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A broader understanding of oral and ocular late effects in head and neck cancer (HNC) patients who underwent intensity-modulated radiotherapy (IMRT) may provide valuable information in follow-up and improve quality of life. Twenty-nine HNC patients treated at least 6 months earlier and 30 age-matched controls were recruited. After completing several questionnaires: Oral Health Impact Profile-14 (OHIP-14), Shortened Xerostomia Inventory (SXI), Ocular Surface Disease Index (OSDI) and McMonnies Dry Eye questionnaire (MDEQ), participants underwent oral and ocular examinations. Oral examination included clinical oral dryness score (CODS) and secretion rates of unstimulated and stimulated saliva (UWS, SWS). Ocular examination included tear film break-up time, Schirmer test and ocular surface staining. The patients had more problems related to dry mouth than controls based on CODS and SXI, and more complaints of dry eye disease based on OSDI and MDEQ. UWS and SWS rates and oral health related quality of life were significantly lower in the patient group. Subjective oral dryness (SXI) correlated significantly with subjective ocular dryness (OSDI and MDEQ). Our study demonstrates that HNC patients treated with IMRT experience late effects in terms of xerostomia and ocular dryness underlining the importance of interdisciplinary approach in the evaluation and follow-up of HNC patients.

Patients undergoing intensity-modulated radiotherapy (IMRT) for head and neck cancer may have increased incidence of dry eye disease and the exact mechanism is unclear. The present study aims to assess tear film and meibomian gland (MG) features in patients who received IMRT for head and neck cancer not involving the orbital area. Twenty-seven patients (64.7 ± 9.8 years) and 30 age-matched controls (61.4 ± 11.0 years) underwent a comprehensive dry eye work-up. Compared to the control group, the patients had more lid margin abnormalities, and worse meibum quality. The MG loss, calculated as (tarsal area-MG area)/tarsal area, was higher in the patient group in both the upper (53.0 ± 12.0% vs. 35.1 ± 10.3%, p < 0.001) and lower lids (69.5 ± 12.6% vs. 48.5 ± 12.5%, p < 0.001). In the patient group, more MG loss in the lower lids correlated with worse meibum quality (r = 0.445, p = 0.029). In contrast, there was no significant difference in aqueous tear production level, measured with Schirmer test. Patients treated with IMRT for head and neck cancer seemed to have comparable lacrimal gland function to the controls despite more dry eye symptoms. However, the patients had MG functional and morphological changes, which may present a higher risk for developing dry eye disease.

Investigating cytokines in tear fluid and saliva may offer valuable information for understanding the pathogenesis of primary Sjögren’s syndrome (pSS). Cytokine profiles in both tear fluid and saliva of pSS patients, non-Sjögren’s syndrome (non-SS) subjects with sicca symptoms, and healthy controls without sicca complaints were analysed. Furthermore, relationships associating the severity of clinical ocular and oral manifestations with the upregulated cytokines were assessed. In tear fluid, pSS patients showed elevated levels of IL-1ra, IL-2, IL-4, IL-8, IL-12p70, IL-17A, IFN-γ, IP-10, MIP-1b, and Rantes compared to non-SS subjects and healthy controls. The increased cytokine levels (except IP-10) correlated significantly with reduced tear production, less stable tear film, and greater ocular surface damage. In saliva, pSS patients had a higher IP-10 level, which correlated with higher candida score; and an elevated MIP-1a level, which correlated significantly with lower unstimulated and stimulated whole saliva secretion rates. The upregulated cytokines identified in tear fluid and saliva of pSS patients show a clear interplay between innate and adaptive immune responses that may contribute to disease pathogenesis. The increase of IP-10 and MIP in both tears and saliva further emphasises the essential role of macrophages and innate immunity in pSS.

Osteonecrosis of the jaw (ONJ) is a severe side effect associated with antiresorptive treatment. Monitoring of ONJ using routine databases in Scandinavian countries is a challenge owing to lack of valid algorithms and to heterogeneous referral practices. The aim of this paper is to describe the process of establishing a Scandinavian ONJ Cohort enrolling all ONJ cases related to antiresorptive treatment arising in Denmark, Norway, and Sweden between 2011 and 2019. The initial purpose of the cohort is to support an ongoing pharmacovigilance study of denosumab and zoledronic acid in Denmark, Norway, and Sweden. The three countries, with their 199 clinics, departments, and units of oral and maxillofacial surgery, both hospital-based and freestanding, differ somewhat in referral practices of the ONJ patients. By directly contacting all providers of care to ONJ patients in the three countries, we established a network for reporting incident cases to each country's research database directly or through a member of the Scandinavian ONJ task force as a liaison. The task force includes a Scandinavian coordinator and three national coordinators collaborating directly with the clinics. A uniform ONJ registration form has been developed, and the relevant medical community has been informed either directly or through presentations at professional meetings. A website with study information is published in each country, and data entry is ongoing. This large-scale systematic uniform registration of ONJ cases in Denmark, Norway, and Sweden, with an underlying total population of more than 20 million people, merged into the Scandinavian ONJ Cohort, will contribute to better knowledge and understanding of this challenging group of patients, and ultimately, help improve patient care. The Scandinavian ONJ Cohort as a whole and its component national ONJ research databases may offer the potential for large-scale multinational intervention and safety studies in the future.

Patients with head and neck cancer (HNC) and patients with primary Sjögren’s syndrome (pSS) may exhibit similar symptoms of dry mouth and dry eyes, as a result of radiotherapy (RT) or a consequence of disease progression. To identify the proteins that may serve as promising disease biomarkers, we analysed saliva and tears from 29 radiated HNC patients and 21 healthy controls, and saliva from 14 pSS patients by mass spectrometry-based proteomics. The study revealed several upregulated, and in some instances overlapping, proteins in the two patient groups. Histone H1.4 and neutrophil collagenase were upregulated in whole saliva of both patient groups, while caspase-14, histone H4, and protein S100-A9 were upregulated in HNC saliva only. In HCN tear fluid, the most highly upregulated protein was mucin-like protein 1. These overexpressed proteins in saliva and tears play central roles in inflammation, host cell injury, activation of reactive oxygen species, and tissue repair. In conclusion, the similarities and differences in overexpressed proteins detected in saliva from HNC and pSS patients may contribute to the overall understanding of the different pathophysiological mechanisms inducing dry mouth. Thus, the recurring proteins identified could possibly serve as future promising biomarkers

Purpose Long-term survivors (LTSs) of allogeneic hematopoietic stem cell transplantation (allo-HCT) may experience oral long-term effects like chronic graft-versus-host disease (oral cGVHD). The aim of this study was to investigate oral cGVHD in patients treated at a young age (< 30 years) more than 5 years after allo-HCT without total body irradiation (TBI). Methods All 94 participants went through a semi-structured interview, and an oral examination. Diagnosis of oral cGVHD was based on the “National Institutes of Health (NIH) cGVHD diagnosis and staging consensus criteria” from 2014. Results Mean age at transplantation was 17.5 years (range 0.4–29.9 years), and mean time since transplantation was 16.7 years (range 6–26 years). Oral cGVHD was diagnosed in 26 (28%) of 94 LTSs. Of which 20 (21.5%) showed lichen planus-like (LPL) changes, and additionally six (6.5%) also fulfilled the diagnostic criteria of oral cGVHD since they had one or more distinctive signs and symptoms of oral cGVHD combined with definite cGVHD in another organ. No LTSs reported oral cGVHD (NIH) grade 3. There was a significant association between cGVHD in the oral cavity and cGVHD in another organ (77% vs 29%, p  < 0.001). Out of 72 LTSs, who answered the questions regarding taste disturbances, 16 (22%) reported dysgeusia. No LTSs developed secondary malignancies in the oral cavity during follow-up time. Conclusion Oral long-term effects, such as oral cGVHD, may persist for many years after allo-HCT without TBI-conditioning in patients treated at a young age.

BackgroundFew clinical studies evaluate interventions to reduce oral discomfort among patients in palliative care.AimThis study examines the efficacy of a Salvia officinalis (SO) based herbal mouth rinse compared to conventional normal saline (NS) in order to improve oral health.DesignA block-randomized controlled trial. Data were collected before and after a 4-day intervention with either SO (n=44) or NS (n=44). Numerical rating scales (NRS, 0–10) and 12 items from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Oral Health 17 (EORTC QLQ-OH17) measured patient-reported oral symptoms. An oral examination was performed before and after the intervention.Setting/participantsThis study included adult patients with late-stage cancer in an inpatient hospice unit.ResultsOf the 88 patients included (mean age=63.9 years, SD=10.6), 73 (83%) completed the study. At baseline, 78% reported dry mouth on the EORTC QLQ-OH17, and 80% rated dry mouth ≥4 on the NRS. Total oral health scores based on the 12 EORTC QLQ-OH17 items improved similarly in both groups (p<0.001). However, dry mouth ratings on both the EORTC QLQ-OH17 (p=0.036) and NRS (p=0.045) improved more in the SO group than in the NS group. Plaque on the teeth improved in both the SO (p=0.008) and NS (p=0.018) groups, but plaque on the tongue and erythema only improved with NS.ConclusionsThis study did not detect an overall significant difference between SO and NS. Both mouth rinses improved oral health parameters, indicating that systematic assessment and oral care may reduce oral discomfort.Trial registrationNCT02067572

Background Symptom assessment is key to effective symptom management and palliative care for patients with advanced cancer. Symptom prevalence and severity estimates vary widely, possibly dependent on the assessment tool used. Are symptoms specifically asked about or must the patients add them as additional symptoms? This study compared the prevalence and severity of patient-reported symptoms in two different versions of a multi-symptom assessment tool. In one version, three symptoms dry mouth, constipation, sleep problems were among those systematically assessed, while in the other, these symptoms had to be added as an “Other problem”. Methods This retrospective cross-sectional study included adult patients with advanced cancer at an inpatient palliative care unit. Data were collected from two versions of the Edmonton Symptom Assessment System (ESAS): modified (ESAS-m) listed 11 symptoms and revised (ESAS-r) listed 9 and allowed patients to add one “Other problem”. Seven similar symptoms were listed in both versions. Results In 2013, 184 patients completed ESAS-m, and in 2017, 156 completed ESAS-r. Prevalence and severity of symptoms listed in both versions did not differ. In ESAS-m, 83% reported dry mouth, 73% constipation, and 71% sleep problems, but on ESAS-r, these symptoms were reported by only 3%, 15% and < 1%, respectively. Although ESAS-r severity scores for these three symptoms were higher than on ESAS-m, differences did not reach statistical significance. Conclusion We identified significant differences in patient symptom reporting based on whether symptoms like dry mouth, obstipation and sleep problems were specifically assessed or had to be added by patients as an “Other problem”.

Background Patients with advanced cancer are prone to develop different opportunistic oral infection due to anti-cancer treatment or the malignancies themselves. Studies of oral fungal samples show an increased prevalence of non- Candida albicans species in mixed oral infections with Candida albicans . Non- C. albicans and C. albicans are associated with varying degrees of resistance to azoles, which may have implications for treatment. This study aimed to assess the diversity and antifungal susceptibility of Candida species detected in the oral cavity. Methods An observational study with microbiological analysis was conducted. Clinical fungal isolates were collected from patients in a hospice unit in 2014–2016. Isolates were re-grown on chromID® Candida plates in 2020. Single colony of each species was re-cultivated and prepared for biochemical identification with a VITEK2® system and verified by gene sequencing. Etest was performed on RPMI agar, and the antifungals fluconazole, amphotericin B, anidulafungin and nystatin were applied. Results Fifty-six isolates from 45 patients were identified. Seven different Candida species and one Saccharomyces species were detected. The results of biochemical identification were confirmed with sequencing analysis. Thirty-six patients had mono infection, and nine out of 45 patients had 2–3 different species detected. Of C. albicans strains, 39 out of 40 were susceptible to fluconazole. Two non- C. albicans species were resistant to fluconazole, one to amphotericin B and three to anidulafungin. Conclusion C. albicans was the predominant species, with a high susceptibility to antifungal agents. Different Candida species occur in both mono and mixed infections. Identification and susceptibility testing may therefore lead to more effective treatment and may prevent the development of resistance among patients with advanced cancer. Trail registration The study Oral Health in Advanced Cancer was registered at ClinicalTrials.gov (#NCT02067572) in 20/02/2014.

Senses of smell and taste, saliva flow, and dental status are considered as important factors for the maintenance of a good nutritional status. Salivary secretory rates, chemosensory function, burning mouth sensation, halitosis and dental status were investigated in 58 patients with primary Sjögren’s syndrome (pSS), 22 non-Sjögren’s syndrome sicca (non-SS) patients, and 57 age-matched healthy controls. A significantly greater proportion of patients with pSS and non-SS had ageusia, dysgeusia, burning mouth sensation, and halitosis compared to controls. Patients with pSS had significantly lower olfactory and gustatory scores, and significantly higher caries experience compared to controls. Patients with pSS and non-SS patients had significantly lower unstimulated and stimulated whole saliva secretory rates compared to controls. The findings indicated that several different aspects of oral health were compromised in both, patients with pSS and non-SS, and this may affect their food intake and, hence, their nutritional status. Although non-SS patients do not fulfill Sjögren’s syndrome classification criteria, they have similar or, in some cases, even worse oral complaints than the patients with pSS. Further studies are needed to investigate food preferences, dietary intake, and nutritional status in these two patient groups in relation to their health condition.