Programmed necrosis in acute kidney injury

Programmed cell death (PCD) had been widely used synonymously to caspase-mediated apoptosis until caspase-independent cell death was described. Identification of necrosis as a regulated process in ischaemic conditions has recently changed our understanding of PCD. At least three pathways of programmed necrosis (PN) have been identified. First, receptor-interacting protein kinase 3 (RIP3)-dependent necroptosis causes organ failure following stroke, myocardial infarction and renal ischaemia/reperfusion injury. Necroptosis can be mediated either by a large intracellular caspase-8-containing signalling complex called the ripoptosome or by the RIP1-/RIP3-containing necroptosome and is controlled by a caspase-8/FLICE inhibitory protein(long) heterodimer at least in the latter case. Second, mitochondrial permeability transition mediates apoptotic or necrotic stimuli and depends on the mitochondrial protein cyclophilin D. The third PN pathway involves the poly(ADP-ribose) polymerase-calpain axis that contributes to acute kidney injury (AKI). Preclinical interference with the PN pathways therefore raises expectations for the future treatment of ischaemic conditions. In this brief review, we aim to summarize the clinically relevant PCD pathways and to transfer the basic science data to settings of AKI. We conclude that pathologists were quite right to refer to ischaemic kidney injury as 'acute tubular necrosis'.     

Na+/H+ exchange inhibition and antioxidants lack additive protective effects after reperfusion injury in the working heterotopic rat heart isograft.

BACKGROUND: The utility of combining strategies of myocardial protection was studied in intact rat hearts subjected to 1 hour of ischemia and 40 minutes blood reperfusion. METHODS: Lewis rats (n = 48) were divided into 4 transplant groups. Twenty-four hearts were arrested by coronary perfusion with hypothermic Celsior solution at 60 mm Hg. The aortic valve was punctured to introduce volume into the left ventricle (LV), and the hearts were abdominally isografted. Animals were either given both the antioxidant probucol (300 mg/kg) and the sodium-hydrogen exchange inhibitor cariporide (5 mg/kg) (CP; n = 6), just cariporide (CAR; n = 6), just probucol (PROB; n = 6), or neither drug (CON; n = 6). After 40 minutes of blood reperfusion, transplanted hearts were rearrested. The control recipients' native hearts (native; n = 6) were also arrested. Postmortem LV compliance relations and myocardial water content (MWC) were measured. RESULTS: Grafts protected by probucol were significantly more compliant than controls and significantly less compliant than grafts protected by cariporide alone and with both cariporide and probucol (p = 0.0001, analysis of variance). Compliance relations for CP overlapped those for CAR. All grafts were less compliant than natives. MWC was significantly greater in controls and PROB than in natives. CONCLUSIONS: Pretreatment with cariporide in the setting of ischemia-reperfusion injury provides greater protection against the development of diastolic abnormalities than probucol when Celsior solution is used for both arrest and preservation. In this model, there is no advantage to combining the drugs, supporting the hypothesis that there is an overlapping mechanism of protection.     

Subsequent displacement of initially nondisplaced and minimally displaced fractures of the lateral humeral condyle in children

BACKGROUND: Although conservative treatment is a well-established method for treating nondisplaced and minimally displaced (< or =2 mm) fractures of the lateral humeral condyle in children, there is still great uncertainty concerning the rate and time course of subsequent displacement. Therefore, the appropriate frequency of radiographic follow-up remains unclear. The aim of the study was to determine the rate of subsequent displacement after conservative treatment of nondisplaced and minimally displaced fractures of the lateral humeral condyle in children. METHODS: A retrospective analysis of 51 consecutive patients with nondisplaced and minimally displaced fractures of the lateral humeral condyle was performed. RESULTS: Five fractures (9.8%) displaced within 5 days while immobilized and were safely detected by a follow-up radiograph within 1 week after trauma. Additional follow-up radiographs between the first and third weeks did not show relevant alterations in the fracture gap. Mean time of cast immobilization was 22 days, with a range of 17 to 34 days. No pseudarthrosis occurred. CONCLUSION: Fractures with less than or equal to 2 mm of displacement can probably be primarily treated safely by cast immobilization. Anteroposterior and lateral radiographs out of plaster between the fourth and sixth days are necessary to diagnose subsequent displacement of unstable fractures, whereas further "late" displacement did not occur.     

Anatomic Bladder Neck Preservation During Robotic-Assisted Laparoscopic Radical Prostatectomy: Description of Technique and Outcomes

Background

Robotic-assisted laparoscopic radical prostatectomy (RALP) has been rapidly adopted despite a daunting learning curve with bladder neck dissection as a challenging step for newcomers.

Objective

To describe an anatomic, reproducible technique of bladder neck preservation (BNP) and associated perioperative and long-term outcomes.

Design, settings, and participants

From September 2005 to May 2009, data from 619 consecutive RALP were prospectively collected and compared on the basis of bladder neck dissection technique with 348 BNP and 271 standard technique (ST).

Surgical procedure

RALP with BNP.

Measurements

Tumor characteristics, perioperative complications, and post-operative urinary control were evaluated at 4, 12 and 24 months using (1) the Expanded Prostate Cancer Index (EPIC) urinary function scale scored from 0–100; and (2) continence defined as zero pads per day.

Results and limitations

Mean age for BNP versus ST was 57.1 ± 6.6 yr versus 58.9 ± 6.7 yr (p = 0.033), while complication rates did not vary significantly by technique. Estimated blood loss was 183.7 ± 95.8 ml versus 224.6 ± 108 ml (p = 0.938) in men who underwent BNP versus ST. The overall positive margin rate was 12.8%, which did not differ at the prostate base for BNP versus ST (1.4% vs. 2.2%, p = 0.547). Mean urinary function scores for BNP versus ST at 4, 12, and 24 mo were 64.6 versus 57.2 (p = 0.037), 80.6 versus 79.0 (p = 0.495), and 94.1 versus 86.8 (p < 0.001). Similarly, BNP versus ST continence rates at 4, 12, and 24 mo were 65.6% versus 26.5% (p < 0.001), 86.4% versus 81.4% (p = 0.303), and 100% versus 96.1% (p = 0.308).

Conclusions

BNP versus ST is associated with quicker recovery of urinary function and similar cancer control.     

Multislice computed tomography coronary angiography: risk stratification of patients in the perioperative period

Multislice computed tomography coronary angiography is emerging as a reliable non-invasive method for the assessment of coronary artery disease, coronary anatomy and cardiac function. Improvements in computed tomography technology hold the promise of replacing the standard invasive procedure of conventional coronary angiography in selected patient groups. The ability of a six-second scan to identify flow-limiting coronary artery stenoses as well as characterising coronary atheromatous plaque components provides valuable information that can assist in refining perioperative cardiovascular risk. Multislice computed tomography's high negative predictive value and high specificity for stenoses allows it to effectively rule out coronary artery disease in patients with cardiac risk factors who have non-diagnostic or equivocal non-invasive cardiac stress tests. Other uses include evaluating patients who are symptomatic following percutaneous coronary intervention, evaluating coronary artery bypass grafts and coronary stent patency, detecting coronary stenosis prior to valve surgery and assessing coronary anatomy in patients with technically difficult arterial access. Avoiding the small but definite risks of conventional coronary angiography makes cardiac computed tomography an appealing alternative. An overview of multislice computed tomography is presented with particular attention placed on its role in the risk stratification of selected patients in the perioperative period. A risk stratification algorithm is suggested.