Impact of Sugammadex Versus Neostigmine Reversal on Postoperative Recovery Time in Patients With Obstructive Sleep Apnea Undergoing Bariatric Surgery: A Double-Blind, Randomized Controlled Trial.

BACKGROUND: Residual neuromuscular blockade can be associated with serious postoperative complications. Sugammadex is a newer neuromuscular blocking drug (NMBD) reversal agent that rapidly and completely reverses rocuronium. Whether sugammadex has any advantages over neostigmine in morbidly obese patients with obstructive sleep apnea (OSA) is unclear. We investigated whether sugammadex would reduce discharge time from the operating room (OR) compared with neostigmine in morbidly obese patients with OSA undergoing bariatric surgery. METHODS: This was a prospective, double-blinded randomized controlled superiority trial with 2 parallel groups. Patients were randomized 1:1 into reversal of NMBD with sugammadex or neostigmine. Our inclusion criteria were morbidly obese adult patients with OSA undergoing elective bariatric surgery under general anesthesia. Our exclusion criteria were allergy to rocuronium, sugammadex or neostigmine, malignant hyperthermia, hepatic or renal insufficiency, neuromuscular diseases, and an inability to give consent. The primary outcome was the time from administration of the NMBD reversal agent to discharge from the OR. Secondary outcomes included the time from administration of the NMBD reversal agent to the time the patient opened eyes to command, and the time to extubation. The Mann-Whitney test was used to compare the outcomes between treatment groups. RESULTS: We randomized 120 patients into 2 groups of 60 patients. Overall median body mass index (BMI) was 48.1 kg/m2 ([interquartile range, IQR]) [43.0-53.5]. The time from drug administration to discharge from OR was 13.0 minutes [10.0-17.0] in the sugammadex group and 13.5 minutes [11.0-18.3] in the neostigmine group (P = .27). The treatment effect estimate with a bootstrapped 95% confidence interval [CI] for time from admission to discharge from OR was -0.5 [-2.5 to 3]. No differences were observed in postoperative complications and other secondary outcomes. CONCLUSIONS: No difference was observed in OR discharge time in morbidly obese patients with OSA when sugammadex was administered instead of neostigmine.

Intraoperative hypotension and the risk of acute kidney injury following liver transplantation.

BACKGROUND: Acute kidney injury (AKI) is a frequent adverse outcome following liver transplantation (LT) with a multifactorial etiology. It is critical to identify modifiable risk factors to mitigate the risk. One key area of interest is the role of intraoperative hypotension, which remains relatively unexplored in liver transplant cohorts. METHODS: This was a retrospective observational cohort study of 1292 adult patients who underwent LT (between 2009 and 2019). Multivariable logistic regression analysis was used to explore the association between intraoperative hypotension, quantified by time duration (in min) under various mean arterial pressure (MAP) thresholds, and the primary outcome of early postoperative AKI according to the KDIGO criteria. RESULTS: AKI occurred in 40% of patients and was independently associated with greater than 20 min spent below MAP thresholds of 55 mm Hg (adjusted OR = 1.866; 95% CI = 1.037-3.44; P = 0.041) and 50 mm Hg (adjusted OR = 1.801; 95% CI = 1.087-2.992; P = 0.023). Further sensitivity analyses demonstrated that the association between intraoperative hypotension and postoperative AKI was accentuated after restricting the analysis to patients with a normal preoperative renal function. CONCLUSIONS: Prolonged (>20 min) intraoperative hypotension (below a MAP of 55 mm Hg) was independently associated with AKI following LT, after adjusting for several known confounders.

Comparing vitamin B2 versus 5% dextrose in water for optimal ureteric jet visualisation at the time of pelvic reconstructive surgery: A randomised controlled trial.

OBJECTIVE: To compare preoperative vitamin B2 versus intraoperative cystoscopy distension using 5% dextrose in water (D5W) for ureteric jet visualisation during pelvic reconstructive surgery. DESIGN: Double-blinded, randomised controlled trial. SETTING: Three tertiary hospitals in Toronto, Canada. POPULATION: Adult women undergoing pelvic reconstructive surgery. METHODS: Patients were randomised to receive 100 mg of vitamin B2 preoperatively versus bladder distension with D5W intraoperatively. MAIN OUTCOMES: The primary outcome was the rate of accurate detection of bilateral ureteric jets during cystoscopy. Secondary outcomes included the time elapsed until visualisation, use of intravenous furosemide or fluorescein to assist with visualisation, surgeon satisfaction, and positive urine culture 1 week after surgery. RESULTS: The intervention was completed by 236 patients (vitamin B2 n = 117, D5W n = 119). Preoperative characteristics were similar across groups. Accurate detection of both ureteric jets was high in both groups (vitamin B2 97.4% vs. D5W 90.8%, p = 0.051). The vitamin B2 group had significantly lower use of fluorescein rescue compared with the D5W group (3.4% vs. 11.8%, respectively, p = 0.025). Surgeon satisfaction while using vitamin B2 was significantly higher (p < 0.001). There were no significant differences in the time elapsed until visualisation, the use of furosemide, or the incidence of positive urine culture at 1 week after surgery. CONCLUSIONS: Both preoperative vitamin B2 and intraoperative cystoscopy distension with D5W are highly available and inexpensive methods to detect ureteric jets with high accuracy at the time of pelvic reconstructive surgery. Vitamin B2 was shown to have lower rates of fluorescein rescue for visualisation and higher rates of surgeon satisfaction.

Acute kidney injury during cisplatin therapy and associations with kidney outcomes 2 to 6 months post-cisplatin in children: a multi-centre, prospective observational study.

BACKGROUND: Few studies describe acute kidney injury (AKI) burden during paediatric cisplatin therapy and post-cisplatin kidney outcomes. We determined risk factors for and rate of (1) AKI during cisplatin therapy, (2) chronic kidney disease (CKD) and hypertension 2-6 months post-cisplatin, and (3) whether AKI is associated with 2-6-month outcomes. METHODS: This prospective cohort study enrolled children (aged < 18 years at cancer diagnosis) treated with cisplatin from twelve Canadian hospitals. AKI during cisplatin therapy (primary exposure) was defined based on Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria (≥ stage one). Severe electrolyte abnormalities (secondary exposure) included ≥ grade three hypophosphatemia, hypokalemia, or hypomagnesemia (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0). CKD was albuminuria or decreased kidney function for age (KDIGO guidelines). Hypertension was defined based on the 2017 American Academy of Pediatrics guidelines. RESULTS: Of 159 children (median [interquartile range [IQR]] age: 6 [2-12] years), 73/159 (46%) participants developed AKI and 55/159 (35%) experienced severe electrolyte abnormalities during cisplatin therapy. At median [IQR] 90 [76-110] days post-cisplatin, 53/119 (45%) had CKD and 18/128 (14%) developed hypertension. In multivariable analyses, AKI was not associated with 2-6-month CKD or hypertension. Severe electrolyte abnormalities during cisplatin were associated with having 2-6-month CKD or hypertension (adjusted odds ratio (AdjOR) [95% CI]: 2.65 [1.04-6.74]). Having both AKI and severe electrolyte abnormalities was associated with 2-6-month hypertension (AdjOR [95% CI]: 3.64 [1.05-12.62]). CONCLUSIONS: Severe electrolyte abnormalities were associated with kidney outcomes. Cisplatin dose optimization to reduce toxicity and clear post-cisplatin kidney follow-up guidelines are needed. A higher resolution version of the Graphical abstract is available as Supplementary information.

Urinary Amino-Polycyclic Aromatic Hydrocarbons in Urban Residents: Finding a Biomarker for Residential Exposure to Diesel Traffic.

Despite substantial evidence of marked exposure to and ill-health effects from diesel exhaust (DE) emissions among occupational population (e.g., miners, truck drivers, and taxi drivers), it is less understood to what extent non-occupational population was exposed to DE among various combustion sources, largely due to the lack of biomarkers that would indicate specific exposure to DE. We evaluated whether urinary amino-polycyclic aromatic hydrocarbons (APAHs), such as major metabolites of DE-specific nitrated PAHs, can be used as DE exposure biomarkers in residential settings. We measured five urinary APAHs in 177 urine samples from 98 UK residents, 89 (91%) of them were London residents, and estimated their residential proximity to various traffic indicators (e.g., the road type, road length, traffic flow, and traffic volume). Participants living within 100 m of major roads exhibited increased levels of all five APAHs, among which 2-amino-fluorene (2-AFLU) reached statistical significance (p < 0.05). We estimated that a 10 m increase in the length of nearby major roads (<100 m) was associated with a 4.4% (95% CI of 1.1 to 7.6%) increase in 2-AFLU levels. Levels of 2-AFLU were significantly associated with the traffic flow of nearby buses and heavy-duty vehicles but not motorbikes, taxis, or coaches. We did not observe a significant association between distance to major roads or the sum of the major road length within 100 m with the other four biomarker concentrations. These results suggest the use of urinary 2-AFLU as a biomarker of DE exposure in urban residents.

Distribution of Iliac Artery Calcification on Unenhanced Computed Tomography Scans Performed on Potential Recipients Prior to Renal Transplantation.

PURPOSE: To investigate whether a significant difference exists between the calcification of the common iliac arteries (CIAs) and the external iliac arteries (EIAs) and test for associations between clinical factors and the distribution of calcification. METHODS: A retrospective review of renal transplant candidates who underwent a routine preoperative unenhanced computed tomography yielded 214 patients. Agatston scores for the patients' left CIA, left EIA, right CIA, and right EIA were assigned. A retrospective search of patient records screened for 5 clinical factors (diabetes, hypertension, coronary artery disease [CAD], smoking, and dialysis). Data were assessed using a 2-sided t test, odds ratio, and a multivariate linear regression calculated through generalized estimating equation (GEE). RESULTS: The log-transformed Agatston scores in the CIA were found to be significantly greater than that in the EIA (t = 9.57, P < .0001), with a mean difference of 1.5078 (95% confidence interval: 1.1962-1.8194), indicating relative EIA sparing. There were no significant differences in calcification between the right and left sides. Generalized estimating equation found that CAD and smoking demonstrated independent positive associations with EIA sparing (GEE = 2.6464 [P = .0197] and 1.9092 [P = .0470], respectively). Age was also significantly associated and indicated that EIA sparing remained relatively constant throughout patients' lives (GEE = 1.0711 [P < .0001]). CONCLUSION: This study has demonstrated statistically significant EIA sparing in end-stage renal disease patients and identified CAD and smoking as associated factors. This phenomenon warrants further investigation into its biological mechanisms and the impact of EIA sparing on outcomes following transplants.

Revisiting the public awareness, attitudes, and understanding towards epilepsy among Singapore residents.

A survey to assess the familiarity, attitudes, and knowledge about epilepsy was done using a questionnaire identical to the one used in 1999. Two hundred forty-six people participated in our survey in 2017 as compared with 214 in the 1999 survey. In terms of familiarity about epilepsy, 76% had heard or read about epilepsy, 55.7% had witnessed a seizure, and 35.8% knew someone with epilepsy (85%, 56%, and 36% respectively in 1999). Forty point five percent were not familiar with or did not know what to do if they witnessed a seizure (44% in 1999); 25.6% would put something in the mouth of a person having a seizure (32% in 1999). In terms of attitudes towards epilepsy, 14.6% would object to their children associating with one with epilepsy while 19.9% would object to their children marrying a person with epilepsy (13% and 36% respectively in 1999). Only 43.1% would employ a person with epilepsy while 68.3% would employ if seizures do not interfere with the job (42 and 66% respectively in 1999). In terms of knowledge of seizures and epilepsy, 66.3% associated epileptic attack with convulsion (68% in 1999). Only 37.5% were aware of nonconvulsive forms of epilepsy (25% in 1999). Twenty-six point eight percent did not know what treatment to recommend to relatives/friends with epilepsy while 60.6% recommend western medicine (22% and 60% respectively in 1999). CONCLUSION: The awareness, attitudes, and understanding towards epilepsy does not seem to show any significant difference when compared with that in 1999. Reluctance to marry and employ a person with epilepsy persists. The awareness about first aid of a patient having a seizure, attitudes towards marrying a person with epilepsy, and the understanding of cause of epilepsy have shown some positive changes over 17 years.

Safety, Pharmacokinetics, and Pharmacodynamics of the New Aldose Reductase Inhibitor Govorestat (AT-007) After a Single and Multiple Doses in Participants in a Phase 1/2 Study.

In classic galactosemia (CG) patients, aldose reductase (AR) converts galactose to galactitol. In a phase 1/2, placebo-controlled study (NCT04117711), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of govorestat were evaluated after single and multiple ascending doses (0.5-40 mg/kg) in healthy adults (n = 81) and CG patients (n = 14). Levels of govorestat in plasma and cerebrospinal fluid (CSF) and blood levels of galactitol, galactose, and galactose-1-phosphate (Gal-1p) were measured for population PK and PK/PD analyses. Govorestat was well tolerated. Adverse event frequency was comparable between placebo and govorestat. Govorestat PK displayed a 2-compartment model with sequential zero- and first-order absorption, and no effect of demographic factors. Multiple-dose PK of govorestat was linear in the 0.5-40 mg/kg range, and CSF levels increased dose dependently. Elimination half-life was ∼10 h. PK/PD modeling supported once-daily dosing. Change from baseline in galactitol was -15% ± 9% with placebo and -19% ± 10%, -46% ± 4%, and -51% ± 5% with govorestat 5, 20, and 40 mg/kg, respectively, thus was similar for 20 and 40 mg/kg. Govorestat did not affect galactose or Gal-1p levels. In conclusion, govorestat displayed a favorable safety, PK, and PD profile in humans, and reduced galactitol levels in the same magnitude (∼50%) as in a rat model of CG that demonstrated an efficacy benefit on neurological, behavioral, and ocular outcomes.

Intraoperative hypotension during critical phases of liver transplantation and its impact on acute kidney injury: a retrospective cohort study.

INTRODUCTION: Acute Kidney Injury (AKI) following Liver Transplantation (LT) is associated with prolonged ICU and hospital stay, increased risk of chronic renal disease, and decreased graft survival. Intraoperative hypotension is a modifiable risk factor associated with postoperative AKI. We aimed to determine in which phase of LT hypotension has the strongest association with AKI: the anhepatic or neohepatic phase. METHODS: This retrospective cohort study included adult patients undergoing LT between January 2010 and June 2022. Exclusion criteria were re-do or combined transplantations, preoperative dialysis, and early graft failure or death. Primary outcome was AKI as defined by KDIGO. Hypotension was Mean Arterial Pressure (MAP) below predefined thresholds in minutes. Risk adjusted logistic regression analysis considered hypotension in 3 periods: the total procedure, anhepatic phase, and neohepatic phase. RESULTS: Our cohort included 1153 patients. The median MELD-NA score was 19 (IQR 11-28), and 412 (35.9%) were living-related donations. AKI occurred in 544 patients (47.2%). The unadjusted model showed an association with AKI for MAP < 60 mmHg (OR = 1.011 [1.0, 1.022], p = 0.047) and MAP < 55 mmHg (OR = 1.023 [1.002, 1.047], p = 0.040) in the anhepatic phase, and for MAP < 60 mmHg (OR = 1.032 [1.01, 1.056], p = 0.006) in the neohepatic phase. The adjusted model did not reach significance in the subgroups but did in the total procedure: MAP < 60 mmHg (OR = 1.005 [1.002, 1.008], p < 0.001) and MAP < 55 mmHg (OR = 1.008 [1.003-1.013], p = 0.004). CONCLUSION: Intraoperative hypotension is independently associated with AKI following LT. This association is seen during the anhepatic phase. Maintaining MAP above 60 mmHg may improve kidney function after LT.

Nocturnal Cardiac Arrhythmias in Heart Failure With Obstructive and Central Sleep Apnea.

BACKGROUND: Both OSA and central sleep apnea (CSA) may contribute to nocturnal cardiac arrhythmias (NCAs). Data are scarce regarding the prevalence of clinically important nocturnal atrial and ventricular arrythmias in patients with heart failure with reduced ejection fraction (HFrEF) and OSA or CSA. RESEARCH QUESTION: In a cohort of patients with HFrEF, how does the prevalence of NCA compare among those with OSA, CSA, and those with no to mild sleep apnea? Is the severity of OSA or CSA associated with atrial and ventricular NCAs? STUDY DESIGN AND METHODS: This cross-sectional analysis is an ancillary study of the Effect of Adaptive Servo Ventilation on Survival and Hospital Admissions in Heart Failure (ADVENT-HF) trial. We compared the prevalence of NCAs (excessive supraventricular ectopic activity [ESVEA], defined as premature atrial complexes ≥30/h or supraventricular tachycardia ≥ 20 beats); atrial fibrillation/flutter [AF]; and > 10 premature ventricular complexes [PVC/h]) on ECGs from polysomnograms of patients with HFrEF between those with OSA (apnea-hypopnea index [AHI ≥ 15 events/h]), those with CSA (AHI ≥ 15 events/h), and those with no to mild sleep apnea (AHI < 15 events/h [control]). RESULTS: The prevalence of ESVEA was higher in patients with OSA (n = 430) and CSA (n = 150) compared with control participants (n = 76): 0%, 9%, and 12%, respectively. The prevalence of AF in the control, OSA, and CSA groups was 9%, 17%, and 27%; the prevalence of > 10 PVC/h was 45%, 59%, and 63%. In multivariable regression analyses, premature atrial complexes/h was associated with OSA severity (obstructive AHI: 22.4% increase per 10 events/h [95% CI, 5.2-42.3; P = .009), although neither obstructive nor central AHI was associated with AF or > 10 PVC/h. INTERPRETATION: In patients with HFrEF, the prevalences of nocturnal ESVEA, AF, and PVC > 10/h were higher in those with OSA or CSA than in those without OSA or CSA, and OSA severity was related to the burden of nocturnal atrial ectopy. Severity of OSA or CSA was not significantly related to AF or > 10 PVC/h. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01128816; URL: www. CLINICALTRIALS: gov.

Direct-bonded diamond membranes for heterogeneous quantum and electronic technologies.

Diamond has superlative material properties for a broad range of quantum and electronic technologies. However, heteroepitaxial growth of single crystal diamond remains limited, impeding integration and evolution of diamond-based technologies. Here, we directly bond single-crystal diamond membranes to a wide variety of materials including silicon, fused silica, sapphire, thermal oxide, and lithium niobate. Our bonding process combines customized membrane synthesis, transfer, and dry surface functionalization, allowing for minimal contamination while providing pathways for near unity yield and scalability. We generate bonded crystalline membranes with thickness as low as 10 nm, sub-nm interfacial regions, and nanometer-scale thickness variability over 200 by 200 µm2 areas. We measure spin coherence times T2 for nitrogen vacancy centers in 150 nm-thick bonded membranes of up to 623 ± 21 µs, suitable for advanced quantum applications. We demonstrate multiple methods for integrating high quality factor nanophotonic cavities with the diamond heterostructures, highlighting the platform versatility in quantum photonic applications. Furthermore, we show that our ultra-thin diamond membranes are compatible with total internal reflection fluorescence (TIRF) microscopy, which enables interfacing coherent diamond quantum sensors with living cells while rejecting unwanted background luminescence. The processes demonstrated herein provide a full toolkit to synthesize heterogeneous diamond-based hybrid systems for quantum and electronic technologies.

Measuring vibration and shock in power wheelchairs for clinical application.

Research evidence demonstrates the negative effects of Whole-Body Vibration (WBV) and correlation between exposure to WBV and detriment to health. ISO Standard 2631-1 (1997) is the accepted standard for human exposure to WBV in vehicle vibration, and provides vibration guidelines for health and comfort. These standards have not been applied to power wheelchairs (PWC), and no clinical tool exists that measures vibration levels during live power wheelchair driving. This study measures WBV and shock levels during PWC driving, considering the impact of terrains, base configurations, and seat cushions. A sensor tag accelerometer was used to measure vibration and shock in three different PWC configurations driven over seven different terrains. Data was collected for two runs per wheelchair, per terrain type, per cushion type. Differences were significant (p < .001) for overall mean and median peak vibration compared across the seven terrains, and for overall mean vibration for basic and enhanced cushions. Differences were also noted in mean and peak vibration in the three different base configurations (p = .0052). Results were compared with ISO 2631-1 guidelines. Mechanical shock on certain terrains created peak vibration levels with likely health risk. Results from this study can inform PWC prescription process.

Understanding the patient experience of Classic Galactosemia in pediatric and adult patients: increased disease burden, challenges with daily living, and how they evolve over time.

BACKGROUND: Classic Galactosemia (CG) is a rare, autosomal recessive condition. Newborn screening and a timely galactose-restricted diet can resolve acute symptoms and decrease fatalities, but significant chronic, progressive morbidities remain and significantly impact daily life. The objective of this study was to better understand the burden of disease in children and adults with CGs and describe how morbidities evolve over time. METHODS: A total of 49 individuals with CG from the United States (US) were included in the qualitative surveys (13 adults [9 self-reported] and 36 pediatric patients). Fifteen follow-up interviews were conducted with 5 adults and 10 caregivers, discussing 17 individuals with CG overall (2 caregivers each discussed 2 children). RESULTS: Qualitative survey and interview data demonstrated the substantial burden of CG. Difficulties in a wide range of functions were experienced, which included: speech articulation; language and communication; cognition, memory and learning; emotions; and social interactions. Most difficulties appeared in childhood and persisted or worsened with age. Most adults did not live independently. Others lived semi-independently and experienced many daily challenges and required support. Caregivers also described the burden of caring for someone with CG and spoke about the impact this has on their day-to-day life, work, and relationships. CONCLUSIONS: These findings demonstrate the pronounced and persistent burden of disease encountered by individuals with CG, and that the condition has a significant impact on the quality of life of caregivers.

Incidence of post-transplant cytomegalovirus viremia in patients receiving lungs after ex vivo lung perfusion.

Objectives: Cytomegalovirus infection after lung transplant is associated with increased morbidity and mortality. Inflammation, infection, and longer ischemic times are important risk factors for cytomegalovirus infection. Ex vivo lung perfusion has helped to successfully increase the use of high-risk donors over the last decade. However, the impact of ex vivo lung perfusion on post-transplant cytomegalovirus infection is unknown. Methods: We performed a retrospective analysis of all adult lung transplant recipients from 2010 to 2020. The primary end point was comparison of cytomegalovirus viremia between patients who received ex vivo lung perfusion donor lungs and patients who received non-ex vivo lung perfusion donor lungs. Cytomegalovirus viremia was defined as cytomegalovirus viral load greater than 1000 IU/mL within 2 years post-transplant. Secondary end points were the time from lung transplant to cytomegalovirus viremia, peak cytomegalovirus viral load, and survival. Outcomes were also compared between the different donor recipient cytomegalovirus serostatus matching groups. Results: Included were 902 recipients of non-ex vivo lung perfusion lungs and 403 recipients of ex vivo lung perfusion lungs. There was no significant difference in the distribution of the cytomegalovirus serostatus matching groups. A total of 34.6% of patients in the non-ex vivo lung perfusion group developed cytomegalovirus viremia, as did 30.8% in the ex vivo lung perfusion group (P = .17). There was no difference in time to viremia, peak viral loads, or survival when comparing both groups. Likewise, all outcomes were comparable in the non-ex vivo lung perfusion and ex vivo lung perfusion groups within each serostatus matching group. Conclusions: The practice of using more injured donor organs via ex vivo lung perfusion has not affected cytomegalovirus viremia rates and severity in lung transplant recipients in our center.

Outcomes of lung transplantation from donors with a history of substance abuse.

OBJECTIVE: The study objective was to determine whether donor substance abuse (opioid overdose death, opioid use, cigarette or marijuana smoking) impacts lung acceptance and recipient outcomes. METHODS: Donor offers to a single center from 2013 to 2019 were reviewed to determine if lung acceptance rates and recipient outcomes were affected by donor substance abuse. RESULTS: There were 3515 donor offers over the study period. A total of 154 offers (4.4%) were opioid use and 117 (3.3%) were opioid overdose deaths. A total of 1744 donors (65.0%) smoked cigarettes and 69 donors (2.6%) smoked marijuana. Of smokers, 601 (35.0%) had less than 20 pack-year history and 1117 (65.0%) had more than 20 pack-year history. Substance abuse donors were younger (51.5 vs 55.2 P < .001), more often male (65.6 vs 54.8%, P < .001), more often White (86.2 vs 68.7%, P < .001), and had hepatitis C (8.3 vs 0.8%, P < .001). Donor acceptance was significantly associated with brain dead donors (odds ratio, 1.56, P < .001), donor smoking history (odds ratio, 0.56, P < .001), hepatitis C (odds ratio, 0.35, P < .001), younger age (odds ratio, 0.98, P < .001), male gender (odds ratio, 0.74, P = .004), and any substance abuse history (odds ratio, 0.50, P < .001), but not opioid use, opioid overdose death, or marijuana use. Recipient survival was equivalent when using lungs from donors who had opioid overdose death, who smoked marijuana, or who smoked cigarettes for less than 20 patient-years or more than 20 patient-years, and significantly longer in recipients of opioid use lungs. There was no significant difference in time to chronic lung allograft dysfunction for recipients who received lungs from opioid overdose death or with a history of opioid use, marijuana smoking, or cigarette smoking. CONCLUSIONS: Donor acceptance was impacted by cigarette smoking but not opioid use, opioid overdose death, or marijuana use. Graft outcomes and recipient survival were similar for recipients of lungs from donors who abused substances.

Perspectives of Pediatric Nephrologists, Intensivists and Nurses Regarding AKI Management and Expected Outcomes.

Background: Acute kidney injury (AKI) in critically ill children is associated with increased risk for short- and long-term adverse outcomes. Currently, there is no systematic follow-up for children who develop AKI in intensive care unit (ICU). Objective: This study aimed to assess variation regarding management, perceived importance, and follow-up of AKI in the ICU setting within and between healthcare professional (HCP) groups. Design: Anonymous, cross-sectional, web-based surveys were administered nationally to Canadian pediatric nephrologists, pediatric intensive care unit (PICU) physicians, and PICU nurses, via professional listservs. Setting: All Canadian pediatric nephrologists, PICU physicians, and nurses treating children in the ICU were eligible for the survey. Patients: N/A. Measurements: Surveys included multiple choice and Likert scale questions on current practice related to AKI management and long-term follow-up, including institutional and personal practice approaches, and perceived importance of AKI severity with different outcomes. Methods: Descriptive statistics were performed. Categorical responses were compared using Chi-square or Fisher's exact tests; Likert scale results were compared using Mann-Whitney and Kruskal-Wallis tests. Results: Surveys were completed by 34/64 (53%) pediatric nephrologists, 46/113 (41%) PICU physicians, and 82 PICU nurses (response rate unknown). Over 65% of providers reported hemodialysis to be prescribed by nephrology; a mix of nephrology, ICU, or a shared nephrology-ICU model was reported responsible for peritoneal dialysis and continuous renal replacement therapy (CRRT). Severe hyperkalemia was the most important renal replacement therapy (RRT) indication for both nephrologists and PICU physicians (Likert scale from 0 [not important] to 10 [most important]; median = 10, 10, respectively). Nephrologists reported a lower threshold of AKI for increased mortality risk; 38% believed stage 2 AKI was the minimum compared to 17% of PICU physicians and 14% of nurses. Nephrologists were more likely than PICU physicians and nurses to recommend long-term follow-up for patients who develop any AKI during ICU stay (Likert scale from 0 [none] to 10 [all patients]; mean=6.0, 3.8, 3.7, respectively) (P < .05). Limitations: Responses from all eligible HCPs in the country could not obtained. There may be differences in opinions between HCPs that completed the survey compared to those that did not. Additionally, the cross-sectional design of our study may not adequately reflect changes in guidelines and knowledge since survey completion, although no specific guidelines have been released in Canada since survey dissemination. Conclusions: Canadian HCP groups have variable perspectives on pediatric AKI management and follow-up. Understanding practice patterns and perspectives will help optimize pediatric AKI follow-up guideline implementation.

Contexte: L'insuffisance rénale aiguë (IRA) chez les enfants gravement malades est associée à un risque accru d'issues défavorables à court et à long terme. En ce moment, il n'existe aucun suivi systématique pour les enfants qui développent une IRA pendant un séjour à l'unité des soins intensifs (USI). Objectif: Cette étude visait à évaluer les variations dans la prise en charge de l'IRA, de son importance perçue et de son suivi, tant au sein des groupes de professionnels de la santé (PS) qu'entre les différents groupes de PS. Conception: Des sondages transversaux à remplir de façon anonyme en ligne ont été menés à l'échelle nationale auprès de néphrologues pédiatriques canadiens, de médecins des unités de soins intensifs pédiatriques (USIP) et de membres du personnel infirmier des USIP ayant été répertoriés à partir de listes professionnelles. Cadre: Tous les néphrologues pédiatriques canadiens, médecins et membres du personnel infirmier qui traitent des enfants en USI étaient admissibles à répondre au sondage. Patients: S/O. Mesures: Les sondages comportaient des questions à choix multiples et des questions de type échelle de Likert qui portaient sur les pratiques actuelles de la gestion et de suivi à long terme de l'IRA, notamment sur les approches institutionnelles et personnelles de pratique et sur l'importance perçue de la gravité de l'IRA avec différents résultats. Méthodologie: Des statistiques descriptives ont été réalisées. Les réponses catégorielles ont été comparées à l'aide du chi-carré ou de tests exacts de probabilité de Fisher; les résultats des échelles de Likert ont été comparés à l'aide de tests de Mann-Whitney et de Kruskal-Wallis. Résultats: Les sondages ont été complétés par 53 % des néphrologues pédiatriques (34/64), 41 % des médecins d'USIP (46/113) et par 82 membres du personnel infirmier d'USIP (taux de réponse inconnu). Plus de 65 % des prestataires de soins ont déclaré que l'hémodialyse était prescrite par le service de néphrologie, alors que la dialyze péritonéale et la thérapie de remplacement rénal continu (TRRC) étaient confiées à la fois à la néphrologie, à l'USI ou à un modèle partagé néphrologie-USI. L'hyperkaliémie grave était l'indication la plus importante de la TRR pour les néphrologues et les médecins en USIP (échelle de Likert de 0 [pas important] à 10 [le plus important]; médiane = 10, 10, respectivement). Les néphrologues ont signalé un seuil inférieur d'IRA pour l'augmentation du risque de mortalité; 38 % d'entre eux estimaient que l'IRA de stade 2 était le seuil minimum, contre 17 % des médecins en USI et 14 % du personnel infirmier. Les néphrologues étaient plus susceptibles que les médecins et le personnel infirmier des USIP de recommander un suivi à long terme pour les patients qui développent une IRA pendant leur séjour en USI (échelle Likert de 0 [aucun] à 10 [tous les patients]; moyennes respectives = 6,0; 3,8 et 3,7 [p < 0,05]). Limites: Il n'a pas été possible d'obtenir les réponses de tous les PS admissibles au pays. Des différences d'opinions sont possibles entre les PS qui ont répondu au sondage et ceux qui ne l'ont pas fait. De plus, la conception transversale de notre étude pourrait ne pas refléter adéquatement les changements apportés aux lignes directrices et aux connaissances depuis la fin de cette enquête, bien qu'aucune ligne directrice particulière n'ait été publiée au Canada depuis la diffusion du sondage. Conclusion: Les divers groupes de professionnels de la santé canadiens ont des points de vue différents en ce qui concerne la prise en charge et le suivi de l'IRA chez les enfants. La compréhension des modèles de pratique et des perspectives permettra d'optimiser la mise en œuvre de directives de suivi de l'IRA pédiatrique.

α2-fraction and haptoglobin as biomarkers for disease activity in oligo- and polyarticular juvenile idiopathic arthritis.

OBJECTIVES: Unlike in adult rheumatology, for most forms of juvenile idiopathic arthritis (JIA) no reliable biomarkers currently exist to assess joint and disease activity. However, electrophoresis is frequently found changed in active juvenile arthritis. The objective of this study was to evaluate the α2-fraction of serum electrophoresis and its main components as biomarkers for JIA, categories extended/persistent oligoarthritis and seronegative polyarthritis, in comparison with the conventionally used erythrocyte sedimentation rate and C-reactive protein. METHODS: Serum samples and clinical data from 181 patients with JIA were collected. Serum electrophoresis and α2-fraction and its components were determined using standard methods. Relationship between calculated α2-fraction of serum electrophoresis (CA2F) and its components, acute-phase parameters and cJADAS27 was assessed using Pearson's correlation coefficient and linear regression modelling, adjusting for confounding effects. Results were confirmed in a second cohort with 223 serum samples from 37 patients, using a mixed model to account for repeated measures. RESULTS: Compared to ESR and CRP, CA2F showed higher correlation to cJADAS27, in particular for persistent oligoarthritis. Of the three components of the α2-fraction, haptoglobin showed the highest correlation to cJADAS27. Regression analysis demonstrated higher ability to predict cJADAS27 for CA2F, and especially for haptoglobin as a component thereof, than for CRP and ESR. CONCLUSION: Compared to conventional methods, α2-fraction of serum electrophoresis and specifically, haptoglobin show higher correlations with disease activity in common subtypes of JIA, representing excellent candidates as biomarkers for disease activity. Further studies are necessary to determine diagnostic value and correlations in other subtypes.

Qualitative interviews with adults with Classic Galactosemia and their caregivers: disease burden and challenges with daily living.

BACKGROUND: Classic Galactosemia is a rare, autosomal recessive disease in which galactose is not metabolized properly due to severe deficiency/absence of the galactose-1-phosphate uridylyltransferase (GALT) enzyme, converting to an aberrant and toxic metabolite, galactitol. Newborn screening and timely galactose-restricted diet can resolve acute symptoms and decrease fatalities. However, despite this, significant chronic, progressive morbidities remain which have a real impact upon daily life. To better understand the burden of disease, 20 in-depth qualitative interviews were undertaken with adult patients (n = 12), and their caregivers (n = 8), enrolled in the ACTION-Galactosemia trial, part of a clinical program designed to investigate the safety and efficacy of AT-007 (govorestat) in reducing toxic galactitol and long-term clinical outcomes in Classic Galactosemia. RESULTS: Interviews revealed the substantial burden of Classic Galactosemia on patients and families. Most adults were not able to live independently, and all required support with day-to-day activities. Short- and long-term memory difficulties and tremors were identified as the most frequently experienced and challenging symptoms. Other difficulties such as fine motor skills and slow/slurred speech contribute to the significant impact on daily activities, affecting ability to communicate and interact with others. Symptoms were first noticed in early childhood and worsened with age. Classic Galactosemia impacted all areas of daily functioning and quality of life, leading to social isolation, anxiety, anger/frustration and depression. This demonstrates the significant burden of disease and challenges associated with Classic Galactosemia. CONCLUSIONS: The impact on both patients and caregivers underscores the severity of the unmet medical need and the importance of pharmacological intervention to halt or prevent disease progression. Any treatment that could reduce symptoms or slow functional decline would ease the burden of this condition on patients and caregivers.

Inactive Lifestyles Among Young Children With Innocent Murmurs or Congenital Heart Disease, Regardless of Disease Severity or Treatment.

BACKGROUND: Sedentary lifestyle morbidities are common among children with congenital heart disease (CHD). Understanding the physical activity trajectory from early childhood could enhance timing and effectiveness of interventions. METHODS: We recruited 154 children (56% male) at 12 to 47 months of age for this prospective, longitudinal, observational study. Physical activity and sedentary behaviour (7-day accelerometry) and motor skill (Peabody Developmental Motor Scales-2) were assessed every 8 months until 5 years of age and then annually. Mixed-effect repeated measures regression models described outcome trajectories across study assessments. RESULTS: Children had innocent heart murmurs (n = 28), CHD with insignificant hemodynamics not requiring treatment (n = 47), CHD treated by catheterization or surgery without cardiopulmonary bypass (n = 31), or CHD treated surgically with bypass (n = 48). Motor skill was age appropriate (Peabody 49.0 ± 8.4), but participants had lower physical activity (143 ± 41 minutes per day) and higher sedentary time (598 ± 89 minutes per day) than healthy peers, starting at 18 months of age. Movement behaviours were not related to treatment group (P > 0.10), and physical activity was below the recommended 180 minutes per day. Over time, physical activity, sedentary time, and motor skills were primarily related to the baseline measure of each outcome (P < 0.001). CONCLUSIONS: Children with simple or complex CHD or innocent heart murmurs have increased risk for sedentary lifestyles. Their physical activity and sedentary behaviours are established before 2 years of age, persist until school age, and are unrelated to motor skills. These results emphasize the need for interventions targeting the youngest children seen in cardiac clinics, regardless of diagnoses of CHD or innocent murmur.

Urine Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 to Detect Pediatric Cisplatin-Associated Acute Kidney Injury.

Background: Few studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin. Methods: Participants (n=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured (1) pre-cisplatin infusion, (2) post-infusion (morning after), and (3) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher). Results: Of 159 children, 156 (median [interquartile range (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty six of the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0-232.7] versus 14.9 [5.4-29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083-9077] versus 1049 [358-3326] pg/mg creatinine; P<0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56-0.72; KIM-1, 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54-0.75) versus early infusions (AUC-ROC range, 0.48-0.65). Conclusions: Urine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes.