Harnessing tumor immunity with cytotoxics: T cells monitoring in mice bearing lung tumors treated with anti-VEGF and pemetrexed-cisplatin doublet.

BACKGROUND: Successful immunotherapy is restricted to some cancers only, and combinatorial strategies with other drugs could help to improve their efficacy. Here, we monitor T cells in NSCLC model after treatment with cytotoxics (CT) and anti-VEGF drugs, to understand when immune checkpoint inhibitors should be best associated next. METHODS: In vivo study was performed on BALB/c mice grafted with KLN205 cells. Eight treatments were tested including control, cisplatin and pemetrexed as low (LD CT) and full (MTD CT) dose as single agents, flat dose anti-VEGF and the association anti-VEGF + CT. Full immunomonitoring was performed by flow cytometry on tumor, spleen and blood over 3 weeks. RESULTS: Immunomodulatory effect was dependent upon both treatments and time. In tumors, combination groups shown numerical lower Treg cells on Day 21. In spleen, anti-VEGF and LD CT group shown higher CD8/Treg ratio on Day 7; on Day 14, higher T CD4 were observed in both combination groups. Finally, in blood, Tregs were lower and CD8/Treg ratio higher, on Day 14 in both combination groups. On Day 21, CD4 and CD8 T cells were higher in the anti-VEGF + MTD CT group. CONCLUSIONS: Anti-VEGF associated to CT triggers notable increase in CD8/Tregs ratio. Regarding the scheduling, a two-week delay after using anti-VEGF and CT could be the best sequence to optimize antitumor efficacy.

Benchmarking a Center of Excellence in Vascular Surgery: Using Acute Physiology and Chronic Health Evaluation II to Validate Outcomes in a Tertiary Care Institute.

OBJECTIVE: The Society of Vascular Surgery (SVS) has made it a top priority to implement verification of vascular "centers of excellence". Our institutional aortic network was established in 2008 in order to standardize care of patients with suspected acute aortic pathology. The implementation and success of this program has been previously reported. We sought to use our experience as a benchmark for which to develop prognostic modeling to quantify clinical status upon admission and help predict outcomes. Our objective was to validate the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system using a cohort of aortic emergencies transferred by an organized transfer network. METHOD: This was a retrospective, single institution review of patients transferred through an institutional aortic network for acute aortic pathology from 2017-2018. Demographics, comorbidities, aortic diagnosis, APACHE II score, as well as 30-day mortality were recorded. Associations with 30-day mortality were evaluated using two-sample t-tests, ANOVA models, Pearson chi-square tests and Fisher exact tests. Receiver operating characteristic (ROC) curves were fit overall and by pathology to predict 30-day mortality by Apache II total score. RESULTS: There were 395 consecutive transfers were identified. The mean age was 64.7 years. Diagnoses included Type A Dissection (n = 134), Type B (n = 81), Aortic Aneurysm (n = 122), and PAU/IMH (n = 27). Mean APACHE II score on arrival was 12. Overall there were 53 deaths (13.4%) in the cohort. Patients that died had significantly higher Apache II total scores (11.3 vs 16.5, P < .001). The area under the receiver operator characteristic (ROC) curve (AUC) was .66 for the full cohort, indicating a poor clinical prediction test. CONCLUSION: APACHE II score is a poor predictor of 30-day mortality in a large transfer network accepting all aortic emergencies. The authors believe further refining a prognostic model for diverse population will not only help in predicting outcomes but to objectively quantify illness severity in order to have a basis for comparison among institutions and verification of "centers of excellence".

Unravelling direct and indirect contact patterns between duck farms in France and their association with the 2016-2017 epidemic of Highly Pathogenic Avian Influenza (H5N8).

Live animal movements generate direct contacts (via the exchange of live animals) and indirect contacts (via the transit of transport vehicles) between farms, which can contribute to the spread of pathogens. However, most analyses focus solely on direct contacts and can therefore underestimate the contribution of live animal movements in the spread of infectious diseases. Here, we used French live duck movement data (2016-2018) from one of the largest transport companies to compare direct and indirect contact patterns between duck farms and evaluate how these patterns were associated with the French 2016-2017 epidemic of highly pathogenic avian influenza H5N8. A total number of 614 farms were included in the study, and two directed networks were generated: the animal introduction network (exchange of live ducks) and the transit network (transit of transport vehicles). Following descriptive analyses, these two networks were scrutinized in relation to farm infection status during the epidemic. Results showed that farms were substantially more connected in the transit network than in the animal introduction network and that the transit of transport vehicles generated more opportunities for transmission than the exchange of live animals. We also showed that animal introduction and transit networks' statistics decreased substantially during the epidemic (January-March 2017) compared to non-epidemic periods (January-March 2016 and January-March 2018). We estimated a probability of 33.3 % that a farm exposed to the infection through either of the two live duck movement networks (i.e. that was in direct or indirect contact with a farm that was reported as infected in the following seven days) becomes infected within seven days after the contact. However, we also demonstrated that the level of exposure of farms by these two contact patterns was low, leading only to a handful of transmission events through these routes. As a consequence, we showed that live animal movement patterns are efficient transmission routes for HPAI but have been efficiently reduced to limit the spread during the French 2020-2021 epidemic. These results underpin the relevance of studying indirect contacts resulting from the movement of animals to understand their transmission potential and the importance of accounting for both routes when designing disease control strategies.

Prototyping Trastuzumab Docetaxel Immunoliposomes with a New FCM-Based Method to Quantify Optimal Antibody Density on Nanoparticles.

Developing targeted nanoparticles is a rising strategy to improve drug delivery in oncology. Antibodies are the most commonly used targeting agents. However, determination of their optimal number at the surface remains a challenging issue, mainly due to the difficulties in measuring precisely surface coating levels when prototyping nanoparticles. We developed an original quantitative assay to measure the exact number of coated antibodies per nanoparticle. Using flow cytometry optimized for submicron particle analysis and beads covered with known amounts of human IgG-kappa mimicking various amounts of antibodies, this new method was tested as part of the prototyping of docetaxel liposomes coated with trastuzumab against Her2+ breast cancer. This quantification method allowed to discriminate various batches of immunoliposomes depending on their trastuzumab density on nanoparticle surface (i.e., 330 (Immunoliposome-1), 480 (Immunoliposome-2) and 690 (Immunoliposome-3), p = 0.004, One-way ANOVA). Here we showed that optimal number of grafted antibodies on nanoparticles should be finely tuned and highest density of targeting agent is not necessarily associated with highest efficacy. Overall, this new method should help to better prototype third generation nanoparticles.

Benefits and risks of oxygen therapy during acute medical illness: Just a matter of dose!

Oxygen therapy is used to reverse hypoxemia since more than a century. Current usage is broader and includes routine oxygen administration despite normoxemia which may result in prolonged periods of hyperoxemia. While systematic oxygen therapy was expected to be of benefit in some ischemic diseases such as stroke or acute myocardial infarction, recent randomised controlled trials (RCTs) have challenged this hypothesis by showing the absence of clinical improvement. Although oxygen is known to be toxic at high inspired oxygen fractions, a recent meta-analysis of RCTs revealed the life-threatening effect of hyperoxemia, with a dose-dependent relationship. Several recommendations have therefore been updated: (i) to monitor peripheral oxygen saturation (SpO2) as a surrogate for arterial oxygen saturation (SaO2); (ii) to initiate oxygen only when the lower SpO2 threshold is crossed; (iii) to titrate the delivered oxygen fraction to maintain SpO2 within a target range; and (iv) to stop supplying oxygen when the upper limit of SpO2 is surpassed, in order to prevent hyperoxemia. The lower and upper limits of SpO2 depend on the presence of risk factors for oxygen-induced hypercapnia (Chronic obstructive pulmonary disease, asthma, and obesity-associated hypoventilation). For patients at risk, oxygen therapy should be started when SpO2 is≤88% and stopped when it is>92%. For patients without risk factors, oxygen therapy should be started when SpO2 is≤92% and stopped when it is >96%. High-flow oxygen should only be used in a few diseases such as carbon monoxide poisoning, cluster headaches, sickle cell crisis and pneumothorax.

Perceptual blending in odor mixtures depends on the nature of odorants and human olfactory expertise.

Our olfactory system is confronted with complex mixtures of odorants, often recognized as single entities due to odor blending (e.g., coffee). In contrast, we are also able to discriminate odors from complex mixtures (e.g., off-odors). Therefore, the olfactory system is able to engage either configural or elemental processes when confronted with mixtures. However, the rules that govern the involvement of these processes during odor perception remain poorly understood. In our first experiment, we examined whether simple odorant mixtures (binary/ternary) could elicit configural perception. Twenty untrained subjects were asked to evaluate the odor typicality of mixtures and their constituents. The results revealed a significant increase in odor typicality in some but not all mixtures as compared with the single components, which suggest that perceptual odor blending can occur only in specific mixtures (configural processing). In our second experiment, we tested the hypothesis that general olfactory expertise can improve elemental perception of mixtures. Thirty-two trained subjects evaluated the odor typicality of the stimuli presented during the first experiment, and their responses were compared with those obtained from the untrained panelists. The results support the idea that general training with odors increases the elemental perception of binary and ternary blending mixtures.

Initial 200 cases of carotid artery stenting using a reversal-of-flow cerebral protection device.

AIM: Because embolic complications can occur during carotid angioplasty and stenting (CAS), a new device, the Parodi Anti-Emboli System (PAES) was developed to protect the brain from embolization. We describe our initial experience with this device. METHODS: Between September 1999 and December 2003, CAS was performed in 200 consecutive patients (146 men; mean age, 70.4 years) with symptomatic (52%) or asymptomatic (48%) severe carotid artery stenosis (>70%). De novo lesions were present in 169 patients, restenosis in 18, and radiation-induced stenosis in 13. Wallstents were inserted in all cases, with selective predilatation, and the PAES was employed during all CAS procedures. Patients were evaluated by a neurologist before and after CAS. Minor strokes, major or fatal strokes, and myocardial infarctions that occurred within 30 days of the procedure were recorded. RESULTS: The overall technical success rate for CAS using the PAES (with the PAES placed in position percutaneously) was 99%. The overall perioperative stroke and death rate was 1.5%. There were four transient neurologic events after CAS, three of which were related to hemodynamic instability and one to postoperative embolization. CONCLUSIONS: Our experience indicates that CAS using the PAES is safe and effective. The protection device may prevent the debris released by angioplasty from entering the cerebral circulation. Additional studies of this device are warranted.

Abdominal aortic aneurysm repair in high-risk and elderly patients.

Elective open repair of abdominal aortic aneurysm (AAA) is a proven surgical therapy with acceptable rates of perioperative mortality. Open AAA repair in elderly and high-risk patients, however, carries a significantly greater risk of surgical mortality and perioperative complications. Given the steady increase of life expectancy in developed nations, assessment of surgical outcomes and clarification of the role of emerging therapies in the aging population are of significant interest to the vascular surgeon. Selection of treatment options for these patients must be based on an individual approach, and assessment of outcomes must include more subtle parameters, such as quality of life, in addition to operative survival. Recent studies assessing the applicability of endoluminal graft repair in the elderly demonstrate that this avenue of treatment may offer substantial benefit to selected patients. We review the historical data regarding operative aneurysm repair in the high-risk and elderly population, and examine the impact of endoluminal therapy of AAAs in these challenging patients.

Odor and color of cosmetic products: correlations between subjective judgement and autonomous nervous system response.

The color and odor of cosmetics have been shown to be crucial for affective states and able to influence autonomic responses. We report an original procedure to measure the effect on subjects of the color and odor of cosmetic products, and to quantify the correlation between objective (psychophysiological recording) and subjective (psychophysics) responses. Several cosmetic products (lipsticks and nail varnishes) of different colors (white, brown, red, orange, and pink) and odors (two per product) were presented. In a first step, autonomous parameters (skin conductance (SC) and heart rate (HR)) were recorded, and in the second step, subjects rated their sensations on subjective scales (overall appreciation, pleasantness, and emotional arousal). Results indicated that certain color and odor additives in cosmetics act on relaxation, excitation, perceived pleasantness, and emotional arousal. It was also found that certain colors, perceived as pleasant, decreased HR, and that the perception of an 'arousing' perfume significantly increased SC.

Evaluation of 5 types of fishing material, 2 sterilization methods, and a crimp-clamp system for extra-articular stabilization of the canine stifle joint.

OBJECTIVE: To evaluate the mechanical properties of 5 types of fishing material, 2 sterilization methods, and a commercially designed crimp-clamp system for the extra-articular repair of the canine stifle joint. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Animals were not used in this study. METHODS: Two brands of monofilament nylon fishing line and 3 brands of monofilament nylon leader line were used to determine the effect of steam and ethylene oxide sterilization on strength and elongation of the material. A strand of 36-kg test monofilament nylon fishing material was wrapped around 2 rods or knotted to form a loop around 2 rods on a materials-testing machine. Ten trials of each brand of unsterilized, steam-sterilized, and ethylene oxide-sterilized fishing material were tested. A strand of each material was elongated to failure at a constant displacement of 1,000 mm/min to determine strength. A strand of each material was cycled 10 times to a load of 50 N to determine percent elongation. The brand of fishing material with the greatest strength and least elongation was crimped to form a loop around 2 rods on a materials-testing machine and tested as described above. ANOVA was used to determine the effect of sterilization method, brand of material, knot, wrap, and crimp on strength and elongation of the material, and a post-hoc t test was used when significant differences were found. A Student t test was used to compare fixation techniques (wrap, knot, and crimp). RESULTS: Sterilization by steam or ethylene oxide had no significant effect on the strength of the nylon fishing material. Steam sterilization resulted in significant increases (2- to 4-fold) in elongation of most nylon fishing material when compared with unsterilized material. Ethylene oxide sterilization had minimal effect on elongation of the fishing material. Mason leader line showed no significant change in strength or elongation regardless of sterilization method. Significantly less strength and significantly less elongation were demonstrated in Mason leader line that was crimped as compared with Mason leader line that was knotted. CONCLUSION: Ethlylene oxide was the preferred method of sterilization to preserve strength and minimize elongation of the fishing material. Of the materials tested, Mason leader line had the least elongation and the greatest preservation of strength when ethylene oxide was used as the sterilization method. Mason leader line and Sufix fishing line were comparable choices when steam was used as the sterilization method. Significantly less elongation was demonstrated in crimped Mason leader line as compared with knotted Mason leader line. CLINICAL RELEVANCE: Of the materials tested, Mason leader line and Sufix fishing line had the best mechanical properties for extracapsular stabilization of the canine stifle joint. Crimping is an attractive alternative to knotting and results in a reduction in elongation of the nylon fishing material.

Endovascular abdominal aortic aneurysm repair in 144 patients: correlation of aneurysm size, proximal aortic neck length, and procedure-related complications.

PURPOSE: During endovascular abdominal aortic aneurysm (AAA) repair, larger aneurysms often present formidable anatomic challenges to the insertion of the delivery catheter and graft deployment. The authors sought to evaluate whether large-diameter aneurysms and those with short proximal aortic necks might be associated with a higher frequency of insertion-related and short-term complications. MATERIALS AND METHODS: From October 1999 to August 2000, 144 patients underwent elective endovascular graft placement for infrarenal AAA disease at the authors' institution. These patients were treated with use of the AneuRx bifurcated endoprosthesis. AAA size (maximum aneurysm diameter) and proximal aortic neck length were compared to estimated blood loss, operative time, accuracy of graft placement, presence of endoleak, intraoperative and postoperative complications (such as limb occlusion or vascular injury), length of hospital stay, and mortality. Statistical methods included correlation analysis and logistic regression. RESULTS: There were 121 men and 23 women whose aneurysms ranged in size from 3 cm to 9.8 cm (mean, 5.6 cm; 95% CI, 5.4-5.8 cm). Endograft insertion was successful in all cases. There were three deaths within 30 days (2.1%) and seven deaths overall (4.9%). There were 43 intraoperative complications (29.9%) in 31 patients (21.5%), most of them minor. Patients with major intraoperative complications had significantly longer procedure times than those without complications (337 vs. 149 min; P <.0001). In the postoperative period (within 30 days), 31 complications (21.5%) occurred in 28 patients (19.4%), again most of them minor. AAA size was unrelated in any way to the rate of complications, but short proximal aortic neck length was associated with more serious intraoperative and postoperative complications (P =.0404 and P =.0230, respectively), and decreased 30-day and overall survival (P =.0240 and P =.0152, respectively). CONCLUSIONS: Endovascular repair of large AAAs can be challenging; however, the size of the AAA does not influence the rate of complications. A short proximal aortic neck is the only significant risk factor for more serious complications.

Use of aortic cuffs to exclude iliac artery aneurysms during AneuRx stent-graft placement: initial experience.

PURPOSE: As many as 39% of patients who undergo aortic endografting for abdominal aortic aneurysm disease will have ectasia of the iliac arteries that will require intervention. Coil embolization of the internal iliac artery and extension of the graft to the external iliac artery is one solution to this problem. However, 19%-41% of these patients experience buttock claudication, which may be permanent, after unilateral embolization. The authors examined an alternative: the use of larger-sized aortic cuffs to seal the iliac limb. Outcomes and short-term results are presented in this article. MATERIALS AND METHODS: From October 1999 to August 2000, 144 AneuRx stent-grafts were placed at the authors' institution. Among the population receiving stent-grafts, 14 patients had 15 aortic cuffs placed across the distal iliac graft limbs to seal them and preserve flow to the internal iliac artery. One patient had bilateral cuffs placed. Five patients had embolization of the contralateral internal iliac artery because of bilateral disease. Patients were followed with computed tomography (CT) at 1, 6, and 12 months to evaluate for endoleaks. RESULTS: One- and 6-month endoleak rates, determined from only those patients with follow-up CT, were 0% and 10%, respectively. One type II endoleak was first discovered 9 months after graft placement. It sealed spontaneously at 15-month follow-up. One patient among the five who had internal iliac artery embolization had claudication. Mean CT follow-up was 7.8 months (range, 1-15). One patient declined CT but was alive and well 11 months after endografting. One patient moved across the country and declined follow-up. CONCLUSION: Placement of aortic cuffs in dilated iliac arteries can preserve flow to the ipsilateral internal iliac artery and provide an adequate seal. Additionally, the option of later treatment is maintained. Patients with bilateral iliac ectasia can undergo stent-graft placement without bilateral internal iliac artery embolization. Longer-term follow-up in larger numbers of patients will be important to determine the ultimate durability of this technique.

Novel MRI contrast agent for molecular imaging of fibrin: implications for detecting vulnerable plaques.

BACKGROUND: Molecular imaging of thrombus within fissures of vulnerable atherosclerotic plaques requires sensitive detection of a robust thrombus-specific contrast agent. In this study, we report the development and characterization of a novel ligand-targeted paramagnetic molecular imaging agent with high avidity for fibrin and the potential to sensitively detect active vulnerable plaques. METHODS AND RESULTS: The nanoparticles were formulated with 2.5 to 50 mol% Gd-DTPA-BOA, which corresponds to >50 000 Gd(3+) atoms/particle. Paramagnetic nanoparticles were characterized in vitro and evaluated in vivo. In contradistinction to traditional blood-pool agents, T1 relaxation rate as a function of paramagnetic nanoparticle number was increased monotonically with Gd-DTPA concentration from 0.18 mL. s(-1). pmol(-1) (10% Gd-DTPA nanoparticles) to 0.54 mL. s(-1). pmol(-1) for the 40 mol% Gd-DTPA formulations. Fibrin clots targeted in vitro with paramagnetic nanoparticles presented a highly detectable, homogeneous T1-weighted contrast enhancement that improved with increasing gadolinium level (0, 2.5, and 20 mol% Gd). Higher-resolution scans and scanning electron microscopy revealed that the nanoparticles were present as a thin layer over the clot surface. In vivo contrast enhancement under open-circulation conditions was assessed in dogs. The contrast-to-noise ratio between the targeted clot (20 mol% Gd-DTPA nanoparticles) and blood was approximately 118+/-21, and that between the targeted clot and the control clot was 131+/-37. CONCLUSIONS: These results suggest that molecular imaging of fibrin-targeted paramagnetic nanoparticles can provide sensitive detection and localization of fibrin and may allow early, direct identification of vulnerable plaques, leading to early therapeutic decisions.

Endoluminal graft repair for abdominal aortic aneurysms in high-risk patients and octogenarians: is it better than open repair?

OBJECTIVE: To analyze the short-term and midterm results of open and endoluminal repair of abdominal aortic aneurysms (AAA) in a large single-center series and specifically in octogenarians. METHODS: Between January 1997 and October 2000, 470 consecutive patients underwent elective repair of AAA. Conventional open repair (COR) was performed in 210 patients and endoluminal graft (ELG) repair in 260 patients. Ninety of the patients were 80 years of age or older; of these, 38 underwent COR and 52 ELG repair. RESULTS: Patient characteristics and risk factors were similar for both the entire series and the subgroup of patients 80 years or older. The overall complication rate was reduced by 70% or more in the ELG versus the COR groups. The postoperative death rate was similar for the COR and ELG groups in the entire series and lower (but not significantly) in the ELG 80 years or older subgroup versus the COR group. The 36-month rates of freedom from endoleaks, surgical conversion, and secondary intervention were 81%, 98.2%, and 88%, respectively. CONCLUSION: The short-term and midterm results of AAA repair by COR or ELG are similar. The death rate associated with this new technique is low and comparable, whereas the complication rate associated with COR in all patients and those 80 years or older in particular is greater and more serious than ELG repair. Long-term results will establish the role of ELG repair of AAA, especially in elderly and high-risk patients.

Increased expression of HDJ-2 (hsp40) in carotid artery atherosclerosis: a novel heat shock protein associated with luminal stenosis and plaque ulceration.

PURPOSE: Evidence suggests that both humoral and cellular autoimmune processes directed toward heat shock proteins (hsp) contribute to the pathogenesis of atherosclerosis. We characterized a human hsp distinct from those previously characterized in atherosclerotic lesions, termed HDJ-2. METHODS: To determine the role of HDJ-2 in atherosclerosis, we compared the level of HDJ-2 mRNA expression with the level of hsp60 and hsp70 mRNA expression in 26 carotid endarterectomy specimens and 17 normal arteries. The level of expression of HDJ-2 mRNA was also correlated to the presence of plaque ulceration and the degree of luminal stenosis associated with the lesion. RESULTS: The expression of HDJ-2 and hsp70 was significantly higher in carotid artery plaques as compared with normal arteries: HDJ-2, 6.7 +/- 1.6 vs 0.1 +/- 0.04, (P =.001); hsp70, 9.5 +/- 0.9 vs 3.7 +/- 0.8, (P =.002). There was no significant difference in hsp60 expression between carotid artery plaques and normal arteries (21.0 +/- 0.9 vs 20.6 +/- 0.8, P =.65). Increased HDJ-2 expression in carotid artery plaques was independent of hsp70 (Pearson correlation, r = 0.11; Bartlett chi(2) analysis, P =.71). Within the ulcerated plaque group, there was a correlation between degree of stenosis and high HDJ-2 mRNA expression (r = 0.896, P =.016). However, there was no correlation between degree of stenosis and high HDJ-2 mRNA expression within the nonulcerated plaque group (r = 0.530, P =.076) or within the entire group of patients (r = 0.0085, P =.97). CONCLUSION: These results demonstrate that expression of HDJ-2 is significantly increased in atherosclerotic carotid artery plaques as compared with hsp60 and hsp70 and correlates with luminal stenosis in ulcerated atherosclerotic carotid artery plaques.

Granulosa cell tumor in a guinea pig.

Abdominal distention is a common clinical sign in guinea pigs and may have many causes. Abdominal ultrasonography may be a useful diagnostic tool in differentiation of abdominal disorders in guinea pigs. Ovariohysterectomy is indicated for granulosa cell tumors and cystic rete ovarii in guinea pigs.

Evolution of vascular fellowship training in the new era of endovascular techniques.

PURPOSE: The endovascular technique has revolutionized the treatment of infrarenal abdominal aortic aneurysm (AAA). At our institution, we examined the impact of an endovascular program on the traditional operative training of the vascular fellows in the treatment of infrarenal AAA. METHODS: We examined the records of our vascular fellows' experience from July 1995 to May 2000. We introduced the endovascular treatment for infrarenal AAA in 1995. RESULTS: The fellows have performed increasing numbers of endovascular cases each year, with a predicted number of 124 cases for 1999-2000. However, despite an increase in the overall volume of patients with infrarenal AAA (102 cases in 1998-1999 and a predicted 160 cases in 1999-2000), the trainees will experience a reduction in the number of open AAAs from 61 cases in 1998-1999 to a predicted 36 cases in 1999-2000. However, the volume of open suprarenal AAA has also increased from eight cases in 1998 to 1999 to a predicted 24 cases in 1999-2000. With no significant change in the open aortoiliac occlusive cases from previous years, the current fellows will graduate with a similar volume of open aortic procedures as their predecessors. CONCLUSION: With the recent advances in endovascular technology, our traditional operative approach to the treatment of AAA disease may be lacking in the training of future vascular surgeons. At our institution, although fewer open infrarenal AAA cases were performed, the trainees have maintained the open aortic experience by performing an increased volume of suprarenal AAAs. We have to critically reevaluate and redefine what constitutes adequate vascular fellow experience in the surgical treatment of abdominal aortic aneurysms.

The Hemobahn endoprosthesis: a self-expanding polytetrafluoroethylene-covered endoprosthesis for the treatment of peripheral arterial occlusive disease after balloon angioplasty.

Endoluminal management of occlusive arterial disease has previously been limited to balloon angioplasty, either alone or with stent placement. This article discusses the Hemobahn endoprosthesis, a polytetraflouroethylene-covered nitinol stent graft. The Hemobahn device design characteristics, Food and Drug Administration phase I feasibility trial design and results, phase II pivotal trial design, and single-site phase II trial results are reviewed. The long-term outcomes of patients treated with angioplasty and Hemobahn stent grafting will determine the role of stent grafting in the management of occlusive arterial lesions below the aortic bifurcation.

Factors increasing the mortality rate for patients with ruptured abdominal aortic aneurysms.

The objective of this report was to analyze the current surgical results of operative treatment in patients suffering ruptured AAA (abdominal aortic aneurysms) and to define those independent predictive factors for mortality. During a period of 2 years, from January 1996 to December 1997, 144 patients operated on for ruptured AAA in 10 hospitals were included in a multicenter retrospective study. Among the collected variables concerning each patient, those with potential relation to surgical mortality were studied: gender, age, diabetes, hypertension, cardiopathy, pulmonary obstructive disease, preoperative renal dysfunction, symptomatic cerebrovascular disease, peripheral vascular disease, hematocrit on admission, preoperative hypotension < 80 mmHg, loss of consciousness, cardiac arrest, aortic aneurysm location (infrarenal versus non-infrarenal), iliac involvement, aneurysm size, type of rupture, left renal vein ligature, ligature of a patent inferior mesenteric artery, place of aortic cross-clamping, type of grafting, exclusion of both hypogastric arteries, venous technical complications, associated surgery, use of cell saver, intraoperative blood loss, and postoperative complications (renal failure, sepsis, coagulopathy, cardiac complications, pulmonary complications, colon ischemia, prosthetic graft complications, and need for reoperation). Those variables with statistical significance in the univariate analysis were introduced into a multivariate logistic regression model to determine the independent predictors of death. From our results we concluded that surgery for ruptured abdominal aortic aneurysms continues to have an excessively high mortality rate. Even though some preoperative variables could be identified as predictors of mortality, an absolute mortality risk has not yet been determined and the decision to negate surgery should be individualized rather than taken on that basis only. Early diagnosis and treatment of symptomatic aneurysms would improve mortality figures and selective screening should be contemplated.

A novel mechanism for skeletal resistance in uremia.

BACKGROUND: In treating secondary hyperparathyroidism, the target level of serum intact parathyroid hormone (I-PTH) should be three to five times normal to prevent adynamic bone disease. In circulation, there is a non-(1-84) PTH-truncated fragment, likely 7-84, which, in addition to PTH 1-84, is measured by most I-PTH immunoradiometric (IRMA) assays, giving erroneously high I-PTH values. We have developed a new IRMA assay in which the labeled antibody recognizes only the first six amino acids of the PTH molecule. Thus, this new IRMA assay (Whole PTH) measures only the biologically active 1-84 PTH molecule. METHODS: Using this new IRMA assay (Whole PTH) and the Nichols "intact" PTH assay, we compared the ability of each assay to recognize human PTH (hPTH) 1-84 and hPTH 7-84 and examined the percentage of non-1-84 PTH in circulation and in parathyroid glands. Possible antagonistic effects of the 7-84 PTH fragment on the biological activity of 1-84 PTH in rats were also tested. RESULTS: In 28 uremic patients, PTH values measured with the Nichols assay, representing a combined measurement of both hPTH 1-84 and hPTH 7-84, were 34% higher than with the Whole assay (hPTH 1-84 only); the median PTH was 523 versus 318 pg/mL (P < 0.001). Similar results were found in 14 renal transplant patients. In osteoblast-like cells, ROS 17.2, 1-84 PTH (10-8 mol/L) increased cAMP from 18.1 +/- 1.25 to 738 +/- 4.13 mmol/well. Conversely, the same concentration of 7-84 PTH had no effect. In parathyroidectomized rats fed a calcium-deficient diet, 7-84 PTH was not only biologically inactive, but had antagonistic effects on 1-84 PTH in bone. Plasma calcium was increased (0.65 mg/dL) two hours after 1-84 PTH treatment, while 7-84 PTH had no effect. When 1-84 PTH and 7-84 PTH were given simultaneously in a 1:1 molar ratio, the calcemic response to 1-84 PTH was decreased by 94%. In normal rats, the administration of 1-84 PTH increased renal fractional excretion of phosphate (11.9 to 27.7%, P < 0.001). However, when 1-84 PTH and 7-84 PTH were given simultaneously, the 7-84 PTH decreased the phosphaturic response by 50.2% (P < 0.005). Finally, in surgically excised parathyroid glands from six uremic patients, we found that 44.1% of the total intracellular PTH was the non-PTH (1-84), most likely PTH 7-84. CONCLUSION: In patients with chronic renal failure, the presence of high circulating levels of non-1-84 PTH fragments (most likely 7-84 PTH) detected by the "intact" assay and the antagonistic effects of 7-84 PTH on the biological activity of 1-84 PTH explain the need of higher levels of "intact" PTH to prevent adynamic bone disease.