Objective: To identify the initial chest computed tomography (CT) findings and clinical characteristics associated with the course of coronavirus disease 2019 (COVID-19) pneumonia. Materials and Methods: Baseline CT scans and clinical and laboratory data of 72 patients admitted with COVID-19 pneumonia (39 men, 46.2 ± 15.9 years) were retrospectively analyzed. Baseline CT findings including lobar distribution, presence of ground glass opacities, consolidation, linear opacities, and lung severity score were evaluated. The outcome event was recovery with hospital discharge. The time from symptom onset to discharge or the end of follow-up (for those remained hospitalized) was recorded. Data were censored in events such as death or discharge without recovery. Multivariable Cox proportional hazard regression was used to explore the association between initial CT, clinical or laboratory findings, and discharge with recovery, whereby hazard ratio (HR) values < 1 indicated a lower rate of discharge at four weeks and longer time until discharge. Results: Thirty-two patients recovered and were discharged during the study period with a median length of admission of 16 days (range, 9 to 25 days), while the rest remained hospitalized at the end of this study (median, 17.5 days; range, 4 to 27 days). None died during the study period. After controlling for age, onset time, lesion characteristics, number of lung lobes affected, and bilateral involvement, the lung severity score on baseline CT (> 4 vs. ≤ 4 [reference]: adjusted HR = 0.41 [95% confidence interval, CI = 0.18-0.92], p = 0.031) and initial lymphocyte count (reduced vs. normal or elevated [reference]: adjusted HR = 0.14 [95% CI = 0.03-0.60], p = 0.008) were two significant independent factors that influenced recovery and discharge. Conclusion: Lung severity score > 4 and reduced lymphocyte count at initial evaluation were independently associated with a significantly lower rate of recovery and discharge and extended hospitalization in patients admitted for COVID-19 pneumonia.

Objectives To delineate the evolution of CT findings in patients with mild COVID-19 pneumonia. Methods CT images and medical records of 88 patients with confirmed mild COVID-19 pneumonia, a baseline CT, and at least one follow-up CT were retrospectively reviewed. CT features including lobar distribution and presence of ground glass opacities (GGO), consolidation, and linear opacities were analyzed on per-patient basis during each of five time intervals spanning the 3 weeks after disease onset. Total severity scores were calculated. Results Of patients, 85.2% had travel history to Wuhan or known contact with infected individuals. The most common symptoms were fever (84.1%) and cough (56.8%). The baseline CT was obtained on average 5 days from symptom onset. Four patients (4.5%) had negative initial CT. Significant differences were found among the time intervals in the proportion of pulmonary lesions that are (1) pure GGO, (2) mixed attenuation, (3) mixed attenuation with linear opacities, (4) consolidation with linear opacities, and (5) pure consolidation. The majority of patients had involvement of ≥ 3 lobes. Bilateral involvement was more prevalent than unilateral involvement. The proportions of patients observed to have pure GGO or GGO and consolidation decreased over time while the proportion of patients with GGO and linear opacities increased. Total severity score showed an increasing trend in the first 2 weeks. Conclusions While bilateral GGO are predominant features, CT findings changed during different time intervals in the 3 weeks after symptom onset in patients with COVID-19. Key Points • Four of 88 (4.5%) patients with COVID-19 had negative initial CT.• Majority of COVID-19 patients had abnormal CT findings in ≥ 3 lobes.• A proportion of patients with pure ground glass opacities decreased over the 3 weeks after symptom onset.

The major concern of living donor liver transplantation is small-for-size graft injury at the early phase after transplantation. Novel therapeutic strategies should be developed. To investigate the protective effect of somatostatin related to hemodynamic stress on small-for-size liver graft injury, we applied a treatment regimen of low-dose somatostatin in a rat orthotopic liver transplantation model using small-for-size grafts (median, 38.7%; range, 35-42%). Somatostatin was given at 5 minutes before total hepatectomy and immediately after reperfusion in the recipient (20 g/kg). Graft survival, portal hemodynamics, intragraft gene expression and hepatic ultrastructural changes were compared between the rats with or without somatostatin treatment. Seven-day graft survival rates in the somatostatin treatment group were significantly improved compared to the control group (66.7% vs. 16.7%, P ϭ 0.036). In the treatment group, portal pressure and hepatic surface blood flow were significantly decreased within the first 30 minutes after reperfusion, whereas in the control group, transient portal hypertension and excessive hepatic blood flow were observed. Intragraft expression (both messenger RNA and protein) of endothelin-1 was significantly downregulated accompanied with upregulation of heme oxygenase-1 and A20. Better preservation of liver function was found in the treatment group. Hepatic ultrastructure, especially the integrity of sinusoids, was well protected in the treatment group. In conclusion, low-dose somatostatin rescues small-for-size grafts from acute phase injury in liver transplantation by attenuation of acute-phase shear stress that resulted from transient portal hypertension. Therapeutic strategies for attenuation of small-for-size liver graft injury have been investigated recently according to its distinct pattern of hepatic ischemia-reperfusion injury. [1][2][3][4][5][6] Since the severe shear stress that results from transient portal hypertension at the early phase after liver transplantation is the major cause of acute-phase graft failure, treatments focusing on portal decompression should be applied first. In addition to the transient portal hypertension, intragraft overexpression of endothelin-1 (ET-1), which leads to direct sinusoidal contraction, 7 is also the therapeutic target. Previously, our pharmaceutical strategy to ameliorate small-for-size liver graft injury using FK409 demonstrated that attenuation of transient portal hypertension is pivotal to rescue the liver graft from acute phase injury.1 However, FK409 has not yet been approved for clinical use. It is therefore necessary to explore the portal decompression function of the currently available drugs.Somatostatin (SMT), a 14 -amino acid polypeptide, has been known as a multifunctional peptide and used for the treatment of acute variceal hemorrhage because of its selective effect in decreasing splanchnic blood flow and portal pressure without significant hemodynamic effects. [8][9][10] The effect of SMT on portal hypertension may be...

Low-dose FK 409 rescues small-for-size grafts in liver transplantation by attenuation of portal hypertension and amelioration of acute phase inflammatory response by down-regulation of Egr-1, together with prior induction of heat shock proteins.

FOLFIRINOX chemotherapy has shown remarkable responses in patients with metastatic pancreatic cancer (MPC), and has significantly improved prognosis. However, FOLFIRINOX is currently not frequently applied in China because of its high incidence of adverse events, and there is no recognized optimization for this therapy in Chinese population. Modification of FOLFIRINOX may be better for its acceptance in China. In this study, we evaluated the efficacy and safety of modified-FOLFIRINOX in patients with MPC. A total of 62 MPC patients were treated with modified-FOLFIRINOX (no Fluorouracil bolus, 85% Oxaliplatin and 75% Irinotecan) between April 2014 and April 2017 in our institute. 40 of them were evaluated, with a response rate of 32.5% (13/40). The frequent grade 3/4 adverse events are neutropenia (29%) and alanine aminotransferase elevation (14.5%). No treatment-related death was observed. The median overall survival and median progression-free survival are 10.3 months and 7.0 months, respectively. In conclusion, modified-FOLFIRINOX had significantly improved tolerance with similar efficacy to FOLFIRINOX. These findings may provide evidence for the use of FOLFIRINOX in Chinese patients with MPC.

INTRODUCTION: Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized. METHODS: Hospitalized patients with COVID-19 in Zhejiang Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/ L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared. RESULTS: Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median [interquartile range {IQR}] age, 47.0 [35.0-55.0] years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2-6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11-16). No differences in disease severity and clinical outcomes were noted between the groups. DISCUSSION: We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.

mTOR is aberrantly activated in hepatocellular carcinoma (HCC) and plays pivotal roles in tumorigenesis and chemoresistance. Rapamycin has been reported to exert antitumor activity in HCC and sensitizes HCC cells to cytotoxic agents. However, due to feedback activation of AKT after mTOR complex 1 (mTORC1) inhibition, simultaneous targeting of mTORC1/2 may be more effective. In this study, we examined the interaction between the dual mTORC1/2 inhibitor OSI-027 and doxorubicin in vitro and in vivo. OSI-027 was found to reduce phosphorylation of both mTORC1 and mTORC2 substrates, including 4E-BP1, p70S6K, and AKT (Ser473), and inhibit HCC cell proliferation. Similar to OSI-027 treatment, knockdown of mTORC2 induced G0–G1 phase cell-cycle arrest. In contrast, rapamycin or knockdown of mTORC1 increased phosphorylation of AKT (Ser473), yet had little antiproliferative effect. Notably, OSI-027 synergized with doxorubicin for the antiproliferative efficacy in a manner dependent of MDR1 expression in HCC cells. The synergistic antitumor effect of OSI-027 and doxorubicin was also observed in a HCC xenograft mouse model. Moreover, AKT was required for OSI-027–induced cell-cycle arrest and downregulation of MDR1. Our findings provide a rationale for dual mTORC1/mTORC2 inhibitors, such as OSI-027, as monotherapy or in combination with cytotoxic agents to treat HCC.

Lung cancer is the most common malignancy and leads to around one-quarter of all cancer deaths. Great advances have been achieved in the treatment of lung cancer with novel anticancer agents and improved technology. However, morbidity and mortality rates remain extremely high, calling for an urgent need to develop novel anti–lung cancer agents. 1,2,3-Triazole could be readily interact with diverse enzymes and receptors in organisms through weak interaction. 1,2,3-Triazole can not only be acted as a linker to tether different pharmacophores but also serve as a pharmacophore. This review aims to summarize the recent advances in 1,2,3-triazole–containing compounds with anti–lung cancer potential, and their structure–activity relationship (SAR) together with mechanisms of action is also discussed to pave the way for the further rational development of novel anti–lung cancer candidates.