Plus moist HS-W®: a new nasal packing material for the middle meatus in endoscopic sinus surgery.

PURPOSE: Removal of the current calcium alginate packing materials to the middle meatus in endoscopic sinus surgery (ESS) is usually accompanied by discomfort or pain owing to the hard and brittle nature of these materials. Plus moist HS-W® is a new calcium alginate packing material released in 2022 developed to overcome this issue by changing the uronic acid component. We aimed to compare the discomfort/pain during the removal of Plus moist HS-W® with Kaltostat®, as well as their suitability as packing materials in ESS. METHODS: Kaltostat® and Plus moist HS-W® were used as packing materials in 22 and 21 patients who underwent ESS in 2021 and 2022, respectively. Patients were asked to rate the pain during the packing removal 10 days after ESS using the Numerical Rating Scale (NRS). The ratio of residual packing materials, number of suctions (insertions/extractions of the suction cannula), and time required to remove packing materials were measured. Postoperative complications such as hemorrhage, local infection, lateralization of the middle turbinate, and synechia of the middle meatus were also evaluated. RESULTS: The Plus moist HS-W® group exhibited significantly lower NRS pain scores, a lower ratio of residual packing materials, a reduced number of suctions, and a shorter time required to remove the packing. No obvious postoperative complications occurred in both groups except for one suspicious case of a slight infection in the Kaltostat® group. CONCLUSION: Compared with Kaltostat®, Plus moist HS-W®, characterized by better gelatinization than Kaltostat®, benefits patients by minimizing discomfort/pain during removal. LEVEL OF EVIDENCE: Level 3.

Treatment Outcome in Head and Neck Cancer With Distant Metastasis at Initial Diagnosis.

OBJECTIVE: Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) treatment has changed dramatically with the introduction of immune checkpoint inhibitors (ICIs). However, there are few reports of treatment outcomes on HNSCC with distant metastasis (M1) at initial diagnosis, and its treatment strategy has not been standardized. We aimed to analyze the treatment outcome and prognostic factors of patients with HNSCC with initial M1 disease. METHODS: In this multi-institutional retrospective study, 98 patients with HNSCC were initially diagnosed with M1 disease between 2007 and 2021. The patients were divided into the non-palliative (received any systemic chemotherapy, n = 60) and palliative (did not receive systemic chemotherapy, n = 38) groups. Overall survival (OS) was compared between the groups. In the non-palliative group, predictors of OS were explored based on patient characteristics and treatment details. RESULTS: The median OS in the non-palliative group was 15 months (95% confidence interval [CI], 10-20), which was significantly longer than that in the palliative group (3 months, 95% CI, 2-5) (p < 0.001). Multivariate analysis revealed that administration of locoregional radiation therapy (RT) (hazard ratio [HR] 0.407 [95% CI 0.197-0.844]; p = 0.016), ICIs (HR 0.216 [95% CI 0.088-0.532]; p < 0.001) and RT/surgery for distant metastasis (HR 0.373 [95% CI 0.150-0.932]; p = 0.034) were the independent prognostic factors of OS. CONCLUSION: An intensive treatment strategy combining systemic therapy using ICIs with RT/surgery for locoregional or distant metastasis may yield a survival benefit for patients with HNSCC with M1 disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1679-1686, 2024.

Multicenter prospective phase II trial of concurrent chemoradiotherapy with weekly low-dose carboplatin for cisplatin-ineligible patients with advanced head and neck squamous cell carcinoma.

BACKGROUND: The optimal chemotherapy regimen in concurrent chemoradiotherapy (CCRT) for cisplatin-ineligible head and neck squamous cell carcinoma (HNSCC) has not been established. We aimed to evaluate the feasibility, efficacy, and safety of CCRT with weekly low-dose carboplatin for the treatment of advanced HNSCC in patients who are cisplatin-ineligible. METHODS: This prospective phase II study enrolled adult patients (age ≥ 20 years) with HNSCC receiving whole-neck irradiation including bilateral levels II-IV and who were aged (≥ 75-year-old patients with 40 mL/min estimated glomerular filtration rate [eGFR] or better) or had renal dysfunction (< 75-year-old patients with 30-60 mL/min eGFR). Carboplatin was administered weekly (area under the plasma concentration-time curve = 2.0) for up to seven cycles during concurrent radiotherapy (70 Gy/35 Fr). The primary endpoint was the completion rate of CCRT. Secondary endpoints included overall response rate and incidence of adverse events. RESULTS: Among the 30 patients enrolled, 28 were men. The median age was 73.5 years. Seventeen patients were < 75 years whereas 13 were ≥ 75 years old. The completion rate of CCRT was 90%. The overall response rate was 90%. Grade 3 adverse events that occurred in 10% or more patients were oral/pharyngeal mucositis (47%), leukocytopenia (20%), and neutropenia (10%). Grade 4 adverse events occurred in one patient (elevation of alanine aminotransferase level). No treatment-related deaths occurred. CONCLUSION: CCRT with weekly low-dose carboplatin is a promising treatment option, with favorable feasibility, efficacy, and acceptable toxicity, for patients who are cisplatin-ineligible with advanced HNSCC. CLINICAL TRIAL REGISTRATION NUMBER: jRCTs031190028.

Involvement of ionic interactions in self-assembly and resultant rodlet formation of class I hydrophobin RolA from Aspergillus oryzae.

Hydrophobins are small amphiphilic proteins that are conserved in filamentous fungi. They localized on the conidial surface to make it hydrophobic, which contributes to conidial dispersal in the air, and helps fungi to infect plants and mammals and degrade polymers. Hydrophobins self-assemble and undergo structural transition from the amorphous state to the rodlet (rod-like multimeric structure) state. However, it remains unclear whether the amorphous or rodlet state is biologically functional and what external factors regulate state transition. In this study, we analyzed the self-assembly of hydrophobin RolA of Aspergillus oryzae in detail and identified factors regulating this process. Using atomic force microscopy, we observed RolA rodlet formation over time, and determined "rodlet elongation rate" and "rodlet formation frequency." Changes in these kinetic parameters in response to pH and salt concentration suggest that RolA rodlet formation is regulated by the strength of ionic interactions between RolA molecules.

Evaluation of the effect of a glass ionomer cement containing fluoro-zinc-silicate glass on dentin remineralization using the ultrasonic pulse-echo method.

The purpose of this study was to investigate the protective effect of a glass ionomer cement (GIC) consisting of fluoro-zinc-silicate glass on the demineralization of bovine dentin using the ultrasonic pulse-echo method. The findings were compared with those obtained using a conventional GIC. Slabs of dentin from bovine teeth were sliced, shaped into a rectangular form, and immersed in 0.5 M ethylenediaminetetraacetic acid solution at 25ºC for 6 days, followed by storage in distilled water for 3 days. After demineralization, they were immersed in artificial saliva with and without the GIC specimens. The propagation times of the longitudinal ultrasonic waves in the samples were measured. The ultrasonic velocities of the fluoro-zinc-silicate glass-containing GICs were significantly increased 2-3 days after the start of the experiment and showed an upward trend thereafter. These findings indicate that the GICs containing fluoro-zinc-silicate glass might exhibit the potential to promote remineralization in the dentin.

Chemoradiotherapy with 3-weekly CDDP 80†mg/m2 for head and neck squamous cell carcinoma: 5-year survival data from a phase 2 study.

Objective: The global standard for chemoradiation therapy (CCRT) for head and neck squamous cell carcinoma is cisplatin 100 mg/m2 administered once every three weeks, although cisplatin 80 mg/m2 is also widely used as an alternative treatment to reduce adverse events in Japan. We aimed to assess the long-term survival outcomes and late adverse events associated with CCRT with a 3-weekly cisplatin dose of 80 mg/m2. Methods: A phase 2 study on CCRT with a 3-weekly cisplatin dose of 80 mg/m2 was performed in 47 patients between April 2015 and December 2016 at four centers in Japan. Survival outcomes and late adverse events at 5 years after this phase 2 trial were investigated. Results: The median follow-up period was 61 months. The 5-year progression-free survival/overall survival of all 47 patients was 66.0%/76.6%, while that of patients with stage III, IV disease (UICC) was 65.6%/71.9%. Seventeen patients (36%) experienced dysphagia as a late adverse event. Univariate and multivariate analyses revealed a significant association between acute mucositis/low body mass index (BMI) during CCRT and late dysphagia. Conclusion: The survival outcomes of CCRT with a 3-weekly cisplatin dose of 80 mg/m2 may be comparable to the previously reported dose of 100 mg/m2. Acute mucositis and low BMI at CCRT were risk factors for late dysphagia, indicating the importance of managing these conditions during CCRT to prevent late adverse events. Caution and care for acute mucositis and swallowing training in patients with low BMI may be important for preventing late-stage dysphagia.

Bonding ability of resin cements to different types of CAD/CAM composite blocks.

This study investigated the bonding performance of two different types of resin cements to computer-aided design/computer-aided manufacturing (CAD/CAM) composite blocks based on the shear bond strength (SBS) test. A silane-containing self-adhesive resin cement (Panavia SA Cement Universal) and resin luting cement (Block HC Cem) with a primer, were used. Specimens were fabricated from three different types of CAD/CAM composite blocks, and their surfaces were blasted with alumina. Resin cements were bonded to the specimens, and their SBSs were measured after 15 min, 24 h, and after being subjected to thermal cycling for 10,000 and 30,000 cycles. Three-way ANOVA for bond strength revealed that CAD/CAM composite block, resin cement and storage time significantly influenced the SBS values, and the three-way interactions between the evaluated factors, and all the interactions were significant. It was concluded that the bonding performance of resin cements to CAD/CAM composite blocks were material and storage period dependent.

Prevention of acidic attack on tooth enamel surfaces using polishing paste containing ion-releasing filler.

The purpose of this study was to investigate the ability of polishing paste containing surface pre-reacted glass-ionomer (S-PRG) filler to prevent acidic attack on tooth enamel surfaces. Resin composites were filled in the standardized cavities and finished with silicon carbide paper. These specimens were divided into three groups: the unpolished "control" group, the "PRG" group polished with S-PRG paste, and the "DDP" group polished with diamond-containing polishing paste. Following polishing, the specimens were immersed in a lactic acid buffer solution for 28 days. Optical coherence tomography (OCT) signals were measured to obtain the signal intensity and width at 1/e2 at selected locations on the enamel surface adjacent to the restoration. Although signal intensity significantly increased in all groups, widths at 1/e2 did not change significantly in the PRG group. For both the control and DDP groups, signal intensity and width at 1/e2 increased and decreased over time, respectively.

Prediction of effectiveness of potassium-competitive acid blocker and serotonin noradrenaline reuptake inhibitor on abnormal sensation in the throat: use of patient-reported outcome measures (PROMs).

PURPOSE: To determine patients with abnormal sensation in the throat (AST) who would respond to potassium-competitive acid blocker (P-CAB) or serotonin noradrenaline reuptake inhibitor (SNRI) treatment. METHODS: AST patients were randomly divided into two groups. Thirty-one and 21 patients received P-CAB and SNRI treatment, respectively. GETS-J, the Japanese version of Glasgow Edinburgh Throat Scales (GETS), consisted of three subscales of throat symptoms (globus sensation, pain/swelling of the throat, and dysphagia) and somatic distress due to the disease, Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (FSSG), and Hospital Anxiety and Depression Scale (HADS) were used before and after treatments. Responders to treatments were defined as those who showed 50% or more decrease in symptom scores or somatic distress. RESULTS: Pre-treatment GETS-J pain/swelling scores and FSSG acid reflux scores were higher in P-CAB responders and decreased after treatment. Receiver operating characteristic curve for pain/swelling subscale had an area under the curve (AUC) of 0.792 to predict P-CAB responders and a score of 11 provided the best combination of sensitivity (62.5%) and specificity (80%). Somatic distress and HADS anxiety scores, but no other GETS-J symptom scores, decreased after SNRI treatment. Pre-treatment globus scores were lower in SNRI responders. AUC value for globus subscale to predict SNRI responders was 0.741 and a score of 6.5 provided the best combination of sensitivity (70%) and specificity (73%). CONCLUSIONS: Pain/swelling is a characteristic symptom in AST patients who respond to P-CAB treatment. SNRI treatment would be effective for somatic distress in cases with mild symptoms.

Aberrant mucosal immunoreaction to tonsillar microbiota in immunoglobulin A nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by mesangial polymeric IgA1 deposition. IgAN is believed to develop owing to aberrant mucosal immunoreaction against commensals in the tonsils. However, the exact interrelation between pathogenic IgA and mucosal microbiota in IgAN patients is unclear. METHODS: Biopsy-proven IgAN or recurrent tonsillitis (RT) patients who had undergone tonsillectomy were enrolled. We used 16S ribosomal RNA gene amplicon sequencing with a flow cytometry-based bacterial cell sorting technique) and immunoglobulin repertoire sequencing of the IgA heavy chain to characterize IgA-coated bacteria of the tonsillar microbiota (IgA-SEQ) and their corresponding IgA repertoire. Furthermore, we fractionated patient serum using gel-filtration chromatography and performed flow cytometry-based analysis of IgA binding to bacteria cultured from incised tonsils. RESULTS: Tonsillar proliferation-inducing ligand and B-cell activating factor levels were significantly higher in IgAN than in RT patients. IgA-SEQ for tonsillar microbiota revealed the preferential binding ability of IgA to Bacteroidetes in IgAN tonsils compared with those from RT patients. Expression of immunoglobulin heavy (IGH) constant alpha 1 with IGH variable 3-30 was significantly higher in IgAN than that in RT, and positively correlated with the IgA-coated enrichment score of Bacteroidetes. Serum polymeric IgA, comprising high levels of GdIgA1, exhibited considerable binding to Bacteroidetes strains cultured from the tonsils of IgAN patients. CONCLUSIONS: These findings provide evidence that aberrant mucosal immune responses to tonsillar anaerobic microbiota, primarily consisting of members of the phylum Bacteroidetes, are involved in IgAN pathophysiology.

Influence of surface treatment on bonding of resin luting cement to CAD/CAM composite blocks.

The aim of this study was to determine the influence of different surface treatments of CAD/CAM composite blocks on bonding effectiveness of resin cements, based on the shear bond strength test and the surface science examination. Specimens were fabricated from two types of CAD/CAM composite blocks (Cerasmart and VITA Enamic), and the specimen surfaces were alumina sandblasted. Specimen surfaces were treated with i) silane, ii) primer, and iii) silane+primer, then two types of cements (Block HC Cem and Super Bond) were bonded. After 24 h storage, bond strengths were measured. Surface free energy measurements were performed of the treated CAD/CAM composite blocks surfaces. The groups ii) and iii) showed significantly higher bond strengths than the group i), apart from VITA Enamic with Block HC Cem. Although the total surface free energy showed different trends in different surface treatments, a similar trend was found in both CAD/CAM composite blocks.

Effects of unilateral sinonasal surgery on sleep-disordered breathing.

Aims/objectives: To examine the effects of surgery for unilateral sinonasal lesions on sleep-disordered breathing (SDB). Material and methods: Oxygen desaturation index (3%ODI) as a marker of SDB and bilateral/unilateral nasal resistance were measured before and after surgery for 18 patients with unilateral sinonasal lesions. Various parameters were compared between those who achieved 60% or less decrease of 3%ODI and those who did not. Results: Bilateral nasal resistance as well as that of the surgical side five days after surgery was significantly lower than those of pre-operative value. Preoperative 3%ODI (times/hour) was 10.08 ± 7.32, which significantly decreased to 7.67 ± 5.79 five days after surgery. Even in unilateral patients, sinonasal surgery could reduce the bilateral nasal resistance, resulting in a decrease in 3%ODI. Age was younger and postoperative nasal resistance of the surgical side was significantly lower in the group who achieved 60% or less decrease in 3%ODI than those who did not. Conclusions and significance: SDB is influenced by even unilateral nasal obstruction. Surgery for unilateral lesion can improve the respiration during sleep as well as bilateral nasal resistance. Favorable outcome by surgery could be brought about in younger patients and those for whom sufficient improvement of nasal resistance was expected by surgery.

[RESULTS OF TONSILLECTOMY AND STEROID PULSE THERAPY IN 20 CASES OF RECURRENT IgA NEPHROPATHY AFTER KIDNEY TRANSPLANTATION].

(Background) The standard treatment for recurrent immunoglobulin A nephropathy (rIgAN) after kidney transplantation (KTx) has not been established. (Methods) The results of treatment consisting of tonsillectomy and steroid pulse therapy in 20 recipients who were diagnosed as rIgAN were retrospectively analyzed. (Results) The level of proteinuria significantly decreased from 0.84±0.81 g/day to 0.27±0.31 g/day after treatment (P=0.007). Microscopic hematuria disappeared or improved in 58.3% and 66.6% of recipients 6 and 12 months after treatment, respectively. Serum creatinine levels remained stable for 5 years by the treatment, except for 3 cases of graft loss. Sixteen recipients received renal graft biopsies before and after treatment. Mesangial IgA deposition were dramatically decreased in 7 recipients (43.75%). The degree of mesangial hypercellularity, endocapillary hypercellularity, and crescents formation improved in 3 (18.8%), 6 (37.5%), and 4 (25%) recipients after treatment. (Conclusion) Steroid pulse therapy combined with tonsillectomy may be clinically and histopathologically effective treatment for rIgAN after KTx.

Polysomnography as an indicator for cervicomedullary decompression to treat foramen magnum stenosis in achondroplasia.

OBJECTIVE: Management of cervicomedullary compression due to foramen magnum stenosis in achondroplasia remains controversial, especially for patients with no symptoms or mild symptoms. We examined the effectiveness of polysomnography (PSG) as an indicator for cervicomedullary decompression treatment. METHODS: We retrospectively reviewed nine achondroplasia cases (mean age 1 year and 9 months) treated from 2008 to 2015. All patients were examined by PSG, magnetic resonance imaging (MRI), and otolaryngeal fibroscopy. We analyzed demographic data, clinical presentation, degree and type of respiratory impairment, severity of foramen magnum stenosis and concomitant cervicomedullary compression, treatment (conservative or surgical), and clinical outcome. RESULTS: Eight of nine patients presented with no severe symptoms in the daytime. However, MRI revealed four severe, four moderate, and one mild case of cervicomedullary compression, and PSG demonstrated severe sleep apnea in four cases and moderate sleep apnea in five cases. All sleep apnea cases were obstructive or obstructive-dominant. Fibroscopy revealed no upper airway stenosis in six cases and mild stenosis in three cases. Four patients who had severe sleep-related respiratory disturbance on PSG and severe or moderate cervicomedullary compression were treated by cervicomedullary decompression. Three of these patients demonstrated improved sleep respiration soon after surgery, while one required temporary tracheostomy due to bilateral vocal cord paralysis caused by compression during intratracheal intubation. CONCLUSION: Polysomnography can be a useful indicator for cervicomedullary decompression surgery, especially in cases of seemingly asymptomatic achondroplasia with severe foramen magnum stenosis.

Reliability and validity of the Japanese version of the Glasgow Edinburgh Throat Scale (GETS-J): Use for a symptom scale of globus sensation.

OBJECTIVE: Globus sensation, a feeling of lump or something stuck in the throat, could be caused by structural, functional, and psychogenic diseases. Due to a possible multifactorial nature of the disease, neither diagnosing test battery nor standard treatment for globus sensation has been established. Therefore, a questionnaire to accurately identify globus patients and evaluate the severity of the disease is desired. Glasgow Edinburgh Throat Scale (GETS) is a 10-item questionnaire about the throat symptoms consisting of three subscales relating to dysphagia, globus sensation, and pain/swelling in the throat. It was reported that globus patients marked high scores specifically for the globus scale among three scales, indicating that GETS can be used as a valid symptom scale for globus sensation. Aims of this study were to translate GETS into Japanese and to test its reliability and validity. METHODS: Fifty-five patients complaining of globus sensation without abnormal endoscopic and CT findings were enrolled into the study. They were asked to answer the questions of GETS translated into Japanese (GETS-J). Reliability (internal consistency) of the questionnaire was tested using Cronbach's coefficient alpha. To test the validity, principal components analysis was used to identify the factorial structure of the questionnaire and GETS-J data were compared with those reported in the original GETS. Contribution of psychiatric comorbidities to globus sensation was also investigated by examining the correlation between Hospital Anxiety and Depression Scale (HADS) and GETS-J. RESULTS: Reliability of the questionnaire examined by the Cronbach's coefficient alpha was satisfactory and all higher than 0.75. Principal components analysis identified following three questions as the globus scale: Q1, Feeling something stuck in the throat; Q5, Throat closing off; Q9, Want to swallow all the time. Somatic distress, i.e., patients' reaction to throat symptoms, was significantly correlated with globus scale (r=0.680). Anxiety component of HADS was significantly correlated with somatic distress but not with globus scale. These results were consistent with those of the original GETS except for the replacement of Q3 (discomfort/irritation in the throat) to Q5 (throat closing off) for globus scale in GETS-J. CONCLUSION: Translation of GETS into Japanese showed high reliability and validity, suggesting that translation and cross-cultural adaptation were not problematic. High correlation of globus scale of GETS-J with somatic distress indicated that GETS-J could be a useful questionnaire to identify the globus patients and evaluate the severity of the disease. Anxiety may complicate the somatic distress in patients with globus sensation.

Surgical treatment of enterovirus D68 brainstem encephalitis-induced dysphagia.

Cluster of acute flaccid paralysis and cranial nerve dysfunction was associated with a 2014 outbreak of enterovirus D68 (EV-D68) respiratory illness in US. We describe a 33 year-old male patient of refractory dysphagia due to EV-D68-induced brainstem encephalitis successfully treated by surgery. Following acute upper respiratory tract infection, he developed dysphagia and bilateral facial paralysis. A coughing reflex was readily produced when the laryngopharyngeal fiberscope touched the epiglottis, however, water infusion induced only very weak and slow swallowing reflex, suggesting that only motor component was impaired but sensory function was preserved during swallowing. Despite eight months-conservative rehabilitations, Food Intake Level Scale (FILS) remained level 4. Therefore, corrective surgeries including cricopharyngeal myotomy, laryngeal suspension, and pharyngeal flap were performed. Thirty-six days after surgery, FILS rapidly and dramatically improved to level 8. This is the first report describing a successful surgical intervention for EV-D68-induced refractory dysphagia. Surgical treatment was suitable for EV-D68-induced dysphagia, perhaps because sensory function was preserved and only motor disturbance was present during the pharyngeal stage of swallowing.

Comprehensive microbiome analysis of tonsillar crypts in IgA nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most prevalent primary chronic glomerular disease, in which the mucosal immune response elicited particularly in the tonsils or intestine has been estimated to be involved in the development of the disease. To explore the relationship between IgAN and bacterial flora in the tonsils, we conducted a comprehensive microbiome analysis. METHODS: We enrolled 48 IgAN patients, 21 recurrent tonsillitis (RT) patients without urine abnormalities and 30 children with tonsillar hyperplasia (TH) who had undergone tonsillectomy previously. Genomic DNA from tonsillar crypts of each patient was extracted, and V4 regions of the 16S ribosomal RNA gene were amplified and analysed using a high-throughput multiplexed sequencing approach. Differences in genus composition among the three study groups were statistically analysed by permutational multivariate analysis of variance and visualized by principal component analysis (PCA). RESULTS: Substantial diversity in bacterial composition was detected in each sample. Prevotella spp., Fusobacterium spp., Sphingomonas spp. and Treponema spp. were predominant in IgAN patients. The percentage of abundance of Prevotella spp., Haemophilus spp., Porphyromonas spp. and Treponema spp. in IgAN patients was significantly different from that in TH patients. However, there was no significant difference in the percentage of abundance of any bacterial genus between IgAN and RT patients. PCA did not distinguish IgAN from RT, although it discriminated TH. No significant differences in microbiome composition among the groups of IgAN patients according to clinicopathological parameters were observed. CONCLUSIONS: Similar patterns of bacteria are present in tonsillar crypts of both IgAN and RT patients, suggesting that the host response to these bacteria might be important in the development of IgAN.