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Grade 2/3 late xerostomia is a chronic, debilitating complication of radiotherapy for head and neck cancers. We assessed the safety and efficacy of AAV2-hAQP1 gene therapy as a treatment for this condition. Twenty-four participants with grade 2/3 xerostomia at least 5 years after completing radiotherapy (2 years if HPV+) were enrolled in this multicenter, open-label, dose-escalation study. AAV2‑hAQP1 was delivered to the parotid gland(s) via cannulation of the Stensen duct. Twelve participants received AAV2-hAQP1 in 1 gland and 12 in both glands. Participants were followed for 12 months posttreatment. Safety parameters included adverse events, physical examinations, laboratory tests, and electrocardiograms. Efficacy assessments included the Xerostomia-specific Questionnaire (XQ), MD Anderson Symptom Inventory-Head and Neck Module (MDASI-HN), Global Rate of Change Questionnaire (GRCQ), and measurement of unstimulated and stimulated whole saliva flow rates (UWSFR, SWSFR). No treatment-related serious adverse events or dose-limiting toxicities were reported, and all participants completed the study. Statistically significant improvements were seen in the patient-reported outcome instruments by day 30 and were maintained through month 12, with greater improvement in the bilateral versus unilateral cohorts. At month 12, the mean percent change from baseline (%CFB) was −39.5% and −42.2% for the XQ Total Score and the Dry Mouth question of the MDASI-HN, respectively, and the mean GRCQ symptom score was 3.8. Overall, 16 of 24 participants reported an improvement of ≥8 points in the XQ Total Score, and 19 of 24 participants reported important improvements in xerostomia symptoms based on the GRCQ. The improvement reported across patient-reported outcome instruments, measuring different aspects of xerostomia symptoms, provides compelling evidence of treatment effectiveness. The mean %CFB in UWSFR at month 12 was 112.5%, and a trend toward improved SWSFR was observed. Treatment with AAV2-hAQP1 was safe and well-tolerated at all doses and resulted in meaningful improvements in xerostomia symptoms and unstimulated whole saliva flow rate. [ABSTRACT FROM AUTHOR]

Candidiasis is a highly pervasive infection posing major health risks, especially for immunocompromised populations. Pathogenic Candida species have evolved intrinsic and acquired resistance to a variety of antifungal medications. The primary goal of this literature review is to summarize the molecular mechanisms associated with antifungal resistance in Candida species. Resistance can be conferred via gain-of-function mutations in target pathway genes or their transcriptional regulators. Therefore, an overview of the known gene mutations is presented for the following antifungals: azoles (fluconazole, voriconazole, posaconazole and itraconazole), echinocandins (caspofungin, anidulafungin and micafungin), polyenes (amphotericin B and nystatin) and 5-fluorocytosine (5-FC). The following mutation hot spots were identified: (1) ergosterol biosynthesis pathway mutations (ERG11 and UPC2), resulting in azole resistance; (2) overexpression of the efflux pumps, promoting azole resistance (transcription factor genes: tac1 and mrr1; transporter genes: CDR1, CDR2, MDR1, PDR16 and SNQ2); (3) cell wall biosynthesis mutations (FKS1, FKS2 and PDR1), conferring resistance to echinocandins; (4) mutations of nucleic acid synthesis/repair genes (FCY1, FCY2 and FUR1), resulting in 5-FC resistance; and (5) biofilm production, promoting general antifungal resistance. This review also provides a summary of standardized inhibitory breakpoints obtained from international guidelines for prominent Candida species. Notably, N. glabrata, P. kudriavzevii and C. auris demonstrate fluconazole resistance. [ABSTRACT FROM AUTHOR]

Objective: The aim of this sub-analysis was to highlight the MASCC/ISOO clinical practice guidelines for the management of oral mucositis (OM) in pediatric patients and to present unique considerations in this patient population.Methods: This sub-analysis of the pediatric patient population is based on the systematic review conducted by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISSO) published in 2019/2020. Studies were scored and assigned a level of evidence based on previously published criteria. Data regarding adverse effects and compliance was collected from the original publications.Results: A total of 45 papers were included and assessed in this sub-analysis, including 21 randomized controlled trials (RCTs). Chewing gum was demonstrated to be not effective in preventing OM in pediatric cancer patients in 2 RCTs. The efficacy of all other interventions could not be determined based on the available literature.Conclusion: There is limited or conflicting evidence about interventions for the management of OM in pediatric cancer patients, except for chewing gum which was ineffective for prevention. Therefore, currently, data from adult studies may need to be extrapolated for the management of pediatric patients. Honey and photobiomodulation therapy in this patient population had encouraging potential. Implementation of a basic oral care protocol is advised amid lack of high level of evidence studies. [ABSTRACT FROM AUTHOR]

Background: Mucositis is a significant toxicity of cancer therapy with numerous systemic sequelae. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for the management of mucositis.Methods: The literature was reviewed systematically to identify interventions for mucositis. Studies were rated according to the presence of major and minor flaws according to previously published criteria. The body of evidence for each intervention and in each treatment setting was assigned a level of evidence based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible.Results: The guideline covers evidence from 1197 publications related to oral or gastrointestinal mucositis. Thirteen new guidelines were developed for or against the use of various interventions in specific treatment settings, and 11 previous guidelines were confirmed after aa review of new evidence. Thirteen previously established guidelines were carried over because there was no new evidence for these interventions.Conclusions: The updated MASCC/ISOO Clinical Practice Guidelines for mucositis provide professional health caregivers with a clinical setting-specific, evidence-based tool to help with the management of mucositis in patients who have cancer. [ABSTRACT FROM AUTHOR]

Purpose: To update the clinical practice guidelines for the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and/or treatment of oral mucositis (OM).Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible.Results: A total of 9 new papers were identified within the scope of this section, adding to the 62 papers reviewed in this section previously. A new Suggestion was made for topical 0.2% morphine for the treatment of OM-associated pain in head and neck (H&N) cancer patients treated with RT-CT (modification of previous guideline). A previous Recommendation against the use of sucralfate-combined systemic and topical formulation in the prevention of OM in solid cancer treatment with CT was changed from Recommendation Against to No Guideline Possible. Suggestion for doxepin and fentanyl for the treatment of mucositis-associated pain in H&N cancer patients was changed to No Guideline Possible.Conclusions: Of the agents studied for the management of OM in this paper, the evidence supports a Suggestion in favor of topical morphine 0.2% in H&N cancer patients treated with RT-CT for the treatment of OM-associated pain. [ABSTRACT FROM AUTHOR]

The article discusses popular notions on stop-smoking treatments and its medical validity. It notes that nicotine is not essentially the harmful ingredient in cigarettes but rather the presence of toxins such as vinyl chloride, nickel, and arsenic and other tobacco combustion products may lead to cancer. It also states that nicotine replacement therapy (NRT) is medically safe as it provides the same effect of smoking without its combustible toxins.

The article features the position statement of the Ontario Dental Association (ODA) regarding electronic cigarettes (e-cigarettes). Topics covered include over-the-counter nicotine replacement therapy (NRT) and pharmacotherapy, increase in the number of young people who use e-cigarettes, lack of research on e-cigarette use's behavioural and long-term effects, and ODA's support for e-cigarette regulation in Ontario and for continued scientific study regarding e-cigarette use and its effects.

An abstract of the articles about the screening tools for the identification of patients with obstructive sleep apnea (OSA) including the Epworth Sleepiness Scale (ESS), the Four-Variable Screening Tool (FVST) and the Upper Airway Physical Examination Protocol (UAPP) is presented.

The article presents a summary of the Clinical Guidelines for Evaluation, Management and Long-Term Care of Obstructive Sleep Apnea (OSA) in Adults, which were established by the Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Apnea. It characterizes OSA and describes the basis for the diagnosis of the disorder. It points out the importance of patient education and offers information on the treatment options for the management of OSA, including oral appliances.