Autotaxin is a potential predictive marker for the development of veno-occlusive disease/sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation.

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT), and stratification of the high-risk group before transplantation is significant. Serum autotaxin (ATX) levels have been reported to increase in patients with liver fibrosis caused by metabolic inhibition from liver sinusoidal endothelial cells. Considering that the pathophysiology of VOD/SOS begins with liver sinusoidal endothelial cell injury, an increase in serum ATX levels may precede the onset of VOD/SOS. A retrospective study with 252 patients, including 12 patients with VOD/SOS, who had received allo-HCT was performed. The cumulative incidence of VOD/SOS was higher in the group with serum ATX levels before conditioning (baseline ATX) above the upper reference limit (high ATX group, p < 0.001), and 1-year cumulative incidences were 22.7% (95% confidence interval [95%CI], 3.1-42.4%) and 3.5% (95%CI, 1.1-5.8%), respectively. In the multivariate analysis, elevated baseline ATX was identified as an independent risk factor for VOD/SOS development and showed an additive effect on the predictive ability of known risk factors. Furthermore, the incidence of VOD/SOS-related mortality was greater in the high ATX group (16.7% vs. 1.3%; p = 0.005). Serum ATX is a potential predictive marker for the development of VOD/SOS.

Association of serum autotaxin levels with liver fibrosis in patients pretreatment and posttreatment with chronic hepatitis C.

BACKGROUND AND AIM: The evaluation of liver fibrosis in patients with chronic hepatitis C virus (HCV) infection is important as it is a risk factor for hepatocellular carcinoma. In the recent years, autotaxin (ATX) has been established as a new noninvasive biomarker to predict liver fibrosis. However, antiviral treatment has been reported to decrease serum ATX, but it is unclear whether posttreatment ATX levels reflect liver fibrosis. In the present study, the correlation between ATX and liver fibrosis in pretreatment and posttreatment patients with HCV infection was analyzed. METHODS: A total of 199 samples from 136 patients with HCV infection who had undergone hepatic biopsy before and/or after antiviral treatment at Osaka City University Hospital were used. Posttreatment patients included 38 interferon-treated patients and 80 interferon-free direct-acting antiviral-treated patients; all patients achieved a sustained virological response (SVR). Serum ATX levels were determined by enzyme immunoassay with an AIA-2000 analyzer. RESULTS: Serum ATX levels were largely correlated with liver fibrosis stage in patients with HCV infection before and after antiviral treatment. The measured values decreased even in similar liver fibrosis stages after treatment. The area under the receiver operating characteristic curve for the ability of ATX to diagnose above F2 stage before treatment was 0.81 (both male and female) and that after achieving SVR, it was 0.71 (male) and 0.72 (female). CONCLUSIONS: Serum ATX levels were correlated with histological liver fibrosis stage after achieving SVR. However, separate cutoff values before and after antiviral therapy should be established.

Post-Treatment M2BPGi Level and the Rate of Autotaxin Reduction are Predictive of Hepatocellular Carcinoma Development after Antiviral Therapy in Patients with Chronic Hepatitis C.

Patients with chronic hepatitis C virus (HCV) develop hepatocellular carcinoma (HCC) regardless of achieving a sustained viral response (SVR). Because advanced liver fibrosis is a powerful risk factor for HCC, we analyzed the association between autotaxin (ATX), a liver fibrosis marker, and post-SVR HCC development within 3 years after antiviral treatment. We included 670 patients with HCV who received direct-acting antivirals, achieved SVR and were followed up for at least 6 months (270 of them were followed up for 3 years or more). We measured serum ATX levels before treatment and 12/24 weeks after treatment. The diagnosis of HCC was based on imaging modalities, such as dynamic computed tomography and dynamic magnetic resonance imaging and/or liver biopsy. The present study revealed that high levels of serum ATX predicted post-SVR HCC development (area under the receiver operating characteristic: 0.70-0.76). However, Wisteria floribunda agglutinin positive Mac-2 binding protein (M2BPGi), another liver fibrosis marker, was a more useful predictive marker especially post-treatment according to a multivariate analysis. Patients with a high rate of ATX reduction before and after antiviral treatment did not develop HCC regardless of high pretreatment ATX levels. In conclusion, post-treatment M2BPGi level and the combination of pretreatment ATX levels and rate of ATX reduction were useful predictive markers for post-SVR HCC development in patients with chronic HCV infection.

Design of a highly sensitive and versatile membrane-based immunosensor using a Cu-free click reaction.

A highly sensitive immunosensor is developed using membrane pores as the recognition interface. In this sensor, a Cu-free click reaction is used to efficiently immobilize antibodies, and the sensor inhibits the adsorption of nonspecific proteins that degrade sensitivity. Furthermore, the sensor demonstrates rapid interleukin-6 detection in the picogram per milliliter range.

A Case of IgG1-Lambda Multiple Myeloma With Hyperviscosity Syndrome and Cryoglobulinemia: Identification of the Subclass Fraction by Immunoelectrophoresis and Immunofixation Electrophoresis.

Hyperviscosity syndrome (HVS) is a complication of monoclonal plasma cell tumors. The frequency of HVS depends on the type of monoclonal protein. Immunoglobulin M (IgM) is more closely associated with HVS than IgG, and among IgG subclass monoclonal proteins, IgG3 is most frequently associated with HVS. We herein report a 44-year-old woman with multiple myeloma (MM), HVS, and cryoglobulinemia. Her monoclonal protein and cryoglobulin were IgG1-lambda (λ). She developed HVS at a lower monoclonal protein level because of the properties of the IgG1-derived monoclonal protein and cryoglobulin. Our case highlights the fact that identifying the IgG subclass is useful in predicting the risk of complicating HVS.

Associations between autoimmune thyroid disease prognosis and functional polymorphisms of susceptibility genes, CTLA4, PTPN22, CD40, FCRL3, and ZFAT, previously revealed in genome-wide association studies.

PURPOSE: Genome-wide association studies have revealed several susceptibility genes among patients with autoimmune thyroid disease (AITD), including CTLA4, PTPN22, FCRL3, and ZFAT. However, any possible association between these genes and AITD prognosis remains unknown. The objective of this study was to identify associations between polymorphisms of these genes and AITD prognosis. METHODS: We genotyped functional polymorphisms, including CTLA4 CT60, CTLA4 +49A/G, CTLA4 -1147C/T, CTLA4 -318C/T, PTPN22 -1123C/G, PTPN22 SNP37, CD40 -1C/T, FCRL3 -169C/T, ZFAT Ex9b-SNP10, and ZFAT Ex9b-SNP2, in 197 AITD patients carefully selected from 456 registered AITD patients, and 86 control subjects. The restriction fragment length polymorphism method was used for genotyping. RESULTS: The CD40 -1CC genotype and C allele were significantly more frequent in patients with Graves' disease (GD) in remission than in those with intractable GD (P = 0.041 and P = 0.031, respectively). The FCRL3 -169TT genotype was significantly less frequent in patients with intractable GD than in those with GD in remission (P = 0.0324). For a ZFAT Ex9b-SNP10 polymorphism, the TT genotype and T allele were significantly more frequent in patients with severe Hashimoto's disease (HD) than in those with mild HD (P = 0.0029 and P = 0.0049, respectively). For a CTLA4 CT60 polymorphism, the antithyrotropin receptor antibody levels at the onset of GD were significantly higher in those with the GG genotype than in those with other genotypes (P = 0.0117). CONCLUSIONS: CD40 and FCRL3 gene polymorphisms were associated with GD intractability, and ZFAT polymorphism was associated with HD severity but not its development.

Sphenopalatine artery surgery for refractory idiopathic epistaxis: Systematic review and meta-analysis.

OBJECTIVES: Epistaxis, especially posterior epistaxis, is occasionally refractory to treatment. In these cases, sphenopalatine artery surgeries, including cauterization and ligation, are required. Previous reports have demonstrated treatment results for these procedures but failed to provide high-level evidence. The aim of this study was to quantify the rates of failure and perioperative complications of these procedures by using a meta-analysis technique. METHODS: We systematically searched electronic databases and identified articles regarding epistaxis, sphenopalatine artery ligation, or cauterization. Pooled rebleeding and complication rates were calculated by using a random effects model. RESULTS: A total of 896 cases of sphenopalatine ligation or cauterization for epistaxis were analyzed. Pooled rebleeding rates for the entire cohort, cauterization group, and ligation group were 13.4% (95% confidence interval [CI] 10.0-17.8, P < 0.001), 7.2% (95% CI 4.6-11.0, P < 0.001), and 15.1% (95% CI 9.8-22.5, P < 0.001), respectively. Pooled perioperative complication rates for the entire cohort, cauterization group, and ligation group were 8.7% (95% CI 4.9-15.1, P < 0.001), 10.2% (95% CI 3.8-24.5, P < 0.001), and 6.4% (95% CI 1.8-20.9, P < 0.001), respectively. CONCLUSION: Overall, sphenopalatine surgery for refractory epistaxis is an effective method because of its low rates of failure and complications. Cauterization is more effective than ligation, whereas complications are comparable between the two procedures. Laryngoscope, 129:1731-1736, 2019.

A case of adult congenital laryngeal cleft asymptomatic until hypopharynx cancer treatment.

Laryngeal cleft is an anomaly of failed posterior closure of the larynx. Most cases are diagnosed and need treatment early in life due to respiratory and swallowing problems. We report an unusual case of a 66-year-old man with an asymptomatic laryngeal cleft until treatment for hypopharyngeal cancer. During concurrent chemoradiotherapy (CCRT), despite reduced tumor volume, he presented severe dysphagia and dyspnea, followed by severe pneumonia twice. Because CCRT had to be discontinued, a pharyngolaryngectomy was performed for the cancer treatment. The resected specimen showed total removal of the tumor and a total longitudinal cleft of the cricoid cartilage, classified as a type III laryngeal cleft by the Benjamin and Inglis' classification. A review of computed tomography images indicated that the redundant mucosa from bilateral edges closed the separation of the posterior cricoid cartilage and narrowed the laryngeal airway during CCRT. Adult presentations of laryngeal cleft are quite rare with only ten reported cases in English literature; the present case is of the oldest patient. Undiagnosed cases with laryngeal cleft may exist asymptomatically or without severe symptoms. The awareness of this condition may increase its diagnosis as a cause of diseases such as aspiration and recurrent pneumonia even in adult patients.

Platelet count and platelet-lymphocyte ratio as prognostic markers for head and neck squamous cell carcinoma: Meta-analysis.

BACKGROUND: Thrombocytosis is associated with the prognosis of various types of cancer. The purpose of this study was to quantify the prognostic impact of platelet count and platelet-lymphocyte ratio (PLR) in head and neck squamous cell carcinoma (HNSCC). METHODS: We systematically searched electronic databases and identified articles reporting an association between platelet count or PLR and HNSCC prognosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) were extracted, and the pooled HRs were estimated using random effect models. RESULTS: Eight studies that enrolled 4096 patients and 9 studies that enrolled 2327 patients were included in the platelet count and PLR analyses, respectively. A platelet count greater than the cutoff value was associated with poor OS (HR 1.81; 95% CI 1.16-2.82) and any PLR greater than the cutoff value was associated with poor OS (HR 1.64; 95% CI 1.13-2.37). CONCLUSION: Elevated platelet count and PLR are associated with poor prognosis in patients with HNSCC.

Prognostic role of neutrophil-to-lymphocyte ratio in head and neck cancer: A meta-analysis.

BACKGROUND: Neutrophils play substantial roles in cancer progression. Previous reports demonstrated the prognostic impact of the pretreatment neutrophil-to-lymphocyte ratio (NLR) in various types of solid cancers. The purpose of this study was to quantify the prognostic impact of NLR on head and neck squamous cell carcinoma (HNSCC). METHODS: We systematically searched electronic databases, identified articles regarding NLR and HNSCC mortality, and extracted hazard ratios (HRs) and 95% confidence intervals (CIs). Pooled HRs for overall survival (OS) and disease-specific survival (DSS) were estimated using random effect models. RESULTS: Nineteen studies enrolling 3770 patients were included in the analyses. Overall, NLR greater than the cutoff value was associated with poorer OS and DSS (HR 1.69; 95% CI 1.47-1.93; P < .001 and HR 1.88; 95% CI 1.20-2.95; P = .006, respectively). CONCLUSION: Elevated NLR predicts worse outcomes in patients with HNSCC.

Pretreatment serum lactate dehydrogenase as a prognostic indicator for oral cavity squamous cell carcinoma.

OBJECTIVES: To examine whether lactate dehydrogenase (LDH) can predict the prognosis of oral cavity squamous cell carcinoma (OSCC) and to determine the optimal cut-off values for LDH. METHODS: This retrospective study included 184 patients with OSCC, treated with surgery between 2006 and 2014. The association between LDH and T, N classification was investigated using the Mann-Whitney test. Cut-off values for LDH were determined with a recursive partitioning analysis (RPA). Survival rates were estimated using the Kaplan-Meier method. A Cox hazard model was used to assess the prognostic capability of LDH. RESULTS: There was no association between LDH and T or N classification (p = .657, .619, respectively). RPA determined the cut-off values for LDH as 160 and 220 IU/L. The five year survival for low-, moderate-, and high-LDH groups were 87.7, 73.7, and 50.9%, respectively (p < .001). The hazard ratios (HRs) for death in moderate- and high-LDH groups were 2.92 (95%CI =1.02-12.30, p = .001) and 7.36 (95%CI =2.54-31.20, p < .001), respectively. The model including LDH-based stratification (Akaike's information criterion (AIC) = 516) was better than the model including clinical stage (AIC =528). CONCLUSION: Pretreatment serum LDH is an independent prognostic factor for overall survival in patients with OSCC.

Polymorphisms in Th17-related genes and the pathogenesis of autoimmune thyroid disease.

The prognosis of autoimmune thyroid disease (AITD) including Graves' disease (GD) and Hashimoto's disease (HD) is difficult to predict. We previously suggested that Th17 cells may be associated with the pathogenesis of AITD. However, the association between gene polymorphisms in Th17-related genes and the prognosis of AITD was not clarified. To clarify this association, we genotyped 12 polymorphisms in 11 Th17-related genes (IL1Ra, IL6R, IL17R, IL21R, IL23R, CCR6, SOCS3, RORC, IL17A, IL17F and IL21) in 142 HD patients including 58 patients with severe HD and 48 patients with mild HD, 170 patients with GD including 81 patients with intractable GD and 49 patients with GD in remission, and 84 healthy volunteers. The frequency of the IL17F rs763780 T allele was higher in patients with severe HD than in patients with mild HD (p = .008). The frequency of the IL17R rs9606615 T allele was higher in patients with HD than in normal subjects (p = .011). The frequencies of the SOCS3 rs4969170 AA genotype, CCR6 rs3093024 AA genotype, and IL21 rs907715 AA genotype were higher in patients with intractable GD than in patients with GD in remission (p = .035, p = .002 and p = .030, respectively). In conclusion, IL17R rs9607715 and IL17F rs763780 polymorphisms are associated with the susceptibility and severity of HD, respectively. IL21 rs907715, SOCS3 rs4969170 and CCR6 rs3093024 polymorphisms are associated with the intractability of GD.

Surgery With or Without Postoperative Radiation Therapy for Early-stage External Auditory Canal Squamous Cell Carcinoma: A Meta-analysis.

OBJECTIVE: External auditory canal squamous cell carcinoma (EACSCC) is a rare disease with no standard treatment supported by high-level evidence. The aim of this study was to investigate EACSCC prognoses according to treatment modality and thus determine the optimal intervention for early-stage disease. DATA SOURCES: PubMed, Scopus, and Ichushi-Web searches of the English and Japanese-language literature published between January 1, 2006 and December 31, 2016 were performed using the key words "external auditory canal cancer" and "temporal bone cancer." STUDY SELECTION: Articles related to EACSCC that include the 5-year overall survival rate or individual patient data for histological types, follow-up periods, and final outcomes were enrolled. DATA EXTRACTION: Sex, age, Moody's modified Pittsburgh stage, type of treatment modality, type of operation, follow-up period, and 5-year survival rates were extracted. DATA SYNTHESIS: Twenty articles were used for the aggregate meta-analysis using a random-effects model, and 18 articles that reported 99 patients with early-stage EACSCC were used for the individual patient data meta-analysis. CONCLUSION: The 5-year overall survival rate of early-stage EACSCC was 77%. Postoperative radiation therapy (PORT) was performed in 45% of stage I patients and 68% of stage II patients. Survival analysis of all patients showed no differences between the surgery-only and PORT groups; however, PORT exhibited a better prognosis than surgery alone among patients with stage I disease (p = 0.003, log-rank test). This result indicated that PORT can be the standard therapy for stages I and II EACSCC.

Age-adjusted Charlson Comorbidity Index predicts prognosis of laryngopharyngeal cancer treated with radiation therapy.

OBJECTIVES: To examine the ability of comorbidity indices to predict the prognosis of laryngopharyngeal cancer and their association with treatment modalities. METHODS: This retrospective study included 198 patients with laryngeal, hypopharyngeal, and oropharyngeal cancers. The effect of comorbidity indices on overall survival between surgery and (chemo)-radiation therapy ((C)RT) groups was analyzed. The cumulative incidence rates for cancer mortality and other mortalities according to the age-adjusted Charlson Comorbidity Index (ACCI) and Charlson Comorbidity Index (CCI) were compared. RESULTS: Univariate survival analyses showed a significant association between the ACCI and overall survival in the (C)RT group, but not in the surgery group. The association between the CCI and overall survival was not significant in either group. In multivariate analyses, a high ACCI score was an independent prognostic factor in the (C)RT group (HR 2.89, 95% confidence interval (CI) 1.28-6.49), but not in the surgery group (HR 1.39, 95%CI 0.27-5.43). The higher ACCI group had increased mortality from other causes compared with the lower ACCI group (5-year cumulative incidence, 8.5% and 17.8%, respectively, p = .003). CONCLUSION: The ACCI was a better prognostic factor than the CCI. Surgery may be more beneficial than radiation for patients with a high ACCI.

Prognostic role of neutrophil-lymphocyte ratio in nasopharyngeal carcinoma: A meta-analysis.

BACKGROUND: Inflammatory markers are used to predict prognosis of nasopharyngeal carcinoma (NPC). Previous reports of neutrophil-to-lymphocyte ratio (NLR) and NPC mortality are inconsistent. This study aimed to quantify the prognostic impact of NLR on NPC. METHODS: The primary outcome was overall survival (OS), and the secondary outcomes were disease-specific survival (DSS), progression-free survival (PFS) and distant metastasis-free survival (DMFS). We systematically searched electronic databases, identified articles reporting an association between NLR and NPC prognosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted, and pooled HRs for each outcome were estimated using random effect models. RESULTS: Nine studies enrolling 5397 patients were included in the analyses. NLR greater than the cutoff value was associated with poor overall survival (HR 1.51, 95% CI 1.27-1.78), disease-specific survival (HR 1.44, 95% CI 1.22-1.71), progression-free survival (HR 1.53, 95% CI 1.22-1.90), and distant metastasis-free survival (HR 1.83, 95% CI 1.14-2.95). CONCLUSIONS: Elevated NLR predicts worse OS, DSS, PFS and DMFS in patients with NPC.

Development and validation of a new comorbidity index for patients with head and neck squamous cell carcinoma in Japan.

Due to habitual drinking and smoking and advanced age at diagnosis, patients with head and neck squamous cell carcinoma (HNSCC) frequently present with comorbidities. Several comorbidity indices have been developed and validated for HNSCC. However, none have become the standard method. In this study, we developed a new comorbidity index for Japanese patients with HNSCC, which was validated against an independent data set. A Cox proportional hazards analysis of 698 patients identified dementia, connective tissue diseases, and second primary malignancies in the oesophagus, head and neck, lungs, and stomach as prognostic comorbidities for overall survival. The Osaka head and neck comorbidity index (OHNCI) was generated from the weighted points of these comorbidities. In the independent data set, the 5-year overall survival rates for the low, moderate, and high scoring OHNCI groups were 62.1%, 64.3%, and 37.7%, respectively. In the multivariate analysis, the high scoring OHNCI group was an independent prognostic factor for overall survival (hazard ratio: 1.81, 95% confidence interval: 1.05-3.13; P = 0.031). The model including the OHNCI exhibited a higher prognostic capability compared to those including other commonly used comorbidity indices. The OHNCI could become the primary choice for comorbidity assessment in patients with HNSCC in Japan.

Induction and inhibition of cyclobutane pyrimidine dimer photolyase in etiolated cucumber (Cucumis sativus) cotyledons after ultraviolet irradiation depends on wavelength.

Under polychromatic ultraviolet (UV) irradiation (maximum energy at 327 nm) the activity of DNA photolyase specific to cyclobutane pyrimidine dimers (CPDs), CPD photolyase, increased by an amount which depended on UV irradiance, and the level of CPD photolyase gene (CsPHR) transcripts temporarily increased before the activity reached a constant level. UV light (>320 nm) was more effective than visible light at increasing CPD photolyase activity. In contrast, monochromatic UV irradiation at wavelengths <300 nm increased the level of CsPHR transcripts similarly to irradiation at wavelengths >320 nm, but reduced CPD photolyase activity compared with the dark control. Exposure of a CPD photolyase solution to UV-C (254 nm) reduced enzyme activity and induced accumulation of H(2)O(2). Addition of H(2)O(2) to the enzyme solution also inactivated CPD photolyase activity. These results suggest the possibility that reactive oxygen species participate in the inactivation of CPD photolyase in cotyledons exposed to UV irradiation of <300 nm.