Urinary angiotensinogen as a marker of intrarenal angiotensin II activity in adolescents with primary hypertension

Background

Experimental and epidemiological studies have demonstrated that urinary angiotensinogen (AGT) is a novel biomarker for the intrarenal activity of the renin–angiotensin system in hypertension (HT). Several large-scale epidemiological studies have shown that an elevated serum uric acid (SUA) level is associated with HT. The aim of our study was to assess urinary AGT excretion and its correlation with SUA level, the lipid profile, and the body mass index (BMI) Z-score in hypertensive adolescents.

Methods

Participants were divided into two groups: (1) the group with confirmed HT consisting of 55 subjects with primary HT and (2) the reference (R) group consisting of 33 subjects with white-coat HT. A commercial enzyme-linked immunosorbent assay (ELISA) kit was used to determine urinary AGT concentration.

Results

The urinary AGT/creatinine (cr.) ratio in subjects in the HT group was significantly higher than that in the reference group (p?<?0.01) and showed a strong positive correlation with SUA (r?=?0.47, p?<?0.01). The relationship between the AGT/cr. ratio and SUA levels after controlling for age, gender and BMI Z-score continued to show a significant association.

Conclusions

The most obvious finding to emerge from this study is that in adolescents with primary HT, the increased urinary excretion of AGT correlated with hyperuricemia, although large, multicenter studies are needed to confirm this observation.     

Urinary Evaluation After RYGBP: a Lithogenic Profile with Early Postoperative Increase in the Incidence of Urolithiasis

Background

The objective of this study was to assess predictors for new-onset stone formers after Roux-en-Y gastric bypass (RYGBP).

Methods

One hundred and fifty-one obese patients underwent RYGBP and were followed for 1 year. The analysis comprised two study time points: preoperative (T0) and 1 year after surgery (T1). They were analyzed for urinary stones, blood tests, and 24-h urinary evaluation. Nonparametric tests, logistic regression, and multivariate analysis were conducted using SPSS 17.

Results

Median BMI decreased from 44.1 to 27.0 kg/m² (p?<?0.001) in the postoperative period. Urinary oxalate (24 versus 41 mg; p?<?0.001) and urinary uric acid (545 versus 645 mg; p?<?0.001) increased significantly postoperatively (preoperative versus postoperative, respectively). Urinary volume (1310 versus 930 ml; p?<?0.001), pH (6.3 versus 6.2; p?=?0.019), citrate (268 versus 170 mg; p?<?0.001), calcium (195 versus 105 mg; p?<?0.001), and magnesium (130 versus 95 mg; p?=?0.004) decreased significantly postoperatively (preoperative versus postoperative, respectively). Stone formers increased from 16 (10.6 %) to 27 (17.8 %) patients in the postoperative analysis (p?=?0.001). Predictors for new stone formers after RYGBP were postoperative urinary oxalate (p?=?0.015) and uric acid (p?=?0.044).

Conclusions

RYGBP determined profound changes in urinary composition which predisposed to a lithogenic profile. The prevalence of urinary lithiasis increased almost 70 % in the postoperative period. Postoperative urinary oxalate and uric acid were the only predictors for new stone formers.     

Obesity, But Not High-Fat Diet, Promotes Murine Pancreatic Cancer Growth

Background

Obesity accelerates pancreatic cancer growth; the mechanisms underlying this association are poorly understood. This study evaluated the hypothesis that obesity, rather than high-fat diet, is responsible for accelerated pancreatic cancer growth.

Methods

Male C57BL/6J mice were studied after 19?weeks of high-fat (60?% fat; n?=?20) or low-fat (10?% fat; n?=?10) diet and 5?weeks of Pan02 murine pancreatic cancer growth (flank).

Results

By two-way ANOVA, diet did not (p?=?0.58), but body weight, significantly influenced tumor weight (p?=?0.01). Tumor weight correlated positively with body weight (R ²?=?0.562; p?<?0.001). Tumors in overweight mice were twice as large as those growing in lean mice (1.2?±?0.2?g vs. 0.6?±?.01?g, p?<?0.01), had significantly fewer apoptotic cells than those in lean mice (0.8?±?0.4 vs 2.4?±?0.5; p?<?0.05), and greater adipocyte volume (3.7 vs. 2.2?%, p?<?0.05). Apoptosis (R ²?=?0.472; p?=?0.008) and serum adiponectin correlated negatively with tumor weight (R?=?0.45; p?<?0.05).

Conclusions

These data suggest that body weight, and not high-fat diet, is responsible for accelerated murine pancreatic cancer growth observed in this model of diet-induced obesity. Decreased tumor apoptosis appears to play an important mechanistic role in this process. The concept that decreased apoptosis is potentiated by hypoadiponectinemia (seen in obesity) deserves further investigation.     

Serum copeptin levels in adolescents with primary hypertension

Background

The prevalence of hypertension continues to rise in the pediatric population. In recent years, there has been an increasing amount of reports on serum arginine vasopressin and its derivative, copeptin, in blood pressure control, but its role is still unclear. The objective of this study was to assess serum copeptin in adolescents with essential hypertension.

Methods

The study cohort consisted of 84 subjects (30 girls and 54 boys) aged 11–18 years, divided into two groups: hypertension (HT) – 53 subjects with confirmed primary hypertension and R - reference group – 31 subjects in whom hypertension was excluded on the basis of ambulatory blood pressure monitoring (ABPM) (white-coat hypertension). Serum copeptin concentration was measured using a commercially available enzyme-linked immunosorbent assay kit (USCN).

Results

Hypertensive patients had higher serum copeptin levels (median, 267 [Q1–Q3: 151.1–499.7 pg/ml]) than controls (median, 107.3 [Q1–Q3: 36.7–203.4 pg/ml]), (p?<?0.01). Statistically significant difference was found both in males and females. In both groups, positive correlations between serum copeptin and uric acid levels (r?=?0.31, p?<?0.01), albuminuria (r?=?0.45, p?<?0.01), serum triglycerides (r?=?0.3, p?<?0.05), body mass index (BMI) standard deviation score (SDS) (r?=?0.24, p?<?0.05) and 24-h systolic blood pressure (SBP) (r?=?0.37, p?<?0.01) and diastolic blood pressure (DBP) (r?=?0.23, p?<?0.05) were found.

Conclusions

In summary, higher serum copeptin levels, a surrogate for arginine vasopressin (AVP) release, are associated not only with systolic and diastolic blood pressure but also with several components of metabolic syndrome including obesity, elevated concentration of triglycerides, albuminuria, and serum uric acid level. However, for the time being, more research is needed in order to confirm the role of serum copeptin as a novel marker of elevated blood pressure and predictor of metabolic syndrome.     

The impact of serum uric acid reduction on renal function and blood pressure in chronic kidney disease patients with hyperuricemia

Background

Febuxostat is tolerable in chronic kidney disease (CKD) patients with hyperuricemia. However, the long-term effect of lowering uric acid with febuxostat on renal function and blood pressure has not been elucidated.

Methods

This was a 2 years retrospective observational study. 86 CKD patients with hyperuricemia who continued with allopurinol (allopurinol group, n?=?30), switched from allopurinol to febuxostat (switched group, n?=?25), or were newly prescribed febuxostat (febuxostat group, n?=?31) were included in this study. Serum uric acid, estimated glomerular filtration rate (eGFR), blood pressure, and urinary protein were analyzed. Moreover, the impact of serum uric acid reduction on renal function and blood pressure was assessed.

Results

Serum uric acid in the switched and febuxostat groups was significantly reduced at 6 months (switched group; 8.49?±?1.32–7.19?±?1.14 mg/dL, p?<?0.0001, febuxostat group; 9.43?±?1.63–6.31?±?0.90 mg/dL, p?<?0.0001). In the allopurinol group, serum uric acid was increased (6.86?±?0.87–7.10?±?0.85 mg/dL, p?=?0.0213). eGFR was significantly increased (35.2?±?12.8–37.3?±?13.9 mL/min/1.73 m², p?=?0.0232), while mean arterial pressure (93.1?±?10.8–88.2?±?9.5 mmHg, p?=?0.0039) was significantly decreased at 6 months in the febuxostat group, resulting in the retention of eGFR for 2 years.

Conclusions

The impact of serum uric acid reduction might have beneficial effects on CKD progression and blood pressure. However, a large prospective study is needed to determine the long-term efficacy of febuxostat therapy in CKD patients with hyperuricemia.

     

Subclinical cardiovascular disease and its association with risk factors in children with steroid-resistant nephrotic syndrome

Background

The aim of this study was to evaluate the presence of subclinical cardiovascular disease (CVD) and its relation to risk factors in pediatric patients with steroid-resistant nephrotic syndrome (NS).

Methods

Thirty-seven patients with normal renal function were compared with 22 healthy controls regarding the presence of subclinical CVD. Measurements included aortic pulse wave velocity (PWV), carotid intima media thickness (IMT), and left ventricular mass (LVM). Patients were additionally assessed for blood pressure (BP) pattern and the presence of hypertension by 24-h ambulatory blood pressure monitoring.

Results

Compared with the controls, patients had significantly higher mean aortic PWV-standard deviation scores (SDS), mean carotid IMT-SDS, and LVM index (p?<?0.001 for all). Increased aortic PWV was noted in 5 % of patients, increased carotid IMT in 22 %, and increased LVM index in 19 %. Five patients (14 %) were hypertensive, and mean BP indexes, SDS, and BP loads during nighttime were significantly higher than those during daytime (p?<?0.001 for all). Multivariate analysis revealed a significant relationship between PWV-SDS and ferritin (R ²?=?0.269, p?=?0.006) and between carotid IMT-SDS and proteinuria (R ²?=?0.141, p?=?0.022). The LVM index was independently associated only with higher body mass index SDS (R ²?=?0.317, p?<?0.001). In addition, six patients (16 %) had multiple abnormal subclinical CVD markers, and increased subclinical CVD risk was independently associated only with higher low-density lipoprotein cholesterol (R ²?=?0.292, p?=?0.044).

Conclusions

Based on these results, steroid-resistant NS children generally are at high risk of cardiovascular complications, but the increased risk is likely to be multifactorial.     

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis

PurposeTo investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis.MethodsA retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI.ResultsThe level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h (p < 0.01). The ROC analysis showed the combined detection of urine IL-8, NGAL and KIM-1 at 12 h had a larger area under curve (AUC) than a single marker (0.997, 95% CI: 0.991–0.998), and the sensitivity and specificity were 98.2% and 96.7%, respectively. Pearson correlation analysis showed that the levels of urine NGAL at 4, 12, 24 and 48 h in AKI patients were positively correlated with the levels of urine KIM-1 and IL-18 (p < 0.01).ConclusionAKI could be quickly recognized by the elevated level of urine IL-8, NGAL and KIM-1 in patients with URL-related urosepsis. Combined detection of the three urine biomarkers at 12 h after surgery had a better diagnostic performance, which may be an important reference for the early diagnosis of AKI.     

Uric acid-lowering and renoprotective effects of topiroxostat,a selective xanthine oxidoreductase inhibitor,in patients with diabetic nephropathy and hyperuricemia: a randomized,double-blind,placebo-controlled,parallel-group study (UPWARD study)

Background

Hyperuricemia is supposed to be an independent risk factor for kidney dysfunction in diabetic patients. We attempted to examine the uric acid-lowering effect and the renoprotective effect of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia in this pilot study.

Methods

The study design was randomized, double-blind, placebo-controlled, parallel-group study. A total of 65 patients with hyperuricemia and diabetic nephropathy with microalbuminuria were enrolled and assigned to either the topiroxostat group or the placebo group. Topiroxostat (stepwise dosing from 40 to 160 mg/day) or matching placebo was administered BID for 28 weeks. The primary endpoint was a change in the urinary albumin-to-creatinine ratio in the first-morning-void urine sample. Secondary endpoints were changes in the estimated glomerular filtration rate and the serum uric acid level.

Results

At 28 weeks, there was no significant difference in the percent change from baseline in the urinary albumin-to-creatinine ratio between the two groups (topiroxostat: 0 vs. placebo: 17%, p?=?0.3206), but the changes in the estimated glomerular filtration rate (? 0.2 vs. ? 4.0 mL/min/1.73 m², p?=?0.0303) and the serum uric acid level (? 2.94 vs. ? 0.20 mg/dL, p?<?0.0001) were significantly different between the topiroxostat and placebo groups. Gouty arthritis occurred in 1 patient in the placebo group and no patients in the topiroxostat group.

Conclusion

These findings support that diabetic nephropathy combined with hyperuricemia may be associated with kidney dysfunctions. Topiroxostat provides strict control of the serum uric acid level preventing decline of eGFR in these patients.

     

Renal calcium, phosphorus, magnesium and uric acid handling: comparison between stage III chronic kidney disease patients and healthy oldest old

Introduction

It is known that chronic kidney disease (CKD) and senescence bring about a progressive reduction in glomerular filtration rate (GFR) and that in the former this is usually associated with an increase in the fractional excretion of calcium, phosphorus, magnesium, and uric acid. However, it has not yet been explained how these substances are excreted in the healthy oldest old. Thus, in the present study, we examined the renal handling of these substances in very aged people in comparison with CKD patients with similar GFR levels (stage III??CKD).

Materials and methods

Twenty volunteers were studied; 10 of them were healthy very old (VO) (??75?years old) individuals and 10 were stage III CKD patients. Exclusion criteria were as follows: presence of altered (abnormally high or low) plasma calcium, phosphorus, magnesium and uric acid, as well as previous diagnoses of diabetes mellitus and obstructive uropathy and use of drugs that could alter plasma levels of the studied substances. All volunteers were on a diet with the same content of these elements (3-day dietary register). We measured calcium, phosphorus, magnesium, uric acid, creatinine in serum plasma and morning urine, as well as serum parathyroid hormone level, in each volunteer. From these data, fractional excretion (FE) of these substances was obtained. A statistical analysis was carried out using the Wilcoxon test.

Results

Serum creatinine: 1.8?±?0.4?mg/dl (CKD) versus 0.8?±?0.2?mg/dl (VO), p?=?0.0002; serum calcium: 9.1?±?0.3?mg/dl (CKD) versus 8.7?±?0.4 (VO), p?=?0.022; serum magnesium: 2.3?±?0.2?mg/dl (CKD) versus 2.0?±?0.1 (VO), p?=?0.05; serum phosphorus: 3.9?±?0.5?mg/dl (CKD) versus 3.0?±?0.4?mg/dl (VO), p?=?0.002; serum uric acid: 6.6?±?1.5 (CKD) versus 5.2?±?1.4?mg/dl (VO), p?=?0.04; FE of calcium: 2.5?±?1?% (CKD) versus 0.8?±?0.3?% (VO), p?=?0.04; FE of magnesium: 7.2?±?4.1?% (CKD) versus 2.9?±?0.9?% (VO), p?=?0.02; FE of phosphorus: 25?±?9?% (CKD) versus 9.1?±?5.7(VO), p?=?0.001; FE of uric acid: 10?±?3?% (CKD) versus 8?±?5?% (VO), p?=?0.05.

Conclusion

Serum levels and FE of calcium, phosphorus, magnesium and uric acid were significantly higher in CKD patients compared to healthy very old people with similar GFR, except for serum magnesium and FE of uric acid, which were similar in both groups.     

Novel urinary tubular injury markers reveal an evidence of underlying kidney injury in children with reduced left ventricular systolic function: a pilot study

Background

Evolving data suggest tubular injury markers (TIM) to be diagnostic and prognostic biomarkers of kidney injury in adults with chronic cardiac dysfunction. Such data are not well delineated in asymptomatic children with cardiomyopathy. This study sought to evaluate kidney involvement in children with left ventricular (LV) systolic dysfunction.

Methods

We conducted a cross-sectional case–control study in 61 asymptomatic children (aged 1.7–21.9 years) with dilated cardiomyopathy (DCM) and LV ejection fraction (LVEF)?<?55 %. Routine conventional kidney function markers and the following urinary TIM were measured: KIM-1, IL-18, neutrophil gelatinase-associated lipocalin (NGAL), and L-FABP. Characteristics and TIM data of cases were compared with those of 61 age- and gender-matched healthy controls.

Results

Children with DCM had higher TIM concentrations compared with controls for IL-18 (28.2 pg/mg, IQR [15.9–42.5] vs19.0 [12.6–28.6], p?<?0.001), NGAL (13.2 ng/mg [6.5–44.3] vs 8.3 [3.1–17.5], p?=?0.01), and KIM-1 (386 pg/mg (248–597) vs 307 [182–432], p?=?0.02). All conventional kidney function markers were within normal limits in the DCM cohort. A combined model using cut-off values of KIM-1?≥?235, IL-18?≥?17.5, and (BNP)?>?15 pg/ml resulted in distinction between patients with mildly depressed LV (55?>?LVEF?≥?45) and those with LVEF?<?45 %. The sensitivity of this model was ≥80 % when any of the cut-off values was met and specificity 83 % when all cut-off values were met.

Conclusions

Our data suggest that asymptomatic children with LVEF?<?55 % might have subclinical kidney injury that cannot be detected with conventional kidney function markers. TIM in conjunction with other cardiac function markers may be utilized to distinguish asymptomatic children with DCM and moderate or worse LV dysfunction (LFEV?<?45 %) from those with mild LV dysfunction (55?>?LVEF?≥?45 %).

     

Physical activity, calcium intake and childhood bone mineral: a population-based cross-sectional study

Summary

In a free-living cohort of 4-year old children, mean daily time in moderate?Cvigorous physical activity and daily calcium intake at 3?years, were positively related to hip bone size and density. Relationships between physical activity and bone indices were stronger when calcium intake was above compared with below median (966?mg/day).

Introduction

We examined the cross-sectional relationships between childhood physical activity, dietary calcium intake and bone size and density.

Methods

Children aged 4?years were recruited from the Southampton Women's Survey. They underwent measurement of bone mass by DXA (Hologic Discovery). Physical activity was assessed by accelerometry (Actiheart, Cambridge Neurotechnology Ltd, Cambridge, UK) for seven continuous days.

Results

Four hundred twenty-two children (212 boys) participated. In a cross-sectional analysis, after adjusting for gender, daily mean time(minutes per day) spent in moderate to very vigorous activity (MVPA) was positively related to hip BA (R ²?=?3%, p?<?0.001), BMC (R ²?=?4%, p?<?0.001), aBMD (R ²?=?3%, p?=?0.001) and estimated vBMD (R ²?=?2%, p?=?0.01), but not height (r _s?=?0.04, p?=?0.42) or weight (r _s?=?0.01, p?=?0.76). Mean daily calcium intake (assessed at 3?years old) positively predicted bone indices in those with a calcium intake below the median (966?mg/day), but there was a much attenuated relationship in those above this. These associations persisted after inclusion of total energy, protein and phosphorus in multivariate models. The relationships between MVPA and bone indices were stronger in children with calcium intakes above the median. Thus, for aBMD, the variance explained by MVPA when daily calcium intake was below the median was 2% (p?=?0.1) and above median was 6% (p?=?0.001).

Conclusions

These results support the notion that adequate calcium intake may be required for optimal action of physical activity on bone development and that improving levels of physical activity and calcium intake in childhood may help to optimise accrual of bone mass.     

α-Fetoprotein-to-Total Tumor Volume Ratio Predicts Post-operative Tumor Recurrence in Hepatocellular Carcinoma

Background/Aims

Serum α-fetoprotein (AFP) and total tumor volume (TTV) are important factors linked with post-operative tumor recurrence in hepatocellular carcinoma (HCC) patients. We investigated the role of a new prognostic marker, AFP-to-TTV ratio, in predicting HCC recurrence.

Methods

A total of 655 HCC patients undergoing resection were analyzed.

Results

In the multivariate logistic model, serum AFP level [odds ratio (OR) 32.459, p?=?0.012] and TTV (OR 0.006, p?=?0.01) were independently associated with a higher AFT/TTV ratio. The 1-, 3-, and 5-year tumor recurrence rates were 29 %, 55 %, and 68 %, respectively. In the Cox proportional hazards model, alcoholism (hazard ratio [HR], 1.354, p?=?0.028), international normalized ratio of prothrombin time ≥1.01 (HR, 1.349, p?<?0.001), multiple nodules (HR, 1.381, p?=?0.004), main tumor diameter ≥4?cm (HR, 1.535, p?=?0.001), macrovascular invasion (HR, 1.362, p?=?0.016), and AFP/TTV ratio ≥1.5 (HR, 1.49, p?<?0.001) were independently associated with tumor recurrence. In subgroup analysis, a higher AFP/TTV ratio was significantly associated with tumor recurrence in patients characterized by macrovascular invasion, TTV?≥?40 cm³, or main tumor diameter ≥4cm (all p?=?0.001).

Conclusion

The AFP/TTV ratio, a newly proposed marker for predicting post-operative tumor recurrence in HCC, is a feasible surrogate and may be useful in selecting super-high-risk patients for tumor recurrence.     

Fibroblast growth factor 21 (FGF21) and bone: is there a relationship in humans?

Summary

In animals, high fibroblast growth factor 21 (FGF21) states improve insulin resistance but induce bone loss. Whether FGF21 relates to bone mineral density (BMD) is unknown in humans. Contrary to prediction from animal findings, we found higher FGF21 levels associating with greater BMD in women, independent of age and body composition.

Introduction

Recent laboratory studies suggest that FGF21 is involved in reciprocal regulation of bone and energy homeostasis. Systemic administration of FGF21 protects animals from obesity and diabetes but causes severe bone loss, smothering the enthusiasm over FGF21 as a potential antiobesity therapeutic. To date, there is no information on whether FGF21 relates to BMD in humans. We thus studied the relationship between plasma FGF21 levels and BMD in healthy adults.

Methods

Fasting plasma FGF21 levels were measured by enzyme-linked immunosorbent assay and body composition by dual-energy X-ray absorptiometry.

Results

Among 40 healthy volunteers (age 32?±?10 year, 16 women), men had significantly higher lean body mass (p?<?0.01) and total BMD (p?<?0.05), and lower percent body fat than women (p?<?0.01). Median plasma FGF21 levels were not different between the sexes. While there was no association between FGF21 concentrations and body composition in men, FGF21 levels correlated positively with fat mass (p?<?0.01) in women. In men, no significant correlation between FGF21 with BMD was observed. However, in women, FGF21 correlated positively with total BMD (R ²?=?0.69, p?=?0.003) and spine BMD (R ²?=?0.76, p?=?0.001); the correlation remained significant after adjusting for age, ethnicity, and body composition.

Conclusions

This study reveals for the first time a strong positive association between plasma FGF21 levels and BMD in healthy women, suggesting the association between bone loss and high FGF21 states in animals may not be directly translated to humans in physiologic states. We hypothesize that FGF21 may increase bone mass particularly in women through paracrine mechanisms in the bone–adipose interface.     

Kinematic factors affecting postoperative knee flexion after cruciate-retaining total knee arthroplasty

Purpose

The purpose of this study was to investigate kinematic factors affecting postoperative knee flexion after cruciate-retaining (CR) total knee arthroplasty (TKA) by analysing pre- and postoperative knee kinematics.

Methods

We retrospectively analysed 58 patients with osteoarthritis who received the same implant series. Pre- and postoperative kinematics were measured intraoperatively using a navigation system. As a clinical outcome, we measured the knee flexion angle before and one year after surgery. Correlations among pre- and postoperative kinematics and postoperative flexion were analysed using simple linear regression analyses.

Results

Preoperative knee kinematics, including tibial internal rotation and anterior translation (R?=?0.87, P?<?0.001; R?=?0.53, P?<?0.001, respectively), were significantly correlated with postoperative kinematics. Preoperative varus–valgus movements improved significantly postoperatively; however, tibial internal rotation remained unchanged. Furthermore, postoperative knee flexion angle was significantly correlated with postoperative tibial internal rotation (R?=?0.45, P?<?0.001).

Conclusions

Preoperative knee kinematics were unchanged even after CR-TKA. Postoperative tibial internal rotation is one of the most important factors affecting postoperative knee flexion.     

Histomorphometric changes by teriparatide in alendronate-pretreated women with osteoporosis

Summary

The level of increased bone formation after 24 months of treatment with teriparatide (rhPTH (1–34), TPTD) is similar in patients who were either treatment-naïve (TN) or had lower bone turnover initially due to previous alendronate (ALN) therapy.

Introduction

Bone anabolic effects of TPTD in postmenopausal women with osteoporosis may be blunted during the initial phase after switching from ALN to TPTD. To explore the long-term implications, we examined histomorphometric and biochemical markers of bone turnover of patients on TPTD therapy after long-term ALN treatment.

Methods

Paired biopsies were obtained after tetracycline double labeling at baseline and after 24 months of TPTD treatment from 29 ALN-pretreated (64.5?±?16.4 months) and 16 TN patients. Biochemical markers were measured at baseline, during the treatment, or at study end.

Results

Compared with the baseline, after 24-month TPTD, activation frequency (Ac.F.) and osteoid surface (OS) increased in both groups: 0.11–0.34 cycles per year, 3.96–9.8% in the ALN-pretreated group and 0.19–0.33 cycles per year, 6.2–11.3% (p?<?0.05) in the TN group, respectively. Biochemical and histomorphometric markers correlated positively both at baseline and endpoint. Serum amino terminal propeptide of type I procollagen (PINP) correlated with Ac.F. (r?=?0.57, p?<?0.001 and r?=?0.48, p?<?0.01) and OS (r?=?0.51, p?<?0.01 and r?=?0.56, p?<?0.01) at baseline and endpoint, respectively. Following 3 months of treatment, increases in biochemical markers like PINP predicted the increase in Ac.F. (r?=?0.52, p?<?0.01) and OS (r?=?0.54, p?<?0.01) after 24 months.

Conclusions

The increased level of formation is similar in patients who were either TN or had lower bone turnover initially due to previous ALN therapy. Elevated bone formation in postmenopausal women with osteoporosis was sustained over a 24-month period by TPTD. Biochemical markers of bone formation are a good surrogate for the assessment of TPTD effects.     

Sugammadex Allows Fast-Track Bariatric Surgery

Background

Morbidly obese (MO) patients are at increased risk for postoperative anesthesia-related complications. We evaluated the role of sugammadex versus neostigmine in the quality of recovery from profound rocuronium-induced neuromuscular blockade (NMB) in patients with morbid obesity.

Methods

We studied 40 female MO patients who received desflurane and remifentanil anesthesia for laparoscopic removal of adjustable gastric banding. NMB was achieved with rocuronium. At the end of the surgical procedure, complete reversal of NMB was obtained with sugammadex (SUG group, n?=?20) or neostigmine plus atropine (NEO group, n?=?20) in the presence of profound NMB.

Results

No difference in surgical time or anesthetic drugs was found between the groups. Anesthesia time was significantly greater in the NEO group than in the SUG group (95?±?21 vs. 47.9?±?6.4 min, p?<?0.0001), which was mainly due to a longer time to reach a train-of-four ratio (TOFR)?≥?0.9 in the NEO group (48.6?±?18 vs. 3.1?±?1.3 min, p?<?0.0001) during reversal of profound NMB. Upon admission to the postanesthesia care unit, level of SpO₂ (p?=?0.018), TOFR (p?<?0.0001), ability to swallow (p?=?0.0027), and ability to get into bed independently (p?=?0.022) were better in the SUG group than in the NEO group. Patients in the SUG group were discharged to the surgical ward earlier than patients in the NEO group were (p?=?0.013).

Conclusions

Sugammadex allowed a safer and faster recovery from profound rocuronium-induced NMB than neostigmine did in patients with MO. Sugammadex may play an important role in fast-track bariatric anesthesia     

Resection for Hilar Cholangiocarcinoma: Analysis of Prognostic Factors and the Impact of Systemic Inflammation on Long-term Outcome

Introduction

Resection for hilar cholangiocarcinoma is the single hope for long-term survival.

Methods

Ninety patients underwent curative intent surgery for hilar cholangiocarcinoma between 1996 and 2012. The potential prognostic factors were assessed by univariate (Kaplan–Meier curves and log-rank test) and multivariate analyses (Cox proportional hazards model).

Results

The median overall and disease-free survivals were 26 and 17 months, respectively. The multivariate analysis identified R0 resection (HR?=?0.03, 95 % CI 0–0.19, p?<?0.001), caudate lobe invasion (HR?=?6.33, 95 % CI 1.31–30.46, p?=?0.021), adjuvant gemcitabine-based chemotherapy (HR?=?0.38, 95 % CI 0.15–0.94, p?=?0.037), and the neutrophil-to-lymphocyte ratio (HR?=?0.78, 95 % CI 0.62–0.98, p?=?0.036) as independent prognostic factors for disease-free survival. The independent prognostic factors for overall survival were R0 resection (HR?=?0.03, 95 % CI 0–0.22, p?<?0.001), caudate lobe invasion (HR?=?11.75, 95 % CI 1.65–83.33, p?=?0.014), and adjuvant gemcitabine-based chemotherapy (HR?=?0.19, 95 % CI 0.06–0.56, p?=?0.003).

Conclusions

The negative resection margin represents the most important prognostic factor. Adjuvant gemcitabine-based chemotherapy appears to benefit survival. The neutrophil-to-lymphocyte ratio may potentially be used to stratify patients for future clinical trials.     

Skeletal health in adult patients with classic galactosemia

Summary

This study evaluated bone health in adults with galactosemia. Associations between bone mineral density (BMD) and nutritional and biochemical variables were explored. Calcium level predicted hip and spine BMD, and gonadotropin levels were inversely associated with spinal BMD in women. These results afford insights into management strategies for these patients.

Introduction

Bone loss is a complication of galactosemia. Dietary restriction, primary ovarian insufficiency in women, and disease-related alterations of bone metabolism may contribute. This study examined relationships between clinical factors and BMD in patients with galactosemia.

Methods

This cross-sectional sample included 33 adults (16 women) with classic galactosemia, mean age 32.0?±?11.8 years. BMD was measured by dual-energy X-ray absorptiometry, and was correlated with age, height, weight, fractures, nutritional factors, hormonal status, and bone biomarkers.

Results

There was a significant difference in hip BMD between women and men (0.799 vs. 0.896 g/cm², p?=?0.014). The percentage of subjects with BMD-Z <?2.0 was also greater for women than men [33 vs. 18 % (spine), 27 vs. 6 % (hip)], and more women reported sustaining fractures. Bivariate analyses yielded correlations between BMI and BMD-Z [at the hip in women (r?=?0.58, p?<?0.05) and spine in men (r?=?0.53, p?<?0.05)]. In women, weight was also correlated with BMD-Z (r?=?0.57, p?<?0.05 at hip), and C-telopeptides (r?=??0.59 at spine and ?0.63 hip, p?<?0.05) and osteocalcin (r?=??0.71 at spine and ?0.72 hip, p?<?0.05) were inversely correlated with BMD-Z. In final regression models, higher gonadotropin levels were associated with lower spinal BMD in women (p?=?0.017); serum calcium was a significant predictor of hip (p?=?0.014) and spine (p?=?0.013) BMD in both sexes.

Conclusions

Bone density in adults with galactosemia is low, indicating the potential for increased fracture risk, the etiology of which appears to be multifactorial.     

Liver Resection in the Elderly: Significance of Comorbidities and Blood Loss

Objective

Liver resection is increasingly performed in elderly patients who are suspected of increased postoperative morbidity (PM) and reduced overall survival (OS). Patient selection based on the identification of age-adjusted risk factors may help to decrease PM and OS.

Design and Participants

Prospectively collected data of 879 patients undergoing elective hepatic resection were analyzed. This population was stratified into three age cohorts: >70 years (n?=?228; 26 %), 60–69 years (n?=?309; 35 %), and <60 years (n?=?342; 39 %). Multivariate survival analysis was performed.

Results

The incidence of severe (p?<?0.01) and non-surgical (p?<?0.001) postoperative complications was higher in older compared to younger patients. Major estimated blood loss (EBL; p?=?0.039) and comorbidities (p?=?0.002) independently increased PM. EBL was comparable between all age cohorts. However, preexisting comorbidities, major EBL, and postoperative complications markedly decreased OS in contrast to younger patients. Adjusted for age, independent predictors of OS were comorbidities (HR?=?1.51; p?=?0.001), major hepatectomy (HR?=?1.33; p?=?0.025), increased EBL (HR?=?1.32; p?=?0.031), and postoperative complications (HR?=?1.64; p?<?0.001).

Conclusion

Although increased age should not be a contraindication for liver resection, this study accents the avoidance of major blood loss in elderly patients and a stringent patient selection based on preexisting comorbidities.     

Complications and outcome after laparoscopic bariatric surgery: LAGB versus LRYGB

Background and aims

Unsatisfactory patient compliance and unfavorable results of weight loss let centers prefer the Roux-en-Y gastric bypass (RYGB) as a combined restrictive and malabsorptive procedure. The aim of this study was to evaluate results of laparoscopic adjustable gastric banding (LAGB) versus laparoscopic RYGB.

Setting

The study was conducted at Centre Hospitalier Emil Mayrisch Clinic for specialized care (n?=?618 beds) in Luxembourg (South).

Materials and methods

Of 620 procedures, 204 patients had LAGB and 416 LRYGB. Short-term (t ₁, 6?months to 2?years), middle-term (t₂, 2 to 5?years), and long-term follow-up (t ₃, >5?years) were performed, including weight loss evolution, Bariatric Analysis, and Reporting Outcome System (BAROS).

Results

Percent EBWL mean values for LAGB vs. LRYGB were at t ₁ 64.3 vs. 79.5, p?=?0.01; at t ₂ 49.4 vs. 91, p?<?0.0001; and at t₃ 52.6 vs. 79.9, p?<?0.0001. The BAROS mean values were at t ₁ 3.81 vs. 4.00, p?=?0.183; at t ₂ 3.57 vs. 4.12, p?<?0.001; and at t ₃ 3.71 vs. 4.04, p?=?0.02. Major complication rate (<30?days) was similar (p?=?0.601). Long-term (>30?days) complications were more common after LAGB (14.3 versus 3.6?%, p?<?0.001). Fifty patients (25?%) required a second and 36 patients (18?%) a third operation (LRYGB).

Conclusion

The significant difference in %EBWL and BAROS and late adverse events with high re-operation rates in LAGB made the LRYGB more attractive.