1.Biomarker-Guided Risk Assessment for Acute Kidney Injury: Time for Clinical Implementation?
Christian ALBERT ; Michael HAASE ; Annemarie ALBERT ; Antonia ZAPF ; Rüdiger Christian BRAUN-DULLAEUS ; Anja HAASE-FIELITZ
Annals of Laboratory Medicine 2021;41(1):1-15
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.
2.Urinary Biomarkers may Complement the Cleveland Score for Prediction of Adverse Kidney Events After Cardiac Surgery: A Pilot Study
Christian ALBERT ; Michael HAASE ; Annemarie ALBERT ; Siegfried KROPF ; Rinaldo BELLOMO ; Sabine WESTPHAL ; Mark WESTERMAN ; Rüdiger Christian BRAUN-DULLAEUS ; Anja HAASE-FIELITZ
Annals of Laboratory Medicine 2020;40(2):131-141
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.
3.Predictive Value of Plasma NGAL:Hepcidin-25 for Major Adverse Kidney Events After Cardiac Surgery with Cardiopulmonary Bypass: A Pilot Study
Christian ALBERT ; Michael HAASE ; Annemarie ALBERT ; Martin ERNST ; Siegfried KROPF ; Rinaldo BELLOMO ; Sabine WESTPHAL ; Rüdiger C. BRAUN-DULLAEUS ; Anja HAASE-FIELITZ ; Saban ELITOK
Annals of Laboratory Medicine 2021;41(4):357-365
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.
4.Neutrophil Gelatinase-Associated Lipocalin Cutoff Value Selection and Acute Kidney Injury Classification System Determine Phenotype Allocation and Associated Outcomes
Annemarie ALBERT ; Sebastian RADTKE ; Louisa BLUME ; Rinaldo BELLOMO ; Michael HAASE ; Philipp STIEGER ; Ulrich Paul HINKEL ; Rüdiger C. BRAUN-DULLAEUS ; Christian ALBERT
Annals of Laboratory Medicine 2023;43(6):539-553
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.
5.Incidence and predictors of radial nerve palsy with the anterolateral brachialis splitting approach to the humeral shaft.
Mohamad GOUSE ; Sandeep ALBERT ; Dan-Barnabas INJA ; Manasseh NITHYANANTH
Chinese Journal of Traumatology 2016;19(4):217-220
PURPOSEFractures of the humeral shaft are common and account for 3%-5% of all orthopedic injuries. This study aims to estimate the incidence of radial nerve palsy and its outcome when the anterior approach is employed and to analyze the predictive factors.
METHODSThe study was performed in the department of orthopaedics unit of a tertiary care trauma referral center. Patients who underwent surgery for acute fractures and nonunions of humerus shaft through an anterior approach from January 2007 to December 2012 were included. We retrospectively analyzed medical records, including radiographs and discharge summaries, demographic data, surgical procedures prior to our index surgery, AO fracture type and level of fracture or nonunion, experience of the operating surgeon, time of the day when surgery was performed, and radial nerve palsy with its recovery condition. The level of humerus shaft fracture or nonunion was divided into upper third, middle third and lower third. Irrespective of prior surgeries done elsewhere, the first surgery done in our institute through an anterior approach was considered as the index surgery and subsequent surgical exposures were considered as secondary procedures.
RESULTSOf 85 patients included, 19 had preoperative radial nerve palsy. Eleven (16%) patients developed radial nerve palsy after our index procedure. Surgeons who have two or less than two years of surgical experience were 9.2 times more likely to induce radial nerve palsy (p=0.002). Patients who had surgery between 8 p.m. and 8 a.m. were about 8 times more likely to have palsy (p=0.004). The rest risk factor is AO type A fractures, whose incidence of radial nerve palsy was 1.3 times as compared with type B fractures (p =0.338). For all the 11 patients, one was lost to follow-up and the others recovered within 6 months.
CONCLUSIONContrary to our expectations, secondary procedures and prior multiple surgeries with failed implants and poor soft tissue were not predictive factors of postoperative deficit. From our study, we also conclude that radial nerve recovery can be reasonably expected in all patients with a postoperative palsy following the anterolateral approach.
Adult ; Female ; Fractures, Ununited ; surgery ; Humans ; Humeral Fractures ; surgery ; Incidence ; Male ; Postoperative Complications ; epidemiology ; etiology ; Radial Neuropathy ; epidemiology ; etiology ; Retrospective Studies
6.Transcutaneous Partial Pressure of Oxygen Measurement in Advanced Chronic Venous Insufficiency as a Marker of Tissue Oxygenation
Ludia JOHN ; Albert Abhinay KOTA ; Vimalin SAMUEL ; Prabhu PREMKUMAR ; Dheepak SELVARAJ ; Edwin STEPHEN ; Sunil AGARWAL ; Pranay GAIKWAD
Vascular Specialist International 2021;37(3):21-
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.
7.Transcutaneous Partial Pressure of Oxygen Measurement in Advanced Chronic Venous Insufficiency as a Marker of Tissue Oxygenation
Ludia JOHN ; Albert Abhinay KOTA ; Vimalin SAMUEL ; Prabhu PREMKUMAR ; Dheepak SELVARAJ ; Edwin STEPHEN ; Sunil AGARWAL ; Pranay GAIKWAD
Vascular Specialist International 2021;37(3):21-
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.
8.Greater Trochanter Tip as an Anatomical Reference to Minimize Leg Length Discrepancy following Hip Arthroplasty
John Christian Parsaoran BUTARBUTAR ; Gian IVANDER ; Albert RIANTHO ; Kevin FIDIASRIANTO ; Joshua EDWARD ; Earlene TASYA
Hip & Pelvis 2024;36(4):302-309
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.
9.Greater Trochanter Tip as an Anatomical Reference to Minimize Leg Length Discrepancy following Hip Arthroplasty
John Christian Parsaoran BUTARBUTAR ; Gian IVANDER ; Albert RIANTHO ; Kevin FIDIASRIANTO ; Joshua EDWARD ; Earlene TASYA
Hip & Pelvis 2024;36(4):302-309
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.
10.Greater Trochanter Tip as an Anatomical Reference to Minimize Leg Length Discrepancy following Hip Arthroplasty
John Christian Parsaoran BUTARBUTAR ; Gian IVANDER ; Albert RIANTHO ; Kevin FIDIASRIANTO ; Joshua EDWARD ; Earlene TASYA
Hip & Pelvis 2024;36(4):302-309
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.