Association of preoperative serum CRP with PD-L1 expression in 508 patients with non-small cell lung cancer: A comprehensive analysis of systemic inflammatory markers

Objectives

Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have been approved as a standard therapy for metastatic non-small cell lung cancer (NSCLC). Although PD-L1 expression serves as a predictive biomarker for the efficacy of immunotherapy, there are no established biomarkers to predict the expression of PD-L1. The inflammatory markers C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) were recently shown to predict the efficacy of nivolumab for NSCLC patients. Therefore, here we investigated the potential association of PD-L1 expression with systemic inflammatory markers, including CRP, NLR, lymphocyte-monocyte ratio and platelet-lymphocyte ratio.

TPA-enhanced invasion of matrigel associated with augmentation of cell motility but not metalloproteinase activity in a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1

We previously found that the enhanced activity to invade Matrigel upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA) was one of the major properties of a highly metastatic variant (L-10) of a human rectal adenocarcinoma cell line RCM-1. To clarify the mechanism of this enhancement, we examined the effect of TPA on 2 major biological factors involved in tumor cell invasion: cell motility and matrix-degrading metalloproteinase activity. The enhanced invasiveness was inhibited by protein-kinase-C inhibitors. TPA markedly enhanced both haptotactic response to type-IV collagen and motility on tissue-culture glass substrate of L-10 cells in a dose-response manner quite similar to that of TPA-enhanced invasion of Matrigel. On the other hand, TPA showed little enhancement of metalloproteinase production, which was assessed by gelatin- and casein-zymography, and of type-IV collagenolytic activity. Addition of TIMP (tissue inhibitors of metalloproteinase)-1 inhibited TPA-enhanced invasion of Matrigel by only up to 13%. Thus, TPA treatment of L-10 cells enhanced invasion of Matrigel in association with augmentation of cell motility but did not enhance metalloproteinase activity.     

Urodynamic Analysis of Age-Related Changes of alpha sub 1 -Adrenoceptor Responsiveness in Female Beagle Dogs

Purpose

We have evaluated age-related changes of alpha₁-adrenoceptor responsiveness in the lower urinary tract of female beagle dogs by urodynamic analyses.

Materials and Methods

Six aged parous and 6 young nonparous female beagle dogs were studied. Mean ages (plus/minus standard error of the mean) of the 2 groups were 68.3 plus/minus 2.3 and 12.4 plus/minus 0.08 months. Before and after 4 administrations of alpha₁-adrenoceptor agonist (midodrine hydrochloride 0.03, 0.1, 0.3 and 1.0 mg./kg. intravenously), cystometry, urethral pressure profilometry and external urethral sphincter electromyography were performed.

Results

After 0.3 mg./kg. midodrine administration, mean bladder capacity in the aged dogs significantly decreased, compared with that in the young dogs (p less than 0.05). After the minimum dose administration (0.03 mg./kg.), the urethral closing pressure in both groups increased significantly (p less than 0.05) with no changes in bladder capacity or arterial blood pressure. The proximal urethral closing pressure in the aged dogs increased dose dependently. After administration of 1.0 mg./kg. drug it reached 257 percent of the initial values (p less than 0.01), which was significantly greater than that in the young dogs (p less than 0.05).

Conclusions

These findings suggest that 1) age-related increase of alpha₁-adrenoceptor responsiveness occurs in the bladder and in the proximal urethra. The former may be one of the etiologies of detrusor instability in the elderly. 2) A lower dose of midodrine hydrochloride may be useful for the treatment of stress incontinence, independent of age.     

Evaluation of left ventricular ejection fraction from radial long-axis tomography: A new reconstruction algorithm for ECG-gated technetium-99m sestamibi SPECT

Methods

ECG-gated Tc-99m MIBI SPECT was performed with a temporal resolution of 10 frames per R-R interval. LVEF was calculated on the basis of left ventricular volume estimates at end diastole (ED) and end systole (ES) with using an ellipsoid body model. To validate this method, LVEF’s derived from ECG-gated Tc-99m MIBI SPECT were compared with those from LVG in 11 patients with coronary artery disease.

Results

There was a close linear correlation between LVEF values calculated from Tc-99m MIBI SPECT and those from LVG (r = 0.89, p < 0.001), although the gated SPECT underestimated LVEF compared to LVG. The technique showed excellent reproducibility (intra-observer variability, r = 0.96, p < 0.001; inter-observer variability, r = 0.71, p < 0.005).

Conclusion

The radial long-axis tomography technique gives a good estimate of LVEF, in agreement with estimates based on LVG. ECG-gated Tc-99m MIBI SPECT can, therefore, be applicable to assess myocardial perfusion and ventricular function at the same time.     

Quantitative assessment technique of HyperEye medical system angiography for coronary artery bypass grafting

Purpose

The HyperEye Medical System (HEMS) uses indocyanine green (ICG) to visualize blood vessels in coronary artery bypass grafting (CABG). We performed quantitative HEMS assessment to detect grafts at risk of occlusion.

Methods

We assessed the HEMS angiograms of 177 grafts from 69 patients who underwent CABG and compared the results with those of fluoroscopic coronary angiography, by measuring the increasing rate of ICG intensity, average acceleration value, and time to peak luminance intensity.

Results

Grafts in the patent and failed groups showed significant differences in their increasing rate of intensity and average acceleration value. The average accelerations value of ICG intensity of internal thoracic artery (ITA) and saphenous vein (SV) grafts were 112.3 and 144.9 intensity/s² in the patent group, and 71.0 and 91.8 intensity/s² in the failed group. The time to peak luminance intensity was 1.7 and 1.4 s in the patent group and 2.3 and 1.9 s in the failed group; these values were not significantly different.

Conclusion

Significant reductions in the ICG intensity rate and average acceleration value can occur in failed grafts. Therefore, quantifiable changes in ICG intensity may help detect minute changes in blood flow.

     

Impact of urgent resuscitative surgery for life-threatening torso trauma

Purpose

This study investigated the advantages of performing urgent resuscitative surgery (URS) in the emergency department (ED); namely, our URS policy, to avoid a delay in hemorrhage control for patients with severe torso trauma and unstable vital signs.

Methods

We divided 264 eligible cases into a URS group (n = 97) and a non-URS group (n = 167) to compare, retrospectively, the observed survival rate with the predicted survival using the Trauma and Injury Severity Score (TRISS).

Results

While the revised trauma score and the injury severity score were significantly lower in the URS group than in the non-URS group, the observed survival rate was significantly higher than the predicted rate in the URS (48.5 vs. 40.2%; p = 0.038). URS group patients with a systolic blood pressure (SBP) <90 mmHg and a Glasgow coma scale (GCS) score of ≥9 had significantly higher observed survival rates than predicted survival rates (0.433 vs. 0.309, p = 0.008), (0.795 vs. 0.681, p = 0.004). The implementation of damage control surgery (DCS) was found to be a significant predictor of survival (OR 5.23, 95% CI 0.113–0.526, p < 0.010).

Conclusion

The best indications for the URS policy are an SBP <90 mmHg, a GCS ≥9 on ED arrival, and/or the need for DCS. By implementing our URS policy, satisfactory survival of patients requiring immediate hemostatic surgery was achieved.

     

Taxonomic examination of longgu (Fossilia Ossis Mastodi, “dragon bone”) and a related crude drug,longchi (Dens Draconis, “dragon tooth”), from Japanese and Chinese crude drug markets

Longgu (“dragon bone,” Ryu-kotsu, Fossilia Ossis Mastodi, or Os Draconis) is the only fossil crude drug listed in the Japanese Pharmacopoeia. All longgu in the current Japanese market is imported from China, where its resources are being depleted. Therefore, effective countermeasures are urgently needed to prevent resource depletion. One possible solution is the development of a substitute made from bones of contemporary animals that are closely related to the original animal source of the current longgu. However, no research has been conducted on the original animal source of longgu, except for a report on the longgu specimens present in the Shosoin Repository. Taxonomic examination was performed on the fossil specimens related to longgu which are owned by the Museum of Osaka University, Japan. In total, 20,939 fossil fragments were examined, of which 20,886 were mammalian fossils, and 246 of these fossils were classified into nine families. The longgu specimens from the Japanese market belonged to a relatively smaller variety of taxa than those from the Chinese market. Despite the variety of taxa in longgu, medical doctors using Kampo preparations with longgu have not reported any problems due to the presence of impurities in the original animal source. These results suggest that the effect of longgu is independent of its origin as long as it is closely related to the origin of the current longgu. Thus, despite the considerable effects of fossilization, our results could help in developing an optimal substitute for longgu.