Grip Strength in Patients with Gastrointestinal Diseases.

We sought to elucidate factors contributing to the grip strength (GS) decline in patients with gastrointestinal diseases (Ga-Ds, n = 602, 379 males, median age = 72 years). The GS decline in males and females was defined as <28 kg and <18 kg, respectively, following the current Asian guidelines. The median GS (male) was 28.8 kg, and GS decline (male) was found in 169 patients (44.6%). The median GS (female) was 17.5 kg, and GS decline (female) was found in 122 patients (54.7%). Advanced cancer was identified in 145 patients (24.1%). In terms of the univariate analysis of parameters of the GS decline, age (p < 0.0001), gender (p = 0.0181), body mass index (BMI, p = 0.0002), ECOG-PS (p < 0.0001), SARC-F score (p < 0.0001), hemoglobin value (p < 0.0001), total lymphocyte count (p < 0.0001), serum albumin value (p < 0.0001), C reactive protein (CRP) value (p < 0.0001), and estimated glomerular filtration rate were statistically significant. In terms of the multivariate analysis, age (p < 0.0001), BMI (p = 0.0223), hemoglobin value (p = 0.0186), serum albumin value (p = 0.0284), the SARC-F score (p = 0.0003), and CRP value (p < 0.0001) were independent parameters. In conclusion, the GS decline in patients with Ga-Ds is closely associated with not only the primary factor (i.e., aging) but also secondary factors such as inflammatory factors and nutritional factors.

The Relevance in the Neutrophil to Lymphocyte Ratio and the SARC-F Score in Gastrointestinal Diseases.

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 <4 (n = 588) was 5.87 and 2.48 (p < 0.0001). In all subgroup analyses, similar trends were seen. In the multivariate analysis, ECOG-PS (p < 0.0001) and NLR (p < 0.0001) were independent factors, while age had a trend for significance (p = 0.0686). In conclusion, we would like to emphasize the usefulness of NLR, a simple marker assessed only by blood tests, in predicting the possibility for sarcopenia by the SARC-F in G-Ds.

The Relationship between the SARC-F Score and the Controlling Nutritional Status Score in Gastrointestinal Diseases.

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.

Comparison of SARC-F Score among Gastrointestinal Diseases.

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 < 0.0001), gender (p = 0.0011), serum albumin (p < 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.

Exacerbation of liver dysfunction in non-alcoholic steatohepatitis patients during the coronavirus disease 2019 (COVID-19) pandemic.

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.

Prognostic Impact of the SARC-F Score in Gastrointestinal Advanced Cancers.

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.

Comparison of the 2018 and 2003 International Society of Nephrology/Renal Pathology Society classification in terms of renal prognosis in patients of lupus nephritis: a retrospective cohort study.

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.

Liver dysfunction is associated with poor prognosis in patients after immune checkpoint inhibitor therapy.

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.

Programmed Death 1 Ligand Expression in the Monocytes of Patients with Hepatocellular Carcinoma Depends on Tumor Progression.

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 naïve 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 naïve 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.

Increased both PD-L1 and PD-L2 expressions on monocytes of patients with hepatocellular carcinoma was associated with a poor prognosis.

Anti-programmed cell death-1 (PD-1) antibodies has been approved to treat HCC. Some PD-1 ligands (PD-L1 and PD-L2) negative tumors respond to treatment of anti-PD-1 antibodies, and this fact may be caused by the expression of PD-1 ligands on non-tumor cells. PD-L1 was recently found to be expressed on CD14+ cells from cancer patients. We investigate PD-1 ligands expression on CD14+ cells of patients with HCC and the role of CD14+ cells in an antitumor response. In this study, 87 patients diagnosed with HCC were enrolled. CD14+ cells from patients with HCC expressed PD-L1 (4.5-95.5%) and PD-L2 (0.2-95.0%). According to cut-off values, we classified patients as those either with PD-L1+PD-L2+CD14+ cells or other types of CD14+ cells. The overall survival of patients with PD-L1+PD-L2+CD14+ cells was shorter than that of patients with other types of CD14+ cells (p = 0.0023). PD-L1+PD-L2+CD14+ cells produced IL-10 and CCL1, and showed little tumoricidal activity against HepG2 cells. The tumoricidal activity of CD8+ cells from patients with PD-L1+PD-L2+CD14+ cells were suppressed by co-cultivation with CD14+ cells from the syngeneic patient. Furthermore, anti-PD-1 antibody restored their tumoricidal activity of CD8+ cells. In conclusion, some patients with HCC have PD-L1+PD-L2+CD14+ cells that suppress their antitumor response. These inhibitory functions of CD14+ cells may be associated with a poor prognosis in these patients.

[Mixed connective tissue disease with pulmonary hypertension developing in a chronic myeloid leukemia patient on dasatinib treatment].

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.

Successful laparoscopic treatment of advanced rectal cancer in an extremely elderly man (101 years and 9 months).

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 preventive effect of the impaired liver function for antiemetic therapy against chemotherapy-induced nausea and vomiting in hepatocellular carcinoma patients.

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.