AIM: To assess the agreement within 3 commonly used symptom-reflux association analysis (SAA) parameters investigating gastroesophageal reflux disease (GERD) in infants. METHODS: Twenty three infants with suspected GE...AIM: To assess the agreement within 3 commonly used symptom-reflux association analysis (SAA) parameters investigating gastroesophageal reflux disease (GERD) in infants. METHODS: Twenty three infants with suspected GERD were included in this study. Symptom index (SI), Symptom sensitivity index (SSI) and symptom association probability (SAP) related to cough and irritability were calculated after 24 h combined pH/multiple intraluminal impedance (MII) monitoring. Through defined cutoff values, SI, SSI and SAP values are differentiated in normal and abnormal, whereas abnormal values point towards gastroesophageal reflux (GER) as the origin of symptoms. We analyzed the correlation and the concordance of the diagnostic classification of these 3 SAA parameters.RESULTS: Evaluating the GER-irritability association, SI, SSI and SAP showed non-identical classification of normal and abnormal cases in 39.2% of the infants. When irritability was taken as a symptom, there was only a poor inter-parameter association between SI and SSI, and between SI and SAP (Kendall’s tau b = 0.37, P < 0.05; Kendall’s tau b = 0.36, P < 0.05, respectively). Evaluating the GER-cough association, SI, SSI and SAP showed non-identical classification of normal and abnormal cases in 52.2% of the patients. When cough was taken as a symptom, only SI and SSI showed a poor inter-parameter association (Kendall’s tau b = 0.33, P < 0.05). CONCLUSION: In infants investigated for suspected GERD with pH/MII-monitoring, SI, SSI and SAP showed a poor inter-parameter association and important dis-agreements in diagnostic classification. These limitations must be taken into consideration when interpreting the results of SAA in infants.展开更多
Photoimmunotherapy(PIT)combines the specificity of antibodies with the cytotoxicity of light activatable photosensitizers(PS)and is a promising new cancer therapy.We designed and synthesized,in a highly convergent man...Photoimmunotherapy(PIT)combines the specificity of antibodies with the cytotoxicity of light activatable photosensitizers(PS)and is a promising new cancer therapy.We designed and synthesized,in a highly convergent manner,the silicon phthalocyanine dye WB692-CB2,which is novel for being the first light-activatable PS that can be directly conjugated via a maleimide linker to cysteines.In the present study we conjugated WB692-CB2 to a humanized antibody with engineered cysteines in the heavy chains that specifically targets the prostate-specific membrane antigen(PSMA).The resulting antibody dye conjugate revealed high affinity and specificity towards PSMA-expressing prostate cancer cells and induced cell death after irradiation with red light.Treated cells exhibited morphological characteristics associated with pyroptosis.Mechanistic studies revealed the generation of reactive oxygen species,triggering a cascade of intracellular events involving lipid peroxidation,caspase-1 activation,gasdermin D cleavage and membrane rupture followed by release of pro-inflammatory cellular contents.In first in vivo experiments,PIT with our antibody dye conjugate led to a significant reduction of tumor growth and enhanced overall survival in mice bearing subcutaneous prostate tumor xenografts.Our study highlights the future potential of the new phthalocyanine dye WB692-CB2 as PS for the fluorescence-based detection and PIT of cancer,including local prostate tumor lesions,and systemic activation of anti-tumor immune responses by the induction of pyroptosis.展开更多
文摘AIM: To assess the agreement within 3 commonly used symptom-reflux association analysis (SAA) parameters investigating gastroesophageal reflux disease (GERD) in infants. METHODS: Twenty three infants with suspected GERD were included in this study. Symptom index (SI), Symptom sensitivity index (SSI) and symptom association probability (SAP) related to cough and irritability were calculated after 24 h combined pH/multiple intraluminal impedance (MII) monitoring. Through defined cutoff values, SI, SSI and SAP values are differentiated in normal and abnormal, whereas abnormal values point towards gastroesophageal reflux (GER) as the origin of symptoms. We analyzed the correlation and the concordance of the diagnostic classification of these 3 SAA parameters.RESULTS: Evaluating the GER-irritability association, SI, SSI and SAP showed non-identical classification of normal and abnormal cases in 39.2% of the infants. When irritability was taken as a symptom, there was only a poor inter-parameter association between SI and SSI, and between SI and SAP (Kendall’s tau b = 0.37, P < 0.05; Kendall’s tau b = 0.36, P < 0.05, respectively). Evaluating the GER-cough association, SI, SSI and SAP showed non-identical classification of normal and abnormal cases in 52.2% of the patients. When cough was taken as a symptom, only SI and SSI showed a poor inter-parameter association (Kendall’s tau b = 0.33, P < 0.05). CONCLUSION: In infants investigated for suspected GERD with pH/MII-monitoring, SI, SSI and SAP showed a poor inter-parameter association and important dis-agreements in diagnostic classification. These limitations must be taken into consideration when interpreting the results of SAA in infants.
基金German Research Foundation(DFG,grant no.WO 2178/3–1 to PW)Federal Ministry of Economic Affairs and Climate Action(BMWK,grant no.03THW15H04 to RB and PW)supported by the Open Access Publication Fund of the University of Freiburg.
文摘Photoimmunotherapy(PIT)combines the specificity of antibodies with the cytotoxicity of light activatable photosensitizers(PS)and is a promising new cancer therapy.We designed and synthesized,in a highly convergent manner,the silicon phthalocyanine dye WB692-CB2,which is novel for being the first light-activatable PS that can be directly conjugated via a maleimide linker to cysteines.In the present study we conjugated WB692-CB2 to a humanized antibody with engineered cysteines in the heavy chains that specifically targets the prostate-specific membrane antigen(PSMA).The resulting antibody dye conjugate revealed high affinity and specificity towards PSMA-expressing prostate cancer cells and induced cell death after irradiation with red light.Treated cells exhibited morphological characteristics associated with pyroptosis.Mechanistic studies revealed the generation of reactive oxygen species,triggering a cascade of intracellular events involving lipid peroxidation,caspase-1 activation,gasdermin D cleavage and membrane rupture followed by release of pro-inflammatory cellular contents.In first in vivo experiments,PIT with our antibody dye conjugate led to a significant reduction of tumor growth and enhanced overall survival in mice bearing subcutaneous prostate tumor xenografts.Our study highlights the future potential of the new phthalocyanine dye WB692-CB2 as PS for the fluorescence-based detection and PIT of cancer,including local prostate tumor lesions,and systemic activation of anti-tumor immune responses by the induction of pyroptosis.
