Validation of the revised Schwartz estimating equation in a predominantly non-CKD population

Recently, Schwartz et al. (J Am Soc Nephrol 20:629–637, 2009) used data from the National Institutes of Health-funded Chronic Kidney Disease in Children (CKiD) study to generate new equations for estimating the glomerular filtration rate (eGFR), including an update of the commonly used bedside equation. However, it is unclear if the equation can be generalized to a broader pediatric population. We have used the updated equation on a sample of pediatric patients with less impaired renal function to evaluate the correlation between the new Schwartz equation and measured GFR by iothalamate clearance. We retrospectively analyzed 738 iothalamate clearance tests from 503 patients with a mean serum creatinine of 0.50 mg/dl whose ages ranged from 1 to 16 years. We measured bias, precision, and accuracy and performed a Bland–Altman plot to determine the measure of agreement between the two methods. The mean GFR by iothalamate clearance was 110.6 ml/min/1.73 m² and by the new Schwartz estimation 104.7 ml/min/1.73 m². The mean difference was 5.84 ml/min/1.73 m² (95% CI 4.00–7.67). The newly purposed bedside Schwartz equation therefore demonstrated good agreement with the iothalamate renal clearances in our patient population and appears to be a valid bedside estimating equation for GFR in this sample of children.     

Failure of Mesenteric Defect Closure After Roux-en-Y Gastric Bypass

Background and Objectives:

Bowel obstructions following Roux-en-Y gastric bypass (RYGB) are a significant issue often caused by internal herniation. Controversy continues as to whether mesenteric defect closure is necessary to decrease the incidence of internal hernias after RYGB. Our purpose was to evaluate the effectiveness of closing the mesenteric defect at the jejunojejunostomy in patients who underwent RYGB by examining this potential space at reoperation for any reason.

Methods:

We retrospectively reviewed medical records of patients undergoing surgery after RYGB from August 1999 to October 2008 to determine the status of the mesentery at the jejunojejunostomy.

Results:

Eighteen patients underwent surgery 2 to 19 months after open (n=8) or laparoscopic (n=10) RYGB. All patients had documented suture closure of their jejunojejunostomy at the time of RYGB. Permanent (n=12) or absorbable (n=6) sutures were used for closures. Patients lost 23.6kg to 62.1kg before a reoperation was required for a ventral hernia (n=8), cholecystectomy (n=4), abdominal pain (n=4), or small bowel obstruction (n=2). Fifteen of the 18 patients had open mesenteric defects at the jejunojejunostomy despite previous closure; none were the cause for reoperation.

Conclusion:

Routine suture closure of mesenteric defects after RYGB may not be an effective permanent closure likely due to the extensive fat loss and weight loss within the mesentery.     

Interaction of an idealized cavopulmonary circulation with mechanical circulatory assist using an intravascular rotary blood pump

This study evaluated the performance of an intravascular, percutaneously-inserted, axial flow blood pump in an idealized total cavopulmonary connection (TCPC) model of a Fontan physiology. This blood pump, intended for placement in the inferior vena cava (IVC), is designed to augment pressure and blood flow from the IVC to the pulmonary circulation. Three different computational models were examined: (i) an idealized TCPC without a pump; (ii) an idealized TCPC with an impeller pump; and (iii) an idealized TCPC with an impeller and diffuser pump. Computational fluid dynamics analyses of these models were performed to assess the hydraulic performance of each model under varying physiologic conditions. Pressure-flow characteristics, fluid streamlines, energy augmentation calculations, and blood damage analyses were evaluated. Numerical predictions indicate that the pump with an impeller and diffuser blade set produces pressure generations of 1 to 16 mm Hg for rotational speeds of 2000 to 6000 rpm and flow rates of 1 to 4 L/min. In contrast, for the same flow range, the model with the impeller only in the IVC demonstrated pressure generations of 1 to 9 mm Hg at rotational speeds of 10,000 to 12,000 rpm. Influence of blood viscosity was found to be insignificant at low rotational speeds with minimal performance deviation at higher rotational speeds. Results from the blood damage index analyses indicate a low probability for damage with maximum damage index levels less than 1% and maximum fluid residence times below 0.6 s. The numerical predictions further indicated successful energy augmentation of the TCPC with a pump in the IVC. These results support the continued design and development of this cavopulmonary assist device.     

Predicting fractures in an international cohort using risk factor algorithms without BMD

Clinical risk factors are associated with increased probability of fracture in postmenopausal women. We sought to compare prediction models using self‐reported clinical risk factors, excluding BMD, to predict incident fracture among postmenopausal women. The GLOW study enrolled women aged 55 years or older from 723 primary‐care practices in 10 countries. The population comprised 19,586 women aged 60 years or older who were not receiving antiosteoporosis medication and were followed annually for 2 years. Self‐administered questionnaires were used to collect data on characteristics, fracture risk factors, previous fractures, and health status. The main outcome measure compares the C index for models using the WHO Fracture Risk (FRAX), the Garvan Fracture Risk Calculator (FRC), and a simple model using age and prior fracture. Over 2 years, 880 women reported incident fractures including 69 hip fractures, 468 “major fractures” (as defined by FRAX), and 583 “osteoporotic fractures” (as defined by FRC). Using baseline clinical risk factors, both FRAX and FRC showed a moderate ability to correctly order hip fracture times (C index for hip fracture 0.78 and 0.76, respectively). C indices for “major” and “osteoporotic” fractures showed lower values, at 0.61 and 0.64. Neither algorithm was better than the model based on age + fracture history alone (C index for hip fracture 0.78). In conclusion, estimation of fracture risk in an international primary‐care population of postmenopausal women can be made using clinical risk factors alone without BMD. However, more sophisticated models incorporating multiple clinical risk factors including falls were not superior to more parsimonious models in predicting future fracture in this population. © 2011 American Society for Bone and Mineral Research     

Impact of Routine Cavity Shave Margins on Breast Cancer Re-excision Rates

Purpose

Breast-conserving therapy (BCT) is an accepted method of treating early breast cancer. We hypothesized that routine excision of additional cavity shave margins (CSM) at time of initial partial mastectomy reduces the need for additional surgery.

Methods

A single-institution retrospective review was performed of women, 18 years or older, with a new diagnosis of breast cancer who underwent partial mastectomy between 1 January 2004 and 1 October 2009. Five hundred thirty-three charts were reviewed. Of those, 69 patients underwent CSM at time of initial operation. These 69 patients were matched with patients who had undergone partial mastectomy without CSM by tumor size, presence of extensive intraductal component, and primary histology.

Results

The two groups were well matched for age, nuclear grade, associated lymphovascular invasion (LVI), receptor status, and multifocality. We found that 31.9% (44/138) required return to the operating room (OR) for re-excision of margins. Rate of return to the OR was 21.7% (15/69) in the CSM group and 42.0% (29/69) in the matched group (p = 0.011). Multivariate analysis found factors significantly associated with need for additional operation included lack of CSM (odds ratio 9.2, 95% CI 2.8–30.5, p = 0.0003), larger extent of intraductal component (odds ratio 7.0, 95% CI 1.8–27.0, p = 0.005), and lack of directed re-excision (odds ratio 6.4, 95% CI 1.7–25.1, p = 0.007).

Conclusions

CSM at time of initial partial mastectomy decreases rate of re-excision by as much as ninefold. CSM should be considered at time of initial operation to reduce the need for subsequent reoperation.     

Causative agents of osteomyelitis induce death domain-containing TNF-related apoptosis-inducing ligand receptor expression on osteoblasts

Bacteria and their products are potent inducers of bone destruction. While inflammatory damage during conditions such as osteomyelitis is associated with increased formation and activity of bone-resorbing osteoclasts, it is likely that bone loss also results from the elimination of the cells responsible for matrix deposition. Consistent with this notion, we have previously demonstrated that bone-forming osteoblasts undergo apoptosis following bacterial challenge and that this cell death is due, at least in part, to the actions of TNF-related apoptosis-inducing ligand (TRAIL). In the present study, we demonstrate that primary osteoblasts constitutively express death domain containing TRAIL receptors. Importantly, we show that cell surface expression of the death-inducing receptors DR4 and DR5 on murine and human osteoblasts is restricted to cells infected with the principle causative agents of osteomyelitis, Staphylococcus aureus and Salmonella. In addition, we show that the robust constitutive production by osteoblasts of the decoy TRAIL receptor, OPG, is inhibited following bacterial infection. Finally, we report that while exogenous administration of TRAIL fails to activate apoptosis signaling pathways in uninfected osteoblasts, acute bacterial exposure sensitizes these cells to this ligand. Based upon these findings we suggest a model in which bacterially challenged osteoblasts express TRAIL while concomitantly decreasing the production of the decoy receptor OPG and upregulating cell surface death receptor expression. Such an increase in TRAIL bioavailability and induced sensitivity of infected osteoblasts to this ligand would result in apoptotic cell death of this bone-forming population, providing an additional mechanism underlying inflammatory bone loss during diseases such as osteomyelitis.     

Differential effects of advanced glycation end-products on renal tubular cell inflammation

Aim: The authors recently showed that advanced glycation end‐products (AGE) in the form of glycated albumin (GA) upregulated renal tubular expression of interleukin (IL)‐8 and soluble intercellular adhesion molecule‐1 (sICAM‐1), but not other important cytokines known to mediate diabetic nephropathy. This implies that other molecules such as the carbonyl intermediates of AGE or other modified protein lysine‐albumin may participate in diabetic tubular injury. Methods: Human proximal tubular epithelial cells (PTEC) were growth‐arrested and exposed to methylglyoxal (MG), MG‐bovine serum albumin (BSA)‐AGE, carboxymethyllysine (CML)‐BSA, AGE‐BSA or BSA with or without prior addition of rosiglitazone that was previously shown to attenuate the pro‐inflammatory effect of GA alone. Results: MG‐BSA‐AGE and AGE‐BSA upregulated tubular expression of connective tissue growth factor (CTGF), transforming growth factor (TGF)‐β, and vascular endothelial growth factor (VEGF), whereas CML‐BSA stimulated expression of IL‐6, CCL‐2, CTGF, TGF‐β and VEGF. These AGE compounds also activated nuclear factor (NF)‐κB and their effects were attenuated by pre‐incubation with anti‐RAGE antibody. MG and BSA did not affect the expression of any of these molecules. Rosiglitazone did not affect the in vitro biological effects of MG, MG‐BSA‐AGE, AGE‐BSA or CML‐BSA on PTEC. Conclusion: AGE exhibit differential inflammatory and fibrotic effects on PTEC via RAGE activation and NF‐κB signal transduction. Rosiglitazone had no effect on these responses. Further investigations on compounds that nullify the downstream effects of these AGE are warranted.     

Patient access to transplantation with an Internet-identified live kidney donor: a survey of U.S. centers

BACKGROUND: To investigate legitimate transplantation in the United States with an Internet-identified live donor organ, from the patient's perspective, kidney centers were contacted by a researcher posing as an ideal patient and recipient pair seeking to find a center to perform their transplant. METHODS: Responses were obtained with fewer than three phone calls and within less than 2 wk from 100 of 206 UNOS listed centers; 42 pediatric or inactive centers were excluded. RESULTS: A total of 37% (76 of 100) indicated a willingness to consider such a transplant. Eight centers acknowledged having previously performed one, with 100% (8/8) of these indicating that they would still consider future participation. CONCLUSION: Large numbers of Internet-facilitated transplants are not yet being performed in the United States. Because it was possible to elicit a definite answer with 3 or fewer calls at only 49% of centers, we conclude that a significant proportion of centers are not providing easy access to potential donors and recipients. Agreeable centers were clustered geographically, suggesting that multiple factors may be influencing opinions. 100% of agreeable centers required their own standard evaluation of the donor and recipient and indicated that financial exchange between the pair was illegal. We conclude that Internet-based live donor kidney transplants are occurring and have received cautious acceptance at a significant number of legitimate centers. The utility of asking "How did the recipient-donor pair present to our institution" may no longer be relevant. We suggest that every pair seeking access to legitimate transplantation should undergo standardized evaluation with open acknowledgment of the relationship as a modifier.     

Profile and significance of emergency colonic resections

The objectives of this study are to define the distinguishing features between elective and emergency colonic surgery. The records of adult patients who underwent elective and emergent colonic resection over a 4-year period were retrospectively reviewed. Univariate analysis was performed to compare outcomes for elective and emergency procedures and multiple logistic regression analysis was performed to identify the significant predictors of outcome. Three hundred and thirty-eight elective and 147 emergency colonic resections were performed. Diverticular disease was most common in the emergency group (43.5% vs 14.2%, P = 0.001) whereas malignancy predominated in the elective group (56.2% vs 5.4%, P = 0.001). The emergency group accounted for 54.7 per cent and 79.3 per cent of the total morbidity and mortality. Emergency colonic surgery has distinctive features and significance. Emergency surgery for colonic obstruction and total/subtotal resection are associated with higher morbidity and mortality. Diverticular disease compares favorably to other pathologies in postoperative outcome.