Impact of Subclinical and Clinical Kidney Allograft Rejection Within 1 Year Posttransplantation Among Compatible Transplant With Steroid Withdrawal Protocol.

Early acute kidney rejection remains an important clinical issue. METHODS: The current study included 552 recipients who had 1-2 surveillance or indication biopsy within the 1 y posttransplant. We evaluated the impact of type of allograft inflammation on allograft outcome. They were divided into 5 groups: no inflammation (NI: 95), subclinical inflammation (SCI: 244), subclinical T cell-mediated rejection (TCMR) (SC-TCMR: 110), clinical TCMR (C-TCMR: 83), and antibody-mediated rejection (AMR: 20). Estimated glomerular filtration rate (eGFR) over time using linear mixed model, cumulative chronic allograft scores/interstitial fibrosis and tubular atrophy (IFTA) ≥2 at 12 mo, and survival estimates were compared between groups. RESULTS: The common types of rejections were C-TCMR (15%), SC-TCMR (19.9%), and AMR (3.6%) of patients. Eighteen of 20 patients with AMR had mixed rejection with TCMR. Key findings were as follows: (i) posttransplant renal function: eGFR was lower for patients with C-TCMR and AMR (P < 0.0001) compared with NI, SCI, and SC-TCMR groups. There was an increase in delta-creatinine from 3 to 12 mo and cumulative allograft chronicity scores at 12 mo (P < 0.001) according to the type of allograft inflammation. (ii) Allograft histology: the odds of IFTA ≥2 was higher for SC-TCMR (3.7 [1.3-10.4]; P = 0.04) but was not significant for C-TCMR (3.1 [1.0-9.4]; P = 0.26), and AMR (2.5 [0.5-12.8]; P = 0.84) compared with NI group, and (iii) graft loss: C-TCMR accounted for the largest number of graft losses and impending graft losses on long-term follow-up. Graft loss among patient with AMR was numerically higher but was not statistically significant. CONCLUSIONS: The type of kidney allograft inflammation predicted posttransplant eGFR, cumulative chronic allograft score/IFTA ≥2 at 12 mo, and graft loss.

Outcomes of Deceased Donor Kidney Transplantation Using Expanded Criteria Donor Kidneys Following Pulsatile Preservation.

Aim We compared the outcomes of transplanting expanded criteria donor (ECD) kidneys undergoing machine perfusion (MP) versus cold storage (CS). Material and methods Data on all expanded criteria deceased donor kidney transplants performed at the University of Pittsburgh Medical Center from January 2003 through December 2012 were collected from an in-house electronic repository. There were 78 patients in the MP group and 101 patients in the CS group. The majority of the ECD kidneys were imported from other organ procurement organizations: 69 of 73 in the MP group (94.5%, 5 from unknown sources); and 90 of 99 in the CS group (91%), 2 from an unknown source). Most of the patients in the MP group (77 of 78) received a combination of MP and static CS. MP was performed just prior to transplantation in all MP patients. We used descriptive statistics to characterize our sample. We used logistic regression analysis to model the binary outcome of delayed graft function (DGF; i.e., "yes/no") and Cox (proportional hazard) regression to model time until graft failure. The Kaplan-Meier product-limit method was used to estimate survival curves for graft and patient survival. Results A total of 179 transplants were done from ECD donors (MP, 78; CS, 101). The mean static cold storage time was 14 ± 4.1 hours and the mean machine perfusion time was 11.2 ± 6.3 hours in the MP group. The donor creatinine was higher (1.3 ± 0.6 mg/dl vs. 1.2 ± 0.4 mg/dl, p = 0.01) and the cold ischemia time was longer (28.9 ± 10 hours vs. 24 ± 7.9 hours, p = 0.0003) in the MP patients. There were no differences between the two groups in DGF rate (20.8% [MP] vs. 25.8% [CS], p = 0.46), six-year patient survival (74% [MP] vs. 63.2% [CS], p = 0.11), graft survival (64.3% [MP] vs. 51.5% [CS], p = 0.22), and serum creatinine levels (1.5 mg/dl vs. 1.5 mg/dl) on univariate analysis. On unadjusted analysis, MP subjects without DGF had longer graft survival compared to CS subjects with DGF (p < 0.0032) and MP subjects with DGF (p < 0.0005). MP subjects without DGF had longer death-censored graft survival compared to CS subjects with DGF (p < 0.0077) and MP subjects with DGF (p < 0.0016). However, on regression analysis, MP subjects had longer graft survival than CS subjects when DGF was not present. MP subjects without DGF had longer patient survival compared to CS subjects with DGF (p < 0.0289), on unadjusted analysis. MP subjects had a reduced risk of graft failure (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.17, 0.68) and death-censored graft failure (HR, 0.44; 95% CI, 0.19, 1.00), compared to CS subjects when DGF was not present. Conclusions Reduction of DGF rates for imported ECD kidneys is vital to optimize outcomes and increase their utilization. One strategy to decrease DGF rates may be to reduce static CS time during transportation, by utilizing a portable kidney perfusion machine.

The Impact of Early Clinical and Subclinical T Cell-mediated Rejection After Kidney Transplantation.

BACKGROUND: We investigated the effect of clinical and subclinical T cell-mediated rejection (C-TCMR and SC-TCMR) on allograft histology, function, and progression. METHODS: Adult kidney recipients with 2 protocol biopsies were divided into No-TCMR on biopsies (n = 104), SC-TCMR (n = 56), and C-TCMR (n = 32) in at least 1 biopsy. Chronicity (ci + ct + cg + cv) scores, renal function, and the burden of renal disease measured by area under the curve (serum creatinine, mg mo/dL) were compared. RESULTS: Baseline characteristics were similar except for mean donor age and Kidney Donor Profile index scores. Patients with C-TCMR had higher mean serum creatinine, lower mean estimated glomerular filtration rate, and higher area under the curve with 95% confidence interval (75.2 [67.7-82.7]) as opposed to patients with SC-TCMR and No-TCMR (58.3 [53.6-62.9], 65.1 [58.8-71.5]), P = 0.0004. Chronicity scores were higher at 3 months in C-TCMR (2.30 ± 1.58) compared with SC-TCMR (2.02 ± 1.42) and No-TCMR (1.31 ± 1.18), P = 0.0001 and also at 12 months. At last follow-up, 18.8% patients with C-TCMR had ≥50% decline in estimated glomerular filtration rate from 3 months compared with 7% and 1% among No-TCMR and SC-TCMR groups (P = 0.038). Multivariate analyses revealed higher odds of Δ-creatinine ≥ 0.5 mg/dL from 3 months to last follow-up for C-TCMR (3.39 [95% confidence interval, 1.25-9.20]) versus No-TCMR (P = 0.016). CONCLUSIONS: Kidney transplant recipients with C-/SC-TCMR have heightened early allograft chronicity and worse renal function compared with those with No-TCMR. Progressive renal dysfunction was noted among patients with C-TCMR as opposed to SC-TCMR and No-TCMR.

Triple confusion: An interesting case of proteinuria in pregnancy.

Pregnancy-related renal diseases are unique and need special attention, both for diagnosis and management. The major confounding factors for diagnosis are the physiological multiorgan changes that occur throughout the gestational period. Proper diagnosis of the renal disease is also important, given the impact of varied management options both on the maternal and fetal health. A young middle-aged female with a long-standing history of diabetes presented to the hospital with worsening proteinuria in her second trimester of pregnancy. Clinical history, examinations, and laboratory analysis did not give any clues for diagnosis of a specific disease entity. This led us to take the risk of renal biopsy for a tissue diagnosis. The odds of renal biopsy favored the management decision in her case, thereby avoiding the confusions prior to biopsy. The pathological diagnosis is a surprise though not a unique entity on its own (minimal change disease in pregnancy). The case illustrates the disparity of clinical presentations and the pathology in patients, and the importance of renal biopsy in pregnant patients in particular.

Biomechanical strain characteristics of soft tissue biceps tenodesis and bony tenodesis.

BACKGROUND: Biomechanical analysis of biceps tenodesis procedures has historically focused on load to failure models. Minimal data exists for the analysis of biomechanical strain properties of the biceps tendon in a sub-failure, physiologic cadaver model. HYPOTHESIS: Tendon strain characteristics are different between bony and soft tissue tenodesis surgery, and the soft tissue tenodesis procedure reproduces a strain pattern more similar to the native biceps tendon. METHODS: Eight fresh frozen cadaver upper extremities were mounted onto a custom device that controls shoulder abduction and rotation. Strain on the tendon was measured using a differential variable reluctance transducer as the arm was moved through cycles of abduction and external rotation. Each arm was mounted once, and all 3 testing procedures were performed on each of the 8 specimens. Statistical analysis was completed using ANOVA, followed by multiple comparisons with Bonferroni correction. RESULTS: The bony tenodesis model placed higher strain on the biceps tendon than the soft tissue tenodesis (p = 0.025). Also, the bony tenodesis model increased the strain on the biceps tendon when compared to the native tendon (p = 0.031). In contrast, the soft tissue tenodesis did not significantly alter strain when compared to the native tendon (p = 0.089). CONCLUSION: The soft tissue tenodesis procedure better maintained the native strain environment when compared to the bony tenodesis using an interference screw. Due to this closer approximation of native biceps tendon biomechanics, the soft tissue procedure may be more preferable clinically than the bony tenodesis. LEVEL OF EVIDENCE: 1, Controlled Laboratory Study.

Supramolecular design of self-assembling nanofibers for cartilage regeneration.

Molecular and supramolecular design of bioactive biomaterials could have a significant impact on regenerative medicine. Ideal regenerative therapies should be minimally invasive, and thus the notion of self-assembling biomaterials programmed to transform from injectable liquids to solid bioactive structures in tissue is highly attractive for clinical translation. We report here on a coassembly system of peptide amphiphile (PA) molecules designed to form nanofibers for cartilage regeneration by displaying a high density of binding epitopes to transforming growth factor beta-1 (TGFbeta-1). Growth factor release studies showed that passive release of TGFbeta-1 was slower from PA gels containing the growth factor binding sites. In vitro experiments indicate these materials support the survival and promote the chondrogenic differentiation of human mesenchymal stem cells. We also show that these materials can promote regeneration of articular cartilage in a full thickness chondral defect treated with microfracture in a rabbit model with or even without the addition of exogenous growth factor. These results demonstrate the potential of a completely synthetic bioactive biomaterial as a therapy to promote cartilage regeneration.

Scapulothoracic dissociation with acromioclavicular separation: a case report of a novel fixation method.

We present a case of 39-year-old female with a scapulothoracic dissociation and acromioclavicular (AC) separation and who had fixation of the AC joint with a locking plate, coracoclavicular screw, and transarticular AC screw. The coracoclavicular and AC relationships were maintained during postoperative rehabilitation and after hardware removal. Use of a locking plate can lead to good functional outcome without the complications associated with the use of pin and wire constructs or without violating the subacromial space.

Upper extremity dog bite wounds and infections.

Upper extremity dog bite wounds comprise a large percentage of all mammalian bite wounds. The purpose of the study was to assess the bacteriology of patients presenting with such injuries to the emergency room that required consultation by a hand surgeon. The study also analyzed the effect of delayed intervention on growth of invasive pathogens, on the incidence of multiple pathogens, on treatment interventions, and on length of hospital stay. Objective data and subjective descriptions of the wound were collected on 32 patients who presented to Chicago area hospitals. The authors retrospectively analyzed the data and grouped the patients into two categories based on time of intervention: early or those treated within 48 hours, and delayed to include those treated after 48 hours. Incidence of bacterial growth and Pasteurella species growth in cultures was similar to that reported in the literature. Delayed patients had a significantly higher incidence of positive bacterial growth from wound cultures (100%) compared with nondelayed patients (54%). Delayed patients also had a higher incidence of treatment intervention (delayed group 86% surgical irrigation and debridement compared with 48% for the early group). There was a trend toward increased length of hospital stay (delayed group 4.6 days compared with 2.6 days), although this was not significant. The growth of multiple pathogens between the two groups was similar and not significant (delayed group 43% compared with 54% early group).