Pan AMPK Activation Protects Tubules in Rat Ischemic Acute Kidney Injury.

Acute Kidney Injury (AKI) is characterized by an abrupt decline in kidney function and has been associated with excess risks of death, kidney disease progression, and cardiovascular events. The kidney has a high energetic demand with mitochondrial health being essential to renal function and damaged mitochondria has been reported across AKI subtypes. 5' adenosine monophosphate-activated protein kinase (AMPK) activation preserves cellular energetics through improvement of mitochondrial function and biogenesis when ATP levels are low such as under ischemia-induced AKI. We developed a selective potent small molecule pan AMPK activator, compound 1, and tested its ability to increase AMPK activity and preserve kidney function during ischemia/reperfusion injury in rats. A single administration of 1 caused sustained activation of AMPK for at least 24 hours, protected against acute tubular necrosis, and reduced clinical markers of tubular injury such as NephroCheck and Fractional Excretion of Sodium (FENa). Reduction in plasma creatinine and increased Glomerular Filtration Rate (GFR) indicated preservation of kidney function. Surprisingly, we observed a strong diuretic effect of AMPK activation associated with natriuresis both with and without AKI. Our findings demonstrate that activation of AMPK leads to protection of tubular function under hypoxic/ischemic conditions which holds promise as a potential novel therapeutic approach for AKI. Significance Statement No approved pharmacological therapies currently exist for acute kidney injury. We developed Compound 1 which dose-dependently activated AMPK in the kidney and protected kidney function and tubules after ischemic renal injury in the rat. This was accompanied by natriuresis in injured as well as uninjured rats.

Fomepizole use reported to United States Poison Centers from 2010 to 2021.

BACKGROUND: The diagnosis of toxic alcohol poisoning is often based on clinical presentation and nonspecific surrogate laboratory studies due to limited testing availability. Fomepizole is the recommended antidote and often administered empirically. The objective of this study is to identify substances that mimic toxic alcohols and compare key clinical factors between toxic alcohol and non-toxic alcohol exposures when fomepizole was administered. METHODS: This study was a retrospective evaluation using the National Poison Data System from January 1, 2010 through December 31, 2021. Exposures were included if fomepizole was administered. Toxic alcohol exposures had ethylene glycol or methanol as a coded substance. For exposures not coded as a toxic alcohol, the first substance was described. Paracetamol (acetaminophen) exposures from 2020 and 2021 were excluded. RESULTS: Fomepizole was reportedly used 25,110 times over 12 years. Use increased from 1,955 in 2010 to 2,710 in 2021. Most administrations were for reported toxic alcohol poisoning (60 percent) but use in reported non-toxic alcohol poisoning was greater starting in 2020. Toxic alcohol exposures were older (43.3 versus 39.8 years; P < 0.001) and more likely male (65.7 percent versus 58.2 percent). Level of care was mostly a critical care unit (67.7 percent), which was less common in toxic alcohol (63.3 percent) than non-toxic alcohol exposures (74.2 percent). The most common non-toxic alcohol substances were ethanol (24.9 percent) or an unknown drug (17.5 percent). Acidosis, increased creatinine concentration, anion gap, and osmolal gap, and kidney failure were coded in a lower proportion of toxic alcohol exposures than non-toxic alcohol exposures (P < 0.001). DISCUSSION: The inability to provide rapid clinical confirmation of toxic alcohol poisoning results in the empiric administration of fomepizole to many patients who will ultimately have other diagnoses. Although fomepizole is relative well tolerated we estimated that this practice costs between $1.5 to $2.5 million. The major limitations of this work include the biases associated with retrospective record review, and the inability to confirm the exposures which may have resulted in allocation error. CONCLUSION: Most fomepizole use was for a presumed toxic alcohol. This recently shifted to greater use in likely non-toxic alcohol poisoning. Key difference between the groups suggest fomepizole administration was likely due to the difficulty in diagnosis of toxic alcohol poisoning along with the efficacy and safety of fomepizole. Increased toxic alcohol laboratory testing availability could improve timely diagnosis, reserving fomepizole use for toxic alcohol poisoning.

Risk of post-tonsillectomy hemorrhage among COVID-19 positive pediatric patients.

OBJECTIVE: COVID-19 infection has been demonstrated to increase risk for post-operative bleeding. This study investigated the impact of COVID-19 infection on post-tonsillectomy hemorrhage in pediatric patients, a potentially devastating complication. STUDY DESIGN: Retrospective cohort study. METHODS: The TriNetX database was queried for pediatric patients who underwent tonsillectomy and evaluated for outcomes of primary and secondary post-tonsillectomy hemorrhage. RESULTS: Among subjects 18 years and younger, 1226 were COVID-19 positive and 38,241 were COVID-19 negative in the perioperative period. There was statistically significant increased risk of bleeding with perioperative COVID-19 infection at postoperative days 1, 5, and 10. Additionally, when assessing the role of COVID-19 infection before or after surgery, the risk of bleeding remained statistically significant at all three time points, however these results did not suggest that infection before surgery confers more/less risk compared to infection after. CONCLUSION: The results of this investigation suggest that the presence of COVID-19 in the perioperative period may pose an increased risk for acute or delayed post tonsillectomy hemorrhage. This study employed a large, diverse population and is the first to address this clinical question.

Recalcitrant Stenosis Following Pediatric LTR: Contributing Factors and Clinical Impact.

OBJECTIVES: Laryngotracheal reconstruction (LTR) has revolutionized the management of pediatric subglottic stenosis (SGS). However, postoperative stenosis remains a difficult hurdle to overcome. Our goal is to determine the clinical impact of recalcitrant stenosis after LTR and the factors contributing to postoperative stenosis. STUDY DESIGN: Retrospective review of 181 open LTR patients between 2008 and 2021. SETTING: Stand-alone tertiary children's hospital. METHODS: Recalcitrant stenosis was defined as new or worsening stenosis despite open LTR. Fisher's exact and Mann-Whitney tests were used to detect differences in categorical and continuous clinical data between patients with and without treatment-resistant stenosis. Time-to-decannulation analysis of both groups was performed using Kaplan-Meier analysis and evaluated with log-rank and Cox proportional hazards regression. Multivariate logistical regression was used to assess the validity of associations found in univariate analysis. RESULTS: As expected, the 27 patients with postoperative stenosis were less likely to be decannulated (P < .001, Fisher's Exact), more likely to require a postoperative tracheostomy (P < .001, Fisher's Exact) or revision LTR (P < .001, Fisher's Exact) and had prolonged time to decannulation (P < .001, Log-rank). Children with Grade IV SGS (P = .004, Fisher's Exact), and those with longer suprastomal stent duration (P = .03, Fisher's Exact) were more likely to suffer from recalcitrant stenosis. Stent duration longer than 4 weeks (P = .01) contributed to refractory stenosis when controlling for all aforementioned variables using multivariable logistic regression. Interposition grafts had a protective effect (P = .005). CONCLUSION: Maintaining suprastomal stents over 4 weeks after LTR increases the risk for postoperative stenosis and its sequelae.

Decannulation in Revision Pediatric Laryngotracheal Reconstruction.

OBJECTIVES: To evaluate how patient characteristics and surgical techniques influence the rate of and time to decannulation after pediatric revision laryngotracheal reconstruction. METHODS: The study was a retrospective cohort investigation of children with a history of laryngotracheal stenosis treated between 2008 and 2021 with revision open airway surgery. The primary outcome evaluated was decannulation. The secondary outcome analyzed was time to decannulation. RESULTS: Thirty-nine children were included in the study with median age 49 months; 61.5% were male. Children undergoing single stage revision surgery were far more likely to be decannulated (OR 6.25, 95% CI 1.33-45.97, p = 0.0343). Rolling logistic regression of the probability of decannulation stratified by time between open surgeries demonstrated significantly decreased chance of decannulation with reoperation within 6 months. Children managed with anterior/posterior grafting compared with a single graft were observed to have an increased time to decannulation, (HR 0.365, 95% CI 0.148-0.899, p = 0.005, Log-Rank). CONCLUSION: We observe that in the case of revision pediatric open airway surgery, chance of decannulation is improved when surgery is performed in a single stage as well as 6 months after the most recent procedure. Patients and families should be counseled that complex stenosis requiring double stage procedures or anterior/posterior grafting is associated with a decreased probability of decannulation and increased postoperative time with a tracheostomy, respectively. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1926-1932, 2024.

Pediatric Airway Balloon Dilation: Urge for Safety Redesign.

Airway balloons are widely used by otolaryngologists to treat laryngotracheal stenosis. We review an adverse event and interventions that may prevent similar occurrences. There are no other reports of similar incidents in the Food and Drug Administration Manufacturer and User Facility Device Experience. We implore Acclarent to redesign their airway balloon device to prevent accidental airway irrigation.

A retrospective analysis of pain and opioid usage in head and neck free flap reconstruction.

Objectives: Investigate opioid usage and postoperative pain in patients undergoing head and neck free flap surgery. Methods: A retrospective review of 100 consecutive patients undergoing head and neck free flap reconstruction at two academic centers was performed. Data captured included demographics, postoperative inpatient pain, pain at postoperative visits, morphine equivalent doses (MEDs) administration, medication history, and comorbidities. Data were analyzed using regression models, χ 2 tests, and student's t-tests. Results: Seventy-three percent of patients were discharged with opioid medication, with over half (53.4%) continuing to take opioids at their second postoperative visit, and over one-third (34.2%) continuing to take them around 4-month postoperatively. One out of every five (20.3%) opioid-naïve patients chronically took opioids postoperatively. There was a poor association between inpatient postoperative pain scores and daily MEDs administered (R 2 = 0.13, 0.17, and 0.22 in postoperative Days 3, 5, and 7, respectively). Neither preoperative radiotherapy nor postoperative complications were associated with an increase in opioid usage. Conclusions: For patients undergoing head and neck free flap operations, opioid medications are commonly used for postoperative analgesia. This practice may increase the chance an opioid-naïve patient uses opioids chronically. We found a poor association between MEDs administered and patient-reported pain scores, which suggests that standardized protocols aimed at optimizing analgesia while reducing opioid administration may be warranted. Level of Evidence: 3 (Retrospective cohort study).

Complications associated with costal cartilage harvest in pediatric laryngotracheal reconstruction.

Objective: We aimed to determine the rate of complications associated with autologous costal cartilage graft harvest for pediatric laryngotracheal reconstruction (LTR). Secondarily, we sought to identify risk factors associated with the harvest of autologous costal cartilage, as well as evaluate management strategies. Data Sources: An electronic database search of Ovid MEDLINE, Ovid EMBASE, and PubMed was completed for articles pertaining to complications in autologous costal cartilage harvest for pediatric LTR. Review Methods: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The study characteristics, operative information, and patient demographics were collected. The data concerning postoperative complications, risk factors, and management strategies were collected and analyzed for patterns. Results: A total of 31 manuscripts representing 745 patients were included for analysis. The reported donor site complications included pneumothorax (n = 13, 1.74%), pleural tear (n = 5, 0.67%), infection (n = 8, 1.07%), and scar-related problems (n = 2, 0.26%). There were no reported cases of seroma, persistent pain, or chest wall deformity. Only five studies discussed the management of donor site complications, with intervention in 11 (39.28%) patients including chest tube drainage and steroid injection. Conclusion: There is significant variability in the literature regarding complication rates in autologous costal cartilage harvest for pediatric LTR. The incidence of major postoperative complications is low and supports the use of autologous costal cartilage as graft material for pediatric LTR. Level of Evidence: NA.

Laryngotracheal Reconstruction Outcomes in Children Born Extremely Premature.

INTRODUCTION: There has been a notable increase in the number of neonates born 28 weeks gestational age or younger in the United States. Many of these patients require tracheostomy early in life and subsequent laryngotracheal reconstruction (LTR). Although extremely premature infants often undergo LTR, there is no known study to date examining their post-surgical outcomes. OBJECTIVES: To compare decannulation rates, time to decannulation and complication rates between LTR patients born extremely premature to those born preterm and term. METHODS: We identified 179 patients treated at a stand-alone tertiary children's hospital who underwent open airway reconstruction from 2008 to 2021. A Chi Squared test was used to detect differences in categorical clinical data between the groups of patients. A Mann-Whitney test was used to analyze continuous data within these same groups. Time to decannulation analysis was performed using Kaplan Meier analysis and evaluated with log-rank and Cox proportional hazards regression. RESULTS: Children born extremely premature were more likely to incur complications following LTR (OR = 2.363, p = 0.005, CI 1.295-4.247). There was no difference in time to decannulation (p = 0.0543, Log-rank) or rate of decannulation (OR = 0.4985, p = 0.05, CI 0.2511-1.008). Extremely premature infants were more likely to be treated with an anterior and posterior grafts (OR = 2.471, p = 0.004, CI 1.297-4.535) and/or an airway stent (OR = 3.112, p < 0.001, CI 1.539-5.987). CONCLUSION: Compared with all other patients, extremely premature infants have equivalent decannulation success, but are at an increased risk for complications following LTR. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3608-3614, 2023.

Medical Outcomes of Acute Aspirin Single Substance Poisoning in Pediatric Patients.

BACKGROUND: A consensus guideline on salicylate poisoning recommends referring patients to the emergency department if they ingested 150 mg/kg of aspirin. The dose of aspirin associated with severe poisoning in pediatric patients has not been investigated. OBJECTIVE: This study aims to associate medical outcomes with aspirin overdoses in patients 5 years old and younger. METHODS: A retrospective review of data on pediatric patients with single substance aspirin exposures reported from poison centers across the country was conducted. The primary endpoint was to associate aspirin doses with medical outcomes. Secondary endpoints included evaluation of the signs, symptoms, and treatments of ingestion and their association with medical outcomes. RESULTS: There were 26 488 included exposures with aspirin exposures resulting in no effect (92.5%), minor effect (6.0%), moderate effect (1.4%), major effect (0.2%), and death (0.02%). There were 8921 cases with available weight-based dosing information. Median doses associated with no effect, minor effects, moderate effects, major effects, and death ranged between 28.4 and 40.9 mg/kg, 52.5 and 82.3 mg/kg, 132.1 and 182.3 mg/kg, 132.3 and 172.8 mg/kg, and 142.2 and 284.4 mg/kg, respectively. Minor effect and moderate effect exposures were more likely to have alkalinization documented compared to no effect exposures (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.41-2.17; OR = 1.79, 95% CI = 1.12-2.86). There was no difference in rates of alkalinization between minor and moderate exposures (OR = 1.02, 95% CI: 0.61-1.7). CONCLUSIONS AND RELEVANCE: Reevaluation of the current recommendation of 150 mg/kg for referral to a healthcare facility is necessary for pediatric acute salicylate overdoses.

A descriptive study of aripiprazole, brexpiprazole, and cariprazine exposures in children ages 0 to 5 years reported to United States poison centers.

INTRODUCTION: Increased prescribing of antipsychotics and availability of new antipsychotics has resulted in increased exposures in children. Current data on aripiprazole, brexpiprazole, and cariprazine are limited. METHODS: This was a retrospective database study utilizing the National Poison Data System from 2015 through 2021. We included cases of single substance exposures to aripiprazole, brexpiprazole, cariprazine, or lumateperone in children ages 0 to 5 years old with follow-up to a known outcome. Key outcomes were medical outcomes, clinical effects, and level of care if treated in a healthcare facility. RESULTS: There were 3,573 aripiprazole, 137 brexpiprazole, 249 cariprazine, and one lumateperone exposure over the period. Primary outcomes were evaluated in 2,655 cases (2,390 aripiprazole, 96 brexpiprazole, and 169 cariprazine). Fifty-one percent were male and 77% were between 0 and 2 years old. Moderate effect was coded in 16.6% of aripiprazole, 23% of brexpiprazole, and 12% of cariprazine exposures. Major effect was coded in 0.6% of aripiprazole, 1% of brexpiprazole, and 2.4% of cariprazine exposures. Duration of symptoms was mostly between 8 and 24 h for 34.6% of aripiprazole, 30% of brexpiprazole, and 32% of cariprazine exposures. Over 60% of the children seen in a health care facility were discharged from the emergency department. The lowest doses resulting in at least a moderate effect and admission to a health care facility was 0.46 mg/kg for aripiprazole, 2.1 mg/kg for brexpiprazole, and 1.9 mg/kg for cariprazine. Important clinical effects included central nervous system depression, tremors, tachycardia, agitation, and vomiting. CONCLUSION: Reported ingestions of aripiprazole, brexpiprazole, or cariprazine may result in neurologic symptoms like central nervous system depression or seizures in children. The prolonged duration of symptoms resulted in admission for at least a day for many cases. Further research should address optimal monitoring time and location for these exposures.

Surgically treated pediatric tongue masses: A 20 Year review.

OBJECTIVE: Pediatric tongue lesions represent a rare, diverse group of pathologies related to congenital malformations, inflammatory changes, and neoplastic masses. We present the largest-to-date series of pediatric tongue lesions managed surgically. SETTING: Charts of all pediatric patients with a tongue lesion surgically treated at a regional children's hospital from February 1st, 1997 to August 30th, 2019 were reviewed. METHODS: After obtaining institutional review board approval, a retrospective review was completed of all pediatric patients with a tongue lesion surgically treated at a regional children's hospital from February 1st, 1997 through August 30th, 2019. Charts were evaluated for patient demographics as well as symptoms at presentation, surgical details, pathologic evaluation of the lesion, and rates of recurrence. Categorical variables were compared between various groups using Chi-square and/or Fisher's exact tests. Univariate and multivariable logistic regression analysis was performed unadjusted and adjusted to further explore these relationships. RESULTS: 159 patients were included in the study with ages distributed relatively even across infants (27.7%), children 1-5 years (27.7%), 6-10 years (23.3%), and greater than 10 years of age (21.4%). Patient/family reported race/ethnic background was most commonly Caucasian (34.8%) or Hispanic/Latino/Spanish Origin (34.0%) followed by Black or African American (21.3%). The most commonly reported symptoms were pain (23.3%), difficulty with oral intake (12.6%), bleeding (11.3%), and respiratory distress (11%). Patients with lesions of the base of tongue were significantly more likely to present with respiratory distress or difficulty with oral intake (p < 0.001). The likelihood of recurrence was observed to be higher with lesions managed in infancy (OR 3.85, CI 1.47-10.0, p = 0.005), those greater than 2 cm (OR 3.45, CI 1.34-8.71, p = 0.009), or with laser (OR 4.52, CI 1.25-15.00), p = 0.015). CONCLUSION: Pediatric patients with tongue lesions may present with a wide array of symptoms. Base of tongue lesions should be managed carefully as they are most likely to create barriers to the airway and oral intake. Larger lesions and those managed in infancy are at increased risk for recurrence.

Benzonatate Safety and Effectiveness: A Systematic Review of the Literature.

OBJECTIVE: To review the available literature regarding the treatment effects and efficacy of benzonatate needed to better inform patients, providers, and regulators evaluating its role in modern medical therapies. DATA SOURCES: Comprehensive literature searches were conducted in PubMed, Embase (Elsevier), Cochrane Library, and Scopus for original research articles evaluating the effectiveness, tolerability, and safety profile of benzonatate from January 1956 through August 2022. STUDY SELECTION AND DATA EXTRACTION: The identified studies were screened for relevance and then assessed for inclusion through a full-text review, data extraction, and quality assessment by multiple reviewers using the online software Covidence. DATA SYNTHESIS: The selection process resulted in 37 articles consisting of 21 cohort studies, 5 experimental studies, and 11 case studies and series. Initial clinical studies exploring potential therapeutic benefits collected data from very small populations and limited clinical settings. Safety is primarily assessed in terms of toxicity due to overdose or inappropriate use. Quality assessment raised concerns for high degrees of biases primarily related to the limited sample size, data collection, generalizability, and study design. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review reveals substantial limitations within existing evidence pertaining to the safety and clinical effectiveness of benzonatate and thus, a need for large observational studies or randomized trials to better characterize its role and value in modern medical practice. CONCLUSIONS: Rising safety concerns should bring closer scrutiny upon the prescription of benzonatate whose approval is founded upon evidence that would not stand up to current regulatory review.

Systematic Review of Slide Tracheoplasty Outcomes.

OBJECTIVE: To identify factors predicting success in slide tracheoplasty surgery at a regional children's hospital and compare with available published literature. MEASURES: Retrospective chart review comparing demographics (age, weight) and clinical (operative and hospital course, need for additional airway intervention) factors experienced with slide tracheoplasty. Findings were compared with a systematic review of published literature. RESULTS: Of the 16 tracheal stenosis patients in our cohort, 13 (81.3%) presented with an additional congenital or cardiovascular anomaly. When adjusted for cardiovascular anomalies, congenital tracheal stenosis patients had a mean age of 5.2 months (range 6 days-17 months), mean weight of 5.04 kg, and average ICU and hospital length of stay of 31.5 and 36.0 days, respectively. Tracheostomy was required for 4 patients and no early deaths were recorded. Of the 391 children in the grouped cohort, mean age and weight was older at 7.67 months and larger at 5.70 kg. Length of stay in both ICU and overall hospital course was 31.6 and 43.5 days, respectively. Mortality etiology for 44 patients was reported: 17 (38.6%) cardiac-related and 28 (63.6%) late mortalities. Our overall calculated mortality risk of 1.26 (P < .05) was lower than reported ratios of 2.0+. CONCLUSION: Despite the numerous institutional studies involving tracheal stenosis, mortality and surgical challenges remain high. Future studies with the inclusion of specific perioperative data can prove to further evaluate correlations between presentation characteristics and mortality.

Decannulation in Trisomy 21 patients undergoing laryngotracheal reconstruction.

BACKGROUND: Down Syndrome (DS) patients are more susceptible to either congenital or acquired subglottic stenosis (SGS). This often creates a multilevel airway obstruction and can lead to tracheostomy dependence early in life. As a result, they may require Laryngotracheal Reconstruction (LTR) to achieve decannulation. The primary objective of this study was to assess decannulation rates, time to decannulation and potential barriers to decannulation in DS patients undergoing LTR. METHODS: We performed a retrospective chart review from 2008 to 2021 of 193 children who underwent LTR for treatment for laryngotracheal stenosis at a stand-alone tertiary children's hospital. The relationship between clinical data and decannulation status was evaluated using multivariable logistic regression and Fisher exact tests. Time to decannulation analysis was performed using Kaplan Meier analysis and evaluated with log-rank and Cox proportional hazards regression. RESULTS: We determined that DS patients carry an inherit risk for decannulation failure compared to the general population (OR: 6.112, P = . 044, CI 1.046-35.730). Of the 8 patients with DS only three were decannulated. Overall, patients with Trisomy 21 had a significantly increased time to decannulation when compared to all LTR patients (P = .008, Log-rank). We found that these patients are more likely to have both suprastomal collapse (P = .0004, Fischer's Exact) and Tracheomalacia (P = .034, Fischer's Exact) compared to all other LTR patients. While post-operative tracheomalacia did not significantly affect decannulation failure (P = .056, Fischer's Exact) it did significantly prolong decannulation in all LTR patients (P = .018, Log-rank). CONCLUSION: Trisomy 21 patients are at an increased risk for decannulation failure. Our study illustrates that these poor outcomes are likely a result of conditions more commonly found in this cohort including: narrow tracheal caliber, tracheomalacia and hypotonia.

Malnutrition universal screening tool predicts postoperative complications following major head and neck cancer surgery.

BACKGROUND: Head and neck cancer patients are at risk for malnutrition, which can impact postoperative outcomes. This study evaluates the Malnutrition Universal Screening Tool (MUST) to predict outcomes in major head and neck surgeries. METHODS: A retrospective chart review included 275 major surgical procedures performed on 242 patients over the age of 18 years between May 2015 and May 2020. RESULTS: The majority of patients had a MUST score of zero (68.7%). Just under 17% scored 2 or greater indicating malnourishment. Having a MUST score of 2 or higher was associated with occurrence of a postoperative complication (p < 0.001). Patients with alcohol use disorder or depression were 5.2 (CI: 2.0-13.7, p = 0.001) and 2.75 (CI 1.1-7.0; p = 0.033) times more likely to develop a postoperative complication, respectively. CONCLUSIONS: Malnutrition and comorbidities were associated with complications in our surgical cohort. MUST is a novel tool to identify patients who may benefit from nutritional interventions.

Adolescent Occupational Exposures Reported to United States Poison Centers, 2011-2020.

OBJECTIVE: The aim of this study was to perform an updated description of adolescent occupational exposures reported to the US poison centers. METHODS: We performed a descriptive analysis of adolescents aged 13 to 19 years with unintentional occupational exposures from 2011 to 2020 using the National Poison Data System. A clinically significant occupational poisoning (CSOP) case is defined as exposures with moderate effect, major effect, or death. Differences in substance categories between younger (13 to 17 years) and older (18 to 19 years) adolescents with CSOP were compared. RESULTS: There were 14,374 adolescent occupational exposures. There were 2151 CSOPs. The most common substance categories associated with CSOP were household cleaners (22.3%), chemicals (20.8%), industrial cleaners (14.2%), fumes/gases/vapors (10.8%), and hydrocarbons (5.9%). Categories of exposures were similar across age groups. CONCLUSIONS: This study found that, despite a reduction in the number of adolescent occupational exposures, CSOPs persist.

Review of the Real and Sometimes Hidden Costs in Proteomics Experimental Workflows.

A typical proteomics workflow covers all the steps from growing or collecting the cells/tissues/organism, protein extraction, digestion and cleanup, mass spectrometric analysis, and, finally, extensive bioinformatics to derive biological insight from the data. The details of the procedures employed for this can vary widely by laboratory and by sample type: e.g., hard tissues or cells with walls require much more mechanical disruption to extract proteins than do soft tissues, biological fluids, or wall-less cells. Everything then converges on the mass spectrometer, where there are further choices to be made about how to do the analysis. There is one commonality, however, virtually every group around the world now uses liquid chromatography on-line coupled to tandem mass spectrometry, which means that significant amounts of instrument time are dedicated to every sample. There are many other reviews or methods papers, including in this volume, that cover the details of the various procedures involved in proteomic analyses of all types of samples. Our focus here will be on the cost considerations for such analyses, including considerations to ensure that useful data can be obtained the first time a sample is analyzed. Some of these costs are often overlooked, particularly for those groups who operate their own mass spectrometer(s) and do not have to go to a fee-for-service facility to have something analyzed. The chapter presents several challenges and key suggestions in proving hypotheses in proteomics experimental workflow in different biological systems with specific regard to the costs involved, both real and hidden. The detailed methodology for cost-based studies reported in this chapter can help researchers to set up their laboratory with appropriate equipment as well as to identify potential collaborations based on their analytical instrumentation.

Editorial Commentary: A Complex Network of Bony and Soft-Tissue Stabilizers-and Overall Limb Alignment-Determines Patellofemoral Stability.

Patellofemoral stability is maintained through a complex network of static and dynamic soft-tissue stabilizers, the osseous structure of the patella and trochlea, and overall limb alignment. Thus, determining the risk of recurrent patellar instability must account for as many of these factors as possible in the clinical decision-making process. The tibial tubercle-trochlear groove distance is the most common parameter used for this evaluation but may be limited because of methodologic issues and because this distance is an absolute value. Indices that incorporate other predisposing factors, including trochlear dysplasia, increase the accuracy of predicting recurrent patellar instability and can be used to generate a patient-specific treatment plan.

Single-substance trazodone exposures reported to US poison centers from 2000 to 2019.

BACKGROUND: Individual case reports describe trazodone overdose resulting in QTc prolongation and cardiac arrhythmias. The clinical effects and outcomes associated with trazodone exposures on a large-scale basis are less well known. OBJECTIVE: The primary objective was to characterize the severity of single substance trazodone exposures and identify any relationships that may exist between dose of trazodone and severity of exposure. The secondary objective was to describe these exposures from a demographic and clinical symptom standpoint. METHODS: A retrospective review of single-substance trazodone exposures reported to the National Poison Data System (NPDS) from 1 January 2000 to 31 December 2019 was performed. The primary objective was to characterize the severity of trazodone exposures and relationships between ingested dose and level of care required or medical outcome. RESULTS: A total of 118,773 cases were included in the analysis of demographics and level of care required. A majority (59.5%) of cases did not require medical admission. Of the 81,698 cases with known medical outcomes, the most common clinical effects included mild-moderate CNS depression (49.7%), QTc prolongation (12.2% of cases in 2019), vomiting (9.0%), hypotension (7.0%), and tachycardia (7.0%). The median ingested dose associated with treatment, and release from the emergency department was 600 mg compared to 1500 mg in those admitted to the intensive care unit (ICU). Regarding medical outcome, median ingested dose ranged from 600 mg in those experiencing no effect to 1500 mg in those experiencing major effects. Cardiac-related clinical effects and the need for cardiac-specific interventions were overall infrequent. A dose-response relationship was identified for level of care and medical outcome. CONCLUSIONS: Many trazodone exposures can be characterized as low severity due to the infrequent need for healthcare facility admission and large proportion of cases that experienced no effects or only minor effects.