Repeated piezoelectric lithotripsy for gallstones with and without ursodeoxycholic acid dissolution: A multicenter study

The use of bile acid dissolution therapy in extracorporeal shockwave lithotripsy of gallstones, remains controversial. Our study examined whether chemolitholysis after sufficient disintegration enhanced stone clearance within 6 months of the first lithotripsy. A total of 143 patients who developed one to three radiolucent stones measuring⪯30 mm in diameter were randomly separated into two treatment groups: 47% were given lithotripsy alone, and 53% lithotripsy plus ursodeoxycholic acid (UDCA). Repeated piezoelectric lithotripsy was given, with no limit on the total number of treatment sessions, to pulverize or disintegrate stones into fragments<3 mm. Stones were disintegrated in 97% of all patients, and the fragments were ⪯2 mm in 50% of these patients. According to an intention-to-treat analysis, 52% in the lithotripsy alone group and 58% in the UDCA group were free of stones 6 months after the first lithotripsy (P=0.61). Of the patients with fragments⪯2 mm, 71% in the former and 86% in the latter group were free of stones 6 months after the first lithotripsy, with no significant difference between the groups. Biliary pain occurred in 25% of all patients, including 3 with acute cholecystitis. We concluded that the sufficient disintegration of gallstones achieved with repeated lithotripsy enhanced the early clearance of fragments, regardless of whether chemolitholysis was employed.     

Cyclosporin-A increases synthesis of 1,25-dihydroxyvitamin D3 in the rat and mouse

We have previously observed elevated serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D] levels in male rats treated with oral cyclosporin-A (CsA). This elevation was independent of changes in PTH, ionized calcium, or phosphate. This paper investigates the potential sources and mechanisms for this increase in both rats and mice. Kidney homogenates from rats treated for 14 days with (15 mg/kg) had a significant increase in 25-hydroxyvitamin D (25OHD)-24-hydroxylase (24-hydroxylase) activity (149 +/- 20 vs. 89 +/- 16 fmol/mg.min; P less than 0.05), but nonsignificant increases in 25OHD-1 alpha-hydroxylase (1 alpha-hydroxylase) activity compared to controls. Kidney homogenates from C57b16J mice after the administration of 30-50 mg/kg CsA for 3 days revealed a linear dose-related increase in renal 1 alpha-hydroxylase (r = 0.96; P less than 0.05), which became significant with doses of 30 mg/kg CsA or more (P less than 0.05). To investigate the source of this 1,25-(OH)2D production, serum 1,25-(OH)2D was measured before and 48 h after bilateral nephrectomy in rats receiving CsA for 16 days. The percent decrease in serum 1,25-(OH)2D values was not significantly different in CsA-treated and untreated rats (33.9 +/- 4.9% vs. 47.5 +/- 4.9%), indicating little or no contribution from nonrenal sources. Studies of MCRs and production rates (PRs) revealed that the elevated 1,25-(OH)2D values were due to enhanced production and not altered clearance (PR, 12.4 +/- 1.2 vs. 19.1 +/- 1.9 fmol/mg.min; P less than 0.01). CsA increases 1 alpha-hydroxylase activity and produces significant elevations in serum 1,25-(OH)2D levels in both rats and mice. This increase may have an impact on bone mineral metabolism and immune modulation in postorgan transplantation patients.     

Autochthonous Dengue Fever,Tokyo, Japan, 2014

After 70 years with no confirmed autochthonous cases of dengue fever in Japan, 19 cases were reported during August–September 2014. Dengue virus serotype 1 was detected in 18 patients. Phylogenetic analysis of the envelope protein genome sequence from 3 patients revealed 100% identity with the strain from the first patient (2014) in Japan.     

Type 1 Autoimmune Pancreatitis Extending along the Main Pancreatic Duct: IgG4-related Pancreatic Periductitis

We herein report a unique form of autoimmune pancreatitis (AIP) spreading along the main pancreatic duct (MPD). A 70-year-old man was referred for a small lesion at the pancreatic neck, accompanying an adjacent cyst and dilated upstream MPD. Four years earlier, health checkup images had shown a pancreatic cyst but no mass lesion. Endoscopic ultrasonography showed a contrast-enhanced, tumorous lesion, mainly occupying the MPD. With a preoperative diagnosis of ductal neoplasms mainly spreading in the MPD, Whipple''s resection was performed. The resected specimens showed MPD periductitis with IgG4-related pathology, indicating type 1 AIP. Clinicians should practice caution concerning the various AIP forms.     

Efficacy and Safety of Ramucirumab in Patients with Unresectable Hepatocellular Carcinoma with Progression after Treatment with Lenvatinib

Objective A survival benefit was demonstrated for ramucirumab (RAM) in patients with unresectable hepatocellular carcinoma (uHCC) and α-fetoprotein (AFP) concentrations ≥400 ng/mL who had previously received sorafenib (SOR). However, it is unclear whether RAM has a similar efficacy in patients with uHCC that progresses after lenvatinib (LEN) treatment. This study aimed to evaluate the early anti-tumor response to RAM as a second-line treatment for advanced uHCC after LEN treatment. Methods We retrospectively assessed the efficacy and safety of RAM at 6 weeks after initiation. The therapeutic effects were evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. Patients We evaluated 7 patients with uHCC who received RAM as a second- or third-line treatment after LEN failure. Results The disease control rate (DCR) was 28.6% (2 of 7 patients). After the initiation of RAM, a rapid disease progression resulted in 1 patient death after 19 days. The median progression-free survival (PFS) was 41 days. There were no grade 3 or 4 treatment-related adverse events. At 6 weeks, there was no deterioration in the modified albumin-bilirubin (mALBI) grade. In patients with an imaging response of stable disease (SD), the rate of AFP production decreased from the baseline. Conclusion RAM may have a therapeutic potential for the suppression of uHCC progression in patients previously treated with LEN, as well as for maintaining the liver function during treatment. Evaluating the AFP trends may therefore be useful for predicting RAM effectiveness.     

Analysis of nocturnal desaturation waveforms using algorithms in patients with idiopathic pulmonary fibrosis

Purpose

Sleep-disordered breathing is recognized as a comorbidity in patients with idiopathic pulmonary fibrosis (IPF). Among them, nocturnal hypoxemia has been reported to be associated with poor prognosis and disease progression. We developed a diagnostic algorithm to classify nocturnal desaturation from percutaneous oxygen saturation (SpO₂) waveform patterns: sustained pattern, periodic pattern, and intermittent pattern. We then investigated the prevalence of nocturnal desaturation and the association between the waveform patterns of nocturnal desaturation and clinical findings of patients with IPF.

Methods

We prospectively enrolled patients with IPF from seven general hospitals between April 2017 and March 2020 and measured nocturnal SpO₂ and nasal airflow by using a home sleep apnea test. An algorithm was used to classify the types of nocturnal desaturation. We evaluated the association between sleep or clinical parameters and each waveform pattern of nocturnal desaturation.

Results

Among 60 patients (47 men) who met the eligibility criteria, there were 3 cases with the sustained pattern, 49 cases with the periodic pattern, and 41 cases with the intermittent pattern. Lowest SpO₂ during sleep and total sleep time spent with SpO₂?<?90% were associated with the sustained pattern, and apnea–hypopnea index was associated with the intermittent pattern.

Conclusion

We demonstrated the prevalence of each waveform and association between each waveform and sleep parameters in patients with IPF. This classification algorithm may be useful to predict the degree of hypoxemia or the complication of obstructive sleep apnea.

     

Effect of IgE-stimulated alveolar macrophages on tracheal epithelial bioelectric properties in dogs

To investigate a possible interaction between pulmonary alveolar macrophages (AMs) and airway epithelial cells in patients with allergic conditions, we studied the effect of AMs on bioelectric properties of canine tracheal epithelium under short-circuited conditions in vitro. Mucosal addition of the supernatants from AMs stimulated with monoclonal antidinitrophenyl (DNP) IgE antibody and DNP-human serum albumin (DNP-HSA) increased short-circuit current (Isc) of cultured epithelium in a dose-dependent manner. The maximal increase from the baseline value and the EC₅₀ were 10.2±2.0μA/cm² (mean ± SE, p<0.01) and 3×10⁵ AMs/ml, respectively. This effect was accompanied by the release of prostaglandin E₂ and F_2α from AMs. In contrast, AMs incubated with anti-DNP IgE antibody alone or DNP-HSA alone had no effect. The AM-induced increase in Isc was attenuated by diphenylamine-2-carboxylate and Cl-free medium but not by amiloride. Pretreatment of AMs with indomethacin or piroxicam inhibited the effect of AMs on epithelial Isc. These results suggest that AMs may stimulate Cl secretion across the airway mucosa through an IgE-dependent release of prostaglandins.     

CD13/aminopeptidase N in collagen vascular diseases

To determine the significance of CD13/aminopeptidase N in collagen vascular diseases (CVD), we examined its activity and expression in sera and disease sites of patients with CVD. Significantly higher aminopeptidase activity was detected in bronchoalveolar lavage fluid from patients with interstitial lung diseases due to rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM), systemic sclerosis (SSc), and Sjögren's syndrome than from control subjects. Increased aminopeptidase activity and increased expression of CD13/aminopeptidase N protein were found in alveolar macrophages from CVD patients with interstitial lung diseases. Significantly higher aminopeptidase activity was detected in pleural effusions from patients with systemic lupus erythematosus (SLE) than in transudate effusions. The mean aminopeptidase activity in synovial fluids from RA patients was significantly higher than from patients with osteoarthritis. The mean value of serum aminopeptidase activity was significantly higher in patients with SLE, RA, SSc, and PM/DM than in normal subjects. This study suggests that the activity of CD13/aminopeptidase N, locally produced in the disease site, is a useful marker for CVD and that CD13/aminopeptidase N may have an important role in the pathogenesis of CVD.