Compensation in Verbal and Nonverbal Communication after Total Laryngectomy

Total laryngectomy is a major surgical procedure with life-changing consequences. As a result of the surgery, the upper and lower airways are disconnected, the natural voice is lost, and patients breathe through a tracheostoma in the neck. Tracheoesophageal speech is the most common speech rehabilitation technique. Due to the lack of air volume, and the amount of muscle tension in the esophagus, some patients may suffer from a hyper- or hypo-tonic voice, resulting in less intelligible speech. To communicate as intelligibly as possible, patients likely adapt their verbal and nonverbal communication to their physical disabilities. The current study aimed to explore the compensation techniques in verbal and nonverbal communication after total laryngectomy focusing on the complexity of grammar and the use of co-speech gestures. We analyzed previously obtained interviews of eight laryngectomized women on the syntactic complexity in speech and the use and type of co-speech gestures. Results were compared with analyses of productions by healthy controls. We found that laryngectomized women reduce the syntactic complexity of their speech, and use nonverbal gestures in their communication. Further research is needed with systematically obtained data and more suitable match-groups

Translation of c-Met targeted image-guided surgery solutions in oral cavity cancer: initial proof of concept data

Simple SummaryTranslation of tumor-specific fluorescent tracers is crucial in the realization intraoperative of tumor identification during fluorescence-guided surgery. Ex vivo assessment of surgical specimens after topical tracer application has the potential to reveal the suitability of a potential surgical target prior to in vivo use in patients. In this study, the c-Met receptor was identified as a possible candidate for fluorescence-guided surgery in oral cavity cancer. Freshly excised tumor specimens obtained from ten patients with squamous cell carcinoma of the tongue were incubated with EMI-137 and imaged with a clinical-grade Cy5 prototype fluorescence camera. In total, 9/10 tumors were fluorescently illuminated, while non-visualization could be linked to non-superficial tumor localization. Immunohistochemistry revealed c-Met expression in all ten specimens. Tumor assessment was improved via video representation of the tumor-to-background ratio.Intraoperative tumor identification (extension/margins/metastases) via receptor-specific targeting is one of the ultimate promises of fluorescence-guided surgery. The translation of fluorescent tracers that enable tumor visualization forms a critical component in the realization of this approach. Ex vivo assessment of surgical specimens after topical tracer application could help provide an intermediate step between preclinical evaluation and first-in-human trials. Here, the suitability of the c-Met receptor as a potential surgical target in oral cavity cancer was explored via topical ex vivo application of the fluorescent tracer EMI-137. Freshly excised tumor specimens obtained from ten patients with squamous cell carcinoma of the tongue were incubated with EMI-137 and imaged with a clinical-grade Cy5 prototype fluorescence camera. In-house developed image processing software allowed video-rate assessment of the tumor-to-background ratio (TBR). Fluorescence imaging results were related to standard pathological evaluation and c-MET immunohistochemistry. After incubation with EMI-137, 9/10 tumors were fluorescently illuminated. Immunohistochemistry revealed c-Met expression in all ten specimens. Non-visualization could be linked to a more deeply situated lesion. Tumor assessment was improved via video representation of the TBR (median TBR: 2.5 (range 1.8-3.1)). Ex vivo evaluation of tumor specimens suggests that c-Met is a possible candidate for fluorescence-guided surgery in oral cavity cancer.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

A phase I study of a new polyamine biosynthesis inhibitor, SAM486A, in cancer patients with solid tumours

Because tumour cell proliferation is highly dependent upon up-regulation of de-novo polyamine synthesis, inhibition of the polyamine synthesis pathway represents a potential target for anticancer therapy. SAM486A (CGP 48664) is a new inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (SAMDC), more potent and specific than the first-generation SAMDC inhibitor methylglyoxal (bis) guanylhydrazone (MGBG). Preclinical testing confirmed promising antiproliferative activity. In this phase I study, SAM486A was given 4-weekly as a 120 h infusion. 39 adult cancer patients were enrolled with advanced/refractory disease not amenable to established treatments, PS ≤ 2, adequate marrow, liver, renal and cardiac function. Doses were escalated in 100% increments without toxicity in 24 pts from 3 mg m–2cycle–1up to 400 mg m–2cycle–1. At 550 and 700 mg m–2cycle–1reversible dose-limiting neutropenia occurred. Other toxicities included mild fatigue, nausea and vomiting. No objective remission was seen. Pharmakokinetic analysis showed a terminal half-life of approximately 2 days. AUC and Cmax were related to dose; neutropenia correlated with AUC. The recommended dose for further phase II studies on this schedule is 400 mg m–2cycle–1. © 2000 Cancer Research Campaig

A DROP-IN beta probe for robot-assisted 68Ga-PSMA radioguided surgery: first ex vivo technology evaluation using prostate cancer specimens

Background: Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. In parallel, a novel approach to achieve sensitive radioguidance using beta-emitting PET isotopes has been proposed. Integration of these two concepts would allow to exploit the use of PET tracers during robot-assisted tumor-receptor-targeted. In this study, we have engineered and validated the performance of a novel DROP-IN beta particle (DROP-INβ) detector. Methods: Seven prostate cancer patients with PSMA-PET positive tumors received an additional intraoperative injection of ~ 70 MBq 68Ga-PSMA-11, followed by robot-assisted prostatectomy and extended pelvic lymph node dissection. The surgical specimens from these procedures were used to validate the performance of our DROP-INβ probe prototype, which merged a scintillating detector with a housing optimized for a 12-mm trocar and prograsp instruments. Results: After optimization of the detector and probe housing via Monte Carlo simulations, the resulting DROP-INβ probe prototype was tested in a robotic setting. In the ex vivo setting, the probe—positioned by the robot—was able to identify 68Ga-PSMA-11 containing hot-spots in the surgical specimens: signal-to-background (S/B) was > 5 when pathology confirmed that the tumor was located < 1 mm below the specimen surface. 68Ga-PSMA-11 containing (and PET positive) lymph nodes, as found in two patients, were also confirmed with the DROP-INβ probe (S/B > 3). The rotational freedom of the DROP-IN design and the ability to manipulate the probe with the prograsp tool allowed the surgeon to perform autonomous beta-tracing. Conclusions: This study demonstrates the feasibility of beta-radioguided surgery in a robotic context by means of a DROP-INβ detector. When translated to an in vivo setting in the future, this technique could provide a valuable tool in detecting tumor remnants on the prostate surface and in confirmation of PSMA-PET positive lymph nodes. © 2020, The Author(s)

Patient-derived oral mucosa organoids as an in vitro model for methotrexate induced toxicity in pediatric acute lymphoblastic leukemia

We have recently established a protocol to grow wildtype human oral mucosa organoids. These three-dimensional structures can be maintained in culture long-term, do not require immortalization, and recapitulate the multilayered composition of the epithelial lining of the oral mucosa. Here, we validate the use of this model to study the effect of Leucovorin (LV) on Methotrexate (MTX)-induced toxicity. MTX is a chemotherapeutic agent used in the treatment of pediatric acute lymphoblastic leukemia. Although effective, the use of MTX often results in s

Feasibility and applicability of the paper and electronic COPD assessment test (CAT) and the clinical COPD questionnaire (CCQ) in primary care:A clinimetric study

Three questionnaires are recommended in the management of chronic obstructive pulmonary disease by the global initiative for obstructive lung disease, of which two are the more comprehensive assessments: the chronic obstructive pulmonary disease assessment test and the clinical chronic obstructive pulmonary disease questionnaire. Both are carefully designed high-quality questionnaires, but information on the feasibility for routine use is scarce. The aim of this study was to compare the time to complete the chronic obstructive pulmonary disease assessment test and the clinical chronic obstructive pulmonary disease questionnaire and the acceptability of the questionnaires. Furthermore, the agreement between electronic and paper versions of the questionnaires was explored. The time to complete the electronic versions of the questionnaires was 99.6 [IQR 74; 157] vs. 97.5 [IQR 68; 136] seconds for clinical clinical chronic obstructive pulmonary disease questionnaire and chronic obstructive pulmonary disease assessment test, respectively. The difference in time to complete the questionnaire was not significant. The two questionnaires did not differ in "easiness to complete" or "importance of issues raised in questionnaires". Electronic vs. paper versions revealed high agreement (ICC CCQ = 0.815 [0.712; 0.883] and ICC CAT = 0.751 [0.608; 0.847]) between the administration methods. Based on this study it can be concluded that both questionnaires are equally suitable for use in routine clinical practice, because they are both quick to complete and have a good acceptability by the patient. Agreement between electronic and paper versions of the questionnaires was high, so use of electronic versions is justified

Teaching word recognition to children with severe learning difficulties: an exploratory comparison of teaching methods

Background: Some children with severe learning difficulties fail to begin word recognition. For these children there is a need for an effective and appropriate pedagogy. However, conflicting advice can be found regarding this derived from teaching approaches that are not based on a shared understanding of how reading develops or the skills that the non-reader needs to master. Purpose: In this research, three techniques for teaching word recognition in this context are described and compared: (1) the handle technique, (2) morphing method and (3) word alone. It also discusses whether it is appropriate for such small-scale research to influence pedagogy. Programme description: The handle technique uses an abstract mnemonic cue used to teach word recognition, and previous research indicates it is more successful than the presentation of words alone. The morphing method transforms a word into a photographic picture and a previous study suggested that it might also be more effective that presenting words alone. Sample: Six children between 11 and 13 years of age were selected. The criterion for selection was being unable to recognise any words from the British Ability Scales Reading Test. All the children attended a school for children with severe learning difficulties. Design and methods: A three-condition related design was used. The order in which the conditions were presented was counterbalanced and each child was taught 12 words, four words in each experimental condition. The children encountered each of the three methods and overall each word was taught via each method. Within conditions (teaching methods), the presentation of words was randomised. The number of words that the children could read (without cues) before each session was recorded, following the presentation of the uncued words in a random order. The difference in the number of words recognised between the three conditions was considered using a non-parametric statistical analysis. Results: The results suggest that the handle approach might be a more effective method of teaching word recognition. Conclusion: Research in this area is necessarily small in scale. However, it is ongoing and cumulative, and can give insights into potentially beneficial changes in classroom practice

The evaluation of red blood cell folate and methotrexate levels during protocol M in childhood acute lymphoblastic leukemia

Background: After High-Dose Methotrexate (HD-MTX), folinic acid rescue therapy (Leucovorin) is administered to reduce side effects in pediatric acute lymphoblastic leukemia (ALL) patients. Leucovorin and MTX are structural analogues, possibly competing for cellular transport and intracellular metabolism. We hypothesize that Leucovorin accumulates during consecutive courses, which might result in a lower MTX uptake. Methods: We prospectively measured red blood cell (RBC) folate and MTX levels during four HD-MTX and Leucovorin courses in 43 patients treated according the DCOG ALL-11 protocol with 2-weekly HD-MTX (5 g/m2 /dose) and Leucovorin (15 mg/m2 /dose) using LC-MS/MS. We estimated a linear mixed model to assess the relationship between these variables over time. Results: Both RBC MTX-PG and folate levels increased significantly during protocol M. MTX-PG2–5 levels increased most substantially after the first two HD-MTX courses (until median 113.0 nmol/L, IQR 76.8–165.2) after which levels plateaued during the 3d and 4th course (until median 141.3 nmol/L, IQR 100.2–190.2). In parallel, folate levels increased most substantially after the first two HD-MTX courses (until median 401.6 nmol/L, IQR 163.3–594.2) after which levels plateaued during the 3d and 4th course (until median 411.5 nmol/L, IQR 240.3–665.6). The ratio folate/MTX-PG decreased significantly over time, which was mostly due to the relatively higher increase (delta) of MTX-PG. Conclusion: These results suggest that the increase in RBC folate levels does not seem to have a large effect on RBC MTX levels. Future studies, assessing competition of Leucovorin and MTX on other cellular mechanisms which might negatively affect treatment efficacy, are necessary