Purpose Muscle atrophy is a major clinical feature of chronic obstructive pulmonary disease (COPD) and is considered a predictor of mortality in COPD patients. Recently, the cross-sectional area (CSA) of the erector spinae muscles measured by chest computed tomography (CT) scans (ESM CSA ) has been reported as a clinical parameter reflecting disease severity and future prognosis in patients with COPD. In addition, the serum creatinine (Cr)/cystatin C (CysC) ratio has been considered a quantitative marker of residual muscle mass, because serum Cr levels are affected by muscle mass, and correction by CysC counteracts the effect of renal function on serum Cr levels. The purpose of this study was to assess whether the serum Cr level corrected by serum CysC can be used as a predictive marker of pulmonary function and disease severity in patients with COPD. Patients and Methods A total of 99 patients without COPD and 201 patients with COPD, with a smoking history of more than 10 pack-years were enrolled in this study, and serum Cr and CysC levels were measured. On chest high-resolution CT images, %low attenuation area (LAA%) (≤960 Hounsfield units (HU)) and ESM CSA at the Th 12 level were identified. Results There was a significant correlation between the ESM CSA and the Cr/CysC ratio. The Cr/CysC ratio was significantly associated with forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) values, especially in former smokers. Conclusion The serum Cr/CysC ratio could be a convenient substitute for the measurement of muscle atrophy and pulmonary function testing in patients with COPD.

Background: The efficacy of rechallenge with immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients has not yet been fully clarified. This study aimed to identify the clinical characteristics of patients with NSCLC who benefited from rechallenge with ICIs. Methods: We retrospectively reviewed the clinical records of 24 patients who were diagnosed with NSCLC and rechallenged with ICIs between August 2016 and July 2021.Results: Of the 24 patients included in the study, 11 were in the responder group (45.8%) and 13 in the nonresponder group (54.2%). The number of patients who used a different ICI from that used in the initial therapy was significantly higher in the responder group than in the nonresponder group (p = 0.006). Multivariate analysis identified lung metastasis and female sex as significant independent risk factors for nonresponse to rechallenge with ICIs. Compared to the nonresponder group, the duration of treatment after rechallenge with ICIs was significantly longer in the responder group (p = 0.016), and there was a trend toward longer overall survival (p = 0.059). Conclusions: Patients with lung cancer who were rechallenged with ICIs and without progressive disease after initial ICI therapy were able to continue ICI therapy for a longer period of time. This may be associated with longer survival. Patients with lung metastases and female patients are more likely to be nonresponsive to rechallenge with ICIs. Administration of a different type of ICI from that used in the initial ICI therapy may result in disease control. K E Y W O R D S immune checkpoint inhibitors, lung neoplasm, non-small-cell lung carcinoma

To determine fluid extravasation in the splanchnic vascular bed during anaphylactic hypotension, the mesenteric lymph flow (Q(lym)) was measured in anesthetized rats sensitized with ovalbumin, along with the systemic arterial pressure (P(sa)) and portal venous pressure (P(pv)). When the antigen was injected into the sensitized rats (n = 10), P(sa) decreased from 125 ± 4 to 37 ± 2 mmHg at 10 min with a gradual recovery, whereas P(pv) increased by 16 mmHg at 2 min and returned to the baseline at 10 min. Q(lym) increased 3.3-fold from the baseline of 0.023 ± 0.002 g/min to the peak levels of 0.075 ± 0.009 g/min at 2 min and returned to the baseline within 12 min. The lymph protein concentrations increased after antigen, a finding indicating increased vascular permeability. To determine the role of the P(pv) increase in the antigen-induced increase in Q(lym), P(pv) of the nonsensitized rats (n = 10) was mechanically elevated in a manner similar to that of the sensitized rats by compressing the portal vein near the hepatic hilus. Unexpectedly, P(pv) elevation alone produced a similar increase in Q(lym), with the peak comparable to that of the sensitized rats. This finding aroused a question why the antigen-induced increase in Q(lym) was limited despite the presence of increased vascular permeability. Thus the changes in splanchnic vascular surface area were assessed by measuring the mesenteric arterial flow. The mesenteric arterial flow was decreased much more in the sensitized rats (75%; n = 5) than the nonsensitized P(pv) elevated rats (50%; n = 5). In conclusion, mesenteric lymph flow increases transiently after antigen presumably due to increased capillary pressure of the splanchnic vascular bed via downstream P(pv) elevation and perfusion and increased vascular permeability in anesthetized rats. However, this increased extravasation is subsequently limited by decreases in vascular surface area and filtration pressure.

Vasopressin, a vasoactive peptide, causes vasoconstriction via V1a vasopressin receptors. Unlike other vasoconstrictor agents, vasopressin also has vasodilatory properties. The purpose of this study was to determine the effect of vasopressin on hepatic and splanchnic circulation in SpragueDawley rats. The experiments were conducted in not only isolated blood-and constant flowperfused livers but also anesthetized spontaneously breathing rats. In anesthetized rats, portal venous pressure (Ppv), systemic arterial pressure (Psa), central venous pressure, and hepatic blood flow (HBF) of combined portal venous and hepatic arterial blood flow were continuously measured, and splanchnic vascular bed resistance (Rspl) defined by (Psa − Ppv) / HBF was determined. In perfused livers, vasopressin at 0.1-1,000 nM caused weak venoconstriction as evidenced by small increase in Ppv. In anesthetized rats, when vasopressin was injected into the portal vein as a bolus consecutively at 0.01-100 nmol/kg, Psa increased dose-dependently with the peak increment of 60 ± 18 mmHg at 100 nmol/kg. Ppv and HBF decreased, with resultant increase in Rspl, indicating splanchnic vasoconstriction. In conclusion, hepatic venoconstrictor action of vasopressin was weak in rats. Vasopressin causes splanchnic vasoconstriction, resulting in a decrease in HBF and Ppv in anesthetized rats.Vasopressin, a vasoactive peptide, causes vasoconstriction via V1a vasopressin receptor of vascular smooth muscle cells (1, 5). Vasopressin has been a well-established therapeutic agent controlling severe hypotension such as hemorrhagic shock due to gastrointestinal bleeding (21), septic shock (6, 8), and anaphylactic shock (13). Its beneficial effects on hypotension are usually ascribed to its strong arteriolar constrictor activity in most peripheral vascular beds, especially splanchnic vascular beds. Vasopressin-induced vasoconstriction in the intestinal and splenic vascular beds results in a reduction of portal blood flow with a fall in hepatic portal venous pressure (Ppv). Vasopressin causes vasoconstriction in most vascular beds. Paradoxically, vasopressin has also been demonstrated to cause vasodilation in numerous vascular beds (2,3,9,10,12,16,17,19), a feature not shared by other vasoconstrictor agents. For rats which are one of the most frequently used animals for experiments, the investigations on the effect of vasopressin on the splanchnic vascular bed in vivo are limited (11): blood flow to liver was not measured, although a decrease in Ppv was reported. A decrease in Ppv could be theoretically induced by vasodilation, rather than vasoconstriction, in the hepatic vessels. On the other hand, there are reports on the hepatic vascular response of perfused rat livers to vasopressin, indicating absence of constriction or dilatation (14,18). However, these experiments

Background: The use of microscopic computed tomography to assess the key functional parameters of systolic emptying or diastolic filling in small animals has not been previously reported. The aim of the study was to test whether microscopic computed tomography can assess the dynamics of both left ventricle and right ventricle (RV) diastolic filling and systolic emptying in an experimental model of pulmonary arterial hypertension Methods and Results: The Wistar-Kyoto rats were injected subcutaneously with the VEGF (vascular endothelial growth factor)-receptor inhibitor SU5416 (20 mg/kg body weight) and were then exposed to chronic hypoxia (10% oxygen) for 21 days (SU5416-hypoxia) followed by normoxia for an additional 2 weeks. Thereafter, multiphase cine cardiac images were acquired using a microscopic computed tomography scanner in conjunction with a blood-pool iodinated contrast agent. Examination of the 3-dimensional images of SU5416-hypoxia rats confirmed the presence of severe pulmonary arterial hypertension. Functional parameters that describe the dynamics of ventricular systolic ejection and diastolic filling were calculated. RV peak ejection rate was significantly decreased ( P <0.03) in SU5416-hypoxia rats compared with controls. RV peak filling rate had a significant decrease compared with controls ( P <0.03), particularly in the early phase of diastole ( P <0.03). This was accompanied by increased time to peak filling rate ( P <0.03) and total filling time ( P <0.06). Spearman analysis between microscopic computed tomography RV diastolic indices and invasively derived RV end-diastolic pressure indicated excellent correlation. Conclusions: We developed a method that allows rapid and accurate assessment of cardiac functional indices and that paves the way for more extensive preclinical cardiovascular research.