Transcriptional and functional profiling identifies inflammation and endothelial-to-mesenchymal transition as potential drivers for phenotypic heterogeneity within a cohort of endothelial colony forming cells.

BACKGROUND: Endothelial colony-forming cells (ECFCs) derived from patients can be used to investigate pathogenic mechanisms of vascular diseases like von Willebrand disease. Considerable phenotypic heterogeneity has been observed between ECFC clones derived from healthy donors. This heterogeneity needs to be well understood in order to use ECFCs as endothelial models for disease. OBJECTIVES: Therefore, we aimed to determine phenotypic and gene expression differences between control ECFCs. METHODS: A total of 34 ECFC clones derived from 16 healthy controls were analyzed. The transcriptome of a selection of ECFC clones (n = 15) was analyzed by bulk RNA sequencing and gene set enrichment analysis. Gene expression was measured in all ECFC clones by quantitative polymerase chain reaction. Phenotypic profiling was performed and migration speed of the ECFCs was measured using confocal microscopy, followed by automated quantification of cell morphometrics and migration speed. RESULTS: Through hierarchical clustering of RNA expression profiles, we could distinguish 2 major clusters within the ECFC cohort. Major differences were associated with proliferation and migration in cluster 1 and inflammation and endothelial-to-mesenchymal transition in cluster 2. Phenotypic profiling showed significantly more and smaller ECFCs in cluster 1, which contained more and longer Weibel-Palade bodies. Migration speed in cluster 1 was also significantly higher. CONCLUSION: We observed a range of different RNA expression patterns between ECFC clones, mostly associated with inflammation and clear differences in Weibel-Palade body count and structure. We developed a quantitative polymerase chain reaction panel that can be used for the characterization of ECFC clones, which is essential for the correct analysis of pathogenic mechanisms in vascular disorders.

Decisional Conflict and Decision Regret in Head and Neck Oncology: A Systematic Review and Meta-Analysis.

Importance: Head and neck cancer (HNC) often requires treatment with a major impact on quality of life. Treatment decision-making is often challenging, as it involves balancing survival against the preservation of quality of life and choosing among treatments with comparable outcomes but variation in morbidity and adverse events; consequently, the potential for decisional conflict (DC) and decision regret (DR) is high. Objectives: To summarize the literature on DC and DR in HNC, to give an overview of its prevalence and extent, and to advise on clinical practice and future research. Data Sources: Embase, Web of Science, MEDLINE, and PsycINFO were searched up to February 24, 2023, including all years of publication. Study Selection: Eligible studies addressed DC and/or DR as primary or secondary outcomes with any instrument in HNC, except cutaneous tumors. Two mutually blinded researchers conducted screening and inclusion with support of an artificial intelligence assistant and conducted risk of bias (ROB) assessment. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were followed for data extraction. ROB assessments were done using Critical Appraisal Skills Programme (qualitative) and CLARITY (quantitative). Meta-analysis with a random-effects model was used to obtain pooled prevalence estimates for DC and DR when at least 4 sufficiently clinically homogeneous studies were available. Main Outcomes and Measures: Prevalence of DC (qualitative, Decisional Conflict Scale, SURE questionnaire) and DR (qualitative, study-specific questionnaires, Decision Regret Scale, Shame and Stigma Scale). Results: Overall, 28 studies were included, with 16 included in meta-analyses for DR prevalence. The pooled prevalence of clinically relevant DR above the cutoff score for validated questionnaires (11 studies; 2053 participants) was 71% (95% CI, 58%-82%; I2 = 94%), while for study-specific questionnaires (5 studies; 674 participants) it was 11% (95% CI, 5%-22%; I2 = 92%). Only 4 studies investigated DC, showing a prevalence of 22.6% to 47.5% above cutoff values. Derived overarching themes found in qualitative studies were preparation, shared decision-making roles, information, time pressure, stress of diagnosis, and consequences. Conclusions and Relevance: Although limited data on DC and DR were available, the studies performed indicated that DC and DR are highly prevalent issues in HNC. Results suggest that study-specific questionnaires underestimated DR. The findings underscore the rationale to improve counseling and shared decision-making for this patient population.

Impact of allele-selective silencing of von Willebrand factor in mice based on a single nucleotide allelic difference in von Willebrand factor.

INTRODUCTION: Von Willebrand factor (VWF) plays a pathophysiological role in hemostatic disorders. Partial inhibition of the VWF gene through small interfering RNA (siRNA)-mediated allele-selective silencing could be a promising therapeutic strategy. For von Willebrand disease, allele-selectively inhibiting dominant-negative VWF-alleles might ameliorate the phenotype. For thrombotic disorders, partial VWF reduction can lower thrombotic risk, while avoiding bleeding. Previously, we demonstrated the feasibility of Vwf-silencing in homozygous C57BL/6J (B6) or 129S1/SvImJ (129S) mice. The present study investigated allele-selective Vwf-silencing in a complex heterozygous setting of crossed B6 and 129S mice and its subsequent hemostatic impact. MATERIALS AND METHODS: Heterozygous B6.129S mice were treated with siRNAs targeting Vwf expressed from either B6- (siVwf.B6) or 129S-alleles (siVwf.129S). Plasma VWF and lung Vwf mRNA were determined. siVwf.B6-treated B6.129S mice were subjected to ferric chloride-induced mesenteric vessel thrombosis and tail-bleeding. RESULTS: In B6.129S mice, siVwf.B6 reduced Vwf mRNA of the targeted B6-allele by 72% vs. only 12% of the non-targeted 129S-allele (41% total mRNA reduction), lowering plasma VWF by 46%. Oppositely, siVwf.129S reduced Vwf mRNA by 45%, now selectively inhibiting the 129S-allele over the B6-allele (58% vs. 9%), decreasing plasma VWF by 43%. The allele-selective VWF reduction by siVwf.B6 coincided with decreased thrombus formation in mesenteric arterioles, without prolonging tail-bleeding times. CONCLUSIONS: This study demonstrates the feasibility of allele-selective Vwf-silencing in a heterozygous setting, achieving a controlled close to 50% reduction of plasma VWF. The observed thromboprotection and absence of prolonged bleeding times underline the potential of allele-selective Vwf-silencing as a therapeutic strategy in hemostatic disorders.

Approaches to induce the maturation process of human induced pluripotent stem cell derived-endothelial cells to generate a robust model.

BACKGROUND: Endothelial cells generated from induced pluripotent stem cells (hiPSC-ECs) show the majority of endothelial cell characteristics and markers, such as cobblestone morphology and the expression of VEGF and VE-cadherin. However, these cells are failing to show a mature endothelial cell phenotype, which is represented by the low expression and production of von Willebrand Factor (VWF) leading to the round morphology of the Weibel Palade Bodies (WPBs). The aim of this study was to improve the maturation process of hiPSC-ECs and to increase the levels of VWF. METHODS: hiPSC-ECs were differentiated by a standard differentiation protocol from hiPSCs generated from healthy control donors. To induce maturation, the main focus was to increase the expression and/or production of VWF by the adjustment of potential parameters influencing differentiation and maturation. We also compared alternative differentiation protocols. Cells were analyzed for the expression of endothelial cell markers, WPB structure, and the production and secretion of VWF by flow cytometry, confocal microscopy and ELISA. RESULTS: The generated hiPSC-ECs have typical endothelial cell surface expression profiles, with low expression levels of non-endothelial markers as expected. Co-culture with pericytes, varying concentrations and timing of differentiation factors, applying some level of flow, and the addition of HDAC inhibitors did not substantially improve maturation of hiPSC-ECs. Transfection with the transcription factor ETV2 to induce a faster hiPSC-EC differentiation process resulted in a limited increase in VWF production, secretion, and elongation of WPB structure. Alternative differentiation protocols had limited effect. CONCLUSION: hiPSCs-ECs have the potential to show a more mature endothelial phenotype with elongated WPBs after >30 days in culture. However, this comes with limitations as there are very few cells detected, and cells are deteriorating after being in culture for extended periods of time.

The implementation of a multidisciplinary, electronic health record embedded care pathway to improve structured data recording and decrease electronic health record burden.

INTRODUCTION: Theoretically, the added value of electronic health records (EHRs) is extensive. Reusable data capture in EHRs could lead to major improvements in quality measurement, scientific research, and decision support. To achieve these goals, structured and standardized recording of healthcare data is a prerequisite. However, time spent on EHRs by physicians is already high. This study evaluated the effect of implementing an EHR embedded care pathway with structured data recording on the EHR burden of physicians. MATERIALS AND METHODS: Before and six months after implementation, consultations were recorded and analyzed with video-analytic software. Main outcome measures were time spent on specific tasks within the EHR, total consultation duration, and usability indicators such as required mouse clicks and keystrokes. Additionally, a validated questionnaire was completed twice to evaluate changes in physician perception of EHR system factors and documentation process factors. RESULTS: Total EHR time in initial oncology consultations was significantly reduced by 3.7 min, a 27 % decrease. In contrast, although a decrease of 13 % in consultation duration was observed, no significant effect on EHR time was found in follow-up consultations. Additionally, perceptions of physicians regarding the EHR and documentation improved significantly. DISCUSSION: Our results have shown that it is possible to achieve structured data capture while simultaneously reducing the EHR burden, which is a decisive factor in end-user acceptance of documentation systems. Proper alignment of structured documentation with workflows is critical for success. CONCLUSION: Implementing an EHR embedded care pathway with structured documentation led to decreased EHR burden.

Decisional Conflict in Patients with Advanced Laryngeal Carcinoma: A Multicenter Study.

OBJECTIVES: Decision-making for patients with a locally advanced laryngeal carcinoma (T3 and T4) is challenging due to the treatment choice between organ preservation and laryngectomy, both with different and high impact on function and quality of life (QoL). The complexity of these treatment decisions and their possible consequences might lead to decisional conflict (DC). This study aimed to explore the level of DC in locally advanced laryngeal carcinoma patients facing curative decision-making, and to identify possible associated factors. METHODS: In this multicenter prospective cohort study, participants completed questionnaires on DC, level of shared decision-making (SDM), and a knowledge test directly after counseling and 6 months after treatment. Descriptive statistics and Spearman correlation tests were used to analyze the data. RESULTS: Directly after counseling, almost all participants (44/45; 98%) experienced Clinically Significant DC score (CSDC >25, scale 0-100). On average, patients scored 47% (SD 20%) correct on the knowledge test. Questions related to radiotherapy were answered best (69%, SD 29%), whilst only 35% (SD 29%) of the questions related to laryngectomy were answered correctly. Patients' perceived level of SDM (scale 0-100) was 70 (mean, SD 16.2), and for physicians this was 70 (SD 1.7). CONCLUSION: Most patients with advanced larynx cancer experience high levels of DC. Low knowledge levels regarding treatment aspects indicate a need for better patient counseling. LEVEL OF EVIDENCE: Level IV Laryngoscope, 2024.

Optimizing Wound Care after Surgery of the Head and Neck: A Review of Dressing Materials.

Wound healing is a complex biological process subject to complications that might jeopardize the patient's postoperative care. Appropriately approaching surgical wounds after head and neck surgery positively influences the quality and speed of wound healing and increases patient comfort. A large variety of dressing materials currently exist that allow the care of different types of wounds. Nevertheless, there is limited literature on the most suitable types of dressings after head and neck surgery. The objective of the present article is to review the most commonly used wound dressings, their benefits, indications, and disadvantages, and to provide a systematic approach for wound care within the head and neck. The Woundcare Consultant Society distinguishes wounds into three groups: black, yellow, and red. Each type of wound represents distinctive underlying pathophysiological processes with unique needs. Utilizing this classification along with the TIME model allows a proper characterization of wounds and the identification of potential healing barriers. This evidence-based and systematic approach can facilitate and guide the head and neck surgeon in selecting a wound dressing upon acknowledging their properties, which are herein reviewed and exemplified with representative cases.

Maximal cardiopulmonary exercise testing in laryngectomised patients using different heat and moisture exchangers - feasibility and exercise responses.

OBJECTIVE: After laryngectomy, the breathing resistance of heat and moisture exchangers may limit exercise capacity. Breathing gas analysis during cardiopulmonary exercise testing is not possible using regular masks. This study tested the feasibility of cardiopulmonary exercise testing with a heat and moisture exchanger in situ, using an in-house designed connector. Additionally, we explored the effect of different heat and moisture exchanger resistances on exercise capacity in this group. METHODS: Ten participants underwent two cardiopulmonary exercise tests using their daily life heat and moisture exchanger (0.3 hPa or 0.6 hPa) and one specifically developed for activity (0.15 hPa). Heat and moisture exchanger order was randomised and blinded. RESULTS: All participants completed both tests. No (serious) adverse events occurred. Only four subjects reached a respiratory exchange ratio of more than 1.1 in at least one test. Maximum exercise levels using heat and moisture exchangers with different resistances did not differ. CONCLUSION: Cardiopulmonary exercise testing in laryngectomees with a heat and moisture exchanger is feasible; however, the protocol does not seem appropriate to reach this group's maximal exercise capacity. Lowering heat and moisture exchanger resistance does not increase exercise capacity in this sample.

The development of a decision aid for patients with operable oropharyngeal carcinoma in the Netherlands - A mixed methods study.

OBJECTIVE: The aim of this project is to create an interactive online patient decision aid (PDA) for oropharyngeal cancer (OPSCC) patients, eligible for transoral (robotic) surgery with an ultimate goal to assist both physicians and patients in making treatment choices. MATERIALS AND METHODS: Following the International Patient Decision Aid Standards, a mixed-methods approach was employed. The study involved semi-structured in-depth interviews with patients and physicians, thinking-out-loud sessions, and study-specific questionnaires. Thematic coding and analysis were conducted on verbatim transcriptions of audio-recorded interviews. RESULTS: The PDA drafts were evaluated by twenty OPSCC survivors and twenty multidisciplinary specialists. Significant revisions were made after phase 1 to enhance readability and reduce text, whilst incorporating videos and graphics. Following all phases, both patients and specialists rated the PDA as comprehensible, feasible, and a valuable addition to regular counseling. CONCLUSION: This study showcases the development of a PDA for early stage oropharyngeal cancer patients considering surgery and radiotherapy options. The decision aid emphasizes the disparities in short- and long-term side effects between the two treatments. Patients and physicians found the decision aid to be understandable, user-friendly, and helpful for future patients. The PDA is available on https://beslissamen.nl/.

The acceptance and voice quality of a new voice prosthesis 'Vega High performance' - a feasibility study.

BACKGROUND: The Provox Vega High Performance (PVHP) is a newly developed voice prosthesis (VP) with an aim to achieve a longer and more predictable lifetime. OBJECTIVES: This feasibility study aims to assess patient acceptance of the PVHP VP, evaluate adverse events, voice quality, and device lifetime. METHODS: Laryngectomized patients previously using a Provox Vega or ActiValve Light were included. Acceptance and voice outcomes were evaluated at two-time points with a 2-week interval. Baseline measurements were taken with the standard VP, followed by placement of the PVHP for the 2-week assessment. RESULTS: Fifteen participants completed the study, with thirteen being initial Vega-users. PVHP acceptance was 87% 2 weeks after placement. Median device lifetime for all VPs was 64 d (range 14-370). In the subgroup without periprosthetic leakage, the median device lifetime was 101 d (range 31-370). Acceptance dropped to 40% after device failure. Voice quality did not differ between PVHP and baseline VP. The most reported adverse event was PVHP valve stickiness (46%). CONCLUSION AND SIGNIFICANCE: Acceptance of the PVHP is largely dependent on device lifetime, decreasing from 87% to 40% after leakage or replacement. Voice quality remains consistent across different VPs. Developing a long-lasting VP remains a challenge.

Small interfering RNA-mediated allele-selective silencing of von Willebrand factor in vitro and in vivo.

An imbalance in von Willebrand factor (VWF) may either lead to bleeding (von Willebrand disease, VWD) or thrombosis. Both disorders have shortcomings in the currently available treatments. VWF itself could be a potential therapeutic target because of its role in both bleeding and thrombosis. Inhibiting VWF gene expression through allele-selective silencing of VWF with small interfering RNAs (siRNAs) could be a personalized approach to specifically inhibit mutant VWF in VWD or to normalize increased VWF levels in thrombotic disorders without complete VWF knockdown. Therefore, we investigated a method to allele-selectively silence the VWF gene in mice as a therapeutic strategy. Fourteen candidate siRNAs targeting murine Vwf of either the C57BL/6J (B6) or the 129S1/SvImJ (129S) strain were tested in vitro in cells expressing B6- and 129S-Vwf for inhibitory effect and allele-selective potential. Together with a nonselective siVwf, 2 lead candidate siRNAs, siVwf.B6 and siVwf.129S, were further tested in vivo in B6 and 129S mice. Efficient endothelial siRNA delivery was achieved by siRNA encapsulation into 7C1 oligomeric lipid nanoparticles. Treatment with the nonselective siVwf resulted in dose-dependent inhibition of up to 80% of both lung messenger RNA and plasma VWF protein in both mouse strains. In contrast, the allele-selective siVwf.B6 and siVwf.129S were shown to be effective in and selective solely for their corresponding mouse strain. To conclude, we showed efficient endothelial delivery of siRNAs that are highly effective in allele-selective inhibition of Vwf in mice, which constitutes an in vivo proof of principle of allele-selective VWF silencing as a therapeutic approach.

Automated segmentation and quantitative analysis of organelle morphology, localization and content using CellProfiler.

One of the most used and versatile methods to study number, dimensions, content and localization of secretory organelles is confocal microscopy analysis. However, considerable heterogeneity exists in the number, size and shape of secretory organelles that can be present in the cell. One thus needs to analyze large numbers of organelles for valid quantification. Properly evaluating these parameters requires an automated, unbiased method to process and quantitatively analyze microscopy data. Here, we describe two pipelines, run by CellProfiler software, called OrganelleProfiler and OrganelleContentProfiler. These pipelines were used on confocal images of endothelial colony forming cells (ECFCs), which contain unique secretory organelles called Weibel-Palade bodies (WPBs), and on early endosomes in ECFCs and human embryonic kidney 293T (HEK293T) cells. Results show that the pipelines can quantify the cell count, size, organelle count, organelle size, shape, relation to cells and nuclei, and distance to these objects in both endothelial and HEK293T cells. Additionally, the pipelines were used to measure the reduction in WPB size after disruption of the Golgi and to quantify the perinuclear clustering of WPBs after triggering of cAMP-mediated signaling pathways in ECFCs. Furthermore, the pipeline is able to quantify secondary signals located in or on the organelle or in the cytoplasm, such as the small WPB GTPase Rab27A. Cell profiler measurements were checked for validity using Fiji. To conclude, these pipelines provide a powerful, high-processing quantitative tool for the characterization of multiple cell and organelle types. These pipelines are freely available and easily editable for use on different cell types or organelles.

Improving Hands-Free Speech Rehabilitation in Laryngectomized Patients with a Moldable Adhesive.

OBJECTIVE: This study aims to assess the product performance of a new moldable peristomal adhesive with corresponding heating pad designed to facilitate and improve automatic speaking valve (ASV) fixation for hands-free speech in laryngectomized patients. METHODS: Twenty laryngectomized patients, all regular adhesive users with prior ASV experience, were included. Study-specific questionnaires were used for data collection at baseline and after two weeks of moldable adhesive use. The primary outcome parameters were adhesive lifetime during hands-free speech, use and duration of hands-free speech, and patient preference. Additional outcome parameters were satisfaction, comfort, fit, and usability. RESULTS: The moldable adhesive enabled ASV fixation adequate for hands-free speech in the majority of participants. Overall, the moldable adhesive significantly increased adhesive lifetime and duration of hands-free speech compared to participants' baseline adhesives (p < 0.05), regardless of stoma depth, skin irritation, or regular use of hands-free speech at baseline. The participants who preferred the moldable adhesive (55% of participants) experienced a significant increase in the adhesive lifetime (median of 24 h, range 8-144 h) and improved comfort, fit, and ease of speech. CONCLUSION: The moldable adhesive's lifetime and functional aspects, including the ease of use and custom fit, are encouraging outcomes and enable more laryngectomized patients to use hands-free speech more regularly. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2965-2970, 2023.

Understanding and predicting the performance of passive heat and moisture exchangers using a numerical model.

BACKGROUND: To improve the understanding of the thermodynamics and performance of small passive hygroscopic Heat and Moisture Exchangers (HMEs), a computer model simulating HME function is required. METHODS: We developed a numerical HME model to calculate the HME's water and heat exchange. The model was tuned and verified with experimental data and validated by applying it to HME design variations. RESULTS: Verification of the model's results to the experimental data shows that the tuned model yields reliable results. The mass of the core, which determines the HME's total heat capacity, is the most important parameter influencing the performance of passive HMEs. CONCLUSIONS: Increasing the HME's diameter is an effective way to improve an HME, as it yields higher performance and lowers breathing resistance. HMEs intended for use in warm or dry climates should contain more and those for use in cold humid climates should contain less hygroscopic salt.

Does Prophylactic Replacement of Voice Prosthesis Make Sense? A Study to Predict Prosthesis Lifetime.

OBJECTIVE: Voice prosthesis leakage significantly affects the quality of life of patients undergoing laryngectomy, causing insecurity and frequent unplanned hospital visits and costs. In this study, the concept of prophylactic voice prosthesis replacement was explored to prevent leakages. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary hospital. METHODS: This study included all patients who underwent laryngectomy between 2000 and 2012 in the Netherlands Cancer Institute. Device lifetimes and voice prosthesis replacements of a retrospective cohort were used to calculate the number of needed voice prostheses per patient per year to prevent 70% of the leakages by prophylactic replacement. Various strategies for the timing of prophylactic replacement were considered: adaptive strategies based on the individual patient's history of replacement and fixed strategies based on the results of patients with similar voice prosthesis or treatment characteristics. RESULTS: Patients used a median 3.4 voice prostheses per year (range, 0.1-48.1). We found high inter- and intrapatient variability in device lifetime. When prophylactic replacement is applied, this would become a median 9.4 voice prostheses per year, which means replacement every 38 days, implying >6 additional voice prostheses per patient per year. The individual adaptive model showed that preventing 70% of the leakages was impossible for most patients and only a median 25% can be prevented. Monte-Carlo simulations showed that prophylactic replacement is not feasible due to the high coefficient of variation (SD/mean) in device lifetime. CONCLUSION: Based on our simulations, prophylactic replacement of voice prostheses is not feasible due to high inter- and intrapatient variation in device lifetime.

Quantifying the Electronic Health Record Burden in Head and Neck Cancer Care.

BACKGROUND: Although the main task of health care providers is to provide patient care, studies show that increasing amounts of time are spent on documentation. OBJECTIVE: To quantify the time and effort spent on the electronic health record (EHR) in head and neck cancer care. METHODS: Cross-sectional time-motion study. Primary outcomes were the percentages of time spent on the EHR and the three main tasks (chart review, input, placing orders), number of mouse events, and keystrokes per consultation. Secondary outcome measures were perceptions of health care providers regarding EHR documentation and satisfaction. RESULTS: In total, 44.0% of initial oncological consultation (IOC) duration and 30.7% of follow-up consultation (FUC) duration are spent on EHR tasks. During 80.0% of an IOC and 67.9% of a FUC, the patient and provider were actively communicating. Providers required 593 mouse events and 1,664 keystrokes per IOC and 140 mouse events and 597 keystrokes per FUC, indicating almost 13 mouse clicks and close to 40 keystrokes for every minute of consultation time. Less than a quarter of providers indicated that there is enough time for documentation. CONCLUSION: This study quantifies the widespread concern of high documentation burden for health care providers in oncology, which has been related to burnout and a decrease of patient-clinician interaction. Despite excessive time and effort spent on the EHR, health care providers still felt this was insufficient for proper documentation. However, the need for accurate and complete documentation is high, as reuse of information becomes increasingly important. The challenge is to decrease the documentation burden while increasing the quality of EHR data.

The Impact of Structured and Standardized Documentation on Documentation Quality; a Multicenter, Retrospective Study.

The reuse of healthcare data for various purposes will become increasingly important in the future. To enable the reuse of clinical data, structured and standardized documentation is conditional. However, the primary purpose of clinical documentation is to support high-quality patient care. Therefore, this study investigated the effect of increased structured and standardized documentation on the quality of notes in the Electronic Health Record. A multicenter, retrospective design was used to assess the difference in note quality between 144 unstructured and 144 structured notes. Independent reviewers measured note quality by scoring the notes with the Qnote instrument. This instrument rates all note elements independently using and results in a grand mean score on a 0-100 scale. The mean quality score for unstructured notes was 64.35 (95% CI 61.30-67.35). Structured and standardized documentation improved the Qnote quality score to 77.2 (95% CI 74.18-80.21), a 12.8 point difference (p < 0.001). Furthermore, results showed that structured notes were significantly longer than unstructured notes. Nevertheless, structured notes were more clear and concise. Structured documentation led to a significant increase in note quality. Moreover, considering the benefits of structured data recording in terms of data reuse, implementing structured and standardized documentation into the EHR is recommended.

Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma.

Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO's MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC.

Adjustable breathing resistance for laryngectomized patients: Proof of principle in a novel heat and moisture exchanger cassette.

BACKGROUND: Due to the heat and moisture exchanger's (HME) breathing resistance, laryngectomized patients cannot always use an (optimal) HME during physical exercise. We propose a novel HME cassette concept with adjustable "bypass," to provide adjustment between different breathing resistances within one device. METHODS: Under standardized conditions, the resistance and humidification performance of a high resistance/high humidification HME (XM) foam in a cassette with and without bypass were compared to a lower resistance/lesser humidification HME (XF) foam in a closed cassette. RESULTS: With a bypass in the cassette, the resistance and humidification performance of XM foam were similar to those of XF foam in the closed cassette. Compared to XM foam in the closed cassette, introducing the bypass resulted in a 40% resistance decrease, whereas humidification performance was maintained at 80% of the original value. CONCLUSIONS: This HME cassette prototype allows adjustment between substantially different resistances while maintaining appropriate humidification performances.