Interdisciplinary Collaboration in Head and Neck Cancer Care: Optimizing Oral Health Management for Patients Undergoing Radiation Therapy.

Radiation therapy (RT) plays a crucial role in the treatment of head and neck cancers (HNCs). This paper emphasizes the importance of effective communication and collaboration between radiation oncologists and dental specialists in the HNC care pathway. It also provides an overview of the role of RT in HNC treatment and illustrates the interdisciplinary collaboration between these teams to optimize patient care, expedite treatment, and prevent post-treatment oral complications. The methods utilized include a thorough analysis of existing research articles, case reports, and clinical guidelines, with terms such as 'dental management', 'oral oncology', 'head and neck cancer', and 'radiotherapy' included for this review. The findings underscore the significance of the early involvement of dental specialists in the treatment planning phase to assess and prepare patients for RT, including strategies such as prophylactic tooth extraction to mitigate potential oral complications. Furthermore, post-treatment oral health follow-up and management by dental specialists are crucial in minimizing the incidence and severity of RT-induced oral sequelae. In conclusion, these proactive measures help minimize dental and oral complications before, during, and after treatment.

International Expert-Based Consensus Definition, Staging Criteria, and Minimum Data Elements for Osteoradionecrosis of the Jaw: An Inter-Disciplinary Modified Delphi Study.

Purpose: Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy (RT) to the head and neck. With over 9 published definitions and at least 16 diagnostic/staging systems, the true incidence and severity of ORNJ are obscured by lack of a standard for disease definition and severity assessment, leading to inaccurate estimation of incidence, reporting ambiguity, and likely under-diagnosis worldwide. This study aimed to achieve consensus on an explicit definition and phenotype of ORNJ and related precursor states through data standardization to facilitate effective diagnosis, monitoring, and multidisciplinary management of ORNJ. Methods: The ORAL Consortium comprised 69 international experts, including representatives from medical, surgical, radiation oncology, and oral/dental disciplines. Using a web-based modified Delphi technique, panelists classified descriptive cases using existing staging systems, reviewed systems for feature extraction and specification, and iteratively classified cases based on clinical/imaging feature combinations. Results: The Consortium ORNJ definition was developed in alignment with SNOMED-CT terminology and recent ISOO-MASCC-ASCO guideline recommendations. Case review using existing ORNJ staging systems showed high rates of inability to classify (up to 76%). Ten consensus statements and nine minimum data elements (MDEs) were outlined for prospective collection and classification of precursor/ORNJ stages. Conclusion: This study provides an international, consensus-based definition and MDE foundation for standardized ORNJ reporting in cancer survivors treated with RT. Head and neck surgeons, radiation, surgical, medical oncologists, and dental specialists should adopt MDEs to enable scalable health information exchange and analytics. Work is underway to develop both a human- and machine-readable knowledge representation for ORNJ (i.e., ontology) and multidisciplinary resources for dissemination to improve ORNJ reporting in academic and community practice settings.

Update on Oral and Oropharyngeal Cancers: A guide for oral health care providers.

Oral squamous cell carcinomas (OSCC) signs and symptoms may be first identified by dental hygienists during routine extra and intra-oral examinations. A comprehensive extra-oral and intra-oral examination during regular dental hygiene assessment is paramount to identifying oral potentially malignant disorders (OPMD) and cancerous lesions for timely referral and treatment. Integrating a systematic list of questions during the medical and dental assessment along with careful visual and tactile examinations is critical to identifying OPMDs and cancerous lesions. Understanding the relationship between oropharyngeal squamous cell carcinomas (OPSCC) and Human Papilloma Virus (HPV) and how vaccination can prevent HPV-related OPSCC is critical to providing evidence-based recommendations and care. The purpose of this report is to provide an update on current epidemiological trends of OSCC and OPSCC rates in the United States (US) and provide the latest evidence on what dental hygienists must know to improve health outcomes and mitigate the consequences of undiagnosed cancer. This report considers enduring challenges with the annual rise in OPSCC rates and the public health burden of HPV-related cancers in the US. Emphasis on regular, quality continuing education about OSCC and OPSCC is emphasized along with recommendations for evidence-based training.

Detection of quadratic phase coupling by cross-bicoherence and spectral Granger causality in bifrequencies interactions.

Quadratic Phase Coupling (QPC) serves as an essential statistical instrument for evaluating nonlinear synchronization within multivariate time series data, especially in signal processing and neuroscience fields. This study explores the precision of QPC detection using numerical estimates derived from cross-bicoherence and bivariate Granger causality within a straightforward, yet noisy, instantaneous multiplier model. It further assesses the impact of accidental statistically significant bifrequency interactions, introducing new metrics such as the ratio of bispectral quadratic phase coupling and the ratio of bivariate Granger causality quadratic phase coupling. Ratios nearing 1 signify a high degree of accuracy in detecting QPC. The coupling strength between interacting channels is identified as a key element that introduces nonlinearities, influencing the signal-to-noise ratio in the output channel. The model is tested across 59 experimental conditions of simulated recordings, with each condition evaluated against six coupling strength values, covering a wide range of carrier frequencies to examine a broad spectrum of scenarios. The findings demonstrate that the bispectral method outperforms bivariate Granger causality, particularly in identifying specific QPC under conditions of very weak couplings and in the presence of noise. The detection of specific QPC is crucial for neuroscience applications aimed at better understanding the temporal and spatial coordination between different brain regions.

Common Oral Conditions: A Review.

Importance: Dry mouth, oral candidiasis, and recurrent aphthous ulcers are 3 of the most common oral conditions that may be associated with patient discomfort, decreased quality of life, and morbidity. Observations: In a meta-analysis of 26 population-based cohort and cross-sectional studies, the global prevalence of dry mouth symptoms was 23% (95% CI, 18% to 28%), placing individuals at risk of oral candidiasis, dental caries, dysgeusia, masticatory/speech impairment, and oropharyngeal dysphagia. Dry mouth is associated with using more than 3 oral medications per day (odds ratio [OR], 2.9 [95% CI, 1.4 to 6.2]), head and neck radiation, and Sjögren disease. Symptoms may include difficulty swallowing and speaking, thirst, and halitosis. Dry mouth is associated with an 11.5% (95% CI, 3.6% to 27%) higher risk of oral candidiasis, based on a meta-analysis of 6 observational cohorts. Management of dry mouth includes mechanical salivary stimulants, oral moisturizers, and/or systemic sialagogues. Oral candidiasis is an opportunistic fungal infection caused by overgrowth of the Candida genus with C albicans, which accounts for 76.8% of infections. The prevalence of oral candidiasis is higher in patients who are immunosuppressed, for example, those with HIV (35% [95% CI, 28% to 42%]) and those with salivary gland hypofunction (OR, 3.02 [95% CI, 1.73 to 5.28]). Common risk factors associated with oral candidiasis include use of antibiotics (P = .04) and oral mucosal disorders such as lichen planus. Oral burning and dysgeusia are common symptoms of oral candidiasis. Treatment includes addressing risk factors and use of topical and/or systemic antifungal medications. Recurrent aphthous stomatitis is characterized by symptomatic round or oval oral ulcers, which are covered by a gray-white fibrin layer and encircled by an erythematous ring. A meta-analysis of 10 case-controlled studies revealed an increased risk of recurrent aphthous stomatitis associated with polymorphism of IL-1ß (+3954C/T) (OR, 1.52 [95% CI, 1.07 to 2.17]) and IL-1ß (-511C/T) (OR, 1.35 [95% CI, 1.09 to 1.67]). Another meta-analysis of 9 case-control studies reported that patients with recurrent aphthous stomatitis had a higher frequency of nutritional deficiencies, including vitamin B12 (OR, 3.75 [95% CI, 2.38 to 5.94]), folic acid (OR, 7.55 [95% CI, 3.91 to 14.60]), and ferritin (OR, 2.62 [95% CI, 1.69 to 4.06]). Recurrent aphthous stomatitis can be associated with systemic diseases. A meta-analysis of 21 case-control studies revealed that celiac disease is associated with a higher incidence of recurrent aphthous stomatitis (25% vs 11%; OR, 3.79 [95% CI, 2.67 to 5.39]; P <.001). Topical corticosteroids are first-line agents to manage recurrent aphthous stomatitis; however, systemic medications may be necessary in more severe cases. Conclusions and Relevance: Dry mouth, oral candidiasis, and recurrent aphthous ulcers are common oral conditions that may be associated with patient discomfort, decreased quality of life, and morbidity. First-line treatment includes over-the-counter sialagogues for dry mouth, topical antifungals for oral candidiasis, and topical corticosteroids for aphthous ulcers. Oral conditions that do not improve with first-line treatment may require treatment with systemic medications.

Design and validation of a reporter mouse to study the dynamic regulation of TFEB and TFE3 activity through in vivo imaging techniques.

TFEB and TFE3 belong to the MiT/TFE family of transcription factors that bind identical DNA responsive elements in the regulatory regions of target genes. They are involved in regulating lysosomal biogenesis, function, exocytosis, autophagy, and lipid catabolism. Precise control of TFEB and TFE3 activity is crucial for processes such as senescence, stress response, energy metabolism, and cellular catabolism. Dysregulation of these factors is implicated in various diseases, thus researchers have explored pharmacological approaches to modulate MiT/TFE activity, considering these transcription factors as potential therapeutic targets. However, the physiological complexity of their functions and the lack of suitable in vivo tools have limited the development of selective MiT/TFE modulating agents. Here, we have created a reporter-based biosensor, named CLEARoptimized, facilitating the pharmacological profiling of TFEB- and TFE3-mediated transcription. This innovative tool enables the measurement of TFEB and TFE3 activity in living cells and mice through imaging and biochemical techniques. CLEARoptimized consists of a promoter with six coordinated lysosomal expression and regulation motifs identified through an in-depth bioinformatic analysis of the promoters of 128 TFEB-target genes. The biosensor drives the expression of luciferase and tdTomato reporter genes, allowing the quantification of TFEB and TFE3 activity in cells and in animals through optical imaging and biochemical assays. The biosensor's validity was confirmed by modulating MiT/TFE activity in both cell culture and reporter mice using physiological and pharmacological stimuli. Overall, this study introduces an innovative tool for studying autophagy and lysosomal pathway modulation at various biological levels, from individual cells to the entire organism.Abbreviations: CLEAR: coordinated lysosomal expression and regulation; MAR: matrix attachment regions; MiT: microphthalmia-associated transcription factor; ROI: region of interest; TBS: tris-buffered saline; TF: transcription factor; TFE3: transcription factor binding to IGHM enhancer 3; TFEB: transcription factor EB; TH: tyrosine hydroxylase; TK: thymidine kinase; TSS: transcription start site.

Characterization of orofacial features in sclerodermatous chronic graft-versus-host disease.

BACKGROUND: Chronic graft-versus-host disease (cGVHD) is a leading cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (alloHCT). The sclerodermatous form of cGVHD can be particularly debilitating; however, orofacial sclerodermatous involvement remains poorly described. OBJECTIVE: To characterize orofacial features of sclerodermatous cGVHD in a single center cohort of patients who underwent alloHCT. STUDY DESIGN: Retrospective data were collected from electronic medical records and analyzed descriptively. RESULTS: There were 39 patients who received alloHCT between 1993 and 2017 and developed orofacial sclerodermatous cGVHD. Concomitant cutaneous sclerodermatous cGVHD was common (n = 20, 51%). Orofacial sclerodermatous cGVHD features included fibrous bands of the buccal mucosa (n = 23, 59%), limited mouth opening (n = 19, 54%), perioral fibrosis (n = 8, 21%), and focal gingival recession (n = 4, 10%). Oral mucosal fibrosis was observed at the site of active or resolved chronic lichenoid inflammation in 30 patients, with all but two also presenting with a history of ulcerations. Management included jaw stretching exercises (n = 10; 6 stable/improved), surgery (n = 3; 2 improved), and intralesional corticosteroid injections (n = 2; 2 improved). CONCLUSIONS: Orofacial involvement with sclerodermatous cGVHD can present with multiple manifestations including fibrous banding, limited mouth opening, perioral fibrosis, and focal gingival recession. Surgical and non-surgical management strategies may improve clinical function and reduce morbidity.

Canine glioblastoma-derived extracellular vesicles as precise carriers for glioblastoma imaging: Targeting across the blood-brain barrier.

The treatment of glioblastoma (GBM) faces significant challenges due to the difficulty of delivering drugs through the blood-brain barrier (BBB). Extracellular vesicles (EVs) have emerged as potential carriers for targeted drug delivery to brain tumors. However, their use and distribution in the presence of an intact BBB and their ability to target GBM tissue are still under investigation. This study explored the use of EVs for GBM targeting across the BBB. Canine plasma EVs from healthy dogs and dogs with glioma were isolated, characterized, and loaded with diagnostic agents. Biodistribution studies were conducted in healthy murine models and a novel intranasal model that preserved BBB integrity while initiating early-stage GBM growth. This model assessed EVs' potential for delivering the contrast agent gadoteric acid to intracranial tumors. Imaging techniques, such as bioluminescence and MRI, confirmed EVs' targeting and delivery capabilities thus revealing a selective accumulation of canine glioma-derived EVs in brain tissue under physiological conditions. In the model of brain tumor, MRI experiments demonstrated the ability of EVs to accumulate gadoteric acid within GBM to enhance contrast of the tumoral mass, even when BBB integrity is maintained. This study underscores the potential of EVs derived from glioma for the targeted delivery of drugs to glioblastoma. EVs from dogs with glioma showed capacity to traverse the BBB and selectively accumulate within the brain tumor. Overall, this research represents a foundation for the application of autologous EVs to precision glioblastoma treatment, addressing the challenge of BBB penetration and targeting specificity in brain cancer therapy.

Patient communication protocols for sexually transmitted infections: A systematic review.

AIMS: We conducted a systematic review of post-test communication protocols and observational studies regarding counseling for a positive sexually transmitted infection (STI) result and also discuss the role of dental specialist (e.g., oral medicine) in this sense. METHODS AND RESULTS: The search process followed the parameters of PRISMA 2020 guidelines. MEDLINE/PubMed, Web of Science, Scopus, EMBASE, and LILACS were consulted with a specific search strategy for each one. Additionally, the references of the included studies, grey literature, and experts were consulted. Four protocols and 18 observational studies were included in this systematic review, published between 1997 and 2022 in the Americas and Europe. The communication protocols emphasized the importance of conducting personal and private discussions with patients to address their fears and questions. Among the observational studies, 56% indicated that post-test counseling was either ineffective or absent. Furthermore, 22% of the studies used telephone communication to deliver results to patients. CONCLUSIONS: Our study showed that the communication process of a positive STI result affects the patients in several aspects, as treatment adherence and their relationship with the community. Nevertheless, this process of STI post-test communication seems to be flawed, which brings potential negative effects to patients.

Oral Toxicities of PSMA-Targeted Immunotherapies for The Management of Prostate Cancer.

INTRODUCTION: Prostate Specific Membrane Antigen (PSMA)-targeted radionucleotide therapy has been shown to cause dry mouth, but the oral manifestations of PSMA-targeted immunotherapy have not been extensively studied. The aim of this study was to describe and quantify the oral manifestations of PSMA-targeted immunotherapies (bispecific antibodies or Chimeric Antigen Receptor T cell therapies) in the management of metastatic castration resistant prostate cancer. PATIENTS AND METHODS: We performed a retrospective analysis of the oral toxicities of PSMA-targeted immunotherapies of the patients seen at a single institution's cancer center between 2020 and 2023. Descriptive statistics were used to summarize the data. RESULTS: In a total of 19 patients treated with PSMA-targeted immunotherapies between 2020 and 2023, 9 patients (47%) experienced the following oral toxicities: xerostomia (n = 6; 32%), mucositis (n = 2; 10%), dysgeusia, dry throat and teeth sensitivity in (n = 1 each; 5%), respectively. Oral infections, such as candidiasis and herpes simplex, were not observed in any patients. Mucositis was managed with salt rinses and resolved within few months from onset. Xerostomia persisted in all the patients (median: 306 days, range: 98-484 days) among those who reported dry mouth at the time of data collection, despite treatment with salivary stimulants (n = 5; 83%). Dysgeusia was also persistent, although it was not specifically treated. CONCLUSIONS: Patients treated with PSMA-targeted immunotherapies for prostate cancer can present with various short-term and long-term off-tumor on-target oral toxicities including xerostomia and dysgeusia that may affect quality of life. This study serves as a foundation to future prospective studies with a larger sample size and also helps oncologists managing prostate cancer patients with targeted immunotherapies to familiarize common oral toxicities. Furthermore, we emphasize the importance of oral medicine consultation for a comprehensive oral examination and management of oral complications.

Orofacial complications from immune checkpoint inhibitors: A retrospective analysis from two academic medical centers.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are FDA-approved for various cancers, yet their orofacial immune-related adverse events (irAEs) remain poorly understood. Our two-center retrospective study aims to better understand the prevalence and nature of these orofacial irAEs. METHODS: We retrospectively collected demographics, ICI details, and onset of orofacial irAEs in ICI-treated patients at University of California San Francisco and City of Hope (2013-2021). Orofacial irAEs were identified by ICD-10 codes and data categorized as dry mouth/xerostomia, oral mucosal lesions, and orofacial neuropathies. Patients with pre-existing orofacial conditions resembling the reported irAEs were excluded. RESULTS: Among 3768 ICI-treated patients, 408 (10.8%) developed 467 orofacial irAEs: oral mucosal diseases (41.4%), dry mouth/xerostomia (41.0%), and orofacial neuropathies (17.6%). Notably, head and neck cancers had the highest incidence of orofacial irAEs. CONCLUSIONS: Orofacial irAEs are relatively common in patients receiving ICIs, necessitating careful monitoring and management of these complications during and after the treatment.

Nivolumab for Patients With High-Risk Oral Leukoplakia: A Nonrandomized Controlled Trial.

Importance: Proliferative verrucous leukoplakia (PVL) is an aggressive oral precancerous disease characterized by a high risk of transformation to invasive oral squamous cell carcinoma (OSCC), and no therapies have been shown to affect its natural history. A recent study of the PVL immune landscape revealed a cytotoxic T-cell-rich microenvironment, providing strong rationale to investigate immune checkpoint therapy. Objective: To determine the safety and clinical activity of anti-programmed cell death 1 protein (PD-1) therapy to treat high-risk PVL. Design, Setting, and Participants: This nonrandomized, open-label, phase 2 clinical trial was conducted from January 2019 to December 2021 at a single academic medical center; median (range) follow-up was 21.1 (5.4-43.6) months. Participants were a population-based sample of patients with PVL (multifocal, contiguous, or a single lesion ≥4 cm with any degree of dysplasia). Intervention: Patients underwent pretreatment biopsy (1-3 sites) and then received 4 doses of nivolumab (480 mg intravenously) every 28 days, followed by rebiopsy and intraoral photographs at each visit. Main Outcomes and Measures: The primary end point was the change in composite score (size and degree of dysplasia) from before to after treatment (major response [MR]: >80% decrease in score; partial response: 40%-80% decrease). Secondary analyses included immune-related adverse events, cancer-free survival (CFS), PD-1 ligand 1 (PD-L1) expression, 9p21.3 deletion, and other exploratory immunologic and genomic associations of response. Results: A total of 33 patients were enrolled (median [range] age, 63 [32-80] years; 18 [55%] were female), including 8 (24%) with previously resected early-stage OSCC. Twelve patients (36%) (95% CI, 20.4%-54.8%) had a response by composite score (3 MRs [9%]), 4 had progressive disease (>10% composite score increase, or cancer). Nine patients (27%) developed OSCC during the trial, with a 2-year CFS of 73% (95% CI, 53%-86%). Two patients (6%) discontinued because of toxic effects; 7 (21%) experienced grade 3 to 4 immune-related adverse events. PD-L1 combined positive scores were not associated with response or CFS. Of 20 whole-exome sequenced patients, all 6 patients who had progression to OSCC after nivolumab treatment exhibited 9p21.3 somatic copy-number loss on pretreatment biopsy, while only 4 of the 14 patients (29%) who did not develop OSCC had 9p21.3 loss. Conclusions and Relevance: This immune checkpoint therapy precancer nonrandomized clinical trial met its prespecified response end point, suggesting potential clinical activity for nivolumab in high-risk PVL. Findings identified immunogenomic associations to inform future trials in this precancerous disease with unmet medical need that has been difficult to study. Trial Registration: ClinicalTrials.gov Identifier: NCT03692325.

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.

Ofatumumab in Rituximab-Resistant and Rituximab-Intolerant Patients With Primary Membranous Nephropathy: A Case Series.

RATIONALE & OBJECTIVE: Rituximab is the first-choice therapy for patients with primary membranous nephropathy (MN) and nephrotic syndrome. However, approximately 30% of patients are treatment-resistant or become treatment-intolerant with hypersensitivity reactions upon repeated drug exposures. We aimed to assess whether ofatumumab, a fully human second-generation anti-CD20 antibody, could be a valuable alternative to rituximab in this population. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 7 rituximab-intolerant and 10 rituximab-resistant patients with MN who consented to receive ofatumumab (50-300mg, single intravenous infusion) and were followed at the nephrology unit of Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII (Bergamo, Italy) between September 2015 and January 2019. FINDINGS: Over a median (IQR) follow-up of 5.0 (3.0-9.8) months, all 7 rituximab-intolerant and 3 of the 10 rituximab-resistant patients exhibited complete (proteinuria<0.3g/d) or partial (proteinuria<3.5g/d with≥50% reduction vs baseline) remission of nephrotic syndrome. Circulating B cells were similarly depleted in all patients by 1 week, and serum anti-phospholipase A2 receptor antibody concentrations decreased to<2.7 relative units/mL in 3 of 4 rituximab-intolerant and 4 of 8 rituximab-resistant patients with phospholipase A2 receptor-related disease. Ofatumumab significantly reduced 24-hour urinary protein and immunoglobulin G excretion and increased serum albumin and immunoglobulin G levels. These effects were greater in rituximab-intolerant than in rituximab-resistant patients. Measured glomerular filtration rate significantly increased by an average of 13.4% at 24 months compared with baseline (P=0.036) among all patients in the series. There were 14 nonserious infusion-related adverse events in 9 patients that recovered with temporary infusion interruption. LIMITATIONS: Retrospective design, limited number of patients. CONCLUSIONS: Ofatumumab may represent an effective and safe treatment for rituximab-intolerant cases of MN. Larger prospective studies will be needed to validate these preliminary findings and explore the effectiveness of other second-generation anti-CD20 antibodies in this clinical setting. PLAIN-LANGUAGE SUMMARY: Primary membranous nephropathy (MN) is one of the most frequent causes of nephrotic syndrome (NS) in adults. In this case series, we explored the efficacy of ofatumumab, a fully human second-generation anti-CD20 antibody, in 17 patients with MN and NS who were intolerant or unresponsive to rituximab. All 7 rituximab-intolerant patients exhibited complete or partial clinical remission, compared with only 3 of the 10 rituximab-resistant patients. Autoantibody levels decreased in all patients with phospholipase A2 receptor-related disease. Ofatumumab achieved a significant reduction in urinary protein and immunoglobulin G excretion while increasing serum albumin and immunoglobulin G levels. Ofatumumab may be a promising option for patients with MN who are rituximab-intolerant. Further investigations are warranted to validate these preliminary findings.

Topical gabapentin solution for the management of burning mouth syndrome: A retrospective study.

OBJECTIVE: The aim of this retrospective study was to evaluate the effectiveness and safety of topical gabapentin solution (250 mg/mL) for the management of burning mouth syndrome (BMS). STUDY DESIGN: A retrospective chart review was conducted of all patients diagnosed with BMS and managed with gabapentin 250 mg/mL solution (swish and spit) between January 2021 and October 2022. Patient-reported outcomes included changes in burning score ranked on a 10-point numeric rating scale (NRS) and reported adverse drug reactions (ADR). Wilcoxon signed-rank test was used to assess differences in the oral burning score ranked on a NRS (0-10) between the baseline visit and the second visit. RESULTS: A total of 19 patients (68.4% females) with BMS were included and evaluated for follow-up at a median of 86 days (range: 29-195). Overall, patients reported a median 2-point burning decrease on a 0-10 NRS between the baseline visit and the second visit (p < 0.01). ADRs were reported by 3 patients (15.8%). CONCLUSION: Although this was a small retrospective study, BMS management with topical gabapentin (250 mg/mL) appears to be effective and well-tolerated. Future randomized prospective studies are needed to verify these preliminary findings.

Specific Oral Microbial Differences in Proteobacteria and Bacteroidetes Are Associated with Distinct Sites When Moving from Healthy Mucosa to Oral Dysplasia-A Microbiome and Gene Profiling Study and Focused Review.

Oral potentially malignant disorders (OPMDs) are a group of conditions that carry a risk of oral squamous cell carcinoma (OSCC) development. Recent studies indicate that periodontal disease-associated pathogenic bacteria may play a role in the transition from healthy mucosa to dysplasia and to OSCC. Yet, the microbial signatures associated with the transition from healthy mucosa to dysplasia have not been established. To characterize oral microbial signatures at these different sites, we performed a 16S sequencing analysis of both oral swab and formalin-fixed, paraffin-embedded tissue (FFPE) samples. We collected oral swabs from healthy mucosa (from healthy patients), histologically normal mucosa adjacent to dysplasia, and low-grade oral dysplasia. Additionally, FFPE samples from histologically normal mucosa adjacent to OSCC, plus low grade and high-grade oral dysplasia samples were also collected. The collected data demonstrate significant differences in the alpha and beta microbial diversities of different sites in oral mucosa, dysplasia, and OSCC, as well as increased dissimilarities within these sites. We found that the Proteobacteria phyla abundance increased, concurrent with a progressive decrease in the Firmicutes phyla abundance, as well as altered levels of Enterococcus cecorum, Fusobacterium periodonticum, Prevotella melaninogenica, and Fusobacterium canifelinum when moving from healthy to diseased sites. Moreover, the swab sample analysis indicates that the oral microbiome may be altered in areas that are histologically normal, including in mucosa adjacent to dysplasia. Furthermore, trends in specific microbiome changes in oral swab samples preceded those in the tissues, signifying early detection opportunities for clinical diagnosis. In addition, we evaluated the gene expression profile of OSCC cells (HSC-3) infected with either P. gingivalis, T. denticola, F. nucelatum, or S. sanguinis and found that the three periodontopathogens enrich genetic processes related to cancer progression, including skin keratinization/cornification, while the commensal enriched processes related to RNA processing and adhesion. Finally, we reviewed the dysplasia microbiome literature and found a significant decrease in commensal bacteria, such as the Streptococci genus, and a simultaneous increase in pathogenic bacteria, mainly Bacteroidetes phyla and Fusobacterium genus. These findings suggest that features of the oral microbiome can serve as novel biomarkers for dysplasia and OSCC disease progression.

On the semantics of ecoacoustic codes.

Ecological codes have been defined as every biological code integrated by factors originated by the environmental context that participates in the codepoiesis process. Ecological codes create a strict relationship between the inner world of organsims and the external relational world, and represent the mechanism with which the vivo-scape is realized. Acoustic codes are used in nature to decode acoustic signals between individuals of the same or different species and belong to the category of biological codes. Ecoacoustic codes are the outcome of the evolution of acoustic codes, and results as the interplay between acoustic codes and environmental factors. Soundtope codes represent the results of emerging properties of the acoustic communities.

An Interactive Educational Tool to Improve Human Papillomavirus Vaccine Knowledge and Recommendation Among Nurses.

In United States, only 57% of  women and 53% of men in the recommended age groups have received all recommended doses of the human papillomavirus (HPV) vaccine. Healthcare provider education has been associated with strong vaccine recommendation and vaccination uptake. Our objective was to create a 7-min interactive online educational tool to improve knowledge and willingness to recommend the HPV vaccine among nurses. This is a prospective pre-test/post-test study to evaluate the effectiveness of the educational tool consisting of 10 flashcards in a question-answer format. Oncology nurses at our cancer center were invited to participate by email, which led them to the educational tool (i.e., intervention) along with pre- and post-test questions on HPV-associated cancers, vaccine-eligible age groups, dosing schedules, adverse events, and willingness to recommend. Of the 110 participants (mean age of 41.2 ± 11.4, 98% female, 64% >10 years of practice), there was improvement in knowledge after intervention in HPV-associated cancers (81% to 97%; p = 0.02), percentage of cervical caused by HPV (33% to 64%; p < 0.05), and dosing schedule (47% to 93%; p < 0.05). All participants correctly stated that continued screening is needed after vaccination both pre- and post-intervention. Eighty-five percent strongly agreed that the intervention improved their HPV knowledge, and 77% stated they were more likely to recommend the HPV vaccine after the intervention. While nurses are willing to recommend the vaccine, there remains persistent knowledge gaps. A brief 7-min self-administered online interactive flashcard educational intervention is effective in improving the HPV vaccine knowledge among nurses.