Development of predictive equation and score for 5-year metabolic syndrome incidence in Japanese adults.

BACKGROUND: Predicting metabolic syndrome (MetS) is important for identifying high-risk cardiovascular disease individuals and providing preventive interventions. We aimed to develop and validate an equation and a simple MetS score according to the Japanese MetS criteria. METHODS: In total, 54,198 participants (age, 54.5±10.1 years; men, 46.0%), with baseline and 5-year follow-up data were randomly assigned to 'Derivation' and 'Validation' cohorts (ratio: 2:1). Multivariate logistic regression analysis was performed in derivation cohort and scores were assigned to factors corresponding to ß-coefficients. We evaluated predictive ability of the scores using area under the curve (AUC), then applied them to validation cohort to assess reproducibility. RESULTS: The primary model ranged 0-27 points had an AUC of 0.81 (sensitivity: 0.81, specificity: 0.81, cut-off score: 14), and consisted of age, sex, blood pressure (BP), body mass index (BMI), serum lipids, glucose measurements, tobacco smoking, and alcohol consumption. The simplified model (excluding blood tests) ranged 0-17 points with an AUC of 0.78 (sensitivity: 0.83, specificity: 0.77, cut-off score: 15) and included: age, sex, systolic BP, diastolic BP, BMI, tobacco smoking, and alcohol consumption. We classified individuals with a score <15 and ≥15 points as low- and high-risk MetS, respectively. Furthermore, the equation model generated an AUC of 0.85 (sensitivity: 0.86, specificity: 0.55). Analysis of the validation and derivation cohorts yielded similar results. CONCLUSION: We developed a primary score, an equation model, and a simple score. The simple score is convenient, well-validated with acceptable discrimination, and could be used for early detection of MetS in high-risk individuals.

Current status and future prospects of the Japanese orthopaedic association national registry (JOANR), Japan's first national registry of orthopaedic surgery.

The Japanese Orthopaedic Association National Registry (JOANR) is Japan's first national registry of orthopaedic surgery, which has been developed after having been selected for the Project for Developing a Database of Clinical Outcome approved by the Health Policy Bureau of the Ministry of Health, Labour and Welfare. Its architecture has two levels of registration, one being the basic items of surgical procedure, disease, information on surgeons, surgery-related information, and outcome, and the other being detailed items in the affiliated registries of partner medical associations. It has a number of features, including the facts that, because it handles medical data, which constitute special care-required personal information, data processing is conducted entirely in a cloud environment with the imposition of high-level data security measures; registration of the implant data required to assess implant performance has been automated via a bar code reader app; and the system structure enables flexible collaboration with the registries of partner associations. JOANR registration is a requirement for accreditation as a core institution or partner institution under the board certification system, and the total number of cases registered during the first year of operation (2020) was 899,421 registered by 2,247 institutions, providing real-world evidence concerning orthopaedic surgery.

Luseogliflozin and caloric intake restriction increase superoxide dismutase 2 expression, promote antioxidative effects, and attenuate aortic endothelial dysfunction in diet-induced obese mice.

AIMS/INTRODUCTION: The mechanisms underlying the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on aortic endothelial dysfunction in diet-induced obesity are not clearly understood. This study investigated whether SGLT2 inhibition by luseogliflozin improved free fatty acid (FFA)-induced endothelial dysfunction in high-fat diet (HFD)-induced obese mice. MATERIALS AND METHODS: Mice were fed a control diet or high-fat diet for 8 weeks, and then each diet with or without luseogliflozin was provided for an additional 8 weeks under free or paired feeding. Afterward, the thoracic aortas were removed and utilized for the experiments. RESULTS: Luseogliflozin treatment decreased body weight, fasting blood glucose, insulin, and total cholesterol in HFD-fed mice only under paired feeding but not under free feeding. Endothelial-dependent vasodilation under FFA exposure conditions was significantly lower in HFD-fed mice than in control diet-fed mice, and luseogliflozin treatment ameliorated FFA-induced endothelial dysfunction. Reactive oxygen species (ROS) production induced by FFA was significantly increased in HFD-induced obese mice. Luseogliflozin treatment increased the expression of superoxide dismutase 2 (SOD2), an antioxidative molecule, and reduced FFA-induced ROS production in the thoracic aorta. Superoxide dismutase reversed FFA-induced endothelial dysfunction in HFD-fed mice. CONCLUSIONS: It was shown that caloric restriction is important for the effect of luseogliflozin on metabolic parameters and endothelial dysfunction. Furthermore, SGLT2 inhibition by luseogliflozin possibly ameliorates FFA-induced endothelial dysfunction by increasing SOD2 expression and decreasing reactive oxygen species production in the thoracic aorta.

Delayed postoperative hyponatremia in patients with acromegaly: incidence and predictive factors.

PURPOSE: Delayed postoperative hyponatremia (DPH) is a unique complication of transsphenoidal surgery (TSS) in pituitary tumors. Growth hormone (GH) enhances renal sodium reabsorption; however, the association between postoperative GH reduction and DPH in acromegaly is unclear. This study was performed to clarify the incidence of and the predictive factors for DPH in patients with acromegaly who underwent TSS. METHODS: Ninety-four patients with active acromegaly were examined retrospectively. During the postoperative course, patients with serum sodium levels ≤ 134 mEq/L were classified into the DPH group. We compared basic clinical characteristics, tumor characteristics, and preoperative and postoperative examination findings between the DPH and non-DPH groups. RESULTS: DPH occurred in 39 patients (41.5%), and the lowest serum sodium levels were generally observed during postoperative days (PODs) 7-9. They needed a 3-day longer hospital stay than those without DPH. The DPH group had lower preoperative body weight and body mass index. In addition, a transient increase in body weight during PODs 5-7 occurred with a transient decrease in urinary volume in the DPH group. Preoperative and postoperative GH and insulin-like growth factor-1 levels did not differ between the two groups. CONCLUSION: The findings suggested that lower preoperative weight and a postoperative transient gain in body weight are associated with an increased risk of DPH in acromegaly patients undergoing transsphenoidal surgery.

Dietary obesity and glycemic excursions cause a parallel increase in STEAP4 and pro-inflammatory gene expression in murine PBMCs.

Background: The balance between pro-atherogenic and anti-atherogenic factors is very crucial in the development of atherosclerotic lesions. Although the expression of the six-transmembrane epithelial antigen of the prostate 4 (STEAP4) in myeloid cells is known to be atheroprotective, there is not a single study reporting on the status of STEAP4 expression in circulating monocytes in the early stages of diet-induced obesity or in events of glycemic excursions. Methods: We induced glycemic spikes twice daily for a 1-week duration to rats fed on regular chow and western diet, and analyzed gene expression changes in the peripheral blood mononuclear cells (PBMCs). We also conducted experiments on RAW 264.7 cells to gain insight into some of our in vivo findings. Results: Diet-induced obesity and glycemic excursions independently caused a significant increase in STEAP4 mRNA expression in PBMCs. This was also accompanied by an induction of a substantial number of pro-inflammatory cytokines, chemokines, and chemokine receptors. However, the combined effect of western diet and hyperglycemic spikes was subtle and non-additive. In the in vitro setting, either glucose spikes, persistent hyperglycemia, or a combination of palmitic acid and insulin resulted in a parallel increase in expression of STEAP4 and pro-inflammatory genes. This was, however, significantly abrogated with 4-octyl itaconate or attenuated by inhibitors of p38MAPK and NF-kB. Conclusions: STEAP4 expression in mononuclear cells is induced by increasing inflammation or oxidative stress. The observed increase in STEAP4 expression in circulating monocytes due to visceral obesity or glycemic excursions is a compensatory response. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-021-00542-1.

Correction to: Dietary obesity and glycemic excursions cause a parallel increase in STEAP4 and pro-inflammatory gene expression in murine PBMCs.

[This corrects the article DOI: 10.1007/s13340-021-00542-1.].

Repeated glucose spikes and insulin resistance synergistically deteriorate endothelial function and bardoxolone methyl ameliorates endothelial dysfunction.

BACKGROUND: Both insulin resistance and postprandial glucose spikes are known for their potential to induce vascular endothelial dysfunction in individuals with metabolic syndrome. However, these factors are inextricable, and therefore, their relative contributions to inducing endothelial dysfunction remain elusive. In this study, we aimed to disentangle the effects of these factors and clarify whether bardoxolone methyl (CDDO-Me), a novel nuclear factor erythroid 2-related factor 2 (Nrf2) activator, protects against glucose spike-induced endothelial dysfunction. METHODS: We induced glucose spikes twice daily for a duration of 1 week to rats fed a standard/control diet (CD) and Western-type diet (WTD). Endothelium-dependent relaxation (EDR) was evaluated using isolated thoracic aortas. Gene expression and dihydroethidium (DHE)-fluorescence studies were carried out; the effect of CDDO-Me on aortic endothelial dysfunction in vivo was also evaluated. RESULTS: Neither WTD-induced insulin resistance nor pure glucose spikes significantly deteriorated EDR. However, under high-glucose (20 mM) conditions, the EDR of thoracic aortas of WTD-fed rats subjected to glucose spikes was significantly impaired. In this group of rats, we observed significantly enhanced DHE fluorescence as a marker of reactive oxygen species, upregulation of an oxidative stress-related gene (NOX2), and downregulation of an antioxidant gene (SOD2) in the thoracic aortas. As expected, treatment of the thoracic aorta of this group of rats with antioxidant agents significantly improved EDR. We also noted that pretreatment of aortas from the same group with CDDO-Me attenuated endothelial dysfunction, accompanied by a correction of the redox imbalance, as observed in gene expression and DHE fluorescence studies. CONCLUSIONS: For the first time, we showed that insulin resistance and glucose spikes exert a synergistic effect on aortic endothelial dysfunction. Furthermore, our study reveals that CDDO-Me ameliorates endothelial dysfunction caused by glucose spikes in a rat model of metabolic syndrome.

Nerve Block for Pain Relief During Arthroscopic Rotator Cuff Repair.

BACKGROUND: Although arthroscopic rotator cuff repair (ARCR) often results in good outcomes, some patients have severe pain postoperatively. This study investigated the efficacy of nerve block for ARCR. METHODS: This study was retrospective, and consent was obtained from all patients. We divided 50 patients who had undergone ARCR into 4 groups: continuous interscalene nerve block was performed for 11 patients (continuous-injection group), single interscalene nerve block for 10 (single-injection group), suprascapular nerve block for 8 (suprascapular group), and intravenous analgesic administration for 10 (intravenous group). Eleven patients received no nerve block (control group). We evaluated diclofenac sodium and pentazocine dosing, visual analog scale (VAS) scores, and perioperative complications in each group. VAS scoring was done immediately after surgery and 1 and 6 hours and 1, 2, 3, 7, and 14 days postoperatively. RESULTS: The doses of diclofenac sodium and pentazocine did not differ between groups. VAS scores immediately after surgery and at 1 and 6 hours after surgery were significantly lower in the single-injection and continuous-injection groups than in the suprascapular, intravenous, and control groups. VAS score at 1 day postoperatively was significantly lower in the continuous-injection group than in the other groups. One patient in the continuous group reported temporary paralysis of the fingers and drug solution leakage. CONCLUSION: Interscalene nerve blocks yielded good pain relief for ARCR. Although continuous interscalene nerve block produced continuous pain relief, complications are a concern.

Association between changes in the mRNA expression of platelet-activating factor receptor in peripheral blood mononuclear cells and progression of diabetic nephropathy.

INTRODUCTION: Several studies have recently pointed out the role of many inflammatory mediators in the progression of diabetes complications. We had previously demonstrated that mRNA expression of platelet-activating factor receptor (PAFR) in peripheral blood mononuclear cells (PBMCs) was associated with urinary albumin to creatinine ratio (ACR) and forearm flow-mediated dilatation in patients with type 2 diabetes. In an attempt to elucidate this association, patients were followed up for 1 year. MATERIALS AND METHODS: We recruited 95 patients from the hospital outpatient clinic, among whom 86 were followed up for 1 year (normoalbuminuria: 40 patients, microalbuminuria: 25 patients, macroalbuminuria: 21 patients). We then measured their baseline and 12 month characteristics and collected blood samples to extract PBMCs and measure gene expressions. RESULTS: Despite higher mRNA expression of PAFR in PBMCs among patients with macroalbuminuria, the rise in its value was not associated with biomarkers of nephropathy, while baseline values were not associated with progression of nephropathy. Moreover, changes in mRNA expression of PAFR were correlated with changes in ACR in all patients (r = 0.225, p = 0.037) and estimated glomerular filtration rate in patients with macroalbuminuria (r = - 0.438, p = 0.047) during the follow-up period. CONCLUSION: Our findings indicate that even though no causal relationship exists between diabetic nephropathy and elevated expression of PAFR in PBMCs, their close association signifies the presence of another common mechanism that could induce both events. Given these findings, the PAF/PAFR interaction could clarify corresponding mechanisms involved in diabetic complications.

Morphological evaluation of the scapula by three-dimensional computed tomography to elucidate shoulder joint function.

INTRODUCTION: There are many variations of scapula morphology. Evaluation of scapula morphology is necessary to elucidate shoulder joint movement. We aimed to analyze the bone morphology of various parts constituting the scapula to identify certain conserved features among them. MATERIALS AND METHODS: Thirty-one healthy individuals were the subjects. We created a scapular three-dimensional (3D) model using computed tomography (CT). X and Y axes were set on a glenoid surface. We measured the approximate plane of the upper and lower scapular bodies and scapular spine and the central axis of the coracoid and acromion. The anatomical position of the scapular spine, upper and lower bodies, coracoid, and acromion was measured. The positional relationship between the upper and lower bodies and scapular spine and the coracoid and acromion was evaluated. The average angle of the upper and lower scapular bodies and the scapular spine with respect to the XZ plane was calculated. The average angle of the coracoid and acromion with the X-axis on the XY plane and Z-axis on the YZ plane was calculated. RESULTS: On the XY plane, approximate planes of the upper and lower part of the body and the scapular spine were significantly correlated to each inclination. On the XY plane, inclinations of the central axes of the coracoid and acromion were significantly correlated. CONCLUSIONS: The findings revealed for the first time the correlation between the inclinations of the scapular body and scapular spine and the inclination angle between the coracoid and acromion.

Benefits of bone graft augmentation to arthroscopic Bankart repair for recurrent anterior shoulder instability with glenoid bone loss.

PURPOSE: Glenoid bone loss contributes to recurrent instability after arthroscopic Bankart repair alone. With significant glenoid bone loss, better results have been reported after arthroscopic Bankart repair with glenoid arc reconstruction. However, no reports compare augmentation using bone graft with non-augmentation for glenoid bone loss. The purpose of this study was to assess clinical results of an arthroscopic Bankart repair with or without arthroscopic bone graft augmentation. It was hypothesized that such bone graft augmentation would restore shoulder stability, and lead to excellent outcomes. METHODS: Of 552 patients treated for anterior glenohumeral instability with arthroscopic Bankart repair, 68 met this study's inclusion criteria of glenoid bone loss over 20% and follow-up of at least 2 years. Patients were divided into 2 groups based on whether with bone graft augmentation for glenoid bone loss [Group A: n = 35, median age; 21 years (range 13-72 years)], or not (Group B: n = 33, median age; 21 years (range 13-50 years)]. For grafting, either autologous iliac bone or artificial bone made of hydroxyapatite was used. Rowe score, recurrence rate, and return to sport were used to assess the results. RESULTS: Mean Rowe score was 95.0 (SD 10.6) in Group A and 69.7 (SD 27.2) in Group B (p < 0.05). The recurrence rate was 2.9% (1/36) in Group A and 48.5% (16/33) in Group B (p < 0.05). Regarding contact/collision athletes, 24 were contained in Group A and 22 in Group B. Of the patients with recurrence in Group B, 13 (59.1%) were contact/collision athletes. Finally, 50% of the contact/collision sports athletes for both groups returned to their sports at the same as pre-injury level. Of the 11 patients who returned to the same level of contact/collision sports in Group B, seven returned with residual instability. Nine athletes in Group A and 3 in Group B quit their sports for personal or social reasons. CONCLUSIONS: Bone graft augmentation was beneficial when used with Arthroscopic Bankart repair for recurrent anterior shoulder instability with glenoid bone loss. Especially, for recurrent anterior shoulder instability with glenoid bone loss in contact/collision sports athletes, bone graft augmentation should be strongly considered as beneficial. LEVEL OF EVIDENCE: Level IV.

Effects of glycemic control and hypoglycemia on Thrombus formation assessed using automated microchip flow chamber system: an exploratory observational study.

BACKGROUND: Thrombus formation is an important factor affecting cardiovascular events and venous thromboembolism in type 2 diabetes. However, it is unclear whether glycemic control reduces thrombogenicity. We investigated the effect of short-term glycemic control (STUDY 1) and hypoglycemia (STUDY 2) on thrombus formation using an automated microchip flow chamber system. METHODS: For STUDY 1, we recruited 10 patients with type 2 diabetes. Before and after 2 weeks of treatment, blood glucose was analyzed with a continuous glucose monitoring system, and thrombogenicity was analyzed with an automated microchip flow chamber system. For STUDY 2, we recruited 10 subjects without diabetes who underwent an insulin tolerance test. We evaluated the change in thrombogenic potential with hypoglycemia. RESULTS: STUDY1: The mean blood glucose level reduced from 10.1 ± 2.6 to 6.9 ± 0.97 mM (P < 0.01). T10, an indicator of thrombogenicity, significantly attenuated after glycemic control (338 ± 65 vs. 425 ± 117 s, P < 0.05). The attenuation in T10 was significantly correlated with changes in mean blood glucose level after treatment (r = - 0.718, P < 0.05). STUDY 2: Platelet function was enhanced with decreasing blood glucose; increased platelet function was strongly correlated with an increase in epinephrine. CONCLUSIONS: We demonstrated attenuation in thrombogenicity with short-term comprehensive diabetes care and enhancement in thrombogenicity with hypoglycemia, using a new flow chamber system. TRIAL REGISTRATION: UMIN-CTR UMIN 000019899, registered 26-Jan-2015 (STUDY 2).

Tarsal Navicular Stress Fracture in a Young Athlete: A Case Report.

Approximately 30% of tarsal navicular stress fractures are missed by physicians because plain radiographs often show no diagnostic clues. If early diagnosis and treatment are not obtained, such fractures will become refractory and the patient will no longer be able to actively participate as an athlete. We herein describe our experience treating a 14-year-old female track sprinter with persistent foot pain. Magnetic resonance imaging 6 months after the onset of pain showed a stress fracture of the tarsal navicular bone. Computed tomography showed the tarsal navicular stress fracture as well as sclerosis at the fracture edges. We diagnosed a refractory tarsal navicular stress fracture. Conservative management in the form of non-weight-bearing cast immobilization is the standard treatment for both partial and complete stress fractures of the tarsal navicular bone. However, surgical treatment is required in refractory cases. We treated the herein-described refractory case with 6 weeks of non-weight-bearing cast immobilization. We instructed the patient to perform quad muscle training at the same time as casting. Six weeks later, follow-up computed tomography showed callus formation and disappearance of the fracture line. The patient thus began full weight bearing with daily use of arch support equipment, and we allowed her to gradually return to sports. We gradually increased her activity intensity from jogging to running. She completely and successfully returned to sports after 3 months of treatment.

Factors influencing outcomes of nonsurgical treatment for baseball players with SLAP lesion.

BACKGROUND/OBJECTIVE: Superior labrum anterior posterior (SLAP) lesion of the shoulder joint occurs in throwing athletes as a results of overuse, such as from repetitive baseball pitching. Nonsurgical treatments are usually the first-line therapy for symptomatic SLAP lesion. However, some patients cannot obtain satisfactory improvement of their symptoms, leading to dysfunction of the shoulder and diminished pitching performance. The purpose of this study was to analyze factors that influence outcomes of nonsurgical treatments for SLAP lesion. METHODS: Forty-five baseball players with SLAP lesion, whose mean age was 21.6 (range, 16-36) years and who underwent nonsurgical treatments, were the subjects of this study. SLAP lesion was diagnosed by shoulder arthrography and magnetic resonance imaging (MRI). Exclusion criteria included definite associated trauma such as dislocation, fracture or injuries related to sports activities. Playing positions included pitcher (21 patients), catcher (3 patients), infielder (13 patients) and outfielder (8 patients). Mean symptomatic duration from the onset of shoulder pain to the beginning of nonsurgical treatments was 8.5 (range, 1-72) months. Nonsurgical treatments included physical therapy, such as range of motion, stretching, and rotator cuff exercises, as well as prescription of nonsteroidal anti-inflammatory drugs if necessary. To identify factors that influenced outcomes of nonsurgical treatments for SLAP lesion, various factors of 13 nonresponsive patients were compared with those of 32 patients who responded to nonsurgical treatment. The factors were as follows: patient background, such as age or playing position; range of shoulder motion; shoulder joint laxity; and findings of radiographs and MRI. All data were statistically assessed using logistic analysis and Spearman's correlation coefficient. The significance level was set at P < 0.05, and odds ratios were determined. RESULTS: Factors identified as having significant difference between the 2 groups were age, duration of baseball experience, symptomatic period, playing position, range of internal and external rotation in the first medical examination, range of total rotation of 90° abduction 2 months after nonsurgical treatments, and presence of Bennett spur and partial-thickness tears of the articular-side rotator cuff. Factors with high odds ratios were symptomatic period, range of total rotation of 90° abduction 2 months after the treatment, age, and duration of baseball experience. CONCLUSION: Symptomatic period, duration of baseball experience, age, and findings of radiographs and MRI are inevitable factors that cannot be improved by nonsurgical treatment. On the other hand, restriction of shoulder motion due to posterior muscular tightness is a factor that can be improved by nonsurgical treatment. Early improvement of shoulder motion is important to obtain satisfactory outcomes of nonsurgical treatments for SLAP lesion.

Arthroscopic Coracoclavicular Ligament Reconstruction for Acromioclavicular Joint Dislocation.

BACKGROUND: The purpose of this study was to evaluate mid- and long-term clinical and radiologic outcomes of arthroscopic coracoclavicular ligament reconstruction (ACCLR) with an artificial ligament for acute dislocation of the acromioclavicular joint (ACJ). METHODS: Twelve male patients (average age at the time of surgery: 40.8 years, range: 21-64 years) underwent ACCLR with an artificial ligament for acute dislocation of the ACJ type III or type V according to the Rockwood classification. Arthroscopic surgery was performed with the patient under general anesthesia and interscalene brachial plexus block in the beach-chair position. Reduction of the ACJ was performed manually or using an elevator under control of an imaging intensifier. The ACJ was fixed temporarily with a Kirschner wire. Bone tunnels of the coracoid process and clavicle were made with a cannulated drill. An artificial ligament was pulled out through the bone tunnels and fixed on the upper surface of the clavicle with a staple and interference screw, and on the undersurface of the coracoid process with an Endobutton. The shoulder was immobilized with a shoulder brace for 4 weeks postoperatively, and rehabilitation was started in the first postoperative week. The Japan Shoulder Society Acromioclavicular Joint Function Assessment (JSS-ACJ) score was used for evaluation of clinical outcomes, and plain radiographs were performed after a minimum follow-up period of 5 years postoperatively. RESULTS: The average follow-up period after surgery was 106.3 months (range: 62-128 months). The average postoperative JSS-ACJ score was 97.2 points (range: 92-100). The seven patients who had been playing sports before injury all returned to their pre-injury level. No patients complained of pain or shoulder dysfunction in daily activities, work, or sports. There were no complications such as neurovascular injuries during surgery, infection, or foreign body reaction from the artificial ligament. Radiographs at the final follow-up showed subluxation of the ACJ and non-symptomatic osteoarthritic changes of the ACJ in two patients, respectively. CONCLUSION: ACCLR for acute dislocation of the ACJ is a useful surgical procedure that gives satisfactory clinical and radiologic outcomes on mid- and long-term follow-up. ACCLR can stabilize vertical instability of the ACJ. If instability in the horizontal direction remains, repair or reconstruction of the acromioclavicular ligament should be added to prevent osteoarthritic changes of the ACJ.

Characteristics of the patients with delaminated rotator cuff tear.

PURPOSE: The purpose of this study was to analyze factors relating to delamination in full-thickness rotator cuff tears. METHODS: 126 patients with full-thickness rotator cuff tears treated by arthroscopic rotator cuff repair were the subjects of this study. There were 52 females and 74 males whose average age was 64.2 years. Fifty-three patients had history of trauma. The average duration of disorder was 29.5 weeks. Nineteen patients were diagnosed with diabetes. On types of the tears, small tear was observed in 59 patients, medium tear in 47 patients, large tear in 6 patients, and massive tear in 14 patients. The average size of tear was 1.98 cm. Delamination of the torn cuff was observed in 45 patients. Factors compared between the patients without delamination and those with delamination were as follows: gender and age of the patients, history of trauma, duration of disorder, diabetes, smoking, size and number of rotator cuff tears. RESULTS: The delamination rate of the smoking patients was significantly higher than non-smoking patients. The delamination rate of patients with more than two tendon tears was significantly higher than those with only one tendon tear. The average size of tear with delamination was significantly larger than that of tear without delamination. The other factors were not related to delamination. CONCLUSIONS: This study suggests that smoking, size of tear and number of torn cuffs are associated with delamination. The progression of torn cuff, anatomical features and nicotine of smoking affect the causes of delaminated tear of rotator cuff.

Clinical outcomes and structural integrity of arthroscopic double-row versus suture-bridge repair for rotator cuff tears.

The purpose of this study was to compare clinical outcomes and retear rate between arthroscopic double row (DR) and suture bridge (SB) repair for rotator cuff tears. Postoperative Constant score and MRI findings were compared between 52 patients underwent DR repair and 63 patients underwent SB repair with medium tear of the supraspinatus. There was no significant difference in Constant score between the two groups. Postoperative MRI revealed that retear rate of SB group was significantly lower than DR group. This study suggests that SB repair can provide better clinical and structural outcomes compared with DR repair.

mRNA expression of platelet activating factor receptor (PAFR) in peripheral blood mononuclear cells is associated with albuminuria and vascular dysfunction in patients with type 2 diabetes.

AIMS: Renal dysfunction in addition to diabetes is a serious risk factor for cardiovascular events. We hypothesized that some of the changes in gene expression in blood cells cause renal dysfunction and macrovascular disease through impaired endothelial function. This study aimed to define which changes in gene expression in peripheral blood mononuclear cells (PBMCs) are related to renal function parameters and endothelial function of large arteries in patients with type 2 diabetes mellitus (T2DM). METHODS: We recruited 95 patients with T2DM. After matching for gender, age, BMI and HbA1c levels, the patient cohort included 42 with normoalbuminuria, 28 with microalbuminuria, and 25 with macroalbuminuria. All patients in the three groups were assessed for urinary albumin to creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), flow-mediated dilatation (FMD), and mRNA expression in PBMCs. RESULTS: The mRNA expression of platelet activating factor receptor (PAFR) differed most markedly between the three groups and was significantly higher in the macroalbuminuric group (p < 0.001 vs. normoalbuminuric group; p < 0.05 vs. microalbuminuric group). PAFR mRNA expression significantly correlated with log transformed ACR (ρ = 0.424, p < 0.001) but not eGFR. PAFR mRNA expression also had a significant negative correlation with FMD (ρ = -0.379, p < 0.001). Furthermore, the prevalence of macrovascular complications, particularly stroke, was significantly higher in patients with elevated PAFR mRNA expression in PBMCs. CONCLUSIONS: PAFR overexpression in PBMCs may link diabetic nephropathy to macroangiopathy through impairment of endothelial function in patients with T2DM.

Direct versus indirect actions of ghrelin on hypothalamic NPY neurons.

OBJECTIVES: Assess direct versus indirect action(s) of ghrelin on hypothalamic NPY neurons. MATERIALS AND METHODS: Electrophysiology was used to measure ion channel activity in NPY-GFP neurons in slice preparations. Ca2+ imaging was used to monitor ghrelin activation of isolated NPY GFP-labeled neurons. Immunohistochemistry was used to localize Trpm4, SUR1 and Kir6.2 in the hypothalamus. RESULTS: Acylated ghrelin depolarized the membrane potential (MP) of NPY-GFP neurons in brain slices. Depolarization resulted from a decreased input resistance (IR) in ~70% of neurons (15/22) or an increased IR in the remainder (7/22), consistent with the opening or closing of ion channels, respectively. Although tetrodotoxin (TTX) blockade of presynaptic action potentials reduced ghrelin-induced changes in MP and IR, ghrelin still significantly depolarized the MP and decreased IR in TTX-treated neurons, suggesting that ghrelin directly opens cation channel(s) in NPY neurons. In isolated NPY-GFP neurons, ghrelin produced a sustained rise of [Ca2+]c, with an EC50 ~110 pM. Pharmacologic studies confirmed that the direct action of ghrelin was through occupation of the growth hormone secretagogue receptor, GHS-R, and demonstrated the importance of the adenylate cyclase/cAMP/protein kinase A (PKA) and phospholipase C/inositol triphosphate (PLC/IP3) pathways as activators of 5' AMP-activated protein kinase (AMPK). Activation of isolated neurons was not affected by CNQX or TTX, but reducing [Na+]o suppressed activation, suggesting a role for Na+-permeable cation channels. SUR1 and two channel partners, Kir6.2 and Trpm4, were identified immunologically in NPY-GFP neurons in situ. The actions of SUR1 and Trpm4 modulators were informative: like ghrelin, diazoxide, a SUR1 agonist, elevated [Ca2+]c and glibenclamide, a SUR1 antagonist, partially suppressed ghrelin action, while 9-phenanthrol and flufenamic acid, selective Trpm4 antagonists, blocked ghrelin actions on isolated neurons. Ghrelin activation was unaffected by nifedipine and ω-conotoxin, inhibitors of L- and N-type Ca2+ channels, respectively, while Ni2+, mibefradil, and TTA-P2 completely or partially inhibited ghrelin action, implicating T-type Ca2+ channels. Activation was also sensitive to a spider toxin, SNX-482, at concentrations selective for R-type Ca2+ channels. Nanomolar concentrations of GABA markedly inhibited ghrelin-activation of isolated NPY-GFP neurons, consistent with chronic suppression of ghrelin action in vivo. CONCLUSIONS: NPY neurons express all the molecular machinery needed to respond directly to ghrelin. Consistent with recent studies, ghrelin stimulates presynaptic inputs that activate NPY-GFP neurons in situ. Ghrelin can also directly activate a depolarizing conductance. Results with isolated NPY-GFP neurons suggest the ghrelin-activated, depolarizing current is a Na+ conductance with the pharmacologic properties of SUR1/Trpm4 non-selective cation channels. In the isolated neuron model, the opening of SUR1/Trpm4 channels activates T- and SNX482-sensitive R-type voltage dependent Ca2+ channels, which could contribute to NPY neuronal activity in situ.

The Combination Therapy of Fenofibrate and Ezetimibe Improved Lipid Profile and Vascular Function Compared with Statins in Patients with Type 2 Diabetes.

AIM: Elevated level of serum triglyceride (TG) is a characteristic of type 2 diabetes. We evaluated the clinical significance of intervention for the serum TG levels in the fasting and postprandial states in patients with type 2 diabetes. METHODS: Fifty patients with type 2 diabetes, treated with statins, were selected and divided into two groups. One group was treated with a combination of fenofibrate and ezetimibe (F/E group) and the other group with statins (statin group) for 12 weeks. The lipoprotein profile of both groups was compared using high-performance liquid chromatography, and the vascular function was assessed using flow-mediated dilation (FMD) at the forearm. RESULTS: The levels of very low-density lipoprotein (VLDL) cholesterol, malondialdehyde low-density lipoprotein (MDA-LDL), total TG, chylomicron-TG, VLDL-TG, and HDL-TG decreased in the F/E group, whereas those of HDL cholesterol increased. Furthermore, the peak particle size of LDL increased, but that of HDL decreased in the F/E group. The combination treatment significantly improved the FMD. The change in the cholesterol level in a very small fraction of HDL was a significant independent predictor for determining the improvement of FMD (p＜0.01). CONCLUSIONS: Compared with the treatment with statins, the treatment with the combination of fenofibrate and ezetimibe effectively controlled the LDL cholesterol and TG levels, increased the HDL cholesterol level, especially in its small fraction, and improved vascular function of patients with type 2 diabetes.