Preparation of high-efficiency HILIC capillary columns utilizing slurry packing at 2100 bar.

Complex mixture analysis requires high-efficiency chromatography columns. Although reversed phase liquid chromatography (RPLC) is the dominant approach for such mixtures, hydrophilic interaction liquid chromatography (HILIC) is an important complement to RPLC by enabling the separation of polar compounds. Chromatography theory predicts that small particles and long columns will yield high efficiency; however, little work has been done to prepare HILIC columns longer than 25 cm packed with sub-2 µm particles. In this work, we tested the slurry packing of 75 cm long HILIC columns with 1.7 µm bridged-ethyl-hybrid amide HILIC particles at 2,100 bar (30,000 PSI). Acetonitrile, methanol, acetone, and water were tested as slurry solvents, with acetonitrile providing the best columns. Slurry concentrations of 50-200 mg/mL were assessed, and while 50-150 mg/mL provided comparable results, the 150 mg/mL columns provided the shortest packing times (9 min). Columns prepared using 150 mg/mL slurries in acetonitrile yielded a reduced minimum plate height (hmin) of 3.3 and an efficiency of 120,000 theoretical plates for acenaphthene, an unretained solute. Para-toluenesulfonic acid produced the lowest hmin of 1.9 and the highest efficiency of 210,000 theoretical plates. These results identify conditions for producing high-efficiency HILIC columns with potential applications to complex mixture analysis.

Revisiting Feeding Tube Utilization in Oropharynx Cancer: 6-Year Prospective Registry Analysis.

OBJECTIVE: Patients treated for oropharyngeal cancer (OPC) have historically demonstrated high feeding tube rates for decreased oral intake and malnutrition. We re-examined feeding tube practices in these patients. STUDY DESIGN: Retrospective analysis of prospective cohort from 2015 to 2021. SETTING: Single-institution NCI-Designated Comprehensive Cancer Center. METHODS: With IRB approval, patients with new oropharyngeal squamous cell cancer or (unknown primary with neck metastasis) were enrolled. Baseline swallowing was assessed via videofluoroscopy and Performance Status Scale for Head and Neck Cancer (PSSHN). G-tubes or nasogastric tubes (NGT) were placed for weight loss before, during, or after treatment. Prophylactic NGT were placed during transoral robotic surgery (TORS). Tube duration was censored at last disease-free follow-up. Multivariate regression was performed for G-tube placement (odds ratio [OR] [95% confidence interval [CI]) and removal (Cox hazard ratio, hazard ratio [HR] [95% CI]). RESULTS: Of 924 patients, most had stage I to II (81%), p16+ (89%), node-positive (88%) disease. Median follow-up was 2.6 years (interquartile range 1.5-3.9). Most (91%) received radiation/chemoradiation, and 16% received TORS. G-tube rate was 27% (5% after TORS). G-tube risk was increased with chemoradiation (OR 2.78 [1.87-4.22]) and decreased with TORS (OR 0.31 [0.15-0.57]) and PSSHN-Diet score ≥60 (OR 0.26 [0.15-0.45]). G-tube removal probability over time was lower for T3 to T4 tumors (HR 0.52 [0.38-0.71]) and higher for PSSHN-Diet score ≥60 (HR 1.65 [1.03-2.66]). CONCLUSIONS: In this modern cohort of patients treated for OPC, 27% received G-tubes-50% less than institutional rates 10 years ago. Patients with preserved baseline swallowing and/or those eligible for TORS may have lower G-tube risk and duration.

Do Buccal Flaps Improve Velopharyngeal Insufficiency in Conversion Furlow Palatoplasty for Patients with Cleft Palate?

SUMMARY: Velopharyngeal insufficiency (VPI) is a complication following primary palatoplasty that can lead to hypernasality of the voice and other speech problems. The conversion Furlow palatoplasty for VPI can be performed with the addition of buccal flaps to provide additional tissue for palatal repair. In this study, the authors aimed to determine the effectiveness of buccal flaps with conversion Furlow palatoplasty in secondary management of VPI. A retrospective review of patients undergoing surgical repair of VPI between 2016 and 2020 was performed. Patients underwent either conversion Furlow palatoplasty alone (FA) or conversion Furlow palatoplasty with buccal flaps (FB) for VPI after primary straight-line repair of the palate. The authors reviewed medical records to collect demographics, operative information, and preoperative and postoperative speech scores. Of the 77 patients in the study, 16 (21%) had a revision that incorporated buccal flaps. The median age at cleft palate revision surgery was 8.97 years in the FA group and 7.96 years in the FB group ( P = 0.337). In the FA group, four patients (7%) developed a postoperative fistula, compared with zero patients in the FB group. The average time to follow-up after revision surgery was 3.4 years (range, 7 months to 5.9 years). Both cohorts demonstrated a decrease in hypernasality and total parameter scores postoperatively. The use of buccal flaps in revision Furlow palatoplasty could decrease the risk for postoperative complications. The use of data from a larger patient population from multiple institutions is warranted to determine true significance. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Report from the 24th Annual Western Canadian Gastrointestinal Cancer Consensus Conference on Colorectal Cancer, Richmond, British Columbia, 28-29, October 2022.

The 24th annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Richmond, British Columbia, on 28-29 October 2022. The WCGCCC is an interactive multidisciplinary conference attended by healthcare professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals such as dieticians, nurses and a genetic counsellor participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer.

Offline Two-dimensional Liquid Chromatography-Mass Spectrometry for Deep Annotation of the Fecal Metabolome.

Compound identification is an essential task in the workflow of untargeted metabolomics since the interpretation of the data in a biological context depends on the correct assignment of chemical identities to the features it contains. Current techniques fall short of identifying all or even most observable features in untargeted metabolomics data, even after rigorous data cleaning approaches to remove degenerate features are applied. Hence, new strategies are required to annotate the metabolome more deeply and accurately. The human fecal metabolome, which is the focus of substantial biomedical interest, is a more complex, more variable, yet lesser-investigated sample matrix compared to widely studied sample types like human plasma. This manuscript describes a novel experimental strategy using multidimensional chromatography to facilitate compound identification in untargeted metabolomics. Pooled fecal metabolite extract samples were fractionated using offline semi-preparative liquid chromatography. The resulting fractions were analyzed by an orthogonal LC-MS/MS method, and the data were searched against commercial, public, and local spectral libraries. Multidimensional chromatography yielded more than a 3-fold improvement in identified compounds compared to the typical single-dimensional LC-MS/MS approach and successfully identified several rare and novel compounds, including atypical conjugated bile acid species. Most features identified by the new approach could be matched to features that were detectable but not identifiable in the original single-dimension LC-MS data. Overall, our approach represents a powerful strategy for deeper annotation of the metabolome that can be implemented with commercially-available instrumentation, and should apply to any dataset requiring deeper annotation of the metabolome.

Canada's First Joint Oncology-Allergy Clinic: Successful Desensitization to Trastuzumab Following Severe Anaphylactic Reaction in Which Epinephrine Was Inappropriately Withheld.

BACKGROUND: Recognition of anaphylaxis and differentiation from other infusion reactions in an oncology setting is imperative; epinephrine is the recommended treatment for anaphylaxis and should be administered immediately to patients in whom anaphylaxis is suspected. Trastuzumab has a potentially tremendous oncological benefit, and when hypersensitivity reactions occur, rechallenge with desensitization protocols has become more common. Oncology presents a unique situation in which repeat drug exposure after a serious adverse reaction is often warranted due to the mortality risk of untreated cancer-allergists can assist with both symptom assessment and risk mitigation. CASE PRESENTATION: This case showcases successful desensitization in a 43-year-old female with locally advanced HER2-positive breast cancer following a severe anaphylactic reaction to trastuzumab, in which epinephrine was not administered. We report the establishment of the Medical Oncology and Allergy Clinic: Canada's first multidisciplinary clinic aimed at expediting the assessment and management of oncology patients with adverse drug reactions (including chemotherapy, contrast media, antimicrobials) and those with primary and acquired immunodeficiency. CONCLUSIONS: We propose this multidisciplinary clinic model as a treatment framework moving forward, with the goal of continuing first-line therapies in cancer patients who develop drug-hypersensitivity (i.e., through desensitization). This case highlights the unmet need for a multidisciplinary approach to the management of oncology patients who experience hypersensitivity reactions.

Otolaryngology consultations for COVID-19 patients: A retrospective cohort study of indications, interventions, and considerations.

OBJECTIVE: To identify differences in inpatient otolaryngology consultations and interventions for patients based on COVID-19. METHODS: Records were reviewed for all patients for whom otolaryngology was consulted at a high-volume tertiary care hospital from April 30, 2020 to October 1, 2020. Demographic information, length of stay, COVID-19 status, indication for consultation, and otolaryngology interventions were recorded. Statistical analysis was performed using R software. RESULTS: Bleeding composed a significantly higher proportion of otolaryngology consults in COVID-19 positive patients (28% vs. 8.4%, p<0.0001). Management of bleeding was the most common procedure performed in positive patients (n=37, 35%), and they had a higher median number of interventions performed when compared to bleeding patients who tested negative (1, IQR 1-2 vs. 1, IQR 0-1, p=0.04). COVID-19 positive patients with bleeding were more likely to expire than those with other indications for otolaryngology consultation (50% vs. 7%, p<0.001). CONCLUSION: Bleeding and associated interventions comprised the predominant discrepancy between COVID-19 positive and negative patients in our cohort. We encourage routine use of simple and cost-effective methods to decrease risk of bleeding.

A call to action for blood flow restriction training in older adults with or susceptible to sarcopenia: A systematic review and meta-analysis.

Background: The extent to which exercise training with blood flow restriction (BFR) improves functional performance (FP) in people with sarcopenia remains unclear. We performed a comprehensive search of BFR training in subjects with sarcopenia or susceptible to sarcopenia hoping to perform a systematic review and meta-analysis on the effects of BFR on FP in older adults without medical disorders, but with or susceptible to sarcopenia. Methods: PubMed and the Cochrane library were searched through February 2022. Inclusion criteria were: 1) the study examined older adults (>55 years of age) with or susceptible to sarcopenia and free of overt acute or chronic diseases, 2) there was a random allocation of participants to BFR and active control groups, 3) BFR was the sole intervention difference between the groups, and 4) the study provided post-intervention measures of skeletal muscle and physical function which were either the same or comparable to those included in the revised European Working Group on Sarcopenia in Older People (EWGSOP) diagnostic algorithm. Results: No studies of BFR training in individuals with sarcopenia were found and no study included individuals with FP values below the EWGSOP criteria. However, four studies of BFR training in older adults in which FP was examined were found. BFR training significantly improved the timed up and go (MD = -0.46, z = 2.43, p = 0.02), 30-s chair stand (MD = 2.78, z = 3.72, p < 0.001), and knee extension strength (standardized MD = 0.5, z = 2.3, p = 0.02) in older adults. Conclusion: No studies of BFR exercise appear to have been performed in patients with or suspected sarcopenia based on latest diagnostic criteria. Despite the absence of such studies, BFR training was found to significantly improve the TUG, 30-s chair stand, and knee extension strength in older adults. Studies examining the effects of BFR in subjects below EWGSOP cut-off points are needed.

Beneficial Role of Blood Flow Restriction Exercise in Heart Disease and Heart Failure Using the Muscle Hypothesis of Chronic Heart Failure and a Growing Literature.

Background: Blood flow restriction exercise (BFRE) has become a common method to increase skeletal muscle strength and hypertrophy for individuals with a variety of conditions. A substantial literature of BFRE in older adults exists in which significant gains in strength and functional performance have been observed without report of adverse events. Research examining the effects of BFRE in heart disease (HD) and heart failure (HF) appears to be increasing for which reason the Muscle Hypothesis of Chronic Heart Failure (MHCHF) will be used to fully elucidate the effects BFRE may have in patients with HD and HF highlighted in the MHCHF. Methods: A comprehensive literature review was performed in PubMed and the Cochrane library through February 2022. Inclusion criteria were: 1) the study was original research conducted in human subjects older than 18 years of age and diagnosed with either HD or HF, 2) study participants performed BFRE, and 3) post-intervention outcome measures of cardiovascular function, physical performance, skeletal muscle function and structure, and/or systemic biomarkers were provided. Exclusion criteria included review articles and articles on viewpoints and opinions of BFRE, book chapters, theses, dissertations, and case study articles. Results: Seven BFRE studies in HD and two BFRE studies in HF were found of which four of the HD and the two HF studies examined a variety of measures reflected within the MHCHF over a period of 8-24 weeks. No adverse events were reported in any of the studies and significant improvements in skeletal muscle strength, endurance, and work as well as cardiorespiratory performance, mitochondrial function, exercise tolerance, functional performance, immune humoral function, and possibly cardiac performance were observed in one or more of the reviewed studies. Conclusion: In view of the above systematic review, BFRE has been performed safely with no report of adverse event in patients with a variety of different types of HD and in patients with HF. The components of the MHCHF that can be potentially improved with BFRE include left ventricular dysfunction, inflammatory markers, inactivity, a catabolic state, skeletal and possibly respiratory muscle myopathy, dyspnea and fatigue, ANS activity, and peripheral blood flow. Furthermore, investigation of feasibility, acceptability, adherence, adverse effects, and symptoms during and after BFRE is needed since very few studies have examined these important issues comprehensively in patients with HD and HF.

Forecasting the flap: predictors for pediatric lower extremity trauma reconstruction.

BACKGROUND: Predicting the need for post-traumatic reconstruction of lower extremity injuries remains a challenge. Due to the larger volume of cases in adults than in children, the majority of the medical literature has focused on adult lower extremity reconstruction. This study evaluates predictive risk factors associated with the need for free flap reconstruction in pediatric patients following lower extremity trauma. METHODS: An IRB-approved retrospective chart analysis over a 5-year period (January 1, 2012 to December 31, 2017) was performed, including all pediatric patients (<18 years old) diagnosed with one or more lower extremity wounds. Patient demographics, trauma information, and operative information were reviewed. The statistical analysis consisted of univariate and multivariate regression models to identify predictor variables associated with free flap reconstruction. RESULTS: In total, 1,821 patients were identified who fit our search criteria, of whom 41 patients (2.25%) required free flap reconstruction, 65 patients (3.57%) required local flap reconstruction, and 19 patients (1.04%) required skin graft reconstruction. We determined that older age (odds ratio [OR], 1.134; P =0.002), all-terrain vehicle accidents (OR, 6.698; P<0.001), and trauma team activation (OR, 2.443; P=0.034) were associated with the need for free flap reconstruction following lower extremity trauma in our pediatric population. CONCLUSIONS: Our study demonstrates a higher likelihood of free flap reconstruction in older pediatric patients, those involved in all-terrain vehicle accidents, and cases involving activation of the trauma team. This information can be implemented to help develop an early risk calculator that defines the need for complex lower extremity reconstruction in the pediatric population.

Predictive Factors for Velopharyngeal Insufficiency Following Primary Cleft Palate Repair.

OBJECTIVE: Velopharyngeal insufficiency (VPI) remains a known complication of primary palatoplasty. We sought to identify factors associated with the incidence of VPI and create a predictive model for VPI development in our population. DESIGN: A single-institution, retrospective review. SETTING: Multidisciplinary clinic in a tertiary academic institution. PATIENTS: A total of 453 consecutive patients undergoing primary palatoplasty from 1999 to 2016 were reviewed. Inclusion required follow-up past age 5. Patients who were non-verbal, and thus unable to undergo speech evaluation, were excluded. MAIN OUTCOME MEASURES: Primary outcome was VPI, defined as revision palatoplasty or recommendation by speech-language pathology. RESULTS: Of 318 patients included, 179 (56%) were male. Median age at primary repair was 1.0 years (0.9-1.1) with a median age of 8.8 years at last follow-up. One hundred nineteen (37%) patients developed VPI at a median age of 5.0 years (3.8-6.5). Higher rates were seen with posterior fistula (65% vs 14%, P <.01) and straight-line repair (41% vs 9%, P <.01), with lower rates in patients with Veau I clefts (22% vs 39%, P <.05). Patients with VPI were older at last follow-up. Following multivariate regression, factors remaining significant were posterior fistula (odds ratio [OR]: 11.3, 95% CI: 6.1-22.0), primary Furlow repair (OR: 0.18, 95% CI: 0.03-0.68), genetic diagnoses (OR: 2.92, 95% CI: 1.1-7.9), and age at last follow-up (OR: 1.11, 95% CI: 1.01-1.2). CONCLUSIONS: Length of follow-up, posterior fistulae, and genetic diagnoses are associated with VPI formation. Furlow repair may protect against formation of VPI. Use of allograft, Veau class, birth type, birth weight, and race are not independently associated with VPI formation.

Traumatic xylophagia leading to foreign body removal and tracheostomy in the setting of postpartum psychosis.

Postpartum psychosis (PPP) is a severe mood disorder following childbirth that rarely leads to injurious or suicidal behavior. This report illustrates otolaryngologic intervention for pharyngeal laceration and airway instability following traumatic foreign body ingestion in the setting of PPP. A 25-year-old woman with PPP presented with hemoptysis after attempting suicide by traumatically forcing tree branches into her oropharynx. Imaging revealed pneumomediastinum, and flexible laryngoscopy and esophagoscopy showed a large foreign body (tree branch) extending from the hypopharynx to the gastroesophageal junction. She was taken to the operating room for direct microlaryngoscopy, bronchoscopy and esophagoscopy with removal of the 25-cm tree branch. Panendoscopy revealed a mucosal laceration at the cricopharyngeus with supraglottic and hypopharyngeal edema but no injury to the larynx. Due to airway concerns, a cuffed tracheostomy was placed along with a gastrostomy tube for feeding access. She tolerated her postoperative course with successful decannulation and oral feeding prior to discharge.

Modifying Chromatography Conditions for Improved Unknown Feature Identification in Untargeted Metabolomics.

Untargeted metabolomics is an essential component of systems biology research, but it is plagued by a high proportion of detectable features not identified with a chemical structure. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) experiments produce spectra that can be searched against databases to help identify or classify these unknowns, but many features do not generate spectra of sufficient quality to enable successful annotation. Here, we explore alterations to gradient length, mass loading, and rolling precursor ion exclusion parameters for reversed phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC) that improve compound identification performance for human plasma samples. A manual review of spectral matches from the HILIC data set was used to determine reasonable thresholds for search score and other metrics to enable semi-automated MS/MS data analysis. Compared to typical LC-MS/MS conditions, methods adapted for compound identification increased the total number of unique metabolites that could be matched to a spectral database from 214 to 2052. Following data alignment, 68.0% of newly identified features from the modified conditions could be detected and quantitated using a routine 20-min LC-MS run. Finally, a localized machine learning model was developed to classify the remaining unknowns and select a subset that shared spectral characteristics with successfully identified features. A total of 576 and 749 unidentified features in the HILIC and RPLC data sets were classified by the model as high-priority unknowns or higher-importance targets for follow-up analysis. Overall, our study presents a simple strategy to more deeply annotate untargeted metabolomics data for a modest additional investment of time and sample.

Early Tracheostomy Change in Neonates: Feasibility and Benefits.

OBJECTIVES: To compare outcomes of early and late tracheostomy change in neonatal patients. Early tracheostomy change (ETC) occurred 3 to 4 days after surgery, and late tracheostomy change (LTC) occurred 5 to 7 days after surgery. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary neonatal/pediatric intensive care unit. METHODS: A retrospective review of patients who underwent tracheostomy from 2015 to 2019 was performed for infants <1 year old. Data were recorded regarding age at tracheostomy, days until tracheostomy tube change, postoperative complications, and total number of days on sedative or paralytic drugs. RESULTS: Forty-six patients were included: 18 (39%) were male, with a mean age of 140 days (SD, 78). Of these, 28 (61%) received ETC. There were no accidental decannulation events in either group. Wound breakdown developed in 4 (14%) patients with ETC versus 5 (28%) with LTC (P = .3). Use of FlexTend tracheostomy tubes was associated with decreased odds of breakdown (odds ratio, 0.03; P = .01). Postoperatively, 46 (100%) patients received sedation, and 12 (26%) received paralysis. Mean duration of paralysis was 0.5 days in ETC as opposed to 2.2 days in LTC (P = .02) on univariate analysis, but the significance was not maintained on multivariate regression (P = .07). CONCLUSIONS: ETC appears to be feasible in children less than a year of age. There does not appear to be an increased risk of accidental decannulation events or false passage tracts. Further investigations are warranted to investigate safety and possible impact on wound breakdown.

Liquid chromatography above 20,000 PSI.

Continued improvements in HPLC have led to faster and more efficient separations than previously possible. One important aspect of these improvements has been the increase in instrument operating pressure and the advent of ultrahigh pressure LC (UHPLC). Commercial instrumentation is now capable of up to ~20 kpsi, allowing fast and efficient separations with 5-15 cm columns packed with sub-2 µm particles. Home-built instruments have demonstrated the benefits of even further increases in instrument pressure. The focus of this review is on recent advancements and applications in liquid chromatography above 20 kpsi. We outline the theory and advantages of higher pressure and discuss instrument hardware and design capable of withstanding 20 kpsi or greater. We also overview column packing procedures and stationary phase considerations for HPLC above 20 kpsi, and lastly highlight a few recent applicatioob pressure instruments for the analysis of complex mixtures.

Effects of compression on muscle tissue oxygenation at the onset of exercise.

The effects of compression on gastrocnemius medialis muscle oxygenation and hemodynamics during a short-term dynamic exercise was investigated in a sample of 15 male subjects (mean ± SD; age 25.8 ± 4.9 years; mass 70.6 ± 4.3 kg). Elastic compression sleeves were used to apply multiple levels of compression to the calf muscles during exercise, and noncompressive garments were used for the control condition. Tissue hemoglobin oxygen saturation was measured as the relative "tissue oxygen index" (TOI) with a near-infrared spectrometer. The recovery of TOI during exercise was determined from the slope of oxygenation recovery in a nonoccluded situation. The TOI recovery rate during the first 2 minutes of the exercise was 24% higher (p = 0.042) for the compression condition than for the control condition. A significant correlation (r = 0.61, p = 0.012) between the level of compression and the tissue oxygenation recovery during exercise was observed. Muscle energy use was determined from the rate of decline of TOI immediately upon arterial occlusion during early exercise. Muscle energy use measured during the occluded situation was not significantly influenced by compression. Based on these results, it was concluded that compression induced changes in tissue blood flow and perfusion appear to result in improved oxygenation during short-term exercise. Assuming that increased muscle oxygen availability positively influences performance, compression of muscles may enhance performance especially in sports that require repeated short bouts of exercise.

The effects of comfort care on the pain response in preterm infants undergoing screening for retinopathy of prematurity.

OBJECTIVE: The aim of the study was to determine if pain and distress during the retinopathy of prematurity (ROP) screening examination could be ameliorated by providing comfort care. STUDY DESIGN: This study was a prospective, randomized, controlled trial of 30 stable preterm infants who underwent initial ROP screening examinations. Fourteen study infants were swaddled, held, and given 24% sucrose solution during the examination. Sixteen controls were examined while lying in their cribs. Vital signs (i.e., pulse rate, respiratory rate, and oxygen saturation), crying time, and time for the vital signs to return to baseline values were recorded at different times during the examination. RESULTS: The vital signs did not vary significantly between the two groups. The participants in the control group had a trend of longer crying time, but this trend did not reach a level of statistical significance. In addition, The time required for the vital signs to return to their baseline values did not vary significantly. CONCLUSION: ROP screening is very distressful for preterm infants. The routine use of comfort care to reduce pain during the examination could not be supported by this study.