Changes in renal function over time in outpatients with eGFR ≥ 30 mL/min/1.73 m2: implication for timing of renal function testing before contrast-enhanced CT imaging.

PURPOSE: To evaluate the associations between comorbidities and kidney function decline at 6-month and 1-year follow-up in outpatients with initial estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2. MATERIALS AND METHODS: Outpatients aged 18 and older with confirmed diagnosis, who had eGFR ≥ 30 mL/min/1.73 m2 measured between April 2017 and March 2019, were included in this retrospective observational study. Of them, 30,595 included outpatients had 6-month eGFR test and 27,698 included outpatients had 1-year eGFR test. The outpatients were further divided into two groups based on initial eGFR: between 30 and 59 and ≥ 60 mL/min/1.73 m2. Impaired renal function was defined as eGFR declined to below 30 mL/min/1.73 m2. The comorbidities with P values less than 0.1 identified in univariable logistic regression models were entered into the multivariable analysis with backward selection, thereby identifying comorbidities that increased the risk of eGFR decline at 6-month and 1-year follow-up. RESULTS: Outpatients with initial eGFR between 30 and 59 mL/min/1.73 m2 were 175.94 times more likely to have eGFR decline at 6 months, and were 94.10 times more likely to have eGFR decline at 1 year, compared with their corresponding initial eGFR ≥ 60 counterparts. Multivariable logistic regression analyses disclosed that chronic kidney disease, hypertension, and heart failure were independent risk factors for eGFR decline in outpatients with initial eGFR between 30 and 59 mL/min/1.73 m2. CONCLUSIONS: Outpatients with initial eGFR ≥ 60 mL/min/1.73 m2 might not need routine eGFR test prior to contrast-enhanced CT scan for 1 year. In addition, chronic kidney disease, hypertension, and heart failure increased the risk of declined renal function, particularly, in outpatients with initial eGFR between 30 and 59 mL/min/1.73 m2.

Validation of algorithms to identify colorectal cancer patients from administrative claims data of a Japanese hospital.

BACKGROUND: Administrative claims data are a valuable source for clinical studies; however, the use of validated algorithms to identify patients is essential to minimize bias. We evaluated the validity of diagnostic coding algorithms for identifying patients with colorectal cancer from a hospital's administrative claims data. METHODS: This validation study used administrative claims data from a Japanese university hospital between April 2017 and March 2019. We developed diagnostic coding algorithms, basically based on the International Classification of Disease (ICD) 10th codes of C18-20 and Japanese disease codes, to identify patients with colorectal cancer. For random samples of patients identified using our algorithms, case ascertainment was performed using chart review as the gold standard. The positive predictive value (PPV) was calculated to evaluate the accuracy of the algorithms. RESULTS: Of 249 random samples of patients identified as having colorectal cancer by our coding algorithms, 215 were confirmed cases, yielding a PPV of 86.3% (95% confidence interval [CI], 81.5-90.1%). When the diagnostic codes were restricted to site-specific (right colon, left colon, transverse colon, or rectum) cancer codes, 94 of the 100 random samples were true cases of colorectal cancer. Consequently, the PPV increased to 94.0% (95% CI, 87.2-97.4%). CONCLUSION: Our diagnostic coding algorithms based on ICD-10 codes and Japanese disease codes were highly accurate in detecting patients with colorectal cancer from this hospital's claims data. The exclusive use of site-specific cancer codes further improved the PPV from 86.3 to 94.0%, suggesting their desirability in identifying these patients more precisely.

Validation of Algorithms to Identify Bone Metastases Using Administrative Claims Data in a Japanese Hospital.

BACKGROUND: Validated coding algorithms are essential to generate high-quality, real-world evidence from claims data studies. OBJECTIVE: We aimed to evaluate the validity of the algorithms to identify patients with bone metastases using claims data from a Japanese hospital. PATIENTS AND METHODS: This study used administrative claims data and electronic medical records at Juntendo University Hospital from April 2017 to March 2019. We developed two candidate claims-based algorithms to detect bone metastases, one based on diagnosis codes alone (Algorithm 1) and the other based on the combination of diagnosis and imaging test codes (Algorithm 2). Of the patients identified by Algorithm 1, 100 patients were randomly sampled. Among these 100 patients, 88 patients met the conditions of Algorithm 2; further, 12 additional patients were randomly sampled from those identified by Algorithm 2, thus obtaining a total of 100 patients for Algorithm 2. They were evaluated for their true diagnosis using the patient chart review as the gold standard. The positive predictive value (PPV) was calculated to assess the accuracy of each algorithm. RESULTS: For Algorithm 1, 82 patients were analyzed after excluding 18 patients without diagnostic imaging reports. Of these, 69 patients were true positive by chart review, resulting in a PPV of 84.1% (95% confidence interval (CI) 74.5-90.6). For Algorithm 2, 92 patients were analyzed after excluding eight patients whose diagnoses were not judged by chart review. Of these, 76 patients were confirmed positive by chart review, yielding a PPV of 82.6% (95% CI 73.4-89.1). CONCLUSION: Both claims-based algorithms yielded high PPVs of approximately 85%, with no improvement in PPV by adding imaging test conditions. The diagnosis code-based algorithm is sufficient and valid for identifying bone metastases in this Japanese hospital.

Structure-activity relationship studies on an antitumor marine macrolide using aplyronine a-swinholide A hybrid.

An aplyronine A-swinholide A hybrid, consisting of the macrolactone part of aplyronine A and the side chain part of swinholide A, was designed, synthesized, and biologically evaluated. This hybrid induced protein-protein interactions between two major cytoskeletal proteins actin and tubulin in the same manner as aplyronine A, and exhibited potent cytotoxicity and actin-depolymerizing activity. The importance of the methoxy group in the N,N,O-trimethylserine ester was clarified by the structure-activity relationship studies of the amino acid moiety by using the hybrid analogs. Furthermore, the comparison of the actin-depolymerizing activities between the side chain analogs of aplyronine A and swinholide A showed that the side chain analog of swinholide A had much weaker actin-depolymerizing activity than that of aplyronine A.

A Novel Interaction between FLICE-Associated Huge Protein (FLASH) and E2A Regulates Cell Proliferation and Cellular Senescence via Tumor Necrosis Factor (TNF)-Alpha-p21WAF1/CIP1 Axis.

Dysregulation of the cell proliferation has been implicated in the pathophysiology of a number of diseases. Cellular senescence limits proliferation of cancer cells, preventing tumorigenesis and restricting tissue damage. However, the role of cellular senescence in proliferative nephritis has not been determined. The proliferative peak in experimental rat nephritis coincided with a peak in E2A expression in the glomeruli. Meanwhile, E12 (an E2A-encoded transcription factor) did not promote proliferation of Mesangial cells (MCs) by itself. We identified caspase-8-binding protein FLICE-associated huge protein (FLASH) as a novel E2A-binding partner by using a yeast two-hybrid screening. Knockdown of FLASH suppressed proliferation of MCs. This inhibitory effect was partially reversed by the knockdown of E2A. In addition, the knockdown of FLASH induced cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21) expression, but did not affect p53 expression. Furthermore, overexpression of E12 and E47 induced p21, but not p53 in MCs, in the absence of FLASH. We also demonstrated that E2A and p21 expression at the peak of proliferation was followed by significant induction of FLASH in mesangial areas in rat proliferative glomerulonephritis. Moreover, we revealed that FLASH negatively regulates cellular senescence via the interaction with E12. We also demonstrated that FLASH is involved in the TNF-α-induced p21 expressions. These results suggest that the functional interaction of E2A and FLASH play an important role in cell proliferation and cellular senescence via regulation of p21 expression in experimental glomerulonephritis.

[An attempt to degradation of anticancer drug and odor in the medical environment by photocatalyst].

Currently, there is a need to reduce the occupational exposure of health care workers to anticancer drugs. Environmental contamination by anticancer drugs and subsequent exposure of health care workers are associated with vaporization of anticancer drugs. Furthermore, carcinomatous unpleasant odor is an additional problem to vaporized anticancer drugs in the field of clinical cancer therapy. We attempted to degrade vaporized anticancer drug and unpleasant odor using a photocatalyst. Cyclophosphamide or unpleasant odors (ammonia, formaldehyde, isovaleric acid, and butyric acid) were vaporized by heating in a closed chamber. Plates of photocatalyst coated with titanium dioxide were placed into the chamber and irradiated by light source. Vaporized cyclophosphamide in the chamber was recovered by bubbling the internal air through acetone and derivatized by trifluoroacetic anhydride for analysis by gas chromatographic-mass spectrometric assay. Vaporized odors were determined using a gas-detector tube, which changed color depending on the concentration. Following activation of the photocatalyst by a light source, the residual amounts of anticancer drug and unpleasant odor components were significantly decreased compared with when the photocatalyst was not activated without a light source. These results indicate that the photocatalysts can accelerate the degradation of vaporized anticancer drugs and odor components. Air-cleaning equipment using a photocatalyst is expected to be useful in improving the QOL of cancer patients experiencing carcinomatous unpleasant odor, and in reducing occupational exposure of health care workers to anticancer drugs.

Involvement of apoptosis in patients with diabetic nephropathy: A study on plasma soluble Fas levels and pathological findings.

AIMS: We investigated the relationship between levels of plasma soluble Fas (sFas) and stages of diabetic nephropathy, with special reference to apoptosis and clinical features of diabetic nephropathy in 168 patients with diabetic nephropathy. RESULTS: There was a positive correlation between plasma sFas and creatinine levels, between sFas levels and urinary protein levels, and between sFas levels and urinary albumin. There was a negative correlation between plasma sFas levels and creatinine clearance. Plasma sFas levels in the early stage (stages 1, 2, 3A) and advanced stage (stages 3B and 4) were 2.6 +/- 0.1 and 5.4 +/- 0.5 ng/mL, respectively. Plasma sFas level of the advanced stage was significantly higher than that of the early stage. The number of proliferating cell nuclear antigen (PCNA) positive cells was significantly lower in the advanced stage than in the early stage. The number of in situ nick-end labelling (TUNEL) positive cells was also significantly lower in the advanced stage than in the early stage, suggesting the suppression of apoptosis. CONCLUSION: These data suggest that apoptosis is involved in the advancement of diabetic nephropathy, and that plasma sFas level might be a predicting factor for prognosis.

Characterization of orally active nonpeptide vasopressin V(2) receptor agonist. Synthesis and biological evaluation of both the (5R)- and (5S)-enantioisomers of 2-[1-(2-Chloro-4-pyrrolidin-1-yl-benzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepin- 5-yl]-N-isopropylacetamide.

The synthesis and evaluation of both the (R)- and (S)-enantioisomers about the 5-position on a tetrahydro-1H-1-benzazepine derivative were described. The absolute configuration of the (R,R)-isomer (10) was determined by X-ray crystallographic analysis. After evaluation of both enantiomers (compounds R-2, S-2) for binding affinity, cAMP accumulation, and an in vivo study using Brattleboro rats, R-2 showed more potent activity as a V(2) receptor agonist than S-2.