L-glutamic acid-g-poly hydroxyethyl methacrylate nanoparticles: acute and sub-acute toxicity and biodistribution potential in mice

The aim of this safety study in mice was to determine in vivo toxicity and biodistribution potential of a single and multiple doses of L-glutamic acid-g-p(HEMA) polymeric nanoparticles as a drug delivery system. The single dose did not cause any lethal effect, and its acute oral LD₅₀ was >2.000 mg/kg body weight (bw). Multiple doses (25, 50, or 100 mg/kg bw) given over 28 days resulted in no significant differences in body and relative organ weights compared to control. These results are supported by biochemical and histological findings. Moreover, nanoparticle exposure did not result in statistically significant differences in micronucleus counts in bone marrow cells compared to control. Nanoparticle distribution was time-dependent, and they reached the organs and even bone marrow by hour 6, as established by ex vivo imaging with the IVIS^® spectrum imaging system. In conclusion, L-glutamic acid-g-p(HEMA) polymeric nanoparticles appear biocompatible and have a potential use as a drug delivery system.KEY WORDS: biocompatibility, blood biochemistry, genotoxicity, histology, in vivo toxicity, micronucleus test, polymers     

Comparing bone resorption after anatomical shoulder arthroplasty between various surgical procedures using a single-stem model

BackgroundIn shoulder arthroplasty, bone resorption around the stem can lead to stem loosening and makes surgery difficult at the time of revision. Proximal bone resorption after reverse shoulder arthroplasty can cause instability because of a decrease of deltoid wrapping effect. As factors of the stem itself, such as stem coating, shape, length, and use of bone cement, may also affect bone resorption, a single-stem model should be used to compare bone resorptions between different pathologies and surgical procedures. However, to date, a few reports have compared these differences in detail using a single-stem model. Therefore, we investigated the prevalence and location of humeral bone resorption in a single-stem model.MethodsThe study included 100 shoulders that underwent anatomical total shoulder arthroplasty (TSA) or humeral head replacement (HHR) with a single uncemented humeral stem from 2008 to 2018. The patients were 31 men and 69 women. The mean age at surgery was 72.9 years (range, 41-86 years). The patients were divided into three groups: especially, 25, 61, and 14 shoulders received TSA for primary osteoarthritis without rotator cuff tears (TSA group), HHR using an anatomical head with rotator cuff repair for cuff tear arthropathy (CTA) (HHR group), and HHR using a CTA head without rotator cuff repair (CTA group), respectively. Patients were monitored for a mean of 56 months (range, 12-98 months). The location of bone resorption was divided into seven zones as follows: zone 1, greater tuberosity; zone 2, lateral diaphysis; zone 3, lateral diaphysis beyond the deltoid tuberosity; zone 4, tip of the stem; zone 5, medial diaphysis beyond the deltoid tuberosity; zone 6, medial diaphysis; and zone 7, calcar region. The degree of bone resorption was classified from grade 0 to 4.ResultsBone resorption of grade 3 or higher was significantly more frequent at the greater tuberosity in the HHR and CTA groups (P < .001 and P < .001, respectively) than that in the TSA group. Grade 4 bone resorption was significantly more frequent in the CTA than that in the TSA and HHR groups in zone 1 (P = .016 and P = .041, respectively).ConclusionThe state of attachment of the rotator cuff to the greater tuberosity might affect bone resorption at the greater tuberosity, such as the greater tuberosity after shoulder arthroplasty. In cases of shoulder arthroplasty for arthropathy with rotator cuff tear, performing rotator cuff repair might prevent bone resorption.Level of evidenceLevel IV; Prognosis Study     

Sustainability and switching of biologics for psoriasis and psoriatic arthritis at Fukuoka University Psoriasis Registry

Biologics are efficacious for treating psoriasis vulgaris (PsV) and psoriatic arthritis (PsA), but sometimes must be terminated or changed for various reasons including ineffectiveness or adverse events. To find the optimal choice of biologics for treating psoriasis, we analyzed the real‐world data on drug survival and the reason for terminating or switching biologics. Medical records from patients with PsV or PsA, who visited the Department of Dermatology, Fukuoka University Hospital from 2010 to 2017, were analyzed. Two hundred and eleven patients received biologics, and 147 patients (69.7%) were treated with only one biologic, while 64 patients (30.3%) were switched to different products. Frequently used biologics in PsV were ustekinumab (UST), infliximab and adalimumab when calculated by patient‐year. Tumor necrosis factor inhibitor (TNFi) use decreased while UST and interleukin (IL)‐17 inhibitors increased in newly introduced patients. UST showed the highest survival rate as a first‐line drug, but the advantage was lost in the second reagent's group. The major reasons for terminating/switching biologics were as follows: primary ineffectiveness (26.4%), secondary loss of efficacy (36.5%), patient's preference, including referral to nearby hospital, or stopped visiting (22.6%), side‐effects (7.7%), comorbidities (3.4%) and economic burden (2.4%). In PsA patients, TNFi are more frequently employed than in PsV patients, although switching to UST or IL‐17 inhibitors showed an increasing trend. Biologic reagents were changed mostly because of primary or secondary loss of efficacy, which affected drug survival. Further research is needed to find the optimal choice of biologics with larger samples at multiple facilities.     

Time-Dependent Effects of Cryoablation for Renal Tumor on Overall and Split Renal Function

Purpose

To evaluate the influence of percutaneous cryoablation for renal cell carcinoma on function of the affected kidney.