Rehabilitation Interventions in Head and Neck Cancer: A Scoping Review.

OBJECTIVE: The aim of the study is to identify and appraise current evidence for rehabilitation interventions in head and neck cancer. DESIGN: A previously published scoping review spanning 1990 through April 2017 was updated through January 11, 2023 and narrowed to include only interventional studies (Arch Phys Med Rehabil. 2019;100(12):2381-2388). Included studies had a majority head and neck cancer population and rehabilitation-specific interventions. Pairs of authors extracted data and evaluated study quality using the PEDro tool. Results were organized by intervention type. RESULTS: Of 1338 unique citations, 83 studies with 87 citations met inclusion criteria. The median study sample size was 49 (range = 9-399). The most common interventions focused on swallow (16 studies), jaw (11), or both (6), followed by whole-body exercise (14) and voice (10). Most interventions took place in the outpatient setting (77) and were restorative in intent (65 articles). The overall study quality was fair (median PEDro score 5, range 0-8); none were of excellent quality (PEDro >9). CONCLUSIONS: Most head and neck cancer rehabilitation interventions have focused on restorative swallow and jaw exercises and whole-body exercise to address dysphagia, trismus, and deconditioning. More high-quality evidence for head and neck cancer rehabilitation interventions that address a wider range of impairments and activity and social participation limitations during various cancer care phases is urgently needed to reduce head and neck cancer-associated morbidity.

The Role of Outpatient Physical Medicine and Rehabilitation in a Multidisciplinary Prehabilitation Program for Older Adults before Allogeneic Hematopoietic Stem Cell Transplant.

INTRODUCTION: Physical rehabilitation is increasingly incorporated throughout the allogeneic hematopoietic stem cell transplant (allo-HSCT) journey for older adults. OBJECTIVE: This study aimed to describe physical medicine and rehabilitation (PM&R)-related diagnoses, exercise barriers, and management recommendations for older adults before allo-HSCT. DESIGN: Fifty PM&R consults as part of the Enhanced Recovery-Stem Cell Transplant (ER-SCT) multidisciplinary prehabilitation program at a comprehensive cancer center were retrospectively reviewed. RESULTS: Many PM&R-related diagnoses (173), exercise barriers (55), and management recommendations (112) were found. Common diagnoses were musculoskeletal dysfunction (more commonly back, shoulder, then knee) (n = 39, 23%) and fatigue (n = 36, 21%). Common exercise barriers were also musculoskeletal dysfunction (more commonly back, knee, then shoulder) (total n = 20, 36%) and fatigue (n = 20, 36%). Most patients (n = 32, 64%) had 1 or more exercise barriers. Common PM&R management recommendations were personalized exercise counseling (n = 37, 33%), personalized nutrition management (n = 19, 17%), body composition recommendations (n = 17, 15%), medications (n = 15, 13%), and orthotics and durable medical equipment (n = 8, 7%). CONCLUSION: Routine PM&R referral of older allo-HSCT patients for prehabilitation resulted in the identification of many rehabilitative needs and substantial additional management recommendations. Increased early, collaborative prehabilitation efforts between PM&R and allo-HSCT teams to optimize care for these patients is recommended.

Rehabilitation Interventions for Head and Neck Cancer-Associated Lymphedema: A Systematic Review.

Importance: Head and neck cancer-associated lymphedema (HNCaL) affects up to 90% of survivors of head and neck cancer and is a substantial contributor to disability following head and neck cancer treatment. Despite the prevalence and morbidity associated with HNCaL, rehabilitation interventions are not well studied. Objective: To identify and appraise the current evidence for rehabilitation interventions in HNCaL. Evidence Review: Five electronic databases were searched systematically from inception to January 3, 2023, for studies on HNCaL rehabilitation interventions. Study screening, data extraction, quality rating, and risk of bias assessment were performed by 2 independent reviewers. Findings: Of 1642 citations identified, 23 studies (1.4%; n = 2147 patients) were eligible for inclusion. Six studies (26.1%) were randomized clinical trials (RCTs) and 17 (73.9%) were observational studies. Five of the 6 RCTs were published during 2020 to 2022. Most studies had fewer than 50 participants (5 of 6 RCTs; 13 of 17 observational studies). Studies were categorized by intervention type, including standard lymphedema therapy (11 studies [47.8%]) and adjunct therapy (12 studies [52.2%]). Lymphedema therapy interventions included standard complete decongestive therapy (CDT) (2 RCTs, 5 observational studies), modified CDT (3 observational studies), therapy setting (1 RCT, 2 observational studies), adherence (2 observational studies), early manual lymphatic drainage (1 RCT), and inclusion of focused exercise (1 RCT). Adjunct therapy interventions included advanced pneumatic compression devices (APCDs) (1 RCT, 5 observational studies), kinesio taping (1 RCT), photobiomodulation (1 observational study), acupuncture/moxibustion (1 observational study), and sodium selenite (1 RCT, 2 observational studies). Serious adverse events were either not found (9 [39.1%]) or not reported (14 [60.9%]). Low-quality evidence suggested the benefit of standard lymphedema therapy, particularly in the outpatient setting and with at least partial adherence. High-quality evidence was found for adjunct therapy with kinesio taping. Low-quality evidence also suggested that APCDs may be beneficial. Conclusions and Relevance: The results of this systematic review suggest that rehabilitation interventions for HNCaL, including standard lymphedema therapy with kinesio taping and APCDs, appear to be safe and beneficial. However, more prospective, controlled, and adequately powered studies are needed to clarify the ideal type, timing, duration, and intensity of lymphedema therapy components before treatment guidelines can be established.

Integrative Oncology and the Clinical Care Network: Challenges and Opportunities.

Integrative oncology is a new and growing field of cancer care. Integrative oncology is a patient-centered, evidence-based field of comprehensive cancer care that utilizes integrative therapies such as mind-body practices, acupuncture, massage, music therapy, nutrition, and exercise in collaboration with conventional cancer treatments. Patient interest and utilization has been growing over the past two decades. Clinical research has shown the benefits of these approaches to improving symptom management and quality of life, and is now being incorporated into national guidelines from the National Comprehensive Cancer Network (NCCN) and American Society for Clinical Oncology (ASCO). The availability of these services at cancer centers is growing, although the structure and implementation of integrative oncology remains highly variable. This article discusses the benefits of integrative oncology and provides an overview of the current state of integrative oncology programs nationwide. Current challenges and opportunities for cancer centers to provide integrative services is reviewed in the areas of programmatic structure, clinical service, education, and research.

Diet Improvements in Community-Dwelling Older Adults in the Mobility and Vitality Lifestyle Program.

This analysis examined whether a community-based intervention produced measurable improvements in dietary habits. MOVE UP combined translational, evidence-based weight management and healthy aging interventions using a non-randomized design. This 13-month intervention included 32 group sessions, explicit calorie and physical activity goals, self-monitoring, and nutrition education. Participants were (N = 297) older adults (mean = 68.0 years) with overweight and obesity. Diet was measured using Rate Your Plate (RYP)-Heart. Changes in scores from baseline to 5, 9, and 13 months were assessed using mixed models. MOVE UP successfully shifted eating patterns from baseline (mean = 50.9) to 5 months (mean = 55.1) (p < .0001) adjusted for age, sex, and race. Improvements persisted through 9 (mean = 54.7) and 13 months (mean = 55.0) (p < .0001). Although participants were not prescribed a specific diet, RYP-Heart indicated positive dietary shifts. Community-implemented behavioral weight loss interventions may assess the modifiability of dietary habits with a simple, easy-to-administer tool.

State of Rehabilitation Research in the Head and Neck Cancer Population: Functional Impact vs. Impairment-Focused Outcomes.

PURPOSE OF REVIEW: Management of head and neck cancer (HNC) typically involves a morbid combination of surgery, radiation, and systemic therapy. As the number of HNC survivors grows, there is growing interest in rehabilitation strategies to manage HNC-related comorbidity. In this review, we summarize the current state of HNC rehabilitation research. RECENT FINDINGS: We have organized our review using the World Health Organization's International Classification of Function (ICF) model of impairment, activity, and participation. Specifically, we describe the current research on rehabilitation strategies to prevent and treat impairments including dysphagia, xerostomia, dysgeusia, dysosmia, odynophagia, trismus, first bite syndrome, dysarthria, dysphonia, lymphedema, shoulder syndrome, cervicalgia, cervical dystonia and dropped head syndrome, deconditioning, and fatigue. We also discuss the broader impact of HNC-related impairment by exploring the state of rehabilitation literature on activity, participation, psychosocial distress, and suicidality in HNC survivors. We demonstrate that research in HNC rehabilitation continues to focus primarily on impairment-driven interventions. There remains a dearth of HNC rehabilitation studies directly examining the impact of rehabilitation interventions on outcomes related to activity and participation. More high-quality interventional studies and reviews are needed to guide prevention and treatment of functional loss in HNC survivors.

Nutritional support in allogeneic hematopoietic stem cell transplantation Asian perspective.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an integral part of the treatment strategy for patients with malignant or non-malignant hematological diseases. Clinical outcomes of patients undergoing allo-HSCT have significantly improved in recent decades. However, transplant-related morbidity and mortality remain major issues for allo-HSCT recipients. With regard to nutrition, patients undergoing allo-HSCT are at high risk for malnutrition. It is expected that clinical practice concerning nutritional support in allo-HSCT has been improving in recent decades; however, no data directly support this expectation. One major issue in managing nutritional support during allo-HSCT is the lack of large-scale randomized prospective studies, which leads to a lack of well-established strategies. Accordingly, we need to gather data from studies in non-HSCT and allo-HSCT settings. In some Asia-Pacific countries, a physician's lack of knowledge of nutritional support may impede the application of nutritional support practices recommended by existing guidelines. Another barrier may be the lack of access to an adequately qualified or trained registered dietitian (RD) at allo-HSCT units. Adequate training in the nutritional management of allo-HSCT patients should be provided to all RDs working with HSCT. Herein, we summarize the information on nutritional support in allo-HSCT, focusing on an Asian perspective.

Notch signaling induces a transcriptionally permissive state at the Complement C3d Receptor 2 (CR2) promoter in a pre-B cell model.

During mammalian lymphoid development, Notch signaling is necessary at multiple stages of T lymphopoiesis, including lineage commitment, and later stages of T cell effector differentiation. In contrast, outside of a defined role in the development of splenic marginal zone B cells, there is conflicting evidence regarding whether Notch signaling plays functional roles in other B cell sub-populations. Complement receptor 2 (CR2) modulates BCR-signaling and is tightly regulated throughout differentiation. During B lymphopoiesis, CR2 is detected on immature and mature B cells with high surface expression on marginal zone B cells. Here, we have explored the possibility that Notch regulates human CR2 transcriptional activity using in vitro models including a co-culture system, co-transfection gene reporters and chromatin accessibility assays. We provide evidence that Notch signaling regulates CR2 promoter activity in a mature B cell line, as well as the induction of endogenous CR2 mRNA in a non-expressing pre-B cell line. The dynamics of endogenous gene activation suggests additional unidentified factors are required to mediate surface CR2 expression on immature and mature B lineage cells.

The SMARTER Trial: Design of a trial testing tailored mHealth feedback to impact self-monitoring of diet, physical activity, and weight.

BACKGROUND: Self-monitoring food intake and physical activity (PA) is positively related to weight loss and the addition of feedback (FB) messages has been shown to reinforce behavior change. Moreover, the more immediate the delivery of reinforcing FB messages, the more likely they will promote the desired behaviors. PURPOSE: Describe design and rationale of SMARTER, a National Institute of Heart, Lung, and Blood (NHLBI)-sponsored randomized, controlled trial, which compares the differential efficacy of two weight loss treatments among 530 adults, ages 18 and older. METHODS: Single-site, 2-group design trial with subjects randomized 1:1 to either: 1) self-monitoring (SM), where participants self-monitor diet, PA, and weight using a commercial smartphone application (app); or 2) SM + FB, where participants self-monitor and receive real-time, tailored feedback (FB) as pop-up messages up to 3 times/day for 12 months. Daily FB messages address diet and PA behaviors and a weekly FB message addresses self-weighing. We hypothesize that subjects assigned to SM + FB will show greater weight loss at 6 and 12 months and greater sustained engagement in the program than the SM group, measured by adherence to the study's lifestyle and SM protocol. We will explore temporal relationships of the frequency, timing, and type of FB delivered and subsequent lifestyle behaviors through examination of serially collected real-time SM (diet, PA, weight) data over 12 months. CONCLUSIONS: If efficacious, this fully scalable intervention could be efficiently translated and disseminated to reach large numbers of individuals through commercial apps at lower cost than existing in-person weight loss programs.

Iron(ii) coordination polymer catalysed hydroboration of ketones.

Catalytic hydroboration of ketones with pinacolborane was achieved with a 2D iron(ii) coordination polymer (CP) of a divergent 4,2';6',4''-terpyridine (tpy) derivative under mild conditions with high efficiency. This solid iron catalyst system is more active towards the hydroboration of ketones than that of aldehydes, displaying a different trend of reactivity from known homogeneous iron hydroboration catalysts.

Interaction between ethnicity and smoker type with dependence: A comparison of daily and intermittent African American and Caucasian smokers.

Ethnic differences in smoking patterns and dependence have been observed between Caucasian and African American smokers: African Americans who smoke are more likely to be intermittent smokers (ITS), and daily smokers (DS) consume fewer cigarettes yet report more dependence. Participants' (N = 482, 67% Caucasian, 54% ITS) dependence was assessed by primary and secondary dependence subscales of the Wisconsin Inventory of Smoking Dependence Motives, the Nicotine Dependence Syndrome Scale, the Hooked on Nicotine Checklist, the Fagerström Test of Nicotine Dependence, and time to first cigarette after waking. We tested associations with dependence for ethnicity, smoker type, and an Ethnicity × Smoker Type interaction, using multivariable linear regression, with adjustment for age, sex, and education. Additional models adjusted for cigarettes per day and history of daily smoking. There was a significant interaction between ethnicity and smoker type for 5 of 6 measures of dependence (each scale assessed separately), such that African American ITS reported more dependence than Caucasian ITS, whereas dependence did not differ by ethnicity among DS. African American ITS smoked more cigarettes per day and were more likely to have a history of daily smoking than Caucasian ITS; after further adjustments for these differences, there were no significant interactions of ethnicity and smoker type for any measure. Among DS, dependence did not differ by race. African American ITS were more dependent than Caucasian ITS; this difference was explained by higher cigarette consumption and a higher proportion converted from DS to ITS among African Americans versus Caucasians. (PsycINFO Database Record

Inadvertently boarding a pirate ship: disease progression in a paediatric patient with relapsed metastatic Ewing sarcoma receiving treatment at a centre for alternative therapy in Mexico.

Complementary and alternative medicine (CAM) therapies are commonly incorporated into the care of patients with paediatric cancer. Many modalities are safe and effective during cancer treatment and have proved beneficial for symptom relief and quality of life. However, situations where alternative therapy is provided without allopathic medical care supportive care resources can pose a safety risk to patients. This report describes the case of a 16-year-old Chinese girl with metastatic Ewing sarcoma who sought treatment with alternative treatment in Mexico. When her disease progressed with an ensuing significant loss of function, the centre personnel were unable to respond to her acute deterioration or provide necessary medical care. This resulted in her being stranded in a foreign country paralysed, isolated, and with large unanticipated financial expenditures.

Runx2/DICER/miRNA Pathway in Regulating Osteogenesis.

DICER is the central enzyme that cleaves precursor microRNAs (miRNAs) into 21-25 nucleotide duplex in cell lineage differentiation, identity, and survival. In the current study, we characterized the specific bone metabolism genes and corresponding miRNAs and found that DICER and Runt-related transcription factor 2 (Runx2) expressions increased simultaneously during osteogenic differentiation. Luciferase assay showed that Runx2 significantly increased the expression levels of DICER luciferase promoter reporter. Our analysis also revealed weaker DICER expression in embryos of Runx2 knock out mice (Runx2 -/-) compared with that of Runx2 +/- and Runx2 +/+ mice. We further established the calvarial bone critical-size defect (CSD) mouse model. The bone marrow stromal cells (BMSCs) transfected with siRNA targeting DICER were combined with silk scaffolds and transplanted into calvarial bone CSDs. Five weeks post-surgery, micro-CT analysis revealed impaired bone formation, and repairing in calvarial defects with the siRNA targeting DICER group. In conclusion, our results suggest that DICER is specifically regulated by osteogenic master gene Runx2 that binds to the DICER promoter. Consequently, DICER cleaves precursors of miR-335-5p and miR-17-92 cluster to form mature miRNAs, which target and decrease the Dickkopf-related protein 1 (DKK1), and proapoptotic factor BIM levels, respectively, leading to an enhanced Wnt/ß-catenin signaling pathway. These intriguing results reveal a central mechanism underlying lineage-specific regulation by a Runx2/DICER/miRNAs cascade during osteogenic differentiation and bone development. Our study, also suggests a potential application of modulating DICER expression for bone tissue repair and regeneration. J. Cell. Physiol. 232: 182-191, 2017. © 2016 Wiley Periodicals, Inc.

Radiotherapy patterns of care in gastric adenocarcinoma: a single institution experience.

BACKGROUND: Gastric adenocarcinoma (GAC) is one of the most commonly diagnosed cancers worldwide. Two standard approaches for treatment of resectable GAC include adjuvant 5-fluorouracil-based chemoradiotherapy [per Intergroup 0116 (INT-0116) trial and perioperative epirubicin, cisplatin, fluorouracil (ECF) chemotherapy per Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial]. Controversy remains regarding the most appropriate treatment strategy to decrease recurrence rates and improve survival following surgery. The purpose of this study was to analyze how patterns of care for patients with GAC treated at Emory University Hospital changed following publication of the MAGIC trial in 2006. METHODS: We analyzed a prospectively maintained database of 150 patients who underwent resection for GAC between December 2000 and June 2013. Patients were divided into two cohorts, Early [2000-2006] and late [2007-2013]. The primary objective was to compare the number of patients assigned to adjuvant chemoradiotherapy (aCRT) vs. perioperative chemotherapy (PC) throughout the study period and secondarily assess for recurrence patterns and survival outcomes for patients assigned to those two strategies. RESULTS: Between 2000 and 2013, 124 patients received adjuvant therapy for GAC. Fifty-four patients were treated with PC and 70 patients with aCRT. The early cohort included 56 patients, and the late cohort included 94 patients. There was no statistical difference in the number of patients receiving aCRT between the Early and Late cohorts [n=23 (50%) vs. 35 (38%) respectively, P=0.21]. PC increased from 2 patients (3.6%) in the Early cohort to 32 patients (34%) in the Late cohort (P<0.001). Four-year overall survival (OS) was 32.6% for the Early cohort and 68.8% for the Late cohort (P=0.010). Overall recurrence rate was 25.3% with no significant difference in rates of recurrence seen between the Early and Late cohorts. CONCLUSIONS: PC has become more prevalent in patients treated at Emory following publication of the MAGIC trial in 2006. OS, but not recurrence rates, has also improved since publication. Although improved survival is suggestive of improved care, the question of optimal treatment regimen remains open. Further prospective comparisons of PC and aCRT are needed to identify patient and disease parameters that may guide therapy selection.

Adiponectin regulates bone marrow mesenchymal stem cell niche through a unique signal transduction pathway: an approach for treating bone disease in diabetes.

Adiponectin (APN) is an adipocyte-secreted adipokine that exerts well-characterized antidiabetic properties. Patients with type 2 diabetes (T2D) are characterized by reduced APN levels in circulation and impaired stem cell and progenitor cell mobilization from the bone marrow for tissue repair and remodeling. In this study, we found that APN regulates the mobilization and recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) to participate in tissue repair and regeneration. APN facilitated BMSCs migrating from the bone marrow into the circulation to regenerate bone by regulating stromal cell-derived factor (SDF)-1 in a mouse bone defect model. More importantly, we found that systemic APN infusion ameliorated diabetic mobilopathy of BMSCs, lowered glucose concentration, and promoted bone regeneration in diet-induced obesity mice. In vitro studies allowed us to identify Smad1/5/8 as a novel signaling mediator of APN receptor (AdipoR)-1 in BMSCs and osteoblasts. APN stimulation of MC3T3-E1 osteoblastic cells led to Smad1/5/8 phosphorylation and nuclear localization and increased SDF-1 mRNA expression. Although APN-mediated phosphorylation of Smad1/5/8 occurred independently from adaptor protein, phosphotyrosine interaction, pleckstrin homology domain, and leucine zipper containing 1, it correlated with the disassembly of protein kinase casein kinase 2 and AdipoR1 in immunoprecipitation experiments. Taken together, this study identified APN as a regulator of BMSCs migration in response to bone injury. Therefore, our findings suggest APN signaling could be a potential therapeutic target to improve bone regeneration and homeostasis, especially in obese and T2D patients.

Central adiponectin administration reveals new regulatory mechanisms of bone metabolism in mice.

Adiponectin (APN), the most abundant adipocyte-secreted adipokine, regulates energy homeostasis and exerts well-characterized insulin-sensitizing properties. The peripheral or central effects of APN regulating bone metabolism are beginning to be explored but are still not clearly understood. In the present study, we found that APN-knockout (APN-KO) mice fed a normal diet exhibited decreased trabecular structure and mineralization and increased bone marrow adiposity compared with wild-type (WT) mice. APN intracerebroventricular infusions decreased uncoupling protein 1 (UCP1) expression in brown adipose tissue, epinephrine and norepinephrine serum levels, and osteoclast numbers, whereas osteoblast osteogenic marker expression and trabecular bone mass increased in APN-KO and WT mice. In addition, centrally administered APN increased hypothalamic tryptophan hydroxylase 2 (TPH2), cocaine- and amphetamine-regulated transcript (CART), and 5-hydroxytryptamine (serotonin) receptor 2C (Htr2C) expressions but decreased hypothalamic cannabinoid receptor-1 expression. Treatment of immortalized mouse neurons with APN demonstrated that APN-mediated effects on TPH2, CART, and Htr2C expression levels were abolished by downregulating adaptor protein containing pleckstrin homology domain, phosphotyrosine domain, and leucine zipper motif (APPL)-1 expression. Pharmacological increase in sympathetic activity stimulated adipogenic differentiation of bone marrow stromal cells (BMSC) and reversed APN-induced expression of the lysine-specific demethylases involved in regulating their commitment to the osteoblastic lineage. In conclusion, we found that APN regulates bone metabolism via central and peripheral mechanisms to decrease sympathetic tone, inhibit osteoclastic differentiation, and promote osteoblastic commitment of BMSC.

SOX4 interacts with plakoglobin in a Wnt3a-dependent manner in prostate cancer cells.

BACKGROUND: SOX4 is a developmental transcription factor that is required for differentiation and proliferation in multiple tissues. SOX4 is overexpressed in many human malignancies, but the precise role of SOX4 in cancer progression is still not well understood. Thus, the identification of additional SOX4 binding partners is essential for elucidating the mechanism of SOX4-mediated effects in cancer progression. RESULTS: Here, we have adapted a one-step affinity purification method that enables rapid purification of SOX4 complexes via intracellular biotinylation of the amino-terminus of SOX4 to perform large-scale proteomics analysis. We have discovered that junction plakoglobin (JUP) interacts with SOX4 in both the cytosol and the nucleus and the interaction between SOX4 and plakoglobin is significantly increased when prostate and breast cancer cells are stimulated with WNT3A. Interactions between SOX4 and plakoglobin were further enhanced by the nuclear export inhibitor leptomycin B (LMB), suggesting that plakoglobin promotes nuclear export of SOX4. The SOX4-plakoglobin complex affected the expression of Wnt pathway target genes and SOX4 downstream targets, such as AXIN2, DICER1, and DHX9. In addition, SOX4 DNA binding activity to the promoters of DICER1, AXIN2, DHX9 and SOX4 itself was reduced by conditions that promote SOX4-plakoglobin complex formation. Conditions that enhanced SOX4-plakoglobin interactions resulted in reduced transcriptional activity of ß-catenin luciferase reporters. CONCLUSIONS: These data suggest that this newly identified interaction between SOX4 and plakoglobin is inhibitory and provides new insights into the role of SOX4 in key pathways in cell proliferation, development, and cancer progression.