Improvements of Age-Related Cognitive Decline in Mice by Lactobacillus helveticus WHH1889, a Novel Strain with Psychobiotic Properties.

A gradual decline in cognitive function occurs with age. Accumulating evidence suggests that certain probiotic strains exert beneficial effects on age-related cognitive decline. Our previous study revealed that Lactobacillus helveticus WHH1889 attenuated symptoms of anxiety and depression in depressed mice via shaping the 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP) metabolism and gut microbial community, indicating the psychobiotic potential of WHH1889. In the present study, the effects of WHH1889 on age-related cognitive decline were investigated. WHH1889 was orally administrated (1 × 109 CFU/day) for twelve weeks in aged mice, and their cognitive behaviors, neurochemical factors, cognitive-related gene expressions, neuroinflammation, and serum tryptophan pathway-targeted metabolic profiling, as well as gut microbiome composition were assessed. WHH1889 demonstrated improvement of the cognitive behaviors via the novel object recognition test (NORT), the active shuttle avoidance test (ASAT), the Y-maze test, and the passive avoidance test (PAT). The hippocampal neuronal loss; the declined concentrations of BDNF, 5-HT, and 5-HTP; the decreased gene expressions of neurodegeneration biomarkers; and the increased production of hippocampal inflammatory cytokines in aged mice were restored by WHH1889. In addition, WHH1889 increased the 5-HT/5HTP levels and decreased the serum levels of tryptophan-derived metabolites (e.g., kynurenine, xanthurenic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid). Furthermore, WHH1889 was revealed to shape the gut microbiota community by reversing the relative abundances of Bacteroidota and Firmicutes. The present findings suggest that L. helveticus WHH1889 exerted cognitive improving effects on aged mice, which was associated with the modulation of 5-HT and 5-HTP metabolism and gut microbial composition. The supplementation of WHH1889 may therefore be a promising therapeutic agent for age-related cognitive deficits.

Leuconostoc mesenteroides WHH1141 ameliorates ovalbumin-induced food allergy in mice.

Food allergy (FA) is acknowledged as a significant public health and food safety issue, due to its manifestation as an amplified immune reaction to food antigens. Recently, probiotics within Lactobacillus and Bifidobacterium have been highlighted as a promising strategy against allergic disease by modulating the balance of Th1/Th2 responses. However, the allergy-alleviating effects of probiotic Leuconostoc mesenteroides strains are unknown. Therefore, this study investigated the potentials of eleven L. mesenteroides strains on the Th1/Th2 balance in vitro by evaluating the expression patterns of interferon-gamma (IFN-γ) (Th1 cytokine) and interleukin-4 (IL-4) (Th2 cytokine) in mesenteric lymph node-derived lymphocytes from ovalbumin (OVA)-sensitized mice. Among strains, WHH1141 incubation caused the highest IFN-γ/IL-4 ratio. Oral administration of WHH1141 (1 × 109  CFU/mL) in the OVA-induced FA mouse model for 40 days improved the weight loss and FA pathological symptoms and normalized the serum immunoglobulin E levels. Meanwhile, the OVA-induced elevated gene expressions of cytokines (IL-4, IL-5, and IL-13) and tight-junction proteins (ZO-1 and Occludin) and levels of cytokines (IL-4, IL-5, and IL-13) and histamine in the jejunum were restored by WHH1141. Furthermore, WHH1141 reversed the reduced gut microbial diversity and short-chain fatty acid (SCFA) levels, specifically increased Bacteroidota abundance, and decreased Firmicutes abundance in OVA-induced mice. Overall, these findings suggest that WHH1141 exerts FA-alleviating effects on OVA-induced mice, which is involved with the inhibition of the jejunal Th2 immune responses and the modulation of gut microbiome composition and SCFA productions. PRACTICAL APPLICATION: Leuconostoc mesenteroides WHH1141 with FA-alleviating potentials may be considered a promising approach in the mitigation of FA symptoms.

Oral administration of Bifidobacterium longum WHH2270 ameliorates type 2 diabetes in rats.

Accumulating evidence suggests that specific probiotic strains exert hypoglycemic effects on type 2 diabetes mellitus (T2DM), and probiotic strains within Bifidobacterium exhibit potential beneficial effects on T2DM. In this study, α-glucosidase inhibitory activities of 14 Bifidobacterium strains were assessed in vitro. The hypoglycemic effects of Bifidobacterium longum WHH2270 with high α-glucosidase inhibitory activity (42.03%) were then investigated in a high-fat diet/streptozotocin-induced T2DM rat model. Oral administration of WHH2270 (4 × 109 CFU/kg/day) for 8 weeks significantly reversed the reduced body weight and ameliorated the levels of fasting blood glucose, serum triglyceride, serum total cholesterol, glucose tolerance, and insulin resistance in T2DM rats. Using 16S rRNA high-throughput sequencing of feces, WHH2270 was revealed to reshape the gut microbiome composition by increasing the abundances of Lactobacillus and Bifidobacterium and decreasing the abundances of UCG_005, Clostridium, and Faecalibacterium in T2DM rats. Besides, the fecal levels of short-chain fatty acids (SCFAs) including acetate, propionate, and butyrate were also elevated after WHH2270 administration. Moreover, the gene expressions of SCFA receptors FFAR2 and FFAR3 in the colon and pancreas of T2DM rats were restored by WHH2270 administration, accompanied by increased levels of serum acetate. In summary, these results provide evidence that WHH2270 has the potential to improve T2DM symptoms by alleviating hyperglycemia, which was associated with changes in the gut microbiome composition and SCFA production. PRACTICAL APPLICATION: Bifidobacterium longum WHH2270 with high α-glucosidase inhibitory activity may serve as a promising hypoglycemic agent for the treatment of T2DM.

Efficacy Assessment and Analysis of Related Factors of Ultrasound-Guided Percutaneous Lauromacrogol Injection for Cystic Thyroid Nodules.

OBJECTIVES: This study aimed to investigate the factors influencing the short-term and long-term efficacy of sclerotherapy for cystic thyroid nodules. METHODS: Ninety-nine cystic thyroid nodules that underwent ultrasound-guided fine-needle aspiration biopsy, detection of thyroglobulin in fine needle aspirate (Tg-FNA), and ultrasound-guided percutaneous lauromacrogol injection were retrospectively enrolled from July 2018 to July 2021. All nodules were followed up at 3 and 12 months after the procedure. Factors related to lauromacrogol injection efficacy, including initial volume, vascularity, pathological types, and Tg-FNA level, were analyzed. The nodules were classified as non-effective (VRR <50%) and effective groups (VRR ≥50%) at 3 months to evaluate short-term prognosis, and non-cured (VRR <90%) and cured groups (VRR ≥90%) at 12 months to evaluate long-term prognosis. RESULTS: The volume of cystic thyroid nodules tended to shrink during follow-up. The resolution rate was 79.80% (79/99) at 3 months and 96.91% (94/97) at 12 months. The cure rate was 80.41% (78/97) at 12 months. Independent factors for the long-term prognosis included Tg-FNA level and vascularity (P  < .05). Only Tg-FNA level was an independent factor for the short-term prognosis (P  < .05). The area under the receiver operating characteristic curve for assessing the efficacy at 3 months was 0.79 (95% confidence interval [CI]: 0.65-0.89). With a cutoff value of Tg-FNA 126.92 ng/mL, the specificity was 0.70, and the sensitivity was 0.85. CONCLUSIONS: Ultrasound-guided percutaneous lauromacrogol injection is an effective treatment option for cystic thyroid nodules. It is less effective in viscous or vascular predominantly cystic nodules.

The supplementation of the multi-strain probiotics WHHPRO™ alleviates high-fat diet-induced metabolic symptoms in rats via gut-liver axis.

Metabolic syndrome (MS) has emerged as one of the major global health concerns, accompanied by a series of related complications, such as obesity and type-2 diabetes. The gut-liver axis (GLA) is a bidirectional communication between the gut and the liver. The GLA alterations have been revealed to be closely associated with the development of MS. Probiotics within Lactobacillus and Bifidobacterium confer beneficial effects on improving MS symptoms. WHHPRO™ is a mixture of four probiotic strains, with potential MS-improving abilities. This study aimed to investigate the effects of WHHPRO™ on MS symptoms using a high-fat diet (HFD) rat model. Oral administration of WHHPRO™ for 12 weeks improved glucose tolerance, blood lipid, body weight, and liver index in HFD rats. WHHPRO™ shaped the gut microbiome composition by increasing the abundance of Lactobacillus and Akkermansia and normalized the reduced SCFA levels in HFD rats. Besides, WHHPRO™ modulated the fecal bile acids (BAs) profile, with decreased levels of T-b-MCA and 12-KDCA and increased levels of LCA and ILCA. Meanwhile, WHHPRO™ increased total unconjugated BAs in feces and liver and reduced the accumulation of total hepatic BA pool size in HFD rats. Moreover, WHHPRO™ reversed the expression of genes associated with impaired BA metabolism signaling in the ileum and liver. Our findings suggest that WHHPRO™ exerted beneficial effects on improving MS symptoms, involving the modulation of the gut microbiome composition, SCFAs, and the FXR-FGF15 signaling along the GLA. Supplementation of WHHPRO™ may serve as a novel strategy for improving MS symptoms.

Probiotic effects of Lacticaseibacillus rhamnosus 1155 and Limosilactobacillus fermentum 2644 on hyperuricemic rats.

Hyperuricemia is the main cause of gout and involved in the occurrence of multiple diseases, such as hypertension, metabolic disorders and chronic kidney disease. Emerging evidence suggests that lactic acid bacteria (LAB) have shown the beneficial effects on the prevention or treatment of hyperuricemia. In this study, the urate-lowering effect of two LAB strains, Lacticaseibacillus rhamnosus 1155 (LR1155) and Limosilactobacillus fermentum 2644 (LF2644) on hyperuricemic rats were investigated. A hyperuricemic rat model was induced by the intragastric treatment of potassium oxonate, combined with a high purine diet. The oral administration of LR1155, LF2644, or a combination of LR1155 and LF2644 for 4 weeks significantly prevented the rise of the serum uric acid (UA) induced by hyperuricemia. LR1155 and LF2644 significantly elevated the fecal UA levels, increased the UA content and up-regulated gene expression of UA transporter, ATP-binding cassette subfamily G-2 (ABCG2), in colon and jejunum tissues, suggesting the accelerated UA excretion from the intestine. Besides, LR1155 significantly inhibited the activity of xanthine oxidase (XOD) in liver and serum, benefited the reduce of UA production. In addition, LF2644 strengthened the gut barrier functions through an up-regulation of the gene expressions for occluding and mucin2, accompanied with the reduced inflammatory indicators of lipopolysaccharide (LPS) and interleukin-1ß (IL-1ß) in hyperuricemic rat. Moreover, using 16s rDNA high-throughput sequencing of feces, LR1155 was shown to improve the hyperuricemia induced gut microbial dysbiosis. The genera Roseburia, Butyricicoccus, Prevotella, Oscillibacter, and Bifidobacterium may associate with the effect of LR1155 on microbiota in hyperuricemic rats. Collectively, the results indicated that LR1155 and LF2644 exhibit urate-lowering effects and could be used alone or in combination as a new adjuvant treatment for hyperuricemia.

Screening of lactic acid bacteria strains with urate-lowering effect from fermented dairy products.

Hyperuricemia is a well-known cause of gout and also a risk factor for various comorbidities. Current agents like xanthine oxidase inhibitors prevent hyperuricemia, but usually induce severe side effects. Alternative strategies, such as novel dietary supplementations, are necessary for the management of hyperuricemia. Lactic acid bacteria (LAB) have been used in human diet for a long time with a good safety record. In this study, 345 LAB strains isolated from traditional fermented dairy products were tested for assimilating abilities of guanosine. Two LAB strains, Lacticaseibacillus rhamnosus 1155 (LR1155) and Limosilactobacillus fermentum 2644 (LF2644), showing great capacities of guanosine transformation and degradation were selected. Compared to LR1155, LF2644 showed a better effect with 100.00% transforming rate and 55.10% degrading rate. In an in vivo test, a hyperuricemic rat model was established and the results showed that administration of LR1155 (p < 0.01) or LF2644 (p < 0.01) prevented the rise of serum uric acid with more than 20% decrease when compared with the hyperuricemia rats. In addition, an increased fecal uric acid level was observed in LF2644 or LR1155 treated rats (LR1155-M p < 0.05, others p < 0.01). This study proved that LR1155 and LF2644 can be promising candidates of dietary supplements for prevention or improvement of hyperuricemia. PRACTICAL APPLICATION: The LAB strains tested in this study could be considered as good potential probiotic candidates for dietary supplements because of their urate-lowering effects, which provide a novel antihyperuricemic strategy with advantages of safety and sustainability.

Recursive Partitioning to Determine Order of Significance of Regional Metastasis Characteristics in Head and Neck Cutaneous Squamous Cell Carcinoma.

BACKGROUND: The order of significance of clinicopathologic characteristics for the prognosis of patients with regional metastases from head and neck cutaneous squamous cell carcinoma (HNcSCC) is not well characterized. This study aimed to understand the impact of the known characteristics, including the presence of immunosuppression, number of deposits, largest deposit size, location and laterality of deposits, and presence of extranodal extension (ENE) on overall survival (OS) and disease-specific survival (DSS). METHODS: A retrospective study of 366 patients treated with curative intent for HNcSCC with regional metastatic disease was undertaken using recursive partitioning analysis (RPA). RESULTS: Using RPA modeling, the study determined that number of metastatic deposits carried the highest impact for both OS and DSS, followed by largest deposit size. The presence of ENE and immunosuppression was less significant. CONCLUSIONS: The results from this study provide new evidence for identifying and stratifying high-risk patients with metastatic HNcSCC. This information will be valuable in determining future HNcSCC staging systems.

CERS6-AS1 promotes cell proliferation and represses cell apoptosis in pancreatic cancer via miR-195-5p/WIPI2 axis.

Pancreatic cancer (PC) is a lethal malignancy that threatens human health. Long noncoding RNAs (lncRNAs) act as important mediators in PC development. Our study aimed to investigate the function and mechanism of lncRNA ceramide synthase 6 antisense RNA 1 (CERS6-AS1) in PC. As shown by RT-qPCR, CERS6-AS1 was significantly upregulated in PC cells and tissues. Silencing CERS6-AS1 suppressed PC cell viability and proliferation while enhancing cell apoptosis according to colony formation assays, EdU assays, and flow cytometry analyses. Mechanistically, CERS6-AS1 interacted with miR-195-5p to elevate the expression level of the WD repeat domain phosphoinositide interacting 2 (WIPI2), which is a downstream target gene of miR-195-5p in PC. Moreover, miR-195-5p expression was negatively associated with CERS6-AS1 expression (or WIPI2 expression) in PC tissues. Rescue assays revealed that WIPI2 overexpression rescued the effects of CERS6-AS1 deficiency on cell viability, proliferation, and apoptosis. In summary, CERS6-AS1 facilitates PC cell proliferation while inhibiting PC cell apoptosis by upregulating WIPI2 via miR-195-5p. This study might provide promising insight into the role of CERS6-AS1 in PC development.

Oral administration of Lactococcus lactis WHH2078 alleviates depressive and anxiety symptoms in mice with induced chronic stress.

Depression is a mood disorder with a high prevalence rate globally, which is associated with abnormalities in 5-hydroxytryptamine (5-HT) metabolism. Emerging evidence suggests that certain probiotics that modulate 5-HT metabolism confer beneficial effects on depression. In this study, in vitro enterochromaffin RIN14B cells were used for screening potential antidepressant probiotic Lactococcus lactis strains. The L. lactis strain WHH2078 increased to high levels the 5-HT precursor 5-hydroxytryptophan (5-HTP) and the expression of tryptophan hydroxylase 1 (Tph1), which converts tryptophan to 5-HTP in RIN14B cells. The oral administration of WHH2078 (1 × 109 CFU mL-1) in mice with induced chronic unpredictable mild stress (CUMS) for 5 weeks significantly ameliorated depressive and anxiety-like behaviors in the tail suspension test, forced swim test, sucrose preference test, and open field test. Besides, WHH2078 significantly reduced the serum corticosterone level and restored the central levels of 5-HT, 5-HTP, and brain-derived neurotrophic factor in CUMS-induced mice. Moreover, WHH2078 also reversed the 5-HTP levels in the serum and colon, accompanied by an upregulation in colonic Tph1 gene expression. Using 16S rRNA high-throughput sequencing of feces, WHH2078 was shown to improve the CUMS-induced gut microbial dysbiosis, through restoring alpha diversity and the abundances of Firmicutes and Bacteroidetes. In summary, these results indicate that WHH2078 can alleviate rodent depressive and anxiety-like behaviors in response to CUMS, which is associated with the improvement of 5-HT metabolism and modulation of the gut microbiome composition. Therefore, supplementation of the L. lactis strain WHH2078 with antidepressant properties may serve as a promising therapeutic strategy for chronic stress-induced depression.

Avoidance of primary site adjuvant radiotherapy following transoral robotic surgery: a cohort study.

BACKGROUND: Post-operative radiotherapy (PORT) volumes and dose to target structures likely influence swallowing function and quality of life following transoral robotic surgery (TORS). The aim of this study is to analyse disease control and swallowing outcomes in patients undergoing TORS for oropharyngeal squamous cell carcinoma (OPSCC) to determine the impact of omitting the primary site from the PORT treatment volume. METHODS: Prospectively collected data from patients that underwent TORS between March 2013 and April 2021 were reviewed. Patients were categorized into three groups: (1) no PORT, (2) PORT to the neck alone or (3) PORT to the primary site and neck. Survival curves were generated according to the Kaplan-Meier method and swallowing was assessed using the Functional Oral Intake Scale, Public Status Scale Head and Neck, MD Anderson Dysphagia Inventory and feeding tube/gastrostomy dependence. RESULTS: A total of 121 patients underwent TORS, of which 103 met inclusion criteria with a median follow up of 2.6 years. No patients developed local recurrence. The 3-year regional control rates were 90%, 100% and 100% for groups 1, 2 and 3, respectively. Disease-specific survival was 97% over the study period. Patients that received PORT to both the primary site and the neck (group 3) had worse swallowing outcomes at 12 months. CONCLUSION: Following TORS for OPSCC, avoiding PORT to the primary site, in appropriately selected patients, appears to be oncologically safe and is associated with superior swallowing outcomes.

Cognitive behavioral therapy for irritable bowel syndrome induces bidirectional alterations in the brain-gut-microbiome axis associated with gastrointestinal symptom improvement.

BACKGROUND: There is growing recognition that bidirectional signaling between the digestive tract and the brain contributes to irritable bowel syndrome (IBS). We recently showed in a large randomized controlled trial that cognitive behavioral therapy (CBT) reduces IBS symptom severity. This study investigated whether baseline brain and gut microbiome parameters predict CBT response and whether response is associated with changes in the brain-gut-microbiome (BGM) axis. METHODS: Eighty-four Rome III-diagnosed IBS patients receiving CBT were drawn from the Irritable Bowel Syndrome Outcome Study (IBSOS; ClinicalTrials.gov NCT00738920) for multimodal brain imaging and psychological assessments at baseline and after study completion. Fecal samples were collected at baseline and post-treatment from 34 CBT recipients for 16S rRNA gene sequencing, untargeted metabolomics, and measurement of short-chain fatty acids. Clinical measures, brain functional connectivity and microstructure, and microbiome features associated with CBT response were identified by multivariate linear and negative binomial models. RESULTS: At baseline, CBT responders had increased fecal serotonin levels, and increased Clostridiales and decreased Bacteroides compared to non-responders. A random forests classifier containing 11 microbial genera predicted CBT response with high accuracy (AUROC 0.96). Following treatment, CBT responders demonstrated reduced functional connectivity in regions of the sensorimotor, brainstem, salience, and default mode networks and changes in white matter in the basal ganglia and other structures. Brain changes correlated with microbiome shifts including Bacteroides expansion in responders. CONCLUSIONS: Pre-treatment intestinal microbiota and serotonin levels were associated with CBT response, suggesting that peripheral signals from the microbiota can modulate central processes affected by CBT that generate abdominal symptoms in IBS. CBT response is characterized by co-correlated shifts in brain networks and gut microbiome that may reflect top-down effects of the brain on the microbiome during CBT. Video abstract.

Low crude protein diets supplemented with casein hydrolysate enhance the intestinal barrier function and decrease the pro-inflammatory cytokine expression in the small intestine of pigs.

To reduce nitrogen excretion and lower feeding costs, low crude protein (CP) diets are sometimes proposed, however, a great reduction of dietary CP concentration (>4% reduction vs. recommended concentration), even supplemented with essential and nonessential amino acids (AA) can detrimentally affect small intestinal barrier function and immunity, possibly due to the excessive lack of peptides. Here we hypothesize that with an extremely low CP concentration diet, protein-derived peptides, rather than AA supplementation, can improve intestinal barrier development and health. To test this hypothesis, 21 growing pigs (19.90 ± 1.00 kg body weight) were randomly assigned to 3 treatments with control diet (16% CP), or low CP diets (13% CP) supplemented with AA (LCPA) or casein hydrolysate (LCPC) for 28 days. In comparison with the control diet, the LCPA diet decreased the protein expression level of jejunal barrier factor zonula occludens-1 (ZO-1) and stem cell proliferation factor leucine-rich repeat-containing G-protein-coupled receptor-5, whereas the LCPC diet enhanced intestinal barrier function by increasing the protein expression level of jejunal occludin and ZO-1 and ileal mucin-2. The LCPA diet reduced Lactobacillus counts, whereas the LCPC diet increased Lactobacillus counts and reduced Escherichia coli counts in the ileum. The LCPA diet also increased protein expression levels of pro-inflammatory cytokine interleukin-6 (IL-6) and IL-22, whereas the LCPC diet decreased protein expression levels of pro-inflammatory IL-1ß, IL-17A and tumor necrosis factor-α in the ileum. Collectively, the casein hydrolysate supplementation of low CP diets showed beneficial effects on the small intestinal barrier, bacterial community, and immunity in pigs, pointing to the important role of protein-derived peptides in small intestinal health in cases of low crude protein diets.

Early life adversity predicts brain-gut alterations associated with increased stress and mood.

Alterations in the brain-gut system have been implicated in various disease states, but little is known about how early-life adversity (ELA) impacts development and adult health as mediated by brain-gut interactions. We hypothesize that ELA disrupts components of the brain-gut system, thereby increasing susceptibility to disordered mood. In a sample of 128 healthy adult participants, a history of ELA and current stress, depression, and anxiety were assessed using validated questionnaires. Fecal metabolites were measured using liquid chromatography tandem mass spectrometry-based untargeted metabolomic profiling. Functional brain connectivity was evaluated by magnetic resonance imaging. Sparse partial least squares-discriminant analysis, controlling for sex, body mass index, age, and diet was used to predict brain-gut alterations as a function of ELA. ELA was correlated with four gut-regulated metabolites within the glutamate pathway (5-oxoproline, malate, urate, and glutamate gamma methyl ester) and alterations in functional brain connectivity within primarily sensorimotor, salience, and central executive networks. Integrated analyses revealed significant associations between these metabolites, functional brain connectivity, and scores for perceived stress, anxiety, and depression. This study reveals a novel association between a history of ELA, alterations in the brain-gut axis, and increased vulnerability to negative mood and stress. Results from the study raise the hypothesis that select gut-regulated metabolites may contribute to the adverse effects of critical period stress on neural development via pathways related to glutamatergic excitotoxicity and oxidative stress.

The significance of regional metastasis location in head and neck cutaneous squamous cell carcinoma.

BACKGROUND: Regional metastasis of head and neck cutaneous squamous cell carcinoma (HNcSCC) can be seen in either parotid and/or cervical lymph nodes. The aim of this study was to assess whether there was a difference in prognosis between parotid and cervical nodal metastases. METHODS: Patients with regional metastasis from HNcSCC were identified from an institutional database. Disease-specific (DSS) and overall survival (OS) were calculated using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: Five hundred and thirty-five patients were identified with median follow-up of 26.4 months (3-255 months). Two hundred and thirty-five patients had parotid metastasis, 96 patients had neck metastasis, and 204 patients had both. On multivariable analysis, any regional metastasis to the neck when compared to parotid alone conferred worse DSS (HR 1.8, p = 0.007) and OS (HR 1.3, p = 0.024). CONCLUSION: Regional metastasis of HNcSCC to the neck confers worse outcomes compared to metastasis to the parotid alone.

Metrics of pN-staging in oral squamous cell carcinoma: An analysis of 1,905 patients.

BACKGROUND: We aimed to compare the predictive performance of pN-categories in oral squamous cell carcinoma (OSCC) encompassing the most recent 8th edition (TNM8), its predecessor (TNM7), and a newly proposed algorithm (pN-N+), which classifies patients according to the number of positive lymph nodes and extranodal extension. METHODS: Consecutive, primary OSCC patients from seven previously published cohorts were included and classified according to the three pN-classifications: TNM7, TNM8 and pN-N+. Overall survival probabilities were summarised with the Kaplan-Meier method. We added each of the three metrics to a Cox regression adjusted for pT-category, lymph nodal yield, age, sex, radiotherapy and chemotherapy, and trained these models in one institution. We evaluated the predictive performance in the remaining six institutions and assessed the predicted 5-year risk of death using the area under the receiver operating characteristics curve (AUC) and Brier scores. RESULTS: All 1,905 included patients were classified according to TNM7 and pN-N+. A subset of 1,575 patients was additionally classified according to TNM8, leading to upstaging in 27.0%. The pN-N+ ranked overall best determined by the obtained AUC and Brier scores. In contrast to pN-N+, TNM7 and TNM8 both suffered from disproportionate patient distribution across pN-categories and poor pN-categorial discrimination on overall survival. CONCLUSIONS: The TNM8 pN-classification designates a larger subset to more advanced disease stages but failed to show improvement of its predictive performance compared to TNM7. The pN-categories of TNM7/8 are disproportionate and inconsistently discriminated. The pN-N+ conveyed the best measures of prognosis and should be considered in future TNM iterations.

Age-Related Changes in Shear Wave Elastography Parameters of the Gastrocnemius Muscle in Association with Physical Performance in Healthy Adults.

BACKGROUND/AIMS: to investigate new indicators for early recognition of physical performance decline. Shear wave elastrography, a new ultrasound technique, was discussed in this study. METHODS: Gastrocnemius muscle thickness and muscle stiffness were detected by traditional ultrasound and shear wave elastrography in 108 Chinese aged 20-85 years, and then analyzed with physical performance together. RESULTS: After 70 years old, the decline rate of muscle stiffness under contractive state was significantly faster than that of muscle thickness, muscle relaxed stiffness, and physical performance indicators. The correlation analysis showed that gastrocnemius contractive stiffness was positively related with handgrip strength, step length, and fast gait speed after adjusted by age and gender. Among physical performance variants, step length had closer relationship with muscle strength than repeated chair stands. CONCLUSIONS: The detection of gastrocnemius muscle by shear wave elastography reflected the change of lower-limb muscle stiffness with aging. Muscle contractive stiffness and step length measurement supplied novel ways for muscle performance and motor function assessment.

Distributed optical fiber hydrophone based on Φ-OTDR and its field test.

In this letter, a distributed optical fiber hydrophone (DOFH) based on Φ-OTDR is demonstrated and tested in the field. The specially designed sensitized optical cable with sensitivity up to -146 dB rad/µPa/m is introduced, and an array signal processing model for DOFH is constructed to analyze the equivalence and specificity of the distributed array of acoustic sensors. In the field test, a 104-meter-long optical cable and a Φ-OTDR system based on heterodyne coherent detection (Het Φ-OTDR) is utilized, and underwater acoustic signal spatial spectrum estimation, beamforming and motion trajectory tracking with high accuracy can be realized. As far as we know, this is the first report on the field trial of DOFH based on Φ-OTDR. The DOFH has the potential to achieve an array range of tens of kilometers, with elements spaced up to the meter level and flexible configuration, which has a broad application prospect for marine acoustic detection.

Soft Tissue Metastases in Head and Neck Cutaneous Squamous Cell Carcinoma.

OBJECTIVE: Soft tissue metastases (STM) in head and neck cutaneous squamous cell carcinoma (HNcSCC) are non-nodal based metastases to the parotid and cervical soft tissues of the head and neck. This is a unique subgroup of regional metastases amongst patients with cSCC and have been shown to be associated with poor prognosis. Detailed studies of this subgroup are lacking in the literature. A retrospective cohort analysis was performed to characterize the prognostic significance of STM in HNcSCC based on individual clinicopathological features. METHODS: Patients with HNcSCC with STM were identified from the Sydney Head and Neck Cancer Institute database. Clinicopathological characteristics were extracted from the histopathological reports. Recurrence and follow-up data were analyzed to determine disease-free and overall survival using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: After excluding all patients with lymph node metastasis with no STM, there were 200 patients identified (161 parotid, 32 cervical, and seven with concurrent parotid and cervical STM) with a 5-year overall survival of 36%. In univariable analysis, age of patients, size of the deposits, location of the deposits, and patients that were not offered adjuvant radiotherapy have worse overall survival. However, on multivariable analysis, age and the number of STM deposits were independent factors that predict for worse survival. CONCLUSION: The presence of STM in patients with HNcSCC is associated with poor prognosis. Increasing number of STM deposits, as well as involved margin of the regional excision, negatively impacted on the overall prognosis. LEVEL OF EVIDENCE: Level III - retrospective cohort study. Laryngoscope, 131:E1209-E1213, 2021.