MASCC/ISOO Clinical Practice Statement: Adjuvant bone-modifying agents in primary breast cancer patients - prevention of medication-related osteonecrosis of the jaw.

PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS raises awareness to the prevention of medication-related osteonecrosis of the jaw (MRONJ) in patients with breast cancer treated with adjuvant bone-modifying agents (BMA). METHODS: This CPS was developed based on a critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and tables to generate a short manual about the best standard of care. RESULTS: In patients treated with adjuvant BMA, dento-alveolar surgery poses a moderate risk for MRONJ that ranges between the high risk for MRONJ in patients with metastatic breast cancer and the low risk for MRONJ in patients with osteoporosis. Existing MRONJ guidelines serve as a starting point for adjuvant BMA use. Urgent procedures should be delivered without delay using the accepted precautions to prevent MRONJ. If elective surgery is considered, the individual risk for MRONJ following surgery should be assessed according to common risk factors. CONCLUSION: Prevention of MRONJ in primary breast cancer patients treated with adjuvant BMA requires risk-benefit assessment; collaboration between the medical team, dental professional, and patient; and patient-specific tailored dental treatment planning. The patient should be informed about this risk. Additional research is needed to define optimal MRONJ care for this population.

Preventive versus curative photobiomodulation for oral mucositis in patients with multiple myeloma undergoing hematopoietic stem cell transplantation: which approach is more effective?

PURPOSE: There is increasing evidence that photobiomodulation (PBM) therapy is both an effective and safe approach in hematopoietic stem cell transplantation (HSCT) for both prevention and management of oral mucositis (OM), but its use in clinical practice is still limited and the timing of application is under discussion. The aim of this retrospective study was to evaluate possible differences between patients treated either with preventive or curative PBM therapy. METHODS: The retrospective case series included 24 patients suffering from multiple myeloma who underwent the same conditioning and transplantation protocol. Patients were treated either with preventive PBM starting from the first day of conditioning up to two days post-HSCT or with curative PBM (starting at OM onset for four consecutive days). OM score, pain, and functional parameters were recorded. RESULTS: All patients developed OM. Preventive PBM was significantly more effective in reducing OM severity (p < 0.0001) and pain (p < 0.0001) post-HSCT than curative PBM. Furthermore, we found a lower number of patients reporting discomfort in all subjective parameters (pain during swallowing, chewing, and speaking) in the preventive PBM group. No adverse events related to PBM therapy were recorded in both groups. CONCLUSION: The timing for PBM therapy in patients undergoing HSCT is crucial: when started on the first day of conditioning, it significantly reduces both pain and OM severity, providing an important benefit also in subjective oral functions such as speaking, swallowing, and chewing, thus increasing the overall adherence to the oncological therapies.

Updated perspectives on the contribution of the microbiome to the pathogenesis of mucositis using the MASCC/ISOO framework.

Advances in the treatment of cancer have significantly improved mortality rates; however, this has come at a cost, with many treatments still limited by their toxic side effects. Mucositis in both the mouth and gastrointestinal tract is common following many anti-cancer agents, manifesting as ulcerative lesions and associated symptoms throughout the alimentary tract. The pathogenesis of mucositis was first defined in 2004 by Sonis, and almost 20 years on, the model continues to be updated reflecting ongoing research initiatives and more sophisticated analytical techniques. The most recent update, published by the Multinational Association for Supportive Care in Cancer and the International Society for Oral Oncology (MASCC/ISOO), highlights the numerous co-occurring events that underpin mucositis development. Most notably, a role for the ecosystem of microorganisms that reside throughout the alimentary tract (the oral and gut microbiota) was explored, building on initial concepts proposed by Sonis. However, many questions remain regarding the true causal contribution of the microbiota and associated metabolome. This review aims to provide an overview of this rapidly evolving area, synthesizing current evidence on the microbiota's contribution to mucositis development and progression, highlighting (i) components of the 5-phase model where the microbiome may be involved, (ii) methodological challenges that have hindered advances in this area, and (iii) opportunities for intervention.

Effect of repeated topical capsaicin gel administration on oral thermal quantitative sensory testing: A two-arm longitudinal study.

OBJECTIVES: Few studies used thermal quantitative sensory testing to assess the effects of repeated capsaicin gel administration in the oral cavity. This study aimed to investigate thermal sensory and pain thresholds before and after repeated capsaicin gel administration. SUBJECTS AND METHODS: Ten healthy females (22 ± 2 years) applied a capsaicin gel on the gingival mucosa twice daily for 14 days, and heat pain threshold, warm detection threshold, cold pain threshold, and cold detection threshold were assessed on the oral mucosa. Measurements were performed before and after the 14 days and were compared to a control sample (n = 10, all females, 23 ± 3 years). RESULTS: Capsaicin increased heat pain threshold in the anterior maxilla by 2.9°C (95% CI: 1.6-4.2) (p < 0.001) and in the anterior mandible by 2.2°C (95% CI: 1.0-3.4) (p = 0.001), similar to warm detection threshold that increased by Δ1.1°C (95% CI: 0.3-1.9) (p = 0.009). No significant changes were found in the controls. CONCLUSIONS: These findings encourage the use of thermal quantitative sensory testing in the oral cavity to assess thermal sensation, which might be useful for assessing the effects of therapies aimed at reducing pain.

COVID-19 impact on post-traumatic stress symptoms in burning mouth syndrome: A multicentric study.

OBJECTIVES: This study investigates the psychological impact of COVID-19 on burning mouth syndrome (BMS) patients. It focuses on comparing post-traumatic stress symptoms (PTSS), post-traumatic growth (PTG), and resilience between BMS patients and Controls. METHODS: A total of 100 BMS patients and 100 Controls from five Italian centers participated in this observational cross-sectional study. They completed several assessments, including the General Health Questionnaire, Depression Anxiety and Stress Scale, Insomnia Severity Index, National Stressful Events Survey Short Scale, Impact of Event Scale-Revised, Post Traumatic Growth Inventory Short Form, and Connor-Davidson Resilience Scale. RESULTS: BMS patients had significantly higher stress, anxiety, and depression (DASS-21 score) and post-traumatic stress symptoms (IES-R-6 score), particularly in terms of intrusive thoughts. They showed lower post-traumatic growth (PTGI-SF score) compared to Controls. The resilience scale (CDRS-10) was a key predictor of PTG in both groups, explaining a significant variance in PTGI-SF scores. CONCLUSIONS: BMS patients experienced heightened post-traumatic stress, stress, anxiety, and depression during the COVID-19 pandemic, with reduced post-traumatic growth. This highlights the need to prioritize their psychological well-being, focusing on stress management and fostering post-traumatic growth in challenging times.

Changes in mandibular radiomorphometric indices in osteoporosis patients treated with denosumab: a retrospective case-control study.

BACKGROUND: Radiomorphometric indices measured on Dental Panoramic Radiography (DPR) can reflect Bone Mineral Density (BMD). The aim of our study is to evaluate changes in DPR radiographic markers in patients undergoing antiresorptive therapy with denosumab and correlate them to BMD and serum bone turnover markers (BTM). METHODS: We evaluated two radiomorphometric indices: Mandibular Cortical Width (MCW) and Panoramic Mandibular Index (PMI), in patients undergoing antiresorptive therapy with denosumab at T0 (before starting the therapy) and at T1 (after 12 months), comparing results with a control group of healthy patients who performed two DPRs at a one-year time distance. Correlation analysis was performed in the denosumab group, as well as ROC curves were obtained for both indices. RESULTS: The study included 18 patients and 21 controls according to specific inclusion and exclusion criteria, matched by gender and age. Both MCW and PMI were significantly lower at T0 in the denosumab group, consistently with lower BMD. MCW showed significant correlation with femoral and lumbar DEXA and was significantly lower in patients with osteoporosis compared to osteopenia. Only PMI index increased significantly in the denosumab group from T0 to T1. After one year (T1), there weren't any differences between patients and controls for both indices. No significant correlations were found with BTMs. Sensitivity and specificity for MCW and PMI were also calculated. CONCLUSIONS: Our results show how CMW shows sufficient sensitivity and specificity to be used as a radiographic marker to screen and intercept patients with osteoporosis. PMI seems to be able to reflect changes in response to antiresorptive therapy with denosumab. Further studies are needed to confirm our hypothesis.

Chronic Diffuse Sclerosing Osteomyelitis of the Mandible: The Use of Bisphosphonates as a Treatment for a Rare and Challenging Condition.

Chronic diffuse sclerosing osteomyelitis is a very rare condition, described as a non-suppurative, inflammatory disease of the bone and characterized by a proliferative endosteal reaction, which clinically reveals itself with cyclic pain of the jaw and swelling. We reported two clinical cases, where patients suffered recurrent swelling and pain at the mandible irradiating to the preauricular area, denying any previous trauma or significant medical history. Odontogenic causes were excluded. An initial treatment with antibiotics and NSAIDs temporarily relieved the symptoms without complete resolution, prompting further investigations. After a comprehensive array of diagnostic tools (X-rays, CT scans, scintigraphy, bone biopsy, serum markers), both patients were diagnosed with chronic diffuse sclerosing osteomyelitis of the mandible. Bisphosphonates (clodronate and zolendronate) with different treatment schemes were used to treat the condition, until a full recovery from symptoms was reported. Bisphosphonates could therefore represent an effective option in managing this rare but impactful condition. Further research is warranted to better understand the underlying mechanisms of the disease and to optimize treatment strategies.

Dental Treatment in Special Needs Patients and Uncooperative Young Children: A Retrospective Study.

Background and Objectives: Special Needs Patients (SNPs) and young non-collaborative children are more predisposed to develop oral pathologies due to poor collaboration and scarce access to dental treatment. The aim of this retrospective study was to analyze a sample of SNPs who received dental treatments either under general anesthesia (GA) or deep sedation (DS) over a period of 6 years. The number and type of procedure were analyzed. Materials and Methods: In total, 131 patients were included and mostly (>90%) treated under GA. Patients were either uncooperative and phobic (Group 1) or affected by mental, behavioral, and neurological disorders (Group 2), diseases of the nervous system (Group 3), or developmental anomalies (Group 4). Results: Patients in Group 2 required more invasive dental treatments than those in the other groups. Therapies were mainly preventive and restorative, except in Groups 3 and 4, where extractions were more frequent. The type of dental treatment significantly varied according to age and systemic condition. Only 5.3% of the patients needed a second intervention, despite only 17.6% of patients respecting the scheduled follow-up. Conclusions: Treatment under GA is effective, but the poor adherence to follow-ups and the risk of reintervention should be contrasted by improving the perception by parents/guardians of the importance of oral hygiene and periodic visits.

Quality assessment of PBM protocols for oral complications in head and neck cancer patients: part 2.

PURPOSE: To investigate the role of photobiomodulation (PBM) in patients undergoing head and neck cancer (HNC) treatment. We focused on the consequences of the main complications, such as quality of life (QoL), analgesia, functional impairment, and nutritional status, as well as on the impact on survival/ recurrences, radiotherapy (RT) interruption, adherence, cost-effectiveness, safety, feasibility, and tolerability. METHODS: An electronic search in PubMed and Scopus databases was performed. Full texts were carefully assessed, and data were assimilated into a tabular form for discussion and consensus among the expert panel. RESULTS: A total of 22 papers were included. Overall, a beneficial effect of PBM was evidenced in the amelioration of QoL, nutritional status, the reduction of pain, and functional impairment. Preventive PBM may reduce the incidence and duration of RT interruptions, potentially contributing to improved cancer treatment outcomes. PBM treatments are safe and recommended for routine use, with the caveat of avoiding direct tumor exposures where feasible. However, it does not appear to impact cancer survivorship/recurrences directly. Despite additional clinical efforts involving routine PBM use, the individual and public health benefits will positively impact oncology care. CONCLUSIONS: Quality of life, pain and functional impairment, nutritional status, and survival may be effectively improved with PBM. Given its established efficacy also in reducing RT interruptions and its safety, feasibility, and tolerability, PBM should be included in the field of supportive cancer care in HNC patients. Improved understanding of PBM mechanisms and precise dose parameters is enabling the generation of more robust, safe, and reproducible protocols; thus, it is imperative to support further clinical implementation as well as both applied and basic science research in this novel field.

Histopathology of oral lichen planus and oral lichenoid lesions: An exploratory cross-sectional study.

OBJECTIVE: To better characterize the histopathology of oral lichen planus and oral lichenoid lesions and to highlight the differences between them in order to support the clinician in the diagnostic and therapeutic management of such conditions. SUBJECTS AND METHODS: Fifty-five patients, clinically diagnosed with oral lichen planus (n = 25) or oral lichenoid lesions (n = 30), were consecutively enrolled in the present study. Subsequently, one blind pathologist reviewed all the biopsy specimens of enrolled subjects following a specific protocol to provide a detailed histopathological description. Demographic, anamnestic, and clinical data were also recorded from all the participants. Patients' data were analysed and compared using the chi-squared test, to provide distinguishing features between the studied conditions. RESULTS: We found a higher and statistically significant number of eosinophils in the oral lichenoid lesions compared with the oral lichen planus group (p < 0.01), an equally promising result was seen regarding plasma cells, which were more represented (p = 0.05) in the oral lichenoid lesions than in the oral lichen planus cases. No statistically significant differences were detected in demographic, anamnestic and clinical data. CONCLUSION: A mixed lichenoid inflammatory infiltrate, consisting of eosinophils and plasma cells, could be used as reliable histological features for the diagnosis of oral lichenoid lesions, as long as compared with findings obtained from the patients' history and clinical examination.

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO.

OBJECTIVES: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. METHODS: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. RESULTS: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). CONCLUSIONS: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. CLINICAL RELEVANCE: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients.

ACE2 Down-Regulation May Act as a Transient Molecular Disease Causing RAAS Dysregulation and Tissue Damage in the Microcirculatory Environment Among COVID-19 Patients.

Severe acute respiratory syndrome coronavirus 2, the etiologic agent of coronavirus disease 2019 (COVID-19) and the cause of the current pandemic, produces multiform manifestations throughout the body, causing indiscriminate damage to multiple organ systems, particularly the lungs, heart, brain, kidney, and vasculature. The aim of this review is to provide a new assessment of the data already available for COVID-19, exploring it as a transient molecular disease that causes negative regulation of angiotensin-converting enzyme 2, and consequently, deregulates the renin-angiotensin-aldosterone system, promoting important changes in the microcirculatory environment. Another goal of the article is to show how these microcirculatory changes may be responsible for the wide variety of injury mechanisms observed in different organs in this disease. The new concept of COVID-19 provides a unifying pathophysiological picture of this infection and offers fresh insights for a rational treatment strategy to combat this ongoing pandemic.

Where do you live? North versus Central-South differences in relation to Italian patients with oral lichen planus: a cross-sectional study from the SIPMO (Italian Society of Oral Pathology and Medicine).

BACKGROUND: Oral lichen planus (OLP) is an immune-mediated inflammatory chronic disease of the oral mucosa, with different patterns of clinical manifestations which range from keratotic manifestations (K-OLP) to predominantly non-keratotic lesions (nK-OLP). The aim of the study was to analyze the differences in the clinical, psychological profile and symptoms between Italian patients of the North and Central-South with K-OLP and nK-OLP. METHODS: 270 K-OLP and 270 nK-OLP patients were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) were administered. RESULTS: The Central-South K-OLP (CS-K-OLP) patients reported a higher frequency of pain/burning compared with the K-OLP patients of the North (N-K-OLP) with higher scores in the NRS and T-PRI (p value < 0.001**). The CS-K-OLP and the CS-nK-OLP patients showed higher scores in the HAM-D, HAM-A, PSQI and ESS compared with the Northern patients (p value < 0.001**). Multivariate logistic regression revealed that the NRS and T-PRI showed the greatest increase in the R2 value for the CS-K-OLP (DR2 = 9.6%; p value < 0.001**; DR2 = 9.7% p value < 0.001**; respectively) and that the oral symptoms (globus, itching and intraoral foreign body sensation) and PSQI showed the greatest increase in the R2 value for the CS-nK-OLP (DR2 = 5.6%; p value < 0.001**; DR2 = 4.5% p value < 0.001** respectively). CONCLUSIONS: Pain and mood disorders are predominant in patients with OLP in the Central-South of Italy. Clinicians should consider that the geographical living area may explain the differences in oral symptoms and psychological profile in OLP.

Photobiomodulation modulates inflammation and oral microbiome: a pilot study.

INTRODUCTION: Oral mucositis (OM) is a severe side effect in patients undergoing anticancer therapies, which negatively impacts on their quality of life often leading to either the interruption of the therapy. Photobiomodulation (PBM) is emerging as an effective strategy allowing a faster wound healing. OBJECTIVES: This pilot study aims at verifying whether PBM modulates the inflammatory response in patients and its effect on the oral microbiome composition. MATERIALS AND METHODS: Buccal swabs were collected from four patients affected by OM, both on ulcerated and clinically healthy areas, before and on the last day of PBM therapy, as well as on the first day after treatment discontinuation. The concentration of 38 cytokines and the composition of oral microbiome were measured. RESULTS: Most of the pro-inflammatory cytokines were reduced, whereas anti-inflammatory cytokines resulted up-regulated by PBM. In addition, PBM influenced the composition of oral microbiome, by decreasing the amount of pathogenic species and promoting the growth of commensal bacteria. These changes were even more evident when separately analysing patients who clinically responded to PBM and the only patient who did not respond. CONCLUSIONS: PBM reduces inflammatory burden in patients affected by OM and positively influences the composition of the oral microbiome.

Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - part 2: honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.

OBJECTIVE: To update the clinical practice guidelines for the management of oral mucositis (OM) that were developed by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). This part focuses on honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents. METHODS: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The body of evidence for each intervention, in each clinical 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, one of the following guidelines were determined: Recommendation, Suggestion, No Guideline Possible. RESULTS: A total of 78 papers were identified within the scope of this section, of which 49 were included in this review and merged with nine publications that were reported in the previous guidelines update. A new Suggestion was made for honey (combined topical and systemic delivery) for the prevention of OM in head and neck cancer patients receiving radiotherapy with or without chemotherapy. A new Suggestion clarified that chewing gum is not effective for the prevention of OM in pediatric patients with hematological or solid cancer treated with chemotherapy. No guideline was possible for other interventions. CONCLUSIONS: Numerous natural products and herbal remedies were studied for the management of OM. Of the agents reviewed in this systematic review, a guideline in favor was made for honey (combined topical and systemic), while a guideline against was made for chewing gum. Additional research is warranted to clarify the potential of other interventions.

Photobiomodulation therapy for male infertility.

Male infertility is a worldwide critical condition that affects about the 7.5% of males in Europe leading to an increment of the couples referring to reproductive medicine units to achieve pregnancy. Moreover, in the recent years, an increased number of patients have required to freeze their gametes in order to preserve their fertility. Photobiomodulation (PBM) therapy is a potential treatment that has been used for different clinical application basically aimed at biostimulating cells and tissues. Here, we report a deep overview of the published studies, focusing on PBM mechanism of action, with the aim of expanding the knowledge in the field of laser light for a rational utilization of irradiation in the clinical practice. In the field of reproductive science, PBM was employed to increment spermatozoa's metabolism, motility, and viability, due to its beneficial action on mitochondria, leading to an activation of the mitochondrial respiratory chain and to the ATP production. This treatment can be particularly useful to avoid the use of chemicals in the spermatozoa culture medium as well as to promote the spermatozoa survival and movement especially after thawing or in largely immotile sperm samples.

Correction to: Photobiomodulation therapy at different wavelength impacts on retinoid acid-dependent SH-SY5Y differentiation.

After publication of this paper, the authors determined an error in the author group. The correct presentation of authors are below.

Campaign to Increase Awareness of Oral Cancer Risk Factors Among Preadolescents.

Oral squamous cell carcinoma (OSCC) represents one of the most common but scarcely known malignancies worldwide. The etiology of OSCC is strongly related to lifestyle habits and behavior, especially tobacco smoking and alcohol abuse. The mean age of individuals who start smoking and drinking alcohol is decreasing; thus, the aim of our campaign was to test the awareness and increase knowledge of oral cancer and its risk factors among young preadolescents. Six schools with 460 students aged 12-14 years were included in the campaign. A lecture about carcinogenesis and oral cancer was provided. Anonymous questionnaires were submitted to the students before and after the lecture, to test their knowledge, awareness, and understanding. Before the lecture, the students showed very little awareness of oral cancer (26.8%), although almost all of them identified tobacco smoking as a risk factor (92.2%). After the lecture, the students showed a significant understanding of the provided information, thus increasing their awareness. On scales of 1-10, the students rated the appropriateness of the campaign at 8.9 and their overall appreciation at 8.7. Social campaigns, especially among young students, seem to be appreciated and may represent a powerful strategy for increasing knowledge about cancer risk factors, especially when they are highly related to lifestyle habits and behavior.

Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines-part 1: vitamins, minerals, and nutritional supplements.

PURPOSE: To update the clinical practice guidelines for the use of natural and miscellaneous agents 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 78 papers were identified within the scope of this section, out of which 29 were included in this part, and were analyzed with 27 previously reviewed studies. A new Suggestion was made for oral glutamine for the prevention of OM in head and neck (H&N) cancer patients receiving radiotherapy with concomitant chemotherapy. The previous Recommendation against the use of parenteral glutamine for the prevention of OM in hematopoietic stem cell transplantation (HSCT) patients was re-established. A previous Suggestion for zinc to prevent OM in H&N cancer patients treated with radiotherapy or chemo-radiotherapy was reversed to No Guideline Possible. No guideline was possible for other interventions. CONCLUSIONS: Of the vitamins, minerals, and nutritional supplements studied for the management of OM, the evidence supports a Recommendation against parenteral glutamine in HSCT patients and a Suggestion in favor of oral glutamine in H&N cancer patients for the management of OM.