Salivary antioxidant enzymes associated with oral toxicity in haematopoietic cell transplantation: An observational study.

BACKGROUND: In haematopoietic cell transplantation (HCT), oral mucositis and xerostomia are related to conditioning-related oxidative stress. The role of salivary antioxidant enzymes in oral toxicity is poorly described. The aim of this study was to verify the association between salivary antioxidant enzymes and oral mucositis and xerostomia in HCT. DESIGN: Saliva from autologous and allogeneic HCT patients (n = 77) was selected before conditioning (T0), during the neutropenia period (T1) and after marrow engraftment (T2). Salivary flow, total salivary proteins, and superoxide dismutase, catalase and glutathione reductase activities were measured. RESULTS: There were no significant differences in salivary flow, total salivary proteins and catalase at the three HCT time points. Glutathione reductase levels were reduced at T1 compared to T0 (P = .013) and T2 (P = .001). Superoxide dismutase levels were increased from T0 to T2 (P = .013). Neither of these enzymes was associated with oral mucositis. Increased superoxide dismutase levels were associated with xerostomia frequency. Levels of this enzyme also showed significant correlation with days of xerostomia in T2 (ρ = .40, P = .002). CONCLUSIONS: Salivary antioxidant enzymes changed before and during early periods after HCT. The increase in salivary superoxide dismutase suggested partial activation of the salivary antioxidant system and was associated with xerostomia.

Long-term safety of photobiomodulation therapy for oral mucositis in hematopoietic cell transplantation patients: a 15-year retrospective study.

Photobiomodulation therapy (PBMT) has demonstrated efficacy in the prevention and treatment of oral mucositis (OM) in hematopoietic cell transplantation (HCT). However, based on the cell stimulation properties, its long-term safety has been questioned, mainly in relation to risk for secondary malignancies in the oral cavity. The aim of this study was to investigate if different PBMT protocols for OM control have association with immediate and late adverse effects in HCT patients. Data on autologous and allogeneic transplantation, conditioning regimen, PBMT protocols, and OM severity were retrospectively collected from medical and dental records. Presence of secondary malignancies in the oral cavity was surveyed during a 15-year follow-up. Impact of OM on overall survival was also analyzed. Different PBMT protocols for prevention and treatment of OM were recorded over the years. Severe OM (grades 3 and 4) was infrequently observed. When present, we observed a significant decrease of the overall survival. No immediate adverse effect and secondary malignancy was associated to PBMT. In conclusion, the PBMT protocols used in the study were considered safe. The low frequency of severe OM observed encourages the implementation of this technique, with a special emphasis on the dosimetry adjustments focused on the HCT context.

Impact of Oral and Gastrointestinal Mucositis on Body Weight Alterations during Hematopoietic Stem Cell Transplantation.

The aim of this study was to evaluate whether digestive tract mucositis is a predictive factor for body weight (BW) alterations during hematopoietic stem cell transplantation (HSCT). Data about characteristics of transplantation, initial nutritional conditions and gastrointestinal mucositis were collected from adult patients (n = 105) who underwent autologous and allogeneic HSCT. Oral mucositis (OM) was not a predictive factor for BW loss, but it was an independent factor for BW gain in autologous HSCT (ß = 0.329, P = 0.021). Busulfan-fludarabine conditioning regimen (ß = 1.531, P = 0.011) and gender (ß = 1.109, P = 0.038) were significant independent risk factors for BW loss in allogeneic HSCT. Overall survival (OS) was significantly affected by the duration of OM in autologous HSCT (HR = 1.243, P = 0.008). In allogeneic HSCT, BW loss (HR = 1.308, P = 0.049) and diarrhea (HR = 1.139, P = 0.012) interfered significantly with OS. In conclusion, OM was not a risk factor for BW loss, but it influenced BW gain and had a negative impact on OS in autologous HSCT patients. Intestinal mucositis explained partially the BW loss and had a negative impact on OS in allogeneic HSCT.

Oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation: clinical outcomes in a context of specialized oral care using low-level laser therapy.

OM is a painful inflammatory condition of the oral mucosa, derived from the toxic effects of chemotherapy and radiotherapy. High OM severity is frequently present in HSCT pediatric patients, who exhibit multiple painful ulcers that limit their mastication and swallowing, leading to poor nutritional status. Few studies have demonstrated OM clinical outcomes in young patients undergoing HSCT. Feasibility of oral care and LLLT on OM prophylaxis and treatment is also poorly discussed. The aim of this study was to describe a specialized oral care protocol that included LLLT for pediatric patients undergoing transplantation and to demonstrate the clinical outcomes after OM prevention and treatment. Data from OM-related morbidity were collected from 51 HSCT pediatric patients treated daily with LLLT, followed by standard oral care protocols. All the patients, even infants and young children, accepted the daily oral care and LLLT well. The majority (80.0%) only exhibited erythema in the oral mucosa, and the maximum OM degree was WHO II. Patients who had undergone autologous and HLA-haploidentical transplants showed OM with the lowest severity. The frequency of total body irradiation and methotrexate prescriptions was higher in adolescents when compared with infants (p = 0.044), and adolescents also exhibited OM more severely than infants and young children. We found that good clinical outcomes were obtained using this therapy, mainly in regard to the control of OM severity and pain reduction in the oral cavity. Specialized oral care, including LLLT, is feasible and affordable for HSCT pediatric patients, although some adaptation in the patient's oral hygiene routine must be adopted with help from parents/companions and clinical staff.

Antimicrobial oral lavage reduces the SARS-CoV-2 load in intubated patients: randomized clinical trial.

Background: The oral cavity can be a reservoir for SARS-CoV-2 and may play a crucial role in the viral transmission in the hospital environment. Objective: To investigate whether an oral hygiene protocol with chlorhexidine (CHX) used alone and in combination with hydrogen peroxide (HP) in the intensive care unit was effective in reducing the SARS-CoV-2 viral load in the oral cavity. Methods: SARS-CoV-2 viral load was measured on oral fluid samples collected from patients undergoing orotracheal intubation. The study sample was randomly in: CHX group (n = 19) - oral rinse using only 0.12% CHX solution; HP+CHX group (n = 24) - oral rinse with 1.5% HP and 0.12% CHX. The samples were collected before the interventions (T0), immediately (T1), 30 minutes (T2) and 60 minutes (T3) after the procedure. Results: A significant viral load reduction was observed at T1 (mean ± SD:-0.57 ± 0.19 log10;-73.2%;p = 0.022) in the HP+CHX group. No statistically significant differences between any time points were observed in the CHX group. Conclusion: The HP+CHX oral rinses significantly reduced the SARS-CoV-2 viral load in the oral fluid immediately after the procedure. The CHX oral rinse alone did not result in any significant viral load reductions.

Dentistry consensus on HSCT - Part III: Special topics - Dentistry on HSCT.

Patients undergoing hematopoietic stem cell transplantation (HSCT) might present acute and late toxicities and the oral tissues are frequently affected. With the survival increasing, patients show late and long-term morbidities, and there is an important association between the general and the oral health. The first and second parts of this Consensus have showed the importance of the adequacy of oral health in the pre-HSCT, and the main alterations and oral care during the period of admission for HSCT. This third part aims to review specific themes of post-HSCT dental care, such as graft-versus-host disease (GVHD) and the pediatric patient. It also aims to review pertinent subjects, both during the HSCT period and post-HSCT, concerning quality of life, pain, cost-effectiveness, and remote care. Based on this review, it is evident the importance of the work of the dental surgeon (DS) in the follow-up and treatment of the HSCT patient, always collaborating with the whole multidisciplinary team.

Brazilian dental consensus on dental management in hematopoietic stem cell transplantation - Part I - pre-HSCT.

The oral involvement in the Hematopoietic Stem Cell Transplantation is well described in the literature. The goal of the dental treatment and management of the oral lesions related to the HSCT is to reduce the harm caused by preexisting oral infection or even the worsening of oral acute/chronic GVHD and late effects. The aim of this guideline was to discuss the dental management of patients subjected to HSCT, considering three phases of the HSCT: pre-HSCT, acute phase, and late phase. The literature published from 2010 to 2020 was reviewed in order to identify dental interventions in this patient population. The selected papers were divided into three groups: pre-HSCT, acute and late, and were reviewed by the SBTMO Dental Committee's members. When necessary, an expertise opinion was considered for better translating the guideline recommendations to our population dental characteristics. This manuscript focused on the pre-HSCT dental management. The objective of the pre-HSCT dental management is to identify possible dental situations that can worsening during the acute phase after the HSCT. Each guideline recommendations were made considering the Dentistry Specialties. The clinical consensus on dental management prior to HSCT provides professional health caregivers with clinical setting-specific information to help with the management of dental problems in patients to be subjected to HSCT.

Dental consensus on HSCT - Part II: dental Care during HSCT.

During the state of immune vulnerability in hematopoietic stem cell transplantation (HSCT), the patient has an increased risk of developing a vast number of complications, including severe problems in the oral cavity. These situations require professional oral care to act in the diagnosis and treatment of these conditions, as well as to develop prevention protocols to minimize patient's complications. Oral mucositis, opportunistic infections, bleeding, specific microbiota, taste, and salivary alterations are complications that can occur during HSCT and interfere with various aspects, such as pain control, oral intake, nutrition, bacteremia and sepsis, days of hospitalization and morbidity. Several guidelines have been published to address the role of professional oral care during the HSCT, we describe a consensus regarding these recommendations.

Severe oral ulcerative and lichenoid lesions associated with adrenal insufficiency in a patient treated with nivolumab: Report of a case and review of literature.

Nivolumab, an antibody against anti-programmed death type 1, has been used for treatment of advanced non-small cell lung cancer with improvement of overall survival. Usually, diarrhea, cutaneous rash, and pruritus are reported as the most common immune-related adverse effects of nivolumab therapy. Oral lesions and secondary adrenal insufficiency sometimes occur but usually are rare events. We report a case of a patient treated with nivolumab who then showed persistent oral ulcerative and lichenoid lesions, which were refractory to topical corticosteroids. The oral lesions were concomitant to nivolumab-induced adrenal insufficiency. These adverse events led to nivolumab discontinuation, which favored oral lesion healing and adrenal insufficiency remission. Through a brief review of the literature concerning nivolumab toxicity in the oral cavity, we discuss the clinical aspect and management of these lesions.

Oral ulcers and sarcoid-like reaction in lymph nodes after cemiplimab therapy for locally advanced cutaneous squamous cell carcinoma: a case report.

Cemiplimab is a novel programmed death-1 inhibitor recently approved for advanced cutaneous squamous cell carcinoma. Immune-related adverse events derived from cemiplimab are similar to other anti-PD-1 drugs, including gastrointestinal and cutaneous toxicities. Oral immune-related adverse events were not reported with cemiplimab in previous studies; thus this case report warns of the fact that the oral cavity may be a site of immune-related adverse events during programmed death-1 block therapy and that this can lead to significant limitations when not properly treated. The present report describes the case of a patient with locally advanced cutaneous squamous cell carcinoma metastatic to cervical lymph nodes who developed dysphagia due to large and painful oral ulcers after a single dose of cemiplimab. The patient also exhibited a sarcoid-like reaction in mediastinal lymph nodes. No immune-related adverse events were found in any other organs. The oral lesions showed significant improvement after topical and short-course systemic corticosteroids, and low-level laser therapy was also performed in the oral lesions. The patient achieved a near-complete response and treatment was discontinued. This article discusses in detail the clinical outcomes and oral toxicity management of cemiplimab therapy for cutaneous squamous cell carcinoma.

Oral lesions and saliva alterations of COVID-19 patients in an intensive care unit: A retrospective study.

AIM: To detect the type and frequency of oral lesions and clinical conditions suggestive of saliva alterations in COVID-19 patients in an intensive care unit (ICU), as well as to describe the patient´s management in each case METHODS: Information about oral conditions and mechanical ventilation was collected from oral medicine records of COVID-19 patients in an ICU (n = 519) RESULTS: From the total collected, 472 patients (90.9%) were examined by the oral medicine staff. In 242/472 patients (51.3%), alterations in the oral cavity were noted. The most frequent changes were mechanical trauma (18.1%, derived mainly from intubation), vascular/coagulation disturbances (24.1%, petechiae, bruises, varicoses, and oral bleeding), and saliva alterations (24.4%, dry mouth, and sialorrhea). Infectious lesions were mentioned in the oral medicine records (16.9%), most associated with a viral infection (15.7%), mainly herpesvirus. Improved oral change protocols included oral hygiene, use of specific medications, and laser therapy CONCLUSION: COVID-19 patients in the ICU often showed dryness in the oral and mucosa oral lesions related to vascular/coagulation disturbances, and mechanical trauma derived from orotracheal tube. An oral medicine staff must be aligned with the ICU multidisciplinary team to manage COVID-19 patients, as well as to establish diagnoses and oral cavity treatments.

Special care in dental curriculum: A transversal axis for integrating oral health with systemic health.

AIMS: Distance between dentistry and medicine is a traditional and historical obstacle that affects multiple levels of the health system, especially the health policies to improve health service quality. Changes in dental education, especially involving the adoption of integrative health models in professional development, are considered essential for reducing this gap. We aimed to show a dental curriculum focused on special care as a tool for medicine-dentistry integration. METHODS: In this study, we present a new proposal for an undergraduate dental curriculum in which topics related to special care are addressed transversally and are the core for interdisciplinary integration of oral health with systemic health. We also describe how themes related to dental home care and hospital dentistry were included in this course as basic professional competencies. RESULTS AND CONCLUSION: This initiative is aligned with the global trend to adopt educational systems that contribute to the reduction of health care inequalities and improve health service quality.

Salivary SARS-CoV-2 load reduction with mouthwash use: A randomized pilot clinical trial.

The saliva of patients with COVID-19 has a high SARS-CoV-2 viral load. The risk of spreading the virus is high, and procedures for viral load reduction in the oral cavity are important. Little research to date has been performed on the effect of mouthwashes on the salivary SARS-CoV-2 viral load. This pilot randomized single-center clinical trial investigated whether three types of mouthwash with solutions containing either 0.075% cetylpyridinium chloride plus 0.28% zinc lactate (CPC + Zn), 1.5% hydrogen peroxide (HP), or 0.12% chlorhexidine gluconate (CHX) reduce the SARS-CoV-2 viral load in saliva at different time points. Sixty SARS-CoV-2-positive patients were recruited and randomly partitioned into a placebo (oral rinsing with distilled water) group and other groups according to the type of mouthwash. Saliva samples were collected from the participants before rinsing (T0), immediately after rinsing (T1), 30 min after rinsing (T2), and 60 min after rinsing (T3). The salivary SARS-CoV-2 viral load was measured by qRT-PCR assays. Rinsing with HP and CPC + Zn resulted in better reductions in viral load, with 15.8 ± 0.08- and 20.4 ± 3.7-fold reductions at T1, respectively. Although the CPC + Zn group maintained a 2.6 ± 0.1-fold reduction at T3, this trend was not observed for HP. HP mouthwash resulted in a significant reduction in the SARS-CoV-2 viral load up to 30 min after rinsing (6.5 ± 3.4). The CHX mouthwash significantly reduced the viral load at T1, T2, and T3 (2.1 ± 1.5-, 6.2 ± 3.8-, and 4.2 ± 2.4-fold reductions, respectively). In conclusion, mouthwash with CPC + Zinc and CHX resulted in significant reductions of the SARS-CoV-2 viral load in saliva up to 60 mins after rinsing, while HP mouthwash resulted in a significant reduction up to 30 mins after rinsing. Despite this transitory effect, these results encourage further studies and suggest that these products could be considered as risk-mitigation strategies for patients infected with SARS-CoV-2.

Dental consensus on HSCT - Part II: dental Care during HSCT

ABSTRACT During the state of immune vulnerability in hematopoietic stem cell transplantation (HSCT), the patient has an increased risk of developing a vast number of complications, including severe problems in the oral cavity. These situations require professional oral care to act in the diagnosis and treatment of these conditions, as well as to develop prevention protocols to minimize patient's complications. Oral mucositis, opportunistic infections, bleeding, specific microbiota, taste, and salivary alterations are complications that can occur during HSCT and interfere with various aspects, such as pain control, oral intake, nutrition, bacteremia and sepsis, days of hospitalization and morbidity. Several guidelines have been published to address the role of professional oral care during the HSCT, we describe a consensus regarding these recommendations.

Brazilian dental consensus on dental management in hematopoietic stem cell transplantation− Part I− pre-HSCT

ABSTRACT The oral involvement in the Hematopoietic Stem Cell Transplantation is well described in the literature. The goal of the dental treatment and management of the oral lesions related to the HSCT is to reduce the harm caused by preexisting oral infection or even the worsening of oral acute/chronic GVHD and late effects. The aim of this guideline was to discuss the dental management of patients subjected to HSCT, considering three phases of the HSCT: pre-HSCT, acute phase, and late phase. The literature published from 2010 to 2020 was reviewed in order to identify dental interventions in this patient population. The selected papers were divided into three groups: pre-HSCT, acute and late, and were reviewed by the SBTMO Dental Committee's members. When necessary, an expertise opinion was considered for better translating the guideline recommendations to our population dental characteristics. This manuscript focused on the pre-HSCT dental management. The objective of the pre-HSCT dental management is to identify possible dental situations that On behalf of the Dental Committee of the Brazilian Society of Gene Therapy and Bone Marrow Transplantation (SBTMO) can worsening during the acute phase after the HSCT. Each guideline recommendations were made considering the Dentistry Specialties. The clinical consensus on dental management prior to HSCT provides professional health caregivers with clinical setting-specific information to help with the management of dental problems in patients to be subjected to HSCT.

Dentistry consensus on HSCT - Part III: Special topics - Dentistry on HSCT

ABSTRACT Patients undergoing hematopoietic stem cell transplantation (HSCT) might present acute and late toxicities and the oral tissues are frequently affected. With the survival increasing, patients show late and long-term morbidities, and there is an important association between the general and the oral health. The first and second parts of this Consensus have showed the importance of the adequacy of oral health in the pre-HSCT, and the main alterations and oral care during the period of admission for HSCT. This third part aims to review specific themes of post-HSCT dental care, such as graft-versus-host disease (GVHD) and the pediatric patient. It also aims to review pertinent subjects, both during the HSCT period and post-HSCT, concerning quality of life, pain, cost-effectiveness, and remote care. Based on this review, it is evident the importance of the work of the dental surgeon (DS) in the follow-up and treatment of the HSCT patient, always collaborating with the whole multidisciplinary team.

Oral ulcers and sarcoid-like reaction in lymph nodes after cemiplimab therapy for locally advanced cutaneous squamous cell carcinoma: a case report

ABSTRACT Cemiplimab is a novel programmed death-1 inhibitor recently approved for advanced cutaneous squamous cell carcinoma. Immune-related adverse events derived from cemiplimab are similar to other anti-PD-1 drugs, including gastrointestinal and cutaneous toxicities. Oral immune-related adverse events were not reported with cemiplimab in previous studies; thus this case report warns of the fact that the oral cavity may be a site of immune-related adverse events during programmed death-1 block therapy and that this can lead to significant limitations when not properly treated. The present report describes the case of a patient with locally advanced cutaneous squamous cell carcinoma metastatic to cervical lymph nodes who developed dysphagia due to large and painful oral ulcers after a single dose of cemiplimab. The patient also exhibited a sarcoid-like reaction in mediastinal lymph nodes. No immune-related adverse events were found in any other organs. The oral lesions showed significant improvement after topical and short-course systemic corticosteroids, and low-level laser therapy was also performed in the oral lesions. The patient achieved a near-complete response and treatment was discontinued. This article discusses in detail the clinical outcomes and oral toxicity management of cemiplimab therapy for cutaneous squamous cell carcinoma.

Peripheral Calcifying Epithelial Odontogenic Tumour Mimicking a Gingival Inflammation: A Diagnostic Dilemma.

The calcifying epithelial odontogenic tumour (CEOT) is an extremely rare benign neoplasia, accounting for approximately 1% of all odontogenic tumours. CEOT can have two clinical manifestations: central or intraosseous (94% of the cases) and peripheral or extraosseous (6% of the cases). Although the latter is less common, the peripheral variant has been described as an insidious lesion, since it is usually asymptomatic and may be erroneously mistaken with gingival hyperplasia, hamartomas, or even metastasis of malignant neoplasia. We report a case of a young male patient presenting with a peripheral CEOT in the mandibular posterior region, mimicking a located gingival inflammation.