Multicentre validation of CT grey-level co-occurrence matrix features for overall survival in primary oesophageal adenocarcinoma.

BACKGROUND: Personalising management of primary oesophageal adenocarcinoma requires better risk stratification. Lack of independent validation of proposed imaging biomarkers has hampered clinical translation. We aimed to prospectively validate previously identified prognostic grey-level co-occurrence matrix (GLCM) CT features for 3-year overall survival. METHODS: Following ethical approval, clinical and contrast-enhanced CT data were acquired from participants from five institutions. Data from three institutions were used for training and two for testing. Survival classifiers were modelled on prespecified variables ('Clinical' model: age, clinical T-stage, clinical N-stage; 'ClinVol' model: clinical features + CT tumour volume; 'ClinRad' model: ClinVol features + GLCM_Correlation and GLCM_Contrast). To reflect current clinical practice, baseline stage was also modelled as a univariate predictor ('Stage'). Discrimination was assessed by area under the receiver operating curve (AUC) analysis; calibration by Brier scores; and clinical relevance by thresholding risk scores to achieve 90% sensitivity for 3-year mortality. RESULTS: A total of 162 participants were included (144 male; median 67 years [IQR 59, 72]; training, 95 participants; testing, 67 participants). Median survival was 998 days [IQR 486, 1594]. The ClinRad model yielded the greatest test discrimination (AUC, 0.68 [95% CI 0.54, 0.81]) that outperformed Stage (ΔAUC, 0.12 [95% CI 0.01, 0.23]; p = .04). The Clinical and ClinVol models yielded comparable test discrimination (AUC, 0.66 [95% CI 0.51, 0.80] vs. 0.65 [95% CI 0.50, 0.79]; p > .05). Test sensitivity of 90% was achieved by ClinRad and Stage models only. CONCLUSIONS: Compared to Stage, multivariable models of prespecified clinical and radiomic variables yielded improved prediction of 3-year overall survival. CLINICAL RELEVANCE STATEMENT: Previously identified radiomic features are prognostic but may not substantially improve risk stratification on their own. KEY POINTS: • Better risk stratification is needed in primary oesophageal cancer to personalise management. • Previously identified CT features-GLCM_Correlation and GLCM_Contrast-contain incremental prognostic information to age and clinical stage. • Compared to staging, multivariable clinicoradiomic models improve discrimination of 3-year overall survival.

The effect of dehydration, hyperchloremia and volume of fluid resuscitation on acute kidney injury in children admitted to hospital with diabetic ketoacidosis.

BACKGROUND: Acute kidney injury (AKI) is a recognized comorbidity in pediatric diabetic ketoacidosis (DKA), although the exact etiology is unclear. The unique physiology of DKA makes dehydration assessments challenging, and these patients potentially receive excessive amounts of intravenous fluids (IVF). We hypothesized that dehydration is over-estimated in pediatric DKA, leading to over-administration of IVF and hyperchloremia that worsens AKI. METHODS: Retrospective cohort of all DKA inpatients at a tertiary pediatric hospital from 2014 to 2019. A total of 145 children were included; reasons for exclusion were pre-existing kidney disease or incomplete medical records. AKI was determined by change in creatinine during admission, and comparison to a calculated baseline value. Linear regression multivariable analysis was used to identify factors associated with AKI. True dehydration was calculated from patients' change in weight, as previously validated. Fluid over-resuscitation was defined as total fluids given above the true dehydration. RESULTS: A total of 19% of patients met KDIGO serum creatinine criteria for AKI on admission. Only 2% had AKI on hospital discharge. True dehydration and high serum urea levels were associated with high serum creatinine levels on admission (p = 0.042; p < 0.001, respectively). Fluid over-resuscitation and hyperchloremia were associated with delayed kidney recovery (p < 0.001). Severity of initial AKI was associated with cerebral edema (p = 0.018). CONCLUSIONS: Dehydration was associated with initial AKI in children with DKA. Persistent AKI and delay to recovery was associated with hyperchloremia and over-resuscitation with IVF, potentially modifiable clinical variables for earlier AKI recovery and reduction in long-term morbidity. This highlights the need to re-address fluid protocols in pediatric DKA.

Evaluating Airway Management in Patients With Trisomy 21 in the PICU and Cardiac ICU: A Retrospective Cohort Study.

OBJECTIVES: Children with trisomy 21 often have anatomic and physiologic features that may complicate tracheal intubation (TI). TI in critically ill children with trisomy 21 is not well described. We hypothesize that in children with trisomy 21, TI is associated with greater odds of adverse airway outcomes (AAOs), including TI-associated events (TIAEs), and peri-intubation hypoxemia (defined as > 20% decrease in pulse oximetry saturation [Sp o2 ]). DESIGN: Retrospective database study using the National Emergency Airway Registry for Children (NEAR4KIDS). SETTING: Registry data from 16 North American PICUs and cardiac ICUs (CICUs), from January 2014 to December 2020. PATIENTS: A cohort of children under 18 years old who underwent TI in the PICU or CICU from in a NEAR4KIDS center. We identified patients with trisomy 21 and selected matched cohorts within the registry. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 8401 TIs in the registry dataset. Children with trisomy 21 accounted for 274 (3.3%) TIs. Among those with trisomy 21, 84% had congenital heart disease and 4% had atlantoaxial instability. Cervical spine protection was used in 6%. The diagnosis of trisomy 21 (vs. without) was associated with lower median weight 7.8 (interquartile range [IQR] 4.5-14.7) kg versus 10.6 (IQR 5.2-25) kg ( p < 0.001), and more higher percentage undergoing TI for oxygenation (46% vs. 32%, p < 0.001) and ventilation failure (41% vs. 35%, p = 0.04). Trisomy 21 patients had more difficult airway features (35% vs. 25%, p = 0.001), including upper airway obstruction (14% vs. 8%, p = 0.001). In addition, a greater percentage of trisomy 21 patients received atropine (34% vs. 26%, p = 0.004); and, lower percentage were intubated with video laryngoscopy (30% vs. 37%, p = 0.023). After 1:10 (trisomy 21:controls) propensity-score matching, we failed to identify an association difference in AAO rates (absolute risk difference -0.6% [95% CI -6.1 to 4.9], p = 0.822). CONCLUSIONS: Despite differences in airway risks and TI approaches, we have not identified an association between the diagnosis of trisomy 21 and higher AAOs.

Tracheal Intubation by Advanced Practice Registered Nurses in Pediatric Critical Care: Retrospective Study From the National Emergency Airway for Children Registry (2015-2019).

OBJECTIVES: To describe tracheal intubation (TI) practice by Advanced Practice Registered Nurses (APRNs) in North American PICUs, including rates of TI-associated events (TIAEs) from 2015 to 2019. DESIGN/SETTING: Retrospective study using the National Emergency Airway Registry for Children with all TIs performed in PICU and pediatric cardiac ICU between January 2015 and December 2019. The primary outcome was first attempt TI success rate. Secondary outcomes were TIAEs, severe TIAEs, and hypoxemia. SUBJECTS: Critically ill children requiring TI in a PICU or pediatric cardiac ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 11,012 TIs, APRNs performed 1,626 (14.7%). Overall, TI by APRNs, compared with other clinicians, occurred less frequently in patients with known difficult airway (11.1% vs. 14.3%; p < 0.001), but more frequently in infants younger than 1 year old (55.9% vs. 44.4%; p < 0.0001), and in patients with cardiac disease (26.3% vs. 15.9%; p < 0.0001).There was lower odds of success in first attempt TI for APRNs vs. other clinicians (adjusted odds ratio, 0.70; 95% CI, 0.62-0.79). We failed to identify a difference in rates of TIAE, severe TIAE, and oxygen desaturation events for TIs by APRNs compared with other clinicians. The TI first attempt success rate improved with APRN experience (< 1 yr: 54.2%, 1-5 yr: 59.4%, 6-10 yr: 67.6%, > 10 yr: 63.1%; p = 0.021). CONCLUSIONS: TI performed by APRNs was associated with lower odds of first attempt success when compared with other ICU clinicians although there was no appreciable difference in procedural adverse events. There appears to be a positive relationship between experience and success rates. These data suggest there is an ongoing need for opportunities to build on TI competency with APRNs.

Adverse Tracheal Intubation Events in Critically Ill Underweight and Obese Children: Retrospective Study of the National Emergency Airway for Children Registry (2013-2020).

OBJECTIVES: Extremes of patient body mass index are associated with difficult intubation and increased morbidity in adults. We aimed to determine the association between being underweight or obese with adverse airway outcomes, including adverse tracheal intubation (TI)-associated events (TIAEs) and/or severe peri-intubation hypoxemia (pulse oximetry oxygen saturation < 80%) in critically ill children. DESIGN/SETTING: Retrospective cohort using the National Emergency Airway for Children registry dataset of 2013-2020. PATIENTS: Critically ill children, 0 to 17 years old, undergoing TI in PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Registry data from 24,342 patients who underwent TI between 2013 and 2020 were analyzed. Patients were categorized using the Centers for Disease Control and Prevention weight-for-age chart: normal weight (5th-84th percentile) 57.1%, underweight (< 5th percentile) 27.5%, overweight (85th to < 95th percentile) 7.2%, and obese (≥ 95th percentile) 8.2%. Underweight was most common in infants (34%); obesity was most common in children older than 8 years old (15.1%). Underweight patients more often had oxygenation and ventilation failure (34.0%, 36.2%, respectively) as the indication for TI and a history of difficult airway (16.7%). Apneic oxygenation was used more often in overweight and obese patients (19.1%, 19.6%) than in underweight or normal weight patients (14.1%, 17.1%; p < 0.001). TIAEs and/or hypoxemia occurred more often in underweight (27.1%) and obese (24.3%) patients ( p < 0.001). TI in underweight children was associated with greater odds of adverse airway outcome compared with normal weight children after adjusting for potential confounders (underweight: adjusted odds ratio [aOR], 1.09; 95% CI, 1.01-1.18; p = 0.016). Both underweight and obesity were associated with hypoxemia after adjusting for covariates and site clustering (underweight: aOR, 1.11; 95% CI, 1.02-1.21; p = 0.01 and obesity: aOR, 1.22; 95% CI, 1.07-1.39; p = 0.002). CONCLUSIONS: In underweight and obese children compared with normal weight children, procedures around the timing of TI are associated with greater odds of adverse airway events.

Ketamine Use in the Intubation of Critically Ill Children with Neurological Indications: A Multicenter Retrospective Analysis.

BACKGROUND: Ketamine has traditionally been avoided for tracheal intubations (TIs) in patients with acute neurological conditions. We evaluate its current usage pattern in these patients and any associated adverse events. METHODS: We conducted a retrospective observational cohort study of critically ill children undergoing TI for neurological indications in 53 international pediatric intensive care units and emergency departments. We screened all intubations from 2014 to 2020 entered into the multicenter National Emergency Airway Registry for Children (NEAR4KIDS) registry database. Patients were included if they were under the age of 18 years and underwent TI for a primary neurological indication. Usage patterns and reported periprocedural composite adverse outcomes (hypoxemia < 80%, hypotension/hypertension, cardiac arrest, and dysrhythmia) were noted. RESULTS: Of 21,562 TIs, 2,073 (9.6%) were performed for a primary neurological indication, including 190 for traumatic brain injury/trauma. Patients received ketamine in 495 TIs (23.9%), which increased from 10% in 2014 to 41% in 2020 (p < 0.001). Ketamine use was associated with a coindication of respiratory failure, difficult airway history, and use of vagolytic agents, apneic oxygenation, and video laryngoscopy. Composite adverse outcomes were reported in 289 (13.9%) Tis and were more common in the ketamine group (17.0% vs. 13.0%, p = 0.026). After adjusting for location, patient age and codiagnoses, the presence of respiratory failure and shock, difficult airway history, provider demographics, intubating device, and the use of apneic oxygenation, vagolytic agents, and neuromuscular blockade, ketamine use was not significantly associated with increased composite adverse outcomes (adjusted odds ratio 1.34, 95% confidence interval CI 0.99-1.81, p = 0.057). This paucity of association remained even when only neurotrauma intubations were considered (10.6% vs. 7.7%, p = 0.528). CONCLUSIONS: This retrospective cohort study did not demonstrate an association between procedural ketamine use and increased risk of peri-intubation hypoxemia and hemodynamic instability in patients intubated for neurological indications.

Implementation of Video Laryngoscope-Assisted Coaching Reduces Adverse Tracheal Intubation-Associated Events in the PICU.

OBJECTIVES: To evaluate implementation of a video laryngoscope (VL) as a coaching device to reduce adverse tracheal intubation associated events (TIAEs). DESIGN: Prospective multicenter interventional quality improvement study. SETTING: Ten PICUs in North America. PATIENTS: Patients undergoing tracheal intubation in the PICU. INTERVENTIONS: VLs were implemented as coaching devices with standardized coaching language between 2016 and 2020. Laryngoscopists were encouraged to perform direct laryngoscopy with video images only available in real-time for experienced supervising clinician-coaches. MEASUREMENTS AND MAIN RESULTS: The primary outcome was TIAEs. Secondary outcomes included severe TIAEs, severe hypoxemia (oxygen saturation < 80%), and first attempt success. Of 5,060 tracheal intubations, a VL was used in 3,580 (71%). VL use increased from baseline (29.7%) to implementation phase (89.4%; p < 0.001). VL use was associated with lower TIAEs (VL 336/3,580 [9.4%] vs standard laryngoscope [SL] 215/1,480 [14.5%]; absolute difference, 5.1%; 95% CI, 3.1-7.2%; p < 0.001). VL use was associated with lower severe TIAE rate (VL 3.9% vs SL 5.3%; p = 0.024), but not associated with a reduction in severe hypoxemia (VL 15.7% vs SL 16.4%; p = 0.58). VL use was associated with higher first attempt success (VL 71.8% vs SL 66.6%; p < 0.001). In the primary analysis after adjusting for site clustering, VL use was associated with lower adverse TIAEs (odds ratio [OR], 0.61; 95% CI, 0.46-0.81; p = 0.001). In secondary analyses, VL use was not significantly associated with severe TIAEs (OR, 0.72; 95% CI, 0.44-1.19; p = 0.20), severe hypoxemia (OR, 0.95; 95% CI, 0.73-1.25; p = 0.734), or first attempt success (OR, 1.28; 95% CI, 0.98-1.67; p = 0.073). After further controlling for patient and provider characteristics, VL use was independently associated with a lower TIAE rate (adjusted OR, 0.65; 95% CI, 0.49-0.86; p = 0.003). CONCLUSIONS: Implementation of VL-assisted coaching achieved a high level of adherence across the PICUs. VL use was associated with reduced adverse TIAEs.

Biallelic variants in ribonuclease inhibitor (RNH1), an inflammasome modulator, are associated with a distinctive subtype of acute, necrotizing encephalopathy.

PURPOSE: Mendelian etiologies for acute encephalopathies in previously healthy children are poorly understood, with the exception of RAN binding protein 2 (RANBP2)-associated acute necrotizing encephalopathy subtype 1 (ANE1). We provide clinical, genetic, and neuroradiological evidence that biallelic variants in ribonuclease inhibitor (RNH1) confer susceptibility to a distinctive ANE subtype. METHODS: This study aimed to evaluate clinical data, neuroradiological studies, genomic sequencing, and protein immunoblotting results in 8 children from 4 families who experienced acute febrile encephalopathy. RESULTS: All 8 healthy children became acutely encephalopathic during a viral/febrile illness and received a variety of immune modulation treatments. Long-term outcomes varied from death to severe neurologic deficits to normal outcomes. The neuroradiological findings overlapped with ANE but had distinguishing features. All affected children had biallelic predicted damaging variants in RNH1: a subset that was studied had undetectable RNH1 protein. Incomplete penetrance of the RNH1 variants was evident in 1 family. CONCLUSION: Biallelic variants in RNH1 confer susceptibility to a subtype of ANE (ANE2) in previously healthy children. Intensive immunological treatments may alter outcomes. Genomic sequencing in children with unexplained acute febrile encephalopathy can detect underlying genetic etiologies, such as RNH1, and improve outcomes in the probands and at-risk siblings.

Effect of apneic oxygenation with intubation to reduce severe desaturation and adverse tracheal intubation-associated events in critically ill children.

BACKGROUND: Determine if apneic oxygenation (AO) delivered via nasal cannula during the apneic phase of tracheal intubation (TI), reduces adverse TI-associated events (TIAEs) in children. METHODS: AO was implemented across 14 pediatric intensive care units as a quality improvement intervention during 2016-2020. Implementation consisted of an intubation safety checklist, leadership endorsement, local champion, and data feedback to frontline clinicians. Standardized oxygen flow via nasal cannula for AO was as follows: 5 L/min for infants (< 1 year), 10 L/min for young children (1-7 years), and 15 L/min for older children (≥ 8 years). Outcomes were the occurrence of adverse TIAEs (primary) and hypoxemia (SpO2 < 80%, secondary). RESULTS: Of 6549 TIs during the study period, 2554 (39.0%) occurred during the pre-implementation phase and 3995 (61.0%) during post-implementation phase. AO utilization increased from 23 to 68%, p < 0.001. AO was utilized less often when intubating infants, those with a primary cardiac diagnosis or difficult airway features, and patient intubated due to respiratory or neurological failure or shock. Conversely, AO was used more often in TIs done for procedures and those assisted by video laryngoscopy. AO utilization was associated with a lower incidence of adverse TIAEs (AO 10.5% vs. without AO 13.5%, p < 0.001), aOR 0.75 (95% CI 0.58-0.98, p = 0.03) after adjusting for site clustering (primary analysis). However, after further adjusting for patient and provider characteristics (secondary analysis), AO utilization was not independently associated with the occurrence of adverse TIAEs: aOR 0.90, 95% CI 0.72-1.12, p = 0.33 and the occurrence of hypoxemia was not different: AO 14.2% versus without AO 15.2%, p = 0.43. CONCLUSION: While AO use was associated with a lower occurrence of adverse TIAEs in children who required TI in the pediatric ICU after accounting for site-level clustering, this result may be explained by differences in patient, provider, and practice factors. Trial Registration Trial not registered.

Digital Informed Consent: Modernising Information Sharing in Surgery to Empower Patients.

BACKGROUND: Despite the 2015 Montgomery Ruling highlighting key requisites for informed consent, little has changed to modernise data-sharing and documentation of the consent process. It can be difficult to gauge patient understanding and address all patient concerns in time-limited appointments. We aimed to assess the feasibility of a digital information-sharing platform to support a move towards a digital informed consent process. METHODS: All adult patients referred to a single centre with symptomatic gallstones were invited to use a digital information-sharing platform to support the informed consent process prior to their first surgical clinic appointment. The platform provided patients with multimedia information on gallstones and available treatment options. It recorded the time spent accessing information, asked patients multiple choice questions (MCQs) to allow a self-test of understanding, documented a summary medical history, and allowed free text for patient questions. This information was summarised into a clinical report to support outpatient clinic consultations. RESULTS: Of the 349 patients registered to use the digital platform, 203 (58.2%) [165 (81.3%) female, mean age 47.6 years (range 19-84 years)] completed all modules necessary to generate a clinical report. Some 130 patients (64.0%) answered all 10 MCQs correctly and spent a mean of 18.7 min (range 3-88 min) reading the consent information. Most patient-reported medical histories were deemed to be accurate. CONCLUSION: Despite difficulties with access, resulting in drop-outs, patients welcomed the opportunity to receive information digitally, prior to their consultation. Patients described feeling empowered and better informed to be involved in decision-making.

Unplanned Extubations Requiring Reintubation in Pediatric Critical Care: An Epidemiological Study.

OBJECTIVES: Unplanned extubations are an infrequent but life-threatening adverse event in pediatric critical care. Due to the rarity of these events, previous studies have been small, limiting the generalizability of findings and the ability to detect associations. Our objectives were to describe unplanned extubations and explore predictors of unplanned extubation requiring reintubation in PICUs. DESIGN: Retrospective observational study and multilevel regression model. SETTING: PICUs participating in Virtual Pediatric Systems (LLC). PATIENTS: Patients (≤ 18 yr) who had an unplanned extubation in PICU (2012-2020). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed and trained a multilevel least absolute shrinkage and selection operator (LASSO) logistic regression model in the 2012-2016 sample that accounted for between-PICU variations as a random effect to predict reintubation after unplanned extubation. The remaining sample (2017-2020) was used to externally validate the model. Predictors included age, weight, sex, primary diagnosis, admission type, and readmission status. Model calibration and discriminatory performance were evaluated using Hosmer-Lemeshow goodness-of-fit (HL-GOF) and area under the receiver operating characteristic curve (AUROC), respectively. Of the 5,703 patients included, 1,661 (29.1%) required reintubation. Variables associated with increased risk of reintubation were age (< 2 yr; odds ratio [OR], 1.5; 95% CI, 1.1-1.9) and diagnosis (respiratory; OR, 1.3; 95% CI, 1.1-1.6). Scheduled admission was associated with decreased risk of reintubation (OR, 0.7; 95% CI, 0.6-0.9). With LASSO (lambda = 0.011), remaining variables were age, weight, diagnosis, and scheduled admission. The predictors resulted in AUROC of 0.59 (95% CI, 0.57-0.61); HL-GOF showed the model was well calibrated (p = 0.88). The model performed similarly in external validation (AUROC, 0.58; 95% CI, 0.56-0.61). CONCLUSIONS: Predictors associated with increased risk of reintubation included age and respiratory primary diagnosis. Including clinical factors (e.g., oxygen and ventilatory requirements at the time of unplanned extubation) in the model may increase predictive ability.

Utilising Electronic PROMs to Measure a Change in Health Following Elective Laparoscopic Cholecystectomy: A Feasibility Study.

BACKGROUND: The collection of patient-reported outcome measures (PROMs) has many benefits for clinical practice. However, there are many barriers that prevent them from becoming a part of routine clinical care. The aim of this feasibility study was to pilot the use of a digital platform to facilitate the routine collection of pre- and post-operative electronic PROMs (ePROMs) in participants undergoing elective laparoscopic cholecystectomy and to validate the use of existing patient-reported outcomes for our population. METHODS: Participants scheduled for elective laparoscopic cholecystectomy were asked to complete digital versions of the Otago gallstones Condition-Specific Questionnaire (CSQ), and the RAND 36-item health survey (SF36). An assessment of methodological quality of ePROM questionnaires was also performed. RESULTS: Preoperative ePROMs were completed by 200 participants undergoing laparoscopic cholecystectomy. Post-operatively attrition was high (completion at 30 days, 3 months, and 6months: n = 61, 54, and 38, respectively) due to difficulties accessing our ePROMs portal. Of those able to complete, a significant improvement in quality of life was seen across all health domains post-operatively when compared with baseline preoperative values for both disease-specific and generic PROMs. Methodological quality was assessed as good to excellent in both digital questionnaires. CONCLUSION: The collection of ePROMs is possible with current technological advances. Although it may be an acceptable, and convenient process for patients, and a useful measure of quality-of-life trends for clinicians, further developmental work is necessary to improve accessibility for patients, improve compliance, and reduce reporting bias from high attrition rates.

Digital Follow-Up After Elective Laparoscopic Cholecystectomy: A Feasibility Study.

BACKGROUND: Although recommendations exist for patients to be offered a post-operative helpline or telephone follow-up appointment at discharge after cholecystectomy, implementation of these is resource-intensive. Whilst the benefits of telephone follow-up are well documented, the use of digital modalities is less so. We aimed to identify if digital follow-up (DFU) was equivalent to routine care with telephone follow-up (TFU), for patients undergoing elective laparoscopic cholecystectomy. METHODS: All patients listed for elective laparoscopic cholecystectomy between August 2016 and March 2018 were offered routine post-operative care (TFU or no follow-up) or DFU at a tertiary referral centre in Nottingham. RESULTS: Of 597 patients undergoing laparoscopic cholecystectomy, 199 (33.3%) opted for TFU, and 98 (16.4%) for DFU. DFU was completed for 85 (86.7%) participants and TFU for 125 (62.8%), p < 0.0001. Over 5 times as many patients who chose TFU missed their appointment compared to DFU (5.6% vs. 30.9%, p < 0.001). At 30-days post-operatively, patients undergoing TFU had significantly more post-operative wound infections identified then those undergoing DFU (17.6% vs 5.9%, p = 0.01). However, this did not impact the incidence of 30-day readmissions between groups (7.2% TFU vs. 7.1% DFU). No complications were missed by either the DFU or TFU modalities. DFU was completed significantly earlier than TFU (median 6 days vs. 13.5 days, p = 0.001) with high patient acceptability, identifying complications and alerting clinicians to those patients requiring an early review. CONCLUSION: This feasibility study has demonstrated that digital follow-up is an acceptable alternative to telephone follow-up after elective laparoscopic cholecystectomy.

From Gas Phase Observations to Solid State Reality: The Identification and Isolation of Trinuclear Salicylaldoximato Copper Complexes.

Conditions have been identified in which phenolic aldoximes and ketoximes of the types used in commercial solvent extraction processes can be doubly deprotonated and generate polynuclear Cu complexes with lower extractant:Cu molar ratios than those found in commercial operations. Electrospray mass spectrometry has provided an insight into the solution speciation in extraction experiments and has identified conditions to allow isolation and characterization of polynuclear Cu-complexes. Elevation of pH is effective in enhancing the formation of trinuclear complexes containing planar {Cu3-µ3-O}4+ or {Cu3-µ3-OH}5+ units. DFT calculations suggest that such trinuclear complexes are more stable than other polynuclear species. Solid structures of complexes formed by a salicylaldoxime with a piperidino substituent ortho to the phenolic OH group (L9H2) contain two trinuclear units in a supramolecular assembly, {[Cu3OH(L9H)3(ClO4)](ClO4)} 2, formed by H-bonding between the central {Cu3-µ3-OH}5+ units and oxygen atoms in the ligands of an adjacent complex. Whilst the lower ligand:Cu molar ratios provide more efficient Cu-loading in solvent extraction processes, the requirement to raise the pH of the aqueous phase to achieve this will make it impractical in most commercial operations because extraction will be accompanied by the precipitation (as oxyhydroxides) of Fe(III) which is present in significant quantities in feed solutions generated by acid leaching of most Cu ores.

Outcomes Following an Index Emergency Admission With Cholecystitis: A National Cohort Study.

OBJECTIVE: The objective of this study was to evaluate the differences between patients who undergo cholecystectomy following index admission for cholecystitis, and those who are managed nonoperatively. SUMMARY BACKGROUND DATA: Index emergency cholecystectomy following acute cholecystitis is widely recommended by national guidelines, but its effect on clinical outcomes remains uncertain. METHODS: Data collected routinely from the Hospital Episode Statistics database (all admissions to National Health Service organizations in England and Wales) were extracted between April 1, 2002 and March 31, 2015. Analyses were limited to patients aged over 18 years with a primary diagnosis of cholecystitis. Exclusions included records with missing or invalid datasets, patients who had previously undergone a cholecystectomy, patients who had died without a cholecystectomy, and those undergoing cholecystectomy for malignancy, pancreatitis, or choledocholithiasis. Patients were grouped as either "no cholecystectomy" where they had never undergone a cholecystectomy following discharge, or "cholecystectomy." The latter group was then subdivided as "emergency cholecystectomy" when cholecystectomy was performed during their index emergency admission, or "interval cholecystectomy" when a cholecystectomy was performed within 12 months following a subsequent (emergency or elective) admission. Propensity Score Matching was used to match emergency and interval cholecystectomy groups. Main outcome measures included 1) One-year total length of hospital stay due to biliary causes following an index emergency admission with cholecystitis. 2) One-year mortality; defined as death occurring within 1 year following the index emergency admission with acute cholecystitis. RESULTS: Of the 99,139 patients admitted as an emergency with acute cholecystitis, 51.1% (47,626) did not undergo a cholecystectomy within 1 year of index admission. These patients were older, with more comorbidities (Charlson Comorbidity Score ≥ 5 in 23.5% vs. 8.1%, P < 0.001) when compared to patients who did have a cholecystectomy. While all-cause 1-year mortality was higher in the nonoperated versus the operated group (12.2% vs. 2.0%, P < 0.001), gallbladder-related deaths were significantly lower than all other causes of death in the non-operated group (3.3% vs. 8.9%, P < 0.001). Following matching, 1-year total hospital admission time was significantly higher following emergency compared with interval cholecystectomy (17.7 d vs. 13 d, P < 0.001). CONCLUSIONS: Over 50% of patients in England did not undergo cholecystectomy following index admission for acute cholecystitis. Mortality was higher in the nonoperated group, which was mostly due to non-gallbladder pathologies but total hospital admission time for biliary causes was lower over 12 months. Increasing the numbers of emergency cholecystectomy may risk over-treating patients with acute cholecystitis and increasing their time spent admitted to hospital.

Ketamine Use for Tracheal Intubation in Critically Ill Children Is Associated With a Lower Occurrence of Adverse Hemodynamic Events.

OBJECTIVES: Tracheal intubation in critically ill children with shock poses a risk of hemodynamic compromise. Ketamine has been considered the drug of choice for induction in these patients, but limited data exist. We investigated whether the administration of ketamine for tracheal intubation in critically ill children with or without shock was associated with fewer adverse hemodynamic events compared with other induction agents. We also investigated if there was a dose dependence for any association between ketamine use and adverse hemodynamic events. DESIGN: We performed a retrospective analysis using prospectively collected observational data from the National Emergency Airway Registry for Children database from 2013 to 2017. SETTING: Forty international PICUs participating in the National Emergency Airway Registry for Children. PATIENTS: Critically ill children 0-17 years old who underwent tracheal intubation in a PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The association between ketamine exposure as an induction agent and the occurrence of adverse hemodynamic events during tracheal intubation including dysrhythmia, hypotension, and cardiac arrest was evaluated. We used multivariable logistic regression to account for patient, provider, and practice factors with robust SEs to account for clustering by sites. Of 10,750 tracheal intubations, 32.0% (n = 3,436) included ketamine as an induction agent. The most common diagnoses associated with ketamine use were sepsis and/or shock (49.7%). After adjusting for potential confounders and sites, ketamine use was associated with fewer hemodynamic tracheal intubation associated adverse events compared with other agents (adjusted odds ratio, 0.74; 95% CI, 0.58-0.95). The interaction term between ketamine use and indication for shock was not significant (p = 0.11), indicating ketamine effect to prevent hemodynamic adverse events is consistent in children with or without shock. CONCLUSIONS: Ketamine use for tracheal intubation is associated with fewer hemodynamic tracheal intubation-associated adverse events.

Quantum chemical topology and natural bond orbital analysis of M-O covalency in M(OC6H5)4 (M = Ti, Zr, Hf, Ce, Th, Pa, U, Np).

Covalency is complex yet central to our understanding of chemical bonding, particularly in the actinide series. Here we assess covalency in a series of isostructural d and f transition element compounds M(OC6H5)4 (M = Ti, Zr, Hf, Ce, Th, Pa, U, Np) using scalar relativistic hybrid density functional theory in conjunction with the Natural Bond Orbital (NBO), quantum theory of atoms in molecules (QTAIM) and interacting quantum atoms (IQA) approaches. The IQA exchange-correlation covalency metric is evaluated for the first time for actinides other than uranium, in order to assess its applicability in the 5f series. It is found to have excellent correlation with NBO and QTAIM covalency metrics, making it a promising addition to the computational toolkit for analysing metal-ligand bonding. Our range of metrics agree that the actinide-oxygen bonds are the most covalent of the elements studied, with those of the heavier group 4 elements the least. Within the early actinide series, Th stands apart from the other three elements considered, being consistently the least covalent.

The New Trainee Effect in Tracheal Intubation Procedural Safety Across PICUs in North America: A Report From National Emergency Airway Registry for Children.

OBJECTIVES: Tracheal intubation carries a high risk of adverse events. The current literature is unclear regarding the "New Trainee Effect" on tracheal intubation safety in the PICU. We evaluated the effect of the timing of the PICU fellow academic cycle on tracheal intubation associated events. We hypothesize 1) PICUs with pediatric critical care medicine fellowship programs have more adverse tracheal intubation associated events during the first quarter (July-September) of the academic year compared with the rest of the year and 2) tracheal intubation associated event rates and first attempt success performed by pediatric critical care medicine fellows improve through the 3-year clinical fellowship. DESIGN: Retrospective cohort study. SETTING: Thirty-seven North American PICUs participating in National Emergency Airway Registry for Children. PATIENTS: All patients who underwent tracheal intubations in the PICU from July 2013 to June 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The occurrence of any tracheal intubation associated events during the first quarter of the academic year (July-September) was compared with the rest in four different types of PICUs: PICUs with fellows and residents, PICUs with fellows only, PICUs with residents only, and PICUs without trainees. For the second hypothesis, tracheal intubations by critical care medicine fellows were categorized by training level and quarter for 3 years of fellowship (i.e., July-September of 1st yr pediatric critical care medicine fellowship = first quarter, October-December of 1st yr pediatric critical care medicine fellowship = second quarter, and April-June during 3rd year = 12th quarter). A total of 9,774 tracheal intubations were reported. Seven-thousand forty-seven tracheal intubations (72%) were from PICUs with fellows and residents, 525 (5%) with fellows only, 1,201 (12%) with residents only, and 1,001 (10%) with no trainees. There was no difference in the occurrence of tracheal intubation associated events in the first quarter versus the rest of the year (all PICUs: July-September 14.9% vs October-June 15.2%; p = 0.76). There was no difference between these two periods in each type of PICUs (all p ≥ 0.19). For tracheal intubations by critical care medicine fellows (n = 3,836), tracheal intubation associated events significantly decreased over the fellowship: second quarter odds ratio 0.64 (95% CI, 0.45-0.91), third quarter odds ratio 0.58 (95% CI, 0.42-0.82), and 12th quarter odds ratio 0.40 (95% CI, 0.24-0.67) using the first quarter as reference after adjusting for patient and device characteristics. First attempt success significantly improved during fellowship: second quarter odds ratio 1.39 (95% CI, 1.04-1.85), third quarter odds ratio 1.59 (95% CI, 1.20-2.09), and 12th quarter odds ratio 2.11 (95% CI, 1.42-3.14). CONCLUSIONS: The New Trainee Effect in tracheal intubation safety outcomes was not observed in various types of PICUs. There was a significant improvement in pediatric critical care medicine fellows' first attempt success and a significant decline in tracheal intubation associated event rates, indicating substantial skills acquisition throughout pediatric critical care medicine fellowship.

The management and long-term outcomes of endoscopic and surgical treatment of early esophageal adenocarcinoma.

Endoscopic resection (ER) for early (pT1) esophageal adenocarcinoma can be justified if the rate of coexisting lymph node (LN) metastasis is less than the mortality rate from esophagectomy. This study examines endoscopic and surgical outcomes, histological assessment of submucosal (sm) disease, factors influencing LN metastasis, and the safety of treating pT1b disease endoscopically. Histopathological reexamination recorded thickness, width and depth of sm invasion, grade, presence of lymphovascular invasion (LVI), resection margin status and tumor stage. Multivariate analysis was employed to evaluate the factors influencing survival and LN metastasis. Rate of LN metastasis for pT1 low-risk (LR: sm invasion < 500 µm, G1-2, no LVI) or high-risk (HR: sm invasion >500 µm, G3-4 or LVI) disease were analyzed. Ninety three patients underwent ER and 96 underwent esophagectomy. We demonstrate conflicting histological methods of sm disease reporting, which may explain the difference in LN metastasis rate between reported surgical & endoscopic series. Multivariate analysis confirmed age, T stage, and presence of LN metastases were the independent factors predicting poor prognosis. Tumor thickness as well as grade, T stage, LVI were predictors of LN metastasis. Rates of LN metastasis are <2% in LR sm1 disease, and >15% in HR sm1 disease. Pathological reporting of sm invasion should be updated for uniform analysis of endoscopic and surgical specimens. Following rigorous histopathological examination and within a close endoscopic follow-up regimen, pT1a and pT1b LRsm1 disease may be treated with curative intent endoscopically, whereas pT1b HRsm1-sm3 disease should be offered surgery.

Single-Crystal X-Ray Diffraction Study of Pressure and Temperature-Induced Spin Trapping in a Bistable Iron(II) Hofmann Framework.

High-pressure single-crystal X-ray diffraction has been used to trap both the low-spin (LS) and high-spin (HS) states of the iron(II) Hofmann spin crossover framework, [FeII (pdm)(H2 O)[Ag(CN)2 ]2 ⋅H2 O, under identical experimental conditions, allowing the structural changes arising from the spin-transition to be deconvoluted from previously reported thermal effects.