Arginine: A potential prophylactic supplement for transthyretin amyloidosis.

Transthyretin (TTR) is an amyloidogenic protein associated with TTR amyloidosis (ATTR). Dissociation of TTR tetramers into TTR monomers causes TTR misfolding, resulting in amyloid fibril formation and triggering the onset of ATTR. Low-molecular-weight tetrameric TTR stabilizers are potential therapeutic agents to delay ATTR progression. However, the currently available drugs are expensive and cannot be used for prophylaxis. Therefore, in this study, we aimed to identify a prophylactic supplement that suppresses TTR amyloid formation. We investigated whether arginine, an amyloidogenic protein aggregation inhibitor, stabilizes tetrameric TTR, thereby preventing amyloid fibril formation. Immunoblotting showed that arginine mixed with wild-type TTR (TTRwt), amyloidogenic TTR Val30Met (ATTR V30M), and human serum samples reduced the amount of monomeric TTR but increased the tetramer/monomer ratio of TTR compared to those in the samples without arginine. Additionally, oral administration of arginine (5000 mg for 5 days) to healthy volunteers effectively increased the tetramer/monomer ratio of TTR in the serum. Thioflavin T test, a quantitative analysis method for amyloid fibril formation, showed that amyloid fibril formation was significantly suppressed with arginine compared to that without arginine. As arginine is a common supplement and non-toxic amino acid, it can be used as a promising prophylactic supplement to suppress amyloid fibril formation in ATTR.

Guideline-based Treatment of Glucocorticoid-induced Osteoporosis in Patients with Rheumatoid Arthritis: A Retrospective Study with the AORA Registry.

Glucocorticoid-induced osteoporosis (GIOP) is one of the side effects associated with glucocorticoid (GC) therapy. In 2014, the Japanese Society for Bone and Mineral Research (JSBMR) provided new guidelines for the management and treatment of GIOP. The aim of the present study was to clarify the prevalence of patients with rheumatoid arthritis (RA) requiring treatment according to the new guidelines and to identify risk factors associated with lack of treatment in these patients. Patients in the 2018 Akita Orthopedic group on Rheumatoid Arthritis (AORA) database were enrolled. Of 2,234 patients with RA in the database, 683 (30.6%) met the 2014 JSBMR guideline treatment criteria, and 480 (70.3%) had been treated. The untreated group included a larger number of males, younger patients, and patients treated in clinics rather than hospital (p<0.001, p=0.015, and p<0.001, respectively). Multivariate analyses found that male sex, younger age, and clinic-based RA care were significant risk factors associated with lack of treatment (p<0.001, p=0.013, and p<0.001, respectively). Thus, male sex, younger age, and clinic-based care were identified as risk factors.

Pre-hospital Diagnosis of Large Vessel Occlusion in Patients Being Transported by Helicopter.

BACKGROUND: During the helicopter transportation of patients suspected of large vessel occlusion (LVO), an accurate and rapid decision-making process is required. AIMS: We attempted to create an algorithm for the pre-hospital diagnosis of the presence of LVO in patients suspected of stroke using data from patients transported urgently by helicopter. METHODS: One hundred and sixty-five patients transported by helicopter were divided into two subgroups: a training dataset and a validation dataset. We extracted clinical information obtained on site, the unadjusted score of the National Institutes of Health Stroke Scale, and previously reported pre-hospital scales as an LVO screen. On the basis of the analyses of these factors, an algorithm was devised to predict the presence of LVO and its predictive accuracy was evaluated using the validation dataset. RESULTS: Ischemic stroke with LVO was diagnosed in 36 out of 121 cases (29.8%) in the training dataset and in 10 out of 44 cases (22.7%) in the validation dataset. Combining five factors (conjugate deviation, upper limb paresis, atrial fibrillation, Japan Coma Scale ≥ 200, and systolic blood pressure ≥ 180), an algorithm was created to classify cases into six groups with different likelihoods of LVO presence. The algorithm predicted correctly 6 out of 10 cases in the validation dataset. Furthermore, it definitively ruled out 17 out of 34 cases in the validation dataset. CONCLUSIONS: Using the newly created algorithm, emergency staff could easily and accurately distinguish patients suitable for urgent endovascular thrombectomy from patients with non-LVO or stroke mimics.

Quantitative measurements of hip abduction strength in lumbar surgery patients.

BACKGROUND: We sought to evaluate the hip abduction strength in patients before and after lumbar surgery. MATERIALS AND METHODS: Eighty-four patients (51 males and 33 females) undergoing surgery for lumbar disc herniation or lumbar canal stenosis were selected. Mean age was 64.7 ± 13.8 years. Seven patients (8.3%) had surgery at multiple levels, including L2-L3 (group A), 27 (32.1%) patients had surgery at multiple levels including L3-L4 (group B), 32 (38.1%) patients had surgery at the L4-L5 level only (group C), and 18 (21.4%) patients had surgery at the L5-S1 level only (group D). Hip abduction strength was measured in the 84 patients preoperatively and in 49 patients postoperatively. RESULTS: In all patients, preoperative mean hip abduction strength on the symptomatic side and the asymptomatic side was 71.4 ± 34.5 N and 90.7 ± 36.5 N, respectively (p = 0.0008). In groups A and B, there were no significant differences between the mean hip abduction strength on the symptomatic and contralateral side. In group C, those on the symptomatic and contralateral side were 68.0 ± 33.5 N and 89.3 ± 34.8 N, respectively (p = 0.0181). In group D, those on the symptomatic and contralateral side were 74.3 ± 42.4 N and 101.7 ± 44.7 N, respectively (p = 0.0314). In the 49 patients of all groups that could be measured postoperatively, there were no significant differences between the mean hip abduction strength on both sides. CONCLUSIONS: It was confirmed that the gluteus medius, which was main hip abductor, was mainly innervated by L5 and its mean strength significantly improved postoperatively. The possibility of improvement of hip abduction strength, especially with unchanged tibialis anterior strength, could be very useful for operative decisions.

Comparison of the efficacy of denosumab and bisphosphonates for treating secondary osteoporosis in patients with rheumatoid arthritis.

OBJECTIVES: This study aimed to investigate the efficacy of denosumab (compared with that of bisphosphonates) for preventing secondary osteoporosis and inflammation caused by excessive bone resorption in Japanese rheumatoid arthritis (RA) patients never previously treated for osteoporosis. METHODS: Ninety-eight patients with coexisting RA and osteoporosis were enrolled. The patients were subdivided by whether they were treated with denosumab (n = 49) or traditional bisphosphonates (n = 49). RA disease activity, bone turnover markers, and bone mineral density (BMD) were compared between the two groups before treatment, and after 6 and 12 months of treatment. RESULTS: There was no significant difference between the groups in any of the disease activity indices and BMD at any of the measured time points. With regard to bone metabolism, denosumab significantly reduced bone-specific alkaline phosphatase at 6 and 12 months compared with pretreatment, but had no effect on tartrate-resistant acid phosphatase 5b levels, suggesting an effect on the bone formation rate, but not on the bone resorption rate. CONCLUSIONS: Neither denosumab nor bisphosphonates could suppress inflammation or RA disease activity, but denosumab significantly suppressed a marker of bone metabolism in Japanese RA patients never previously treated for osteoporosis.

Prevalence of and factors associated with lumbar spondylolisthesis in patients with rheumatoid arthritis.

OBJECTIVES: To investigate the prevalence of and elucidate risk factors for lumbar spondylolisthesis in patients with rheumatoid arthritis (RA). METHODS: From 1843 patients registered to the Akita Orthopedic Group on Rheumatoid Arthritis registry, participants comprised 128 patients who had undergone comprehensive radiographic examinations. The presence of lumbar spondylolisthesis (≥5% slip percentage) was assessed from L1 to L5 on lateral plain radiographs. At the time of radiographic evaluation, we also determined the following: RA disease duration; stage and class of Steinbrocker's classification; serum levels of C-reactive protein (CRP) and matrix metalloproteinase-3; disease activity for RA; history of joint surgery; the presence of cervical spinal instability; and details and doses of medications for RA. RESULTS: Forty-seven (36.7%) patients showed lumbar spondylolisthesis (L4, 48%; L3, 29%; L2, 13%; L5, 10%). Among these, Meyerding Grade was I in 89% and II in 11%. Multivariate analysis showed lumbar spondylolisthesis as significantly and independently associated with higher serum CRP level (odds ratio (OR), 1.50; 95% confidence interval (CI), 1.00-2.25; p = 0.048) and history of joint surgery (OR, 2.87; 95%CI, 1.22-6.72; p = 0.015). CONCLUSIONS: More than one-third of patients with RA in this cohort had lumbar spondylolisthesis, and significant associations with higher serum CRP levels and history of joint surgery were identified.

A case of adult-onset Still's disease complicated by thrombotic thrombocytopenic purpura with retinal microangiopathy and rapidly fatal cerebral edema.

We present a patient who had adult-onset Still's disease (AOSD) complicated by thrombotic thrombocytopenic purpura (TTP) that resulted in retinal microangiopathy and rapidly fatal cerebral edema. The patient was a 37-year-old male who developed fever, eruption, arthritis and hepatic dysfunction, that, based on close examination, was diagnosed as AOSD. Despite treatment with corticosteroids, the patient developed acute visual field defect, neurological deterioration including convulsions and impaired consciousness, as well as acute renal failure that ultimately resulted in death. Pathological examination of autopsy specimens revealed multiple fibrin thrombi disseminated in small vessels of the brain and kidney, which was consistent with TTP, along with marked cerebral edema. Although TTP has rarely been reported in association with AOSD, awareness of the possible coexistence of these two diseases is important for diagnosis and treatment.

Risk Factors for Glenohumeral Internal Rotation Deficit in Adolescent Athletes: A Comparison of Overhead Sports and Non-overhead Sports.

Background A glenohumeral internal rotation deficit (GIRD) occurs in baseball players due to the repetitive pitching motion. However, few reports have addressed associations between GIRD and sports other than baseball. In this study, we investigated whether GIRD occurs in adolescent athletes playing overhead sports other than baseball, and also, the risk factors that cause GIRD in these sports were examined. Methods A total of 214 junior high school athletes who had undergone medical checks were evaluated. Seventy-five athletes playing sports requiring overhead motions were classified into the overhead sports group (39 tennis, 18 handball, 12 badminton, and 6 softball players). Eighty athletes participating in sports requiring the use of the upper limbs but not requiring frequent overhead motions were classified into the non-overhead sports group (31 kendo, 20 fencing, 19 basketball, and 10 table tennis players); 59 athletes who mainly did not use an upper limb were classified into the contact sports group (22 judo, 15 wrestling, 13 soccer, and 9 rugby football players). The range of shoulder motion (internal rotation, external rotation, and total arc), background factors, general laxity, and flexibility of the lower body were compared among the three groups. Results Thirty-four (16%) of 214 players were classified as having GIRD (internal rotation deficit >15°). Significantly more athletes had GIRD in the overhead sports group than in the other groups (p=0.007). The internal rotation deficit was significantly worse in the overhead sports group than in the other groups (p=0.006, p=0.02, respectively). Background factors, general laxity, and lower body flexibility did not differ significantly among the groups. Conclusion The sole risk factor for GIRD was participating in any sport that required overhead movements. Thus, not only baseball players, but also other athletes who participate in sports requiring overhead movements should receive correct information to prevent GIRD.

Questionnaire survey on pharmacists' roles among non- and health care professionals in medium-sized cities in Japan.

Although the scope of pharmacists' work has expanded in Japan, people's perception of this is unclear. To contribute to medical care together with non- and health care professionals, clarifying the perceptions of these groups is important to best utilize pharmacist professionals. We conducted a cross-sectional questionnaire survey among non-health care professionals (n = 487) and nurses (n = 151), medical doctors (n = 133), and pharmacists (n = 204) regarding the work of pharmacists. The questionnaire comprised 56 items in four categories associated with the roles of pharmacists. For each questionnaire item, we performed logistic regression analysis to compare pharmacists' opinions with those of other professionals and non-health care professionals. Opinions were similar between pharmacists and nurses or medical doctors regarding "collecting patient information" and "providing drug information to patients." However, there were differences in perceptions regarding "medical collaboration" (nurses; 8/23 items, physicians; 11/23 items) and "community medicine" (nurses; 9/15 items, physicians; 11/15 items), and pharmacists themselves perceived greater roles related to health care collaboration and community health care. Perceptions of non-health care professionals were poorer than those of pharmacists in all categories (47/56 items). These results suggest that pharmacists must actively communicate to help others understand their specialty and build trusting relationships to improve patient care.

Percutaneous Transluminal Angioplasty as Potentially Effective Treatment for Persistent Cognitive Decline due to Intracranial Carotid Artery Stenosis.

Objective: We describe a male patient with covert sustained cognitive impairment who underwent endovascular treatment for severe stenosis in the left intracranial internal carotid artery (ICA). Case Presentation: A 64-year-old man presented with transient dysarthria and dysphagia. Although he was alert, a cognitive evaluation revealed significant dysgraphia and a remarkable reduction in cognitive function. Diffusion-weighted imaging (DWI) revealed scattered high-intensity regions in the watershed area of the left cerebral hemisphere and severe stenosis in the C2 portion of the left ICA. Percutaneous transluminal angioplasty (PTA) was performed; a detailed examination revealed significantly improved cognitive function. One year later, the patient demonstrated further cognitive improvement, without any recurrent stroke. Conclusions: We consider that patients with severe intracranial stenosis, who have covert cognitive decline without apparent sustained symptoms, might be promising candidates for revascularization. Higher brain function in patients with severe intracranial arterial stenosis should be carefully screened because cognitive decline might not be evident at the time of initial presentation.

Stent Retriever-Assisted Continuous Aspiration for Distal Intracranial Vessel Embolectomy: The Distal Combined Technique.

OBJECTIVE: We investigated the efficacy of a combined approach with stent retriever-assisted aspiration catheter for distal intracranial vessel occlusion (distal combined technique [DCT]). METHODS: We evaluated consecutive patients with acute ischemic stroke with distal occlusion in anterior circulation, including occlusions of the M2/M3 or A2/A3 segments, who received endovascular therapy (EVT) in a single center. Modified Thrombolysis in Cerebral Infraction (mTICI) score including TICI 2C category, processing time from puncture to reperfusion, proportion of a favorable clinical outcome at discharge (modified Rankin Scale [mRS] score ≤2), and incidence of symptomatic intracranial hemorrhage (sICH) were compared between the DCT and single device approach technique (non-DCT) groups. RESULTS: Of 65 patients, 28 were treated with EVT using the DCT and 37 were treated with EVT with a single device approach (non-DCT). In the DCT group, a higher reperfusion rate at the first pass (mTICI score ≥2B, 92% vs. 54%; P = 0.0008; mTICI score ≥2C, 71% vs. 16%; P < 0.0001; mTICI score 3, 57% vs. 14%; P = 0.0004) and shorter time from puncture to successful reperfusion (median, 31 vs. 43 minutes; P = 0.0006) were achieved, respectively. The final successful reperfusion rate was also higher in the DCT group than in the non-DCT group (mTICI score ≥2C, 85% vs. 51%; P = 0.004; mTICI score 3, 75% vs. 43%; P = 0.012), respectively. sICH occurred in 2 patients in the non-DCT group. Patients with mRS score ≤2 at discharge were more prevalent in the DCT than in the non-DCT group (57% vs. 27%, respectively; P = 0.021). CONCLUSIONS: This retrospective analysis indicated that the DCT is a useful and safe strategy for patients with distal anterior intracranial vessel occlusion.

Histological evaluation of symptomatic ossification of the anterior longitudinal ligament treated with etidronate disodium: a case report.

BACKGROUND: Here we report the first autopsied case involving pathological examination after two resections of symptomatic ossification of the anterior longitudinal ligament with anterior osteophytes and etidronate treatment with more than 8 years of follow-up. CASE PRESENTATION: A 51-year-old Japanese man complained of severe dysphagia due to esophageal compression by ossification of his anterior longitudinal ligament with anterior cervical osteophytes. Although surgical removal of the anterior cervical osteophytes was performed following etidronate treatment (800 mg/day for 6 months), dysphagia occurred secondary to recurrent ossification of his anterior longitudinal ligament with anterior osteophytes 7 years after the initial resection. A second resection of the anterior cervical osteophytes was performed, and cyclic administration of etidronate disodium (1000 mg/day, 3-month administration and 3-month cessation) did not result in re-outgrowth of ossification of his anterior longitudinal ligament with anterior osteophytes. At 1 year and 6 months after the second surgery, he suddenly died. The pathological findings associated with the ossification of his anterior longitudinal ligament during etidronate therapy showed no recurrence of ossification of the anterior longitudinal ligament with anterior osteophytes. CONCLUSION: A recurrence of ossification of the anterior longitudinal ligament with anterior osteophytes formation, which caused dysphagia, was not observed with the cyclic administration of etidronate disodium at a dose of 1000 mg/day every 3 months for a period of 1 year and 5 months in the present case.

Comminuted distal humeral fracture treated using the Ilizarov technique in a patient with rheumatoid arthritis and osteoporosis.

The goal of treatment for distal humeral fractures in patients with rheumatoid arthritis (RA) is to obtain sufficient bone union and good elbow function. However, treating comminuted distal humeral fractures in patients with RA and osteoporosis is challenging. We present the case of a 58-year-old woman with RA and osteoporosis who suffered a comminuted distal humeral fracture and was successfully treated with the Ilizarov technique. The Ilizarov technique is minimally invasive compared with conventional open surgery, can obtain good stabilization, and allows earlier rehabilitation, even if the fractured bone is severely osteoporotic. The patient exhibited good elbow function and alignment at the final follow-up examination (18 postoperative months). To the best of our knowledge, the present case is the first in which a comminuted distal humeral fracture in a patient with RA and severe osteoporosis was successfully treated with an Ilizarov external fixator.

A comparative study between intravenous and oral alendronate administration for the treatment of osteoporosis.

It has recently been reported that bisphosphonates are the most common treatment for osteoporotic patients. However, they are many problems, including poor bioavailability and adherence, as well as adverse drug reactions. Therefore, intravenous administration of bisphosphonates has been developed to resolve these problems. In Japan today, alendronate and ibandronate have been approved for intravenous administration, and they have advantages, such as good adherence and better gastrointestinal tolerability, compared to oral administration. We attempted to confirm the effects of administration of intravenous alendronate, which is not inferior to oral administration, for osteoporotic patients in earlier research. 200 consecutive Japanese over 70 years-old postmenopausal women who visited the first author's orthopedic clinic and had femoral neck or lumbar spine bone mineral density (BMD) values more than 2.5 SD lower than the reference values were randomly enrolled in this study. 100 subjects were recruited for administration of intravenous alendronates because of their poor adherence, no respond of treatment status, and gastrointestinal adverse effects. Furthermore, 10 of these subjects were excluded due to discontinuation, and a total of 90 subjects were eligible for the intravenous group. The remaining 50 patients received oral alendronate. The present study also showed no significant difference between intravenous and oral administration with respect to BMD, biochemical bone turnover markers, and the incidence of fractures. These results show that intravenous administration of alendronate is not inferior to oral alendronate for the treatment of osteoporosis. Therefore, intravenous administration of alendronate can be recommended if patients do not tolerate or adhere to oral bisphosphonates.