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PURPOSE: Recent advances have made possible the treatment of small invasive colorectal cancer by means of polypectomy or endoscopic mucosal resection. CD44 expression in cancer cells was identified as an indicator of lymph-node metastasis, which could be evaluated in specimens removed by colonoscopy. METHODS: The correlation between lymph-node metastasis and the expression of standard-type CD44 in cancer cells was examined immunohistologically using the invaded cancer cells of 61 tissue samples of superficially invasive colorectal cancer. We defined the above as invasive cancer restricted within the colorectal wall. Of the 61 samples, 31 had submucosal invasion and 30 had muscular invasion. RESULTS: Standard-type CD44 expression in the area of invasion in cases with lymph-node metastasis was remarkably down-regulated. In 43 cases with no lymph-node metastasis, 36 (83.7 percent) of patients had CD44 expression in invaded cells, whereas only two of 18 cases (11.1 percent) with lymph-node metastasis had expression of standard-type CD44 in the same area (P < 0.0001). A total of 69 6 percent (16/23) of patients with loss of standard-type CD44 expression in invaded sites were found to have positive metastasis in the lymph nodes. These results suggest that standard-type CD44 in invasive colon cancer cells could suppress metastasis to the regional lymph nodes. CONCLUSION; In cases of invasive colorectal cancer, the loss of standard-type CD44 expression in the invaded area is a sensitive marker for metastasis to the lymph nodes. Further investigation with larger patient groups is required to clarify the reliability of loss of standard-type CD44 expression as an indicator for additional surgery after endoscopic resection of submucosal invasive colorectal carcinoma. [ABSTRACT FROM AUTHOR]

Background: Empagliflozin reduces the risk of hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease. We sought to elucidate the effect of empagliflozin as an add-on therapy on decongestion and renal function in patients with type 2 diabetes admitted for acute decompensated heart failure. Methods: The study was terminated early due to COVID-19 pandemic. We enrolled 59 consecutive patients with type 2 diabetes admitted for acute decompensated heart failure. Patients were randomly assigned to receive either empagliflozin add-on (n=30) or conventional glucose-lowering therapy (n=29). We performed laboratory tests at baseline and 1, 2, 3, and 7 days after randomization. Percent change in plasma volume between admission and subsequent time points was calculated using the Strauss formula. Results: There were no significant baseline differences in left ventricular ejection fraction and serum NT-proBNP (N-terminal pro-B-type natriuretic peptide), hematocrit, or serum creatinine levels between the 2 groups. Seven days after randomization, NT-proBNP level was significantly lower in the empagliflozin group than in the conventional group (P =0.040), and hemoconcentration (≥3% absolute increase in hematocrit) was more frequently observed in the empagliflozin group than in the conventional group (P =0.020). The decrease in percent change in plasma volume between baseline and subsequent time points was significantly larger in the empagliflozin group than in the conventional group 7 days after randomization (P =0.017). The incidence of worsening renal function (an increase in serum creatinine ≥0.3 mg/dL) did not significantly differ between the 2 groups. Conclusions: In this exploratory analysis, empagliflozin achieved effective decongestion without an increased risk of worsening renal function as an add-on therapy in patients with type 2 diabetes with acute decompensated heart failure. Registration: URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000026315. [ABSTRACT FROM AUTHOR]

The principal hypothesis for pathogenesis of Alzheimer disease (AD) is the amyloid cascade hypothesis, which emphasizes an imbalance between production and clearance of β-amyloid (Aβ) in the brain. Insulin has important effects on the regulation of the Aβ level in the brain, modulating both Aβ production and clearance. An optimal brain insulin level promotes Aβ clearance, which may play protective roles against AD. A functional human leptin receptor gene (LEPR) polymorphism, a glutamine to an arginine substitution at codon 223 (Gln223Arg), has been associated with insulin resistance capacity and an altered leptin-binding activity. The LEPR Gln223Arg polymorphism may thus play an important role in the pathogenesis of AD. In this study, we examined the association between the LEPR Gln223Arg polymorphism and late-onset Alzheimer disease (LOAD) in a Japanese population. Our sample includes 49 patients with LOAD and 134 normal controls. Our preliminary data showed no significant association between the LEPR Gln223Arg polymorphism and LOAD (genotype distribution: χ² = 0.11, df = 2, P = 0.945; allele frequency: χ² =0.058, df= 1,P = 0.81, odds ratio =1.08, 95% confidence interval = 0.59 to 2.03). Our results suggest that the LEPR polymorphism may not play a major role in the development of LOAD. [ABSTRACT FROM AUTHOR]

Double-stapling techniques for restorative rectal resection have been effective in minimizing local contamination compared with open circular stapling techniques. Inclusion of the transverse staple line closure of the distal rectal stump in the circular stapled anastomosis may minimize the risk of suture line recurrence. A technique for formation of such an anastomosis is described that avoids use of a distal purse string. [ABSTRACT FROM AUTHOR]

Backgrounds: Cardio-renal anemia syndrome (CRAS) has the prognostic significance in patients with heart failure. We previously reported that the product of creatinine (Cr) and blood urea nitrogen (BUN) divided by hemoglobin (Hb), CrхBUN/Hb as an index of CRAS, was associated with poor outcome in the analysis of the retrospective cohort of patients with acute decompensated heart failure (ADHF). On the other hand, a new group of heart failure patients with mid-range ejection fraction (HFmrEF) has recently been defined, separated from heart failure patients with reduced and preserved ejection fraction (HFrEF and HFpEF). The aim of this study was to prospectively validate the prognostic value of the CRAS index in ADHF patients, relating to HFrEF, HFmrEF and HFpEF. Methods and Results: We studied 368 patients (HFrEF: n=129, HFmrEF: n=86, HFpEF: n=153) admitted for ADHF with survival discharge in our prospective cohort study. Echocardiography and venous blood sampling were performed just before discharge, and we obtained CrхBUN/Hb at the discharge. The endpoint of this study was all-cause death (ACD). During a follow-up period of 2.5±1.4 years, 109 pts had ACD. At multivariate Cox analysis, CrхBUN/Hb was significantly and independently associated with ACD after the adjustment with age, NYHA class, systolic blood pressure and plasma BNP level, in all of the three groups. Patients with high CrхBUN/Hb (>2.248 determined from the retrospective cohort) had a significantly greater risk of ACD than low CrхBUN/Hb, in HFrEF(hazard ratio 5.52[2.80-11.89], p<0.0001), HFmrEF (hazard ratio 5.05[1.90-17.41], p=0.0011) and HFpEF (hazard ratio 3.50[1.79-7.53], p=0.0002) groups. Conclusion: CrхBUN/Hb as an index of CRAS, which is easily obtained in the usual clinical setting, would be useful to stratify the risk of all-cause death in ADHF patients, irrespective of HFrEF, HFmrEF and HFpEF. [ABSTRACT FROM AUTHOR]

Objective: Recent studies have revealed positive associations between tardive dyskinesia (TD) and genetic polymorphisms of several cytochrome P450 (CYP) subfamilies that are involved in pharmacokinetic process of antipsychotic drugs. In the present study, we analyzed the relationship between TD and two polymorphisms of the CYP1A2 gene, 734C/A and -2964G/A, in a sample of Japanese patients with schizophrenia., Methods: We studied 199 Japanese patients with schizophrenia. We used the Abnormal Involuntary Movement Scale to evaluate TD. Two polymorphisms of the CYP1A2 gene, 734C/A and -2964 G/A were genotyped by means of polymerase chain reaction and restriction fragment length polymorphism analysis., Results: Neither the 734C/A nor the -2964G/A polymorphism was associated with TD [734C/A genotype: chi2=0.02, degrees of freedom (df)=2, P=1.00; allele: chi2=0.02, df=1, P=0.89; -2964G/A genotype: chi2=0.21, df=2, P=0.90; allele: chi2=0.15, df=1, P=0.70]. In addition, CYP1A2 haplotype was associated with TD (chi2=0.24, df=3, P=0.97). Furthermore, in both the subgroup of smokers and the subgroup of patients receiving high-dosage antipsychotics (chlorpromazine equivalent >1000 mg), neither the 734C/A nor the -2964G/A polymorphism was associated with TD., Conclusions: We did not find significant associations between the 734C/A and -2964G/A polymorphisms of CYP1A2 gene and TD in Japanese patients with schizophrenia. Our results suggest that these CYP1A2 gene polymorphisms may not contribute to TD susceptibility.

Objective: Oxidative stress such as free radical-mediated neuronal dysfunction may be involved in the pathophysiology of schizophrenia. The human glutathione peroxidase (GPX1) is a selenium-dependent enzyme, which plays an important role in the detoxification of free radicals. We therefore hypothesized that the GPX1 gene, which is located on chromosome 3p21.3, may be involved in the pathophysiology of schizophrenia. The aim of this study is to examine whether a potentially functional polymorphism, a proline (Pro) to leucine (Leu) substitution at codon 197 (Pro197Leu) of the human GPX1 gene, is associated with susceptibility to schizophrenia., Methods: We genotyped the Pro197Leu polymorphism in a total of 113 nuclear families that had a proband with schizophrenia. Genetic association was tested using the transmission disequilibrium test (TDT), the sib transmission disequilibrium test (STDT), and the family-based association test (FBAT)., Results: The minor allele (Leu) frequency was calculated to be 0.282. We could not find significant transmission disequilibrium of the alleles for the Pro197Leu polymorphism in the GPX1 gene in association with the presence of schizophrenia in our family sample (TDT, chi2=0.03, degrees of freedom=1, P=0.86; combined TDT-STDT, Z'=-0.052, P=0.47; FBAT, Z=0.000, P=1.000)., Conclusion: The results of this study suggest that the GPX1 polymorphism is unlikely to be associated with susceptibility to schizophrenia.