Cytotoxic lymphocytes employ Granzyme B as a potent initiator of apoptosis to cleave and activate effector caspases. Unexpectedly, cells transfected with Bcl-2 were resistant to granzyme B-induced killing, suggesting that a mitochondrial pathway was critical. Utilizing cells expressing a dominant-negative caspase 9, the current study demonstrated that caspase activation via the apoptosome was not required. Indeed, cleavage of caspase 3 to p20 still occurred in Bcl-2-transfectants but processing to p17 was blocked. This blockade was recapitulated by the Inhibitor-of-Apoptosis-Protein XIAP and relieved by Smac/DIABLO. Thus granzyme B mediates direct cleavage of caspase 3 and also activates mitochondrial disruption, resulting in the release of proapoptotic proteins that suppress caspase inhibition. Engagement of both pathways is critical for granzyme-induced killing.
Background Dysphagia is one consequence of head and neck cancer that has a significant impact on quality of life for head and neck cancer survivors. While survival rates continue to improve, focus has shifted to maximizing long-term function, with prevention or prehabilitation programs becoming more common. Prehabilitation programs typically include an exercise regime that specifies the exercise type, the number of repetitions to complete per set, the number of sets of each exercise to complete per day, as well as the length of the treatment block. Ideally, exercise programs are designed with principles of neuromuscular plasticity in mind. Methods Twenty-nine original research articles published between 2006 and 2020 were included in this state-of-the-art review and examined for program timing and details. Results Two definitions for prehabilitation were noted: one third of the studies defined prehabilitation as preventative exercises prior to the start of acute cancer treatment; the remaining two thirds defined prehabilitation as treatment concurrent prehabilitation. Exercises prescribed ranged from general stretching and range of motion exercises, to trismus and swallowing specific exercises. The most common swallowing specific exercise was the Mendelsohn’s maneuver, followed by the effortful swallow, Shaker, and Masako maneuver. The most common dose was 10 repetitions of an exercise, three times per day for the duration of radiation therapy. The most common measures were questionnaires, followed by g-tube dependence, mouth opening, and MBS reports. Conclusion This review of the literature has shed light on the variability of prehabilitation timing, exercise type, dose, duration of treatment, and outcomes associated with prehabilitation, making the selection of an optimal prehabilitation program difficult at this time.
Purpose A large knowledge gap related to dysphagia treatment adherence was identified by a recent systematic review: Few existing studies report on adherence, and current adherence tracking relies heavily on patient self-report. This study aimed to report weekly adherence and dysphagia-specific quality of life following home-based swallowing therapy in head and neck cancer (HNC). Method This was a quasi-experimental pretest–posttest design. Patients who were at least 3 months post–HNC treatment were enrolled in swallowing therapy using a mobile health (mHealth) swallowing system equipped with surface electromyography (sEMG) biofeedback. Participants completed a home dysphagia exercise program across 6 weeks, with a target of 72 swallows per day split between three different exercise types. Adherence was calculated as percent trials completed of trials prescribed. The M. D. Anderson Dysphagia Inventory (MDADI) was administered before and after therapy. Results Twenty participants (75% male), with an average age of 61.9 years ( SD = 8.5), completed the study. The majority had surgery ± adjuvant (chemo)radiation therapy for oral (10%), oropharyngeal (80%), or other (10%) cancers. Using an intention-to-treat analysis, adherence to the exercise regimen remained high from 84% in Week 1 to 72% in Week 6. Radiation therapy, time since cancer treatment, medical difficulties, and technical difficulties were all found to be predictive of poorer adherence at Week 6. A statistically significant improvement was found for composite, emotional, and physical MDADI subscales. Conclusions When using an mHealth system with sEMG biofeedback, adherence rates to home-based swallowing exercise remained at or above 72% over a 6-week treatment period. Dysphagia-specific quality of life improved following this 6-week treatment program.
BackgroundAdherence to swallowing rehabilitation exercises is important to develop and maintain functional improvement, yet more than half of head and neck cancer (HNC) patients report having difficulty adhering to prescribed regimens. Health apps with game elements have been used in other health domains to motivate and engage patients. Understanding the factors that impact adherence may allow for more effective gamified solutions.ObjectiveThe aim of our study was to (1) identify self-reported factors that influence adherence to conventional home therapy without a mobile device in HNC patients and (2) identify appealing biofeedback designs that could be used in a health app.MethodsA total of 10 (4 females) HNC patients (mean=60.1 years) with experience completing home-based rehabilitation programs were recruited. Thematic analysis of semi-structured interviews was used to answer the first objective. Convergent interviews were used to obtain reactions to biofeedback designs.ResultsFacilitators and barriers of adherence to home therapy were described through 6 themes: patient perceptions on outcomes and progress, clinical appointments, cancer treatment, rehabilitation program, personal factors, and connection. App visuals that provide feedback on performance during swallowing exercises should offer an immediate representation of effort relative to a goal. Simple, intuitive graphics were preferred over complex, abstract ones. Continued engagement with the app could be facilitated by tracking progress and by using visuals that build structures with each use.ConclusionsThis is a detailed documentation of the initial steps in designing a health app for a specific patient group. Results revealed the importance of patient engagement in early stages of app development.
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