The effect of L-Arginine therapy on achilles tendon healing: A histological and biomechanical investigation in an animal model.

PURPOSE: Several clinical and experimental studies have revealed that L-Arginine, which has antioxidant properties, accelerates tissue healing. This study examined the in vivo effects of oral L - Arginine supplementation on tendon regeneration in Wistar rats. METHOD: For each weighting of an average of 250-300 g, 24 Wistar rats were separated into three equal groups. Each rat's right hind leg Achilles tendons were tenotomized and then repaired. The first group (Control) was followed up with a regimen of standard food and water. In the second group (L-Arg Low Dose), 300 mg/kg, and in the third group (L-Arg High Dose), 600 mg/kg L-Arginine was administered in water daily with a regimen of standard food and water ad libitum. After eight weeks, the rats were sacrificed, and the tendons were histologically and biomechanically analyzed. RESULTS: Tendon peak strength values of the L-Arg Low Dose and L-Arg High Dose groups were similar but significantly higher than the control group. A statistically significant difference was observed between the groups in terms of ground substance, fiber arrangement, cellularity, hyalinization, and GAG properties ( p = 0.05, p = 0.002, p = 0.016, p = 0.027, p = 0.05). There was no statistically significant difference between the groups according to the histological examination of collagen properties, fiber structure, tenocyte properties, rounding of the nuclei, and collagen stainability. (p = 0.999, p = 0.061, p = 0.195, p = 0.195, p = 0.130). No mortality, wound complications, or re-ruptures were observed. CONCLUSION: Compared with the control group, histologically and biomechanically distinct therapeutic effects of L-Arginine supplementation on tendon healing were determined. LEVEL OF CLINICAL EVIDENCE: 5.

In vivo study of the role of hyaluronic acid, N-acetyl cysteine, and deproteinized calf serum on injury-induced cartilage degeneration.

OBJECTIVES: The aim of this study was to compare the effects of hyaluronic acid (HA), N-acetyl cysteine (NAC), and deproteinized calf serum on cartilage healing after the creation of traumatic cartilage injury in a rat model. MATERIALS AND METHODS: A total of 48 rats, each weighing an average of 350 g, were randomly separated into four groups of 12. An osteochondral defect was created, 2-mm-wide and 3-mm deep in each rat. Injections were made to the knees of the rats as saline solution in Group 1, deproteinized calf serum in Group 2, NAC in Group 3, and HA in Group 4. At the end of 12 weeks, all rats were sacrificed and tissues were evaluated histologically. RESULTS: The HA group had a better cell morphology, tissue morphology, surface architecture, and vascularity than the other groups (p<0.001). Matrix staining, chondrocyte clustering, and the assessment scores of the mid, deep, superficial zones, and overall were higher in the HA group than in the other groups (p<0.001). The NAC showed a better tissue morphology, cell morphology, and vascularity than the control group (p=0.003, p<0.001, and p<0.001, respectively). CONCLUSION: Hyaluronic acid was the most effective agent in cartilage healing compared to NAC and deproteinized calf serum. In addition, the NAC was more effective compared to the control group.

Does Early-Period Patient Dissatisfaction Turn Into Satisfaction Over Time After Total Knee Replacement?

BACKGROUND Total knee arthroplasty (TKA) is frequently used in the treatment of end-stage gonarthrosis, and the patient satisfaction rate varies. This study aimed to reveal the change in mid-term patient satisfaction results and functional scores of patients with low early postoperative satisfaction scores. MATERIAL AND METHODS We included 163 patients who underwent total knee prosthesis between September 2017 and February 2018. Among these patients, early (6 months) and mid-term (24 months) satisfaction and functional results of 34 patients with low satisfaction scores (Likert evaluations 1, 2, and 3) were evaluated. We assessed early-term functional results and satisfaction rates, mid-term analysis of patients who were not satisfied in the early period, and the relationship between functional scores and satisfaction. RESULTS The Likert score was 4 or 5 in 124 (80%) of 158 patients, and early dissatisfaction was detected in 34 patients (20%). In the early-period dissatisfied group, satisfaction scores 6 months after surgery were 1.9±1.1 (1-3) and 4.2±1 (3-5) 24 months after surgery. A statistically significant difference was observed between the dissatisfied group's early and mid-term KSS and KS values. A correlation was observed between satisfaction scores and KS and KSS scores (P<0.05). CONCLUSIONS Patients who do not have mechanical problems with total knee arthroplasty but are not satisfied with the surgery in the early period can be satisfied over time after regular follow-up, appropriate communication and information, and effective rehabilitation.

Cardiovascular drugs and analysis of potential risk factors associated with mortality in severe coronavirus disease 2019 patients.

OBJECTIVES: Cardiovascular diseases are also considered to increase the risk of death in COVID-19 patients. However, real-world data concerning the risk factors for death in patients with severe COVID-19 still remain vague. This study aimed to identify the potential risk factors associated with mortality in severe COVID-19 patients. METHODS: All consecutive patients admitted to the intensive care unit (ICU) of our institute for COVID-19 for severe COVID-19 pneumonia from April 1, 2020 to July 20, 2020 were included in the analysis. Patient characteristics, including complete medical history and comorbid diseases, blood test results during admission and on day 7, and clinical characteristics were compared between survivors and nonsurvivors. RESULTS: There was no significant difference between survivors and nonsurvivors regarding age, gender, and preexisting cardiovascular diseases. Moreover, the rate of the medications including angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blockers did not differ between survivors and nonsurvivors. The peak C-reactive protein (CRP), procalcitonin, fibrinogen, and d-dimer levels and the rate for chronic renal failure were significantly higher in nonsurvivors compared with survivors. Intubated patients had a higher risk of death than the others had. CONCLUSIONS: This study failed to demonstrate a significant difference in preexisting cardiovascular diseases and cardiovascular medications between survivors and nonsurvivors who were admitted to ICU for severe COVID-19. Our findings indicate that the presence of chronic renal failure, a high peak ferritin concentration, and the need for invasive mechanical ventilation appear predictive for mortality. We propose that these risk factors should be taken into account in defining the risk status of severe COVID-19 patients admitted to the ICU.

The Fate of Failed Debridement, Antibiotics, and Implant Retention in Infected Knee Arthroplasties: Nothing to Lose.

Purpose The frequency of periprosthetic knee infections increases yearly because of the popularity of the total knee prostheses. Revision knee arthroplasty is an annoying problem for both the surgeons and the patients. Debridément, antibiotics, and implant retention (DAIR) is a popular alternative for the treatment of periprosthetic knee infections. Little is known about the fate of the failed DAIR patients. This study aims to investigate the effect of the failed DAIR on the clinical result after two-staged revision arthroplasty. Method Ninety-nine two-staged revision arthroplasties and 85 DAIR patients from two reference clinics were retrospectively analyzed. The minimum follow-up was 36 months. Patients were grouped according to the treatment as, two-staged revision without DAIR, two-staged revision after failed DAIR, and successful DAIR. Their Knee Society Scores (KSS), functional KSS (KSS-f) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were analyzed and compared. Results DAIR has a 52.9% success rate for the treatment of infection. Elevated erythrocyte sedimentation rates and C-reactive peptide levels are not risk factors for failure, but the time passed since the index surgery is a risk factor for worse outcome scores. Failed DAIR is not a risk factor for reinfection after two-staged revision. Last KSS after failed DAIR, successful DAIR, and two-staged revision were 83.98±7.033, 91.89±4.386, and 91.38±4.735, respectively. Last KSS-f after failed DAIR, successful DAIR, and two-staged revision were 86.25±9.524, 94.56±8.106, and 94.85±5.996, respectively. Last WOMAC after failed DAIR, successful DAIR, and two-staged revision were 86.16±7.745, 94.750±4.964, and 93.319±5.961, respectively.  Conclusion Failed DAIR is associated with lesser, but still good, or excellent clinical scores. DAIR is suggested as a promising treatment option for periprosthetic knee infections in well-selected patients.

Oxidants and antioxidants in myocardial infarction (MI): Investigation of ischemia modified albumin, malondialdehyde, superoxide dismutase and catalase in individuals diagnosed with ST elevated myocardial infarction (STEMI) and non-STEMI (NSTEMI).

BACKGROUND: Coronary ischemia can lead to myocardial damage and necrosis. The pathogenesis of cardiovascular diseases often includes increased oxidative stress and decreased antioxidant defense. The study aimed to assess levels of ischemia modified albumin (IMA), malondialdehyde acid (MDA), superoxide dismutase (SOD), and catalase in individuals diagnosed with ST elevated myocardial infarction (STEMI) and non-STEMI. METHODS: The present study prospectively included 50 STEMI patients, 55 NSTEMI patients, and 55 healthy subjects. Only patients who were recently diagnosed with STEMI or NSTEMI were included in this study. IMA, MDA, SOD, and catalase activities were measured spectrophotometrically. Significant coronary artery lesions were determined by angiography. RESULTS: Patients with ACS had significantly greater IMA and MDA values than the healthy controls (p<0.001). Besides, patients with STEMI had IMA levels that were significantly greater than those of the patients with NSTEMI (p<0.001), while the reverse was true for MDA levels (p<0.001). The healthy controls had the highest levels of SOD and catalase levels, followed by patients with STEMI and patients with NSTEMI, respectively (p<0.001). There was a significant negative correlation among MDA and SOD with catalase levels (r = -0.771 p<0.001 MDA vs catalase; r = -0.821 p<0.001 SOD vs catalase). CONCLUSIONS: Data obtained in this study reveals that compared to healthy controls, STEMI and NSTEMI patients had increased levels of MDA and IMA and decreased levels of SOD and catalase.

The Association of Glomerular Filtration Rate With Echocardiographic Parameters in Chronic Kidney Disease.

BACKGROUND: Cardiovascular disease (CVD) is the primary cause of mortality and morbidity in chronic kidney disease (CKD) patients. Aortic propagation velocity (APV), epicardial fat thickness (EFT) and carotid intima-media thickness (CIMT) measurements could provide additional information on assessing renal decline in CKD patients. The study aimed to evaluate EFT, AVP and CIMT in CKD patients and then investigate the association among those parameters. METHODS: A total of 170 CKD consecutive subjects were enrolled in the study. Patients were divided into five groups according to their estimated glomerular filtration rate (eGFR) values. Each patient underwent complete transthoracic echocardiography examination. APV, EFT and CIMT were measured for analyses. A multivariate linear regression model was used for analysis to determine the independent predictors of eGFR. RESULTS: The lowest APV was observed in stage IV-V, and the highest APV was observed in stage I-II (P < 0.001). Stage IV-V patients had the highest EFT and stage I-II patients had the lowest EFT (P < 0.001). Moreover, the lowest CIMT was observed in stage III, and the highest CIMT was observed in stage V (P < 0.001). eGFR was significantly and positively correlated with APV and negatively correlated with EFT and CIMT. In multivariate analyses, APV (odds ratio (OR): 0.289, P < 0.001), EFT (OR: -0.135, P < 0.001) and CIMT (OR: -0.388, P < 0.001) were independent predictors of eGFR. CONCLUSION: We found that APV decreased, and EFT and CIMT increased as CKD progress. The present study suggests that APV, EFT and CIMT might be incorporated with the examination of CKD patients in daily practice.

Evaluation of Epicardial Adipose Tissue by Echocardiography and Its Correlation with Aortic Velocity Propagation and Carotid Intima-Media Thickness in Patients of Type 2 Diabetes Mellitus.

Epicardial fat thickness (EFT) is associated with aortic stiffness in diabetic patients. In this study, we aimed to determine if there is an association among the parameters of EFT, aortic velocity propagation (AVP), and carotid intima-media thickness (CIMT) in patients with non-insulin dependent diabetes mellitus. This study included 55 non-insulin dependent diabetes mellitus patients and 40 non-diabetic control patients. For all participants, EFT and AVP were determined by echocardiographic method and CIMT was calculated using an ultrasonographic exam. The EFT and CIMT values were found to be significantly increased in the non-insulin dependent diabetes mellitus group. On the other hand, aortic velocity propagation was decreased in the non-insulin dependent diabetes mellitus group compared to non-diabetic patients (EFT; 8.43 ± 1.68 versus 6.36 ± 2.21 mm, p < 0.001; CIMT; 0.92 ± 0.24 versus 0.58 ± 0.18 mm, p < 0.001; and AVP; 28.20 ± 16.02 versus 58.10 ± 17.50, p < 0.01, respectively). Significantly higher EFT and CIMT values were found in addition to lower AVP values in non-insulin dependent diabetes mellitus patients. Moreover, we demonstrated that there was a strong correlation between EFT, CIMT, and AVP.

The role of monocyte to HDL ratio in predicting clinically significant carotid stenosis in patients with asymptomatic carotid artery disease.

OBJECTIVE: Monocyte count to HDL-C Ratio (MHR) and Fibrinogen to Albumin Ratio (FAR) have recently emerged as markers of inflammation in atherosclerotic diseases. Our goal was to investigate the relationships of MHR and FAR with the severity of carotid artery stenosis (CAS) in patients with asymptomatic carotid artery disease. METHODS: This retrospective study consisted of 300 patients with asymptomatic CAS. Pre-angiographic MHR, FAR, and high-sensitive C-reactive protein (hsCRP) were measured. Carotid angiography was performed in patients with ≥50% stenosis on carotid ultrasonography. Patients were first split into 2 groups based on the degree of CAS and then tertiles (T) of MHR. RESULTS: 96 patients had clinically insignificant CAS (<50%) (Group-1), and 204 patients had clinically significant CAS (≥50%) (Group-2). Group-2 had higher MHR, FAR, and hsCRP than group-1. Patients in T3 had higher MHR, FAR, and hsCRP than in T1 and T2. MHR, FAR, and hsCRP were correlated with each other (p<0.001, for all). MHR, FAR, and hsCRP were independent predictors of significant CAS. MHR better predicted a significant CAS than FAR and hsCRP (p<0.05). CONCLUSION: Pre-angiographic MHR may be a better predictor than FAR and hsCRP in identifying a clinically significant carotid stenosis in patients with asymptomatic CAS. Patients with asymptomatic CAS and a high level of MHR should be followed-up closely to supervise risk-factor control and intensify treatment.

The role of monocyte to HDL ratio in predicting clinically significant carotid stenosis in patients with asymptomatic carotid artery disease

SUMMARY OBJECTIVE Monocyte count to HDL-C Ratio (MHR) and Fibrinogen to Albumin Ratio (FAR) have recently emerged as markers of inflammation in atherosclerotic diseases. Our goal was to investigate the relationships of MHR and FAR with the severity of carotid artery stenosis (CAS) in patients with asymptomatic carotid artery disease. METHODS This retrospective study consisted of 300 patients with asymptomatic CAS. Pre-angiographic MHR, FAR, and high-sensitive C-reactive protein (hsCRP) were measured. Carotid angiography was performed in patients with ≥50% stenosis on carotid ultrasonography. Patients were first split into 2 groups based on the degree of CAS and then tertiles (T) of MHR. RESULTS 96 patients had clinically insignificant CAS (<50%) (Group-1), and 204 patients had clinically significant CAS (≥50%) (Group-2). Group-2 had higher MHR, FAR, and hsCRP than group-1. Patients in T3 had higher MHR, FAR, and hsCRP than in T1 and T2. MHR, FAR, and hsCRP were correlated with each other (p<0.001, for all). MHR, FAR, and hsCRP were independent predictors of significant CAS. MHR better predicted a significant CAS than FAR and hsCRP (p<0.05). CONCLUSION Pre-angiographic MHR may be a better predictor than FAR and hsCRP in identifying a clinically significant carotid stenosis in patients with asymptomatic CAS. Patients with asymptomatic CAS and a high level of MHR should be followed-up closely to supervise risk-factor control and intensify treatment.

RESUMO OBJETIVO Recentemente, a contagem de monócitos para a proporção HDL-C (MHR) e a relação fibrinogênio para albumina (FAR) emergiram como marcadores de inflamação em doenças ateroscleróticas. Nosso objetivo é investigar a relação da MHR e FAR com a gravidade da estenose da artéria carótida (CAS) em pacientes com doença assintomática da artéria carótida. MÉTODOS Este estudo retrospectivo incluiu 300 pacientes com CAS assintomática. MHR pré-angiográfica, FAR e proteína C reativa de alta sensibilidade (hsCRP) foram medidas. A angiografia carotídea foi realizada em pacientes com estenose ≥50% na ultrassonografia carotídea. Os pacientes foram primeiramente divididos em dois grupos com base no grau de CAS e depois nos tercis (T) da MHR. RESULTADOS Noventa e seis pacientes apresentaram um CAS clinicamente insignificante (<50%) (grupo 1) e 204 pacientes apresentaram CAS clinicamente significativo (≥50%) (grupo 2). O grupo 2 apresentou MHR, FAR e hsCRP superior ao grupo 1. Pacientes em T3 apresentaram maior MHR, FAR e hsCRP do que em T1 e T2. MHR, FAR e hsCRP foram correlacionados entre si (p<0,001, para todos). MHR, FAR e hsCRP foram preditores independentes de CAS significativa. MHR predisse melhor uma CAS significativa que FAR e hsCRP (p<0,05). CONCLUSÕES A MHR pré-angiográfica pode ser um melhor preditor que a FAR e a hsCRP na identificação de estenose carotídea clinicamente significativa em pacientes com CAS assintomática. Pacientes com CAS assintomática e alto nível de MHR devem ser acompanhados de perto para supervisionar o controle dos fatores de risco e intensificar o tratamento.

Fibrinogen to albumin ratio as a powerful predictor of the exaggerated morning blood pressure surge in newly diagnosed treatment-naive hypertensive patients.

BACKGROUND: The exaggerated morning blood pressure surge (MS) is a risk factor for cardiovascular diseases. Inflammation is associated with the pathogenesis of hypertension. We aimed to investigate the association between fibrinogen, albumin, fibrinogen to albumin ratio (FAR), and exaggerated MS, and which of those variables is a better predictor for identifying an exaggerated MS in newly diagnosed treatment-naive hypertensive patients. MATERIAL AND METHODS: The study included 249 treatment-naive patients who were newly diagnosed with hypertension in both clinical and ambulatory blood pressure (BP) monitoring measurements. Morning BP was defined as the mean of BPs measured during the first 2 hours after wake-up. The lowest BP was defined as the mean of 3 BP measurements focused on the lowest nighttime computations. The MS was calculated as the morning systolic BP minus the lowest systolic BP. Fibrinogen and albumin levels were measured from venous blood. FAR was obtained by dividing the fibrinogen to the albumin. RESULTS: Patients with higher-value MS had a higher fibrinogen, FAR, and a lower albumin than those with low-value MS. MS was positively correlated with fibrinogen and FAR, and negatively correlated with albumin (for all, p < .001). Fibrinogen, albumin, and FAR were independent predictors of exaggerated MS. FAR was a more powerful predictor than fibrinogen (p < .001) and albumin (p = .02) in determining exaggerated MS. CONCLUSION: Patients with exaggerated MS had a higher fibrinogen and FAR, and a lower albumin level than those without exaggerated MS. FAR may be a better predictor than fibrinogen and albumin for determining exaggerated MS.

An Upfront Two-Stent Strategy for True Coronary Bifurcation Lesions with A Large Side Branch in Acute Coronary Syndrome: A Two-Year Follow-Up Study.

Background and Objectives: Little is known about the upfront two-stent strategy (U2SS) for true coronary bifurcation lesions (CBLs) in acute coronary syndrome (ACS). We aimed to present our two-year follow-up results on the U2SS by using different two-stent techniques for the true CBL with a large side branch (SB) in ACS patients, including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI), and to identify independent predictors of the presence of major adverse cardiac events (MACEs) after intervention. Materials and Methods: The study included 201 consecutive ACS patients with true CBLs who underwent percutaneous coronary intervention (PCI) using U2SS from October 2015 to March 2018. Clinical outcomes at follow-up were assessed. MACE was defined as a composite of cardiac death, non-fatal myocardial infarction, and target lesion revascularization (TLR). Results: 31.3% of the patients had an UA, 46.3% had an NSTEMI, and 22.4% had an STEMI. CBL was most frequently located in the left anterior descending (LAD)/diagonal artery (59.2%). In total, 71.1% of the patients had a Medina classification (1,1,1). Overall, 62.2% of cases were treated with mini-crush stenting. Clopidogrel was given in 23.9% of the patients; 71.1% of the patients received everolimus eluting stent (EES); and 11.9% received a sirolimus eluting stent (SES). Final kissing balloon inflation was carried out in all patients, with an unsatisfactory rate of 5%. A proximal optimization technique sequence was successfully carried out in all patients. The MACE incidence was 16.9% with a median follow-up period of 2.1 years. There were seven cardiac deaths (3.5%). The TLR rate was 13.4% (n = 27), with PCI treatment in 16 patients, and coronary artery bypass grafting treatment in 11 patients. After multivariate penalized logistic regression analysis (Firth logistic regression), clopidogrel use (odds ratio (OR): 2.19; 95% confidence interval (CI): 0.41-2.51; p = 0.007) and SES use (OR: 1.86; 95% CI: 0.31-2.64; p = 0.014) were independent predictors of the presence of MACE. Conclusion: U2SS is feasible and safe for the true CBLs with large and diseased SB in ACS patients, and is related to a relatively low incidence of MACE. Clopidogrel use and SES use may predict the MACE development in ACS patients treated using U2SS.

Evaluation of Cardiac Repolarization Indices in Epilepsy Patients Treated with Carbamazepine and Valproic Acid.

BACKGROUND AND OBJECTIVES: Epilepsy patients have a higher risk of sudden unexplained death compared to the rest of the population. Cardiac repolarization abnormalities might be seen in epilepsy during interictal periods. We aimed to evaluate the changes in electrocardiography (ECG) parameters in generalized tonic-clonic seizure patients treated with carbamazepine or valproic acid (VPA) drug. MATERIALS AND METHODS: A totally of 129 subjects (66 epilepsy patients, 63 healthy subjects) were enrolled in the study. Of the patients, 36 were on carbamazepine and 30 were on VPA. There were 12-lead ECGs obtained from all participants. RR interval (time between consecutive R peaks), QT interval (defines the period of ventricular repolarization), corrected QT (QT interval corrected for heart rate; QTc), QTc-maximum (QTc-max), QTc-minimum (QTc-min), QTc dispersion (QTcd), P (atrial depolarization )-maximum (P-max), P-minimum (P-min) and P dispersion (Pd) were measured. RESULTS: QTd (QT dispersion), QTcd, and Pd values were significantly higher in the patients compared to the controls (p < 0.01). QTcd, Pd, and P-max values were statistically higher in male patients compared to healthy male controls. QTcd values were significantly higher in female patients using carbamazepine compared to the female patients on VPA and healthy controls (p = 0.01). Male patients using VPA had significantly higher QTcd values against the male population in carbamazepine and control groups. CONCLUSION: This study demonstrated that QTd, QTcd, and Pd values were significantly higher in epilepsy patients than in healthy controls. In addition, female patients using carbamazepine and male patients using VPA were prone to ventricular arrhythmia compared to the control group.

The modified Kostuik transilial bar technique has acceptable results in neuromuscular spinal deformity correction.

The aim of this study is to evaluate the results of the modified Kostuik transilial bar technique for neuromuscular scoliosis (NS). We reviewed the records of 21 patients treated for NS with this instrumentation. There were 14 females and seven males, with an average age of 15.6 years (range: 9-21 years). We determined patients' demographics, correction ratio of both curve and pelvic obliquity, loss of correction, screw loosening at first sacral vertebra, and clinical outcomes. Mean follow-up was 56 months (range: 34-96 months). There were no reoperations, no screw breakage, and no significant loss of correction. The mean preoperative coronal Cobb angle was 71.4°±8.7°, the initial postoperative measurements had a mean Cobb angle of 19.2°±7.2°, and at the last follow-up, the mean Cobb angle was 23.6°±6.9° (P<0.001). Pelvic obliquity decreased from 27.7°±12.4° to 9.1°±5.3° at follow-up and to 11.9°±6.3° at the last follow-up (P<0.001). The preoperative pelvic obliquity angle was significantly higher at the patients with screw loosening (P=0.016). There was one established as well as one possible pseudoarthrosis in our patients. The new technique does appear to possibly become an alternative to conventional lumbosacral fixation techniques. Integration of the bar with pipe-type connector onto the long spinal instrumentation with oblique connectors can prevent the most unenviable complications such as wide exposure, hardware prominence, reoperation, and pseudoarthrosis.

Association of Heart Rate Recovery With Microalbuminuria in Non-Obstructive Coronary Artery Disease.

BACKGROUND: Non-obstructive coronary artery disease (CAD) is associated with significantly increased risk for myocardial infarction. Heart rate recovery (HRR), a measure of autonomic function, is a strong predictor of all-cause mortality. Microalbuminuria, a marker of early arterial disease, is an independent risk factor for cardiovascular disease and mortality. We aimed to investigate HRR and determine its relationship with microalbuminuria in patients with non-obstructive CAD. METHODS: We prospectively studied 565 patients who underwent elective coronary angiography. All participants underwent urinary analysis and then an exercise test. Microalbuminuria was defined as an urinary albumin-to-creatinine ratio (UACR) of 30 - 299 mg/g. The HRR was abnormal if ≤ 12 beats/min during the first minute after exercise. First, all patients were divided into two groups, patients with microalbuminuria (n = 152) and patients without microalbuminuria (n = 413). Then, all patients were re-divided into two groups, those with lower HRR (≤ 12 beats/min, n = 126) and those with higher HRR (> 12 beats/min, n = 439). RESULTS: Patients with microalbuminuria had lower HRR and patients with lower HRR had higher UACR. While UACR was negatively correlated with HRR in patients with microalbuminuria (r = -0.424; P < 0.001) and in patients with lower HRR (r = -0.192; P= 0.042), there was no correlation of UACR with HRR in neither patients with normoalbuminuria nor patients with higher HRR, respectively. In the all study population, there was a significant inverse association between UACR and HRR (r = -0.445, P < 0.001), and UACR independently predicted the presence of lower HRR (P < 0.001). CONCLUSIONS: Our findings showed that there was a significant inverse association between UACR and HRR in patients especially with microalbuminuria, and that albuminuria might predict cardiac autonomic imbalance evaluated by HRR in patients with non-obstructive CAD.

Intraobserver and interobserver reliability assessment of tibial plateau fracture classification systems.

OBJECTIVES: This study aims to assess the intra- and interobserver reliability of commonly used tibial plateau fracture classification systems. PATIENTS AND METHODS: This retrospective cohort study included computed tomography (CT) and plain radiographic images (lateral and anteroposterior X-rays) of 60 patients (40 males, 20 females; mean age 45.9 years; range 18 to 80 years) who presented to two orthopaedic clinics between January 2011 and January 2015 with unilateral tibial plateau fractures. All plain X-rays (XR) and CT images were evaluated by four observers on two separate occasions, 1.5 months apart. All fractures were classified according to the Arbeitsgemeinschaft für Osteosynthesefragen-Orthopaedic Trauma Association (AO-OTA), Schatzker, Hohl and Moore, Luo and revised Duparc systems. Intraobserver reliability was measured with Cohen's kappa (κ) coefficient and interobserver reliability with Fleiss' kappa coefficient. RESULTS: When Schatzker classification was performed, interobserver reliability was in moderate level for (κ=0.51) for XR and in substantial level for CT (κ=0.61). When AO/OTA classification was used, interobserver reliability was in moderate level for both methods of diagnosis (κXR=0.43 and κCT=0.54, respectively). In the Hohl and Moore classification, the interobserver reliability was also moderate for both methods of diagnosis (κXR=0.45 and κCT=0.51, respectively). Revised Duparc classification showed the lowest interobserver reliability ranging from fair to moderate level (κXR=0.27-0.55 and κCT=0.44-0.61). Interobserver reliability for Luo classification was κCT=0.47. Intraobserver reliability for CT in Luo classification was in substantial level for observers 1, 2 and 3 (κCT=0.67-0.71) and in perfect level for observer 4 (κCT=0.84). Intraobserver reliability was in substantial level in Schatzker classification and in moderate level at the other classifications. CONCLUSION: Among the classification systems compared in this study, Schatzker was the most reliable particularly when CT was used. On the other hand, revised Duparc classification presented the worse reliability results due to its complexity and different morphological subtypes.

Ticagrelor-Associated Conduction Disorder: A Case Report and Review of the Literature.

A 47-year-old female presented to emergency clinic due to non-ST-elevation myocardial infarction (NSTEMI). After receiving acetylsalicylic acid, a loading dose of ticagrelor 180 mg and intravenous unfractionated heparin, she underwent successful placement of drug eluting stent on the distal part of non-dominant left circumflex artery. The patient had no pre-existing atrioventricular (AV) block and did not use AV blocking agent. Approximately 10 h after taking a loading dose of ticagrelor, baseline normal rhythm degenerated to the first and then complete AV block, with mild dizziness. Following cessation of ticagrelor, cardiac rhythm returned to normal level within 2 days. The close monitoring of patients after starting ticagrelor is imperative, so ticagrelor may result in advanced conduction disorders. Here, we report a patient who developed various types of AV block associated with the ticagrelor taken during successful percutaneous coronary intervention for NSTEMI. We also reviewed the literature on the association between ticagrelor use and conduction abnormalities.

Affective temperament does not influence satisfaction after total knee arthroplasty.

BACKGROUND: Inherent temperament of the patient may predict the outcome of the surgical procedure. The purpose of this study was to ascertain whether negative affective temperament affects patient satisfaction and outcome measures. METHODS: This prospective study included 143 patients who underwent total knee arthroplasty for primary arthrosis. Preoperatively, the Memphis, Pisa, Paris and San Diego-Auto questionnaire was used to define the temperament of the patient. Knee Society Score (KSS) and short form-36 (SF-36) outcome measures were used to evaluate the functional outcome. RESULTS: No relationship was determined between temperament and satisfaction (P = .734). Overall, the satisfaction rate of the procedure in our patients was 93%. The KSS improved from a mean of 47.9 to 70.1 (F = 124.275; P < .05) and the SF-36 physical component summary, and SF-36 mental component summary scores improved to a mean of 39.5 and 43.04 points, respectively. CONCLUSION: Temperament was not found to have any effect on patient satisfaction. However, patient satisfaction was directly related to better functional outcomes.

The CYP2C19*2 and CYP2C19*17 Polymorphisms play a Vital Role in Clopidogrel Responsiveness after Percutaneous Coronary Intervention: A Pharmacogenomics Study.

Clopidogrel inhibits platelet activation and aggregation by blocking the P2Y12 receptor. Dual antiplatelet therapy with clopidogrel and aspirin is recommended treatment by current guidelines for patients undergoing percutaneous interventions. Recurrent ischaemic cardiac events after this treatment showed lack of clopidogrel responsiveness. We aimed to investigate the most noticeable variants in the genes involved in clopidogrel pharmacokinetics and pharmacodynamics. A total of 347 Turkish patients who underwent percutaneous coronary interventions with stent implantation were included in our study. Platelet reactivity (PRU) and % inhibition were measured with VerifyNow P2Y12 assay in blood samples collected from patients who took a standard dose of clopidogrel (75 mg/day) for at least 7 days. The variants in the CYP2C19, CYP3A4, CYP2B6, ABCB1, ITGB3 and PON1 genes were genotyped using the Sequenom MassARRAY system. When grouped, the patients with PRU values >208 as non-responsiveness to clopidogrel therapy; 104 (30%) patients were non-responders and 243 (70%) patients were responders. A significant association was found between the CYP2C19*2 (G636A) polymorphism and non-responsiveness to clopidogrel therapy (p < 0.001). An allele frequency of this single nucleotide polymorphism was high in non-responders; its odds ratio was 2.92 compared with G allele (p < 0.001). PRU values of CT genotypes were lower (p = 0.029) and % inhibition values of CT genotypes were higher (p = 0.008) compared with CC genotypes for the CYP2C19*17 (C806T) polymorphism. None of the other genetic variants were found to be statistically associated with non-responsiveness to clopidogrel and antiplatelet activity. Our findings suggest that the CYP2C19*2 polymorphism is associated with non-responsiveness to clopidogrel therapy and the CYP2C19*17 polymorphism enhances antiplatelet activity of clopidogrel. Depending on haplotypes of these two polymorphisms, clopidogrel-treated patients can be protected or not from stent thrombosis and ischaemic events.

The absorption kinetics of ketoconazole plays a major role in explaining the reported variability in the level of interaction with midazolam: Interplay between formulation and inhibition of gut wall and liver metabolism.

The impact of different single oral doses of ketoconazole (KTZ) (100, 200 and 400 mg) and of staggering its dosage (400 mg at -12, -2, 0, 2 and 4 h), with respect to the administration of a single 5 mg oral dose of midazolam (MDZ) on the extent of inhibition of the metabolism of the latter, was evaluated in healthy subjects in two separate studies. Escalation of the ketoconazole dosage resulted in 2.3 (1.9), 2.7 (1.7) and 4.2 (2.5) -fold increases in the mean AUC(0,12h) (and Cmax ) values of midazolam. Dose-staggering was associated with 3.9 (2.5), 4.9 (2.9), 5.4 (2.8), 2.0 (1.3) and 1.2 (0.9) -fold increases in the mean AUC(0,12h) (and Cmax ) of midazolam. These findings could be predicted by physiologically based pharmacokinetic (PBPK) modelling using the ADAM (advanced dissolution absorption and metabolism) model within the Simcyp Simulator (Version 12 Release 2) to characterize the absorption kinetics of ketoconazole with respect to disintegration time, supersaturation ratio and precipitation rate. This study also emphasizes a need to account for inter-individual variability in the gut wall and systemic exposure of inhibitors with physicochemical properties similar to ketoconazole, in particular in their rate of oral absorption and when using different pharmaceutical formulations, in designing and evaluating the extent of drug-drug interactions. Copyright © 2016 John Wiley & Sons, Ltd.