Search

Background This report describes 9 high-risk neonates and infants with hypoplastic left heart syndrome (HLHS) who were stabilized with a combined hybrid approach and ventricular assist device (VAD) insertion (HYBRID+VAD) in preparation for heart transplantation. Methods A total of 9 patients with HLHS (7 neonates, 2 infants) presented with anatomic or physiologic features associated with an increased risk for conventional univentricular palliation with the Norwood operation (large coronary sinusoids or fistulas, severe tricuspid regurgitation, cardiogenic shock, restrictive atrial septum). These patients underwent combined VAD insertion (Berlin EXCOR, Berlin Heart, Inc, Berlin, Germany) and Stage 1 hybrid palliation (application of bilateral pulmonary bands, stent placement in the patent arterial duct, and atrial septectomy if needed). During this same era, at the Congenital Heart Center, University of Florida, Gainesville, Florida, 46 neonates underwent a Norwood operation, 4 neonates underwent a hybrid approach “Stage 1” without VAD, and 3 patients with HLHS were supported with prostaglandin while awaiting heart transplantation. Results At HYBRID+VAD insertion, the median age was 20 days (range, 13 to 143 days), and median weight was 3.25 kg (range, 2.43 to 4.2 kg). Six patients survive (67%), and 3 patients died (33%). Five survivors are at home doing well after successful heart transplantation, and 1 survivor is doing well in the intensive care unit on VAD support while awaiting transplantation. Only 1 of 6 survivors (16.7%) required intubation more than 10 days after HYBRID+VAD insertion. In 8 patients no longer undergoing VAD support, the median length of VAD support was 119.5 days (range, 56 to 196 days). Conclusions High-risk patients with HLHS who are suboptimal candidates for Norwood palliation can be successfully stabilized with pulsatile VAD insertion along with hybrid palliation while awaiting cardiac transplantation. These patients may be extubated and optimized for transplantation while undergoing VAD support.

Transcatheter aortic valve implantation is a fast-growing procedure. Expanding to low-risk patients, it has surpassed surgical aortic valve implantation in frequency and has been associated with excellent outcomes. Stroke is a devastating complication after transcatheter aortic valve implantation. Silent brain infarcts identified by diffusion-weighted magnetic resonance imaging are present in most patients following transcatheter aortic valve implantation. Postoperative delirium and cognitive dysfunction are common neurologic complications. The stroke and silent brain infarcts are likely caused by particulate emboli released during the procedure. Intravascularly positioned cerebral embolic protection devices are designed to prevent debris from entering the aortic arch vessels to avoid stroke. Despite promising design, randomized clinical trials have not demonstrated a reduction in stroke in patients receiving cerebral embolic protection devices. Similarly, the association of cerebral embolic protection devices with silent brain infarcts, post-operative delirium and cognitive dysfunction is uncertain. Monitored anesthesia care or conscious sedation is as safe as general anesthesia and is associated with lower cost but different anesthetic techniques have not been shown to decrease stroke risk, postoperative delirium, or cognitive dysfunction. Anesthesiologists play important roles in providing perioperative care including management of neurologic events in patients undergoing transcatheter aortic valve implantation. Large randomized clinical trials are needed that focus on the correlation between perioperative interventions and neurologic outcomes.

Some neonates with functionally univentricular hearts are extremely high risk for conventional surgical palliation. Primary cardiac transplantation offers the best option for survival of these challenging neonates; however, waitlist mortality must be minimized. We have developed a comprehensive strategy for the management of neonates with functionally univentricular hearts that includes the selective use of conventional neonatal palliation in standard risk patients, hybrid approaches in neonates with elevated risk secondary to noncardiac etiology, and neonatal palliation combined with insertion of a single ventricular assist device (VAD) in neonates with elevated risk secondary to cardiac etiology. The purpose of this manuscript is to describe our selection criteria, technical details, management strategies, pitfalls, and current outcomes for neonates with functionally univentricular hearts supported with VAD. Our experience documents that extremely high-risk patients with functionally univentricular hearts who are poor candidates for conventional palliation can be successfully stabilized with concomitant palliation and pulsatile VAD insertion while awaiting transplantation.

Objectives To assess the utility of genomic testing in risk-stratifying Black patients with low and intermediate risk prostate cancer. Methods We retrospectively identified 63 Black men deemed eligible for active surveillance based on National Comprehensive Cancer Network® (NCCN) guidelines, who underwent OncotypeDx® Genomic Prostate Score™ testing between April 2016 and July 2020. Nonparametric statistical testing was used to compare relevant features between patients reclassified to a higher NCCN risk after genomic testing and those who were not reclassified. Results The median age was 66 years and median pre-biopsy PSA was 7.3. Initial risk classifications were: very low risk: seven(11.1%), low risk: 24(38.1%), favorable intermediate risk: 31(49.2%), and unfavorable intermediate risk: one(1.6%). Overall, NCCN risk classifications after Genomic Prostate Score testing were significantly higher than initial classifications (p=0.003, Wilcoxon signed-rank). Among patients with discordant risk designations, 28(28/40, 70%) were reclassified to a higher NCCN risk after genomic testing. A pre-biopsy prostate specific antigen of greater than 10 did not have significantly higher odds of HBR (OR:2.16 [95% CI: 0.64,7.59, p=0.2). Of favorable intermediate risk patients, 20(64.5%) were reclassified to a higher NCCN risk. Ultimately, 18 patients underwent definitive treatment. Conclusions Incorporation of genomic testing in risk stratifying Black men with low and intermediate-risk prostate cancer resulted in overall higher NCCN risk classifications. Our findings suggest a role for increased utilization of genomic testing in refining risk-stratification within this patient population. These tests may better inform treatment decisions on an individualized basis.

New therapies are needed for patients with relapsed/refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL) who do not benefit from or are ineligible for stem cell transplant and chimeric antigen receptor therapy. The CD30-targeted, antibody-drug conjugate brentuximab vedotin (BV) and the immunomodulator lenalidomide (Len) have demonstrated promising activity as single agents in this population. We report the results of a phase 1/dose expansion trial evaluating the combination of BV/Len in rel/ref DLBCL. Thirty-seven patients received BV every 21 days, with Len administered continuously for a maximum of 16 cycles. The maximum tolerated dose of the combination was 1.2 mg/kg BV with 20 mg/d Len. BV/Len was well tolerated with a toxicity profile consistent with their use as single agents. Most patients required granulocyte colony-stimulating factor support because of neutropenia. The overall response rate was 57% (95% CI, 39.6-72.5), complete response rate, 35% (95% CI, 20.7-52.6); median duration of response, 13.1 months; median progression-free survival, 10.2 months (95% CI, 5.5-13.7); and median overall survival, 14.3 months (95% CI, 10.2-35.6). Response rates were highest in patients with CD30+ DLBCL (73%), but they did not differ according to cell of origin (P = .96). NK cell expansion and phenotypic changes in CD8+ T-cell subsets in nonresponders were identified by mass cytometry. BV/Len represents a potential treatment option for patients with rel/ref DLBCL. This combination is being further explored in a phase 3 study (registered on https://clinicaltrials.org as NCT04404283). This trial was registered on https://clinicaltrials.gov as NCT02086604.

OBJECTIVE There is little research on the effect of social determinants of health on Chiari malformation type I (CM-I). The authors analyzed data on all children evaluated for CM-I at a single institution to assess how socioeconomic factors and race affect the surgical treatment of this population. METHODS Medical records of patients treated for CM-I at the authors’ institution between 1992 and 2017 were reviewed. Area Deprivation Index (ADI) and Rural-Urban Commuting Area (RUCA) codes for each patient were used to measure neighborhood disadvantage. Non-Hispanic White patients were compared to non-White patients and Hispanic patients of any race (grouped together as non-White in this study) in terms of insurance status, ADI, and RUCA. Patients with initially benign CM-I, defined as not having undergone surgery within 9 months of their initial visit, were then stratified by having delayed symptom presentation or not, and compared on these same measures. RESULTS The sample included 665 patients with CM-I: 82% non-Hispanic White and 18% non-White. The non-White patients were more likely to reside in disadvantaged (OR 3.4, p < 0.001) and urban (OR 4.66, p < 0.001) neighborhoods and to have public health insurance (OR 3.11, p < 0.001). More than one-quarter (29%) of patients underwent surgery. The non-White and non-Hispanic White patients had similar surgery rates (29.5% vs 28.9%, p = 0.895) at similar ages (8.8 vs 9.7 years, p = 0.406). There were no differences by race/ethnicity for symptoms at presentation. Surgical and nonsurgical patients had similar ADI scores (3.9 vs 4.2, p = 0.194), RUCA scores (2.1 vs 2.3, p = 0.252), and private health insurance rates (73.6% vs 74.2%, p = 0.878). A total of 153 patients underwent surgery within 9 months of their initial visit. The remaining 512 were deemed to have benign CM-I. Of these, 40 (7.8%) underwent decompression surgery for delayed symptom presentation. Patients with delayed symptom presentation were from less disadvantaged (ADI 3.2 vs 4.2; p = 0.025) and less rural (RUCA 1.8 vs 2.3; p = 0.023) areas than those who never underwent surgery. CONCLUSIONS Although non-White patients were more likely to be socioeconomically disadvantaged, race and socioeconomic disadvantage were not associated with undergoing surgical treatment. However, among patients with benign CM-I, those undergoing decompression for delayed symptom presentation resided in more affluent and urban areas.

Background The Society of Thoracic Surgeons (STS) Quality Measurement Task Force has developed risk models and composite performance measures for isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR), isolated mitral valve replacement or repair (MVRR), AVR+CABG, and MVRR+CABG. To further enhance its portfolio of risk-adjusted performance metrics, STS has developed new risk models for multiple valve operations ± CABG procedures. Methods Using July 2011 to June 2019 STS Adult Cardiac Surgery Database data, risk models for AVR+MVRR (n = 31,968) and AVR+MVRR+CABG (n = 12,650) were developed with the following endpoints: Operative Mortality, major morbidity (any 1 or more of the following: cardiac reoperation, deep sternal wound infection/mediastinitis, stroke, prolonged ventilation, and renal failure), and combined mortality and/or major morbidity. Data were divided into development (July 2011 to June 2017; n = 35,109) and validation (July 2017 to June 2019; n = 9509) samples. Predictors were selected by assessing model performance and clinical face validity of full and progressively more parsimonious models. Performance of the resulting models was evaluated by assessing discrimination and calibration. Results C-statistics for the overall population of multiple valve ± CABG procedures were 0.7086, 0.6734, and 0.6840 for mortality, morbidity, and combined mortality and/or morbidity in the development sample, and 0.6953, 0.6561, and 0.6634 for the same outcomes, respectively, in the validation sample. Conclusions New STS Adult Cardiac Surgery Database risk models have been developed for multiple valve ± CABG operations, and these models will be used in subsequent STS performance metrics.

OBJECTIVE Pediatric stereoelectroencephalography (SEEG) has been increasingly performed in the United States, with published literature being limited primarily to large single-center case series. The purpose of this study was to evaluate the experience of pediatric epilepsy centers, where the technique has been adopted in the last several years, via a multicenter case series studying patient demographics, outcomes, and complications. METHODS A retrospective cohort methodology was used based on the STROBE criteria. ANOVA was used to evaluate for significant differences between the means of continuous variables among centers. Dichotomous outcomes were assessed between centers using a univariate and multivariate logistic regression. RESULTS A total of 170 SEEG insertion procedures were included in the study from 6 different level 4 pediatric epilepsy centers. The mean patient age at time of SEEG insertion was 12.3 ± 4.7 years. There was no significant difference between the mean age at the time of SEEG insertion between centers (p = 0.3). The mean number of SEEG trajectories per patient was 11.3 ± 3.6, with significant variation between centers (p < 0.001). Epileptogenic loci were identified in 84.7% of cases (144/170). Patients in 140 cases (140/170, 82.4%) underwent a follow-up surgical intervention, with 47.1% (66/140) being seizure free at a mean follow-up of 30.6 months. An overall postoperative hemorrhage rate of 5.3% (9/170) was noted, with patients in 4 of these cases (4/170, 2.4%) experiencing a symptomatic hemorrhage and patients in 3 of these cases (3/170, 1.8%) requiring operative evacuation of the hemorrhage. There were no mortalities or long-term complications. CONCLUSIONS As the first multicenter case series in pediatric SEEG, this study has aided in establishing normative practice patterns in the application of a novel surgical technique, provided a framework for anticipated outcomes that is generalizable and useful for patient selection, and allowed for discussion of what is an acceptable complication rate relative to the experiences of multiple institutions.

OBJECTIVE To evaluate outcomes in cats undergoing subtotal colectomy for the treatment of idiopathic megacolon and to determine whether removal versus nonremoval of the ileocecocolic junction (ICJ) was associated with differences in outcome. ANIMALS 166 client-owned cats. PROCEDURES For this retrospective cohort study, medical records databases of 18 participating veterinary hospitals were searched to identify records of cats with idiopathic megacolon treated by subtotal colectomy from January 2000 to December 2018. Data collection included perioperative and surgical variables, complications, outcome, and owner perception of the procedure. Data were analyzed for associations with outcomes of interest, and Kaplan-Meier survival time analysis was performed. RESULTS Major perioperative complications occurred in 9.9% (15/151) of cats, and 14% (12/87) of cats died as a direct result of treatment or complications of megacolon. The median survival time was not reached. Cats with (vs without) a body condition score < 4/9 (hazard ratio [HR], 5.97), preexisting heart disease (HR, 3.21), major perioperative complications (HR, 27.8), or long-term postoperative liquid feces (HR, 10.4) had greater hazard of shorter survival time. Constipation recurrence occurred in 32% (24/74) of cats at a median time of 344 days and was not associated with retention versus removal of the ICJ; however, ICJ removal was associated with long-term liquid feces (OR, 3.45), and a fair or poor outcome on owner assessment (OR, 3.6). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that subtotal colectomy was associated with long survival times and a high rate of owner satisfaction. Removal of the ICJ was associated with less favorable outcomes in cats of the present study.

Clinical Practice Points • Cutaneous lymphangitic carcinomatosis is a rare form of cutaneous metastatic disease which can appear to be a variety of different dermatologic conditions. Clinicians should maintain a high index of suspicion in order to avoid delays in diagnosis and treatment given the poor prognosis of cutaneous metastatic disease. • While the skin is an uncommon site of metastatic disease, it is important to remember that cutaneous metastases can be the sole presenting sign of malignancy or extra nodal disease. • Skin metastases more commonly present within the first 3 years after discovery of a primary tumor. However, they can occur at any time and have been reported up to 22 years after an initial cancer diagnosis. Clinicians should consider this with any new skin lesion in a patient with a history of malignancy.

PURPOSE Approximately 10%-40% of patients with lung cancer report no history of tobacco smoking (never-smokers). We analyzed whole-exome and RNA-sequencing data of 160 tumor and normal lung adenocarcinoma (LUAD) samples from never-smokers to identify clinically actionable alterations and gain insight into the environmental and hereditary risk factors for LUAD among never-smokers. METHODS We performed whole-exome and RNA-sequencing of 88 and 69 never-smoker LUADs. We analyzed these data in conjunction with data from 76 never-smoker and 299 smoker LUAD samples sequenced by The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium. RESULTS We observed a high prevalence of clinically actionable driver alterations in never-smoker LUADs compared with smoker LUADs (78%-92% v 49.5%; P < .0001). Although a subset of never-smoker samples demonstrated germline alterations in DNA repair genes, the frequency of samples showing germline variants in cancer predisposing genes was comparable between smokers and never-smokers (6.4% v 6.9%; P = .82). A subset of never-smoker samples (5.9%) showed mutation signatures that were suggestive of passive exposure to cigarette smoke. Finally, analysis of RNA-sequencing data showed distinct immune transcriptional subtypes of never-smoker LUADs that varied in their expression of clinically relevant immune checkpoint molecules and immune cell composition. CONCLUSION In this comprehensive genomic and transcriptome analysis of never-smoker LUADs, we observed a potential role for germline variants in DNA repair genes and passive exposure to cigarette smoke in the pathogenesis of a subset of never-smoker LUADs. Our findings also show that clinically actionable driver alterations are highly prevalent in never-smoker LUADs, highlighting the need for obtaining biopsies with adequate cellularity for clinical genomic testing in these patients.

Diffuse lung disease, frequently referred to as interstitial lung disease, encompasses numerous disorders affecting the lung parenchyma. The potential etiologies of diffuse lung disease are broad with several hundred established clinical syndromes and pathologies currently identified. Imaging plays a critical role in diagnosis and follow-up of many of these diseases, although multidisciplinary discussion is the current standard for diagnosis of several DLDs. This document aims to establish guidelines for evaluation of diffuse lung diseases for 1) initial imaging of suspected diffuse lung disease, 2) initial imaging of suspected acute exacerbation or acute deterioration in cases of confirmed diffuse lung disease, and 3) clinically indicated routine follow-up of confirmed diffuse lung disease without acute deterioration. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Chronic cough is defined by a duration lasting at least 8 weeks. The most common causes of chronic cough include smoking-related lung disease, upper airway cough syndrome, asthma, gastroesophageal reflux disease, and nonasthmatic eosinophilic bronchitis. The etiology of chronic cough in some patients may be difficult to localize to an isolated source and is often multifactorial. The complex pathophysiology, clinical presentation, and variable manifestations of chronic cough underscore the challenges faced by clinicians in the evaluation and management of these patients. Imaging plays a role in the initial evaluation, although there is a lack of high-quality evidence guiding which modalities are useful and at what point in time the clinical evaluation should be performed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

The ongoing injection drug use (IDU) crisis in the United States has been complicated by an emerging epidemic of Staphylococcus aureus IDU-associated bloodstream infections (IDU-BSI). We performed a case-control study comparing S. aureus IDU-BSI and non-IDU BSI cases identified in a large US Midwestern academic medical center between Jan 1, 2016 and Dec 21, 2019. We obtained the whole-genome sequences of 154 S. aureus IDU-BSI and 91 S. aureus non-IDU BSI cases, which were matched with clinical data. We performed phylogenetic and comparative genomic analyses to investigate clonal expansion of lineages and molecular features characteristic of IDU-BSI isolates. Here we show that patients with IDU-BSI experience longer durations of bacteremia and have lower medical therapy completion rates. In phylogenetic analyses, 45/154 and 1/91 contemporaneous IDU-BSI and non-IDU BSI staphylococcal isolates, respectively, group into multiple, unique clonal clusters, revealing that pathogen community transmission distinctively spurs IDU-BSI. Lastly, multiple S. aureus lineages deficient in canonical virulence genes are overrepresented among IDU-BSI, which may contribute to the distinguishable clinical presentation of IDU-BSI cases. We identify clonal expansion of multiple S. aureus lineages among IDU-BSI isolates, but not non-IDU BSI isolates, in a community with limited access to needle exchange facilities. In the setting of expanding numbers of staphylococcal IDU-BSI cases consideration should be given to treating IDU-associated invasive staphylococcal infections as a communicable disease. Marks and Calix et al. perform a case-control genomic epidemiology study comparing Staphylococcus aureus isolates from intravenous drug use-associated bloodstream infections with those from other bloodstream infections. The authors show there is clonal expansion of lineages in intravenous drug use-associated bloodstream infections suggesting person-to-person transmission of S. aureus. Persons who inject drugs are at increased risk of developing a bloodstream infection caused by the bacterium Staphylococcus aureus. To investigate whether this risk is due to transmission of the bacterium within this community, we compared the complete set of genes (genome) of S. aureus isolated from people with bloodstream infections who do and do not inject drugs. S. aureus causing bloodstream infections in persons who inject drugs were much more likely to belong to one of multiple networks of very closely related subtypes, demonstrating that in some communities the bacteria causing this type of infection can likely be directly transmitted from person to person through high-risk injection drug use practices, such as sharing needles. Therefore, invasive infections in persons who inject drugs can spread like communicable diseases and this can inform future policy on how to prevent them.

Chest pain is a common reason that patients may present for evaluation in both ambulatory and emergency department settings, and is often of musculoskeletal origin in the former. Chest wall syndrome collectively describes the various entities that can contribute to chest wall pain of musculoskeletal origin and may affect any chest wall structure. Various imaging modalities may be employed for the diagnosis of nontraumatic chest wall conditions, each with variable utility depending on the clinical scenario. We review the evidence for or against use of various imaging modalities for the diagnosis of nontraumatic chest wall pain. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Background Mesenchymal stem cells have been proven to promote cellular recruitment and remodeling during healing. Considering challenges encountered in the healing process of esophageal injury, we sought to evaluate the effect of human adipose derived stem cells (hASC) on esophageal injury with stent and to assess the feasibility of submucosal hASC injection as a mechanism of delivery. Methods An intrabdominal esophagotomy was created in rodents with placement of an expandable fully covered metal esophageal stent. A submucosal injection of 2 × 106 hASC was delivered in experimental animals. Animals were sacrificed on postoperative day 3 (POD3) or 7 (POD7). Macroscopic, immunohistochemical and immunofluorescence analyses were conducted to assess for markers of healing and viability of transplanted cells. Results hASC were identified within submucosal and muscular layers with proliferation demonstrated in respective areas on anti-Ki67 stained sections. Lower adhesion and abscess scores were observed in hASC specimens without significant statistical difference. Prevalence of submucosal collagen was increased in samples treated with hASC compared to control, with abundant collagen deposition demonstrated within the POD7 group. Granulation tissue at the site of esophageal injury was more prominent in tissue sections treated with hASC compared to control, with significantly higher density at POD3 (control 1.94 versus hASC 2.83, P Conclusions Presence of hASC at the site of an esophageal injury may enhance wound healing predominantly through increased granulation and decreased inflammation in conjunction with esophageal stent placement. Targeted submucosal injection at the time of esophageal stent placement is an effective delivery method of hASC therapy.

Verapamil has been used in perfusion solution to improve kidney performance, but evidence was anecdotal, and no research has been reported on recipient outcomes. Our organization began a program to evaluate Verapamil’s effect on pump performance, transplant rate, and recipient outcomes. One kidney in a pair was treated with Verapamil and one with standard perfusion. Donor inclusion criteria were age 18 or older and both kidneys were placed on the pump. The laterality of the treated kidney was changed every month to reduce bias. From January 1, 2020 to June 30, 2020, 88 kidneys were evaluated. Of those, 21 donors had both kidneys transplanted to different recipients, so for those 42 kidneys, recipient outcomes were evaluated. Small improvements in pump performance were observed in the Verapamil-treated kidneys and more were transplanted. No clinical differences were found in recipients between the Verapamil-treated and standard perfused kidneys. A larger cohort is needed to determine whether differences are significant.

Objectives/hypothesis Hashimoto's Thyroiditis (HT) is a common cause of hypothyroidism. Among adults with differentiated thyroid cancer (DTC), HT appears to be associated with less severe disease burden. In the absence of information regarding HT and disease burden among children with DTC, we assessed the relationship between pediatric DTC severity and HT. Study design Retrospective cohort. Methods Charts from 90 pediatric patients who underwent surgical removal of DTC from 2002 to 2017 at tertiary-care children's hospital were reviewed. Demographic, clinical, surgical, pathology, and outcome details were compared between patients with and without HT. Consistency among diagnostic modalities of HT was also evaluated. Results Median age at presentation was 16.0 years (range 4.2-18.9 years). Twenty-two patients were male (24%). Forty-five patients (50%) had HT based on presence of thyroid autoantibodies and/or surgical pathology findings and 45 patients did not have HT. Patients with HT had increased odds of microcalcifications (odds ratio [OR]: 3.01, P = .031) and decreased odds of palpable nodules (OR: 0.212, P = .024) and T2 lesions (vs. T1) (OR: 0.261, P = .015) compared with non-HT. No significant differences in demographics and the incidence of multifocality, extrathyroidal extension, lymphovascular invasion, lymph node or pulmonary metastases, disease recurrence, or radioactive iodine treatment were found between the two groups. Thyroglobulin/thyroid peroxidase autoantibodies and surgical pathology indicative of HT were concordant in 82.4% (κ = 0.635, P Conclusion HT was present in 50% of children with DTC. Patients with DTC and HT presented with smaller tumors compared to non-HT patients. No significant differences in other markers of disease aggressiveness were found between the two groups. Level of evidence 3 Laryngoscope, 2021.

Background We aimed to investigate the detection rate of body CT or PET/CT for sites of extracranial disease in patients with a new pathological diagnosis of CNS DLBCL and to identify factors associated with sites of extracranial disease. Methods An international multicenter cohort study of consecutive immunocompetent patients with a new diagnosis of CNS DLBCL confirmed by brain biopsy who underwent CT and/or PET/CT to evaluate for sites of extracranial disease between 1998 and 2019. The primary outcome was the detection rate of extracranial lymphoma by CT or PET/CT. Subgroup analyses according to age and EBV status were also performed. Logistic regression analyses were performed to determine factors related to sites of extracranial disease. Detection rates of CT and PET/CT were compared. Results One thousand and forty-three patients were included. The overall detection rate of CT or PET/CT was 2.6% (27/1043). The treatment approach was adjusted in 74% of these patients. Multivariable analysis demonstrated that age >61 years (OR, 3.10; P = .016) and EBV positivity (OR, 3.78; P = .045) were associated with greater odds of extracranial lymphoma. There was no statistically significant difference in detection rate between CT and PET/CT (P = .802). In patients ≤61 years old, the false-referral rates were significantly higher than the detection rates (P < .001). Conclusion Our results showed increased odds of extracranial lymphoma in patients with older age or EBV-positive lymphoma. Treatment was adjusted in a majority of patients diagnosed with extracranial lymphoma, thereby supporting the current guidelines for the use of contrast-enhanced body CT or PET/CT in patients with newly diagnosed CNS DLBCL.

Cancer progression has been attributed to somatic changes in single-nucleotide variants, copy-number aberrations, loss of heterozygosity, chromosomal instability, epistatic interactions, and the tumor microenvironment. It is not entirely clear which of these changes are essential and which are ancillary to cancer. The dynamic nature of cancer evolution in a patient can be illuminated using several concepts and tools from classical evolutionary biology. Neutral mutation rates in cancer cells are calculable from genomic data such as synonymous mutations, and selective pressures are calculable from rates of fixation occurring beyond the expectation by neutral mutation and drift. However, these cancer effect sizes of mutations are complicated by epistatic interactions that can determine the likely sequence of gene mutations. In turn, longitudinal phylogenetic analyses of somatic cancer progression offer an opportunity to identify key moments in cancer evolution, relating the timing of driver mutations to corresponding landmarks in the clinical timeline. These analyses reveal temporal aspects of genetic and phenotypic change during tumorigenesis and across clinical timescales. Using a related framework, clonal deconvolution, physical locations of clones, and their phylogenetic relations can be used to infer tumor migration histories. Additionally, genetic interactions with the tumor microenvironment can be analyzed with longstanding approaches applied to organismal genotype-by-environment interactions. Fitness landscapes for cancer evolution relating to genotype, phenotype, and environment could enable more accurate, personalized therapeutic strategies. An understanding of the trajectories underlying the evolution of neoplasms, primary, and metastatic tumors promises fundamental advances toward accurate and personalized predictions of therapeutic response.

Background e-Cigarette or vaping-induced lung injury (EVALI) causes a spectrum of CT lung injury patterns. Relative frequencies and associations with vaping behavior are unknown. Research Question What are the frequencies of imaging findings and CT patterns in EVALI and what is the relationship to vaping behavior? Study Design and Methods CT scans of 160 subjects with EVALI from 15 institutions were retrospectively reviewed. CT findings and patterns were defined and agreed on via consensus. The parenchymal organizing pneumonia (OP) pattern was defined as regional or diffuse ground-glass opacity (GGO) ± consolidation without centrilobular nodules (CNs). An airway-centered OP pattern was defined as diffuse CNs with little or no GGO, whereas a mixed OP pattern was a combination of the two. Other patterns included diffuse alveolar damage (DAD), acute eosinophilic-like pneumonia, and pulmonary hemorrhage. Cases were classified as atypical if they did not fit into a pattern. Imaging findings, pattern frequencies, and injury severity were correlated with substance vaped (marijuana derives [tetrahydrocannabinol] [THC] only, nicotine derivates only, and both), vaping frequency, regional geography, and state recreational THC legality. One-way analysis of variance, χ2 test, and multivariable analyses were used for statistical analysis. Results A total of 160 patients (79.4% men) with a mean age of 28.2 years (range, 15-68 years) with EVALI underwent CT scan. Seventy-seven (48.1%), 15 (9.4%), and 68 (42.5%) patients admitted to vaping THC, nicotine, or both, respectively. Common findings included diffuse or lower lobe GGO with subpleural (78.1%), lobular (59.4%), or peribronchovascular (PBV) sparing (40%). Septal thickening (50.6%), lymphadenopathy (63.1%), and CNs (36.3%) were common. PBV sparing was associated with younger age (P = .02). Of 160 subjects, 156 (97.5%) had one of six defined patterns. Parenchymal, airway-centered, and mixed OP patterns were seen in 89 (55.6%), 14 (8.8%), and 32 (20%) patients, respectively. Acute eosinophilic-like pneumonia (six of 160, 3.8%), DAD (nine of 160, 5.6%), pulmonary hemorrhage (six of 160, 3.8%), and atypical (four of 160, 2.5%) patterns were less common. Increased vaping frequency was associated with more severe injury (P = .008). Multivariable analysis showed a negative association between vaping for > 6 months and DAD pattern (P = .03). Two subjects (1.25%) with DAD pattern died. There was no relation between pattern and injury severity, geographic location, and state legality of recreational use of THC. Interpretation EVALI typically causes an OP pattern but exists on a spectrum of acute lung injury. Vaping habits do not correlate with CT patterns except for negative correlation between vaping > 6 months and DAD pattern. PBV sparing, not previously described in acute lung injury, is a common finding.

Importance Immune checkpoint inhibitors (ICIs) have emerged as active therapies for a variety of cancers. Cutaneous toxicities are common immune-related adverse events and patients will often be referred to dermatologists for evaluation. Observations Cutaneous adverse events to ICIs can have a variety of clinical presentations. Among the more common are eczematous, morbilliform, and lichenoid dermatoses, as well as vitiligo and pruritus. Less common adverse events include psoriasiform dermatoses, bullous disorders, and severe cutaneous adverse reactions, including Stevens–Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. Because of the immunologic mechanism of ICIs, there are also a variety of rheumatologic adverse reactions with cutaneous manifestations, such as scleroderma, dermatomyositis, cutaneous lupus erythematosus, and various vasculitides. These cutaneous reactions often respond to topical or systemic steroids, although specific toxicities may have alternative treatments available. Conclusions and relevance As they become more widely prescribed, dermatologists will see an increasing number of patients with cutaneous adverse events caused by ICI therapies. Accurately diagnosing and treating these toxicities is paramount to achieving the most favorable outcomes for patients.

The objective of this study was to develop a portal natural language processing approach to aid in the identification of postoperative venous thromboembolism events from free-text clinical notes.We abstracted clinical notes from 25,494 operative events from 2 independent health care systems. A venous thromboembolism detected as part of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) was used as the reference standard. A natural language processing engine, easy clinical information extractor-pulmonary embolism/deep vein thrombosis (EasyCIE-PEDVT), was trained to detect pulmonary embolism and deep vein thrombosis from clinical notes. International Classification of Diseases (ICD) discharge diagnosis codes for venous thromboembolism were used as baseline comparators. The classification performance of EasyCIE-PEDVT was compared with International Classification of Diseases codes using sensitivity, specificity, area under the receiver operating characteristic curve, using an internal and external validation cohort.To detect pulmonary embolism, EasyCIE-PEDVT had a sensitivity of 0.714 and 0.815 in internal and external validation, respectively. To detect deep vein thrombosis, EasyCIE-PEDVT had a sensitivity of 0.846 and 0.849 in internal and external validation, respectively. EasyCIE-PEDVT had significantly higher discrimination for deep vein thrombosis compared with International Classification of Diseases codes in internal validation (area under the receiver operating characteristic curve: 0.920 vs 0.761; P.001) and external validation (area under the receiver operating characteristic curve: 0.921 vs 0.794; P.001). There was no significant difference in the discrimination for pulmonary embolism between EasyCIE-PEDVT and ICD codes.Accurate surveillance of postoperative venous thromboembolism may be achieved using natural language processing on clinical notes in 2 independent health care systems. These findings suggest natural language processing may augment manual chart abstraction for large registries such as NSQIP.

Objective: The beta-cell stress hypothesis suggests that increased insulin demand contributes to the development of type 1 diabetes. In the TRIGR trial we set out to assess the profile of plasma glucose and HbA1c before the diagnosis of clinical diabetes compared to nondiabetic children. Research Design and Methods: A cohort of children (N = 2159) with an affected first-degree relative and increased HLA risk were recruited 2002-2007 and followed until 2017. To study the relationship between plasma glucose/HbA1c and the development of autoantibodies or clinical disease Kaplan-Meir curves were developed. Mixed models were constructed for plasma glucose and HbA1c separately. Results: A family history of type 2 diabetes was related to an increase in plasma glucose (p < 0.001). An increase in glucose from the previous sample predicted clinical diabetes (p < 0.001) but not autoantibodies. An increase of HbA1c of 20% or 30% from the previous sample predicted the development of any autoantibody (p < 0.003 resp < 0.001) and the development of diabetes (p < 0.002 resp < 0.001. Participants without autoantibodies had lower HbA1c (mean 5.18%, STD 0.24; mean 33.08 mmol/mol, STD 2.85) than those who progressed to clinical disease (5.31%, 0.42; 34.46 mmol/mol, 4.68; p < 0.001) but higher than those who developed any autoantibody (5.10%, 0.30; 32.21 mmol/mol, 3.49; p < 0.001), or multiple autoantibodies (5.11%, 0.35; 32.26 mmol/mol, 3.92; p < 0.003). Conclusions: A pronounced increase in plasma glucose and HbA1c precedes development of clinical diabetes, while the association between plasma glucose or HbA1c and development of autoantibodies is complex. Increased insulin demand may contribute to development of type 1 diabetes. Funding Agencies|Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [HD040364, HD042444, HD051997]; Special Statutory Funding Program for Type 1 Diabetes Research; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR); Juvenile Diabetes Research Foundation InternationalJuvenile Diabetes Research Foundation; Academy of FinlandAcademy of FinlandEuropean Commission; Commission of the European CommunitiesEuropean Commission [QLK1-2002-00372]; EFSD/JDRF/Novo Nordisk Focused Research Grant

BACKGROUND: Current literature on robot-assisted S2 alar-iliac (S2AI) screw placement shows favorable outcomes and screw accuracy; however, the data is limited by a few retrospective, single-surgeon studies. To the author’s knowledge, this is the first multicenter study which evaluates the accuracy of robot-assisted S2AI screws. METHODS: Adult (≥18 years old) patients who underwent robot-assisted S2AI screw placement from 2017–2019 were reviewed. All surgeries used the same proprietary robotic guidance system, Mazor X (Mazor Robotics Ltd). RESULTS: A total of 65 screws were assessed in 31 patients. The mean follow-up ± standard deviation was 362±190 days (minimum was 90 days). The mean age was 61.1±11 years old, and 54.8% (n=17) of patients were female. Nearly half of the patients had a primary diagnosis of degenerative scoliosis (48.4%, n=15). Other diagnosis included pseudarthrosis (22.6%, n=7), degenerative disc disease (16.1%, n=5), and high-grade spondylolisthesis (12.9%, n=4). The mean length and diameter of screws were 84.6±6.1 mm and 8.4±0.7, respectively. The mean axial and sagittal angles were 50.0±6.3 and 24.0±10.5, respectively. The overall screw accuracy was 93.8% (n=61). There were four iliac cortex breaches (anterior =3, inferior 1) with a mean breach distance of 3.5±3.2. No statistically significant differences in screw length, diameter, axial angle, and sagittal angle were observed between screws with and without a breach. No intraoperative neurologic, vascular, or visceral complications from the S2AI screw were observed. No post-discharge wound complications, screw prominence issues, or revision of S2AI screws were observed during the study’s follow-up period. CONCLUSIONS: Robot-assisted S2AI screw placement was found to be safe and accurate in this multicenter study. This is largely attributed to the versatility of the robotic guidance software that allows for detailed and precise preoperative and intraoperative planning.

This systematic review aims to clarify and comprehensively detail the sometimes variable published imaging features as well as the pathogenesis, clinical diagnostic criteria, and treatment options of IgG4-Related Diseases (IgG4-RD) in the head and neck to aid the radiologist in diagnosing relapse and new sites of disease. A literature search in PubMed and EMBASE for reported cases of IgG4-RD was performed in December 2019. Case reports or series of IgG4-RD in the head and neck in adults that included sufficient imaging and pathology findings were included. This yielded 50 reports. IgG4-RD locations included the orbits, thyroid, pituitary gland, paranasal sinuses, salivary and parotid glands, larynx, pharynx, cervical lymph nodes, meninges, and skull base. Most lesions demonstrated non-specific homogenous CT attenuation, diffuse enhancement, isointense/low T2 signal intensity, and low T1 signal intensity. 6 cases from our institution followed previously reported imaging patterns.

Background Elevated epidermal interleukin (IL)-36 expression distinguishes psoriasis from eczematous dermatitis, but other psoriasiform dermatitides (PDs) have not been thoroughly investigated for IL-36 expression. In this study, we assess the IL-36 staining pattern (IL36-SP) in psoriasis variants and other PDs including lichen simplex chronicus (LSC), prurigo nodularis (PN), lichen planus (LP), tinea, pityriasis rubra pilaris (PRP), mycosis fungoides (MF), pemphigus foliaceus (PF), acute generalized exanthematous pustulosis (AGEP), impetigo (IMP), and syphilis (SY). Methods IL-36 immunostaining was performed on 307 cases of psoriasis and various PDs. IL36-SP in the upper epidermis was graded on a scale of 0-4. Results High IL36-SP occurred in all variants of psoriasis, as well as in AGEP, PRP, PN, tinea, IMP, and LP (P > 0.05). SY, PF, LSC, and MF showed a lower IL36-SP (P ≤ 0.05) compared with psoriasis. Conclusion All variants of psoriasis exhibit high IL36-SP. IL-36 staining can assist in differentiating MF, PF, SY, and LSC from psoriasis, particularly MF and LSC, which have consistent low IL-36 expression. AGEP, PRP, tinea, IMP, PN, and LP exhibit high IL-36 expression similar to psoriasis, indicating Th17 activation in these diseases.

Background Most studies of patients with isolated proximal left anterior descending (PLAD) coronary artery disease do not include all 3 procedural options: percutaneous coronary intervention (PCI), conventional coronary artery bypass graft (CABG) surgery, or minimally invasive CABG. Methods New York’s cardiac registries were used to identify patients who underwent revascularization for isolated PLAD disease between January 1, 2010, and November 30, 2016, in New York State. After exclusions, 14,327 patients, of whom 13,115 received PCI, 1001 of whom underwent CABG surgery, and 211 of whom underwent minimally invasive CABG were monitored through the end of 2017 to compare outcomes. Registry data were matched to vital statistics data to obtain deaths occurring after discharge and matched to claims data to obtain subsequent admissions for myocardial infarction and stroke. Results There were no significant differences in mortality or in mortality/myocardial infarction/stroke after 7 years (with median follow-up times in excess of 4 years) among the 3 procedures after adjusting for differences in patient risk factors. However, conventional CABG surgery was associated with a lower subsequent revascularization rate than PCI (adjusted hazard ratio, 0.45; 95% confidence interval, 0.35-0.58) and minimally invasive CABG surgery (adjusted hazard ratio, 0.46; 95% confidence interval, 0.32-0.66). Conclusions Among patients with isolated PLAD disease undergoing any of 3 revascularization options (PCI, conventional CABG surgery, or minimally invasive CABG surgery), conventional CABG surgery was associated with lower subsequent revascularization rates, but there were no differences in mortality or mortality/myocardial infarction/stroke rates.

AIMS/HYPOTHESIS: Prognostic factors and characteristics of children diagnosed with type 1 diabetes before 6years of age were compared with those diagnosed at 6-13years of age in the TEDDY study. METHODS: Genetically high-risk children (n = 8502) were followed from birth for a median of 9.9years; 328 (3.9%) were diagnosed with type 1 diabetes. Cox proportional hazard model was used to assess the association of prognostic factors with the risk of type 1 diabetes in the two age groups. RESULTS: Children in the younger group tended to develop autoantibodies earlier than those in the older group did (mean age 1.5 vs 3.5years), especially insulin autoantibodies (IAA), which developed earlier than GAD autoantibodies (GADA). Children in the younger group also progressed to diabetes more rapidly than the children in the older group did (mean duration 1.9 vs 5.4 years). Children with autoantibodies first appearing against insulinoma antigen-2 (IA-2A) were found only in the older group. The significant diabetes risk associated with the country of origin in the younger group was no longer significant in the older group. Conversely, the diabetes risk associated with HLA genotypes was statistically significant also in the older group. Initial seroconversion after and before 2years of age was associated with decreased risk for diabetes diagnosis in children positive for multiple autoantibodies, but the diabetes risk did not decrease further with increasing age if initial seroconversion occurred after age 2. Diabetes risk associated with the minor alleles of rs1004446 (INS) was decreased in both the younger and older groups compared with other genotypes (HR 0.67). Diabetes risk was significantly increased with the minor alleles of rs2476601 (PTPN22) (HR 2.04 and 1.72), rs428595 (PPIL2) (HR 2.13 and 2.10), rs113306148 (PLEKHA1) (HR 2.34 and 2.21) and rs73043122 (RNASET2) (HR 2.31 and 2.54) (HR values represent the younger and older groups, respectively). CONCLUSIONS/INTERPRETATIONS: Diabetes at an early age is likely to be preceded by IAA autoantibodies and is a more aggressive form of the disease. Among older children, once multiple autoantibodies have been observed there does not seem to be any association between progression to diabetes and the age of the child or family history. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00279318.

OBJECTIVES: To evaluate the performance of 4-dimensional computed tomography (4D-CT) in assessing upper airway obstruction (UAO) in patients with Robin Sequence (RS) and compare the accuracy and reliability of 4D-CT and flexible fiberoptic laryngoscopy (FFL). STUDY DESIGN: Prospective survey of retrospective clinical data. SETTING: Single, tertiary care pediatric hospital. METHODS: At initial and 30-day timepoints, a multidisciplinary group of 11 clinicians who treat RS rated UAO severity in 36 sets of 4D-CT visualizations and FFL videos (dynamic modalities), and static CT images. Raters assessed UAO at the velopharynx and oropharynx (1-none to 5-complete) and noted confidence levels (LOC) of each rating. Intraclass correlation and Krippendorff’s Alpha were used to assess intra- and inter-rater reliability, respectively. Accuracy was assessed by comparing clinician ratings with Quantitative Percent Constriction (QPC) Ratings, calculated based on 4D-CT airway cross-sectional area. Results were compared using Wilcoxon rank-sum and signed-rank tests. RESULTS: 4D-CT and FFL demonstrated similar intra-rater agreement (moderate to substantial) and both demonstrated fair inter-rater agreement. Both modalities underestimated UAO severity, though 4D-CT ratings were significantly more accurate, as determined by QPC similarity, than FFL (−1.06 and −1.46 vs QPC Ratings, p=0.004). Overall LOC was similar for 4D-CT and FFL, but other specialists were significantly less confident in FFL ratings than were otolaryngologists (2.25 and 3.92, p

BACKGROUND: Breastfeeding has beneficial effects on numerous health outcomes. OBJECTIVES: We investigated whether breastfeeding duration is associated with the development of early childhood autoimmunity, allergies, or obesity in a multinational prospective birth cohort. METHODS: Infants with genetic susceptibility for type 1 diabetes (n=8676) were followed for the development of autoantibodies to islet autoantigens or transglutaminase, allergies, and for anthropometric measurements to a median age of 8.3 y (IQR: 2.8-10.2y). Information on breastfeeding was collected at 3 mo of age and prospectively thereafter. A propensity score for longer breastfeeding was calculated from the variables that were likely to influence any or exclusive breastfeeding. The risks of developing autoimmunity or allergy were assessed using Cox proportional hazards models, and the risk of obesity at 5.5 y of age was assessed using logistic regression with adjustment by the propensity score. RESULTS: Breastfeeding duration was not associated with a lower risk of either islet or transglutaminase autoimmunity (any breastfeeding>6 mo, adjusted HR: 1.07; 95% CI: 0.96, 1.19; exclusive breastfeeding>3 mo, adjusted HR: 1.03; 95% CI: 0.92, 1.15). Exclusive breastfeeding>3 mo was associated with a decreased risk of seasonal allergic rhinitis (adjusted HR: 0.70; 95% CI: 0.53, 0.92; P6 mo and exclusive breastfeeding>3mo were associated with decreased risk of obesity (adjusted OR: 0.62; 95% CI: 0.47, 0.81; P&nbsp

The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) tested the hypothesis whether extensively hydrolyzed casein‐based versus regular cow's milk‐based infant formula reduces the risk of type 1 diabetes. We describe dietary compliance in the trial in terms of study formula intake, feeding of nonrecommended foods, and serum cow's milk antibody concentration reflecting intake of cow's milk protein among 2,159 eligible newborn infants with a biological first‐degree relative affected by type 1 diabetes and with HLA‐conferred susceptibility to type 1 diabetes. The participating infants were introduced to the study formula feeding at the median age of 15 days with a median duration of study formula use of 63 days. During the intervention, 80% of the infants received study formula. Of these, 57% received study formula for at least 2 months. On average, 45.5 l of study formula were used per infant. Only 13% of the population had received a nonrecommended food by the age of 6 months. The dietary compliance was similar in the intervention and control arm. The reported cow's milk consumption by the families matched very well with measured serum casein IgA and IgG antibody concentration. To conclude, good compliance was observed in this randomized infant feeding trial. Compliance varied between the regions and those infants who were breastfed for a longer period of time had a shorter exposure to the study formula. High dietary compliance in infant feeding trial is necessary to allow accurate interpretation of study results., The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) tested the hypothesis whether extensively hydrolyzed casein‐based versus regular cow's milk‐based infant formula reduces the risk of type 1 diabetes. We describe good dietary compliance in the trial in terms of study formula feeding, feeding of non‐recommended foods, and serum cow's milk antibody concentration reflecting intake of cow's milk protein among 2,159 eligible newborn infants with a biological first degree relative affected by type 1 diabetes and with HLA‐conferred susceptibility to type 1 diabetes.

Study design Multicenter cohort. Objective To compare the robot time/screw, radiation exposure, robot abandonment, screw accuracy, and 90-day outcomes between robot-assisted percutaneous and robot-assisted open approach for short lumbar fusion (1-and 2-level). Summary of background data There is conflicting literature on the superiority of robot-assisted minimally invasive spine surgery to open techniques. A large, multicenter study is needed to further elucidate the outcomes and complications between these two approaches. Methods We included adult patients (≥18 years old) who underwent robot-assisted short lumbar fusion surgery from 2015-2019 at four independent institutions. A propensity score matching (PSM) algorithm was employed to control for the potential selection bias between percutaneous and open surgery. The minimum follow-up was 90 days after the index surgery. Results After PSM, 310 patients remained. The mean (standard deviation) charlson comorbidity index was 1.6 (1.5) and 53% of patients were female. The most common diagnoses included high grade spondylolisthesis (grade >2)(48%), degenerative disc disease (22%), and spinal stenosis (25%), and the mean number of instrumented levels was 1.5(0.5). The operative time was longer in the open (198 minutes) vs. the percutaneous group (167 minutes, P-value=0.007). However, the robot time/screw was similar between cohorts (P-value>0.05). The fluoroscopy time/screw for percutaneous (14.4 seconds) was longer than the open group (10.1 seconds, P-value=0.021). The rates for screw exchange and robot abandonment, were similar between groups (P-value>0.05). The estimated blood loss (open:146 mL vs. percutaneous:61.3 mL, P-value 0.05). Conclusion Percutaneous robot-assisted spine surgery may increase radiation exposure, but can achieve a shorter operative time and lower risk for intraoperative blood loss for short-lumbar fusion. Percutaneous approaches do not appear to have an advantage for other short-term postoperative outcomes. Future multicenter studies on longer fusion surgeries and the inclusion of patient-reported outcomes are needed.Level of Evidence: 3.

OBJECTIVE In Chiari malformation type I (CM-I), a variety of imaging findings have been purported to be important; however, results have been inconclusive, inconsistent, or not replicated in independent studies. The purpose of this study was to report imaging characteristics for a large cohort of patients with CM-I and identify the imaging findings associated with surgical decompression. METHODS Patients were identified using ICD-9 codes for CM-I for the period from 1996 to 2017. After review of the medical records, patients were excluded if they 1) did not have a diagnosis of CM-I, 2) were not evaluated by a neurosurgeon, or 3) did not have available preoperative MRI. Retrospective chart review was performed to collect demographic and clinical data. Imaging parameters were measured according to the Chiari I Malformation Common Data Elements. RESULTS A total of 731 patients were included for analysis, having a mean follow-up duration of 25.5 months. The mean age at presentation was 8.5 years. The mean tonsil position was 11.4 mm below the foramen magnum, and 62.8% of patients had a pegged tonsil shape. Two hundred patients (27.4%) underwent surgery for life-dominating tussive headache, lower cranial nerve dysfunction, syrinx, and/or brainstem dysfunction. Surgical treatment was associated with a syrinx (OR 20.4, 95% CI 12.3–33.3, p < 0.0001), CM-1.5 (OR 1.797, 95% CI 1.08–2.98, p = 0.023), lower tonsil position (OR 1.130, 95% CI 1.08–1.18, p < 0.0001), and congenital fusion of cervical vertebrae (OR 5.473, 95% CI 1.08–27.8, p = 0.040). Among patients with benign CM-I, tonsil position was statistically significantly associated with future surgery. CONCLUSIONS Comprehensive imaging characteristics for a large cohort of patients with CM-I are reported. Analysis showed that a lower tonsillar position, a syrinx, and CM-1.5 were associated with undergoing posterior fossa decompression. This study demonstrates the importance of considering imaging findings in the context of patient symptomatology.

Metastatic adamantinoma involving the spine is an extremely rare occurrence. In this case report, we present a patient with recurrent adamantinoma of the tibia which was found to have metastasized to the spine. The metastatic involvement was diagnosed pathologically, status post CT guided percutaneous core needle biopsy, performed after the patient returned with concerning symptoms and imaging findings suggestive of metastasis. The patient was ultimately treated surgically with vertebrectomy and reconstruction. A thoughtful review of this disease process is explored, emphasizing the pathology, imaging characteristics, and pertinent differential diagnostic considerations. While uncommon, knowledge of this rare disease process and its presentation can improve future patient diagnosis and outcomes.

Purpose To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib. Methods We report on six patients with NF‐1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively. Results Subjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4–28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life‐threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1–2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy. Conclusion Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF‐1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients., Here, we report on response to Trametinib, a MEK inhibitor in children with NF‐1. Our experience presented in this report demonstrates that Trametinib is an effective therapy for advanced, life‐threatening PNF, and treatment‐refractory PLGG in patients with NF‐1 and is well tolerated in children.

Infection with SARS-CoV-2 ranges from an asymptomatic condition to a severe and sometimes fatal disease, with mortality most frequently being the result of acute lung injury. The role of imaging has evolved during the pandemic, with CT initially being an alternative and possibly superior testing method compared with reverse transcriptase-polymerase chain reaction (RT-PCR) testing and evolving to having a more limited role based on specific indications. Several classification and reporting schemes were developed for chest imaging early during the pandemic for patients suspected of having COVID-19 to aid in triage when the availability of RT-PCR testing was limited and its level of performance was unclear. Interobserver agreement for categories with findings typical of COVID-19 and those suggesting an alternative diagnosis is high across multiple studies. Furthermore, some studies looking at the extent of lung involvement on chest radiographs and CT images showed correlations with critical illness and a need for mechanical ventilation. In addition to pulmonary manifestations, cardiovascular complications such as thromboembolism and myocarditis have been ascribed to COVID-19, sometimes contributing to neurologic and abdominal manifestations. Finally, artificial intelligence has shown promise for use in determining both the diagnosis and prognosis of COVID-19 pneumonia with respect to both radiography and CT.

This series describes three adolescent females who presented with chest pain and ventricular dysfunction related to acute coronary ischemia secondary to Takayasu’s arteritis with varied courses of disease progression leading to a diverse range of therapies including cardiac transplantation. While Takayasu’s arteritis is rare in childhood, it should be strongly considered in any adolescent female presenting with systemic inflammation and chest pain consistent with myocardial infarction. A high index of suspicion can lead to early detection and aggressive management of the underlying vasculitis reducing associated morbidity and mortality. The purpose of this report is to describe the challenges in the clinical diagnosis and management of Takayasu’s arteritis with myocardial infarction. We also seek to enhance awareness about unique presentations of Takayasu’s arteritis within the paediatric community.

Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder caused by a trinucleotide expansion in exon 1 of the huntingtin (HTT) gene. Cell death in HD occurs primarily in striatal medium spiny neurons (MSNs), but the involvement of specific MSN subtypes and of other striatal cell types remains poorly understood. To gain insight into cell type-specific disease processes, we studied the nuclear transcriptomes of 4524 cells from the striatum of a genetically precise knock-in mouse model of the HD mutation, Htt(Q175/+), and from wild-type controls. We used 14- to 15-month-old male mice, a time point at which multiple behavioral, neuroanatomical, and neurophysiological changes are present but at which there is no known cell death. Thousands of differentially expressed genes (DEGs) were distributed across most striatal cell types, including transcriptional changes in glial populations that are not apparent from RNA-seq of bulk tissue. Reconstruction of cell type-specific transcriptional networks revealed a striking pattern of bidirectional dysregulation for many cell type-specific genes. Typically, these genes were repressed in their primary cell type, yet de-repressed in other striatal cell types. Integration with existing epigenomic and transcriptomic data suggest that partial loss-of-function of the polycomb repressive complex 2 (PRC2) may underlie many of these transcriptional changes, leading to deficits in the maintenance of cell identity across virtually all cell types in the adult striatum. SIGNIFICANCE STATEMENT Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder characterized by specific loss of medium spiny neurons (MSNs) in the striatum, accompanied by more subtle changes in many other cell types. It is thought that changes in transcriptional regulation are an important underlying mechanism, but cell type-specific gene expression changes are not well understood, particularly at time points relevant to the onset of disease-related symptoms. Single-nucleus (sn)RNA-seq in a genetically precise mouse model enabled us to identify novel patterns of transcriptional dysregulation because of HD mutations, including bidirectional dysregulation of many cell type identity genes that may be driven by partial loss-of-function of the polycomb repressive complex (PRC). Identifying these regulators of transcriptional dysregulation in HD can be leveraged to design novel disease-modifying therapeutics.

Locally advanced or metastatic basal cell carcinomas (laBCCs or mBCCs) are rare, with few case series providing information on their epidemiology. We aimed to describe the clinical and histologic features of locally advanced and metastatic basal cell carcinomas. Forty cases of laBCC or mBCC were identified by searching Vanderbilt's database from 1984 to January 2019. A retrospective chart review was performed. Pathology slides were available for 23 cases (13 mBCCs and 10 laBCCs). Twenty-one of 23 cases were Clark level IV or V, with a mean depth of invasion of >7 mm for both types. The mean mitotic rate was 4.4 mitoses/mm2 for laBCCs and 3.3 mitoses/mm2 for mBCCs. Ulceration was identified in 7 laBCC and 8 mBCC cases. Perineural invasion was present in 2 laBCC and 6 mBCC cases, with 3 mBCCs invading nerves >0.1 mm. Of 13 mBCC cases, histologic subtypes included infiltrative (n = 9), nodular (n = 7), morpheaform (n = 4), and superficial (n = 2), with multiple patterns present in some specimens. 10 of 13 patients with mBCC had local recurrence before metastasis. In summary, we identified several potential markers of high-risk BCC, including perineural invasion, deep invasion, elevated mitotic rate, and local recurrence of the primary tumor.

Aims To assess the efficacy of traditional first-line non-antidiuretic pharmacotherapy for nocturia in the real-world outpatient urology setting. Methods We retrospectively analyzed voiding diaries from adult men treated for lower urinary tract symptoms (LUTS) at an outpatient urology clinic to identify pairs of voiding diaries with ≥1 nocturnal void at baseline and a corresponding follow-up diary completed within 1 year. We compared the odds of nocturia improvement (decrease of ≥1 nocturnal void) in patients started on LUTS pharmacotherapy versus behavioral modification alone. Results Two hundred and thirteen diary pairs from 93 patients were included. Fifty-seven diary pairs were identified from patients prescribed at least one LUTS drug on the initial visit and 156 diary pairs were identified from patients receiving behavioral modification alone. All standard voiding diary parameters were assessed, and only maximum voided volume differed at baseline (240 ml [interquartile range: 200-330 ml] vs. 280 ml [200-400 ml] with and without pharmacotherapy, respectively, p = 0.04). The odds of nocturia improvement did not significantly differ between pharmacotherapy and behavioral modification treatment groups (crude odds ratio [OR]: 1.16 [95% confidence interval: 0.63-2.16], p = 0.63; maximum voided volume [MVV]-adjusted OR: 1.19 [0.63-2.22], p = 0.59). In contrast, improvement in 24-h urinary frequency was more likely with pharmacotherapy versus behavioral modification alone (crude OR: 2.36 [1.22-4.56], p = 0.01; MVV-adjusted OR: 2.05 [1.05-4.01], p = 0.04). Results were consistent on subgroup analyses restricted to first diary pairs from each patient. Conclusion Despite improvement in 24-h voiding frequency, there was no evidence that adjunctive pharmacotherapy provided a benefit in the treatment of nocturia in men receiving behavioral counseling.

Rationale and objectives Evaluate whether intraprocedural MRI monitoring of percutaneous cryoablation procedures of head and neck, and spine lesions is effective for avoiding iatrogenic neurovascular and mucosal injury. Materials and methods We retrospectively reviewed 64 consecutive percutaneous head and neck, and spine cryoablation procedures with intraprocedural MRI monitoring performed on 45 patients (mean age 55 years, range 17–91 years). Ablation goals were either complete local control of primary or metastatic lesions or pain relief. Results The technical success rate was 100%. The complication rate was 13% with only 2 complications (3%) requiring further intervention. There were no deaths or persistent neurological or vascular complications. Subsequent cryoablation in the same location was performed in 12 patients (27%). Subsequent surgical intervention in the same location was performed in 7 patients (16%) for progressive disease or worsening symptoms. Conclusions MRI provides excellent visualization of the ice ball margin during percutaneous cryoablation procedures. Accurate intraprocedural visualization of the ice ball allows for adjustment of cryoablation parameters to avoid damage to adjacent vital neurovascular structures or mucosal surfaces. Intraprocedural MRI monitoring is thus a novel and highly effective method that allows a high rate of technical success for cryoablation in the head and neck, and spine while avoiding iatrogenic injury.

In children, seizures represent an extremely heterogeneous group of medical conditions ranging from benign cases, such as a simple febrile seizure, to life-threatening situations, such as status epilepticus. Underlying causes of seizures also represent a wide range of pathologies from idiopathic cases, usually genetic, to a variety of acute and chronic intracranial or systemic abnormalities. This document discusses appropriate utilization of neuroimaging tests in a child with seizures. The clinical scenarios in this document take into consideration different circumstances at the time of a child's presentation including the patient's age, precipitating event (if any), and clinical and electroencephalogram findings and include neonatal seizures, simple and complex febrile seizures, post-traumatic seizures, focal seizures, primary generalized seizures in a neurologically normal child, and generalized seizures in neurologically abnormal child. This practical approach aims to guide clinicians in clinical decision-making and to help identify efficient and appropriate imaging workup. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

The optimal training of the highly specialized congenital heart surgeon is a long and complex process, which is a significant challenge in most parts of the world. The World Society for Pediatric and Congenital Heart Surgery (WSPCHS) has established the Global Council on Education for Congenital Heart Surgery as a nonprofit organization with the goal of assessing current training and certification and ultimately establishing standardized criteria for the training, evaluation, and certification of congenital heart surgeons around the world. The Global Council and the WSPCHS have reviewed the present status of training and certification for congenital cardiac surgery around the world. There is currently lack of consensus and standardized criteria for training in congenital heart surgery, with significant disparity between continents and countries. This represents significant obstacles to international job mobility of competent congenital heart surgeons and to the efforts to improve the quality of care for patients with Congenital Heart Disease worldwide. The purpose of this article is to summarize and document the present state of training and certification in congenital heart surgery around the world.

OBJECTIVE The aims of this study were to review the National Spina Bifida Patient Registry (NSBPR) data set to study the rates of tethered spinal cord release (TCR) among patients with myelomeningocele and variability between centers, to compare TCR rates between males and females, and to study the relationships between TCR rates and other condition-specific characteristics. METHODS The NSBPR registry was queried to identify all patients with myelomeningocele. TCR rates were calculated over time using survival analyses; rates between centers and between males and females were compared. Cox proportional hazards models were constructed to identify relationships between TCR rates and sex, functional lesion level, ambulation status, treated hydrocephalus, and prior Chiari decompression. RESULTS Of 6339 patients with information about their operations, 1366 (21.5%) underwent TCR, with significant variability between centers. The majority (75.8%) underwent a single TCR. The annual TCR rate was linear between birth and 13 years (1.8%/year) but declined sharply from 14 to 21 years (0.7%/year). There was no period of time at which the TCR rate accelerated. There were no significant differences in TCR rates between males and females. TCR rate was not related to functional lesion level but was lower among nonambulators compared with community ambulators (p = 0.005) and among those with treated hydrocephalus (HR 0.30, p < 0.001), and higher among those having prior Chiari decompression (HR 1.71, p < 0.001). CONCLUSIONS These results extend the results of prior single-institution studies, demonstrate significant treatment variability between institutions, and challenge the traditional concept that tethering is related to spinal cord stretching due to spinal growth.

OBJECTIVE Posterior fossa decompression with duraplasty (PFDD) is commonly performed for Chiari I malformation (CM-I) with syringomyelia (SM). However, complication rates associated with various dural graft types are not well established. The objective of this study was to elucidate complication rates within 6 months of surgery among autograft and commonly used nonautologous grafts for pediatric patients who underwent PFDD for CM-I/SM. METHODS The Park-Reeves Syringomyelia Research Consortium database was queried for pediatric patients who had undergone PFDD for CM-I with SM. All patients had tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and ≥ 6 months of postoperative follow-up after PFDD. Complications (e.g., pseudomeningocele, CSF leak, meningitis, and hydrocephalus) and postoperative changes in syrinx size, headaches, and neck pain were compared for autograft versus nonautologous graft. RESULTS A total of 781 PFDD cases were analyzed (359 autograft, 422 nonautologous graft). Nonautologous grafts included bovine pericardium (n = 63), bovine collagen (n = 225), synthetic (n = 99), and human cadaveric allograft (n = 35). Autograft (103/359, 28.7%) had a similar overall complication rate compared to nonautologous graft (143/422, 33.9%) (p = 0.12). However, nonautologous graft was associated with significantly higher rates of pseudomeningocele (p = 0.04) and meningitis (p < 0.001). The higher rate of meningitis was influenced particularly by the higher rate of chemical meningitis (p = 0.002) versus infectious meningitis (p = 0.132). Among 4 types of nonautologous grafts, there were differences in complication rates (p = 0.02), including chemical meningitis (p = 0.01) and postoperative nausea/vomiting (p = 0.03). Allograft demonstrated the lowest complication rates overall (14.3%) and yielded significantly fewer complications compared to bovine collagen (p = 0.02) and synthetic (p = 0.003) grafts. Synthetic graft yielded higher complication rates than autograft (p = 0.01). Autograft and nonautologous graft resulted in equal improvements in syrinx size (p < 0.0001). No differences were found for postoperative changes in headaches or neck pain. CONCLUSIONS In the largest multicenter cohort to date, complication rates for dural autograft and nonautologous graft are similar after PFDD for CM-I/SM, although nonautologous graft results in higher rates of pseudomeningocele and meningitis. Rates of meningitis differ among nonautologous graft types. Autograft and nonautologous graft are equivalent for reducing syrinx size, headaches, and neck pain.

Objective Hydrocephalus is a disorder of cerebrospinal fluid dynamics, traditionally treated by placement of a ventricular shunt. Shunts are effective but imperfect as they fail in an unpredictable pattern, and the patient's well-being is dependent on adequate shunt function. The omnipresent threat of shunt failure along with the potential need for invasive investigations can be stressful for patients and caregivers. Our objective was to measure post-traumatic stress symptoms (PTSS) in children with hydrocephalus and their caregivers. Methods A cross-sectional analysis of children with hydrocephalus and their caregivers was conducted. Caregivers completed a measure of their own PTSS (the Post-Traumatic Stress Disorders Checklist for the Diagnostic and Statistical Manual of Mental Disorders−V) and resilience (the Connor Davidson Resilience Scale). Pediatric patients rated their own PTSS and resilience using the Acute Stress Checklist for Kids and Connor Davidson Resilience Scale. Results Ninety-one caregivers completed the Post-Traumatic Stress Disorders Checklist for the Diagnostic and Statistical Manual of Mental Disorders−V. Mean score was 17.0 (standard deviation 15.7; median 13.0). Fourteen percent scored above 33, the threshold suggestive of a preliminary diagnosis of post-traumatic stress disorder. There was a statistically significant association between caregiver post-traumatic stress and marital status, child's race, and caregiver education. More than half (52%) of caregivers reported their child's hydrocephalus as the most significant source of their PTSS. Children did not have markedly elevated levels of PTSS. Forty-one percent of caregivers and 60% of children scored in the lowest resilience quartile compared with the general population. Conclusions Results from this study suggest that post-traumatic stress affects caregivers with hydrocephalus, yet levels of resilience for caregivers and pediatric patients are low.

The role of extracorporeal membrane oxygenation (ECMO) in the management of severely ill patients with coronavirus disease 2019 (COVID-19) continues to evolve. The purpose of this study is to review a multi-institutional clinical experience in 100 consecutive patients, at 20 hospitals, with confirmed COVID-19 supported with ECMO. This analysis includes our first 100 patients with complete data who had confirmed COVID-19 and were supported with ECMO. The first patient in the cohort was placed on ECMO on March 17, 2020. Differences by the mortality group were assessed using χ2 tests for categorical variables and Kruskal-Wallis rank-sum tests and Welch's analysis of variance for continuous variables. The median time on ECMO was 12.0 days (IQR = 8-22 days). All 100 patients have since been separated from ECMO: 50 patients survived and 50 patients died. The rate of survival with veno-venous ECMO was 49 of 96 patients (51%), whereas that with veno-arterial ECMO was 1 of 4 patients (25%). Of 50 survivors, 49 have been discharged from the hospital and 1 remains hospitalized at the ECMO-providing hospital. Survivors were generally younger, with a lower median age (47 versus 56.5 years, p = 0.014). In the 50 surviving patients, adjunctive therapies while on ECMO included intravenous steroids (26), anti-interleukin-6 receptor blockers (26), convalescent plasma (22), remdesivir (21), hydroxychloroquine (20), and prostaglandin (15). Extracorporeal membrane oxygenation may facilitate salvage and survival of selected critically ill patients with COVID-19. Survivors tend to be younger. Substantial variation exists in the drug treatment of COVID-19, but ECMO offers a reasonable rescue strategy.

AIMS/HYPOTHESIS: We aimed to investigate the association between maternal consumption of gluten-containing foods and other selected foods during late pregnancy and offspring risk of islet autoimmunity (IA) and type 1 diabetes in The Environmental Determinants of Diabetes in the Young (TEDDY) study. METHODS: The TEDDY study recruited children at high genetic risk for type 1 diabetes at birth, and prospectively follows them for the development of IA and type 1 diabetes (n=8556). A questionnaire on the mother’s diet in late pregnancy was completed by 3-4 months postpartum. The maternal daily intake was estimated from a food frequency questionnaire for eight food groups: gluten-containing foods, non-gluten cereals, fresh milk, sour milk, cheese products, soy products, lean/medium-fat fish and fatty fish. For each food, we described the distribution of maternal intake among the four participating countries in the TEDDY study and tested the association of tertile of maternal food consumption with risk of IA and type 1 diabetes using forward selection time-to-event Cox regression. RESULTS: By 28 February 2019, 791 cases of IA and 328 cases of type 1 diabetes developed in TEDDY. There was no association between maternal late-pregnancy consumption of gluten-containing foods or any of the other selected foods and risk of IA, type 1 diabetes, insulin autoantibody-first IA or GAD autoantibody-first IA (all p≥0.01). Maternal gluten-containing food consumption in late pregnancy was higher in Sweden (242 g/day), Germany (247 g/day) and Finland (221 g/day) than in the USA (199 g/day) (pairwise p