The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies.

Oral mucositis (OM) is a common, highly symptomatic complication of cancer therapy that affects patients' function, quality of life, and ability to tolerate treatment. In certain patients with cancer, OM is associated with increased mortality. Research on the management of OM is ongoing. Oral mucosal toxicities are also reported in targeted and immune checkpoint inhibitor therapies. The objective of this article is to present current knowledge about the epidemiology, pathogenesis, assessment, risk prediction, and current and developing intervention strategies for OM and other ulcerative mucosal toxicities caused by both conventional and evolving forms of cancer therapy.

Influence of oral microbiome on longitudinal patterns of oral mucositis severity in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: This study investigated the influence of oral microbial features on the trajectory of oral mucositis (OM) in patients with squamous cell carcinoma of the head and neck. METHODS: OM severity was assessed and buccal swabs were collected at baseline, at the initiation of cancer treatment, weekly during cancer treatment, at the termination of cancer treatment, and after cancer treatment termination. The oral microbiome was characterized via the 16S ribosomal RNA V4 region with the Illumina platform. Latent class mixed-model analysis was used to group individuals with similar trajectories of OM severity. Locally estimated scatterplot smoothing was used to fit an average trend within each group and to assess the association between the longitudinal OM scores and longitudinal microbial abundances. RESULTS: Four latent groups (LGs) with differing patterns of OM severity were identified for 142 subjects. LG1 has an early onset of high OM scores. LGs 2 and 3 begin with relatively low OM scores until the eighth and 11th week, respectively. LG4 has generally flat OM scores. These LGs did not vary by treatment or clinical or demographic variables. Correlation analysis showed that the abundances of Bacteroidota, Proteobacteria, Bacteroidia, Gammaproteobacteria, Enterobacterales, Bacteroidales, Aerococcaceae, Prevotellaceae, Abiotrophia, and Prevotella_7 were positively correlated with OM severity across the four LGs. Negative correlation was observed with OM severity for a few microbial features: Abiotrophia and Aerococcaceae for LGs 2 and 3; Gammaproteobacteria and Proteobacteria for LGs 2, 3, and 4; and Enterobacterales for LGs 2 and 4. CONCLUSIONS: These findings suggest the potential to personalize treatment for OM. PLAIN LANGUAGE SUMMARY: Oral mucositis (OM) is a common and debilitating after effect for patients treated for squamous cell carcinoma of the head and neck. Trends in the abundance of specific microbial features may be associated with patterns of OM severity over time. Our findings suggest the potential to personalize treatment plans for OM via tailored microbiome interventions.

Mechanisms driving fasting-induced protection from genotoxic injury in the small intestine.

Genotoxic agents such as doxorubicin (DXR) can cause damage to the intestines that can be ameliorated by fasting. How fasting is protective and the optimal timing of fasting and refeeding remain unclear. Here, our analysis of fasting/refeeding-induced global intestinal transcriptional changes revealed metabolic shifts and implicated the cellular energetic hub mechanistic target of rapamycin complex 1 (mTORC1) in protecting from DXR-induced DNA damage. Our analysis of specific transcripts and proteins in intestinal tissue and tissue extracts showed that fasting followed by refeeding at the time of DXR administration reduced damage and caused a spike in mTORC1 activity. However, continued fasting after DXR prevented the mTORC1 spike and damage reduction. Surprisingly, the mTORC1 inhibitor, rapamycin, did not block fasting/refeeding-induced reduction in DNA damage, suggesting that increased mTORC1 is dispensable for protection against the initial DNA damage response. In Ddit4-/- mice [DDIT4 (DNA-damage-inducible transcript 4) functions to regulate mTORC1 activity], fasting reduced DNA damage and increased intestinal crypt viability vs. ad libitum-fed Ddit4-/- mice. Fasted/refed Ddit4-/- mice maintained body weight, with increased crypt proliferation by 5 days post-DXR, whereas ad libitum-fed Ddit4-/- mice continued to lose weight and displayed limited crypt proliferation. Genes encoding epithelial stem cell and DNA repair proteins were elevated in DXR-injured, fasted vs. ad libitum Ddit4-/- intestines. Thus, fasting strongly reduced intestinal damage when normal dynamic regulation of mTORC1 was lost. Overall, the results confirm that fasting protects the intestines against DXR and suggests that fasting works by pleiotropic - including both mTORC1-dependent and independent - mechanisms across the temporally dynamic injury response.NEW & NOTEWORTHY New findings are 1) DNA damage reduction following a 24-h fast depends on the timing of postfast refeeding in relation to chemotherapy initiation; 2) fasting/refeeding-induced upregulation of mTORC1 activity is not required for early (6 h) protection against DXR-induced DNA damage; and 3) fasting increases expression of intestinal stem cell and DNA damage repair genes, even when mTORC1 is dysregulated, highlighting fasting's crucial role in regulating mTORC1-dependent and independent mechanisms in the dynamic recovery process.

Comparisons of Non-Oral Immune-Related Adverse Events Among Patients With Cancer With Different Oral Toxicity Profiles.

OBJECTIVES: Immune-related adverse events (irAEs) are common. Oral irAEs tend to cluster in patients who experience concurrent toxicities. We aimed to characterize the frequency and trajectory of non-oral irAEs in patients who developed oral irAEs, assess their relationship with non-oral irAEs, and compare those characteristics with patients without oral irAEs. METHODS: A retrospective chart review was conducted to identify patients who started ICIT between December 11, 2011, and September 15, 2019 (n = 4683) in the Mass General Brigham Registered Patient Data Registry. Demographic information, cancer diagnosis, ICIT regimen, treatment duration, and time and number of infusions to irAE onset were recorded. Non-oral irAEs were categorized into 13 groups. Patients with melanoma, pulmonary cancer, or head and neck cancer who had oral irAEs were then matched with those without oral irAEs to compare the prevalence of concomitant non-oral irAEs. RESULTS: Three hundred and fourteen patients with oral irAEs with a mean age of 65.9 ±â€…12.6 years (43.3% females) were included. Patients with multiple oral irAEs were more likely to have non-oral irAEs (OR: 2.7, 95% CI, 1.3-3.5), including cutaneous (OR: 1.7, 95% CI, 1.1-3.0), rheumatological (OR: 2.2, 95% CI, 1.1-4.2), thyroid (OR: 2.4, 95% CI, 1.2-4.9), and neurological irAEs (OR: 2.5, 95% CI, 1.0-6.3). Compared to matched patients with non-oral irAEs, patients with oral irAEs were more likely to have cutaneous (OR: 1.7, 95% CI, 1.0-2.8) and thyroid (OR: 2.86, 95% CI, 1.1-7.5) irAEs. The development of oral and non-oral irAEs is often coincidental. CONCLUSION: Patients who have non-oral irAEs should be monitored for development of oral irAEs for prompt management.

Efficacy of probiotics in the treatment of oral mucositis in head and neck cancer patients: A systematic review and meta-analysis.

OBJECTIVES: To assess the effect of probiotics in oral mucositis induced by chemotherapy or radiotherapy on patients with head and neck cancer (HNC). METHODS: The PubMed, Embase, Cochrane Library, Clinical trials were screened from January 2010 to April 2024. Randomized clinical trials (RCTs) comparing the efficacy of probiotics in treatment of oral mucositis in HNC were eligible. Outcomes of interest were incidence of oral mucositis and severe oral mucositis. The PROSPERO registration number was 42 022 384 685. The Cochrane risk-of-bias tool (RoB2) was used to assess methodological quality of studies and GRADE criteria (GRADEpro) was applied for rating the certainty of evidence. Meta-analysis was performed by using RevMan 5.4. RESULTS: A total of eight RCTs comprising 691 patients with HNC were included in this meta-analysis. Probiotics administration significantly reduced the incidence of SOM (RR = 0.60, 95%CI: 0.46-0.78, P = 0.0002). However, it showed no distinct advantage in reducing the overall incidence of oral mucositis (RR = 0.88, 95%CI: 0.76-1.02, P = 0.08). Subgroup analysis found more benefit for reducing SOM in multi-bacterial treated group (RR = 0.35, 95%CI: 0.17-0.73, P = 0.005) than mono-bacterial treated group (RR = 0.69, 95%CI: 0.58-0.82, P < 0.0001). In Addition, probiotics could reduce the incidence of SOM in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (RR = 0.43, 95%CI: 0.26-0.70, P = 0.0006). CONCLUSION: Probiotics reduced the incidence of SOM caused by chemotherapy or radiotherapy for HNC. The multi-bacterial combination therapy was more efficacious than the mono-bacterial therapy. Moreover, probiotics also reduced the incidence of SOM in nasopharyngeal carcinoma. However, the advantage of probiotics had not been established in the overall incidence of OM.

MicroRNA hsa-let-7e-5p in hUC-MSC-EVs alleviates oral mucositis by targeting TAB2.

Oral mucositis (OM) is a severe side effect of anti-cancer therapy, with limited available treatments. Mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs) have demonstrated effective protection against OM. However, the underlying mechanism remains elusive. In the current study, we purified EVs secreted by human umbilical cord MSCs (hUC-MSC-EVs) and investigated their role in lipopolysaccharide (LPS)-induced human oral keratinocytes (HOKs). We observed that treatment with hUC-MSC-EVs significantly reduced the inflammatory response of HOKs to LPS induction. Through small RNA-seq using miRNAs extracted from hUC-MSC-EVs, we identified hsa-let-7e-5p as one of the most highly expressed miRNAs. Bioinformatic analysis data indicated that hsa-let-7e-5p may inhibit the NF-κB signalling pathway by targeting TAB2. Overexpression of the hsa-let-7e-5p inhibitor significantly attenuated the anti-inflammatory effect of hUC-MSC-EVs in LPS-induced HOKs, which could be reversed by the knockdown of TAB2. In addition, we administered hUC-MSC-EVs in a hamster model for OM and observed that these EVs alleviated OM phenotypes. Taken together, our observations suggest that hsa-let-7e-5p in hUC-MSC-EVs could protect the oral mucosa from OM by repressing TAB2 expression.

Multidisciplinary survey on use of feeding tubes in head and neck cancer patients undergoing chemoradiotherapy in Germany-the SUFEETUBE project.

BACKGROUND AND OBJECTIVE: Data on enteral tube feeding in head and neck cancer (HNC) patients undergoing chemoradiotherapy vary considerably between German institutions. This survey aims to investigate the management of feeding tubes in an interdisciplinary context across Germany. MATERIALS AND METHODS: Between December 2022 and May 2023, 70 participants (42 radiation oncologists, 12 medical oncologists, 14 head and neck surgeons, and 2 physicians covering several specialties) responded to our web-based survey. In addition to the type of institution (university hospital, private practice, etc.), their age, and professional experience (in years), participants were asked several questions on the indication and institutional policy for tube placement and management (prophylactic/reactive nasogastric or gastrostomy tube). All questions were mandatory single- or multiple-choice questions, while additional comments were possible by email. RESULTS: Most participants were employed at a university hospital (n = 52; 74.3%) and came from a radiation oncology background (n = 42; 60%). Fifty-four contributors (77.1%) reported that no nutritional risk screening prior to chemoradiotherapy was routinely performed, and 71.4% (n = 50) stated that no standardized protocol was used at the institution to set the indication for tube placement. Generally, policies and methods of tube feeding vary considerably between the individual institutions and specialties. However, the majority (n = 56, 80%) recommended a prophylactic percutaneous enteral gastrostomy (PEG) tube to their patients before chemoradiotherapy. Still, there was no consistent trend regarding the approach for reactive tube feeding. CONCLUSION: The policies and methods of tube feeding vary considerably between the individual institutions and specialties in Germany. In the era of individualized medicine, uniform protocols are difficult to establish. However, a baseline nutritional risk screening could simplify decision-making in clinical practice.

Impact of dose volume parameters and clinical characteristics on radiation-induced acute oral mucositis for head and neck cancer patients treated with carbon-ion radiotherapy dose volume outcome analysis.

OBJECTIVES: To assess the predictive value of different dosimetric parameters for acute radiation oral mucositis (ROM) in head and neck cancer (HNCs) patients treated with carbon-ion radiotherapy (CIRT). METHODS: 44 patients with HNCs treated with CIRT were evaluated for acute ROM which was defined as severe when the score ≥3 (acute ROM was scored prospectively using the Radiation Therapy Oncology Group (RTOG) score system). Predictive dosimetric factors were identified by using univariate and multivariate analysis. RESULTS: Male gender, weight loss >5%, and total dose/fractions were related factors to severe ROM. In multivariate analysis, grade ≥3 ROM was significantly related to the Dmax, D10, D15, and D20 (P < 0.05, respectively). As the receiver operating characteristics (ROC) curve shows, the area under the curve (AUC) for D10 was 0.77 (p = 0.003), and the cutoff value was 51.06 Gy (RBE); The AUC for D15 was 0.75 (p = 0.006), and the cutoff value was 42.82 Gy (RBE); The AUC for D20 was 0.74 (p = 0.009), and the cutoff value was 30.45 Gy (RBE); The AUC for Dmax was 0.81 (p < 0.001), and the cutoff value was 69.33 Gy (RBE). CONCLUSION: Male gender, weight loss, and total dose/fractions were significantly association with ROM. Dmax, D10, D15 and D20 were identified as the most valuable predictor and we suggest a Dmax limit of 69.33 Gy (RBE), D10 limit of 51.06 Gy (RBE), D15 limit of 42.82 Gy (RBE), and D20 limit of 30.45 Gy (RBE) and for oral mucosa.

Implementation of a light therapy team to administer photobiomodulation therapy: A standardized protocol to prevent and treat oral mucositis in the pediatric hematopoietic stem cell transplant population.

BACKGROUND: Oral mucositis (OM) is a painful and common complication of hematopoietic stem cell transplant (HSCT). The Children's Oncology Group recently published guidelines recommending photobiomodulation (PBM) for preventing and treating OM in pediatric HSCT patients. However, this is a rarely used intervention in pediatric hospitals. PROCEDURE: Patients undergoing allogeneic HSCT, or autologous HSCT for a neuroblastoma diagnosis, had PBM administered from the first day of conditioning to transplant Day +20. We successfully developed a standardized treatment protocol and workflow to ensure consistent and uniform delivery of PBM. In addition, clinical patient data were compared before and after PBM implementation. RESULTS: The administration of PBM at our center was feasible, but required dedicated staff. A registered nurse (RN) was determined to be the best fit to deliver PBM. Sixty-two patients received PBM from October 2022 to September 2023; patients from 2021 before PBM implementation were used for comparison. Patients receiving PBM were more likely (p = .03) to engage in teeth brushing (56/62 = 90%) compared to baseline (61/81 = 75%). Mean days of OM decreased from 11.3 to 9 days; patients who received PBM were less likely (p < .001) to be discharged on total parental nutrition (TPN) (11/62 = 18%) compared to baseline (50/82 = 61%). OM-related supportive care costs (TPN and patient-controlled anesthesia [PCA]) were lower (p = .02) for those who received PBM (median cost = $31,229.87 vs. $37,370.66). CONCLUSION: PBM, as the standard of care in the pediatric HSCT population, is safe, feasible, and well-tolerated. At our center, a dedicated RN was critical to providing standardized treatment and ensuring sustainability.

Photobiomodulation CME part II: Clinical applications in dermatology.

Photobiomodulation (PBM) is an emerging treatment modality in dermatology with increasing office and home-based use. PBM is the use of various light sources in the red light (620-700 nm) and near-infrared (700-1440 nm) spectrum as a form of light therapy. PBM is often administered through low-level lasers or light-emitting diodes. Studies show that PBM can be used effectively to treat conditions secondary to cancer therapies, alopecia, ulcers, herpes simplex virus, acne, skin rejuvenation, wounds, and scars. PBM offers patients many benefits compared to other treatments. It is noninvasive, cost-effective, convenient for patients, and offers a favorable safety profile. PBM can be used as an alternative or adjuvant to other treatment modalities including pharmacotherapy. It is important for dermatologists to gain a better clinical understanding of PBM for in-office administration and to counsel patients on proper application for home-use devices to best manage safety and expectations as this technology develops. PBM wavelengths can induce varied biological effects in diverse skin types, races, and ethnicities; therefore, it is also important for dermatologists to properly counsel their skin of color patients who undergo PBM treatments. Future clinical trials are necessary to produce standardized recommendations across conditions and skin types.

Oral Complications and Management Strategies for Cancer Patients: Principles of Supportive Oncology in Dentistry.

PURPOSE OF REVIEW: It is recognized that patients undergoing cancer treatment experience different adverse effects depending on the type of therapy they received. The objective of this work is to provide a scientific evidence-based protocol for oral care in cancer patients. Cancer resection surgery, chemotherapy, and radiotherapy can cause important complications that impact patients' quality of life. RECENT FINDINGS: Cancer patients, from the moment of diagnosis to the end of treatment and subsequent follow-up, have diverse care needs, both from a systemic and local point of view. The implementation of oral care protocols before, during, and after cancer therapy is essential because it helps to identify risk factors for the development of predictable oral complications. It is essential to establish that all cancer patients, before starting treatment, undergo a systematic dental check-up to avoid limitations during treatment and also alter their quality of life. Regular professional oral care maintenance and follow-up programs are essential to maintaining a patient's long-term oral health.

Oral Mucositis and Nutritional Status in Children Who Underwent Hematopoietic Cell Transplantation: A Comparison Between Nonmalignant and Malignant Primary Diseases.

BACKGROUND: There is a lack of studies analyzing the association between oral mucositis (OM) and nutritional imbalance in children during hematopoietic stem cell transplantation (HSCT). The aim of this study was to compare the risk factors for OM and nutritional imbalance during HSCT in pediatric patients with nonmalignant diseases (NMD) and malignant diseases (MD). METHODS: Data on age, sex, primary disease, transplantation type, conditioning regimen, GVHD prophylaxis, gastrointestinal toxicity, OM, percent body weight loss or gain, nutritional repositioning, and overall survival (OS) were retrospectively collected from the 132 medical records. The data were then compared between patients with NMD (n = 70) and MD (n = 62). RESULTS: OM had a similar severity between the groups. The primary risk factor for OM in the NMD group was the conditioning regimen with busulfan, while in the MD group it was GVHD prophylaxis with cyclosporin and methotrexate. OM did not have an impact on body weight loss or gain in any of the groups. In the NMD, body weight gain due to fluid overload was more pronounced and associated with a lower age range. OS was similar between the groups and was not affected by OM. CONCLUSIONS: OM pattern was similar in pediatric patients with or without MD, but the factors that determined these oral lesions were different. There were disparities in body weight changes between the two groups, and these changes were not associated to OM.

Association of oral mucositis induced by anthracycline-cyclophosphamide and subsequent docetaxel treatment for perioperative breast cancer.

PURPOSE: Anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy is effective for perioperative breast cancer treatment. However, these treatments frequently induce oral mucositis (OM), with an incidence ranging from 20 to 50%. The association of OM development between different chemotherapeutic treatments remains unclear. Consequently, this study aimed to compare OM development during docetaxel-containing chemotherapy between patients with and without OM experience during previous anthracycline-cyclophosphamide treatments to assess the association between OM development and treatment regimens. METHODS: Seventy-two patients with breast cancer receiving anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy as a perioperative treatment were categorized into the control (no prior OM experience with anthracycline-cyclophosphamide) and OM-experience (OM development during previous treatment) groups and retrospectively evaluated. The primary endpoint was the incidence of all-grade OM in the first docetaxel-containing chemotherapy cycle. Additionally, the incidences of OM and dysgeusia during all treatment cycles and factors associated with the incidence of OM were evaluated. RESULTS: The incidence of all-grade OM in the first cycle was significantly higher in the OM-experience group (54.2%) than in the control group (10.4%; P < 0.0001). Furthermore, its incidence in all treatment cycles was higher in the OM-experience group (66.7%) than in the control group (12.5%, P < 0.0001). However, the incidence of dysgeusia did not differ between the groups. Multivariate logistic regression analysis revealed OM experience during previous anthracycline-cyclophosphamide treatment and concomitant pertuzumab use as independent risk factors for OM development in subsequent docetaxel-containing chemotherapy. CONCLUSION: Our study suggests that patients experiencing OM with anthracycline-cyclophosphamide during perioperative breast cancer treatment exhibit symptoms following subsequent docetaxel-containing chemotherapy.

Single nucleotide polymorphisms conferring susceptibility to leukemia and oral mucositis: a multi-center pilot study of patients prior to conditioning therapy for hematopoietic cell transplant.

PURPOSE: Leukemias have been associated with oral manifestations, reflecting susceptibility to cancer therapy-induced oral mucositis. We sought to identify SNPs associated with both leukemia and oral mucositis (OM). METHODS: Whole exome sequencing was performed on leukemia and non-cancer blood disorder (ncBD) patients' saliva samples (N = 50) prior to conditioning therapy. WHO OM grading scores were determined: moderate to severe (OM2-4) vs. none to mild (OM0-1). Reads were processed using Trim Galorev0.6.7, Bowtie2v2.4.1, Samtoolsv1.10, Genome Analysis Toolkit (GATK)v4.2.6.1, and DeepVariantv1.4.0. We utilized the following pipelines: P1 analysis with PLINK2v3.7, SNP2GENEv1.4.1 and MAGMAv1.07b, and P2 [leukemia (N = 42) vs. ncBDs (N = 8)] and P3 [leukemia + OM2-4 (N = 18) vs. leukemia + OM0-1 (N = 24)] with Z-tests of genotypes and protein-protein interaction determination. GeneCardsSuitev5.14 was used to identify phenotypes (P1 and P2, leukemia; P3, oral mucositis) and average disease-causing likelihood and DGIdb for drug interactions. P1 and P2 genes were analyzed with CytoScape plugin BiNGOv3.0.3 to retrieve overrepresented Gene Ontology (GO) terms and Ensembl's VEP for SNP outcomes. RESULTS: In P1, 457 candidate SNPs (28 genes) were identified and 21,604 SNPs (1016 genes) by MAGMAv1.07b. Eighteen genes were associated with "leukemia" per VarElectv5.14 analysis and predicted to be deleterious. In P2 and P3, 353 and 174 SNPs were significant, respectively. STRINGv12.0 returned 77 and 32 genes (C.L. = 0.7) for P2 and P3, respectively. VarElectv5.14 determined 60 genes from P2 associated with "leukemia" and 11 with "oral mucositis" from P3. Overrepresented GO terms included "cellular process," "signaling," "hemopoiesis," and "regulation of immune response." CONCLUSIONS: We identified candidate SNPs possibly conferring susceptibility to develop leukemia and oral mucositis.

Effectiveness of intraoral stents in reducing oral adverse events during radiotherapy for maxillary or nasal cavity malignant tumors.

PURPOSE: Many patients experience oral adverse events during head and neck cancer radiotherapy (RT). The methods of management of such events are under debate. One such technique is the intraoral stent (IOS) technique, which removes normal tissue from the irradiation field. This retrospective study examined the factors associated with the occurrence of oral mucositis (OM) and dysgeusia and the efficacy of IOSs in preventing them. METHODS: Twenty-nine patients who underwent RT in the maxilla or nasal cavity between 2016 and 2022 were included. They were investigated for background characteristics, treatment factors (IOS and dose-volume histogram), and oral adverse events (OM and dysgeusia). RESULTS: Significant risk factors for the incidence of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) OM were the non-use of IOSs (p = 0.004) and diabetes (p = 0.025). A significant risk factor for the incidence of grade ≥ 1 dysgeusia was concomitant chemotherapy (p = 0.019). The radiation dose to the tongue was significantly lower in the IOS group than in the non-IOS group. CONCLUSION: Our findings suggest that the use of an IOS during RT reduces the severity of OM by reducing irradiation to the tongue. Therefore, the use of an IOS is recommended during RT performed in the maxilla or nasal cavity.

Might photobiomodulation therapy interfere with the frequency of severe mucositis and oral candidiasis? A retrospective analysis in patients with head and neck carcinoma.

PURPOSE: Considering the tumor in the oral cavity or the oropharynx and nasopharynx region might be an aggravating factor for oral mucositis (OM) manifestation, the present study aimed to evaluate whether the location of the tumor and the use of photobiomodulation therapy (PBMT) might affect the frequency of oral candidiasis (OC) during radiotherapy (RT) and/or chemotherapy (CT) treatments. METHODS: The medial records of seventy-four patients with head and neck cancer treated in a public service from 2016 to 2019 were evaluated. All these patients were submitted to RT in an accumulated dose of 48 to 70 Gy of radiation. Data about OM and OC were collected and presented according to the application of a therapeutic protocol with laser photobiomodulation (PBMT) to control oral mucositis, or not (No-PBM), and the location of tumor (head and neck or oral cavity). In the PBMT group patients, a low-power laser device composed of InGaAlP diode (maximum output power of 86.7 mW, active tip area of 0.1256 cm2, and continuous wavelength of 660 nm), was applied to the lips (three points each), right and left jugal mucosa (three points each), the limit between hard and soft palate (three points), buccal floor/sublingual gland (one point), lateral edge of the tongue (three points on each side), and back of the tongue (six points), three times weekly, for 5 weeks. The dosimetry used in each application was 2 J for 3 s, thus totaling 56 J. The correlation between clinical characteristics such as age, tumor size (T), metastatic lymph node (N), number of RT and CT sessions, candidiasis, and OM were analyzed. RESULTS: Mucositis grades 1 and 2 were the most common among all patients, especially before the 12th radiotherapy session, regardless of the treatment with PBM (p > 0.05). Additionally, no difference in the grade of OM and OC was significantly observed when comparing the two laser therapy groups. OC was more frequent after the 12th radiotherapy session in all groups. Nonetheless, OM and OC had a different correlation regarding to tumor location (head and neck and oral cavity) being PBMT a positive therapy to delay OM. It was observed a positive and statistically significant correlation between tumors at oral cavity and OM, regardless PBMT (R = 0.84, p < 0.05 to PBMT and R = 0.13, p < 0.05 to No-PBM). Otherwise, OC was positively correlated to local metastasis in patients with oral tumors undergoing PBMT (R = 0.84, p < 0.05). CONCLUSION: Patients with oral cavity tumor presented more OM, especially high grades, then patients with tumors in other regions of the head and neck, which seems to be related to the irradiation parameters of radiotherapy and/or with the limitation of conduction of PBMT in tumor areas. OM and OC were not changed by PBMT, although it helped to reduce the incidence of severe cases of OM.

Comparing the risk of severe oral mucositis associated with methotrexate as graft-versus host-disease prophylaxis to other immunosuppressive prophylactic agents in hematopoietic cell transplantation: a systematic review and meta-analysis.

PURPOSE: This study examines the risk of severe oral mucositis (SOM) in graft-versus-host disease prophylaxis (GVHD) compared to other agents in hematopoietic cell transplantation patients. METHODS: A comprehensive search of four databases, including PubMed, Embassy, Web of Science, and Scopus, was conducted to identify studies reporting frequency and severity of oral mucositis in association with GVHD prophylactic regimens. RevMan 5.4 was used to perform the meta-analysis. Risk of bias assessment was carried out using the Rob-2 tool for randomized clinical trials (RCTs) and ROBINS-I tool for observational studies. RESULTS: Twenty-five papers, including 11 RCTs and 14 observational studies, met the inclusion criteria. The pooled results from eight RCTs showed a higher risk of SOM in patients receiving MTX or MTX-inclusive GVHD prophylaxis versus non-MTX alternatives (RR = 1.50, 95% CI [1.20, 1.87], I2 = 36%, P = 0.0003). Mycophenolate mofetil (MMF) and post-transplant cyclophosphamide (Pt-Cy) consistently showed lower risk of mucositis than MTX. Folinic acid (FA) rescue and mini-dosing of MTX were associated with reduced oral mucositis severity. CONCLUSION: Patients receiving MTX have a higher SOM risk compared to other approaches to prevent GVHD, which should be considered in patient care. When appropriate, MMF, FA, and a mini-dose of MTX may be an alternative that is associated with less SOM. This work also underlines the scarcity of RCTs on MTX interventions to provide the best evidence-based recommendations.

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.

Critical appraisal of YouTube videos regarding peri-implant diseases and conditions: A cross-sectional analysis.

PURPOSE: To critically appraise the quality and reliability of YouTube videos regarding peri-implant diseases and conditions as a source of information for patients, students, and young clinicians. MATERIALS AND METHODS: In March 2023, electronic searches were performed on YouTube website to identify videos related to peri-implant diseases and conditions. We considered only the relevant 250 English-language videos with durations between 3 and 30 min for final analyses. Following the eligibility criteria videos were evaluated for their demographic data, including number of views; number of likes, dislikes, and comments; days since upload; duration; and number of subscribers. Moreover, two assessors independently evaluated the quality and reliability of the included videos using the DISCERN and Video Information and Quality Index (VIQI) tools. Statistical analyses were performed using the Kruskal-Wallis test and Spearman correlation analysis (∝ = 0.05). RESULTS: A total of 69 videos were included for profound analyses. The average DISCERN and VIQI scores were 35.04 ± 6.3 and 14.18 ± 2.46, with 53 videos categorized as "poor" quality using the DISCERN tool. A Spearman rank correlation analysis presented a strong agreement between the DISCERN and VIQI scores (r = .753; p < .001). Nevertheless, based on different sources of upload, no statistically significant differences were reported for video demographics, interaction index, and DISCERN and VIQI scores. CONCLUSIONS: Although YouTube videos on peri-implant diseases and conditions present accurate preliminary information, their reliability still remains uncertain. Hence, we urge respective policymakers to recognize, endorse and produce high-quality videos for accurate information dissemination.

The effect of one-time abutment placement on clinical and radiographic outcomes: A 5-year randomized clinical trial.

OBJECTIVE: The aim of this study was to evaluate the long-term (5 years) clinical efficacy of the one-abutment one-time protocol (test) versus the standard of care by placing the definitive abutment on the day of the prosthetic delivery (control). MATERIALS AND METHODS: In this study, 39 subjects with 60 implants were randomly allocated to either the test or the control group. Changes in the radiographic interproximal bone levels (DIB), modified sulcus bleeding index, probing depth, modified plaque index, papilla fill (Jemt score), incidence of peri-implantitis and peri-implant mucositis as well as patient-reported outcomes measures (PROMs) were collected and compared at 1, 3 and 5 years. RESULTS: At 5 years, the control group showed a greater, although not statistically significant, change in mean DIB values (0.97 mm vs. 0.53 mm). Regarding the other clinical parameters evaluated, no statistically significant differences were observed between groups at any time point. At 5 years, 51% of the implants presented peri-implant mucositis (25.5% in the control and 23.5% in the test), and only one implant in the test group developed peri-implantitis. CONCLUSIONS: The connection and disconnection of healing abutments during the healing period was not associated with higher long-term bone loss. Clinical outcomes and PROMs were similar between groups.