructions cover pertinent topics and may enhance patient education. Delphi methodology is useful for developing post-surgical instructions. PRACTICE IMPLICATIONS: Patient education materials need appropriate readability levels and content. We recommend the Delphi method to select content using consensus expert opinion whenever higher level data is lacking.

Mixed-Methods Analysis of Factors Impacting Use of a Postoperative mHealth App.

BACKGROUND: Limited communication and care coordination following discharge from hospitals may contribute to surgical complications. Smartphone apps offer a novel mechanism for communication and care coordination. However, factors which may affect patient app use in a postoperative, at-home setting are poorly understood. OBJECTIVE: The objectives of this study were to (1) gauge interest in smartphone app use among patients after colorectal surgery and (2) better understand factors affecting patient app use in a postoperative, at-home setting. METHODS: A prospective feasibility study was performed at a hospital that principally serves low socioeconomic status patients. After colorectal surgery, patients were enrolled and given a smartphone app, which uses previously validated content to provide symptom-based recommendations. Patients were instructed to use the app daily for 14 days after discharge. Demographics and usability data were collected at enrollment. Usability was measured with the System Usability Scale (SUS). At follow-up, the SUS was repeated and patients underwent a structured interview covering ease of use, willingness to use, and utility of use. Two members of the research team independently reviewed the field notes from follow-up interviews and extracted the most consistent themes. Chart and app log reviews identified clinical endpoints. RESULTS: We screened 115 patients, enrolled 20 patients (17.4%), and completed follow-up interviews with 17 patients (85%). Reasons for nonenrollment included: failure to meet inclusion criteria (47/115, 40.9%), declined to participate (26/115, 22.6%), and other reasons (22/115, 19.1%). There was no difference in patient ratings between usability at first-use and after extended use, with SUS scores greater than the 95th percentile at both time points. Despite high usability ratings, 6/20 (30%) of patients never used the app at home after hospital discharge and 2/20 (10%) only used the app once. Interviews revealed three themes related to app use: (1) patient-related barriers could prevent use even though the app had high usability scores; (2) patients viewed the app as a second opinion, rather than a primary source of information; and (3) many patients viewed the app as an external burden. CONCLUSIONS: Use patterns in this study, and response rates after prompts to contact the operative team, suggest that apps need to be highly engaging to be adopted by patients. The growing penetration of smartphones and the proliferation of app-based interventions are unlikely to improve care coordination and communication, unless apps address the barriers and patient perceptions identified in this study. This study shows that high usability alone is not sufficient to motivate patients to use smartphone apps in the postoperative period.

The yeast-phase virulence requirement for α-glucan synthase differs among Histoplasma capsulatum chemotypes.

Histoplasma capsulatum strains can be classified into two chemotypes based on cell wall composition. The cell wall of chemotype II yeast contains a layer of α-(1,3)-glucan that masks immunostimulatory ß-(1,3)-glucans from detection by the Dectin-1 receptor on host phagocytes. This α-(1,3)-glucan cell wall component is essential for chemotype II Histoplasma virulence. In contrast, chemotype I yeast cells lack α-(1,3)-glucan in vitro, yet they remain fully virulent in vivo. Analysis of the chemotype I α-glucan synthase (AGS1) locus revealed a 2.7-kb insertion in the promoter region that diminishes AGS1 expression. Nonetheless, AGS1 mRNA can be detected during respiratory infection with chemotype I yeast, suggesting that α-(1,3)-glucan could be produced during in vivo growth despite its absence in vitro. To directly test whether AGS1 contributes to chemotype I strain virulence, we prevented AGS1 function by RNA interference and by insertional mutation. Loss of AGS1 function in chemotype I does not impair the cytotoxicity of ags1(-) mutant yeast to cultured macrophages, nor does it affect the intracellular growth of yeast. In a murine model of histoplasmosis, the ags1(-) chemotype I mutant strains show no defect in lung infection or in extrapulmonary dissemination. Together, these studies demonstrate that AGS1 expression is dispensable for chemotype I yeast virulence, in contrast to the case for chemotype II yeast. Despite the absence of cell wall α-(1,3)-glucan, chemotype I yeast can avoid detection by Dectin-1 in a growth stage-dependent manner. This suggests the production of a unique Histoplasma chemotype I factor that, at least partially, circumvents the α-(1,3)-glucan requirement for yeast virulence.