This systematic review aimed to assess the updated literature for the prevention of salivary gland hypofunction and xerostomia induced by non-surgical cancer therapies. Electronic databases of MEDLINE/PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials (RCT) that investigated interventions to prevent salivary gland hypofunction and/or xerostomia. Literature search began from the 2010 systematic review publications from the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) up to February 2024. Two independent reviewers extracted information regarding study design, study population, cancer treatment modality, interventions, outcome measures, methods, results, risk of bias (RoB version 2), and conclusions for each article. A total of 51 publications addressing preventive interventions were included. Eight RCTs on tissue-sparing radiation modalities were included showing significant lower prevalence of xerostomia, with unclear effect on salivary gland hypofunction. Three RCTs on preventive acupuncture showed reduced prevalence of xerostomia but not of salivary gland hypofunction. Two RCTs on muscarinic agonist stimulation with bethanechol suggested a preventive effect on saliva flow rate and xerostomia in patients undergoing head and neck radiation or radioactive iodine therapy. Two studies on submandibular gland transfer showed higher salivary flow rates compared to pilocarpine and lower prevalence of xerostomia compared to no active intervention. There is insufficient evidence on the effectiveness of vitamin E, amifostine, photobiomodulation, and miscellaneous preventive interventions. This systematic review continues to support the potential of tissue-sparing tecniques and intensity-modulated radiation therapy (IMRT) to preserve salivary gland function in patients with head and neck cancer, with limited evidence on other preventive strategies, including acupuncture and bethanecol. Preventive focus should be on optimized and new approaches developed to further reduce radiation dose to the parotid, the submandibular, and minor salivary glands. As these glands are major contributors to moistening of the oral cavity, limiting the radiation dose to the salivary glands through various modalities has demonstrated reduction in prevalence and severity of salivary gland hypofunction and xerostomia. There remains no evidence on preventive approaches for checkpoint inhibitors and other biologicals due to the lack of RCTs.

6107 Background: Lymphedema is common in head and neck cancer survivors (HNCS). Published data indicate that an Advanced Pneumatic Compression Device (APCD) is an effective intervention for lymphedema refractory to Therapist Guided Lymphedema Treatment (TGLT). It may also address barriers to TGLT. We therefore conducted a study in which HNCS with previously untreated lymphedema were randomized to APCD or Usual Care. We report short-term, two-month outcomes. Methods: This was a six-month, multi-site (community/academic), stratified, randomized effectiveness trial. Eligible patients were lymphedema therapy naïve HNCS with internal or external lymphedema on exam or imaging and at least 1 moderate (≥ 4/10) lymphedema associated symptom. Participants were randomized (1:1) to APCD or Usual Care. Those randomized to APCD were to use the device for 32 minutes per day. Participants randomized to Usual Care were referred for lymphedema therapy per institutional standards. The primary outcome was improvement in lymphedema associated symptom severity. Additional outcomes included anatomical measures, patient reported biopsychosocial outcomes, barriers to care, and patient satisfaction. Results: 236 participants were enrolled (119 APCD group, 117 Usual Care group). At two-months there was a similar decrease in lymphedema associated symptom burden and internal soft tissue swelling in both groups. We demonstrated a statistically significant external soft tissue swelling benefit favoring the APCD group as measured by the Head and Neck Cancer Related Lymphedema and Fibrosis Grading score (p=0.016). Digital photography identified a reduction in number of grids with swelling (p=<0.001) in the APCD group only. No reduction of internal swelling was noted in either group by imaging measures. 95% of APCD participants and 71% of Usual Care participants received assigned therapy. Time to therapy initiation was 29.8 days (SD 23.5) for Usual Care and 17.86 days (SD 10.53) for APCD. Conclusions: We demonstrated that APCD therapy is an effective treatment modality in lymphedema therapy naïve HNCS. Furthermore, participants experienced significant barriers to TGLT which may be effectively addressed with use of the APCD. A hybrid multi-modal approach to treatment associated lymphedema may further optimize patient outcomes. Clinical trial information: NCT04797390 .

OBJECTIVES:Acute kidney injury (AKI) predicts death after cardiac and vascular surgery. Higher preoperative high-density lipoprotein (HDL) concentrations are associated with less postoperative AKI. In animals, HDL's anti-inflammatory capacity to suppress endothelial cell adhesion molecule expression reduces kidney damage due to ischemia and hemorrhagic shock. The objective of this study is to evaluate the statistical relationship between HDL anti-inflammatory capacity and AKI after major cardiac and vascular surgery.DESIGN:Prospective observational study.SETTING:Quaternary medical center.PATIENTS:One hundred adults with chronic kidney disease on long-term statin therapy undergoing major elective cardiac and vascular surgery.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Apolipoprotein B-depleted serum collected at anesthetic induction was incubated with tumor necrosis factor alpha stimulated human endothelial cells. Reverse transcriptase-polymerase chain reaction was used to measure intercellular adhesion molecule-1 (ICAM-1) messenger RNA. Enzyme-linked immunosorbent assay assays were used to measure apolipoprotein A-I and postoperative soluble ICAM-1 concentrations in patient plasma. HDL concentration did not correlate with HDL ICAM-1 suppression capacity (Spearman R = 0.05; p = 0.64). Twelve patients (12%) were found to have dysfunctional, pro-inflammatory HDL. Patients with pro-inflammatory HDL had a higher rate of postoperative AKI than patients with anti-inflammatory HDL (p = 0.046). After adjustment for AKI risk factors, a higher preoperative HDL capacity to suppress endothelial ICAM-1 was independently associated with lower odds of AKI (odds ratio, 0.88; 95% CI, 0.80-0.98; p = 0.016). The association between HDL anti-inflammatory capacity and postoperative AKI was independent of HDL concentration (p = 0.018). Further, a higher long-term statin dose was associated with higher HDL capacity to suppress endothelial ICAM-1 (p = 0.045).CONCLUSIONS:Patients with chronic kidney disease undergoing cardiac and vascular surgery who have dysfunctional, pro-inflammatory HDL have a higher risk of postoperative AKI compared with patients with anti-inflammatory HDL. Conversely, a higher HDL anti-inflammatory capacity is associated with a lower risk of postoperative AKI, independent of HDL concentration. Higher long-term statin dose is associated with higher HDL anti-inflammatory capacity.

Acute kidney injury (AKI) is a serious complication after vascular surgery. Reduced synthesis of nicotinamide adenine dinucleotide (NAD+) from tryptophan is associated with an increased risk of AKI in critically ill patients, patients hospitalized with COVID-19, and cardiac surgery patients, and is marked by elevated urinary quinolinate and quinolinate to tryptophan ratios. We measured quinolinate concentrations in vascular surgery patients to determine if impaired NAD+ synthesis was associated with AKI in this patient population. Eight preoperative and eight postoperative vascular surgery patients who developed AKI were selected from a parent study to participate in this single-center case-control study. They were matched with controls who did not develop AKI based on age, sex, BMI, eGFR, hypertension, and diabetes. Urinary quinolinate and tryptophan concentrations were measured at anesthetic induction and on postoperative day one. Two-sided Mann–Whitney U tests were used to compare quinolinate and quinolinate to tryptophan ratios. Multivariate linear regression modeling was used to estimate the relationship between quinolinate and serum creatinine. There was no difference in preoperative or postoperative urine quinolinate concentrations or the preoperative quinolinate to tryptophan ratio between patients that did and did not develop AKI (p = 0.07, 0.50, and 0.32, respectively). However, postoperative quinolinate to tryptophan ratios were higher in AKI patients (p = 0.04). Further, after adjustment for AKI risk factors, higher preoperative quinolinate concentrations and higher postoperative quinolinate to tryptophan ratios were associated with greater postoperative creatinine increases (p = 0.04 and 0.04, respectively). These data suggest that impaired NAD+ synthesis may contribute to AKI development in vascular surgery patients.

Purpose Patient-reported outcome measures (PRO) are critical tools to developing an understanding of cancer patients’ experience. This paper presents some of the lesser-understood implications of using patient-reported outcome measures in clinical research. Methods This study uses a combination of literature sources, real-world examples from supportive care studies, and statistical simulations to demonstrate the operating characteristics of patient-reported measures. Results It is demonstrated that care must be taken in the analysis of PROs as the assumptions of the most common mean-based approaches are often violated including linearity, normally distributed errors, interference with asymptotic convergence via boundary values, and more. Further, the implications of subjective discretization are shown to reduce the apparent statistical power of PRO-based studies. Conclusions PRO-based studies must be designed conscientiously as each PRO item will demonstrate a varying degree of subjectivity in a given population. Sample sizes of randomized studies using PROs must be inflated to account for this. Analyses should consider using ordinal statistical models until such time as the assumptions of mean-based models can be verified.

OBJECTIVES:To explore factors influencing research interest and productivity and perceived barriers to conducting research in Oral Medicine (OM). METHODS:Invitations to participate in an online survey were e-mailed to a network of international OM practitioners and related professional organizations. Questions captured respondents' demographic/professional variables and gauged research interest, productivity, and perceived barriers to conducting research specifically in OM. Statistical analysis was conducted via descriptive, logistic regression, and multivariate modeling. RESULTS:Five hundred and ninety-three OM practitioners from 55 countries completed the survey, with 54%, 25%, and 21% practicing in high, upper-middle, and lower-middle-income countries, respectively. Eighty-six percent of respondents were interested in conducting research. Age (less interest with an increase in age), working in academia, and practicing in a lower-middle vs high-income country were significant predictors of research interest. Self-reported research productivity was significantly greater among males, those working in academia, and those who graduated from programs that mandated research presentation/publication. Obtaining research funding was a significant barrier among respondents from lower and upper-middle-income countries, whereas finding time for research was a reported barrier by respondents from high-income countries. CONCLUSION:The results of this survey identified perceived barriers to conducting research in OM and highlighted solutions to address such barriers.

BackgroundThis study leverages a large retrospective cohort of head and neck cancer patients in order to develop machine learning models to predict radiation induced hyposalivation from dose-volume histograms of the parotid glands.MethodsThe pre and post-radiotherapy salivary flow rates of 510 head and neck cancer patients were used to fit three predictive models of salivary hypofunction, (1) the Lyman-Kutcher-Burman (LKB) model, (2) a spline-based model, (3) a neural network. A fourth LKB-type model using literature reported parameter values was included for reference. Predictive performance was evaluated using a cut-off dependent AUC analysis.ResultsThe neural network model dominated the LKB models demonstrating better predictive performance at every cutoff with AUCs ranging from 0.75 to 0.83 depending on the cutoff selected. The spline-based model nearly dominated the LKB models with the fitted LKB model only performing better at the 0.55 cutoff. The AUCs for the spline model ranged from 0.75 to 0.84 depending on the cutoff chosen. The LKB models had the lowest predictive ability with AUCs ranging from 0.70 to 0.80 (fitted) and 0.67 to 0.77 (literature reported).ConclusionOur neural network model showed improved performance over the LKB and alternative machine learning approaches and provided clinically useful predictions of salivary hypofunction without relying on summary measures.

Purpose This review was designed to compile the currently available evidence on the prophylactic use of gabapentin in the head and neck cancer patient population. Methods A systematic search was conducted of PubMed, Web of Science, and Google Scholar to identify articles related to the use of prophylactic gabapentin in patients undergoing head and neck cancer therapy. Candidate studies were screened for inclusion and a subsequent bias assessment was conducted by multiple reviewers. Meta-analysis was conducted in cases in which the studies used compatible outcome measures. Results Ten studies were identified that met the inclusion criteria and were assessed for bias. Among the four small studies that examined pain prevention, 2 were positive and 2 were inconclusive. Three of the four studies examiniRDng opioid use noted less need for opioids in the treatment arm. Meta-analysis of the pertinent studies showed no difference in feeding tube placement (RD = 0.64%, 95%CI: (− 25.8%, 27.1%), p = 0.962) but substantially less weight loss among those in the treatment arm ( p = 0.047). Conclusion Prophylactic gabapentin appears to be a promising treatment option for preventing pain, reducing opioids, and reducing weight loss in patients undergoing head and neck cancer therapy. However, the studies on the treatment to date are small and several have a substantial risk of bias.

Patients with head and neck cancer undergo a variety of side effects during chemoradiation therapy. Mucositis related pain is one of the most important because it affects speech and swallow function and can be responsible for treatment delays. In a recently published study, Cook et al 1 Cook A Modh A Ali H et al. Randomized phase 3, double-blind, placebo-controlled study of prophylactic gabapentin for the reduction of oral mucositis pain during the treatment of oropharyngeal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2022; 112: 926-937 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar add to the literature on the use of prophylactic gabapentin for the mitigation of mucositis-related pain in survivors of head and neck cancer, detailing their recently completed randomized trial. Cook et al failed to detect an effect for gabapentin in this population, which contrasts our groups’ previously published trial that found a substantial effect. 2 Smith DK Cmelak A Niermann K et al. Preventive use of gabapentin to decrease pain and systemic symptoms in patients with head and neck cancer undergoing chemoradiation. Head Neck. 2020; 42: 3497-3505 Crossref PubMed Scopus (10) Google Scholar

The authors deny any conflict of interest. This study used publicly available data from the National Health and Nutrition Examination Survey.2

Oxidative stress promotes acute kidney injury (AKI). Higher HDL cholesterol concentrations are associated with less AKI. To test the hypothesis that HDL antioxidant activity is associated with AKI after cardiac surgery, we quantified HDL particle (HDL-P) size and number, paraoxonase-1 (PON-1) activity, and isofuran concentrations in 75 patients who developed AKI and 75 matched control patients. Higher preoperative HDL-P was associated with less AKI (OR: 0.80; 95% CI, 0.71–0.91; P = 0.001), higher PON-1 activity ( P < 0.001), and lower plasma concentrations of isofurans immediately after surgery (P = 0.02). Similarly, higher preoperative small HDL-P was associated with less AKI, higher PON-1 activity, and lower isofuran concentrations. Higher intraoperative particle losses were associated with less AKI (OR: 0.79; 95% CI 0.67–0.93; P = 0.005), and with decreased postoperative isofuran concentrations (P = 0.04) . Additionally, higher preoperative small HDL-P and increased intraoperative small particle loss were associated with improved long-term renal function (P = 0.003, 0.01, respectively). In conclusion, a higher preoperative concentration of HDL-P, particularly small particles, is associated with lower oxidative damage and less AKI. Perioperative changes in HDL-P concentrations are also associated with AKI. Small HDL-P may represent a novel modifiable risk factor for AKI.

Acute kidney injury (AKI) after endovascular aortic repair (EVAR) occurs in 20% of patients and is an independent predictor of death. Higher preoperative high-density lipoprotein (HDL) cholesterol concentration before revascularization of chronic limb ischemia is associated with a lower risk of AKI. Further, preoperative statin use has been shown to be associated with a decreased risk of AKI after EVAR. We hypothesized that both preoperative statin use and higher preoperative HDL are associated with a lower risk of AKI in patients undergoing EVAR. Charts from adult patients that underwent EVAR were selected using the ICD codes (n=251). Each chart was reviewed for demographic and medical information, preoperative and postoperative serum creatinine concentrations, and preoperative HDL concentration. One hundred and three patients had available statin medication, serum creatinine, and HDL concentrations. The associations between statin dose, HDL concentration and maximum serum creatinine change from baseline in the first 48 postoperative hours was assessed using multivariable linear regression models, adjusted for AKI risk factors. Preoperative HDL concentration was not correlated with preoperative statin dose (Pearson’s R=0.0515, p=0.57). Higher preoperative statin doses (atorvastatin equivalents) and higher preoperative HDL concentrations were associated with lower serum creatinine rise (p=0.042 and 0.002 respectively, Figure). When both preoperative statin dose and preoperative HDL concentration were included in the model, both variables lost significance, suggesting HDL may mediate the relationship between preoperative statin dose and postoperative AKI. Higher preoperative HDL concentrations and statin doses were associated with less postoperative AKI. Future work involves identifying the biological mechanism underlying these associations as a first step towards developing new therapies to prevent AKI following EVAR.

OBJECTIVE:This proof of concept study uses data from the National Health and Nutrition Examination Survey (NHANES) to explore potential associations between oral and systemic health in a survey-wide association study (SWAS). BASIC RESEARCH DESIGN:Data from n=9,971 records in the 2015-2016 NHANES survey were used to evaluate associations between self-rated oral health and the various systemic health conditions that are included in the survey. Associations were estimated using survey-weighted linear regression models adjusted for age, sex, race, and smoking status. RESULTS:Substantial associations with self-rated oral health were evident after correction for multiple comparisons. The study revealed associations in categories of mental health, cardiovascular disease, and diabetes adding to the body of evidence. The study also suggested associations with physical functioning, vision, hearing, genitourinary symptoms, and the prevalence of hepatitis. CONCLUSIONS:The SWAS method demonstrated the ability to identify associations between oral health and systemic health. Suggested associations should be investigated further investigated with emphasis on both biologic and societal mechanisms. The noteworthy associations with mental health, physical activity, and cardiovascular disease in this study inform clinicians from each of these disciplines that they may benefit from collaborations with oral health care providers to promote whole-person health.

PURPOSE To provide evidence-based recommendations for prevention and management of salivary gland hypofunction and xerostomia induced by nonsurgical cancer therapies. METHODS Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials published between January 2009 and June 2020. The guideline also incorporated two previous systematic reviews conducted by MASCC/ISOO, which included studies published from 1990 through 2008. RESULTS A total of 58 publications were identified: 46 addressed preventive interventions and 12 addressed therapeutic interventions. A majority of the evidence focused on the setting of radiation therapy for head and neck cancer. For the prevention of salivary gland hypofunction and/or xerostomia in patients with head and neck cancer, there is high-quality evidence for tissue-sparing radiation modalities. Evidence is weaker or insufficient for other interventions. For the management of salivary gland hypofunction and/or xerostomia, intermediate-quality evidence supports the use of topical mucosal lubricants, saliva substitutes, and agents that stimulate the salivary reflex. RECOMMENDATIONS For patients who receive radiation therapy for head and neck cancer, tissue-sparing radiation modalities should be used when possible to reduce the risk of salivary gland hypofunction and xerostomia. Other risk-reducing interventions that may be offered during radiation therapy for head and neck cancer include bethanechol and acupuncture. For patients who develop salivary gland hypofunction and/or xerostomia, interventions include topical mucosal lubricants, saliva substitutes, and sugar-free lozenges or chewing gum. For patients with head and neck cancer, oral pilocarpine and oral cevimeline, acupuncture, or transcutaneous electrostimulation may be offered after radiation therapy. Additional information can be found at www.asco.org/supportive-care-guidelines .

BACKGROUND:Commonly used predictive models for postoperative pulmonary complications (PPCs) do not perform when applied to head and neck cases. A head and neck-specific risk prediction tool is needed. METHODS:Data on 794 free flap head and neck surgery cases at a single center were abstracted from the electronic medical record. Each case was reviewed for the development of PPCs. A predictive model was developed and was then compared to existing predictive models for PPCs. RESULTS:The least absolute shrinkage and selection operator procedure identified age, alcohol use, history of congestive heart failure, preoperative packed cell volume, preoperative oxygen saturation, and preoperative metabolic equivalents as predictors of PPCs in the head and neck population. The model demonstrated an area under the receiving operating characteristic curve of 0.75 (0.69-0.80) with moderately good calibration. Comparisons to the performance of existing models demonstrate superior performance. CONCLUSIONS:The model for the development of PPCs developed in this article displays superior performance to existing models.

A major challenge emerging in genomic medicine is how to assess best disease risk from rare or novel variants found in disease-related genes. The expanding volume of data generated by very large phenotyping efforts coupled to DNA sequence data presents an opportunity to reinterpret genetic liability of disease risk. Here we propose a framework to estimate the probability of disease given the presence of a genetic variant conditioned on features of that variant. We refer to this as the penetrance, the fraction of all variant heterozygotes that will present with disease. We demonstrate this methodology using a well-established disease-gene pair, the cardiac sodium channel gene SCN5A and the heart arrhythmia Brugada syndrome. From a review of 756 publications, we developed a pattern mixture algorithm, based on a Bayesian Beta-Binomial model, to generate SCN5A penetrance probabilities for the Brugada syndrome conditioned on variant-specific attributes. These probabilities are determined from variant-specific features (e.g. function, structural context, and sequence conservation) and from observations of affected and unaffected heterozygotes. Variant functional perturbation and structural context prove most predictive of Brugada syndrome penetrance.