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Background Although the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification was proposed recently, until now, no reports have been made comparing the association of renal prognosis between the 2018 revised ISN/RPS classification and the 2003 ISN/RPS classification. The present study aimed to assess the usefulness, especially of activity and chronicity assessment, of the 2018 revised ISN/RPS classification for lupus nephritis (LN) in terms of renal prognosis compared to the classification in 2003. Methods We retrospectively collected medical records of 170 LN patients from the database of renal biopsy at Fujita Health University from January 2003 to April 2019. Each renal biopsy specimen was reevaluated according to both the 2003 ISN/RPS classification and the 2018 revised ISN/RPS classification. Renal endpoint was defined as a 30% decline of estimated glomerular filtration rate (eGFR). Results A total of 129 patients were class III/IV±V (class III, 44 patients; class IV, 35 patients; class III/IV+V, 50 patients). The mean age was 42 years, 88% were female, and the median observation period was 50.5 months. Renal prognosis was significantly different among the classes and significantly poor in the patients with higher modified National Institute of Health (mNIH) chronicity index (C index, ≥ 4) by a log-rank test (p = 0.05 and p = 0.02, respectively). By Cox proportional hazard models, only the C index was significantly associated with renal outcome (hazard ratio 1.32, 95% CI 1.11–1.56, p ≤ 0.01), while the classes, the 2003 activity and chronicity subdivision, and the mNIH activity index had no significant association with renal outcome. Each component of the C index was significantly associated with renal outcome in different models. Conclusion This study demonstrates that the 2018 revised ISN/RPS classification was more useful in terms of association with renal prognosis compared to the 2003 ISN/RPS classification.

Immune-related adverse events (irAEs) are induced by immune checkpoint inhibitors (ICIs). Liver is one of the main target organs which irAEs occur and we investigated the influence of liver dysfunction on prognosis of patients after ICIs. From July 2014 to December 2018, 188 patients with diverse cancers who received ICIs (nivolumab or pembrolizumab) were enrolled. Twenty-nine patients experienced liver dysfunction of any grades after ICIs. Progression-free survival (PFS) was significantly shorter in the liver dysfunction-positive group than in the liver dysfunction-negative group, and a similar result was obtained for Overall survival (OS). Multiple logistic regression analysis revealed liver metastasis and alanine aminotransferase before ICIs were associated with a higher incidence of liver dysfunction after ICIs. Regardless of liver metastasis, PFS and OS were significantly shorter in the liver dysfunction-positive group. In conclusion, this study suggests liver dysfunction is associated with poor prognosis in patients after ICIs with diverse cancers.

Simple Summary There have been few reports with regard to the relevance between the SARC-F score and the prognosis in patients with gastrointestinal advanced cancers, and we aimed to elucidate these issues (n = 421, median age = 73 years). During the follow-up period, 145 patients (34.4%) died. The 1-year cumulative overall survival rate in patients with SARC-F ≥ 4 (recommended cutoff point, n = 103) and SARC-F < 4 (n = 318) was 33.9% and 61.6% (p < 0.0001). In the multivariate analysis for the overall survival, total lymphocyte count ≥ 1081/μL (p = 0.0014), the SARC-F score ≥ 4 (p = 0.0096), Glasgow prognostic score 1 (p = 0.0147) and 2 (p < 0.0001), ECOG-PS 2 (p < 0.0001), and 3 (p < 0.0001) and 4 (p < 0.0001) were independent predictors. In the receiver operating characteristic curve analysis on the prognostic value of the SARC-F score, the sensitivity/specificity was 0.59/0.70, and the best cutoff point of the SARC-F score was two. The SARC-F score appears to be useful in patients with gastrointestinal advanced malignancies. Abstract We sought to elucidate the prognostic impact of the SARC-F score among patients with gastrointestinal advanced malignancies (n = 421). A SARC-F score ≥ 4 was judged to have a strong suspicion for sarcopenia. In patients with ECOG-PS 4 (n = 43), 3 (n = 61), and 0–2 (n = 317), 42 (97.7%), 53 (86.9%) and 8 (2.5%) had the SARC-F score ≥ 4. During the follow-up period, 145 patients (34.4%) died. All deaths were cancer-related. The 1-year cumulative overall survival (OS) rate in patients with SARC-F ≥ 4 (n = 103) and SARC-F < 4 (n = 318) was 33.9% and 61.6% (p < 0.0001). In the multivariate analysis for the OS, total lymphocyte count ≥ 1081/μL (p = 0.0014), the SARC-F score ≥ 4 (p = 0.0096), Glasgow prognostic score (GPS) 1 (p = 0.0147, GPS 0 as a standard), GPS 2 (p < 0.0001, GPS 0 as a standard), ECOG-PS 2 (p < 0.0001, ECOG-PS 0 as a standard), ECOG-PS 3 (p < 0.0001, ECOG-PS 0 as a standard), and ECOG-PS 4 (p < 0.0001, ECOG-PS 0 as a standard) were independent predictors. In the receiver operating characteristic curve analysis on the prognostic value of the SARC-F score, the sensitivity/specificity was 0.59/0.70, and best cutoff point of the SARC-F score was two. In conclusion, the SARC-F score is useful in patients with gastrointestinal advanced malignancies.

Many people were forced to stay at home, including non-alcoholic steatohepatitis (NASH) patients, however it is unclear how this home-life has affected the prognosis of NASH. In this study, we examined the influences of living at home during the coronavirus disease 2019 (COVID-19) pandemic NASH patients. In this study, we compared the clinical parameters of NASH patients without COVID-19 infection 3 months before with those 3 months after the declaration of a state of emergency. In the results, the changes of aspartate transaminase and alanine aminotransferase in the 3 months before (aspartate transaminase, -3.6 ± 13.8 U/L; alanine aminotransferase, -6.8 ± 19.5 U/L) was significantly exacerbated in the 3 months after (aspartate transaminase, 2.3 ± 7.5 U/L; alanine aminotransferase, 1.7 ± 10.4 U/L). Furthermore, the changes of the fibrosis-4 index in the 3 months before (-0.27 ± 0.84) was also significantly exacerbated in the 3 months after (0.38 ± 0.96). In conclusion, liver dysfunctions in NASH patients were exacerbated due to the emergency declaration and outing restriction which accompanied COVID-19.

We sought to clarify the relevance in the neutrophil to lymphocyte ratio (NLR) and the SARC-F score in patients with gastrointestinal diseases (G-Ds, n = 672, median age = 73 years). Univariate and multivariate analysis for the SARC-F score were performed. Advanced malignancy was identified in 162 patients (24.1%). The median of NLR for all cases was 2.65. The median of NLR in ECOG-PS 0 (n = 436), 1 (n = 128), 2 (n = 49) and 3 or 4 (n = 59) was 2.26, 2.97, 4.41 and 5.99 (overall p < 0.0001). NLR had a significant correlation with the SARC-F score (r = 0.54, p < 0.0001). The median of NLR in the SARC-F score ≥4 (recommended value for sarcopenia, n = 84) and

Background: Although 2018 revised ISN/RPS classification was proposed recently, until now, no reports have been made comparing the association of renal prognosis between 2018 revised ISN/RPS classification and 2003 ISN/RPS classification. The present study aimed to assess the usefulness, especially of activity and chronicity assessment, of the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification for lupus nephritis (LN) in terms of renal prognosis compared to the classification in 2003.Methods: We retrospectively collected medical records of 170 LN patients from the database of renal biopsy in Fujita Health University from January 2003 to April 2019. Each renal biopsy specimen was reevaluated according to both the 2003 ISN/RPS classification and the 2018 revised ISN/RPS classification. Renal endpoint was defined as 30% decline of estimated glomerular filtration rate (eGFR). Results: A total 129 patients were class III/IV±V (class III, 44 patients; class IV, 35 patients; class III/IV+V, 50 patients). Mean age was 42 years, 88% were female, and median observation period was 50.5 months. Renal prognosis was significantly different among the classes, and significantly poor in the patients with higher modified National Institute of Health (mNIH) Chronicity index (C index, ≥4) by a log-rank test (p=0.05, p=0.02 respectively). By Cox proportional hazard models, only C index was significantly associated with renal outcome (Hazard Ratio; 1.32, 95% CI; 1.11-1.56, p≤0.01), while the classes, the 2003 activity and chronicity subdivision, and mNIH activity index had no significant association with renal outcome. Each component of C index was significantly associated with renal outcome in different models. Conclusion: This study demonstrates that the 2018 revised ISN/RPS classification was more useful in terms of association with renal prognosis compared to the 2003 ISN/RPS classification

Monocytes (CD14+ cells) from advanced-stage hepatocellular carcinoma (HCC) patients express programmed death 1 ligand (PD-L)/PD-1 and suppress the host antitumor immune response. However, it is unclear whether cancer progression is associated with CD14+ cells. We compared CD14+ cell properties before and after cancer progression in the same HCC patients and examined their role in antitumor immunity. CD14+ cells were isolated from 15 na&iuml, ve early-stage HCC patients before treatment initiation and after cancer progression to advanced stages. Although CD14+ cells from patients at early HCC stages exhibited antitumor activity in humanized murine chimera, CD14+ cells from the same patients after progression to advanced stages lacked this activity. Moreover, CD14+ cells from early HCC stages scantly expressed PD-L1 and PD-L2 and produced few cytokines, while CD14+ cells from advanced stages showed increased PD-L expression and produced IL-10 and CCL1. CD14+ cells were also isolated from five na&iuml, ve advanced-stage HCC patients before treatment as well as after treatment-induced tumor regression. The CD14+ cells from patients with advanced-stage HCC expressed PD-L expressions, produced IL-10 and CCL1, and exhibited minimal tumoricidal activity. After treatment-induced tumor regression, CD14+ cells from the same patients did not express PD-Ls, failed to produce cytokines, and recovered tumoricidal activity. These results indicate that PD-L expression as well as CD14+ cell phenotype depend on the tumor stage in HCC patients. PD-L expressions of monocytes may be used as a new marker in the classification of cancer progression in HCC.

We sought to examine the relationship between the SARC-F score and the Controlling Nutritional Status (CONUT) score in patients with gastrointestinal diseases (GDs, n = 735, median age = 71 years, and 188 advanced cancer cases). The SARC-F score ≥ 4 (highly suspicious of sarcopenia) was found in 93 cases (12.7%). Mild malnutritional condition was seen in 310 cases (42.2%), moderate in 127 (17.3%) and severe in 27 (3.7%). The median SARC-F scores in categories of normal, mild, moderate and severe malnutritional condition were 0, 0, 1 and 1 (overall p < 0.0001). The percentage of SARC-F score ≥ 4 in categories of normal, mild, moderate and severe malnutritional condition were 4.4%, 12.9%, 26.8% and 25.9% (overall p < 0.0001). The SARC-F score was an independent factor for both the CONUT score ≥ 2 (mild, moderate or severe malnutrition) and ≥5 (moderate or severe malnutrition). In the receiver operating characteristic (ROC) curve analysis for the CONUT score ≥ 2, C reactive protein (CRP) had the highest area under the ROC (AUC = 0.70), followed by the SARC-F score (AUC = 0.60). In the ROC analysis for the CONUT score ≥ 5, CRP had the highest AUC (AUC = 0.79), followed by the SARC-F score (AUC = 0.63). In conclusion, the SARC-F score in patients with GDs can reflect malnutritional status.

SARC-F is a screening tool for sarcopenia. We sought to compare the SARC-F scores of patients with different gastrointestinal diseases (n = 1282 (762 males): upper gastrointestinal disease (UGD, n = 326), lower gastrointestinal disease (LGD, n = 357), biliary and pancreatic disease (BPD, n = 416), and liver disease (LD, n = 183)). Factors associated with SARC-F ≥4 points (highly suspicious of sarcopenia) were also examined. The median age was 71 years. Patients with SARC-F ≥4 points were found in 197 (15.4%). Advanced cancer was found in 339 patients (26.4%). The proportion of SARC-F ≥4 points in groups of UGD, LGD, BPD, and LD were 17.5% (57/326) in UGD, 12.0% (43/357) in LGD, 17.3% (72/416) in BPD, and 13.7% (25/183) in LD, respectively (overall p = 0.1235). In patients with and without advanced cancer, similar tendencies were observed. In the multivariate analysis, age (p &lt, 0.0001), gender (p = 0.0011), serum albumin (p &lt, 0.0001), lymphocyte count (p = 0.0019), C reactive protein (p = 0.0197), and the presence of advanced cancer (p = 0.0424) were significant factors linked to SARC-F ≥4 points. In patients with advanced cancer, SARC-F scores correlated well with their Glasgow prognostic scores. In conclusion, sarcopenia in gastrointestinal diseases may be affected not by disease type (i.e., the primary origin of the disease) but by aging, nutritional condition, inflammatory condition, and cancer burden.

Transarterial chemoembolization and hepatic arterial infusion chemotherapy are recommended for the treatment in patients with intermediate stage of hepatocellular carcinoma. Impaired liver function was sometime observed in patients with hepatocellular carcinoma after transarterial chemoembolization or hepatic arterial infusion chemotherapy. However, what kinds of factors deeply influence in impaired liver function are not clear. A retrospective study was performed to evaluate the risk factors of impaired liver function in cisplatin-naïve patients treated with these therapies using cisplatin. Prior to and 2 months after these therapies, we analyzed the liver function by Child-Pugh score in these patients. For assessing the severity of chemotherapy-induced nausea and vomiting, we utilized the Common Terminology Criteria for Adverse Events ver. 4.0. In hepatocellular carcinoma patients received these therapies using cisplatin, the cancer stage and treatment without neurokinin-1 (NK1) antagonist were found to be independent risk factors of the impaired liver function. The treatment with NK1 antagonist was effective in reducing chemotherapy-induced nausea and vomiting and patients treated with NK1 antagonist kept their liver functions after cisplatin-used these therapies. The treatment with NK1 antagonist was effective in chemotherapy-induced nausea and vomiting and prevented the impaired liver function associated with cisplatin-used these therapies in hepatocellular carcinoma patients.

An extremely elderly man (age, 101 years and 9 months) visited our hospital because of recurrent and worsening anal bleeding. Type 2 rectal cancer was found in his rectum during colonoscopy. He did not have any severe coexisting diseases and had not suffered any episodes of dementia. Laparoscopy-assisted anterior resection combined with D2 lymph node dissection was performed with minimal bleeding. The operation time was 128 min. The patient suffered mild reflux pneumonia on postoperative day 6 and was administered additional antibiotics. He recovered within 2 days. He was discharged on postoperative day 17, at which point he was able to walk.

The prognosis of patients with hepatocellular carcinoma (HCC) is poor. Anti–programmed death-1 (PD-1) antibodies (Abs) has been approved to treat HCC. Some PD-1 ligands (PD-L1 and PD-L2) negative tumors respond to anti–PD-1 Abs. This response may be caused by the expression of PD-1 ligands on non-tumor cells. PD-1 ligands were recently found to be expressed on monocytes (CD14+ cells) from diverse cancer patients. In this study, we investigate the expression of PD-1 ligands on CD14+ cells from HCC patients and the role of CD14+ cells in an antitumor response. From October 2017 to June 2019, 67 patients with HCC were enrolled. The expression of PD-L1 and PD-L2 on CD14+ cells was analyzed by flow cytometry. Their prognosis was evaluated by overall survival (OS). Tumoricidal activities of both CD14+ and CD8+ cells were calculated by LDH release assay. In the results, CD14+ cells from the patients expressed PD-L1 (4.5–95.5%) and PD-L2 (1.6–90.2%). We set cut-off values as the mean values of PD-L1 (50.2%) and PD-L2 (50.5%) expression. In addition, according to the cut-off value, we classified patients as those either with PD-L1+PD-L2+CD14+ cells or other types of CD14+ cells. The OS of patients with PD-L1+PD-L2+CD14+ cells was significantly shorter than that of patients with other types of CD14+ cells (p = 0.0145). The tumoricidal activity of CD8+ cells from patients with PD-L1+PD-L2+CD14+ cells was suppressed by co-cultivation with syngeneic CD14+ cells. Furthermore, anti–PD-1 Ab restored the tumoricidal activity of CD8+ cells. In conclusions, some patients with HCC have PD-L1+PD-L2+CD14+ cells that suppress their antitumor response of CD8+ cells. These inhibitory functions of CD14+ cells may be associated with a poor prognosis in such patients.

Two hepatic macrophage (MΦ) populations have been described in the inflamed liver: F4/80+CD11b+ cells and F4/80+CD68+ cells. In normal conditions, hepatic F4/80+CD11b+ cells are involved in host antibacterial resistance. However, these cells in total body irradiated mice (TBI mice) are unfunctional for the elimination of bacteria translocated from intestinal tracts. In this study, the properties of hepatic MΦ populations in TBI mice were characterized. Normal mice and mice 7 days after exposure to 4 Gy of X-rays were infected i.v. with 107 CFU/mouse of Enterococcus faecalis (E. faecalis). Three day after infection, F4/80+CD11b+ cells and F4/80+CD68+ cells isolated from the liver of these mice were cultured for 24 hrs, and culture fluids were assayed for IL-12, IL-10 and CCL1 by ELISA. NSG mice were inoculated i.v. with these MΦ preparations (2 × 105 cells/mouse), then infected i.v. with 5 × 104 CFU/mouse of E. faecalis. In the results, all TBI mice died within 2 weeks, while all normal mice survived. IL-12 was produced by F4/80+CD11b+ cells from normal mice, but not by both MΦ preparations from TBI mice. IL-10 was produced by F4/80+CD68+ cells from TBI mice (529.9 ± 272.6 pg/ml) and normal mice (445.8 ± 147.7 pg/ml). Large amounts of IL-10 (912.1 ± 103.7 pg/ml) was produced by F4/80+CD11b+ cells from TBI mice, and these cells produced CCL1 (327.5 ± 9.1 pg/ml), while other MΦ preparations did not. NSG mice inoculated with F4/80+CD11b+ cells from normal mice were resistant to infection; however, NSG mice inoculated with F4/80+CD11b+ cells from TBI mice did not. These results indicate hepatic F4/80+CD11b+ cells are polarized to M2bMΦ in response to total body irradiation, and these MΦ are involved in the decreased host antibacterial resistance in TBI mice.

M2b macrophages (Mf)/monocytes play a role in the increased susceptibility of alcoholics to infections. However, the mechanism involved in M2bMf polarization remains unclear. In this study, we investigated the role of CD34+CD10+CD19−Pax5+ cells (Pre/Pro-B cells) in the peripheral blood of alcoholics on alcohol-related M2bMf/monocyte polarization through the production of high mobility group box-1 (HMGB1). M2b monocytes were identified as few bactericidal activity, IL-10 and CCL1 productions. Pre/Pro-B cells isolated from 18 alcoholics and 11 healthy donors (HD) were cultured with 10 nM of retinoic acid for 24hrs and culture medium obtained were assayed for HMGB1 by ELISA. CD14+cells (1 × 106 cells/ml) from HD were stimulated with 10% (v/v) of each culture media of Pre/Pro-B cells for 24hrs and their producing abilities of IL-10 and CCL1 were assayed. And 1 × 106 cells/ml of these cells were infected with 2 × 106 CFU /ml Enterococcus faecalis (E. faecalis). The bactericidal activity was assayed for colony counting methods. In the results, Pre/Pro-B cells from HD did not produce HMGB1(10.5 ± 5.5 ng/mL), while these cells from alcoholics did (70.3 ± 20.2 ng/mL). When CD14+ cells from HD were stimulated with each culture media from alcoholics, these CD14+ cells produced IL-10 (102.3 ± 1.7 pg/mL) and CCL1 (3.12 ± 1.33 ng/mL) and did not have bactericidal activity against E. faecalis (17.0 ± 8.6%). However, same CD14+ cells from HD were stimulated with each culture media from HD, these cells did not produce IL-10 (10.3 ± 3.4 pg/mL) and CCL1 (0.3 ± 0.01 ng/mL) and have the bactericidal activity (62.8 ± 3.8%). These results indicate that Pre/Pro-B cells play a crucial role in M2bMf/monocyte polarization via HMGB1 production in alcoholics.

A 37-year-old woman was diagnosed with chronic phase chronic myeloid leukemia. Nilotinib treatment was initiated; however, it had to be discontinued due to an allergic reaction one month later, and dasatinib treatment was provided. Although favorable response was obtained, she started complaining of shortness of breath 7 months after initiating dasatinib treatment. Chest X-ray and echocardiography indicated pulmonary congestion and hypertension. Further, she was diagnosed with mixed connective tissue disease (MCTD) based on Raynaud phenomenon, swollen fingers, sclerodactyly, pancytopenia, hypocomplementemia, and positive anti-U1-RNP antibody. Consequently, dasatinib treatment was discontinued, and she was administered prednisolone (1 mg/kg/day), which was effective and successfully tapered with concomitant administration of cyclophosphamide. This is the first case of MCTD that developed during dasatinib treatment. However, because the present case was a young woman, the development of MCTD could probably be attributed to autoimmune diatheses or it may be a coincidence. However, the possibility of patients receiving dasatinib treatment developing autoimmune diseases needs to be assessed.

Hepatocellular carcinoma (HCC) is the fifth common cancer in the world. In previous study, we reported that M2b monocytes which predominately generated in advanced-stage HCC patients were important target for HCC immunotherapy. Recently, an anti-PD-1 antibody has been approved for the treatment against HCC. In this study, we tried to analyzed for immunological characters of monocytes isolated from patients with several stages of HCC. From 2017 August to 2017 December, nine patients diagnosed as advanced-stage HCC patients and five patients diagnosed as early-stage HCC patients were enrolled in this study. Monocytes from peripheral blood of these patients were stained for anti-PD-1 antibody, anti-PD-L1 antibody and anti-PD-L2 antibody. These cells were analyzed for flow cytometry. Furthermore, five healthy donors were used for the control groups. In the results, a majority of monocytes from advanced-stage HCC patients were expressed PD-L1 (81.5 ± 14.7%) and PD-L2 (71.6 ± 18.5%), but not PD-1(20.2 ± 18.6%). And, monocytes from early-stage HCC patients were expressed PD-L1 (9.9 ± 4.1%), PD-L2 (38.74 ± 9.9%) and PD-1 (23.5 ± 9.8%). As the contorls, monocytes from healthy donors were not expressed PD-L1 (21.7 ± 5.5%), PD-L2 (31.7 ± 23.8%) and PD-1 (11.6 ± 6.4%). The PD-L1 expression in monocytes was increased as HCC progressed. These results indicate the PD-L1 expression may be used as a new marker for the classification of the cancer progression. And, PD-1−PD-L1+PD-L2+ monocytes which were predominantly generated in advanced-stage HCC patients, may target for the treatment of anti-PD-L1 antibody.

AUD patients have an increased risk of serious opportunistic infections. IMCs have been described as suppressor cells for host antibacterial defenses. In this study, IMCs isolated from AUD patients were examined for their inhibitory functions on the bactericidal activity of healthy donor (HD) monocytes. IMCs and monocytes were isolated from the peripheral blood of 10 AUD patients admitted to Osaka Medical Collage and 5 HD. HD monocytes (1 × 105 cells/ml) were stimulated with heat-killed Enterococcus faecalis, then cultured in media supplemented with the conditioned media of patient IMCs (24 hr-culture fluids, 10% v/v, 1 × 106 cells/ml). Twenty-four hrs after the cultivation, monocytes were harvested and tested for their bactericidal activities against E. faecalis. In some cases, patient IMCs, cultured with 5 μg/ml of retinoic acid (RA) for 24 hrs, were utilized for the experiments. Also, both groups of IMCs were analyzed for RA receptor (RAR) expression by flow cytometry. In the results, as compared to HD peripheral blood IMCs, the numbers of IMCs increased in AUD patients. HD monocytes were shown to be bactericidal against E. faecalis. However, the bactericidal activity of HD monocytes was not demonstrated when they were cultured with media supplemented with the conditioned media of patient IMCs. HD IMCs differentiated to monocytes or dendritic cells after cultivation with RA. However, AUD patient IMCs were shown to be not susceptible to RA treatment (patient IMCs, RAR−; HD IMCs, RAR+). These results suggest that, through the production of some soluble factors active against killing functions of monocytes, patient IMCs increase the susceptibility of AUD patients to opportunistic infections.