Endoluminal treatment for traumatic aortic rupture. Case report and literature review

Traumatic rupture of the thoracic aorta is a near-lethal event presenting on-scene mortality rates of 80% and 60-80% perioperatively with an overall survival rate of 15%. Conventional treatment includes thoracotomy with aortic clamping and aortic replacement but this implies high complication and mortality rates with extended inpatient care. Endoluminal treatment has recently become an attractive treatment option with advantages such as lower death and complication rates as well as shorter inpatient care. We present an 18-year-old female victim of a frontal automobile crash who presented mediastinal enlargement and underwent CT evaluation confirming pericardial effusion, left hemothorax and a contained traumatic rupture of the thoracic aorta. She was sent to our hospital where aortography was performed identifying the injury, and a preperitoneal left iliac artery approach was made to insert a Medtronic Talent 24F endograft. Under fluoroscopic guidance the graft was placed below the subclavian ostium. There was no endoleak after the procedure. A left iliac-femoral bypass was performed and a chest tube was inserted. The patient was managed in the ICU, being later operated by reconstructive and orthopedic surgeons for injuries related to the initial trauma. The patient was released from the hospital on the 10th postoperative day after a satisfactory evolution. We present also a brief review of recent articles.     

Return to dialysis after renal transplantation. Which would be the best way?

The exact moment to return to dialysis when a graft fails has not clearly been established. Furthermore, there is no agreement with respect to whether the guidelines accepted for patients entering dialysis for the first time are adequate for this subgroup of patients with advanced renal failure, due to the special characteristics of these patients, derived from the immunosuppressive medications they are taking among other accompanying factors. We reviewed a group of renal transplant patients who returned to dialysis and compared them with a group of patients entering dialysis for the first time. Patients with chronic renal failure due to graft failure had a poorer renal function at the time entering dialysis and a more profound anemia. Additionally, complications considered such as the number of hospital admissions during the first year after initiation of dialysis were considerably higher in the group of transplanted patients. We advocate for an earlier referral to the dialysis unit, a more aggressive erythropoietin therapy in the phase of advanced renal failure due to chronic allograft nephropathy, and in selected cases retransplantation before definitive graft loss.     

Parametric uncertainty and disturbance attenuation in the suboptimal control of a non‐linear electrochemical process

The optimal control of the hydrogen evolution reactions is attempted for the regulation and change of set‐point problems, taking into account that model parameters are uncertain and I/O signals are corrupted by noise. Bilinear approximations are constructed, and their dimension eventually increased to meet accuracy requirements with respect to the trajectories of the original plant. The current approximate model is used to evaluate the optimal feedback through integration of the Hamiltonian equations. The initial value for the costate is found by solving a state‐dependent algebraic Riccati equation, and the resulting control is then suboptimal for the electrochemical process. The bilinear model allows for an optimal Kalman–Bucy filter application to reduce external noise. The filtered output is reprocessed through a non‐linear observer in order to obtain a state‐estimation as independent as possible from the bilinear model. Uncertainties on parameters are attenuated through an adaptive control strategy that exploits sensitivity functions in a novel fashion. The whole approach to this control problem can be applied to a fairly general class of non‐linear continuous systems subject to analogous stochastic perturbations. All calculations can be handled on‐line by standard ordinary differential equations integration software. Copyright © 2007 John Wiley & Sons, Ltd.     

Mechanism of vascular smooth muscle cells activation by hydrogen peroxide: role of phospholipase C gamma.

BACKGROUND: Hydrogen peroxide (H2O2) formation is a critical factor in processes involving ischaemia/ reperfusion. However, the precise mechanism by which reactive oxygen species (ROS) induce vascular damage are insufficiently known. Specifically, activation of phospholipase C gamma (PLCgamma) is a probable candidate pathway involved in vascular smooth muscle cells (VSMC) activation by H2O2. METHODS: The activation of human venous VSMC was measured as cytosolic free calcium mobilization, shape change and protein phosphorylation, focusing on the role of tyrosine phosphorylation-activated PLCgamma. RESULTS: The exposure of VSMC to exogenous H2O2 caused a rapid increase in cytosolic free calcium concentration ([Ca2+]i), and induced a significant VSMC shape change. Both effects were dependent on a tyrosine kinase-mediated mechanism, as determined by the blockade of short-term treatment of VSMC with the protein tyrosine kinase inhibitor, genistein. Giving further support to the putative role of phospholipase C (PLC)-dependent pathways, the [Ca2+]i and VSMC shape change response were equally inhibited by the specific PLC blocker, 1-(6-((17-beta-methoxyestra-1,3,5(10)trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). In addition, U73122 had a protective effect against the deleterious action (24 h) of H2O2 on non-confluent VSMC. As a further clarification of the specific pathway involved, the exposure to H2O2 significantly stimulated the tyrosine phosphorylation of PLCgamma with a concentration- and time-profile similar to that of [Ca(2+)](i) mobilization. CONCLUSIONS: The present study reveals that H(2)O(2) activates PLCgamma on VSMC through tyrosine phosphorylation and that this activation has a major role in rapid [Ca(2+)](i) mobilization, shape-changing actions and damage by H(2)O(2) in this type of cells. These findings have direct implications for understanding the mechanisms of the vascular actions of H(2)O(2) and may help to design pharmacologically protective strategies.     

Requirement and postoperative outcomes of abdominal panniculectomy alone or in combination with other procedures in a bariatric surgery unit

Background

A high percentage of patients present with redundant skin folds after bariatric surgery. This study aims to quantify the need for panniculectomy after open bariatric surgery and to analyze the postoperative outcomes.

Methods

A retrospective cohort study was performed. The patients were divided into 2 groups: group DLP, patients who underwent an abdominal panniculectomy alone and group DLP+, those who underwent panniculectomy in association with another surgical procedure.

Results

Four hundred forty-six patients underwent open bariatric surgery and 130 patients (29%) subsequently required an abdominal dermolipectomy. Seventy-six percent presented also incisional hernia and 8% presented cholelithiasis. Forty-six percent of patients presented postoperative complications: wound seroma/infection (21%), wound dehiscence due to skin necrosis (13%), and hemorrhage/hematoma (10%) were the most frequent. There were no major complications or mortality. DLP+ was not associated with an increase in complications.

Conclusions

After open bariatric surgery, an abdominal panniculectomy is often required. This procedure has a high postoperative morbidity in these patients, although complications are usually mild. There is not an increase in the rate of complications when panniculectomy is associated with other procedures.     

抗体介导的排斥反应与临床

随着器官移植体液免疫理论的发展与抗体检测技术的进步,抗体介导的排斥反应(AMR)已逐渐被认识和引起关注。其治疗难度大、逆转率较低,已成为导致移植物失功的重要原因。本文较为系统地介绍了AMR的免疫机制、诊断与防治进展,以及供者特异性抗体的检测技术和临床意义,从而提出供者特异性抗体是引起移植物排斥反应特别是慢性排斥反应的主要原因,移植受者需常规监测抗体以利及时干预和治疗。     

Trastuzumab in Primary Inflammatory Breast Cancer (IBC): High Pathological Response Rates and Improved Outcome

Abstract: Inflammatory breast cancer (IBC) represents a rare but aggressive and lethal form of locally advanced breast cancer (LABC) and frequently with HER‐2 neu overexpressed or amplified. We retrospectively identified 16 newly diagnosed HER‐2/neu‐positive IBC patients who were treated with preoperative trastuzumab. We determined the pathological complete response rate (pCR) when trastuzumab was added to preoperative chemotherapy in patients with HER2/neu‐positive IBC. Furthermore, we assessed the expression of CXCR4 in metastatic recurrence sites. Ten patients (62.5%) achieved a pCR. Six patients (37.5%) achieved a partial response. Median follow‐up of all patients was 24.2 months. Four (25%) patients have experienced a progression, of which three were in the brain. Two‐year progression‐free survival was 59.4% (95% CI 35–100). High expression of CXCR4 was detected in the brain metastases. We conclude that in spite of high pCR rates among women with HER‐2/neu‐positive IBC treated with neoadjuvant trastuzumab‐based regimens the outcome remains dismal and brain recurrences are frequent. CXCR4 may represent a novel therapeutic target.     

Comparison of methods for determining renal function decline in early autosomal dominant polycystic kidney disease: the consortium of radiologic imaging studies of polycystic kidney disease cohort

A decline in renal function suggests progression of chronic kidney disease. This can be determined by measured GFR (e.g., iothalamate clearance), serum creatinine (SCr)-based GFR estimates, or creatinine clearance. A cohort of 234 patients with autosomal dominant polycystic kidney disease and baseline creatinine clearance>70 ml/min were followed annually for four visits. Iothalamate clearance, SCr, and creatinine clearance were obtained at each visit. Estimated GFR (eGFR) was determined with the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault equations. Renal function slopes had a mean residual SD of 10.7% by iothalamate clearance, 8.2% by MDRD equation, 7.7% by Cockcroft-Gault equation, and 14.8% by creatinine clearance. By each method, a decline in renal function (lowest quintile slope) was compared among baseline predictors. Hypertension was associated with a decline in iothalamate clearance (odds ratio [OR] 5.8; 95% confidence interval [CI] 2.3 to 14), eGFR (OR [MDRD] 2.0 [95% CI 1.0 to 4.2] or OR [Cockcroft-Gault] 1.9 [95% CI 0.9 to 3.9]), and creatinine clearance (OR 2.0; 95% CI 1.0 to 4.2). Each doubling of kidney volume at baseline was associated with a decline in iothalamate clearance (OR 2.4; 95% CI 1.5 to 3.7), eGFR (OR 1.7 [95% CI 1.1 to 2.6] or 2.1 [95% CI 1.4 to 3.3]), and creatinine clearance (OR 1.7; 95% CI 1.1 to 2.5). Predictor associations were strongest with measured GFR. Misclassification from changes in non-GFR factors (e.g., creatinine production, tubular secretion) conservatively biased associations with eGFR. Misclassification from method imprecision attenuated associations with creatinine clearance.     

Genetic Variation of DKK3 May Modify Renal Disease Severity in ADPKD

Significant variation in the course of autosomal dominant polycystic kidney disease ( ADPKD) within families suggests the presence of effect modifiers. Recent studies of the variation within families harboring PKD1 mutations indicate that genetic background may account for 32 to 42% of the variance in estimated GFR (eGFR) before ESRD and 43 to 78% of the variance in age at ESRD onset, but the genetic modifiers are unknown. Here, we conducted a high-throughput single-nucleotide polymorphism (SNP) genotyping association study of 173 biological candidate genes in 794 white patients from 227 families with PKD1. We analyzed two primary outcomes: (1) eGFR and (2) time to ESRD (renal survival). For both outcomes, we used multidimensional scaling to correct for population structure and generalized estimating equations to account for the relatedness among individuals within the same family. We found suggestive associations between each of 12 SNPs and at least one of the renal outcomes. We genotyped these SNPs in a second set of 472 white patients from 229 families with PKD1 and performed a joint analysis on both cohorts. Three SNPs continued to show suggestive/significant association with eGFR at the Dickkopf 3 (DKK3) gene locus; no SNPs significantly associated with renal survival. DKK3 antagonizes Wnt/β-catenin signaling, which may modulate renal cyst growth. Pending replication, our study suggests that genetic variation of DKK3 may modify severity of ADPKD resulting from PKD1 mutations.Autosomal dominant polycystic kidney disease ( ADPKD) is the most common monogenic kidney disease worldwide, affecting one in 500 to 1000 births.^1,2 It is characterized by focal development of renal cysts in an age-dependent manner. Typically, only a few renal cysts are clinically detectable during the first three decades of life; however, by the fifth decade, tens of thousands of renal cysts of different sizes can be found in most patients.³ Progressive cyst expansion with age leads to massive enlargement and distortion of the normal architecture of both kidneys and, ultimately, ESRD in most patients. ADPKD is also associated with an increased risk for cardiac valvular defects, colonic diverticulosis, hernias, and intracranial arterial aneurysms. Overall, ADPKD accounts for approximately 5% of ESRD in North America.²Mutations of PKD1 and PKD2 respectively account for approximately 85% and approximately 15% of linkage-characterized European families. Polycystin-1 (PC-1) and PC-2, the proteins encoded by PKD1 and PKD2, respectively, function as a macromolecular complex and regulate multiple signaling pathways to maintain the normal tubular structure and function.¹ Monoclonal expansion of individual epithelial cells that have undergone a somatic “second hit” mutation, resulting in biallelic inactivation of either PKD1 or PKD2, seems to provide a major mechanism for focal cyst initiation,⁴ possibly through the loss of polycystin-mediated mechanosensory function in the primary cilium.⁵ In addition, a large prospective, observational study indicated that renal cysts in ADPKD expand exponentially with increasing age, and patients with large polycystic kidneys are at higher risk for developing kidney failure⁶; however, the key factors that modulate renal disease progression in ADPKD remain incompletely understood.Renal disease severity in ADPKD is highly variable, with the age of onset of ESRD ranging from childhood to old age.^7–11 A strong genetic locus effect has been noted in ADPKD. Adjusted for age and gender, patients with PKD1 have larger kidneys and earlier onset at ESRD than patients with PKD2 (mean age at ESRD 53.4 versus 72.7 years, respectively).^8,9 By contrast, a weak allelic effect (based on the 5′ versus 3′ location of the germline mutations) on renal disease severity may be present for PKD1¹⁰ but not PKD2.¹¹ Marked intrafamilial variability in renal disease is well documented in ADPKD and suggests a strong modifier effect.^10–15 In an extreme example, large polycystic kidneys were present in utero in one of a pair of dizygotic twins affected with the same germline PKD1 mutation, whereas the kidneys of the co-twin remained normal at 5 years of age.¹² Several studies have quantified the role of genetic background in the phenotypic expression of ADPKD. In a comparison of monozygotic twins and siblings, greater variance in the age of onset of ESRD in the siblings supported a role for genetic modifiers.¹³ Two other studies of intrafamilial disease variability in PKD1 have estimated that genetic factors may account for 32 to 42% of the variance of creatinine clearance before ESRD and 43 to 78% of the variance in age at ESRD.^14,15 The magnitude of the modifier gene effect from these studies suggests that mapping such factors is feasible. Here, we report the results of an association study of modifier genes for PKD1 renal disease severity.     

Extent of surgery in the management of locally advanced sinonasal malignancies

BACKGROUND: The relative importance of surgery within multimodality regimens commonly used to treat advanced sinonasal malignancies remains unknown. METHODS: One hundred two patients with locally advanced sinonasal cancers treated with proton beam radiation therapy with or without surgery were retrospectively reviewed. Extent of surgery and outcome variables of local control, disease-free survival, and overall survival were evaluated. Patterns of failure were also assessed. RESULTS: Extent of surgery correlated with disease-free survival and overall survival rates. Local control rate, however, was independent of the degree of surgical resection achieved. Overall, treatment failure most commonly resulted from distant metastases, which occurred in 30% of patients and also correlated with extent of surgical resection. Tumor type-specific outcomes reveal differences associated with the extent of surgery achieved. CONCLUSION: High-dose radiotherapy with proton beam resulted in excellent local control rates in patients with locally advanced sinonasal cancer, irrespective of the extent of surgery. Complete resection, however, was predictive of improved disease-free survival and decreased rate of distant metastasis.