Purpose: The objective of the current study is to introduce a proposed method and evaluate its efficacy using the greater trochanter (GT) tip rather than the lesser trochanter (LT) as an anatomical landmark to reduce leg length discrepancy (LLD) during performance of hip arthroplasty. Materials and Methods: Thirty-two patients who underwent hip arthroplasty were divided according to the GT group (n=17) and the LT control group (n=11); four patients were excluded. LLD was determined by assessing the vertical lengths parallel to the line connecting the lower margin of the teardrop to the most prominent part of the LT on a standing anteroposterior pelvic X-ray taken 30 days after the procedure. The mean and median LLD of the two groups were compared. Analysis of planning for femoral stem depth insertion and postoperative results was also performed. Results: No significant differences in characteristics including age, sex, or body mass index were observed between the two groups. However, the type of arthroplasty differed significantly between groups (P=0.016). The mean postoperative LLD was significantly smaller in the GT group compared with the control group (P=0.004). The results of linear regression of femoral stem depth showed a significant association between intraoperative planning and postoperative measurement (t=2.705, r2=0.672, P=0.016). Conclusion Preoperative measurement in determining femoral stem depth insertion using the GT tip as an anatomical reference can effectively minimize LLD in patients who underwent hip arthroplasty.

Purpose: The objective of the current study is to introduce a proposed method and evaluate its efficacy using the greater trochanter (GT) tip rather than the lesser trochanter (LT) as an anatomical landmark to reduce leg length discrepancy (LLD) during performance of hip arthroplasty. Materials and Methods: Thirty-two patients who underwent hip arthroplasty were divided according to the GT group (n=17) and the LT control group (n=11); four patients were excluded. LLD was determined by assessing the vertical lengths parallel to the line connecting the lower margin of the teardrop to the most prominent part of the LT on a standing anteroposterior pelvic X-ray taken 30 days after the procedure. The mean and median LLD of the two groups were compared. Analysis of planning for femoral stem depth insertion and postoperative results was also performed. Results: No significant differences in characteristics including age, sex, or body mass index were observed between the two groups. However, the type of arthroplasty differed significantly between groups (P=0.016). The mean postoperative LLD was significantly smaller in the GT group compared with the control group (P=0.004). The results of linear regression of femoral stem depth showed a significant association between intraoperative planning and postoperative measurement (t=2.705, r2=0.672, P=0.016). Conclusion Preoperative measurement in determining femoral stem depth insertion using the GT tip as an anatomical reference can effectively minimize LLD in patients who underwent hip arthroplasty.

Purpose: The objective of the current study is to introduce a proposed method and evaluate its efficacy using the greater trochanter (GT) tip rather than the lesser trochanter (LT) as an anatomical landmark to reduce leg length discrepancy (LLD) during performance of hip arthroplasty. Materials and Methods: Thirty-two patients who underwent hip arthroplasty were divided according to the GT group (n=17) and the LT control group (n=11); four patients were excluded. LLD was determined by assessing the vertical lengths parallel to the line connecting the lower margin of the teardrop to the most prominent part of the LT on a standing anteroposterior pelvic X-ray taken 30 days after the procedure. The mean and median LLD of the two groups were compared. Analysis of planning for femoral stem depth insertion and postoperative results was also performed. Results: No significant differences in characteristics including age, sex, or body mass index were observed between the two groups. However, the type of arthroplasty differed significantly between groups (P=0.016). The mean postoperative LLD was significantly smaller in the GT group compared with the control group (P=0.004). The results of linear regression of femoral stem depth showed a significant association between intraoperative planning and postoperative measurement (t=2.705, r2=0.672, P=0.016). Conclusion Preoperative measurement in determining femoral stem depth insertion using the GT tip as an anatomical reference can effectively minimize LLD in patients who underwent hip arthroplasty.

Background: We explored the extent to which neutrophil gelatinase-associated lipocalin (NGAL) cutoff value selection and the acute kidney injury (AKI) classification system determine clinical AKI-phenotype allocation and associated outcomes. Methods: Cutoff values from ROC curves of data from two independent prospective cardiac surgery study cohorts (Magdeburg and Berlin, Germany) were used to predict Kidney Disease: Improving Global Outcome (KDIGO)- or Risk, Injury, Failure, Loss of kidney function, End-stage (RIFLE)-defined AKI. Statistical methodologies (maximum Youden index, lowest distance to [0, 1] in ROC space, sensitivity≈specificity) and cutoff values from two NGAL meta-analyses were evaluated. Associated risks of adverse outcomes (acute dialysis initiation and in-hospital mortality) were compared. Results: NGAL cutoff concentrations calculated from ROC curves to predict AKI varied according to the statistical methodology and AKI classification system (10.6–159.1 and 16.85–149.3 ng/mL in the Magdeburg and Berlin cohorts, respectively). Proportions of attributed subclinical AKI ranged 2%–33.0% and 10.1%–33.1% in the Magdeburg and Berlin cohorts, respectively. The difference in calculated risk for adverse outcomes (fraction of odds ratios for AKI-phenotype group differences) varied considerably when changing the cutoff concentration within the RIFLE or KDIGO classification (up to 18.33- and 16.11-times risk difference, respectively) and was even greater when comparing cutoff methodologies between RIFLE and KDIGO classifications (up to 25.7-times risk difference). Conclusions NGAL positivity adds prognostic information regardless of RIFLE or KDIGO classification or cutoff selection methodology. The risk of adverse events depends on the methodology of cutoff selection and AKI classification system.

Objective The mangrove tree Xylocarpus granatum J. Koenig (X. granatum) is a medicinal plant used to treat various diseases in several Asian countries. Many bioactive natural products have been isolated from the plants, particularly several groups of limonoids, including 18 xylogranatins (Xyl-A to R), all of which bear a furyl-δ-lactone core commonly found in limonoids. Based on a structural analogy with the limonoids obacunone and gedunin, we hypothesized that xylogranatins could target the enzyme glycogen synthase kinase-3β (GSK-3β), a major target for the treatment of neurodegenerative pathologies, viral infections, and cancers. Methods We investigated the binding of the 18 xylogranatins to GSK-3β using molecular docking in comparison with two known reference GSK-3β ATP-competitive inhibitors, LY2090314 and AR-A014418. For each compound bound to GSK-3β, the empirical energy of interaction (ΔE) was calculated and compared to that obtained with known GSK-3β inhibitors and limonoid triterpenes that target this enzyme. Results Five compounds were identified as potential GSK-3β binders, Xyl-A, -C, -J, -N, and -O, for which the calculated empirical ΔE was equivalent to that calculated using the best reference molecule AR-A014418. The best ligand is Xyl-C, which is known to have marked anticancer properties. Binding of Xyl-C to the ATP-binding pocket of GSK-3β positions the furyl-δ-lactone unit deep into the binding-site cavity. Other xylogranatin derivatives bearing a central pyridine ring or a compact polycyclic structure are much less adapted for GSK-3β binding. Structure-binding relationships are discussed. Conclusion GSK-3β may contribute to the anticancer effects of X. granatum extract. This study paves the way for the identification of other furyl-δ-lactone-containing limonoids as GSK-3β modulators.

Acute kidney injury (AKI) is a common and serious complication in hospitalized patients, which continues to pose a clinical challenge for treating physicians. The most recent Kidney Disease Improving Global Outcomes practice guidelines for AKI have restated the importance of earliest possible detection of AKI and adjusting treatment accordingly. Since the emergence of initial studies examining the use of neutrophil gelatinase-associated lipocalin (NGAL) and cycle arrest biomarkers, tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein (IGFBP7), for early diagnosis of AKI, a vast number of studies have investigated the accuracy and additional clinical benefits of these biomarkers. As proposed by the Acute Dialysis Quality Initiative, new AKI diagnostic criteria should equally utilize glomerular function and tubular injury markers for AKI diagnosis.In addition to refining our capabilities in kidney risk prediction with kidney injury biomarkers, structural disorder phenotypes referred to as “preclinical-” and “subclinical AKI” have been described and are increasingly recognized. Additionally, positive biomarker test findings were found to provide prognostic information regardless of an acute decline in renal function (positive serum creatinine criteria). We summarize and discuss the recent findings focusing on two of the most promising and clinically available kidney injury biomarkers, NGAL and cell cycle arrest markers, in the context of AKI phenotypes. Finally, we draw conclusions regarding the clinical implications for kidney risk prediction.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin-25 are involved in catalytic iron-related kidney injury after cardiac surgery with cardiopulmonary bypass. We explored the predictive value of plasma NGAL, plasma hepcidin-25, and the plasma NGAL:hepcidin-25 ratio for major adverse kidney events (MAKE) after cardiac surgery. Methods: We compared the predictive value of plasma NGAL, hepcidin-25, and plasma NGAL:hepcidin-25 with that of serum creatinine (Cr) and urinary output and protein for primary-endpoint MAKE (acute kidney injury [AKI] stages 2 and 3, persistent AKI > 48 hours, acute dialysis, and in-hospital mortality) and secondary-endpoint AKI in 100 cardiac surgery patients at intensive care unit (ICU) admission. We performed ROC curve, logistic regression, and reclassification analyses. Results: At ICU admission, plasma NGAL, plasma NGAL:hepcidin-25, plasma interleukin-6, and Cr predicted MAKE (area under the ROC curve [AUC]: 0.77, 0.79, 0.74, and 0.74, respectively) and AKI (0.73, 0.89, 0.70, and 0.69). For AKI prediction, plasma NGAL:hepcidin-25 had a higher discriminatory power than Cr (AUC difference 0.26 [95% CI 0.00–0.53]). Urinary output and protein, plasma lactate, C-reactive protein, creatine kinase myocardial band, and brain natriuretic peptide did not predict MAKE or AKI (AUC < 0.70). Only plasma NGAL:hepcidin-25 correctly reclassified patients according to their MAKE and AKI status (category-free net reclassification improvement: 0.82 [95% CI 0.12–1.52], 1.03 [0.29–1.77]). After adjustment to the Cleveland risk score, plasma NGAL:hepcidin-25 ≥ 0.9 independently predicted MAKE (adjusted odds ratio 16.34 [95% CI 1.77–150.49], P = 0.014). Conclusions Plasma NGAL:hepcidin-25 is a promising marker for predicting postoperative MAKE.

Purpose: Determination of oxygen concentration in tissues affected by chronic venous insufficiency (CVI) has shown inconsistent results over the years and has confounded the pathophysiology of venous diseases. This study measured transcutaneous partial oxygen pressure (TcPO2 ) levels in patients with CVI to assess oxygenation and variation in oxygenation according to CVI stage. Materials and Methods: A prospective study was performed on consecutive patients with unilateral CVI. TcPO2 of diseased and unaffected limbs was measured in the supine and dependent positions. A single TcPO2 value was measured at the site of greatest skin change or at the edge of the ulcer. The TcPO2 values were analyzed and compared according to stage. Results: A total of 96 patients were included in the study with C4 (24.0%), C5 (19.8%), and C6 (56.3%) disease. The mean age was 44.7 years, and 85 (88.5%) were male. There was a statistically significant (P<0.01) difference in mean TcPO2 levels between the unaffected limb (supine, 32.1 mmHg; dependent, 50.7 mmHg), C5 diseased limb (supine, 16.6 mmHg; dependent, 35.5 mmHg), and C6 diseased limb (supine, 24.2 mmHg; dependent, 40.4 mmHg). In the supine and dependent positions, the mean TcPO2 in the affected limb was significantly lower (P<0.01) than that in the unaffected limb. Conclusion TcPO2 in advanced CVI can be used as a marker of oxygenation status. This is the first study in an Indian population looking at the relevance of TcPO2in the prognostication of advanced CVI.

Purpose: Determination of oxygen concentration in tissues affected by chronic venous insufficiency (CVI) has shown inconsistent results over the years and has confounded the pathophysiology of venous diseases. This study measured transcutaneous partial oxygen pressure (TcPO2 ) levels in patients with CVI to assess oxygenation and variation in oxygenation according to CVI stage. Materials and Methods: A prospective study was performed on consecutive patients with unilateral CVI. TcPO2 of diseased and unaffected limbs was measured in the supine and dependent positions. A single TcPO2 value was measured at the site of greatest skin change or at the edge of the ulcer. The TcPO2 values were analyzed and compared according to stage. Results: A total of 96 patients were included in the study with C4 (24.0%), C5 (19.8%), and C6 (56.3%) disease. The mean age was 44.7 years, and 85 (88.5%) were male. There was a statistically significant (P<0.01) difference in mean TcPO2 levels between the unaffected limb (supine, 32.1 mmHg; dependent, 50.7 mmHg), C5 diseased limb (supine, 16.6 mmHg; dependent, 35.5 mmHg), and C6 diseased limb (supine, 24.2 mmHg; dependent, 40.4 mmHg). In the supine and dependent positions, the mean TcPO2 in the affected limb was significantly lower (P<0.01) than that in the unaffected limb. Conclusion TcPO2 in advanced CVI can be used as a marker of oxygenation status. This is the first study in an Indian population looking at the relevance of TcPO2in the prognostication of advanced CVI.

BACKGROUND: The ability of urinary biomarkers to complement established clinical risk prediction models for postoperative adverse kidney events is unclear. We assessed the effect of urinary biomarkers linked to suspected pathogenesis of cardiac surgery-induced acute kidney injury (AKI) on the performance of the Cleveland Score, a risk assessment model for postoperative adverse kidney events. METHODS: This pilot study included 100 patients who underwent open-heart surgery. We determined improvements to the Cleveland Score when adding urinary biomarkers measured using clinical laboratory platforms (neutrophil gelatinase-associated lipocalin [NGAL], interleukin-6) and those in the preclinical stage (hepcidin-25, midkine, alpha-1 microglobulin), all sampled immediately post-surgery. The primary endpoint was major adverse kidney events (MAKE), and the secondary endpoint was AKI. We performed ROC curve analysis, assessed baseline model performance (odds ratios [OR], 95% CI), and carried out statistical reclassification analyses to assess model improvement. RESULTS: NGAL (OR [95% CI] per 20 concentration-units wherever applicable): (1.07 [1.01–1.14]), Interleukin-6 (1.51 [1.01–2.26]), midkine (1.01 [1.00–1.02]), 1-hepcidin-25 (1.08 [1.00–1.17]), and NGAL/hepcidin-ratio (2.91 [1.30–6.49]) were independent predictors of MAKE and AKI (1.38 [1.03–1.85], 1.08 [1.01–1.15], 1.01 [1.00–1.02], 1.09 [1.01–1.18], and 3.45 [1.54–7.72]). Category-free net reclassification improvement identified interleukin-6 as a model-improving biomarker for MAKE and NGAL for AKI. However, only NGAL/hepcidin-25 improved model performance for event- and event-free patients for MAKE and AKI. CONCLUSIONS NGAL and interleukin-6 measured immediately post cardiac surgery may complement the Cleveland Score. The combination of biomarkers with hepcidin-25 may further improve diagnostic discrimination.