Characterization of dysgeusia and xerostomia in patients with multiple myeloma treated with the T-cell redirecting GPRC5D bispecific antibody talquetamab.

PURPOSE: In recent years, various immunotherapies have improved the survival of patients with multiple myeloma (MM). However, there remains an unmet need for novel agents. Talquetamab is the first-in-class GPRC5D-targeting T-cell redirecting bispecific antibody, which has substantial activity in advanced MM. Rapidly after the start of talquetamab treatment, patients reported taste changes (dysgeusia; 60% of patients), and a feeling of dry mouth (xerostomia; 30-57% of patients), which may be related to expression of the target antigen in healthy tissues, such as taste buds. Here, we aimed at better characterizing these oral toxicities. METHODS: We measured salivary flow and the ability to taste (objectively and patient-reported), assessed the feeling of dry mouth, and evaluated quality of life before and 8 weeks after the start of talquetamab therapy in eight heavily pretreated MM patients. RESULTS: Talquetamab treatment led to the rapid and significant decrease in objectively measured taste scores (total score 8.8 ± 2.0 vs 4.9 ± 2.5). All patients reported moderate to severe taste changes. Moreover, patients experienced severe xerostomia after the initiation of talquetamab treatment, in the absence of changes in unstimulated and stimulated salivary flow. Because of these oral toxicities a significant impairment in global health status/(oral health related) quality of life was reported. CONCLUSION: Studying taste changes in patients treated with talquetamab following up on the described leads provides a new and unique opportunity to further unravel the pathophysiology of taste changes after cancer treatment.

The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach.

BACKGROUND: Oral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score ≥ 2) or not (NON-OM). METHODS: In the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 weeks and 3 months after ASCT and compared these with pooled samples from 5 NON-OM patients. For the label-free analysis we analyzed saliva samples from 9 ULC-OM and 10 NON-OM patients at 6 different timepoints (including 12 months after ASCT) with Data-Independent Acquisition (DIA). As spectral library, all samples were grouped (ULC-OM vs NON-OM) and analyzed with Data Dependent Analysis (DDA). PCA plots and a volcano plot were generated in RStudio and differently regulated proteins were analyzed using GO analysis with g:Profiler. RESULTS: A different clustering of ULC-OM pools was found at baseline, weeks 2 and 3 after ASCT with TMT-labelled analysis. Using label-free analysis, week 1-3 samples clustered distinctly from the other timepoints. Unique and up-regulated proteins in the NON-OM group (DDA analysis) were involved in immune system-related processes, while those proteins in the ULC-OM group were intracellular proteins indicating cell lysis. CONCLUSIONS: The salivary proteome in ASCT recipients has a tissue protective or tissue-damage signature, that corresponded with the absence or presence of ulcerative oral mucositis, respectively. TRIAL REGISTRATION: The study is registered in the national trial register (NTR5760; automatically added to the International Clinical Trial Registry Platform).

[Oral chronic graft versus host disease, what is it and how is it treated?] / Orale chronische graft-versus-hostziekte, wat is het en hoe wordt het behandeld?

Allogeneic stem cell transplantation can cause chronic graft versus host disease (cGVHD). A number of patients manifest cGVHD in and around the mouth. It can present itself as clinically as mucosal lesions and/or salivary gland dysfunction and/or sclerotic changes. Cheeks and tongue are most commonly affected, but the palate, gingiva and lips can also be impacted. Oral cGVHD is associated with mucosal sensitivity, pain, (severe) oral dryness, altered taste, restricted mouth opening and difficulty swallowing, all of which may contribute to a significant decrease of the patient's quality of life. Patients also run an increased risk of developing squamous cell carcinoma of the oral mucosa. The diagnosis of cGVHD is almost always based on the patient's medical history and clinical picture. Treatment of symptoms is based on the patient's problem(s). Dental professionals can provide patients with supportive preventive care aimed at reducing symptoms and preventing further deterioration of oral health.

[Cross contamination: spatters, aerosols, and biofilm in dental practices]. / Kruiscontaminatie: spatten, aerosolen en biofilm in de mondzorgpraktijk.

During treatment in dental practices, drops of different sizes are produced (spats and aerosols). Microorganisms in these drops are of human origin or originate from the water in the dental unit. Therefore, these drops can contribute to cross contamination in dental practices. Large drops settle quickly, while smaller drops can remain suspended in the air for a longer period of time. The highest level of contamination is found in the immediate vicinity of the source (the patient's mouth). Further away from the source and after stopping drop producing activities, the level of contamination in the air is comparable to control circumstances. Studies into the spread of viruses via this route in the dental practice have not yet been conducted. The risk of catching an infectious disease in the dental practice seems limited, but can be high in the case of a virulent microorganism, when the circumstances for spread of the virus are favorable, or if the recipient is immunocompromised.

Significant salivary changes in relation to oral mucositis following autologous hematopoietic stem cell transplantation.

The aim of this multicentre, longitudinal study was to determine salivary changes in relation to oral mucositis (OM) in multiple myeloma patients following high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT). Unstimulated and stimulated whole-mouth saliva samples (UWS and SWS) were collected before ASCT, 1×/wk during the hospitalisation phase, and 3 and 12 months post-ASCT. During the hospitalisation period OM was scored 3×/wk (WHO system). Flow rate, pH, total protein concentration (Nanodrop), albumin, lactoferrin, neutrophil defensin-1 (HNP1), total IgA and S100A8/A9 (ELISA) were determined. Mixed models were used to evaluate differences between ulcerative (u)OM (≥2 WHO, n = 20) and non-uOM (n = 31) groups. Until 18 days after ASCT, flow rate, pH, total IgA and HNP1 levels decreased in UWS and/or SWS, while log lactoferrin levels were significantly increased (UWS: p = 0.016 95% CI [0.36, 3.58], SWS: p < 0.001 95% CI [1.14, 3.29]). Twelve months post-ASCT, salivary protein levels were similar to baseline except for log total IgA, which was higher (UWS: p < 0.001 95% CI [0.49, 1.29], SWS: p < 0.001 95% CI [0.72, 1.45]). No differences between uOM and non-uOM groups were observed. Changes in salivary proteins indicated an inflammatory reaction in salivary glands coinciding with mucosal and systemic reactions in response to high-dose melphalan.

Modeling of the Transmission of Coronaviruses, Measles Virus, Influenza Virus, Mycobacterium tuberculosis, and Legionella pneumophila in Dental Clinics.

Dental health care workers are in close contact to their patients and are therefore at higher risk for contracting airborne infectious diseases. The transmission rates of airborne pathogens from patient to dental health care workers are unknown. With the outbreaks of infectious diseases, such as seasonal influenza, occasional outbreaks of measles and tuberculosis, and the current pandemic of the coronavirus disease COVID-19, it is important to estimate the risks for dental health care workers. Therefore, the transmission probability of these airborne infectious diseases was estimated via mathematical modeling. The transmission probability was modeled for Mycobacterium tuberculosis, Legionella pneumophila, measles virus, influenza virus, and coronaviruses per a modified version of the Wells-Riley equation. This equation incorporated the indoor air quality by using carbon dioxide as a proxy and added the respiratory protection rate from medical face masks and N95 respirators. Scenario-specific analyses, uncertainty analyses, and sensitivity analyses were run to produce probability rates. A high transmission probability was characterized by high patient infectiousness, the absence of respiratory protection, and poor indoor air quality. The highest transmission probabilities were estimated for measles virus (100%), coronaviruses (99.4%), influenza virus (89.4%), and M. tuberculosis (84.0%). The low-risk scenario leads to transmission probabilities of 4.5% for measles virus and 0% for the other pathogens. From the sensitivity analysis, it shows that the transmission probability is strongly driven by indoor air quality, followed by patient infectiousness, and the least by respiratory protection from medical face mask use. Airborne infection transmission of pathogens such as measles virus and coronaviruses is likely to occur in the dental practice. The risk magnitude, however, is highly dependent on specific conditions in each dental clinic. Improved indoor air quality by ventilation, which reduces carbon dioxide, is the most important factor that will either strongly increase or decrease the probability of the transmission of a pathogen.

Heterogeneity in the efficacy of dental chemical disinfectants on water-derived biofilms in vitro.

Conditions in dental unit waterlines are favourable for biofilm growth and contamination of dental unit water. The aim of this study was to assess the effect of several chemical disinfectants on bacteria in a biofilm model. Water-derived biofilms were grown in a static biofilm model (Amsterdam Active Attachment model), using two growth media. Biofilms were challenged with Alpron/Bilpron, Anoxyl, Citrisil, Dentosept, Green & Clean, ICX and Oxygenal in shock dose and maintenance doses. The concentration and the composition of the chemical disinfectants influenced the number of culturable bacteria in the biofilms. The application of a single shock dose followed by a low dose of the same chemical disinfectants resulted in the greatest suppression of viable bacteria in the biofilms. Exposure to Citrisil and ICX consistently resulted in failure to control the biofilms, while Alpron/Bilpron had a substantial and relevant effect on the number of bacteria in the biofilms.

Dental aerosols: microbial composition and spatial distribution.

Background: High-speed dental instruments produce aerosols, which can contribute to the transmission of pathogenic microorganisms. The aim of this study is to describe the microbial load and - composition and spatial distribution of aerosols in dental clinics. Methods: In four dental clinics active and passive sampling methods were used before, during and after treatment and at different locations. Retrieved colony forming units (CFU) were sequenced for taxon identification. Results: The samples contained up to 655 CFU/plate/30 minutes and 418 CFU/m3/30 minutes during dental treatment for active and passive sampling, respectively. The level of contamination after treatment and at 1.5 m distance from the patient's head was similar to the start of the day. The highest contamination was found at the patient's chest area. The aerosols consisted of 52 different taxa from human origin and 36 from water. Conclusion: Contamination in dental clinics due to aerosols is mainly low, although high level of contamination with taxa from both human and water origin was found within 80 cm around the head of the patient. Our results stress the importance of infection control measures on surfaces in close proximity to the head of the patient as well as in dental water lines.

[Oral graft-versus-host-disease: implications for dental professionals]. / Orale graft-versus-hostziekte: implicaties voor mondzorgverleners.

Graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transpl antation, which frequently affects the mouth. GVHD is the result of an immunological attack of donor-derived cells against the tissue of patients. Chronic oral GVHD can affect the mucosa and/or damage salivary glands and can cause sclerotic changes to the head and neck area. Patients can experience painful oral and gingival mucosa, dry mouth, taste changes and limited mouth opening. Due to painful mucosa and salivary glands, and limited mouth opening, performing oral hygiene and dental interventions can be difficult. Immunosuppression in combination with altered salivary production increases the risk of secondary infectious complications, such as dental caries and candida infections. Dental professionals can play an important role in the prevention of oral complications.

[Implementation of effective infection control: furnishing a -dental practice]. / Infectiepreventie in de praktijk ­ het inrichten van de tandartspraktijk.

The increasing resistance to antibiotics and the aging of the population of patients who visit the dental practice can lead to more frequent infections with (resistant) microorganisms. The prevention of cross contamination by the implementation of effective measures in the area of hygiene and procedures of infection control is therefore important. The furnishing of a dental practice can play an important part in prevention. What are the important issues in furnishing a practice? A distinction is made between 'critical' and 'non-critical' rooms. Patients are only treated and instruments are only prepared for reuse in critical rooms. In these rooms, a strict separation is maintained between clean and contaminated, in both place and time. Only furniture that is strictly necessary for the treatment of patients is present in the critical rooms. Materials and equipment that are kept within the splatter area must be stored as much as possible in drawers and closed cabinets. Water taps can be controlled in a touch-free manner and are located within the present walking routes of the practice.

Healthcare-associated viral and bacterial infections in dentistry.

Infection prevention in dentistry is an important topic that has gained more interest in recent years and guidelines for the prevention of cross-transmission are common practice in many countries. However, little is known about the real risks of cross-transmission, specifically in the dental healthcare setting. This paper evaluated the literature to determine the risk of cross-transmission and infection of viruses and bacteria that are of particular relevance in the dental practice environment. Facts from the literature on HSV, VZV, HIV, Hepatitis B, C and D viruses, Mycobacterium spp., Pseudomonas spp., Legionella spp. and multi-resistant bacteria are presented. There is evidence that Hepatitis B virus is a real threat for cross-infection in dentistry. Data for the transmission of, and infection with, other viruses or bacteria in dental practice are scarce. However, a number of cases are probably not acknowledged by patients, healthcare workers and authorities. Furthermore, cross-transmission in dentistry is under-reported in the literature. For the above reasons, the real risks of cross-transmission are likely to be higher. There is therefore a need for prospective longitudinal research in this area, to determine the real risks of cross-infection in dentistry. This will assist the adoption of effective hygiene procedures in dental practice.

Viral loads and antiviral resistance of herpesviruses and oral ulcerations in hematopoietic stem cell transplant recipients.

Ulcerative oral mucositis and infection are frequent complications in hematopoietic stem cell transplant (HSCT) recipients. The aim of this study was to investigate the relationship between oral ulcerations and HSV-1, EBV and CMV excretion and the presence of aciclovir-resistant HSV-1 strains in HSCT recipients. This prospective observational study included 49 adult patients who underwent allogeneic HSCT. In total, 26 patients received myeloablative and 23 received non-myeloablative conditioning. Ulcerations on non-keratinized and keratinized oral mucosa were scored and oral rinsing samples were taken twice weekly. Viral loads were determined by real-time PCR. Samples from patients remaining HSV-1 positive despite antiviral treatment were studied for resistance to antivirals. Having an HSV-1 or EBV DNA-positive sample was a significant predictor for ulceration of keratinized mucosa. HSV-1 was a significant predictor for ulcerations on non-keratinized mucosa as well. Persistent HSV-1 infection occurred in 12 of 28 patients treated with antiviral medication and aciclovir-resistant HSV-1 was found in 5 persistent infections. In conclusion, HSV-1 is a predictor of ulcerations on non-keratinized as well as keratinized oral mucosa following HSCT. The role of EBV deserves further study. Persistent HSV-1 replication despite antiviral treatment is common and is due to resistance in 18% of treated patients.

In situ remineralisation of enamel and dentin after the use of an amine fluoride mouthrinse in addition to twice daily brushings with amine fluoride toothpaste.

It is often claimed that 3 fluoride moments a day significantly reduce the caries risk compared to 2 daily fluoride moments. However, previous research is not conclusive. Therefore, the aim of this study was to compare the effect on lesion progression of 2 versus 3 fluoride moments a day. A double-blind, randomized, cross-over in situ experiment was designed. The experiment comprised 2 in situ periods of 3 weeks with a washout period of 3 weeks in between. Sixteen participants wore an enamel and a dentine specimen with a preformed lesion placed buccally in their partial prosthesis. The participants brushed twice a day with a 1,400 ppm F (amine fluoride) toothpaste and rinsed once a day with either 250 ppm F (amine F/NaF) or a placebo rinse. At the end of the experiment the specimens were retrieved for fluoride analysis and the assessment of integrated mineral loss with transversal microradiography. The fluoride analysis showed a statistically significant increase in structurally bound fluoride in dentine, but not in enamel, when comparing the fluoride mouthrinse group with the placebo rinse group. The amounts of loosely bound, KOH-soluble fluoride were not different between both groups neither for enamel nor for dentine. In dentine IML gain was significantly (p < 0.05) higher for the fluoride mouthrinse group than for the placebo mouthrinse group. In enamel no statistically significant differences in IML gain were found. For dentine a third fluoride moment may be beneficial in enhancing remineralisation, even under the remineralising conditions as in this study.