OBJECTIVETo review hearing results after implantation of a self‐crimping stapes prosthesis.STUDY DESIGN AND SETTINGAnalysis of hearing results in patients implanted with a self‐crimping stapes prosthesis at two academic hospitals from 2000 to 2004.RESULTSSeventy‐nine ears were divided into short‐term and intermediate follow‐up groups. The mean postoperative air‐bone gap (ABG), preoperative minus postoperative ABG, and preoperative minus postoperative bone conduction values were 5.7, 21.4, and 4.1 dB, respectively, for the short‐term group, and 6.3, 22.3, and 4.7dB, respectively, for the intermediate group. The ABG was <10 dB in 88 percent of the short‐term group and in 79 percent of the intermediate group.CONCLUSIONSThe self‐crimping Nitinol stapes prosthesis provides excellent short‐term and intermediate postoperative hearing results, and may overcome the limitations of stapes prostheses requiring manual crimping.SIGNIFICANCEThis paper provides evidence for the use of a self‐crimping Nitinol stapes prosthesis, which may simplify hearing restoration surgery for stapes fixation.
Serial Biomarker Measurements in Ambulatory Patients With Chronic Heart Failure
Background— Cardiac troponin T (cTnT) and B-type natriuretic peptide (BNP) have been used to estimate prognosis in heart failure; however, most studies have evaluated decompensated patients with single measurements. To determine if there are advantages to serial measurements, we evaluated stable chronic heart failure patients every 3 months for 2 years. Methods and Results— A cohort of 190 New York Heart Association class III–IV heart failure patients was prospectively enrolled from June 2001 to January 2004. Primary end points were death, cardiac transplantation, or hospitalization. At study enrollment cTnT was <0.01 ng/mL in 87 (45.8%) patients, 0.01 to 0.03 ng/mL in 50 (26.3%) patients, and >0.03 ng/mL in 53 (27.9%) patients. An increase in cTnT above normal (<0.01 ng/mL) carried a 3.4-fold increased risk ( P =0.019). Further increases (≥20%) from an elevated level worsened the overall risk (hazard ratio, 5.09; P <0.001). BNP was elevated (>95th percentile for age and gender normal population) in 122 (64.2%) patients. An elevation of BNP from normal at any time during the study was associated with a poor outcome, but, once elevated, further changes in BNP (increases or decreases) remained associated with the same risk (hazard ratio, 5.09; P <0.001). Combined elevations of cTnT (>0.03 ng/mL) and BNP defined the highest risk group (hazard ratio, 8.58; P <0.001). Conclusions— Elevations of cTnT or BNP from normal detected at any time during clinical follow-up in ambulatory patients with chronic heart failure are highly associated with an increased risk of events. Further increases in cTnT contribute to additional risk. Combined elevations of cTnT and BNP contribute the highest risk. The ability to monitor changes by serial measurements adds substantially to the assessment of risk in this patient population.
WAVE2 Regulates High-Affinity Integrin Binding by Recruiting Vinculin and Talin to the Immunological Synapse
Neuropeptide signaling requires the presence of G protein-coupled receptors (GPCRs) at the cell surface. Activated GPCRs interact with β-arrestins, which mediate receptor desensitization, endocytosis, and mitogenic signaling, and the peptide–receptor–arrestin complex is sequestered into endosomes. Although dissociation of β-arrestins is required for receptor recycling and resensitization, the critical event that initiates this process is unknown. Here we report that the agonist availability in the endosomes, controlled by the membrane metalloendopeptidase endothelin-converting enzyme 1 (ECE-1), determines stability of the peptide–receptor–arrestin complex and regulates receptor recycling and resensitization. Substance P (SP) binding to the tachykinin neurokinin 1 receptor (NK 1 R) induced membrane translocation of β-arrestins followed by trafficking of the SP–NK 1 R–β-arrestin complex to early endosomes containing ECE-1a–d. ECE-1 degraded SP in acidified endosomes, disrupting the complex; β-arrestins returned to the cytosol, and the NK 1 R, freed from β-arrestins, recycled and resensitized. An ECE-1 inhibitor, by preventing NK 1 R recycling in endothelial cells, inhibited resensitization of SP-induced inflammation. This mechanism is a general one because ECE-1 similarly regulated NK 3 R resensitization. Thus, peptide availability in endosomes, here regulated by ECE-1, determines the stability of the peptide–receptor–arrestin complex. This mechanism regulates receptor recycling, which is necessary for sustained signaling, and it may also control β-arrestin-dependent mitogenic signaling of endocytosed receptors. We propose that other endosomal enzymes and transporters may similarly control the availability of transmitters in endosomes to regulate trafficking and signaling of GPCRs. Antagonism of these endosomal processes represents a strategy for inhibiting sustained signaling of receptors, and defects may explain the tachyphylaxis of drugs that are receptor agonists.
The coexistence of urologic malignancy (UM) and abdominal aortic aneurysm (AAA) is rare. Simultaneous treatment may increase morbidity, whereas staged operations delay necessary treatment. We reviewed our experience to develop guidelines for evaluation and management. Clinical data of all patients diagnosed between 1980 and 1998 with both AAA and UM, who also had staged or simultaneous surgical treatment were reviewed. Four thousand forty-seven patients underwent AAA repair during the study period at our institution. Of these, 18 (0.44%) patients, 16 men and two women (mean age: 74 years, range: 61 to 92) had UM. UM was discovered incidentally in nine patients with AAA with computed tomography (CT) scan (7) and ultrasonography (2). In one patient with AAA, hematuria raised the suspicion of UM. Eight patients were diagnosed with AAA during evaluation of UM by CT scan or ultrasound (7) or during laparotomy (1). Initial signs and symptoms included abdominal pain (33%), gross hematuria (33%), and urinary tract infections (17%), although 33% were asymptomatic. The AAA was symptomatic at first examination in three (17%) patients, 14 (78%) patients had hypertension, and two (11%) had renal insufficiency (overall mean serum creatinine: 1.6, range: 0.8 to 3.7). Mean AAA diameter was 5.8 cm (range: 3.8 to 8 cm). Aortography documented significant contralateral renal artery disease in two patients. Twelve patients underwent simultaneous AAA repair and resection of UM; the operations were staged in six (AAA repair first in 2, nephrectomy first in 4). One patient required emergent repair of a ruptured AAA three days after nephrectomy. UM was treated with nephrectomy in 17 patients, and with bilateral ureterectomy and cystectomy in one. A straight aortic graft was implanted in seven patients, a bifurcated graft in ten, and one had extra-anatomic reconstruction. Two patients required reconstruction of the contralateral renal artery. The 30-day mortality rate was 0% after staged and 6% after simultaneous repair (p= >0.1). Major perioperative complications occurred more frequently after simultaneous (42%) than after staged repair (33%), although the difference was not significant (p= >0.1). Two patients developed postoperative renal failure. Seventeen patients were followed for an average of 3.9 years (14 days to 10.8 years). Three (17%) patients died of recurrent cancer at 1, 10.7, and 10.8 years after surgery. Patients with resectable UM have satisfactory long-term survival, which justifies aggressive treatment of concomitant AAA. Aortography in these patients is suggested to exclude contralateral renal artery disease. Complications were frequent, but simultaneous repair did not increase morbidity or mortality significantly. The risk of AAA rupture after nephrectomy, need to correct contralateral renal artery disease at the time of nephrectomy, and disadvantage of delaying treatment of UM are compelling reasons to favor simultaneous treatment of AAA and UM.
Superior Vena Cava Reconstruction Using An Iliocaval Allograft
Successful replacements of the superior vena cava (SVC) using autogenous saphenous or superficial femoral vein or prosthetic grafts have been previously performed, but the use of allograft for treatment of SVC syndrome has not been reported. The patient treated by the authors was a forty-one-year-old woman who presented with severe venous congestion of the head and neck caused by fibrosing mediastinitis. In addition, she had sclerosing cholangitis and chronic liver failure. To treat her SVC syndrome and provide access for fluid and blood transfusion and for possible venovenous bypass, SVC reconstruction was performed concomitant to orthotopic liver transplantation. A left innominate vein-right atrial bypass was inserted using an iliocaval allograft. The patient had an uncomplicated recovery, and at six months after surgery her SVC allograft is widely patent and her transplanted liver is functioning well. The venous allograft is an excellent conduit for those patients who are receiving immunosuppression therapy to avoid rejection of a transplanted organ.
Endovascular Repair of an Infrarenal Abdominal Aortic Aneurysm with a Dominant Middle Mesenteric Artery
The middle mesenteric artery is a rare anomalous mesenteric vessel that may supply variable segments of the colon. Occlusion of this artery during endovascular aortic aneurysm repair may bear a significant risk of bowel ischemia. We report the successful interventional treatment of a patient with a 5.3 cm infrarenal abdominal aortic aneurysm, sparing a dominant middle mesenteric artery.
Aorto Uni-iliac Modification of a Bifurcated Stent Graft for Endovascular Aneurysm Repair: Expanding the Versatility of a Modular Device
As endografting technology advances, anatomical constraints limiting access and deployment have become less of a burden. While unsuitable candidates for endografting exist, these patients are becoming less frequent. To broaden the applicability of endovascular abdominal aortic aneurysm repair (EVAR), we have modified the bifurcated AneuRx™ device into a unilimb modular prosthesis, by placing an aortic extender cuff across the flow divider, thus excluding its contralateral limb. This technique was used with success in 3 groups of patients: with occlusion of 1 iliac artery, with a nontraversable iliac stenosis, or with a small calcific aortic bifurcation. In these patients, anatomy can make it difficult, if not impossible, to place a bifurcated stent graft. Whether as a planned preoperative procedure or as a ‘bail-out’ maneuver, this procedure has been successful in avoiding open surgical conversion.