Thickening human milk: the effect of time, temperature, and thickener for infants with dysphagia.

The aim of this study was to investigate the effect of time, temperature, and thickener on expressed human milk thickened for infants with dysphagia. Thickening agents included raw oatmeal cereal, commercial thickeners (Gelmix, Purathick), pureed fruits, pureed vegetables, yogurt, and pudding. The International Dysphagia Diet Standardisation Initiative (IDDSI) flow test was used to measure the thickness level across samples at various temperatures (40 °F/4.4 °C, 70 °F/21.1 °C, and 98.6 °F/37 °C) and times (0, 5, 10, and 20 min). Statistical analysis included one-way ANOVA with Tukey post hoc test and multiple linear regression. Fruit purees, particularly banana, achieved the thickest mixtures at all temperatures and maintained a similar thickness over time (20 min). Vegetable puree mixtures were minimally effective at thickening, i.e., between 0 and 1 ml on IDDSI flow test, with exception of squash at 40 °F/4.4 °C. Commercial thickener (Gelmix and Purathick) mixtures continued to thicken over time. The yogurt mixture at 40 °F/4.4 °C thickened initially and thinned slightly over time. The pudding mixture at 40 °F/4.4 °C thickened immediately but quickly became a thin liquid. The raw oatmeal cereal mixtures thinned or thickened over time dependent on the temperature of the human milk (40 °F/4.4 °C mixture thinned over time, while the 70 °F/21.1 °C, and 98.6 °F/37 °C mixtures thickened over time). CONCLUSION: Time, temperature, and thickening agents have a significant impact on the thickness level when added to expressed human milk. Certain foods such as fruit purees, squash, yogurt, and raw oatmeal may effectively thicken human milk, and the IDDSI flow test can assess if the mixture maintains a similar thickness level over time. These foods could be considered for older infants with dysphagia. When thickening human milk for infants with dysphagia, close physician and clinician monitoring is recommended given the potential positive and/or negative consequences on oral feeding and overall health. WHAT IS KNOWN: • Thin liquids can be challenging for infants with dysphagia to safely swallow Human milk is difficult to thicken. WHAT IS NEW: • Pureed fruits and pureed squash thicken human milk effectively at various temperatures and maintain thickness level over 20 minutes. • Pureed fruits and pureed squash thicken human milk effectively at various temperatures and maintain thickness level over 20 Raw oatmeal cereal either thins over time or thickens over time depending on the temperature of the base liquid.

Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma.

INTRODUCTION: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy. METHODS: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763). RESULTS: Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD). CONCLUSIONS: This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.

Pediatric Medullary Stroke, Severe Dysphagia, and Multimodal Intervention.

Lateral medullary syndrome/Wallenberg syndrome is a stroke in the lateral medulla with symptoms often including dysphagia and dysphonia. In adults, this stroke is the most common brainstem stroke, but it is rare in the pediatric population. Insults to the medulla can involve the "swallowing centers," the nucleus ambiguus and nucleus tractus solitarius, and the cranial nerves involved in swallowing, namely IX (glossopharyngeal) and X (vagus). These individuals can develop severe dysphagia with an inability to trigger a swallow due to pharyngeal weakness and impaired mechanical opening of the upper esophageal sphincter (UES) which can result in aspiration. We present a 7-year-old male with 22q11.2 deletion syndrome (velocardiofacial syndrome) and velopharyngeal insufficiency who underwent pharyngeal flap surgery at an outside hospital whose post-operative course was complicated by adenovirus, viral myocarditis, and dorsal medullary stroke. He required a tracheostomy and gastrostomy tube. He was discharged from that hospital and readmitted to our hospital 4 months later for increased oxygen requirement, requiring a 5 month admission in the intensive care units. His initial VFSS revealed absent UES opening with the entire bolus remaining in the pyriform sinuses resulting in aspiration. His workup over the course of his admission included multiple videofluoroscopic swallow studies (VFSS), flexible endoscopic evaluation of swallowing (FEES), and pharyngeal and esophageal manometry. Intervention included intensive speech therapy, cricopharyngeal Botox® injection, and cricopharyngeal myotomy. Nineteen months after his stroke, he transitioned to oral intake of solids and liquids with adequate movement of the bolus through the pharynx and UES and no aspiration on his VFSS.

Swallowing Outcomes Following Supraglottoplasty: A Retrospective Review.

OBJECTIVES/HYPOTHESIS: Determine the incidence of short- and long-term dysphagia in pediatric patients with and without syndromes/neurodevelopmental delay following supraglottoplasty (SGP) at our institution. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective cohort study of children ≤18 years old who underwent SGP from 2014 to 2019 was undertaken. Age at surgery, sex, race, insurance, underlying syndromes/neurodevelopmental delay, concurrent surgical procedures, and clinical swallowing assessments were reviewed. Logistic regression was performed to identify factors associated with postoperative feeding difficulties. Time-to-event analysis was performed to assess time to resolution of dysphagia. RESULTS: A total of 231 patients were identified. Average age at time of SGP was 13.7 months. Of 231 patients, 88 (38.1%) had a syndrome/neurodevelopmental delay. Of these 231 patients, 112 had a preoperative videofluoroscopic swallow study or fiberoptic endoscopic evaluation of swallowing, of whom 53/112 (47.3%) had dysphagia. After SGP, 138/231 (59.7%) underwent clinical/instrumental swallowing assessments, of whom 95/138 (68.8%) had immediate postsurgical dysphagia. At last follow-up (1 month to 45 months), 15/95 (15.8%) had persistent dysphagia on instrumental assessment, 14/15 of whom had syndromes/neurodevelopmental delay. Time-to-event analysis revealed that for the nonsyndromic cohort, 25% had resolution of dysphagia by 4 months, 50% by 10 months, and 75% by 14 months. Cox proportional hazards regression revealed that the presence of underlying syndromes/neurodevelopmental delay was the only factor predictive of long-term postoperative dysphagia (hazard ratio of resolution 0.21 [95% confidence interval 0.096-0.48]). CONCLUSIONS: While short-term feeding difficulties following SGP in pediatric patients are not uncommon, long-term dysphagia is rare in patients without syndromes/neurodevelopmental delay. These data can be used when counseling caregivers about the risks and benefits of SGP. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2817-2822, 2021.

Dying persons' perspectives on, or experiences of, participating in research: An integrative review.

BACKGROUND: Conducting research with dying persons can be controversial and challenging due to concerns for the vulnerability of the dying and the potential burden on those who participate with the possibility of little benefit. AIM: To conduct an integrative review to answer the question 'What are dying persons' perspectives or experiences of participating in research? DESIGN: A structured integrative review of the empirical literature was undertaken. DATA SOURCES: Cumulative Index Nursing and Allied Health Complete, PsycINFO, MEDLINE, Informit and Embase databases were searched for the empirical literature published since inception of the databases until February 2017. RESULTS: From 2369 references, 10 papers were included in the review. Six were qualitative studies, and the remaining four were quantitative. Analysis revealed four themes: value of research, desire to help, expression of self and participation preferences. Dying persons value research participation, regarding their contribution as important, particularly if it provides an opportunity to help others. Participants perceived that the potential benefits of research can and should be measured in ways other than life prolongation or cure. Willingness to participate is influenced by study type or feature and degree of inconvenience. CONCLUSION: Understanding dying persons' perspectives of research participation will enhance future care of dying persons. It is essential that researchers do not exclude dying persons from clinically relevant research due to their prognosis, fear or burden or perceived vulnerability. The dying should be afforded the opportunity to participate in research with the knowledge it may contribute to science and understanding and improve the care and treatment of others.

Correlation of lactate dehydrogenase isoenzyme profile with outcome in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab or cediranib: Retrospective analysis of the HORIZON I study.

INTRODUCTION: Bevacizumab improves outcome for patients with advanced colorectal cancer (CRC) when added to chemotherapy. The HORIZON I trial resulted in similar outcome with bevacizumab or cediranib, a small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF) receptor, as treatment of advanced CRC. The spectrum of lactate dehydrogenase (LDH) isoenzyme expression was examined in serum samples of HORIZON I participants to identify biomarkers predictive of efficacy of VEGF pathway inhibitors. MATERIALS AND METHODS: Total LDH levels, as well as LDH isoenzyme levels in frozen baseline serum samples, were retrospectively evaluated. Total LDH serum levels measured during the study, progression-free survival (PFS), and overall survival (OS) were available from the HORIZON I study data. RESULTS: Total LDH levels measured in the frozen serum samples correlated with those measured in fresh samples. The expected reciprocal correlation was found between hypoxic and oxic LDH isoenzymes. High total LDH correlated with shorter PFS, and high hypoxia-related LDH isoenzymes correlated with shorter PFS and OS. The difference in outcome of the cediranib-treated patients vs. those treated with bevacizumab was not substantially different in the various LDH isoform expression subgroups. In patients with a hypoxic LDH pattern of expression, there was a nonsignificant trend of better outcome in cediranib-treated patients. CONCLUSION: Evaluation of total LDH and its isoforms in frozen serum samples is feasible. High total LDH and high hypoxic LDH isoenzymes were associated with poor prognosis. Further studies are needed to evaluate the predictive value of LDH isoenzyme expression pattern for VEGF-pathway inhibition efficacy.

KRAS mutations are associated with inferior clinical outcome in patients with metastatic colorectal cancer, but are not predictive for benefit with cediranib.

PURPOSE: The prognostic potential of KRAS mutations in advanced colorectal cancer (CRC) patients and the impact of KRAS mutation status on the effectiveness of chemotherapy or vascular endothelial growth factor (VEGF) signalling inhibitor therapy remain unclear. KRAS mutation status was evaluated retrospectively as a potential prognostic/predictive marker of clinical outcomes using tumour samples from patients with metastatic CRC receiving cediranib or placebo plus FOLFOX/XELOX in a Phase III trial (HORIZON II; NCT00399035). METHODS: KRAS codon 12 and 13 mutation analyses were performed using a commercially available, allele-specific, amplification refractory mutation system (ARMS)-based polymerase chain reaction (PCR) assay. Retrospective analyses of progression-free survival (PFS) and overall survival (OS) according to KRAS mutation status were performed for patients randomised to cediranib 20mg or placebo. RESULTS: KRAS status was determined in 599/1076 patients (cediranib 20mg, n=285/502; cediranib 30 mg, n=110/216; placebo, n=204/358). Baseline characteristics were similar across KRAS mutant (n=258; 24.0%), wild-type (n=341; 31.7%) and status unknown (n=477; 44.3%) groups. There was a trend towards improved PFS and OS in the wild-type versus mutant subgroups independent of treatment (cediranib 20 mg and placebo: PFS hazard ratio (HR)=0.85 [median PFS: wild-type=8.5 months; mutant=8.3 months]; OS HR=0.71 [median OS: wild-type=20.9 months; mutant=16.9 months]). Treatment effects were similar between KRAS subgroups for cediranib 20mg versus placebo (PFS: wild-type HR=0.78, mutant HR=0.82; OS: wild-type HR=0.92, mutant HR=1.01). CONCLUSION: Data from this large randomised Phase III study show that KRAS codon 12/13 mutations have negative prognostic value in metastatic CRC patients receiving treatment with FOLFOX/XELOX, but KRAS mutation status is not predictive of treatment benefit with cediranib, using PFS or OS.

Canada: an external quality review process--the Wellspring model.

Wellspring is a group of cancer support centers in Ontario, Canada. The centers provide information, support, and coping-skills programs for people with cancer and their families. To ascertain that all centers provide the same high quality of programs, the board at Wellspring established a panel of external oncology experts and asked them to establish a process to review program quality in each center. This article outlines the process undertaken to provide quality improvement in a nonprofit charitable organization.