Tolvaptan reduces the required amount of albumin infusion in patients with decompensated cirrhosis with uncontrolled ascites : a multicenter retrospective propensity score-matched cohort study.

Background: The aim of this retrospective study was to determine whether tolvaptan treatment reduces the amount of albumin administered, volume of ascites removed, and frequency of paracentesis procedures in patients with decompensated cirrhosis with uncontrolled ascites with conventional diuretics. Patients and methods: The control (C) group included patients treated with conventional diuretics. The tolvaptan (T) group included patients treated with both tolvaptan and conventional diuretics. Both groups were matched according to baseline parameters. The amount of albumin administered, volume of ascites removed, and frequency of paracentesis within 30 days of onset of uncontrolled ascites were compared between the two groups. Results: After matching, 74 patients (C=37, T=37) were included. Baseline parameters (C vs. T group) were as follows: age, 69.5 ± 9.3 vs. 70.4 ± 11.0 years (p = 0.702) ; males, 24 (64.9%) vs. 25 (67.6%) (p = 0.999) ; patients with hepatocellular carcinoma, 17 (45.9%) vs. 18 (48.6%) (p = 0.999) ; serum albumin levels at treatment initiation, 2.76 ± 0.48 vs. 2.73 ± 0.49 g/dL (p = 0.773), and serum creatinine levels at treatment initiation, 1.18 ± 1.23 vs. 1.09 ± 0.48 g/dL (p = 0.679). In the C vs. T groups, respectively, mean amount of albumin administered was 51.0 ± 31.4 vs. 33.4 ± 29.8 g/month (p = 0.016) ; mean volume of ascites removed was 2,905 ± 4,921 vs. 1,824 ± 3,185 mL/month (p = 0.266) ; and mean frequency of paracentesis was 0.92 ± 1.46 vs. 0.89 ± 1.45 procedures (p = 0.937). Conclusions: Tolvaptan reduced the use of albumin infusion in patients with decompensated cirrhosis and was effective and acceptable for uncontrolled ascites.

A change in the timing for starting systemic therapies for hepatocellular carcinoma: the comparison of sorafenib and lenvatinib as the first-line treatment.

Aim: The aim of this retrospective multicenter study was to evaluate the differences in the timing for starting systemic therapies as the first-line treatment for hepatocellular carcinoma (HCC). Methods: A total of 375 patients with HCC treated with sorafenib from May 2009 to March 2018 and 56 patients treated with lenvatinib from March 2018 to November 2018 at our affiliated hospitals were included in this study. Results: The median ages of the sorafenib and lenvatinib groups were 71.0 (interquartile range [IQR]: 64.0-77.0) and 73.5 (IQR: 68.0 -80.0) years old, and 300 (80.0%) and 42 (75.0%) patients were men, respectively. The Barcelona Clinic Liver Cancer stage was early, intermediate and advanced in 39 patients (10.4%), 133 patients (35.5%) and 203 patients (54.1%) in the sorafenib group and 1 patient (1.8%), 17 patients (30.4%) and 38 patients (67.9%) in the lenvatinib group, respectively. In the analysis of intermediate HCC, patients who satisfied the criteria of TACE failure/refractoriness (P=0.017), those with ALBI grade 1 (P=0.040), and those with a serum AFP level < 200 ng/ml (P=0.027) were found more frequently in the lenvatinib group than in the sorafenib group, with statistical significance. The objective response rate (ORR) of lenvatinib was 34.8% in the overall patients and 46.7% in the intermediate-stage HCC patients, which was significantly higher than sorafenib (P=0.001, P=0.017). Conclusions: The emergence of lenvatinib has encouraged physicians to start systemic chemotherapy earlier in intermediatestage HCC patients.

[Pathophysiology of established urinary incontinence (UI) in the elderly and an ameliorative method for disuse syndrome including UI seen in the bed-ridden elderly--using prone position and its variations].

Multipathology is the physical characteristics of the elderly, and their established urinary incontinence (UI) is usually based on multiple causal diseases and types of UI. Decubitus voiding (urination and defecation) inevitably causes UI and fecal incontinence (FI). Difficulty in controlling UI and FI seen in bed-ridden elderly results in long-term use of diapers and indwelling catheters, which eventually leads to the progression of disuse syndrome and decline of ADL (activity of daily living). Most elderly UI cases have only a few major causal diseases. Arrangement of relationship between the diseases and the existing types of the UI; recognition of gender gap in urination; determination and execution of various kinds of treatment in a methodical way; and the maintenance of the proper medication dosage are the four keys to the effective and safe control of the UI. For bed-ridden elderly, passively provided suitable positions on urination and defeca-tion has become a prerequisite condition. These are not supine or Fowler (semi-reclining) positions, but normal sitting, or prone and its variation forward-tilting positions. The latter two positions, which ameliorate UI and FI in the bed-ridden elderly, have been found to improve all of the pathologies including the disuse syndrome as well. The Seikatsudai (Life rack), which provides a forward-tilting position, not only has such an effect, but also offers the possibility to make the bed-ridden elderly more independent in their lives.

Amino acids and peptides. XXV. Preparation of fibronectin-related peptide poly(ethylene glycol) hybrids and their inhibitory effect on experimental metastasis.

Hybrids of fibronectin-related peptides [Arg-Gly-Asp (RGD), Arg-Gly-Asp-Ser (RGDS)] and poly(ethylene glycol) (PEG) were prepared and their inhibitory effects on experimental metastasis in mice were examined. The inhibitory effect of RGD was markedly potentiated by hybrid formation with poly(ethylene glycol) #6000. As to inhibitory effect, RGD was more potent than RGDS and RGD PEG hybrids were superior to RGDS PEG hybrids. Hybrid formation with PEG #6000 was more effective than that with PEG #4000.

Amino acids and peptides. XXVI. Laminin-related peptide poly(ethylene glycol) hybrids and their inhibitory effect on experimental metastasis.

Laminin-related peptide poly(ethylene glycol) hybrid, Tyr-Ile-Gly-Ser-Arg-aminopoly(ethylene glycol) was prepared by the solution method and carboxylated poly(ethylene glycol)-Tyr-Ile-Gly-Ser-Arg was prepared by the solid phase method. Their inhibitory effects on experimental tumor metastasis were examined in mice. The inhibitory effect of Tyr-Ile-Gly-Ser-Arg was significantly potentiated by hybrid formation with poly(ethylene glycol) either at amino- or carboxyl terminals of the peptide. Of the hybrids, Tyr-Ile-Gly-Ser-Arg-amino(polyethylene glycol) #6000 hybrid exhibited about 10 times more potent anti-metastatic effect than the peptide itself. The inhibitory effect of a mixture of the carboxylated poly(ethylene glycol) hybrid and Arg-Gly-Asp-aminopoly(ethylene glycol) hybrid also exhibited an inhibitory effect.

Amino acids and peptides. XX. Preparation of beta-cyclododecyl aspartate and its application to synthesis of fibronectin- and laminin-related peptides.

beta-Cyclododecyl aspartate was prepared and its application to peptide synthesis was examined. Derivatives of beta-cyclododecyl aspartate are more likely to crystallize and should be useful for peptide synthesis. The cyclododecyl ester was much stable to bases than the benzyl ester and rather more stable than the cyclohexyl ester. It was removable by HF treatment and trifluoromethanesulfonic acid treatment. beta-Cyclododecyl aspartate was used for synthesis of laminin- and fibronectin-related peptides by solid phase and liquid phase methods.

Amino acids and peptides. XXI. Laminin-related peptide analogs including poly(ethylene glycol) hybrids and their inhibitory effect on experimental metastasis.

Laminin-related peptides, Tyr-Ile-Gly-Ser-Arg analogs, were prepared and their inhibitory effects on experimental metastasis were examined. Of the amino acids in the Tyr-Ile-Gly-Ser-Arg sequence, L-Arg was very important and Ile was not essential for the inhibitory effect. To obtain a potent inhibitor of metastasis, hybrids of Tyr-Ile-Gly-Ser-Arg-Gly and 2 types of poly(ethylene glycol) were prepared. The inhibitory effects of the hybrids were more potent than that of Tyr-Ile-Gly-Ser-Arg-Gly.

Preparation of [Arg-Gly-Asp]-[amino-poly(ethylene glycol)] hybrids and their inhibitory effect on experimental metastasis.

Hybrids of a fibronectin-related tripeptide (Arg-Gly-Asp) and amino-poly(ethylene glycol) were prepared and their inhibitory effect on experimental metastasis in mice was examined. The hybrids exhibited a potent inhibitory effect on the metastasis of B16 melanoma BL6.

Amino acids and peptides. XIV. Laminin related peptides and their inhibitory effect on experimental metastasis formation.

Inhibitory effects of synthetic laminin related peptides on experimental metastasis formation in mice were examined. Of the synthetic peptides, YIGSRG-[amino-poly(ethylene glycol)] hybrid exhibited the most potent inhibitory effect on the metastasis of B16 melanoma BL6.

[Ultrasonographic assessment of intravesical urine volume].

The assessment of intravesical urine volume is very important in the management of the patients with lower urinary tract obstruction or incontinence. As the non-invasive method for measuring residual urine volume, accuracy and usefulness of ultrasonographic measurement was evaluated in a total of 116 occasions in comparison with the conventional catheter technique. The values of the maximum transverse (W), cranio-caudal (H) and antero-posterior distance (D) of the inflated bladder were obtained by trans-abdominal scanning. These parameters were used for the ellipsoid formula (pi/6 x W x H x D). The ultrasonographic measurement of urine volume showed a high coefficiency against the conventional catheterized volume (r = 0.9543). Although a mean standard error was 56.3% of the actual volume, the amount of residual urine at the target of 50 ml and 100 ml could be accurately assessed by ultrasound with an accuracy of 90.5%. The method was also valid in follow-up study to monitor the changes of residual urine volume. The ultrasonographic assessment of intravesical urine volume is, thus, a non-invasive, useful tool in the management of the patients with voiding disturbance.

Effects of low dose L-triiodothyronine administration on mental, behavioural and thyroid states in elderly subjects.

Decreased serum T3 concentrations in elderly subjects and their possible relationship with the development of dementia have been indicated. To see the effects of a passive increase in the serum T3 concentration, low dose T3 administration was undertaken. Forty-four subjects from 65 to 93 years of age (average 81.0 +/- 7.8) were divided into 2 groups. The grade of dementia was determined by Hasegawa's dementia rating scale (DR score). In 22 subjects, 25 micrograms per day of T3 was administered for 4 W, while the control group was given a placebo. The DR score was measured before and immediately after the study. Changes in behaviour were monitored in a double-blind fashion. The administration of T3 induced a 0.65 nmol/l increase in serum T3 in 2 W and 0.36 nmol/l in 4 W. These T3 increases were not associated with significant changes in the DR score but 7 of 22 subjects showed apparent improvement in behaviour. TSH was suppressed to less than 1 mU/l in 2 W and then slightly increased by the 4th week, but T4, rT3 and fT4 all showed significant and progressive decreases. The DR score after T3 correlated significantly with the rT3/T4 ratio (before T3: -0.55, changes: +0.50) and also with changes in rT3 (r = 0.49). In conclusion, T3 administration to the elderly subjects was associated with behavioural improvement in some individuals, but the intellectual ability as assessed by the DR score in those with low T3 or elevated rT3 were hardly improved by passive T3 elevation.

Significance of serum thyrotropin and plasma dopamine concentration in the regulation of thyroid function in elderly subjects.

In our previous study, we observed a tendency towards an age-related increase in the serum thyrotropin (TSH) concentration. Regulatory mechanisms of TSH secretion in elderly subjects were studied. In 43 elderly subjects, serum TSH did not correlate significantly with serum T4, T3 free T4 or rT3. Further, those with increased TSH (greater than 5 mU/l, 9 subjects) did not overlap with those with low T3 (less than 0.92 nmol/1, 8 subjects). Increases in serum TSH were not associated with the presence of circulating anti-thyroid autoantibodies. A TRH test using a 500 micrograms single bolus injection was performed in 15 subjects. TSH response (basal: 1.92 +/- 1.42 (s.d.) mU/1, peak: 11.25 +/- 5.33 mU/1, sigma: 26.74 +/- 12.89 mU/1, respectively) did not differ significantly from that of younger subjects. T3 response after TRH varied greatly and a close correlation was observed between basal T3 and peak T3 (r = 0.86), and also between peak T3 and delta T3 (r = 0.81). A significant correlation was observed between sigma TSH and basal T3 (r = 0.60). Neither plasma cortisol, epinephrine nor norepinephrine concentrations showed any significant correlation with basal and TRH-stimulated TSH or T3 concentrations. However, the plasma dopamine concentration correlated significantly with sigma TSH (r = 0.60) and basal T3 (r = 0.52), respectively. In conclusion, the increase in serum TSH observed in elderly subjects was felt to represent a physiological adaptation to maintain serum T3. Low T3 subjects appear to have a disturbance in this mechanism, with decreased TSH and T3 response to TRH stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)