Head and neck cancer patients show poor oral health as compared to those with other types of cancer.

PURPOSE: Several studies have found associations between periodontitis and various types of cancer. Since the site of head and neck cancer (HNC) has contiguity or proximity to the oral cavity, it may be particularly influenced by oral inflammation. This study aimed to determine whether HNC patients have poor oral health as compared to those with other types of cancer. METHODS: This study retrospectively examined oral environmental factors including periodontal inflamed surface area (PISA), a new periodontal inflammatory parameter. A total of 1030 cancer patients were divided into the HNC (n = 142) and other cancer (n = 888) groups. Furthermore, the HNC group was divided into high (n = 71) and low (n = 71) PISA subgroups, and independent risk factors affecting a high PISA value were investigated. RESULTS: Multivariate logistic regression analysis showed that number of missing teeth (odds ratio 1.72, 95% CI 1.15-2.56, P < 0.01), PISA (odds ratio 1.06, 95% CI 1.03-1.06, P < 0.05), and oral bacterial count (odds ratio 1.02, 95% CI 1.01-1.03, P < 0.01) were independent factors related to HNC. In addition, multivariate logistic regression analysis indicated that current smoker (odds ratio 7.51, 95% CI 1.63-34.71, P < 0.01) and presence of untreated dental caries (odds ratio 3.33, 95% CI 1.23-9.00, P < 0.05) were independent risk factors affecting high PISA values in HNC patients. CONCLUSION: HNC patients have higher levels of gingival inflammation and poor oral health as compared to patients with other types of cancer, indicating that prompt oral assessment and an effective oral hygiene management plan are needed at the time of HNC diagnosis.

Identification of genotype-biochemical phenotype correlations associated with fructose 1,6-bisphosphatase deficiency.

Fructose-1,6-bisphosphatase (FBPase) deficiency, caused by an FBP1 mutation, is an autosomal recessive disorder characterized by hypoglycemic lactic acidosis. Due to the rarity of FBPase deficiency, the mechanism by which the mutations cause enzyme activity loss still remains unclear. Here we identify compound heterozygous missense mutations of FBP1, c.491G>A (p.G164D) and c.581T>C (p.F194S), in an adult patient with hypoglycemic lactic acidosis. The G164D and F194S FBP1 mutants exhibit decreased FBP1 protein expression and a loss of FBPase enzyme activity. The biochemical phenotypes of all previously reported FBP1 missense mutations in addition to G164D and F194S are classified into three functional categories. Type 1 mutations are located at pivotal residues in enzyme activity motifs and have no effects on protein expression. Type 2 mutations structurally cluster around the substrate binding pocket and are associated with decreased protein expression due to protein misfolding. Type 3 mutations are likely nonpathogenic. These findings demonstrate a key role of protein misfolding in mediating the pathogenesis of FBPase deficiency, particularly for Type 2 mutations. This study provides important insights that certain patients with Type 2 mutations may respond to chaperone molecules.

Severe multiple simultaneous immune-related adverse events in a patient with head and neck cancer.

Nivolumab, an immune checkpoint inhibitor (ICI) against the programmed death-1 pathway, has been used for the treatment of recurrent metastatic head and neck cancer. However, the management of immune-related adverse events (irAEs), a unique side effect of ICI therapy, can be problematic. Although severe irAEs have been reported to result from multi-ICI therapy, we report a case of multiple severe irAEs caused by single-agent nivolumab treatment. Nivolumab was administered to treat a case of hypopharyngeal cancer recurrence. However, when first-line chemotherapy of nivolumab was replaced with a second chemotherapeutic agent because of insufficient effectiveness, the patient showed anorexia, dermatitis, and mucositis; upper gastrointestinal endoscopy yielded a diagnosis of irAEs. Additional examinations revealed simultaneous multiple irAEs, including hypothyroidism, dermatitis, eyelid conjunctivitis, tracheal mucositis, upper gastrointestinal ulcer, and type 1 diabetes. Since all symptoms improved after steroid treatment, the patient was treated with subsequent chemotherapy. However, he died from uncontrolled cancer recurrence. Thus, even a single ICI agent can cause life-threatening irAEs. Moreover, the management of irAEs requires early recognition and close multidisciplinary collaboration in accordance with the countermeasure manual.

Determining Invasion Depth in Superficial Pharyngeal Carcinoma by Transoral Ultrasonography.

OBJECTIVES: To examine the clinical usefulness of transoral ultrasonography (US) in determining the invasion depth of superficial pharyngeal carcinoma (SPC). Determining the invasion depth of SPC is crucial for transoral surgery including determining treatment strategy. This study aimed to examine the usefulness of transoral US in determining the invasion depth of SPC. METHODS: Forty-six patients with 51 lesions who underwent both magnifying endoscopy with narrow-band imaging (ME-NBI) and transoral US were included. The primary outcomes were the sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of ME-NBI and transoral US findings for pathological tumor depth in SPCs. RESULTS: The accuracy (82.4%), sensitivity (85.2%), PPV (82.1%), and NPV (82.6%) rates of US for subepithelial propria (SEP) were higher than those of ME-NBI and macroscopic classification, indicating that transoral US is superior to ME-NBI in determining the invasion depth. All cases where the SEP was clearly invaded (SEP deep) could be diagnosed as SEP by transoral US. CONCLUSIONS: Transoral US may be useful in determining the invasion depth of SPCs. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2192-2197, 2023.

Evaluation of standardized uptake value on 131I-6ß-iodomethyl-19-norcholesterol scintigraphy for diagnosis of primary aldosteronism and correspondence with adrenal venous sampling.

PURPOSE: Adrenal venous sampling (AVS) is a reliable method for lateralization of adrenal hormone secretion, which is important for discriminating between aldosterone-producing adenoma and bilateral adrenal hyperplasia, both of which cause primary aldosteronism (PA). The aim of this study was to evaluate the diagnostic accuracy of the maximum and mean standardized uptake values (SUVmax and SUVmean, respectively) of 131I-6ß-iodomethyl-19-norcholesterol (NP-59) single-photon emission computed tomography (SPECT) for PA and its correspondence with AVS. METHODS: Adrenal NP-59 scintigraphy was performed in 14 patients with suspected PA, and AVS was also performed in 7 of them. SUVmax and SUVmean of the adrenal lesions on the dominant side and their ratios to the values on the non-dominant side (SUVRmax and SUVRmean, respectively) were calculated on SPECT images using ordered-subset conjugate gradient minimization (OSCGM) and three-dimensional ordered-subset expectation maximization (3D-OSEM) reconstruction algorithms. RESULTS: SUVmax and SUVmean on NP-59 SPECT images were significantly higher for aldosterone-producing adenoma than for bilateral adrenal hyperplasia or non-functioning adenoma and slightly superior to SUVRmax and SUVRmean (P = 0.0475 and P = 0.0447 vs. P = 0.124 and P = 0.132, respectively, with OSCGM). The respective areas under the receiver-operating characteristic curve for SUV and SUVR were 0.933 and 0.725 with OSCGM and 0.844 and 0.750 with 3D-OSEM, while SUVmax and SUVRmax had exactly the same diagnostic accuracy as SUVmean and SUVRmean. SUV and SUVR were associated with the diagnostic features on AVS and consistent with lateralization by AVS in most patients. CONCLUSION: In this study, SUV on NP-59 SPECT helped in the diagnosis of PA and was consistent with the results of AVS in nearly all cases.

Effectiveness of Expanded Instantaneous Input Dynamic Range Adjustment on Speech Perception.

Instantaneous input dynamic range (IIDR), as defined by Cochlear Ltd. (Sydney, Australia), refers to the acoustic level of short-term input dynamic range (IDR). Our aim was to evaluate the efficacy of expanding IIDR to improve speech understanding. We enrolled 11 unilateral Cochlear Ltd. patients with post-lingual hearing loss. The two types of IIDR settings (T-SPL/C-SPL of 25/65 dB (default IIDR) and 25/80 dB (wide IIDR)) were blindly assigned, and only one IIDR setting selected according to their preference was used for at least three months. Each IIDR group was evaluated with both default and wide IIDR conditions using the recorded word and sentence test materials of the Japanese CD speech discrimination scoring system (CI-2004 test) in quiet and noise with a signal-to-noise ratio (SNR) of +10 dB, presented at 65/80 dB SPL. Wide IIDR significantly improved speech perception in all tests, except for sentences in quiet conditions at a presentation level of 65 dB. Improvements during loud conversations in noisy environments were obtained without any adaptation period. Wide IIDR should become a new individual configuration setting method in Cochlear Ltd. devices to improve hearing in loud conversations and noisy environments.

Deep Association between Transglutaminase 1 and Tissue Eosinophil Infiltration Leading to Nasal Polyp Formation and/or Maintenance with Fibrin Polymerization in Chronic Rhinosinusitis with Nasal Polyps.

Transglutaminase (TGM) isoform catalyze the cross-linking reaction of identical or different substrate proteins. Eosinophil has been recognized in chronic rhinosinusitis with nasal polyps (CRSwNP) forming tissue eosinophil in nasal polyp (NP), and TGM isoforms are suggested to be associated with a critical role in asthma and other allergic conditions. The aim of this study was to reveal the association of specific TGM isoform with both the tissue eosinophil infiltration deeply concerning with the intractable severity of CRSwNP and the fibrin polymerization ability of TGM isoform associated with the tissue eosinophil infiltration, which lead to NP formation and/or maintenance in CRSwNP. NP tissues (CRSwNP group) and uncinate process (UP) (control group) were collected from patients with CRSwNP and control subjects. We examined: (1) the expression level of TGM isoforms by using a real-time polymerase chain reaction (PCR) and the comparison to the issue eosinophil count in the CRSwNP group, (2) the location of specific TGM isoform in the mucosal tissue using immunohistochemistry, (3) the inflammatory cell showing the colocalization of specific TGM isoform in Laser Scanning Confocal Microscopy (LSCM) imaging, and (4) the fibrin polymerase activity of specific TGM isoform using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). A certain level of TGM 1, 2, 3, 5 expression was present in both the CRSwNP group and the control group. Only TGM 1 expression showed a positive significant correlation with the tissue eosinophil count in the CRSwNP group. The localization of TGM 1 in NP (CRSwNP) laid mainly in a submucosal layer as inflammatory cells and was at the cytoplasm in the tissue eosinophil. Fibrin polymerase activity of TGM 1 showed the same polymerase ability of factor XIIIA. TGM 1 might influence the NP formation and/or maintenance in CRSwNP related to the tissue eosinophil infiltration, which formed fibrin mesh composing NP stroma.

Proteogenomic landscape and clinical characterization of GH-producing pituitary adenomas/somatotroph pituitary neuroendocrine tumors.

The clinical characteristics of growth hormone (GH)-producing pituitary adenomas/somatotroph pituitary neuroendocrine tumors (GHomas/somatotroph PitNETs) vary across patients. In this study, we aimed to integrate the genetic alterations, protein expression profiles, transcriptomes, and clinical characteristics of GHomas/somatotroph PitNETs to identify molecules associated with acromegaly characteristics. Targeted capture sequencing and copy number analysis of 36 genes and nontargeted proteomics analysis were performed on fresh-frozen samples from 121 sporadic GHomas/somatotroph PitNETs. Targeted capture sequencing revealed GNAS as the only driver gene, as previously reported. Classification by consensus clustering using both RNA sequencing and proteomics revealed many similarities between the proteome and the transcriptome. Gene ontology analysis was performed for differentially expressed proteins between wild-type and mutant GNAS samples identified by nontargeted proteomics and involved in G protein-coupled receptor (GPCR) pathways. The results suggested that GNAS mutations impact endocrinological features in acromegaly through GPCR pathway induction. ATP2A2 and ARID5B correlated with the GH change rate in the octreotide loading test, and WWC3, SERINC1, and ZFAND3 correlated with the tumor volume change rate after somatostatin analog treatment. These results identified a biological connection between GNAS mutations and the clinical and biochemical characteristics of acromegaly, revealing molecules associated with acromegaly that may affect medical treatment efficacy.

Utility of plasma circulating tumor DNA and tumor DNA profiles in head and neck squamous cell carcinoma.

Early recurrence detection of head and neck squamous cell carcinoma (HNSCC) is important for improving prognosis. Recently, circulating tumor DNA (ctDNA) has been reported to be useful in early detection or treatment response determination in various carcinomas. This study aimed to identify the utility of ctDNA for predicting recurrent metastasis in patients with HNSCC. We collected pre-treatment tissues (malignant and normal tissues) and multiple plasma samples before and after treatment for 20 cases of HNSCC treated with radical therapy. ctDNA was detected in pre-treatment plasma in 10 cases; however, there were no significant associations with tumor recurrence and staging. During follow-up, ctDNA was detected in 5 of the 7 plasma samples of recurrent cases but not in the 13 recurrence-free cases. Moreover, there was a significant difference in post-treatment relapse-free survival time between the groups with and without detected ctDNA (20.6 ± 7.7 vs. 9.6 ± 9.1 months, respectively; log-rank test, p < 0.01). Moreover, for two of the five cases with ctDNA detected after treatment, ctDNA detection was a more sensitive predictor of recurrence than imaging studies. ctDNA detection during treatment follow-up was useful in patients with HNSCC for predicting the response to treatment and recurrent metastasis.

Swallowing function after transoral surgery for laryngopharyngeal cancer.

Transoral surgery (TOS) has been widely used to treat laryngopharyngeal cancers. Although TOS is a minimally invasive procedure, postoperative complications, such as postoperative dysphagia, may occur, which can lead to a poor quality of life for patients undergoing TOS. This study aimed to investigate factors that may affect swallowing function in patients who underwent TOS for laryngopharyngeal cancers. Swallowing function of 84 patients who underwent endoscopic resection for oropharyngeal, hypopharyngeal, and supraglottic lesions was evaluated by the Functional Outcome Swallowing Scale, and predictors for postoperative dysphagia were identified. Multivariate analysis identified the following factors as independent predictors for postoperative dysphagia: Eastern Cooperative Oncology Group Performance Status (ECOG PS, p = 0.008), prior neck radiation therapy (p = 0.008), and operative time (p = 0.021). This study suggests that patients with poor ECOG PS or those who received prior neck radiation therapy should be fully assessed for preoperative swallowing function. In the future, we would like to clarify the criteria for preoperative swallowing evaluation to create a system that can identify patients suitable for TOS.

Distinct Gene Set Enrichment Profiles in Eosinophilic and Non-Eosinophilic Chronic Rhinosinusitis with Nasal Polyps by Bulk RNA Barcoding and Sequencing.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with a high symptom burden, including nasal congestion and smell disorders. This study performed a detailed transcriptomic analysis in CRSwNP classified as eosinophilic CRS (ECRS), nonECRS according to the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) criteria, and a group of ECRS with comorbid aspirin intolerant asthma (Asp). Gene expression profiles of nasal polyps and the uncinate process in CRSwNP patients and normal subjects (controls) were generated by bulk RNA barcoding and sequencing (BRB-seq). A differentially expressed genes (DEGs) analysis was performed using DESeq2 software in iDEP to clarify any relationship between gene expression and disease backgrounds. A total of 3004 genes were identified by DEGs analysis to be associated with ECRS vs control, nonECRS vs control, and Asp vs control. A pathway analysis showed distinct profiles between the groups. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) showed distinct phenotype-specific pathways of expressed genes. In the specific pathway of "cytokine-cytokine receptor interaction", the differentially expressed genes were widely distributed. This study indicates that transcriptome analysis using BRB-seq may be a valuable tool to explore the pathogenesis of type 2 inflammation in CRSwNP.

A Case of Primary Osteosarcoma of the Mandible That Responded to Preoperative Chemotherapy: p16 as a Potential Prognostic Factor.

We report a case of mandibular osteosarcoma in a Japanese woman in her 70s who was p16-positive. Despite the rapid growth of the tumor, the patient responded well to chemotherapy and was then able to undergo surgery. Head and neck osteosarcoma (HNOS) is a very rare cancer, and although the importance of surgery has been pointed out, the effectiveness of chemotherapy is unclear. Resection margin negativity and response to chemotherapy have been reported as prognostic factors; another report assessed the effectiveness of the immunohistochemical expression of p16 protein as a predictor of response to chemotherapy.

A long survival patient of anaplastic thyroid carcinoma treated with lenvatinib.

Anaplastic thyroid carcinoma (ATC) accounts for 1-2% of all malignant thyroid tumors. There are only a small number of patients with ATC and most of them die within 6 months after diagnosis, making it difficult to establish a standard treatment strategy. Although multimodal therapy, including radical surgery, radiotherapy, and chemotherapy, has been introduced, the survival rate remains poor. The use of molecular-targeted drugs for cancer therapy has become widely popular. Lenvatinib, a new molecular-targeted anticancer drug, is a multi-targeted receptor tyrosine kinase inhibitor (TKI). We report a rare case of a patient with ATC (T4N0M0) who responded extremely well to the administration of lenvatinib after radical surgery. Although ATC is one of the most fatal neoplasms, lenvatinib is a promising drug.

Baseline Neutrophil-to-Lymphocyte Ratio and Glasgow Prognostic Score are Associated with Clinical Outcome in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Treated with Nivolumab.

Recurrent or metastatic head and neck squamous cell carcinoma (R/MHNSCC) has a poor prognosis. Although nivolumab is approved in Japan for treating R/MHNSCC, the response rate is low. Therefore, identifying pretreatment prognostic factors is necessary. This study assessed the utility of the neutrophil-to-lymphocyte ratio (NLR) and Glasgow Prognostic Score (GPS) as biomarkers of response to nivolumab. We retrospectively collected the data of 56 R/MHNSCC patients treated with nivolumab between May 2017 and December 2019. The Kaplan-Meier method and log-rank test were used to estimate overall survival (OS) and progression-free survival (PFS), and multivariate Cox hazard regression analysis was used to identify independent predictors of survival. Patients with a low pretreatment NLR had prolonged OS, and patients with a low pretreatment GPS had increased OS and PFS. A performance score (PS) of 0-1, development of immune-related adverse events, and GPS of 0-1 were significantly associated with OS in multivariate analysis. In summary, baseline pretreatment NLR and GPS are independently associated with OS in R/MHNSCC patients treated with nivolumab. Administration of nivolumab while maintaining the PS reflects a immune status of the host and leads to a good OS.

Identification of a Novel Copy Number Variation of EYA4 Causing Autosomal Dominant Non-syndromic Hearing Loss.

OBJECTIVE: Eyes absent 4 (EYA4) is the causative gene of autosomal dominant non-syndromic hereditary hearing loss, DFNA10. We aimed to identify a copy number variation of EYA4 in a non-syndromic sensory neural hearing loss pedigree. FAMILY AND CLINICAL EVALUATION: A Japanese family showing late-onset and progressive hearing loss was evaluated. A pattern of autosomal dominant inheritance of hearing loss was recognized in the pedigree. No cardiac disease was observed in any of the individuals. METHODS: Targeted exon sequencing was performed using massively parallel DNA sequencing (MPS) analysis. Scanning of the array comparative genomic hybridization (aCGH) was completed and the copy number variation (CNV) data from the aCGH analysis was confirmed by matching all CNV calls with MPS analysis. Breakpoint detection was performed by whole-genome sequencing and direct sequencing. Sequencing results were examined, and co-segregation analysis of hearing loss was completed. RESULTS: We identified a novel hemizygous indel that showed CNV in the EYA4 gene from the position 133,457,057 to 133,469,892 on chromosome 6 (build GRCh38/hg38) predicted as p.(Val124_Pro323del), and that was segregated with post-lingual and progressive autosomal dominant sensorineural hearing loss by aCGH analysis. CONCLUSION: Based on the theory of genotype-phenotype correlation with EYA4 mutations in terms of hearing loss and comorbid dilated cardiomyopathy, the region of amino acids 124 to 343 is hypothesized not to be the pathogenic region causing dilated cardiomyopathy. Additionally, the theory of genotype-phenotype correlation about the prevalence of dilated cardiomyopathy is thought to be rejected because of no correlation of deleted amino acid region with the prevalence of dilated cardiomyopathy. These results will help expand the research on both the coordination of cochlear transcriptional regulation and normal cardiac gene regulation via EYA4 transcripts and provide information on the genotype-phenotype correlations of DFNA10 hearing loss.

Visualizing Half-Metallic Bulk Band Structure with Multiple Weyl Cones of the Heusler Ferromagnet.

Using a well-focused soft x-ray synchrotron radiation beam, angle-resolved photoelectron spectroscopy was applied to a full-Heusler-type Co_{2}MnGe alloy to elucidate its bulk band structure. A large parabolic band at the Brillouin zone center and several bands that cross the Fermi level near the Brillouin zone boundary were identified in line with the results from first-principles calculations. These Fermi-level crossings are ascribed to majority spin bands that are responsible for electron transport with extremely high spin polarization especially along the direction perpendicular to the interface of magnetoresistive devices. The spectroscopy confirms there is no contribution of the minority spin bands to the Fermi surface, signifying half-metallicity for the alloy. Furthermore, two topological Weyl cones with band crossing points were identified around the X point, yielding the conclusion that Co_{2}MnGe could exhibit topologically meaningful behavior such as large anomalous Hall and Nernst effects driven by the Berry flux in its half-metallic band structure.

Small intestinal bacterial overgrowth as a cause of protracted wound healing and vitamin D deficiency in a spinal cord injured patient with a sacral pressure sore: a case report.

BACKGROUND: Pressure sores are sometimes refractory to treatment, often due to malnutrition. Small intestinal bacterial overgrowth (SIBO) obstructs absorption in the digestive tract and causes malnutrition. However, little is known about the association between pressure sore wound healing and SIBO. Here, we report a case of a patient with a refractory sacral pressure sore and SIBO. CASE PRESENTATION: A 66-year-old woman who was spinal cord injured 14 years before visiting our hospital presented with the chief complaint of a sacral pressure sore, 10.0 × 6.5 cm in size, which was refractory to treatment. Physical examination showed abdominal distension and emaciation, with a body mass index of 15. Further examination revealed elevated serum alkaline phosphatase (1260 U/L), bilateral tibial fracture, multiple rib fracture, and osteoporosis. We diagnosed the patient with osteomalacia with vitamin D deficiency. Despite oral supplementation, serum levels of calcium, phosphorous, and vitamin D remained low. Also, despite concentrative wound therapy for the sacral pressure sore by plastic surgeons, no wound healing was achieved. Due to a suspicion of disturbances in nutrient absorption, we performed bacterial examination of collected gastric and duodenal fluid, which showed high numbers of bacteria in gastric content (104 E. coli, 105 Streptococcus species, and 105 Neisseria species) and duodenal content (106 E. coli, 104 Candida glabrata). Therefore, we diagnosed the patient with SIBO and started selective decontamination of the digestive tract using polymyxin B sulfate and amphotericin B. After starting treatment for SIBO, the sacral pressure sore began to heal and was nearly healed after 285 days. The patient's serum levels of calcium, phosphorous, vitamin D, and other fat-soluble vitamins also gradually increased after starting treatment for SIBO. CONCLUSION: We report a case of a patient with a refractory sacral pressure sore that healed after starting treatment for SIBO. We conclude that SIBO may be an overlooked cause of malnutrition and poor wound healing in patients with chronic pressure sores.

Baseline neutrophil-to-lymphocyte ratio (NLR) is associated with clinical outcome in recurrent or metastatic head and neck cancer patients treated with nivolumab.

Background: Nivolumab has been approved for recurrent or metastatic head and neck cancer (R/M HNC) on March 2017 in Japan. Recently, many researchers have been actively studying the prognostic and predictive markers. However, they have not been clarified. In this study, we evaluate the prognostic and predictive markers of the anticancer effect of nivolumab.Objective: This study assessed baseline neutrophil-to-lymphocyte ratio (NLR) as a prognostic and predictive marker for nivolumab efficacy in patients with recurrent/metastatic head and neck cancer (R/M HNC).Material and methods: This retrospective cohort study used medical records of patients with R/M HNC treated with nivolumab from May 2017 to January 2018 at a university hospital in Japan.Results: Twenty-nine patients (median age, 64 years) were included. In univariate analyses, baseline NLR ≥5 was significantly associated with overall survival (HR 4.88; p = .045) and progressive disease (HR 5.0; p = .046). More patients with baseline NLR ≥5 changed from nivolumab to best supportive care, compared to patients with baseline NLR <5 (64.3% vs 26.7%, respectively).Conclusions and significance: Baseline NLR was associated with clinical benefit from nivolumab in patients with R/M HNC. We propose that baseline NLR be used as a predictive or prognostic marker for nivolumab efficacy in these patients.

Aldosterone Reduction Rate After Saline Infusion Test May Be a Novel Prediction in Patients With Primary Aldosteronism.

OBJECTIVE: Accurate assessment and localization of aldosterone-producing adenomas (APAs) are essential for the treatment of primary aldosteronism (PA). Although adrenal venous sampling (AVS) is the standard method of reference for subtype diagnosis in PA, controversy exists concerning the criteria for its interpretation. This study aims to determine better indicators that can reliably predict subtypes of PA. METHOD: Retrospective, single-cohort analysis including 209 patients with PA who were subjected to AVS. Eighty-two patients whose plasma aldosterone concentrations (PAC) were normalized after surgery were histopathologically or genetically diagnosed with APA. The accuracy of image findings was compared to AVS results. Receiver operating characteristic (ROC) curve analysis between the operated and the no-apparent laterality groups was performed using AVS parameters and loading test for diagnosis of PA. RESULT: Agreement between image findings and AVS results was 56.3%. ROC curve analysis revealed that the lateralization index (LI) after adrenocorticotropin stimulation cutoff was 2.40, with 98.8% sensitivity and 97.1% specificity. The contralateral suppression index (CSI) cutoff value was 1.19, with 98.0% sensitivity and 93.9% specificity. All patients over the LI and CSI cutoff values exhibited unilateral subtypes. Among the loading test, the best classification accuracy was achieved using the PAC reduction rate after a saline infusion test (SIT) >33.8%, which yielded 87.2% sensitivity or a PAC after a SIT <87.9 pg/mL with 86.2% specificity for predicting bilateral PA. CONCLUSION: The combined criteria of the PAC reduction rate and PAC after the SIT can determine which subset of patients with APA who should be performed AVS for validation.

Nasal nitric oxide in the inferior turbinate surface decreases with intranasal steroids in allergic rhinitis: A prospective study.

OBJECTIVE: It remains controversial whether nasal nitric oxide (NO) serves as a reliable parameter to evaluate treatment efficacy in patients with allergic rhinitis (AR). The measurement of local nasal NO levels has been shown to be a sensitive marker for the diagnosis of symptomatic AR patients. Here we assessed the applicability of nasal NO to evaluations of the efficacy of intranasal steroids (INS) in a prospective design. METHODS: We enrolled 25 patients with perennial AR and 10 age-matched healthy participants. The AR patients received fluticasone furoate (FF) once daily for 2 months. Fractional exhaled NO and nasal NO measurements were carried out using an electrochemical analyzer at pretreatment and at 2 weeks and 2 months after treatment. Nasal NO levels were directly measured at two different areas of the nasal cavity: the surface of the inferior turbinate (IT area) and the front of the middle meatus (MM area). Subjective nasal symptoms were also recorded at each visit. RESULTS: The mean total nasal symptom score in the AR patients decreased significantly after FF treatment (p<0.0001). The mean nasal NO levels in the IT area in the AR patients were significantly higher at pretreatment than those of the healthy participants (109 vs. 62.5 ppb, respectively; p<0.001). After FF administration, the nasal NO levels in the IT area of the AR group showed a significant reduction at both 2 weeks and 2 months (79.1 and 71.9 ppb, respectively; p<0.05 and p<0.01). There was no significant difference in nasal NO levels in the MM area between the controls and the AR group at any visit timepoint. When the ratio of the MM area to the IT area (MM/IT ratio) was plotted for each subject, the untreated AR patients showed a marked decrease in the ratio, whereas after the FF treatment, the AR patients' mean MM/IT ratios showed a significant increase. No significant difference compared to the control group existed at 2 months. CONCLUSION: Nasal NO measurement around the inferior turbinate is an objective measure to evaluate allergic conditions and is useful to monitor therapeutic effects of INS.