Pilot randomized controlled trial of restricted versus liberal crystalloid fluid management in pediatric post-operative and trauma patients.

BACKGROUND: Intravenous (IV) fluid therapy is essential in the treatment of critically ill pediatric surgery and trauma patients. Recent studies have suggested that aggressive fluids may be detrimental to patients. Prospective studies are needed to compare liberal to restricted fluid management in these patients. The primary objective of this pilot trial is to test study feasibility-recruitment and adherence to the study treatment algorithm. METHODS: We conducted a two-part pilot randomized controlled trial (RCT) comparing liberal to restricted crystalloid fluid management in 50 pediatric post-operative (1-18 years) and trauma (1-15 years) patients admitted to our pediatric intensive care unit (PICU). Patients were randomized to a high (liberal) volume or low (restricted) volume algorithm using unblinded, blocked randomization. A revised treatment algorithm was used after the 29th patient for the second part of the RCT. The goal of the trial was to determine the feasibility of conducting an RCT at a single site for recruitment and retention. We also collected data on the safety of study interventions and clinical outcomes, including pulmonary, infectious, renal, post-operative, and length of stay outcomes. RESULTS: Fifty patients were randomized to either liberal (n = 26) or restricted (n = 24) fluid management strategy. After data was obtained on 29 patients, a first study analysis was performed. The volume of fluid administered and triggers for intervention were adapted to optimize the treatment effect and clarity of outcomes. Updated and refined fluid management algorithms were created. These were used for the second part of the RCT on patients 30-50. During this second study period, 54% (21/39, 95% CI 37-70%) of patients approached were enrolled in the study. Of the patients enrolled, 71% (15/21, 95% CI 48-89%) completed the study. This met our a priori recruitment and retention criteria for success. A data safety monitoring committee concluded that no adverse events were related to study interventions. Although the study was not powered to detect differences in outcomes, after the algorithm was revised, we observed a non-significant trend towards improved pulmonary outcomes in patients on the restricted arm, including decreased need for and time on oxygen support and decreased need for mechanical ventilation. CONCLUSION: We demonstrated the feasibility and safety of conducting a single-site RCT comparing liberal to restricted crystalloid fluid management in critically ill pediatric post-operative and trauma patients. We observed trends in improved pulmonary outcomes in patients undergoing restricted fluid management. A definitive multicenter RCT comparing fluid management strategies in these patients is warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04201704 . Registered 17 December 2019-retrospectively registered.

Congenital Heart Disease with Congenital Diaphragmatic Hernia: Surgical Decision Making and Outcomes.

OBJECTIVE: To describe the types of congenital heart disease (CHD) in a congenital diaphragmatic hernia (CDH) cohort in a large volume center and evaluate surgical decision making and outcomes based on complexity of CHD and associated conditions. STUDY DESIGN: A retrospective review of patients with CHD and CDH diagnosed by echocardiogram between 01/01/2005 and 07/31/2021. The cohort was divided into 2 groups based on survival at discharge. RESULTS: Clinically important CHD was diagnosed in 19% (62/326) of CDH patients. There was 90% (18/20) survival in children undergoing surgery for both CHD and CDH as neonates, and 87.5 (22/24) in those undergoing repair initially for CDH alone. A genetic anomaly identified on clinical testing was noted in 16% with no significant association with survival. A higher frequency of other organ system anomalies was noted in nonsurvivors compared with survivors. Nonsurvivors were more likely to have unrepaired CDH (69% vs 0%, P < .001) and unrepaired CHD (88% vs 54%, P < .05), reflecting a decision not to offer surgery. CONCLUSIONS: Survival was excellent in patients who underwent repair of both CHD and CDH. Patients with univentricular physiology have poor survival and this finding should be incorporated into pre and postnatal counseling about eligibility for surgery. In contrast, patients with other complex lesions including transposition of the great arteries have excellent outcomes and survival at 5 years follow-up at a large pediatric and cardiothoracic surgical center.

Limited disease progression in endocrine surgery patients with treatment delays due to COVID-19.

BACKGROUND: The COVID-19 pandemic profoundly impacted the delivery of care and timing of elective surgical procedures. Most endocrine-related operations were considered elective and safe to postpone, providing a unique opportunity to assess clinical outcomes under protracted treatment plans. METHODS: American Association of Endocrine Surgeon members were surveyed for participation. A Research Electronic Data Capture survey was developed and distributed to 27 institutions to assess the impact of COVID-19-related delays. The information collected included patient demographics, primary diagnosis, resumption of care, and assessment of disease progression by the surgeon. RESULTS: Twelve out of 27 institutions completed the survey (44.4%). Of 850 patients, 74.8% (636) were female; median age was 56 (interquartile range, 44-66) years. Forty percent (34) of patients had not been seen since their original surgical appointment was delayed; 86.2% (733) of patients had a delay in care with women more likely to have a delay (87.6% vs 82.2% of men, χ2 = 3.84, P = .05). Median duration of delay was 70 (interquartile range, 42-118) days. Among patients with a delay in care, primary disease site included thyroid (54.2%), parathyroid (37.2%), adrenal (6.5%), and pancreatic/gastrointestinal neuroendocrine tumors (1.3%). In addition, 4.0% (26) of patients experienced disease progression and 4.1% (24) had a change from the initial operative plan. The duration of delay was not associated with disease progression (P = .96) or a change in operative plan (P = .66). CONCLUSION: Although some patients experienced disease progression during COVID-19 delays to endocrine disease-related care, most patients with follow-up did not. Our analysis indicated that temporary delay may be an acceptable course of action in extreme circumstances for most endocrine-related surgical disease.

Extending PICO with Observation Normalization for Evidence Computing.

While the PICO framework is widely used by clinicians for clinical question formulation when querying the medical literature, it does not have the expressiveness to explicitly capture medical findings based on any standard. In addition, findings extracted from the literature are represented as free-text, which is not amenable to computation. This research extends the PICO framework with Observation elements, which capture the observed effect that an Intervention has on an Outcome, forming Intervention-Observation-Outcome triplets. In addition, we present a framework to normalize Observation elements with respect to their significance and the direction of the effect, as well as a rule-based approach to perform the normalization of these attributes. Our method achieves macro-averaged F1 scores of 0.82 and 0.73 for identifying the significance and direction attributes, respectively.

Representation and Normalization of Complex Interventions for Evidence Computing.

Complex interventions are ubiquitous in healthcare. A lack of computational representations and information extraction solutions for complex interventions hinders accurate and efficient evidence synthesis. In this study, we manually annotated and analyzed 3,447 intervention snippets from 261 randomized clinical trial (RCT) abstracts and developed a compositional representation for complex interventions, which captures the spatial, temporal and Boolean relations between intervention components, along with an intervention normalization pipeline that automates three tasks: (i) treatment entity extraction; (ii) intervention component relation extraction; and (iii) attribute extraction and association. 361 intervention snippets from 29 unseen abstracts were included to report on the performance of the evaluation. The average F-measure was 0.74 for treatment entity extraction on an exact match and 0.82 for attribute extraction. The F-measure for relation extraction of multi-component complex interventions was 0.90. 93% of extracted attributes were correctly attributed to corresponding treatment entities.

Ethanol ablation for the treatment of benign thyroid nodules.

BACKGROUND: Ethanol ablation (EA) is a non-surgical option for the treatment of benign cystic thyroid nodules. This study summarizes our preliminary experience with the efficacy and safety of EA. METHODS: A retrospective analysis was performed of patients undergoing EA for symptomatic, benign, cystic and predominantly cystic (≥75%) thyroid nodules. Baseline nodule volume, cosmetic scores, and symptom scores were assessed, as well as volume reduction ratio (VRR), cosmetic and symptom scores at post-procedure months 1, 3, 6, and 12. RESULTS: 31 patients underwent an uncomplicated EA for a single cyst with an average volume of 21.3 cc (range: 1.7-101.4 cc). Follow-up was limited by the COVID-19 pandemic. Mean nodule VRRs were 66 ± 20% (1 m, n = 17), 87 ± 15% (3 m, n = 9), 72 ± 20% (6 m, n = 7), and 78% (12 m, n = 3). Mean symptom and cosmetic scores decreased concurrently post-procedure. CONCLUSION: EA is a safe, effective option for benign cystic and predominantly cystic thyroid nodules.

Extracorporeal Membrane Oxygenation (ECMO) and its complications in newborns with congenital diaphragmatic hernia.

BACKGROUND: Extracorporeal Membrane Oxygenation (ECMO) is offered to patients with congenital diaphragmatic hernia (CDH) who are in severe respiratory and cardiac failure. We aim to describe the types of complications among these patients and their impact on survival. METHODS: A single-center, retrospective review of CDH patients cannulated onto ECMO between January 2005 and November 2020 was conducted. ECMO complications, as categorized by the Extracorporeal Life Support Organization (ELSO), were correlated with survival status. Descriptive statistics were used to compare observed complications between survivors and non-survivors. RESULTS: In our cohort of CDH neonates, 21% (54/258) were supported with ECMO, of whom, 61% (33/54) survived. Survivors and non-survivors were similar in baseline characteristics except for birthweight z-score (p = 0.043). Seventy percent of CDH neonates experienced complications during their ECMO run, with the most common categories being metabolic (48.1%) and mechanical (38.9%), followed by hemorrhage (22.2%), neurological (18.5%), renal (11.1%), pulmonary (7.4%), and cardiovascular (7.4%). The median number of complications per patient was higher in the non-survivor group  (2 (IQR: 1-4) vs 1 (IQR: 0-2), p = 0.043). In addition, mechanical (57.1% vs 27.3%, p = 0.045) and renal (28.6% vs 0%, p = 0.002) complications were more common among non-survivors compared to survivors. CONCLUSION: Complications occur frequently among ECMO-treated newborns with CDH, some of which have serious long-term consequences. Survivors had higher birth weight z-scores, shorter ECMO runs, and fewer complications per patient. Mechanical and renal complications were independently associated with mortality, emphasizing the utility of more focused strategies to target fluid balance and renal protection and to prevent circuit and cannula complications.

Long-term outcomes of congenital diaphragmatic hernia: A single institution experience.

BACKGROUND/PURPOSE: As survival rates for patients with congenital diaphragmatic hernia (CDH) increase, long-term sequelae become increasingly prevalent. We present the outcomes of patients who underwent CDH repair at our institution and discuss standardization of follow-up care in our long-term multidisciplinary follow-up clinic. METHODS: A retrospective review of patients followed in multidisciplinary clinic after CDH repair at our institution from January 1, 2005 to December 1, 2020. RESULTS: A total of 193 patients met inclusion criteria, 73 females (37.8%) and 120 males (62.2%). Left-sided defects were most common (75.7%), followed by right-sided defects (20.7%). Median age at repair was 4 days (IQR 3-6) and 59.6% of all defects required patch repair. Median length of stay was 29 days (IQR 16.8-50.0). Median length of follow up was 49 months (IQR 17.8-95.3) with 25 patients followed for more than 12 years. Long-term outcomes included gastroesophageal reflux disease (42.0%), diaphragmatic hernia recurrence (10.9%), asthma (23.6%), neurodevelopmental delay (28.6%), attention deficit hyperactivity disorder (7.3%), autism (1.6%), chest wall deformity (15.5%), scoliosis (11.4%), and inguinal hernia (6.7%). CONCLUSION: As survival of patients with CDH improves, long-term care must be continuously studied and fine-tuned to ensure appropriate surveillance and optimization of long-term outcomes.

Primary Hyperparathyroidism Is Associated With Shorter QTc Intervals, but Not Arrhythmia.

CONTEXT: Primary hyperparathyroidism (PHPT) is associated with subclinical cardiovascular disease, but data regarding cardiac conduction abnormalities are limited. OBJECTIVE AND DESIGN: Retrospective cross-sectional comparison of cardiac conduction in patients with PHPT or thyroid disease (TD). PARTICIPANTS AND SETTING: Patients ≥40 years old who underwent parathyroidectomy or thyroidectomy at a single tertiary institution from 2013 to 2018. METHODS AND OUTCOMES: Demographics and preoperative electrocardiogram (EKG) parameters were compared using the Mann-Whitney U, chi-square test, and linear regression. RESULTS: A total of 1242 patients were included: 49.8% PHPT (n = 619) and 50.2% TD (n = 623). Median age was 60.5 years [interquartile range (IQR) 53.6-67.9]. Compared to controls, PHPT patients had higher median serum calcium [10.7 mg/dL (IQR 10.4-11.1) vs 9.5 mg/dL (IQR 9.3-9.8), P < 0.001] as expected, as well as, a higher prevalence of hyperlipidemia (49% vs 36%, P < 0.001) and hypertension (50.1% vs 42.2%, P < 0.01). Based on EKG, there was no difference in PR interval or the prevalence of arrhythmia, atrioventricular block, ST segment/T wave changes, premature ventricular complexes, right bundle branch block, or left bundle branch block after adjusting for covariates. The PHPT group had a lower mean corrected QT interval (414 ± 24) ms vs 422 ± 24 ms, P < 0.01), adjusted for covariates. Serum calcium predicted QTc independently of age, sex, and other covariates. CONCLUSIONS: In the largest study to date, PHPT patients had shorter QTc intervals compared to TD controls but no increased prevalence of arrhythmia based on preoperative EKG.

Advancements in the treatment of differentiated thyroid cancer.

Derived from follicular epithelial cells, differentiated thyroid cancer (DTC) accounts for the majority of thyroid malignancies. The threefold increase in DTC incidence over the last three decades has been largely attributed to advancements in detection of papillary thyroid microcarcinomas. Efforts to address the issue of overtreatment have notably included the reclassification of encapsulated follicular variant papillary thyroid cancers (EFVPTC) to non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). In the last 5 years, the overall management approach for this relatively indolent cancer has become less aggressive. Although surgery and radioiodine ablation remain the mainstay of DTC therapy, the role of active surveillance is being explored. Furthermore, the most recent American Thyroid Association (ATA) guidelines offer flexibility between lobectomy and total thyroidectomy for thyroid nodules between 1 cm and 4 cm in the absence of extrathyroidal extension or nodal disease. As our understanding of the natural history and molecular underpinnings of DTC evolves, so might our approach to managing low-risk patients, obviating the need for invasive intervention. Simultaneously, advances in interventional and systemic therapies have greatly expanded treatment options for high-risk surgical candidates and patients with widespread disease, and continue to be areas of active investigation. Continued research efforts are essential to improve our ability to offer effective individualized therapy to patients at all disease stages and to reduce the incidence of recurrent and progressive disease.

Building an OMOP common data model-compliant annotated corpus for COVID-19 clinical trials.

Clinical trials are essential for generating reliable medical evidence, but often suffer from expensive and delayed patient recruitment because the unstructured eligibility criteria description prevents automatic query generation for eligibility screening. In response to the COVID-19 pandemic, many trials have been created but their information is not computable. We included 700 COVID-19 trials available at the point of study and developed a semi-automatic approach to generate an annotated corpus for COVID-19 clinical trial eligibility criteria called COVIC. A hierarchical annotation schema based on the OMOP Common Data Model was developed to accommodate four levels of annotation granularity: i.e., study cohort, eligibility criteria, named entity and standard concept. In COVIC, 39 trials with more than one study cohorts were identified and labelled with an identifier for each cohort. 1,943 criteria for non-clinical characteristics such as "informed consent", "exclusivity of participation" were annotated. 9767 criteria were represented by 18,161 entities in 8 domains, 7,743 attributes of 7 attribute types and 16,443 relationships of 11 relationship types. 17,171 entities were mapped to standard medical concepts and 1,009 attributes were normalized into computable representations. COVIC can serve as a corpus indexed by semantic tags for COVID-19 trial search and analytics, and a benchmark for machine learning based criteria extraction.

Towards clinical data-driven eligibility criteria optimization for interventional COVID-19 clinical trials.

OBJECTIVE: This research aims to evaluate the impact of eligibility criteria on recruitment and observable clinical outcomes of COVID-19 clinical trials using electronic health record (EHR) data. MATERIALS AND METHODS: On June 18, 2020, we identified frequently used eligibility criteria from all the interventional COVID-19 trials in ClinicalTrials.gov (n = 288), including age, pregnancy, oxygen saturation, alanine/aspartate aminotransferase, platelets, and estimated glomerular filtration rate. We applied the frequently used criteria to the EHR data of COVID-19 patients in Columbia University Irving Medical Center (CUIMC) (March 2020-June 2020) and evaluated their impact on patient accrual and the occurrence of a composite endpoint of mechanical ventilation, tracheostomy, and in-hospital death. RESULTS: There were 3251 patients diagnosed with COVID-19 from the CUIMC EHR included in the analysis. The median follow-up period was 10 days (interquartile range 4-28 days). The composite events occurred in 18.1% (n = 587) of the COVID-19 cohort during the follow-up. In a hypothetical trial with common eligibility criteria, 33.6% (690/2051) were eligible among patients with evaluable data and 22.2% (153/690) had the composite event. DISCUSSION: By adjusting the thresholds of common eligibility criteria based on the characteristics of COVID-19 patients, we could observe more composite events from fewer patients. CONCLUSIONS: This research demonstrated the potential of using the EHR data of COVID-19 patients to inform the selection of eligibility criteria and their thresholds, supporting data-driven optimization of participant selection towards improved statistical power of COVID-19 trials.

The COVID-19 Trial Finder.

Clinical trials are the gold standard for generating reliable medical evidence. The biggest bottleneck in clinical trials is recruitment. To facilitate recruitment, tools for patient search of relevant clinical trials have been developed, but users often suffer from information overload. With nearly 700 coronavirus disease 2019 (COVID-19) trials conducted in the United States as of August 2020, it is imperative to enable rapid recruitment to these studies. The COVID-19 Trial Finder was designed to facilitate patient-centered search of COVID-19 trials, first by location and radius distance from trial sites, and then by brief, dynamically generated medical questions to allow users to prescreen their eligibility for nearby COVID-19 trials with minimum human computer interaction. A simulation study using 20 publicly available patient case reports demonstrates its precision and effectiveness.

Mucosal Melanoma: New Insights and Therapeutic Options for a Unique and Aggressive Disease.

Mucosal melanoma is a rare disease that is distinct from melanomas arising at other sites in the body. While melanocytes are most abundant in the skin, they can be found in smaller numbers in the mucous membranes, as well as in the eye. There are epidemiologic, genetic, and other physiologic differences between melanomas arising from melanocytes at these various sites, and these differences have important implications for both disease prognosis and treatment. Here, we review the features of mucosal melanoma that distinguish it from melanomas arising at other sites, and we highlight recent biological discoveries and emerging treatment options for this aggressive disease.